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Sample records for malaria transmission blocking

  1. Modulation of human malaria transmission by anti-gamete transmission blocking immunity.

    PubMed

    de Zoysa, A P; Herath, P R; Abhayawardana, T A; Padmalal, U K; Mendis, K N

    1988-01-01

    Natural Plasmodium vivax malaria infections in man evoke anti-gamete transmission blocking antibodies which influence the infectivity of malaria patients to the vector mosquito. In this study, entomological, immunological and parasitological data obtained through the monitoring of an epidemic of human vivax malaria in Sri Lanka were used in a mathematical simulation to assess the effect of naturally induced transmission blocking immunity on malaria transmission. A mathematical model to describe malaria transmission accounting for transmission blocking immunity was developed from the basic differential equations originally stated by R. Ross and the epidemic was simulated using the available data. An attempt was made to predict the monthly malaria incidence by means of the mathematical simulation, with and without accounting for transmission blocking immunity. A plausible mathematical solution of the epidemic could be obtained when transmission blocking immunity was accounted for, and it was not possible to obtain such a plausible solution in the absence of immunity. Thus, the postulated occurrence of transmission blocking immunity was essential to describe adequately this malaria epidemic, indicating that, at least in epidemic situations, naturally occurring transmission blocking immunity has a controlling influence on malaria incidence. PMID:3076711

  2. Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America.

    PubMed

    Arévalo-Herrera, Myriam; Solarte, Yezid; Marin, Catherin; Santos, Mariana; Castellanos, Jenniffer; Beier, John C; Valencia, Sócrates Herrera

    2011-08-01

    Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America. PMID:21881775

  3. Transmission blocking malaria vaccines: Assays and candidates in clinical development.

    PubMed

    Sauerwein, R W; Bousema, T

    2015-12-22

    Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. PMID:26409813

  4. A Class of Tricyclic Compounds Blocking Malaria Parasite Oocyst Development and Transmission

    PubMed Central

    Eastman, Richard T.; Pattaradilokrat, Sittiporn; Raj, Dipak K.; Dixit, Saurabh; Deng, Bingbing; Miura, Kazutoyo; Yuan, Jing; Tanaka, Takeshi Q.; Johnson, Ronald L.; Jiang, Hongying; Huang, Ruili; Williamson, Kim C.; Lambert, Lynn E.; Long, Carole; Austin, Christopher P.; Wu, Yimin

    2013-01-01

    Malaria is a deadly infectious disease in many tropical and subtropical countries. Previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. ATP-binding cassette (ABC) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. To investigate whether a Plasmodium falciparum ABC transporter (Pf14_0244 or PfABCG2) modulates parasite susceptibility to chemical compounds or plays a role in drug resistance, we disrupted the gene encoding PfABCG2, screened the recombinant and the wild-type 3D7 parasites against a library containing 2,816 drugs approved for human or animal use, and identified an antihistamine (ketotifen) that became less active against the PfABCG2-disrupted parasite in culture. In addition to some activity against asexual stages and gametocytes, ketotifen was highly potent in blocking oocyst development of P. falciparum and the rodent parasite Plasmodium yoelii in mosquitoes. Tests of structurally related tricyclic compounds identified additional compounds with similar activities in inhibiting transmission. Additionally, ketotifen appeared to have some activity against relapse of Plasmodium cynomolgi infection in rhesus monkeys. Further clinical evaluation of ketotifen and related compounds, including synthetic new derivatives, in blocking malaria transmission may provide new weapons for the current effort of malaria eradication. PMID:23129054

  5. Expression, immunogenicity, histopathology, and potency of a mosquito-based malaria transmission-blocking recombinant vaccine.

    PubMed

    Mathias, D K; Plieskatt, J L; Armistead, J S; Bethony, J M; Abdul-Majid, K B; McMillan, A; Angov, E; Aryee, M J; Zhan, B; Gillespie, P; Keegan, B; Jariwala, A R; Rezende, W; Bottazzi, M E; Scorpio, D G; Hotez, P J; Dinglasan, R R

    2012-04-01

    Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model. PMID:22311924

  6. Toward the development of effective transmission-blocking vaccines for malaria.

    PubMed

    Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi

    2015-05-01

    The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments. PMID:25597923

  7. The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope.

    PubMed

    Atkinson, Sarah C; Armistead, Jennifer S; Mathias, Derrick K; Sandeu, Maurice M; Tao, Dingyin; Borhani-Dizaji, Nahid; Tarimo, Brian B; Morlais, Isabelle; Dinglasan, Rhoel R; Borg, Natalie A

    2015-07-01

    Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however, AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antibodies functionally block parasite transmission have remained elusive. Here we present the 2.65-Å crystal structure of AnAPN1 and the immunoreactivity and transmission-blocking profiles of three monoclonal antibodies (mAbs) to AnAPN1, including mAb 4H5B7, which effectively blocks transmission of natural strains of Plasmodium falciparum. Using the AnAPN1 structure, we map the conformation-dependent 4H5B7 neoepitope to a previously uncharacterized region on domain 1 and further demonstrate that nonhuman-primate neoepitope-specific IgG also blocks parasite transmission. We discuss the prospect of a new biological function of AnAPN1 as a receptor for Plasmodium in the mosquito midgut and the implications for redesigning the AnAPN1 mTBV. PMID:26075520

  8. Active Compounds Against Anopheles minimus Carboxypeptidase B for Malaria Transmission-Blocking Strategy.

    PubMed

    Mongkol, Watcharakorn; Arunyawat, Uraiwan; Surat, Wunrada; Kubera, Anchanee

    2015-11-01

    Malaria transmission-blocking compounds have been studied to block the transmission of malaria parasites, especially the drug-resistant Plasmodium. Carboxypeptidase B (CPB) in the midgut of Anopheline mosquitoes has been demonstrated to be essential for the sexual development of Plasmodium in the mosquito. Thus, the CPB is a potential target for blocking compounds. The aim of this research was to screen compounds from the National Cancer Institute (NCI) diversity dataset and U.S. Food and Drug Administration (FDA)-approved drugs that could reduce the Anopheles CPB activity. The cDNA fragment of cpb gene from An. minimus (cpbAmi) was amplified and sequenced. The three-dimensional structure of CPB was predicted from the deduced amino acid sequence. The virtual screening of the compounds from NCI diversity set IV and FDA-approved drugs was performed against CPBAmi. The inhibition activity against CPBAmi of the top-scoring molecules was characterized in vitro. Three compounds-NSC-1014, NSC-332670, and aminopterin with IC50 at 0.99 mM, 1.55 mM, and 0.062 mM, respectively-were found to significantly reduce the CPBAmi activity. PMID:26352934

  9. Targeting mosquito FREP1 with a fungal metabolite blocks malaria transmission

    PubMed Central

    Niu, Guodong; Wang, Bin; Zhang, Genwei; King, Jarrod B.; Cichewicz, Robert H.; Li, Jun

    2015-01-01

    Inhibiting Plasmodium development in mosquitoes will block malaria transmission. Fibrinogen-related protein 1 (FREP1) is critical for parasite infection in Anopheles gambiae and facilitates Plasmodium invasion in mosquitoes through interacting with gametocytes and ookinetes. To test the hypothesis that small molecules that disrupt this interaction will prevent parasites from infecting mosquitoes, we developed an ELISA-based method to screen a fungal extract library. We obtained a candidate fungal extract of Aspergillus niger that inhibited the interaction between FREP1 and P. falciparum infected cells by about 92%. The inhibition specificity was confirmed by immunofluorescence assays. Notably, feeding mosquitoes with the candidate fungal extract significantly inhibited P. falciparum infection in the midgut without cytotoxicity or inhibition of the development of P. falciparum gametocytes or ookinetes. A bioactive natural product that prevents FREP1 from binding to gametocytes or ookinetes was isolated and identified as P-orlandin. Importantly, the nontoxic orlandin significantly reduced P. falciparum infection intensity in mosquitoes. Therefore, disruption of the interaction between FREP1 and parasites effectively reduces Plasmodium infection in mosquitoes. Targeting FREP1 with small molecules is thus an effective novel approach to block malaria transmission. PMID:26437882

  10. Splenic Retention of Plasmodium falciparum Gametocytes To Block the Transmission of Malaria

    PubMed Central

    Duez, Julien; Holleran, John P.; Ndour, Papa Alioune; Loganathan, Sasdekumar; Amireault, Pascal; Français, Olivier; El Nemer, Wassim; Le Pioufle, Bruno; Amado, Inês F.; Garcia, Sylvie; Chartrel, Nathalie; Le Van Kim, Caroline; Lavazec, Catherine; Avery, Vicky M.

    2015-01-01

    Plasmodium falciparum is transmitted from humans to Anopheles mosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them from the blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized to a 96-well microtiter plate format, and gametocyte retention in the microsphere filters was quantified by high-content imaging. The stiffening activity of 40 pharmacological compounds was assessed in microtiter plates, using a small molecule (calyculin) as a positive control. The stiffening activity of calyculin was assessed in spleen-mimetic microfluidic chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%) of mature gametocytes was obtained in microplates following exposure to calyculin at concentrations with no effect on parasite viability. Of the 40 compounds tested, including 20 antimalarials, only 5 endoperoxides significantly increased gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 μM). Mature gametocytes exposed to calyculin accumulated in microfluidic chips and were cleared from the circulation of macrophage-depleted mice as rapidly as heat-stiffened erythrocytes, thus confirming results obtained using the microsphiltration assay. An automated miniaturized approach to select compounds for their gametocyte-stiffening effect has been established. Stiffening induces gametocyte clearance both in vitro and in vivo. Based on physiologically validated tools, this screening cascade can identify novel compounds and uncover new targets to block malaria transmission. Innovative applications in hematology are also envisioned. PMID:25941228

  11. A mathematical model for Plasmodium vivax malaria transmission: estimation of the impact of transmission-blocking immunity in an endemic area.

    PubMed

    De Zoysa, A P; Mendis, C; Gamage-Mendis, A C; Weerasinghe, S; Herath, P R; Mendis, K N

    1991-01-01

    We have developed a multi-state mathematical model to describe the transmission of Plasmodium vivax malaria; the model accommodates variable transmission-blocking/enhancing immunity during the course of a blood infection, a short memory for boosting immunity, and relapses. Using the model, we simulated the incidence of human malaria, sporozoite rates in the vector population, and the level of transmission-blocking immunity for the infected population over a period of time. Field data from an epidemiological study conducted in Kataragama in the south of Sri Lanka were used to test the results obtained. The incidence of malaria during the study period was simulated satisfactorily. The impact of naturally-acquired transmission-blocking immunity on malaria transmission under different vectorial capacities was also simulated. The results show that at low vectorial capacities, e.g., just above the threshold for transmission, the effect of transmission-blocking immunity is very significant; however, the effect is lower at higher vectorial capacities. PMID:1786621

  12. Blocking Plasmodium falciparum Malaria Transmission with Drugs: The Gametocytocidal and Sporontocidal Properties of Current and Prospective Antimalarials

    PubMed Central

    Kiszewski, Anthony E.

    2011-01-01

    Drugs that kill or inhibit the sexual stages of Plasmodium could potentially amplify or synergize the impact of other interventions by blocking transmission to mosquitoes. Primaquine and other 8-aminoquinolines have long offered such potential, but safety and other concerns have limited their use. Although transmission-blocking properties are not often a priority of drug discovery efforts, a number of interesting gametocytocidal and/or sporontocidal drug candidates have emerged in recent years. Some still bear significant technical and safety concerns, while others have passed clinical trials and are on the verge of entering the antimalarial armamentarium. Recent advances in our knowledge of gametocyte differentiation, gametogenesis and sporogony have also led to the identification of a large array of potential new targets for drugs that might interfere with malaria transmission. This review examines the properties of existing and prospective drugs, mechanisms of action, counter-indications and their potential role in regional malaria elimination efforts.

  13. Recombinant Pvs48/45 Antigen Expressed in E. coli Generates Antibodies that Block Malaria Transmission in Anopheles albimanus Mosquitoes

    PubMed Central

    Arévalo-Herrera, Myriam; Vallejo, Andrés F.; Rubiano, Kelly; Solarte, Yezid; Marin, Catherin; Castellanos, Angélica; Céspedes, Nora; Herrera, Sócrates

    2015-01-01

    Transmission of malaria parasites from humans to Anopheles mosquitoes can be inhibited by specific antibodies elicited during malaria infection, which target surface Plasmodium gametocyte/gamete proteins. Some of these proteins may have potential for vaccine development. Pvs48/45 is a P. vivax gametocyte surface antigen orthologous to Pfs48/45, which may play a role during parasite fertilization and thus has potential for transmission blocking (TB) activity. Here we describe the expression of a recombinant Pvs48/45 protein expressed in Escherichia coli as a ∼60kDa construct which we tested for antigenicity using human sera and for its immunogenicity and transmission blocking activity of specific anti-mouse and anti-monkey Pvs48/45 antibodies. The protein reacted with sera of individuals from malaria-endemic areas and in addition induced specific IgG antibody responses in BALB/c mice and Aotus l. griseimembra monkeys. Sera from both immunized animal species recognized native P. vivax protein in Western blot (WB) and immunofluorescence assays. Moreover, sera from immunized mice and monkeys produced significant inhibition of parasite transmission to An. Albimanus mosquitoes as shown by membrane feeding assays. Results indicate the presence of reactive epitopes in the Pvs48/45 recombinant product that induce antibodies with TB activity. Further testing of this protein is ongoing to determine its vaccine potential. PMID:25775466

  14. Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology

    PubMed Central

    Li, Yuanyuan; Leneghan, Darren B.; Miura, Kazutoyo; Nikolaeva, Daria; Brian, Iona J.; Dicks, Matthew D. J.; Fyfe, Alex J.; Zakutansky, Sarah E.; de Cassan, Simone; Long, Carole A.; Draper, Simon J.; Hill, Adrian V. S.; Hill, Fergal; Biswas, Sumi

    2016-01-01

    Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine. PMID:26743316

  15. Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology.

    PubMed

    Li, Yuanyuan; Leneghan, Darren B; Miura, Kazutoyo; Nikolaeva, Daria; Brian, Iona J; Dicks, Matthew D J; Fyfe, Alex J; Zakutansky, Sarah E; de Cassan, Simone; Long, Carole A; Draper, Simon J; Hill, Adrian V S; Hill, Fergal; Biswas, Sumi

    2016-01-01

    Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine. PMID:26743316

  16. Structural analysis of Anopheles midgut aminopeptidase N reveals a novel malaria transmission-blocking vaccine B-cell epitope

    PubMed Central

    Atkinson, Sarah C.; Armistead, Jennifer S.; Mathias, Derrick K.; Sandeu, Maurice M.; Tao, Dingyin; Borhani-Dizaji, Nahid; Tarimo, Brian B.; Morlais, Isabelle; Dinglasan, Rhoel R.; Borg, Natalie A.

    2015-01-01

    Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antibodies functionally block parasite transmission remains elusive. Here we present the 2.65 Å crystal structure of AnAPN1 and the immunoreactivity and transmission-blocking profile of three AnAPN1 monoclonal antibodies (mAb), including mAb 4H5B7, which effectively block transmission of natural strains of Plasmodium falciparum. Utilizing the AnAPN1 structure we map the conformation-dependent 4H5B7 neo-epitope to a previously uncharacterized region on domain 1, and further demonstrate that non-human primate neo-epitope-specific IgG also block parasite transmission. We discuss the prospect of a novel biological function of AnAPN1 as a receptor for Plasmodium in the mosquito midgut and the implications for redesigning the AnAPN1 mTBV. PMID:26075520

  17. Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites

    PubMed Central

    Mizutani, Masanori; Iyori, Mitsuhiro; Blagborough, Andrew M.; Fukumoto, Shinya; Funatsu, Tomohiro; Sinden, Robert E.

    2014-01-01

    A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen. PMID:25092912

  18. Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer

    PubMed Central

    Miura, Kazutoyo; Keister, David B; Muratova, Olga V; Sattabongkot, Jetsumon; Long, Carole A; Saul, Allan

    2007-01-01

    Background Mosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and consequently block transmission of the parasite. A mosquito membrane-feeding assay (MFA) is used to test transmission-blocking activity (TBA), but in this technique cannot accommodate many samples. A clear understanding of the relationship between antibody levels and TBA may allow ELISA determinations to be used to predict TBA and assist in planning vaccine development. Methods Rabbit anti-Pfs25 sera and monkey anti-Pvs25 sera were generated and the antibody titers were determined by a standardized ELISA. The biological activity of the same sera was tested by MFA using Plasmodium gametocytes (cultured Plasmodium falciparum or Plasmodium vivax from malaria patients) and Anopheles mosquitoes. Results Anti-Pfs25 and anti-Pvs25 sera showed that ELISA antibody units correlate with the percent reduction in the oocyst density per mosquito (Spearman Rank correlations: 0.934 and 0.616, respectively), and fit a hyperbolic curve when percent reduction in oocyst density is plotted against antibody units of the tested sample. Antibody levels also correlated with the number of mosquitoes that failed to become infected, and this proportion can be calculated from the reduction in oocyst numbers and the distribution of oocysts per infected mosquito in control group. Conclusion ELISA data may be used as a surrogate for the MFA to evaluate transmission-blocking vaccine efficacy. This will facilitate the evaluation of transmission-blocking vaccines and implementation of this malaria control strategy. PMID:17686163

  19. A plant-produced Pfs25 VLP malaria vaccine candidate induces persistent transmission blocking antibodies against Plasmodium falciparum in immunized mice.

    PubMed

    Jones, R Mark; Chichester, Jessica A; Mett, Vadim; Jaje, Jennifer; Tottey, Stephen; Manceva, Slobodanka; Casta, Louis J; Gibbs, Sandra K; Musiychuk, Konstantin; Shamloul, Moneim; Norikane, Joey; Mett, Valentina; Streatfield, Stephen J; van de Vegte-Bolmer, Marga; Roeffen, Will; Sauerwein, Robert W; Yusibov, Vidadi

    2013-01-01

    Malaria transmission blocking vaccines (TBVs) are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs). We engineered VLPs (Pfs25-CP VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP) and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter) with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases. PMID:24260245

  20. Alga-produced malaria transmission-blocking vaccine candidate Pfs25 formulated with a human use-compatible potent adjuvant induces high-affinity antibodies that block Plasmodium falciparum infection of mosquitoes.

    PubMed

    Patra, Kailash P; Li, Fengwu; Carter, Darrick; Gregory, James A; Baga, Sheyenne; Reed, Steven G; Mayfield, Stephen P; Vinetz, Joseph M

    2015-05-01

    A vaccine to prevent the transmission of malaria parasites from infected humans to mosquitoes is an important component for the elimination of malaria in the 21st century, yet it remains neglected as a priority of malaria vaccine development. The lead candidate for Plasmodium falciparum transmission-blocking vaccine development, Pfs25, is a sexual stage surface protein that has been produced for vaccine testing in a variety of heterologous expression systems. Any realistic malaria vaccine will need to optimize proper folding balanced against cost of production, yield, and potentially reactogenic contaminants. Here Chlamydomonas reinhardtii microalga-produced recombinant Pfs25 protein was formulated with four different human-compatible adjuvants (alum, Toll-like receptor 4 [TLR-4] agonist glucopyranosal lipid A [GLA] plus alum, squalene-oil-in-water emulsion, and GLA plus squalene-oil-in-water emulsion) and compared for their ability to induce malaria transmission-blocking antibodies. Alga-produced recombinant Pfs25 plus GLA plus squalene-oil-in-water adjuvant induced the highest titer and avidity in IgG antibodies, measured using alga-produced recombinant Pfs25 as the enzyme-linked immunosorbent assay (ELISA) antigen. These antibodies specifically reacted with the surface of P. falciparum macrogametes and zygotes and effectively prevented parasites from developing within the mosquito vector in standard membrane feeding assays. Alga-produced Pfs25 in combination with a human-compatible adjuvant composed of a TLR-4 agonist in a squalene-oil-in-water emulsion is an attractive new vaccine candidate that merits head-to-head comparison with other modalities of vaccine production and administration. PMID:25690099

  1. Alga-Produced Malaria Transmission-Blocking Vaccine Candidate Pfs25 Formulated with a Human Use-Compatible Potent Adjuvant Induces High-Affinity Antibodies That Block Plasmodium falciparum Infection of Mosquitoes

    PubMed Central

    Patra, Kailash P.; Li, Fengwu; Carter, Darrick; Gregory, James A.; Baga, Sheyenne; Reed, Steven G.; Mayfield, Stephen P.

    2015-01-01

    A vaccine to prevent the transmission of malaria parasites from infected humans to mosquitoes is an important component for the elimination of malaria in the 21st century, yet it remains neglected as a priority of malaria vaccine development. The lead candidate for Plasmodium falciparum transmission-blocking vaccine development, Pfs25, is a sexual stage surface protein that has been produced for vaccine testing in a variety of heterologous expression systems. Any realistic malaria vaccine will need to optimize proper folding balanced against cost of production, yield, and potentially reactogenic contaminants. Here Chlamydomonas reinhardtii microalga-produced recombinant Pfs25 protein was formulated with four different human-compatible adjuvants (alum, Toll-like receptor 4 [TLR-4] agonist glucopyranosal lipid A [GLA] plus alum, squalene–oil-in-water emulsion, and GLA plus squalene–oil-in-water emulsion) and compared for their ability to induce malaria transmission-blocking antibodies. Alga-produced recombinant Pfs25 plus GLA plus squalene–oil-in-water adjuvant induced the highest titer and avidity in IgG antibodies, measured using alga-produced recombinant Pfs25 as the enzyme-linked immunosorbent assay (ELISA) antigen. These antibodies specifically reacted with the surface of P. falciparum macrogametes and zygotes and effectively prevented parasites from developing within the mosquito vector in standard membrane feeding assays. Alga-produced Pfs25 in combination with a human-compatible adjuvant composed of a TLR-4 agonist in a squalene–oil-in-water emulsion is an attractive new vaccine candidate that merits head-to-head comparison with other modalities of vaccine production and administration. PMID:25690099

  2. Using rainfall estimates to predict malaria transmission

    NASA Astrophysics Data System (ADS)

    Tretkoff, Ernie

    2011-05-01

    Malaria kills nearly a million people each year, mostly in rural Africa. The disease is spread by mosquitoes, which thrive in wet areas, so malaria transmission is closely linked to rainfall. Rainfall estimates could therefore be used to help predict potential malaria transmission. However, rain gauge networks are sparse in many of the rural areas that are hit hardest by malaria.

  3. Mapping residual transmission for malaria elimination.

    PubMed

    Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon; Ntshalintshali, Nyasatu; Hsiang, Michelle S; Perkins, T Alex; Greenhouse, Bryan; Tatem, Andrew J; Cohen, Justin M; Smith, David L

    2015-01-01

    Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections . In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show 'malariogenic potential', a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination. PMID:26714110

  4. Mapping residual transmission for malaria elimination

    PubMed Central

    Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon; Ntshalintshali, Nyasatu; Hsiang, Michelle S; Perkins, T Alex; Greenhouse, Bryan; Tatem, Andrew J; Cohen, Justin M; Smith, David L

    2015-01-01

    Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections . In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show ‘malariogenic potential’, a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination. DOI: http://dx.doi.org/10.7554/eLife.09520.001 PMID:26714110

  5. Discovering New Transmission-Blocking Antimalarial Compounds: Challenges and Opportunities.

    PubMed

    Birkholtz, Lyn-Marie; Coetzer, Theresa L; Mancama, Dalu; Leroy, Didier; Alano, Pietro

    2016-09-01

    The ability to target human-mosquito parasite transmission challenges global malaria elimination. However, it is not obvious what a transmission-blocking drug will look like; should it target only parasite transmission stages; be combined with a partner drug killing the pathogenic asexual stages; or kill both the sexual and asexual blood stages, preferably displaying polypharmacology? The development of transmission-blocking antimalarials requires objective analyses of the current strategies. Here, pertinent issues and questions regarding the target candidate profile of a transmission-blocking compound, and its role in malaria elimination strategies, are highlighted and novel perspectives proposed. The essential role of a test cascade that integrates screening and validation strategies to identify next-generation transmission-blocking antimalarials is emphasised. PMID:27209388

  6. Climate, environment and transmission of malaria.

    PubMed

    Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Zaramella, Marco; Caputo, Annamaria; Garavelli, Pietro Luigi

    2016-06-01

    Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political

  7. Malaria transmission modelling: a network perspective

    PubMed Central

    2012-01-01

    Malaria transmission can be affected by multiple or even hidden factors, making it difficult to timely and accurately predict the impact of elimination and eradication programs that have been undertaken and the potential resurgence and spread that may continue to emerge. One approach at the moment is to develop and deploy surveillance systems in an attempt to identify them as timely as possible and thus to enable policy makers to modify and implement strategies for further preventing the transmission. Most of the surveillance data will be of temporal and spatial nature. From an interdisciplinary point of view, it would be interesting to ask the following important as well as challenging question: Based on the available surveillance data in temporal and spatial forms, how can we build a more effective surveillance mechanism for monitoring and early detecting the relative prevalence and transmission patterns of malaria? What we can note from the existing clustering-based surveillance software systems is that they do not infer the underlying transmission networks of malaria. However, such networks can be quite informative and insightful as they characterize how malaria transmits from one place to another. They can also in turn allow public health policy makers and researchers to uncover the hidden and interacting factors such as environment, genetics and ecology and to discover/predict malaria transmission patterns/trends. The network perspective further extends the present approaches to modelling malaria transmission based on a set of chosen factors. In this article, we survey the related work on transmission network inference, discuss how such an approach can be utilized in developing an effective computational means for inferring malaria transmission networks based on partial surveillance data, and what methodological steps and issues may be involved in its formulation and validation. PMID:23849949

  8. Socio-Demographics and the Development of Malaria Elimination Strategies in the Low Transmission Setting

    PubMed Central

    Chuquiyauri, Raul; Paredes, Maribel; Peñataro, Pablo; Torres, Sonia; Marin, Silvia; Tenorio, Alexander; Brouwer, Kimberly C.; Abeles, Shira; Llanos-Cuentas, Alejandro; Gilman, Robert H.; Kosek, Margaret; Vinetz, Joseph M.

    2011-01-01

    This analysis presents a comprehensive description of malaria burden and risk factors in Peruvian Amazon villages where malaria transmission is hypoendemic. More than 9,000 subjects were studied in contrasting village settings within the Department of Loreto, Peru, where most malaria occurs in the country. Plasmodium vivax is responsible for more than 75% of malaria cases; severe disease from any form of malaria is uncommon and death rare. The association between lifetime malaria episodes and individual and household covariates was studied using polychotomous logistic regression analysis, assessing effects on odds of some vs. no lifetime malaria episodes. Malaria morbidity during lifetime was strongly associated with age, logging, farming, travel history, and living with a logger or agriculturist. Select groups of adults, particularly loggers and agriculturists acquire multiple malaria infections in transmission settings outside of the main domicile, and may be mobile human reservoirs by which malaria parasites move within and between micro-regions within malaria endemic settings. For example, such individuals might well be reservoirs of transmission by introducing or reintroducing malaria into their home villages and their own households, depending on vector ecology and the local village setting. Therefore, socio-demographic studies can identify people with the epidemiological characteristic of transmission risk, and these individuals would be prime targets against which to deploy transmission blocking strategies along with insecticide treated bednets and chemoprophylaxis. PMID:22100446

  9. Targeting Human Transmission Biology for Malaria Elimination

    PubMed Central

    Buckee, Caroline; Marti, Matthias

    2015-01-01

    Malaria remains one of the leading causes of death worldwide, despite decades of public health efforts. The recent commitment by many endemic countries to eliminate malaria marks a shift away from programs aimed at controlling disease burden towards one that emphasizes reducing transmission of the most virulent human malaria parasite, Plasmodium falciparum. Gametocytes, the only developmental stage of malaria parasites able to infect mosquitoes, have remained understudied, as they occur in low numbers, do not cause disease, and are difficult to detect in vivo by conventional methods. Here, we review the transmission biology of P. falciparum gametocytes, featuring important recent discoveries of genes affecting parasite commitment to gametocyte formation, microvesicles enabling parasites to communicate with each other, and the anatomical site where immature gametocytes develop. We propose potential parasite targets for future intervention and highlight remaining knowledge gaps. PMID:26086192

  10. Hydrological and geomorphological controls of malaria transmission

    NASA Astrophysics Data System (ADS)

    Smith, M. W.; Macklin, M. G.; Thomas, C. J.

    2013-01-01

    Malaria risk is linked inextricably to the hydrological and geomorphological processes that form vector breeding sites. Yet environmental controls of malaria transmission are often represented by temperature and rainfall amounts, ignoring hydrological and geomorphological influences altogether. Continental-scale studies incorporate hydrology implicitly through simple minimum rainfall thresholds, while community-scale coupled hydrological and entomological models do not represent the actual diversity of the mosquito vector breeding sites. The greatest range of malaria transmission responses to environmental factors is observed at the catchment scale where seemingly contradictory associations between rainfall and malaria risk can be explained by hydrological and geomorphological processes that govern surface water body formation and persistence. This paper extends recent efforts to incorporate ecological factors into malaria-risk models, proposing that the same detailed representation be afforded to hydrological and, at longer timescales relevant for predictions of climate change impacts, geomorphological processes. We review existing representations of environmental controls of malaria and identify a range of hydrologically distinct vector breeding sites from existing literature. We illustrate the potential complexity of interactions among hydrology, geomorphology and vector breeding sites by classifying a range of water bodies observed in a catchment in East Africa. Crucially, the mechanisms driving surface water body formation and destruction must be considered explicitly if we are to produce dynamic spatial models of malaria risk at catchment scales.

  11. Malaria transmission in Tripura: disease distribution & determinants

    PubMed Central

    Dev, Vas; Adak, Tridibes; Singh, Om P.; Nanda, Nutan; Baidya, Bimal K.

    2015-01-01

    Background & objectives: Malaria is a major public health problem in Tripura and focal disease outbreaks are of frequent occurrence. The State is co-endemic for both Plasmodium falciparum and P. vivax and transmission is perennial and persistent. The present study was aimed to review data on disease distribution to prioritize high-risk districts, and to study seasonal prevalence of disease vectors and their bionomical characteristics to help formulate vector species-specific interventions for malaria control. Methods: Data on malaria morbidity in the State were reviewed retrospectively (2008-2012) for understanding disease distribution and transmission dynamics. Cross-sectional mass blood surveys were conducted in malaria endemic villages of South Tripura district to ascertain the prevalence of malaria and proportions of parasite species. Mosquito collections were made in human dwellings of malaria endemic villages aiming at vector incrimination and to study relative abundance, resting and feeding preferences, and their present susceptibility status to DDT. Results: The study showed that malaria was widely prevalent and P. falciparum was the predominant infection (>90%), the remaining were P. vivax cases. The disease distribution, however, was uneven with large concentration of cases in districts of South Tripura and Dhalai coinciding with vast forest cover and tribal populations. Both Anopheles minimus s.s. and An. baimaii were recorded to be prevalent and observed to be highly anthropophagic and susceptible to DDT. Of these, An. minimus was incriminated (sporozoite infection rate 4.92%), and its bionomical characteristics revealed this species to be largely indoor resting and endophagic. Interpretation & conclusions: For effective control of malaria in the State, it is recommended that diseases surveillance should be robust, and vector control interventions including DDT spray coverage, mass distribution of insecticide-treated nets/long-lasting insecticidal nets

  12. Modeling Malaria Transmission in Thailand and Indonesia

    NASA Technical Reports Server (NTRS)

    Kiang, Richard; Adimi, Farida; Nigro, Joseph

    2007-01-01

    Malaria Modeling and Surveillance is a project in the NASA Applied Sciences Public Health Applications Program. The main objectives of this project are: 1) identification of the potential breeding sites for major vector species: 2) implementation of a malaria transmission model to identify they key factors that sustain or intensify malaria transmission; and 3) implementation of a risk algorithm to predict the occurrence of malaria and its transmission intensity. Remote sensing and GIs are the essential elements of this project. The NASA Earth science data sets used in this project include AVHRR Pathfinder, TRMM, MODIS, NSIPP and SIESIP. Textural-contextual classifications are used to identify small larval habitats. Neural network methods are used to model malaria cases as a function of precipitation, temperatures, humidity and vegetation. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Examples for spatio-temporal modeling of malaria transmissions in Southeast Asia are given. Discrete event simulations were used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors. The output of the model includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Results are in good agreement with mosquito vector and human malaria data acquired by Coleman et al. over 4.5 years in Kong Mong Tha, a remote village in western Thailand. Application of our models is not restricted to Southeast Asia. The model and techniques are equally applicable to other regions of the world, when appropriate epidemiological and vector ecological parameters are used as input.

  13. Modelling climate change and malaria transmission.

    PubMed

    Parham, Paul E; Michael, Edwin

    2010-01-01

    The impact of climate change on human health has received increasing attention in recent years, with potential impacts due to vector-borne diseases only now beginning to be understood. As the most severe vector-borne disease, with one million deaths globally in 2006, malaria is thought most likely to be affected by changes in climate variables due to the sensitivity of its transmission dynamics to environmental conditions. While considerable research has been carried out using statistical models to better assess the relationship between changes in environmental variables and malaria incidence, less progress has been made on developing process-based climate-driven mathematical models with greater explanatory power. Here, we develop a simple model of malaria transmission linked to climate which permits useful insights into the sensitivity of disease transmission to changes in rainfall and temperature variables. Both the impact of changes in the mean values of these key external variables and importantly temporal variation in these values are explored. We show that the development and analysis of such dynamic climate-driven transmission models will be crucial to understanding the rate at which P. falciparum and P. vivax may either infect, expand into or go extinct in populations as local environmental conditions change. Malaria becomes endemic in a population when the basic reproduction number R0 is greater than unity and we identify an optimum climate-driven transmission window for the disease, thus providing a useful indicator for determing how transmission risk may change as climate changes. Overall, our results indicate that considerable work is required to better understand ways in which global malaria incidence and distribution may alter with climate change. In particular, we show that the roles of seasonality, stochasticity and variability in environmental variables, as well as ultimately anthropogenic effects, require further study. The work presented here

  14. Predicting optimal transmission investment in malaria parasites.

    PubMed

    Greischar, Megan A; Mideo, Nicole; Read, Andrew F; Bjørnstad, Ottar N

    2016-07-01

    In vertebrate hosts, malaria parasites face a tradeoff between replicating and the production of transmission stages that can be passed onto mosquitoes. This tradeoff is analogous to growth-reproduction tradeoffs in multicellular organisms. We use a mathematical model tailored to the life cycle and dynamics of malaria parasites to identify allocation strategies that maximize cumulative transmission potential to mosquitoes. We show that plastic strategies can substantially outperform fixed allocation because parasites can achieve greater fitness by investing in proliferation early and delaying the production of transmission stages. Parasites should further benefit from restraining transmission investment later in infection, because such a strategy can help maintain parasite numbers in the face of resource depletion. Early allocation decisions are predicted to have the greatest impact on parasite fitness. If the immune response saturates as parasite numbers increase, parasites should benefit from even longer delays prior to transmission investment. The presence of a competing strain selects for consistently lower levels of transmission investment and dramatically increased exploitation of the red blood cell resource. While we provide a detailed analysis of tradeoffs pertaining to malaria life history, our approach for identifying optimal plastic allocation strategies may be broadly applicable. PMID:27271841

  15. Measuring malaria endemicity from intense to interrupted transmission

    PubMed Central

    Hay, Simon I; Smith, David L; Snow, Robert W

    2008-01-01

    Summary The quantification of malaria transmission for the classification of malaria risk has long been a concern for epidemiologists. During the era of the Global Malaria Eradication Programme, measurements of malaria endemicity were institutionalised by their incorporation into rules outlining defined action points for malaria control programmes. We review the historical development of these indices and their contemporary relevance. This is at a time when many malaria-endemic countries are scaling-up their malaria control activities and reconsidering their prospects for elimination. These considerations are also important to an international community that has recently been challenged to revaluate the prospects for malaria eradication. PMID:18387849

  16. Microbiota Control of Malaria Transmission.

    PubMed

    Soares, Miguel P; Yilmaz, Bahtiyar

    2016-02-01

    Stable mutualistic interactions between multicellular organisms and microbes are an evolutionarily conserved process with a major impact on host physiology and fitness. Humans establish such interactions with a consortium of microorganisms known as the microbiota. Despite the mutualistic nature of these interactions, some bacterial components of the human microbiota express immunogenic glycans that elicit glycan-specific antibody (Ab) responses. The ensuing circulating Abs are protective against infections by pathogens that express those glycans, as demonstrated for Plasmodium, the causative agent of malaria. Presumably, a similar protective Ab response acts against other vector-borne diseases. PMID:26774793

  17. Spatio-temporal analysis of malaria within a transmission season in Bandiagara, Mali

    PubMed Central

    2013-01-01

    Background Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old”. Methods Children’s households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station. Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan® software according to a Bernoulli model. Results From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two “hot spots” of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the north-eastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. Conclusion These results confirm the existence of a marked spatial

  18. Quantifying Transmission Investment in Malaria Parasites

    PubMed Central

    Greischar, Megan A.; Mideo, Nicole; Read, Andrew F.; Bjørnstad, Ottar N.

    2016-01-01

    Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment. PMID:26890485

  19. Quantifying Transmission Investment in Malaria Parasites.

    PubMed

    Greischar, Megan A; Mideo, Nicole; Read, Andrew F; Bjørnstad, Ottar N

    2016-02-01

    Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment. PMID:26890485

  20. Larvivorous fish for preventing malaria transmission

    PubMed Central

    Walshe, Deirdre P; Garner, Paul; Abdel-Hameed Adeel, Ahmed A; Pyke, Graham H; Burkot, Tom

    2013-01-01

    Background Adult anopheline mosquitoes transmit Plasmodium parasites that cause malaria. Some fish species eat mosquito larvae and pupae. In disease control policy documents, the World Health Organization includes biological control of malaria vectors by stocking ponds, rivers, and water collections near where people live with larvivorous fish to reduce Plasmodium parasite transmission. The Global Fund finances larvivorous fish programmes in some countries, and, with increasing efforts in eradication of malaria, policy makers may return to this option. We therefore assessed the evidence base for larvivorous fish programmes in malaria control. Objectives Our main objective was to evaluate whether introducing larvivorous fish to anopheline breeding sites impacts Plasmodium parasite transmission. Our secondary objective was to summarize studies evaluating whether introducing larvivorous fish influences the density and presence of Anopheles larvae and pupae in water sources, to understand whether fish can possibly have an effect. Search methods We attempted to identify all relevant studies regardless of language or publication status (published, unpublished, in press, or ongoing). We searched the following databases: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; CABS Abstracts; LILACS; and the metaRegister of Controlled Trials (mRCT) until 18 June 2013. We checked the reference lists of all studies identified by the above methods. We also examined references listed in review articles and previously compiled bibliographies to look for eligible studies. Selection criteria Randomized controlled trials and non-randomized controlled trials, including controlled before-and-after studies, controlled time series and controlled interrupted time series studies from malaria-endemic regions that introduced fish as a larvicide and reported on malaria in

  1. Mapping Malaria Risk in Low Transmission Settings: Challenges and Opportunities.

    PubMed

    Sturrock, Hugh J W; Bennett, Adam F; Midekisa, Alemayehu; Gosling, Roly D; Gething, Peter W; Greenhouse, Bryan

    2016-08-01

    As malaria transmission declines, it becomes increasingly focal and prone to outbreaks. Understanding and predicting patterns of transmission risk becomes an important component of an effective elimination campaign, allowing limited resources for control and elimination to be targeted cost-effectively. Malaria risk mapping in low transmission settings is associated with some unique challenges. This article reviews the main challenges and opportunities related to risk mapping in low transmission areas including recent advancements in risk mapping low transmission malaria, relevant metrics, and statistical approaches and risk mapping in post-elimination settings. PMID:27238200

  2. Prevalence of Plasmodium falciparum transmission reducing immunity among primary school children in a malaria moderate transmission region in Zimbabwe.

    PubMed

    Paul, Noah H; Vengesai, Arthur; Mduluza, Takafira; Chipeta, James; Midzi, Nicholas; Bansal, Geetha P; Kumar, Nirbhay

    2016-11-01

    transmission reducing immunity in school age children from a moderate transmission area of malaria, and provide further support to exploit target antigens such as Pfs48/45 for further development of a malaria transmission blocking vaccine. PMID:27491342

  3. Climate drivers on malaria transmission in Arunachal Pradesh, India.

    PubMed

    Upadhyayula, Suryanaryana Murty; Mutheneni, Srinivasa Rao; Chenna, Sumana; Parasaram, Vaideesh; Kadiri, Madhusudhan Rao

    2015-01-01

    The present study was conducted during the years 2006 to 2012 and provides information on prevalence of malaria and its regulation with effect to various climatic factors in East Siang district of Arunachal Pradesh, India. Correlation analysis, Principal Component Analysis and Hotelling's T² statistics models are adopted to understand the effect of weather variables on malaria transmission. The epidemiological study shows that the prevalence of malaria is mostly caused by the parasite Plasmodium vivax followed by Plasmodium falciparum. It is noted that, the intensity of malaria cases declined gradually from the year 2006 to 2012. The transmission of malaria observed was more during the rainy season, as compared to summer and winter seasons. Further, the data analysis study with Principal Component Analysis and Hotelling's T² statistic has revealed that the climatic variables such as temperature and rainfall are the most influencing factors for the high rate of malaria transmission in East Siang district of Arunachal Pradesh. PMID:25803481

  4. Malaria on the move: human population movement and malaria transmission.

    PubMed Central

    Martens, P.; Hall, L.

    2000-01-01

    Reports of malaria are increasing in many countries and in areas thought free of the disease. One of the factors contributing to the reemergence of malaria is human migration. People move for a number of reasons, including environmental deterioration, economic necessity, conflicts, and natural disasters. These factors are most likely to affect the poor, many of whom live in or near malarious areas. Identifying and understanding the influence of these population movements can improve prevention measures and malaria control programs. PMID:10756143

  5. Defining the Global Spatial Limits of Malaria Transmission in 2005

    PubMed Central

    Guerra, C.A.; Snow, R.W.; Hay, S.I.

    2011-01-01

    There is no accurate contemporary global map of the distribution of malaria. We show how guidelines formulated to advise travellers on appropriate chemoprophylaxis for areas of reported Plasmodium falciparum and Plasmodium vivax malaria risk can be used to generate crude spatial limits. We first review and amalgamate information on these guidelines to define malaria risk at national and sub-national administrative boundary levels globally. We then adopt an iterative approach to reduce these extents by applying a series of biological limits imposed by altitude, climate and population density to malaria transmission, specific to the local dominant vector species. Global areas of, and population at risk from, P. falciparum and often-neglected P. vivax malaria are presented for 2005 for all malaria endemic countries. These results reveal that more than 3 billion people were at risk of malaria in 2005. PMID:16647970

  6. Early warnings of the potential for malaria transmission in Rural Africa using the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS)

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2010-12-01

    Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems, as outlined by the Roll Back Malaria Initiative. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics. HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future. Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone.

  7. Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data.

    PubMed

    Ruktanonchai, Nick W; DeLeenheer, Patrick; Tatem, Andrew J; Alegana, Victor A; Caughlin, T Trevor; Zu Erbach-Schoenberg, Elisabeth; Lourenço, Christopher; Ruktanonchai, Corrine W; Smith, David L

    2016-04-01

    Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model. PMID:27043913

  8. Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data

    PubMed Central

    Ruktanonchai, Nick W.; DeLeenheer, Patrick; Tatem, Andrew J.; Alegana, Victor A.; Caughlin, T. Trevor; zu Erbach-Schoenberg, Elisabeth; Lourenço, Christopher; Ruktanonchai, Corrine W.; Smith, David L.

    2016-01-01

    Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model. PMID:27043913

  9. A review of malaria transmission dynamics in forest ecosystems

    PubMed Central

    2014-01-01

    Malaria continues to be a major health problem in more than 100 endemic countries located primarily in tropical and sub-tropical regions around the world. Malaria transmission is a dynamic process and involves many interlinked factors, from uncontrollable natural environmental conditions to man-made disturbances to nature. Almost half of the population at risk of malaria lives in forest areas. Forests are hot beds of malaria transmission as they provide conditions such as vegetation cover, temperature, rainfall and humidity conditions that are conducive to distribution and survival of malaria vectors. Forests often lack infrastructure and harbor tribes with distinct genetic traits, socio-cultural beliefs and practices that greatly influence malaria transmission dynamics. Here we summarize the various topographical, entomological, parasitological, human ecological and socio-economic factors, which are crucial and shape malaria transmission in forested areas. An in-depth understanding and synthesis of the intricate relationship of these parameters in achieving better malaria control in various types of forest ecosystems is emphasized. PMID:24912923

  10. Transmission dynamics & epidemiology of malaria in two tribal districts in Madhya Pradesh, India

    PubMed Central

    Chand, Gyan; Chaudhary, N.K.; Soan, V.; Kaushal, L.S.; Sharma, R.K.; Singh, Neeru

    2015-01-01

    Background and objectives: Epidemiology and transmission of malaria vary within the tribal areas with the variation in topography, forest cover and type of forest. For the control of disease, understanding of the dynamics of transmission in the varied ecological situation is essential. This study was carried out in the two distinct tribal areas- Baiga Chak (thick forested area) of Dindori district and Bichhia block (forest fringe area) of Mandla district, Madhya Prasdesh, India, to understand the epidemiology and transmission dynamics of malaria. Methods: Mosquitoes were collected using hand catch and whole night collections to determine the proportion of vectors, their density and seasonality. Vector incrimination was done by sporozoite ELISA and feeding preferences of vector by gel diffusion method. Active fever surveys were carried out fortnightly to determine the age specific malaria parasite rates among the inhabitants of two areas. Results: Density of Anopheles culicifacies was significantly higher in Bichhia while the density of An. fluviatilis was higher in Baiga Chak. An. culicifacies was incriminated from both the areas while An. fluviatilis was incriminated from Baiga Chak only. Malaria slide positivity rate (SPR) was significantly higher (OR=3.7 95%CI, 3.1-4.4) in Baiga Chak (28.2%) than Bichhia (9.6%). Interpretation & conclusions: The features of malaria transmission in tribal areas differed from those reported in rural or semirural population. Site-specific and region-specific studies are required to develop appropriate intervention measures to control malaria. PMID:26139772

  11. Antibodies to Malaria Vaccine Candidates Pvs25 and Pvs28 Completely Block the Ability of Plasmodium vivax To Infect Mosquitoes

    PubMed Central

    Hisaeda, Hajime; Stowers, Anthony W.; Tsuboi, Takafumi; Collins, William E.; Sattabongkot, Jetsumon S.; Suwanabun, Natavadee; Torii, Motomi; Kaslow, David C.

    2000-01-01

    Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently cloned Plasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivax malaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed in Saccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response. PMID:11083773

  12. Optimal temperature for malaria transmission is dramaticallylower than previously predicted

    USGS Publications Warehouse

    Mordecai, Eerin A.; Paaijmans, Krijin P.; Johnson, Leah R.; Balzer, Christian; Ben-Horin, Tal; de Moor, Emily; McNally, Amy; Pawar, Samraat; Ryan, Sadie J.; Smith, Thomas C.; Lafferty, Kevin D.

    2013-01-01

    The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life-history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal-response models will aid in understanding the effects of current and future temperature regimes on disease transmission.

  13. Costs of crowding for the transmission of malaria parasites

    PubMed Central

    Pollitt, Laura C; Churcher, Thomas S; Dawes, Emma J; Khan, Shahid M; Sajid, Mohammed; Basáñez, María-Gloria; Colegrave, Nick; Reece, Sarah E

    2013-01-01

    The utility of using evolutionary and ecological frameworks to understand the dynamics of infectious diseases is gaining increasing recognition. However, integrating evolutionary ecology and infectious disease epidemiology is challenging because within-host dynamics can have counterintuitive consequences for between-host transmission, especially for vector-borne parasites. A major obstacle to linking within- and between-host processes is that the drivers of the relationships between the density, virulence, and fitness of parasites are poorly understood. By experimentally manipulating the intensity of rodent malaria (Plasmodium berghei) infections in Anopheles stephensi mosquitoes under different environmental conditions, we show that parasites experience substantial density-dependent fitness costs because crowding reduces both parasite proliferation and vector survival. We then use our data to predict how interactions between parasite density and vector environmental conditions shape within-vector processes and onward disease transmission. Our model predicts that density-dependent processes can have substantial and unexpected effects on the transmission potential of vector-borne disease, which should be considered in the development and evaluation of transmission-blocking interventions. PMID:23789029

  14. Effect of malaria on HIV/AIDS transmission and progression

    PubMed Central

    2013-01-01

    Malaria and HIV are among the two most important global health problems of developing countries. They cause more than 4 million deaths a year. These two infections interact bidirectionally and synergistically with each other. HIV infection increases the risk of an increase in the severity of malaria infection and burdens of malaria, which in turn facilitates the rate of malaria transmission. Malaria infection is also associated with strong CD4+ cell activation and up-regulation of proinflammatory cytokines and it provides an ideal microenvironment for the spread of the virus among the CD4+ cells and for rapid HIV-1 replication. Additionally, malaria increases blood viral burden by different mechanisms. Therefore, high concentrations of HIV-1 RNA in the blood are predictive of disease progression, and correlate with the risk of blood-borne, vertical, and sexual transmission of the virus. Therefore, this article aims to review information about HIV malaria interactions, the effect of malaria on HIV transmission and progression and the implications related to prevention and treatment of coinfection. PMID:23327493

  15. Urbanization, malaria transmission and disease burden in Africa

    PubMed Central

    Hay, Simon I.; Guerra, Carlos A.; Tatem, Andrew J.; Atkinson, Peter M.; Snow, Robert W.

    2011-01-01

    Many attempts have been made to quantify Africa’s malaria burden but none has addressed how urbanization will affect disease transmission and outcome, and therefore mortality and morbidity estimates. In 2003, 39% of Africa’s 850 million people lived in urban settings; by 2030, 54% of Africans are expected to do so. We present the results of a series of entomological, parasitological and behavioural meta-analyses of studies that have investigated the effect of urbanization on malaria in Africa. We describe the effect of urbanization on both the impact of malaria transmission and the concomitant improvements in access to preventative and curative measures. Using these data, we have recalculated estimates of populations at risk of malaria and the resulting mortality. We find there were 1,068,505 malaria deaths in Africa in 2000 — a modest 6.7% reduction over previous iterations. The public-health implications of these findings and revised estimates are discussed. PMID:15608702

  16. Influence of climate on malaria transmission depends on daily temperature variation.

    PubMed

    Paaijmans, Krijn P; Blanford, Simon; Bell, Andrew S; Blanford, Justine I; Read, Andrew F; Thomas, Matthew B

    2010-08-24

    Malaria transmission is strongly influenced by environmental temperature, but the biological drivers remain poorly quantified. Most studies analyzing malaria-temperature relations, including those investigating malaria risk and the possible impacts of climate change, are based solely on mean temperatures and extrapolate from functions determined under unrealistic laboratory conditions. Here, we present empirical evidence to show that, in addition to mean temperatures, daily fluctuations in temperature affect parasite infection, the rate of parasite development, and the essential elements of mosquito biology that combine to determine malaria transmission intensity. In general, we find that, compared with rates at equivalent constant mean temperatures, temperature fluctuation around low mean temperatures acts to speed up rate processes, whereas fluctuation around high mean temperatures acts to slow processes down. At the extremes (conditions representative of the fringes of malaria transmission, where range expansions or contractions will occur), fluctuation makes transmission possible at lower mean temperatures than currently predicted and can potentially block transmission at higher mean temperatures. If we are to optimize control efforts and develop appropriate adaptation or mitigation strategies for future climates, we need to incorporate into predictive models the effects of daily temperature variation and how that variation is altered by climate change. PMID:20696913

  17. Agent-Based Simulations of Malaria Transmissions with Applications to a Study Site in Thailand

    NASA Technical Reports Server (NTRS)

    Kiang, Richard K.; Adimi, Farida; Zollner, Gabriela E.; Coleman, Russell E.

    2006-01-01

    The dynamics of malaria transmission are driven by environmental, biotic and socioeconomic factors. Because of the geographic dependency of these factors and the complex interactions among them, it is difficult to generalize the key factors that perpetuate or intensify malaria transmission. Methods: Discrete event simulations were used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors. Meteorological and environmental parameters may be derived from satellite data. The output of the model includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Results were compared with mosquito vector and human malaria data acquired over 4.5 years (June 1999 - January 2004) in Kong Mong Tha, a remote village in Kanchanaburi Province, western Thailand. Results: Three years of transmissions of vivax and falciparum malaria were simulated for a hypothetical hamlet with approximately 1/7 of the study site population. The model generated results for a number of scenarios, including applications of larvicide and insecticide, asymptomatic cases receiving or not receiving treatment, blocking malaria transmission in mosquito vectors, and increasing the density of farm (host) animals in the hamlet. Transmission characteristics and trends in the simulated results are comparable to actual data collected at the study site.

  18. A weather-driven model of malaria transmission

    PubMed Central

    Hoshen, Moshe B; Morse, Andrew P

    2004-01-01

    Background Climate is a major driving force behind malaria transmission and climate data are often used to account for the spatial, seasonal and interannual variation in malaria transmission. Methods This paper describes a mathematical-biological model of the parasite dynamics, comprising both the weather-dependent within-vector stages and the weather-independent within-host stages. Results Numerical evaluations of the model in both time and space show that it qualitatively reconstructs the prevalence of infection. Conclusion A process-based modelling structure has been developed that may be suitable for the simulation of malaria forecasts based on seasonal weather forecasts. PMID:15350206

  19. Estimating malaria transmission from humans to mosquitoes in a noisy landscape.

    PubMed

    Reiner, Robert C; Guerra, Carlos; Donnelly, Martin J; Bousema, Teun; Drakeley, Chris; Smith, David L

    2015-10-01

    A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the 'colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine. PMID:26400195

  20. Estimating malaria transmission from humans to mosquitoes in a noisy landscape

    PubMed Central

    Reiner, Robert C.; Guerra, Carlos; Donnelly, Martin J.; Bousema, Teun; Drakeley, Chris; Smith, David L.

    2015-01-01

    A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the ‘colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine. PMID:26400195

  1. Malaria, miseria, and underpopulation in Sardinia: the "malaria blocks development" cultural model.

    PubMed

    Brown, P J

    1997-05-01

    Until the late Nineteenth century, endemic malaria was a serious public health problem in Sardinia, as in much of Southern Italy. As the poorest region of the new Italian nation, Sardinia was characterized by poor health, very low population densities, low agricultural productivity, and weak state authority associated with banditry. In this context, however, malaria was singled out as a key underlying problem for the situation of "internal underdevelopment." This paper describes the Italian scholarly literature about the relationship of malaria and economic productivity as a cultural model that can be labeled as "malaria blocks development" (MBD). Anti-malaria programs, including the state control of the distribution of quinine as well as land reclamation projects, played a major role in the decrease of malaria mortality in the first part of this century. Based on the logic of the MBD model, the decrease in malaria was expected to decrease an obstacle to "natural processes" of economic development. During the Fascist era, scientifically based antimalaria efforts formed a key element in centralized attempts for agricultural intensification and encouragement of immigration from over-populated parts of the country. Immediately after W.W.II, Sardinia was the site of a successful American-sponsored eradication project that represented one of the first uses of DDT against an indigenous anopheles vector. Hypotheses based on the MBD model about the nature of economic change after the removal of malaria are not supported. Nevertheless, variations of the MBD cultural model continue to be used in the field of International Health to the present day. PMID:9311225

  2. Study protocol for a three-armed randomized controlled trial to assess whether house screening can reduce exposure to malaria vectors and reduce malaria transmission in The Gambia

    PubMed Central

    Kirby, Matthew J; Milligan, Paul J; Conway, David J; Lindsay, Steve W

    2008-01-01

    Background Mosquito-proofing homes was one of the principal methods of environmental management in the early 1900s. House screening provides protection against malaria by reducing exposure to malaria parasites and has the added benefit of protecting everyone sleeping in the house, avoiding issues of inequity within the household. The aim of this study is to determine whether house screening protects people against malaria in Africa. It is hoped that this study will mark the beginning of a series of trials assessing a range of environmental interventions for malaria control in Africa. Design A 3-armed randomised-controlled trial will be conducted in and around Farafenni town in The Gambia, West Africa, to assess whether screening windows, doors and closing eaves or installing netting ceilings in local houses can substantially reduce malaria transmission and anaemia compared to homes with no screening. Eligible houses will be sorted and stratified by location and the number of children in each house, then randomly allocated to the interventions in blocks of 5 houses (2 with full screening, 2 with screened ceilings and 1 control house without screening). Risk of malaria transmission will be assessed in each house by routine collections of mosquitoes using light traps and an anaemia prevalence study in children at the end of the main transmission period. Discussion Practical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed. Trial Registration ISRCTN51184253 – Screening-homes to prevent malaria PMID:18538004

  3. The role of submicroscopic malaria in malaria transmission: what is the evidence?

    PubMed Central

    Lin, Jessica T.; Saunders, David L.; Meshnick, Steven R.

    2014-01-01

    Achieving malaria elimination requires targeting the human reservoir of infection, including those with asymptomatic infection. Smear-positive asymptomatic infections detectable by microscopy are an important reservoir because they often persist for months and harbor gametocytes, the parasite stage infectious to mosquitoes. However, many asymptomatic infections are submicroscopic and can only be detected by molecular methods. While there is some evidence that persons with submicroscopic malaria can infect mosquitoes, transmission is much less likely to occur at submicroscopic gametocyte levels. As malaria elimination programs pursue mass screening and treatment of asymptomatic individuals, further research should strive to define the degree to which submicroscopic malaria contributes to the infectious reservoir, and in turn, what diagnostic detection threshold is needed to effectively interrupt transmission. PMID:24642035

  4. High-Throughput Assay and Discovery of Small Molecules that Interrupt Malaria Transmission

    PubMed Central

    Plouffe, David M.; Wree, Melanie; Du, Alan Y.; Meister, Stephan; Li, Fengwu; Patra, Kailash; Lubar, Aristea; Okitsu, Shinji L.; Flannery, Erika L.; Kato, Nobutaka; Tanaseichuk, Olga; Comer, Eamon; Zhou, Bin; Kuhen, Kelli; Zhou, Yingyao; Leroy, Didier; Schreiber, Stuart L.; Scherer, Christina A.; Vinetz, Joseph; Winzeler, Elizabeth A.

    2016-01-01

    Summary Preventing transmission is an important element of malaria control. However, most of the current available methods to assay for malaria transmission blocking are relatively low throughput and cannot be applied to large chemical libraries. We have developed a high-throughput and cost-effective assay, the Saponin-lysis Sexual Stage Assay (SaLSSA), for identifying small molecules with transmission-blocking capacity. SaLSSA analysis of 13,983 unique compounds uncovered that >90% of well-characterized antimalarials, including endoperoxides and 4-aminoquinolines, as well as compounds active against asexual blood stages, lost most of their killing activity when parasites developed into metabolically quiescent stage V gametocytes. On the other hand, we identified compounds with consistent low nanomolar transmission-blocking activity, some of which showed cross-reactivity against asexual blood and liver stages. The data clearly emphasize substantial physiological differences between sexual and asexual parasites and provide a tool and starting points for the discovery and development of transmission-blocking drugs. PMID:26749441

  5. Malaria transmission potential could be reduced with current and future climate change

    PubMed Central

    Murdock, C. C.; Sternberg, E. D.; Thomas, M. B.

    2016-01-01

    Several studies suggest the potential for climate change to increase malaria incidence in cooler, marginal transmission environments. However, the effect of increasing temperature in warmer regions where conditions currently support endemic transmission has received less attention. We investigate how increases in temperature from optimal conditions (27 °C to 30 °C and 33 °C) interact with realistic diurnal temperature ranges (DTR: ± 0 °C, 3 °C, and 4.5 °C) to affect the ability of key vector species from Africa and Asia (Anopheles gambiae and An. stephensi) to transmit the human malaria parasite, Plasmodium falciparum. The effects of increasing temperature and DTR on parasite prevalence, parasite intensity, and mosquito mortality decreased overall vectorial capacity for both mosquito species. Increases of 3 °C from 27 °C reduced vectorial capacity by 51–89% depending on species and DTR, with increases in DTR alone potentially halving transmission. At 33 °C, transmission potential was further reduced for An. stephensi and blocked completely in An. gambiae. These results suggest that small shifts in temperature could play a substantial role in malaria transmission dynamics, yet few empirical or modeling studies consider such effects. They further suggest that rather than increase risk, current and future warming could reduce transmission potential in existing high transmission settings. PMID:27324146

  6. Malaria transmission potential could be reduced with current and future climate change.

    PubMed

    Murdock, C C; Sternberg, E D; Thomas, M B

    2016-01-01

    Several studies suggest the potential for climate change to increase malaria incidence in cooler, marginal transmission environments. However, the effect of increasing temperature in warmer regions where conditions currently support endemic transmission has received less attention. We investigate how increases in temperature from optimal conditions (27 °C to 30 °C and 33 °C) interact with realistic diurnal temperature ranges (DTR: ± 0 °C, 3 °C, and 4.5 °C) to affect the ability of key vector species from Africa and Asia (Anopheles gambiae and An. stephensi) to transmit the human malaria parasite, Plasmodium falciparum. The effects of increasing temperature and DTR on parasite prevalence, parasite intensity, and mosquito mortality decreased overall vectorial capacity for both mosquito species. Increases of 3 °C from 27 °C reduced vectorial capacity by 51-89% depending on species and DTR, with increases in DTR alone potentially halving transmission. At 33 °C, transmission potential was further reduced for An. stephensi and blocked completely in An. gambiae. These results suggest that small shifts in temperature could play a substantial role in malaria transmission dynamics, yet few empirical or modeling studies consider such effects. They further suggest that rather than increase risk, current and future warming could reduce transmission potential in existing high transmission settings. PMID:27324146

  7. Malaria Prevalence among Young Infants in Different Transmission Settings, Africa

    PubMed Central

    Ceesay, Serign J.; Koivogui, Lamine; Nahum, Alain; Taal, Makie Abdoulie; Okebe, Joseph; Affara, Muna; Kaman, Lama Eugène; Bohissou, Francis; Agbowai, Carine; Tolno, Benoit Gniouma; Amambua-Ngwa, Alfred; Bangoura, NFaly; Ahounou, Daniel; Muhammad, Abdul Khalie; Duparc, Stephan; Hamed, Kamal; Ubben, David; Bojang, Kalifa; Achan, Jane

    2015-01-01

    The prevalence and consequences of malaria among infants are not well characterized and may be underestimated. A better understanding of the risk for malaria in early infancy is critical for drug development and informed decision making. In a cross-sectional survey in Guinea, The Gambia, and Benin, countries with different malaria transmission intensities, the overall prevalence of malaria among infants <6 months of age was 11.8% (Guinea, 21.7%; The Gambia, 3.7%; and Benin, 10.2%). Seroprevalence ranged from 5.7% in The Gambia to 41.6% in Guinea. Mean parasite densities in infants were significantly lower than those in children 1–9 years of age in The Gambia (p<0.0001) and Benin (p = 0.0021). Malaria in infants was significantly associated with fever or recent history of fever (p = 0.007) and anemia (p = 0.001). Targeted preventive interventions, adequate drug formulations, and treatment guidelines are needed to address the sizeable prevalence of malaria among young infants in malaria-endemic countries. PMID:26079062

  8. Mosquitoes and transmission of malaria parasites – not just vectors

    PubMed Central

    Paul, Richard EL; Diallo, Mawlouth; Brey, Paul T

    2004-01-01

    The regional malaria epidemics of the early 1900s provided the basis for much of our current understanding of malaria epidemiology. Colonel Gill, an eminent malariologist of that time, suggested that the explosive nature of the regional epidemics was due to a sudden increased infectiousness of the adult population. His pertinent observations underlying this suggestion have, however, gone unheeded. Here, the literature on Plasmodium seasonal behaviour is reviewed and three historical data sets, concerning seasonal transmission of Plasmodium falciparum, are examined. It is proposed that the dramatic seasonal increase in the density of uninfected mosquito bites results in an increased infectiousness of the human reservoir of infection and, therefore, plays a key role in "kick-starting" malaria parasite transmission. PMID:15533243

  9. A simple model for the transmission of malaria

    NASA Astrophysics Data System (ADS)

    Dickman, Adriana

    2011-03-01

    We study a simple lattice model describing the transmission of malaria. The transmission of the disease to humans occurs through contact with an infected mosquito, while a healthy mosquito can become infected through contact with an infected human. Recovered individuals are susceptible to re-infection. The mosquitoes diffuse through the lattice, spreading the disease. We show preliminary results for the model obtained via site approximation (mean-field theory).

