Cupp, E W; Bernardo, M J; Kiszewski, A E; Collins, R C; Taylor, H R; Aziz, M A; Greene, B M
Ivermectin, given to onchocerciasis patients as a single oral dose of 200 micrograms per kilogram of body weight, substantially reduced the uptake of Onchocerca volvulus microfilariae by Simulium yahense, an efficient black fly vector of the parasite in the tropical rain forests of West Africa. Three months after treatment, patients given ivermectin infected flies at a significantly lower rate than those who had received diethylcarbamazine or placebo, thereby reducing the number of developing larvae in the vector population. This diminished rate of infectiousness was also evident 6 months after treatment. These results strongly suggest that ivermectin could be effective in interrupting transmission of Onchocerca volvulus for epidemiologically important periods of time.
Convit, Jacinto; Schuler, Harland; Borges, Rafael; Olivero, Vimerca; Domínguez-Vázquez, Alfredo; Frontado, Hortencia; Grillet, María E
Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10-12 years of 6-monthly Mectizan (ivermectin) treatment to all the eligible residents. In-depth entomologic and epidemiologic surveys were serially conducted from 2001-2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. From 2007-2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children < 15 years-old demonstrated that 0 out of 6,590 individuals were harboring antibodies to Ov-16. Finally, epidemiological surveys made during 2010 (NC) and 2012 (NE) showed no evidence of microfilariae in the skin and eyes of the population. These results meet the WHO criteria for absence of parasite transmission and disease morbidity in these endemic areas which represent 91% of the population previously at-risk in the country. Consequently, the two
Background Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10–12 years of 6-monthly Mectizan® (ivermectin) treatment to all the eligible residents. Methods In-depth entomologic and epidemiologic surveys were serially conducted from 2001–2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. Results From 2007–2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children < 15 years-old demonstrated that 0 out of 6,590 individuals were harboring antibodies to Ov-16. Finally, epidemiological surveys made during 2010 (NC) and 2012 (NE) showed no evidence of microfilariae in the skin and eyes of the population. Conclusions These results meet the WHO criteria for absence of parasite transmission and disease morbidity in these endemic areas which represent 91% of the population previously at
Cruz-Ortiz, Nancy; Gonzalez, Rodrigo J.; Lindblade, Kim A.; Richards, Frank O.; Sauerbrey, Mauricio; Zea-Flores, Guillermo; Dominguez, Alfredo; Oliva, Orlando; Catú, Eduardo; Rizzo, Nidia
In Latin America, onchocerciasis is targeted for elimination by 2012 through twice-yearly mass treatment of the eligible population with ivermectin. In Guatemala, two of the four historical endemic foci have demonstrated elimination of transmission, following World Health Organization guidelines. Using established guidelines ophthalmological, serological, and entomological evaluations were conducted in 2007-8 to determine the transmission status of onchocerciasis in the Huehuetenango focus. The prevalence of Onchocerca volvulus microfilariae in the anterior segment of the eye in 365 residents was 0% (95% confidence interval [CI] 0–0.8%), the prevalence of infection of O. volvulus in Simulium ochraceum among 8252 flies collected between November 2007 and April 2008 was 0% (95% CI 0–0.02%), and the prevalence of antibodies to a recombinant O. volvulus antigen in 3118 school age children was 0% (95% CI 0–0.1%). These results showed transmission interruption; thus, in 2009 mass treatment was halted and posttreatment surveillance began. To verify for potential recrudescence an entomological evaluation (from December 2010 to April 2011) was conducted during the 2nd and 3rd year of posttreatment surveillance. A total of 4587 S. ochraceum were collected, and the prevalence of infection of O. volvulus was 0% (95% CI 0–0.04%). Transmission of onchocerciasis in the Huehuetenango focus has been eliminated. PMID:22970346
Gonzalez, Rodrigo J.; Cruz-Ortiz, Nancy; Rizzo, Nidia; Richards, Jane; Zea-Flores, Guillermo; Domínguez, Alfredo; Sauerbrey, Mauricio; Catú, Eduardo; Oliva, Orlando; Richards, Frank O.; Lindblade, Kim A.
Background Elimination of onchocerciasis (river blindness) through mass administration of ivermectin in the six countries in Latin America where it is endemic is considered feasible due to the relatively small size and geographic isolation of endemic foci. We evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of Escuintla-Guatemala in Guatemala, based on World Health Organization criteria for the certification of elimination of onchocerciasis. Methodology/Principal Findings We conducted evaluations of ocular morbidity and past exposure to Onchocerca volvulus in the human population, while potential vectors (Simulium ochraceum) were captured and tested for O. volvulus DNA; all of the evaluations were carried out in potentially endemic communities (PEC; those with a history of actual or suspected transmission or those currently under semiannual mass treatment with ivermectin) within the focus. The prevalence of microfilariae in the anterior segment of the eye in 329 individuals (≥7 years old, resident in the PEC for at least 5 years) was 0% (one-sided 95% confidence interval [CI] 0–0.9%). The prevalence of antibodies to a recombinant O. volvulus antigen (Ov-16) in 6,432 school children (aged 6 to 12 years old) was 0% (one-sided 95% IC 0–0.05%). Out of a total of 14,099 S. ochraceum tested for O. volvulus DNA, none was positive (95% CI 0–0.01%). The seasonal transmission potential was, therefore, 0 infective stage larvae per person per season. Conclusions/Significance Based on these evaluations, transmission of onchocerciasis in the Escuintla-Guatemala focus has been successfully interrupted. Although this is the second onchocerciasis focus in Latin America to have demonstrated interruption of transmission, it is the first focus with a well-documented history of intense transmission to have eliminated O. volvulus. PMID:19333366
Higazi, Tarig B.; Zarroug, Isam M. A.; Mohamed, Hanan A.; ElMubark, Wigdan A.; Deran, Tong Chor M.; Aziz, Nabil; Katabarwa, Moses; Hassan, Hassan K.; Unnasch, Thomas R.; Mackenzie, Charles D.; Richards, Frank; Hashim, Kamal
Abu Hamed, Sudan, the northernmost location of onchocerciasis in the world, began community-directed treatment with ivermectin (CDTI) in 1998, with annual treatments enhanced to semiannual in 2007. We assessed the status of the parasite transmission in 2011 entomologically, parasitologically, and serologically. O-150 pool screening showed no parasite DNA in 17,537 black flies collected in 2011 (95% confidence interval upper limit [95% CI UL] = 0.023). Skin microfilariae, nodules, and signs of skin disease were absent in 536 individuals in seven local communities. Similarly, no evidence of Onchocerca volvulus Ov16 antibodies was found in 6,756 school children ≤ 10 years (95% CI UL = 0.03%). Because this assessment of the focus meets the 2001 World Health Organization (WHO) criteria for interrupted transmission, treatment was halted in 2012, and a post-treatment surveillance period was initiated in anticipation of declaration of disease elimination in this area. We provide the first evidence in East Africa that long-term CDTI alone can interrupt transmission of onchocerciasis. PMID:23690554
Rodríguez-Pérez, Mario A.; Domínguez-Vázquez, Alfredo; Unnasch, Thomas R.; Hassan, Hassan K.; Arredondo-Jiménez, Juan I.; Orozco-Algarra, María Eugenia; Rodríguez-Morales, Kristel B.; Rodríguez-Luna, Isabel C.; Prado-Velasco, Francisco Gibert
Background The Southern Chiapas focus of onchocerciasis in Southern Mexico represents one of the major onchocerciasis foci in Latin America. All 559 endemic communities of this focus have undergone semi-annual mass treatment with ivermectin since 1998. In 50 communities of this focus, ivermectin frequency shifted from twice to four times a year in 2003; an additional 113 communities were added to the quarterly treatment regimen in 2009 to achieve a rapid suppression of transmission. Methodology/Principal findings In-depth epidemiologic and entomologic assessments were performed in six sentinel communities (which had undergone 2 rounds of ivermectin treatment per year) and three extra-sentinel communities (which had undergone 4 rounds of ivermectin treatment per year). None of the 67,924 Simulium ochraceum s.l. collected from this focus during the dry season of 2011 were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.06/2,000 flies examined. Serological assays testing for Onchocerca volvulus exposure conducted on 4,230 children 5 years of age and under (of a total population of 10,280 in this age group) revealed that 2/4,230 individuals were exposed to O. volvulus (0.05%; one sided 95% confidence interval = 0.08%). Conclusions/Significance The in-depth epidemiological and entomological findings from the Southern Chiapas focus meet the criteria for interruption of transmission developed by the international community. PMID:23556018
Rodríguez-Pérez, Mario A.; Unnasch, Thomas R.; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L.; Richards, Frank; Peña-Flores, Graciela P.; Orozco-Algarra, María Eugenia; Prado-Velasco, Gibert
The northern Chiapas onchocerciasis focus has undergone 11 years of ivermectin mass treatment. No evidence of microfilariae in the cornea and/or anterior chamber of the eye or in skin snips was seen in residents examined in 2006 in two sentinel communities (upper limit of the 95% confidence interval [UL 95% CI] = 0.5% and 0.3%, respectively). In children 10 and under, 0 of 305 were found to harbor antibodies to Ov16, a marker of parasite exposure; 0 of 4,400 Simulium ochraceum s.l. collected in 2005 contained parasite DNA, giving an UL 95% CI for the infective rate of 0.9/2,000, and an UL 95% CI of the seasonal transmission potential of 1.2 L3/person. These data, assumed to be representative of the focus as a whole, suggest that there is no ongoing transmission of Onchocerca volvulus in the northern Chiapas focus. Community-wide treatments with ivermectin were halted in 2008, and a post-treatment surveillance phase was initiated. PMID:20595471
Eberhard, M L; Melemoko, G; Zee, A K; Weisskopf, M G; Ruiz-Tiben, E
Over the past 10 years, the status of human infection with guinea worm (Dracunculus medinensis) in the Central African Republic (CAR) has been difficult to ascertain. It is unclear if indigenous cases are occurring and whether cases are migrating into the CAR from surrounding countries. A team of investigators visited the CAR in July-August 2000, to attempt to ascertain the presence of indigenous transmission. No cases of true guinea-worm infection (i.e. dracunculiasis) were detected, but three cases of human infection with Onchocerca volvulus, each of which had been misidentified as dracunculiasis, were detected. The unusual presentation of skin blisters and extraction of an intact female O. volvulus are described. As a result of this investigation, and the confusion of onchocerciasis being misidentified as dracunculiasis, the presence of endemic transmission of guinea worm in the CAR remains in question.
Rodríguez-Pérez, Mario A; Lutzow-Steiner, Miguel A; Segura-Cabrera, Aldo; Lizarazo-Ortega, Cristian; Domínguez-Vázquez, Alfredo; Sauerbrey, Mauricio; Richards, Frank; Unnasch, Thomas R; Hassan, Hassan K; Hernández-Hernández, Raymundo
The impact of quarterly Mectizan (ivermectin) treatments on transmission, microfiladermia, and ocular lesions was evaluated in two formerly hyperendemic communities (Las Golondrinas and Las Nubes II) located in the main endemic focus for onchocerciasis in Southern Chiapas, Mexico. The data suggest that Onchocerca volvulus transmission has been suppressed after elimination of microfiladermia in these two communities. Increasing the frequency of Mectizan treatment to four times per year appears to have resulted in the rapid suppression of transmission in communities with residual transmission.
Eisenbarth, Albert; Achukwi, Mbunkah Daniel; Renz, Alfons
Background Recent reports of transmission interruption of Onchocerca volvulus, the causing agent of river blindness, in former endemic foci in the Americas, and more recently in West and East Africa, raise the question whether elimination of this debilitating disease is underway after long-term treatment of the population at risk with ivermectin. The situation in Central Africa has not yet been clearly assessed. Methods and findings Entomologic data from two former endemic river basins in North Cameroon were generated over a period of 43 and 48 months to follow-up transmission levels in areas under prolonged ivermectin control. Moreover, epidemiologic parameters of animal-borne Onchocerca spp. transmitted by the same local black fly vectors of the Simulium damnosum complex were recorded and their impact on O. volvulus transmission success evaluated. With mitochondrial DNA markers we unambiguously confirmed the presence of infective O. volvulus larvae in vectors from the Sudan savannah region (mean Annual Transmission Potential 2009–2012: 98, range 47–221), but not from the Adamawa highland region. Transmission rates of O. ochengi, a parasite of Zebu cattle, were high in both foci. Conclusions/significance The high cattle livestock density in conjunction with the high transmission rates of the bovine filaria O. ochengi prevents the transmission of O. volvulus on the Adamawa plateau, whereas transmission in a former hyperendemic focus was markedly reduced, but not completely interrupted after 25 years of ivermectin control. This study may be helpful to gauge the impact of the presence of animal-filariae for O. volvulus transmission in terms of the growing human and livestock populations in sub-Saharan countries. PMID:26926855
Rodríguez-Pérez, Mario A.; Lutzow-Steiner, Miguel A.; Segura-Cabrera, Aldo; Lizarazo-Ortega, Cristian; Domínguez-Vázquez, Alfredo; Sauerbrey, Mauricio; Richards, Frank; Unnasch, Thomas R.; Hassan, Hassan K.; Hernández-Hernández, Raymundo
The impact of quarterly Mectizan (ivermectin) treatments on transmission, microfiladermia, and ocular lesions was evaluated in two formerly hyperendemic communities (Las Golondrinas and Las Nubes II) located in the main endemic focus for onchocerciasis in Southern Chiapas, Mexico. The data suggest that Onchocerca volvulus transmission has been suppressed after elimination of microfiladermia in these two communities. Increasing the frequency of Mectizan treatment to four times per year appears to have resulted in the rapid suppression of transmission in communities with residual transmission. PMID:18689630
Rodríguez-Pérez, Mario A.; Unnasch, Thomas R.; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L.; Peña-Flores, Graciela P.; Orozco-Algarra, María E.; Arredondo-Jiménez, Juan I.; Richards, Frank; Vásquez-Rodríguez, Miguel A.; Rendón, Vidal García
All endemic communities of the Oaxaca focus of onchocerciasis in southern Mexico have been treated annually or semi-annually with ivermectin since 1994. In-depth epidemiologic assessments were performed in communities during 2007 and 2008. None of the 52,632 Simulium ochraceum s.l. collected in four sentinel communities was found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the infection rate in the vectors of 0.07/2,000. The prevalence of microfilariae (mf) in the cornea and/or anterior chamber of the eye was also zero (0 of 1,039 residents examined; 95%-UL = 0.35%). Similarly, all 1,164 individuals examined by skin biopsy were mf negative (95%-UL = 0.31%), and sera collected from 3,569 children from 25 communities did not harbor Ov16 IgG4-antibodies (95%-UL = 0.09%). These meet the criteria for absence of morbidity and parasite transmission in the Oaxaca focus. As a result mass treatments with ivermectin were halted in 2009. PMID:20595472
Rodríguez-Pérez, Mario A; Unnasch, Thomas R; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L; Peña-Flores, Graciela P; Orozco-Algarra, María E; Arredondo-Jiménez, Juan I; Richards, Frank; Vásquez-Rodríguez, Miguel A; Rendón, Vidal García
All endemic communities of the Oaxaca focus of onchocerciasis in southern Mexico have been treated annually or semi-annually with ivermectin since 1994. In-depth epidemiologic assessments were performed in communities during 2007 and 2008. None of the 52,632 Simulium ochraceum s.l. collected in four sentinel communities was found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the infection rate in the vectors of 0.07/2,000. The prevalence of microfilariae (mf) in the cornea and/or anterior chamber of the eye was also zero (0 of 1,039 residents examined; 95%-UL = 0.35%). Similarly, all 1,164 individuals examined by skin biopsy were mf negative (95%-UL = 0.31%), and sera collected from 3,569 children from 25 communities did not harbor Ov16 IgG4-antibodies (95%-UL = 0.09%). These meet the criteria for absence of morbidity and parasite transmission in the Oaxaca focus. As a result mass treatments with ivermectin were halted in 2009.
Pedersen, E M; Maegga, B T
A survey of the Simulium breeding and the transmission of Onchocerca volvulus was carried out in and around the Tukuyu valley, S.W. Tanzania, S. damnosum s.l. was found breeding in the midstretches of the main rivers in the valley and their bigger tributaries, and also in the boundary river to Malawi and the most northerly of the three rivers draining the Livingstone Mts. to Lake Nyasa (L. Malawi). A total of 19,500 S. damnosum s.l. females was caught and 13,200 dissected. The annual biting rate varied between 2,000 and 23,800. 7.6% of all the flies were infected with O. volvulus and 1.5% carried infective larvae in the head capsule, on average 2.7 per fly. The transmission was mainly in the dry season and the annual transmission potential varied between 0 and 1,120. The entomological data showed many similarities to those from the Mahenge Mts., Tanzania, and correlation of places with comparable transmission potentials suggests a similarity in the relationship parasite-human host between the West African rain forest and the two Tanzanian foci.
Eberhard, Mark L.; Ruiz-Tiben, Ernesto; Korkor, Andrew S.; Roy, Sharon L.; Downs, Philip
We describe 11 cases of suspected Dracunculus medinensis infection in which the worm recovered was identified as Onchocerca volvulus. Identification was based on morphology of the examined specimen. PMID:21118947
Duke, B O
The best hope for the control of transmission of Onchocerca volvulus over much of Africa lies in combining larvicidal measures directed against the Simulium vectors with chemotherapeutic measures designed to reduce the reservoir of transmissible microfilariae in man.There are few drugs effective against O. volvulus. Diethylcarbamazine kills the microfilariae but has virtually no effect on the adult worms. Suramin kills adult worms and many, but not all, of the microfilariae. Mel W kills adult worms but has little or no action on microfilariae. All these drugs suffer at present from disadvantages of toxicity, which tend to limit their use on a mass scale in the field. Nevertheless, before they, or indeed any new drugs with similar actions on the parasites, can be used intelligently for the control of onchocerciasis transmission, it is necessary to have accurate quantitative information on the effect that each of them has on the microfilarial population available for intake by Simulium, as well as on their actions on the developmental potential of those microfilariae ingested by the flies.The present paper describes the effects of treatment with various courses of diethylcarbamazine, suramin or Mel W on the numbers of microfilariae ingested by groups of S. damnosum and on the numbers of infective larvae developing therefrom.
Duke, B. O. L.
The best hope for the control of transmission of Onchocerca volvulus over much of Africa lies in combining larvicidal measures directed against the Simulium vectors with chemotherapeutic measures designed to reduce the reservoir of transmissible microfilariae in man. There are few drugs effective against O. volvulus. Diethylcarbamazine kills the microfilariae but has virtually no effect on the adult worms. Suramin kills adult worms and many, but not all, of the microfilariae. Mel W kills adult worms but has little or no action on microfilariae. All these drugs suffer at present from disadvantages of toxicity, which tend to limit their use on a mass scale in the field. Nevertheless, before they, or indeed any new drugs with similar actions on the parasites, can be used intelligently for the control of onchocerciasis transmission, it is necessary to have accurate quantitative information on the effect that each of them has on the microfilarial population available for intake by Simulium, as well as on their actions on the developmental potential of those microfilariae ingested by the flies. The present paper describes the effects of treatment with various courses of diethylcarbamazine, suramin or Mel W on the numbers of microfilariae ingested by groups of S. damnosum and on the numbers of infective larvae developing therefrom. PMID:4881069
Richards, Frank; Rizzo, Nidia; Diaz Espinoza, Carlos Enrique; Monroy, Zoraida Morales; Crovella Valdez, Carol Guillermina; de Cabrera, Renata Mendizabal; de Leon, Oscar; Zea-Flores, Guillermo; Sauerbrey, Mauricio; Morales, Alba Lucia; Rios, Dalila; Unnasch, Thomas R; Hassan, Hassan K; Klein, Robert; Eberhard, Mark; Cupp, Ed; Domínguez, Alfredo
We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000-2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9-69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ. © The American Society of Tropical Medicine and Hygiene.
Richards, Frank; Rizzo, Nidia; Espinoza, Carlos Enrique Diaz; Monroy, Zoraida Morales; Valdez, Carol Guillermina Crovella; de Cabrera, Renata Mendizabal; de Leon, Oscar; Zea-Flores, Guillermo; Sauerbrey, Mauricio; Morales, Alba Lucia; Rios, Dalila; Unnasch, Thomas R.; Hassan, Hassan K.; Klein, Robert; Eberhard, Mark; Cupp, Ed; Domínguez, Alfredo
We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000–2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9–69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ. PMID:26503275
Duke, B. O. L.
It is important to standardize quantitative methods for assessing the action of drugs on Onchocerca volvulus in man. There are certain disadvantages to making observations on adult worms removed from excised nodules in treated patients, but a great deal of information on drug action can be obtained by making a careful study of the concentrations of microfilariae in multiple weighed skin snips taken before treatment and at intervals after treatment. Before drug trials can be carried out intelligently by this method it is necessary to know the normal length of life of the various stages of the parasite in man. By a variety of experimental methods the life-spans of the adult worms and the microfilariae have been determined, as well as the duration of the prepatent interval. Diethylcarbamazine can be used at doses that are effectively microfilaricidal but have no action on the adult worms. This drug can therefore be used to eliminate any residual microfilariae that remain after treatment with a new drug under trial, thus permitting a more rapid assessment of the latter's action on adult worms. PMID:4881066
Meyers, W M; Neafie, R C; Connor, D H
Autopsies of two patients with onchocerciasis in the Republic of Zaïre are reported. In one patient elephantiasis who died following diethylcarbamazine therapy there were large numbers of microfilariae of Onchocerca volvulus in the kidney, liver, pancreas, and lung. In the second patient, who also had leprosy and hyperinfection strongyloidiasis, we found an encapsulated adult O. volvulus in the wall of the thoracic aorta.
Duke, B. O. L.
Suramin and Mel W are the only two drugs at present known to be effective against the adult worms of Onchocerca volvulus, but in view of the unpredictable occurrence of fatal arsenical encephalopathy in a small proportion of patients receiving Mel W, suramin remains the preferred macrofilaricide in the treatment of onchocerciasis. It is therefore important to determine the suramin dosage schedules that will produce parasitological cures with minimal concomitant risks of toxic reactions. The criteria by which cures should be judged must also be appreciated. Courses of different duration and employing doses of 1.0 g, 0.5 g and 0.25 g suramin have been investigated for their action on adult worms and microfilariae, for the toxic reactions which they produce on the kidney, and for the level of suramin reached in the serum during treatment. A course of 5 or 6 weekly doses of 1.0 g has been shown to be the optimum for adults. It is sometimes stated without good foundation that different brands of suramin differ in their purity and chemical composition, thus producing inconsistent effects on the parasites and grave risks of toxic manifestations. The three main brands in current use in Africa (Antrypol, Moranyl and Naganol) have therefore been compared in a group of patients, using the same optimum dosage schedule for each preparation and recording the action of the various brands on the parasites, as well as their comparative toxicities and the serum suramin levels achieved. No significant differences between the brands were recorded. PMID:4881068
Manchang, T K; Ajonina-Ekoti, I; Ndjonka, D; Eisenbarth, A; Achukwi, M D; Renz, A; Brattig, N W; Liebau, E; Breloer, M
Onchocerca volvulus is a tissue-dwelling, vector-borne nematode parasite of humans and is the causative agent of onchocerciasis or river blindness. Natural infections of BALB/c mice with Litomosoides sigmodontis and of cattle with Onchocerca ochengi were used as models to study the immune responses to O. volvulus-derived recombinant proteins (OvALT-2, OvNLT-1, Ov103 and Ov7). The humoral immune response of O. volvulus-infected humans against OvALT-2, OvNLT-1 and Ov7 revealed pronounced immunoglobulin G (IgG) titres which were, however, significantly lower than against the lysate of O. volvulus adult female worms. Sera derived from patients displaying the hyperreactive form of onchocerciasis showed a uniform trend of higher IgG reactivity both to the single proteins and the O. volvulus lysate. Sera derived from L. sigmodontis-infected mice and from calves exposed to O. ochengi transmission in a hyperendemic area also contained IgM and IgG1 specific for O. volvulus-derived recombinant proteins. These results strongly suggest that L. sigmodontis-specific and O. ochengi-specific immunoglobulins elicited during natural infection of mice and cattle cross-reacted with O. volvulus-derived recombinant antigens. Monitoring O. ochengi-infected calves over a 26-month period, provided a comprehensive kinetic of the humoral response to infection that was strictly correlated with parasite load and occurrence of microfilariae.
Crainey, James L; da Silva, Túllio RR; Encinas, Fernando; Marín, Michel A; Vicente, Ana Carolina P; Luz, Sérgio LB
We report here the first complete mitochondria genome of Onchocerca volvulus from a focus outside of Africa. An O. volvulus mitogenome from the Brazilian Amazonia focus was obtained using a combination of high-throughput and Sanger sequencing technologies. Comparisons made between this mitochondrial genome and publicly available mitochondrial sequences identified 46 variant nucleotide positions and suggested that our Brazilian mitogenome is more closely related to Cameroon-origin mitochondria than West African-origin mitochondria. As well as providing insights into the origins of Latin American onchocerciasis, the Brazilian Amazonia focus mitogenome may also have value as an epidemiological resource. PMID:26814648
Crainey, James L; Silva, Túllio R R da; Encinas, Fernando; Marín, Michel A; Vicente, Ana Carolina P; Luz, Sérgio L B
We report here the first complete mitochondria genome of Onchocerca volvulus from a focus outside of Africa. An O. volvulus mitogenome from the Brazilian Amazonia focus was obtained using a combination of high-throughput and Sanger sequencing technologies. Comparisons made between this mitochondrial genome and publicly available mitochondrial sequences identified 46 variant nucleotide positions and suggested that our Brazilian mitogenome is more closely related to Cameroon-origin mitochondria than West African-origin mitochondria. As well as providing insights into the origins of Latin American onchocerciasis, the Brazilian Amazonia focus mitogenome may also have value as an epidemiological resource.
Duke, B O
Previous work on monkeys and on human volunteers led to the development of a schedule of diethylcarbamazine dosage suitable for the chemoprophylaxis of loiasis. In several parts of Africa where this chemoprophylaxis is practised against Loa loa, infections with Onchocerca volvulus are also common. Attempts were therefore made to determine whether diethylcarbamazine has any prophylactic action against the latter parasite by making use of chimpanzees exposed to experimental infections, and also by using biopsy techniques to study the fate of infective larvae inoculated into volunteers.Both experimental methods proved more difficult to apply in O. volvulus infections than had been the case with L. loa, but evidence was obtained that diethylcarbamazine is not an effective chemoprophylactic for O. volvulus.Further experiments were then carried out with suramin and with melarsonyl potassium (Mel W). Although both gave some evidence of partial prophylactic activity, their use for this purpose is at present neither practical nor safe.
Duke, B. O. L.
Previous work on monkeys and on human volunteers led to the development of a schedule of diethylcarbamazine dosage suitable for the chemoprophylaxis of loiasis. In several parts of Africa where this chemoprophylaxis is practised against Loa loa, infections with Onchocerca volvulus are also common. Attempts were therefore made to determine whether diethylcarbamazine has any prophylactic action against the latter parasite by making use of chimpanzees exposed to experimental infections, and also by using biopsy techniques to study the fate of infective larvae inoculated into volunteers. Both experimental methods proved more difficult to apply in O. volvulus infections than had been the case with L. loa, but evidence was obtained that diethylcarbamazine is not an effective chemoprophylactic for O. volvulus. Further experiments were then carried out with suramin and with melarsonyl potassium (Mel W). Although both gave some evidence of partial prophylactic activity, their use for this purpose is at present neither practical nor safe. ImagesFIG. 1FIG. 2FIG. 3 PMID:4881070
Mackenzie, C D; Huntington, M K; Wanji, S; Lovato, R V; Eversole, R R; Geary, T G
Immunocytochemical examination of onchocercal nodule tissues containing adult Onchocerca volvulus using immuno-markers for blood and lymphatic vessels (vWF, D2-40, podoplanin, Prox-1, and Lyve1) shows a distinct pattern of distribution of these vessels within nodules. Blood vessels were commonly seen associated with organized lymphoid cellular aggregates in the both the outer and inner areas of the nodules. In contrast, the majority of the lymphatic vessel positivity was seen in the central zone in close apposition to the adult parasites, and the remainder usually associated with microfilariae in the outer areas of the nodule. These findings suggest an intimate relationship between adult O. volvulus and lymphatic vessels, including the likely proliferation of lymphatic endothelial cells (lymphangectasia) akin to that seen with other filariae. These findings indicate that adult O. volvulus may migrate via the lymphatic system, and that clinical manifestations of this disease that involve tissue edema may be the result of the location of these worms in the lymphatic system.
Cotton, James A.; Bennuru, Sasisekhar; Grote, Alexandra; Harsha, Bhavana; Tracey, Alan; Beech, Robin; Doyle, Stephen R.; Dunn, Matthew; Dunning Hotopp, Julie C.; Holroyd, Nancy; Kikuchi, Taisei; Lambert, Olivia; Mhashilkar, Amruta; Mutowo, Prudence; Nursimulu, Nirvana; Ribeiro, Jose M. C.; Rogers, Matthew B.; Stanley, Eleanor; Swapna, Lakshmipuram S.; Tsai, Isheng J.; Unnasch, Thomas R.; Voronin, Denis; Parkinson, John; Nutman, Thomas B.; Ghedin, Elodie; Berriman, Matthew; Lustigman, Sara
Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development. PMID:27869790
Cotton, James A; Bennuru, Sasisekhar; Grote, Alexandra; Harsha, Bhavana; Tracey, Alan; Beech, Robin; Doyle, Stephen R; Dunn, Matthew; Hotopp, Julie C Dunning; Holroyd, Nancy; Kikuchi, Taisei; Lambert, Olivia; Mhashilkar, Amruta; Mutowo, Prudence; Nursimulu, Nirvana; Ribeiro, Jose M C; Rogers, Matthew B; Stanley, Eleanor; Swapna, Lakshmipuram S; Tsai, Isheng J; Unnasch, Thomas R; Voronin, Denis; Parkinson, John; Nutman, Thomas B; Ghedin, Elodie; Berriman, Matthew; Lustigman, Sara
Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development.