  10. Vulnerability to changes in malaria transmission due to climate change in West Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2012-12-01

    Malaria transmission in West Africa is strongly tied to climate; temperature affects the development rate of the malaria parasite, as well as the survival of the mosquitoes that transmit the disease, and rainfall is tied to mosquito abundance, as the vector lays its eggs in rain-fed water pools. As a result, the environmental suitability for malaria transmission in this region is expected to change as temperatures rise and rainfall patterns are altered. The vulnerability to changes in transmission varies throughout West Africa. Areas where malaria prevalence is already very high will be less sensitive to changes in transmission. Increases in environmental suitability for malaria transmission in the most arid regions may still be insufficient to allow sustained transmission. However, areas were malaria transmission currently occurs at low levels are expected to be the most sensitive to changes in environmental suitability for transmission. Here, we use data on current environment and malaria transmission rates to highlight areas in West Africa that we expect to be most vulnerable to an increase in malaria under certain climate conditions. We then analyze climate predictions from global climate models in vulnerable areas, and make predictions for the expected change in environmental suitability for malaria transmission using the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a mechanistic model developed to simulate village-scale response of malaria transmission to environmental variables in West Africa.

  11. Malaria Transmission, Infection, and Disease at Three Sites with Varied Transmission Intensity in Uganda: Implications for Malaria Control

    PubMed Central

    Kamya, Moses R.; Arinaitwe, Emmanuel; Wanzira, Humphrey; Katureebe, Agaba; Barusya, Chris; Kigozi, Simon P.; Kilama, Maxwell; Tatem, Andrew J.; Rosenthal, Philip J.; Drakeley, Chris; Lindsay, Steve W.; Staedke, Sarah G.; Smith, David L.; Greenhouse, Bryan; Dorsey, Grant

    2015-01-01

    The intensification of control interventions has led to marked reductions in malaria burden in some settings, but not others. To provide a comprehensive description of malaria epidemiology in Uganda, we conducted surveillance studies over 24 months in 100 houses randomly selected from each of three subcounties: Walukuba (peri-urban), Kihihi (rural), and Nagongera (rural). Annual entomological inoculation rate (aEIR) was estimated from monthly Centers for Disease Control and Prevention (CDC) light trap mosquito collections. Children aged 0.5–10 years were provided long-lasting insecticidal nets (LLINs) and followed for measures of parasite prevalence, anemia and malaria incidence. Estimates of aEIR were 2.8, 32.0, and 310 infectious bites per year, and estimates of parasite prevalence 7.4%, 9.3%, and 28.7% for Walukuba, Kihihi, and Nagongera, respectively. Over the 2-year study, malaria incidence per person-years decreased in Walukuba (0.51 versus 0.31, P = 0.001) and increased in Kihihi (0.97 versus 1.93, P < 0.001) and Nagongera (2.33 versus 3.30, P < 0.001). Of 2,582 episodes of malaria, only 8 (0.3%) met criteria for severe disease. The prevalence of anemia was low and not associated with transmission intensity. In our cohorts, where LLINs and prompt effective treatment were provided, the risk of complicated malaria and anemia was extremely low. However, malaria incidence was high and increased over time at the two rural sites, suggesting improved community-wide coverage of LLIN and additional malaria control interventions are needed in Uganda. PMID:25778501

  12. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control.

    PubMed

    Kamya, Moses R; Arinaitwe, Emmanuel; Wanzira, Humphrey; Katureebe, Agaba; Barusya, Chris; Kigozi, Simon P; Kilama, Maxwell; Tatem, Andrew J; Rosenthal, Philip J; Drakeley, Chris; Lindsay, Steve W; Staedke, Sarah G; Smith, David L; Greenhouse, Bryan; Dorsey, Grant

    2015-05-01

    The intensification of control interventions has led to marked reductions in malaria burden in some settings, but not others. To provide a comprehensive description of malaria epidemiology in Uganda, we conducted surveillance studies over 24 months in 100 houses randomly selected from each of three subcounties: Walukuba (peri-urban), Kihihi (rural), and Nagongera (rural). Annual entomological inoculation rate (aEIR) was estimated from monthly Centers for Disease Control and Prevention (CDC) light trap mosquito collections. Children aged 0.5-10 years were provided long-lasting insecticidal nets (LLINs) and followed for measures of parasite prevalence, anemia and malaria incidence. Estimates of aEIR were 2.8, 32.0, and 310 infectious bites per year, and estimates of parasite prevalence 7.4%, 9.3%, and 28.7% for Walukuba, Kihihi, and Nagongera, respectively. Over the 2-year study, malaria incidence per person-years decreased in Walukuba (0.51 versus 0.31, P = 0.001) and increased in Kihihi (0.97 versus 1.93, P < 0.001) and Nagongera (2.33 versus 3.30, P < 0.001). Of 2,582 episodes of malaria, only 8 (0.3%) met criteria for severe disease. The prevalence of anemia was low and not associated with transmission intensity. In our cohorts, where LLINs and prompt effective treatment were provided, the risk of complicated malaria and anemia was extremely low. However, malaria incidence was high and increased over time at the two rural sites, suggesting improved community-wide coverage of LLIN and additional malaria control interventions are needed in Uganda. PMID:25778501

  13. Rationale for the Coadministration of Albendazole and Ivermectin to Humans for Malaria Parasite Transmission Control

    PubMed Central

    Kobylinski, Kevin C.; Alout, Haoues; Foy, Brian D.; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E.; Richardson, Jason H.

    2014-01-01

    Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression. PMID:25070998

  14. Rationale for the coadministration of albendazole and ivermectin to humans for malaria parasite transmission control.

    PubMed

    Kobylinski, Kevin C; Alout, Haoues; Foy, Brian D; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E; Richardson, Jason H

    2014-10-01

    Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression. PMID:25070998

  15. Mapping Malaria Transmission Intensity in Malawi, 2000–2010

    PubMed Central

    Bennett, Adam; Kazembe, Lawrence; Mathanga, Don P.; Kinyoki, Damaris; Ali, Doreen; Snow, Robert W.; Noor, Abdisalan M.

    2013-01-01

    Substantial development assistance has been directed towards reducing the high malaria burden in Malawi over the past decade. We assessed changes in transmission over this period of malaria control scale-up by compiling community Plasmodium falciparum rate (PfPR) data during 2000–2011 and used model-based geostatistical methods to predict mean PfPR2–10 in 2000, 2005, and 2010. In addition, we calculated population-adjusted prevalences and populations at risk by district to inform malaria control program priority setting. The national population-adjusted PfPR2–10 was 37% in 2010, and we found no evidence of change over this period of scale-up. The entire population of Malawi is under meso-endemic transmission risk, with those in districts along the shore of Lake Malawi and Shire River Valley under highest risk. The lack of change in prevalence confirms modeling predictions that when compared with lower transmission, prevalence reductions in high transmission settings require greater investment and longer time scales. PMID:24062477

  16. Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission

    PubMed Central

    Yilmaz, Bahtiyar; Portugal, Silvia; Tran, Tuan M.; Gozzelino, Raffaella; Ramos, Susana; Gomes, Joana; Regalado, Ana; Cowan, Peter J.; d’Apice, Anthony J.F.; Chong, Anita S.; Doumbo, Ogobara K.; Traore, Boubacar; Crompton, Peter D.; Silveira, Henrique; Soares, Miguel P.

    2014-01-01

    Summary Glycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) gene, which ablated the expression of the Galα1-3Galβ1-4GlcNAc-R (α-gal) glycan and allowed for the production of anti-α-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, the causative agent of malaria and a major driving force in human evolution. We demonstrate that both Plasmodium spp. and the human gut pathobiont E. coli O86:B7 express α-gal and that anti-α-gal Abs are associated with protection against malaria transmission in humans as well as in α1,3GT-deficient mice, which produce protective anti-α-gal Abs when colonized by E. coli O86:B7. Anti-α-gal Abs target Plasmodium sporozoites for complement-mediated cytotoxicity in the skin, immediately after inoculation by Anopheles mosquitoes. Vaccination against α-gal confers sterile protection against malaria in mice, suggesting that a similar approach may reduce malaria transmission in humans. PaperFlick PMID:25480293

  17. Sensitivity analysis of the age-structured malaria transmission model

    NASA Astrophysics Data System (ADS)

    Addawe, Joel M.; Lope, Jose Ernie C.

    2012-09-01

    We propose an age-structured malaria transmission model and perform sensitivity analyses to determine the relative importance of model parameters to disease transmission. We subdivide the human population into two: preschool humans (below 5 years) and the rest of the human population (above 5 years). We then consider two sets of baseline parameters, one for areas of high transmission and the other for areas of low transmission. We compute the sensitivity indices of the reproductive number and the endemic equilibrium point with respect to the two sets of baseline parameters. Our simulations reveal that in areas of either high or low transmission, the reproductive number is most sensitive to the number of bites by a female mosquito on the rest of the human population. For areas of low transmission, we find that the equilibrium proportion of infectious pre-school humans is most sensitive to the number of bites by a female mosquito. For the rest of the human population it is most sensitive to the rate of acquiring temporary immunity. In areas of high transmission, the equilibrium proportion of infectious pre-school humans and the rest of the human population are both most sensitive to the birth rate of humans. This suggests that strategies that target the mosquito biting rate on pre-school humans and those that shortens the time in acquiring immunity can be successful in preventing the spread of malaria.

  18. Highly focused anopheline breeding sites and malaria transmission in Dakar

    PubMed Central

    Machault, Vanessa; Gadiaga, Libasse; Vignolles, Cécile; Jarjaval, Fanny; Bouzid, Samia; Sokhna, Cheikh; Lacaux, Jean-Pierre; Trape, Jean-François; Rogier, Christophe; Pagès, Frédéric

    2009-01-01

    Background Urbanization has a great impact on the composition of the vector system and malaria transmission dynamics. In Dakar, some malaria cases are autochthonous but parasite rates and incidences of clinical malaria attacks have been recorded at low levels. Ecological heterogeneity of malaria transmission was investigated in Dakar, in order to characterize the Anopheles breeding sites in the city and to study the dynamics of larval density and adult aggressiveness in ten characteristically different urban areas. Methods Ten study areas were sampled in Dakar and Pikine. Mosquitoes were collected by human landing collection during four nights in each area (120 person-nights). The Plasmodium falciparum circumsporozoite (CSP) index was measured by ELISA and the entomological inoculation rates (EIR) were calculated. Open water collections in the study areas were monitored weekly for physico-chemical characterization and the presence of anopheline larvae. Adult mosquitoes and hatched larvae were identified morphologically and by molecular methods. Results In September-October 2007, 19,451 adult mosquitoes were caught among which, 1,101 were Anopheles gambiae s.l. The Human Biting Rate ranged from 0.1 bites per person per night in Yoff Village to 43.7 in Almadies. Seven out of 1,101 An. gambiae s.l. were found to be positive for P. falciparum (CSP index = 0.64%). EIR ranged from 0 infected bites per person per year in Yoff Village to 16.8 in Almadies. The An. gambiae complex population was composed of Anopheles arabiensis (94.8%) and Anopheles melas (5.2%). None of the An. melas were infected with P. falciparum. Of the 54 water collection sites monitored, 33 (61.1%) served as anopheline breeding sites on at least one observation. No An. melas was identified among the larval samples. Some physico-chemical characteristics of water bodies were associated with the presence/absence of anopheline larvae and with larval density. A very close parallel between larval and adult

  19. Malaria transmission in Libreville: results of a one year survey

    PubMed Central

    2012-01-01

    Background In Gabon, vector transmission has been poorly studied. Since the implementation of the Roll Back malaria recommendations, clinical studies have shown a decline in the burden of malaria in Libreville, the capital city of Gabon. To better understand the transmission dynamic in Libreville, an entomological survey was conducted in five districts of the city. Methods Mosquitoes were sampled by human landing collection during 1 year in five districts of Libreville: Alibandeng, Beauséjour, Camp des Boys and Sotega. Mosquitoes were identified morphologically and by molecular methods. The Plasmodium falciparum circumsporozoïte indices were measured by ELISA, and the entomological inoculation rates (EIR) were calculated for all areas. Molecular assessments of pyrethroid knock down resistance (kdr) and of insensitive acetylcholinesterase resistance were conducted. Results A total of 57,531 mosquitoes were caught during 341 person-nights (161 person-nights indoor and 180 person-nights outdoor) among which, 4,223 were Anopheles gambiae s.l. The average Human Biting Rate fell from 15.5 bites per person during the rainy season to 4.7 during the dry season. The An. gambiae complex population was composed of An. gambiae s.s molecular form S (99.5%), Anopheles melas (0.3%) and An. gambiae s.s. form M (0.2%). Thirty-three out of 4,223 An. gambiae s.l. were found to be infected by P. falciparum (CSP index = 0.78%). The annual EIR was estimated at 33.9 infected bites per person per year ranging from 13 in Alibandeng to 88 in Sotega. No insensitive AChE mutation was identified but both kdr-w and kdr-e mutations were present in An. gambiae molecular form S with a higher frequency of the kdr-w allele (76%) than the kdr-e allele (23.5%). Conclusion Malaria transmission in Libreville occurred mainly during the rainy season but also during the dry season in the five districts. Transmission level is high and seems to be very heterogeneous in the town. Interestingly, the highest

  20. Rationale for short course primaquine in Africa to interrupt malaria transmission

    PubMed Central

    2012-01-01

    Following the recent successes of malaria control in sub-Saharan Africa, the gametocytocidal drug primaquine needs evaluation as a tool to further reduce the transmission of Plasmodium falciparum malaria. The drug has scarcely been used in Africa because of concerns about its safety in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The evidence base for the use of primaquine as a transmission blocker is limited by a lack of comparable clinical and parasitological endpoints between trials. In March 2012, a group of experts met in London to discuss the existing evidence on the ability of primaquine to block malaria transmission, to define the roadblocks to the use of primaquine in Africa and to develop a roadmap to enable its rapid, safe and effective deployment. The output of this meeting is a strategic plan to optimize trial design to reach desired goals efficiently. The roadmap includes suggestions for a series of phase 1, 2, 3 and 4 studies to address specific hurdles to primaquine’s deployment. These include ex-vivo studies on efficacy, primaquine pharmacokinetics and pharmacodynamics and dose escalation studies for safety in high-risk groups. Phase 3 community trials are proposed, along with Phase 4 studies to evaluate safety, particularly in pregnancy, through pharmacovigilance in areas where primaquine is already deployed. In parallel, efforts need to be made to address issues in drug supply and regulation, to map G6PD deficiency and to support the evaluation of alternative gametocytocidal compounds. PMID:23130957

  1. Interruption of malaria transmission by chloroquinized salt in Guyana

    PubMed Central

    Giglioli, George; Rutten, Frans J.; Ramjattan, S.

    1967-01-01

    Malaria and its local vector, Anopheles darlingi, were eradicated from the coastlands and near interior of Guyana by DDT house-spraying in 1945-51. In the remote interior, where 10% of the population live, only partial control could be achieved, owing to the semi-silvatic habits of A. darlingi and the considerable movement of the sparse population; low malaria endemicity persisted in these areas with occasional localized outbreaks. In the south-west the problem was further complicated by the presence of malaria across the frontier. During the years 1961-65, the use of chloroquinized salt was made compulsory over an area of some 109 000 km2, covering a population of 48 500. Satisfactory results were obtained over 84% of this area within 6 months of the start of the campaign; only four cases of malaria were seen in four years. In the south-west, however, an initially favourable trend was reversed in 1962 with the introduction of a chloroquine-resistant strain of Plasmodium falciparum from Brazil. The situation was brought under control by house-spraying with DDT and interruption of transmission is expected. PMID:4864651

  2. Malaria transmission dynamics at a site in northern Ghana proposed for testing malaria vaccines.

    PubMed

    Appawu, Maxwell; Owusu-Agyei, Seth; Dadzie, Samuel; Asoala, Victor; Anto, Francis; Koram, Kwadwo; Rogers, William; Nkrumah, Francis; Hoffman, Stephen L; Fryauff, David J

    2004-01-01

    We studied the malaria transmission dynamics in Kassena Nankana district (KND), a site in northern Ghana proposed for testing malaria vaccines. Intensive mosquito sampling for 1 year using human landing catches in three micro-ecological sites (irrigated, lowland and rocky highland) yielded 18 228 mosquitoes. Anopheles gambiae s.l. and Anopheles funestus constituted 94.3% of the total collection with 76.8% captured from the irrigated communities. Other species collected but in relatively few numbers were Anopheles pharoensis (5.4%) and Anopheles rufipes (0.3%). Molecular analysis of 728 An. gambiae.s.l. identified Anopheles gambiae s.s. as the most dominant sibling species (97.7%) of the An. gambiae complex from the three ecological sites. Biting rates of the vectors (36.7 bites per man per night) were significantly higher (P<0.05) in the irrigated area than in the non-irrigated lowland (5.2) and rocky highlands (5.9). Plasmodium falciparum sporozoite rates of 7.2% (295/4075) and 7.1% (269/3773) were estimated for An. gambiae s.s. and An. funestus, respectively. Transmission was highly seasonal, and the heaviest transmission occurred from June to October. The intensity of transmission was higher for people in the irrigated communities than the non-irrigated ones. An overall annual entomological inoculation rate (EIR) of 418 infective bites was estimated in KND. There were micro-ecological variations in the EIRs, with values of 228 infective bites in the rocky highlands, 360 in the lowlands and 630 in the irrigated area. Approximately 60% of malaria transmission in KND occurred indoors during the second half of the night, peaking at daybreak between 04.00 and 06.00 hours. Vaccine trials could be conducted in this district, with timing dependent on the seasonal patterns and intensity of transmission taking into consideration the micro-geographical differences and vaccine trial objectives. PMID:14728621

  3. Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory

    PubMed Central

    Molina-Cruz, Alvaro; Canepa, Gaspar E.; Kamath, Nitin; Pavlovic, Noelle V.; Mu, Jianbing; Ramphul, Urvashi N.; Ramirez, Jose Luis; Barillas-Mury, Carolina

    2015-01-01

    Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the “lock-and-key theory” of P. falciparum globalization, is proposed, and its implications are discussed. PMID:26598665

  4. Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory.

    PubMed

    Molina-Cruz, Alvaro; Canepa, Gaspar E; Kamath, Nitin; Pavlovic, Noelle V; Mu, Jianbing; Ramphul, Urvashi N; Ramirez, Jose Luis; Barillas-Mury, Carolina

    2015-12-01

    Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the "lock-and-key theory" of P. falciparum globalization, is proposed, and its implications are discussed. PMID:26598665

  5. Impact of Schistosoma mansoni on Malaria Transmission in Sub-Saharan Africa

    PubMed Central

    Ndeffo Mbah, Martial L.; Skrip, Laura; Greenhalgh, Scott; Hotez, Peter; Galvani, Alison P.

    2014-01-01

    Background Sub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children. Methodology We developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities. Principal Findings Our results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities. Conclusions/Significance Schistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also

  6. Relationship Between Exposure, Clinical Malaria, and Age in an Area of Changing Transmission Intensity

    PubMed Central

    O’Meara, Wendy P.; Mwangi, Tabitha W.; Williams, Thomas N.; McKenzie, F. Ellis; Snow, Robert W.; Marsh, Kevin

    2008-01-01

    The relationship between malaria transmission intensity and clinical disease is important for predicting the outcome of control measures that reduce transmission. Comparisons of hospital data between areas of differing transmission intensity suggest that the mean age of hospitalized clinical malaria is higher under relatively lower transmission, but the total number of episodes is similar until transmission drops below a threshold, where the risks of hospitalized malaria decline. These observations have rarely been examined longitudinally in a single community where transmission declines over time. We reconstructed 16 years (1991–2006) of pediatric hospital surveillance data and infection prevalence surveys from a circumscribed geographic area on the Kenyan coast. The incidence of clinical malaria remained high, despite sustained reductions in exposure to infection. However, the age group experiencing the clinical attacks of malaria increased steadily as exposure declined and may precede changes in the number of episodes in an area with declining transmission. PMID:18689622

  7. Malaria

    MedlinePlus

    Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever; Tertian malaria; Plasmodium ... Malaria is caused by a parasite that is passed to humans by the bite of infected Anopheles ...

  8. Acquired transmission-blocking immunity to Plasmodium vivax in a population of southern coastal Mexico.

    PubMed

    Ramsey, J M; Salinas, E; Rodríguez, M H

    1996-05-01

    Naturally acquired transmission-blocking immunity to Plasmodium vivax was studied in three groups of patients from the southern coast of Mexico: primary cases (Group A, 61% of the study population), secondary cases with the prior infection seven or more months earlier (Group B, 23%), and secondary cases with the previous malaria experience within six months of the present study (Group C, 16%). Anopheles albimanus mosquitoes were fed with patients' infected blood cells in the presence of autologous or control serum, with or without heat-inactivation. Patients from all three groups had transmission-blocking immunity, although the quality and quantity of this blocking activity was significantly higher in the two secondary patient groups (B and C). Only primary malaria cases produced transmission-enhancing activity (23% of the cases), which was dependent on heat-labile serum components. The levels of patient group transmission-blocking immunity and mosquito infectivity were used to calculate the probabilities of a mosquito becoming infective after taking a blood meal from a P. vivax-infected patient from any one of the three groups. This probability was 0.025, with Group A patients providing the major source of these infections (92% risk from Group A and 4% risk for Groups B and C). PMID:8644898

  9. Evolution of Plastic Transmission Strategies in Avian Malaria

    PubMed Central

    Cornet, Stéphane; Nicot, Antoine; Rivero, Ana; Gandon, Sylvain

    2014-01-01

    Malaria parasites have been shown to adjust their life history traits to changing environmental conditions. Parasite relapses and recrudescences—marked increases in blood parasite numbers following a period when the parasite was either absent or present at very low levels in the blood, respectively—are expected to be part of such adaptive plastic strategies. Here, we first present a theoretical model that analyses the evolution of transmission strategies in fluctuating seasonal environments and we show that relapses may be adaptive if they are concomitant with the presence of mosquitoes in the vicinity of the host. We then experimentally test the hypothesis that Plasmodium parasites can respond to the presence of vectors. For this purpose, we repeatedly exposed birds infected by the avian malaria parasite Plasmodium relictum to the bites of uninfected females of its natural vector, the mosquito Culex pipiens, at three different stages of the infection: acute (∼34 days post infection), early chronic (∼122 dpi) and late chronic (∼291 dpi). We show that: (i) mosquito-exposed birds have significantly higher blood parasitaemia than control unexposed birds during the chronic stages of the infection and that (ii) this translates into significantly higher infection prevalence in the mosquito. Our results demonstrate the ability of Plasmodium relictum to maximize their transmission by adopting plastic life history strategies in response to the availability of insect vectors. PMID:25210974

  10. Adult vector control, mosquito ecology and malaria transmission

    PubMed Central

    Brady, Oliver J.; Godfray, H. Charles J.; Tatem, Andrew J.; Gething, Peter W.; Cohen, Justin M.; McKenzie, F. Ellis; Alex Perkins, T.; Reiner, Robert C.; Tusting, Lucy S.; Scott, Thomas W.; Lindsay, Steven W.; Hay, Simon I.; Smith, David L.

    2015-01-01

    Background Standard advice regarding vector control is to prefer interventions that reduce the lifespan of adult mosquitoes. The basis for this advice is a decades-old sensitivity analysis of ‘vectorial capacity’, a concept relevant for most malaria transmission models and based solely on adult mosquito population dynamics. Recent advances in micro-simulation models offer an opportunity to expand the theory of vectorial capacity to include both adult and juvenile mosquito stages in the model. Methods In this study we revisit arguments about transmission and its sensitivity to mosquito bionomic parameters using an elasticity analysis of developed formulations of vectorial capacity. Results We show that reducing adult survival has effects on both adult and juvenile population size, which are significant for transmission and not accounted for in traditional formulations of vectorial capacity. The elasticity of these effects is dependent on various mosquito population parameters, which we explore. Overall, control is most sensitive to methods that affect adult mosquito mortality rates, followed by blood feeding frequency, human blood feeding habit, and lastly, to adult mosquito population density. Conclusions These results emphasise more strongly than ever the sensitivity of transmission to adult mosquito mortality, but also suggest the high potential of combinations of interventions including larval source management. This must be done with caution, however, as policy requires a more careful consideration of costs, operational difficulties and policy goals in relation to baseline transmission. PMID:25733562

  11. Anopheles mortality is both age- and Plasmodium-density dependent: implications for malaria transmission

    PubMed Central

    2009-01-01

    Background Daily mortality is an important determinant of a vector's ability to transmit pathogens. Original simplifying assumptions in malaria transmission models presume vector mortality is independent of age, infection status and parasite load. Previous studies illustrate conflicting evidence as to the importance of Plasmodium-induced vector mortality, but very few studies to date have considered the effect of infection density on mosquito survival. Methods A series of three experiments were conducted, each consisting of four cages of 400-1,000 Anopheles stephensi mosquitoes fed on blood infected with different Plasmodium berghei ookinete densities per microlitre of blood. Twice daily the numbers of dead mosquitoes in each group were recorded, and on alternate days a sample of live mosquitoes from each group were dissected to determine parasite density in both midgut and salivary glands. Results Survival analyses indicate that mosquito mortality is both age- and infection intensity-dependent. Mosquitoes experienced an initially high, partly feeding-associated, mortality rate, which declined to a minimum before increasing with mosquito age and parasite intake. As a result, the life expectancy of a mosquito is shown to be dependent on both insect age and the density of Plasmodium infection. Conclusion These results contribute to understanding in greater detail the processes that influence sporogony in the mosquito, indicate the impact that parasite density could have on malaria transmission dynamics, and have implications for the design, development, and evaluation of transmission-blocking strategies. PMID:19822012

  12. Cyclic GMP Balance Is Critical for Malaria Parasite Transmission from the Mosquito to the Mammalian Host

    PubMed Central

    Lakshmanan, Viswanathan; Fishbaugher, Matthew E.; Morrison, Bob; Baldwin, Michael; Macarulay, Michael; Vaughan, Ashley M.; Mikolajczak, Sebastian A.

    2015-01-01

    ABSTRACT Transmission of malaria occurs during Anopheles mosquito vector blood meals, when Plasmodium sporozoites that have invaded the mosquito salivary glands are delivered to the mammalian host. Sporozoites display a unique form of motility that is essential for their movement across cellular host barriers and invasion of hepatocytes. While the molecular machinery powering motility and invasion is increasingly well defined, the signaling events that control these essential parasite activities have not been clearly delineated. Here, we identify a phosphodiesterase (PDEγ) in Plasmodium, a regulator of signaling through cyclic nucleotide second messengers. Reverse transcriptase PCR (RT-PCR) analysis and epitope tagging of endogenous PDEγ detected its expression in blood stages and sporozoites of Plasmodium yoelii. Deletion of PDEγ (pdeγ−) rendered sporozoites nonmotile, and they failed to invade the mosquito salivary glands. Consequently, PDEγ deletion completely blocked parasite transmission by mosquito bite. Strikingly, pdeγ− sporozoites showed dramatically elevated levels of cyclic GMP (cGMP), indicating that a perturbation in cyclic nucleotide balance is involved in the observed phenotypic defects. Transcriptome sequencing (RNA-Seq) analysis of pdeγ− sporozoites revealed reduced transcript abundance of genes that encode key components of the motility and invasion apparatus. Our data reveal a crucial role for PDEγ in maintaining the cyclic nucleotide balance in the malaria parasite sporozoite stage, which in turn is essential for parasite transmission from mosquito to mammal. PMID:25784701

  13. Predicted impacts of climate change on malaria transmission in West Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A. B.

    2014-12-01

    Increases in temperature and changes in precipitation due to climate change are expected to alter the spatial distribution of malaria transmission. This is especially true in West Africa, where malaria prevalence follows the current north-south gradients in temperature and precipitation. We assess the skill of GCMs at simulating past and present climate in West Africa in order to select the most credible climate predictions for the periods 2030-2060 and 2070-2100. We then use the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a mechanistic model of malaria transmission, to translate the predicted changes in climate into predicted changes availability of mosquito breeding sites, mosquito populations, and malaria prevalence. We investigate the role of acquired immunity in determining a population's response to changes in exposure to the malaria parasite.

  14. Plasmodium falciparum STEVOR phosphorylation regulates host erythrocyte deformability enabling malaria parasite transmission.

    PubMed

    Naissant, Bernina; Dupuy, Florian; Duffier, Yoann; Lorthiois, Audrey; Duez, Julien; Scholz, Judith; Buffet, Pierre; Merckx, Anais; Bachmann, Anna; Lavazec, Catherine

    2016-06-16

    Deformability of Plasmodium falciparum gametocyte-infected erythrocytes (GIEs) allows them to persist for several days in blood circulation and to ensure transmission to mosquitoes. Here, we investigate the mechanism by which the parasite proteins STEVOR (SubTElomeric Variable Open Reading frame) exert changes on GIE deformability. Using the microsphiltration method, immunoprecipitation, and mass spectrometry, we produce evidence that GIE stiffness is dependent on the cytoplasmic domain of STEVOR that interacts with ankyrin complex at the erythrocyte skeleton. Moreover, we show that GIE deformability is regulated by protein kinase A (PKA)-mediated phosphorylation of the STEVOR C-terminal domain at a specific serine residue (S324). Finally, we show that the increase of GIE stiffness induced by sildenafil (Viagra) is dependent on STEVOR phosphorylation status and on another independent mechanism. These data provide new insights into mechanisms by which phosphodiesterase inhibitors may block malaria parasite transmission. PMID:27136945

  15. Projected Impacts of Climate Change on Environmental Suitability for Malaria Transmission in West Africa

    PubMed Central

    Eltahir, Elfatih A.B.

    2013-01-01

    Background: Climate change is expected to affect the distribution of environmental suitability for malaria transmission by altering temperature and rainfall patterns; however, the local and global impacts of climate change on malaria transmission are uncertain. Objective: We assessed the effect of climate change on malaria transmission in West Africa. Methods: We coupled a detailed mechanistic hydrology and entomology model with climate projections from general circulation models (GCMs) to predict changes in vectorial capacity, an indication of the risk of human malaria infections, resulting from changes in the availability of mosquito breeding sites and temperature-dependent development rates. Because there is strong disagreement in climate predictions from different GCMs, we focused on the GCM projections that produced the best and worst conditions for malaria transmission in each zone of the study area. Results: Simulation-based estimates suggest that in the desert fringes of the Sahara, vectorial capacity would increase under the worst-case scenario, but not enough to sustain transmission. In the transitional zone of the Sahel, climate change is predicted to decrease vectorial capacity. In the wetter regions to the south, our estimates suggest an increase in vectorial capacity under all scenarios. However, because malaria is already highly endemic among human populations in these regions, we expect that changes in malaria incidence would be small. Conclusion: Our findings highlight the importance of rainfall in shaping the impact of climate change on malaria transmission in future climates. Even under the GCM predictions most conducive to malaria transmission, we do not expect to see a significant increase in malaria prevalence in this region. Citation: Yamana TK, Eltahir EA. 2013. Projected impacts of climate change on environmental suitability for malaria transmission in West Africa. Environ Health Perspect 121:1179–1186; http://dx.doi.org/10.1289/ehp

  16. Optimal Population-Level Infection Detection Strategies for Malaria Control and Elimination in a Spatial Model of Malaria Transmission

    PubMed Central

    Gerardin, Jaline; Bever, Caitlin A.; Hamainza, Busiku; Miller, John M.; Eckhoff, Philip A.; Wenger, Edward A.

    2016-01-01

    Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment. While selective targeting of hotspots of transmission has been proposed as a strategy for malaria control, such targeting has not been tested in the context of malaria elimination. Using household locations, demographics, and prevalence data from a survey of four health facility catchment areas in southern Zambia and an agent-based model of malaria transmission and immunity acquisition, a transmission intensity was fit to each household based on neighborhood age-dependent malaria prevalence. A set of individual infection trajectories was constructed for every household in each catchment area, accounting for heterogeneous exposure and immunity. Various campaign strategies—mass drug administration, mass screen and treat, focal mass drug administration, snowball reactive case detection, pooled sampling, and a hypothetical serological diagnostic—were simulated and evaluated for performance at finding infections, minimizing overtreatment, reducing clinical case counts, and interrupting transmission. For malaria control, presumptive treatment leads to substantial overtreatment without additional morbidity reduction under all but the highest transmission conditions. Compared with untargeted approaches, selective targeting of hotspots with drug campaigns is an ineffective tool for elimination due to limited sensitivity of available field diagnostics. Serological diagnosis is potentially an effective tool for

  17. Optimal Population-Level Infection Detection Strategies for Malaria Control and Elimination in a Spatial Model of Malaria Transmission.

    PubMed

    Gerardin, Jaline; Bever, Caitlin A; Hamainza, Busiku; Miller, John M; Eckhoff, Philip A; Wenger, Edward A

    2016-01-01

    Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment. While selective targeting of hotspots of transmission has been proposed as a strategy for malaria control, such targeting has not been tested in the context of malaria elimination. Using household locations, demographics, and prevalence data from a survey of four health facility catchment areas in southern Zambia and an agent-based model of malaria transmission and immunity acquisition, a transmission intensity was fit to each household based on neighborhood age-dependent malaria prevalence. A set of individual infection trajectories was constructed for every household in each catchment area, accounting for heterogeneous exposure and immunity. Various campaign strategies-mass drug administration, mass screen and treat, focal mass drug administration, snowball reactive case detection, pooled sampling, and a hypothetical serological diagnostic-were simulated and evaluated for performance at finding infections, minimizing overtreatment, reducing clinical case counts, and interrupting transmission. For malaria control, presumptive treatment leads to substantial overtreatment without additional morbidity reduction under all but the highest transmission conditions. Compared with untargeted approaches, selective targeting of hotspots with drug campaigns is an ineffective tool for elimination due to limited sensitivity of available field diagnostics. Serological diagnosis is potentially an effective tool for

  18. The Role of Rainfall Patterns in Seasonal Malaria Transmission

    NASA Astrophysics Data System (ADS)

    Bomblies, A.

    2010-12-01

    Seasonal total precipitation is well known to affect malaria transmission because Anopheles mosquitoes depend on standing water for breeding habitat. However, the within-season temporal pattern of the rainfall influences persistence of standing water and thus rainfall patterns also affect mosquito population dynamics. In this talk, I show that intraseasonal rainfall pattern describes 40% of the variance in simulated mosquito abundance in a Niger Sahel village where malaria is endemic but highly seasonal, demonstrating the necessity for detailed distributed hydrology modeling to explain the variance from this important effect. I apply a field validated, high spatial- and temporal-resolution hydrology model coupled with an entomology model. Using synthetic rainfall time series generated using a stationary first-order Markov Chain model, I hold all variables except hourly rainfall constant, thus isolating the contribution of rainfall pattern to variance in mosquito abundance. I further show the utility of hydrology modeling to assess precipitation effects by analyzing collected water. Time-integrated surface area of pools explains 70% of the variance in mosquito abundance, and time-integrated surface area of pools persisting longer than seven days explains 82% of the variance, showing an improved predictive ability when pool persistence is explicitly modeled at high spatio-temporal resolution. I extend this analysis to investigate the impacts of this effect on malaria vector mosquito populations under climate shift scenarios, holding all climate variables except precipitation constant. In these scenarios, rainfall mean and variance change with climatic change, and the modeling approach evaluates the impact of non-stationarity in rainfall and the associated rainfall patterns on expected mosquito activity.

  19. Conditions of malaria transmission in Dakar from 2007 to 2010

    PubMed Central

    2011-01-01

    Background Previous studies in Dakar have highlighted the spatial and temporal heterogeneity of Anopheles gambiae s.l. biting rates. In order to improve the knowledge of the determinants of malaria transmission in this city, the present study reports the results of an extensive entomological survey that was conducted in 45 areas in Dakar from 2007 to 2010. Methods Water collections were monitored for the presence of anopheline larvae. Adult mosquitoes were sampled by human landing collection. Plasmodium falciparum circumsporozoïte (CSP) protein indexes were measured by ELISA (enzyme-linked immunosorbent assay), and the entomological inoculation rates were calculated. Results The presence of anopheline larvae were recorded in 1,015 out of 2,683 observations made from 325 water collections. A water pH of equal to or above 8.0, a water temperature that was equal to or above 30°C, the absence of larvivorous fishes, the wet season, the presence of surface vegetation, the persistence of water and location in a slightly urbanised area were significantly associated with the presence of anopheline larvae and/or with a higher density of anopheline larvae. Most of the larval habitats were observed in public areas, i.e., freely accessible. A total of 496,310 adult mosquitoes were caught during 3096 person-nights, and 44967 of these specimens were identified as An.gambiae s.l. The mean An. gambiae s.l. human-biting rate ranged from 0.1 to 248.9 bites per person per night during the rainy season. Anopheles arabiensis (93.14%), Anopheles melas (6.83%) and An. gambiae s.s. M form (0.03%) were the three members of the An. gambiae complex. Fifty-two An. arabiensis and two An. melas specimens were CSP-positive, and the annual CSP index was 0.64% in 2007, 0.09% in 2008-2009 and 0.12% in 2009-2010. In the studied areas, the average EIR ranged from 0 to 17.6 infected bites per person during the entire transmission season. Conclusion The spatial and temporal heterogeneity of An

  20. Quantifying the impact of decay in bed-net efficacy on malaria transmission.

    PubMed

    Ngonghala, Calistus N; Del Valle, Sara Y; Zhao, Ruijun; Mohammed-Awel, Jemal

    2014-12-21

    Insecticide-treated nets (ITNs) are at the forefront of malaria control programs and even though the percentage of households in sub-Saharan Africa that owned nets increased from 3% in 2000 to 53% in 2012, many children continue to die from malaria. The potential impact of ITNs on reducing malaria transmission is limited due to inconsistent or improper use, as well as physical decay in effectiveness. Most mathematical models for malaria transmission have assumed a fixed effectiveness rate for bed-nets, which can overestimate the impact of nets on malaria control. We develop a model for malaria spread that captures the decrease in ITN effectiveness due to physical and chemical decay, as well as human behavior as a function of time. We perform uncertainty and sensitivity analyses to identify and rank parameters that play a critical role in malaria transmission. These analyses show that the basic reproduction number R0, and the infectious human population are most sensitive to bed-net coverage and the biting rate of mosquitoes. Our results show the existence of a backward bifurcation for the case in which ITN efficacy is constant over time, which occurs for some range of parameters and is characterized by high malaria mortality in humans. This result implies that bringing R0 to less than one is not enough for malaria elimination but rather additional efforts will be necessary to control the disease. For the case in which ITN efficacy decays over time, we determine coverage levels required to control malaria for different ITN efficacies and demonstrate that ITNs with longer useful lifespans perform better in malaria control. We conclude that malaria control programs should focus on increasing bed-net coverage, which can be achieved by enhancing malaria education and increasing bed-net distribution in malaria endemic regions. PMID:25158163

  1. A novel plant-produced Pfs25 fusion subunit vaccine induces long-lasting transmission blocking antibody responses

    PubMed Central

    Jones, R Mark; Chichester, Jessica A; Manceva, Slobodanka; Gibbs, Sandra K; Musiychuk, Konstantin; Shamloul, Moneim; Norikane, Joey; Streatfield, Stephen J; van de Vegte-Bolmer, Marga; Roeffen, Will; Sauerwein, Robert W; Yusibov, Vidadi

    2014-01-01

    Malaria transmission blocking vaccines (TBV) directed against proteins expressed on sexual stages of Plasmodium falciparum in the mosquito midgut are considered an effective means to reduce malaria transmission. Antibodies induced by TBV block sporogonic development in the mosquito, and thus transmission to the next human host. The Pfs25 protein, expressed on the surface of gametes, zygotes and ookinetes, is one of the primary targets for TBV development. Using a plant virus-based transient expression system, we have successfully produced Pfs25 fused to a modified lichenase (LicKM) carrier in Nicotiana benthamiana, purified and characterized the protein (Pfs25-FhCMB), and evaluated this vaccine candidate in animal models for the induction of transmission blocking antibodies. Soluble Pfs25-FhCMB was expressed in plants at a high level, and induced transmission blocking antibodies that persisted for up to 6 months post immunization in mice and rabbits. These data demonstrate the potential of the new malaria vaccine candidate and also support feasibility of expressing Plasmodium antigens in a plant-based system. PMID:25483525

  2. Climatic variables and malaria transmission dynamics in Jimma town, South West Ethiopia

    PubMed Central

    2011-01-01

    Background:- In Ethiopia, malaria is seasonal and unstable, causing frequent epidemics. It usually occurs at altitudes < 2,000 m above sea level. Occasionally, transmission of malaria occurs in areas previously free of malaria, including areas > 2,000 m above sea level. For transmission of malaria parasite, climatic factors are important determinants as well as non-climatic factors that can negate climatic influences. Indeed, there is a scarcity of information on the correlation between climatic variability and malaria transmission risk in Ethiopia in general and in the study area in particular. Therefore, the aim of this study was to determine the level of correlation between meteorological variables and malaria cases. Methods: - Time-series analysis was conducted using data on monthly meteorological variables and monthly total malaria in Jimma town, south west Ethiopia, for the period 2000-2009. All the data were entered and analyzed using SPSS-15 database program. Spearman correlation and linear regression analysis were used to asses association between the variables. Results: - During last ten years (2000-2009), a fluctuating trend of malaria transmission was observed with P.vivax becoming predominant species. Spearman correlation analysis showed that monthly minimum temperature, total rainfall and two measures of relative humidity were positively related with malaria but monthly maximum temperature negatively related. Also regression analysis suggested that monthly minimum (p = 0.008), monthly maximum temperature (p = 0.013) and monthly total rainfall (p = 0.040), at one month lagged effect, were significant meteorological factors for transmission of malaria in the study area. Conclusion: - Malaria incidences in the last decade seem to have a significant association with meteorological variables. In future, prospective and multidisciplinary cooperative research involving researchers from the fields of parasitology, epidemiology, botany, agriculture and

  3. [Evidence of an urban, local transmission of malaria in Antananarivo, Madagascar].

    PubMed

    Cot, S; Matra, R; Rabarijaona, L; Robert, V; Raharimalala, L; Raveloson, A; Ariey, F

    2006-04-01

    Madagascar presents a large heterogeneity in terms of climate and altitude, which explains the uneven spread of malaria throughout the island. The capital, Antananarivo, counts more than one million inhabitants, altitude between 1250 and 1470 m, in an area where the transmission is low but malaria may cause deadly epidemic outbreaks. Numerous malaria cases are reported, without biological confirmation, and reliable data about urban malaria transmission are lacking. The " Institut Pasteur de Madagascar" together with the Malagasy Ministry of Health performed in 2003 a study about malaria transmission in Antananarivo. A prevalence survey of malaria among fever syndromes, with data collected from 43 urban dispensaries, showed that confirmed malaria cases represented only 2% of the total fever cases (15 cases out of 779 fever syndromes). The vast majority was imported from costal areas (13 cases out of 15), where malaria is hyperendemic. However, a local urban transmission was found for two patients and five other subjects identified during a proximity survey. Vectors A. arabiensis and A. funestus were found inside the patient houses, located in close proximity of flooded rice fields. Genetic analysis of P. falciparum strains allowed to distinguish three genotypes, aggregated by house. The analysis of parasite genome polymorphism proves here its validity for epidemic surveys in areas where malaria is unstable, with no premunition in the local urban population. PMID:16775937

  4. Threshold dynamics of a malaria transmission model in periodic environment

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Teng, Zhidong; Zhang, Tailei

    2013-05-01

    In this paper, we propose a malaria transmission model with periodic environment. The basic reproduction number R0 is computed for the model and it is shown that the disease-free periodic solution of the model is globally asymptotically stable when R0<1, that is, the disease goes extinct when R0<1, while the disease is uniformly persistent and there is at least one positive periodic solution when R0>1. It indicates that R0 is the threshold value determining the extinction and the uniform persistence of the disease. Finally, some examples are given to illustrate the main theoretical results. The numerical simulations show that, when the disease is uniformly persistent, different dynamic behaviors may be found in this model, such as the global attractivity and the chaotic attractor.

  5. The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

    PubMed Central

    2010-01-01

    Background The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. Methods Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. Results In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years. Conclusion The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It

  6. The effects of urbanization on global Plasmodium vivax malaria transmission

    PubMed Central

    2012-01-01

    Background Many recent studies have examined the impact of urbanization on Plasmodium falciparum malaria endemicity and found a general trend of reduced transmission in urban areas. However, none has examined the effect of urbanization on Plasmodium vivax malaria, which is the most widely distributed malaria species and can also cause severe clinical syndromes in humans. In this study, a set of 10,003 community-based P. vivax parasite rate (PvPR) surveys are used to explore the relationships between PvPR in urban and rural settings. Methods The PvPR surveys were overlaid onto a map of global urban extents to derive an urban/rural assignment. The differences in PvPR values between urban and rural areas were then examined. Groups of PvPR surveys inside individual city extents (urban) and surrounding areas (rural) were identified to examine the local variations in PvPR values. Finally, the relationships of PvPR between urban and rural areas within the ranges of 41 dominant Anopheles vectors were examined. Results Significantly higher PvPR values in rural areas were found globally. The relationship was consistent at continental scales when focusing on Africa and Asia only, but in the Americas, significantly lower values of PvPR in rural areas were found, though the numbers of surveys were small. Moreover, except for the countries in the Americas, the same trends were found at national scales in African and Asian countries, with significantly lower values of PvPR in urban areas. However, the patterns at city scales among 20 specific cities where sufficient data were available were less clear, with seven cities having significantly lower PvPR values in urban areas and two cities showing significantly lower PvPR in rural areas. The urban–rural PvPR differences within the ranges of the dominant Anopheles vectors were generally, in agreement with the regional patterns found. Conclusions Except for the Americas, the patterns of significantly lower P. vivax transmission in

  7. Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission.

    PubMed

    Glennon, Elizabeth K K; Adams, L Garry; Hicks, Derrick R; Dehesh, Katayoon; Luckhart, Shirley

    2016-06-01

    Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation. PMID:27001761

  8. Insecticide-Treated Net Campaign and Malaria Transmission in Western Kenya: 2003–2015

    PubMed Central

    Zhou, Guofa; Lee, Ming-Chieh; Githeko, Andrew K.; Atieli, Harrysone E.; Yan, Guiyun

    2016-01-01

    Insecticide-treated nets (ITNs) are among the three major intervention measures that have reduced malaria transmission in the past decade. However, increased insecticide resistance in vectors, together with outdoor transmission, has limited the efficacy of the ITN scaling-up efforts. Observations on longitudinal changes in ITN coverage and its impact on malaria transmission allow policy makers to make informed adjustments to control strategies. We analyzed field surveys on ITN ownership, malaria parasite prevalence, and malaria vector population dynamics in seven sentinel sites in western Kenya from 2003 to 2015. We found that ITN ownership has increased from an average of 18% in 2003 to 85% in 2015. Malaria parasite prevalence in school children decreased by about 70% from 2003 to 2008 (the first mass distribution of free ITNs was in 2006) but has resurged by >50% since then. At the community level, use of ITNs reduced infections by 23% in 2008 and 43% in 2010, although the reduction was down to 25% in 2011. The indoor-resting density of the predominant vector, Anopheles gambiae, has been suppressed since 2007; however, Anopheles funestus populations have resurged and have increased 20-fold in some places since 2007. In conclusion, there is limited room for further increase in ITN coverage in western Kenya. The rebounding in malaria transmission highlights the urgent need of new or improved malaria control interventions so as to further reduce malaria transmission. PMID:27574601

  9. Insecticide-Treated Net Campaign and Malaria Transmission in Western Kenya: 2003-2015.

    PubMed

    Zhou, Guofa; Lee, Ming-Chieh; Githeko, Andrew K; Atieli, Harrysone E; Yan, Guiyun

    2016-01-01

    Insecticide-treated nets (ITNs) are among the three major intervention measures that have reduced malaria transmission in the past decade. However, increased insecticide resistance in vectors, together with outdoor transmission, has limited the efficacy of the ITN scaling-up efforts. Observations on longitudinal changes in ITN coverage and its impact on malaria transmission allow policy makers to make informed adjustments to control strategies. We analyzed field surveys on ITN ownership, malaria parasite prevalence, and malaria vector population dynamics in seven sentinel sites in western Kenya from 2003 to 2015. We found that ITN ownership has increased from an average of 18% in 2003 to 85% in 2015. Malaria parasite prevalence in school children decreased by about 70% from 2003 to 2008 (the first mass distribution of free ITNs was in 2006) but has resurged by >50% since then. At the community level, use of ITNs reduced infections by 23% in 2008 and 43% in 2010, although the reduction was down to 25% in 2011. The indoor-resting density of the predominant vector, Anopheles gambiae, has been suppressed since 2007; however, Anopheles funestus populations have resurged and have increased 20-fold in some places since 2007. In conclusion, there is limited room for further increase in ITN coverage in western Kenya. The rebounding in malaria transmission highlights the urgent need of new or improved malaria control interventions so as to further reduce malaria transmission. PMID:27574601

  10. Highly Effective Therapy for Maternal Malaria Associated With a Lower Risk of Vertical Transmission

    PubMed Central

    Poespoprodjo, J. R.; Fobia, W.; Kenangalem, E.; Hasanuddin, A.; Sugiarto, P.; Tjitra, E.; Anstey, N. M.

    2011-01-01

    Background. The epidemiology of congenital malaria was investigated in a hospital-based malaria surveillance study in Papua, Indonesia. Methods. From April 2005 to January 2010, 4878 delivering women and their newborns underwent prospective clinical review and malaria screening by peripheral blood microscopy. Findings. Congenital malaria occurred in 8 per 1000 (38/4884) live births, with Plasmodium falciparum accounting for 76.3% (29) and P. vivax for 15.8% (6) of infections. Maternal malaria at delivery (adjusted odds ratio [AOR], 9.5; 95% confidence interval [CI], 4.2–21.5; P < .001), age ≤ 16 years (AOR, 4; 95% CI, 1.4–12.1; P = .011), and prior malaria during pregnancy (AOR, 2.2; 95% CI, 1.1–4.4, P = .022) were independent risk factors for vertical transmission. Of 29 mothers and neonates with contemporaneous peripheral parasitemia, 17% (5) had discordant parasite species, suggesting possible antenatal malaria transmission. Newborns with malaria were at significantly greater risk of low birth weight (AOR, 2.8; 95% CI, 1.2–6.6; P = .002). Following introduction of dihydroartemisinin-piperaquine for uncomplicated malaria in the second and third trimesters of pregnancy, congenital malaria incidence fell from 3.2% to 0.2% (odds ratio, 0.07; 95% CI, .03–.15; P < .001). Conclusions. Congenital malaria is an important cause of neonatal morbidity in this region co-endemic for P. falciparum and P. vivax malaria. The introduction of artemisinin-combination therapy was associated with a significant risk reduction in the vertical transmission of malaria. PMID:21908728

  11. Epidemic and Endemic Malaria Transmission Related to Fish Farming Ponds in the Amazon Frontier

    PubMed Central

    Barcellos, Christovam; Kitron, Uriel; Camara, Daniel Cardoso Portela; Pereira, Glaucio Rocha; Keppeler, Erlei Cassiano; da Silva-Nunes, Mônica

    2015-01-01

    Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003–2013) was divided into two phases (epidemic and post-epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011–2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region. PMID:26361330

  12. Epidemic and Endemic Malaria Transmission Related to Fish Farming Ponds in the Amazon Frontier.

    PubMed

    Reis, Izabel Cristina Dos; Honório, Nildimar Alves; Barros, Fábio Saito Monteiro de; Barcellos, Christovam; Kitron, Uriel; Camara, Daniel Cardoso Portela; Pereira, Glaucio Rocha; Keppeler, Erlei Cassiano; da Silva-Nunes, Mônica; Codeço, Cláudia Torres

    2015-01-01

    Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003-2013) was divided into two phases (epidemic and post-epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011-2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region. PMID:26361330

  13. Interrupting Malaria Transmission: Quantifying the Impact of Interventions in Regions of Low to Moderate Transmission

    PubMed Central

    Gatton, Michelle L.; Cheng, Qin

    2010-01-01

    Malaria has been eliminated from over 40 countries with an additional 39 currently planning for, or committed to, elimination. Information on the likely impact of available interventions, and the required time, is urgently needed to help plan resource allocation. Mathematical modelling has been used to investigate the impact of various interventions; the strength of the conclusions is boosted when several models with differing formulation produce similar data. Here we predict by using an individual-based stochastic simulation model of seasonal Plasmodium falciparum transmission that transmission can be interrupted and parasite reintroductions controlled in villages of 1,000 individuals where the entomological inoculation rate is <7 infectious bites per person per year using chemotherapy and bed net strategies. Above this transmission intensity bed nets and symptomatic treatment alone were not sufficient to interrupt transmission and control the importation of malaria for at least 150 days. Our model results suggest that 1) stochastic events impact the likelihood of successfully interrupting transmission with large variability in the times required, 2) the relative reduction in morbidity caused by the interventions were age-group specific, changing over time, and 3) the post-intervention changes in morbidity were larger than the corresponding impact on transmission. These results generally agree with the conclusions from previously published models. However the model also predicted changes in parasite population structure as a result of improved treatment of symptomatic individuals; the survival probability of introduced parasites reduced leading to an increase in the prevalence of sub-patent infections in semi-immune individuals. This novel finding requires further investigation in the field because, if confirmed, such a change would have a negative impact on attempts to eliminate the disease from areas of moderate transmission. PMID:21152042

  14. Transmission Risk from Imported Plasmodium vivax Malaria in the China–Myanmar Border Region

    PubMed Central

    Wang, Duoquan; Li, Shengguo; Cheng, Zhibin; Cotter, Chris; Hwang, Jimee; Li, Xishang; Yin, Shouqin; Wang, Jiazhi; Bai, Liang; Zheng, Zhi; Wang, Sibao

    2015-01-01

    Malaria importation and local vector susceptibility to imported Plasmodium vivax infection are a continuing risk along the China–Myanmar border. Malaria transmission has been prevented in 3 border villages in Tengchong County, Yunnan Province, China, by use of active fever surveillance, integrated vector control measures, and intensified surveillance and response. PMID:26401843

  15. Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45.

    PubMed

    Pritsch, Michael; Ben-Khaled, Najib; Chaloupka, Michael; Kobold, Sebastian; Berens-Riha, Nicole; Peter, Annabell; Liegl, Gabriele; Schubert, Sören; Hoelscher, Michael; Löscher, Thomas; Wieser, Andreas

    2016-01-01

    Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT) and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 10(5) could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases. PMID:27239480

  16. Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45

    PubMed Central

    Pritsch, Michael; Ben-Khaled, Najib; Chaloupka, Michael; Kobold, Sebastian; Berens-Riha, Nicole; Peter, Annabell; Liegl, Gabriele; Schubert, Sören; Hoelscher, Michael; Löscher, Thomas; Wieser, Andreas

    2016-01-01

    Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT) and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 105 could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases. PMID:27239480

  17. Modelling heterogeneity in malaria transmission using large sparse spatio-temporal entomological data

    PubMed Central

    Rumisha, Susan Fred; Smith, Thomas; Abdulla, Salim; Masanja, Honorath; Vounatsou, Penelope

    2014-01-01

    Background Malaria transmission is measured using entomological inoculation rate (EIR), number of infective mosquito bites/person/unit time. Understanding heterogeneity of malaria transmission has been difficult due to a lack of appropriate data. A comprehensive entomological database compiled by the Malaria Transmission Intensity and Mortality Burden across Africa (MTIMBA) project (2001–2004) at several sites is the most suitable dataset for studying malaria transmission–mortality relations. The data are sparse and large, with small-scale spatial–temporal variation. Objective This work demonstrates a rigorous approach for analysing large and highly variable entomological data for the study of malaria transmission heterogeneity, measured by EIR, within the Rufiji Demographic Surveillance System (DSS), MTIMBA project site in Tanzania. Design Bayesian geostatistical binomial and negative binomial models with zero inflation were fitted for sporozoite rates (SRs) and mosquito density, respectively. The spatial process was approximated from a subset of locations. The models were adjusted for environmental effects, seasonality and temporal correlations and assessed based on their predictive ability. EIR was calculated using model-based predictions of SR and density. Results Malaria transmission was mostly influenced by rain and temperature, which significantly reduces the probability of observing zero mosquitoes. High transmission was observed at the onset of heavy rains. Transmission intensity reduced significantly during Year 2 and 3, contrary to the Year 1, pronouncing high seasonality and spatial variability. The southern part of the DSS showed high transmission throughout the years. A spatial shift of transmission intensity was observed where an increase in households with very low transmission intensity and significant reduction of locations with high transmission were observed over time. Over 68 and 85% of the locations selected for validation for SR and

  18. Optimal temperature for malaria transmission is dramatically lower than previously predicted

    USGS Publications Warehouse

    Mordecai, Erin A.; Paaijmans, Krijn P.; Johnson, Leah R.; Balzer, Christian; Ben-Horin, Tal; de Moor, Emily; McNally, Amy; Pawar, Samraat; Ryan, Sadie J.; Smith, Thomas C.; Lafferty, Kevin D.

    2013-01-01

    The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life-history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal-response models will aid in understanding the effects of current and future temperature regimes on disease transmission.

  19. Urban Malaria: Understanding its Epidemiology, Ecology, and Transmission across Seven Diverse ICEMR Network Sites

    PubMed Central

    Wilson, Mark L.; Krogstad, Donald J.; Arinaitwe, Emmanuel; Arevalo-Herrera, Myriam; Chery, Laura; Ferreira, Marcelo U.; Ndiaye, Daouda; Mathanga, Don P.; Eapen, Alex

    2015-01-01

    A major public health question is whether urbanization will transform malaria from a rural to an urban disease. However, differences about definitions of urban settings, urban malaria, and whether malaria control should differ between rural and urban areas complicate both the analysis of available data and the development of intervention strategies. This report examines the approach of the International Centers of Excellence for Malaria Research (ICEMR) to urban malaria in Brazil, Colombia, India (Chennai and Goa), Malawi, Senegal, and Uganda. Its major theme is the need to determine whether cases diagnosed in urban areas were imported from surrounding rural areas or resulted from transmission within the urban area. If infections are being acquired within urban areas, malaria control measures must be targeted within those urban areas to be effective. Conversely, if malaria cases are being imported from rural areas, control measures must be directed at vectors, breeding sites, and infected humans in those rural areas. Similar interventions must be directed differently if infections were acquired within urban areas. The hypothesis underlying the ICEMR approach to urban malaria is that optimal control of urban malaria depends on accurate epidemiologic and entomologic information about transmission. PMID:26259941

  20. Assessing the Role of Climate Change in Malaria Transmission in Africa

    PubMed Central

    Ngarakana-Gwasira, E. T.; Bhunu, C. P.; Masocha, M.; Mashonjowa, E.

    2016-01-01

    The sensitivity of vector borne diseases like malaria to climate continues to raise considerable concern over the implications of climate change on future disease dynamics. The problem of malaria vectors shifting from their traditional locations to invade new zones is of important concern. A mathematical model incorporating rainfall and temperature is constructed to study the transmission dynamics of malaria. The reproduction number obtained is applied to gridded temperature and rainfall datasets for baseline climate and future climate with aid of GIS. As a result of climate change, malaria burden is likely to increase in the tropics, the highland regions, and East Africa and along the northern limit of falciparum malaria. Falciparum malaria will spread into the African highlands; however it is likely to die out at the southern limit of the disease. PMID:27066290

  1. Assessing the Role of Climate Change in Malaria Transmission in Africa.

    PubMed

    Ngarakana-Gwasira, E T; Bhunu, C P; Masocha, M; Mashonjowa, E

    2016-01-01

    The sensitivity of vector borne diseases like malaria to climate continues to raise considerable concern over the implications of climate change on future disease dynamics. The problem of malaria vectors shifting from their traditional locations to invade new zones is of important concern. A mathematical model incorporating rainfall and temperature is constructed to study the transmission dynamics of malaria. The reproduction number obtained is applied to gridded temperature and rainfall datasets for baseline climate and future climate with aid of GIS. As a result of climate change, malaria burden is likely to increase in the tropics, the highland regions, and East Africa and along the northern limit of falciparum malaria. Falciparum malaria will spread into the African highlands; however it is likely to die out at the southern limit of the disease. PMID:27066290

  2. Antibodies to a single, conserved epitope in Anopheles APN1 inhibit universal transmission of Plasmodium falciparum and Plasmodium vivax malaria.

    PubMed

    Armistead, Jennifer S; Morlais, Isabelle; Mathias, Derrick K; Jardim, Juliette G; Joy, Jaimy; Fridman, Arthur; Finnefrock, Adam C; Bagchi, Ansu; Plebanski, Magdalena; Scorpio, Diana G; Churcher, Thomas S; Borg, Natalie A; Sattabongkot, Jetsumon; Dinglasan, Rhoel R

    2014-02-01

    Malaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of the Plasmodium parasite, the Anopheles mosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission of Plasmodium falciparum and Plasmodium vivax across distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria. PMID:24478095

  3. Targeting of blood safety measures to affected areas with ongoing local transmission of malaria.

    PubMed

    Domanović, D; Kitchen, A; Politis, C; Panagiotopoulos, T; Bluemel, J; Van Bortel, W; Overbosch, D; Lieshout-Krikke, R; Fabra, C; Facco, G; Zeller, H

    2016-06-01

    An outbreak of locally acquired Plasmodium vivax malaria in Greece started in 2009 and peaked in 2011. Targeting of blood safety measures to affected areas with ongoing transmission of malaria raised questions of how to define spatial boundaries of such an area and when to trigger any specific blood safety measures, including whether and which blood donation screening strategy to apply. To provide scientific advice the European Centre for Disease Prevention and Control (ECDC) organised expert meetings in 2013. The outcomes of these consultations are expert opinions covering spatial targeting of blood safety measures to affected areas with ongoing local transmission of malaria and blood donation screening strategy for evidence of malaria infection in these areas. Opinions could help EU national blood safety authorities in developing a preventive strategy during malaria outbreaks. PMID:27238883

  4. Comparative Assessment of Transmission-Blocking Vaccine Candidates against Plasmodium falciparum

    PubMed Central

    Kapulu, M. C.; Da, D. F.; Miura, K.; Li, Y; Blagborough, A. M.; Churcher, T. S.; Nikolaeva, D.; Williams, A. R.; Goodman, A. L.; Sangare, I.; Turner, A. V.; Cottingham, M. G.; Nicosia, A.; Straschil, U.; Tsuboi, T.; Gilbert, S. C.; Long, Carole A.; Sinden, R. E.; Draper, S. J.; Hill, A. V. S.; Cohuet, A.; Biswas, S.