Osei-Atweneboana, Mike Y.; Awadzi, Kwablah; Attah, Simon K.; Boakye, Daniel A.; Gyapong, John O.; Prichard, Roger K.
Background Ivermectin (IVM) has been used in Ghana for over two decades for onchocerciasis control. In recent years there have been reports of persistent microfilaridermias despite multiple treatments. This has necessitated a reexamination of its microfilaricidal and suppressive effects on reproduction in the adult female Onchocerca volvulus. In an initial study, we demonstrated the continued potent microfilaricidal effect of IVM. However, we also found communities in which the skin microfilarial repopulation rates at days 90 and 180 were much higher than expected. In this follow up study we have investigated the reproductive response of female worms to multiple treatments with IVM. Methods and Findings The parasitological responses to IVM in two hundred and sixty-eight microfilaridermic subjects from nine communities that had received 10 to 19 annual doses of IVM treatment and one pre-study IVM-naïve community were followed. Skin snips were taken 364 days after the initial IVM treatment during the study to determine the microfilaria (mf) recovery rate. Nodules were excised and skin snips taken 90 days following a second study IVM treatment. Nodule and worm density and the reproductive status of female worms were determined. On the basis of skin mf repopulation and skin mf recovery rates we defined three categories of response—good, intermediate and poor—and also determined that approximately 25% of subjects in the study carried adult female worms that responded suboptimally to IVM. Stratification of the female worms by morphological age and microfilarial content showed that almost 90% of the worms were older or middle aged and that most of the mf were produced by the middle aged and older worms previously exposed to multiple treatments with little contribution from young worms derived from ongoing transmission. Conclusions The results confirm that in some communities adult female worms were non-responsive or resistant to the anti-fecundity effects of multiple
Choi, Young-Jun; Tyagi, Rahul; McNulty, Samantha N; Rosa, Bruce A; Ozersky, Philip; Martin, John; Hallsworth-Pepin, Kymberlie; Unnasch, Thomas R; Norice, Carmelle T; Nutman, Thomas B; Weil, Gary J; Fischer, Peter U; Mitreva, Makedonka
Ongoing elimination efforts have altered the global distribution of Onchocerca volvulus, the agent of river blindness, and further population restructuring is expected as efforts continue. Therefore, a better understanding of population genetic processes and their effect on biogeography is needed to support elimination goals. We describe O. volvulus genome variation in 27 isolates from the early 1990s (before widespread mass treatment) from four distinct locales: Ecuador, Uganda, the West African forest and the West African savanna. We observed genetic substructuring between Ecuador and West Africa and between the West African forest and savanna bioclimes, with evidence of unidirectional gene flow from savanna to forest strains. We identified forest:savanna-discriminatory genomic regions and report a set of ancestry informative loci that can be used to differentiate between forest, savanna and admixed isolates, which has not previously been possible. We observed mito-nuclear discordance possibly stemming from incomplete lineage sorting. The catalogue of the nuclear, mitochondrial and endosymbiont DNA variants generated in this study will support future basic and translational onchocerciasis research, with particular relevance for ongoing control programmes, and boost efforts to characterize drug, vaccine and diagnostic targets.
Bourguinat, Catherine; Pion, Sébastien D. S.; Kamgno, Joseph; Gardon, Jacques
Background Onchocerca volvulus is the causative agent of onchocerciasis, or “river blindness”. Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure. Methods and Findings O. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 µg/kg or 800 µg/kg. Genotype frequencies were determined in β-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between β-tubulin genotype and female parasite fertility. We found a significant selection for β-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the β-tubulin “aa” homozygotes from 68.6% to 25.6%, while the “ab” heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the β-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p = 0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly. Conclusions The results indicate that ivermectin is causing genetic selection on
Boussinesq, M; Chippaux, J P
A clinical trial was conducted in Cameroon in order to evaluate in humans the possible effect of a single dose of ivermectin (150 micrograms per kg) on the pre-adult stages of Onchocerca volvulus. The incidence of the skin microfilariae was measured in two groups of patients who initially had negative biopsies, and who were subsequently treated, immediately after the seasonal peak of transmission of O. volvulus, either with a combination of ivermectin + ferrous sulphate, or with ferrous sulphate alone. One year after the treatment, i.e. 14 months after the start of the transmission period, the proportion of patients with positive skin biopsies, and their mean microfilarial loads, did not differ significantly between the two groups. Thus a single dose of ivermectin does not seem to have any perceptible prophylactic effect against O. volvulus.
Duke, B O
The paper records the numbers of 1-2 mm shotty papules developing in the author's skin after 2-day courses of diethylcarbamazine (DEC) repeated every 16 days before, during and after a 7.1 G suramin course for cutaneous onchocerciasis. Assuming, from biopsy evidence, that each papule represented a dead Onchocerca volvulus microfilaria (mf), the number of mfs reaching the skin every 16 days did not begin to fall until 96 days after the first full dose of suramin; and only reached zero by day 224. The histopathology of nodules excised from Cameroonian patients before, and at intervals of 56-335 days after, the start of a 7.1 G suramin course, revealed changes in the worms that correlated over time with the disappearance of mfs from the skin. Suramin sterilized and killed the male worms between days 77 and 105 and, in the females, it adversely affected the staining and subsequent development of small morulae from about day 56. It was estimated that new embryogenesis ceased about 56-77 days after the first full dose; development of the last viable embryos to mfs was complete by about 136 days; and the last mfs, perhaps having reduced vitality, emerged from the females by 160 days and reached the skin within 16-32 days.
Norice-Tra, Carmelle T; Ribeiro, José; Bennuru, Sasisekhar; Fay, Michael P; Tyagi, Rahul; Mitreva, Makedonka; Nutman, Thomas B
We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides derived from 8 of 10 proteins tested: OVOC1192(1-15), OVOC9988(28-42), OVOC9225(320-334), OVOC7453(22-36), OVOC11517(14-28), OVOC3177(283-297), OVOC7911(594-608), and OVOC12628(174-188). Our data show that differences in immunoreactivity to variant antigenic peptides may be used to characterize Ov populations, thereby elucidating features of Ov population biology previously inaccessible because of the limited availability of parasite material. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Specht, Sabine; Brattig, Norbert; Büttner, Marcelle; Büttner, Dietrich W
Drugs exist that show long-lasting inhibition of embryogenesis and microfilaria production or macrofilaricidal activity against Onchocerca volvulus. Therefore, the patients have to be followed-up for several years. Clinical drug trials have to be performed in areas with ongoing transmission to assess the efficacy on younger worms. In addition, future vaccine trials may also require demonstrating efficacy against establishment of new worms. For the evaluation of the efficacy, it is necessary to differentiate between older worms, which were exposed to the drug, and younger worms newly acquired after drug treatment or vaccination. Here, we describe criteria for the differentiation between young and old filariae based on histological studies of worms with a known age from travellers, or from children, or patients living in areas with interrupted transmission in Burkina Faso, Ghana or Uganda. Older worms were larger and presented degenerated tissues. Gomori's iron stain showed that the worms accumulated more iron with increasing age, first in the gut and later in other organs. Using an antibody against O. volvulus lysosomal aspartic protease, the gut of young worms was stained only weakly; whereas, it was stronger labelled in older worms, accompanied by additional staining of hypodermis and epithelia. Using morphological and immunohistological criteria, it was possible to differentiate young (1-3 years old) from older females and to identify young males.
Prost, A; Gorim de Ponsay, E
Between April 1977 and June 1978, 214 babies born of 210 mothers infected with Onchocerciasis, were examined at the maternity of Po Hospital (Upper Volta). In four of them (1.9%) dermal microfilariae of Onchocerca volvulus were found during the first week after birth. In two other cases microfilariae were seen in the tissue of the umbilical cord. All specimens from placentas and amniotic fluid gave negative results. The infected babies were reexamined monthly monthly from 2 to 18 months, depending on the cases. One child remained positive until the 6th month follow-up. The base-line examination of 5.757 children less than 2 years old from different villages in the WHO Onchocerciasis Control Programme in the Volta River Basin Area showed that 1% of children less than one year old and 2% of children of 12 to 23 months old were carriers of dermal microfilariae. These results indicate that in meso- or hyperendemic areas children less than one year old and carriers of microfilariae of Onchocerca volbulus may have been infected in utero. The existence of such cases, in an area of vector control, does not prove a residual vector borne transmission.
Korten, Simone; Büttner, Dietrich W; Schmetz, Christel; Hoerauf, Achim; Mand, Sabine; Brattig, Norbert
Transforming growth factor-beta (TGF-beta) is a highly conserved cytokine that has a well-known regulatory role in immunity, but also in organ development of most animal species including helminths. Homologous tgf-b genes and mRNA have been detected in the filaria Brugia malayi. The in situ protein expression is unknown for filariae. Therefore, we examined several filariae for the expression and localization of latent (stable) TGF-beta in adult and larval stages. A specific goat anti-human latency associated protein (LAP, TGF-beta 1) antibody, purified by affinity chromatography, was used for light and electron microscopic immunohistochemistry. Adult Onchocerca volvulus, Onchocerca gibsoni, Onchocerca ochengi, Onchocerca armillata, Onchocerca fasciata, Onchocerca flexuosa, Wuchereria bancrofti, Dirofilaria sp., B. malayi, and infective larvae of W. bancrofti reacted with the antibody. Labeling of worm tissues varied between negative and all degrees of positive reactions. Latent TGF-beta was strongly expressed adjacent to the cell membranes of the hypodermis, epithelia, and muscles and adjacent to many nuclei in all organs. TGF-beta was well expressed in worms without Wolbachia endobacteria eliminated by doxycycline treatment. Pleomorphic neoplasms in O. volvulus were also labeled. We conclude that latent TGF-beta protein is expressed by filariae independently of Wolbachia, possibly regulating worm tissue homeostasis.
Gómez-Priego, Alberto; Mendoza, Raymundo; de-la-Rosa, Jorge-Luis
Studies to determine the prevalence of antibodies to Onchocerca volvulus, prior to and after actions carried out to interrupt transmission, are scarce in Mexico. Here we report the prevalence of immunoglobulin G (IgG) and IgG4 antibodies in an enzyme-linked immunosorbent assay (ELISA) against a crude extract of O. volvulus adult worm in serum samples from persons under noninterrupted biannual treatment with ivermectin in areas of onchocercosis endemicity in Mexico. To perform the prevalence studies, the ELISA procedures were first evaluated. Serological studies were performed with serum samples from skin microfilaria carriers from Guatemala and from people microfilariodermic negative living in the same area as the Guatemalan patients. Sensitivity values for IgG or IgG4 detection were 71 and 86%, while specificities were 92 and 100%, respectively. No anti-O. volvulus antibodies were found in samples from nonendemic controls from Mexico, but 3 of 71 samples from residents in the onchocercosis area of Oaxaca, Mexico, and who have been under ivermectin treatment during the last 10 years were only positive to IgG. Notwithstanding that the IgG4 isotype was not detected and a low (4.2%) anti-O. volvulus IgG antibody prevalence was found, a seroepidemiological follow-up must be performed in order to confirm interruption of onchocercosis transmission in the area of Oaxaca, Mexico, in which onchocercosis is endemic. PMID:15642982
James, E R; McLean, D C; Perler, F
Onchocerca volvulus, a human parasitic nematode, is the third leading cause of preventable blindness worldwide. This study describes the molecular cloning of a novel superoxide dismutase (SOD) from the parasite. This putative O. volvulus extracellular SOD (OvEcSOD) is 628 nucleotides (nt) long, including a 22-nt 5' spliced leader (SL1) and a portion encoding an N-terminal hydrophobic 42-amino-acid signal peptide. The remainder of the cDNA shares 71% identity with an O. volvulus cytosolic SOD sequence and is 3 nt longer. All residues involved in metal ion binding, active site formation, folding, and dimer formation in SODs are conserved. Data indicate the OvEcSOD and O. volvulus cytosolic SOD are separate gene products and that the OvEcSOD appears to possess the characteristics of a membrane-bound or secreted enzyme which may be involved in the parasite defense against phagocyte-generated reactive oxygen species. Images PMID:8300230
Gopal, Hemavathi; Hassan, Hassan K.; Rodríguez-Pérez, Mario A.; Toé, Laurent D.; Lustigman, Sara; Unnasch, Thomas R.
Background Entomological surveys of Simulium vectors are an important component in the criteria used to determine if Onchocerca volvulus transmission has been interrupted and if focal elimination of the parasite has been achieved. However, because infection in the vector population is quite rare in areas where control has succeeded, large numbers of flies need to be examined to certify transmission interruption. Currently, this is accomplished through PCR pool screening of large numbers of flies. The efficiency of this process is limited by the size of the pools that may be screened, which is in turn determined by the constraints imposed by the biochemistry of the assay. The current method of DNA purification from pools of vector black flies relies upon silica adsorption. This method can be applied to screen pools containing a maximum of 50 individuals (from the Latin American vectors) or 100 individuals (from the African vectors). Methodology/Principal Findings We have evaluated an alternative method of DNA purification for pool screening of black flies which relies upon oligonucleotide capture of Onchocerca volvulus genomic DNA from homogenates prepared from pools of Latin American and African vectors. The oligonucleotide capture assay was shown to reliably detect one O. volvulus infective larva in pools containing 200 African or Latin American flies, representing a two-four fold improvement over the conventional assay. The capture assay requires an equivalent amount of technical time to conduct as the conventional assay, resulting in a two-four fold reduction in labor costs per insect assayed and reduces reagent costs to $3.81 per pool of 200 flies, or less than $0.02 per insect assayed. Conclusions/Significance The oligonucleotide capture assay represents a substantial improvement in the procedure used to detect parasite prevalence in the vector population, a major metric employed in the process of certifying the elimination of onchocerciasis. PMID:22724041
Kläger, S; Whitworth, J A; Post, R J; Chavasse, D C; Downham, M D
The persistence of the effects of ivermectin on the viability, morphology and reproductivity of adult Onchocerca volvulus was examined eighteen months after treatment with a single or five six-monthly doses of ivermectin and compared with untreated controls. Treated nodules were removed from patients participating in a randomised controlled trial of ivermectin in Sierra Leone. Adult filariae, 545 females and 348 males, were isolated by collagenase digestion. The nodules were significantly smaller, contained fewer young worms and supported lower microfilarial production in those treated with five doses of ivermectin. The productivity index, a measure of the reproductive potential of a worm population, was still reduced by 83% eighteen months after five doses and by 63% after a single dose compared to controls. These results show that worms recover their fertility even after multiple doses of ivermectin, but do so slowly compared to standard dosage intervals. In addition ivermectin may have a partial chemoprophylactic effect which contributes to the maintenance of low microfilarial production in conditions of on-going transmission.
Senyonjo, Laura; Oye, Joseph; Bakajika, Didier; Biholong, Benjamin; Tekle, Afework; Boakye, Daniel; Schmidt, Elena; Elhassan, Elizabeth
Background Community Directed Treatment with ivermectin is the cornerstone of current efforts to eliminate onchocerciasis. However recent studies suggest there are foci where long-term annual distribution of the drug alone has failed to ensure elimination thresholds are reached. It is important to achieve high levels of compliance in order to obtain elimination targets. An epidemiological and entomological evaluation conducted in the western region of Cameroon in 2011 revealed that two health districts remained with a high prevalence of infection, despite long-term distribution of ivermectin since 1996. This paper explores potential factors that may have contributed to the non-interruption of transmission, focusing on ivermectin treatment compliance and the importance of systematic non-compliance within the population. Methodology/Principal findings A mixed methods approach was used, including a population-based survey to assess treatment compliance and factors associated and qualitative assessments including focus group discussions and in-depth interviews with key programme stakeholders and drug distributors. Compliance was reported at 71.2% (95%CI: 61.7–79.2%;n = 853/1198). The key factors related to compliance in the most recent round related to either programmatic and delivery issues, primarily absenteeism at the time of the campaign or alternatively individual determinants. An individual’s experience of side effects in the past was strongly associated with non-compliance to ivermectin. Other factors included ethnicity, how long lived in the village and age. There was a high percentage of reported systematic non-compliance at 7.4% (95% CI: 4.3–12.3%; n = 86/1165), higher amongst females. This group may be important in facilitating the sustainment of on-going transmission. Conclusions/Significance Efforts to reduce the number of systematic non-compliers and non-compliance in certain groups may be important in ensuring the interruption of transmission in
Senyonjo, Laura; Oye, Joseph; Bakajika, Didier; Biholong, Benjamin; Tekle, Afework; Boakye, Daniel; Schmidt, Elena; Elhassan, Elizabeth
Community Directed Treatment with ivermectin is the cornerstone of current efforts to eliminate onchocerciasis. However recent studies suggest there are foci where long-term annual distribution of the drug alone has failed to ensure elimination thresholds are reached. It is important to achieve high levels of compliance in order to obtain elimination targets. An epidemiological and entomological evaluation conducted in the western region of Cameroon in 2011 revealed that two health districts remained with a high prevalence of infection, despite long-term distribution of ivermectin since 1996. This paper explores potential factors that may have contributed to the non-interruption of transmission, focusing on ivermectin treatment compliance and the importance of systematic non-compliance within the population. A mixed methods approach was used, including a population-based survey to assess treatment compliance and factors associated and qualitative assessments including focus group discussions and in-depth interviews with key programme stakeholders and drug distributors. Compliance was reported at 71.2% (95%CI: 61.7-79.2%;n = 853/1198). The key factors related to compliance in the most recent round related to either programmatic and delivery issues, primarily absenteeism at the time of the campaign or alternatively individual determinants. An individual's experience of side effects in the past was strongly associated with non-compliance to ivermectin. Other factors included ethnicity, how long lived in the village and age. There was a high percentage of reported systematic non-compliance at 7.4% (95% CI: 4.3-12.3%; n = 86/1165), higher amongst females. This group may be important in facilitating the sustainment of on-going transmission. Efforts to reduce the number of systematic non-compliers and non-compliance in certain groups may be important in ensuring the interruption of transmission in the study area. However, in areas with high pre-control force of
Ortega, M; Oliver, M; Ramírez, A
In Guatemala, there is no doubt about the participation of Simulium ochraceum as vector of Onchocerciasis. However, in Mexico practically there are not studies focussed to determine the role of this species in the transmission. The objective of the present investigation was to determine which of the 3 species of Simulium founded in the Soconusco region of Chiapas, is the main, and which were secondary in the transmission of Onchocerciasis in that area. The locality of Morelos, in the Huixtla "municipio" of Chiapas, localized a 1200 meters over the sea level (mosl) were selected to carried out the present study. According to own parasitological studies, this locality is considered as highly endemic (more than 66% prevalence). From March 1979 to March, 1981, we performed captures of Simulium sp caught on human bait. Quantitative studies and of transmission potentials were also performed. The following results were obtained: a) Absolute black flies densities (nulliparous and pariparous) and infected black flies (with L1 and L2 larvae): S. ochraceum, S. metallicum and S. callidum, in that order was the distribution of densities. Infected black flies were obtained in the 3 species. However, in despite of an irregular distribution in all the year, it was possible to identify 2 peaks of maximum infection of S. ochraceum in March, 1979 and March 1981. b) Monthly bite densities and infective bites.(ABSTRACT TRUNCATED AT 250 WORDS)
Enyong, P; Traoré, S; Louango, E; Fobi, G; Noma, M; Yaméogo, L; Kayembé, D; Sékétéli, A
Entomological baseline data were collected in the villages of Zinga and Boali-Falls in Central African Republic (CAR) in view of the long term impact assessment of community-directed treatment with ivermectin (CDTI). Morphological determinations revealed that flies caught in both sites belong to the sub-group Sou/Sq. In Boali, the nuisance was relatively high with biting rates averaging 243 bites/man/day, with a parous rate of 61.6% and a crude annual transmission potential (ATP) of 8,259 infective larvae/man/year; and the average number of infective larvae per 1,000 parous flies was 177. In Zinga, the mean biting rate was 191 bites/man/day, with a parous rate of 51.6%, a crude ATP of 3,422, and 86 infective larvae per 1,000 porous flies. In conclusion, the vectorial capacity and the entomological indices recorded are characteristic of high onchocerciasis transmission zones. However, some of the infective larvae found, maybe of animal origin, need identification to better determine the real level of endemicity.
Katabarwa, Moses N.; Lakwo, Tom; Habomugisha, Peace; Agunyo, Stella; Byamukama, Edson; Oguttu, David; Tukesiga, Ephraim; Unoba, Dickson; Dramuke, Patrick; Onapa, Ambrose; Tukahebwa, Edridah M.; Lwamafa, Dennis; Walsh, Frank; Unnasch, Thomas R.
The objective of the study was to determine whether annual ivermectin treatment in the Nyagak-Bondo onchocerciasis focus could safely be withdrawn. Baseline skin snip microfilariae (mf) and nodule prevalence data from six communities were compared with data collected in the 2011 follow-up in seven communities. Follow-up mf data in 607 adults and 145 children were compared with baseline (300 adults and 58 children). Flies collected in 2011were dissected, and poolscreen analysis was applied to ascertain transmission. Nodule prevalence in adults dropped from 81.7% to 11.0% (P < 0.0001), and mf prevalence dropped from 97.0% to 23.2% (P < 0.0001). In children, mf prevalence decreased from 79.3% to 14.1% (P < 0.0001). Parous and infection rates of 401 flies that were dissected were 52.9% and 1.5%, respectively, whereas the infective rate on flies examination by polymerase chain reaction (PCR) was 1.92% and annual transmission potential was 26.9. Stopping ivermectin treatment may result in onchocerciasis recrudescence. PMID:23690555
Katabarwa, Moses N; Lakwo, Tom; Habomugisha, Peace; Agunyo, Stella; Byamukama, Edson; Oguttu, David; Tukesiga, Ephraim; Unoba, Dickson; Dramuke, Patrick; Onapa, Ambrose; Tukahebwa, Edridah M; Lwamafa, Dennis; Walsh, Frank; Unnasch, Thomas R
The objective of the study was to determine whether annual ivermectin treatment in the Nyagak-Bondo onchocerciasis focus could safely be withdrawn. Baseline skin snip microfilariae (mf) and nodule prevalence data from six communities were compared with data collected in the 2011 follow-up in seven communities. Follow-up mf data in 607 adults and 145 children were compared with baseline (300 adults and 58 children). Flies collected in 2011 were dissected, and poolscreen analysis was applied to ascertain transmission. Nodule prevalence in adults dropped from 81.7% to 11.0% (P < 0.0001), and mf prevalence dropped from 97.0% to 23.2% (P < 0.0001). In children, mf prevalence decreased from 79.3% to 14.1% (P < 0.0001). Parous and infection rates of 401 flies that were dissected were 52.9% and 1.5%, respectively, whereas the infective rate on flies examination by polymerase chain reaction (PCR) was 1.92% and annual transmission potential was 26.9. Stopping ivermectin treatment may result in onchocerciasis recrudescence.
Meyrowitsch, D W; Simonsen, P E; Magnussen, P
The tolerance of Onchocerca volvulus-infected individuals to diethylcarbamazine (DEC)-medicated salt (0.33% w/w) was assessed in 1996 in Tanzania in a double-blind placebo-controlled hospital-based trial involving 4 groups, each of 10 adult males. Groups I and II had O. volvulus microfilariae (mf) only, group III had both O. volvulus and Wuchereria bancrofti mf, and group IV had W. bancrofti mf only. Groups I, III and IV received DEC-medicated salt, whereas group II was a control to group I and received normal cooking salt. Medication was given for 10 days. The most pronounced adverse reactions in groups I and III were mild-to-moderate itching and rash, beginning after 3-4 days and lasting for the remaining medication period. The reactions did not interfere with normal daily activities. By 20 days after the end of medication, adverse reactions had disappeared in all individuals. The low daily dose of DEC had no significant effect on the O. volvulus pre-medication mf geometric mean intensities (GMIs). In contrast, the medication significantly reduced the pre-medication W. bancrofti mf GMIs. The prospects for using DEC-medicated salt for control of bancroftian filariasis in areas where incidental infections with O. volvulus occur are discussed.
Büttner, D W; Albiez, E J; von Essen, J; Erichsen, J
The methods used for the assessment of adult Onchocerca volvulus by histology are described. Based on the results of several studies, mainly in Liberia and Burkina Faso, the morphology of the adult filariae in histological sections is represented as far as it is relevant for the evaluation. Especially are described the morphological alterations due to old age of the worms, to chronic hyperreactivity of the human host (sowda) and effects of the macrofilaricidal suramin and of microfilaricidal drugs. Quantitative results are reported on untreated adult O. volvulus from various countries, the changes of the worm population during 12 years of vector control in Burkina Faso and the effects of suramin, diethylcarbamazine, metrifonate, and ivermectin. The data from the histological examinations are compared with those gained from the examination of worms isolated by the collagenase technique in the same studies.
Zeng, W L; Alarcon, C M; Donelson, J E
Genomic DNAs of the related parasitic nematodes Onchocerca volvulus and Dirofilariae immitis, and a cDNA library of O. volvulus, were examined for the presence of the 22-nucleotide spliced leader (SL) found at the 5' ends of 10 to 15% of the mRNAs in the free-living nematode Caenorhabditis elegans. As in C. elegans, genes for the SL RNA are linked to the repetitive 5S rRNA genes of O. volvulus and D. immitis, but unlike C. elegans, they are in the same orientation as the 5S rRNA genes within the repeat unit. In O. volvulus the SL sequence is also encoded at more than 30 additional genomic locations and occurs at interior sites within many transcripts. Sequence determinations of four different cDNAs of O. volvulus, each containing an internal copy of the SL within a conserved 25mer, and one corresponding genomic DNA clone indicate that this sequence is not trans spliced onto these RNAs, but is encoded within the genes. The RNAs of two of these cDNAs appear to be developmentally regulated, since they occur in adult O. volvulus but were not detected in the infective L3 stage larvae. In contrast, actin mRNAs are present at all developmental stages, and at least one actin mRNA species contains a trans-spliced 5' SL. The internal locations of the SL in various transcripts and its perfect sequence conservation among parasitic and free-living nematodes argues that it serves specific, and perhaps multiple, functions for these organisms. Images PMID:1692960
Lu, W; Egerton, G L; Bianco, A E; Williams, S A
Random screening of an Onchocerca volvulus third-stage (L3) cDNA library identified a highly abundant cDNA encoding a newly discovered antioxidant enzyme, thioredoxin peroxidase (TPx), a member of the peroxidoxin superfamily. This TPx cDNA (Ov-tpx-2) encodes a polypeptide of 199 amino acid residues with a calculated molecular weight of 21,890 Da. The Ov-tpx-2 cDNA represents roughly 2.5% of the total cDNAs from the L3 cDNA library. The gene was expressed in Escherichia coli and the protein product was shown to have antioxidant activity. Antiserum raised against Ov-TPX-2 recognized a native protein from extracts of both the L3 and adult-stages with a molecular weight of 22 kD. The localization and stage-specificity of Ov-TPX-2 protein was analyzed by immunocytochemistry and immunoelectron microscopy using monospecific antibodies. Expression was detected in late first-stage larvae during development in the vector and increased in intensity during differentiation to the infective L3-stage. The antigen was also detected in post-infective larvae and adult worms. In larvae, Ov-TPX-2 protein was predominantly localized to the hypodermis and cuticle, with additional sites in the hypodermal chords and multivesicular bodies. In adult worms, the primary sites of expression were the uterine epithelium and intestine, with additional labeling of the body wall and cuticle. Developing embryos and microfilariae in utero were bathed in Ov-TPX-2 protein discharged from epithelial cells. These results suggest that Ov-TPX-2 may protect the parasites from being damaged by host-generated oxidative stress and that Ov-TPX-2 protein provides the H2O2-detoxifying activity predicted but not previously identified in filarial parasites. Its highly upregulated expression in infective larvae may aid in parasite establishment following transmission to the definitive host.
Campbell, C C; Collins, R C; Huong, A Y; Marroquin, H F
In Guatemala, 16 wild Simulium ochraceum were permitted to feed on a 15" x 15" grid on the back of each of 13 persons infected with Onchocerca volvulus. Based on 6 skin biopsies, the mean microfilarial density (mfd) in these study participants ranged from 1.256 mf/mg of skin to 111.824 mf/mg. The files were dissected 6 to 10 hours after feeding and the number of microfilariae in the blood meal and escaping the midgut into the thoracic musculature were counted. A nearly linear relationship was found between the mean skin mfd and the mean microfilarial uptake by S. ochraceum (rs = 0.868). An even stronger relation existed between the mean mfd and the mean number of microfilariae escaping the midgut (rs = 0.915). Because the approximate 1:1 relationship observed between the number of microfilariae escaping the midgut and the subsequent number of infective (L3) larvae has been previously demonstrated, it can be concluded that a similar linear relationship exists between microfilarial skin densities and the number of L3 larvae available for transmission of O. volvulus by the Guatemalan vector.
Basset, D; Bouree, P; Basset, A; Lariviere, M
Microfilaria of Onchocerca volvulus are localized in superficial dermis. However, they are sometimes noticed in the blood and urines, when there is an important infestation. Diethylcarbamazine (DEC) bring on an increase of microfilaria, successively in the blood and after, in the urines. This study of 30 patients, treated in double blind by placebo, DEC and ivermectin, a new molecule with spectacular action on this filariasis, allowed to compare effect of each one on apparition of microfilariae in the blood and urines. Ivermectin bring on very important increase of microfilaremia without microfilaruria, unlike diethylcarbamazine. This establishment bring to discuss very different physiologic mechanisms between them. It should have an incidence on diagnosis and treatment of this dangerous parasite.
Basáñez, María-Gloria; Pion, Sébastien D S; Boakes, Eve; Filipe, João A N; Churcher, Thomas S; Boussinesq, Michel
The broad-spectrum antiparasitic drug ivermectin was licensed for use against onchocerciasis in 1987, yet the mechanisms by which it exerts a fast decrease and long-lasting suppression of Onchocerca volvulus microfilaridermia, and inhibition of microfilarial release by female worms remain largely unknown. A better understanding of the effects of ivermectin on O volvulus microfilariae and macrofilariae is crucial to improve our ability to predict the long-term effect of treatment. We did a systematic review of individual and population-based ivermectin trials to investigate the temporal dynamics of the drug's microfilaricidal and embryostatic efficacy after administration of a single, standard dose (150 microg/kg). Meta-analyses on data from 26 microfilarial and 15 macrofilarial studies were linked by a mathematical model describing the dynamics of potentially fertile female parasites to skin microfilariae. The model predicts that after treatment, microfilaridermia would be reduced by half after 24 h, by 85% after 72 h, by 94% after 1 week, and by 98-99% after 1-2 months, the latter also corresponding to the time when the fraction of females harbouring live microfilariae is at its lowest (reduced by around 70% from its original value). Our results provide a baseline microfilarial skin repopulation curve against which to compare studies done after long-term treatment.
Chavasse, D C; Post, R J; Davies, J B; Whitworth, J A
It is already known that multiple doses of ivermectin have a profound effect on embryonic development in Onchocerca volvulus and that this appears to operate mainly at the single cell stage. To investigate this further, we examined adult female O. volvulus originating from patients treated either with placebo or one, four or five doses of ivermectin. The reproductive organs were dissected out of the worm and examined for evidence of oogenesis and for the quantity of sperm and oocytes in the seminal receptacles. A single dose of ivermectin had no measurable effect on oogenesis or on the amount of sperm and oocytes compared to placebo. However after multiple doses of ivermectin a significantly lower proportion of seminal receptacles contained sperm and there was a significantly higher proportion of ovaries with impaired oogenesis compared to placebo. It is concluded that the reduction in the number of multicellular embryonic stages from worms exposed to multiple doses of ivermectin is due, at least in part, to a major reduction in the effective insemination of female worms and to a minor impairment of oogenesis.
Duke, B O; Zea-Flores, G; Muñoz, B
Adult Onchocerca volvulus, extracted from nodules before, and at intervals of two weeks to 12 months after, a single 150 micrograms/kg dose of ivermectin, were examined longitudinally and by sequential transverse sections. The mean number of male worms per nodule fell, and the proportion of nodules with no male worm rose, within two weeks of ivermectin and remained so for 12 months. In female worms, at intervals after ivermectin, the percentages of the length of the lower genital tracts occupied by embryos at each stage of development, or by degenerating ova, embryos and microfilariae (mfs), were recorded: (a) in un(re-)inseminated worms whose original embryogenesis was continuing and in those in which it was completed; and (b) in worms, reinseminated post-ivermectin, in which a new embryogenesis had begun. The results indicated that: (a) the time needed for the zygotes of O. volvulus to develop to mfs is 8-12 weeks; (b) nearly 40 percent of females had not resumed mf production by 12 months after treatment; (c) many intrauterine mfs had not degenerated within the first two weeks of ivermectin; (d) some of the last embryos to mature to mfs did not degenerate but accumulated temporarily in the anterior uteri 8-16 weeks after ivermectin.
Kutin, K; Kruppa, T F; Brenya, R; Garms, R
The role of Simulium sanctipauli Vajime & Dunbar (Diptera: Simuliidae) as a vector of Onchocerca volvulus (Leuckart) (Spirurida: Onchocercidae) in the forest zone of central Ghana was studied in the Upper Denkyira district, where onchocerciasis is hyperendemic. Simulium sanctipauli was found to be a highly efficient vector, with a mean of 377 infective (L3) larvae in the heads of 1000 parous and 122 in the heads of 1000 biting flies. The overall infection rate of 44% of the parous flies with L1, L2 and L3 stages of O. volvulus (identity confirmed by polymerase chain reaction) demonstrates marked anthropophily. Female flies dispersed over a wide area and can transmit onchocerciasis up to at least 10 km away from their breeding sites. Annual community-directed treatments with ivermectin did not have a noticeable effect on the infection rates and parasitic loads of fly populations, which were as high 2 months after as 3 months before the distribution of ivermectin. This failure can be attributed to poor coverage, with treatment taken by only 24.4% of the population of the six study villages.
Duke, B O L; Marty, A M; Peett, D L; Gardo, J; Pion, S D S; Kamgno, J; Boussinesq, M
A pleomorphic neoplasm (PN) is described from sections of Onchocerca volvulus worms in nodules excised from Cameroonian patients. PN is confined to older, non-fecund, female worms, and those classed as moribund/dead. It is mainly composed of small, roundish, basophilic cells of diverse sizes, often forming a 'rosette' pattern around amorphous eosinophilic centres. The cells have a high nuclear/cytoplasmic ratio and up to 2-3 mitoses/high-power field; some become grossly enlarged, highly polymorphic and contain large, irregular blocks of chromatin. The eukaryotic PN cells first appear posteriorly in the pseudocoelom, probably from ovarian cells; they spread anteriorly, invading or compressing the uteri. Ivermectin treatment increased the prevalence PN from 3.7% of 1422 female worms in 637 patients before treatment to 17.5% of 1134 worms in 511 patients after 3 years treatment. Ivermectin at 400-800 microg/kg annually, or at 150 microg/kg or 400-800 microg/kg 3-monthly, over 3 years, did not increase the PN prevalence significantly, as compared with standard doses of 150 microg/kg annually. In other small series of African patients, PN prevalence increased in worms 2, 4, 6 and 10 months after ivermectin treatment; but there was no increase after treatment with amocarzine, albendazole or diethylcarbamazine and suramin. PN may partly account for the increased macrofilaricidal action of ivermectin on female O. volvulus in patients treated for 3 years at 3-monthly intervals.
Discrimination between Onchocerca volvulus and O. ochengi filarial larvae in Simulium damnosum (s.l.) and their distribution throughout central Ghana using a versatile high-resolution speciation assay.
Doyle, Stephen R; Armoo, Samuel; Renz, Alfons; Taylor, Mark J; Osei-Atweneboana, Mike Yaw; Grant, Warwick N
Genetic surveillance of the human filarial parasite, Onchocerca volvulus, from onchocerciasis endemic regions will ideally focus on genotyping individual infective larval stages collected from their intermediate host, Simuliid blackflies. However, blackflies also transmit other Onchocerca species, including the cattle parasite O. ochengi, which are difficult to distinguish from the human parasite based on morphological characteristics alone. This study describes a versatile approach to discriminate between O. volvulus and O. ochengi that is demonstrated using parasite infective larvae dissected from blackflies. A speciation assay was designed based on genetic differentiation between O. volvulus and O. ochengi mitochondrial genome sequences that can be performed in high-throughput high-resolution melt (HRM)- or lower throughput conventional restriction fragment length polymorphism (RFLP) analyses. This assay was validated on 185 Onchocerca larvae dissected from blackflies captured from 14 communities in Ghana throughout 2011-2013. The frequency of O. ochengi was approximately 67 % of all larvae analysed, which is significantly higher than previously reported in this region. Furthermore, the species distribution was not uniform throughout the study region, with 25 %, 47 % and 93 % of O. volvulus being found in the western-most (Black Volta, Tain and Tombe), the central (Pru) and eastern-most (Daka) river basins, respectively. This tool provides a simple and cost-effective approach to determine the identity and distribution of two Onchocerca species, and will be valuable for future genetic studies that focus on parasites collected from blackflies. The results presented highlight the need to discriminate Onchocerca species in transmission studies, as the frequency of each species varied significantly between the communities studied.
Rivas-Alcala, R; Mackenzie, C D; Gomez-Rojo, E; Greene, B M; Taylor, H R
The effects of mebendazole, levamisole, diethylcarbamazine citrate (DEC-C), and the combination of mebendazole and levamisole, on adult Onchocerca volvulus and on the in utero development of microfilariae was studied in nodules excised from patients in Southern Mexico. Adult worms isolated from patients treated with mebendazole showed a reduction in mobility and contained 40 times fewer developing microfilarial forms than did worms from untreated patients. Most of the developmental forms found in adult worms from mebendazole-treated patients were either oocytes or early morulae, with more mature forms being scarce or morphologically abnormal. Treatment with levamisole had a similar effect on embryogenesis, however it was much less marked. The number and distribution of developing forms in worms from patients treated with DEC-C was similar to that found in the control groups. The effect of the same three drugs on microfilariae in vitro was also tested. DEC-C at concentrations of 0.5 microgram - 2000 micrograms/ml did not have any obvious effect on motility or morphology of the worms provided the pH was maintained at physiological levels; levamisole also had no effect in vitro. Mebendazole induced the death of microfilariae when used at concentrations greater than 100 micrograms/ml, however these levels are greater than those found in the blood of patients under treatment. The optimal conditions for short-term maintenance of O. volvulus microfilariae in culture, are discussed. It is apparent from these studies that mebendazole has an effect on the maturation of microfilariae in utero and may also, at high concentrations, have a direct effect on mature microfilariae.
Gbakima, A A; Nutman, T B; Bradley, J E; McReynolds, L A; Winget, M D; Hong, Y; Scott, A L
To characterize the patterns of immunoglobulin G (IgG) subclass and IgE reactivity during the early stages of onchocerciasis, sera were collected from 224 children (age groups, 2 to 5, 6 to 10, and 11 to 15 years) residing in a region of Sierra Leone where Onchocerca volvulus is endemic, and these samples were tested by enzyme-linked immunosorbent assay for their reactivity to adult antigens (OvAg) and against four recombinant proteins (OV11, OV27, OV29, and OV16). Over 88% of the samples contained detectable levels of anti-OvAg IgG. In samples from microfilaria (MF)-positive children, IgG4 responses were significantly elevated and constituted on average 39, 35 and 28% of the total IgG responses for the age groups of 2 to 5, 6 to 10, and 11 to 15 years, respectively. For MF-negative individuals, the mean contributions of IgG4 to the total IgG response were 11% (2 to 5 years), 27% (6 to 10 years), and 56% (11 to 15 years). OvAg-specific IgE was detectable in the sera from both MF-negative and MF-positive individuals. To increase the specificity of the response, recombinant antigens OV11, OV27, and OV29 were tested individually or as a cocktail. Nearly 50% of the MF-negative children and 85% of the MF-positive children had detectable levels of IgG against at least one of the recombinant antigens. Only a small portion of the IgG against the recombinant peptides was IgG4. The prevalence of IgG against OV16 in samples from MF-negative children was 51%, and that for MF-positive children was 75%. The general profile of the humoral immune responses mounted by both MF-positive and a large percentage of the MF-negative children during the initial phases of infection with O. volvulus is similar to the profile reported for adults harboring chronic O. volvulus infections. These results suggest that very quickly after infection, the interactions between parasite and host result in an immunological environment that may contribute to the maintenance of a long-term, chronic
Van Dorst, Bieke; Stuyver, Lieven J.
Understanding the immune response upon infection with the filarial nematode Onchocerca volvulus and the mechanisms that evolved in this parasite to evade immune mediated elimination is essential to expand the toolbox available for diagnostics, therapeutics and vaccines development. Using high-density peptide microarrays we scanned the proteome-wide linear epitope repertoire in Cameroonian onchocerciasis patients and healthy controls from Southern Africa which led to the identification of 249 immunodominant antigenic peptides. Motif analysis learned that 3 immunodominant motifs, encompassing 3 linear epitopes, are present in 70, 43, and 31 of these peptides, respectively and appear to be scattered over the entire proteome in seemingly non-related proteins. These linear epitopes are shown to have an atypical isotype profile dominated by IgG1, IgG3, IgE and IgM, in contrast to the commonly observed IgG4 response in chronic active helminth infections. The identification of these linear epitope motifs may lead to novel diagnostic development but further evaluation of cross-reactivity against common co-infecting human nematode infections will be needed. PMID:28125577
Chavasse, D C; Post, R J; Lemoh, P A; Whitworth, J A
The effects of single and multiple doses of ivermectin on mortality and morphology were assessed in over 700 female Onchocerca volvulus worms and the effects on embryogenesis were assessed in 490. Nodules were surgically removed from Sierra Leoneans recruited from a double-blind placebo controlled study of ivermectin given at six-monthly intervals. Nodules were digested in collagenase to isolate whole adult worms. After four or five doses of ivermectin there were significant increases in the numbers of discoloured and calcified worms and possibly a trend towards increased mortality, but this was not seen consistently. There was no evidence of a prophylactic effect of the drug. Worms were then homogenised and embryograms constructed. A single dose of ivermectin produced large numbers of degenerating intrauterine microfilariae, but embryonic development occurred normally. After multiple doses we observed almost complete cessation of embryogenesis, with a highly significant decrease in the numbers of viable multicellular embryonic stages, while oocytes appeared to be produced normally. Development is probably impeded at the single cell stage, possibly because of reduced fertilization. In planning the future role of ivermectin as a control measure for onchocerciasis it is crucial to determine if these effects on embryogenesis are reversible.
Duke, B O; Pacqué, M C; Muñoz, B; Greene, B M; Taylor, H R
Ivermectin is a safe, effective microfilaricide and microfilarial suppressant for Onchocerca volvulus; but in single doses of 100-200 micrograms/kg body weight it has no macrofilaricidal action. The present trial aimed to determine whether 6 doses of 100 micrograms/kg ivermectin, given at 2-week intervals, would kill the adult worms. Eighty-two nodules from 28 otherwise healthy adult male Liberian patients treated with this ivermectin schedule, and 102 nodules from a similar group of 25 control patients, were removed four months after the last dose of ivermectin. They were coded and assessed in a masked fashion either by routine histology or by examination of whole worms extracted from the nodules after collagenase digestion. The drug had no visible effect on adult male worms. More adult female worms were assessed as moribund or dead in the ivermectin-treated group than in the control group (for the collagenase digests P = 0.09; for the histological assessment P = 0.47). The data suggest that repeated dosage with ivermectin may lead to a slow attrition of some female worms and this possibility should be investigated in patients receiving regular doses every 3, 6 or 12 months as part of onchocerciasis control programmes.
Awadzi, K; Attah, S K; Addy, E T; Opoku, N O; Quartey, B T
Ivermectin, at the standard dose of 150 micrograms/kg bodyweight, does not kill the adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilarial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by an equivalent, single, high dose. One hundred men participated in a double-blind placebo-controlled trial and received increasing doses of ivermectin from 150 micrograms/kg to 1600 micrograms/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 micrograms/kg were not significantly more effective than 150 micrograms/kg. Moreover, they did not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, at comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that repeated high-dose regimens are unlikely to be more effective than a similar number of 150 micrograms/kg doses. This deficiency of ivermectin requires that the search for macrofilaricides remains a top priority.
Lagatie, Ole; Van Dorst, Bieke; Stuyver, Lieven J
Understanding the immune response upon infection with the filarial nematode Onchocerca volvulus and the mechanisms that evolved in this parasite to evade immune mediated elimination is essential to expand the toolbox available for diagnostics, therapeutics and vaccines development. Using high-density peptide microarrays we scanned the proteome-wide linear epitope repertoire in Cameroonian onchocerciasis patients and healthy controls from Southern Africa which led to the identification of 249 immunodominant antigenic peptides. Motif analysis learned that 3 immunodominant motifs, encompassing 3 linear epitopes, are present in 70, 43, and 31 of these peptides, respectively and appear to be scattered over the entire proteome in seemingly non-related proteins. These linear epitopes are shown to have an atypical isotype profile dominated by IgG1, IgG3, IgE and IgM, in contrast to the commonly observed IgG4 response in chronic active helminth infections. The identification of these linear epitope motifs may lead to novel diagnostic development but further evaluation of cross-reactivity against common co-infecting human nematode infections will be needed.
Duke, B. O.; Pacqué, M. C.; Muñoz, B.; Greene, B. M.; Taylor, H. R.
Ivermectin is a safe, effective microfilaricide and microfilarial suppressant for Onchocerca volvulus; but in single doses of 100-200 micrograms/kg body weight it has no macrofilaricidal action. The present trial aimed to determine whether 6 doses of 100 micrograms/kg ivermectin, given at 2-week intervals, would kill the adult worms. Eighty-two nodules from 28 otherwise healthy adult male Liberian patients treated with this ivermectin schedule, and 102 nodules from a similar group of 25 control patients, were removed four months after the last dose of ivermectin. They were coded and assessed in a masked fashion either by routine histology or by examination of whole worms extracted from the nodules after collagenase digestion. The drug had no visible effect on adult male worms. More adult female worms were assessed as moribund or dead in the ivermectin-treated group than in the control group (for the collagenase digests P = 0.09; for the histological assessment P = 0.47). The data suggest that repeated dosage with ivermectin may lead to a slow attrition of some female worms and this possibility should be investigated in patients receiving regular doses every 3, 6 or 12 months as part of onchocerciasis control programmes. PMID:1860146
Langham, M E; Beltranena, F
The response of 45 severely infected onchocerciasis patients to relatively high doses of diethylcarbamazine citrate (DEC-C) has been determined. The treatment comprised two sequential phases; the first phase comprised the topical applications of a DEC-C lotion and of the anti-inflammatory steroid betamethasone. The second phase comprised the daily oral administration of high doses of DEC-C (30 mg/kg body wt) for seven days. Onchocerca volvulus microfilarial (o.v.mf.) counts in skin snips of the 45 patients decreased by 96 +/- 1.5% after 5 days of treatment with topical DEC-C lotion. Following the administration of oral DEC, the average O.v.mf. counts in the skin snips at days 51, 97, and 143 remained decreased by 85 to 93%. The mean O.v.mf. counts in 10 nodules excised from 5 treated patients at day 77 had decreased by 93% compared to the mean O.v.mf. counts in 11 nodules taken from 5 untreated patients with similar initial O.v.mf. infection. No visual loss resulted from the treatment.
Mai, C S; Hamm, D M; Banla, M; Agossou, A; Schulz-Key, H; Heuschkel, C; Soboslay, P T
The recommended control option against onchocerciasis is repeated ivermectin treatment, which will need to be implemented for decades, and it remains unknown how repeated ivermectin therapy might affect immunity against Onchocerca volvulus in the long term. O. volvulus-specific antibody reactivity and cellular cytokine production were investigated in onchocerciasis patients receiving ivermectin (150 µg/kg) annually for 16 years. In treated patients, the T helper type 2 (Th2) cytokine interleukin (IL)-5 and T regulatory IL-10 in response to O. volvulus antigen (OvAg) and bacteria-derived Streptolysin O (SL-O) diminished to levels found in infection-free endemic controls; also, cellular release of Th1-type interferon (IFN)-γ at 16 years post initial ivermectin treatment (p.i.t.) approached control levels. In ivermectin-treated onchocerciasis patients, IL-5 production in responses to the mitogen phytohaemagglutinin (PHA) decreased, but IL-10 in response PHA increased, and neither attained the cytokine production levels of endemic controls. At 16 years p.i.t., O. volvulus-specific IgG1 and IgG4 subclass reactivity still persisted at higher levels in onchocerciasis patients than in O. volvulus exposed but microfilariae-free endemic controls. In addition, cytokine responses remained depressed in onchocerciasis patients infected concurrently with Mansonella perstans and Necator americanus or Entamoeba histolytica/dispar. Thus, long-term ivermectin therapy of onchocerciasis may not suffice to re-establish fully a balanced Th1 and Th2 immune responsiveness in O. volvulus microfilariae-negative individuals. Such deficient reconstitution of immune competence may be due to an as yet continuing and uncontrolled reinfection with O. volvulus, but parasite co-infections can also bias and may prevent the development of such immunity. PMID:17302900
Richards, Frank O; Amann, Josef; Arana, Byron; Punkosdy, George; Klein, Robert; Blanco, Carlos; Lopez, Beatriz; Mendoza, Carlos; Domínguez, Alfredo; Guarner, Jeannette; Maguire, James H; Eberhard, Mark
Endosymbionic Wolbachia bacteria inside adult Onchocerca volvulus worms (causing river blindness) are necessary for female worm fertility. We evaluated whether rifampin and/or azithromycin used in a five-day course could kill Wolbachia. In an open-label trial in Guatemala, 73 patients with 134 palpable onchocercal nodules were randomized into four treatment groups: rifampin, azithromycin, a combination of the two drugs, and controls (multivitamins). After five days of antibiotic treatment, all participants received a single dose of ivermectin on day 6. Nine months after treatment, the nodules were removed and the worms were examined. Skin snips to determine microfilariae were obtained at baseline and nine months. There were no significant differences between any of the treatment groups in the condition of the worms in the nodules, the presence of Wolbachia surface protein, or the number of microfilariae in skin. Short courses with these antibiotics will not clear Wolbachia from O. volvulus.
Wanji, S; Tendongfor, N; Esum, M; Ndindeng, S; Enyong, P
An epidemiological survey was conducted in 16 remote villages of the rain forest of southern Cameroon to ascertain the prevalence and intensity of three species of filariae: Loa loa, Onchocerca volvulus, and Mansonella perstans. We examined 1458 individuals for blood-dwelling microfilariae and 1255 of these were also for the presence of palpable nodules. All the villages surveyed were found highly endemic for onchocerciasis and mansonellosis with prevalence ranging from 28.44% to 87.17% for O. volvulus and 52.48% to 100% for M. perstans. The intensities of infection were also found high for M. perstans with arithmetic means of microfilaremia ranging from 280.94 to 4947.57 mf/ml. The loiasis prevalence was relatively low with value from 2.22% to 19.23%. Males were found more infected than females for the three species of filariae, and the prevalence and intensities of microfilaremia vary differently in males and females at different ages. The three species of filariae displayed different degrees of association in the inhabitants with a low prevalence of co-occurrence between L. loa/O. volvulus and between L. loa/M. perstans. In contrast, there was a high prevalence of co-occurrence between M. perstans and O. volvulus. The implications of the co-occurrence of the three species of filariae in the populations of these remote villages on the intervention programs based on mass treatment with mectizan are discussed.
Duke, B O; Moore, P J; Vincelette, J
The effect of various substances on the output of Onchocerca volvulus microfilariae in the urine was investigated in volunteers infected with the Cameroon forest and Sudan-savanna strains of the parasite. Output of microfilariae in the urine tended to be higher during periods of normal activity than during sleep. During waking hours, the rate of output remained generally steady, but in some patients occasional showers of microfilariae appeared in the urine, possibly associated with the intake of food and drink. Drinking 1.2-2.5 litres water produced a shower of microfilariae in the urine of some subjects. This began within an hour of drinking and its onset preceeded that of the diuresis. Thiazide diuretics, acting on the convoluted tubules, produced no increase in microfilaruria. In savanna subjects intravenous injection of DT TAB vaccine caused pyrexia, and simultaneously large numbers of microfilariae appeared in the urine. There was no associated diuresis, and no increase in the concentration of microfilariae in the venous blood. In forest subjects DT TAB caused no increase in microfilaruria. In all subjects 25-50 mg diethylcarbamazine (DEC) caused large numbers of microfilariae to appear in the urine on day 0, within a few hours of the first dose; and there was an increased output of urine over the first 24 hours. Microfilaruria declined sharply on day 1 of treatment, but in subjects developing a high microfilaraemia, it rose again on day 2, and declined more slowly thereafter. Betamethazone, given in conjunction with DEC, appeared to slow the rate of destruction of microfilariae in the skin and lymph glands, and to prolong the duration of microfilaraemia and microfilaruria. The findings suggest that there is a reservoir of microfilariae in the glomerular capillaries, which fills slowly by accumulating microfilariae from the circulating blood. The microfilariae probably enter the urine by penetrating the glomerular capillary.
Duke, B O
The effects of the arsenical drug melarsonyl potassium on Onchocerca volvulus were investigated in patients in Cameroon infected with the Cameroon forest and Sudan savanna strains of the parasite. Two intramuscular dosage schedules were tested: the first comprised 4 consecutive daily doses of 200 mg repeated once after a 10-14 day interval, i.e., 2 (4x200 mg). The second was a single dose schedule at 7.1 mg/kg-10 mg/kg, with a maximum of 500 mg.In most trials the drug had no immediate action on microfilarial concentrations. Only after the 2(4x200 mg) melarsonyl course against the Sudan savanna strain was a slight microfilaricidal action detected.The 2(4x200 mg) course of melarsonyl apparently killed or sterilized most or all of the adult female worms in the patients tested, leaving the residual population of microfilariae to decline gradually, from natural mortality, over the ensuing 2 years. These residual microfilariae could be killed with diethylcarbamazine.Single doses of melarsonyl at 7.1 mg/kg-10 mg/kg were somewhat less effective in killing or sterilizing adult worms, but it is suggested that if doses at the higher end of this range were to be repeated annually patients could be rendered free from microfilariae by the end of 3 years.It is emphasized that the risks of arsenical encephalopathy should at present preclude the use of melarsonyl potassium in the treatment of onchocerciasis, but that if this danger could be avoided the drug might prove to be of considerable use for mass therapy in control campaigns.
Background Studies on biting behaviours and infectivity status of insect vectors are pre-requisites in understanding the epidemiology of the vector- borne diseases and planning effective control measures. A longitudinal study was carried out to investigate the transmission index of Simulium damnosum complex species along Osun River, South Western Nigeria. Adult flies were collected on human attractants from 07:00 to 18:00 hours for two consecutive days from February 2008 to June 2009 at three communities: Osun Eleja, Osun Ogbere and Osun Budepo. The infectivity rate was determined by dissection and Polymerase Chain Reaction amplification (PCR) of 0-150 genes of Onchocerca parasite using the pool screening technique. Results The results indicated that the majority of the flies collected at the three sampling points were nulliparous as they accounted for 53.90%, 57.86% and 59.58% of the flies dissected at Osun Budepo, Osun Ogbere and Osun Eleja, respectively. The parous rate was higher during the dry season than the wet season but the difference was not statistically significant (p < 0.05). The biting activity of the parous flies showed two peaks at Osun Budepo and three peaks at Osun Eleja and Osun Ogbere. Of the 1,472 flies dissected and 1,235 flies screened by molecular method, none was infected with Onchocerca parasite at the three sampling points however the annual biting rates at the three communities were higher than 1,000 considered as tolerable value for a person living in an onchocerciasis zone by Word Health Organization. Conclusion The study has provided the baseline data for further study on onchocerciasis transmission dynamics and the need to intercept man- simuliid vector contact at the study area. PMID:20929573
Nirmalan, Niroshini; Cordeiro, N. J. V.; Kläger, Sabine L.; Bradley, Janette E.; Allen, Judith E.
Ov20 is a structurally novel 20-kDa retinol binding protein secreted by Onchocerca volvulus. Immunological and biological investigation of this protein has been hampered by the inability to maintain O. volvulus in a laboratory setting. In an effort to find a system more amenable to laboratory investigation, we have cloned, sequenced, and expressed cDNA encoding homologues of Ov20 from two closely related filarial species, Brugia malayi (Bm20) and Acanthocheilonema viteae (Av20). Sequence comparisons have highlighted differences in glycosylation of the homologues. We present here an analysis of mouse immune responses to Ov20, Bm20, and Av20. The results suggest a strong genetic restriction in response to native Bm20 that is overcome when recombinant, nonnative material is used. Reactivity of human filarial sera to the three recombinant proteins confirmed previous specificity studies with Ov20 but highlighted important differences in the reactivity patterns of the O. volvulus and B. malayi homologues that may be due to differences in glycosylation patterns. Ov20 is a dominant antigen in infected individuals, while Bm20 is not. The availability of the B. malayi homologue enabled us to use defined murine reagents and inbred strains for genetic analysis of responsiveness in a way that is not possible for Ov20. However, the close sequence similarity between Ov20 and Av20 suggests that the A. viteae model may be more suited to the investigation of the biological functions of Ov20. PMID:10569745
Brattig, N W; Hoerauf, A; Fischer, P U; Liebau, E; Bandi, C; Debrah, A; Büttner, M; Büttner, D W
Up to 5% of untreated female Onchocerca volvulus filariae develop potentially fatal pleomorphic neoplasms, whose incidence is increased following ivermectin treatment. We studied the occurrence of 8 filarial proteins and of Wolbachia endobacteria in the tumor cells. Onchocercomas from patients, untreated and treated with antibiotics and anthelminthics, were examined by immunohistology. Neoplasms were diagnosed in 112 of 3587 female and in 2 of 1570 male O. volvulus. The following proteins and other compounds of O. volvulus were expressed in the cells of the neoplasms: glutathione S-transferase 1, lysosomal aspartic protease, cAMP-dependent protein kinase, alpha-enolase, aspartate aminotransferase, ankyrin E1, tropomyosin, heat shock protein 60, transforming growth factor-beta, and prostaglandin E(2). These findings prove the filarial origin of the neoplasms and confirm the pleomorphism of the tumor cells. Signs indicating malignancy of the neoplasms are described. Wolbachia were observed in the hypodermis, oocytes, and embryos of tumor-harbouring filariae using antibodies against Wolbachia surface protein, Wolbachia HtrA-type serine protease, and Wolbachia aspartate aminotransferase. In contrast, Wolbachia were not found in the cells of the neoplasms. Further, neoplasm-containing worms were not observed after more than 10 months after the start of sufficient treatment with doxycycline or doxycycline plus ivermectin.
BRATTIG, N. W.; HOERAUF, A.; FISCHER, P. U.; LIEBAU, E.; BANDI, C.; DEBRAH, A.; BÜTTNER, M.; BÜTTNER, D. W.