    2015-01-01

    Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform. PMID:26063320

  5. Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum.

    PubMed

    Kapulu, M C; Da, D F; Miura, K; Li, Y; Blagborough, A M; Churcher, T S; Nikolaeva, D; Williams, A R; Goodman, A L; Sangare, I; Turner, A V; Cottingham, M G; Nicosia, A; Straschil, U; Tsuboi, T; Gilbert, S C; Long, Carole A; Sinden, R E; Draper, S J; Hill, A V S; Cohuet, A; Biswas, S

    2015-01-01

    Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform. PMID:26063320

  6. International Funding for Malaria Control in Relation to Populations at Risk of Stable Plasmodium falciparum Transmission

    PubMed Central

    Snow, Robert W; Guerra, Carlos A; Mutheu, Juliette J; Hay, Simon I

    2008-01-01

    Background The international financing of malaria control has increased significantly in the last ten years in parallel with calls to halve the malaria burden by the year 2015. The allocation of funds to countries should reflect the size of the populations at risk of infection, disease, and death. To examine this relationship, we compare an audit of international commitments with an objective assessment of national need: the population at risk of stable Plasmodium falciparum malaria transmission in 2007. Methods and Findings The national distributions of populations at risk of stable P. falciparum transmission were projected to the year 2007 for each of 87 P. falciparum–endemic countries. Systematic online- and literature-based searches were conducted to audit the international funding commitments made for malaria control by major donors between 2002 and 2007. These figures were used to generate annual malaria funding allocation (in US dollars) per capita population at risk of stable P. falciparum in 2007. Almost US$1 billion are distributed each year to the 1.4 billion people exposed to stable P. falciparum malaria risk. This is less than US$1 per person at risk per year. Forty percent of this total comes from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Substantial regional and national variations in disbursements exist. While the distribution of funds is found to be broadly appropriate, specific high population density countries receive disproportionately less support to scale up malaria control. Additionally, an inadequacy of current financial commitments by the international community was found: under-funding could be from 50% to 450%, depending on which global assessment of the cost required to scale up malaria control is adopted. Conclusions Without further increases in funding and appropriate targeting of global malaria control investment it is unlikely that international goals to halve disease burdens by 2015 will be achieved. Moreover, the

  7. Effect of Transmission Setting and Mixed Species Infections on Clinical Measures of Malaria in Malawi

    PubMed Central

    Bruce, Marian C.; Macheso, Allan; Kelly-Hope, Louise A.; Nkhoma, Standwell; McConnachie, Alex; Molyneux, Malcolm E.

    2008-01-01

    Background In malaria endemic regions people are commonly infected with multiple species of malaria parasites but the clinical impact of these Plasmodium co-infections is unclear. Differences in transmission seasonality and transmission intensity between endemic regions have been suggested as important factors in determining the effect of multiple species co-infections. Principal Findings In order to investigate the impact of multiple-species infections on clinical measures of malaria we carried out a cross-sectional community survey in Malawi, in 2002. We collected clinical and parasitological data from 2918 participants aged >6 months, and applied a questionnaire to measure malaria morbidity. We examined the effect of transmission seasonality and intensity on fever, history of fever, haemoglobin concentration ([Hb]) and parasite density, by comparing three regions: perennial transmission (PT), high intensity seasonal transmission (HIST) and low intensity seasonal transmission (LIST). These regions were defined using multi-level modelling of PCR prevalence data and spatial and geo-climatic measures. The three Plasmodium species (P. falciparum, P. malariae and P. ovale) were randomly distributed amongst all children but not adults in the LIST and PT regions. Mean parasite density in children was lower in the HIST compared with the other two regions. Mixed species infections had lower mean parasite density compared with single species infections in the PT region. Fever rates were similar between transmission regions and were unaffected by mixed species infections. A history of fever was associated with single species infections but only in the HIST region. Reduced mean [Hb] and increased anaemia was associated with perennial transmission compared to seasonal transmission. Children with mixed species infections had higher [Hb] in the HIST region. Conclusions Our study suggests that the interaction of Plasmodium co-infecting species can have protective effects against

  8. Updating Historical Maps of Malaria Transmission Intensity in East Africa Using Remote Sensing

    PubMed Central

    Omumbo, J.A.; Hay, S.I.; Goetz, S.J.; Snow, R.W.; Rogers, D.J.

    2013-01-01

    Remotely sensed imagery has been used to update and improve the spatial resolution of malaria transmission intensity maps in Tanzania, Uganda, and Kenya. Discriminant analysis achieved statistically robust agreements between historical maps of the intensity of malaria transmission and predictions based on multitemporal meteorological satellite sensor data processed using temporal Fourier analysis. The study identified land surface temperature as the best predictor of transmission intensity. Rainfall and moisture availability as inferred by cold cloud duration (ccd) and the normalized difference vegetation index (ndvi), respectively, were identified as secondary predictors of transmission intensity. Information on altitude derived from a digital elevation model significantly improved the predictions. “Malaria-free” areas were predicted with an accuracy of 96 percent while areas where transmission occurs only near water, moderate malaria areas, and intense malaria transmission areas were predicted with accuracies of 90 percent, 72 percent, and 87 percent, respectively. The importance of such maps for rationalizing malaria control is discussed, as is the potential contribution of the next generation of satellite sensors to these mapping efforts. PMID:23814324

  9. Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission

    PubMed Central

    Akinosoglou, Karolina A; Bushell, Ellen S C; Ukegbu, Chiamaka Valerie; Schlegelmilch, Timm; Cho, Jee-Sun; Redmond, Seth; Sala, Katarzyna; Christophides, George K; Vlachou, Dina

    2015-01-01

    The passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. Here, we used DNA microarrays to profile the developmental transcriptomes of the rodent malaria parasite Plasmodium berghei in vivo, in the midgut of Anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. Data analysis identified several distinct transcriptional programmes encompassing genes putatively involved in developmental processes or in interactions with the mosquito. At least two of these programmes are associated with the ookinete development that is linked to mosquito midgut invasion and establishment of infection. Targeted disruption by homologous recombination of two of these genes resulted in mutant parasites exhibiting notable infection phenotypes. GAMER encodes a short polypeptide with granular localization in the gametocyte cytoplasm and shows a highly penetrant loss-of-function phenotype manifested as greatly reduced ookinete numbers, linked to impaired male gamete release. HADO encodes a putative magnesium phosphatase with distinctive cortical localization along the concave ookinete periphery. Disruption of HADO compromises ookinete development leading to significant reduction of oocyst numbers. Our data provide important insights into the molecular framework underpinning Plasmodium development in the mosquito and identifies two genes with important functions at initial stages of parasite development in the mosquito midgut. PMID:25225164

  10. The Limits and Intensity of Plasmodium falciparum Transmission: Implications for Malaria Control and Elimination Worldwide

    PubMed Central

    Guerra, Carlos A; Gikandi, Priscilla W; Tatem, Andrew J; Noor, Abdisalan M; Smith, Dave L; Hay, Simon I; Snow, Robert W

    2008-01-01

    Background The efficient allocation of financial resources for malaria control using appropriate combinations of interventions requires accurate information on the geographic distribution of malaria risk. An evidence-based description of the global range of Plasmodium falciparum malaria and its endemicity has not been assembled in almost 40 y. This paper aims to define the global geographic distribution of P. falciparum malaria in 2007 and to provide a preliminary description of its transmission intensity within this range. Methods and Findings The global spatial distribution of P. falciparum malaria was generated using nationally reported case-incidence data, medical intelligence, and biological rules of transmission exclusion, using temperature and aridity limits informed by the bionomics of dominant Anopheles vector species. A total of 4,278 spatially unique cross-sectional survey estimates of P. falciparum parasite rates were assembled. Extractions from a population surface showed that 2.37 billion people lived in areas at any risk of P. falciparum transmission in 2007. Globally, almost 1 billion people lived under unstable, or extremely low, malaria risk. Almost all P. falciparum parasite rates above 50% were reported in Africa in a latitude band consistent with the distribution of Anopheles gambiae s.s. Conditions of low parasite prevalence were also common in Africa, however. Outside of Africa, P. falciparum malaria prevalence is largely hypoendemic (less than 10%), with the median below 5% in the areas surveyed. Conclusions This new map is a plausible representation of the current extent of P. falciparum risk and the most contemporary summary of the population at risk of P. falciparum malaria within these limits. For 1 billion people at risk of unstable malaria transmission, elimination is epidemiologically feasible, and large areas of Africa are more amenable to control than appreciated previously. The release of this information in the public domain will

  11. Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities

    PubMed Central

    2013-01-01

    In a search for effective compounds against both the blood- and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity. These hybrid compounds showed high potency against both exoerythrocytic and erythrocytic forms of malaria parasites, comparable to representative trioxane-based counterparts. Furthermore, they efficiently blocked the development of the sporogonic cycle in the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker between the two moieties, effectively cleared a patent blood-stage P. berghei infection in mice after i.p. administration. Overall, these results indicate that peroxide-8-aminoquinoline hybrids are excellent starting points to develop an agent that conveys all the desired antimalarial multistage activities in a single chemical entity and, as such, with the potential to be used in malaria elimination campaigns. PMID:24900781

  12. Novel endoperoxide-based transmission-blocking antimalarials with liver- and blood-schizontocidal activities.

    PubMed

    Miranda, Daniela; Capela, Rita; Albuquerque, Inês S; Meireles, Patrícia; Paiva, Isa; Nogueira, Fátima; Amewu, Richard; Gut, Jiri; Rosenthal, Philip J; Oliveira, Rudi; Mota, Maria M; Moreira, Rui; Marti, Francesc; Prudêncio, Miguel; O'Neill, Paul M; Lopes, Francisca

    2014-02-13

    In a search for effective compounds against both the blood- and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity. These hybrid compounds showed high potency against both exoerythrocytic and erythrocytic forms of malaria parasites, comparable to representative trioxane-based counterparts. Furthermore, they efficiently blocked the development of the sporogonic cycle in the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker between the two moieties, effectively cleared a patent blood-stage P. berghei infection in mice after i.p. administration. Overall, these results indicate that peroxide-8-aminoquinoline hybrids are excellent starting points to develop an agent that conveys all the desired antimalarial multistage activities in a single chemical entity and, as such, with the potential to be used in malaria elimination campaigns. PMID:24900781

  13. Activity of Herbal Medicines on Plasmodium falciparum Gametocytes: Implications for Malaria Transmission in Ghana

    PubMed Central

    Amoah, Linda Eva; Kakaney, Courage; Kwansa-Bentum, Bethel; Kusi, Kwadwo Asamoah

    2015-01-01

    Background Malaria still remains a major health issue in Ghana despite the introduction of Artemisinin-based combination therapy (ACT) coupled with other preventative measures such as the use of insecticide treated nets (ITNs). The global quest for eradication of malaria has heightened the interest of identifying drugs that target the sexual stage of the parasite, referred to as transmission-blocking drugs. This study aimed at assessing the efficacy and gametocydal effects of some commonly used herbal malaria products in Ghana. Methodology/Principal Findings After identifying herbal anti-malarial products frequently purchased on the Ghanaian market, ten of them were selected and lyophilized. In vitro drug sensitivity testing of different concentrations of the herbal products was carried out on asexual and in vitro generated gametocytes of the 3D7 strain of Plasmodium falciparum. The efficacies of the products were assessed by microscopy. Cultures containing low dose of RT also produced the least number of late stage gametocytes. Two of the herbal products CM and RT inhibited the growth of late stage gametocytes by > 80% at 100 μg/ml whilst KG was the most inhibitory to early stage gametocytes at that same concentration. However at 1 μg/ml, only YF significantly inhibited the survival of late stage gametocytes although at that same concentration YF barely inhibited the survival of early stage gametocytes. Conclusions/Significance Herbal product RT (Aloe schweinfurthii, Khaya senegalensis, Piliostigma thonningii and Cassia siamea) demonstrated properties of a highly efficacious gametocydal product. Low dose of herbal product RT exhibited the highest gametocydal activity and at 100 μg/ml, RT exhibited >80% inhibition of late stage gametocytes. However inhibition of asexual stage parasite by RT was not optimal. Improving the asexual inhibition of RT could convert RT into an ideal antimalarial herbal product. We also found that generally C. sanguinolenta containing

  14. Meteorological, environmental remote sensing and neural network analysis of the epidemiology of malaria transmission in Thailand.

    PubMed

    Kiang, Richard; Adimi, Farida; Soika, Valerii; Nigro, Joseph; Singhasivanon, Pratap; Sirichaisinthop, Jeeraphat; Leemingsawat, Somjai; Apiwathnasorn, Chamnarn; Looareesuwan, Sornchai

    2006-11-01

    In many malarious regions malaria transmission roughly coincides with rainy seasons, which provide for more abundant larval habitats. In addition to precipitation, other meteorological and environmental factors may also influence malaria transmission. These factors can be remotely sensed using earth observing environmental satellites and estimated with seasonal climate forecasts. The use of remote sensing usage as an early warning tool for malaria epidemics have been broadly studied in recent years, especially for Africa, where the majority of the world's malaria occurs. Although the Greater Mekong Subregion (GMS), which includes Thailand and the surrounding countries, is an epicenter of multidrug resistant falciparum malaria, the meteorological and environmental factors affecting malaria transmissions in the GMS have not been examined in detail. In this study, the parasitological data used consisted of the monthly malaria epidemiology data at the provincial level compiled by the Thai Ministry of Public Health. Precipitation, temperature, relative humidity, and vegetation index obtained from both climate time series and satellite measurements were used as independent variables to model malaria. We used neural network methods, an artificial-intelligence technique, to model the dependency of malaria transmission on these variables. The average training accuracy of the neural network analysis for three provinces (Kanchanaburi, Mae Hong Son, and Tak) which are among the provinces most endemic for malaria, is 72.8% and the average testing accuracy is 62.9% based on the 1994-1999 data. A more complex neural network architecture resulted in higher training accuracy but also lower testing accuracy. Taking into account of the uncertainty regarding reported malaria cases, we divided the malaria cases into bands (classes) to compute training accuracy. Using the same neural network architecture on the 19 most endemic provinces for years 1994 to 2000, the mean training accuracy

  15. Factors Contributing to Urban Malaria Transmission in Sub-Saharan Africa: A Systematic Review

    PubMed Central

    De Silva, Prathiba M.; Marshall, John M.

    2012-01-01

    Sub-Saharan Africa suffers by far the greatest malaria burden worldwide and is currently undergoing a profound demographic change, with a growing proportion of its population moving to urban areas. Urbanisation is generally expected to reduce malaria transmission; however the disease still persists in African cities, in some cases at higher levels than in nearby rural areas. Objective. This paper aims to collate and analyse risk factors for urban malaria transmission throughout sub-Saharan Africa and to discuss their implications for control. Methods. A systematic search on malaria and urbanisation was carried out focusing on sub-Saharan Africa. Particular interest was taken in vector breeding sites in urban and periurban areas. Results. A variety of urban vector breeding sites were catalogued, the majority of which were artificial, including urban agriculture, tyre tracks, and ditches. Natural breeding sites varied according to location. Low socioeconomic status was a significant risk factor for malaria, often present in peri-urban areas. A worrying trend was seen in the adaptation of malaria vector species to the urban environment. Urban malaria is highly focused and control programs should reflect this. Conclusion. As urbanisation continues and vector species adapt, continued monitoring and control of urban malaria in sub-Saharan Africa is essential. PMID:23125863

  16. Factors contributing to urban malaria transmission in sub-saharan Africa: a systematic review.

    PubMed

    De Silva, Prathiba M; Marshall, John M

    2012-01-01

    Sub-Saharan Africa suffers by far the greatest malaria burden worldwide and is currently undergoing a profound demographic change, with a growing proportion of its population moving to urban areas. Urbanisation is generally expected to reduce malaria transmission; however the disease still persists in African cities, in some cases at higher levels than in nearby rural areas. Objective. This paper aims to collate and analyse risk factors for urban malaria transmission throughout sub-Saharan Africa and to discuss their implications for control. Methods. A systematic search on malaria and urbanisation was carried out focusing on sub-Saharan Africa. Particular interest was taken in vector breeding sites in urban and periurban areas. Results. A variety of urban vector breeding sites were catalogued, the majority of which were artificial, including urban agriculture, tyre tracks, and ditches. Natural breeding sites varied according to location. Low socioeconomic status was a significant risk factor for malaria, often present in peri-urban areas. A worrying trend was seen in the adaptation of malaria vector species to the urban environment. Urban malaria is highly focused and control programs should reflect this. Conclusion. As urbanisation continues and vector species adapt, continued monitoring and control of urban malaria in sub-Saharan Africa is essential. PMID:23125863

  17. Purification Methodology for Viable and Infective Plasmodium vivax Gametocytes That Is Compatible with Transmission-Blocking Assays

    PubMed Central

    Vera, Omaira; Brelas de Brito, Paula; Albrecht, Letusa; Martins-Campos, Keillen Monick; Pimenta, Paulo F. P.; Monteiro, Wuelton M.; Lacerda, Marcus V. G.

    2015-01-01

    Significant progress toward the control of malaria has been achieved, especially regarding Plasmodium falciparum infections. However, the unique biology of Plasmodium vivax hampers current control strategies. The early appearance of P. vivax gametocytes in the peripheral blood and the impossibility of culturing this parasite are major drawbacks. Using blood samples from 40 P. vivax-infected patients, we describe here a methodology to purify viable gametocytes and further infect anophelines. This method opens new avenues to validate transmission-blocking strategies. PMID:26239989

  18. Purification Methodology for Viable and Infective Plasmodium vivax Gametocytes That Is Compatible with Transmission-Blocking Assays.

    PubMed

    Vera, Omaira; Brelas de Brito, Paula; Albrecht, Letusa; Martins-Campos, Keillen Monick; Pimenta, Paulo F P; Monteiro, Wuelton M; Lacerda, Marcus V G; Lopes, Stefanie C P; Costa, Fabio T M

    2015-10-01

    Significant progress toward the control of malaria has been achieved, especially regarding Plasmodium falciparum infections. However, the unique biology of Plasmodium vivax hampers current control strategies. The early appearance of P. vivax gametocytes in the peripheral blood and the impossibility of culturing this parasite are major drawbacks. Using blood samples from 40 P. vivax-infected patients, we describe here a methodology to purify viable gametocytes and further infect anophelines. This method opens new avenues to validate transmission-blocking strategies. PMID:26239989

  19. A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes

    PubMed Central

    Vos, Martijn W.; Stone, Will J. R.; Koolen, Karin M.; van Gemert, Geert-Jan; van Schaijk, Ben; Leroy, Didier; Sauerwein, Robert W.; Bousema, Teun; Dechering, Koen J.

    2015-01-01

    Current first-line treatments for uncomplicated falciparum malaria rapidly clear the asexual stages of the parasite, but do not fully prevent parasite transmission by mosquitoes. The standard membrane feeding assay (SMFA) is the biological gold standard assessment of transmission reducing activity (TRA), but its throughput is limited by the need to determine mosquito infection status by dissection and microscopy. Here we present a novel dissection-free luminescence based SMFA format using a transgenic Plasmodium falciparum reporter parasite without resistance to known antimalarials and therefore unrestricted in its utility in compound screening. Analyses of sixty-five compounds from the Medicines for Malaria Venture validation and malaria boxes identified 37 compounds with high levels of TRA (>80%); different assay modes allowed discrimination between gametocytocidal and downstream modes of action. Comparison of SMFA data to published assay formats for predicting parasite infectivity indicated that individual in vitro screens show substantial numbers of false negatives. These results highlight the importance of the SMFA in the screening pipeline for transmission reducing compounds and present a rapid and objective method. In addition we present sixteen diverse chemical scaffolds from the malaria box that may serve as a starting point for further discovery and development of malaria transmission blocking drugs. PMID:26687564

  20. Role of species composition in malaria transmission by the Anopheles funestus group (Diptera: Culicidae) in Ghana.

    PubMed

    Dadzie, Samuel K; Brenyah, Ruth; Appawu, Maxwell A

    2013-06-01

    Malaria remains a public health problem in Ghana, with Anopheles gambiae and Anopheles funestus as the predominant vectors. While much information exists on the species composition of An. gambiae, very little exists for An. funestus. This study was carried out to determine the species composition of An. funestus Giles populations from three ecological areas in Ghana and investigate their role in malaria transmission. Mosquitoes were collected using human landing and pyrethrum spray methods. A total of 10,254 Anopheles individuals were collected, out of which An. funestus constituted 53.6% (5,496). An. funestus sensu stricto (s.s.) and Anopheles lessoni were identified as the only members of the An. funestus group in all three ecological areas. All 62 sporozoite positive specimens that were identified as An. funestus s.s. were highly anthropophilic with a human blood index in the range of 80-96%, whereas more than 83% of the An. leesoni had fed on either bovine, goat, or sheep. Malaria transmission was higher in the Sahel savannah area than the rest of the ecological zones, with An. funestus s.s. being implicated as a vector of malaria in all ecological zones. Anopheles leesoni occurred in all the ecological areas but played no role in malaria transmission. The study established the importance of An. funestus s.s. in malaria transmission in Ghana. PMID:23701614

  1. Application of satellite estimates of rainfall distribution to simulate the potential for malaria transmission in Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2009-12-01

    The Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS) is a mechanistic model developed to assess malaria risk in areas where the disease is water-limited. This model relies on precipitation inputs as its primary forcing. Until now, applications of the model have used ground-based precipitation observations. However, rain gauge networks in the areas most affected by malaria are often sparse. The increasing availability of satellite based rainfall estimates could greatly extend the range of the model. The minimum temporal resolution of precipitation data needed was determined to be one hour. The CPC Morphing technique (CMORPH ) distributed by NOAA fits this criteria, as it provides 30-minute estimates at 8km resolution. CMORPH data were compared to ground observations in four West African villages, and calibrated to reduce overestimation and false alarm biases. The calibrated CMORPH data were used to force HYDREMATS, resulting in outputs for mosquito populations, vectorial capacity and malaria transmission.

  2. The Response of Environmental Capacity for Malaria Transmission in West Africa to Climate Change

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2011-12-01

    The climate of West Africa is characterized by north-south gradients in temperature and rainfall. Environmental capacity for malaria transmission (e.g. as measured by vectorial capacity) is strongly tied to these two variables; temperature affects the development rate of the malaria parasite, as well as the lifespan of the mosquitoes that transmit the disease, and rainfall is tied to mosquito abundance, as the vector lays its eggs in rain-fed water pools. A change in climate is therefore expected to lead to changes in the distribution of malaria transmission. Current general circulation models agree that the temperature in West Africa is expected to increase by several degrees in the next century. However they predict a wide range of possible rainfall scenarios in the future, from intense drying to significant increases in rainfall (Christensen et al., 2007). The effects these changes will have on environmental capacity for malaria transmission depend on the magnitude and direction of the changes, and on current conditions. For example, malaria transmission will be more sensitive to positive changes in rainfall in dry areas where mosquito populations are currently limited by water availability than in relatively wet areas. Here, we analyze combinations of changes in rainfall and temperature within the ranges predicted by GCMs, and assess the impact these combinations will have on the environmental capacity for malaria transmission. In particular, we identify climate change scenarios that are likely to have the greatest impact on environmental capacity for malaria transmission, as well as geographic "hot spots" where the greatest changes are to be expected. Christensen, J. H., Busuioc, A., & et al. (2007). Regional climate projections. In S. Solomon (Ed.), Climate change 2007: The physical science basis. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change.

  3. Transplacental Transmission of Plasmodium falciparum in a Highly Malaria Endemic Area of Burkina Faso

    PubMed Central

    Ouédraogo, Alphonse; Tiono, Alfred B.; Diarra, Amidou; Bougouma, Edith C. Christiane; Nébié, Issa; Konaté, Amadou T.; Sirima, Sodiomon B.

    2012-01-01

    Malaria congenital infection constitutes a major risk in malaria endemic areas. In this study, we report the prevalence of transplacental malaria in Burkina Faso. In labour and delivery units, thick and thin blood films were made from maternal, placental, and umbilical cord blood to determine malaria infection. A total of 1,309 mother/baby pairs were recruited. Eighteen cord blood samples (1.4%) contained malaria parasites (Plasmodium falciparum). Out of the 369 (28.2%) women with peripheral positive parasitemia, 211 (57.2%) had placental malaria and 14 (3.8%) had malaria parasites in their umbilical cord blood. The umbilical cord parasitemia levels were statistically associated with the presence of maternal peripheral parasitemia (OR = 9.24, P ≪ 0.001), placental parasitemia (OR = 10.74, P ≪ 0.001), high-density peripheral parasitemia (OR = 9.62, P ≪ 0.001), and high-density placental parasitemia (OR = 4.91, P = 0.03). In Burkina Faso, the mother-to-child transmission rate of malaria appears to be low. PMID:22174725

  4. Surveillance and Control of Malaria Transmission Using Remotely Sensed Meteorological and Environmental Parameters

    NASA Technical Reports Server (NTRS)

    Kiang, R.; Adimi, F.; Nigro, J.

    2007-01-01

    Meteorological and environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. These parameters can most conveniently be obtained using remote sensing. Selected provinces and districts in Thailand and Indonesia are used to illustrate how remotely sensed meteorological and environmental parameters may enhance the capabilities for malaria surveillance and control. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records.

  5. Malaria

    MedlinePlus

    MENU Return to Web version Malaria Overview What is malaria? Malaria is an infection of a part of the blood called the red blood cells. It is ... by mosquitoes that carry a parasite that causes malaria. If a mosquito carrying this parasite bites you, ...

  6. Malaria transmission in two localities in north-western Argentina

    PubMed Central

    Dantur Juri, María J; Zaidenberg, Mario; Claps, Guillermo L; Santana, Mirta; Almirón, Walter R

    2009-01-01

    Background Malaria is one of the most important tropical diseases that affects people globally. The influence of environmental conditions in the patterns of temporal distribution of malaria vectors and the disease has been studied in different countries. In the present study, ecological aspects of the malaria vector Anopheles (Anopheles) pseudopunctipennis and their relationship with climatic variables, as well as the seasonality of malaria cases, were studied in two localities, El Oculto and Aguas Blancas, in north-western Argentina. Methods The fluctuation of An. pseudopunctipennis and the malaria cases distribution was analysed with Random Effect Poisson Regression. This analysis takes into account the effect of each climatic variable on the abundance of both vector and malaria cases, giving as results predicted values named Incidence Rate Radio. Results The number of specimens collected in El Oculto and Aguas Blancas was 4224 (88.07%) and 572 (11.93%), respectively. In El Oculto no marked seasonality was found, different from Aguas Blancas, where high abundance was detected at the end of spring and the beginning of summer. The maximum mean temperature affected the An. pseudopunctipennis fluctuation in El Oculto and Aguas Blancas. When considering the relationship between the number of malaria cases and the climatic variables in El Oculto, maximum mean temperature and accumulated rainfall were significant, in contrast with Aguas Blancas, where mean temperature and humidity showed a closer relationship to the fluctuation in the disease. Conclusion The temporal distribution patterns of An. pseudopunctipennis vary in both localities, but spring appears as the season with better conditions for mosquito development. Maximum mean temperature was the most important variable in both localities. Malaria cases were influenced by the maximum mean temperature in El Oculto, while the mean temperature and humidity were significant in Aguas Blancas. In Aguas Blancas peaks of

  7. Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity

    PubMed Central

    D'Alessandro, Sarah; Corbett, Yolanda; Ilboudo, Denise P.; Misiano, Paola; Dahiya, Nisha; Abay, Solomon M.; Habluetzel, Annette; Grande, Romualdo; Gismondo, Maria R.; Dechering, Koen J.; Koolen, Karin M. J.; Sauerwein, Robert W.; Taramelli, Donatella; Parapini, Silvia

    2015-01-01

    The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads. PMID:26055362

  8. Surveillance and Control of Malaria Transmission in Thailand using Remotely Sensed Meteorological and Environmental Parameters

    NASA Technical Reports Server (NTRS)

    Kiang, Richard K.; Adimi, Farida; Soika, Valerii; Nigro, Joseph

    2007-01-01

    These slides address the use of remote sensing in a public health application. Specifically, this discussion focuses on the of remote sensing to detect larval habitats to predict current and future endemicity and identify key factors that sustain or promote transmission of malaria in a targeted geographic area (Thailand). In the Malaria Modeling and Surveillance Project, which is part of the NASA Applied Sciences Public Health Applications Program, we have been developing techniques to enhance public health's decision capability for malaria risk assessments and controls. The main objectives are: 1) identification of the potential breeding sites for major vector species; 2) implementation of a risk algorithm to predict the occurrence of malaria and its transmission intensity; 3) implementation of a dynamic transmission model to identify the key factors that sustain or intensify malaria transmission. The potential benefits are: 1) increased warning time for public health organizations to respond to malaria outbreaks; 2) optimized utilization of pesticide and chemoprophylaxis; 3) reduced likelihood of pesticide and drug resistance; and 4) reduced damage to environment. !> Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. The NASA Earth science data sets that have been used for malaria surveillance and risk assessment include AVHRR Pathfinder, TRMM, MODIS, NSIPP, and SIESIP. Textural-contextual classifications are used to identify small larval habitats. Neural network methods are used to model malaria cases as a function of the remotely sensed parameters. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Discrete event simulations are used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors

  9. Simulating malaria transmission in the current and future climate of West Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Bomblies, A.; Eltahir, E. A. B.

    2015-12-01

    Malaria transmission in West Africa is closely tied to climate, as rain fed water pools provide breeding habitat for the anopheles mosquito vector, and temperature affects the mosquito's ability to spread disease. We present results of a highly detailed, spatially explicit mechanistic modelling study exploring the relationships between the environment and malaria in the current and future climate of West Africa. A mechanistic model of human immunity was incorporated into an existing agent-based model of malaria transmission, allowing us to move beyond entomological measures such as mosquito density and vectorial capacity to analyzing the prevalence of the malaria parasite within human populations. The result is a novel modelling tool that mechanistically simulates all of the key processes linking environment to malaria transmission. Simulations were conducted across climate zones in West Africa, linking temperature and rainfall to entomological and epidemiological variables with a focus on nonlinearities due to threshold effects and interannual variability. Comparisons to observations from the region confirmed that the model provides a reasonable representation of the entomological and epidemiological conditions in this region. We used the predictions of future climate from the most credible CMIP5 climate models to predict the change in frequency and severity of malaria epidemics in West Africa as a result of climate change.

  10. Blind Channel Shortening for Block Transmission of Correlated Signals

    NASA Astrophysics Data System (ADS)

    Miyajima, Teruyuki; Watanabe, Yoshihisa

    In block transmission systems, blind channel shortening methods are known to be effective to reduce the influence of interblock interference which degrades the performance when the length of a channel impulse response is extremely long. Conventional methods assume that the transmitted signal is uncorrelated; however, this assumption is invalid in practical systems such as OFDM with null carriers and MC-CDMA. In this paper, we consider blind channel shortening methods for block transmissions when the transmitted samples within a block are correlated. First, the channel shortening ability of a conventional method is clarified. Next, a new method which exploits the fact that the transmitted samples in different blocks are uncorrelated is introduced. It is shown that the proposed method can shorten the channel properly under certain conditions. Finally, simulation results of OFDM and MC-CDMA systems are shown to verify the effectiveness of the proposed method compared with a conventional one.

  11. Modeling the Effects of Weather and Climate Change on Malaria Transmission

    PubMed Central

    Parham, Paul Edward; Michael, Edwin

    2010-01-01

    Background In recent years, the impact of climate change on human health has attracted considerable attention; the effects on malaria have been of particular interest because of its disease burden and its transmission sensitivity to environmental conditions. Objectives We investigated and illustrated the role that dynamic process-based mathematical models can play in providing strategic insights into the effects of climate change on malaria transmission. Methods We evaluated a relatively simple model that permitted valuable and novel insights into the simultaneous effects of rainfall and temperature on mosquito population dynamics, malaria invasion, persistence and local seasonal extinction, and the impact of seasonality on transmission. We illustrated how large-scale climate simulations and infectious disease systems may be modeled and analyzed and how these methods may be applied to predicting changes in the basic reproduction number of malaria across Tanzania. Results We found extinction to be more strongly dependent on rainfall than on temperature and identified a temperature window of around 32–33°C where endemic transmission and the rate of spread in disease-free regions is optimized. This window was the same for Plasmodium falciparum and P. vivax, but mosquito density played a stronger role in driving the rate of malaria spread than did the Plasmodium species. The results improved our understanding of how temperature shifts affect the global distribution of at-risk regions, as well as how rapidly malaria outbreaks take off within vulnerable populations. Conclusions Disease emergence, extinction, and transmission all depend strongly on climate. Mathematical models offer powerful tools for understanding geographic shifts in incidence as climate changes. Nonlinear dependences of transmission on climate necessitates consideration of both changing climate trends and variability across time scales of interest. PMID:20435552

  12. Nanomimics of host cell membranes block invasion and expose invasive malaria parasites.

    PubMed

    Najer, Adrian; Wu, Dalin; Bieri, Andrej; Brand, Françoise; Palivan, Cornelia G; Beck, Hans-Peter; Meier, Wolfgang

    2014-12-23

    The fight against most infectious diseases, including malaria, is often hampered by the emergence of drug resistance and lack or limited efficacies of vaccines. Therefore, new drugs, vaccines, or other strategies to control these diseases are needed. Here, we present an innovative nanotechnological strategy in which the nanostructure itself represents the active substance with no necessity to release compounds to attain therapeutic effect and which might act in a drug- and vaccine-like dual function. Invasion of Plasmodium falciparum parasites into red blood cells was selected as a biological model for the initial validation of this approach. Stable nanomimics-polymersomes presenting receptors required for parasite attachment to host cells-were designed to efficiently interrupt the life cycle of the parasite by inhibiting invasion. A simple way to build nanomimics without postformation modifications was established. First, a block copolymer of the receptor with a hydrophobic polymer was synthesized and then mixed with a polymersome-forming block copolymer. The resulting nanomimics bound parasite-derived ligands involved in the initial attachment to host cells and they efficiently blocked reinvasion of malaria parasites after their egress from host cells in vitro. They exhibited efficacies of more than 2 orders of magnitude higher than the soluble form of the receptor, which can be explained by multivalent interactions of several receptors on one nanomimic with multiple ligands on the infective parasite. In the future, our strategy might offer interesting treatment options for severe malaria or a way to modulate the immune response. PMID:25435059

  13. Gametocytocidal Screen Identifies Novel Chemical Classes with Plasmodium falciparum Transmission Blocking Activity

    PubMed Central

    Sanders, Natalie G.; Sullivan, David J.; Mlambo, Godfree; Dimopoulos, George; Tripathi, Abhai K.

    2014-01-01

    Discovery of transmission blocking compounds is an important intervention strategy necessary to eliminate and eradicate malaria. To date only a small number of drugs that inhibit gametocyte development and thereby transmission from the mosquito to the human host exist. This limitation is largely due to a lack of screening assays easily adaptable to high throughput because of multiple incubation steps or the requirement for high gametocytemia. Here we report the discovery of new compounds with gametocytocidal activity using a simple and robust SYBR Green I- based DNA assay. Our assay utilizes the exflagellation step in male gametocytes and a background suppressor, which masks the staining of dead cells to achieve healthy signal to noise ratio by increasing signal of viable parasites and subtracting signal from dead parasites. By determining the contribution of exflagellation to fluorescent signal and using appropriate cutoff values, we were able to screen for gametocytocidal compounds. After assay validation and optimization, we screened an FDA approved drug library of approximately 1500 compounds, as well as the 400 compound MMV malaria box and identified 44 gametocytocidal compounds with sub to low micromolar IC50s. Major classes of compounds with gametocytocidal activity included quaternary ammonium compounds with structural similarity to choline, acridine-like compounds similar to quinacrine and pyronaridine, as well as antidepressant, antineoplastic, and anthelminthic compounds. Top drug candidates showed near complete transmission blocking in membrane feeding assays. This assay is simple, reproducible and demonstrated robust Z-factor values at low gametocytemia levels, making it amenable to HTS for identification of novel and potent gametocytocidal compounds. PMID:25157792

  14. Simplified Models of Vector Control Impact upon Malaria Transmission by Zoophagic Mosquitoes

    PubMed Central

    Kiware, Samson S.; Chitnis, Nakul; Moore, Sarah J.; Devine, Gregor J.; Majambere, Silas; Merrill, Stephen; Killeen, Gerry F.

    2012-01-01

    Background High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as “very zoophagic,” meaning they feed occasionally (<10% of blood meals) upon humans, so personal protection interventions have negligible impact upon their survival. Methods and Findings We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index). The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1) Rely on only three field-measurable parameters. (2) Predict immediate and delayed (with and without assuming reduced human infectivity, respectively) impacts of personal protection measures upon transmission. (3) Illustrate how appreciable indirect communal-level protection for non-users can be accrued through direct personal protection of users. (4) Suggest the coverage and efficacy thresholds required to attain epidemiological impact. The findings suggest that immediate, indirect, community-wide protection of users and non-users alike may linearly relate to the efficacy of a user’s direct personal protection, regardless of whether that is achieved by killing or repelling mosquitoes. High protective coverage and efficacy (≥80%) are important to achieve epidemiologically meaningful impact. Non-users are indirectly protected because the two most common species of human malaria are strict anthroponoses. Therefore, the small proportion of mosquitoes that are killed or diverted while attacking humans can represent a large proportion of those actually transmitting malaria. Conclusions Simplified models of malaria transmission by very zoophagic vectors may be used by control practitioners to predict intervention impact

  15. Plasmodium knowlesi transmission: integrating quantitative approaches from epidemiology and ecology to understand malaria as a zoonosis.

    PubMed

    Brock, P M; Fornace, K M; Parmiter, M; Cox, J; Drakeley, C J; Ferguson, H M; Kao, R R

    2016-04-01

    The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions. PMID:26817785

  16. Border Malaria Associated with Multidrug Resistance on Thailand-Myanmar and Thailand-Cambodia Borders: Transmission Dynamic, Vulnerability, and Surveillance

    PubMed Central

    Bhumiratana, Adisak; Intarapuk, Apiradee; Sorosjinda-Nunthawarasilp, Prapa; Maneekan, Pannamas; Koyadun, Surachart

    2013-01-01

    This systematic review elaborates the concepts and impacts of border malaria, particularly on the emergence and spread of Plasmodium falciparum and Plasmodium vivax multidrug resistance (MDR) malaria on Thailand-Myanmar and Thailand-Cambodia borders. Border malaria encompasses any complex epidemiological settings of forest-related and forest fringe-related malaria, both regularly occurring in certain transmission areas and manifesting a trend of increased incidence in transmission prone areas along these borders, as the result of interconnections of human settlements and movement activities, cross-border population migrations, ecological changes, vector population dynamics, and multidrug resistance. For regional and global perspectives, this review analyzes and synthesizes the rationales pertaining to transmission dynamics and the vulnerabilities of border malaria that constrain surveillance and control of the world's most MDR falciparum and vivax malaria on these chaotic borders. PMID:23865048

  17. Epidemic and Non-Epidemic Hot Spots of Malaria Transmission Occur in Indigenous Comarcas of Panama

    PubMed Central

    Dutari, Larissa C.; Rovira, Jose R.; Sucupira, Izis M. C.; Póvoa, Marinete M.; Conn, Jan E.; Loaiza, Jose R.

    2016-01-01

    From 2002–2005, Panama experienced a malaria epidemic that has been associated with El Niño Southern Oscillation weather patterns, decreased funding for malaria control, and landscape modification. Case numbers quickly decreased afterward, and Panama is now in the pre-elimination stage of malaria eradication. To achieve this new goal, the characterization of epidemiological risk factors, foci of transmission, and important anopheline vectors is needed. Of the 24,681 reported cases in these analyses (2000–2014), ~62% occurred in epidemic years and ~44% in indigenous comarcas (5.9% of Panama’s population). Sub-analyses comparing overall numbers of cases in epidemic and non-epidemic years identified females, comarcas and some 5-year age categories as those disproportionately affected by malaria during epidemic years. Annual parasites indices (APIs; number of cases per 1,000 persons) for Plasmodium vivax were higher in comarcas compared to provinces for all study years, though P. falciparum APIs were only higher in comarcas during epidemic years. Interestingly, two comarcas report increasing numbers of cases annually, despite national annual decreases. Inclusion of these comarcas within identified foci of malaria transmission confirmed their roles in continued transmission. Comparison of species distribution models for two important anophelines with Plasmodium case distribution suggest An. albimanus is the primary malaria vector in Panama, confirmed by identification of nine P. vivax-infected specimen pools. Future malaria eradication strategies in Panama should focus on indigenous comarcas and include both active surveillance for cases and comprehensive anopheline vector surveys. PMID:27182773

  18. Epidemic and Non-Epidemic Hot Spots of Malaria Transmission Occur in Indigenous Comarcas of Panama.

    PubMed

    Lainhart, William; Dutari, Larissa C; Rovira, Jose R; Sucupira, Izis M C; Póvoa, Marinete M; Conn, Jan E; Loaiza, Jose R

    2016-05-01

    From 2002-2005, Panama experienced a malaria epidemic that has been associated with El Niño Southern Oscillation weather patterns, decreased funding for malaria control, and landscape modification. Case numbers quickly decreased afterward, and Panama is now in the pre-elimination stage of malaria eradication. To achieve this new goal, the characterization of epidemiological risk factors, foci of transmission, and important anopheline vectors is needed. Of the 24,681 reported cases in these analyses (2000-2014), ~62% occurred in epidemic years and ~44% in indigenous comarcas (5.9% of Panama's population). Sub-analyses comparing overall numbers of cases in epidemic and non-epidemic years identified females, comarcas and some 5-year age categories as those disproportionately affected by malaria during epidemic years. Annual parasites indices (APIs; number of cases per 1,000 persons) for Plasmodium vivax were higher in comarcas compared to provinces for all study years, though P. falciparum APIs were only higher in comarcas during epidemic years. Interestingly, two comarcas report increasing numbers of cases annually, despite national annual decreases. Inclusion of these comarcas within identified foci of malaria transmission confirmed their roles in continued transmission. Comparison of species distribution models for two important anophelines with Plasmodium case distribution suggest An. albimanus is the primary malaria vector in Panama, confirmed by identification of nine P. vivax-infected specimen pools. Future malaria eradication strategies in Panama should focus on indigenous comarcas and include both active surveillance for cases and comprehensive anopheline vector surveys. PMID:27182773

  19. Malaria.

    ERIC Educational Resources Information Center

    Dupasquier, Isabelle

    1989-01-01

    Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…

  20. Malaria

    MedlinePlus

    Malaria is a serious disease caused by a parasite. You get it when an infected mosquito bites you. Malaria is a major cause of death worldwide, but ... at risk. There are four different types of malaria caused by four related parasites. The most deadly ...

  1. Routine in vitro culture of P. falciparum gametocytes to evaluate novel transmission-blocking interventions.

    PubMed

    Delves, Michael J; Straschil, Ursula; Ruecker, Andrea; Miguel-Blanco, Celia; Marques, Sara; Baum, Jake; Sinden, Robert E

    2016-09-01

    The prevention of parasite transmission from the human host to the mosquito has been recognized as a vital tool for malaria eradication campaigns. However, transmission-blocking antimalarial drug and/or vaccine discovery and development is currently hampered by the expense and difficulty of producing mature Plasmodium falciparum gametocytes in vitro-the parasite stage responsible for mosquito infection. Current protocols for P. falciparum gametocyte culture usually require complex parasite synchronization and addition of stimulating and/or inhibitory factors, and they may not have demonstrated the essential property of mosquito infectivity. This protocol details all the steps required for reliable P. falciparum gametocyte production and highlights common factors that influence culture success. The protocol can be completed in 15 d, and particular emphasis is placed upon operating a gametocyte culture facility on a continuous cycle. In addition, we show how functionally viable gametocytes can be used to evaluate transmission-blocking drugs both in a field setting and at high throughput (HTP) for drug discovery. PMID:27560172

  2. Linking environmental variability to village-scale malaria transmission using a simple immunity model

    PubMed Central

    2013-01-01

    Background Individuals continuously exposed to malaria gradually acquire immunity that protects from severe disease and high levels of parasitization. Acquired immunity has been incorporated into numerous models of malaria transmission of varying levels of complexity (e.g. Bull World Health Organ 50:347, 1974; Am J Trop Med Hyg 75:19, 2006; Math Biosci 90:385–396, 1988). Most such models require prescribing inputs of mosquito biting rates or other entomological or epidemiological information. Here, we present a model with a novel structure that uses environmental controls of mosquito population dynamics to simulate the mosquito biting rates, malaria prevalence as well as variability in protective immunity of the population. Methods A simple model of acquired immunity to malaria is presented and tested within the framework of the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a coupled hydrology and agent-based entomology model. The combined model uses environmental data including rainfall, temperature, and topography to simulate malaria prevalence and level of acquired immunity in the human population. The model is used to demonstrate the effect of acquired immunity on malaria prevalence in two Niger villages that are hydrologically and entomologically very different. Simulations are conducted for the year 2006 and compared to malaria prevalence observations collected from the two villages. Results Blood smear samples from children show no clear difference in malaria prevalence between the two villages despite pronounced differences in observed mosquito abundance. The similarity in prevalence is attributed to the moderating effect of acquired immunity, which depends on prior exposure to the parasite through infectious bites - and thus the hydrologically determined mosquito abundance. Modelling the level of acquired immunity can affect village vulnerability to climatic anomalies. Conclusions The model presented has a novel structure

  3. Simulation of the Impact of Climate Variability on Malaria Transmission in the Sahel

    NASA Astrophysics Data System (ADS)

    Bomblies, A.; Eltahir, E.; Duchemin, J.

    2007-12-01

    A coupled hydrology and entomology model for simulation of malaria transmission and malaria transmitting mosquito population dynamics is presented. Model development and validation is done using field data and observations collected at Banizoumbou and Zindarou, Niger spanning three wet seasons, from 2005 through 2007. The primary model objective is the accurate determination of climate variability effects on village scale malaria transmission. Malaria transmission dependence on climate variables is highly nonlinear and complex. Temperature and humidity affect mosquito longevity, temperature controls parasite development rates in the mosquito as well as subadult mosquito development rates, and precipitation determines the formation and persistence of adequate breeding pools. Moreover, unsaturated zone hydrology influences overland flow, and climate controlled evapotranspiration rates and root zone uptake therefore also influence breeding pool formation. High resolution distributed hydrologic simulation allows representation of the small-scale ephemeral pools that constitute the primary habitat of Anopheles gambiae mosquitoes, the dominant malaria vectors in the Niger Sahel. Remotely sensed soil type, vegetation type, and microtopography rasters are used to assign the distributed parameter fields for simulation of the land surface hydrologic response to precipitation and runoff generation. Predicted runoff from each cell flows overland and into topographic depressions, with explicit representation of infiltration and evapotranspiration. The model's entomology component interacts with simulated pools. Subadult (aquatic stage) mosquito breeding is simulated in the pools, and water temperature dependent stage advancement rates regulate adult mosquito emergence into the model domain. Once emerged, adult mosquitoes are tracked as independent individual agents that interact with their immediate environment. Attributes relevant to malaria transmission such as gonotrophic

  4. Rapid case-based mapping of seasonal malaria transmission risk for strategic elimination planning in Swaziland

    PubMed Central

    2013-01-01

    Background As successful malaria control programmes move towards elimination, they must identify residual transmission foci, target vector control to high-risk areas, focus on both asymptomatic and symptomatic infections, and manage importation risk. High spatial and temporal resolution maps of malaria risk can support all of these activities, but commonly available malaria maps are based on parasite rate, a poor metric for measuring malaria at extremely low prevalence. New approaches are required to provide case-based risk maps to countries seeking to identify remaining hotspots of transmission while managing the risk of transmission from imported cases. Methods Household locations and travel histories of confirmed malaria patients during 2011 were recorded through routine surveillance by the Swaziland National Malaria Control Programme for the higher transmission months of January to April and the lower transmission months of May to December. Household locations for patients with no travel history to endemic areas were compared against a random set of background points sampled proportionate to population density with respect to a set of variables related to environment, population density, vector control, and distance to the locations of identified imported cases. Comparisons were made separately for the high and low transmission seasons. The Random Forests regression tree classification approach was used to generate maps predicting the probability of a locally acquired case at 100 m resolution across Swaziland for each season. Results Results indicated that case households during the high transmission season tended to be located in areas of lower elevation, closer to bodies of water, in more sparsely populated areas, with lower rainfall and warmer temperatures, and closer to imported cases than random background points (all p < 0.001). Similar differences were evident during the low transmission season. Maps from the fit models suggested better predictive

  5. Epidemiologic aspects of the malaria transmission cycle in an area of very low incidence in Brazil

    PubMed Central

    Cerutti, Crispim; Boulos, Marcos; Coutinho, Arnídio F; Hatab, Maria do Carmo LD; Falqueto, Aloísio; Rezende, Helder R; Duarte, Ana Maria RC; Collins, William; Malafronte, Rosely S

    2007-01-01

    "classical" P. vivax (VK210), VK247, P. vivax-like and P. malariae, respectively. Anopheline captures in the transmission area revealed only zoophilic and exophilic species. Conclusion The low incidence of malaria cases, the finding of asymptomatic inhabitants and the geographic separation of patients allied to serological and molecular results raise the possibility of the existence of a simian reservoir in these areas. PMID:17371598

  6. Malaria

    PubMed Central

    Suh, Kathryn N.; Kain, Kevin C.; Keystone, Jay S.

    2004-01-01

    Malaria is a parasitic infection of global importance. Although relatively uncommon in developed countries, where the disease occurs mainly in travellers who have returned from endemic regions, it remains one of the most prevalent infections of humans worldwide. In endemic regions, malaria is a significant cause of morbidity and mortality and creates enormous social and economic burdens. Current efforts to control malaria focus on reducing attributable morbidity and mortality. Targeted chemoprophylaxis and use of insecticide-treated bed nets have been successful in some endemic areas. For travellers to malaria-endemic regions, personal protective measures and appropriate chemoprophylaxis can significantly reduce the risk of infection. Prompt evaluation of the febrile traveller, a high degree of suspicion of malaria, rapid and accurate diagnosis, and appropriate antimalarial therapy are essential in order to optimize clinical outcomes of infected patients. Additional approaches to malaria control, including genetic manipulation of mosquitoes and malaria vaccines, are areas of ongoing research. PMID:15159369

  7. Malaria Control and the Intensity of Plasmodium falciparum Transmission in Namibia 1969–1992

    PubMed Central

    Noor, Abdisalan M.; Alegana, Victor A.; Kamwi, Richard N.; Hansford, Clifford F.; Ntomwa, Benson; Katokele, Stark; Snow, Robert W.

    2013-01-01

    Background Historical evidence of the levels of intervention scale up and its relationships to changing malaria risks provides important contextual information for current ambitions to eliminate malaria in various regions of Africa today. Methods Community-based Plasmodium falciparum prevalence data from 3,260 geo-coded time-space locations between 1969 and 1992 were assembled from archives covering an examination of 230,174 individuals located in northern Namibia. These data were standardized the age-range 2 to less than 10 years and used within a Bayesian model-based geo-statistical framework to examine the changes of malaria risk in the years 1969, 1974, 1979, 1984 and 1989 at 5×5 km spatial resolution. This changing risk was described against rainfall seasons and the wide-scale use of indoor-residual house-spraying and mass drug administration. Results Most areas of Northern Namibia experienced low intensity transmission during a ten-year period of wide-scale control activities between 1969 and 1979. As control efforts waned, flooding occurred, drug resistance emerged and the war for independence intensified the spatial extent of moderate-to-high malaria transmission expanded reaching a peak in the late 1980s. Conclusions Targeting vectors and parasite in northern Namibia was likely to have successfully sustained a situation of low intensity transmission, but unraveled quickly to a peak of transmission intensity following a sequence of events by the early 1990s. PMID:23667604

  8. The dynamics, transmission, and population impacts of avian malaria in native hawaiian birds: A modeling approach

    USGS Publications Warehouse

    Samuel, M.D.; Hobbelen, P.H.F.; Decastro, F.; Ahumada, J.A.; Lapointe, D.A.; Atkinson, C.T.; Woodworth, B.L.; Hart, P.J.; Duffy, D.C.

    2011-01-01

    We developed an epidemiological model of avian malaria (Plasmodium relictum) across an altitudinal gradient on the island of Hawaii that includes the dynamics of the host, vector, and parasite. This introduced mosquito-borne disease is hypothesized to have contributed to extinctions and major shifts in the altitudinal distribution of highly susceptible native forest birds. Our goal was to better understand how biotic and abiotic factors influence the intensity of malaria transmission and impact on susceptible populations of native Hawaiian forest birds. Our model illustrates key patterns in the malaria-forest bird system: high malaria transmission in low-elevation forests with minor seasonal or annual variation in infection;episodic transmission in mid-elevation forests with site-to-site, seasonal, and annual variation depending on mosquito dynamics;and disease refugia in high-elevation forests with only slight risk of infection during summer. These infection patterns are driven by temperature and rainfall effects on parasite incubation period and mosquito dynamics across an elevational gradient and the availability of larval habitat, especially in mid-elevation forests. The results from our model suggest that disease is likely a key factor in causing population decline or restricting the distribution of many susceptible Hawaiian species and preventing the recovery of other vulnerable species. The model also provides a framework for the evaluation of factors influencing disease transmission and alternative disease control programs, and to evaluate the impact of climate change on disease cycles and bird populations. ??2011 by the Ecological Society of America.

  9. Immune response and insulin signalling alter mosquito feeding behaviour to enhance malaria transmission potential.

    PubMed

    Cator, Lauren J; Pietri, Jose E; Murdock, Courtney C; Ohm, Johanna R; Lewis, Edwin E; Read, Andrew F; Luckhart, Shirley; Thomas, Matthew B

    2015-01-01

    Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding, and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission. PMID:26153094

  10. Population-Based Seroprevalence of Malaria in Hormozgan Province, Southeastern Iran: A Low Transmission Area

    PubMed Central

    Hatam, Gholam Reza; Nejati, Fatemeh; Mohammadzadeh, Tahereh; Shahriari Rad, Reza; Sarkari, Bahador

    2015-01-01

    The seroepidemiological condition of malaria in three main districts of Hormozgan Province, a low transmission area in southeast of Iran, was investigated. Methods. Sera samples (803) were collected from healthy volunteers from the three main districts (Bandar Lengeh in the west, Bandar Abbas in the center, and Bandar Jask in the east) of Hormozgan Province. A questionnaire was used to record the sociodemographic features of the participants during sample collecting. An in-house ELISA test, using crude antigens obtained from cell culture of Plasmodium falciparum, was adapted and used to detect anti-malaria antibodies in the sera. Results. The overall seroprevalence of malaria was 8.7% (70 out of 803 samples). A significant correlation was found between seropositivity and place of residence, where the highest rate of seropositivity was seen in Bandar Lengeh (west of the province). The highest seroprevalence of malaria (13.2%) was seen in the age group of 11–20 years and also in low educated individuals. Correlation between seropositivity and gender, age, and educational levels of the participants was statistically significant (P < 0.05). Conclusion. Findings of this study indicate that the rate of seropositivity to malaria in this area is not high and this might be linked to the success of malaria control programs during the last decades in the region. PMID:26543662

  11. The effect of temperature on Anopheles mosquito population dynamics and the potential for malaria transmission.

    PubMed

    Beck-Johnson, Lindsay M; Nelson, William A; Paaijmans, Krijn P; Read, Andrew F; Thomas, Matthew B; Bjørnstad, Ottar N

    2013-01-01

    The parasites that cause malaria depend on Anopheles mosquitoes for transmission; because of this, mosquito population dynamics are a key determinant of malaria risk. Development and survival rates of both the Anopheles mosquitoes and the Plasmodium parasites that cause malaria depend on temperature, making this a potential driver of mosquito population dynamics and malaria transmission. We developed a temperature-dependent, stage-structured delayed differential equation model to better understand how climate determines risk. Including the full mosquito life cycle in the model reveals that the mosquito population abundance is more sensitive to temperature than previously thought because it is strongly influenced by the dynamics of the juvenile mosquito stages whose vital rates are also temperature-dependent. Additionally, the model predicts a peak in abundance of mosquitoes old enough to vector malaria at more accurate temperatures than previous models. Our results point to the importance of incorporating detailed vector biology into models for predicting the risk for vector borne diseases. PMID:24244467

  12. A New Set of Chemical Starting Points with Plasmodium falciparum Transmission-Blocking Potential for Antimalarial Drug Discovery

    PubMed Central

    Almela, Maria Jesus; Lozano, Sonia; Lelièvre, Joël; Colmenarejo, Gonzalo; Coterón, José Miguel; Rodrigues, Janneth; Gonzalez, Carolina; Herreros, Esperanza

    2015-01-01

    The discovery of new antimalarials with transmission blocking activity remains a key issue in efforts to control malaria and eventually eradicate the disease. Recently, high-throughput screening (HTS) assays have been successfully applied to Plasmodium falciparum asexual stages to screen millions of compounds, with the identification of thousands of new active molecules, some of which are already in clinical phases. The same approach has now been applied to identify compounds that are active against P. falciparum gametocytes, the parasite stage responsible for transmission. This study reports screening results for the Tres Cantos Antimalarial Set (TCAMS), of approximately 13,533 molecules, against P. falciparum stage V gametocytes. Secondary confirmation and cytotoxicity assays led to the identification of 98 selective molecules with dual activity against gametocytes and asexual stages. Hit compounds were chemically clustered and analyzed for appropriate physicochemical properties. The TCAMS chemical space around the prioritized hits was also studied. A selection of hit compounds was assessed ex vivo in the standard membrane feeding assay and demonstrated complete block in transmission. As a result of this effort, new chemical structures not connected to previously described antimalarials have been identified. This new set of compounds may serve as starting points for future drug discovery programs as well as tool compounds for identifying new modes of action involved in malaria transmission. PMID:26317851

  13. Transmission blocking activity of Azadirachta indica and Guiera senegalensis extracts on the sporogonic development of Plasmodium falciparum field isolates in Anopheles coluzzii mosquitoes

    PubMed Central

    2014-01-01

    Background Targeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. However, at present, only two drugs are available, namely primaquine and artesunate, which reportedly act on late stage gametocytes. Methods In this study, we assessed the antiplasmodial effects of 5 extracts obtained from the neem tree Azadirachta indica and Guiera senegalensis against the early vector stages of Plasmodium falciparum, using field isolates. In an ex vivo assay gametocytaemic blood was supplemented with the plant extracts and offered to Anopheles coluzzii females by membrane feeding. Transmission blocking activity was evaluated by assessing oocyst prevalence and density on the mosquito midguts. Results Initial screening of the 5 plant extracts at 250 ppm revealed transmission blocking activity in two neem preparations. Up to a concentration of 70 ppm the commercial extract NeemAzal® completely blocked transmission and at 60 ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5% (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part did not exhibit any activity. No evidence of transmission blocking activity was found using G. senegalensis ethyl acetate extract from stem galls. Conclusions The results of this study highlight the potential of antimalarial plants for the discovery of novel transmission blocking molecules, and open up the potential of developing standardized transmission blocking herbal formulations as malaria control tools to complement currently used antimalarial drugs and combination treatments. PMID:24735564

  14. Hotspots of Malaria Transmission in the Peruvian Amazon: Rapid Assessment through a Parasitological and Serological Survey

    PubMed Central

    Rosas-Aguirre, Angel; Speybroeck, Niko; Llanos-Cuentas, Alejandro; Rosanas-Urgell, Anna; Carrasco-Escobar, Gabriel; Rodriguez, Hugo; Gamboa, Dionicia; Contreras-Mancilla, Juan; Alava, Freddy; Soares, Irene S.; Remarque, Edmond; D´Alessandro, Umberto; Erhart, Annette

    2015-01-01

    Background With low and markedly seasonal malaria transmission, increasingly sensitive tools for better stratifying the risk of infection and targeting control interventions are needed. A cross-sectional survey to characterize the current malaria transmission patterns, identify hotspots, and detect recent changes using parasitological and serological measures was conducted in three sites of the Peruvian Amazon. Material and Methods After full census of the study population, 651 participants were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites (microscopy and PCR) and antibodies against P. vivax (PvMSP119, PvAMA1) and P. falciparum (PfGLURP, PfAMA1) antigens by ELISA. Risk factors for malaria infection (positive PCR) and malaria exposure (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific seroprevalence was analyzed using a reversible catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR, λ). SaTScan was used to detect spatial clusters of serology-positive individuals within each site. Results The overall parasite prevalence by PCR was low, i.e. 3.9% for P. vivax and 6.7% for P. falciparum, while the seroprevalence was substantially higher, 33.6% for P. vivax and 22.0% for P. falciparum, with major differences between study sites. Age and location (site) were significantly associated with P. vivax exposure; while location, age and outdoor occupation were associated with P. falciparum exposure. P. falciparum seroprevalence curves showed a stable transmission throughout time, while for P. vivax transmission was better described by a model with two SCRs. The spatial analysis identified well-defined clusters of P. falciparum seropositive individuals in two sites, while it detected only a very small cluster of P. vivax exposure. Conclusion The use of a single parasitological and serological malaria survey has proven to be an efficient

  15. Relationship between altitude and intensity of malaria transmission in the Usambara Mountains, Tanzania.

    PubMed

    Bødker, R; Akida, J; Shayo, D; Kisinza, W; Msangeni, H A; Pedersen, E M; Lindsay, S W

    2003-09-01

    There is a consensus that malaria is a growing problem in African highlands. This is surprising because many parts of the highlands were considered too cold to support transmission. In this report, we examined how transmission of Plasmodium falciparum in six villages changed along an altitude transect in the Usambara Mountains, Tanzania, from 300 m to 1700 m. Routine entomological collections were made using spray catches and light traps for 15 mo. Direct estimates of entomological inoculation rates and indirect estimates of vectorial capacity suggested a >1000-fold reduction in transmission intensity between the holoendemic lowland and the hypoendemic highland plateau. Lowland transmission was perennial with a significant peak in the cool season after the long rains in May, when vectors densities were high. In the highlands, low temperatures prevented parasite development in mosquitoes during the cool season rains, and highland transmission was therefore limited to the warm dry season when vector densities were low. The primary effect of increasing altitude was a log-linear reduction in vector abundance and, to a lesser extent, a reduction in the proportion of infective mosquitoes. Highland malaria transmission was maintained at extraordinarily low vector densities. We discuss herein the implications of these findings for modeling malaria and suggest that process-based models of malaria transmission risk should be improved by considering the direct effect of temperature on vector densities. Our findings suggest that variation in the short rains in November and changes in agricultural practices are likely to be important generators of epidemics in the Usambaras. PMID:14596287

  16. Remote Sensing-Driven Climatic/Environmental Variables for Modelling Malaria Transmission in Sub-Saharan Africa.

    PubMed

    Ebhuoma, Osadolor; Gebreslasie, Michael

    2016-01-01

    Malaria is a serious public health threat in Sub-Saharan Africa (SSA), and its transmission risk varies geographically. Modelling its geographic characteristics is essential for identifying the spatial and temporal risk of malaria transmission. Remote sensing (RS) has been serving as an important tool in providing and assessing a variety of potential climatic/environmental malaria transmission variables in diverse areas. This review focuses on the utilization of RS-driven climatic/environmental variables in determining malaria transmission in SSA. A systematic search on Google Scholar and the Institute for Scientific Information (ISI) Web of Knowledge(SM) databases (PubMed, Web of Science and ScienceDirect) was carried out. We identified thirty-five peer-reviewed articles that studied the relationship between remotely-sensed climatic variable(s) and malaria epidemiological data in the SSA sub-regions. The relationship between malaria disease and different climatic/environmental proxies was examined using different statistical methods. Across the SSA sub-region, the normalized difference vegetation index (NDVI) derived from either the National Oceanic and Atmospheric Administration (NOAA) Advanced Very High Resolution Radiometer (AVHRR) or Moderate-resolution Imaging Spectrometer (MODIS) satellite sensors was most frequently returned as a statistically-significant variable to model both spatial and temporal malaria transmission. Furthermore, generalized linear models (linear regression, logistic regression and Poisson regression) were the most frequently-employed methods of statistical analysis in determining malaria transmission predictors in East, Southern and West Africa. By contrast, multivariate analysis was used in Central Africa. We stress that the utilization of RS in determining reliable malaria transmission predictors and climatic/environmental monitoring variables would require a tailored approach that will have cognizance of the geographical

  17. Remote Sensing-Driven Climatic/Environmental Variables for Modelling Malaria Transmission in Sub-Saharan Africa

    PubMed Central

    Ebhuoma, Osadolor; Gebreslasie, Michael

    2016-01-01

    Malaria is a serious public health threat in Sub-Saharan Africa (SSA), and its transmission risk varies geographically. Modelling its geographic characteristics is essential for identifying the spatial and temporal risk of malaria transmission. Remote sensing (RS) has been serving as an important tool in providing and assessing a variety of potential climatic/environmental malaria transmission variables in diverse areas. This review focuses on the utilization of RS-driven climatic/environmental variables in determining malaria transmission in SSA. A systematic search on Google Scholar and the Institute for Scientific Information (ISI) Web of KnowledgeSM databases (PubMed, Web of Science and ScienceDirect) was carried out. We identified thirty-five peer-reviewed articles that studied the relationship between remotely-sensed climatic variable(s) and malaria epidemiological data in the SSA sub-regions. The relationship between malaria disease and different climatic/environmental proxies was examined using different statistical methods. Across the SSA sub-region, the normalized difference vegetation index (NDVI) derived from either the National Oceanic and Atmospheric Administration (NOAA) Advanced Very High Resolution Radiometer (AVHRR) or Moderate-resolution Imaging Spectrometer (MODIS) satellite sensors was most frequently returned as a statistically-significant variable to model both spatial and temporal malaria transmission. Furthermore, generalized linear models (linear regression, logistic regression and Poisson regression) were the most frequently-employed methods of statistical analysis in determining malaria transmission predictors in East, Southern and West Africa. By contrast, multivariate analysis was used in Central Africa. We stress that the utilization of RS in determining reliable malaria transmission predictors and climatic/environmental monitoring variables would require a tailored approach that will have cognizance of the geographical

  18. Delayed mortality effects cut the malaria transmission potential of insecticide-resistant mosquitoes.

    PubMed

    Viana, Mafalda; Hughes, Angela; Matthiopoulos, Jason; Ranson, Hilary; Ferguson, Heather M

    2016-08-01

    Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60-100% and 3-61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide-resistant vectors by two-thirds, with delayed effects accounting for at least one-half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance. PMID:27402740

  19. Relationship between malaria and filariasis transmission indices in an endemic area along the Kenyan Coast

    PubMed Central

    Muturi, Ephantus J.; Mbogo, Charles M.; Ng'ang'a, Zipporah W.; Kabiru, Ephantus W.; Mwandawiro, Charles; Novak, Robert J.; Beier, John C.