SUMMARY Up to 5% of untreated female Onchocerca volvulus filariae develop potentially fatal pleomorphic neoplasms, whose incidence is increased following ivermectin treatment. We studied the occurrence of 8 filarial proteins and of Wolbachia endobacteria in the tumor cells. Onchocercomas from patients, untreated and treated with antibiotics and anthelminthics, were examined by immunohistology. Neoplasms were diagnosed in 112 of 3587 female and in 2 of 1570 male O. volvulus. The following proteins and other compounds of O. volvulus were expressed in the cells of the neoplasms: glutathione S-transferase 1, lysosomal aspartic protease, cAMP-dependent protein kinase, alpha-enolase, aspartate aminotransferase, ankyrin E1, tropomyosin, heat shock protein 60, transforming growth factor-beta, and prostaglandin E2. These findings prove the filarial origin of the neoplasms and confirm the pleomorphism of the tumor cells. Signs indicating malignancy of the neoplasms are described. Wolbachia were observed in the hypodermis, oocytes, and embryos of tumor-harbouring filariae using antibodies against Wolbachia surface protein, Wolbachia HtrA-type serine protease, and Wolbachia aspartate aminotransferase. In contrast, Wolbachia were not found in the cells of the neoplasms. Further, neoplasm-containing worms were not observed after more than 10 months after the start of sufficient treatment with doxycycline or doxycycline plus ivermectin. PMID:20199697
Pfarr, K M; Heider, U; Schmetz, C; Büttner, D W; Hoerauf, A
Wolbachia, a genus of endosymbiotic bacteria of filarial worms, represent novel targets for anti-filarial therapy. The efficacy of compounds against Wolbachia has been evaluated using antiserum raised against the 60 kDa heat shock protein (HSP60) which binds specifically to this protein in both Wolbachia and mitochondria. It has been shown that Wolbachia stains (using such specific probes) stronger than the mitochondria in untreated Onchocerca volvulus, whereas after the depletion of Wolbachia (with drugs) staining of the mitochondria is increased. Herein, immunogold electron microscopy showed that specific anti-HSP60 serum specifically labelled Wolbachia and filarial mitochondria, and that both have distinct localization patterns, thus allowing them to be differentiated. Immunohistochemistry of O. volvulus showed that HSP60 staining is increased in the mitochondria after Wolbachia depletion in the hypodermis, epithelia, muscles, oocytes, embryos, and developing spermatozoa. This could have been the result of the antiserum preferentially binding to the Wolbachia when they are present or due to increased expression of the protein in the absence of the bacteria. To address this, mRNA levels of filarial hsp60 in O. volvulus were measured. After the depletion of Wolbachia, the transcription of hsp60 was significantly greater (7.7 fold) compared with untreated worms. We hypothesize that the increased expression of HSP60 in the absence of Wolbachia is due to a disruption of the homeostasis of the endosymbiosis.
Onchocerciasis (river blindness) is a major blinding disease in Africa, Central America, and South America. Loss of vision can be due to corneal change, optic atrophy, or chorioretinal disease. It has been suggested that autoimmunological reactions resulting from crossreactivity between parasite antigens and components of eye tissues contribute to development of ocular pathology. Using sera collected from onchocerciasis patients as a screening reagent, a cDNA clone (Ov39) has been isolated from a lambda gt11 expression library of Onchocerca volvulus. This antigen exhibits immunological crossreactivity with a component of retinal pigment epithelium cells (RPE). Antiserum raised against this recombinant peptide immunoprecipitates a 22,000 Mr antigen of adult O. volvulus and recognizes a 44,000 Mr component of bovine RPE by Western blotting. A 44,000 Mr antigen of cultured human RPE metabolically labeled with 35S- methionine can be immunoprecipitated with the same antiserum. An antigen of the same size is recognized by a rabbit antiserum raised against whole O. volvulus extract. Immunocytochemical studies on cryostat sections of the bovine eye using the antirecombinant sera localizes this antigen to the RPE. PMID:2056276
Gutiérrez-Peña, E J; Knab, J; Büttner, D W
The participation of neutrophil granulocytes in the cellular reaction to skin microfilariae of Onchocerca volvulus was studied by immunohistochemistry. Skin biopsies were obtained from adult Liberian and Ugandan patients with generalized onchocerciasis after exposure to topically applied diethylcarbamazine (DEC) and from untreated patients. After DEC many damaged microfilariae were observed either in dermal infiltrates or in epidermal microabscesses consisting both of neutrophils and eosinophils. Infiltrates and microabscesses contained some intact granulocytes and many neutrophils releasing myeloperoxidase, elastase, lactoferrin, defensin, lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin. Eosinophils discharged peroxidase and cationic proteins. Released granule proteins and remnants of disrupted granulocytes were found on the surface and in close proximity of damaged microfilariae in dermal infiltrates and epidermal microabscesses. In larger microabscesses neutrophils were predominant. These observations show that neutrophils and not only eosinophils recruit, accumulate, localize around and release their helminthotoxic granule proteins such as myeloperoxidase onto or closely around skin microfilariae of O. volvulus after topical DEC administration. The association between these processes and the damage of the microfilariae indicated that neutrophils together with eosinophils attack and damage microfilariae of O. volvulus after DEC treatment in the skin.
Golden, Allison; Stevens, Eric J.; Yokobe, Lindsay; Faulx, Dunia; Kalnoky, Michael; Peck, Roger; Valdez, Melissa; Steel, Cathy; Karabou, Potochoziou; Banla, Méba; Soboslay, Peter T.; Adade, Kangi; Tekle, Afework H.; Cama, Vitaliano A.; Fischer, Peter U.; Nutman, Thomas B.; Unnasch, Thomas R.; de los Santos, Tala; Domingo, Gonzalo J.
Background Serological assays for human IgG4 to the Onchocerca volvulus antigen Ov16 have been used to confirm elimination of onchocerciasis in much of the Americas and parts of Africa. A standardized source of positive control antibody (human anti-Ov16 IgG4) will ensure the quality of surveillance data using these tests. Methodology/Principal Findings A recombinant human IgG4 antibody to Ov16 was identified by screening against a synthetic human Fab phage display library and converted into human IgG4. This antibody was developed into different positive control formulations for enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT) platforms. Variation in ELISA results and utility as a positive control of the antibody were assessed from multiple laboratories. Temperature and humidity conditions were collected across seven surveillance activities from 2011–2014 to inform stability requirements for RDTs and positive controls. The feasibility of the dried positive control for RDT was evaluated during onchocerciasis surveillance activity in Togo, in 2014. When the anti-Ov16 IgG4 antibody was used as a standard dilution in horseradish peroxidase (HRP) and alkaline phosphatase (AP) ELISAs, the detection limits were approximately 1ng/mL by HRP ELISA and 10ng/mL by AP ELISA. Positive control dilutions and spiked dried blood spots (DBS) produced similar ELISA results. Used as a simple plate normalization control, the positive control antibody may improve ELISA data comparison in the context of inter-laboratory variation. The aggregate temperature and humidity monitor data informed temperature parameters under which the dried positive control was tested and are applicable inputs for testing of diagnostics tools intended for sub-Saharan Africa. As a packaged positive control for Ov16 RDTs, stability of the antibody was demonstrated for over six months at relevant temperatures in the laboratory and for over 15 weeks under field conditions. Conclusions The
Cesbron, J Y; Hayasaki, M; Joseph, M; Lutsch, C; Grzych, J M; Capron, A
Over the past 35 yr, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases, particularly in onchocerciasis. The microfilaricidal action of DEC has been recently shown to be mediated by blood platelets with the additional triggering of a filarial excretory Ag (FEA). This FEA could be detected by using mAb in the serum of infected patients. By using one mAb (IA2(23] directed against Onchocerca volvulus and recognizing circulating Ag (Ab1), we purified by affinity chromatography the target molecule of IA2(23) (an O. volvulus glycoprotein recognized by IA2(23) mAb). This compound had a dose-dependent effect on the cytotoxic action of DEC-treated platelets. We subsequently produced an anti-idiotype mAb to Ab1 (Ab2), and considered the possibility of replacing the O. volvulus glycoprotein recognized by IA2(23) mAb by Ab2. Ab2 was selected according to its ability to inhibit the binding of radioiodinated Ab1 to the filarial target Ag. It induced the production of anti-O. volvulus antibodies (Ab3) in rats. At a constant concentration of DEC platelets, the addition of increasing amounts of Ab2 led to a dose-dependent cytotoxic effect against parasite larvae. Experiments performed with Ab2 on detergent solubilized surface proteins of platelets identified four bands of Mr 18, 26, 43.5, and 100 kDa, supporting the idea of the presence of binding sites on the platelets for a FEA required for the microfilaricidal cytotoxicity of DEC-treated platelets.
MacDonald, Angus J; Turaga, Prasad S D; Harmon-Brown, Carolyn; Tierney, Tracy J; Bennett, Kristine E; McCarthy, Maggie C; Simonek, Scott C; Enyong, Peter A; Moukatte, Daniel W; Lustigman, Sara
The possibility of concomitant immunity and its potential mechanisms in Onchocerca volvulus infection were examined by analyzing cytokine and antibody responses to infective larval (third-stage larvae [L3] and molting L3 [mL3]), adult female worm (F-OvAg), and skin microfilaria (Smf) antigens in infected individuals in a region of hyperendemicity in Cameroon as a function of age. Peripheral blood mononuclear cell interleukin 5 (IL-5) responses to F-OvAg and Smf declined significantly with age (equivalent to years of exposure to O. volvulus). In contrast, IL-5 secretion in response to L3 and mL3 remained elevated with increasing age. Gamma interferon responses to L3, mL3, and F-OvAg were low or suppressed and unrelated to age, except for responses to Smf in older subjects. IL-10 levels were uniformly elevated, regardless of age, in response to L3, mL3, and F-OvAg but not to Smf, for which levels declined with age. A total of 49 to 60% of subjects had granulocyte-macrophage colony-stimulating factor responses to all O. volvulus antigens unrelated to age. Analysis of levels of stage-specific immunoglobulin G3 (IgG3) and IgE revealed a striking, age-dependent dissociation between antibody responses to larval antigens (L3 and a recombinant L3-specific protein, O. volvulus ALT-1) which were significantly increased or maintained with age and antibody responses to F-OvAg, which decreased. Levels of IgG1 to L3 and F-OvAg were elevated regardless of age, and levels of IgG4 increased significantly with age, although not to O. volvulus ALT-1, which may have unique L3-specific epitopes. Immunofluorescence staining of whole larvae showed that total anti-L3 immunoglobulin levels also increased with the age of the serum donor. The separate and distinct cytokine and antibody responses to adult and infective larval stages of O. volvulus which are age related are consistent with the acquisition of concomitant immunity in infected individuals.
Osei-Atweneboana, Mike Y.; Boakye, Daniel A.; Awadzi, Kwablah; Gyapong, John O.; Prichard, Roger K.
Ivermectin (IVM) has been in operational use for the control of onchocerciasis for two decades and remains the only drug of choice. To investigate the parasitological responses and genetic profile of Onchocerca volvulus, we carried out a 21 month epidemiological study to determine the response of the parasite to IVM in 10 Ghanaian endemic communities. Onchocerca nodules were surgically removed from patients in three IVM response categories (good, intermediate and poor) and one IVM naïve community. DNA from adult worms was analyzed to determine any association between genotype and IVM response phenotypic. Embryogramme analysis showed significantly higher reproductive activity in worms from poor response communities, which had up to 41% of females with live stretched microfilaria (mf) in utero, despite IVM treatment, compared with good response communities, which had no intra-uterine stretched mf. β-tubulin isotype 1 gene has been shown to be linked to IVM selection in O. volvulus and also known to be associated with IVM resistance in veterinary nematodes. We have genotyped the full length genomic DNA sequence of the β-tubulin gene from 127 adult worms obtained from the four community categories. We found SNPs at 24 sites over the entire 3696 bp. Eight of the SNPs occurred at significantly higher (p < 0.05) frequencies in the poor response communities compared with the good response communities and the IVM naïve community. Phenotypic and genotypic analyses show that IVM resistance has been selected and the genotype (1183GG/1188CC/1308TT/1545GG) was strongly associated with the resistance phenotype. Since the region in the β-tubulin gene where these four SNPs occur is within 362 bp, it is feasible to develop a genetic marker for the early detection of IVM resistance. PMID:24533268
Toé, L.; Back, C.; Adjami, A. G.; Tang, J. M.; Unnasch, T. R.
In recent years, methods for the identification of the filarial worm Onchocerca volvulus and its vector, blackflies of the Simulium damnosum complex (S. damnosum sensu lato (s.l.)), based on the amplification of parasite and vector DNA sequences with the polymerase chain reaction (PCR), have been developed. Routine application of these methods requires techniques for sample collection and preservation that are compatible with the limitations of field collection, yet preserve DNA in a form suitable for PCR. Two different methods for sample preservation were evaluated by the field collection teams and the DNA probe laboratory of the Onchocerciasis Control Programme in West Africa. The most successful involved the preservation of material from O. volvulus and its associated vectors in a dried state on microscope slides. Of over 1200 parasite samples preserved in this manner, more than 93% retained DNA yielding positive results in PCR analysis (1208/1291). Vector material (malpighian tubules and ovaries) preserved in the same manner on the same microscope slides also yielded DNA that was suitable for PCR. Images Fig. 2 PMID:9447777
Schönemeyer, A; Lucius, R; Sonnenburg, B; Brattig, N; Sabat, R; Schilling, K; Bradley, J; Hartmann, S
Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness and a shift of the cytokine balance toward a Th2/Th3 response. This modulation of cellular immune responses is considered as an important mechanism to avoid inflammatory immune responses that could eliminate the parasites. We investigated the immunomodulatory potential of a secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. Recombinant onchocystatin (rOv17), a biologically active cysteine protease inhibitor that inhibited among others the human cysteine proteases cathepsins L and S, suppressed the polyclonally stimulated and the Ag-driven proliferation of human PBMC. Stimulated as well as unstimulated PBMC in the presence of rOv17 produced significantly more IL-10, which was paralleled in some situations by a decrease of IL-12p40 and preceded by an increase of TNF-alpha. At the same time, rOv17 reduced the expression of HLA-DR proteins and of the costimulatory molecule CD86 on human monocytes. Neutralization of IL-10 by specific Abs restored the expression of HLA-DR and CD86, whereas the proliferative block remained unaffected. Depletion of monocytes from the PBMC reversed the rOv17-induced cellular hyporeactivity, indicating monocytes to be the target cells of immunomodulation. Therefore, onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.
Elkassaby, M H
Ten Sudanese patients with Onchocerca volvulus infection were treated with a single oral dose of 150 micrograms/kg of ivermectin. Plasma samples were collected before treatment, 0.5, 1, 3, 4, 6, 12 hours and 1, 2, 3, 7, and 30 days. Four patients were selected for nodulectomies and skin biopsies at 6, 18 and 30 hours and 3 days post treatment. Using these samples O. volvulus worm fragments were dissected free of host nodular tissues for ivermectin extraction. Ivermectin was present in the nodular tissue at 6 hr and persisted for 3 days. It was also detected in an individual worm tissue extract at a concentration similar to the nodule, but in subcutaneous fascial tissue higher concentrations were sometimes found. Ivermectin was detected by radioimmunoassay in the plasma of all patients at 1 hr and peak concentrations were reached in an average of 5.6 hr. The drug persisted at detectable levels for 7 days in 70% of the studied patients. Plasma samples were also collected from 16 treated Mexican onchocerciasis patients before ivermectin treatment and 4 hr treatment and from six individuals who served as controls. The Mexican patients had concentrations of ivermectin in their plasma similar to those in the Sudanese patients.
Bennuru, Sasisekhar; Cotton, James A.; Ribeiro, Jose M. C.; Grote, Alexandra; Harsha, Bhavana; Holroyd, Nancy; Mhashilkar, Amruta; Molina, Douglas M.; Randall, Arlo Z.; Shandling, Adam D.; Unnasch, Thomas R.; Ghedin, Elodie; Berriman, Matthew
ABSTRACT Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified stage-specific pathways important to the parasite’s adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs. PMID:27881553
Ajonina-Ekoti, Irene; Kurosinski, Marc Andre; Younis, Abuelhassan Elshazly; Ndjonka, Dieudonne; Tanyi, Manchang Kingsley; Achukwi, Mbunkah; Eisenbarth, Albert; Ajonina, Caroline; Lüersen, Kai; Breloer, Minka; Brattig, Norbert W; Liebau, Eva
The macrophage migration inhibitory factors (MIFs) from the filarial parasite Onchocerca volvulus (OvMIF) were compared to the MIFs from the free-living nematode Caenorhabditis elegans (CeMIF) with respect to molecular, biochemical and immunological properties. Except for CeMIF-4, all other MIFs demonstrated tautomerase activity. Surprisingly, OvMIF-1 displayed oxidoreductase activity. The strongest immunostaining for OvMIF-1 was observed in the outer cellular covering of the adult worm body, the syncytial hypodermis; moderate immunostaining was observed in the uterine wall. The generation of a strong humoral immune response towards OvMIF-1 and reduced reactivity to OvMIF-2 was indicated by high IgG levels in patients infected with O. volvulus and cows infected with the closely related Onchocerca ochengi, both MIFs revealing identical amino acid sequences. Using Litomosoides sigmodontis-infected mice, a laboratory model for filarial infection, MIFs derived from the tissue-dwelling O. volvulus, the rodent gut-dwelling Strongyloides ratti and from free-living C. elegans were recognized, suggesting that L. sigmodontis MIF-specific IgM and IgG1 were produced during L. sigmodontis infection of mice and cross-reacted with all MIF proteins tested. Thus, MIF apparently functions as a target of B cell response during nematode infection, but in the natural Onchocerca-specific human and bovine infection, the induced antibodies can discriminate between MIFs derived from parasitic or free-living nematodes.
Nana-Djeunga, Hugues C.; Kengne-Ouafo, Jonas A.; Pion, Sébastien D. S.; Bopda, Jean; Kamgno, Joseph; Wanji, Samuel; Che, Hua; Kuesel, Annette C.; Walker, Martin; Basáñez, Maria-Gloria; Boakye, Daniel A.; Osei-Atweneboana, Mike Y.; Boussinesq, Michel; Prichard, Roger K.; Grant, Warwick N.
Background Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to more than a decade of regular ivermectin treatment—have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. Methodology/Principal findings Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. Conclusions/Significance This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different
Doyle, Stephen R; Bourguinat, Catherine; Nana-Djeunga, Hugues C; Kengne-Ouafo, Jonas A; Pion, Sébastien D S; Bopda, Jean; Kamgno, Joseph; Wanji, Samuel; Che, Hua; Kuesel, Annette C; Walker, Martin; Basáñez, Maria-Gloria; Boakye, Daniel A; Osei-Atweneboana, Mike Y; Boussinesq, Michel; Prichard, Roger K; Grant, Warwick N
Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift
Liebau, Eva; Höppner, Jana; Mühlmeister, Mareike; Burmeister, Cora; Lüersen, Kai; Perbandt, Markus; Schmetz, Christel; Büttner, Dietrich; Brattig, Norbert
Onchocerciasis or river blindness, caused by the filarial nematode Onchocerca volvulus, is the second leading cause of blindness due to infectious diseases. The protective role of the omega-class glutathione transferase 3 from O. volvulus (OvGST3) against intracellular and environmental reactive oxygen species has been described previously. In the present study, we continue our investigation of the highly stress-responsive OvGST3. Alternative splicing of two exons and one intron retention generates five different transcript isoforms that possess a spliced leader at their 5'-end, indicating that the mechanism of mature mRNA production involves alternative-, cis- and trans-splicing processes. Interestingly, the first two exons of the ovgst3 gene encode a signal peptide before sequence identity to other omega-class glutathione transferases begins. Only the recombinant expression of the isoform that encodes the longest deduced amino acid sequence (OvGST3/5) was successful, with the purified enzyme displaying modest thiol oxidoreductase activity. Significant IgG1 and IgG4 responses against recombinantly expressed OvGST3/5 were detected in sera from patients with the generalized as well as the chronic hyperreactive form of onchocerciasis, indicating exposure of the secreted protein to the human host's immune system and its immunogenicity. Immunohistological localization studies performed at light and electron microscopy levels support the extracellular localization of the protein. Intensive labeling of the OvGST3 was observed in the egg shell at the morula stage of the embryo, indicating extremely defined, stage-specific expression for a short transient period only.
Kephart, G M; Gleich, G J; Connor, D H; Gibson, D W; Ackerman, S J
We investigated the association between eosinophil degranulation, as evidenced by the deposition of granule major basic protein (MBP), and the killing of microfilariae of Onchocerca volvulus in vivo following treatment with diethylcarbamazine (DEC). Utilizing an immunofluorescence procedure for the cellular and extracellular localization of eosinophil MBP in formalin-fixed, paraffin-embedded tissues, we studied skin biopsies from onchocerciasis patients before and during treatment with topically or orally administered DEC. Before DEC, there was little or no inflammatory response in either dermis or epidermis and microfilariae were essentially intact. Immunofluorescent staining for MBP revealed some filamentous fluorescence associated with dermal collagen fibers, very few eosinophils, and no fluorescence in association with intact microfilariae. In contrast, during treatment with DEC, immunofluorescent staining for MBP revealed extensive eosinophil infiltrates in both dermis and epidermis with numerous intraepidermal eosinophil abscesses containing degenerating microfilariae. An intense extracellular immunofluorescence for MBP surrounded degenerating microfilariae in the dermis and epidermis in both the presence and absence of eosinophil infiltrates as early as 4.5 hours after starting therapy. Many intact nondegenerating microfilariae were also present, but they did not show immunofluorescent staining for MBP nor a surrounding inflammatory infiltrate. The results show that immediately following administration of DEC, eosinophils localize and degranulate around microfilariae in the skin and release granule MBP onto or in close proximity to the parasite's surface. Because of the striking association between eosinophil localization, degranulation, and deposition of MBP onto microfilarial surfaces, and the degeneration of microfilariae in the skin, these observations support the hypothesis that the eosinophil, through helminthotoxic granule proteins such as MBP
Rodríguez-Pérez, Mario A; Cabrera, Aldo Segura; Ortega, Cristian Lizarazo; Basáñez, María-Gloria; Davies, John B
Background Since 1991, in Mexico, ivermectin has been administered twice a year to all residents in the onchocerciasis endemic foci which are mainly located in the coffee growing areas. However, the presence of a potentially infected itinerant seasonal labour force which is not treated regularly could jeopardise the attainment of the 85% coverage which is the present target for elimination of the disease. Methods The prevalence and intensity of Onchocerca volvulus microfilariae (mf), as well as their transmission from humans to vectors, were assessed during the coffee planting-clearing and harvesting seasons of 1997–1998, and 1998–1999 in two localities (I and II) of Southern Chiapas, Mexico, which regularly receive an influx of untreated migrant coffee labourers. Results Localities I and II had, respectively, an average of 391 (± 32) and 358 (± 14) resident inhabitants, and 70 (± 52) and 498 (± 289) temporary labourers. The ratio of migrants to residents ranged from 0.1:1 in locality I to 2.4:1 in locality II. The proportion of infected Simulium ochraceum s.l. parous flies was significantly lower in locality I than in locality II, and significantly higher during the stay of the migrants than before their arrival or after their departure. Parity and infection were higher in May-July than in November-February (in contrast with the latter being typically considered as the peak onchocerciasis transmission season by S. ochraceum s.l.). Conclusion The presence of significant numbers of untreated and potentially infected migrants may contribute to ongoing transmission, and their incorporation into ivermectin programmes should be beneficial for the attainment of the elimination goals of the regional initiative. However, the possibility that the results also reflect transmission patterns for the area cannot be excluded and these should be analyzed further. PMID:18088423
Hess, Jessica A.; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M.; Bottazzi, Maria Elena; Hotez, Peter J.; Klei, Thomas R.; Lustigman, Sara; Abraham, David
Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunization protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. PMID:24907553
Hess, Jessica A; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David
Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Kale, O O
A controlled study was carried out to determine the effect of some known anti-filarial drugs on the pattern of emergence of Onchocerca volvulus microfilariae from skin snips into saline. The results show that before treatment, 81.7 to 92.1% of microfilariae emerge in all the groups within 24 hours. The differences between the groups were not significant. After treatment with oral diethylcarbamazine, metrifonate and topical diethylcarbamazine (DEC) the percentage of microfilariae emerging from the snips dropped significantly to 48.4, 56.0 and 60.1 respectively, whereas no significant change occurred following treatment with levamisole (88.1%) and yeast tablets (89.1%). A pair-wise comparison of the post-treatment microfilarial emergence in all the groups showed statistically significant differences when (i) oral DEC is compared to levamisole, topical DEC and yeast, (ii) metrifonate is compared to levamisole and yeast and (iii) topical DEC is compared to yeast. It is suggested that microfilariae which fail to emerge from snips after treatment are those that have been killed or paralysed by the action of the drugs. The study has thus established that drug action in vivo is one of the factors which affects the proportion of microfilariae which emerge from skin snips and provides an additional parameter for measuring the antimicrofilarial potential of drugs in clinical chemotherapeutic trials.
Newell, E D
Two methods for the detection of Onchocerca volvulus microfilariae in the skin were compared in a population-based survey in Gatete, Murama and Jerama, three 'collines' (administrative units) in Burundi. Of the 513 subjects examined, each by both methods, 131 (25.5%) were found positive by skin scarification and 119 (23.2%) by membrane filtration of the fluid in which two skin snips had been incubated. Whilst the sensitivity of the two methods was similar (90% for scarifications and 82% for skin snips), more microfilariae were found by scarification than by biopsy (with geometric mean numbers of 9.1 and 4.1, respectively). Also, more of the cases with infections of low intensity (i.e. < or = 5 microfilariae detected) were found by scarification than by skin snipping (77.9% v. 60.3%; P = 0.06). The endemicity of onchocerciasis and age- and sex-specific prevalences and intensities of infection could be determined equally well using either method. The shortcomings of past comparisons between scarification and skin-snip methods are discussed. Skin scarification has many advantages for the detection of infected individuals in rural health centres and for use in population-based surveys. It may also be helpful when mixed filarial infections are present (especially where onchocerciasis and loiasis co-occur).
Soboslay, P T; Newland, H S; White, A T; Erttmann, K D; Albiez, E J; Taylor, H R; Williams, P N; Greene, B M
Ivermectin is a broad spectrum anti-helminthic agent which is currently being tested for use in human onchocerciasis. Its activity is believed to result from its effect on GABA-mediated neurotransmission. We examined the effects of ivermectin on motility of microfilariae of O. volvulus following administration to humans. When ivermectin was given in dosages of 100, 150 and 200 mcg/kg on day 1 there was a clear reduction in motility of microfilariae obtained on day 3 when compared to microfilariae from the placebo group. The mean motility scores in microfilariae from ivermectin recipients were 3.1, 2.3, and 2.2 at 0, 12, and 24 hours of incubation compared to 3.3, 2.9, and 2.5, respectively, in microfilariae from placebo recipients (p less than 0.003, p less than 0.005, and p less than 0.012, respectively). Examination of the effect according to dose suggested a dose-response relationship. Microfilariae in the anterior chamber of the eye 2 days after a single oral dose of ivermectin showed abnormal and reduced winding and coiling. Microfilariae in 50% of ivermectin recipients showed abnormal motility compared to no such effects in subjects examined concurrently who received oral DEC, DEC lotion or placebo. These observations indicate that ivermectin has an effect on motility of microfilariae of O. volvulus following administration to humans.
Garner, Amanda L; Gloeckner, Christian; Tricoche, Nancy; Zakhari, Joseph S; Samje, Moses; Cho-Ngwa, Fidelis; Lustigman, Sara; Janda, Kim D
Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3 molting was investigated. Structure-activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.
Tagboto, S K; Townson, S
The activity of the veterinary drug moxidectin against Onchocerca volvulus and On. lienalis microfilariae (mf), both in vitro and in experimentally infected CBA/Ca mice, was compared with that of ivermectin. The in-vitro results demonstrated that both compounds (at a concentration of 10(-7) M) significantly reduced the mf motility index (MI) throughout the 7-day culture period and that this reduction was similar for the two compounds. Mice were treated with moxidectin and ivermectin by subcutaneous injection (sc) or orally (po); the two routes were equally efficacious. When mice infected with On. lienalis were treated with one of the drugs at 3.2, 1.6, 0.8, 0.4 or 0.2 micrograms/kg.day on days 3-7 post-infection, with necropsy on day 18, moxidectin cleared more mf than ivermectin at all of the doses examined. In mice treated with a single dose (on day 3 post-infection), 150 or 15 micrograms/kg moxidectin completely cleared the mf whereas 1.5 micrograms/kg produced a 90%-96% reduction in mf recoveries. Following ivermectin treatment at the same doses, mf were virtually cleared at 150 micrograms/kg, with a 98% reduction at 15 micrograms/kg but no significant effect at 1.5 micrograms/kg. When mice with On. volvulus infections were treated with a single dose of moxidectin at 15 or 1.5 micrograms/kg, there were reductions in mf recoveries of 96% and 23%, respectively, compared with only a 48% reduction with 15 micrograms ivermectin/kg and a 2% increase with 1.5 micrograms ivermectin/kg. In order to examine the persistence and activity of each drug, mice were treated with a single dose of 150 micrograms/kg up to 28 days before infection. Moxidectin was found to be more efficacious (with subsequent 99.9% reduction in mf when given 28 days pre-infection and a 100% reduction when give 16 or 4 days before or 3 days after infection) than ivermectin (giving reductions of 57.1%, 66.7%, 100% and 100%, respectively). The further evaluation of moxidectin and its potential
De Sole, G; Remme, J
A study was done to determine the importance of human migration from non-controlled endemic onchocerciasis foci to the river valleys that have been protected for the past 14 to 15 years by the vector control operations of the Onchocerciasis Control Programme in West Africa. The aim of the study was to assess the contribution of migrants to the prevalence and intensity of infection in villages from 5 major river valleys and their potential role in causing relapse of transmission once the vector is allowed to return. In Burkina Faso the migrant population varied from 0.0% to 18.1% of the village population, and averaged 4.9%. Migrants accounted only for 0.6% of the population in Ghanaian and Ivorian villages along the Black Volta river. The prevalence of infection was significantly higher in migrants (8.2%) than in non migrants (1.1%) in the surveyed villages in Burkina Faso, and 1.5% of migrants had infections with more than 16 microfilariae per snip as against 0.2% of non migrants. Nearly all infected migrants came from the south of the Côte d'Ivoire. The study shows that human migration has caused the importation of Onchocerca volvulus from non-controlled areas. However, the epidemiological importance of this phenomenon is limited because of the very small number of infected migrants per village while two-third of the infected migrants are believed to be infected with the less pathogenic forest strain of the parasite. Because migration patterns changes geographically and over time similar studies will be continued on a regular basis.
Duke, B O; Vincelette, J; Moore, P J
During treatment with suramin the numbers of O. volvulus microfilariae in the blood, urine, sputum, and anterior chambers of the eye fell before those in the skin. When diethylcarbamazine (DEC) was given after suramin, increased numbers of microfilariae appeared in the blood, urine, cerebrospinal fluid (CSF) and sputum, but the increase in the blood was less marked, and of shorter duration, than in similar patients receiving DEC without previous suramin. Microfilariae are thought to enter the urine, sputum and CSF directly from the blood by penetrating the capillary walls in the glomeruli, pulmonary alveoli, and choroid plexuses. Those in the aqueous humour do not appear to come directly from the bloodstream. The total numbers of microfilariae in the skin of some heavily infected onchocerciasis patients are estimated, as are the total numbers moving into the blood-stream under the influence of DEC and the proportion which escape into the urine, sputum and CSF. It is concluded that the majority of the microfilariae which appear in the blood during DEC therapy must be destroyed in the body, probably in the liver.
Steisslinger, Vera; Korten, Simone; Brattig, Norbert W; Erttmann, Klaus D
River blindness, caused by the filarial parasite Onchocerca volvulus, is a major socio-economic and public health problem in Sub-Saharan Africa. In January 2015, The Onchocerciasis Vaccine for Africa (TOVA) Initiative has been launched with the aim of providing new tools to complement mass drug administration (MDA) of ivermectin, thereby promoting elimination of onchocerciasis in Africa. In this context we here present Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) as a possible DNA vaccine candidate. We report that in a laboratory model for filariasis, immunization with Ov-GAPDH led to a significant reduction of adult worm load and microfilaraemia in BALB/c mice after challenge infection with the filarial parasite Litomosoides sigmodontis. Mice were either vaccinated with Ov-GAPDH.DNA plasmid (Ov-pGAPDH.DNA) alone or in combination with recombinantly expressed Ov-GAPDH protein (Ov-rGAPDH). During the following challenge infection of immunized and control mice with L. sigmodontis, those formulations which included the DNA plasmid, led to a significant reduction of adult worm loads (up to 57% median reduction) and microfilaraemia (up to 94% reduction) in immunized animals. In a further experiment, immunization with a mixture of four overlapping, synthetic Ov-GAPDH peptides (Ov-GAPDHpept), with alum as adjuvant, did not significantly reduce worm loads. Our results indicate that DNA vaccination with Ov-GAPDH has protective potential against filarial challenge infection in the mouse model. This suggests a transfer of the approach into the cattle Onchocerca ochengi model, where it is possible to investigate the effects of this vaccination in the context of a natural host-parasite relationship.
Armoo, Samuel; Doyle, Stephen R; Osei-Atweneboana, Mike Y; Grant, Warwick N
Wolbachia are intracellular bacteria found in arthropods and several filarial nematode species. The filarial Wolbachia have been proposed to be involved in the immunopathology associated with onchocerciasis. Higher Wolbachia-to-nematode ratios have been reported in the savannah-ecotype compared to the forest-ecotype, and have been interpreted as consistent with a correlation between Wolbachia density and disease severity. However, factors such as geographic stratification and ivermectin drug exposure can lead to significant genetic heterogeneity in the nematode host populations, so we investigated whether Wolbachia copy number variation is also associated with these underlying factors. Genomic DNA was prepared from single adult nematodes representing forest and savannah ecotypes sampled from Togo, Ghana, Côte d'Ivoire and Mali. A qPCR assay was developed to measure the number of Wolbachia genome(s) per nematode genome. Next-generation sequencing (NGS) was also used to measure relative Wolbachia copy number, and independently verify the qPCR assay. Significant variation was observed within the forest (range: 0.02 to 452.99; median: 10.58) and savannah (range: 0.01 to 1106.25; median: 9.10) ecotypes, however, no significant difference between ecotypes (P = 0.645) was observed; rather, strongly significant Wolbachia variation was observed within and between the nine study communities analysed (P = 0.021), independent of ecotype. Analysis of ivermectin-treated and untreated nematodes by qPCR showed no correlation (P = 0.869); however, an additional analysis of a subset of the nematodes by qPCR and NGS revealed a correlation between response to ivermectin treatment and Wolbachia copy number (P = 0.020). This study demonstrates that extensive within and between population variation exists in the Wolbachia content of individual adult O. volvulus. The origin and functional significance of such variation (up to ~ 100,000-fold between worms; ~10 to 100
Opoku, Nicholas O.; Attah, Simon K.; Lazdins-Helds, Janis; Kuesel, Annette C.
Background Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin's safety and efficacy. Effects on the parasite were also assessed. Methodology/Principal Findings Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44), 4 mg (N = 45) or 8 mg (N = 38) moxidectin or 150 µg/kg ivermectin (N = 45) with 18 months follow up. All ivermectin and 97%–100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%), rash (63% vs. 42%), increased pulse rate (61% vs. 36%) and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%). These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p<0.01). Conclusions/Significance The 8 mg dose of moxidectin was safe enough to initiate the large study. Provided its results confirm those from this study, availability of moxidectin to control
Awadzi, Kwablah; Opoku, Nicholas O; Attah, Simon K; Lazdins-Helds, Janis; Kuesel, Annette C
Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin's safety and efficacy. Effects on the parasite were also assessed. Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44), 4 mg (N = 45) or 8 mg (N = 38) moxidectin or 150 µg/kg ivermectin (N = 45) with 18 months follow up. All ivermectin and 97%-100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%), rash (63% vs. 42%), increased pulse rate (61% vs. 36%) and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%). These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p<0.01). The 8 mg dose of moxidectin was safe enough to initiate the large study. Provided its results confirm those from this study, availability of moxidectin to control programmes could help them achieve onchocerciasis elimination objectives
Bottomley, Christian; Isham, Valerie; Vivas-Martínez, Sarai; Kuesel, Annette C; Attah, Simon K; Opoku, Nicholas O; Lustigman, Sara; Walker, Martin; Basáñez, Maria-Gloria
The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols. We develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment. The sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatment. Our model supports the timelines proposed by APOC for post-MDA follow-up and
Edgeworth, J D; Abiose, A; Jones, B R
of microfilariae (MF) within the same nodules. Since MRP8/MRP14 was seen on the adult worm in the absence of a leucocytic infiltrate, it may have an early role to play in the immune response to Onchocerca volvulus. Images Fig. 2 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8467568
Tang, Thuy-Huong Ta; López-Vélez, Rogelio; Lanza, Marta; Shelley, Anthony John; Rubio, Jose Miguel; Luz, Sérgio Luiz Bessa
We present filaria-nested polymerase chain reaction (PCR), which is based on amplification of first internal transcribed spacer rDNA to distinguish three parasitic filarial species (Onchocerca volvulus, Mansonella ozzardi and Mansonella perstans) that can be found in the Amazon Region. Nested PCR-based identifications yielded the same results as those utilizing morphological characters. Nested PCR is highly sensitive and specific and it detects low-level infections in both humans and vectors. No cross-amplifications were observed with various other blood parasites and no false-positive results were obtained with the nested PCR. The method works efficiently with whole-blood, blood-spot and skin biopsy samples. Our method may thus be suitable for assessing the efficacy of filaria control programmes in Amazonia by recording parasite infections in both the human host and the vector. By specifically differentiating the major sympatric species of filaria, this technique could also enhance epidemiological research in the region.
He, Yuxian; Barker, Sophie J; MacDonald, Angus J; Yu, Yu; Cao, Long; Li, Jingjing; Parhar, Ranjit; Heck, Susanne; Hartmann, Susanne; Golenbock, Douglas T; Jiang, Shibo; Libri, Nathan A; Semper, Amanda E; Rosenberg, William M; Lustigman, Sara
We previously reported that rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, was a potent adjuvant for recombinant protein or synthetic peptide-based Ags. In this study, we further evaluated the adjuvanticity of rOv-ASP-1 and explored its mechanism of action. Consistently, recombinant full-length spike protein of SARS-CoV or its receptor-binding domain in the presence of rOv-ASP-1 could effectively induce a mixed but Th1-skewed immune response in immunized mice. It appears that rOv-ASP-1 primarily bound to the APCs among human PBMCs and triggered Th1-biased proinflammatory cytokine production probably via the activation of monocyte-derived dendritic cells and the TLR, TLR2, and TLR4, thus suggesting that rOv-ASP-1 is a novel potent innate adjuvant.
O’Hanlon, Simon J.; Slater, Hannah C.; Cheke, Robert A.; Boatin, Boakye A.; Coffeng, Luc E.; Pion, Sébastien D. S.; Boussinesq, Michel; Zouré, Honorat G. M.; Stolk, Wilma A.; Basáñez, María-Gloria
Background The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions. Methods and Findings Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson’s correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2–90%) in 1975. Conclusions and Significance This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where
Thiele, Elizabeth A; Cama, Vitaliano A; Lakwo, Thomson; Mekasha, Sindeaw; Abanyie, Francisca; Sleshi, Markos; Kebede, Amha; Cantey, Paul T
Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N= 500 each) and "residual" skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(-) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools. © The American Society of Tropical Medicine and Hygiene.
Bopda, Jean; Kengne-Ouafo, Jonas A.; Njiokou, Flobert; Prichard, Roger K.; Wanji, Samuel; Kamgno, Joseph; Boussinesq, Michel
Background For two decades, onchocerciasis control has been based on mass treatment with ivermectin (IVM), repeated annually or six-monthly. This drug kills Onchocerca volvulus microfilariae (mf) present in the skin and the eyes (microfilaricidal effect) and prevents for 3–4 months the release of new mf by adult female worms (embryostatic effect). In some Ghanaian communities, the long-term use of IVM was associated with a more rapid than expected skin repopulation by mf after treatment. Here, we assessed whether the embryostatic effect of IVM on O. volvulus has been altered following frequent treatment in Cameroonian patients. Methodology Onchocercal nodules were surgically removed just before (D0) and 80 days (D80) after a standard dose of IVM in two cohorts with different treatment histories: a group who had received repeated doses of IVM over 13 years, and a control group with no history of large-scale treatments. Excised nodules were digested with collagenase to isolate adult worms. Embryograms were prepared with females for the evaluation of their reproductive capacities. Principal Findings Oocyte production was not affected by IVM. The mean number of intermediate embryos (morulae and coiled mf) decreased similarly in the two groups between D0 and D80. In contrast, an accumulation of stretched mf, either viable or degenerating, was observed at D80. However, it was observed that the increase in number of degenerating mf between D0 and D80 was much lower in the frequently treated group than in the control one (Incidence Rate Ratio: 0.25; 95% CI: 0.10–0.63; p = 0.003), which may indicate a reduced sequestration of mf in the worms from the frequently treated group. Conclusion/Significance IVM still had an embryostatic effect on O. volvulus, but the effect was reduced in the frequently treated cohort compared with the control population. PMID:24762816
Turner, Joseph D.; Tendongfor, Nicholas; Esum, Mathias; Johnston, Kelly L.; Langley, R. Stuart; Ford, Louise; Faragher, Brian; Specht, Sabine; Mand, Sabine; Hoerauf, Achim; Enyong, Peter; Wanji, Samuel; Taylor, Mark J.
Background The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. Methods A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 µg/kg) at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events. Results One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia
MacDonald, A J; Tawe, W; Leon, O; Cao, L; Liu, J; Oksov, Y; Abraham, D; Lustigman, S
Vaccination of mice with a recombinant protein, Ov-ASP-1, the Onchocerca volvulus homologue of the activation associated secreted gene family stimulated very high titres of both IgG1 and IgG2a without adjuvant. rOv-ASP-1 was also immuno-reactive with IgG isotypes from both O. volvulus-infected (INF) and putatively immune (PI) humans, with higher IgG4 in the former group. The protein also stimulated IFN-gamma secretion by PBMC from INF and PI and IL-5 only in INF. Using a mouse diffusion chamber model, vaccination with rOv-ASP-1 resulted in partial but significant protection against challenge with infective third-stage larvae (L3) but only when formulated with Freund's complete adjuvant (FCA) or alum. Protection was Th1-dependent (highly elevated IgG2a) with FCA and contingent on a strongly Th2-skewed (IgG1) response with alum. IgE responses to rOv-ASP-1 with or without adjuvant were weak or absent. When immunization using rOv-ASP-1 in adjuvant failed to induce adequate Th1 (FCA) or Th2 (alum) responses, protection efficacy was compromised. The recombinant protein appears to stimulate a mixed Th1/Th2 response but the outcome in terms of protective immunity is the result of a subtle interplay of its intrinsic and adjuvant-augmented properties. Ov-ASP-1 is potentially secreted based on its localization in the secretory granules of L3.
Pion, Sébastien D S; Nana-Djeunga, Hugues C; Kamgno, Joseph; Tendongfor, Nicholas; Wanji, Samuel; Njiokou, Flobert; Prichard, Roger K; Boussinesq, Michel
Ivermectin has been the keystone of onchocerciasis control for the last 25 years. Sub-optimal responses to the drug have been reported in Ghanaian communities under long-term treatment. We assessed, in two Cameroonian foci, whether the microfilaricidal and/or embryostatic effects of ivermectin on Onchocerca volvulus have been altered after several years of drug pressure. We compared the dynamics of O. volvulus skin microfilarial densities after ivermectin treatment in two cohorts with contrasting exposure to this drug: one received repeated treatment for 13 years whereas the other had no history of large-scale treatments (referred to as controls). Microfilarial densities were assessed 15, 80 and 180 days after ivermectin in 122 multiply treated and 127 ivermectin-naïve individuals. Comparisons were adjusted for individual factors related to microfilarial density: age and number of nodules. Two weeks post ivermectin, microfilarial density dropped equally (98% reduction) in the ivermectin-naïve and multiply treated groups. Between 15 and 180 days post ivermectin, the proportion of individuals with skin microfilariae doubled (from 30.8% to 67.8%) in controls and quadrupled (from 19.8% to 76.9%) in multiply treated individuals but the mean densities remained low in both sites. In fact, between 15 and 80 days, the repopulation rate was significantly higher in the multiply treated individuals than in the controls but no such difference was demonstrated when extending the follow-up to 180 days. The repopulation rate by microfilariae was associated with host factors: negatively with age and positively with the number of nodules. These observations may indicate that the worms from the multi-treated area recover mf productivity earlier but would be less productive than the worms from the ivermectin-naïve area between 80 and 180 days after ivermectin. Moreover, they do not support the operation of a strong cumulative effect of repeated treatments on the fecundity of female
Korten, Simone; Kaifi, Jussuf T; Büttner, Dietrich W; Hoerauf, Achim
Transforming growth factor-beta (TGF-beta) is a key cytokine in immune regulation, cell differentiation, development, wound healing, and tissue remodelling. It mediates immunosuppression in filarial infections facilitating parasite persistence, while attenuating immunopathology, which is induced by migrating microfilariae. Immunosuppression rises with parasite burden, but it remains unknown whether filariae elicit local release of immunosuppressive cytokines. Therefore, using immunohistology, we investigated the expression of stable, released latent TGF-beta1 in subcutaneous nodules from highly infected, hyporeactive onchocerciasis patients, harbouring adult Onchocerca volvulus. Since many cell types produce TGF-beta, we elucidated the cellular source, distribution and dependency on the worms' sex, productivity and vitality. We found TGF-beta1 to be abundantly expressed by T cells, plasma/B cells, macrophages, mast cells, fibrocytes, and vascular endothelial cells, particularly in onchocercomas with productive or previously productive females, damaged, dead and resorbed adult worms or microfilariae. We conclude TGF-beta to be antigen induced by the filariae since expression was scarce around subcutaneous arthropods or cholesterol crystals in onchocercomas. Enhanced expression after ivermectin or endobacteria-depleting doxycycline treatment indicates induction to depend on filariae and not on Wolbachia endobacteria. TGF-beta(+) cells were reduced in HIV co-infection. This finding of local and sustained TGF-beta induction by vital and dead filariae, untreated and after treatment, adds new aspects to immunomodulation by helminths.
Duke, B O; Zea-Flores, G; Castro, J; Cupp, E W; Munoz, B
Adult Onchocerca volvulus worms, extracted from nodules of Guatemalans by collagenase digestion, were examined whole and by histological techniques. One group of persons received a single 150 micrograms/kg dose of ivermectin; two other groups (one with older and one with younger nodules) received four similar doses of ivermectin at 6-month intervals. For each group, there were comparable untreated controls. All nodules were removed six months after the last dose. After a single dose, the only significant difference from the controls was in the decreased proportion of female worms producing live microfilariae. After four doses, there were significant increases in the proportions of moribund/dead female worms and of live uninseminated females, when compared with the corresponding controls. There were also fewer male worms present, but this difference was not significant. Six months after the conclusion of the 4-dose regimen, the proportion of female worms producing live microfilariae was significantly lower than in the groups that had received a single dose.
Duke, B O
It is important to standardize quantitative methods for assessing the action of drugs on Onchocerca volvulus in man. There are certain disadvantages to making observations on adult worms removed from excised nodules in treated patients, but a great deal of information on drug action can be obtained by making a careful study of the concentrations of microfilariae in multiple weighed skin snips taken before treatment and at intervals after treatment.Before drug trials can be carried out intelligently by this method it is necessary to know the normal length of life of the various stages of the parasite in man. By a variety of experimental methods the life-spans of the adult worms and the microfilariae have been determined, as well as the duration of the prepatent interval.Diethylcarbamazine can be used at doses that are effectively microfilaricidal but have no action on the adult worms. This drug can therefore be used to eliminate any residual microfilariae that remain after treatment with a new drug under trial, thus permitting a more rapid assessment of the latter's action on adult worms.
Segura-Cabrera, Aldo; Bocanegra-García, Virgilio; Lizarazo-Ortega, Cristian; Guo, Xianwu; Correa-Basurto, José; Rodríguez-Pérez, Mario A.
Onchocerciasis is a leading cause of blindness with at least 37 million people infected and more than 120 million people at risk of contracting the disease; most (99%) of this population, threatened by infection, live in Africa. The drug of choice for mass treatment is the microfilaricidal Mectizan® (ivermectin); it does not kill the adult stages of the parasite at the standard dose which is a single annual dose aimed at disease control. However, multiple treatments a year with ivermectin have effects on adult worms. The discovery of new therapeutic targets and drugs directed towards the killing of the adult parasites are thus urgently needed. The chitinase of filarial nematodes is a new drug target due to its essential function in the metabolism and molting of the parasite. Closantel is a potent and specific inhibitor of chitinase of Onchocerca volvulus (OvCHT1) and other filarial chitinases. However, the binding mode and specificity of closantel towards OvCHT1 remain unknown. In the absence of a crystallographic structure of OvCHT1, we developed a homology model of OvCHT1 using the currently available X-ray structures of human chitinases as templates. Energy minimization and molecular dynamics (MD) simulation of the model led to a high quality of 3D structure of OvCHIT1. A flexible docking study using closantel as the ligand on the binding site of OvCHIT1 and human chitinases was performed and demonstrated the differences in the closantel binding mode between OvCHIT1 and human chitinase. Furthermore, molecular dynamics simulations and free-energy calculation were employed to determine and compare the detailed binding mode of closantel with OvCHT1 and the structure of human chitinase. This comparative study allowed identification of structural features and properties responsible for differences in the computationally predicted closantel binding modes. The homology model and the closantel binding mode reported herein might help guide the rational development of
Pion, Sébastien D. S.; Nana-Djeunga, Hugues C.; Kamgno, Joseph; Tendongfor, Nicholas; Wanji, Samuel; Njiokou, Flobert; Prichard, Roger K.; Boussinesq, Michel
Background/Objective Ivermectin has been the keystone of onchocerciasis control for the last 25 years. Sub-optimal responses to the drug have been reported in Ghanaian communities under long-term treatment. We assessed, in two Cameroonian foci, whether the microfilaricidal and/or embryostatic effects of ivermectin on Onchocerca volvulus have been altered after several years of drug pressure. Methods We compared the dynamics of O. volvulus skin microfilarial densities after ivermectin treatment in two cohorts with contrasting exposure to this drug: one received repeated treatment for 13 years whereas the other had no history of large-scale treatments (referred to as controls). Microfilarial densities were assessed 15, 80 and 180 days after ivermectin in 122 multiply treated and 127 ivermectin-naïve individuals. Comparisons were adjusted for individual factors related to microfilarial density: age and number of nodules. Findings Two weeks post ivermectin, microfilarial density dropped equally (98% reduction) in the ivermectin-naïve and multiply treated groups. Between 15 and 180 days post ivermectin, the proportion of individuals with skin microfilariae doubled (from 30.8% to 67.8%) in controls and quadrupled (from 19.8% to 76.9%) in multiply treated individuals but the mean densities remained low in both sites. In fact, between 15 and 80 days, the repopulation rate was significantly higher in the multiply treated individuals than in the controls but no such difference was demonstrated when extending the follow-up to 180 days. The repopulation rate by microfilariae was associated with host factors: negatively with age and positively with the number of nodules. Conclusion These observations may indicate that the worms from the multi-treated area recover mf productivity earlier but would be less productive than the worms from the ivermectin-naïve area between 80 and 180 days after ivermectin. Moreover, they do not support the operation of a strong cumulative effect
Segura-Cabrera, Aldo; Bocanegra-García, Virgilio; Lizarazo-Ortega, Cristian; Guo, Xianwu; Correa-Basurto, José; Rodríguez-Pérez, Mario A
Onchocerciasis is a leading cause of blindness with at least 37 million people infected and more than 120 million people at risk of contracting the disease; most (99%) of this population, threatened by infection, live in Africa. The drug of choice for mass treatment is the microfilaricidal Mectizan(®) (ivermectin); it does not kill the adult stages of the parasite at the standard dose which is a single annual dose aimed at disease control. However, multiple treatments a year with ivermectin have effects on adult worms. The discovery of new therapeutic targets and drugs directed towards the killing of the adult parasites are thus urgently needed. The chitinase of filarial nematodes is a new drug target due to its essential function in the metabolism and molting of the parasite. Closantel is a potent and specific inhibitor of chitinase of Onchocerca volvulus (OvCHT1) and other filarial chitinases. However, the binding mode and specificity of closantel towards OvCHT1 remain unknown. In the absence of a crystallographic structure of OvCHT1, we developed a homology model of OvCHT1 using the currently available X-ray structures of human chitinases as templates. Energy minimization and molecular dynamics (MD) simulation of the model led to a high quality of 3D structure of OvCHIT1. A flexible docking study using closantel as the ligand on the binding site of OvCHIT1 and human chitinases was performed and demonstrated the differences in the closantel binding mode between OvCHIT1 and human chitinase. Furthermore, molecular dynamics simulations and free-energy calculation were employed to determine and compare the detailed binding mode of closantel with OvCHT1 and the structure of human chitinase. This comparative study allowed identification of structural features and properties responsible for differences in the computationally predicted closantel binding modes. The homology model and the closantel binding mode reported herein might help guide the rational development of
Hess, Jessica A; Zhan, Bin; Torigian, April R; Patton, John B; Petrovsky, Nikolai; Zhan, Tingting; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David
In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.
Hess, Jessica A.; Zhan, Bin; Torigian, April R.; Patton, John B.; Petrovsky, Nikolai; Zhan, Tingting; Bottazzi, Maria Elena; Hotez, Peter J.; Klei, Thomas R.; Lustigman, Sara; Abraham, David
Background In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. Methodology/ Principal Findings Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen–specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. Conclusions/Significance The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans. PMID:27387453
Golden, Allison; Steel, Cathy; Yokobe, Lindsay; Jackson, Emily; Barney, Rebecca; Kubofcik, Joseph; Peck, Roger; Unnasch, Thomas R.; Nutman, Thomas B.; de los Santos, Tala; Domingo, Gonzalo J.
Onchocerciasis is a neglected tropical disease caused by infection with the parasite Onchocerca volvulus (Ov). An estimated 180 million people are at risk for Ov infection, and 37 million people are infected, mostly in Africa. A lateral flow-based assay to detect human IgG4 antibodies to the Ov-specific antigen Ov-16 was developed as a rapid tool to detect exposure to Ov. The test, when performed on 449 sera specimens from patients with microfiladermia and Ov-negative patients, has a sensitivity of 89.1% (95% confidence interval: 86.2%–92.0%), and specificity of 97% (95% confidence interval: 95.4%–98.6%). Because the intended use of the test is for surveillance, it is highly desirable to have a stable, long-lasting result. An extended read window is thus desirable for a high-volume, busy workflow and facilitates post-surveillance quality assurance. The main restriction on achieving an extended read window for this assay was the erythrocyte lysis that can alter the signal-to-noise ratio, especially in those with low IgG4 levels (weak positives). We describe a test housing that incorporates a user-independent feature driven by assay fluid and an expanding wick that detaches the blood separation membrane from the nitrocellulose used in the assay, but before hemolysis occurs. We demonstrated material functionality at extreme operational conditions (37°C, 80% relative humidity) and a read window of a minimum of 70 days. The fluid-driven assay device performs equally as well with whole blood as with plasma, as demonstrated with 100 spiked clinical specimens (with a correlation coefficient of 0.96). We show a novel, inexpensive, and simple approach to actuating the detachment of the blood separation membrane from the nitrocellulose test with no impact on the performance characteristics of the test. PMID:23935960
Albiez, E J; Walter, G; Kaiser, A; Newland, H S; White, A T; Greene, B M; Taylor, H R; Büttner, D W
Thirty adult male nodule carriers from a hyperendemic onchocerciasis area in the Liberian rain forest were treated with high doses of diethylcarbamazine (30 mg/kg/d) over one week. Another ten patients received placebo tablets and served as a control. All detectable nodules were removed from half of the patients at two months and from the remaining patients at ten months after chemotherapy. The adult worms in the nodules were examined for pathological alterations by the collagenase technique including embryogram, and by histology. No macrofilaricidal effect was observed at either time, and no significant reduction of microfilariae in the uteri of the female worms or in the tissue of the nodules was seen. Two months after the therapy there was a significant increase of degenerated stretched intrauterine microfilariae but this effect was no longer observed after ten months. No pathological effect was seen on the intrauterine coiled microfilariae. On the contrary, their number had significantly increased after ten months which could mean a stimulation of the embryogenesis. No effect on spermatogenesis was observed. Both techniques, the collagenase digestion and the histological examination of the nodules, provided similar results to demonstrate that there was no marked long lasting effect on O. volvulus after a treatment with high doses of diethylcarbamazine.
Zarroug, Isam M. A.; Hashim, Kamal; Elaagip, Arwa H.; Samy, Abdallah M.; Frah, Ehab A.; ElMubarak, Wigdan A.; Mohamed, Hanan A.; Deran, Tong Chor M.; Aziz, Nabil; Higazi, Tarig B.
collection from April to June. There was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007–2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (rs = 0.799) and were decreased in Kalasecal (rs = - 0.676), Gumaiza (rs = - 0.585), and Hilat Khateir (rs = - 0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00–18:00), while a bimodal pattern with two peaks (07:00–10:00) and (14:00–18:00) was exhibited in Galabat. Conclusion Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan. PMID:26943668
Zarroug, Isam M A; Hashim, Kamal; Elaagip, Arwa H; Samy, Abdallah M; Frah, Ehab A; ElMubarak, Wigdan A; Mohamed, Hanan A; Deran, Tong Chor M; Aziz, Nabil; Higazi, Tarig B
was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007-2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (rs = 0.799) and were decreased in Kalasecal (rs = -0.676), Gumaiza (rs = -0.585), and Hilat Khateir (rs = -0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00-18:00), while a bimodal pattern with two peaks (07:00-10:00) and (14:00-18:00) was exhibited in Galabat. Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan.
Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial
Debrah, Alexander Yaw; Specht, Sabine; Klarmann-Schulz, Ute; Batsa, Linda; Mand, Sabine; Marfo-Debrekyei, Yeboah; Fimmers, Rolf; Dubben, Bettina; Kwarteng, Alexander; Osei-Atweneboana, Mike; Boakye, Daniel; Ricchiuto, Arcangelo; Büttner, Marcelle; Adjei, Ohene; Mackenzie, Charles D.; Hoerauf, Achim
Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839. PMID:25948064
Zhao, Guangyu; Du, Lanying; Xiao, Wenjun; Sun, Shihui; Lin, Yongping; Chen, Min; Kou, Zhihua; He, Yuxian; Lustigman, Sara; Jiang, Shibo; Zheng, Bo-Jian; Zhou, Yusen
Our previous studies have shown the adjuvanticity of an Onchocerca volvulus recombinant protein, Ov-ASP-1 (ASP-1), when administered in an aqueous formulation with bystander vaccine antigens or commercial vaccines. In this study, we reported a novel formulation that took advantage of the protein nature of the ASP-1 adjuvant by creating recombinant fusion protein vaccines linking the highly conserved extracellular domain of M2 protein (M2e) consensus sequence of H5N1 influenza viruses with the ASP-1 adjuvant. Two recombinant fusion proteins designated M2e-ASP-1 and M2e3-ASP-1 were studied, in which ASP-1 was fused with one or three tandem copies of the M2e antigen. Our results show that these novel recombinant influenza vaccines, particularly M2e3-ASP-1, induced strong anti-M2e-specific humoral and cellular immune responses in the established mouse model. Furthermore, M2e3-ASP-1 was able to provide significant cross-clade protection against divergent H5N1 viruses. Consequently, this study has demonstrated a potential novel vaccine formulation that could provide a complementary prophylactic strategy in preventing the threat of future influenza outbreak resulting from rapid evolution of the H5N1 virus and co-circulation of multiple antigenic variants in various regions.