    2009-01-01

    Background & objectives: An entomological survey was conducted to determine the relationship between malaria and lymphatic filariasis transmission by Anopheles gambiae s.l. and An. funestus in two inland villages along the Kenyan coast. Methods: Mosquitoes were sampled inside houses by pyrethrum spray sheet collection (PSC). In the laboratory, the mosquitoes were sorted to species, dissected for examination of filarial infection and the anophelines later tested for Plasmodium falciparum circumsporozoite proteins by an enzyme-linked immunosorbent assay (ELISA). Results: From a total of 2,032 female mosquitoes collected indoors, An. gambiae s.l constituted 94.4% while the remaining 5.6% comprised of An. funestus and Culex quinquefasciatus. None of the Cx. quinquefasciatus was positive for filarial worms. P. falciparum sporozoite rate for An. gambiae s.l. from both villages was significantly higher than Wuchereria bancrofti infectivity rate. Similarly, the entomological inoculation rate for An. gambiae s.l. was significantly higher than the corresponding W. bancrofti infective biting rate and transmission potential for both the villages. Mass treatment of people with filaricidal drugs in Shakahola in the ongoing global elimination of lymphatic filariasis campaign seemed to have reduced the indices of filariasis transmission but had no effect on malaria transmission. Interpretation & conclusion: These results indicate the intensity of malaria transmission by anophelines to be much higher than that of lymphatic filariasis in areas where both diseases co-exist and re-emphasise the need to integrate the control of the two diseases in such areas. PMID:16967820

  20. Dynamics of Forest Malaria Transmission in Balaghat District, Madhya Pradesh, India

    PubMed Central

    Singh, Neeru; Chand, Sunil K.; Bharti, Praveen K.; Singh, Mrigendra P.; Chand, Gyan; Mishra, Ashok K.; Shukla, Man M.; Mahulia, Man M.; Sharma, Ravendra K.

    2013-01-01

    Background An epidemiological and entomological study was carried out in Balaghat district, Madhya Pradesh, India to understand the dynamics of forest malaria transmission in a difficult and hard to reach area where indoor residual spray and insecticide treated nets were used for vector control. Methods This community based cross-sectional study was undertaken from January 2010 to December 2012 in Baihar and Birsa Community Health Centres of district Balaghat for screening malaria cases. Entomological surveillance included indoor resting collections, pyrethrum spray catches and light trap catches. Anophelines were assayed by ELISA for detection of Plasmodium circumsporozoite protein. Findings Plasmodium falciparum infection accounted for >80% of all infections. P. vivax 16.5%, P. malariae 0.75% and remaining were mixed infections of P. falciparum, P. vivax and P. malariae. More than, 30% infections were found in infants under 6 months of age. Overall, an increasing trend in malaria positivity was observed from 2010 to 2012 (chi-square for trend  =  663.55; P<0.0001). Twenty five Anopheles culicifacies (sibling species C, D and E) were positive for circumsporozoite protein of P. falciparum (44%) and P. vivax (56%). Additionally, 2 An. fluviatilis, were found positive for P. falciparum and 1 for P. vivax (sibling species S and T). An. fluviatilis sibling species T was found as vector in forest villages for the first time in India. Conclusion These results showed that the study villages are experiencing almost perennial malaria transmission inspite of indoor residual spray and insecticide treated nets. Therefore, there is a need for new indoor residual insecticides which has longer residual life or complete coverage of population with long lasting insecticide treated nets or both indoor residual spray and long lasting bed nets for effective vector control. There is a need to undertake a well designed case control study to evaluate the efficacy of these

  1. Vector bionomics and malaria transmission in the Upper Orinoco River, Southern Venezuela.

    PubMed

    Magris, Magda; Rubio-Palis, Yasmin; Menares, Cristóbal; Villegas, Leopoldo

    2007-06-01

    A longitudinal epidemiological and entomological study was carried out in Ocamo, Upper Orinoco River, between January 1994 and February 1995 to understand the dynamics of malaria transmission in this area. Malaria transmission occurs throughout the year with a peak in June at the beginning of the rainy season. The Annual Parasite Index was 1,279 per 1,000 populations at risk. Plasmodium falciparum infections accounted for 64% of all infections, P. vivax for 28%, and P. malariae for 4%. Mixed P. falciparum/P. vivax infections were diagnosed in 15 people representing 4% of total cases. Children under 10 years accounted for 58% of the cases; the risk for malaria in this age group was 77% higher than for those in the greater than 50 years age group. Anopheles darlingi was the predominant anopheline species landing on humans indoors with a biting peak between midnight and dawn. A significant positive correlation was found between malaria monthly incidence and mean number of An. darlingi caught. There was not a significant relationship between mean number of An. darlingi and rainfall or between incidence and rainfall. A total of 7295 anophelines were assayed by ELISA for detection of Plasmodium circumsporozoite (CS) protein. Only An. darlingi (55) was positive for CS proteins of P. falciparum (0.42%), P. malariae (0.25%), and P. vivax-247 (0.1%). The overall estimated entomological inoculation rate was 129 positive bites/person/year. The present study was the first longitudinal entomological and epidemiological study conducted in this area and set up the basic ground for subsequent intervention with insecticide-treated nets. PMID:17568935

  2. Daily Rhythms in Mosquitoes and Their Consequences for Malaria Transmission.

    PubMed

    Rund, Samuel S C; O'Donnell, Aidan J; Gentile, James E; Reece, Sarah E

    2016-01-01

    The 24-h day involves cycles in environmental factors that impact organismal fitness. This is thought to select for organisms to regulate their temporal biology accordingly, through circadian and diel rhythms. In addition to rhythms in abiotic factors (such as light and temperature), biotic factors, including ecological interactions, also follow daily cycles. How daily rhythms shape, and are shaped by, interactions between organisms is poorly understood. Here, we review an emerging area, namely the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the parasites they transmit. We focus on mosquitoes, malaria parasites and vertebrate hosts, because this system offers the opportunity to integrate from genetic and molecular mechanisms to population dynamics and because disrupting rhythms offers a novel avenue for disease control. PMID:27089370

  3. Daily Rhythms in Mosquitoes and Their Consequences for Malaria Transmission

    PubMed Central

    Rund, Samuel S. C.; O’Donnell, Aidan J.; Gentile, James E.; Reece, Sarah E.

    2016-01-01

    The 24-h day involves cycles in environmental factors that impact organismal fitness. This is thought to select for organisms to regulate their temporal biology accordingly, through circadian and diel rhythms. In addition to rhythms in abiotic factors (such as light and temperature), biotic factors, including ecological interactions, also follow daily cycles. How daily rhythms shape, and are shaped by, interactions between organisms is poorly understood. Here, we review an emerging area, namely the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the parasites they transmit. We focus on mosquitoes, malaria parasites and vertebrate hosts, because this system offers the opportunity to integrate from genetic and molecular mechanisms to population dynamics and because disrupting rhythms offers a novel avenue for disease control. PMID:27089370

  4. Epidemiology of malaria in an area of seasonal transmission in Niger and implications for the design of a seasonal malaria chemoprevention strategy

    PubMed Central

    2013-01-01

    Background Few data are available about malaria epidemiological situation in Niger. However, implementation of new strategies such as vaccination or seasonal treatment of a target population requires the knowledge of baseline epidemiological features of malaria. A population-based study was conducted to provide better characterization of malaria seasonal variations and population groups the most at risk in this particular area. Methods From July 2007 to December 2009, presumptive cases of malaria among a study population living in a typical Sahelian village of Niger were recorded, and confirmed by microscopic examination. In parallel, asymptomatic carriers were actively detected at the end of each dry season in 2007, 2008 and 2009. Results Among the 965 presumptive malaria cases recorded, 29% were confirmed by microscopic examination. The incidence of malaria was found to decrease significantly with age (p < 0.01). The mean annual incidence was 0.254. The results show that the risk of malaria was higher in children under ten years (p < 0.0001). The number of malaria episodes generally followed the temporal pattern of changes in precipitation levels, with a peak of transmission in August and September. One-thousand and ninety subjects were submitted to an active detection of asymptomatic carriage of whom 16% tested positive; asymptomatic carriage decreased with increasing age. A higher prevalence of gametocyte carriage among asymptomatic population was recorded in children aged two to ten years, though it did not reach significance. Conclusions In Southern Niger, malaria transmission mostly occurs from July to October. Children aged two to ten years are the most at risk of malaria, and may also represent the main reservoir for gametocytes. Strategies such as intermittent preventive treatment in children (IPTc) could be of interest in this area, where malaria transmission is highly seasonal. Based on these preliminary data, a pilot study could be implemented

  5. A vectorial capacity product to monitor changing malaria transmission potential in epidemic regions of Africa

    USGS Publications Warehouse

    Ceccato, Pietro; Vancutsem, Christelle; Klaver, Robert; Rowland, James; Connor, Stephen J.

    2012-01-01

    Rainfall and temperature are two of the major factors triggering malaria epidemics in warm semi-arid (desert-fringe) and high altitude (highland-fringe) epidemic risk areas. The ability of the mosquitoes to transmit Plasmodium spp. is dependent upon a series of biological features generally referred to as vectorial capacity. In this study, the vectorial capacity model (VCAP) was expanded to include the influence of rainfall and temperature variables on malaria transmission potential. Data from two remote sensing products were used to monitor rainfall and temperature and were integrated into the VCAP model. The expanded model was tested in Eritrea and Madagascar to check the viability of the approach. The analysis of VCAP in relation to rainfall, temperature and malaria incidence data in these regions shows that the expanded VCAP correctly tracks the risk of malaria both in regions where rainfall is the limiting factor and in regions where temperature is the limiting factor. The VCAP maps are currently offered as an experimental resource for testing within Malaria Early Warning applications in epidemic prone regions of sub-Saharan Africa. User feedback is currently being collected in preparation for further evaluation and refinement of the VCAP model.

  6. Identification of three ookinete-specific genes and evaluation of their transmission-blocking potentials in Plasmodium berghei.

    PubMed

    Zheng, Wenqi; Kou, Xu; Du, Yunting; Liu, Fei; Yu, Chunyun; Tsuboi, Takafumi; Fan, Qi; Luo, Enjie; Cao, Yaming; Cui, Liwang

    2016-05-17

    With a renewed hope for malaria elimination, interventions that prevent transmission of parasites from humans to mosquitoes have received elevated attention. Transmission-blocking vaccines (TBVs) targeting the sexual stages are well suited for this task. Here, through bioinformatic analysis, we selected two putative Plasmodium berghei ookinete-stage proteins (PBANKA_111920, and PBANKA_145770) and a previously characterized ookinete protein PBANKA_135340 (PSOP7) for evaluation of their transmission-blocking potentials. Fragments of these predicted proteins were expressed in bacteria and purified recombinant proteins were used to immunize mice. Antisera against these recombinant proteins recognized proteins of predicted sizes from ookinete lysates and localized their expression on the surface of ookinetes. Inclusion of these antisera in in vitro ookinete culture significantly inhibited ookinete formation. Mosquitoes fed on mice immunized with the recombinant proteins also showed significantly reduced oocyst densities (60.0-70.7%) and modest reductions of oocyst prevalence (10.7-37.4%). These data, together with the conservation of these genes in Plasmodium, suggest that these three ookinete proteins could be new promising targets for TBVs and are worth of future investigations in the human malaria parasites. PMID:27083421

  7. Impact of land-use on malaria transmission in the Plateau region, southeastern Benin

    PubMed Central

    2013-01-01

    Background The goal of the study is to investigate if local agricultural practices have an impact on malaria transmission in four villages located in the same geographical area within a radius of 15 kilometers. Among the villages, one (Itassoumba) is characterized by the presence of a large market garden and fishpond basins, the three others (Itakpako, Djohounkollé and Ko-koumolou) are characterized by traditional food-producing agriculture. Methods Malaria transmission was evaluated using human-landing catches, both indoors and outdoors, two nights per month for 12 months. Field collected females An. gambiae s.l. were exposed for 1 hour to 0.75% permethrin and 0.05% deltamethrin using WHO insecticide susceptibility test kits and procedures. The presence of the kdr mutation was analyzed by PCR. Results Anopheles gambiae s.s form M (93.65%), was identified as the main malaria vector. Its susceptibility level to pyrethroids was the same (p > 0.05) in all villages. kdr mutation frequencies are 81.08 in Itakpako, 85 in Itassoumba, 79.73 in Djohounkollé and 86.84 in Ko-Koumolou (p = 0.63). The entomological inoculation rate ranged from 9.62 to 21.65 infected bites of An. gambiae per human per year in Djohounkollé, Itakpako and Ko-Koumolou against 1159.62 in Itassoumba (p < 0.0001). Conclusion The level of resistance of An. gambiae to pyrethroids was the same in the four villages. The heterogeneous character of malaria epidemiology was confirmed. The creation of fishponds basins and the development of market-gardening activities increased drastically the malaria transmission in Itassoumba. PMID:24330734

  8. Simulating the spread of malaria using a generic transmission model for mosquito-borne infectious diseases

    NASA Astrophysics Data System (ADS)

    Kon, Cynthia Mui Lian; Labadin, Jane

    2016-06-01

    Malaria is a critical infection caused by parasites which are spread to humans through mosquito bites. Approximately half of the world's population is in peril of getting infected by malaria. Mosquito-borne diseases have a standard behavior where they are transmitted in the same manner, only through vector mosquito. Taking this into account, a generic spatial-temporal model for transmission of multiple mosquito-borne diseases had been formulated. Our interest is to reproduce the actual cases of different mosquito-borne diseases using the generic model and then predict future cases so as to improve control and target measures competently. In this paper, we utilize notified weekly malaria cases in four districts in Sarawak, Malaysia, namely Kapit, Song, Belaga and Marudi. The actual cases for 36 weeks, which is from week 39 in 2012 to week 22 in 2013, are compared with simulations of the generic spatial-temporal transmission mosquito-borne diseases model. We observe that the simulation results display corresponding result to the actual malaria cases in the four districts.

  9. A realistic host-vector transmission model for describing malaria prevalence pattern.

    PubMed

    Mandal, Sandip; Sinha, Somdatta; Sarkar, Ram Rup

    2013-12-01

    Malaria continues to be a major public health concern all over the world even after effective control policies have been employed, and considerable understanding of the disease biology have been attained, from both the experimental and modelling perspective. Interactions between different general and local processes, such as dependence on age and immunity of the human host, variations of temperature and rainfall in tropical and sub-tropical areas, and continued presence of asymptomatic infections, regulate the host-vector interactions, and are responsible for the continuing disease prevalence pattern.In this paper, a general mathematical model of malaria transmission is developed considering short and long-term age-dependent immunity of human host and its interaction with pathogen-infected mosquito vector. The model is studied analytically and numerically to understand the role of different parameters related to mosquitoes and humans. To validate the model with a disease prevalence pattern in a particular region, real epidemiological data from the north-eastern part of India was used, and the effect of seasonal variation in mosquito density was modelled based on local climactic data. The model developed based on general features of host-vector interactions, and modified simply incorporating local environmental factors with minimal changes, can successfully explain the disease transmission process in the region. This provides a general approach toward modelling malaria that can be adapted to control future outbreaks of malaria. PMID:24122398

  10. Modelling entomological-climatic interactions of Plasmodium falciparum malaria transmission in two Colombian endemic-regions: contributions to a National Malaria Early Warning System

    PubMed Central

    Ruiz, Daniel; Poveda, Germán; Vélez, Iván D; Quiñones, Martha L; Rúa, Guillermo L; Velásquez, Luz E; Zuluaga, Juan S

    2006-01-01

    Background Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model. Methods The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process. Results Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897–0.668 (P > 0.95) and 0.0002–0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission. Conclusion The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System. PMID:16882349

  11. School-based surveys of malaria in Oromia Regional State, Ethiopia: a rapid survey method for malaria in low transmission settings

    PubMed Central

    2011-01-01

    Background In Ethiopia, malaria transmission is seasonal and unstable, with both Plasmodium falciparum and Plasmodium vivax endemic. Such spatial and temporal clustering of malaria only serves to underscore the importance of regularly collecting up-to-date malaria surveillance data to inform decision-making in malaria control. Cross-sectional school-based malaria surveys were conducted across Oromia Regional State to generate up-to-date data for planning malaria control interventions, as well as monitoring and evaluation of operational programme implementation. Methods Two hundred primary schools were randomly selected using a stratified and weighted sampling frame; 100 children aged five to 18 years were then randomly chosen within each school. Surveys were carried out in May 2009 and from October to December 2009, to coincide with the peak of malaria transmission in different parts of Oromia. Each child was tested for malaria by expert microscopy, their haemoglobin measured and a simple questionnaire completed. Satellite-derived environmental data were used to assess ecological correlates of Plasmodium infection; Bayesian geostatistical methods and Kulldorff's spatial scan statistic were employed to investigate spatial heterogeneity. Results A total 20,899 children from 197 schools provided blood samples, two selected schools were inaccessible and one school refused to participate. The overall prevalence of Plasmodium infection was found to be 0.56% (95% CI: 0.46-0.67%), with 53% of infections due to P. falciparum and 47% due to P. vivax. Of children surveyed, 17.6% (95% CI: 17.0-18.1%) were anaemic, while 46% reported sleeping under a mosquito net the previous night. Malaria was found at 30 (15%) schools to a maximum elevation of 2,187 metres, with school-level Plasmodium prevalence ranging between 0% and 14.5%. Although environmental variables were only weakly associated with P. falciparum and P. vivax infection, clusters of infection were identified within

  12. Needs for monitoring mosquito transmission of malaria in a pre-elimination world.

    PubMed

    James, Stephanie; Takken, Willem; Collins, Frank H; Gottlieb, Michael

    2014-01-01

    As global efforts to eliminate malaria intensify, accurate information on vector populations and transmission dynamics is critical for directing control efforts, developing new control tools, and predicting the effects of these interventions under various conditions. Currently available sampling tools for mosquito population monitoring suffer from well-recognized limitations. As reported in this workshop summary, a recent gathering of medical entomologists, modelers, and malaria experts reviewed these issues and agreed that efforts are needed to improve methods to monitor key transmission parameters. Identified needs include standardized methods for sampling of both mosquito adults and larvae, improved tools for mosquito species identification and age-grading, and a better means for determining the entomological inoculation rate. PMID:24277786

  13. Malaria transmission and naturally acquired immunity to PfEMP-1.

    PubMed

    Piper, K P; Hayward, R E; Cox, M J; Day, K P

    1999-12-01

    Why there are so few gametocytes (the transmission stage of malaria) in the blood of humans infected with Plasmodium spp. is intriguing. This may be due either to reproductive restraint by the parasite or to unidentified gametocyte-specific immune-mediated clearance mechanisms. We propose another mechanism, a cross-stage immunity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1). This molecule is expressed on the surface of the erythrocyte infected with either trophozoite or early gametocyte parasites. Immunoglobulin G antibodies to PfEMP-1, expressed on both life cycle stages, were measured in residents from an area where malaria is endemic, Papua New Guinea. Anti-PfEMP-1 prevalence increased with age, mirroring the decline in both the prevalence and the density of asexual and transmission stages in erythrocytes. These data led us to propose that immunity to PfEMP-1 may influence malaria transmission by regulation of the production of gametocytes. This regulation may be achieved in two ways: (i) by controlling asexual proliferation and density and (ii) by affecting gametocyte maturation. PMID:10569752

  14. A malaria transmission-directed model of mosquito life cycle and ecology

    PubMed Central

    2011-01-01

    Background Malaria is a major public health issue in much of the world, and the mosquito vectors which drive transmission are key targets for interventions. Mathematical models for planning malaria eradication benefit from detailed representations of local mosquito populations, their natural dynamics and their response to campaign pressures. Methods A new model is presented for mosquito population dynamics, effects of weather, and impacts of multiple simultaneous interventions. This model is then embedded in a large-scale individual-based simulation and results for local elimination of malaria are discussed. Mosquito population behaviours, such as anthropophily and indoor feeding, are included to study their effect upon the efficacy of vector control-based elimination campaigns. Results Results for vector control tools, such as bed nets, indoor spraying, larval control and space spraying, both alone and in combination, are displayed for a single-location simulation with vector species and seasonality characteristic of central Tanzania, varying baseline transmission intensity and vector bionomics. The sensitivities to habitat type, anthropophily, indoor feeding, and baseline transmission intensity are explored. Conclusions The ability to model a spectrum of local vector species with different ecologies and behaviours allows local customization of packages of interventions and exploration of the effect of proposed new tools. PMID:21999664

  15. The concept of specificity and the Italian contribution to the discovery of the malaria transmission cycle.

    PubMed

    Fantini, B

    1999-09-01

    At the dawn of the 20th century, the change in the scientific, political and cultural attitudes towards malaria was the result of the discovery of the theoretical simplicity of the malaria transmission cycle and of the possibility to interrupt it, by avoiding the contacts between people and mosquitoes. The 'mosquito hypothesis', suggested already in the 1880s, had to be included into a coherent scientific theory, in which a fundamental part was played by the concept of specificity. The paper analyses the Italian contribution to this scientific change and the epistemological aspects of the debate between Ronald Ross and Battista Grassi about their respective role in the discovery of the human malaria transmission cycle. This debate has been often interpreted in sociological or psychological terms. However, behind the dispute there is a different definition of what is a scientific explanation in biological sciences and in particular in parasitology. This point is made clear by the analysis of four different theoretical problems implied in the discovery of the transmission cycle: the concept of specificity, the comparative method in parasitology, the specificity of the life-cycle of parasites and vectors, and the role of the analogical reasoning in science and medicine. PMID:10697832

  16. Attributing Climate Conditions for Stable Malaria Transmission to Human Activity in sub-Saharan Africa

    NASA Astrophysics Data System (ADS)

    Sheldrake, L.; Mitchell, D.; Allen, M. R.

    2015-12-01

    Temperature and precipitation limit areas of stable malaria transmission, but the effects of climate change on the disease remain controversial. Previously, studies have not separated the influence of anthropogenic climate change and natural variability, despite being an essential step in the attribution of climate change impacts. Ensembles of 2900 simulations of regional climate in sub-Saharan Africa for the year 2013, one representing realistic conditions and the other how climate might have been in the absence of human influence, were used to force a P.falciparium climate suitability model developed by the Mapping Malaria Risk in Africa project. Strongest signals were detected in areas of unstable transmission, indicating their heightened sensitivity to climatic factors. Evidently, impacts of human-induced climate change were unevenly distributed: the probability of conditions being suitable for stable malaria transmission were substantially reduced (increased) in the Sahel (Greater Horn of Africa (GHOA), particularly in the Ethiopian and Kenyan highlands). The length of the transmission season was correspondingly shortened in the Sahel and extended in the GHOA, by 1 to 2 months, including in Kericho (Kenya), where the role of climate change in driving recent malaria occurrence is hotly contested. Human-induced warming was primarily responsible for positive anomalies in the GHOA, while reduced rainfall caused negative anomalies in the Sahel. The latter was associated with anthropogenic impacts on the West African Monsoon, but uncertainty in the RCM's ability to reproduce precipitation trends in the region weakens confidence in the result. That said, outputs correspond well with broad-scale changes in observed endemicity, implying a potentially important contribution of anthropogenic climate change to the malaria burden during the past century. Results support the health-framing of climate risk and help indicate hotspots of climate vulnerability, providing

  17. Spatial and temporal dynamics of malaria transmission in rural Western Kenya

    PubMed Central

    2012-01-01

    Background Understanding the relationship between Plasmodium falciparum malaria transmission and health outcomes requires accurate estimates of exposure to infectious mosquitoes. However, measures of exposure such as mosquito density and entomological inoculation rate (EIR) are generally aggregated over large areas and time periods, biasing the outcome-exposure relationship. There are few studies examining the extent and drivers of local variation in malaria exposure in endemic areas. Methods We describe the spatio-temporal dynamics of malaria transmission intensity measured by mosquito density and EIR in the KEMRI/CDC health and demographic surveillance system using entomological data collected during 2002–2004. Geostatistical zero inflated binomial and negative binomial models were applied to obtain location specific (house) estimates of sporozoite rates and mosquito densities respectively. Model-based predictions were multiplied to estimate the spatial pattern of annual entomological inoculation rate, a measure of the number of infective bites a person receive per unit of time. The models included environmental and climatic predictors extracted from satellite data, harmonic seasonal trends and parameters describing space-time correlation. Results Anopheles gambiae s.l was the main vector species accounting for 86 % (n = 2309) of the total mosquitoes collected with the remainder being Anopheles funestus. Sixty eight percent (757/1110) of the surveyed houses had no mosquitoes. Distance to water bodies, vegetation and day temperature were strongly associated with mosquito density. Overall annual point estimates of EIR were 6.7, 9.3 and 9.6 infectious bites per annum for 2002, 2003 and 2004 respectively. Monthly mosquito density and EIR varied over the study period peaking in May during the wet season each year. The predicted and observed densities of mosquitoes and EIR showed a strong seasonal and spatial pattern over the study area. Conclusions Spatio

  18. Malaria

    MedlinePlus

    ... a parasite. You get it when an infected mosquito bites you. Malaria is a major cause of ... insect repellent with DEET Cover up Sleep under mosquito netting Centers for Disease Control and Prevention

  19. Malaria

    MedlinePlus

    ... Malaria can be carried by mosquitoes in temperate climates, but the parasite disappears over the winter. The ... a major disease hazard for travelers to warm climates. In some areas of the world, mosquitoes that ...

  20. Malaria.

    PubMed

    White, Nicholas J; Pukrittayakamee, Sasithon; Hien, Tran Tinh; Faiz, M Abul; Mokuolu, Olugbenga A; Dondorp, Arjen M

    2014-02-22

    Although global morbidity and mortality have decreased substantially, malaria, a parasite infection of red blood cells, still kills roughly 2000 people per day, most of whom are children in Africa. Two factors largely account for these decreases; increased deployment of insecticide-treated bednets and increased availability of highly effective artemisinin combination treatments. In large trials, parenteral artesunate (an artemisinin derivative) reduced severe malaria mortality by 22·5% in Africa and 34·7% in Asia compared with quinine, whereas adjunctive interventions have been uniformly unsuccessful. Rapid tests have been an important addition to microscopy for malaria diagnosis. Chemopreventive strategies have been increasingly deployed in Africa, notably intermittent sulfadoxine-pyrimethamine treatment in pregnancy, and monthly amodiaquine-sulfadoxine-pyrimethamine during the rainy season months in children aged between 3 months and 5 years across the sub-Sahel. Enthusiasm for malaria elimination has resurfaced. This ambitious but laudable goal faces many challenges, including the worldwide economic downturn, difficulties in elimination of vivax malaria, development of pyrethroid resistance in some anopheline mosquitoes, and the emergence of artemisinin resistance in Plasmodium falciparum in southeast Asia. We review the epidemiology, clinical features, pathology, prevention, and treatment of malaria. PMID:23953767

  1. A mechanistic approach for accurate simulation of village scale malaria transmission

    PubMed Central

    Bomblies, Arne; Duchemin, Jean-Bernard; Eltahir, Elfatih AB

    2009-01-01

    Background Malaria transmission models commonly incorporate spatial environmental and climate variability for making regional predictions of disease risk. However, a mismatch of these models' typical spatial resolutions and the characteristic scale of malaria vector population dynamics may confound disease risk predictions in areas of high spatial hydrological variability such as the Sahel region of Africa. Methods Field observations spanning two years from two Niger villages are compared. The two villages are separated by only 30 km but exhibit a ten-fold difference in anopheles mosquito density. These two villages would be covered by a single grid cell in many malaria models, yet their entomological activity differs greatly. Environmental conditions and associated entomological activity are simulated at high spatial- and temporal resolution using a mechanistic approach that couples a distributed hydrology scheme and an entomological model. Model results are compared to regular field observations of Anopheles gambiae sensu lato mosquito populations and local hydrology. The model resolves the formation and persistence of individual pools that facilitate mosquito breeding and predicts spatio-temporal mosquito population variability at high resolution using an agent-based modeling approach. Results Observations of soil moisture, pool size, and pool persistence are reproduced by the model. The resulting breeding of mosquitoes in the simulated pools yields time-integrated seasonal mosquito population dynamics that closely follow observations from captured mosquito abundance. Interannual difference in mosquito abundance is simulated, and the inter-village difference in mosquito population is reproduced for two years of observations. These modeling results emulate the known focal nature of malaria in Niger Sahel villages. Conclusion Hydrological variability must be represented at high spatial and temporal resolution to achieve accurate predictive ability of malaria risk

  2. Assessment of Risk Factors Associated with Malaria Transmission in Tubu Village, Northern Botswana

    PubMed Central

    Chirebvu, Elijah; Chimbari, Moses John; Ngwenya, Barbara Ntombi

    2014-01-01

    This study investigated potential risk factors associated with malaria transmission in Tubu village, Okavango subdistrict, a malaria endemic area in northern Botswana. Data was derived from a census questionnaire survey, participatory rural appraisal workshop, field observations, and mosquito surveys. History of malaria episodes was associated with several factors: household income (P < 0.05), late outdoor activities (OR = 7.016; CI = 1.786–27.559), time spent outdoors (P = 0.051), travel outside study area (OR = 2.70; CI = 1.004–7.260), nonpossession of insecticide treated nets (OR = 0.892; CI = 0.797–0.998), hut/house structure (OR = 11.781; CI = 3.868–35.885), and homestead location from water bodies (P < 0.05). No associations were established between history of malaria episodes and the following factors: being a farmer (P > 0.05) and number of nets possessed (P > 0.05). Eave size was not associated with mosquito bites (P > 0.05), frequency of mosquito bites (P > 0.05), and time of mosquito bites (P > 0.05). Possession of nets was very high (94.7%). Close proximity of a health facility and low vegetation cover were added advantages. Some of the identified risk factors are important for developing effective control and elimination strategies involving the community, with limited resources. PMID:24757573

  3. Characterizing microclimate in urban malaria transmission settings: a case study from Chennai, India

    PubMed Central

    2013-01-01

    Background Environmental temperature is an important driver of malaria transmission dynamics. Both the parasite and vector are sensitive to mean ambient temperatures and daily temperature variation. To understand transmission ecology, therefore, it is important to determine the range of microclimatic temperatures experienced by malaria vectors in the field. Methods A pilot study was conducted in the Indian city of Chennai to determine the temperature variation in urban microclimates and characterize the thermal ecology of the local transmission setting. Temperatures were measured in a range of probable indoor and outdoor resting habitats of Anopheles stephensi in two urban slum malaria sites. Mean temperatures and daily temperature fluctuations in local transmission sites were compared with standard temperature measures from the local weather station. The biological implications of the different temperatures were explored using temperature-dependent parasite development models to provide estimates of the extrinsic incubation period (EIP) of Plasmodium vivax and Plasmodium falciparum. Results Mean daily temperatures within the urban transmission sites were generally warmer than those recorded at the local weather station. The main reason was that night-time temperatures were higher (and hence diurnal temperature ranges smaller) in the urban settings. Mean temperatures and temperature variation also differed between specific resting sites within the transmission environments. Most differences were of the order of 1-3°C but were sufficient to lead to important variation in predicted EIPs and hence, variation in estimates of transmission intensity. Conclusions Standard estimates of environmental temperature derived from local weather stations do not necessarily provide realistic measures of temperatures within actual transmission environments. Even the small differences in mean temperatures or diurnal temperature ranges reported in this study can lead to large

  4. Antimalarial Iron Chelator FBS0701 Blocks Transmission by Plasmodium falciparum Gametocyte Activation Inhibition

    PubMed Central

    Ferrer, Patricia; Vega-Rodriguez, Joel; Tripathi, Abhai K.; Jacobs-Lorena, Marcelo

    2014-01-01

    Reducing the transmission of the malarial parasite by Anopheles mosquitoes using drugs or vaccines remains a main focus in the efforts to control malaria. Iron chelators have been studied as potential antimalarial drugs due to their activities against different stages of the parasite. The iron chelator FBS0701 affects the development of Plasmodium falciparum early gametocytes and lowers blood-stage parasitemia. Here, we tested the effect of FBS0701 on stage V gametocyte infectivity for mosquitoes. The incubation of stage V gametocytes for up to 3 days with increasing concentrations of FBS0701 resulted in a significant dose-related reduction in mosquito infectivity, as measured by the numbers of oocysts per mosquito. The reduction in mosquito infectivity was due to the inhibition of male and female gametocyte activation. The preincubation of FBS0701 with ferric chloride restored gametocyte infectivity, showing that the inhibitory effect of FBS0701 was quenched by iron. Deferoxamine, another iron chelator, also reduced gametocyte infectivity but to a lesser extent. Finally, the simultaneous administration of drug and gametocytes to mosquitoes without previous incubation did not significantly reduce the numbers of oocysts. These results show the importance of gametocyte iron metabolism as a potential target for new transmission-blocking strategies. PMID:25512427

  5. Clinical Malaria Transmission Trends and Its Association with Climatic Variables in Tubu Village, Botswana: A Retrospective Analysis.

    PubMed

    Chirebvu, Elijah; Chimbari, Moses John; Ngwenya, Barbara Ntombi; Sartorius, Benn

    2016-01-01

    Good knowledge on the interactions between climatic variables and malaria can be very useful for predicting outbreaks and preparedness interventions. We investigated clinical malaria transmission patterns and its temporal relationship with climatic variables in Tubu village, Botswana. A 5-year retrospective time series data analysis was conducted to determine the transmission patterns of clinical malaria cases at Tubu Health Post and its relationship with rainfall, flood discharge, flood extent, mean minimum, maximum and average temperatures. Data was obtained from clinical records and respective institutions for the period July 2005 to June 2010, presented graphically and analysed using the Univariate ANOVA and Pearson cross-correlation coefficient tests. Peak malaria season occurred between October and May with the highest cumulative incidence of clinical malaria cases being recorded in February. Most of the cases were individuals aged >5 years. Associations between the incidence of clinical malaria cases and several factors were strong at lag periods of 1 month; rainfall (r = 0.417), mean minimum temperature (r = 0.537), mean average temperature (r = 0.493); and at lag period of 6 months for flood extent (r = 0.467) and zero month for flood discharge (r = 0.497). The effect of mean maximum temperature was strongest at 2-month lag period (r = 0.328). Although malaria transmission patterns varied from year to year the trends were similar to those observed in sub-Saharan Africa. Age group >5 years experienced the greatest burden of clinical malaria probably due to the effects of the national malaria elimination programme. Rainfall, flood discharge and extent, mean minimum and mean average temperatures showed some correlation with the incidence of clinical malaria cases. PMID:26983035

  6. Clinical Malaria Transmission Trends and Its Association with Climatic Variables in Tubu Village, Botswana: A Retrospective Analysis

    PubMed Central

    Chimbari, Moses John; Ngwenya, Barbara Ntombi; Sartorius, Benn

    2016-01-01

    Good knowledge on the interactions between climatic variables and malaria can be very useful for predicting outbreaks and preparedness interventions. We investigated clinical malaria transmission patterns and its temporal relationship with climatic variables in Tubu village, Botswana. A 5-year retrospective time series data analysis was conducted to determine the transmission patterns of clinical malaria cases at Tubu Health Post and its relationship with rainfall, flood discharge, flood extent, mean minimum, maximum and average temperatures. Data was obtained from clinical records and respective institutions for the period July 2005 to June 2010, presented graphically and analysed using the Univariate ANOVA and Pearson cross-correlation coefficient tests. Peak malaria season occurred between October and May with the highest cumulative incidence of clinical malaria cases being recorded in February. Most of the cases were individuals aged >5 years. Associations between the incidence of clinical malaria cases and several factors were strong at lag periods of 1 month; rainfall (r = 0.417), mean minimum temperature (r = 0.537), mean average temperature (r = 0.493); and at lag period of 6 months for flood extent (r = 0.467) and zero month for flood discharge (r = 0.497). The effect of mean maximum temperature was strongest at 2-month lag period (r = 0.328). Although malaria transmission patterns varied from year to year the trends were similar to those observed in sub-Saharan Africa. Age group >5 years experienced the greatest burden of clinical malaria probably due to the effects of the national malaria elimination programme. Rainfall, flood discharge and extent, mean minimum and mean average temperatures showed some correlation with the incidence of clinical malaria cases. PMID:26983035

  7. Remotely-sensed, nocturnal, dew point correlates with malaria transmission in Southern Province, Zambia: a time-series study

    PubMed Central

    2014-01-01

    Background Plasmodium falciparum transmission has decreased significantly in Zambia in the last decade. The malaria transmission is influenced by environmental variables. Incorporation of environmental variables in models of malaria transmission likely improves model fit and predicts probable trends in malaria disease. This work is based on the hypothesis that remotely-sensed environmental factors, including nocturnal dew point, are associated with malaria transmission and sustain foci of transmission during the low transmission season in the Southern Province of Zambia. Methods Thirty-eight rural health centres in Southern Province, Zambia were divided into three zones based on transmission patterns. Correlations between weekly malaria cases and remotely-sensed nocturnal dew point, nocturnal land surface temperature as well as vegetation indices and rainfall were evaluated in time-series analyses from 2012 week 19 to 2013 week 36. Zonal as well as clinic-based, multivariate, autoregressive, integrated, moving average (ARIMAX) models implementing environmental variables were developed to model transmission in 2011 week 19 to 2012 week 18 and forecast transmission in 2013 week 37 to week 41. Results During the dry, low transmission season significantly higher vegetation indices, nocturnal land surface temperature and nocturnal dew point were associated with the areas of higher transmission. Environmental variables improved ARIMAX models. Dew point and normalized differentiated vegetation index were significant predictors and improved all zonal transmission models. In the high-transmission zone, this was also seen for land surface temperature. Clinic models were improved by adding dew point and land surface temperature as well as normalized differentiated vegetation index. The mean average error of prediction for ARIMAX models ranged from 0.7 to 33.5%. Forecasts of malaria incidence were valid for three out of five rural health centres; however, with poor

  8. Application of Serological Tools and Spatial Analysis to Investigate Malaria Transmission Dynamics in Highland Areas of Southwest Uganda

    PubMed Central

    Lynch, Caroline A.; Cook, Jackie; Nanyunja, Sarah; Bruce, Jane; Bhasin, Amit; Drakeley, Chris; Roper, Cally; Pearce, Richard; Rwakimari, John B.; Abeku, Tarekegn A.; Corran, Patrick; Cox, Jonathan

    2016-01-01

    Serological markers, combined with spatial analysis, offer a comparatively more sensitive means by which to measure and detect foci of malaria transmission in highland areas than traditional malariometric indicators. Plasmodium falciparum parasite prevalence, seroprevalence, and seroconversion rate to P. falciparum merozoite surface protein-119 (MSP-119) were measured in a cross-sectional survey to determine differences in transmission between altitudinal strata. Clusters of P. falciparum parasite prevalence and high antibody responses to MSP-119 were detected and compared. Results show that P. falciparum prevalence and seroprevalence generally decreased with increasing altitude. However, transmission was heterogeneous with hotspots of prevalence and/or seroprevalence detected in both highland and highland fringe altitudes, including a serological hotspot at 2,200 m. Results demonstrate that seroprevalence can be used as an additional tool to identify hotspots of malaria transmission that might be difficult to detect using traditional cross-sectional parasite surveys or through vector studies. Our study findings identify ways in which malaria prevention and control can be more effectively targeted in highland or low transmission areas via serological measures. These tools will become increasingly important for countries with an elimination agenda and/or where malaria transmission is becoming patchy and focal, but receptivity to malaria transmission remains high. PMID:27022156

  9. Application of Serological Tools and Spatial Analysis to Investigate Malaria Transmission Dynamics in Highland Areas of Southwest Uganda.

    PubMed

    Lynch, Caroline A; Cook, Jackie; Nanyunja, Sarah; Bruce, Jane; Bhasin, Amit; Drakeley, Chris; Roper, Cally; Pearce, Richard; Rwakimari, John B; Abeku, Tarekegn A; Corran, Patrick; Cox, Jonathan

    2016-06-01

    Serological markers, combined with spatial analysis, offer a comparatively more sensitive means by which to measure and detect foci of malaria transmission in highland areas than traditional malariometric indicators. Plasmodium falciparum parasite prevalence, seroprevalence, and seroconversion rate to P. falciparum merozoite surface protein-119 (MSP-119) were measured in a cross-sectional survey to determine differences in transmission between altitudinal strata. Clusters of P. falciparum parasite prevalence and high antibody responses to MSP-119 were detected and compared. Results show that P. falciparum prevalence and seroprevalence generally decreased with increasing altitude. However, transmission was heterogeneous with hotspots of prevalence and/or seroprevalence detected in both highland and highland fringe altitudes, including a serological hotspot at 2,200 m. Results demonstrate that seroprevalence can be used as an additional tool to identify hotspots of malaria transmission that might be difficult to detect using traditional cross-sectional parasite surveys or through vector studies. Our study findings identify ways in which malaria prevention and control can be more effectively targeted in highland or low transmission areas via serological measures. These tools will become increasingly important for countries with an elimination agenda and/or where malaria transmission is becoming patchy and focal, but receptivity to malaria transmission remains high. PMID:27022156

  10. An overview of malaria transmission from the perspective of Amazon Anopheles vectors.

    PubMed

    Pimenta, Paulo F P; Orfano, Alessandra S; Bahia, Ana C; Duarte, Ana P M; Ríos-Velásquez, Claudia M; Melo, Fabrício F; Pessoa, Felipe A C; Oliveira, Giselle A; Campos, Keillen M M; Villegas, Luis Martínez; Rodrigues, Nilton Barnabé; Nacif-Pimenta, Rafael; Simões, Rejane C; Monteiro, Wuelton M; Amino, Rogerio; Traub-Cseko, Yara M; Lima, José B P; Barbosa, Maria G V; Lacerda, Marcus V G

    2015-02-01

    In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Anopheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence. PMID:25742262

  11. An overview of malaria transmission from the perspective of Amazon Anopheles vectors

    PubMed Central

    Pimenta, Paulo FP; Orfano, Alessandra S; Bahia, Ana C; Duarte, Ana PM; Ríos-Velásquez, Claudia M; Melo, Fabrício F; Pessoa, Felipe AC; Oliveira, Giselle A; Campos, Keillen MM; Villegas, Luis Martínez; Rodrigues, Nilton Barnabé; Nacif-Pimenta, Rafael; Simões, Rejane C; Monteiro, Wuelton M; Amino, Rogerio; Traub-Cseko, Yara M; Lima, José BP; Barbosa, Maria GV; Lacerda, Marcus VG; Tadei, Wanderli P; Secundino, Nágila FC

    2015-01-01

    In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence. PMID:25742262

  12. Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections.

    PubMed

    Nagaraj, Viswanathan A; Mukhi, Dhanunjay; Sathishkumar, Vinayagam; Subramani, Pradeep A; Ghosh, Susanta K; Pandey, Rajeev R; Shetty, Manjunatha C; Padmanaban, Govindarajan

    2015-01-01

    The proteins of Plasmodium, the malaria parasite, are strikingly rich in asparagine. Plasmodium depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway for amino acid biosynthesis, but retains a gene encoding asparagine synthetase (AS). Here we show that deletion of AS in Plasmodium berghei (Pb) delays the asexual- and liver-stage development with substantial reduction in the formation of ookinetes, oocysts and sporozoites in mosquitoes. In the absence of asparagine synthesis, extracellular asparagine supports suboptimal survival of PbAS knockout (KO) parasites. Depletion of blood asparagine levels by treating PbASKO-infected mice with asparaginase completely prevents the development of liver stages, exflagellation of male gametocytes and the subsequent formation of sexual stages. In vivo supplementation of asparagine in mice restores the exflagellation of PbASKO parasites. Thus, the parasite life cycle has an absolute requirement for asparagine, which we propose could be targeted to prevent malaria transmission and liver infections. PMID:26531182

  13. Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections

    PubMed Central

    Nagaraj, Viswanathan A.; Mukhi, Dhanunjay; Sathishkumar, Vinayagam; Subramani, Pradeep A.; Ghosh, Susanta K.; Pandey, Rajeev R.; Shetty, Manjunatha C.; Padmanaban, Govindarajan

    2015-01-01

    The proteins of Plasmodium, the malaria parasite, are strikingly rich in asparagine. Plasmodium depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway for amino acid biosynthesis, but retains a gene encoding asparagine synthetase (AS). Here we show that deletion of AS in Plasmodium berghei (Pb) delays the asexual- and liver-stage development with substantial reduction in the formation of ookinetes, oocysts and sporozoites in mosquitoes. In the absence of asparagine synthesis, extracellular asparagine supports suboptimal survival of PbAS knockout (KO) parasites. Depletion of blood asparagine levels by treating PbASKO-infected mice with asparaginase completely prevents the development of liver stages, exflagellation of male gametocytes and the subsequent formation of sexual stages. In vivo supplementation of asparagine in mice restores the exflagellation of PbASKO parasites. Thus, the parasite life cycle has an absolute requirement for asparagine, which we propose could be targeted to prevent malaria transmission and liver infections. PMID:26531182

  14. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes.

    PubMed

    Hallett, Rachel L; Sutherland, Colin J; Alexander, Neal; Ord, Rosalynn; Jawara, Musa; Drakeley, Chris J; Pinder, Margaret; Walraven, Gijs; Targett, Geoffrey A T; Alloueche, Ali

    2004-10-01

    Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resistant parasites from treated patients to mosquito vectors has not been measured directly. In a trial comparing CQ monotherapy to the combination CQ plus artesunate (AS) in Gambian children with uncomplicated falciparum malaria, we measured transmissibility by feeding Anopheles gambiae mosquitoes with blood from 43 gametocyte-positive patients through a membrane. In the CQ-treated group, gametocytes from patients carrying parasites with the CQ resistance-associated allele pfcrt-76T prior to treatment produced infected mosquitoes with 38 times higher Plasmodium falciparum oocyst burdens than mosquitoes fed on gametocytes from patients infected with sensitive parasites (P < 0.001). Gametocytes from parasites carrying the resistance-associated allele pfmdr1-86Y produced 14-fold higher oocyst burdens than gametocytes from patients infected with sensitive parasites (P = 0.011). However, parasites carrying either of these resistance-associated alleles pretreatment were not associated with higher mosquito oocyst burdens in the CQ-AS-treated group. Thus, combination therapy overcomes the transmission advantage enjoyed by drug-resistant parasites. PMID:15388456

  15. Entomological Monitoring and Evaluation: Diverse Transmission Settings of ICEMR Projects Will Require Local and Regional Malaria Elimination Strategies

    PubMed Central

    Conn, Jan E.; Norris, Douglas E.; Donnelly, Martin J.; Beebe, Nigel W.; Burkot, Thomas R.; Coulibaly, Mamadou B.; Chery, Laura; Eapen, Alex; Keven, John B.; Kilama, Maxwell; Kumar, Ashwani; Lindsay, Steve W.; Moreno, Marta; Quinones, Martha; Reimer, Lisa J.; Russell, Tanya L.; Smith, David L.; Thomas, Matthew B.; Walker, Edward D.; Wilson, Mark L.; Yan, Guiyun

    2015-01-01

    The unprecedented global efforts for malaria elimination in the past decade have resulted in altered vectorial systems, vector behaviors, and bionomics. These changes combined with increasingly evident heterogeneities in malaria transmission require innovative vector control strategies in addition to the established practices of long-lasting insecticidal nets and indoor residual spraying. Integrated vector management will require focal and tailored vector control to achieve malaria elimination. This switch of emphasis from universal coverage to universal coverage plus additional interventions will be reliant on improved entomological monitoring and evaluation. In 2010, the National Institutes for Allergies and Infectious Diseases (NIAID) established a network of malaria research centers termed ICEMRs (International Centers for Excellence in Malaria Research) expressly to develop this evidence base in diverse malaria endemic settings. In this article, we contrast the differing ecology and transmission settings across the ICEMR study locations. In South America, Africa, and Asia, vector biologists are already dealing with many of the issues of pushing to elimination such as highly focal transmission, proportionate increase in the importance of outdoor and crepuscular biting, vector species complexity, and “sub patent” vector transmission. PMID:26259942

  16. Entomological Monitoring and Evaluation: Diverse Transmission Settings of ICEMR Projects Will Require Local and Regional Malaria Elimination Strategies.

    PubMed

    Conn, Jan E; Norris, Douglas E; Donnelly, Martin J; Beebe, Nigel W; Burkot, Thomas R; Coulibaly, Mamadou B; Chery, Laura; Eapen, Alex; Keven, John B; Kilama, Maxwell; Kumar, Ashwani; Lindsay, Steve W; Moreno, Marta; Quinones, Martha; Reimer, Lisa J; Russell, Tanya L; Smith, David L; Thomas, Matthew B; Walker, Edward D; Wilson, Mark L; Yan, Guiyun

    2015-09-01

    The unprecedented global efforts for malaria elimination in the past decade have resulted in altered vectorial systems, vector behaviors, and bionomics. These changes combined with increasingly evident heterogeneities in malaria transmission require innovative vector control strategies in addition to the established practices of long-lasting insecticidal nets and indoor residual spraying. Integrated vector management will require focal and tailored vector control to achieve malaria elimination. This switch of emphasis from universal coverage to universal coverage plus additional interventions will be reliant on improved entomological monitoring and evaluation. In 2010, the National Institutes for Allergies and Infectious Diseases (NIAID) established a network of malaria research centers termed ICEMRs (International Centers for Excellence in Malaria Research) expressly to develop this evidence base in diverse malaria endemic settings. In this article, we contrast the differing ecology and transmission settings across the ICEMR study locations. In South America, Africa, and Asia, vector biologists are already dealing with many of the issues of pushing to elimination such as highly focal transmission, proportionate increase in the importance of outdoor and crepuscular biting, vector species complexity, and "sub patent" vector transmission. PMID:26259942

  17. ECOLOGICAL CHANGE AS A FACTOR IN RENEWED MALARIA TRANSMISSION IN AN ERADICATED AREA. A LOCALIZED OUTBREAK OF A. AQUASALIS-TRANSMITTED MALARIA ON THE DEMERARA RIVER ESTUARY, BRITISH GUIANA, IN THE FIFTEENTH YEAR OF A. DARLINGI AND MALARIA ERADICATION.

    PubMed

    GIGLIOLI, G

    1963-01-01

    In British Guiana, the successful eradication of Anopheles darlingi and malaria from the coastal areas has caused a very rapid increase in the population and has favoured a considerable social and economic improvement and expansion of both agriculture and industry. Housing and industrial developments and the constantly expanding rice cultivation have taken over most of the accessible pasture-lands, displacing the livestock which previously abounded around villages and settlements. Mechanization on the roads and in the fields increases daily, and the horse, the mule, the donkey and the ploughing oxen are gradually becoming obsolete.In some areas these changes have already caused such an upset in the balance between the human and the livestock population that A. aquasalis, a very abundant species all along the coast, but until recently entirely "fixed" by the livestock population, is now shifting its attention from livestock to man. On the Demerara river estuary, an area where malaria transmission was interrupted sixteen years ago and where eradication has been continually maintained, this mosquito has been responsible for a sharp, but localized, outbreak of P. vivax malaria. An entirely new epidemiological problem thus presents itself.Environmental changes, introduced and fostered by successful malaria eradication, may thus cause an anopheline species, potentially capable of malaria transmission, but originally inactive and harmless as a vector, to alter its feeding habits and thereby renew transmission. The immediate and long-term significance of some secondary and potential vectors may therefore require renewed evaluation in the planning of malaria eradication campaigns. PMID:14056265

  18. Prospects of intermittent preventive treatment of adults against malaria in areas of seasonal and unstable malaria transmission, and a possible role for chloroquine.

    PubMed

    Giha, Hayder A

    2010-04-01

    Chloroquine (CQ) is outmoded as an antimalarial drug in most of the malarial world because of the high resistance rate of parasites. The parasite resistance to CQ is attributed to pfcrt/pfmdr1 gene mutations. Recent studies showed that parasites with mutations of pfcrt/pfmdr1 genes are less virulent, and that those with dhfr/dhps mutations are more susceptible to host immune clearance; the former and latter mutations are linked. In the era of artemisinin-based combination therapy, the frequency of pfcrt/pfmdr1 wild variants is expected to rise. In areas of unstable malaria transmission, the unpredictable severe epidemics of malaria and epidemics of severe malaria could result in high mortality rate among the semi-immune population. With this in mind, the use of CQ for intermittent preventive treatment of adults (IPTa) is suggested as a feasible control measure to reduce malaria mortality in adults and older children without reducing uncomplicated malaria morbidity. The above is discussed in a multidisciplinary approach validating the deployment of molecular techniques in malaria control and showing a possible role for CQ as a rescue drug after being abandoned. PMID:20307217

  19. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

    PubMed Central

    White, Michael T.; Shirreff, George; Karl, Stephan; Ghani, Azra C.; Mueller, Ivo

    2016-01-01

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes. PMID:27030414

  20. The impact of hotspot-targeted interventions on malaria transmission: study protocol for a cluster-randomized controlled trial

    PubMed Central

    2013-01-01

    Background Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community. Methods/design Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations. Discussion This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection. Trial registration NCT01575613. The protocol was registered online on 20 March 2012; the first community was randomized on 26 March 2012. PMID:23374910

  1. Assessment of antibody responses in local and immigrant residents of areas with autochthonous malaria transmission in Greece.

    PubMed

    Piperaki, Evangelia-Theofano; Mavrouli, Maria; Tseroni, Maria; Routsias, John; Kallimani, Athina; Veneti, Lamprini; Georgitsou, Maria; Chania, Maria; Georgakopoulou, Theano; Hadjichristodoulou, Christos; Tsakris, Athanassios

    2015-07-01

    Greece has been officially malaria free since 1974. However, from 2009 to 2012, several locally acquired, cases of Plasmodium vivax malaria were detected, in immigrants and in Greek citizens. In this study, the antibody (Ab) response of Greeks and immigrants with documented malaria was initially assessed, followed by an Ab screening of Greeks and immigrant residents of local transmission areas. Of the 38 patients tested, 10.5% of Greeks and 15.7% of immigrants were positive 5-7 months after infection. Of the 1,019 individuals from various areas of Greece, including those of autochthonous transmission, 85 of the 721 (11.8%) immigrants were positive, whereas all 298 Greeks were negative. The rapid Ab titer decline observed is reasonable, given the non-endemic epidemiological setting. The seroepidemiological findings indicate that the local Greek population remains malaria naive and that at this point Greeks are unlikely to serve as reservoir for the infection of local mosquitoes. PMID:26013377

  2. A need for better housing to further reduce indoor malaria transmission in areas with high bed net coverage

    PubMed Central

    2013-01-01

    Background The suppression of indoor malaria transmission requires additional interventions that complement the use of insecticide treated nets (ITNs) and indoor residual spraying (IRS). Previous studies have examined the impact of house structure on malaria transmission in areas of low transmission. This study was conducted in a high transmission setting and presents further evidence about the association between specific house characteristics and the abundance of endophilic malaria vectors. Methods Mosquitoes were sampled using CDC light traps from 72 randomly selected houses in two villages on a monthly basis from 2008 to 2011 in rural Southern Tanzania. Generalized linear models using Poisson distributions were used to analyze the association of house characteristics (eave gaps, wall types, roof types, number of windows, rooms and doors, window screens, house size), number of occupants and ITN usage with mean catches of malaria vectors (An.gambiae s.l. and An. funestus). Results A total of 36490 female An. gambiae s.l. were collected in Namwawala village and 21266 in Idete village. As for An. funestus females, 2268 were collected in Namwawala and 3398 in Idete. Individually, each house factor had a statistically significant impact (p < 0.05) on the mean catches for An. gambiae s.l. but not An. funestus. A multivariate analysis indicated that the combined absence or presence of eaves, treated or untreated bed-nets, the number of house occupants, house size, netting over windows, and roof type were significantly related (p < 0.05) to An.gambiae s.l. and An. funestus house entry in both villages. Conclusions Despite significant reductions in vector density and malaria transmission caused by high coverage of ITNs, high numbers of host-seeking malaria vectors are still found indoors due to house designs that favour mosquito entry. In addition to ITNs and IRS, significant efforts should focus on improving house design to prevent mosquito entry and eliminate

  3. Modeling the Influence of Local Environmental Factors on Malaria Transmission in Benin and Its Implications for Cohort Study

    PubMed Central

    Pierrat, Charlotte; le Port, Agnès; Bouraïma, Aziz; Fonton, Noël; Hounkonnou, Mahouton Norbert; Massougbodji, Achille; Corbel, Vincent; Garcia, André

    2012-01-01

    Malaria remains endemic in tropical areas, especially in Africa. For the evaluation of new tools and to further our understanding of host-parasite interactions, knowing the environmental risk of transmission—even at a very local scale—is essential. The aim of this study was to assess how malaria transmission is influenced and can be predicted by local climatic and environmental factors. As the entomological part of a cohort study of 650 newborn babies in nine villages in the Tori Bossito district of Southern Benin between June 2007 and February 2010, human landing catches were performed to assess the density of malaria vectors and transmission intensity. Climatic factors as well as household characteristics were recorded throughout the study. Statistical correlations between Anopheles density and environmental and climatic factors were tested using a three-level Poisson mixed regression model. The results showed both temporal variations in vector density (related to season and rainfall), and spatial variations at the level of both village and house. These spatial variations could be largely explained by factors associated with the house's immediate surroundings, namely soil type, vegetation index and the proximity of a watercourse. Based on these results, a predictive regression model was developed using a leave-one-out method, to predict the spatiotemporal variability of malaria transmission in the nine villages. This study points up the importance of local environmental factors in malaria transmission and describes a model to predict the transmission risk of individual children, based on environmental and behavioral characteristics. PMID:22238582

  4. Simulation of Malaria Transmission among Households in a Thai Village using Remotely Sensed Parameters

    NASA Technical Reports Server (NTRS)

    Kiang, Richard K.; Adimi, Farida; Zollner, Gabriela E.; Coleman, Russell E.

    2007-01-01

    We have used discrete-event simulation to model the malaria transmission in a Thailand village with approximately 700 residents. Specifically, we model the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle under the explicit influences of selected extrinsic and intrinsic factors. Some of the meteorological and environmental parameters used in the simulation are derived from Tropical Rainfall Measuring Mission and the Ikonos satellite data. Parameters used in the simulations reflect the realistic condition of the village, including the locations and sizes of the households, ages and estimated immunity of the residents, presence of farm animals, and locations of larval habitats. Larval habitats include the actual locations where larvae were collected and the probable locations based on satellite data. The output of the simulation includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Simulated transmission under homogeneous environmental condition was compared with that predicted by a SEIR model. Sensitivity of the output with respect to some extrinsic and intrinsic factors was investigated. Results were compared with mosquito vector and human malaria data acquired over 4.5 years (June 1999 - January 2004) in Kong Mong Tha, a remote village in Kanchanaburi Province, western Thailand. The simulation method is useful for testing transmission hypotheses, estimating the efficacy of insecticide applications, assessing the impacts of nonimmune immigrants, and predicting the effects of socioeconomic, environmental and climatic changes.

  5. Primaquine plus artemisinin combination therapy for reduction of malaria transmission: promise and risk.

    PubMed

    John, Chandy C

    2016-01-01

    Reduction of gametocyte transmission from humans to mosquitoes is a key component of malaria elimination. The study by Gonçalves and colleagues provides valuable new data on how the addition of low-dose primaquine to artemether-lumefantrine affects reduction of gametocytemia and transmission of gametocytes to mosquitoes in asymptomatically Plasmodium falciparum-infected children without G6PD deficiency, and on the degree to which low-dose primaquine affects hemoglobin levels in these children. The study sets the stage for future research required for consideration of an artemisinin combination therapy (ACT)-primaquine regimen in mass drug administration campaigns. Future studies will need to evaluate toxicity in adults and G6PD deficient persons, assess gametocyte transmission from adults, evaluate different ACT drugs with primaquine, and assess the implications of "rare" toxicities in large treatment populations, such as hemolysis requiring blood transfusion. The study highlights both the promise and the potential risk of ACT-primaquine treatment in malaria elimination campaigns.Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0581-y . PMID:27039396

  6. Estimation of Recent and Long-Term Malaria Transmission in a Population by Antibody Testing to Multiple Plasmodium falciparum Antigens

    PubMed Central

    Ondigo, Bartholomew N.; Hodges, James S.; Ireland, Kathleen F.; Magak, Ng'wena G.; Lanar, David E.; Dutta, Sheetij; Narum, David L.; Park, Gregory S.; Ofulla, Ayub V.; John, Chandy C.