Determination of sample sizes for the estimation of Onchocerca volvulus (Filarioidea: Onchocercidae) infection rates in biting populations of Simulium ochraceum s.l. (Diptera: Simuliidae) and its application to ivermectin control programs.
Basáñez, M G; Rodríguez-Pérez, M A; Reyes-Villanueva, F; Collins, R C; Rodríguez, M H
Monthly samples of biting Simulium ochraceum s.l. Walker were collected before and after ivermectin treatment in southern Mexico and analyzed for Onchocerca volvulus Leuckart infection rates, infection intensity, and the characteristics of larval distribution among parous flies. The variance over mean ratio (VMR) indicated that in all cases this distribution departed from Poisson and was strongly aggregated (VMR > 1). The negative binomial was found to be an adequate model with a small value of the aggregation parameter k, but the degree of larval overdispersion increased as the mean larval load decreased, invalidating the use of a common kc value. A linear relationship between k and the mean (mu) was established, k(mu) = k1 mu, which permitted exploration of the relationship between the observed proportion of infected flies, p, and the estimated mean larval burden per fly, m (all larval stages in parous flies). This would allow mean numbers of larvae per parous fly to be predicted from presence-absence data (e.g., from infection rates provided by polymerase chain reaction methods applied to pools of flies), assuming that k1 is a known parameter. Given that both p and m are naturally low in S. ochraceum, their relationship was practically linear within the range of observed values. Predictions were tested with the Mexican data from which the clumping parameter was estimated as well as for Guatemalan data for which this information was not available. Results showed a highly satisfactory degree of agreement between predictions and observations. The sample sizes required to estimate mean larval loads from prevalence data for fixed levels of precision (defined as the ratio between SE[m] and m) were calculated for realistic S. ochraceum infection rates (those found in published pre- and postcontrol field surveys as well as in this work). For the special case in which the relationship between k and the mean is linear and goes through the origin, k(mu) = k1 mu, the number
Cantey, Paul T.; Weeks, Jessica; Edwards, Morven; Rao, Suchitra; Ostovar, G. Amin; Dehority, Walter; Alzona, Maria; Swoboda, Sara; Christiaens, Brooke; Ballan, Wassim; Hartley, John; Terranella, Andrew; Weatherhead, Jill; Dunn, James J.; Marx, Douglas P.; Hicks, M. John; Rauch, Ronald A.; Smith, Christiana; Dishop, Megan K.; Handler, Michael H.; Dudley, Roy W. R.; Chundu, Kote; Hobohm, Dan; Feiz-Erfan, Iman; Hakes, Joseph; Berry, Ryan S.; Stepensaski, Shelly; Greenfield, Benjamin; Shroeder, Laura; Bishop, Henry; de Almeida, Marcos; Mathison, Blaine; Eberhard, Mark
This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies. PMID:26611778
Cantey, Paul T; Weeks, Jessica; Edwards, Morven; Rao, Suchitra; Ostovar, G Amin; Dehority, Walter; Alzona, Maria; Swoboda, Sara; Christiaens, Brooke; Ballan, Wassim; Hartley, John; Terranella, Andrew; Weatherhead, Jill; Dunn, James J; Marx, Douglas P; Hicks, M John; Rauch, Ronald A; Smith, Christiana; Dishop, Megan K; Handler, Michael H; Dudley, Roy W R; Chundu, Kote; Hobohm, Dan; Feiz-Erfan, Iman; Hakes, Joseph; Berry, Ryan S; Stepensaski, Shelly; Greenfield, Benjamin; Shroeder, Laura; Bishop, Henry; de Almeida, Marcos; Mathison, Blaine; Eberhard, Mark
This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies.
Immunity to onchocerciasis: cells from putatively immune individuals produce enhanced levels of interleukin-5, gamma interferon, and granulocyte-macrophage colony-stimulating factor in response to Onchocerca volvulus larval and male worm antigens.
Turaga, P S; Tierney, T J; Bennett, K E; McCarthy, M C; Simonek, S C; Enyong, P A; Moukatte, D W; Lustigman, S
Antigen-specific interleukin-5 (IL-5), gamma interferon (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) responses in individuals living in an area of hyperendemicity for onchocerciasis in Cameroon were examined. The responses against antigens prepared from Onchocerca volvulus third-stage larvae (L3), molting L3 (mL3), and crude extract from adult males (M-OvAg) were compared to the responses against antigens from adult female worms and skin microfilariae. Cytokine responses for the putatively immune individuals (PI) and the infected individuals (INF) were compared. A differential cytokine profile of IL-5 (Th2 phenotype) and IFN-gamma (Th1 phenotype) was found in these individuals in response to the antigens. In both the PI and the INF, Th2 responses against all the antigens tested were dominant. However, in the PI group as a whole, there was an enhanced Th2 response against the larval antigens and the adult male and adult female antigens, and a Th1 response in a subgroup of the PI (27 to 54.5%) against L3, mL3, and M-OvAg antigens was present. While the PI produced significantly higher levels of GM-CSF against L3, mL3, and M-OvAg antigens than the INF, there was no difference in the GM-CSF responses of the groups against the other antigens. The present study indicated that, in comparison to the INF, the PI have distinct larva-specific and adult male-specific cytokine responses, thus supporting the premise that immunological studies of the PI would lead to the identification of immune mechanisms and the target genes that play a role in protective immunity.
Lefoulon, Emilie; Giannelli, Alessio; Makepeace, Benjamin L; Mutafchiev, Yasen; Townson, Simon; Uni, Shigehiko; Verocai, Guilherme G; Otranto, Domenico; Martin, Coralie
The genus Onchocerca includes 34 described species and represents one of the largest genera of the filarial nematodes within the family Onchocercidae. Representative members of this genus are mainly parasites of ungulates, with some exceptions such as Onchocerca lupi and Onchocerca volvulus, infecting carnivores and/or humans. For a long time, the evolutionary relationships amongst onchocercids remained poorly studied, as the systematics of this genus was impaired by the high morphological variability of species included in the taxon. Although some molecular phylogenies were developed, these studies were mainly focused on bovine Onchocerca spp. and O. volvulus, including assessments of Wolbachia endosymbionts. In the present study, we analysed 13 Onchocerca spp. from a larger host spectrum using a panel of seven different genes. Analysis of the coxI marker supports its usefulness for the identification of species within the genus. The evolutionary history of the genus has been herein revised by multi-gene phylogenies, presenting three strongly supported clades of Onchocerca spp. Analyses of co-evolutionary scenarios between Onchocerca and their vertebrate hosts underline the effect of domestication on Onchocerca speciation. Our study indicates that a host switch event occurred between Bovidae, Canidae and humans. Cophylogenetic analyses between Onchocerca and the endosymbiotic bacterium Wolbachia indicate the strongest co-evolutionary pattern ever registered within the filarial nematodes. Finally, this dataset indicates that the clade composed by O. lupi, Onchocerca gutturosa, Onchocerca lienalis, Onchocerca ochengi and O. volvulus derived from recent speciation.
Solórzano, J; Acosta, D; Morales, H; Vásquez, F; Mora, G; Chávez, M; Andrade, D; Joutteaux, R; Sánchez, I; García, D; Valenzuela, E
Gastric volvulus is a rare condition in pediatric population in which there is an abnormal rotation of one part of the stomach around itself. It's a surgical emergency. We report a six year old female admitted in the emergency due to upper abdominal distention, nausea without vomiting, physical exam revealed upper abdominal distention and abdominal tenderness, no bowel sounds. Laparotomy was performed and a gastric volvulus with occlusive vascular involvement was found. In the post operative period she required a second laparotomy due to adhesions in small bowel.
Neary, Joseph M.; Trees, Alexander J.; Ekale, David D.; Tanya, Vincent N.; Hetzel, Udo; Makepeace, Benjamin L.
Human onchocerciasis, also known as River Blindness, is a debilitating disease caused by the filarial nematode Onchocerca volvulus. Many, but not all, filarial nematodes carry within their tissues endosymbiotic, Rickettsia-like bacteria of the genus Wolbachia. Onchocerca spp. infections in cattle offer the most relevant, analogous host–parasite model system. West African cattle are commonly co-infected with four Onchocerca spp.; two of these are Wolbachia-positive (Onchocerca gutturosa and Onchocerca ochengi), and the remainder are of unknown Wolbachia status (Onchocerca dukei and Onchocerca armillata). Previous studies have suggested that worm survival is dependent on this bacterium. O. armillata, an abundant parasite of African cattle that has received little attention, is a primitive species that may lack Wolbachia. The objectives of this study were to determine if O. armillata carries Wolbachia and to provide preliminary descriptions of the host inflammatory cell environment around the adult worms. The findings may support or refute the hypothesis that a prime contribution of Wolbachia is to permit long-term survival and reproduction of certain Onchocerca spp. (including O. volvulus in humans). O. armillata adult worms were found in the aorta of 90.7% of cattle (n = 54) slaughtered at an abattoir in Ngaoundéré, Adamawa Region, Cameroon. The presence of Wolbachia in O. armillata was confirmed by a specific anti-Wolbachia surface protein antibody detected using a peroxidase conjugate (immunohistochemistry) and PCR for detection of Wolbachia-specific sequences within DNA extracts from frozen worms. Tissue sections stained with haematoxylin and eosin showed the host cell response to be dominated by macrophages and fibroblasts. This is unusual compared with nodule-dwelling Wolbachia-positive Onchocerca spp., where the host response is typically characterised by granulocytes, and suggests that the mechanisms for worm survival employed by this species (which is
Neary, Joseph M; Trees, Alexander J; Ekale, David D; Tanya, Vincent N; Hetzel, Udo; Makepeace, Benjamin L
Human onchocerciasis, also known as River Blindness, is a debilitating disease caused by the filarial nematode Onchocerca volvulus. Many, but not all, filarial nematodes carry within their tissues endosymbiotic, Rickettsia-like bacteria of the genus Wolbachia. Onchocerca spp. infections in cattle offer the most relevant, analogous host-parasite model system. West African cattle are commonly co-infected with four Onchocerca spp.; two of these are Wolbachia-positive (Onchocerca gutturosa and Onchocerca ochengi), and the remainder are of unknown Wolbachia status (Onchocerca dukei and Onchocerca armillata). Previous studies have suggested that worm survival is dependent on this bacterium. O. armillata, an abundant parasite of African cattle that has received little attention, is a primitive species that may lack Wolbachia. The objectives of this study were to determine if O. armillata carries Wolbachia and to provide preliminary descriptions of the host inflammatory cell environment around the adult worms. The findings may support or refute the hypothesis that a prime contribution of Wolbachia is to permit long-term survival and reproduction of certain Onchocerca spp. (including O. volvulus in humans). O. armillata adult worms were found in the aorta of 90.7% of cattle (n=54) slaughtered at an abattoir in Ngaoundéré, Adamawa Region, Cameroon. The presence of Wolbachia in O. armillata was confirmed by a specific anti-Wolbachia surface protein antibody detected using a peroxidase conjugate (immunohistochemistry) and PCR for detection of Wolbachia-specific sequences within DNA extracts from frozen worms. Tissue sections stained with haematoxylin and eosin showed the host cell response to be dominated by macrophages and fibroblasts. This is unusual compared with nodule-dwelling Wolbachia-positive Onchocerca spp., where the host response is typically characterised by granulocytes, and suggests that the mechanisms for worm survival employed by this species (which is
Crainey, James L; Mattos-Glória, Aline; Hamada, Neusa; Luz, Sérgio L B
Following the success of the Onchocerciasis Elimination Programme for the Americas (OEPA), there is now just one Latin American onchocerciasis focus where onchocerciasis transmission is described as 'on-going:' the Amazonia Onchocerciasis focus. In the hyperendemic highland areas of the Amazonia focus, Simulium guianense s.l. Wise are the most important vectors of the disease. Populations of S. guianense s.l. are, however, known to vary in their cytogenetics and in a range of behaviours, including in their biting habits. In the hypoendemic lowland areas of the Amazonia focus, for example, S. guianense s.l. are generally regarded as zoophilic and consequently unimportant to disease transmission. Robust tools, to discriminate among various populations of S. guianense s.l. have, however, not yet been developed. In the work reported here, we have assessed the utility of a ribosomal DNA sequence fragment spanning the nuclear ribosomal ITS-1, ITS-2 and 5.8S sequence regions and a ∼850 nucleotide portion of the mitochondrial cytochrome oxidase gene (CO1) for species-level identification and for resolving the within species substructuring. We report here how we have generated 78 CO1 sequences from a rich set of both zoophilic and anthropophilic populations of S. guianense s.l. that were collected from eight sites that are broadly distributed across Brazil. Consistent with previous findings, our analysis supports the genetic isolation of Simulium litobranchium from S. guianense s.l. In contrast with previous findings, however, our results did not provide support for the divergence of the two species prior to the radiation of S. guianense s.l. In our analysis of the S. guianense s.l. ribosomal DNA sequence trace files we generated, we provide clear evidence of multiple within-specimen single nucleotide polymorphisms and indels suggesting that S. guianense s.l. ribosomal DNA is not a good target for conventional DNA barcoding. This is the first report of S. guianense s
Vector competence of Simulium oyapockense s.l. and S. incrustatum for Onchocerca volvulus: Implications for ivermectin-based control in the Amazonian focus of human onchocerciasis, a multi-vector-host system.
Grillet, María-Eugenia; Villamizar, Nestor J; Frontado, Hortencia L; Cortez, José; Escalona, Marisela; Botto, Carlos; Basáñez, María-Gloria
Although it is now well established that in the Amazonian onchocerciasis focus, straddling between Venezuela and Brazil, the main vectors in the highland (hyperendemic) and lowland (hypoendemic) areas, are respectively Simulium guianense sensu lato Wise and S. oyapockense s.l. Floch and Abonnenc, investigation of the vectorial role of a third anthropophagic species, Simulium incrustatum Lutz has remained inconclusive. Here we compare the vector competence of S. incrustatum with that of S. oyapockense s.l. by conducting, in the Venezuelan part of the focus, a series of feeding experiments designed to analyze their relative: (a) microfilarial intakes when fed upon the same skin load; (b) proportions of microfilariae (mf) surviving damage inflicted by the cibarial armature (present in both species); and (c) infective (L3) larval outputs. Although the ability of S. oyapockense s.l. to ingest mf, for a given microfilaridermia, was markedly higher than that of S. incrustatum, the (density-dependent) proportions of those ingested mf that were damaged by the armature were also consistently higher, with the resulting output of L3 larvae being significantly lower in S. oyapockense s.l. than in S. incrustatum. These results indicate that S. incrustatum plays a more important role in onchocerciasis transmission in the Amazonian focus than previously realized. We discuss the implications of our findings for the control and elimination of onchocerciasis with mass administration of ivermectin in this focus, where the three main anthropophagic species often co-occur.
Lustigman, Sara; Makepeace, Benjamin L; Klei, Thomas R; Babayan, Simon A; Hotez, Peter; Abraham, David; Bottazzi, Maria Elena
Human onchocerciasis - commonly known as river blindness - is one of the most devastating yet neglected tropical diseases, leaving many millions in sub-Saharan Africa blind and/or with chronic disabilities. Attempts to eliminate onchocerciasis, primarily through the mass drug administration of ivermectin, remains challenging and has been heightened by the recent news that drug-resistant parasites are developing in some populations after years of drug treatment. Needed, and needed now, in the fight to eliminate onchocerciasis are new tools, such as preventive and therapeutic vaccines. This review summarizes the progress made to advance the onchocerciasis vaccine from the research laboratory into the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.
The L3-stage-specific chitinase OvCHT1 has been implicated in the development of Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known anthelmintic drug, was previously discovered as a potent and specific OvCHT1 inhibitor. As closantel is also a known protonophore, we performed a simple scaffold modulation to map out the structural features that are relevant for its individual or dual biochemical roles. Furthermore, we present that either OvCHT1 inhibition or protonophoric activity was capable of affecting O. volvulus L3 molting and that the presence of both activities in a single molecule yielded more potent inhibition of the nematode’s developmental process. PMID:24918716
Gooyit, Major; Tricoche, Nancy; Lustigman, Sara; Janda, Kim D
The L3-stage-specific chitinase OvCHT1 has been implicated in the development of Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known anthelmintic drug, was previously discovered as a potent and specific OvCHT1 inhibitor. As closantel is also a known protonophore, we performed a simple scaffold modulation to map out the structural features that are relevant for its individual or dual biochemical roles. Furthermore, we present that either OvCHT1 inhibition or protonophoric activity was capable of affecting O. volvulus L3 molting and that the presence of both activities in a single molecule yielded more potent inhibition of the nematode's developmental process.
Krueger, A; Fischer, P; Morales-Hojas, R
Filarial parasites of the genus Onchocerca are found in a broad spectrum of ungulate hosts. One species, O. volvulus, is a human parasite that can cause severe disease (onchocerciasis or 'river blindness'). The phylogenetic relationships and the bionomics of many of the nearly 30 known species remain dubious. Here, the phylogeny of 11 species representing most major lineages of the genus is investigated by analysing DNA sequences from three mitochondrial genes (ND5, 12S and 16S rRNA) and portions of the intergenic spacer of the nuclear 5s rRNA. Special emphasis is given to a clade containing a yet unassigned specimen from Uganda (O. sp. 'Siisa'), which appears to be intermediate between O. volvulus and O. ochengi. While the latter can be differentiated by the O-150 tandem repeat commonly used for molecular diagnostics, O. volvulus and O. sp.'Siisa' cannot be differentiated by this marker. In addition, a worm specimen from an African bushbuck appears to be closely related to the bovine O. dukei and represents the basal taxon of the human/bovine clade. At the base of the genus, our data suggest O. flexuosa (red deer), O. ramachandrini (warthog) and O. armillata (cow) to be the representatives of ancient lineages. The results provide better insight into the evolution and zoogeography of Onchocerca. They also have epidemiological and taxonomic implications by providing a framework for more accurate molecular diagnosis of filarial larvae in vectors.
Three cases of volvulus of the caecum are presented and their symptoms and treatment are discussed. It is suggested that this condition may be commoner than is thought and would be diagnosed more frequently if considered in the differential diagnosis. ImagesFig. 1Fig. 2Fig. 3 PMID:13809057
Sana, Landolsi; Ali, Gassara; Kallel, Helmi; Amine, Baklouti; Ahmed, Saadaoui; Mohamed Ali, Elouer; Wajdi, Chaeib; Saber, Mannaï
We report a case of spontaneous transverse colon volvulus in a young healthy woman. It constitutes an unusual case since it occurred in a young healthy woman with a subacute onset and no aetiological factor has been found. Its diagnosis is still challenging. Prompt recognition with emergency intervention constitutes the key to successful outcome. PMID:23785565
Sana, Landolsi; Ali, Gassara; Kallel, Helmi; Amine, Baklouti; Ahmed, Saadaoui; Ali, Elouer Mohamed; Wajdi, Chaeib; Saber, Mannaï
We report a case of spontaneous transverse colon volvulus in a young healthy woman. It constitutes an unusual case since it occurred in a young healthy woman with a subacute onset and no aetiological factor has been found. Its diagnosis is still challenging. Prompt recognition with emergency intervention constitutes the key to successful outcome.
Onchocerciasis is an infection caused by the filarial worm Onchocerca volvulus, which can eventually result in blindness. The lack of an effective macrofilaricide and the possible development of ivermectin-resistant strains of O. volvulus necessitate the need for alternative treatment strategies. We have shown that targeting the L3-stage-specific chitinase OvCHT1 impairs the shedding of the filarial cuticle. In our continued efforts to discover OvCHT1 inhibitors, we identified the β-carboline alkaloid scaffolding as a chitinase inhibitor that is capable of penetrating the worm cuticle. Herein, we disclose the rich polypharmacology of the β-carboline class of compounds as an approach to abrogate the molting of the parasite and thus the initiation of infection in the human host. PMID:25815157
Lamberton, Poppy H. L.; Cheke, Robert A.; Winskill, Peter; Tirados, Iñaki; Walker, Martin; Osei-Atweneboana, Mike Y.; Biritwum, Nana-Kwadwo; Tetteh-Kumah, Anthony; Boakye, Daniel A.; Wilson, Michael D.; Post, Rory J.; Basañez, María-Gloria
Background The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control. We present spatial and temporal patterns of onchocerciasis transmission in relation to ivermectin treatment history. Methodology/Principal Findings Host-seeking and ovipositing blackflies were collected from seven villages in four regions of Ghana with 3–24 years of CDTI at the time of sampling. A total of 16,443 flies was analysed for infection; 5,812 (35.3%) were dissected for parity (26.9% parous). Heads and thoraces of 12,196 flies were dissected for Onchocerca spp. and DNA from 11,122 abdomens was amplified using Onchocerca primers. A total of 463 larvae (0.03 larvae/fly) from 97 (0.6%) infected and 62 (0.4%) infective flies was recorded; 258 abdomens (2.3%) were positive for Onchocerca DNA. Infections (all were O. volvulus) were more likely to be detected in ovipositing flies. Transmission occurred, mostly in the wet season, at Gyankobaa and Bosomase, with transmission potentials of, respectively, 86 and 422 L3/person/month after 3 and 6 years of CDTI. The numbers of L3/1,000 parous flies at these villages were over 100 times the WHO threshold of one L3/1,000 for transmission control. Vector species influenced transmission parameters. At Asubende, the number of L3/1,000 ovipositing flies (1.4, 95% CI = 0–4) also just exceeded the threshold despite extensive vector control and 24 years of ivermectin distribution, but there were no infective larvae in host-seeking flies. Conclusions/Significance Despite repeated ivermectin treatment, evidence of O. volvulus transmission was documented in all seven villages and above the WHO threshold in two. Vector species influences transmission through biting and parous rates and vector competence, and should be included in transmission models
Lamberton, Poppy H L; Cheke, Robert A; Winskill, Peter; Tirados, Iñaki; Walker, Martin; Osei-Atweneboana, Mike Y; Biritwum, Nana-Kwadwo; Tetteh-Kumah, Anthony; Boakye, Daniel A; Wilson, Michael D; Post, Rory J; Basañez, María-Gloria
The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control. We present spatial and temporal patterns of onchocerciasis transmission in relation to ivermectin treatment history. Host-seeking and ovipositing blackflies were collected from seven villages in four regions of Ghana with 3-24 years of CDTI at the time of sampling. A total of 16,443 flies was analysed for infection; 5,812 (35.3%) were dissected for parity (26.9% parous). Heads and thoraces of 12,196 flies were dissected for Onchocerca spp. and DNA from 11,122 abdomens was amplified using Onchocerca primers. A total of 463 larvae (0.03 larvae/fly) from 97 (0.6%) infected and 62 (0.4%) infective flies was recorded; 258 abdomens (2.3%) were positive for Onchocerca DNA. Infections (all were O. volvulus) were more likely to be detected in ovipositing flies. Transmission occurred, mostly in the wet season, at Gyankobaa and Bosomase, with transmission potentials of, respectively, 86 and 422 L3/person/month after 3 and 6 years of CDTI. The numbers of L3/1,000 parous flies at these villages were over 100 times the WHO threshold of one L3/1,000 for transmission control. Vector species influenced transmission parameters. At Asubende, the number of L3/1,000 ovipositing flies (1.4, 95% CI = 0-4) also just exceeded the threshold despite extensive vector control and 24 years of ivermectin distribution, but there were no infective larvae in host-seeking flies. Despite repeated ivermectin treatment, evidence of O. volvulus transmission was documented in all seven villages and above the WHO threshold in two. Vector species influences transmission through biting and parous rates and vector competence, and should be included in transmission models. Oviposition traps could augment vector collector methods for monitoring
Atamanalp, Sabri Selcuk; Kisaoglu, Abdullah; Ozogul, Bunyami; Kantarci, Mecit; Disci, Esra; Bulut, O Hakan; Aksungur, Nurhak; Atamanalp, Refik Selim
Sigmoid volvulus during pregnancy is a rare complication, and as of 2012, fewer than 100 cases had been reported. In this report, we present a 30 year-old pregnant woman with sigmoid volvulus, and we discuss this rare entity.
Djafsia, B; Ndjonka, D; Dikti, J V; van Hoorn, S; Manchang, K; Brattig, N; Liebau, E
Excretory-secretory (ES) products of nematodes and other helminths are the first molecules to interact with cell surfaces and soluble proteins within the host. In the present study, ES products of the filarial nematode Onchocerca ochengi were investigated as a model for Onchocerca volvulus, the causative agent of river blindness. These products were collected from adult and larval stages in vitro over a period of 7 days, to compare their immunological recognition in cattle and human sera, infected with species of Onchocerca. From the 156 sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) ES products or extracts, protein bands showed different patterns between female and male products. A comparison of antibody recognition of the different ES products by sera from infected cattle and humans, when analysed by enzyme-linked immunosorbent assay (ELISA), revealed a relatively higher reactivity of the female somatic extract to human and cattle sera compared to ES products of both genders. Nevertheless, similar reactivity of the O. ochengi male and female ES products to human and cattle sera was noticed. As a result, the interaction of ES products with the surface of the host and immune system often led to host responses, including the generation of antibodies. The O. ochengi ES products are therefore good sources of potential immunogenic proteins. The identification of these ES products is in progress, with the aim of developing vaccine candidates against human onchocerciasis.
Recent studies on the biology and ecology of adult blackflies in relation to the transmission of human onchocerciasis in Guatemala are reviewed. First, earlier studies on the transmission of the disease since its discovery by Dr. R. Robles in 1915 are outlined. Second, eleven blackfly species caught on humans are evaluated for vector status on the basis of their natural and experimental infections with third-stage larvae of Onchocerca volvulus, and Simulium ochraceum,* S. metallicum* and S. callidum are confirmed as natural vectors of the disease in Guatemala in descending order of importance, whereas S. gonzalezi, S. haematopotum, S. veracruzanum and S. horacioi are potential vectors. Third, the migration and fate of O. volvulus microfilariae ingested by female blackflies are highlighted on the basis of the findings of the cibarial armature of S. ochraceum and physiological incompatibility of S. metallicum as main barriers against microfilariae, both of which greatly decrease the number of ingested O. volvulus microfilariae developing to the third-stage larvae per female. Fourth, among many ecological factors of female blackfly populations, geographical and altitudinal distributions, habits of blood feeding, host preferences for blood feeding, preference for human body parts, parous rates, daily and seasonal fluctuations of biting activities, in particular, of parous females, gonotrophic cycle, longevity, flight range, and annual transmission potential are reviewed, and their influences on the transmission dynamics of the disease agents are considered. Fifth, effects of air temperatures on the O. volvulus–S. ochraceum complex are examined, with a special reference to the characteristic altitudinal distributions of the disease. The importance of reliable identification of both the vector blackfly species and filarial larvae found in female blackflies is emphasized to understand the transmission of the disease. [*It is now known that these two species are actually
Background Among ocular vector-borne pathogens, Onchocerca volvulus, the agent of the so-called “river blindness”, affects about 37 million people globally. Other Onchocerca spp. have been sporadically reported as zoonotic agents. Cases of canine onchocerciasis caused by Onchocerca lupi are on the rise in the United States and Europe. Its zoonotic role has been suspected but only recently ascertained in a single case from Turkey. The present study provides further evidence on the occurrence of O. lupi infesting human eyes in two patients from Turkey (case 1) and Tunisia (case 2). The importance of obtaining a correct sample collection and preparation of nematodes infesting human eyes is highlighted. Methods In both cases the parasites were identified with morpho-anatomical characters at the gross examination, histological analysis and anatomical description and also molecularly in case 1. Results The nematode from the first case was obviously O. lupi based on their morphology at the gross examination, histological analysis and anatomical description. In the second case, although the diagnostic cuticular characters were not completely developed, other features were congruent with the identification of O. lupi. Furthermore, the morphological identification was also molecularly confirmed in the Turkish case. Conclusions The results of this study suggest that O. lupi infestation is not an occasional finding but it should be considered in the differential diagnosis of other zoonotic helminths causing eye infestation in humans (e.g., D. immitis and Dirofilaria repens). Both cases came from areas where no cases of canine onchocerciasis were previously reported in the literature, suggesting that an in depth appraisal of the infestation in canine populations is necessary. Physicians and ophthalmologists are advised on how to preserve nematode samples recovered surgically, to allow a definitive, correct etiological diagnosis. PMID:22541132
Cho-Ngwa, Fidelis; Mbua, Eric Ngalle; Nchamukong, Kingsley G; Titanji, Vincent P K
An Onchocerca secretory alkaline phosphatase (E.C. 22.214.171.124) of molecular weight 90 kDa when in crude extract, but which dimerises to about 180 kDa upon purification, was detected, purified and characterised. The enzyme was found to be secreted by both O. ochengi and O. volvulus worms. It was shown to be of Onchocerca origin by Western blotting with bovine onchocerciasis sera and by its time-dependent release in cultures. The O. ochengi enzyme was purified to near homogeneity by a combination of polyethylene glycol precipitation, DEAE-cellulose chromatography and preparative electrophoresis. About 0.96 mg of the active enzyme was purified from 48.4 mg of the crude parasite-released products, giving a purification fold of 71.45 and a yield of 8.7%. The purified enzyme exhibited a typical Michaelis-Menten kinetics with optimum activity on p-nitrophenylphosphate (p-NPP) at pH 10.2. Its apparent K(m) for p-NPP was 0.56+/-0.03 mM and it required Mg(2+) and dithiothreitol (DTT) for stability throughout its purification. Sodium dodecyl sulphate at 2% (w/v) did not inhibit the enzyme activity, but apparently stabilised it during freezing. Inorganic phosphate inhibited the enzyme competitively with an apparent inhibition constant (K(i)) of 3.33+/-0.04 mM, whereas l-phenylalanine inhibited it in a mixed way with a K(i) of 3.18+/-0.03 mM. While contributing to the understanding of metabolism in Onchocerca, the present apparently unique enzyme which is likely to serve in the nutrition of the parasite could be further characterised as a macrofilaricide target or diagnostic marker in onchocerciasis.
Donnelly, J J; Xi, M S; Haldar, J P; Hill, D E; Lok, J B; Khatami, M; Rockey, J H
Hartley guinea pigs were injected with microfilariae (Mf) of Onchocerca lienalis as a model for acute inflammatory responses to Mf in human Onchocerca volvulus infection. IgG autoantibody reactive with a 3 M KCl extract of guinea pig cornea was detected by ELISA in the serum of guinea pigs injected with O. lienalis Mf three or more times sub-conjunctivally, or two or more times subcutaneously. Administration of the microfilaricides diethylcarbamazine citrate and ivermectin did not alter the proportion of animals expressing autoantibody or the mean autoantibody titer. The severity of acute corneal inflammatory reactions to Mf was similar in animals with and without circulating autoantibody. Although autoantibody responses did not correlate with acute corneal inflammatory reactions to dead Mf, the ability of Mf to induce formation of an antibody reactive with a component of autologous cornea suggests that autoimmune mechanisms might participate in chronic onchocercal lesions in the cornea, eg, sclerosing keratitis.
Armstrong, Stuart D.; Xia, Dong; Bah, Germanus S.; Krishna, Ritesh; Ngangyung, Henrietta F.; LaCourse, E. James; McSorley, Henry J.; Kengne-Ouafo, Jonas A.; Chounna-Ndongmo, Patrick W.; Wanji, Samuel; Enyong, Peter A.; Taylor, David W.; Blaxter, Mark L.; Wastling, Jonathan M.; Tanya, Vincent N.; Makepeace, Benjamin L.
Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilize the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin domain family, which was originally described from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp
Attout, Tarik; Hoerauf, Achim; Dénécé, Gaëlle; Debrah, Alexander Yaw; Marfo-Debrekyei, Yeboah; Boussinesq, Michel; Wanji, Samuel; Martinez, Valérie; Mand, Sabine; Adjei, Ohene; Bain, Odile
Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is a parasitic disease leading to debilitating skin disease and blindness, with major economic and social consequences. The pathology of onchocerciasis is principally considered to be a consequence of long-standing host inflammatory responses. In onchocerciasis a subcutaneous nodule is formed around the female worms, the core of which is a dense infiltrate of inflammatory cells in which microfilariae are released. It has been established that the formation of nodules is associated with angiogenesis. In this study, we show using specific markers of endothelium (CD31) and lymphatic endothelial cells (Lyve-1, Podoplanin) that not only angiogenesis but also lymphangiogenesis occurs within the nodule. 7% of the microfilariae could be found within the lymphatics, but none within blood vessels in these nodules, suggesting a possible route of migration for the larvae. The neovascularisation was associated with a particular pattern of angio/lymphangiogenic factors in nodules of onchocerciasis patients, characterized by the expression of CXCL12, CXCR4, VEGF-C, Angiopoietin-1 and Angiopoietin-2. Interestingly, a proportion of macrophages were found to be positive for Lyve-1 and some were integrated into the endothelium of the lymphatic vessels, revealing their plasticity in the nodular micro-environment. These results indicate that lymphatic as well as blood vascularization is induced around O. volvulus worms, either by the parasite itself, e.g. by the release of angiogenic and lymphangiogenic factors, or by consecutive host immune responses. PMID:20011036
Attout, Tarik; Hoerauf, Achim; Dénécé, Gaëlle; Debrah, Alexander Yaw; Marfo-Debrekyei, Yeboah; Boussinesq, Michel; Wanji, Samuel; Martinez, Valérie; Mand, Sabine; Adjei, Ohene; Bain, Odile; Specht, Sabine; Martin, Coralie
Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is a parasitic disease leading to debilitating skin disease and blindness, with major economic and social consequences. The pathology of onchocerciasis is principally considered to be a consequence of long-standing host inflammatory responses. In onchocerciasis a subcutaneous nodule is formed around the female worms, the core of which is a dense infiltrate of inflammatory cells in which microfilariae are released. It has been established that the formation of nodules is associated with angiogenesis. In this study, we show using specific markers of endothelium (CD31) and lymphatic endothelial cells (Lyve-1, Podoplanin) that not only angiogenesis but also lymphangiogenesis occurs within the nodule. 7% of the microfilariae could be found within the lymphatics, but none within blood vessels in these nodules, suggesting a possible route of migration for the larvae. The neovascularisation was associated with a particular pattern of angio/lymphangiogenic factors in nodules of onchocerciasis patients, characterized by the expression of CXCL12, CXCR4, VEGF-C, Angiopoietin-1 and Angiopoietin-2. Interestingly, a proportion of macrophages were found to be positive for Lyve-1 and some were integrated into the endothelium of the lymphatic vessels, revealing their plasticity in the nodular micro-environment. These results indicate that lymphatic as well as blood vascularization is induced around O. volvulus worms, either by the parasite itself, e.g. by the release of angiogenic and lymphangiogenic factors, or by consecutive host immune responses.
Blake, Erin; Gonzalez, Eduardo; Pieracci, Frederic
Background. Sigmoid volvulus is a rare complication of pregnancy and the puerperium. Case. A 19-year-old patient, gravida 1 para 0 at 41 0/7 weeks of gestation, admitted for late-term induction of labor underwent an uncomplicated primary low transverse cesarean delivery for arrest of descent. Her postoperative period was complicated by sudden onset of abdominal pain and the ultimate diagnosis of sigmoid volvulus. Conclusion. Prompt surgical evaluation of an acute abdomen in the postpartum period is essential; delayed diagnosis and treatment can lead to significant maternal morbidity and mortality. PMID:28251004
Metuge, Jonathan Alunge; Nyongbela, Kennedy D; Mbah, James A; Samje, Moses; Fotso, Ghislain; Babiaka, Smith B; Cho-Ngwa, Fidelis
The lack of a safe and effective adult worm drug and the emergence of resistant animal parasite strains to the only recommended drug, the microfilaricide, ivermectin put many at risk of the devastating effects of the onchocerciasis. The present study was undertaken to investigate the acclaimed anti-Onchocerca activity of the roots/rhizomes of Cyperus articulatus in the traditional treatment of onchocerciasis in North Western Cameroon and to assess the plant as a new source of potential filaricidal lead compounds. Crude extracts were prepared from the dried plant parts using hexane, methylene chloride and methanol. The antifilarial activity was evaluated in vitro on microfilariae (Mfs) and adult worms of the bovine derived Onchocerca ochengi, a close relative of Onchocerca volvulus. The viabilities of microfilariae and adult male worms were determined based on motility reduction, while for the adult female worms the viability was based on the standard MTT/formazan assay. Cytotoxicity of the active extract was assessed on monkey kidney epithelial cells in vitro and the selectivity indices (SI) were determined. Acute toxicity of the promising extract was investigated in mice. Chemical composition of the active extract was unraveled by GC/MS analysis. Only the hexane extract, an essential oil exhibited anti-Onchocerca activity. The oil killed both the microfilariae and adult worms of O. ochengi in a dose manner dependently, with IC50s of 23.4 μg/ml on the Mfs, 23.4 μg/ml on adult male worms and 31.25 μg/ml on the adult female worms. Selectivity indices were 4, 4, and 2.99 for Mfs, adult males and adult females, respectively. At a single limit dose of 2000 mg/kg body weight, none of 6 mice that received the essential oil by gavage died. GC/MS analysis revealed the presence of terpenoids, hydrocarbons and fatty acids or fatty acid derivatives as components of the oil. The essential oil from the roots/rhizomes of Cyperus articulatus is active against O. ochengi
Meytes, Vadim; Schulberg, Steven P.; Morin, Nicholas; Glinik, Galina
The incidence of hypothyroidism presenting with sigmoid volvulus, a phenomenon known as myxedema pseudovolvulus, is exceedingly rare. A male in his late thirties presented to our institution with a chief complaint of abdominal pain. The patient underwent CT scan, which was consistent with massive colonic dilatation with sigmoid volvulus. He was taken to the operating room for exploration and was found to have sigmoid volvulus and underwent a segmental resection. Postoperatively, the patient was newly diagnosed with severe hypothyroidism. PMID:27106615
Newland, H S; White, A T; Greene, B M; D'Anna, S A; Keyvan-Larijani, E; Aziz, M A; Williams, P N; Taylor, H R
Ivermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects. Images PMID:3046657
Newland, H S; White, A T; Greene, B M; D'Anna, S A; Keyvan-Larijani, E; Aziz, M A; Williams, P N; Taylor, H R
Ivermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects.
Boatin, B A; Toé, L; Alley, E S; Nagelkerke, N J D; Borsboom, G; Habbema, J D F
The standard assay for onchocerciasis diagnosis is microscopical detection of microfilariae in skin snips. Skin snipping is painful, requires appropriate sterilization of equipment, and may fail to diagnose light infections. Two alternatives are a polymerase chain reaction (PCR) test which detects parasite DNA in pieces or scrapings of skin and a test based on allergic reactions to topical application of diethylcarbamazine (DEC). We compared these 2 diagnostics with standard skin snip microscopy in 313 individuals from 2 villages in Guinea, with low prevalence after over 10 years of control by the Onchocerciasis Control Programme. Lower and upper bounds on sensitivities and specificities of these 3 tests were estimated. In addition, these parameters were estimated using 5 different statistical models. Where prevalence was low, PCR and the DEC patch test appeared to be more sensitive than skin snipping which has low sensitivity. As the DEC test is non-invasive, simple and cheap, it may provide a good alternative to skin snipping alone for surveillance in low prevalence areas.
Kale, O O
The effect of graded doses of diethylcarbamazine on the concentration of microfilariae in the hydrocoele fluid, urine and skin of patients suffering from onchocerciasis was studied. The results showed that a significant number of microfilariae migrated into hydrocoele fluid and urine immediately after the drug was given and thereafter returned to pre-treatment levels rather more quickly in the former than the latter. The increase was found to be roughly directly proportional to the intensity of infection in the skin. By contrast the skin concentration of microfilariae fell sharply after treatment and remained significantly lower than pre-treatment levels for over four weeks. The potential use to which these observations could be put with respect to clinical screening of drugs in onchocerciasis is discussed.
Spevakow, Andrea B.; Nibblett, Belle Marie D.; Carr, Anthony P.; Linn, Kathleen A.
A chronic, partial mesenteric volvulus was found on laparotomy of an adult Bernese mountain dog with a 4-month history of intermittent vomiting, diarrhea, and weight loss. The dog had elevated cholestatic and hepatocellular leakage enzymes, increased bile acids, azotemia, isosthenuria, and a hypokalemic, hypochloremic, metabolic alkalosis. The dog recovered fully following reduction of the volvulus. PMID:20357947
Chittal, R; Harris, D; Patel, A; Goodyear, S; Parkianathan, V
A 71-year-old female presented with recurrent sigmoid volvulus. In the current admission, her symptoms were not settling on conservative measures and subsequently went on to have laparotomy. During laparotomy, along with the sigmoid volvulus, there was associated gallbladder torsion. About 500 cases of gallbladder volvulus have been published in literature, however, in our literature search, the authors did not find any similar published case presenting with volvulus involving the gallbladder and the sigmoid colon at the same time. This patient went onto have cholecystectomy and sigmoid colectomy and had a good postoperative recovery and was discharged on the tenth postoperative day. At 6-week postoperative follow-up, she was doing well with no specific concerns.
Goldman, C D; Rudloff, M A; Ternberg, J L
An accepted experimental model for midgut volvulus was used to produce small bowel strangulation obstruction of 48 hours duration in Sprague-Dawley rats. A 93% perioperative mortality rate resulted after release of the volvulus. Treatment with three cytoprotective agents at the time of volvulus release resulted in the following mortality rates: superoxide dismutase, 89%; ibuprofen, 50%; prostaglandin E1 (PGE1, 11%. The predominant cause of death in all treatment groups was bowel infarction, with a smaller number succumbing to either sepsis or circulatory collapse. Concomitant administration of ephedrine or indomethacin to suppress prostaglandin E1's splanchnic vasodilatory activity did not cause any increase in mortality. A trial of aspirin, to simulate PGE's antiplatelet actions, showed no reduction in mortality when compared with detorsion alone. Prostaglandin E1 and, to a lesser extent, ibuprofen, appear to have cytoprotective effects during reperfusion of bowel compromised by volvulus, independent of their influence on the mesenteric vasculature and thrombogenesis.
Lovato, Raquel; Guevara, Angel; Guderian, Ronald; Proaño, Roberto; Unnasch, Thomas; Criollo, Hipatia; Hassan, Hassan K.; Mackenzie, Charles D.
Introduction: A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. Methodology and Principle Findings: Thirty-five rounds of ivermectin treatment occurred between 1991–2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39–101) and 72.7 (CI 42–116) in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1–15 years (between 82 and 98% of children present in the surveyed villages) tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. Significance: This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption. PMID:24853587
Cuadra, S A; Khalife, M E; Char, D J; Wax, M R; Halpern, D
We present the case of a 30-year-old man who developed a small bowel obstruction from an acute midgut volvulus 8 days after undergoing a laparoscopic appendectomy. There was no evidence of congenital malrotation or midgut volvulus on the initial computed tomography (CT) scan or at laparoscopy. Subsequently, a midgut volvulus developed in the absence of congenital malrotation.
Renz, A; Wenk, P; Anderson, J; Fuglsang, H
The prevalence and intensity of infection with Onchocerca volvulus were assessed in population surveys in nine villages, situated at different distances from Simulium damnosum s.l. breeding sites. The prevalence varied from 48 to 89%, the arithmetic mean densities of microfilariae per skin snip were between 16 and 109, and severe ocular lesions were found in from 1 to 22% of patients. Annual Transmission Potentials (ATP) were measured for up to three years in the near vicinity of nine villages at several fly-catching sites. Weighted means of the ATP over the three years, and of the sojourn times of the human population, were calculated at three of the villages, where the prevalence of onchocerciasis was 51, 61 and 89%. An average ATP of 100 larvae or less in the head, thorax and abdomen of the flies was associated with an onchocerciasis prevalence of 50 to 60%, a mean microfilarial density below 40 microfilariae per skin-snip, less than 5% of ocular lesions, and no onchocercal blindness. This value might therefore be considered to be an indication of the level to which the transmission must be reduced in the savanna in order to prevent the occurrence of severe ocular lesions or blindness. It is lower than the present level accepted by the Onchocerciasis Control Programme in the Volta River Basin.
Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Karcaaltıncaba, Musturay
Abnormal location of the spleen, which is called wandering spleen, results from laxity or absence of the splenic pedicle. In the presence of an elongated splenic pedicle, torsion of the spleen or neighboring organs may occur, which results in acute or chronic abdominal pain. In this case report, we present imaging findings of a wandering spleen that manifested with volvulus of the pancreas.
Mahalik, Santosh K.; Khanna, Sanat; Menon, Prema
A 2-year-old boy with heterotaxy syndrome with associated polysplenia, ventricular septal defect, and malrotation of gut with volvulus is presented. There was delay in diagnosis due to the unusual plain abdominal radiography findings. At laparotomy, the midgut was also found to be enclosed in a thin transparent cocoon. PMID:22869985
Mansoor, Khizer; Al Hamidi, Sa'ad; Khan, Abdul Mannan; Samujh, Ram
An 11-year-old female child presented with abdominal pain, vomiting and constipation. An exploratory laparotomy revealed a cecal volvulus due to a congenital band and malfixation of the cecum. This was treated by excision of the band, derotation and decompression of cecum though an appendiceal stump suction. PMID:20376252
Cho-Ngwa, Fidelis; Monya, Elvis; Azantsa, Boris K; Manfo, Faustin Pascal T; Babiaka, Smith B; Mbah, James A; Samje, Moses
Onchocerciasis is the world's second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L. loa microfilariae (mf). Fourteen extracts from two medicinal plants, Tragia benthami and Piper umbellatum were screened in vitro against Onchocerca ochengi parasite and L. loa mf. Activities of extracts on male worms and microfilariae were assessed by motility reduction, while MTT/Formazan assay was used to assess biochemically the death of female worms. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney cells and Balb/c mice, respectively. At 500 μg/mL, all extracts showed 100 % activity on Onchocerca ochengi males and microfilariae, while 9 showed 100 % activity on female worms. The methylene chloride extract of Piper umbellatum leaves was the most active on adult male and female worms (IC50s: 16.63 μg/mL and 35.65 μg/mL, respectively). The three most active extracts on Onchocerca ochengi females were also highly active on Loa loa microfilariae, with IC50s of 35.12 - 13.9 μg/mL. Active extracts were generally more toxic to the worms than to cells and showed no acute toxicity to Balb/c mice. Phytochemical screening revealed the presence of saponins, steroids, tannins and flavanoids in the promising extracts. These results unfold potential sources of novel anti-Onchocerca lead compounds and validate the traditional use of the plants in onchocerciasis treatment.
Kang, David J.; D'Alessio, Matthew; Pan, Andrew S.; Jaffe, Victor A.
Mesenteroaxial volvulus is a form of gastric volvulus that rotates around the short axis of the stomach. Mesenteroaxial volvulus typically presents secondary to an anatomical defect with symptoms that include epigastric pain, retching, dysphagia and early satiety. Our patient presented with episodic abdominal pain, nausea and vomiting for 2 years. Previous imaging was unremarkable but an esophagogastroduodenoscopy done when the patient most recently presented with abdominal pain revealed a mesenteroaxial volvulus. He underwent a laparoscopic gastrostomy-tube gastropexy and has not had any recurrence of his symptoms to date. This case illustrates the difficulties in diagnosing an intermittent volvulus as untimely imaging of a temporarily unfolded volvulus can delay diagnosis and treatment. PMID:24964322
Botto, Carlos; Basañez, María-Gloria; Escalona, Marisela; Villamizar, Néstor J; Noya-Alarcón, Oscar; Cortez, José; Vivas-Martínez, Sarai; Coronel, Pablo; Frontado, Hortencia; Flores, Jorge; Graterol, Beatriz; Camacho, Oneida; Tovar, Yseliam; Borges, Daniel; Morales, Alba Lucia; Ríos, Dalila; Guerra, Francisco; Margeli, Héctor; Rodriguez, Mario Alberto; Unnasch, Thomas R; Grillet, María Eugenia
The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. From 2010 to 2012-2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012-2013 were, respectively, under 1% and 20 L3/person/transmission season. Serology in children aged 1-10 years demonstrated that although 26 out of 396 (7%) individuals still had Ov-16 antibodies, only 4/218 (2%) seropositives were aged 1-5 years. We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75% of the Yanomami population and 70% of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus.
Cheke, Robert A.; Basáñez, Maria-Gloria; Perry, Malorie; White, Michael T.; Garms, Rolf; Obuobie, Emmanuel; Lamberton, Poppy H. L.; Young, Stephen; Osei-Atweneboana, Mike Y.; Intsiful, Joseph; Shen, Mingwang; Boakye, Daniel A.; Wilson, Michael D.
Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25°C, the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29°C and 34°C, about 3°C and 7°C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 29°C and of savannah flies (Ghana) at 30°C. Small temperature increases (less than 2°C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 33°C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13–41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions. PMID:25688018
Cheke, Robert A; Basáñez, Maria-Gloria; Perry, Malorie; White, Michael T; Garms, Rolf; Obuobie, Emmanuel; Lamberton, Poppy H L; Young, Stephen; Osei-Atweneboana, Mike Y; Intsiful, Joseph; Shen, Mingwang; Boakye, Daniel A; Wilson, Michael D
Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25°C, the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29°C and 34°C, about 3°C and 7°C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 29°C and of savannah flies (Ghana) at 30°C. Small temperature increases (less than 2°C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 33°C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13-41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions.
Rosenblat, Juliana M; Rozenblit, Alla M; Wolf, Ellen L; DuBrow, Ronelle A; Den, Elana I; Levsky, Jeffrey M
To assess the diagnostic performance of computed tomographic (CT) and radiographic (as seen on CT topograms) signs of cecal volvulus. In this institutional review board-approved, HIPAA-compliant retrospective study, the CT and CT topogram findings in 11 patients (one man, 10 women; age range, 26-100 years) with surgically confirmed cecal volvulus and 12 control patients were reviewed. The control subjects had suspicious radiographs, had undergone CT within 24 hours of radiography, and had received a clinical diagnosis other than cecal volvulus. Three radiologists independently evaluated the CT topograms for cecal distention, the coffee bean sign, cecal apex location, and distal colon decompression. CT images were analyzed for cecal distention, cecal apex location, distal colon decompression, and presence or absence of the whirl, ileocecal twist, transition point(s), the X-marks-the-spot, and the split wall. Sensitivity, specificity, and predictive values were computed. Baseline statistical values for the cecal volvulus and control groups were analyzed by using a two-tailed Z test to compare proportions with a threshold confidence interval of 95%. CT findings of bowel ischemia (free air or fluid, pneumatosis intestinalis, portal venous gas, mesenteric stranding) were correlated with pathology report findings. On CT topograms, greater than 10-cm cecal distention, coffee bean sign, and left upper quadrant cecal apex had sensitivities of 45% (five of 11 patients), 27% (three of 11 patients), and 45% (five of 11 patients), respectively, and specificities of 100% (12 of 12 control subjects), 92% (11 of 12 control subjects), and 100% (12 of 12 control subjects), respectively. Distal colon decompression had sensitivities and specificities of 91% (10 of 11 patients) and 83% (10 of 12 control subject), respectively, on topograms and of 91% (10 of 11 patients) and 92% (11 of 12 patients), respectively, on CT images. On cross-sectional CT images, greater than 10-cm cecal
Farber, Benjamin A.; Lim, Irene Isabel P.; Murphy, Jennifer M.; Price, Anita P.; Abramson, Sara J.; La Quaglia, Michael P.
Gastric volvulus is a rare post-pneumonectomy complication. Although it has been described previously, published cases are limited to an older patient population. We report the youngest case of postpneumonectomy gastric volvulus to date, occurring in an 18-year-old male with a history of inflammatory myofibroblastic pseudotumor who underwent left intrapericardial pneumonectomy, and presented 13 years later with chronic intermittent mesenteroaxial gastric volvulus. While postpneumonectomy gastric volvulus is a rare occurrence, it should remain in the differential diagnosis in postoperative thoracic surgical patients presenting with chest pain. PMID:26504742
Trees, A J; McCall, P J; Davies, J B
As part of a study to assess to what extent Onchocerca-like infections in S. damnosum s.l. in the forest zone of Sierra Leone were likely to be of bovine origin, Onchocerca infections were studied by post mortem examination of cattle killed at Bo abattoir and by examination of skin biopsies from cattle born and reared at Njala, in the forest zone, and Musaia, in the savanna zone. Post mortem studies of 45 cattle which had originated from northern Sierra Leone and Guinea revealed a prevalence of infection with microfilariae (mff) of O. gutturosa of 87%, O. ochengi 18% and O. armillata 7%. Examination of indigenous cattle revealed transmission of O. gutturosa in both forest (Njala) and savanna (Musaia) areas, and age prevalence analysis at Njala indicated a high intensity of transmission. Autochthonous transmission of O. armillata occurred at Njala at low intensity. Onchocerca gutturosa from Sierra Leone resembled U.K. isolates of O. gutturosa in terms of glucose phosphate isomerase electrophoretic mobility and acid phosphatase activity of in situ-stained mff. Hide mapping of O. gutturosa revealed skin concentrations of mff dorsally at the withers area and also ventrally at the dewlap, brisket and upper forelegs. It was concluded that only O. gutturosa was transmitted at high intensity to cattle in the forest zone of Sierra Leone. Hence, subsequent studies were directed towards determining the vector of O. gutturosa.
de Korte, Niels; Grutters, Cornelis T; Snellen, Jacob P
A 24-year-old man presented to the emergency department with acute onset, colicky, abdominal pain. A CT scan showed the "whirl sign" diagnostic of small bowel volvulus. Diagnosis of a small bowel volvulus can be challenging, and CT scan is the imaging modality of choice.
Callahan, H.L.; Wakeman, J.M.; Crouch, R.K.; James, E.R.
A radiolabel uptake viability assay for Onchocerca cervicalis using (/sup 3/H)2-deoxy-D-glucose in Hanks' balanced salt solution, pH 7.5, at 30 C is described and compared to the traditional visual motility assay. A correlation of r = 0.92 between the assays was found, with the radiolabel uptake method apparently a more sensitive indicator of microfilarial viability.
Aras, Abbas; Kızıltan, Remzi; Batur, Abdussamet; Çelik, Sebahattin; Yılmaz, Özkan; Kotan, Çetin
Introduction Sigmoid volvulus is the most prevalent type of colonic volvulus. Colon cancer is seen less where sigmoid volvulus is common, so it is rare to see that colon cancer is synchronous with sigmoid volvulus. Presentation of case We would like to present a case of sigmoid volvulus caused by colon cancer in a male patient aged 80 who was referred to the hospital with toxaemic shock presentation. Discussion Sigmoid cancer can be presented as sigmoid volvulus to the emergency department. In intestinal obstruction early diagnosis is of crucial importance. Computarized tomography is a diagnosis tool that should be preferred both in the diagnosis of obstruction and in detecting its cause, localisation, degree and complications. Conclusion When surgery is performed due to the urgent colonic obstruction in colonic volvulus diagnosed patients, a colon tumour should be considered in the same column loops or in the distal colon. We believe that CT is the method that should be preferred in large-bowel obstruction suspected patients. PMID:26519810
Bosch, Felix; Manzanell, Ralph; Mathis, Alexander
Twenty-seven species of the genus Onchocerca (Nematoda; Filarioidea) can cause a vector-borne parasitic disease called onchocercosis. Most Onchocerca species infect wild and domestic ungulates or the dog, and one species causes river blindness in humans mainly in tropical Africa. The European red deer (Cervus e. elaphus) is host to four species, which are transmitted by blackflies (simuliids) or biting midges (ceratopogonids). Two species, Onchocerca flexuosa and Onchocerca jakutensis, produce subcutaneous nodules, whereas Onchocerca skrjabini and Onchocerca garmsi live free in the hypodermal serous membranes. During the hunting season, September 2013, red deer (n = 25), roe deer (Capreolus c. capreolus, n = 6) and chamois (Rupicapra r. rupicapra, n = 7), all shot in the Grisons Region (Switzerland) were investigated for the presence of subcutaneous nodules which were enzymatically digested, and the contained Onchocerca worms were identified to species by light and scanning electron microscopy as well as by PCR/sequencing. In addition, microfilariae from skin samples were collected and genetically characterized. Neither nodules nor microfilariae were discovered in the roe deer and chamois. Adult worms were found in 24% of red deer, and all of them were identified as O. jakutensis. Two morphologically different microfilariae were obtained from five red deer, and genetic analysis of a skin sample of one red deer indicated the presence of another Onchocerca species. This is the first report of O. jakutensis in Switzerland with a prevalence in red deer similar to that in neighbouring Germany.
Macleod, R; Hollowood, A
Gastric volvulus is a rare complication of diaphragmatic rupture. We report the case of an 82-year-old man who presented following an out-of-hospital cardiac arrest. Chest radiography and thoracic computed tomography revealed an acute gastric volvulus and a chronic diaphragmatic hernia containing transverse colon and abdominal viscera. He had complained of retching and associated epigastric pain prior to collapse, and had sustained a motorcycle accident approximately 60 years earlier. Insertion of a nasogastric tube was unsuccessful (completing Borchardt’s diagnostic triad) and his condition prevented both operative and endoscopic reduction of his volvulus. He died soon afterwards. PMID:25245717
Abadía-Barnó, Pedro; Coll-Sastre, Magdalena; Picón-Serrano, Carmen; Sanjuanbenito-Dehesa, Alfonso; Cabañas-Montero, Jacobo
The gallbladder volvulus is defined as the rotation of the gallbladder on its mesentery along the axis of the cystic duct and cystic artery. It is an extremely rare surgical disease and definitive diagnosis is usually made during surgery. A 78 year old woman presented with upper right quadrant abdominal pain, with no comorbidities and no other accompanying symptoms. Analysis revealed haemodynamic instability and leukocytosis. Computed tomography of abdomen showed an acute cholecystitis. During emergency right hypochondrium laparotomy, the gallbladder was found to be twisted counterclockwise with huge gangrenous gallbladder distal. Open cholecystectomy was performed and after the surgery, the patient was discharged in a few days. Gallbladder volvulus, or gallbladder torsion, is a rare condition and should be considered when clinical and imaging findings of complicated cholecystitis are present. The performance of urgent laparoscopic surgery would be first option to avoid perforation, peritonitis and haemodynamic instability. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.