    2014-01-01

    Background. Tools that estimate recent and long-term malaria transmission in a population would be highly useful for malaria elimination programs. Methods. The prevalence of antibodies to 11 Plasmodium falciparum antigens was assessed by cytometric bead assay or enzyme-linked immunosorbent assay in 1000 people in a highland area of Kenya over 14 months, during a period of interrupted malaria transmission. Results. Antibodies differed by antigen in acquisition with age: rapid (>80% antibody positive by age 20 years, 5 antigens), moderate (>40% positive by age 20 years, 3 antigens), or slow (<40% positive by age 20 years, 3 antigens). Antibody seroreversion rates in the 14 months between samples decreased with age rapidly (7 antigens), slowly (3 antigens), or remained high at all ages (schizont extract). Estimated antibody half-lives in individuals >10 years of age were long (40 to >80 years) for 5 antigens, moderate (5–20 years) for 3 antigens, and short (<1 year) for 3 antigens. Conclusions. Antibodies to P. falciparum antigens in malaria-endemic areas vary by age, antigen, and time since last exposure to P. falciparum. Multiplex P. falciparum antibody testing could provide estimates of long-term and recent malaria transmission and potentially of a population's susceptibility to future clinical malaria. PMID:24737801

  7. Malaria vectors and transmission dynamics in Goulmoun, a rural city in south-western Chad

    PubMed Central

    2009-01-01

    Background Knowledge of some baseline entomological data such as Entomological Inoculation Rates (EIR) is crucially needed to assess the epidemiological impact of malaria control activities directed either against parasites or vectors. In Chad, most published surveys date back to the 1960's. In this study, anopheline species composition and their relation to malaria transmission were investigated in a dry Sudanian savannas area of Chad. Methods A 12-month longitudinal survey was conducted in the irrigated rice-fields area of Goulmoun in south western Chad. Human landing catches were performed each month from July 2006 to June 2007 in three compounds (indoors and outdoors) and pyrethrum spray collections were conducted in July, August and October 2006 in 10 randomly selected rooms. Mosquitoes belonging to the Anopheles gambiae complex and to the An. funestus group were identified by molecular diagnostic tools. Plasmodium falciparum infection and blood meal sources were detected by ELISA. Results Nine anopheline species were collected by the two sampling methods. The most aggressive species were An. arabiensis (51 bites/human/night), An. pharoensis (12.5 b/h/n), An. funestus (1.5 b/h/n) and An. ziemanni (1.3 b/h/n). The circumsporozoite protein rate was 1.4% for An. arabiensis, 1.4% for An. funestus, 0.8% for An. pharoensis and 0.5% for An. ziemanni. Malaria transmission is seasonal, lasting from April to December. However, more than 80% of the total EIR was concentrated in the period from August to October. The overall annual EIR was estimated at 311 bites of infected anophelines/human/year, contributed mostly by An. arabiensis (84.5%) and An. pharoensis (12.2%). Anopheles funestus and An. ziemanni played a minor role. Parasite inoculation occurred mostly after 22:00 hours but around 20% of bites of infected anophelines were distributed earlier in the evening. Conclusion The present study revealed the implication of An. pharoensis in malaria transmission in the

  8. Malaria transmission pattern resilience to climatic variability is mediated by insecticide-treated nets

    PubMed Central

    Chaves, Luis Fernando; Kaneko, Akira; Taleo, George; Pascual, Mercedes; Wilson, Mark L

    2008-01-01

    Background Malaria is an important public-health problem in the archipelago of Vanuatu and climate has been hypothesized as important influence on transmission risk. Beginning in 1988, a major intervention using insecticide-treated bed nets (ITNs) was implemented in the country in an attempt to reduce Plasmodium transmission. To date, no study has addressed the impact of ITN intervention in Vanuatu, how it may have modified the burden of disease, and whether there were any changes in malaria incidence that might be related to climatic drivers. Methods and findings Monthly time series (January 1983 through December 1999) of confirmed Plasmodium falciparum and Plasmodium vivax infections in the archipelago were analysed. During this 17 year period, malaria dynamics underwent a major regime shift around May 1991, following the introduction of bed nets as a control strategy in the country. By February of 1994 disease incidence from both parasites was reduced by at least 50%, when at most 20% of the population at risk was covered by ITNs. Seasonal cycles, as expected, were strongly correlated with temperature patterns, while inter-annual cycles were associated with changes in precipitation. Following the bed net intervention, the influence of environmental drivers of malaria dynamics was reduced by 30–80% for climatic forces, and 33–54% for other factors. A time lag of about five months was observed for the qualitative change ("regime shift") between the two parasites, the change occurring first for P. falciparum. The latter might be explained by interspecific interactions between the two parasites within the human hosts and their distinct biology, since P. vivax can relapse after a primary infection. Conclusion The Vanuatu ITN programme represents an excellent example of implementing an infectious disease control programme. The distribution was undertaken to cover a large, local proportion (~80%) of people in villages where malaria was present. The successful

  9. Coagulation and Fibrinolysis Indicators and Placental Malaria Infection in an Area Characterized by Unstable Malaria Transmission in Central Sudan

    PubMed Central

    Mostafa, Amged G.; Bilal, Naser E.; Abass, Awad-Elkareem; Elhassan, Elhassan M.; Mohmmed, Ahmed A.; Adam, Ishag

    2015-01-01

    This study aimed to investigate coagulation, fibrinolysis indicators, and malaria during pregnancy. Methods. A cross-sectional study was conducted at Medani, Sudan. Sociodemographic characteristics were gathered from each parturient woman (163) and malaria was investigated by blood film and placental histology. Protein C, protein S, antithrombin-III, tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 levels (PAI-1) were measured using ELISA. Results. One (0.6%), three (1.8), and 19 (11.7%) of the placentae showed active, chronic, and past infection on a histopathological examination, respectively, while 140 (85.9%) of them showed no signs of malaria infection. While the mean [SD] of the protein C, antithrombin-III, and TFPI was significantly lower, there was no significant difference in protein S and PAI-1 levels in women with placental malaria infection (n = 23) compared to those without placental malaria infection (140). In linear regression, placental malaria infection was associated with antithrombin-III. There was no association between placental malaria infections and protein C, protein S, TFPI, and PAI-1 levels. There was no association between hemoglobin, birth weight, and the investigated coagulation and fibrinolysis indicators. Conclusion. This study showed significantly lower levels of protein C, antithrombin-III, and TFPI in women with placental malaria infections. PMID:26295004

  10. Hyperendemic malaria transmission in areas of occupation-related travel in the Peruvian Amazon

    PubMed Central

    2013-01-01

    Background Plasmodium vivax and Plasmodium falciparum cause a significant illness burden in Peru. Anopheline indices for populated communities in the peri-Iquitos region of Loreto have been reported to be remarkably low, with entomological inoculation rates (EIR) estimated at one to 30 infective bites per year based on a few studies in close proximity to the urban centre of Iquitos and surrounding deforested areas. Local reports suggest that a large number of the reported cases are contracted outside of populated communities in undeveloped riverine areas frequented by loggers and fishermen. Methods To better understand vectorial capacity in suspected high malaria transmission zones in a rural district near Iquitos, Peru, mosquito collections were conducted at different points in the seasonality of malaria transmission in 21 sites frequented by occupational labourers. Prevalence of Plasmodium spp in vectors was determined by circumsporozoite protein ELISA on individual mosquitoes. Slide surveillance was performed for humans encountered in the zone. Results In total, of 8,365 adult female mosquitoes examined, 98.5% were identified as Anopheles darlingi and 117 (1.4%) tested positive for sporozoites (P. falciparum, P. vivax VK210 or P. vivax VK247). Measured human biting rates at these sites ranged from 0.102 to 41.13 bites per person per hour, with EIR values as high as 5.3 infective bites per person per night. Six percent of the 284 blood films were positive for P. vivax or P. falciparum; however, 88% of the individuals found to be positive were asymptomatic at the time of sampling. Conclusions The results of this study provide key missing indices of prominent spatial and temporal heterogeneity of vectorial capacity in the Amazon Basin of Peru. The identification of a target human subpopulation as a principal reservoir and dispersion source of Plasmodium species has important implications for vaccine development and the delivery of effective targeted malaria control

  11. Vectors and malaria transmission in deforested, rural communities in north-central Vietnam

    PubMed Central

    2010-01-01

    Background Malaria is still prevalent in rural communities of central Vietnam even though, due to deforestation, the primary vector Anopheles dirus is uncommon. In these situations little is known about the secondary vectors which are responsible for maintaining transmission. Basic information on the identification of the species in these rural communities is required so that transmission parameters, such as ecology, behaviour and vectorial status can be assigned to the appropriate species. Methods In two rural villages - Khe Ngang and Hang Chuon - in Truong Xuan Commune, Quang Binh Province, north central Vietnam, a series of longitudinal entomological surveys were conducted during the wet and dry seasons from 2003 - 2007. In these surveys anopheline mosquitoes were collected in human landing catches, paired human and animal bait collections, and from larval surveys. Specimens belonging to species complexes were identified by PCR and sequence analysis, incrimination of vectors was by detection of circumsporozoite protein using an enzyme-linked immunosorbent assay. Results Over 80% of the anopheline fauna was made up of Anopheles sinensis, Anopheles aconitus, Anopheles harrisoni, Anopheles maculatus, Anopheles sawadwongporni, and Anopheles philippinensis. PCR and sequence analysis resolved identification issues in the Funestus Group, Maculatus Group, Hyrcanus Group and Dirus Complex. Most species were zoophilic and while all species could be collected biting humans significantly higher densities were attracted to cattle and buffalo. Anopheles dirus was the most anthropophilic species but was uncommon making up only 1.24% of all anophelines collected. Anopheles sinensis, An. aconitus, An. harrisoni, An. maculatus, An. sawadwongporni, Anopheles peditaeniatus and An. philippinensis were all found positive for circumsporozoite protein. Heterogeneity in oviposition site preference between species enabled vector densities to be high in both the wet and dry seasons

  12. Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite.

    PubMed

    Santos, Jorge M; Duarte, Neuza; Kehrer, Jessica; Ramesar, Jai; Avramut, M Cristina; Koster, Abraham J; Dessens, Johannes T; Frischknecht, Friedrich; Chevalley-Maurel, Séverine; Janse, Chris J; Franke-Fayard, Blandine; Mair, Gunnar R

    2016-06-28

    Transmission of the malaria parasite from the mammalian host to the mosquito vector requires the formation of adequately adapted parasite forms and stage-specific organelles. Here we show that formation of the crystalloid-a unique and short-lived organelle of the Plasmodium ookinete and oocyst stage required for sporogony-is dependent on the precisely timed expression of the S-acyl-transferase DHHC10. DHHC10, translationally repressed in female Plasmodium berghei gametocytes, is activated translationally during ookinete formation, where the protein is essential for the formation of the crystalloid, the correct targeting of crystalloid-resident protein LAP2, and malaria parasite transmission. PMID:27303037

  13. Assessing malaria transmission in a low endemicity area of north-western Peru

    PubMed Central

    2013-01-01

    Background Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI using both molecular and serological tools. Methods Epidemiological, parasitological and serological data were collected from 2,667 individuals in three settlements of Bellavista district, in May 2010. Parasite infection was detected using microscopy and polymerase chain reaction (PCR). Antibodies to Plasmodium vivax merozoite surface protein-119 (PvMSP119) and to Plasmodium falciparum glutamate-rich protein (PfGLURP) were detected by ELISA. Risk factors for exposure to malaria (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific antibody prevalence of both P. falciparum and P. vivax were analysed using a previously published catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR). Results The overall parasite prevalence by microscopy and PCR were extremely low: 0.3 and 0.9%, respectively for P. vivax, and 0 and 0.04%, respectively for P. falciparum, while seroprevalence was much higher, 13.6% for P. vivax and 9.8% for P. falciparum. Settlement, age and occupation as moto-taxi driver during previous year were significantly associated with P. falciparum exposure, while age and distance to the water drain were associated with P. vivax exposure. Likelihood ratio tests supported age seroprevalence curves with two SCR for both P. vivax and P. falciparum indicating significant changes in the MTI over time. The SCR for PfGLURP was 19-fold lower after 2002 as compared to before (λ1 = 0.022 versus λ2 = 0.431), and the SCR for PvMSP119 was four-fold higher after 2006 as compared to before (λ1 = 0.024 versus λ2 = 0.006). Conclusion Combining molecular and serological tools

  14. The multiplicity of malaria transmission: a review of entomological inoculation rate measurements and methods across sub-Saharan Africa.

    PubMed

    Kelly-Hope, Louise A; McKenzie, F Ellis

    2009-01-01

    Plasmodium falciparum malaria is a serious tropical disease that causes more than one million deaths each year, most of them in Africa. It is transmitted by a range of Anopheles mosquitoes and the risk of disease varies greatly across the continent. The "entomological inoculation rate" is the commonly-used measure of the intensity of malaria transmission, yet the methods used are currently not standardized, nor do they take the ecological, demographic, and socioeconomic differences across populations into account. To better understand the multiplicity of malaria transmission, this study examines the distribution of transmission intensity across sub-Saharan Africa, reviews the range of methods used, and explores ecological parameters in selected locations. It builds on an extensive geo-referenced database and uses geographical information systems to highlight transmission patterns, knowledge gaps, trends and changes in methodologies over time, and key differences between land use, population density, climate, and the main mosquito species. The aim is to improve the methods of measuring malaria transmission, to help develop the way forward so that we can better assess the impact of the large-scale intervention programmes, and rapid demographic and environmental change taking place across Africa. PMID:19166589

  15. Pattern of malaria transmission along the Rahad River basin, Eastern Sudan

    PubMed Central

    2011-01-01

    Background Understanding malaria vector mosquitoes and their infectivity dynamics is of importance in setting up intervention and control programmes. Patterns of malaria transmission have been shown to differ between non-irrigated and irrigated semi-arid areas of eastern Sudan. However, very little information is available regarding malaria transmission dynamics along the seasonal river's basin. Such information is required for the design of effective vector control strategies. Methods A longitudinal study for mosquito sampling using pyrethrum spray catch (PSC) was conducted in two villages (Koka & Um Salala) along the Rahad River basin from December 2005 to October 2006. The Plasmodium falciparum circumsporozoite (CSP) and human blood index (HBI) were detected by ELISA. Three seasons were considered and the surveys represented cool dry, hot dry and rainy seasons were November - February, March - June, July - October, respectively. The CSP was compared between the seasons and populations using Chi-square test. The differences between the seasons and the populations in the other entomological indices, including Entomological Inoculation Rates (EIR), were measured using Tukey-Kramer HSD and Student T-test, respectively. The association between An. arabiensis density and monthly total rainfall was examined using regression analysis. Results A total of 1,402 adult female anopheline mosquitoes were sampled, of which 98% were An. gambiae complex; the rest were An. rufipes. All specimens of An. gambiae complex identified by the PCR were An. arabiensis. Bimodal annual peaks of An. arabiensis densities were observed following the peak of rainfall and recess of the Rahad River after a time- lag of two months (Koka r = 0.79, d.f. = 1, P = 0.05; Um Salala, r = 0.88, d.f. = 1, P = 0.02). The CSP differed significantly among the seasons only in Koka (P = 0.0009) where the mean was nine times higher than in Um Salala (P = 0.0014). Active transmission was observed in Koka during

  16. Macrophage migration inhibitory factor and placental malaria infection in an area characterized by unstable malaria transmission in central Sudan

    PubMed Central

    Eltayeb, Reem; Bilal, Naser; Abass, Awad-Elkareem; Elhassan, Elhassan M.; Mohammed, Ahmed; Adam, Ishag

    2015-01-01

    Background: The pathogenesis of malaria during pregnancy is not fully understood. A proinflammatory cytokine, macrophage migration inhibitory factor (MIF) is suggested as a factor involved in the pathogenesis of malaria during pregnancy. Methods: A cross-sectional study was conducted in Medani Hospital, Sudan to investigate MIF levels in placental malaria. Obstetrical and medical characteristics were gathered from each parturient woman using questionnaires. All women (151) were investigated for malaria using blood film and placental histology. MIF levels were measured using ELISA in paired maternal and cord blood samples. Results: There were no P. falciparum-positive blood films obtained from maternal peripheral blood, placenta or cord samples. Out of 151 placentae, four (2.6%), one (0.7%), 32 (21.2%) showed acute, chronic and past infection on histopathology examinations respectively, while the rest (114; 75.5%) of them showed no signs of infection.There was no significant difference in the median (interquartile) of maternal [5.0 (3.7─8.8) vs 6.2(3.5─12.0) ng/ml, P=0.643] and cord [8.1(3.3─16.9) vs 8.3(4.2─16.9), ng/ml, P= 0.601] MIF levels between women with a positive result for placental malaria infection (n=37) and women with a negative result for placental malaria infection (n=114). In regression models placental malaria was not associated with maternal MIF, hemoglobin or birth weight. MIF was not associated with hemoglobin or birth weight . Conclusion: There was no association between maternal and cord MIF levels, placental malaria, maternal hemoglobin and birth weight.

  17. Predicting key malaria transmission factors, biting and entomological inoculation rates, using modelled soil moisture in Kenya.

    PubMed

    Patz, J A; Strzepek, K; Lele, S; Hedden, M; Greene, S; Noden, B; Hay, S I; Kalkstein, L; Beier, J C

    1998-10-01

    While malaria transmission varies seasonally, large inter-annual heterogeneity of malaria incidence occurs. Variability in entomological parameters, biting rates and entomological inoculation rates (EIR) have been strongly associated with attack rates in children. The goal of this study was to assess the weather's impact on weekly biting and EIR in the endemic area of Kisian, Kenya. Entomological data collected by the U.S. Army from March 1986 through June 1988 at Kisian, Kenya was analysed with concurrent weather data from nearby Kisumu airport. A soil moisture model of surface-water availability was used to combine multiple weather parameters with landcover and soil features to improve disease prediction. Modelling soil moisture substantially improved prediction of biting rates compared to rainfall; soil moisture lagged two weeks explained up to 45% of An. gambiae biting variability, compared to 8% for raw precipitation. For An. funestus, soil moisture explained 32% variability, peaking after a 4-week lag. The interspecies difference in response to soil moisture was significant (P < 0.00001). A satellite normalized differential vegetation index (NDVI) of the study site yielded a similar correlation (r = 0.42 An. gambiae). Modelled soil moisture accounted for up to 56% variability of An. gambiae EIR, peaking at a lag of six weeks. The relationship between temperature and An. gambiae biting rates was less robust; maximum temperature r2 = -0.20, and minimum temperature r2 = 0.12 after lagging one week. Benefits of hydrological modelling are compared to raw weather parameters and to satellite NDVI. These findings can improve both current malaria risk assessments and those based on El Niño forecasts or global climate change model projections. PMID:9809915

  18. Remote Sensing as a Landscape Epidemiologic Tool to Identify Villages at High Risk for Malaria Transmission

    NASA Technical Reports Server (NTRS)

    Beck, Louisa R.; Rodriquez, Mario H.; Dister, Sheri W.; Rodriquez, Americo D.; Rejmankova, Eliska; Ulloa, Armando; Meza, Rosa A.; Roberts, Donald R.; Paris, Jack F.; Spanner, Michael A.; Washino, Robert K.; Hacker, Carl; Legters, Llewellyn F.

    1994-01-01

    A landscape approach using remote sensing and Geographic Information System (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high ind low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where: 1. the landscape elements critical to vector survival are known and 2. these elements can be detected at remote sensing scales.

  19. The Plasmodium palmitoyl-S-acyl-transferase DHHC2 is essential for ookinete morphogenesis and malaria transmission

    PubMed Central

    Santos, Jorge M.; Kehrer, Jessica; Franke-Fayard, Blandine; Frischknecht, Friedrich; Janse, Chris J.; Mair, Gunnar R.

    2015-01-01

    The post-translational addition of C-16 long chain fatty acids to protein cysteine residues is catalysed by palmitoyl-S-acyl-transferases (PAT) and affects the affinity of a modified protein for membranes and therefore its subcellular localisation. In apicomplexan parasites this reversible protein modification regulates numerous biological processes and specifically affects cell motility, and invasion of host cells by Plasmodium falciparum merozoites and Toxoplasma gondii tachyzoites. Using inhibitor studies we show here that palmitoylation is key to transformation of zygotes into ookinetes during initial mosquito infection with P. berghei. We identify DHHC2 as a unique PAT mediating ookinete formation and morphogenesis. Essential for life cycle progression in asexual blood stage parasites and thus refractory to gene deletion analyses, we used promoter swap (ps) methodology to maintain dhhc2 expression in asexual blood stages but down regulate expression in sexual stage parasites and during post-fertilization development of the zygote. The ps mutant showed normal gamete formation, fertilisation and DNA replication to tetraploid cells, but was characterised by a complete block in post-fertilisation development and ookinete formation. Our report highlights the crucial nature of the DHHC2 palmitoyl-S-acyltransferase for transmission of the malaria parasite to the mosquito vector through its essential role for ookinete morphogenesis. PMID:26526684

  20. The Plasmodium palmitoyl-S-acyl-transferase DHHC2 is essential for ookinete morphogenesis and malaria transmission.

    PubMed

    Santos, Jorge M; Kehrer, Jessica; Franke-Fayard, Blandine; Frischknecht, Friedrich; Janse, Chris J; Mair, Gunnar R

    2015-01-01

    The post-translational addition of C-16 long chain fatty acids to protein cysteine residues is catalysed by palmitoyl-S-acyl-transferases (PAT) and affects the affinity of a modified protein for membranes and therefore its subcellular localisation. In apicomplexan parasites this reversible protein modification regulates numerous biological processes and specifically affects cell motility, and invasion of host cells by Plasmodium falciparum merozoites and Toxoplasma gondii tachyzoites. Using inhibitor studies we show here that palmitoylation is key to transformation of zygotes into ookinetes during initial mosquito infection with P. berghei. We identify DHHC2 as a unique PAT mediating ookinete formation and morphogenesis. Essential for life cycle progression in asexual blood stage parasites and thus refractory to gene deletion analyses, we used promoter swap (ps) methodology to maintain dhhc2 expression in asexual blood stages but down regulate expression in sexual stage parasites and during post-fertilization development of the zygote. The ps mutant showed normal gamete formation, fertilisation and DNA replication to tetraploid cells, but was characterised by a complete block in post-fertilisation development and ookinete formation. Our report highlights the crucial nature of the DHHC2 palmitoyl-S-acyltransferase for transmission of the malaria parasite to the mosquito vector through its essential role for ookinete morphogenesis. PMID:26526684

  1. Low and seasonal malaria transmission in the middle Senegal River basin: identification and characteristics of Anopheles vectors

    PubMed Central

    2012-01-01

    Background During the last decades two dams were constructed along the Senegal River. These intensified the practice of agriculture along the river valley basin. We conducted a study to assess malaria vector diversity, dynamics and malaria transmission in the area. Methods A cross-sectional entomological study was performed in September 2008 in 20 villages of the middle Senegal River valley to evaluate the variations of Anopheles density according to local environment. A longitudinal study was performed, from October 2008 to January 2010, in 5 selected villages, to study seasonal variations of malaria transmission. Results Among malaria vectors, 72.34% of specimens collected were An. arabiensis, 5.28% An. gambiae of the S molecular form, 3.26% M form, 12.90% An. pharoensis, 4.70% An. ziemanni, 1.48% An. funestus and 0.04% An. wellcomei. Anopheles density varied according to village location. It ranged from 0 to 21.4 Anopheles/room/day and was significantly correlated with the distance to the nearest ditch water but not to the river. Seasonal variations of Anopheles density and variety were observed with higher human biting rates during the rainy season (8.28 and 7.55 Anopheles bite/man/night in October 2008 and 2009 respectively). Transmission was low and limited to the rainy season (0.05 and 0.06 infected bite/man/night in October 2008 and 2009 respectively). During the rainy season, the endophagous rate was lower, the anthropophagic rate higher and L1014F kdr frequency higher. Conclusions Malaria vectors are present at low-moderate density in the middle Senegal River basin with An. arabiensis as the predominant species. Other potential vectors are An. gambiae M and S form and An. funestus. Nonetheless, malaria transmission was extremely low and seasonal. PMID:22269038

  2. Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination

    PubMed Central

    Noviyanti, Rintis; Coutrier, Farah; Utami, Retno A. S.; Trimarsanto, Hidayat; Tirta, Yusrifar K.; Trianty, Leily; Kusuma, Andreas; Sutanto, Inge; Kosasih, Ayleen; Kusriastuti, Rita; Hawley, William A.; Laihad, Ferdinand; Lobo, Neil; Marfurt, Jutta; Clark, Taane G.; Price, Ric N.; Auburn, Sarah

    2015-01-01

    Background Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions. Methodology/ Principal Findings Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of diversity, linkage disequilibrium (LD) and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species. Conclusions/ Significance Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given

  3. Air temperature suitability for Plasmodium falciparum malaria transmission in Africa 2000-2012: a high-resolution spatiotemporal prediction

    PubMed Central

    2014-01-01

    Background Temperature suitability for malaria transmission is a useful predictor variable for spatial models of malaria infection prevalence. Existing continental or global models, however, are synoptic in nature and so do not characterize inter-annual variability in seasonal patterns of temperature suitability, reducing their utility for predicting malaria risk. Methods A malaria Temperature Suitability Index (TSI) was created by first modeling minimum and maximum air temperature with an eight-day temporal resolution from gap-filled MODerate Resolution Imaging Spectroradiometer (MODIS) daytime and night-time Land Surface Temperature (LST) datasets. An improved version of an existing biological model for malaria temperature suitability was then applied to the resulting temperature information for a 13-year data series. The mechanism underlying this biological model is simulation of emergent mosquito cohorts on a two-hour time-step and tracking of each cohort throughout its life to quantify the impact air temperature has on both mosquito survival and sporozoite development. Results The results of this research consist of 154 monthly raster surfaces that characterize spatiotemporal patterns in TSI across Africa from April 2000 through December 2012 at a 1 km spatial resolution. Generalized TSI patterns were as expected, with consistently high values in equatorial rain forests, seasonally variable values in tropical savannas (wet and dry) and montane areas, and low values in arid, subtropical regions. Comparisons with synoptic approaches demonstrated the additional information available within the dynamic TSI dataset that is lost in equivalent synoptic products derived from long-term monthly averages. Conclusions The dynamic TSI dataset presented here provides a new product with far richer spatial and temporal information than any other presently available for Africa. As spatiotemporal malaria modeling endeavors evolve, dynamic predictor variables such as the malaria

  4. Transmission electron microscopy of polymer blends and block copolymers

    NASA Astrophysics Data System (ADS)

    Gomez, Enrique Daniel

    -consistent field theory (SCFT). The liquid-like nature of this system at room temperature makes traditional staining methods for the enhancement of contrast ineffective. As an alternative, we take advantage of the large inelastic scattering cross-section of soft materials to generate contrast in zero-loss TEM images. Independent spatially resolved thickness measurements enable quantification of electron scattering. This enabled a comparison between the TEM data and predictions based on SCFT without any adjustable parameters. The second example involves the utilization of energy-filtered transmission electron microscopy (EFTEM) to compute elemental maps by taking advantage of ionization events. Elemental mapping of lithium is used to determine the distribution of salt in nanostructured poly(styrene-block-ethylene oxide) (SEO) copolymer/lithium salt electrolytes. Surprisingly, the concentration of lithium within a poly(ethylene oxide) (PEO) domain is found to be inhomogeneous; the salt is localized to the middle of the channels. Self-consistent field theory simulations suggest that localization of lithium is due to chain stretching at the interface, which increases with molecular weight. EFTEM and SCFT results show that the segregation of lithium salt to the middle of the PEO lamellae is greater for higher molecular weight polymers. This is correlated with the ionic conductivity of the copolymer electrolyte, which is found to show a higher conductivity for thinner lithium lamellae.

  5. Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

    PubMed Central

    Abeles, Shira R.; Chuquiyauri, Raul; Tong, Carlos; Vinetz, Joseph M.

    2013-01-01

    Infection of mosquitoes by humans is not always successful in the setting of patent gametocytemia. This study tested the hypothesis that pro- or anti-inflammatory cytokines are associated with transmission of Plasmodium vivax to Anopheles darlingi mosquitoes in experimental infection. Blood from adults with acute, non-severe P. vivax malaria was fed to laboratory-reared F1 An. darlingi mosquitoes. A panel of cytokines at the time of mosquito infection was assessed in patient sera and levels compared among subjects who did and did not infect mosquitoes. Overall, blood from 43 of 99 (43%) subjects led to mosquito infection as shown by oocyst counts. Levels of IL-10, IL-6, TNF-α, and IFN-γ were significantly elevated in vivax infection and normalized 3 weeks later. The anti-inflammatory cytokine IL-10 was significantly higher in nontransmitters compared with top transmitters but was not in TNF-α and IFN-γ. The IL-10 elevation during acute malaria was associated with P. vivax transmission blocking. PMID:23478585

  6. A Malaria Vaccine Based on the Polymorphic Block 2 Region of MSP-1 that Elicits a Broad Serotype-Spanning Immune Response

    PubMed Central

    Cowan, Graeme J. M.; Creasey, Alison M.; Dhanasarnsombut, Kelwalin; Thomas, Alan W.; Remarque, Edmond J.; Cavanagh, David R.

    2011-01-01

    Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and expressed in E.coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody responses found among immune and semi-immune individuals in malaria endemic areas. The target population for such a vaccine is young children and vulnerable adults, to accelerate the acquisition of a full range of malaria protective antibodies against this polymorphic parasite antigen. PMID:22073118

  7. A malaria vaccine based on the polymorphic block 2 region of MSP-1 that elicits a broad serotype-spanning immune response.

    PubMed

    Cowan, Graeme J M; Creasey, Alison M; Dhanasarnsombut, Kelwalin; Thomas, Alan W; Remarque, Edmond J; Cavanagh, David R

    2011-01-01

    Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and expressed in E.coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody responses found among immune and semi-immune individuals in malaria endemic areas. The target population for such a vaccine is young children and vulnerable adults, to accelerate the acquisition of a full range of malaria protective antibodies against this polymorphic parasite antigen. PMID:22073118

  8. Effective High-Throughput Blood Pooling Strategy before DNA Extraction for Detection of Malaria in Low-Transmission Settings

    PubMed Central

    Nyunt, Myat Htut; Kyaw, Myat Phone; Thant, Kyaw Zin; Shein, Thinzer; Han, Soe Soe; Zaw, Ni Ni; Han, Jin-Hee; Lee, Seong-Kyun; Muh, Fauzi; Kim, Jung-Yeon; Cho, Shin-Hyeong; Lee, Sang-Eun; Yang, Eun-Jeong; Chang, Chulhun L.; Han, Eun-Taek

    2016-01-01

    In the era of (pre) elimination setting, the prevalence of malaria has been decreasing in most of the previously endemic areas. Therefore, effective cost- and time-saving validated pooling strategy is needed for detection of malaria in low transmission settings. In this study, optimal pooling numbers and lowest detection limit were assessed using known density samples prepared systematically, followed by genomic DNA extraction and nested PCR. Pooling strategy that composed of 10 samples in 1 pool, 20 µl in 1 sample, was optimal, and the parasite density as low as 2 p/µl for both falciparum and vivax infection was enough for detection of malaria. This pooling method showed effectiveness for handling of a huge number of samples in low transmission settings (<9% positive rate). The results indicated that pooling of the blood samples before DNA extraction followed by usual nested PCR is useful and effective for detection of malaria in screening of hidden cases in low-transmission settings. PMID:27417078

  9. Effective High-Throughput Blood Pooling Strategy before DNA Extraction for Detection of Malaria in Low-Transmission Settings.

    PubMed

    Nyunt, Myat Htut; Kyaw, Myat Phone; Thant, Kyaw Zin; Shein, Thinzer; Han, Soe Soe; Zaw, Ni Ni; Han, Jin-Hee; Lee, Seong-Kyun; Muh, Fauzi; Kim, Jung-Yeon; Cho, Shin-Hyeong; Lee, Sang-Eun; Yang, Eun-Jeong; Chang, Chulhun L; Han, Eun-Taek

    2016-06-01

    In the era of (pre) elimination setting, the prevalence of malaria has been decreasing in most of the previously endemic areas. Therefore, effective cost- and time-saving validated pooling strategy is needed for detection of malaria in low transmission settings. In this study, optimal pooling numbers and lowest detection limit were assessed using known density samples prepared systematically, followed by genomic DNA extraction and nested PCR. Pooling strategy that composed of 10 samples in 1 pool, 20 µl in 1 sample, was optimal, and the parasite density as low as 2 p/µl for both falciparum and vivax infection was enough for detection of malaria. This pooling method showed effectiveness for handling of a huge number of samples in low transmission settings (<9% positive rate). The results indicated that pooling of the blood samples before DNA extraction followed by usual nested PCR is useful and effective for detection of malaria in screening of hidden cases in low-transmission settings. PMID:27417078

  10. Role for the Plasmodium sporozoite-specific transmembrane protein S6 in parasite motility and efficient malaria transmission.

    PubMed

    Steinbuechel, Marion; Matuschewski, Kai

    2009-02-01

    Malaria transmission occurs by intradermal deposition of Plasmodium sporozoites during the infectious bite of a female Anopheles mosquito. After formation in midgut-associated oocysts sporozoites actively enter mosquito salivary glands and subsequently invade host hepatocytes where they transform into clinically silent liver stages. To date, two sporozoite-specific transmembrane proteins have been identified that perform vital functions in natural malaria transmission. The sporozoite invasin TRAP drives sporozoite motility and target cell entry whereas the adhesin MAEBL mediates sporozoite recognition of and attachment to salivary glands. Here, we demonstrate that the sporozoite-specific transmembrane protein S6 is required for efficient malaria transmission to the vertebrate host. Targeted deletion of S6 results in severe impairment of sporozoite gliding motility and invasion of mosquito salivary glands. During sporozoite maturation S6 expression is tightly regulated by transcriptional and translational control. We propose that S6 functions together with TRAP/MIC2 family invasins to direct fast, efficient and specific cell entry and, ultimately, life cycle progression of the malaria sporozoite. PMID:19016774

  11. How human practices have affected vector-borne diseases in the past: a study of malaria transmission in Alpine valleys

    PubMed Central

    Sérandour, Julien; Girel, Jacky; Boyer, Sebastien; Ravanel, Patrick; Lemperière, Guy; Raveton, Muriel

    2007-01-01

    Background Malaria was endemic in the Rhône-Alpes area of eastern France in the 19th century and life expectancy was particularly shortened in Alpine valleys. This study was designed to determine how the disease affected people in the area and to identify the factors influencing malaria transmission. Methods Demographic data of the 19th century were collected from death registers of eight villages of the flood-plain of the river Isère. Correlations were performed between these demographic data and reconstructed meteorological data. Archive documents from medical practitioners gave information on symptoms of ill people. Engineer reports provided information on the hydraulic project developments in the Isère valley. Results Description of fevers was highly suggestive of endemic malaria transmission in the parishes neighbouring the river Isère. The current status of anopheline mosquitoes in the area supports this hypothesis. Mean temperature and precipitation were poorly correlated with demographic data, whereas the chronology of hydrological events correlated with fluctuations in death rates in the parishes. Conclusion Nowadays, most of the river development projects involve the creation of wet areas, enabling controlled flooding events. Flood-flow risk and the re-emergence of vector-borne diseases would probably be influenced by the climate change. The message is not to forget that human disturbance of any functioning hydrosystem has often been linked to malaria transmission in the past. PMID:17727700

  12. Host cell deformability is linked to transmission in the human malaria parasite Plasmodium falciparum

    PubMed Central

    Aingaran, Mythili; Zhang, Rou; Law, Sue KaYee; Peng, Zhangli; Undisz, Andreas; Meyer, Evan; Diez-Silva, Monica; Burke, Thomas A.; Spielmann, Tobias; Lim, Chwee Teck; Suresh, Subra; Dao, Ming; Marti, Matthias

    2012-01-01

    SUMMARY Gametocyte maturation in Plasmodium falciparum is a critical step in the transmission of malaria. While the majority of parasites proliferate asexually in red blood cells, a small fraction of parasites undergo sexual conversion and mature over two weeks to become competent for transmission to a mosquito vector. Immature gametocytes sequester in deep tissues while mature stages must be able to circulate, pass the spleen and present themselves to the mosquito vector in order to complete transmission. Sequestration of asexual red blood cell stage parasites has been investigated in great detail. These studies have demonstrated that induction of cytoadherence properties through specific receptor-ligand interactions coincides with a significant increase in host cell stiffness. In contrast, the adherence and biophysical properties of gametocyte-infected red blood cells have not been studied systematically. Utilizing a transgenic line for 3D live imaging, in vitro capillary assays and 3D finite element whole cell modeling, we studied the role of cellular deformability in determining the circulatory characteristics of gametocytes. Our analysis shows that the red blood cell deformability of immature gametocytes displays an overall decrease followed by rapid restoration in mature gametocytes. Intriguingly, simulations suggest that along with deformability variations, the morphological changes of the parasite may play an important role in tissue distribution in vivo. Taken together we present a model, which suggests that mature but not immature gametocytes circulate in the peripheral blood for uptake in the mosquito blood meal and transmission to another human host thus ensuring long term survival of the parasite. PMID:22417683

  13. Using the entomological inoculation rate to assess the impact of vector control on malaria parasite transmission and elimination

    PubMed Central

    2010-01-01

    Background Prior studies have shown that annual entomological inoculation rates (EIRs) must be reduced to less than one to substantially reduce the prevalence of malaria infection. In this study, EIR values were used to quantify the impact of insecticide-treated bed nets (ITNs), indoor residual spraying (IRS), and source reduction (SR) on malaria transmission. The analysis of EIR was extended through determining whether available vector control tools can ultimately eradicate malaria. Method The analysis is based primarily on a review of all controlled studies that used ITN, IRS, and/or SR and reported their effects on the EIR. To compare EIRs between studies, the percent difference in EIR between the intervention and control groups was calculated. Results Eight vector control intervention studies that measured EIR were found: four ITN studies, one IRS study, one SR study, and two studies with separate ITN and IRS intervention groups. In both the Tanzania study and the Solomon Islands study, one community received ITNs and one received IRS. In the second year of the Tanzania study, EIR was 90% lower in the ITN community and 93% lower in the IRS community, relative to the community without intervention; the ITN and IRS effects were not significantly different. In contrast, in the Solomon Islands study, EIR was 94% lower in the ITN community and 56% lower in the IRS community. The one SR study, in Dar es Salaam, reported a lower EIR reduction (47%) than the ITN and IRS studies. All of these vector control interventions reduced EIR, but none reduced it to zero. Conclusion These studies indicate that current vector control methods alone cannot ultimately eradicate malaria because no intervention sustained an annual EIR less than one. While researchers develop new tools, integrated vector management may make the greatest impact on malaria transmission. There are many gaps in the entomological malaria literature and recommendations for future research are provided. PMID

  14. Improving malaria control in West Africa: interruption of transmission as a paradigm shift.

    PubMed

    Doumbia, Seydou O; Ndiaye, Daouda; Koita, Ousmane A; Diakité, Mahamadou; Nwakanma, Davis; Coulibaly, Mamadou; Traoré, Sekou F; Keating, Joseph; Milner, Danny A; Ndiaye, Jean-Louis; Sene, Papa Diogoye; Ahouidi, Ambroise; Dieye, Tandakha N; Gaye, Oumar; Okebe, Joseph; Ceesay, Serign J; Ngwa, Alfred; Oriero, Eniyou C; Konaté, Lassana; Sy, Ngayo; Jawara, Musa; Faye, Ousmane; Kéita, Moussa; Cissé, Moussa; Sogoba, Nafomon; Poudiougou, Belco; Diawara, Sory; Sangaré, Lansana; Coulibaly, Tinzana; Seck, Ibrahima; Abubakar, Ismaela; Gomis, Jules; Mather, Frances J; Sissako, Aliou; Diarra, Ayouba; Kandeh, Balla; Whalen, Christopher; Moyer, Brian; Nnedu, Obinna; Thiero, Oumar; Bei, Amy K; Daniels, Rachel; Miura, Kazutoyo; Long, Carole A; Fairhurst, Rick M; Duraisingh, Manoj; Muskavitch, Marc A T; D'Alessandro, Umberto; Conway, David J; Volkman, Sarah K; Valim, Clarissa; Wirth, Dyann F; Krogstad, Donald J

    2012-03-01

    With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: (1) studies of the entire population (that are not restricted to children ≤5 or ≤10 years of age), (2) study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and (3) innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases. PMID:22142790

  15. Ape malaria transmission and potential for ape-to-human transfers in Africa.

    PubMed

    Makanga, Boris; Yangari, Patrick; Rahola, Nil; Rougeron, Virginie; Elguero, Eric; Boundenga, Larson; Moukodoum, Nancy Diamella; Okouga, Alain Prince; Arnathau, Céline; Durand, Patrick; Willaume, Eric; Ayala, Diego; Fontenille, Didier; Ayala, Francisco J; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck; Paupy, Christophe

    2016-05-10

    Recent studies have highlighted the large diversity of malaria parasites infecting African great apes (subgenus Laverania) and their strong host specificity. Although the existence of genetic incompatibilities preventing the cross-species transfer may explain host specificity, the existence of vectors with a high preference for a determined host represents another possibility. To test this hypothesis, we undertook a 15-mo-long longitudinal entomological survey in two forest regions of Gabon, where wild apes live, at different heights under the canopy. More than 2,400 anopheline mosquitoes belonging to 18 species were collected. Among them, only three species of Anopheles were found infected with ape Plasmodium: Anopheles vinckei, Anopheles moucheti, and Anopheles marshallii Their role in transmission was confirmed by the detection of the parasites in their salivary glands. Among these species, An. vinckei showed significantly the highest prevalence of infection and was shown to be able to transmit parasites of both chimpanzees and gorillas. Transmission was also shown to be conditioned by seasonal factors and by the heights of capture under the canopy. Moreover, human landing catches of sylvan Anopheles demonstrated the propensity of these three vector species to feed on humans when available. Our results suggest therefore that the strong host specificity observed in the Laveranias is not linked to a specific association between the vertebrate host and the vector species and highlight the potential role of these vectors as bridge between apes and humans. PMID:27071123

  16. Use of remote sensing to identify spatial risk factors for malaria in a region of declining transmission: a cross-sectional and longitudinal community survey

    PubMed Central

    2011-01-01

    Background The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa. Further malaria control will require targeted control strategies based on evidence of risk. The objective of this study was to identify environmental risk factors for malaria transmission using remote sensing technologies to guide malaria control interventions in a region of declining burden of malaria. Methods Satellite images were used to construct a sampling frame for the random selection of households enrolled in prospective longitudinal and cross-sectional surveys of malaria parasitaemia in Southern Province, Zambia. A digital elevation model (DEM) was derived from the Shuttle Radar Topography Mission version 3 DEM and used for landscape characterization, including landforms, elevation, aspect, slope, topographic wetness, topographic position index and hydrological models of stream networks. Results A total of 768 individuals from 128 randomly selected households were enrolled over 21 months, from the end of the rainy season in April 2007 through December 2008. Of the 768 individuals tested, 117 (15.2%) were positive by malaria rapid diagnostic test (RDT). Individuals residing within 3.75 km of a third order stream were at increased risk of malaria. Households at elevations above the baseline elevation for the region were at decreasing risk of having RDT-positive residents. Households where new infections occurred were overlaid on a risk map of RDT positive households and incident infections were more likely to be located in high-risk areas derived from prevalence data. Based on the spatial risk map, targeting households in the top 80th percentile of malaria risk would require malaria control interventions directed to only 24% of the households. Conclusions Remote sensing technologies can be used to target malaria control interventions in a region of declining malaria transmission in southern Zambia, enabling a more efficient use of

  17. Malaria transmission pattern in an area selected for clinical trials in the sudanian area of senegal (west Africa).

    PubMed

    Niang, El Hadji Amadou; Touré, Aissatou; Ngom, El Hadji Malick; Konaté, Lassana; Faye, Ousmane; Diallo, Mawlouth; Dia, Ibrahima

    2013-01-01

    Malaria transmission pattern was studied in 3 villages (Toubanding, Daga Ndoup, and Keur Samba Guèye) situated within an area selected for clinical trials. The study was conducted in the rainy season from July to December 2011. The main objective of this work was to gather baseline data on malaria transmission intensity and other entomological parameters before the advent of clinical trials. Mosquitoes were collected by Human-Landing Collections (HLCs) and by pyrethrum spray catches (PSCs). Five anopheline species were collected, namely, An. arabiensis, An. gambiae, An. funestus, An. pharoensis, and An. rufipes, giving a heterogeneous distribution within the study area. The populations dynamics of the vectors varied temporarily in each village depending on the pattern of the rainy season. Transmission intensity estimated by the entomological inoculation rate (EIR) was measured in each of the three villages with the variations linked to the microecological differences between the villages. Measurements were calculated for August, September, and October and were found to vary between 4 and 30 infected bites per person over the study period with a peak intensity observed in September. These results indicate that epidemiological field trials on malaria could be conducted in this area on the basis of the differences observed with transmission intensity, micro-ecological variations, and the objectives of the trials. PMID:23476671

  18. Quantifying behavioural interactions between humans and mosquitoes: Evaluating the protective efficacy of insecticidal nets against malaria transmission in rural Tanzania

    PubMed Central

    Killeen, Gerry F; Kihonda, Japhet; Lyimo, Edith; Oketch, Fred R; Kotas, Maya E; Mathenge, Evan; Schellenberg, Joanna A; Lengeler, Christian; Smith, Thomas A; Drakeley, Chris J

    2006-01-01

    Background African malaria vectors bite predominantly indoors at night so sleeping under an Insecticide-Treated Net (ITN) can greatly reduce malaria risk. Behavioural adaptation by mosquitoes to increasing ITN coverage could allow vector mosquitoes to bite outside of peak sleeping hours and undermine efficacy of this key malaria prevention measure. Methods High coverage with largely untreated nets has been achieved in the Kilombero Valley, southern Tanzania through social marketing programmes. Direct surveys of nightly biting activity by An. gambiae Giles were conducted in the area before (1997) and after (2004) implementation of ITN promotion. A novel analytical model was applied to estimate the effective protection provided by an ITN, based on published experimental hut trials combined with questionnaire surveys of human sleeping behaviour and recorded mosquito biting patterns. Results An. gambiae was predominantly endophagic and nocturnal in both surveys: Approximately 90% and 80% of exposure occurred indoors and during peak sleeping hours, respectively. ITNs consistently conferred >70% protection against exposure to malaria transmission for users relative to non-users. Conclusion As ITN coverage increases, behavioural adaptation by mosquitoes remains a future possibility. The approach described allows comparison of mosquito biting patterns and ITN efficacy at multiple study sites and times. Initial results indicate ITNs remain highly effective and should remain a top-priority intervention. Combined with recently developed transmission models, this approach allows rapid, informative and cost-effective preliminary comparison of diverse control strategies in terms of protection against exposure before more costly and intensive clinical trials. PMID:17096840

  19. Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax.

    PubMed

    Blagborough, A M; Musiychuk, K; Bi, H; Jones, R M; Chichester, J A; Streatfield, S; Sala, K A; Zakutansky, S E; Upton, L M; Sinden, R E; Brian, I; Biswas, S; Sattabonkot, J; Yusibov, V

    2016-06-14

    Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy. PMID:27177945

  20. High mosquito burden and malaria transmission in a district of the city of Douala, Cameroon

    PubMed Central

    2012-01-01

    Background Rapid demographic growth in Douala city, Cameroon, has resulted in profound ecological and environmental changes. Although demographic changes can affect anopheline mosquito breeding sites, there is a lack of understanding about the epidemiological impact that such changes might have on vector ecology and malaria transmission. Methods A 12-month entomological study was conducted in a highly populated district of Douala called Ndogpassi. Adult mosquitoes were collected using two methods: 1) human landing catches (HLC); and 2) Centers for Disease Control and Prevention (CDC) light traps; these methods were used twice monthly from January to December 2011. Mosquito genus and species were identified with morphological and molecular diagnostic tools. The sampling efficiency of the CDC light trap and HLC were compared. Anopheles gambiae infection with Plasmodium falciparum was detected using ELISA. Susceptibility to DDT, permethrin, and deltamethrin insecticides were also determined. Results A total of 6923 mosquitoes were collected by HLC (5198) and CDC light traps (1725). There was no equivalence in the sampling efficiency between light traps and human landing catches (P > 0.01). With 51% of the total, Culex was the most common, followed by Anopheles (26.14%), Mansonia (22.7%) and Aedes (0.1%). An. gambiae ss (M form) comprised ~98% of the total anophelines collected. An. gambiae had a biting rate of 0.25 to 49.25 bites per human per night, and was the only species found to be infected with P. falciparum. A P. falciparum infection rate of 0.5% was calculated (based on enzyme-linked immunosorbent assays using the circumsporozoite surface protein). The entomological inoculation rate was estimated at 31 infective bites per annum. Insecticide susceptibility tests on An. gambiae females revealed a mortality rate of 33%, 76% and 98% for DDT, permethrin and deltamethrin, respectively. The West African kdr allele (L1014F) was detected in 38 of the 61 An. gambiae

  1. Transmission-blocking activity is determined by transmission-reducing activity and number of control oocysts in Plasmodium falciparum standard membrane-feeding assay.

    PubMed

    Miura, Kazutoyo; Swihart, Bruce J; Deng, Bingbing; Zhou, Luwen; Pham, Thao P; Diouf, Ababacar; Burton, Timothy; Fay, Michael P; Long, Carole A

    2016-07-29

    Malaria transmission-blocking vaccines (TBVs) are potentially helpful tools for malaria eradication. The standard membrane-feeding assay (SMFA) is considered one of the "gold standard" assays for TBV development. However, lack of consensus in reporting results from SMFA has made it very challenging to compare results from different studies. Two main readouts, % inhibition in mean oocyst count per mosquito (TRA) and % inhibition in prevalence of infected mosquitoes (TBA), have been used widely. In this study, we statistically modeled the oocyst data in SMFA using data from 105 independent feeding experiments including 9804 mosquitoes. The model was validated using an independent data set that included 10,790 mosquitoes from 110 feeding studies. The model delineates a relationship between TRA, the mean oocyst count in the control mosquitoes (mo-contl), and TBA. While TRA was independent from mo-contl, TBA values changed depending on mo-contl. Regardless of monoclonal or polyclonal antibodies tested, there were strong concordances between observed TBA and predicted TBA based on the model using mo-contl and observed TRA. Simulations showed that SMFA with lower true control means had increased uncertainty in TRA estimates. The strong linkage between TBA, TRA and mo-contl inspired creation of a standardized TBA, a model-based TBA standardized to a target control mean, which allows comparison across multiple feeds regardless of mo-contl. This is the first study showing that the observed TBA can be reasonably predicted by mo-contl and the TRA of the test antibody using independent experimental data. This study indicates that TRA should be used to compare results from multiple feeds with different levels of mo-contl. If a measure of TBA is desired, it is better to report standardized TBA rather than observed TBA. These recommendations support rational comparisons of results from different studies, thus benefiting future TBV development. PMID:27372156

  2. The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies

    PubMed Central

    2012-01-01

    A meeting to discuss the latest developments in the biology of sexual development of Plasmodium and transmission-control was held April 5-6, 2011, in Bethesda, MD. The meeting was sponsored by the Bill & Melinda Gates Foundation and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID) in response to the challenge issued at the Malaria Forum in October 2007 that the malaria community should re-engage with the objective of global eradication. The consequent rebalancing of research priorities has brought to the forefront of the research agenda the essential need to reduce parasite transmission. A key component of any transmission reduction strategy must be methods to attack the parasite as it passes from man to the mosquito (and vice versa). Such methods must be rationally based on a secure understanding of transmission from the molecular-, cellular-, population- to the evolutionary-levels. The meeting represented a first attempt to draw together scientists with expertise in these multiple layers of understanding to discuss the scientific foundations and resources that will be required to provide secure progress toward the design and successful implementation of effective interventions. PMID:22424474

  3. One-year delayed effect of fog on malaria transmission: a time-series analysis in the rain forest area of Mengla County, south-west China

    PubMed Central

    Tian, Linwei; Bi, Yan; Ho, Suzanne C; Liu, Wenjie; Liang, Song; Goggins, William B; Chan, Emily YY; Zhou, Shuisen; Sung, Joseph JY

    2008-01-01

    Background Malaria is a major public health burden in the tropics with the potential to significantly increase in response to climate change. Analyses of data from the recent past can elucidate how short-term variations in weather factors affect malaria transmission. This study explored the impact of climate variability on the transmission of malaria in the tropical rain forest area of Mengla County, south-west China. Methods Ecological time-series analysis was performed on data collected between 1971 and 1999. Auto-regressive integrated moving average (ARIMA) models were used to evaluate the relationship between weather factors and malaria incidence. Results At the time scale of months, the predictors for malaria incidence included: minimum temperature, maximum temperature, and fog day frequency. The effect of minimum temperature on malaria incidence was greater in the cool months than in the hot months. The fog day frequency in October had a positive effect on malaria incidence in May of the following year. At the time scale of years, the annual fog day frequency was the only weather predictor of the annual incidence of malaria. Conclusion Fog day frequency was for the first time found to be a predictor of malaria incidence in a rain forest area. The one-year delayed effect of fog on malaria transmission may involve providing water input and maintaining aquatic breeding sites for mosquitoes in vulnerable times when there is little rainfall in the 6-month dry seasons. These findings should be considered in the prediction of future patterns of malaria for similar tropical rain forest areas worldwide. PMID:18565224

  4. A Research Agenda for Malaria Eradication: Vaccines

    PubMed Central

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt malaria transmission” (VIMT), which includes not only “classical” transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented. PMID:21311586

  5. Ethical aspects of malaria control and research.

    PubMed

    Jamrozik, Euzebiusz; de la Fuente-Núñez, Vânia; Reis, Andreas; Ringwald, Pascal; Selgelid, Michael J

    2015-01-01

    Malaria currently causes more harm to human beings than any other parasitic disease, and disproportionally affects low-income populations. The ethical issues raised by efforts to control or eliminate malaria have received little explicit analysis, in comparison with other major diseases of poverty. While some ethical issues associated with malaria are similar to those that have been the subject of debate in the context of other infectious diseases, malaria also raises distinct ethical issues in virtue of its unique history, epidemiology, and biology. This paper provides preliminary ethical analyses of the especially salient issues of: (i) global health justice, (ii) universal access to malaria control initiatives, (iii) multidrug resistance, including artemisinin-based combination therapy (ACT) resistance, (iv) mandatory screening, (v) mass drug administration, (vi) benefits and risks of primaquine, and (vii) malaria in the context of blood donation and transfusion. Several ethical issues are also raised by past, present and future malaria research initiatives, in particular: (i) controlled infection studies, (ii) human landing catches, (iii) transmission-blocking vaccines, and (iv) genetically-modified mosquitoes. This article maps the terrain of these major ethical issues surrounding malaria control and elimination. Its objective is to motivate further research and discussion of ethical issues associated with malaria--and to assist health workers, researchers, and policy makers in pursuit of ethically sound malaria control practice and policy. PMID:26693920

  6. Asymptomatic Plasmodium Infections in Children in Low Malaria Transmission Setting, Southwestern Uganda1

    PubMed Central

    Roh, Michelle E.; Oyet, Caesar; Orikiriza, Patrick; Wade, Martina; Kiwanuka, Gertrude N.; Mwanga-Amumpaire, Juliet; Boum, Yap

    2016-01-01

    A survey of asymptomatic children in Uganda showed Plasmodium malariae and P. falciparum parasites in 45% and 55% of microscopy-positive samples, respectively. Although 36% of microscopy-positive samples were negative by rapid diagnostic test, 75% showed P. malariae or P. ovale parasites by PCR, indicating that routine diagnostic testing misses many non–P. falciparum malarial infections. PMID:27434741

  7. Asymptomatic Plasmodium Infections in Children in Low Malaria Transmission Setting, Southwestern Uganda(1).

    PubMed

    Roh, Michelle E; Oyet, Caesar; Orikiriza, Patrick; Wade, Martina; Kiwanuka, Gertrude N; Mwanga-Amumpaire, Juliet; Parikh, Sunil; Boum, Yap

    2016-08-01

    A survey of asymptomatic children in Uganda showed Plasmodium malariae and P. falciparum parasites in 45% and 55% of microscopy-positive samples, respectively. Although 36% of microscopy-positive samples were negative by rapid diagnostic test, 75% showed P. malariae or P. ovale parasites by PCR, indicating that routine diagnostic testing misses many non-P. falciparum malarial infections. PMID:27434741

  8. An experimental hut study to quantify the effect of DDT and airborne pyrethroids on entomological parameters of malaria transmission

    PubMed Central

    2014-01-01

    Background Current malaria vector control programmes rely on insecticides with rapid contact toxicity. However, spatial repellents can also be applied to reduce man-vector contact, which might ultimately impact malaria transmission. The aim of this study was to quantify effects of airborne pyrethroids from coils and DDT used an indoor residual spray (IRS) on entomological parameters that influence malaria transmission. Methods The effect of Transfluthrin and Metofluthrin coils compared to DDT on house entry, exit and indoor feeding behaviour of Anopheles gambiae sensu lato were measured in experimental huts in the field and in the semi-field. Outcomes were deterrence - reduction in house entry of mosquitoes; irritancy or excito-repellency – induced premature exit of mosquitoes; blood feeding inhibition and effect on mosquito fecundity. Results Transfluthrin coils, Metofluthrin coils and DDT reduced human vector contact through deterrence by 38%, 30% and 8%, respectively and induced half of the mosquitoes to leave huts before feeding (56%, 55% and 48%, respectively). Almost all mosquitoes inside huts with Metofluthrin and Transfluthrin coils and more than three quarters of mosquitoes in the DDT hut did not feed, almost none laid eggs and 67%, 72% and 70% of all mosquitoes collected from Transfluthrin, Metofluthrin and DDT huts, respectively had died after 24 hours. Conclusion This study highlights that airborne pyrethroids and DDT affect a range of anopheline mosquito behaviours that are important parameters in malaria transmission, namely deterrence, irritancy/excito-repellency and blood-feeding inhibition. These effects are in addition to significant toxicity and reduced mosquito fecundity that affect mosquito densities and, therefore, provide community protection against diseases for both users and non-users. Airborne insecticides and freshly applied DDT had similar effects on deterrence, irritancy and feeding inhibition. Therefore, it is suggested that

  9. Clinical signs and symptoms cannot reliably predict Plasmodium falciparum malaria infection in pregnant women living in an area of high seasonal transmission

    PubMed Central

    2013-01-01

    Background Malaria in pregnancy is a major public health problem in endemic countries. Though the signs and symptoms of malaria among pregnant women have been already described, clinical presentation may vary according to intensity of transmission and local perceptions. Therefore, determining common signs and symptoms among pregnant women with a malaria infection may be extremely useful to identify those in need of further investigation by rapid diagnostic test or microscopy. Methods Six hundred pregnant women attending the maternity clinic of Nanoro District Hospital, Burkina Faso were recruited, 200 with suspected clinical malaria and 400 as controls. Cases were matched with controls by gestational age and parity. Signs and symptoms were collected and a blood sample taken for rapid diagnostic test, microscopy and haemoglobin measurement. A multivariate model was used to assess the predictive value of signs and symptoms for malaria infection. Results The overall prevalence of malaria was 42.6% (256/600) while anaemia was found in 60.8% (365/600) of the women. Nearly half (49%) of the cases and 39.5% of the controls had a malaria infection (p = 0.03). The most common signs and symptoms among the cases were fever (36%,72/200), history of fever (29%,58/200) and headache (52%,104/200). The positive predictive value for fever was 53% (95% CI:41–64), history of fever 58% (95% CI:37–63) and headache 51% (95% CI:41–61). Conclusion Signs and symptoms suggestive of malaria are frequent among pregnant women living in areas of intense transmission. Common malaria symptoms are not strong predictors of infection. For a better management of malaria in pregnancy, active screening to detect and treat malaria infection early should be performed on all pregnant women attending a health facility. PMID:24373481

  10. 4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities

    PubMed Central

    Monastyrskyi, Andrii; Kyle, Dennis E.; Manetsch, Roman

    2015-01-01

    Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes will be discussed. PMID:25116582

  11. Establishing the extent of malaria transmission and challenges facing pre-elimination in the Republic of Djibouti

    PubMed Central

    2011-01-01

    Background Countries aiming for malaria elimination require a detailed understanding of the current intensity of malaria transmission within their national borders. National household sample surveys are now being used to define infection prevalence but these are less efficient in areas of exceptionally low endemicity. Here we present the results of a national malaria indicator survey in the Republic of Djibouti, the first in sub-Saharan Africa to combine parasitological and serological markers of malaria, to evaluate the extent of transmission in the country and explore the potential for elimination. Methods A national cross-sectional household survey was undertaken from December 2008 to January 2009. A finger prick blood sample was taken from randomly selected participants of all ages to examine for parasitaemia using rapid diagnostic tests (RDTs) and confirmed using Polymerase Chain Reaction (PCR). Blood spots were also collected on filter paper and subsequently used to evaluate the presence of serological markers (combined AMA-1 and MSP-119) of Plasmodium falciparum exposure. Multivariate regression analysis was used to determine the risk factors for P. falciparum infection and/or exposure. The Getis-Ord G-statistic was used to assess spatial heterogeneity of combined infections and serological markers. Results A total of 7151 individuals were tested using RDTs of which only 42 (0.5%) were positive for P. falciparum infections and confirmed by PCR. Filter paper blood spots were collected for 5605 individuals. Of these 4769 showed concordant optical density results and were retained in subsequent analysis. Overall P. falciparum sero-prevalence was 9.9% (517/4769) for all ages; 6.9% (46/649) in children under the age of five years; and 14.2% (76/510) in the oldest age group (≥ 50 years). The combined infection and/or antibody prevalence was 10.5% (550/4769) and varied from 8.1% to 14.1% but overall regional differences were not statistically significant (χ2

  12. Humoral Responses to Plasmodium falciparum Blood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa▿

    PubMed Central

    Nebie, Issa; Diarra, Amidou; Ouedraogo, Alphonse; Soulama, Issiaka; Bougouma, Edith C.; Tiono, Alfred B.; Konate, Amadou T.; Chilengi, Roma; Theisen, Michael; Dodoo, Daniel; Remarque, Ed; Bosomprah, Samuel; Milligan, Paul; Sirima, Sodiomon B.

    2008-01-01

    There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P = 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development. PMID:18070896

  13. Steps toward a globally available malaria vaccine

    PubMed Central

    Jones, Carla S.; Mayfield, Stephen P.

    2013-01-01

    Malaria is an infectious disease that threatens half of the world’s population. This debilitating disease is caused by infection from parasites of the genus Plasmodium. Insecticides, bed nets and drug therapies have lowered the prevalence and death rate associated with malaria but this disease continues to plague many populations around the world. In recent years, many organizations have suggested developing methods for a complete eradication of malaria. The most straightforward and effective method for this potential eradication will be through the development of a low-cost vaccine. To achieve eradication, it will be necessary to develop new vaccine candidates and novel systems for both the production and delivery of these vaccines. Recently, the green algae Chlamydomonas reinhardtii has been used for the recombinant expression of malaria vaccine candidates including the transmission blocking vaccine candidate Pfs48/45. Here, we discuss the potential of this research on the future development of a low-cost malaria vaccine candidate. PMID:23090388

  14. Can malaria vector control accelerate the interruption of lymphatic filariasis transmission in Africa; capturing a window of opportunity?

    PubMed Central

    2013-01-01

    Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000, and nearly all endemic countries in the Americas, Eastern Mediterranean and Asia-Pacific regions have now initiated the WHO recommended mass drug administration (MDA) campaign to interrupt transmission of the parasite. However, nearly 50% of the LF endemic countries in Africa are yet to implement the GPELF MDA strategy, which does not include vector control. Nevertheless, the recent scale up in insecticide treated /long lasting nets (ITNs/LLINs) and indoor residual spraying (IRS) for malaria control in Africa may significantly impact LF transmission because the parasite is transmitted mainly by Anopheles mosquitoes. This study examined the magnitude, geographical extent and potential impact of vector control in the 17 African countries that are yet to or have only recently started MDA. Methods National data on mosquito bed nets, ITNs/LLINs and IRS were obtained from published literature, national reports, surveys and datasets from public sources such as Demographic Health Surveys, Malaria Indicator Surveys, Multiple Indicator Cluster Surveys, Malaria Report, Roll Back Malaria and President’s Malaria Initiative websites. The type, number and distribution of interventions were summarised and mapped at sub-national level. and compared with known or potential LF distributions, and those which may be co-endemic with Loa loa and MDA is contraindicated. Results Analyses found that vector control activities had increased significantly since 2005, with a three-fold increase in ITN ownership and IRS coverage. However, coverage varied dramatically across the 17 countries; some regions reported >70% ITNs ownership and regular IRS activity, while others had no coverage in remote rural populations where the risk of LF was potentially high and co-endemic with high risk L.loa. Conclusions Despite many African countries being slow to initiate MDA for LF, the continued commitment and

  15. Malaria transmission in a rice-irrigation area in Mali, West Africa: Review of past work and new findings

    NASA Astrophysics Data System (ADS)

    Touré, M. B.; Diuk-Wasser, M. A.; Lozano-Fuentes, S.; Traoré, S.; Taylor, C. E.

    2007-12-01

    The "Office du Niger" in the Niono District of Mali oversees irrigation from a dam on the Niger River -- the largest irrigation project in Mali. The facility was first built in 1932, and now irrigates more than 55,000 hectares for rice. A large reservoir in the center of the area provides water throughout the year through a water-control system. This water-control system enables a double cropping of rice. Nearly all residents located near the irrigated areas practice rice cultivation from that irrigation during the rainy season: some of them double crop. It has been well- established that malaria transmission occurs throughout the year in the irrigated area with two peaks --- one peak in the rainy season and the second peak corresponding to irrigated cultivation that occurs in the dry season due to double cropping. The Niono area has been the subject of several intensive studies during past years. Among the findings has been that the irrigated villages experience very large numbers of mosquitoes (often in excess of 550 bites per person per night), and neighboring non-irrigated villages experience far fewer bites (ca 70 bites per person per night). Paradoxically, the rates of malaria are very much lower in the irrigated villages than in the non-irrigated ones, in spite of the numbers of mosquitoes. We have been studying villages around Niono for the past 10 years, with the hope of understanding what is responsible for the level of malaria transmission and learning how that understanding can be used to control malaria elsewhere. Our work has involved remote sensing, GIS mapping, and collections and modeling of both adult and immature mosquitoes. Recently we have been conducting social surveys as well. In this talk we review our past work and present new results about spatial patterns of vector behavior within villages situated within the irrigated areas.

  16. Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community

    PubMed Central

    Branch, OraLee; Casapia, W Martin; Gamboa, Dionicia V; Hernandez, Jean N; Alava, Freddy F; Roncal, Norma; Alvarez, Eugenia; Perez, Enrique J; Gotuzzo, Eduardo

    2005-01-01

    Background There is a low incidence of malaria in Iquitos, Peru, suburbs detected by passive case-detection. This low incidence might be attributable to infections clustered in some households/regions and/or undetected asymptomatic infections. Methods Passive case-detection (PCD) during the malaria season (February-July) and an active case-detection (ACD) community-wide survey (March) surveyed 1,907 persons. Each month, April-July, 100-metre at-risk zones were defined by location of Plasmodium falciparum infections in the previous month. Longitudinal ACD and PCD (ACP+PCD) occurred within at-risk zones, where 137 houses (573 persons) were randomly selected as sentinels, each with one month of weekly active sampling. Entomological captures were conducted in the sentinel houses. Results The PCD incidence was 0.03 P. falciparum and 0.22 Plasmodium vivax infections/person/malaria-season. However, the ACD+PCD prevalence was 0.13 and 0.39, respectively. One explanation for this 4.33 and 1.77-fold increase, respectively, was infection clustering within at-risk zones and contiguous households. Clustering makes PCD, generalized to the entire population, artificially low. Another attributable-factor was that only 41% and 24% of the P. falciparum and P. vivax infections were associated with fever and 80% of the asymptomatic infections had low-density or absent parasitaemias the following week. After accounting for asymptomatic infections, a 2.6-fold increase in ACD+PCD versus PCD was attributable to clustered transmission in at-risk zones. Conclusion Even in low transmission, there are frequent highly-clustered asymptomatic infections, making PCD an inadequate measure of incidence. These findings support a strategy of concentrating ACD and insecticide campaigns in houses adjacent to houses were malaria was detected one month prior. PMID:15975146

  17. The Dynamics of Transmission and Spatial Distribution of Malaria in Riverside Areas of Porto Velho, Rondônia, in the Amazon Region of Brazil

    PubMed Central

    Katsuragawa, Tony Hiroshi; Gil, Luiz Herman Soares; Tada, Mauro Shugiro; de Almeida e Silva, Alexandre; Costa, Joana D'Arc Neves; da Silva Araújo, Maisa; Escobar, Ana Lúcia; Pereira da Silva, Luiz Hildebrando

    2010-01-01

    The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19th and 20th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate) values. Main results: (i) malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii) asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii) vivax malaria relapses were responsible for 30% of clinical cases; (iv) malaria risk for the residents was evaluated as 20–25% for vivax and 5–7% for falciparum malaria; (v) anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi) very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by the Hydroelectric Power

  18. Long-run relative importance of temperature as the main driver to malaria transmission in Limpopo Province, South Africa: a simple econometric approach.

    PubMed

    Komen, Kibii; Olwoch, Jane; Rautenbach, Hannes; Botai, Joel; Adebayo, Adetunji

    2015-03-01

    Malaria in Limpopo Province of South Africa is shifting and now observed in originally non-malaria districts, and it is unclear whether climate change drives this shift. This study examines the distribution of malaria at district level in the province, determines direction and strength of the linear relationship and causality between malaria with the meteorological variables (rainfall and temperature) and ascertains their short- and long-run variations. Spatio-temporal method, Correlation analysis and econometric methods are applied. Time series monthly meteorological data (1998-2007) were obtained from South Africa Weather Services, while clinical malaria data came from Malaria Control Centre in Tzaneen (Limpopo Province) and South African Department of Health. We find that malaria changes and pressures vary in different districts with a strong positive correlation between temperature with malaria, r = 0.5212, and a weak positive relationship for rainfall, r = 0.2810. Strong unidirectional causality runs from rainfall and temperature to malaria cases (and not vice versa): F (1, 117) = 3.89, ρ = 0.0232 and F (1, 117) = 20.08, P < 0.001 and between rainfall and temperature, a bi-directional causality exists: F (1, 117) = 19.80; F (1,117) = 17.14, P < 0.001, respectively, meaning that rainfall affects temperature and vice versa. Results show evidence of strong existence of a long-run relationship between climate variables and malaria, with temperature maintaining very high level of significance than rainfall. Temperature, therefore, is more important in influencing malaria transmission in Limpopo Province. PMID:25515074

  19. The age patterns of severe malaria syndromes in sub-Saharan Africa across a range of transmission intensities and seasonality settings

    PubMed Central

    2010-01-01

    Background A greater understanding of the relationship between transmission intensity, seasonality and the age-pattern of malaria is needed to guide appropriate targeting of malaria interventions in different epidemiological settings. Methods A systematic literature review identified studies which reported the age of paediatric hospital admissions with cerebral malaria (CM), severe malarial anaemia (SMA), or respiratory distress (RD). Study sites were categorized into a 3 × 2 matrix of Plasmodium falciparum transmission intensity and seasonality. Probability distributions were fitted by maximum likelihood methods, and best fitting models were used to estimate median ages and to represent graphically the age-pattern of each outcome for each transmission category in the matrix. Results A shift in the burden of CM towards younger age groups was seen with increasing intensity of transmission, but this was not the case for SMA or RD. Sites with 'no marked seasonality' showed more evidence of skewed age-patterns compared to areas of 'marked seasonality' for all three severe malaria syndromes. Conclusions Although the peak age of CM will increase as transmission intensity decreases in Africa, more than 75% of all paediatric hospital admissions of severe malaria are likely to remain in under five year olds in most epidemiological settings. PMID:20939931

  20. Local prevalence and transmission of avian malaria in the Alakai Plateau of Kauai, Hawaii, U.S.A.

    PubMed

    Glad, Anouk; Crampton, Lisa H

    2015-12-01

    Avian malaria is among the most important threats to native Hawaiian forest birds. It is caused by the parasite Plasmodium relictum and is transmitted by the introduced mosquito vector Culex quinquefasciatus. Temperature increases and precipitation declines due to climate change over the last decade may be responsible for the observed recent expansion in the range and prevalence of avian malaria on the Alakai Plateau, Kauai Island. To examine the hypothesis that conditions are now favorable for transmission of malaria on the Plateau, mosquitoes were sampled with CO2 and Reiter oviposition traps at three sites (Kawaikoi, Halepa'akai, and Koke'e) on several occasions between October, 2013 and April, 2014. P. relictum infection was assessed by PCR or dissection under a microscope. We also surveyed mosquito larvae along Halepa'akai and Kawaikoi streams. We observed that Cx. quinquefasciatus is well established on the Alakai Plateau, as mosquitoes were caught on all field trips, except in April at Halepa'akai, and larvae were found throughout the year. We observed differences in adult abundance among sites and microhabitats (stream vs ridge lines). PMID:26611954

  1. Is vector body size the key to reduced malaria transmission in the irrigated region of Niono, Mali?

    PubMed

    Manoukis, Nicholas C; Touré, Mahamoudou B; Sissoko, Ibrahim; Doumbia, Seydou; Traoré, Sekou F; Diuk-Wasser, Maria A; Taylor, Charles E

    2006-09-01

    Malaria vectors can reach very high densities in villages near irrigated rice fields in Africa, leading to the expectation that malaria should be especially prevalent there. Surprisingly, this is not always the case. In Niono, Mali, villages from nonirrigated areas have higher malaria prevalence than those within the irrigated regions, which suffer from higher mosquito numbers. One hypothesis explaining this observation is that mosquitoes from irrigated fields with high densities are inefficient vectors. This could occur if higher larval densities lead to smaller mosquitoes that suffer elevated mortality. Three predictions of the hypothesis were studied. First, the effect of larval density on larval body size was measured for both Anopheles gambiae Giles and Anopheles funestus Giles. Second, the relationship between larval and adult body size was tested. Third, evidence of an effect of adult size on survivorship in both irrigated and nonirrigated villages during the wet and dry seasons was sought. There was a modest positive relationship between densities of immatures and larval size, and a strong relationship between larval and adult size. Furthermore, adult survivorship was higher in nonirrigated areas. However, there was no effect of size on survivorship between comparable samples from both the irrigated and nonirrigated zones. Although density may have a causal relationship with reduced transmission in the irrigated areas of Niono, it is unlikely to be because higher density leads to smaller body size and lower survivorship. PMID:17017214

  2. Assessment of Long-Lasting Insecticidal Nets (LLINs) on Vectors and Malaria Transmission in the Commune of Aguegues, Benin

    PubMed Central

    Modeste Gouissi, Fadéby; Salifou, Sahidou; Patrick Edorh, Aléodjrodo; Anges Yadouleton, William; Djenontin, Armel; Bio-Banganna, Sahabi; Geoffroy Augustin Gouissi, Sègbèhin; Akogbeto, Martin

    2012-01-01

    Introduction To overcome the problems of periodic re-impregnation of mosquito nets and low rates of treatment, the commune of Aguegues was chosen to evaluate the effects of Olyset® nets on malaria transmission and against An. gambiae. Methods 87 old Olyset® nets installed five years ago were identified in the village ‘Akpadon’. 10 untreated nets were installed in 10 structures of type “a bedroom and parlour” in the village ‘Akodji’. Four rooms without nets were identified in the village ‘Donoukpa’. Entomological and epidemiological evaluations were conducted during the May to October 2011. 24 sessions of capture or 2088 men-nights resulted in the capture of 30,608 mosquitoes. Results The entrance of anopheles was significantly reduced in the village with Olyset® nets. 45% of mosquitoes captured inside rooms with Olyset® nets were found dead after 24 hrs of obser-vation. Overall, parasitemia was very low in the treated village (4.52%). 18 (4.64%) cases of malaria fever were from Akpadon with 7.5% positive blade smear, 29 (10.98%) were from Akodji with 8.37% positive blade smear, and 80 (95.23%) come from Donoukpa with 38.09% positive blade smear. The Olyset® nets and untreated net were adjusted hemoglobin levels. Conclusion Olyset® net had a very high knock down effect and is an alternative in malaria control. PMID:23678454

  3. Integrated vector management targeting Anopheles darlingi populations decreases malaria incidence in an unstable transmission area, in the rural Brazilian Amazon

    PubMed Central

    2012-01-01

    Plasmodium falciparum carriers during the period of study. Conclusions There is strong evidence of association between the density of An. darlingi and the incidence of malaria in the studies sites, further highlighting the importance of this vector in malaria transmission in this region. An. darlingi susceptibility to control using ITN and IRS is likely to be high in the rural settlements studied. PMID:23088224

  4. Magnitude of Malaria and Factors among Febrile Cases in Low Transmission Areas of Hadiya Zone, Ethiopia: A Facility Based Cross Sectional Study

    PubMed Central

    Gone, Terefe Fuge; Leta, Taye Janfa

    2016-01-01

    Background Despite a remarkable decline in morbidity and mortality since the era of malaria roll back strategy, it still poses a huge challenge in Ethiopia in general and in Hadiya Zone in particular. Although, there are data from routine health management information on few indicators, there is scarcity of data showing magnitude of malaria and associated factors including knowledge and practice in the study area. Therefore, the aim of this study was to assess magnitude and factors affecting malaria in low transmission areas among febrile cases attending public health facilities in Hadiya Zone, Ethiopia. Methods A facility based cross-sectional study was conducted in Hadiya Zone from May 15 to June 15, 2014. Simple random sampling was used to select the health facility while systematic random sampling technique was used to reach febrile patients attending public health facilities. Data were collected by a pre-tested structured questionnaire containing sections of socio demographic risk factors and knowledge and prevention practices of malaria. Data were entered to Epi-Info software version 3.5.4 and exported to SPSS version 16 for descriptive and logistic regression analysis. Results One hundred six (25.8%) of participating febrile patients attending at sampled health facilities were found to have malaria by microscopy. Of which, P.vivax, P.falciparum and mixed infection accounted for 76(71. 7%), 27 (25.5%) and 3 (2.8%), respectively. History of travel to malaria endemic area, [AOR: 2.59, 95% CI: (1.24, 5.38)], not using bed net, [AOR: 4.67, 95%CI:, (2.11, 10.37)], poor practice related to malaria prevention and control, [AOR: 2.28, (95%CI: (1.10, 4.74)], poor knowledge about malaria, [AOR: 5.09,95%CI: (2.26,11.50)] and estimated distance of stagnant water near to the residence, [AOR: 3.32, (95%CI: (1.13, 9.76)] were significantly associated factors of malaria positivity in the study. Conclusion The present study revealed that malaria is still a major source of

  5. Peer-to-peer transmission of remote sensing image data using image subset block

    NASA Astrophysics Data System (ADS)

    Zhang, Feng; Hou, Zhitong; Du, Zhenhong; Liu, Renyi; Yan, Yiming

    2015-09-01

    The unprecedented amount and multiple applications of remote sensing image data have created a strong need for efficient data transmission. Commonly used in the transmission of various types of data, peer-to-peer (P2P) opens up new possibilities for the transmission of remote sensing image data. A considerable amount of work has been done toward the transmission of remote sensing data by using map tiles for fast online browsing. However, issues concerning the transmission of original image data require more volume and flexibility, which is indispensable in the application of remote sensing images. According to the spatial and band characteristics of remote sensing images, an approach using image subset blocks (ISBs) is proposed for P2P transmission of remote sensing image data. The method improves efficiency in two ways: transmitting ISBs on demand to reduce unnecessary transmission and using a P2P method to break the bandwidth bottleneck of the central server. The results of the performance evaluation reveal that compared with the traditional transmission method that uses the central server, the proposed method considerably enhances the efficiency to approach the level of general P2P file transmission.

  6. Impact of operational effectiveness of long-lasting insecticidal nets (LLINs) on malaria transmission in pyrethroid-resistant areas

    PubMed Central

    2013-01-01

    Background A dynamic study on the transmission of malaria was conducted in two areas (R+ area: Low resistance area; R+++ area: High resistance area) in the department of Plateau in South Eastern Benin, where the population is protected by Long Lasting Insecticidal Nets (LLINs). The aim of this study was to determine if the resistance of malaria vectors to insecticides has an impact on their behavior and on the effectiveness of LLINs in the reduction of malaria transmission. Methods Populations of Anopheles gambiae s.l. were sampled monthly by human landing catch in the two areas to evaluate human biting rates (HBR). Collected mosquitoes were identified morphologically and female Anopheles mosquitoes were tested for the presence of Plasmodium falciparum antigen as assessed using ELISA. The entomological inoculation rate (EIR) was also calculated (EIR = HBR x sporozoitic index [S]). We estimated the parity rate by dissecting the females of An. gambiae. Finally, window catch and spray catch were conducted in order to assess the blood feeding rate and the exophily rate of vectors. Results After 6 months of tracking the mosquito's behavior in contact with the LLINs (Olyset) in R+++ and R+ areas, the entomological indicators of the transmission of malaria (parity rate and sporozoitic index) were similar in the two areas. Also, An. gambiae populations showed the same susceptibility to P. falciparum in both R+ and R+++ areas. The EIR and the exophily rate are higher in R+ area than in R+++ area. But the blood-feeding rate is lower in R+ area comparing to R+++. Conclusion The highest entomological inoculation rate observed in R+ area is mostly due to the strong aggressive density of An. gambiae recorded in one of the study localities. On the other hand, the highest exophily rate and the low blood-feeding rate recorded in R+ area compared to R+++ area are not due to the resistance status of An. gambiae, but due to the differences in distribution and availability of

  7. Remote sensing of anophelines in rice-cropping villages in Mali: Patterns of vector abundance and malaria transmission

    NASA Astrophysics Data System (ADS)

    Diuk Wasser, Maria Ana

    The explosive population growth and widespread urbanization in Africa requires a significant increase in food production. Crop irrigation is therefore expected to increase in the future, although it is often blamed for aggravating the health risk of local communities---by providing habitats suitable for mosquitoes vectors of malaria (Anopheles gambiae s.l. and An. funestus in our study area) and other diseases. An epidemiological paradox sometimes occurs, however, when an increase in vector numbers is accompanied by a reduction of the risk of infection, due to a reduction in mosquito longevity and of their tendency to bite human (vs. animals). The objective of this dissertation was to determine how agricultural patterns mapped using satellite data affected vector densities and malaria transmission parameters in 18 rice-cropping villages in Mali. I used a combination of optical (Landsat ETM+) and synthetic aperture radar (ERS-2 SAR). Using Landsat data, rice was distinguished from other land uses with 98% accuracy and rice cohorts were discriminated with 84% accuracy (three classes) or 94% (two classes). ERS-2 SAR backscatter was correlated with the height and biomass of rice plants and was therefore useful to distinguish among rice growth stages. As in previous studies, the early vegetative stage was associated with higher larval production. SAR was further able to distinguish between agronomic practices linked to high and low-production within those early stages. The landcover maps were integrated with archived data on adult and larval anopheline densities and malaria transmission parameters. The area of several landcovers explained up to 89% of the variability in mosquito numbers. The maximum correlation was obtained when landcover was measured in a 1-km buffer area. Vector density was negatively associated to parity and anthropophilic rates. An. gambiae showed higher vectorial capacity (VC) than An. funestus , with seasonal variations. Peak VC for both species

  8. Potential threat of malaria epidemics in a low transmission area, as exemplified by São Tomé and Príncipe

    PubMed Central

    2010-01-01

    Background Plasmodium falciparum is the major cause of malaria infection in the island of São Tomé, in the Republic of São Tomé and Príncipe (STP), with an incidence of 40 - 50% before 2004. Since 2004, through the coordination of the Ministry of Health of STP and their Centro Nacional de Endemias (CNE), an integrated malaria control programme has been intensively deployed on the island of São Tomé. Malaria morbidity and mortality decreased by 95% after three years of effective intervention. In the low transmission settings, however, malaria seasonal fluctuation can be a potential problem directly related to epidemics if ongoing control measures are interrupted. Studies on a number of associated factors with malaria epidemics and the measures taken to respond to outbreaks are presented. Methods The integrated malaria control programme included indoor residual spraying (IRS), long-lasting insecticidal nets (LLINs), intermittent preventive therapy for pregnant women, as well as early diagnosis and prompt treatment with artemisinin-based combination therapy (ACT). Regular implementation of an island-wide IRS programme was carried out yearly in 2004-2007, and enhanced throughout the island in 2009. Malaria incidence and prevalence were estimated based on passive case detection and mass screening, respectively. Slide positivity rates were used for monitoring the beginning of a malaria epidemic or a seasonal peak. Results A steep decline of ca. 95% of malaria morbidity and mortality was observed between 2004 and 2008 with use of the combined control methods. Malaria incidence was 2.0%, 1.5%, and 3.0% for 2007, 2008, and 2009, respectively. In April 2008, a cross-sectional country-wide surveillance showed malaria prevalence of 3.5%, of which 95% cases were asymptomatic carriers. Only 50% of asymptomatic carriers were cured with ACT treatment, while 90% of the symptomatic patients were cured by ACT treatment as confirmed with a follow up study. Malaria morbidity

  9. Intraspecific chromosomal polymorphism in the Anopheles gambiae complex as a factor affecting malaria transmission in the Kisumu area of Kenya.

    PubMed

    Petrarca, V; Beier, J C

    1992-02-01

    The paracentric inversion polymorphisms of Anopheles gambiae and An. arabiensis populations in the Kisumu area of western Kenya were studied in relation to parameters of Plasmodium falciparum transmission. Anopheles gambiae (n = 1,387) was polymorphic for inversions b on chromosomal arm 2R and a on arm 2L, with frequencies of the inverted arrangements of 17% and 43%, respectively. Anopheles arabiensis (n = 484) was polymorphic for inversion b on chromosomal arm 2R and a on 3R, with frequencies of the inverted arrangements of 58% and 5%, respectively. Observed karyotypic frequencies did not deviate from Hardy-Weinberg equilibrium, indicating a condition of panmixia (i.e., random mating) for both species. The overall degree of intraspecific polymorphism was low, confirming findings from other zones of East Africa. No significant differences in inversion frequencies of either An. gambiae or An. arabiensis were observed, either between collecting sites or between similar sampling periods of consecutive years. At the same time, a stable, significant two-fold difference in Plasmodium infection rates was detected among An. gambiae carriers of different inversion karyotypes on chromosome 2. A significant non-uniform distribution of human- and bovid-fed specimens was also detected among the carriers of different 2Rb inversion karyotypes in indoor resting An. arabiensis. Relationships among inversion karyotypes of the two major malaria vectors in the An. gambiae complex and key factors affecting malaria transmission intensity emphasize that intraspecific variation could contribute significantly to the diversity and stability of malaria vectorial systems in Africa. PMID:1539757

  10. Geographic coincidence of increased malaria transmission hazard and vulnerability occurring at the periphery of two Tanzanian villages

    PubMed Central

    2013-01-01

    Background The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Methods Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran’s I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. Results For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. Conclusion The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and

  11. Assessing the potential impact and uncertainty of climate, land use change and demographic trends on malaria transmission in Africa by 2050.

    NASA Astrophysics Data System (ADS)

    Tompkins, Adrian; Caporaso, Luca; Colon-Gonzalez, Felipe

    2014-05-01

    Previous analyses of data has shown that in addition to variability and longer term trends in climate variables, both land use change (LUC) and population mobility and urbanisation trends can impact malaria transmission intensities and socio-economic burden. With the new regional VECTRI dynamical malaria model it is now possible to examine these in an integrated modelling framework. Using 5 global climate models which were bias corrected using the WATCH data for the recent ISIMIP project, the four Representative Concentration Pathways (RCP), population projections disaggregated from the Shared Socioeconomic Pathways (SSP) and Land use change from the HYDE model output used in the CMIP5 process, we construct a multi-member ensemble of malaria transmission intensity projections for 2050. The ensemble integrations indicate that climate has the leading impact on malaria changes, but that population growth and urbanisation can offset the effect of climate locally. LUC impacts can also be significant on the local scale but their assessment is highly uncertain and only indicative in this study. It is argued that the study should be repeated with a range of malaria models or VECTRI configurations in order to assess the additional uncertainty due to the malaria model assumptions.

  12. Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity.

    PubMed

    Bowman, Natalie M; Juliano, Jonathan J; Snider, Cynthia J; Kharabora, Oksana; Meshnick, Steven R; Vulule, John; John, Chandy C; Moormann, Ann M

    2016-09-01

    Naturally acquired immunity to Plasmodium falciparum presents a changing landscape as malaria control programs and vaccine initiatives are implemented. Determining which immunologic indicators remain surrogates of past infection, as opposed to mediators of protection, led us to compare stability of immune responses across regions with divergent malaria transmission intensities. A repeat cross-sectional study of Kenyan children from a malaria-holoendemic area and an epidemic-prone area was used to examine longitudinal antibody and interferon-gamma (IFN-γ) responses to the 3D7 and FVO variants of merozoite surface protein 1 (MSP1). Antibodies to MSP1 were common in both study populations and did not significantly wane over a 21-month time period. IFN-γ responses were less frequent and rapidly disappeared in children after a prolonged period of no malaria transmission. Antibody and IFN-γ responses rarely correlated with each other; however, MSP1-specific IFN-γ response correlated with lack of concurrent P. falciparum parasitemia of the same genotype, though only statistically significantly in the malaria-holoendemic region (odds ratio = 0.31, 95% confidence interval = 0.12-0.84). This study affirms that antimalarial antibodies are informative for evaluation of history of malaria exposure within individuals, whereas cell-mediated immunity, though short lived under natural exposure conditions, might provide an assessment of recent infection and protection from parasitemia. PMID:27481054

  13. The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro.

    PubMed

    Sala, K A; Nishiura, H; Upton, L M; Zakutansky, S E; Delves, M J; Iyori, M; Mizutani, M; Sinden, R E; Yoshida, S; Blagborough, A M

    2015-01-01

    Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical. PMID:25454088

  14. Field Evaluation of a Push-Pull System to Reduce Malaria Transmission

    PubMed Central

    Menger, David J.; Omusula, Philemon; Holdinga, Maarten; Homan, Tobias; Carreira, Ana S.; Vandendaele, Patrice; Derycke, Jean-Luc; Mweresa, Collins K.; Mukabana, Wolfgang Richard; van Loon, Joop J. A.; Takken, Willem

    2015-01-01

    Malaria continues to place a disease burden on millions of people throughout the tropics, especially in sub-Saharan Africa. Although efforts to control mosquito populations and reduce human-vector contact, such as long-lasting insecticidal nets and indoor residual spraying, have led to significant decreases in malaria incidence, further progress is now threatened by the widespread development of physiological and behavioural insecticide-resistance as well as changes in the composition of vector populations. A mosquito-directed push-pull system based on the simultaneous use of attractive and repellent volatiles offers a complementary tool to existing vector-control methods. In this study, the combination of a trap baited with a five-compound attractant and a strip of net-fabric impregnated with micro-encapsulated repellent and placed in the eaves of houses, was tested in a malaria-endemic village in western Kenya. Using the repellent delta-undecalactone, mosquito house entry was reduced by more than 50%, while the traps caught high numbers of outdoor flying mosquitoes. Model simulations predict that, assuming area-wide coverage, the addition of such a push-pull system to existing prevention efforts will result in up to 20-fold reductions in the entomological inoculation rate. Reductions of such magnitude are also predicted when mosquitoes exhibit a high resistance against insecticides. We conclude that a push-pull system based on non-toxic volatiles provides an important addition to existing strategies for malaria prevention. PMID:25923114

  15. Inhibitory and blocking monoclonal antibody epitopes on merozoite surface protein 1 of the malaria parasite Plasmodium falciparum.

    PubMed

    Uthaipibull, C; Aufiero, B; Syed, S E; Hansen, B; Guevara Patiño, J A; Angov, E; Ling, I T; Fegeding, K; Morgan, W D; Ockenhouse, C; Birdsall, B; Feeney, J; Lyon, J A; Holder, A A

    2001-04-13

    binding for all the different antibodies could be distinguished. The incorporation of several specific amino acid changes enabled the design of proteins that bound inhibitory but not blocking antibodies. These may be suitable for the development of MSP-1-based vaccines against malaria. PMID:11292349

  16. The Effect of Indoor Residual Spraying on the Prevalence of Malaria Parasite Infection, Clinical Malaria and Anemia in an Area of Perennial Transmission and Moderate Coverage of Insecticide Treated Nets in Western Kenya

    PubMed Central

    Gimnig, John E.; Otieno, Peter; Were, Vincent; Marwanga, Doris; Abong’o, Daisy; Wiegand, Ryan; Williamson, John; Wolkon, Adam; Zhou, Ying; Bayoh, M. Nabie; Lobo, Neil F.; Laserson, Kayla; Kariuki, Simon; Hamel, Mary J.

    2016-01-01

    Background Insecticide treated nets (ITNs) and indoor residual spraying (IRS) have been scaled up for malaria prevention in sub-Saharan Africa. However, there are few studies on the benefit of implementing IRS in areas with moderate to high coverage of ITNs. We evaluated the impact of an IRS program on malaria related outcomes in western Kenya, an area of intense perennial malaria transmission and moderate ITN coverage (55–65% use of any net the previous night). Methods The Kenya Division of Malaria Control, with support from the US President’s Malaria Initiative, conducted IRS in one lowland endemic district with moderate coverage of ITNs. Surveys were conducted in the IRS district and a neighboring district before IRS, after one round of IRS in July-Sept 2008 and after a second round of IRS in April-May 2009. IRS was conducted with pyrethroid insecticides. At each survey, 30 clusters were selected for sampling and within each cluster, 12 compounds were randomly selected. The primary outcomes measured in all residents of selected compounds included malaria parasitemia, clinical malaria (P. falciparum infection plus history of fever) and anemia (Hb<8) of all residents in randomly selected compounds. At each survey round, individuals from the IRS district were matched to those from the non-IRS district using propensity scores and multivariate logistic regression models were constructed based on the matched dataset. Results At baseline and after one round of IRS, there were no differences between the two districts in the prevalence of malaria parasitemia, clinical malaria or anemia. After two rounds of IRS, the prevalence of malaria parasitemia was 6.4% in the IRS district compared to 16.7% in the comparison district (OR = 0.36, 95% CI = 0.22–0.59, p<0.001). The prevalence of clinical malaria was also lower in the IRS district (1.8% vs. 4.9%, OR = 0.37, 95% CI = 0.20–0.68, p = 0.001). The prevalence of anemia was lower in the IRS district but only in children

  17. Combined DNA extraction and antibody elution from filter papers for the assessment of malaria transmission intensity in epidemiological studies

    PubMed Central

    2013-01-01

    Background Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited. Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution. Methods Filter paper blood spots were collected as part of a large cross-sectional survey in the Kenyan highlands. DNA was extracted using a saponin/chelex method. The eluate of the first wash during the DNA extraction process was used for antibody detection and compared with previously validated antibody elution procedures. Antibody elution efficiency was assessed by total IgG ELISA for malaria antigens apical membrane antigen-1 (AMA-1) and merozoite-surface protein-1 (MSP-142). The sensitivity of nested 18S rRNA and cytochrome b PCR assays and the impact of doubling filter paper material for PCR sensitivity were determined. The distribution of cell material and antibodies throughout filter paper blood spots were examined using luminescent and fluorescent reporter assays. Results Antibody levels measured after the combined antibody/DNA extraction technique were strongly correlated to those measured after standard antibody elution (p < 0.0001). Antibody levels for both AMA-1 and MSP-142 were generally slightly lower (11.3-21.4%) but age-seroprevalence patterns were indistinguishable. The proportion of parasite positive samples ranged from 12.9% to 19.2% in the different PCR assays. Despite strong agreement between outcomes of different PCR assays, none of the assays detected all parasite-positive individuals. For all assays doubling filter paper material for DNA extraction increased sensitivity. The concentration of cell and antibody material was not

  18. Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens.

    PubMed

    Juliano, Jonathan J; Parobek, Christian M; Brazeau, Nicholas F; Ngasala, Billy; Randrianarivelojosia, Milijaona; Lon, Chanthap; Mwandagalirwa, Kashamuka; Tshefu, Antoinette; Dhar, Ravi; Das, Bidyut K; Hoffman, Irving; Martinson, Francis; Mårtensson, Andreas; Saunders, David L; Kumar, Nirbhay; Meshnick, Steven R

    2016-01-01

    Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens. PMID:26503281

  19. Population diversity and antibody selective pressure to Plasmodium falciparum MSP1 block2 locus in an African malaria-endemic setting

    PubMed Central

    2009-01-01

    Background Genetic evidence for diversifying selection identified the Merozoite Surface Protein1 block2 (PfMSP1 block2) as a putative target of protective immunity against Plasmodium falciparum. The locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission is intense and perennial. Results Family distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. Seroreactivity to K1-, Mad20- and R033 families correlated with the relative family genotype distribution within the village. Antibody specificity remained unchanged with cumulated exposure to an increasingly large

  20. A cluster-randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania

    PubMed Central

    2011-01-01

    Background Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission, the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention. The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania. Methods In a cluster-randomized trial in four villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over three days. Intervention and control clusters were 1km apart; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation. Passive case detection was done for the entire cohort and active case detection in 149 children aged 1-10 year from the intervention arm and 143 from the control arm. Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period. Results The coverage rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by molecular detection methods was 2.2-2.7% prior to the intervention and undetectable during follow-up in both the control and intervention clusters. None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities. Three clinical malaria episodes occurred in the intervention (n = 1) and control clusters (n = 2). Conclusions

  1. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites.

    PubMed

    Absalon, Sabrina; Robbins, Jonathan A; Dvorin, Jeffrey D

    2016-01-01

    Blood-stage replication of the human malaria parasite Plasmodium falciparum occurs via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. Here we identify a parasite protein, which we name P. falciparum Merozoite Organizing Protein (PfMOP), as essential for cytokinesis of blood-stage parasites. We show that, following PfMOP knockdown, parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While organelles develop normally, the structural scaffold of daughter parasites, the inner membrane complex (IMC), fails to form in this agglomerate causing flawed segmentation. In PfMOP-deficient gametocytes, the IMC formation defect causes maturation arrest with aberrant morphology and death. Our results provide insight into the mechanisms of replication and maturation of malaria parasites. PMID:27121004

  2. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites

    PubMed Central

    Absalon, Sabrina; Robbins, Jonathan A.; Dvorin, Jeffrey D.

    2016-01-01

    Blood-stage replication of the human malaria parasite Plasmodium falciparum occurs via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. Here we identify a parasite protein, which we name P. falciparum Merozoite Organizing Protein (PfMOP), as essential for cytokinesis of blood-stage parasites. We show that, following PfMOP knockdown, parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While organelles develop normally, the structural scaffold of daughter parasites, the inner membrane complex (IMC), fails to form in this agglomerate causing flawed segmentation. In PfMOP-deficient gametocytes, the IMC formation defect causes maturation arrest with aberrant morphology and death. Our results provide insight into the mechanisms of replication and maturation of malaria parasites. PMID:27121004

  3. Intriguing transmission electron microscopy images observed for perpendicularly oriented cylindrical microdomains of block copolymers

    NASA Astrophysics Data System (ADS)

    Ohnogi, Hiroshi; Isshiki, Toshiyuki; Sasaki, Sono; Sakurai, Shinichi

    2014-08-01

    Intriguing images of dislocation structures were observed by the transmission electron microscopy (TEM) technique for hexagonally packed cylindrical microdomains in a block copolymer (polystyrene-block-polyethylenebutylene-block-polystyrene triblock copolymer) film. The polystyrene (PS) cylinders were embedded in the polyethylenebutylene (PEB) matrix and oriented perpendicular to the surface of the thin section for the TEM observations. In order to understand such strange dislocation structures, we applied an image processing technique using two-dimensional Fourier transform (FT) and inverse Fourier transform (IFT) methods. It was found that these intriguing images were not ascribed to real dislocation structures but were fake ones due to the moiré effect caused by the overlapping of hexagons with a slightly mismatched orientation. Furthermore, grain boundaries in the ultrathin section can be identified by image processing using FT and IFT methods.Intriguing images of dislocation structures were observed by the transmission electron microscopy (TEM) technique for hexagonally packed cylindrical microdomains in a block copolymer (polystyrene-block-polyethylenebutylene-block-polystyrene triblock copolymer) film. The polystyrene (PS) cylinders were embedded in the polyethylenebutylene (PEB) matrix and oriented perpendicular to the surface of the thin section for the TEM observations. In order to understand such strange dislocation structures, we applied an image processing technique using two-dimensional Fourier transform (FT) and inverse Fourier transform (IFT) methods. It was found that these intriguing images were not ascribed to real dislocation structures but were fake ones due to the moiré effect caused by the overlapping of hexagons with a slightly mismatched orientation. Furthermore, grain boundaries in the ultrathin section can be identified by image processing using FT and IFT methods. Electronic supplementary information (ESI) available. See DOI: 10.1039/c

  4. The impact of the expansion of urban vegetable farming on malaria transmission in major cities of Benin

    PubMed Central

    2010-01-01

    Background Urban agricultural practices are expanding in several cities of the Republic of Benin. This study aims to assess the impact of such practices on transmission of the malaria parasite in major cities of Benin. Method A cross sectional entomological study was carried out from January to December 2009 in two vegetable farming sites in southern Benin (Houeyiho and Acron) and one in the northern area (Azèrèkè). The study was based on sampling of mosquitoes by Human Landing Catches (HLC) in households close to the vegetable farms and in others located far from the farms. Results During the year of study, 71,678 female mosquitoes were caught by HLC of which 25% (17,920/71,678) were Anopheles species. In the areas surveyed, the main malaria parasite, Plasmodium falciparum was transmitted in the south by Anopheles gambiae s.s. Transmission was high during the two rainy seasons (April to July and October to November) but declined in the two dry seasons (December to March and August to September). In the north, transmission occurred from June to October during the rainy season and was vehicled by two members of the An. gambiae complex: Anopheles gambiae s.s. (98%) and Anopheles arabiensis (2%). At Houeyiho, Acron and Azèrèkè, the Entomological Inoculation Rates (EIRs) and the Human Biting Rates (HBRs) were significantly higher during the dry season in Households Close to Vegetable Farms (HCVF) than in those located far from the vegetable areas (HFVF) (p < 0.05.). However, there were no significant differences in HBRs or EIRs between HCFV and HFVF during the rainy seasons at these sites (p > 0.05). The knock-down resistance (kdr) mutation was the main resistance mechanism detected at high frequency (0.86 to 0.91) in An. gambiae s.l. at all sites. The ace-1R mutation was also found but at a very low frequency (< 0.1). Conclusion These findings showed that communities living close to vegetable farms are permanently exposed to malaria throughout the year, whereas

  5. The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial

    PubMed Central

    Bradley, John; Knight, Philip; Stone, William; Osoti, Victor; Makori, Euniah; Owaga, Chrispin; Odongo, Wycliffe; China, Pauline; Shagari, Shehu; Doumbo, Ogobara K.; Sauerwein, Robert W.; Kariuki, Simon; Drakeley, Chris; Stevenson, Jennifer; Cox, Jonathan

    2016-01-01

    Background Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities. Methods and Findings Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June–6 July 2012) and 16 wk (21 August–10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI −1.3 to 21.7%) inside hotspots 8 wk post

  6. Giant-enhancement of extraordinary optical transmission through nanohole arrays blocked by plasmonic gold mushroom caps

    NASA Astrophysics Data System (ADS)

    Zhang, Qing; Hu, Pidong; Liu, Chengpu

    2015-01-01

    An improved plasmonic hole array nanostructure model with the holes blocked by gold mushroom caps is proposed and it can realize a giant transmission with efficiency up to 65%, 182% larger than the unblocked nanohole array, due to the strong coupling between caps and holes, which plays the role of a cavity antenna. Moreover, the numerical investigation confirms that it provides more consistency with the practical experimental situations, than the nanodisk model instead. As expected, the light transmission sensitively depends on the geometric parameters of this new nanostructure; as the cap-hole's gap or cap's diameter vary, there always exists an optimal transmission efficiency. More interesting is that the corresponding optimal wavelength decreases with the gap's increment or the diameter's decrement, particularly in an exponential decaying way, and the decay rate is obviously influenced by the cap's parameters.

  7. Predictability of Malaria Transmission Intensity in the Mpumalanga Province, South Africa, Using Land Surface Climatology and Autoregressive Analysis

    NASA Technical Reports Server (NTRS)

    Grass, David; Jasinski, Michael F.; Govere, John

    2003-01-01

    There has been increasing effort in recent years to employ satellite remotely sensed data to identify and map vector habitat and malaria transmission risk in data sparse environments. In the current investigation, available satellite and other land surface climatology data products are employed in short-term forecasting of infection rates in the Mpumalanga Province of South Africa, using a multivariate autoregressive approach. The climatology variables include precipitation, air temperature and other land surface states computed by the Off-line Land-Surface Global Assimilation System (OLGA) including soil moisture and surface evaporation. Satellite data products include the Normalized Difference Vegetation Index (NDVI) and other forcing data used in the Goddard Earth Observing System (GEOS-1) model. Predictions are compared to long- term monthly records of clinical and microscopic diagnoses. The approach addresses the high degree of short-term autocorrelation in the disease and weather time series. The resulting model is able to predict 11 of the 13 months that were classified as high risk during the validation period, indicating the utility of applying antecedent climatic variables to the prediction of malaria incidence for the Mpumalanga Province.

  8. Mosquito immune responses and malaria transmission: lessons from insect model systems and implications for vertebrate innate immunity and vaccine development.

    PubMed

    Barillas-Mury, C; Wizel, B; Han, Y S

    2000-06-01

    The introduction of novel biochemical, genetic, molecular and cell biology tools to the study of insect immunity has generated an information explosion in recent years. Due to the biodiversity of insects, complementary model systems have been developed. The conceptual framework built based on these systems is used to discuss our current understanding of mosquito immune responses and their implications for malaria transmission. The areas of insect and vertebrate innate immunity are merging as new information confirms the remarkable extent of the evolutionary conservation, at a molecular level, in the signaling pathways mediating these responses in such distant species. Our current understanding of the molecular language that allows the vertebrate innate immune system to identify parasites, such as malaria, and direct the acquired immune system to mount a protective immune response is very limited. Insect vectors of parasitic diseases, such as mosquitoes, could represent excellent models to understand the molecular responses of epithelial cells to parasite invasion. This information could broaden our understanding of vertebrate responses to parasitic infection and could have extensive implications for anti-malarial vaccine development. PMID:10802234

  9. Spatial heterogeneity and temporal evolution of malaria transmission risk in Dakar, Senegal, according to remotely sensed environmental data

    PubMed Central

    2010-01-01

    associated with An. arabiensis densities in Dakar urban setting, which allowed to generate malaria transmission risk maps. The evolution of the risk was quantified, and the results indicated there are benefits of urbanization in Dakar, since the proportion of the low risk population increased while urbanization progressed. PMID:20815867

  10. Antibody specificities of children living in a malaria endemic area to inhibitory and blocking epitopes on MSP-1 19 of Plasmodium falciparum.

    PubMed

    Omosun, Y O; Adoro, S; Anumudu, C I; Odaibo, A B; Uthiapibull, C; Holder, A A; Nwagwu, M; Nwuba, R I

    2009-03-01

    Merozoite surface protein-1(19) (MSP-1(19)) specific antibodies which include processing inhibitory, blocking and neutral antibodies have been identified in individuals exposed to Plasmodium falciparum. Here we intend to look at the effect of single and multiple amino acid substitutions of MSP-1(19) on the recognition by polyclonal antibodies from children living in Igbo-Ora, Nigeria. This would provide us with information on the possibility of eliciting mainly processing inhibitory antibodies with a recombinant MSP-1(19) vaccine. Blood was collected from children in the rainy season and binding of anti-MSP-1(19) antibodies to modified mutants of MSP-1(19) was analysed by ELISA. The MSP-1(19) mutant proteins with single substitutions at positions 22 (Leu-->Arg), 43 (Glu-->Leu) and 53 (Asn-->Arg) and the MSP-1(19) mutant protein with multiple substitutions at positions 27+31+34+43 (Glu-->Tyr, Leu-->Arg, Tyr-->Ser, Glu-->Leu); which had inhibitory epitopes; had the highest recognition. Children recognised both sets of mutants with different age groups having different recognition levels. The percentage of malaria positive individuals (32-80%) with antibodies that bound to the mutants MSP-1(19) containing epitopes that recognise only processing inhibitory and not blocking antibodies, were significantly different from those with antibodies that did not bind to these mutants (21-28%). The amino acid substitutions that abolished the binding of blocking antibodies without affecting the binding of inhibitory antibodies are of particular interest in the design of MSP-1(19) based malaria vaccines. Although these MSP-1(19) mutants have not been found in natural population, their recognition by polyclonal antibodies from humans naturally infected with malaria is very promising for the future use of MSP-1(19) mutants in the design of a malaria vaccine. PMID:19081386

  11. Defining Falciparum-Malaria-Attributable Severe Febrile Illness in Moderate-to-High Transmission Settings on the Basis of Plasma PfHRP2 Concentration

    PubMed Central

    Hendriksen, Ilse C. E.; White, Lisa J.; Veenemans, Jacobien; Mtove, George; Woodrow, Charles; Amos, Ben; Saiwaew, Somporn; Gesase, Samwel; Nadjm, Behzad; Silamut, Kamolrat; Joseph, Sarah; Chotivanich, Kesinee; Day, Nicholas P. J.; von Seidlein, Lorenz; Verhoef, Hans; Reyburn, Hugh; White, Nicholas J.; Dondorp, Arjen M.

    2013-01-01

    Background. In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects the total body parasite burden. We aimed to define the malaria-attributable fraction of severe febrile illness, using the distributions of plasma P. falciparum HRP2 (PfHRP2) concentrations from parasitemic children with different clinical presentations. Methods. Plasma samples were collected from and peripheral blood slides prepared for 1435 children aged 6−60 months in communities and a nearby hospital in northeastern Tanzania. The study population included children with severe or uncomplicated malaria, asymptomatic carriers, and healthy control subjects who had negative results of rapid diagnostic tests. The distributions of plasma PfHRP2 concentrations among the different groups were used to model severe malaria-attributable disease. Results. The plasma PfHRP2 concentration showed a close correlation with the severity of infection. PfHRP2 concentrations of >1000 ng/mL denoted a malaria-attributable fraction of severe disease of 99% (95% credible interval [CI], 96%–100%), with a sensitivity of 74% (95% CI, 72%–77%), whereas a concentration of <200 ng/mL denoted severe febrile illness of an alternative diagnosis in >10% (95% CI, 3%–27%) of patients. Bacteremia was more common among patients in the lowest and highest PfHRP2 concentration quintiles. Conclusions. The plasma PfHRP2 concentration defines malaria-attributable disease and distinguishes severe malaria from coincidental parasitemia in African children in a moderate-to-high transmission setting. PMID:23136222

  12. Imaging-Based High-Throughput Screening Assay To Identify New Molecules with Transmission-Blocking Potential against Plasmodium falciparum Female Gamete Formation

    PubMed Central

    Miguel-Blanco, Celia; Lelièvre, Joël; Delves, Michael J.; Bardera, Ana I.; Presa, Jesús L.; López-Barragán, María José; Ruecker, Andrea; Marques, Sara; Sinden, Robert E.

    2015-01-01

    In response to a call for the global eradication of malaria, drug discovery has recently been extended to identify compounds that prevent the onward transmission of the parasite, which is mediated by Plasmodium falciparum stage V gametocytes. Lately, metabolic activity has been used in vitro as a surrogate for gametocyte viability; however, as gametocytes remain relatively quiescent at this stage, their ability to undergo onward development (gamete formation) may be a better measure of their functional viability. During gamete formation, female gametocytes undergo profound morphological changes and express translationally repressed mRNA. By assessing female gamete cell surface expression of one such repressed protein, Pfs25, as the readout for female gametocyte functional viability, we developed an imaging-based high-throughput screening (HTS) assay to identify transmission-blocking compounds. This assay, designated the P. falciparum female gametocyte activation assay (FGAA), was scaled up to a high-throughput format (Z′ factor, 0.7 ± 0.1) and subsequently validated using a selection of 50 known antimalarials from diverse chemical families. Only a few of these agents showed submicromolar 50% inhibitory concentrations in the assay: thiostrepton, methylene blue, and some endoperoxides. To determine the best conditions for HTS, a robustness test was performed with a selection of the GlaxoSmithKline Tres Cantos Antimalarial Set (TCAMS) and the final screening conditions for this library were determined to be a 2 μM concentration and 48 h of incubation with gametocytes. The P. falciparum FGAA has been proven to be a robust HTS assay faithful to Plasmodium transmission-stage cell biology, and it is an innovative useful tool for antimalarial drug discovery which aims to identify new molecules with transmission-blocking potential. PMID:25801574

  13. Rapid Response to Selection, Competitive Release and Increased Transmission Potential of Artesunate-Selected Plasmodium chabaudi Malaria Parasites

    PubMed Central

    Pollitt, Laura C.; Huijben, Silvie; Sim, Derek G.; Salathé, Rahel M.; Jones, Matthew J.; Read, Andrew F.

    2014-01-01

    The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited. Whether slower clearance rates represent true resistance, and how this provides a selective advantage for parasites is uncertain. Here, we show that Plasmodium chabaudi malaria parasites selected for resistance to artesunate (an artemisinin derivative) through a step-wise increase in drug dose evolved slower clearance rates extremely rapidly. In single infections, these slower clearance rates, similar to those seen in the field, provided fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. In mixed infections, removal of susceptible parasites by drug treatment led to substantial increases in the densities and transmission potential of resistant parasites (competitive release). Our results demonstrate the double-edged sword for resistance management: in our initial selection experiments, no parasites survived aggressive chemotherapy, but after selection, the fitness advantage for resistant parasites was greatest at high drug doses. Aggressive treatment of mixed infections resulted in resistant parasites dominating the pool of gametocytes, without providing additional health benefits to hosts. Slower clearance rates can evolve rapidly and can provide a strong fitness advantage during drug treatment in both single and mixed strain

  14. Rapid response to selection, competitive release and increased transmission potential of artesunate-selected Plasmodium chabaudi malaria parasites.

    PubMed

    Pollitt, Laura C; Huijben, Silvie; Sim, Derek G; Salathé, Rahel M; Jones, Matthew J; Read, Andrew F

    2014-04-01

    The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited. Whether slower clearance rates represent true resistance, and how this provides a selective advantage for parasites is uncertain. Here, we show that Plasmodium chabaudi malaria parasites selected for resistance to artesunate (an artemisinin derivative) through a step-wise increase in drug dose evolved slower clearance rates extremely rapidly. In single infections, these slower clearance rates, similar to those seen in the field, provided fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. In mixed infections, removal of susceptible parasites by drug treatment led to substantial increases in the densities and transmission potential of resistant parasites (competitive release). Our results demonstrate the double-edged sword for resistance management: in our initial selection experiments, no parasites survived aggressive chemotherapy, but after selection, the fitness advantage for resistant parasites was greatest at high drug doses. Aggressive treatment of mixed infections resulted in resistant parasites dominating the pool of gametocytes, without providing additional health benefits to hosts. Slower clearance rates can evolve rapidly and can provide a strong fitness advantage during drug treatment in both single and mixed strain

  15. Malaria transmission dynamics in central Côte d'Ivoire: the influence of changing patterns of irrigated rice agriculture.

    PubMed

    Koudou, B G; Tano, Y; Doumbia, M; Nsanzabana, C; Cissé, G; Girardin, O; Dao, D; N'Goran, E K; Vounatsou, P; Bordmann, G; Keiser, J; Tanner, M; Utzinger, J

    2005-03-01

    The dynamics of malaria transmission was studied comparatively in the villages of Zatta and Tiemelekro, central Cote d'Ivoire, from February 2002 to August 2003. Prominent agroecosystems in these villages are irrigated rice growing and vegetable farming, respectively. Mosquitoes (Diptera: Culicidae) were collected on human bait at night and by pyrethrum knock-down spray sheet collections at four randomly selected sentinel sites in each village. In 2002, for a total of 96 man-nights per village, 7716 mosquitoes were collected in Zatta and 3308 in Tiemelekro. In 2003, with half the sampling effort, 859 and 2056 mosquitoes were collected in Zatta and Tiemelekro, respectively. Anopheles gambiae Giles s.l. was the predominant mosquito and the key malaria vector throughout, followed by An. funestus Giles. Anthropophily among adult female Anopheles exceeded 95% in both villages. Comparison between years revealed that the biting rate of An. gambiae s.l. in Zatta decreased several-fold from 49.3 bites per person per night (b/p/n) in 2002 to 7.9 b/p/n in 2003 (likelihood ratio test (LRT) = 1072.66; P < 0.001). Although the biting rate remained fairly constant in Tiemelekro, the difference between years was significant (16.1 vs. 18.2 b/p/n; LRT = 148.06; P < 0.001). These observations were paralleled by a marked decrease in the infective rate of An. gambiae s.l. in Zatta (4.6-1.2%), and an increase in Tiemelekro (3.1-7.6%). Meanwhile, the entomological inoculation rate of An. gambiae s.l. decreased 21-fold in Zatta, from 789 to 38 infective bites per person per year (ib/p/y), whereas it remained high in Tiemelekro (233 vs. 342 ib/p/y). The interruption of irrigated rice growing in Zatta in 2003, consequential to a farmers' conflict over land, might be the underlying cause for the significant reduction in malaria transmission, whereas more stable conditions occurred in Tiemelekro. PMID:15752174

  16. An Epidemiological Model of the Effects of Insecticide-Treated Bed Nets on Malaria Transmission.

    PubMed

    Birget, Philip L G; Koella, Jacob C

    2015-01-01

    Insecticide-treated bed nets (ITNs) have become a central tool for malaria control because they provide personal and community-wide protection through their repellent and insecticidal properties. Here we propose a model that allows to assess the relative importance of those two effects in different epidemiological contexts and we show that these two levels of protection may oppose each other. On the one hand, repellency offers personal protection to the users of ITNs. The repellent action, however, is a two-edged sword, for it diverts infectious mosquitoes to non-users, thereby increasing their risk. Furthermore, with increasing ITN coverage, the personal protection effect of repellency decreases as mosquitoes are forced to perform multiple feeding attempts even on ITN users. On the other hand, the insecticidal property, which offers community-wide protection by killing mosquitoes, requires that mosquitoes contact the insecticide on the ITN and is thus counteracted by the repellency. Our model confirms that ITNs are an effective intervention method by reducing total malaria prevalence in the population, but that there is a conflict between personal protection, offered by repellency, and community-wide protection, which relies on the ITN's insecticidal properties. Crucially, the model suggests that weak repellency allows disease elimination at lower ITN coverage levels. PMID:26636568

  17. An Epidemiological Model of the Effects of Insecticide-Treated Bed Nets on Malaria Transmission

    PubMed Central

    2015-01-01

    Insecticide-treated bed nets (ITNs) have become a central tool for malaria control because they provide personal and community-wide protection through their repellent and insecticidal properties. Here we propose a model that allows to assess the relative importance of those two effects in different epidemiological contexts and we show that these two levels of protection may oppose each other. On the one hand, repellency offers personal protection to the users of ITNs. The repellent action, however, is a two-edged sword, for it diverts infectious mosquitoes to non-users, thereby increasing their risk. Furthermore, with increasing ITN coverage, the personal protection effect of repellency decreases as mosquitoes are forced to perform multiple feeding attempts even on ITN users. On the other hand, the insecticidal property, which offers community-wide protection by killing mosquitoes, requires that mosquitoes contact the insecticide on the ITN and is thus counteracted by the repellency. Our model confirms that ITNs are an effective intervention method by reducing total malaria prevalence in the population, but that there is a conflict between personal protection, offered by repellency, and community-wide protection, which relies on the ITN’s insecticidal properties. Crucially, the model suggests that weak repellency allows disease elimination at lower ITN coverage levels. PMID:26636568

  18. Clonal diversity of a lizard malaria parasite, Plasmodium mexicanum, in its vertebrate host, the western fence lizard: role of variation in transmission intensity over time and space.

    PubMed

    Vardo, A M; Schall, J J

    2007-07-01

    Within the vertebrate host, infections of a malaria parasite (Plasmodium) could include a single genotype of cells (single-clone infections) or two to several genotypes (multiclone infections). Clonal diversity of infection plays an important role in the biology of the parasite, including its life history, virulence, and transmission. We determined the clonal diversity of Plasmodium mexicanum, a lizard malaria parasite at a study region in northern California, using variable microsatellite markers, the first such study for any malaria parasite of lizards or birds (the most common hosts for Plasmodium species). Multiclonal infections are common (50-88% of infections among samples), and measures of genetic diversity for the metapopulation (expected heterozygosity, number of alleles per locus, allele length variation, and effective population size) all indicated a substantial overall genetic diversity. Comparing years with high prevalence (1996-1998 = 25-32% lizards infected), and years with low prevalence (2001-2005 = 6-12%) found fewer alleles in samples taken from the low-prevalence years, but no reduction in overall diversity (H = 0.64-0.90 among loci). In most cases, rare alleles appeared to be lost as prevalence declined. For sites chronically experiencing low transmission intensity (prevalence approximately 1%), overall diversity was also high (H = 0.79-0.91), but there were fewer multiclonal infections. Theory predicts an apparent excess in expected heterozygosity follows a genetic bottleneck. Evidence for such a distortion in genetic diversity was observed after the drop in parasite prevalence under the infinite alleles mutation model but not for the stepwise mutation model. The results are similar to those reported for the human malaria parasite, Plasmodium falciparum, worldwide, and support the conclusion that malaria parasites maintain high genetic diversity in host populations despite the potential for loss in alleles during the transmission cycle or

  19. Assessment of malaria transmission changes in Africa, due to the climate impact of land use change using Coupled Model Intercomparison Project Phase 5 earth system models.

    PubMed

    Tompkins, Adrian M; Caporaso, Luca

    2016-01-01

    Using mathematical modelling tools, we assessed the potential for land use change (LUC) associated with the Intergovernmental Panel on Climate Change low- and high-end emission scenarios (RCP2.6 and RCP8.5) to impact malaria transmission in Africa. To drive a spatially explicit, dynamical malaria model, data from the four available earth system models (ESMs) that contributed to the LUC experiment of the Fifth Climate Model Intercomparison Project are used. Despite the limited size of the ESM ensemble, stark differences in the assessment of how LUC can impact climate are revealed. In three out of four ESMs, the impact of LUC on precipitation and temperature over the next century is limited, resulting in no significant change in malaria transmission. However, in one ESM, LUC leads to increases in precipitation under scenario RCP2.6, and increases in temperature in areas of land use conversion to farmland under both scenarios. The result is a more intense transmission and longer transmission seasons in the southeast of the continent, most notably in Mozambique and southern Tanzania. In contrast, warming associated with LUC in the Sahel region reduces risk in this model, as temperatures are already above the 25-30°C threshold at which transmission peaks. The differences between the ESMs emphasise the uncertainty in such assessments. It is also recalled that the modelling framework is unable to adequately represent local-scale changes in climate due to LUC, which some field studies indicate could be significant. PMID:27063732

  20. Mixed-genotype infections of malaria parasites: within-host dynamics and transmission success of competing clones.

    PubMed Central

    Taylor, L H; Walliker, D; Read, A F

    1997-01-01

    Mixed-genotype infections of microparasites are common, but almost nothing is known about how competitive interactions within hosts affect the subsequent transmission success of individual genotypes. We investigated changes in the composition of mixed-genotype infections of the rodent malaria Plasmodium chabaudi clones CR and ER by monoclonal antibody analysis of the asexual infection in mice, and by PCR amplification of clone-specific alleles in oocysts sampled from mosquitoes which had fed on these mice. Mixed-clone infections were initiated with a 9:1 ratio of the two clones, with ER as the minority in the first experiment and CR as the minority in the second experiment. When beginning as the majority, clones achieved parasite densities in mice comparable to those achieved in control (single-clone) infections. When they began as the minority, clones were suppressed to less than 10% of control parasitaemias during the early part of the infections. However, in mosquitoes, the frequency of the initially rare clone was substantially greater than it was in mice at the start of the infection or four days prior to the feed. In both experiments, the minority clone in the inocula produced as many, or more, oocysts than it did as a single-clone infection. These experiments show that asexual dominance during most of the infection is poorly correlated to transmission probability, and therefore that the assumption that within-host population size correlates to transmission probability may not be warranted. They also raise the fundamental question of why transmission rates of individual genotypes are often higher from mixed than single-clone infections. PMID:9225482

  1. Gestational malaria associated to Plasmodium vivax and Plasmodium falciparum placental mixed-infection followed by foetal loss: a case report from an unstable transmission area in Brazil.

    PubMed

    Carvalho, Bruna O; Matsuda, Joycenéa S; Luz, Sergio L B; Martinez-Espinosa, Flor E; Leite, Juliana A; Franzin, Fernanda; Orlandi, Patrícia P; Gregoracci, Gustavo B; Lacerda, Marcus V G; Nogueira, Paulo A; Costa, Fabio T M

    2011-01-01

    Gestational malaria is a multi-factorial syndrome leading to poor outcomes for both the mother and foetus. Although an unusual increasing in the number of hospitalizations caused by Plasmodium vivax has been reported in Brazil, mortality is rarely observed. This is a report of a gestational malaria case that occurred in the city of Manaus (Amazonas State, Brazil) and resulted in foetal loss. The patient presented placental mixed-infection by Plasmodium vivax and Plasmodium falciparum after diagnosis by nested-PCR, however microscopic analysis failed to detect P. falciparum in the peripheral blood. Furthermore, as the patient did not receive proper treatment for P. falciparum and hospitalization occurred soon after drug treatment, it seems that P. falciparum pathology was modulated by the concurrent presence of P. vivax. Collectively, this case confirms the tropism towards the placenta by both of these species of parasites, reinforces the notion that co-existence of distinct malaria parasites interferes on diseases' outcomes, and opens discussions regarding diagnostic methods, malaria treatment during pregnancy and prenatal care for women living in unstable transmission areas of malaria, such as the Brazilian Amazon. PMID:21708032

  2. Larval habitat, ecology, seasonal abundance and vectorial role in malaria transmission of Anopheles arabiensis in Jazan Region of Saudi Arabia.

    PubMed

    Al-Sheik, Adel A

    2011-12-01

    Studies on the ecology and role in malaria transmission of the local anopheline fauna of An. arabiensis, was undertaken at the Red Sea coastal plain, the Tihama, in Saudi Arabia, an area of moderate malaria endemicity. Studies were carried out over a 13 months period from March 2007, by larval collection and by adult collection using pyrethrum knockdown (PKD), and CDC light-traps at 9 s sites. In total 479,520 mosquitoes of 14 species collected seven anopheles species were identified: An. gambiae s.l Giles, An. dthali Patton, An. pretoriensis Theobald, An. sergentii Theobald, An. multicolour, An. rhodesiensis rupicola Lewis, and An. turkhudi Liston. An. gambiae was the most predominant species. An. arabiensis Patton was identified by PCR as the only member of the An. gambiae complex present. A survey of mosquito breeding sites showed that suitable sites for both An. arabiensis and other anophelines existed all year round. Larvae of An. arabiensis, An. dthali and An. pretoriensis were found every month. In addition to the more typical breeding sites, An. arabiensis larvae were found in rock pools and in domestic water containers and tanks. An. arabiensis was the predominant anopheline species found resting in human habitations but despite its endophily, only 40% bloodmeals were of human origin. The source(s) of the remainder was (were) unknown. Despite its predominance in larval collections, few adult An., dthali and An. pretoriensis were caught in PKD, indicating a zoophilic preference. Other anophelines were rarely found. Sporozoite rate in An. arabiensis was 0.61%, based on 21 posities. None was found in others. PMID:22435155

  3. Retrocyclin RC-101 blocks HIV-1 transmission across cervical mucosa in an Organ Culture

    PubMed Central

    Gupta, Phalguni; Ratner, Deena; Ding, Ming; Patterson, Bruce; Rohan, Lisa C; Reinhart, Todd A.; Ayyavoo, Velpandi; Huang, Xioli; Patton, Dorothy L; Ramratnam, Bharat; Cole, Alexander M

    2012-01-01

    Background Cervical tissue based organ cultures have been used successfully to evaluate microbicides for toxicity and antiviral activity. The antimicrobial peptide retrocyclin RC-101 has been shown to have potent anti-HIV activity in cell culture. Objective To evaluate RC-101 in organ culture for toxicity and its ability to block HIV-1 transmission across cervical mucosa. Methods A Cervical tissue based organ culture was used to measure antiviral activity of RC101. Cytotoxicity in tissues was determined by immunostaining of cellular proteins and by measuring inflammatory cytokines using realtime RTPCR and luminex technology. Results RC-101 blocked transmission of both R5 and X4 HIV-1 across cervical mucosa in this organ culture model. Furthermore, film-formulated RC-101 exhibited potent antiviral activity in organ culture. Such antiviral activity of RC-101 was retained in the presence of semen and vaginal fluid. RC-101 showed no cytotoxicity in cervical tissue. Furthermore, RC-101 did not induce proinflammatory cytokine response in tissues. RC-101 also did not have any effect on NK activity, cell proliferation of CD4 and CD8 cells, and did not show chemotactic activity. Conclusion Therefore, because of strong antiviral activity and low cytotoxicity in cervical tissues, RC-101 should be considered as an excellent microbicide candidate against HIV-1. PMID:22592582

  4. Borrelia burgdorferi BBA52 is a potential target for transmission blocking Lyme disease vaccine

    PubMed Central

    Kumar, Manish; Kaur, Simarjot; Kariu, Toru; Yang, Xiuli; Bossis, Ioannis; Anderson, John F.; Pal, Utpal

    2011-01-01

    The surface-exposed antigens of Borrelia burgdorferi represent important targets for induction of protective host immune responses. BBA52 is preferentially expressed by B. burgdorferi in the feeding tick, and a targeted deletion of bba52 interferes with vector-host transitions in vivo. In this study, we demonstrate that BBA52 is an outer membrane surface-exposed protein and that disulfide bridges take part in the homo-oligomeric assembly of native protein. BBA52 antibodies lack detectable borreliacidal activities in vitro. However, active immunization studies demonstrated that BBA52 vaccinated mice were significantly less susceptible to subsequent tick-borne challenge infection. Similarly, passive transfer of BBA52 antibodies in ticks completely blocked B. burgdorferi transmission from feeding ticks to naïve mice. Taken together, these studies highlight the role of BBA52 in spirochete dissemination from ticks to mice and demonstrate the potential of BBA52 antibody-mediated strategy to complement the ongoing efforts to develop vaccines for blocking the transmission of B. burgdorferi. PMID:21945261

  5. A malaria vaccine for travelers and military personnel: Requirements and top candidates.

    PubMed

    Teneza-Mora, Nimfa; Lumsden, Joanne; Villasante, Eileen

    2015-12-22

    Malaria remains an important health threat to non-immune travelers with the explosive growth of global travel. Populations at high risk of acquiring malaria infections include once semi-immune travelers who visit friends and relatives, military forces, business travelers and international tourists with destinations to sub-Saharan Africa, where malaria transmission intensity is high. Most malaria cases have been associated with poor compliance with existing preventive measures, including chemoprophylaxis. High risk groups would benefit immensely from an efficacious vaccine to protect them against malaria infection and together make up a sizable market for such a vaccine. The attributes of an ideal malaria vaccine for non-immune travelers and military personnel include a protective efficacy of 80% or greater, durability for at least 6 months, an acceptable safety profile and compatibility with existing preventive measures. It is very likely that a malaria vaccine designed to effectively prevent infection and clinical disease in the non-immune traveler and military personnel will also protect semi-immune residents of malaria-endemic areas and contribute to malaria elimination by reducing or blocking malaria transmission. The RTS,S vaccine (GlaxoSmithKline) and the PfSPZ Vaccine (Sanaria Inc) are the leading products that would make excellent vaccine candidates for these vulnerable populations. PMID:26458800

  6. Genetic polymorphisms associated with anti-malarial antibody levels in a low and unstable malaria transmission area in southern Sri Lanka

    PubMed Central

    2012-01-01

    Background The incidence of malaria in Sri Lanka has significantly declined in recent years. Similar trends were seen in Kataragama, a known malaria endemic location within the southern province of the country, over the past five years. This is a descriptive study of anti-malarial antibody levels and selected host genetic mutations in residents of Kataragama, under low malaria transmission conditions. Methods Sera were collected from 1,011 individuals residing in Kataragama and anti-malarial antibodies and total IgE levels were measured by a standardized ELISA technique. Host DNA was extracted and used for genotyping of selected SNPs in known genes associated with malaria. The antibody levels were analysed in relation to the past history of malaria (during past 10 years), age, sex, the location of residence within Kataragama and selected host genetic markers. Results A significant increase in antibodies against Plasmodium falciparum antigens AMA1, MSP2, NANP and Plasmodium vivax antigen MSP1 in individuals with past history of malaria were observed when compared to those who did not. A marked increase of anti-MSP1(Pf) and anti-AMA1(Pv) was also evident in individuals between 45–59 years (when compared to other age groups). Allele frequencies for two SNPs in genes that code for IL-13 and TRIM-5 were found to be significantly different between those who have experienced one or more malaria attacks within past 10 years and those who did not. When antibody levels were classified into a low-high binary trait, significant associations were found with four SNPs for anti-AMA1(Pf); two SNPs for anti-MSP1(Pf); eight SNPs for anti-NANP(Pf); three SNPs for anti-AMA1(Pv); seven SNPs for anti-MSP1(Pv); and nine SNPs for total IgE. Eleven of these SNPs with significant associations with anti-malarial antibody levels were found to be non–synonymous. Conclusions Evidence is suggestive of an age–acquired immunity in this study population in spite of low malaria

  7. Knowledge on the transmission, prevention and treatment of malaria among two endemic populations of Bangladesh and their health-seeking behaviour

    PubMed Central

    Ahmed, Syed Masud; Haque, Rashidul; Haque, Ubydul; Hossain, Awlad

    2009-01-01

    Background Data on sociological and behavioural aspects of malaria, which is essential for an evidence-based design of prevention and control programmes, is lacking in Bangladesh. This paper attempts to fill this knowledge gap by using data from a population-based prevalence survey conducted during July to November 2007, in 13 endemic districts of Bangladesh. Methods A two-stage cluster sampling technique was used to select study respondents randomly from 30 mauzas in each district for the socio-behavioural inquiry (n = 9,750). A pre-tested, semi-structured questionnaire was used to collect data in face-to-face interview by trained interviewers, after obtaining informed consent. Results The overall malaria prevalence rate in the 13 endemic districts was found to be 3.1% by the Rapid Diagnostic Test 'FalciVax' (P. falciparum 2.73%, P. vivax 0.16% and mixed infection 0.19%), with highest concentration in the three hill districts (11%). Findings revealed superficial knowledge on malaria transmission, prevention and treatment by the respondents. Poverty and level of schooling were found as important determinants of malaria knowledge and practices. Allopathic treatment was uniformly advocated, but the 'know-do' gap became especially evident when in practice majority of the ill persons either did not seek any treatment (31%) or practiced self-treatment (12%). Of those who sought treatment, the majority went to the village doctors and drugstore salespeople (around 40%). Also, there was a delay beyond twenty-four hours in beginning treatment of malaria-like fever in more than half of the instances. In the survey, gender divide in knowledge and health-seeking behaviour was observed disfavouring women. There was also a geographical divide between the high endemic south-eastern area and the low-endemicnorth-eastern area, the former being disadvantaged with respect to different aspects of malaria studied. Conclusion The respondents in this study lacked comprehensive knowledge

  8. Accelerating to Zero: Strategies to Eliminate Malaria in the Peruvian Amazon

    PubMed Central

    Quispe, Antonio M.; Llanos-Cuentas, Alejandro; Rodriguez, Hugo; Clendenes, Martin; Cabezas, Cesar; Leon, Luis M.; Chuquiyauri, Raul; Moreno, Marta; Kaslow, David C.; Grogl, Max; Herrera, Sócrates; Magill, Alan J.; Kosek, Margaret; Vinetz, Joseph M.; Lescano, Andres G.; Gotuzzo, Eduardo

    2016-01-01

    In February 2014, the Malaria Elimination Working Group, in partnership with the Peruvian Ministry of Health (MoH), hosted its first international conference on malaria elimination in Iquitos, Peru. The 2-day meeting gathered 85 malaria experts, including 18 international panelists, 23 stakeholders from different malaria-endemic regions of Peru, and 11 MoH authorities. The main outcome was consensus that implementing a malaria elimination project in the Amazon region is achievable, but would require: 1) a comprehensive strategic plan, 2) the altering of current programmatic guidelines from control toward elimination by including symptomatic as well as asymptomatic individuals for antimalarial therapy and transmission-blocking interventions, and 3) the prioritization of community-based active case detection with proper rapid diagnostic tests to interrupt transmission. Elimination efforts must involve key stakeholders and experts at every level of government and include integrated research activities to evaluate, implement, and tailor sustainable interventions appropriate to the region.

  9. Effects of insecticide-treated bednets during early infancy in an African area of intense malaria transmission: a randomized controlled trial.

    PubMed Central

    Müller, Olaf; Traoré, Corneille; Kouyaté, Bocar; Yé, Yazoumé; Frey, Claudia; Coulibaly, Boubacar; Becher, Heiko

    2006-01-01

    OBJECTIVE: Insecticide-impregnated bednets and curtains have been shown by many studies to be effective against malaria. However, because of possible interactions with immunity development, treated bednets may cause no effect at all or even an increase in malaria morbidity and mortality in areas of high transmission. To clarify this issue, we did a randomized controlled trial to assess the long-term effects of bednet protection during early infancy. METHODS: A total of 3387 neonates from 41 villages in rural Burkina Faso were individually randomized to receive either bednet protection from birth (group A) or from age 6 months (group B). Primary outcomes were all-cause mortality in all study children and incidence of falciparum malaria in a representative subsample of the study population. FINDINGS: After a mean follow-up of 27 months, there were 129 deaths in group A and 128 deaths in group B rate ratio (RR) 1.0 (95% confidence interval (CI): 0.78-1.27)). Falciparum malaria incidence was lower in group A than in group B, during early (0-5 months) and late infancy (6-12 months) (RR 3.1, 95% CI: 2.0-4.9; RR 1.3, 95% CI: 1.1-1.6) and rates of moderate to severe anaemia were significantly lower during late infancy (11.5% vs 23.3%, P = 0.008), but there were no differences between groups in these parameters in children older than 12 months. CONCLUSION: The findings from this study provide additional evidence for the efficacy of insecticide-treated nets in young children living in areas of intense malaria transmission. PMID:16501729

  10. Genetic Diversity of the Malaria Vaccine Candidate Plasmodium falciparum Merozoite Surface Protein-3 in a Hypoendemic Transmission Environment

    PubMed Central

    Jordan, Stephen J.; Branch, OraLee H.; Castro, Jean Carlos; Oster, Robert A.; Rayner, Julian C.

    2009-01-01

    The N-terminal domain of Plasmodium falciparum merozoite surface protein-3 (PfMSP3) has been excluded from malaria vaccine development largely because of genetic diversity concerns. However, no study to date has followed N-terminal diversity over time. This study describes PfMSP3 variation in a hypoendemic longitudinal cohort in the Peruvian Amazon over the 2003-2006 transmission seasons. Polymerase chain reaction was used to amplify the N-terminal domain in 630 distinct P. falciparum infections, which were allele-typed by size and also screened for sequence variation using a new high-throughput technique, denaturing high performance liquid chromatography. PfMSP3 allele frequencies fluctuated significantly over the 4-year period, but sequence variation was very limited, with only 10 mutations being identified of 630 infections screened. The sequence of the PfMSP3 N-terminal domain is relatively stable over time in this setting, and further studies of its status as a vaccine candidate are therefore warranted. PMID:19270302

  11. Assessment of a remote sensing-based model for predicting malaria transmission risk in villages of Chiapas, Mexico

    NASA Technical Reports Server (NTRS)

    Beck, L. R.; Rodriguez, M. H.; Dister, S. W.; Rodriguez, A. D.; Washino, R. K.; Roberts, D. R.; Spanner, M. A.

    1997-01-01

    A blind test of two remote sensing-based models for predicting adult populations of Anopheles albimanus in villages, an indicator of malaria transmission risk, was conducted in southern Chiapas, Mexico. One model was developed using a discriminant analysis approach, while the other was based on regression analysis. The models were developed in 1992 for an area around Tapachula, Chiapas, using Landsat Thematic Mapper (TM) satellite data and geographic information system functions. Using two remotely sensed landscape elements, the discriminant model was able to successfully distinguish between villages with high and low An. albimanus abundance with an overall accuracy of 90%. To test the predictive capability of the models, multitemporal TM data were used to generate a landscape map of the Huixtla area, northwest of Tapachula, where the models were used to predict risk for 40 villages. The resulting predictions were not disclosed until the end of the test. Independently, An. albimanus abundance data were collected in the 40 randomly selected villages for which the predictions had been made. These data were subsequently used to assess the models' accuracies. The discriminant model accurately predicted 79% of the high-abundance villages and 50% of the low-abundance villages, for an overall accuracy of 70%. The regression model correctly identified seven of the 10 villages with the highest mosquito abundance. This test demonstrated that remote sensing-based models generated for one area can be used successfully in another, comparable area.

  12. Laboratory studies of alkali metal filter deposition, ultraviolet transmission, and visible blocking.

    PubMed

    Clarke, J T; Skinner, W R; Vincent, M B; Irgang, T; Suratkal, V; Grassl, H; Trauger, J T

    1999-03-20

    Far-ultraviolet alkali metal or Wood's filters have been produced and tested supporting the production of a flight filter for the Wide Field Planetary Camera 2 on the Hubble Space Telescope. Sodium layers 0.5-1-microm thick transmit up to 40% in the ultraviolet while efficiently blocking visible wavelengths. The prevention of visible pinholes is assisted by a clean, sleek-free surface and a cooled substrate during deposition. The coatings are stabilized efficiently by a bismuth overcoating whose transmission spectrum is presented. We also report for the first time, to our knowledge, the first demonstrated long-wavelength cutoff from a lithium filter, with a shorter cutoff wavelength than sodium and potentially higher stability for astronomical imaging. PMID:18305811

  13. Socio-economic determinants for malaria transmission risk in an endemic primary health centre in Assam, India

    PubMed Central

    2014-01-01

    Background Malaria is a major cause of morbidity and mortality in Northeast India. As there is limited information available on the potential influence of socio-economic variables on malaria risk, the present study was conducted to assess the influence of demographic factors, the socio-economic status, and knowledge, awareness and education on malaria occurrence. Methods Demographics, malaria knowledge and socio-economic variables were collected in four randomly selected health sub-centres of the Orang primary health centre in the Udalguri district, Assam and the association of malaria occurrence with different variables were analysed. The trend of malaria occurrence for different income groups, proximity to health centres and number of mosquito bites per day was also determined using the chi-square test. Relative risk (RR) for gender, house type, knowledge and use of bed nets was determined using Katz approximation. Results Out of the 71 household heads interviewed, 70.4% (50/71) were males. About half (54.9%, 39/71) of the participants had a history of malaria in the last two years, of which 64.1% (25/39) were males, while 35.9% (14/39) were females (χ2 = 5.13; p = 0.02; RR = 1.79). Of the total population surveyed, 49.3% lived in bamboo houses and 35.2% lived at a distance of >3 km from the nearest health centre. The number of participants who had a history of malaria decreased with an increasing monthly income (p < 0.0001). Malaria occurrence was higher among the households living in bamboo houses (69.2%), as compared to Kucha houses (20.5%) and Pucca houses (10.3%). No significant association was observed between education level and malaria occurrence (p = 0.93). The participants who did not use bed nets regularly reported a high occurrence of malaria infection as compared to those who used bed nets everyday (p < 0.0001). Conclusions Lower income, house type, distance to health sub-centre, knowledge and awareness about malaria, number of mosquito bites per

  14. Blocking the Transmission of a Noncirculative Vector-Borne Plant Pathogenic Bacterium.

    PubMed

    Labroussaa, Fabien; Zeilinger, Adam R; Almeida, Rodrigo P P

    2016-07-01

    The successful control of insect-borne plant pathogens is often difficult to achieve due to the ecologically complex interactions among pathogens, vectors, and host plants. Disease management often relies on pesticides and other approaches that have limited long-term sustainability. To add a new tool to control vector-borne diseases, we attempted to block the transmission of a bacterial insect-transmitted pathogen, the bacterium Xylella fastidiosa, by disrupting bacteria-insect vector interactions. X. fastidiosa is known to attach to and colonize the cuticular surface of the mouthparts of vectors; a set of recombinant peptides was generated and the chemical affinities of these peptides to chitin and related carbohydrates was assayed in vitro. Two candidates, the X. fastidiosa hypothetical protein PD1764 and an N-terminal region of the hemagglutinin-like protein B (HxfB) showed affinity for these substrates. These proteins were provided to vectors via an artificial diet system in which insects acquire X. fastidiosa, followed by an inoculation access period on plants under greenhouse conditions. Both PD1764 and HxfAD1-3 significantly blocked transmission. Furthermore, bacterial populations within insects over a 10-day period demonstrated that these peptides inhibited cell adhesion to vectors but not bacterial multiplication, indicating that the mode of action of these peptides is restricted to limiting cell adhesion to insects, likely via competition for adhesion sites. These results open a new venue in the search for sustainable disease-control strategies that are pathogen specific and may have limited nontarget effects. PMID:27049684

  15. Secure transmission of images based on chaotic systems and cipher block chaining

    NASA Astrophysics Data System (ADS)

    Lakhani, Mahdieh Karimi; Behnam, Hamid; Karimi, Arash

    2013-01-01

    The ever-growing penetration of communication networks, digital and Internet technologies in our everyday lives has the transmission of text data, as well as multimedia data such as images and videos, possible. Digital images have a vast usage in a number of applications, including medicine and providing security authentication, for example. This applicability becomes evident when images, such as walking or people's facial features, are utilized in their identification. Considering the required security level and the properties of images, different algorithms may be used. After key generation using logistic chaos signals, a scrambling function is utilized for image agitation in both horizontal and vertical axes, and then a block-chaining mode of operation may be applied to encrypt the resultant image. The results demonstrate that using the proposed method drastically degrades the correlation between the image components and also the entropy is increased to an acceptable level. Therefore, the image will become greatly resistant to differential attacks. However, the increasing scrambling rounds and the decreasing number of bits of the blocks result in increasing the entropy and decreasing the correlation.

  16. Good performances but short lasting efficacy of Actellic 50 EC Indoor Residual Spraying (IRS) on malaria transmission in Benin, West Africa

    PubMed Central

    2014-01-01

    Background The National Malaria Control Program (NMCP) has been using pirimiphos methyl for the first time for indoor residual spraying (IRS) in Benin. The first round was a success with a significant decrease of entomological indicators of malaria transmission in the treated districts. We present the results of the entomological impact on malaria transmission. Entomologic parameters in the control area were compared with those in intervention sites. Methods Mosquito collections were carried out in three districts in the Atacora-Dongo region of which two were treated with pirimiphos methyl (Actellic 50EC) (Tanguiéta and Kouandé) and the untreated (Copargo) served as control. Anopheles gambiae s.l. populations were sampled monthly by human landing catch. In addition, window exit traps and pyrethrum spray catches were performed to assess exophagic behavior of Anopheles vectors. In the three districts, mosquito collections were organized to follow the impact of pirimiphos methyl IRS on malaria transmission and possible changes in the behavior of mosquitoes. The residual activity of pirimiphos methyl in the treated walls was also assessed using WHO bioassay test. Results A significant reduction (94.25%) in human biting rate was recorded in treated districts where an inhabitant received less than 1 bite of An. gambiae per night. During this same time, the entomological inoculation rate (EIR) dramatically declined in the treated area (99.24% reduction). We also noted a significant reduction in longevity of the vectors and an increase in exophily induced by pirimiphos methyl on An. gambiae. However, no significant impact was found on the blood feeding rate. Otherwise, the low residual activity of Actellic 50 EC, which is three months, is a disadvantage. Conclusion Pirimiphos methyl was found to be effective for IRS in Benin. However, because of the low persistence of Actellic 50EC used in this study on the treated walls, the recourse to another more residual formulation

  17. Worldwide population genetic analysis and natural selection in the Plasmodium vivax Generative Cell Specific 1 (PvGCS1) as a transmission-blocking vaccine candidate.

    PubMed

    Mehrizi, Akram Abouie; Dodangeh, Fatemeh; Zakeri, Sedigheh; Djadid, Navid Dinparast

    2016-09-01

    GENERATIVE CELL SPECIFIC 1 (GCS1) is one of the Transmission Blocking Vaccine (TBV) candidate antigens, which is expressed on the surface of male gametocytes and gametes of Plasmodium species. Since antigenic diversity could inhibit the successful development of a malaria vaccine, it is crucial to determine the diversity of gcs1 gene in global malaria-endemic areas. Therefore, gene diversity and selection of gcs1 gene were analyzed in Iranian Plasmodium vivax isolates (n=52) and compared with the corresponding sequences from worldwide clinical P. vivax isolates available in PlasmoDB database. Totally 12 SNPs were detected in the pvgcs1 sequences as compared to Sal-1 sequence. Five out of 12 SNPs including three synonymous (T797C, G1559A, and G1667T) and two amino acid replacements (Y133S and Q634P) were detected in Iranian pvgcs1 sequences. According to four amino acid replacements (Y133S, N575S, Q634P and D637N) observed in all world PvGCS1 sequences, totally 5 PvGCS1 haplotypes were detected in the world, that three of them observed in Iranian isolates including the PvGCS-A (133S/634Q, 92.3%), PvGCS-B (133Y/634Q, 5.8%), and PvGCS-C (133S/634P, 1.9%). The overall nucleotide diversity (π) for all 52 sequences of Iranian pvgcs1 gene was 0.00018±0.00006, and the value of dN-dS (-0.00031) were negative, however, it was not statistically significant. In comparison with global isolates, Iranian and PNG pvgcs1 sequences had the lowest nucleotide and haplotype diversity, while the highest nucleotide and haplotype diversity was observed in China population. Moreover, epitope prediction in this antigen showed that all B-cell epitopes were located in conserved regions. However, Q634P (in one Iranian isolate) and D637N (observed in Thailand, China, Vietnam and North Korea) mutations are involved in predicted IURs. The obtained results in this study could be used in development of PvGCS1 based malaria vaccine. PMID:27180894

  18. [Malaria transmission in lagoon areas in Côte d'Ivoire: the villages of N'gatty and Allaba].

    PubMed

    Fofana, D; Koné, Ab; Konan, Yl; Konan, Kl; Doannio, Jmc; N'goran, Ek

    2010-01-01

    The ecological and climatic variations in tropical areas of Africa make the transmission of malaria very heterogeneous. Several species of mosquitoes of the Anopheles genus transmit the disease. In Côte d'Ivoire, studies in the southern and northern forests have shown the involvement of Anopheles gambiae, An. funestus and An. nili in this transmission. This study was conducted in N'gatty and Allaba, two villages in a lagoon area of southern Côte d'Ivoire, in the district of Dabou. The district is located between 05 degrees 18 N and 04 degrees 27 W, about 40 kilometres from the economic capital of Côte d'Ivoire, and has a surface of 2257.8 km2. Two lagoon villages, N'gatty and Allaba, about a kilometre apart, were selected as sites for this research. The topography of N'gatty is rugged, with two important sides: a banana plantation on the west and the lagoon on the east, covered by aquatic plants (Pistia stratiotes, Acrosticum aureum, nympheacae and Eichhornia crassipes). This aquatic vegetation separates the last plots of the village from the lagoon. Mosquito populations were sampled from December 2007 through September 2008 by nighttime captures on volunteers three consecutive nights each month, inside six living rooms (4 in N'gatty and 2 in Allaba, a smaller village). The mosquitoes were captured when they landed on the volunteer's legs. There were two teams of catchers for each home; the first worked from 18:00 h to 24:00 and the second from 24:00 to 06:00. The ovaries and glands of An. gambiae were dissected. The physiological age of the females was determined by the appearance of the trachea on ovarian dissection. The sporozoites were sought by optic microscopy in cooled glands in a drop of physiological salt solution. During the 10 months of this study, 21 137 mosquitoes were caught in N'gatty and 7163 in Allaba. An. gambiae species accounted for less than 2% of the mosquito fauna in the two villages. Overall, the average bite rate was 203.24 bites per man

  19. Plasmodium Cysteine Repeat Modular Proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host

    PubMed Central

    2011-01-01

    Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δpcrmp3 and Δpcrmp4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δpcrmp3 and Δpcrmp4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2. Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δcrmp3 and Δcrmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life cycle; they are essential

  20. A global assessment of closed forests, deforestation and malaria risk

    PubMed Central

    GUERRA, C. A.; SNOW, R. W.; HAY, S. I.

    2011-01-01

    Global environmental change is expected to affect profoundly the transmission of the parasites that cause human malaria. Amongst the anthropogenic drivers of change, deforestation is arguably the most conspicuous, and its rate is projected to increase in the coming decades. The canonical epidemiological understanding is that deforestation increases malaria risk in Africa and the Americas and diminishes it in South–east Asia. Partial support for this position is provided here, through a systematic review of the published literature on deforestation, malaria and the relevant vector bionomics. By using recently updated boundaries for the spatial limits of malaria and remotely-sensed estimates of tree cover, it has been possible to determine the population at risk of malaria in closed forest, at least for those malaria-endemic countries that lie within the main blocks of tropical forest. Closed forests within areas of malaria risk cover approximately 1.5 million km2 in the Amazon region, 1.4 million km2 in Central Africa, 1.2 million km2 in the Western Pacific, and 0.7 million km2 in South–east Asia. The corresponding human populations at risk of malaria within these forests total 11.7 million, 18.7 million, 35.1 million and 70.1 million, respectively. By coupling these numbers with the country-specific rates of deforestation, it has been possible to rank malaria-endemic countries according to their potential for change in the population at risk of malaria, as the result of deforestation. The on-going research aimed at evaluating these relationships more quantitatively, through the Malaria Atlas Project (MAP), is highlighted. PMID:16630376

  1. Year to year and seasonal variations in vector bionomics and malaria transmission in a humid savannah village in west Burkina Faso.

    PubMed

    Dabiré, K R; Diabaté, A; Paré-Toé, L; Rouamba, J; Ouari, A; Fontenille, D; Baldet, T

    2008-06-01

    A longitudinal entomological study was carried out from 1999 to 2001 in Lena, a humid savannah village in the western region of Burkina Faso in order to establish malaria vector bionomics and the dynamics of malaria transmission. In the first year, malaria transmission was mainly due to An. gambiae s.s., but during the two later years was due to An. funestus, which were observed in high frequency towards the end of the rainy season. PCR identification of samples of An. gambiae s.1. showed 93% to be An. gambiae s.s. and 7% An. arabiensis. An. funestus constituting more than 60% of the vectors were identified in PCR as An. funestus s.s. The persistence of intense vectorial activity in this village was probably due to the road building in a swampy area creating a semi-permanent swamp that provided large sites for larval mosquitoes. These swampy sites seemed to be more favorable for An. funestus than for An. gambiae s.s. Thus, land development must be monitored and subjected to planning to minimize vector proliferation. Such a system of planning could lead to the restriction or even elimination of the swamp that is the source of larvae developing in the heart of the village. PMID:18697309

  2. [Comparison of catches by landings on humans and by CDC light traps for sampling of mosquitoes and evaluation of malaria transmission in South Cameroon].

    PubMed

    Le Goff, G; Carnevale, P; Robert, V

    1993-03-01

    The classical method to estimate the malaria transmission in an endemic area is based on the number and infectivity of human landing mosquitoes. To compare this method with CDC Miniature Light Trap a study was carried out in a forested area of South Cameroon. Light-trap and servant were placed in six different houses of the same village from 08 p.m. to 06 a.m. In average the human landing caught 29.9 anopheline females per night, while light-trap 52.4. The ratio of light-trap on human landing was 1.75 for Anopheles genus. This ratio varied with the species: 1.88 for An. nili and 0.54 for An. gambiae s.s. Light-trap showed disadvantages, especially the lack of steadiness and the fact that only 49.6% (n = 238) of potential vectors of malaria were in good standing for dissection of salivary glands. The authors concluded that human landing remained the most efficient method of catching for the estimation of human malaria transmission in the forested area of Africa. Nevertheless, the lower cost of light-trap is an important advantage. PMID:8323408

  3. Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells.

    PubMed

    Yamamoto, Daisuke S; Sumitani, Megumi; Kasashima, Katsumi; Sezutsu, Hideki; Matsuoka, Hiroyuki

    2016-09-01

    Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control. PMID:27598328

  4. Fine-Scale Mapping by Spatial Risk Distribution Modeling for Regional Malaria Endemicity and Its Implications under the Low-to-Moderate Transmission Setting in Western Cambodia

    PubMed Central

    Okami, Suguru; Kohtake, Naohiko

    2016-01-01

    The disease burden of malaria has decreased as malaria elimination efforts progress. The mapping approach that uses spatial risk distribution modeling needs some adjustment and reinvestigation in accordance with situational changes. Here we applied a mathematical modeling approach for standardized morbidity ratio (SMR) calculated by annual parasite incidence using routinely aggregated surveillance reports, environmental data such as remote sensing data, and non-environmental anthropogenic data to create fine-scale spatial risk distribution maps of western Cambodia. Furthermore, we incorporated a combination of containment status indicators into the model to demonstrate spatial heterogeneities of the relationship between containment status and risks. The explanatory model was fitted to estimate the SMR of each area (adjusted Pearson correlation coefficient R2 = 0.774; Akaike information criterion AIC = 149.423). A Bayesian modeling framework was applied to estimate the uncertainty of the model and cross-scale predictions. Fine-scale maps were created by the spatial interpolation of estimated SMRs at each village. Compared with geocoded case data, corresponding predicted values showed conformity [Spearman’s rank correlation r = 0.662 in the inverse distance weighed interpolation and 0.645 in ordinal kriging (95% confidence intervals of 0.414–0.827 and 0.368–0.813, respectively), Welch’s t-test; Not significant]. The proposed approach successfully explained regional malaria risks and fine-scale risk maps were created under low-to-moderate malaria transmission settings where reinvestigations of existing risk modeling approaches were needed. Moreover, different representations of simulated outcomes of containment status indicators for respective areas provided useful insights for tailored interventional planning, considering regional malaria endemicity. PMID:27415623

  5. Impact of permethrin-impregnated mosquito nets compared with DDT house-spraying against malaria transmission by Anopheles farauti and An.punctulatus in the Solomon Islands.

    PubMed

    Hii, J L; Kanai, L; Foligela, A; Kan, S K; Burkot, T R; Wirtz, R A

    1993-10-01

    In villages of northern Guadalcanal in the Solomon Islands, where the predominant malaria vector is An.farauti No. 1 and An.puctulatus is also involved, malaria transmission rates were compared for three zones: (1) non-intervention: 438 people in seventeen villages; (2) residual DDT house-spraying two cycles per year: 644 people in thirty villages; (3) bednets impregnated with permethrin 0.5 g/m2 twice per year, used by 580 people in sixteen villages. Regular DDT spraying in zones 1 and 3 had been withdrawn 18 months previously. Malariological blood smear surveys of children aged 1-9 years in August 1986 to January 1987 showed a mean baseline malaria parasite rate of 38% (32/84). By February 1988, 18 months after introduction of impregnated bednets, the Plasmodium falciparum infection rate in children was lowest in the zone using impregnated bednets (21% of 29), intermediate in the untreated zone (29% of 34) and highest in the DDT zone (46% of 53), but these differences were not statistically significant. P. vivax infection rates were 9-14%. Using ELISA tests for malaria circumsporozoite antigen in the vectors, overall positivity rates were 0.7% of 49,902 An.farauti and 2.54% of 118 An.punctulatus, comprising 228 P.falciparum and 124 P.vivax infections. In the study zones, vector positivity rates were 0.93% of 31,615 An.farauti in the untreated zone; 0.32% of 16,883 An.farauti in the DDT zone; 0.07% of 1404 An.farauti and 2.54% of 118 An.puctulatus in the impregnated bednet zone. here was no significant correlation between malaria parasite rates in the vectors and the children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8268487

  6. Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity

    PubMed Central

    Kangoye, David Tiga; Mensah, Victorine Atanase; Murungi, Linda Muthoni; Nkumama, Irene; Nebie, Issa; Marsh, Kevin; Cisse, Badara; Bejon, Philip; Osier, Faith Hope Among’in; Sirima, Sodiomon Bienvenu; Yaro, Jean-Baptiste; Debe, Siaka; Traore, Safiatou; Ndaw, Aminata; Faye, Babacar; Soulama, Issiaka; Diarra, Amidou; Tiono, Alfred

    2016-01-01

    Background Young infants have reduced susceptibility to febrile malaria compared with older children, but the mechanism for this remains unclear. There are conflicting data on the role of passively acquired antibodies. Here, we examine antibody titres to merozoite surface antigens in the protection of children in their first two years of life in two settings with differing malaria transmission intensity and compare these titres to previously established protective thresholds. Methods Two cohorts of children aged four to six weeks were recruited in Banfora, Burkina and Keur Soce, Senegal and followed up for two years. Malaria infections were detected by light microscopic examination of blood smears collected at active and passive case detection visits. The titres of antibodies to the Plasmodium falciparum recombinant merozoite proteins (AMA1-3D7, MSP1-19, MSP2-Dd2, and MSP3-3D7) were measured by enzyme-linked immunosorbent assay at 1–6, 9, 12, 15 and 18 months of age and compared with the protective thresholds established in Kenyan children. Results Antibody titres were below the protective thresholds throughout the study period and we did not find any association with protection against febrile malaria. Antibodies to AMA1 and MSP1-19 appeared to be markers of exposure in the univariate analysis (and so associated with increasing risk) and adjusting for exposure reduced the strength and significance of this association. Conclusion The antibody levels we measured are unlikely to be responsible for the apparent protection against febrile malaria seen in young infants. Further work to identify protective antibody responses might include functional assays and a wider range of antigens. PMID:26541134

  7. Annual variations in the number of malaria cases related to two different patterns of Anopheles darlingi transmission potential in the Maroni area of French Guiana

    PubMed Central

    2010-01-01

    Background With an Annual Parasite Incidence (API) of 132.1, in the high and moderate risks zones, the Maroni area of French Guiana has the second highest malaria incidence of South-America after Guyana (API = 183.54) and far above Brazil (API = 28.25). Malaria transmission is occurring despite strong medical assistance and active vector control, based on general WHO recommendations. This situation is generated by two main factors that are the social and cultural characteristics of this border area, where several ethnic groups are living, and the lack of understanding of transmission dynamics of the main mosquito vector, Anopheles darlingi. In this context, entomological data collected in two villages belonging to two different ethnic groups of the French border of the Maroni River, were retrospectively analysed to find out how the mosquito bionomics are related to the malaria transmission patterns. Methods Data were provided by human landing catches of mosquitoes carried out each month for two years in two villages belonging to two ethnic groups, the Amerindians Wayanas and the Aloukous of African origin. The mosquitoes were sorted by species, sex, date, hour and place of collection and processed for Plasmodium sp. parasite detection. The data were compiled to provide the following variables: human biting rates (HBR), parity rates (PR), numbers of infective bites (IB), entomological inoculation rates (EIR) and numbers of infected mosquitoes surviving enough to transmit (IMT). Spatial and temporal differences of variables between locations and during the night were tested by the Kruskall-Wallis analysis of variance to find out significant variations. Results The populations of the main mosquito vector An. darlingi showed significant variations in the spatial and temporal HBR/person/night and HBR/person/hour, IB/person/month and IB/person/hour, and IMT/village/night and IMT/village/hour. In the village of Loca (Aloukous), the IMT peaked from June to August with a

  8. Application of a biochemical key to study transmission of malaria and Bancroftian filariasis in sibling species of the Anopheles gambiae complex in north-eastern Tanzania.

    PubMed

    Mnzava, A E; Kilama, W L; Kasigwa, P F

    1989-10-01

    A biochemical key was applied in order to study transmission of malaria and Bancroftian filariasis in Anopheles gambiae sensu stricto, An. arabiensis and An. merus in different localities in north-eastern Tanzania. The technique was found to be a useful additional taxonomic tool for field entomologists. Significant differences between species in the rate of infection with Bancroftian filariasis were obtained between An. gambiae s.s. and An. funestus (P less than 0.005) and between An. funestus and An. arabiensis (P less than 0.0001). There were also significant differences between most of the investigated localities in the rate of filarial infection. However, there were no significant differences between the three species or between localities with respect to malaria sporozoite rates. Possible reasons for the observed variation between species and localities with respect to vectorial activity for Bancroftian filariasis are discussed. PMID:2575868

  9. Variation in exposure to Anopheles gambiae salivary gland peptide (gSG6-P1) across different malaria transmission settings in the western Kenya highlands

    PubMed Central

    2012-01-01

    Background The existing metrics of malaria transmission are limited in sensitivity under low transmission intensity. Robust surveillance systems are needed as interventions to monitor reduced transmission and prevention of rapid reintroduction. Serological tools based on antibody responses to parasite and vector antigens are potential tools for transmission measurements. The current study sought to evaluate antibody responses to Anopheles gambiae salivary gland peptide (gSG6- P1), as a biomarker of human exposure to Anopheles bites, in different transmission settings and seasons. The comparison between anti-MSP-119 IgG immune responders and non-responders allowed exploring the robustness of the gSG6-P1 peptide as a surveillance tool in an area of decreasing malaria transmission. Methods Total IgG levels to gSG6-P1 were measured in an age-stratified cohort (< 5, 5–14 and ≥ 15 years) in a total of 1,366 participants from three localities in western Kenya [Kisii (hypoendemic), Kakamega (mesoendemic), and Kombewa (hyperendemic)] including 607 sera that were additionally tested for MSP-119 specific responses during a low and a high malaria transmission seasons. Antibody prevalence and levels were compared between localities with different transmission intensities. Regression analysis was performed to examine the association between gSG6-P1 and MSP-119 seroprevalence and parasite prevalence. Result Seroprevalence of gSG6-P1 in the uphill population was 36% while it was 50% valley bottom (χ2 = 13.2, df = 1, p < 0.001). Median gSG6-P1 antibody levels in the Valley bottom were twice as high as that observed in the uphill population [4.50 vs. 2.05, p < 0.001] and showed seasonal variation. The odds of gSG6-P1 seropositives having MSP-119 antibodies were almost three times higher than the odds of seronegatives (OR = 2.87, 95% CI [1.977, 4.176]). The observed parasite prevalence for Kisii, Kakamega and Kombewa were 4%, 19.7% and 44.6% whilst the

  10. Three-dimensional analysis of morphological changes in the malaria parasite infected red blood cell by serial block-face scanning electron microscopy.

    PubMed

    Sakaguchi, Miako; Miyazaki, Naoyuki; Fujioka, Hisashi; Kaneko, Osamu; Murata, Kazuyoshi

    2016-03-01

    The human malaria parasite, Plasmodium falciparum, exhibits morphological changes during the blood stage cycle in vertebrate hosts. Here, we used serial block-face scanning electron microscopy (SBF-SEM) to visualize the entire structures of P. falciparum-infected red blood cells (iRBCs) and to examine their morphological and volumetric changes at different stages. During developmental stages, the parasite forms Maurer's clefts and vesicles in the iRBC cytoplasm and knobs on the iRBC surface, and extensively remodels the iRBC structure for proliferation of the parasite. In our observations, the Maurer's clefts and vesicles in the P. falciparum-iRBCs, resembling the so-called tubovesicular network (TVN), were not connected to each other, and continuous membrane networks were not observed between the parasitophorous vacuole membrane (PVM) and the iRBC cytoplasmic membrane. In the volumetric analysis, the iRBC volume initially increased and then decreased to the end of the blood stage cycle. This suggests that it is necessary to absorb a substantial amount of nutrients from outside the iRBC during the initial stage, but to release waste materials from inside the iRBC at the multinucleate stage. Transportation of the materials may be through the iRBC membrane, rather than a special structure formed by the parasite, because there is no direct connection between the iRBC membrane and the parasite. These results provide new insights as to how the malaria parasite grows in the iRBC and remodels iRBC structure during developmental stages; these observation can serve as a baseline for further experiments on the effects of therapeutic agents on malaria. PMID:26772147

  11. A small mitochondrial protein present in myzozoans is essential for malaria transmission

    PubMed Central

    Klug, Dennis; Mair, Gunnar R.; Frischknecht, Friedrich; Douglas, Ross G.

    2016-01-01

    Myzozoans (which include dinoflagellates, chromerids and apicomplexans) display notable divergence from their ciliate sister group, including a reduced mitochondrial genome and divergent metabolic processes. The factors contributing to these divergent processes are still poorly understood and could serve as potential drug targets in disease-causing protists. Here, we report the identification and characterization of a small mitochondrial protein from the rodent-infecting apicomplexan parasite Plasmodium berghei that is essential for development in its mosquito host. Parasites lacking the gene mitochondrial protein ookinete developmental defect (mpodd) showed malformed parasites that were unable to transmit to mosquitoes. Knockout parasites displayed reduced mitochondrial mass without affecting organelle integrity, indicating no role of the protein in mitochondrial biogenesis or morphology maintenance but a likely role in mitochondrial import or metabolism. Using genetic complementation experiments, we identified a previously unrecognized Plasmodium falciparum homologue that can rescue the mpodd(−) phenotype, thereby showing that the gene is functionally conserved. As far as can be detected, mpodd is found in myzozoans, has homologues in the phylum Apicomplexa and appears to have arisen in free-living dinoflagellates. This suggests that the MPODD protein has a conserved mitochondrial role that is important for myzozoans. While previous studies identified a number of essential proteins which are generally highly conserved evolutionarily, our study identifies, for the first time, a non-canonical protein fulfilling a crucial function in the mitochondrion during parasite transmission. PMID:27053680

  12. A small mitochondrial protein present in myzozoans is essential for malaria transmission.

    PubMed

    Klug, Dennis; Mair, Gunnar R; Frischknecht, Friedrich; Douglas, Ross G

    2016-04-01

    Myzozoans (which include dinoflagellates, chromerids and apicomplexans) display notable divergence from their ciliate sister group, including a reduced mitochondrial genome and divergent metabolic processes. The factors contributing to these divergent processes are still poorly understood and could serve as potential drug targets in disease-causing protists. Here, we report the identification and characterization of a small mitochondrial protein from the rodent-infecting apicomplexan parasitePlasmodium bergheithat is essential for development in its mosquito host. Parasites lacking the gene mitochondrial protein ookinete developmental defect (mpodd) showed malformed parasites that were unable to transmit to mosquitoes. Knockout parasites displayed reduced mitochondrial mass without affecting organelle integrity, indicating no role of the protein in mitochondrial biogenesis or morphology maintenance but a likely role in mitochondrial import or metabolism. Using genetic complementation experiments, we identified a previously unrecognizedPlasmodium falciparumhomologue that can rescue thempodd(-)phenotype, thereby showing that the gene is functionally conserved. As far as can be detected,mpoddis found in myzozoans, has homologues in the phylumApicomplexaand appears to have arisen in free-living dinoflagellates. This suggests that the MPODD protein has a conserved mitochondrial role that is important for myzozoans. While previous studies identified a number of essential proteins which are generally highly conserved evolutionarily, our study identifies, for the first time, a non-canonical protein fulfilling a crucial function in the mitochondrion during parasite transmission. PMID:27053680

  13. Migration and Malaria in Europe

    PubMed Central

    Monge-Maillo, Begoña; López-Vélez, Rogelio

    2012-01-01

    The proportion of imported malaria cases due to immigrants in Europe has increased during the lasts decades, with higher rates associated with settled immigrants who travel to visit friends and relatives (VFRs) in their country of origin. Cases are mainly due to P. falciparum and Sub-Saharan Africa is the most common origin. Clinically, malaria in immigrants is characterised by a mild clinical presentation including asymptomatic or delayed malaria cases and low parasitic levels. These characteristics may be explained by a semi-immunity acquired after long periods of time exposed to stable malaria transmission. Malaria cases among immigrants, even asymptomatic patients with sub-microscopic parasitemia, could increase the risk of transmission and cause the reintroduction of malaria in certain areas that have adequate vectors and climate conditions. Moreover, imported malaria cases in immigrants can also play an important role in the non-vector transmission out of endemic areas, through blood transfusions, organ transplantation or congenital transmission or occupational exposures. Consequently, outside of endemic areas, malaria screening should be carried out among recently arrived immigrants coming from malaria endemic countries. The aim of screening is to reduce the risk of clinical malaria in the individual as well as to prevent autochthonous transmission of malaria in areas where it has been eradicated. PMID:22536477

  14. The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission.

    PubMed

    Balaich, Jared N; Mathias, Derrick K; Torto, Baldwyn; Jackson, Bryan T; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B; Cheseto, Xavier; Foster, Woodbridge A; Dinglasan, Rhoel R

    2016-04-01

    Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect onPlasmodiumblood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages ofPlasmodium falciparumas it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin againstP. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal. PMID:26787692

  15. Malaria Research

    MedlinePlus

    ... Malaria > Research Malaria Understanding Research NIAID Role Basic Biology Prevention and Control Strategies Strategic Partnerships and Research ... the malaria parasite. Related Links Global Research​ Vector Biology International Centers of Excellence for Malaria Research (ICEMR) ...

  16. Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.

    PubMed

    Liu, Yang; Zhang, Fuchun; Liu, Jianying; Xiao, Xiaoping; Zhang, Siyin; Qin, Chengfeng; Xiang, Ye; Wang, Penghua; Cheng, Gong

    2014-02-01

    C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1), facilitating the attachment of West Nile virus (WNV) on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E) protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden. PMID:24550728

  17. Quantification of Plasmodium falciparum malaria from complex infections in the Peruvian Amazon using quantitative PCR of the merozoite surface protein 1, block 2 (PfMSP1-B2): in vitro dynamics reveal density-dependent interactions.

    PubMed

    Zervos, Thomas M; Hernandez, Jean N; Sutton, Patrick L; Branch, Oralee H

    2012-05-01

    The majority of Plasmodium falciparum field isolates are defined as complex infections because they contain multiple genetically distinct clones. Studying interactions between clones in complex infections in vivo and in vitro could elucidate important phenomena in malaria infection, transmission and treatment. Using quantitative PCR (qPCR) of the P. falciparum merozoite surface protein 1, block 2 (PfMSP1-B2), we provide a sensitive and efficient genotyping method. This is important for epidemiological studies because it makes it possible to study genotype-specific growth dynamics. We compared 3 PfMSP1-B2 genotyping methods by analysing 79 field isolates from the Peruvian Amazon. In vivo observations from other studies using these techniques led to the hypothesis that clones within complex infections interact. By co-culturing clones with different PfMSP1-B2 genotypes, and measuring parasitaemia using qPCR, we found that suppression of clonal expansion was a factor of the collective density of all clones present in a culture. PfMSP1-B2 qPCR enabled us to find in vitro evidence for parasite-parasite interactions and could facilitate future investigations of growth trends in naturally occurring complex infections. PMID:22339946

  18. Clinical Variation of Plasmodium falciparum eba-175, ama-1, and msp-3 Genotypes in Young Children Living in a Seasonally High Malaria Transmission Setting in Burkina Faso

    PubMed Central

    Soulama, Issiaka; Sermé, Samuel S.; Bougouma, Edith C.; Diarra, Amidou; Tiono, Alfred B.; Ouedraogo, Alphonse; Konate, Amadou T.; Nebie, Issa; Sirima, Sodiomon B.

    2015-01-01

    The association between P. falciparum eba-175, ama-1, and msp-3 polymorphism in the pathogenicity of malaria disease was investigated. We therefore compared the prevalence of different alleles between symptomatic and asymptomatic malarial children under five years of age living in Burkina Faso. Blood filter papers were collected during the 2008 malaria transmission season from 228 symptomatic and 199 asymptomatic children under five years of age. All patients were living in the rural area of Saponé at about 50 km from Ouagadougou, the capital city of Burkina Faso. P. falciparum parasite DNA was extracted using QIAGEN kits and the alleles diversity was assessed by a nested PCR. PCR products were then digested by restriction enzymes based on already described polymorphic regions of the eba-175, ama-1, and msp-3 genes. The individual alleles eba-175_FCR3 and msp-3_K1 frequencies were statistically higher (p < 0.0001) in the asymptomatic group compared to the symptomatic ones. No statistically significant difference was noted in the prevalence of ama-1-3D7, ama-1-K1, and ama-1-HB3 genotypes between the two groups (p > 0.05). The comparative analysis of P. falciparum genotypes indicated that the polymorphism in eba-175 and msp-3 genotypes varied between asymptomatic and symptomatic clinical groups and may contribute to the pathogenesis of malaria. PMID:26634149

  19. Clinical Variation of Plasmodium falciparum eba-175, ama-1, and msp-3 Genotypes in Young Children Living in a Seasonally High Malaria Transmission Setting in Burkina Faso.

    PubMed

    Soulama, Issiaka; Sermé, Samuel S; Bougouma, Edith C; Diarra, Amidou; Tiono, Alfred B; Ouedraogo, Alphonse; Konate, Amadou T; Nebie, Issa; Sirima, Sodiomon B

    2015-01-01

    The association between P. falciparum eba-175, ama-1, and msp-3 polymorphism in the pathogenicity of malaria disease was investigated. We therefore compared the prevalence of different alleles between symptomatic and asymptomatic malarial children under five years of age living in Burkina Faso. Blood filter papers were collected during the 2008 malaria transmission season from 228 symptomatic and 199 asymptomatic children under five years of age. All patients were living in the rural area of Saponé at about 50 km from Ouagadougou, the capital city of Burkina Faso. P. falciparum parasite DNA was extracted using QIAGEN kits and the alleles diversity was assessed by a nested PCR. PCR products were then digested by restriction enzymes based on already described polymorphic regions of the eba-175, ama-1, and msp-3 genes. The individual alleles eba-175_FCR3 and msp-3_K1 frequencies were statistically higher (p < 0.0001) in the asymptomatic group compared to the symptomatic ones. No statistically significant difference was noted in the prevalence of ama-1-3D7, ama-1-K1, and ama-1-HB3 genotypes between the two groups (p > 0.05). The comparative analysis of P. falciparum genotypes indicated that the polymorphism in eba-175 and msp-3 genotypes varied between asymptomatic and symptomatic clinical groups and may contribute to the pathogenesis of malaria. PMID:26634149

  20. MALVAC 2012 scientific forum: accelerating development of second-generation malaria vaccines

    PubMed Central

    2012-01-01

    The World Health Organization (WHO) convened a malaria vaccines committee (MALVAC) scientific forum from 20 to 21 February 2012 in Geneva, Switzerland, to review the global malaria vaccine portfolio, to gain consensus on approaches to accelerate second-generation malaria vaccine development, and to discuss the need to update the vision and strategic goal of the Malaria Vaccine Technology Roadmap. This article summarizes the forum, which included reviews of leading Plasmodium falciparum vaccine candidates for pre-erythrocytic vaccines, blood-stage vaccines, and transmission-blocking vaccines. Other major topics included vaccine candidates against Plasmodium vivax, clinical trial site capacity development in Africa, trial design considerations for a second-generation malaria vaccine, adjuvant selection, and regulatory oversight functions including vaccine licensure. PMID:23140365

  1. Characterization of malaria transmission by vector populations for improved interventions during the dry season in the Kpone-on-Sea area of coastal Ghana

    PubMed Central

    2012-01-01

    Background Malaria is a major public health problem in Ghana. We present a site-specific entomological study of malaria vectors and transmission indices as part of an effort to develop a site for the testing of improved control strategies including possible vaccine trials. Methods Pyrethrum spray catches (PSC), and indoor and outdoor human landing collections of adult female anopheline mosquitoes were carried out over a six-month period (November 2005 - April 2006) at Kpone-on-Sea, a fishing village in southern Ghana. These were morphologically identified to species level and sibling species of the Anopheles gambiae complex further characterized by the polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay was used to detect Plasmodium falciparum mosquito infectivity and host blood meal sources. Parity rate was examined based on dilatation of ovarian tracheoles following dissection. Results Of the 1233 Anopheles mosquitoes collected, An. gambiae s.l. was predominant (99.5%), followed by An. funestus (0.4%) and An. pharoensis (0.1%). All An. gambiae s.l. examined (480) were identified as An. gambiae s.s. with a majority of M molecular form (98.2%) and only 1.8% S form with no record of M/S hybrid. A significantly higher proportion of anophelines were observed outdoors relative to indoors (χ2 = 159.34, df = 1, p < 0.0000). Only An. gambiae M molecular form contributed to transmission with a high degree of anthropophily, parity rate and an estimated entomological inoculation rate (EIR) of 62.1 infective bites/person/year. The Majority of the infective bites occurred outdoors after 09.00 pm reaching peaks between 12.00-01.00 am and 03.00-04.00 am. Conclusion Anopheles gambiae M molecular form is responsible for maintaining the status quo of malaria in the surveyed site during the study period. The findings provide a baseline for evidence-based planning and implementation of improved malaria interventions. The plasticity observed in

  2. Individual and Household Level Risk Factors Associated with Malaria in Nchelenge District, a Region with Perennial Transmission: A Serial Cross-Sectional Study from 2012 to 2015

    PubMed Central

    Pinchoff, Jessie; Chaponda, Mike; Shields, Timothy M.; Sichivula, James; Muleba, Mbanga; Mulenga, Modest; Kobayashi, Tamaki; Curriero, Frank C.; Moss, William J.

    2016-01-01

    Background The scale-up of malaria control interventions has resulted in substantial declines in transmission in some but not all regions of sub-Saharan Africa. Understanding factors associated with persistent malaria transmission despite control efforts may guide targeted interventions to high-risk areas and populations. Methods Household malaria surveys were conducted in Nchelenge District, Luapula Province, in northern Zambia. Structures that appeared to be households were enumerated from a high-resolution satellite image and randomly sampled for enrollment. Households were enrolled into cross-sectional (single visit) or longitudinal (visits every other month) cohorts but analyses were restricted to cross-sectional visits and the first visit to longitudinal households. During study visits, a questionnaire was administered to adults and caretakers of children and a blood sample was collected for a malaria rapid diagnostic test (RDT) from all household residents. Characteristics associated with RDT positivity were analyzed using multi-level models. Results A total of 2,486 individuals residing within 742 households were enrolled between April 2012 and July 2015. Over this period, 51% of participants were RDT positive. Forty-three percent of all RDT positive individuals were between the ages of 5 and 17 years although this age group comprised only 30% of study participants. In a multivariable model, the odds being RDT positive were highest in 5–17 year olds and did not vary by season. Children 5–17 years of age had 8.83 higher odds of being RDT positive compared with those >18 years of age (95% CI: 6.13, 12.71); there was an interaction between age and report of symptoms, with an almost 50% increased odds of report of symptoms with decreasing age category (OR = 1.49; 95% CI 1.11, 2.00). Conclusions Children and adolescents between the ages of 5 and 17 were at the highest risk of malaria infection throughout the year. School-based programs may be effective at

  3. A qualitative study on caretakers' perceived need of bed-nets after reduced malaria transmission in Zanzibar, Tanzania

    PubMed Central

    2012-01-01

    Background The elimination of malaria in Zanzibar is highly dependent on sustained effective coverage of bed-nets to avoid malaria resurgence. The Health Belief Model (HBM) framework was used to explore the perceptions of malaria and bed-net use after a noticeable reduction in malaria incidence. Methods Nineteen in-depth interviews were conducted with female and male caretakers of children under five in North A district, Zanzibar. Deductive content analysis was used to identify meaning units that were condensed, coded and assigned to pre-determined elements of the HBM. Results Awareness of malaria among caretakers was high but the illness was now seen as easily curable and uncommon. In addition to the perceived advantage of providing protection against malaria, bed-nets were also thought to be useful for avoiding mosquito nuisance, especially during the rainy season when the malaria and mosquito burden is high. The discomfort of sleeping under a net during the hot season was the main barrier that interrupted consistent bed-net usage. The main cue to using a bed-net was high mosquito density, and children were prioritized when it came to bed-net usage. Caretakers had high perceived self-efficacy and did not find it difficult to use bed-nets. Indoor Residual Spraying (IRS), which was recognized as an additional means of mosquito prevention, was not identified as an alternative for bed-nets. A barrier to net ownership was the increasingly high cost of bed-nets. Conclusions Despite the reduction in malaria incidence and the resulting low malaria risk perceptions among caretakers, the benefit of bed-nets as the most proficient protection against mosquito bites upholds their use. This, in combination with the perceived high self-efficacy of caretakers, supports bed-net usage, while seasonality interrupts consistent use. High effective coverage of bed-nets could be further improved by reinforcing the benefits of bed-nets, addressing the seasonal heat barrier by using nets

  4. Blocking HIV-1 transmission in the female reproductive tract: from microbicide development to exploring local antiviral responses

    PubMed Central

    Eid, Sahar G; Mangan, Niamh E; Hertzog, Paul J; Mak, Johnson

    2015-01-01

    The majority of new HIV-1 infections are transmitted sexually by penetrating the mucosal barrier to infect target cells. The development of microbicides to restrain heterosexual HIV-1 transmission in the past two decades has proven to be a challenging endeavor. Therefore, better understanding of the tissue environment in the female reproductive tract may assist in the development of the next generation of microbicides to prevent HIV-1 transmission. In this review, we highlight the important factors involved in the heterosexual transmission of HIV-1, provide an update on microbicides' clinical trials, and discuss how different delivery platforms and local immunity may empower the development of next generation of microbicide to block HIV-1 transmission in the female reproductive tract. PMID:26682051

  5. [Identification of anopheles breeding sites in the residual foci of low malaria transmission «hotspots» in Central and Western Senegal].

    PubMed

    Sy, O; Konaté, L; Ndiaye, A; Dia, I; Diallo, A; Taïrou, F; Bâ, E L; Gomis, J F; Ndiaye, J L; Cissé, B; Gaye, O; Faye, O

    2016-02-01

    Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non-hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission. PMID:26830896

  6. Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito

    PubMed Central

    2013-01-01

    Background The transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by dormant sexual precursor cells, the gametocytes, which become activated in the mosquito midgut. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they play a crucial role in spreading the tropical disease. The human-to-mosquito transmission triggers important molecular changes in the gametocytes, which initiate gametogenesis and prepare the parasite for life-cycle progression in the insect vector. Results To better understand gene regulations during the initial phase of malaria parasite transmission, we focused on the transcriptome changes that occur within the first half hour of parasite development in the mosquito. Comparison of mRNA levels of P. falciparum gametocytes before and 30 min following activation using suppression subtractive hybridization (SSH) identified 126 genes, which changed in expression during gametogenesis. Among these, 17.5% had putative functions in signaling, 14.3% were assigned to cell cycle and gene expression, 8.7% were linked to the cytoskeleton or inner membrane complex, 7.9% were involved in proteostasis and 6.4% in metabolism, 12.7% were cell surface-associated proteins, 11.9% were assigned to other functions, and 20.6% represented genes of unknown function. For 40% of the identified genes there has as yet not been any protein evidence. For a subset of 27 genes, transcript changes during gametogenesis were studied in detail by real-time RT-PCR. Of these, 22 genes were expressed in gametocytes, and for 15 genes transcript expression in gametocytes was increased compared to asexual blood stage parasites. Transcript levels of seven genes were particularly high in activated gametocytes, pointing at functions downstream of gametocyte transmission to the mosquito. For selected genes, a regulated expression during gametogenesis was confirmed on the protein level, using

  7. Factors Associated with Sustained Use of Long-Lasting Insecticide-Treated Nets Following a Reduction in Malaria Transmission in Southern Zambia.

    PubMed

    Pinchoff, Jessie; Hamapumbu, Harry; Kobayashi, Tamaki; Simubali, Limonty; Stevenson, Jennifer C; Norris, Douglas E; Colantuoni, Elizabeth; Thuma, Philip E; Moss, William J

    2015-11-01

    Understanding factors influencing sustained use of long-lasting insecticide-treated nets (LLIN) in areas of declining malaria transmission is critical to sustaining control and may facilitate elimination. From 2008 to 2013, 655 households in Choma District, Zambia, were randomly selected and residents were administered a questionnaire and malaria rapid diagnostic test. Mosquitoes were collected concurrently by light trap. In a multilevel model, children and adolescents of 5-17 years of age were 55% less likely to sleep under LLIN than adults (odds ratio [OR] = 0.45; 95% confidence interval [CI] = 0.35, 0.58). LLIN use was 80% higher during the rainy season (OR = 1.8; CI = 1.5, 2.2) and residents of households with three or more nets were over twice as likely to use a LLIN (OR = 2.1; CI = 1.4, 3.1). For every increase in 0.5 km from the nearest health center, the odds of LLIN use decreased 9% (OR = 0.9; CI = 0.88, 0.98). In a second multilevel model, the odds of LLIN use were more than twice high if more than five mosquitoes (anopheline and culicine) were captured in the house compared with households with no mosquitoes captured (OR = 2.1; CI = 1.1, 3.9). LLIN use can be sustained in low-transmission settings with continued education and distributions, and may be partially driven by the presence of nuisance mosquitoes. PMID:26324729

  8. On the use of satellite-based estimates of rainfall temporal distribution to simulate the potential for malaria transmission in rural Africa

    NASA Astrophysics Data System (ADS)

    Yamana, Teresa K.; Eltahir, Elfatih A. B.

    2011-02-01

    This paper describes the use of satellite-based estimates of rainfall to force the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a hydrology-based mechanistic model of malaria transmission. We first examined the temporal resolution of rainfall input required by HYDREMATS. Simulations conducted over Banizoumbou village in Niger showed that for reasonably accurate simulation of mosquito populations, the model requires rainfall data with at least 1 h resolution. We then investigated whether HYDREMATS could be effectively forced by satellite-based estimates of rainfall instead of ground-based observations. The Climate Prediction Center morphing technique (CMORPH) precipitation estimates distributed by the National Oceanic and Atmospheric Administration are available at a 30 min temporal resolution and 8 km spatial resolution. We compared mosquito populations simulated by HYDREMATS when the model is forced by adjusted CMORPH estimates and by ground observations. The results demonstrate that adjusted rainfall estimates from satellites can be used with a mechanistic model to accurately simulate the dynamics of mosquito populations.

  9. Malaria epidemiology and control in Southern Africa.

    PubMed

    Mharakurwa, Sungano; Thuma, Philip E; Norris, Douglas E; Mulenga, Modest; Chalwe, Victor; Chipeta, James; Munyati, Shungu; Mutambu, Susan; Mason, Peter R

    2012-03-01

    The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, following the scale-up of interventions supported by the Roll Back Malaria Partnership, the President's Malaria Initiative and other partners. It is important to appreciate that the reductions in malaria have not been uniform between and within countries, with some areas experiencing resurgence instead. Furthermore, while interventions have greatly reduced the burden of malaria in many countries, it is also recognized that the malaria decline pre-dated widespread intervention efforts, at least in some cases where data are available. This raises more questions as what other factors may have been contributing to the reduction in malaria transmission and to what extent. The International Center of Excellence for Malaria Research (ICEMR) in Southern Africa aims to better understand the underlying malaria epidemiology, vector ecology and parasite genomics using three contrasting settings of malaria transmission in Zambia and Zimbabwe: an area of successful malaria control, an area of resurgent malaria and an area where interventions have not been effective. The Southern Africa ICEMR will capitalize on the opportunity to investigate the complexities of malaria transmission while adapting to intervention and establish the evidence-base to guide effective and sustainable malaria intervention strategies. Key approaches to attain this goal for the region will include close collaboration with national malaria control programs and contribution to capacity building at the individual, institutional and national levels. PMID:21756864

  10. Malaria vaccines and human immune responses.

    PubMed

    Long, Carole A; Zavala, Fidel

    2016-08-01

    Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. PMID:27262417

  11. Transmission block in terminal nerve twigs: a single fibre electromyographic finding in man

    PubMed Central

    Stålberg, Erik; Thiele, Barbara

    1972-01-01

    Single fibre electromyography has been performed in patients with partial nerve lesions, amyotrophic lateral sclerosis, progressive spinal muscle atrophy, muscular dystrophy, and distal hereditary myopathy. The recorded action potentials were often more complex than in the normal muscle due to increased fibre density in the motor unit and the individual spike components showed a large jitter and occasional blockings. Sometimes two or more spikes in a complex disappeared and reappeared simultaneously upon successive discharges. This phenomenon, called `paired blocking', has been further investigated. The jitter of the blocking potentials in relation to the rest of the complex was large, up to 500 μsec. The degree of blocking increased with increasing innervation frequency until it eventually proceeded to total block during continuous activity. Sometimes a slight effect on blocking was seen after edrophonium. This type of block is probably localized in the terminal nerve twigs, perhaps in newly formed sprouts. The phenomenon of neurogenic blocking may contribute to the fatigue clinically experienced in different denervation-reinnervation cases. Images PMID:4337272

  12. [Vectorial transmission of malaria in a village along the Niger River and its fishing hamlet (Kéniéroba and Fourda, Mali)].

    PubMed

    Keïta, M; Baber, I; Sogoba, N; Maïga, H M; Diallo, M'b; Doumbia, S; Traoré, S F

    2014-12-01

    A better understanding of malaria transmission dynamics is an essential element in the development of any targeted vector control strategy. The objective of this study was to better understand malaria transmission dynamics along the Niger River in Sudan savanna zone of Mali. Trough cross-sectional surveys, Anopheline larvae were collected by WHO standard dipping technique, and vector adults by Human Landing and pyrethrum spray catches methods. The vector population was composed of An. gambiae s.l. (> 99%) and An. funestus (< 1%). An. gambiae s.l. was composed of 96% and 98% of An. gambiae s.s. respectively in Kéniéroba and Fourda. An. gambiae s.s. was in majority composed of its molecular form M in both locations. The density of An. gambiae s.l was higher in the dry season in the immediate vicinity of the river (fishing hamlet Fourda) compared to farther inland Kéniéroba. The average infection rate of An. gambiae s.l. was 3.63% and 4.06% in Kéniéroba and Fourda respectively. The average entomological inoculation rate (EIR) during the study period was almost similar in Kéniéroba (0.70 infective bites/person/month) and Fourda (0.69 infective bites/person/month). The means EIRs over each of the rainy season 2006 and 2007 were always higher than the one of the dry season 2007 in both localities, with much smaller amplitude in Fourda than in Kéniéroba. However, the level of the transmission was 2.31 (0.37/0.16) times higher in Fourda than in Kéniéroba during the dry season.We conclude that in Sudan savanna zone of Mali, malaria transmission along the river is continuous throughout the year, but it is more intense in the immediate vicinity of the river during the dry season than during the rainy season in opposition to more distant localities to the river and vector control should not be focused only on the rainy in such setting. PMID:25326713

  13. Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection

    PubMed Central

    Cornejo, Omar E.; Durrego, Ester; Stanley, Craig E.; Castillo, Andreína I.; Herrera, Sócrates; Escalante, Ananias A.

    2016-01-01

    Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28. PMID:27347876

  14. Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection.

    PubMed

    Chaurio, Ricardo A; Pacheco, M Andreína; Cornejo, Omar E; Durrego, Ester; Stanley, Craig E; Castillo, Andreína I; Herrera, Sócrates; Escalante, Ananias A

    2016-06-01

    Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28. PMID:27347876

  15. Mixture block coding with progressive transmission in packet video. Appendix 1: Item 2. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Chen, Yun-Chung

    1989-01-01

    Video transmission will become an important part of future multimedia communication because of dramatically increasing user demand for video, and rapid evolution of coding algorithm and VLSI technology. Video transmission will be part of the broadband-integrated services digital network (B-ISDN). Asynchronous transfer mode (ATM) is a viable candidate for implementation of B-ISDN due to its inherent flexibility, service independency, and high performance. According to the characteristics of ATM, the information has to be coded into discrete cells which travel independently in the packet switching network. A practical realization of an ATM video codec called Mixture Block Coding with Progressive Transmission (MBCPT) is presented. This variable bit rate coding algorithm shows how a constant quality performance can be obtained according to user demand. Interactions between codec and network are emphasized including packetization, service synchronization, flow control, and error recovery. Finally, some simulation results based on MBCPT coding with error recovery are presented.

  16. Abasic phosphorothioate oligomers inhibit HIV-1 reverse transcription and block virus transmission across polarized ectocervical organ cultures.

    PubMed

    Fraietta, Joseph A; Mueller, Yvonne M; Lozenski, Karissa L; Ratner, Deena; Boesteanu, Alina C; Hancock, Aidan S; Lackman-Smith, Carol; Zentner, Isaac J; Chaiken, Irwin M; Chung, Suhman; LeGrice, Stuart F J; Snyder, Beth A; Mankowski, Marie K; Jones, Natalie M; Hope, Jennifer L; Gupta, Phalguni; Anderson, Sharon H; Wigdahl, Brian; Katsikis, Peter D

    2014-12-01

    In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2' deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application in vivo. These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1. PMID:25224013

  17. Abasic Phosphorothioate Oligomers Inhibit HIV-1 Reverse Transcription and Block Virus Transmission across Polarized Ectocervical Organ Cultures

    PubMed Central

    Fraietta, Joseph A.; Mueller, Yvonne M.; Lozenski, Karissa L.; Ratner, Deena; Boesteanu, Alina C.; Hancock, Aidan S.; Lackman-Smith, Carol; Zentner, Isaac J.; Chaiken, Irwin M.; Chung, Suhman; LeGrice, Stuart F. J.; Snyder, Beth A.; Mankowski, Marie K.; Jones, Natalie M.; Hope, Jennifer L.; Gupta, Phalguni; Anderson, Sharon H.; Wigdahl, Brian

    2014-01-01

    In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2′ deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application in vivo. These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1. PMID:25224013

  18. A Bayesian approach for the estimation and transmission of regularization parameters for reducing blocking artifacts.

    PubMed

    Mateos, J; Katsaggelos, A K; Molina, R

    2000-01-01

    With block-based compression approaches for both still images and sequences of images annoying blocking artifacts are exhibited, primarily at high compression ratios. They are due to the independent processing (quantization) of the block transformed values of the intensity or the displaced frame difference. We propose the application of the hierarchical Bayesian paradigm to the reconstruction of block discrete cosine transform (BDCT) compressed images and the estimation of the required parameters. We derive expressions for the iterative evaluation of these parameters applying the evidence analysis within the hierarchical Bayesian paradigm. The proposed method allows for the combination of parameters estimated at the coder and decoder. The performance of the proposed algorithms is demonstrated experimentally. PMID:18262958

  19. Clinical Malaria Diagnosis in Pregnancy in Relation to Early Perinatal Mother-to-Child-Transmission of HIV: A Prospective Cohort Study

    PubMed Central

    Ezeamama, AE; Duggan, C; Manji, KP; Spiegelman, D; Hertzmark, E; Bosch, RJ; Kupka, R; Okuma, JO; Kisenge, R; Aboud, S; Fawzi, WW

    2015-01-01

    Objectives We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2,368 pregnant HIV-positive women and their infants, followed-up from pregnancy until birth and 6 weeks post-delivery in Tanzania. Methods Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal healthcare. Child HIV status was determined via DNA-PCR. Multivariable logistic regression models estimated relative risks (RR) and 95% confidence intervals (CI) for HIV mother-to-child-transmission (MTCT) by 6th week of life. Results Mean gestational age at enrollment was 22.2 weeks. During follow-up, 16.6% had ≥1 MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven percent of HIV-exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinical MIP diagnosed (RR=1.24, 95%CI:0.94–1.64), were diagnosed with 1 vs. 0 clinical MIP episode (RR=1.07;95%CI:0.77–1.48) and had ever vs. never reported fever symptoms (RR=1.04, 95%CI:0.78,1.38) in pregnancy. However, HIV MTCT risk increased by 29% (95%CI:4–58%) per MIP episode. Infants of women with ≥2 vs. 0 MIP diagnoses were 2.1 times more likely to be HIV infected by 6weeks old (95%CI:1.31–3.45). Conclusions Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with elevated risk of early HIV MTCT suggesting that malaria prevention and treatment in pregnant HIV-positive women may enhance the effectiveness of HIV prevention in MTCT programs in this setting. Future studies using laboratory confirmed malaria is needed to confirm this association. PMID:24215465

  20. Evaluation of an algorithm for integrated management of childhood illness in an area of Kenya with high malaria transmission.

    PubMed Central

    Perkins, B. A.; Zucker, J. R.; Otieno, J.; Jafari, H. S.; Paxton, L.; Redd, S. C.; Nahlen, B. L.; Schwartz, B.; Oloo, A. J.; Olango, C.; Gove, S.; Campbell, C. C.

    1997-01-01

    In 1993, the World Health Organization completed the development of a draft algorithm for the integrated management of childhood illness (IMCI), which deals with acute respiratory infections, diarrhoea, malaria, measles, ear infections, malnutrition, and immunization status. The present study compares the performance of a minimally trained health worker to make a correct diagnosis using the draft IMCI algorithm with that of a fully trained paediatrician who had laboratory and radiological support. During the 14-month study period, 1795 children aged between 2 months and 5 years were enrolled from the outpatient paediatric clinic of Siaya District Hospital in western Kenya; 48% were female and the median age was 13 months. Fever, cough and diarrhoea were the most common chief complaints presented by 907 (51%), 395 (22%), and 199 (11%) of the children, respectively; 86% of the chief complaints were directly addressed by the IMCI algorithm. A total of 1210 children (67%) had Plasmodium falciparum infection and 1432 (80%) met the WHO definition for anaemia (haemoglobin < 11 g/dl). The sensitivities and specificities for classification of illness by the health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia (97% sensitivity, 49% specificity); dehydration in children with diarrhoea (51%, 98%); malaria (100%, 0%); ear problem (98%, 2%); nutritional status (96%, 66%); and need for referral (42%, 94%). Detection of fever by laying a hand on the forehead was both sensitive and specific (91%, 77%). There was substantial clinical overlap between pneumonia and malaria (n = 895), and between malaria and malnutrition (n = 811). Based on the initial analysis of these data, some changes were made in the IMCI algorithm. This study provides important technical validation of the IMCI algorithm, but the performance of health workers should be monitored during the early part of their IMCI training. PMID:9529716

  1. High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission

    PubMed Central

    Tutterrow, Yeung L.; Avril, Marion; Singh, Kavita; Long, Carole A.; Leke, Robert J.; Sama, Grace; Salanti, Ali; Smith, Joseph D.; Leke, Rose G. F.

    2012-01-01

    Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity. PMID:22331427

  2. Resting behaviour of Anopheles gambiae s.l. and its implication on malaria transmission in Uyui District, western Tanzania.

    PubMed

    Sindato, Calvin; Kabula, Bilali; Mbilu, Togolai J N K; Manga, Chacha; Tungu, Patrick; Kazimoto, John P; Kibonai, Stafford N; Kisinza, William N; Magesa, Stephen M

    2011-10-01

    An entomological survey to determine resting behaviour and species composition of malaria vectors was carried out in Uyui District in western Tanzania in May 2009. Mosquitoes were collected using indoor resting catch, window exit trap and outdoor "bed-net" techniques. The mosquitoes were identified using morphological key and polymerase chain reaction (PCR). A total of 672 Anopheles gambiae sensu lato were collected. Of these, 661 (98.4%) were collected outdoor whereas few (1.6%) were collected indoor. The exit trap catch: mechanical aspirator catch ratio was 1:1.75. The overall indoor resting density of An. gambiae s.l. as determined by mechanical aspirator and exit trap was 0.7 and 0.5 mosquitoes per room, respectively. The overall density of the host-seeking as determined by bed net trap outdoor was 44.1 mosquitoes per person. A sample of 44 specimens taken randomly from morphologically identified An.gambiae s.l. population was further analyzed to species level using PCR techniques. Of these 44 specimens 26 (59%) and 18 (41%) were Anopheles arabiensis and Anopheles gambiae sensu stricto respectively. This study contributes to the understanding of the distribution of malaria vectors with respect to species composition and their resting behaviour that could contribute to vector control operations in western Tanzania. A longitudinal study considering dry and wet seasons is recommended to provide more information on the seasonal distribution, abundance and biting behaviour of malaria vectors in the study area. PMID:26592058

  3. Effects of transmission-blocking immunity on Plasmodium vivax infections in Anopheles albimanus populations.

    PubMed

    Ramsey, J M; Salinas, E; Rodriguez, M H; Beaudoin, R L

    1994-02-01

    Two colonized populations of Anopheles albimanus isolated from the Suchiate region, Chiapas State, Mexico, were compared for their susceptibility to coindigenous Plasmodium vivax. Groups of mosquitoes were fed in vitro with either autologous donor blood or the same blood cells substituted with serum negative for anti-gametocyte antibody. Significant differences in susceptibility between the 2 colonies were encountered if the autologous blood from a patient was fed to mosquitoes: mean infection rates of AnA2-positive groups was double that in AnA1 mosquitoes. Consistent for both colonies, only 23.6% of samples positive from malaria-negative serum-substituted blood were infected with an autologous blood feed. Vector competence in these mosquito populations was partially linked to the human populations's immune response to the parasite. PMID:8308663

  4. A physiological time analysis of the duration of the gonotrophic cycle of Anopheles pseudopunctipennis and its implications for malaria transmission in Bolivia

    PubMed Central

    Lardeux, Frédéric J; Tejerina, Rosenka H; Quispe, Vicente; Chavez, Tamara K

    2008-01-01

    Background The length of the gonotrophic cycle varies the vectorial capacity of a mosquito vector and therefore its exact estimation is important in epidemiological modelling. Because the gonotrophic cycle length depends on temperature, its estimation can be satisfactorily computed by means of physiological time analysis. Methods A model of physiological time was developed and calibrated for Anopheles pseudopunctipennis, one of the main malaria vectors in South America, using data from laboratory temperature controlled experiments. The model was validated under varying temperatures and could predict the time elapsed from blood engorgement to oviposition according to the temperature. Results In laboratory experiments, a batch of An. pseudopunctipennis fed at the same time may lay eggs during several consecutive nights (2–3 at high temperature and > 10 at low temperature). The model took into account such pattern and was used to predict the range of the gonotrophic cycle duration of An. pseudopunctipennis in four characteristic sites of Bolivia. It showed that the predicted cycle duration for An. pseudopunctipennis exhibited a seasonal pattern, with higher variances where climatic conditions were less stable. Predicted mean values of the (minimum) duration ranged from 3.3 days up to > 10 days, depending on the season and the geographical location. The analysis of ovaries development stages of field collected biting mosquitoes indicated that the phase 1 of Beklemishev might be of significant duration for An. pseudopunctipennis. The gonotrophic cycle length of An. pseudopunctipennis correlates with malaria transmission patterns observed in Bolivia which depend on locations and seasons. Conclusion A new presentation of cycle length results taking into account the number of ovipositing nights and the proportion of mosquitoes laying eggs is suggested. The present approach using physiological time analysis might serve as an outline to other similar studies and allows the

  5. Optimal control problems of epidemic systems with parameter uncertainties: application to a malaria two-age-classes transmission model with asymptomatic carriers.

    PubMed

    Mwanga, Gasper G; Haario, Heikki; Capasso, Vicenzo

    2015-03-01

    The main scope of this paper is to study the optimal control practices of malaria, by discussing the implementation of a catalog of optimal control strategies in presence of parameter uncertainties, which is typical of infectious diseases data. In this study we focus on a deterministic mathematical model for the transmission of malaria, including in particular asymptomatic carriers and two age classes in the human population. A partial qualitative analysis of the relevant ODE system has been carried out, leading to a realistic threshold parameter. For the deterministic model under consideration, four possible control strategies have been analyzed: the use of Long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic and asymptomatic individuals. The numerical results show that using optimal control the disease can be brought to a stable disease free equilibrium when all four controls are used. The Incremental Cost-Effectiveness Ratio (ICER) for all possible combinations of the disease-control measures is determined. The numerical simulations of the optimal control in the presence of parameter uncertainty demonstrate the robustness of the optimal control: the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the designing of cost-effective strategies for disease controls with multiple interventions, even under considerable uncertainty of model parameters. PMID:25481226

  6. Steps toward a globally available malaria vaccine: harnessing the potential of algae for future low cost vaccines.

    PubMed

    Jones, Carla S; Mayfield, Stephen P

    2013-01-01

    Malaria is an infectious disease that threatens half of the world's population. This debilitating disease is caused by infection from parasites of the genus Plasmodium. Insecticides, bed nets and drug therapies have lowered the prevalence and death rate associated with malaria but this disease continues to plague many populations around the world. In recent years, many organizations have suggested developing methods for a complete eradication of malaria. The most straightforward and effective method for this potential eradication will be through the development of a low-cost vaccine. To achieve eradication, it will be necessary to develop new vaccine candidates and novel systems for both the production and delivery of these vaccines. Recently, the green algae Chlamydomonas reinhardtii has been used for the recombinant expression of malaria vaccine candidates including the transmission blocking vaccine candidate Pfs48/45. Here, we discuss the potential of this research on the future development of a low-cost malaria vaccine candidate. PMID:23090388

  7. Properties of Transmission and Leaky Modes in a Plasmonic Waveguide Constructed by Periodic Subwavelength Metallic Hollow Blocks

    PubMed Central

    Jei Wu, Jin; Jang Wu, Chien; Qi Shen, Jian; Hou, Da Jun; Chen Lo, Wen

    2015-01-01

    Based on the concept of low-frequency spoof surface plasmon polaritons (spoof SPPs), a kind of leaky mode is proposed in a waveguide made of a subwavelength metal-block array with open slots. Numerical results reveal that a new transmission mode is found in the periodic subwavelength metal open blocks. This modal field is located inside the interior of a hollow block compared with that in a solid metal block array. The dispersion curve shows that such a new SPPs mode has a negative slope, crossing the light line, and then going into a zone of leaky mode at higher frequencies. The leaky mode has a wider frequency bandwidth, and this can lead to a radiation scanning angle of 53° together with high radiation efficiency. Based on the individual characteristics exhibited by a frequency-dependent radiation pattern for the present leaky mode, the waveguide structure can have potential applications such as frequency dividers and demultiplexers. Experimental verification of such a leaky mode at microwave has been performed, and the experimental results are found to be consistent with the theoretical analysis. PMID:26403387

  8. Properties of Transmission and Leaky Modes in a Plasmonic Waveguide Constructed by Periodic Subwavelength Metallic Hollow Blocks.

    PubMed

    Wu, Jin Jei; Wu, Chien Jang; Shen, Jian Qi; Hou, Da Jun; Lo, Wen Chen

    2015-01-01

    Based on the concept of low-frequency spoof surface plasmon polaritons (spoof SPPs), a kind of leaky mode is proposed in a waveguide made of a subwavelength metal-block array with open slots. Numerical results reveal that a new transmission mode is found in the periodic subwavelength metal open blocks. This modal field is located inside the interior of a hollow block compared with that in a solid metal block array. The dispersion curve shows that such a new SPPs mode has a negative slope, crossing the light line, and then going into a zone of leaky mode at higher frequencies. The leaky mode has a wider frequency bandwidth, and this can lead to a radiation scanning angle of 53° together with high radiation efficiency. Based on the individual characteristics exhibited by a frequency-dependent radiation pattern for the present leaky mode, the waveguide structure can have potential applications such as frequency dividers and demultiplexers. Experimental verification of such a leaky mode at microwave has been performed, and the experimental results are found to be consistent with the theoretical analysis. PMID:26403387

  9. A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

    PubMed Central

    2010-01-01

    Background Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. Methods During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared. Results A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P

  10. Vaccine approaches to malaria control and elimination: Insights from mathematical models.

    PubMed

    White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

    2015-12-22

    A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission. PMID:26476361

  11. Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

    PubMed Central

    Tan, Cheong H; Vythilingam, Indra; Matusop, Asmad; Chan, Seng T; Singh, Balbir

    2008-01-01

    Background A large focus of human infections with Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit. Methods Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites. Results and Discussions Over an 11-month period, a total of 2,504 Anopheles mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. Anopheles latens (62.3%) and Anopheles watsonii (30.6%) were the predominant species caught in the forested ecotypes, while in the farm Anopheles donaldi (49.9%) and An. latens (35.6%) predominated. In the long house, An. latens (29.6%) and An. donaldi (22.8%) were the major Anopheline species. However, An. latens was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. An. latens was found biting early as 18.00 hours. Conclusion Anopheles latens is the main vector for P. knowlesi malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of An. latens makes it an efficient vector for the transmission of P. knowlesi parasites to both human and monkey hosts. PMID:18377652

  12. Malaria proteases mediate inside-out egress of gametocytes from red blood cells following parasite transmission to the mosquito.

    PubMed

    Sologub, Ludmilla; Kuehn, Andrea; Kern, Selina; Przyborski, Jude; Schillig, Rebecca; Pradel, Gabriele

    2011-06-01

    Malaria parasites reside in human erythrocytes within a parasitophorous vacuole. The parasites are transmitted from the human to the mosquito by the uptake of intraerythrocytic gametocytes during a blood meal, which in the midgut become activated by external stimuli and subsequently egress from the enveloping erythrocyte. Gametocyte egress is a crucial step for the parasite to prepare for fertilization, but the molecular mechanisms of egress are not well understood. Via electron microscopy, we show that Plasmodium falciparum gametocytes exit the erythrocyte by an inside-out type of egress. The parasitophorous vacuole membrane (PVM) ruptures at multiple sites within less than a minute following activation, a process that requires a temperature drop and parasite contact with xanthurenic acid. PVM rupture can also be triggered by the ionophore nigericin and is sensitive to the cysteine protease inhibitor E-64d. Following PVM rupture the subpellicular membrane begins to disintegrate. This membrane is specific to malaria gametocytes, and disintegration is impaired by the aspartic protease inhibitor EPNP and the cysteine/serine protease inhibitor TLCK. Approximately 15 min post activation, the erythrocyte membrane ruptures at a single breaking point, which can be inhibited by inhibitors TLCK and TPCK. In all cases inhibitor treatment results in interrupted gametogenesis. PMID:21501358

  13. Is there an efficient trap or collection method for sampling Anopheles darlingi and other malaria vectors that can describe the essential parameters affecting transmission dynamics as effectively as human landing catches? - A Review

    PubMed Central

    Lima, José Bento Pereira; Rosa-Freitas, Maria Goreti; Rodovalho, Cynara Melo; Santos, Fátima; Lourenço-de-Oliveira, Ricardo

    2014-01-01

    Distribution, abundance, feeding behaviour, host preference, parity status and human-biting and infection rates are among the medical entomological parameters evaluated when determining the vector capacity of mosquito species. To evaluate these parameters, mosquitoes must be collected using an appropriate method. Malaria is primarily transmitted by anthropophilic and synanthropic anophelines. Thus, collection methods must result in the identification of the anthropophilic species and efficiently evaluate the parameters involved in malaria transmission dynamics. Consequently, human landing catches would be the most appropriate method if not for their inherent risk. The choice of alternative anopheline collection methods, such as traps, must consider their effectiveness in reproducing the efficiency of human attraction. Collection methods lure mosquitoes by using a mixture of olfactory, visual and thermal cues. Here, we reviewed, classified and compared the efficiency of anopheline collection methods, with an emphasis on Neotropical anthropophilic species, especially Anopheles darlingi, in distinct malaria epidemiological conditions in Brazil. PMID:25185008

  14. [Prospects for malaria elimination in Azerbaijan].

    PubMed

    Kondrashin, A V; Baranova, A M; Mammedov, S; Gasimov, É; Morozova, L F; Stepanova, E V

    2011-01-01

    Epidemiological analysis of the malaria in the Republic of Azerbaijan has revealed that: 1. In the past year, malaria problem has considerably improved in reducing morbidity and the number of active foci of malaria in the republic. 2. All active foci of malaria have been in its endemic area. 3. Despite the presence of favorable climatic preconditions for malaria in a large part of the republic, socioeconomic preconditions are considerably decreased, causing the malariogenic potential to substantially reduce. 4. All sets a favorable stage for possible interruption of local malaria transmission on the whole territory of the republic provided that financial support for the national malaria elimination program will be increased from the country's government and other sources in conjunction with the implementation of revised malaria control strategy and with the use of current methods for the detection, diagnosis, treatment, and prevention of malaria. PMID:21476253

  15. Urbanization and the global malaria recession

    PubMed Central

    2013-01-01

    Background The past century has seen a significant contraction in the global extent of malaria transmission, resulting in over 50 countries being declared malaria free, and many regions of currently endemic countries eliminating the disease. Moreover, substantial reductions in transmission have been seen since 1900 in those areas that remain endemic today. Recent work showed that this malaria recession was unlikely to have been driven by climatic factors, and that control measures likely played a significant role. It has long been considered, however, that economic development, and particularly urbanization, has also been a causal factor. The urbanization process results in profound socio-economic and landscape changes that reduce malaria transmission, but the magnitude and extent of these effects on global endemicity reductions are poorly understood. Methods Global data at subnational spatial resolution on changes in malaria transmission intensity and urbanization trends over the past century were combined to examine the relationships seen over a range of spatial and temporal scales. Results/Conclusions A consistent pattern of increased urbanization coincident with decreasing malaria transmission and elimination over the past century was found. Whilst it remains challenging to untangle whether this increased urbanization resulted in decreased transmission, or that malaria reductions promoted development, the results point to a close relationship between the two, irrespective of national wealth. The continuing rapid urbanization in malaria-endemic regions suggests that such malaria declines are likely to continue, particularly catalyzed by increasing levels of direct malaria control. PMID:23594701

  16. Stress and sex in malaria parasites

    PubMed Central

    Carter, Lucy M.; Kafsack, Björn F.C.; Llinás, Manuel; Mideo, Nicole; Pollitt, Laura C.; Reece, Sarah E.

    2013-01-01

    For vector-borne parasites such as malaria, how within- and between-host processes interact to shape transmission is poorly understood. In the host, malaria parasites replicate asexually but for transmission to occur, specialized sexual stages (gametocytes) must be produced. Despite the central role that gametocytes play in disease transmission, explanations of why parasites adjust gametocyte production in response to in-host factors remain controversial. We propose that evolutionary theory developed to explain variation in reproductive effort in multicellular organisms, provides a framework to understand gametocyte investment strategies. We examine why parasites adjust investment in gametocytes according to the impact of changing conditions on their in-host survival. We then outline experiments required to determine whether plasticity in gametocyte investment enables parasites to maintain fitness in a variable environment. Gametocytes are a target for anti-malarial transmission-blocking interventions so understanding plasticity in investment is central to maximizing the success of control measures in the face of parasite evolution. PMID:24481194

  17. An Economic Evaluation of the Posttreatment Prophylactic Effect of Dihydroartemisinin-Piperaquine Versus Artemether-Lumefantrine for First-Line Treatment of Plasmodium falciparum Malaria Across Different Transmission Settings in Africa.

    PubMed

    Pfeil, Johannes; Borrmann, Steffen; Bassat, Quique; Mulenga, Modest; Talisuna, Ambrose; Tozan, Yesim

    2015-11-01

    Malaria disproportionately affects young children. Clinical trials in African children showed that dihydroartemisinin-piperaquine (DP) is an effective antimalarial and has a longer posttreatment prophylactic (PTP) effect against reinfections than other artemisinin-based combination therapies, including artemether-lumefantrine (AL). Using a previously developed Markov model and individual patient data from a multicenter African drug efficacy trial, we assessed the economic value of the PTP effect of DP versus AL in pediatric malaria patients from health-care provider's perspective in low-to-moderate and moderate-to-high transmission settings under different drug co-payment scenarios. In low-to-moderate transmission settings, first-line treatment with DP was highly cost-effective with an incremental cost-effectiveness ratio of US$5 (95% confidence interval [CI] = -76 to 196) per disability-adjusted life year (DALY) averted. In moderate-to-high transmission settings, DP first-line treatment led to a mean cost saving of US$1.09 (95% CI = -0.88 to 3.85) and averted 0.05 (95% CI = -0.08 to 0.22) DALYs per child per year. Our results suggested that DP might be superior to AL for first-line treatment of uncomplicated childhood malaria across a range of transmission settings in Africa. PMID:26240155

  18. Anopheles (Kerteszia) cruzii (DIPTERA: CULICIDAE) IN PERIDOMICILIARY AREA DURING ASYMPTOMATIC MALARIA TRANSMISSION IN THE ATLANTIC FOREST: MOLECULAR IDENTIFICATION OF BLOOD-MEAL SOURCES INDICATES HUMANS AS PRIMARY INTERMEDIATE HOSTS

    PubMed Central

    Kirchgatter, Karin; Tubaki, Rosa Maria; Malafronte, Rosely dos Santos; Alves, Isabel Cristina; Lima, Giselle Fernandes Maciel de Castro; Guimarães, Lilian de Oliveira; Zampaulo, Robson de Almeida; Wunderlich, Gerhard

    2014-01-01

    Anopheles (Kerteszia) cruzii has been implicated as the primary vector of human and simian malarias out of the Brazilian Amazon and specifically in the Atlantic Forest regions. The presence of asymptomatic human cases, parasite-positive wild monkeys and the similarity between the parasites infecting them support the discussion whether these infections can be considered as a zoonosis. Although many aspects of the biology of An. cruzii have already been addressed, studies conducted during outbreaks of malaria transmission, aiming at the analysis of blood feeding and infectivity, are missing in the Atlantic Forest. This study was conducted in the location of Palestina, Juquitiba, where annually the majority of autochthonous human cases are notified in the Atlantic Forest of the state of São Paulo. Peridomiciliary sites were selected for collection of mosquitoes in a perimeter of up to 100 m around the residences of human malaria cases. The mosquitoes were analyzed with the purpose of molecular identification of blood-meal sources and to examine the prevalence of Plasmodium. A total of 13,441 females of An. (Ker.) cruzii were collected. The minimum infection rate was calculated at 0.03% and 0.01%, respectively, for P. vivax and P. malariae and only human blood was detected in the blood-fed mosquitoes analyzed. This data reinforce the hypothesis that asymptomatic human carriers are the main source of anopheline infection in the peridomiciliary area, making the probability of zoonotic transmission less likely to happen. PMID:25229220

  19. Reflections on Early Malaria Vaccine Studies, the First Successful Human Malaria Vaccination, and Beyond✰

    PubMed Central

    Vanderberg, Jerome P.

    2009-01-01

    Advances towards protective vaccines against malaria were made feasible by the development of a rodent model of mammalian malaria that allowed production of all stages of the malaria parasite for study. Investigations with sporozoites (the stage transmitted by mosquitoes in their saliva) demonstrated that immunization with radiation-attenuated sporozoites could produce a solid, sterile immunity, first shown in studies with mice and later with human volunteers. Protective immune mechanisms involve anti-sporozoite antibodies that immobilize sporozoites injected into the skin by mosquitoes, followed by CD4+ and CD8+ T-cells acting against liver stage parasites produced by sporozoites that have escaped antibody-based immunity and invaded hepatocytes. Two alternative approaches now being used in human trials are immunization with intact, attenuated sporozoites vs. immunization with “sub-unit” vaccines based on immunogenic components of sporozoites or liver stage parasites. In addition to immunization against these pre-erythrocytic stages, encouraging progress is being made on immunization against blood stage parasites and on immunization for production of transmission-blocking antibodies. There is reason to be optimistic that one or more of the approaches will work on a large scale, and that a multi-stage vaccine may be able to combine several of these approaches in a sequential immunological assault against the malaria parasite as it progresses through its stages. PMID:18973784

  20. Blocking pathogen transmission at the source: reservoir targeted OspA-based vaccines against Borrelia burgdorferi

    PubMed Central

    Gomes-Solecki, Maria

    2014-01-01

    Control strategies are especially challenging for microbial diseases caused by pathogens that persist in wildlife reservoirs and use arthropod vectors to cycle amongst those species. One of the most relevant illnesses that pose a direct human health risk is Lyme disease; in the US, the Centers for Disease Control and Prevention recently revised the probable number of cases by 10-fold, to 300,000 cases per year. Caused by Borrelia burgdorferi, Lyme disease can affect the nervous system, joints and heart. No human vaccine is approved by the Food and Drug Administration. In addition to novel human vaccines, new strategies for prevention of Lyme disease consist of pest management interventions, vector-targeted vaccines and reservoir-targeted vaccines. However, even human vaccines can not prevent Lyme disease expansion into other geographical areas. The other strategies aim at reducing tick density and at disrupting the transmission of B. burgdorferi by targeting one or more key elements that maintain the enzootic cycle: the reservoir host and/or the tick vector. Here, I provide a brief overview of the application of an OspA-based wildlife reservoir targeted vaccine aimed at reducing transmission of B. burgdorferi and present it as a strategy for reducing Lyme disease risk to humans. PMID:25309883

  1. Temperature alters Plasmodium blocking by Wolbachia

    NASA Astrophysics Data System (ADS)

    Murdock, Courtney C.; Blanford, Simon; Hughes, Grant L.; Rasgon, Jason L.; Thomas, Matthew B.

    2014-02-01

    Very recently, the Asian malaria vector (Anopheles stephensi) was stably transinfected with the wAlbB strain of Wolbachia, inducing refractoriness to the human malaria parasite Plasmodium falciparum. However, conditions in the field can differ substantially from those in the laboratory. We use the rodent malaria P. yoelii, and somatically transinfected An. stephensi as a model system to investigate whether the transmission blocking potential of wAlbB is likely to be robust across different thermal environments. wAlbB reduced malaria parasite prevalence and oocyst intensity at 28°C. At 24°C there was no effect on prevalence but a marked increase in oocyst intensity. At 20°C, wAlbB had no effect on prevalence or intensity. Additionally, we identified a novel effect of wAlbB that resulted in reduced sporozoite development across temperatures, counterbalancing the oocyst enhancement at 24°C. Our results demonstrate complex effects of temperature on the Wolbachia-malaria interaction, and suggest the impacts of transinfection might vary across diverse environments.

  2. Use of Integrated Malaria Management Reduces Malaria in Kenya

    PubMed Central

    Okech, Bernard A.; Mwobobia, Isaac K.; Kamau, Anthony; Muiruri, Samuel; Mutiso, Noah; Nyambura, Joyce; Mwatele, Cassian; Amano, Teruaki; Mwandawiro, Charles S.

    2008-01-01

    Background During an entomological survey in preparation for malaria control interventions in Mwea division, the number of malaria cases at the Kimbimbi sub-district hospital was in a steady decline. The underlying factors for this reduction were unknown and needed to be identified before any malaria intervention tools were deployed in the area. We therefore set out to investigate the potential factors that could have contributed to the decline of malaria cases in the hospital by analyzing the malaria control knowledge, attitudes and practices (KAP) that the residents in Mwea applied in an integrated fashion, also known as integrated malaria management (IMM). Methods Integrated Malaria Management was assessed among community members of Mwea division, central Kenya using KAP survey. The KAP study evaluated community members' malaria disease management practices at the home and hospitals, personal protection measures used at the household level and malaria transmission prevention methods relating to vector control. Concurrently, we also passively examined the prevalence of malaria parasite infection via outpatient admission records at the major referral hospital in the area. In addition we studied the mosquito vector population dynamics, the malaria sporozoite infection status and entomological inoculation rates (EIR) over an 8 month period in 6 villages to determine the risk of malaria transmission in the entire division. Results A total of 389 households in Mwea division were interviewed in the KAP study while 90 houses were surveyed in the entomological study. Ninety eight percent of the households knew about malaria disease while approximately 70% of households knew its symptoms and methods to manage it. Ninety seven percent of the interviewed households went to a health center for malaria diagnosis and treatment. Similarly a higher proportion (81%) used anti-malarial medicines bought from local pharmacies. Almost 90% of households reported owning and using an

  3. Cost Savings with Rapid Diagnostic Tests for Malaria in Low-Transmission Areas: Evidence from Dar es Salaam, Tanzania

    PubMed Central

    Yukich, Joshua; D'Acremont, Valerie; Kahama, Judith; Swai, Ndeniria; Lengeler, Christian

    2010-01-01

    Rapid diagnostic tests (RDTs) for malaria may help rationalize antimalarial drug use. However, the economic effects of these tests may vary. Data on costs were collected from 259 patients in 6 health facilities by using exit and in-charge interviews and record reviews during a trial of RDT rollout in Dar es Salaam, Tanzania. The RDTs decreased patient expenditure on drugs (savings = U.S. $0.36; P = 0.002) and provider drug costs (savings = U.S. $0.43; P = 0.034) compared with control facilities. However, RDT introduction did not significantly reduce patients' overall expenditures (U.S. $1.02, 95% confidence interval [CI] = $0.76–$1.36 versus U.S. $1.33 95% CI = $0.99–$1.77) and may increase total provider costs (U.S. $3.63, 95% CI = $3.40–$3.89 versus U.S. $2.32, 95% CI = $1.99–$2.69) compared with control facilities. Clinician's compliance with test results was higher with RDTs than with routine microscopy (95% versus 82%; P = 0.002). The RDTs reduced drug costs in this setting but did not offset the cost of the tests, although they also resulted in non-monetary benefits, including improved management of patients and increased compliance with test results. PMID:20595479

  4. Malaria in Kenya's Western Highlands

    PubMed Central

    Hay, Simon I.; Omumbo, Judy A.; Snow, Robert W.

    2005-01-01

    Records from tea estates in the Kericho district in Kenya show that malaria reemerged in the 1980s. Renewed epidemic activity coincided with the emergence of chloroquine-resistant Plasmodium falciparum malaria and may have been triggered by the failure of antimalarial drugs. Meteorologic changes, population movements, degradation of health services, and changes in Anopheles vector populations are possible contributing factors. The highland malaria epidemics of the 1940s were stopped largely by sporontocidal drugs, and combination chemotherapy has recently limited transmission. Antimalarial drugs can limit the pool of gametocytes available to infect mosquitoes during the brief transmission season. PMID:16229773

  5. Malaria Facts

    MedlinePlus

    ... a CDC Malaria Branch clinician. malaria@cdc.gov File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  6. Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons

    PubMed Central

    2014-01-01

    Background Several lines of evidence suggest that CCL2 could initiate the hyperalgesia of neuropathic pain by causing central sensitization of spinal dorsal horn neurons and facilitating nociceptive transmission in the spinal dorsal horn. The cellular and molecular mechanisms by which CCL2 enhances spinal pain transmission and causes hyperalgesia remain unknown. The substantia gelatinosa (lamina II) of the spinal dorsal horn plays a critical role in nociceptive transmission. An activated spinal microglia, which is believed to release pro-inflammatory cytokines including TNF-α, plays an important role in the development of neuropathic pain, and CCL2 is a key mediator for spinal microglia activation. In the present study, we tested the hypothesis that spinal CCL2 causes the central sensitization of substantia gelatinosa neurons and enhances spinal nociceptive transmission by activating the spinal microglia and augmenting glutamatergic transmission in lamina II neurons. Methods CCL2 was intrathecally administered to 2-month-old male rats. An intrathecal injection of CCL2 induced heat hyperalgesia, which was assessed using the hot plate test. Whole-cell voltage-clamp recordings substantia gelatinosa neurons in spinal cord slices were performed to record glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs). Results The hot plate test showed that 1 day after the intrathecal injection of CCL2 (1 μg), the latency of hind-paw withdrawal caused by a heat stimulus was significantly reduced in rats. One day after the intrathecal administration of CCL2, the amplitude of the evoked glutamatergic EPSCs and the frequency of spontaneous glutamatergic miniature EPSCs (mEPSCs) were significantly increased in outer lamina II neurons. Intrathecal co-injection of minocycline, a specific inhibitor of microglial activation, and CCL2 blocked the CCL2-induced reduction in the latency of hind-paw withdrawal and thermal hyperalgesia

  7. Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.

    PubMed

    Yoshida, Shigeto; Shimada, Yohei; Kondoh, Daisuke; Kouzuma, Yoshiaki; Ghosh, Anil K; Jacobs-Lorena, Marcelo; Sinden, Robert E

    2007-12-01

    The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50) of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions. PMID:18159942

  8. Migration statistics relevant for malaria transmission in Senegal derived from mobile phone data and used in an agent-based migration model.

    PubMed

    Tompkins, Adrian M; McCreesh, Nicky

    2016-01-01

    One year of mobile phone location data from Senegal is analysed to determine the characteristics of journeys that result in an overnight stay, and are thus relevant for malaria transmission. Defining the home location of each person as the place of most frequent calls, it is found that approximately 60% of people who spend nights away from home have regular destinations that are repeatedly visited, although only 10% have 3 or more regular destinations. The number of journeys involving overnight stays peaks at a distance of 50 km, although roughly half of such journeys exceed 100 km. Most visits only involve a stay of one or two nights away from home, with just 4% exceeding one week. A new agent-based migration model is introduced, based on a gravity model adapted to represent overnight journeys. Each agent makes journeys involving overnight stays to either regular or random locations, with journey and destination probabilities taken from the mobile phone dataset. Preliminary simulations show that the agent-based model can approximately reproduce the patterns of migration involving overnight stays. PMID:27063741

  9. Naturally Acquired Antibody Responses to Plasmodium vivax and Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) C-Terminal 19 kDa Domains in an Area of Unstable Malaria Transmission in Southeast Asia

    PubMed Central

    Wang, Qinghui; Zhao, Zhenjun; Zhang, Xuexing; Li, Xuelian; Zhu, Min; Li, Peipei; Yang, Zhaoqing; Wang, Ying; Yan, Guiyun; Shang, Hong; Cao, Yaming; Fan, Qi; Cui, Liwang

    2016-01-01

    Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a

  10. Population genetics structure of Plasmodium vivax circumsporozoite protein during the elimination process in low and unstable malaria transmission areas, southeast of Iran.

    PubMed

    Shabani, Samaneh Hemati; Zakeri, Sedigheh; Mehrizi, Akram Abouie; Mortazavi, Yousef; Djadid, Navid Dinparast

    2016-08-01

    In Iran, the prevalence of Plasmodium falciparum and Plasmodium vivax has dropped after a national malaria elimination program was launched. To estimate the likelihood of success and to measure the outcome of malaria intervention tools during elimination programs (2008-2012), the population genetic surveys of Iranian P. vivax isolates (n=60) were carried out using the CSP genetic marker. The results were compared with a similar work that was carried out during a control phase (2000-2003) in the same study areas. Based on PCR-RFLP analysis, 49 (81.67%) of 60 studied samples were VK210 and 11 (18.33%) were VK247 with no mixed genotypes. However, 10.97% of P. vivax isolates of control phase harbored the mixed genotypes. Sequencing analysis of 50 pvcsp gene showed 14 distinct haplotypes, of which 11 and 3 were VK210 and VK247 types, respectively. However, during the control phase, 19 distinct subtypes (11 VK210 and 8 VK247) were reported. Also, 7 of 11 VK210 and the VK247F subtypes were new, and 3 out of 7 new VK210 and VK247F were isolated from the patients with Pakistani nationality. The lower nucleotide diversity per site (π=0.02017±0.00436 and π=0.04525±0.00255) and haplotype diversity (Hd=0.513±0.093 and Hd=0.691±0.128) as well as lower In/Del haplotype [Hd(i)=0.243 and 0] and nucleotide diversity [π(i)=0.00078 and 0] were recorded for VK210 and VK247of the elimination samples, respectively. In conclusion, the comparison of PRMs and RATs in CRR along with the polymorphism analysis of the sequence lengths, SNPs, and In/Del polymorphisms in all analyzed samples showed lower genetic diversity for PvCSP in the elimination samples. Also, although there is a turnover of P. vivax parasite genotypes in the study areas, reduction in genetic diversity and transmission was detected due to scaling-up of the intervention tools during an elimination program in Iran. This notable challenge of the elimination program must be taken into account and controlled by active

  11. Host-pathogen interactions in malaria: cross-kingdom signaling and mitochondrial regulation.

    PubMed

    Luckhart, Shirley; Pakpour, Nazzy; Giulivi, Cecilia

    2015-10-01

    Malaria parasite-host interactions are complex and have confounded available drugs and the development of vaccines. Further, we now appreciate that interventions for malaria elimination and eradication must include therapeutics with intrinsic transmission blocking activity to treat the patient and prevent disease spread. Studies over the past 15 years have revealed significant conservation in the response to infection in mosquito and human hosts. More recently, we have recognized that conserved cell signaling cascades in mosquitoes and humans dictate infection outcome through the regulation of mitochondrial function and biogenesis, which feed back to host immunity, basic intermediary metabolism, and stress responses. These responses - reflected clearly in the primeval insect host - provide fertile ground for innovative strategies for both treatment and transmission blocking. PMID:26210301

  12. Malaria (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Malaria KidsHealth > For Parents > Malaria Print A A A ... Prevention Diagnosis and Treatment en español Malaria About Malaria Malaria is a common infection in hot, tropical ...

  13. Efficacy of permethrin treated long-lasting insecticidal nets on malaria transmission and observations on the perceived side effects, collateral benefits and human safety in a hyperendemic tribal area of Orissa, India.

    PubMed

    Sharma, Surya K; Tyagi, Prajesh K; Upadhyay, Ashok K; Haque, Mohammed A; Mohanty, Suman S; Raghavendra, Kamaraju; Dash, Aditya P

    2009-11-01

    Studies were conducted on the efficacy of Olyset nets-a long-lasting insecticidal net (LLIN) factory treated with 2% (w/w) permethrin on malaria transmission in an area under the influence of pyrethroid susceptible vector species Anopheles culicifacies and A. fluviatilis in Sundargarh District, Orissa, India. The study area comprised 22 villages that were randomized into three clusters and designated as Olyset net, untreated net, and no net area. Malaria incidence in the study population was measured through longitudinal active surveillance at fortnightly intervals. There was a reduction of 65-70% in malaria incidence in Olyset net area as compared to the control areas. The attack rate of Plasmodium falciparum or number of episodes per person per year in different age groups also showed significant reduction in Olyset net area as compared to untreated net and no net areas. Cross-sectional point prevalence surveys showed 45.7% reduction of malaria prevalence in Olyset net users, whereas there was an increase of 33.3% and 51% in untreated net and no net villages respectively. The compliance rate of Olyset net usage in the study population was 80-98% during different months, whereas it was between 70% and 90% for untreated nets. There were minimal complains of skin irritation (4%), itching (8%) and eye irritation (1.2%). However, these effects were only transitory in nature lasting for few hours of the first usage. Olyset nets also provided collateral benefits in terms of relief not only from mosquitoes and malaria but also from other household pests such as head lice, bed bugs, cockroaches, ants and houseflies. The Olyset nets were found to be safe to humans as no adverse event was recorded in the net users that can be attributed to the use of net. The study showed that Olyset nets are effective personal protection tool that can be used in a community based intervention programme. PMID:19647715

  14. [Malaria in the Americas].

    PubMed

    Carme, B; Venturin, C

    1999-01-01

    In 1996, malaria involving Plasmodium vivax, Plasmodium falciparum, and, to a lesser extent, Plasmodium malariae was endemic in 21 countries in the Americas. The Amazon river basin and bordering areas including the Guyanas were the most affected zones. Until the mid 1970s, endemic malaria appeared to be under control. However in the ensuing 15 year period, the situation deteriorated drastically. Although trends varied depending on location, aggregate indexes indicated a twofold increase with recrudescence in previously settled areas and emergence in newly populated zones. Since 1990, the situation has worsened further in some areas where increased incidences have been associated with a high levels of drug-resistant Plasmodium falciparum. However this species remains in minority except in the Guyanas where the highest annual incidences (100 to 500 cases per 1000) and the most drug-resistant Plasmodium have been reported. The causes underlying this deterioration are numerous and complex. In regions naturally prone to transmission of the disease, outbreaks have been intensified by unrestrained settlement. The resulting deforestation has created new breeding areas for Anopheles darlingi, the main vector of malaria in the Americas. Migration of poor populations to newly opened farming and mining areas has created highly exposed areas for malaria infection. Implementation of adequate medical care and prevention measures has been hindered by a lack of money and sociopolitical unrest. Climatic phenomenon related the El Nino have also been favorable to the return of malaria to the region. Except with regard to financial resources and political unrest, the same risk factors for malaria are present in French Guiana. PMID:10701211

  15. Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold nanoparticles.

    PubMed

    Kumar, Rajesh; Ray, Paresh C; Datta, Dibyadyuti; Bansal, Geetha P; Angov, Evelina; Kumar, Nirbhay

    2015-09-22

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinetes. The latter has undergone extensive evaluation in pre-clinical and phase I clinical trials and remains one of the leading target antigens for the development of TBV. Pfs25 has a complex tertiary structure characterized by four EGF-like repeat motifs formed by 11 disulfide bonds, and it has been rather difficult to obtain Pfs25 as a homogenous product in native conformation in any heterologous expression system. Recently, we have reported expression of codon-harmonized recombinant Pfs25 in Escherichia coli (CHrPfs25) and which elicited highly potent malaria transmission-blocking antibodies in mice. In the current study, we investigated CHrPfs25 along with gold nanoparticles of different shapes, size and physicochemical properties as adjuvants for induction of transmission blocking immunity. The results revealed that CHrPfs25 delivered with various gold nanoparticles elicited strong transmission blocking antibodies and suggested that gold nanoparticles based formulations can be developed as nanovaccines to enhance the immunogenicity of vaccine antigens. PMID:26299750

  16. Eradicating malaria.

    PubMed

    Breman, Joel G

    2009-01-01

    The renewed interest in malaria research and control is based on the intolerable toll this disease takes on young children and pregnant women in Africa and other vulnerable populations; 150 to 300 children die each hour from malaria amounting to 1 to 2 million deaths yearly. Malaria-induced neurologic impairment, anemia, hypoglycemia, and low birth weight imperil normal development and survival. Resistance of Plasmodium falciparum to drugs and Anopheles mosquitoes to insecticides has stimulated discovery and development of artemisinin-based combination treatments (ACTs) and other drugs, long-lasting insecticide-treated bednets (with synthetic pyrethroids) and a search for non-toxic, long-lasting, affordable insecticides for indoor residual spraying (IRS). Malaria vaccine development and testing are progressing rapidly and a recombinant protein (RTS,S/AS02A) directed against the circumsporozoite protein is soon to be in Phase 3 trials. Support for malaria control, research, and advocacy through the Global Fund for HIV/AIDS, Tuberculosis and Malaria, the U.S. President's Malaria Initiative, the Bill & Melinda Gates Foundation, WHO and other organizations is resulting in decreasing morbidity and mortality in many malarious countries. Sustainability of effective programs through training and institution strengthening will be the key to malaria elimination coupled with improved surveillance and targeted research. PMID:19544698

  17. Efficacy and safety of nucleoside analogs on blocking father-to-infant vertical transmission of hepatitis B virus

    PubMed Central

    CAO, LI-HAU; ZHAO, PEI-LI; LIU, ZHI-MIN; SUN, SHAO-CHUN; XU, DONG-BO; ZHANG, JI-DONG; SHAO, MEI-HUA

    2015-01-01

    Apgar scores, presence of jaundice, other internal and surgical diseases, delivery mode and other birth information were observed when comparing the case group with the control group. Furthermore, there were no fetal malformations or stillbirths in the two groups. In the HBV DNA-positive fathers prior to pregnancy, antiretroviral therapy resulted in a reduced virus load. Therefore, blocking father-to-infant HBV vertical transmission maximally was important. The use of antiviral nucleoside analogs prior to pregnancy was shown to be safe. When the benefits outweighed the risks, the fathers who wanted to have a child continued to use antiviral therapy. However, the sample size of the present study was small, and an increased number of cases and longer follow-up times are required. In addition, the use of nucleoside analogs requires further in-depth assessment from the point of view of prenatal and postnatal care. PMID:26136969

  18. Antibody response dynamics to the Plasmodium falciparum conserved vaccine candidate antigen, merozoite surface protein-1 C-terminal 19kD (MSP1-19kD), in Peruvians exposed to hypoendemic malaria transmission

    PubMed Central

    Torres, Katherine J; Clark, Eva H; Hernandez, Jean N; Soto-Cornejo, Katherine E; Gamboa, Dionicia; Branch, OraLee H

    2008-01-01

    Background In high-transmission areas, developing immunity to symptomatic Plasmodium falciparum infections requires 2–10 years of uninterrupted exposure. Delayed malaria-immunity has been attributed to difficult-to-develop and then short-lived antibody responses. Methods In a study area with <0.5 P. falciparum infections/person/year, antibody responses to the MSP1-19kD antigen were evaluated and associations with P. falciparum infections in children and adults. In months surrounding and during the malaria seasons of 2003–2004, 1,772 participants received ≥6 active visits in one study-year. Community-wide surveys were conducted at the beginning and end of each malaria season, and weekly active visits were completed for randomly-selected individuals each month. There were 79 P. falciparum infections with serum samples collected during and approximately one month before and after infection. Anti-MSP1-19kD IgG levels were measured by ELISA. Results The infection prevalence during February-July was similar in children (0.02–0.12 infections/person/month) and adults (0.03–0.14 infections/person/month) and was negligible in the four-month dry season. In children and adults, the seroprevalence was maintained in the beginning (children = 28.9%, adults = 61.8%) versus ending malaria-season community survey (children = 26.7%, adults = 64.6%). Despite the four-month non-transmission season, the IgG levels in Plasmodium-negative adults were similar to P. falciparum-positive adults. Although children frequently responded upon infection, the transition from a negative/low level before infection to a high level during/after infection was slower in children. Adults and children IgG-positive before infection had reduced symptoms and parasite density. Conclusion Individuals in low transmission areas can rapidly develop and maintain αMSP1-19kD IgG responses for >4 months, unlike responses reported in high transmission study areas. A greater immune capacity might contribute

  19. Monoclonal And Single Domain Antibodies Targeting β-Integrin Subunits Block Sexual Transmission of HIV-1 in in vitro and in vivo Model Systems

    PubMed Central

    Guedon, Janet Tai; Luo, Kun; Zhang, Hong; Markham, Richard B.

    2015-01-01

    Background Poor adherence to prevention regimens for gel-based anti-HIV-1 microbicides has been a major obstacle to more effective pre-exposure prophylaxis. Concern persists that the antiretroviral drug containing microbicides might promote development of antiretroviral resistance. Methods Using in vitro transwell systems and a humanized mouse model of HIV-1 sexual transmission, we examined, as candidate microbicides, antibodies targeting the heterodimeric leukocyte function associated antigen 1 (LFA-1), a non-virally encoded protein acquired by the virus that also plays a critical role cell movement across endothelial and epithelial barriers. LFA-1 specific single domain variable regions from alpaca heavy-chain only antibodies (VHH) were identified and evaluated for their ability to inhibit HIV-1 transmission in the in vitro transwell system. Results Monoclonal antibodies targeting the CD11a and CD18 components of LFA-1 significantly reduced cell-free and cell-associated HIV-1 transmission in the in vitro transwell culture system and prevented virus transmission in the humanized mouse model of vaginal transmission. The broadly neutralizing monoclonal antibody b12 was unable to block transmission of cell-free virus. CD11a-specific VHH were isolated and expressed and the purified variable region protein domains reduced in vitro transepithelial transmission with an efficacy comparable to that of the CD11a monoclonal antibody. Conclusions Targeting integrins acquired by HIV-1 during budding and which are critical to interactions between epithelial cells and lymphocytes can reduce viral movement across epithelial barriers and prevent transmission in a humanized mouse model of sexual transmission. VHH capable of being produced by transformed bacteria can significantly reduce transepithelial virus transmission in in vitro model systems. PMID:25828964

  20. A sticky situation: the unexpected stability of malaria elimination.

    PubMed

    Smith, David L; Cohen, Justin M; Chiyaka, Christinah; Johnston, Geoffrey; Gething, Peter W; Gosling, Roly; Buckee, Caroline O; Laxminarayan, Ramanan; Hay, Simon I; Tatem, Andrew J

    2013-08-01

    Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination's 'stickiness' must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system's increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination's stickiness at moderate

  1. Preparing for future efficacy trials of severe malaria vaccines.

    PubMed

    Gonçalves, Bronner P; Prevots, D Rebecca; Kabyemela, Edward; Fried, Michal; Duffy, Patrick E

    2016-04-01

    Severe malaria is a major cause of mortality in children, but comprises only a small proportion of Plasmodium falciparum infections in naturally exposed populations. The evaluation of vaccines that prevent severe falciparum disease will require clinical trials whose primary efficacy endpoint will be severe malaria risk during follow-up. Here, we show that such trials are feasible with fewer than 1000 participants in areas with intense malaria transmission during the age interval when severe malaria incidence peaks. PMID:26923455

  2. Malaria Parasites Produce Volatile Mosquito Attractants

    PubMed Central

    Kelly, Megan; Su, Chih-Ying; Schaber, Chad; Crowley, Jan R.; Hsu, Fong-Fu; Carlson, John R.

    2015-01-01

    ABSTRACT The malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid organelle that possesses plant-like metabolic pathways. Plants use the plastidial isoprenoid biosynthesis pathway to produce volatile odorants, known as terpenes. In this work, we describe the volatile chemical profile of cultured malaria parasites. Among the identified compounds are several plant-like terpenes and terpene derivatives, including known mosquito attractants. We establish the molecular identity of the odorant receptors of the malaria mosquito vector Anopheles gambiae, which responds to these compounds. The malaria parasite produces volatile signals that are recognized by mosquitoes and may thereby mediate host attraction and facilitate transmission. PMID:25805727

  3. Malaria successes and challenges in Asia.

    PubMed

    Bhatia, Rajesh; Rastogi, Rakesh Mani; Ortega, Leonard

    2013-12-01

    Asia ranks second to Africa in terms of malaria burden. In 19 countries of Asia, malaria is endemic and 2.31 billion people or 62% of the total population in these countries are at risk of malaria. In 2010, WHO estimated around 34.8 million cases and 45,600 deaths due to malaria in Asia. In 2011, 2.7 million cases and > 2000 deaths were reported. India, Indonesia, Myanmar and Pakistan are responsible for >85% of the reported cases (confirmed) and deaths in Asia. In last 10 yr, due to availability of donor's fund specially from Global fund, significant progress has been made by the countries in Asia in scaling-up malaria control interventions which were instrumental in reducing malaria morbidity and mortality significantly. There is a large heterogeneity in malaria epidemiology in Asia. As a result, the success in malaria control/elimination is also diverse. As compared to the data of the year 2000, out of 19 malaria endemic countries, 12 countries were able to reduce malaria incidence (microscopically confirmed cases only) by 75%. Two countries, namely Bangladesh and Malaysia are projected to reach 75% reduction by 2015 while India is projected to reach 50-75% only by 2015. The trend could not be assessed in four countries, namely Indonesia, Myanmar, Pakistan and Timor-Leste due to insufficient consistent data. Numerous key challenges need to be addressed to sustain the gains and eliminate malaria in most parts of Asia. Some of these are to control the spread of resistance in Plasmodium falciparum to artemisinin, control of outdoor transmission, control of vivax malaria and ensuring universal coverage of key interventions. Asia has the potential to influence the malaria epidemiology all over the world as well as to support the global efforts in controlling and eliminating malaria through production of quality-assured ACTs, RDTs and long-lasting insecticidal nets. PMID:24499845

  4. Ongoing challenges in the management of malaria

    PubMed Central

    Kokwaro, Gilbert

    2009-01-01

    This article gives an overview of some of the ongoing challenges that are faced in the prevention, diagnosis and treatment of malaria. Malaria causes approximately 881,000 deaths every year, with nine out of ten deaths occurring in sub-Saharan Africa. In addition to the human burden of malaria, the economic burden is vast. It is thought to cost African countries more than US$12 billion every year in direct losses. However, great progress in malaria control has been made in some highly endemic countries. Vector control is assuming a new importance with the significant reductions in malaria burden achieved using combined malaria control interventions in countries such as Zanzibar, Zambia and Rwanda. The proportion of patients treated for malaria who have a confirmed diagnosis is low in Africa compared with other regions of the world, with the result that anti-malarials could be used to treat patients without malaria, especially in areas where progress has been made in reducing the malaria burden and malaria epidemiology is changing. Inappropriate administration of anti-malarials could contribute to the spread of resistance and incurs unnecessary costs. Parasite resistance to almost all commonly used anti-malarials has been observed in the most lethal parasite species, Plasmodium falciparum. This has presented a major barrier to successful disease management in malaria-endemic areas. ACT (artemisinin-based combination therapy) has made a significant contribution to malaria control and to reducing disease transmission through reducing gametocyte carriage. Administering ACT to infants and small children can be difficult and time consuming. Specially formulating anti-malarials for this vulnerable population is vital to ease administration and help ensure that an accurate dose is received. Education of healthworkers and communities about malaria prevention, diagnosis and treatment is a vital component of effective case management, especially as diagnostic policies change

  5. Malaria vaccine.

    PubMed

    1994-05-01

    Some have argued that the vaccine against malaria developed by Manuel Pattaroyo, a Colombian scientist, is being tested prematurely in humans and that it is unlikely to be successful. While the Pattaroyo vaccine has been shown to confer protection against the relatively mild malaria found in Colombia, doubts exist over whether it will be effective in Africa. Encouraging first results, however, are emerging from field tests in Tanzania. The vaccine triggered a strong new immune response, even in individuals previously exposed to malaria. Additional steps must be taken to establish its impact upon mortality and morbidity. Five major trials are underway around the world. The creator estimates that the first ever effective malaria vaccine could be available for widespread use within five years and he has no intention of securing a patent for the discovery. In another development, malaria specialists from 35 African countries convened at an international workshop in Zimbabwe to compare notes. Participants disparaged financial outlays for the fight against malaria equivalent to 2% of total AIDS funding as insufficient; noted intercountry differences in prevention, diagnosis, and treatment; and found information exchange between anglophone and francophone doctors to be generally poor. PMID:12287671