Thomson, PM; Bohra, A
Introduction We present a rare case of a liver volvulus, stomach and transverse colon herniating through the diaphragm. This scenario has not been reported previously. We discuss the presentation and management of this interesting case. Case history A 65-year-old woman with a history of sarcoidosis and recurrent pericardial effusions, treated previously with a subxiphoid pericardial oval window fenestration, presented with acute upper abdominal pain radiating to the chest. High contrast computed tomography showed a volvulus of the liver with consequent venous congestion, and herniation of the liver, stomach and transverse colon through an anterior diaphragmatic defect. With liver perfusion threatened, an urgent laparoscopic repair was performed. The stomach and transverse colon were reduced, and the twisted left lobe of the liver was unrotated and reduced into the abdominal cavity. A double-sided synthetic mesh was used to repair the defect. The patient made an uneventful recovery. Conclusions This is a novel complication of a patient presenting with abdominal pain with a previous history of pericardial window fenestration. A laparoscopic reduction and repair can be performed safely with excellent postoperative results. PMID:25245721
Gorsi, Ujjwal; Bhatia, Anmol; Gupta, Rajesh; Bharathi, Saranga; Khandelwal, Niranjan
Wandering spleen is a rare clinical condition which occurs due to laxity or absence of the normal intraperitoneal ligaments that hold the spleen in place. Gastric volvulus and wandering spleen share a common etiology of absence or laxity of intraperitoneal ligaments. The occurrence of simultaneous pancreatic volvulus has never been described before in adolescence. Herein, we report a case having wandering spleen with torsion, and gastric and distal pancreatic volvulus, an unusual triad in acute abdomen in an emergency setting, which has never been described before to the best of our knowledge. PMID:24976284
Gorsi, Ujjwal; Bhatia, Anmol; Gupta, Rajesh; Bharathi, Saranga; Khandelwal, Niranjan
Wandering spleen is a rare clinical condition which occurs due to laxity or absence of the normal intraperitoneal ligaments that hold the spleen in place. Gastric volvulus and wandering spleen share a common etiology of absence or laxity of intraperitoneal ligaments. The occurrence of simultaneous pancreatic volvulus has never been described before in adolescence. Herein, we report a case having wandering spleen with torsion, and gastric and distal pancreatic volvulus, an unusual triad in acute abdomen in an emergency setting, which has never been described before to the best of our knowledge.
Arslan, Serkan; Basuguy, Erol; Zeytun, Hikmet; Okur, Mehmet Hanifi; Aydogdu, Bahattin; Arslan, Mehmet Serif
Foreign body ingestion is a common problem in children, but magnet ingestion is relatively rare. However, when it occurs, it tends to have a high rate of complications. This is a case report of a 3-year-old child who swallowed multiple magnetic toys, subsequently developing jejunoileal perforation and volvulus. This case report indicates that it is best to surgically remove multiple ingested magnets without delay to avoid intestinal perforation, fistula, and other complications such as volvulus.
Franchini, Delia; Giannelli, Alessio; Di Paola, Giancarlo; Cortes, Helder; Cardoso, Luís; Lia, Riccardo Paolo; Campbell, Bronwyn Evelyn; Dantas-Torres, Filipe; Lenoci, Diana; Assad, Eyad Abu; Ricciardi, Mario; Valastro, Carmela; Cavaliere, Leonardo; Di Bello, Antonio; Otranto, Domenico
Onchocerca lupi, a zoonotic nematode infecting the eyes of carnivores, has been increasingly reported in dogs from Europe and the USA. In order to improve the current status of knowledge on this neglected filarioid, diagnostic imaging tools (i.e., ultrasound scan, computed tomography and magnetic resonance imaging) are herein used to diagnose canine onchocercosis in two dogs, which scored positive for O. lupi microfilariae at the skin snip test and to assess the anatomical location of the nematode within the ocular apparatus. Results indicate that ultrasound tools are useful to address the diagnosis of O. lupi in dogs and to evaluate the localization of nodules or cysts containing the adult nematode.
Zuiki, Toru; Hosoya, Yoshinori; Lefor, Alan Kawarai; Tanaka, Hiroyuki; Komatsubara, Toshihide; Miyahara, Yuzo; Sanada, Yukihiro; Ohki, Jun; Sekiguchi, Chuji; Sata, Naohiro
Gastric volvulus is torsion of the stomach and requires immediate treatment. The optimal treatment strategy for patients with gastric volvulus is not established, because of significant variations in the cause and clinical course of this condition. We describe our experience with six elderly patients with gastric volvulus caused by different conditions using various approaches. This includes two patients managed with endoscopic reduction, followed by endoscopic or laparoscopic gastropexy. Endoscopy is a necessary first step to determine the optimal treatment strategy, and endoscopic reduction is often effective. The indications for surgical repair of gastric volvulus depend on the patient's overall condition, and several options are available. In some elderly patients with severe comorbidities, major surgery may have an unacceptably high risk. We propose a novel treatment strategy for gastric volvulus in the elderly and a review of the literature. Early endoscopy is necessary in patients with gastric volvulus. Endoscopic or laparoscopic gastropexy may be adequate therapy in selected elderly patients. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Parolini, Filippo; Orizio, Paolo; Bulotta, Anna Lavinia; Garcia Magne, Miguel; Boroni, Giovanni; Cengia, Gianpaolo; Torri, Fabio; Alberti, Daniele
Sigmoid volvulus (SV) is extremely uncommon in children and is usually associated with a long-standing history of constipation or pseudo-obstruction. An early diagnosis and management are crucial in order to prevent the appearance of hemorrhagic infarction of the twisted loop, avoiding further complications such as necrosis, perforation and sepsis. In patients with no evidence of peritonitis or ischemic bowel, treatment starts with resuscitation and detorsion of the SV, accomplished by means of sigmoidoscopy and concomitant rectal tube placement. The bowel is then prepared and surgery is undertaken electively during the same hospitalization. We report a detailed review of the literature focusing on technical details, risks and benefits of endoscopic management of SV in childhood. PMID:27358669
Duke, J H; Yar, M S
Most reports of patients with primary small bowel volvulus have indicated that the ingestion of a high-bulk vegetable diet in some way contributes to the development of this condition. During a recent 13-month period at Nangarhar University Hospital at Jalalabad, Afghanistan, the frequency of occurrence among 26 patients was found to be related to abrupt changes in dietary intake. The first and last months of the study were Ramadan, the annual period in which Mohammedans abstain from all oral intake during daylight hours and take a single large meal after dark. During these two isolated months, there was a ten fold and nine fold increase, respectively, in the incidence of the condition. Early diagnosis and surgical intervention offer the only possibility for minimizing an otherwise excessive mortality.
Moya, Laura; Herrador, Zaida; Ta-Tang, Thuy Huong; Rubio, Jose Miguel; Perteguer, Maria Jesús; Hernandez-González, Ana; García, Belén; Nguema, Rufino; Nguema, Justino; Ncogo, Policarpo; Garate, Teresa; Benito, Agustín; Sima, Anacleto; Aparicio, Pilar
Onchocerciasis or "river blindness" is a chronic parasitic neglected tropical disease which is endemic both in mainland and insular Equatorial Guinea. We aim to estimate the current epidemiological situation of onchocerciasis in Bioko Island after vector elimination in 2005 and more than sixteen years of Community Directed Treatment with Ivermectin (CDTI) by using molecular and serological approaches for onchocerciasis diagnosis. A community-based cross-sectional study was carried out in Bioko Island from mid-January to mid-February 2014. A total of 544 study participants were recruited. A complete dermatological examination was performed and three skin snips were performed in every participant for parasitological and molecular assessments. Blood spots were also taken for determination of Ov16 IgG4 antibodies trough an "in-house" ELISA assay. Overall, we found 15 out of 522 individuals suffering any onchocerciasis specific cutaneous lesions and 16 out of 528 (3.0%) with onchocercal nodules in the skin. Nodules were significantly associated with age, being more common in subjects older than 10 years than in younger people (3.9% vs. 0%, p = 0.029). Regarding the onchocerciasis laboratory assessment, no positive parasitological test for microfilaria detection was found in the skin snips. The calculated seroprevalence through IgG4 serology was 7.9%. No children less than 10 years old were found to be positive for this test. Only one case was positive for Onchocerca volvulus (O. volvulus) after skin PCR. The present study points out that the on-going mass ivermectin treatment has been effective in reducing the prevalence of onchocerciasis and corroborates the interruption of transmission in Bioko Island. To our knowledge, this is the first time that accurate information through molecular and serological techniques is generated to estimate the onchocerciasis prevalence in this zone. Sustained support from the national program and appropriate communication and health
Herrador, Zaida; Ta-Tang, Thuy Huong; Rubio, Jose Miguel; Perteguer, Maria Jesús; Hernandez-González, Ana; García, Belén; Nguema, Rufino; Nguema, Justino; Ncogo, Policarpo; Garate, Teresa; Benito, Agustín; Sima, Anacleto; Aparicio, Pilar
Onchocerciasis or "river blindness" is a chronic parasitic neglected tropical disease which is endemic both in mainland and insular Equatorial Guinea. We aim to estimate the current epidemiological situation of onchocerciasis in Bioko Island after vector elimination in 2005 and more than sixteen years of Community Directed Treatment with Ivermectin (CDTI) by using molecular and serological approaches for onchocerciasis diagnosis. A community-based cross-sectional study was carried out in Bioko Island from mid-January to mid-February 2014. A total of 544 study participants were recruited. A complete dermatological examination was performed and three skin snips were performed in every participant for parasitological and molecular assessments. Blood spots were also taken for determination of Ov16 IgG4 antibodies trough an “in-house” ELISA assay. Overall, we found 15 out of 522 individuals suffering any onchocerciasis specific cutaneous lesions and 16 out of 528 (3.0%) with onchocercal nodules in the skin. Nodules were significantly associated with age, being more common in subjects older than 10 years than in younger people (3.9% vs. 0%, p = 0.029). Regarding the onchocerciasis laboratory assessment, no positive parasitological test for microfilaria detection was found in the skin snips. The calculated seroprevalence through IgG4 serology was 7.9%. No children less than 10 years old were found to be positive for this test. Only one case was positive for Onchocerca volvulus (O. volvulus) after skin PCR. The present study points out that the on-going mass ivermectin treatment has been effective in reducing the prevalence of onchocerciasis and corroborates the interruption of transmission in Bioko Island. To our knowledge, this is the first time that accurate information through molecular and serological techniques is generated to estimate the onchocerciasis prevalence in this zone. Sustained support from the national program and appropriate communication and health
Prabhu, Shailesh Mukund; Venkatesan, Bhuvaneswari; Shetty, Gurucharan; Narula, Mahender Kaur; Chauhan, Udit; Udiya, Alok Kumar
Recurrent sigmoid volvulus is a clinical entity characterized by recurrent episodes of partial or complete sigmoid volvulus. Although it is commonly seen in the elderly, it can be occasionally seen in younger patients. Patients with recurrent partial sigmoid volvulus are relatively asymptomatic or present with mild abdominal pain. Early diagnosis and treatment is essential to prevent conversion to acute gangrenous volvulus. We present a case of recurrent partial sigmoid volvulus in association with eventration of diaphragm in a 26-year-old man. PMID:25901269
Golshahi, Hannaneh; Tavasoly, Abbas; Namjoo, Abdolrasol; Bahmani, Mahmoud
Volvulus is the torsion of an organ around its root. In dogs, volvulus of the stomach is well known, but volvulus of the small intestine is rare. A dead 3-month-old female terrier puppy was presented for postmortem examination. According to owner statements, the puppy was depressed, lethargic and had abdominal pain, abdominal distension, severe diarrhea and vomiting a few hours before death. With gross and histopathologic studies, the death of this puppy was indorsed to small intestinal volvulus, subsequent infarction, peritonitis and likely acute toxaemia and/or septicaemia. The present case is going to be the first recorded case of small intestinal volvulus in dog in Iran.
Atamanalp, S. Selcuk; Keles, M. Sait; Aydinli, Bulent
Objective: This study aimed to determine the serum potassium concentrations in patients with sigmoid volvulus (SV), which is a rare large bowel obstruction. Materials and Methods: The records of 86 patients with SV were reviewed retrospectively, while the records of 41 patients diagnosed with obstructive rectosigmoid cancer (ORC) were considered as the control group and as such, served as a source for comparison. Results: The analysis revealed a mean serum potassium concentration of 3.9 ± 0.6 mEq/L for the patients with SV, while the mean potassium concentration was 3.9 ± 0.5 mEq/L for the patients diagnosed with ORC (t:0.1, P>0.05). The number of hypokalemic and hyperkalemic patients identified in this study sample were 11 versus 5 patients and 1 versus 0 patients, respectively for the SV and ORC groups (x2 = 0.1 and 0.5, respectively with a P>0.05). Conclusions: No cause-and-effect relationship was observed between the serum potassium concentrations and SV. The serum potassium concentration is not pathognomonic for SV. PMID:25610090
Nuevo, Sergio Pozo; Macías Robles, María Dolores; Sevillano, Ramón Delgado; Pérez-Gallarza, Susana Serrano
We describe a challenging case of sigmoid volvulus where a previously unrecognised anatomical condition, rather than the patient's age, was the main predisposing factor. A man in his thirties presented to the emergency department with a 3-day history of constipation and acute abdominal pain. Initial assessment and studies were inconclusive, but a CT scan revealed torsion of the large bowelSigmoid volvulus is a frequent cause of bowel obstruction that can be missed if appropriate imaging is not available. Clinical presentation and blood analysis can be similar to the findings in acute abdomen caused by other more common causes. PMID:23744852
Santín-Rivero, Jorge; Núñez-García, Edgar; Aguirre-García, Manuel; Hagerman-Ruiz-Galindo, Gonzalo; de la Vega-González, Francisco; Moctezuma-Velasco, Carla Rubi
Small bowel volvulus is a rare cause of intestinal obstruction in adult patients. This disease is more common in children and its aetiology and management is different to that in adults. A 30 year-old male with sarcoidosis presents with acute abdomen and clinical data of intestinal obstruction. Small bowel volvulus is diagnosed by a contrast abdominal tomography and an exploratory laparotomy is performed with devolvulation and no intestinal resection. In the days following surgery, he developed a recurrent small bowel volvulus, which was again managed with surgery, but without intestinal resection. Medical treatment for sarcoidosis was started, and with his clinical progress being satisfactory,he was discharged to home. Making an early and correct diagnosis of small bowel volvulus prevents large intestinal resections. Many surgical procedures have been described with a high rate of complications. Therefore, conservative surgical management (no intestinal resection) is recommended as the best treatment with the lowest morbidity and mortality rate. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
Adeleke, Monsuru Adebayo; Sam-Wobo, Sammy Olufemi; Akinwale, Olaoluwa Pheabian; Olatunde, Ganiyu Olatunji; Mafiana, Chiedu Felix
The biting preference of Simulium vectors has been known to influence the distribution of Onchocerca nodules and microfilariae in human body. There is, however, variation in biting pattern of Simulium flies in different geographical locations. This study investigates the biting pattern on human parts by Simulium vectors along Osun river system where Simulium soubrense Beffa form has been implicated as the dominant vector and its possible implication on the distribution of Onchocerca nodules on human body along the river. Flies were collected by consented fly capturers on exposed human parts namely head/neck region, arms, upper limb and lower limb in Osun Eleja and Osun Budepo along Osun river in the wet season (August-September) and the dry season (November-December) in 2008. The residents of the communities were also screened for palpable Onchocerca nodules. The results showed that number of flies collected below the ankle region was significantly higher than the number collected on other exposed parts (p <0.05) while the least was collected on head/neck region in both seasons. The lower trunk was the most common site (60%) for nodule location at Osun Eleja followed by upper trunk (40%). Nodules were not found in the head and limb regions. At Osun Budepo, the upper trunk was the most common site of the nodule location (53.8%) followed by the lower trunk (38.5%) and head region (7.7%). Though, most of the flies were caught at the ankle region, the biting of other parts coupled with the presence of nodules at the head and upper trunk regions showed that Simulium vectors could obtain microfilariae from any part of the body, thus increasing the risk of onchocerciasis transmission.
McConnell, L. A.; Leid, R. W.
The arachidonic acid pathway plays an important role in many inflammatory reactions. Current evidence suggests that platelets can play a central part in host inflammation. Since microfilariae are mobilized into the bloodstream following diethylcarbamazine (DEC) treatment, we have studied the effects of Onchocerca cervicalis cuticle preparations on equine platelet aggregation. The authors have found that O cervicalis cuticular preparations can induce platelet aggregation in vitro. Furthermore, this activity was abrogated by treatment with collagenase and not hyaluronidase, elastase, or alpha-chymotrypsin. When this evidence is viewed collectively with the evidence for in vivo parasite cuticular damage following DEC treatment, it becomes entirely plausible that the cuticular damage may indeed reveal a platelet-reactive surface, thus permitting platelet-parasite binding to occur. This binding would result in platelet aggregation and the generation and release of platelet-derived arachidonate metabolites. These metabolites may play a very critical role in the development of the described pathologic sequelae observed following DEC treatment. Field studies using cyclooxygenase and lipoxygenase inhibitors might therefore be very efficacious in decreasing the frequency of side effects due to DEC or other potentially effective drug regimens. PMID:6299106
Altintoprak, Fatih; Yalkin, Omer; Dikicier, Enis; Kivilcim, Taner; Arslan, Yusuf; Gunduz, Yasemin; Ozkan, Orhan Veli
INTRODUCTION Gastric volvulus is a rare surgical emergency with a high mortality rate that requires urgent surgical management. PRESENTATION OF CASE A 19-year-old male and 51-year-old female patient underwent emergency surgery with a prediagnosis of acute abdomen syndrome, and a 60-year-old female patient underwent elective surgery due to diaphragmatic hernia. Abdominal exploration revealed gastric volvulus together with perforation in received emergency surgery patients, and a mesenteroaxial gastric volvulus due to diaphragmatic defect in third patient. DISCUSSION Gastric volvulus is classified into four subgroups depending on the mechanism of development, and organoaxial form is the most common type of gastric volvulus. The most challenging step in diagnosing gastric volvulus is the consideration of this diagnosis. CONCLUSION Preoperative diagnosis is often difficult, and its management involves surgical correction of the pathology followed by institution of resuscitative treatment. PMID:25217876
Prabhu, Shailesh M; Anand, Rama; Narula, Mahender K; Shetty, Gurucharan S; Udiya, Alok K; Chauhan, Udit; Shukla, Shailaja; Grover, Jitendra Kumar
Recurrent small-bowel volvulus is a state of recurrent intermittent or long-standing persistent twisting of small-bowel loops around its mesentery. The association of mesenteric cysts with recurrent small-bowel volvulus as the cause or effect is a much debated issue in the literature. We report two cases of mesenteric lymphangioma and one case of enteric duplication cyst seen in association with recurrent small-bowel volvulus of long duration in absence of malrotation.
Karthikeyan, Vilvapathy Senguttuvan; Sistla, Sarath Chandra; Ram, Duvuru; Rajkumar, Nagarajan
Esophagogastroduodenoscopy (EGD) is a commonly used, safe diagnostic modality for evaluation of epigastric pain and rarely its major complications include perforation, haemorrhage, dysrhythmias and death. Gastric volvulus has been reported to complicate percutaneous endoscopic gastrostomy but its occurrence after diagnostic EGD has not yet been reported in literature. The successful management relies on prompt diagnosis and gastric untwisting, decompression and gastropexy or gastrectomy in full thickness necrosis of the stomach wall. A 38-year-old woman presented with epigastric pain and EGD showed pangastritis. Immediately after EGD she developed increased severity of pain, vomiting and abdominal distension. Emergency laparotomy carried out for peritoneal signs revealed eventration of left hemidiaphragm with the stomach twisted anticlockwise in the longitudinal axis. After gastric decompression and untwisting of volvulus, anterior gastropexy and gastrostomy was carried out. Hence, we report this rare complication of diagnostic endoscopy and review the existing literature on the management. PMID:24515235
Neilsen, Colleen; Mans, Christoph; Colopy, Sara A
To describe the successful management of gastric dilatation and volvulus (GDV) in a red panda. Clinical report. Red panda diagnosed with GDV. A 12-year-old male red panda (Ailurus fulgens) was evaluated for acute onset inappetence, staggering, collapse, and tachypnea. Gastric dilatation and volvulus (GDV) was diagnosed by radiography, abdominal ultrasonography, and exploratory celiotomy. Torsion of the stomach was corrected and an incisional gastropexy performed to prevent recurrence. No organs were devitalized, no other abnormalities detected, and the red panda recovered fully within 72 hours. GDV should be considered as a differential diagnosis for red pandas presenting with acute onset of unspecific signs such as collapse, inappetence, and abdominal distension. GDV in red pandas can be diagnosed and successfully treated as described in dogs. © Copyright 2014 by The American College of Veterinary Surgeons.
Neilsen, Colleen; Mans, Christoph; Colopy, Sara A.
A 12-year-old male red panda (Ailurus fulgens) was evaluated for acute onset inappetance, staggering, collapse, and tachypnea. Gastric dilatation and volvulus (GDV) was diagnosed by radiography, abdominal ultrasonography, and exploratory celiotomy. Torsion of the stomach was corrected and an incisional gastropexy performed to prevent recurrence. No organs were devitalized, no other abnormalities detected, and the red panda recovered fully within 72 hours. PMID:24467661
Ifversen, Anne Kathrine Wewer; Kjaer, Daniel Willy
To assess the outcome of patients treated conservatively vs surgically during their first admission for sigmoid volvulus. We conducted a retrospective study of 61 patients admitted to Aarhus University Hospital in Denmark between 1996 and 2011 for their first incidence of sigmoid volvulus. The condition was diagnosed by radiography, sigmoidoscopy or surgery. Patients treated with surgery underwent either a sigmoid resection or a percutaneous endoscopic colostomy (PEC). Conservatively treated patients were managed without surgery. Data was recorded into a Microsoft Access database and calculations were performed with Microsoft Excel. Kaplan-Meier plotting and Mantel-Cox (log-rank) testing were performed using GraphPad Prism software. Mortality was defined as death within 30 d after intervention or surgery. Among the total 61 patients, 4 underwent emergency surgery, 55 underwent endoscopy, 1 experienced resolution of the volvulus after contrast enema, and 1 died without treatment because of large bowel perforation. Following emergency treatment, 28 patients underwent sigmoid resection (semi-elective n = 18; elective n = 10). Two patients who were unfit for surgery underwent PEC and both died, 1 after 36 d and the other after 9 mo, respectively. The remaining 26 patients were managed conservatively without sigmoid resection. Patients treated conservatively on their first admission had a poorer survival rate than patients treated surgically on their first admission (95%CI: 3.67-14.37, P = 0.036). Sixty-three percent of the 26 conservatively treated patients had not experienced a recurrence 3 mo after treatment, but that number dropped to 24% 2 years after treatment. Eight of the 14 patients with recurrence after conservative treatment had surgery with no 30-d mortality. Surgically-treated sigmoid volvulus patients had a higher long-term survival rate than conservatively managed patients, indicating a benefit of surgical resection or PEC insertion if feasible.
Sonthalia, Nikhil; Ray, Sayantan; Khanra, Dibbendhu; Saha, Avishek; Maitra, Subhasis; Saha, Manjari; Talukdar, Arunansu
Intractable vomiting in an elderly patient is an emergency condition requiring prompt diagnosis and intervention. Acute gastric outlet obstruction due to gastric volvulus through Morgagni-type diaphragmatic hernia is an exceedingly rare cause of this nonspecific complaint. Our aim was to highlight that Morgagni hernia, although rare in adults, should be suspected in the appropriate clinical setting, and that a clue toward diagnosis often comes from routine chest and abdominal x-ray studies. In addition, we emphasize the atypical radiological findings and importance of emergency surgical intervention in such a case. We describe the case of a 78-year-old woman who presented to the Emergency Department with a 4-day history of intractable vomiting, and with no definitive clue to the diagnosis on examination. Her routine chest and abdomen x-ray studies suggested abnormal air-fluid level at right hemithorax, which prompted a computed tomography (CT) scan of the abdomen and an upper gastrointestinal contrast study. Gastric volvulus through a foramen of Morgagni was diagnosed and transthoracic reduction of the contents was performed, along with repair of the defect. A symptomatic Morgagni hernia in adults, although rare, can present with a variety of symptoms ranging from nonspecific complaints of bloating and indigestion to the more severe complaint of intestinal obstruction. Gastric volvulus and obstructive features are less frequently reported as acute complications of these hernias, which need early identification and intervention. Copyright © 2013 Elsevier Inc. All rights reserved.
Samuel, Jonathan C; Msiska, Nelson; Muyco, Arturo P; Cairns, Bruce A; Charles, Anthony G
Sigmoid volvulus is a common cause of bowel obstruction. We describe mesosigmoidopexy, an accepted surgical technique for the management of non-gangrenous sigmoid volvulus, and provide anatomic correlations supporting the therapy. Mesosigmoidopexy should be considered as a rational alternative to resection and anastomosis when operating on non-gangrenous sigmoid volvulus.
Giannelli, Alessio; Latrofa, Maria S.; Dantas-Torres, Filipe; Trumble, Nicole Scotty; Chavkin, Matt; Kennard, Gavin; Eberhard, Mark L.; Bowman, Dwight D.
Infections with Onchocerca lupi nematodes are diagnosed sporadically in the United States. We report 8 cases of canine onchocercosis in Minnesota, New Mexico, Colorado, and Florida. Identification of 1 cytochrome c oxidase subunit 1 gene haplotype identical to 1 of 5 from Europe suggests recent introduction of this nematode into the United States. PMID:25897859
Conboy, Gary; Lejeune, Manigandan; Marron, Fany; Hanna, Paul; MacDonald, Erin; Skorobohach, Brian; Wilcock, Brian; Kutz, Susan J.; Gilleard, John S.
The Onchocerca lupi nematode is an emerging helminth capable of infecting pets and humans. We detected this parasite in 2 dogs that were imported into Canada from the southwestern United States, a region to which this nematode is endemic. We discuss risk for establishment of O. lupi in Canada. PMID:27434170
Otranto, Domenico; Dantas-Torres, Filipe; Papadopoulos, Elias; Petrić, Dušan; Ćupina, Aleksandra Ignjatović; Bain, Odile
During a hot Mediterranean summer, an expedition brought parasitologists from Brazil, France, Greece, Italy, and Serbia to a wooded area near Xanthi, Thrace, northeastern Greece, near the Turkish border, on the track of the vector of the little-known nematode Onchocerca lupi. The scientific purposes of the expedition blended then with stories of humans, animals, and parasites in this rural area.
Otranto, Domenico; Giannelli, Alessio; Latrofa, Maria S; Dantas-Torres, Filipe; Trumble, Nicole Scotty; Chavkin, Matt; Kennard, Gavin; Eberhard, Mark L; Bowman, Dwight D
Infections with Onchocerca lupi nematodes are diagnosed sporadically in the United States. We report 8 cases of canine onchocercosis in Minnesota, New Mexico, Colorado, and Florida. Identification of 1 cytochrome c oxidase subunit 1 gene haplotype identical to 1 of 5 from Europe suggests recent introduction of this nematode into the United States.
Otranto, Domenico; Dantas-Torres, Filipe; Giannelli, Alessio; Latrofa, Maria Stefania; Papadopoulos, Elias; Cardoso, Luís; Cortes, Helder
Onchocerca lupi infection is reported primarily in symptomatic dogs. We aimed to determine the infection in dogs from areas of Greece and Portugal with reported cases. Of 107 dogs, 9 (8%) were skin snip-positive for the parasite. DNA sequences of parasites in specimens from distinct dog populations differed genetically from those in GenBank.
A transmission is described which consists of: an input shaft; an output shaft; a first planetary gear set including a first sun gear selectively connectable by a first clutch to the input shaft, a first carrier selectively connectable by a second clutch to the input shaft and a first ring gear connected to the output shaft. The first sun gear selectively held stationary by a first brake, the first carrier is allowed to rotate in the same forward direction as the input shaft when the second clutch is engaged, but prevented from rotating in a reverse direction opposite to the forward direction by a first one-way clutch, the first carrier being selectively held stationary by a second brake; a second planetary gear set including a second sun gear connected to the input shaft, a second carrier connected to the first ring gear and also the the output shaft, and a second ring gear.
Okazaki, Tadaharu; Ohata, Rumi; Miyano, Go; Lane, Geoffrey J; Takahashi, Toshiaki; Yamataka, Atsuyuki
Wandering spleen is not a common condition in childhood and has been described only rarely in association with gastric volvulus. The authors report the successful management of wandering spleen associated with gastric volvulus using laparoscopic splenopexy and gastropexy in a 4-year-old girl.
Tatterton, M; El-Khatib, C
Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterised by recurrent symptoms and signs of intestinal obstruction without an underlying mechanical cause. Caecal volvulus remains a rare cause of intestinal obstruction that often requires operative intervention. We describe the previously unreported case of caecal volvulus occurring in an adult patient with CIPO, together with his subsequent management.
Gillespie, A; Burgess, E; Lanyon, J; Owen, H
An adult female dugong (Dugong dugon) was found dead and floating in Moreton Bay, Queensland, Australia. This animal was found to have a 360° mesenteric volvulus with infarction of the associated segment of small intestine, and fibrinous peritonitis. Mortality was attributed to the volvulus and its sequelae. The cause was not apparent on gross or histological examination.
Nakagawa, Tomoko; Tachibana, Daisuke; Kitada, Kohei; Kurihara, Yasushi; Terada, Hiroyuki; Koyama, Masayasu; Sakae, Yukari; Morotomi, Yoshiki; Nomura, Shiho; Saito, Mika
Fetal intestinal volvulus without malrotation is a rare, life-threatening disease. Left untreated, hemorrhage from necrotic bowel tissue will lead to severe fetal anemia and even intrauterine death. We encountered a case of fetal intestinal volvulus causing severe anemia, which was diagnosed postnatally and successfully treated with surgical intervention. PMID:25628516
Bourguinat, Catherine; Kamgno, Joseph; Boussinesq, Michel; Mackenzie, Charles D.; Prichard, Roger K.; Geary, Timothy G.
Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Loa loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Loa mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs. PMID:20595473
Lee, Hye Yeon; Park, Jung Hyun
Gastric volvulus is an uncommon clinical entity. There are three types of gastric volvulus; organoaxial, mesenteroaxial and combined type. This condition can lead to a closed-loop obstruction or strangulation. Traditional surgical therapy for gastric volvulus is based on an open approach. Here we report a successful case of a patient with chronic gastric volvulus with a laparoscopic treatment. A 79-year-old woman came to the emergency department with epigastric pain accompanied by nausea for 2 weeks. Abdominal computed tomography revealed markedly distended stomach with transposition of gastroesophageal Junction and gastric antrum. Barium meal study revealed presence of the antrum was folded over 180 degrees that was located above gastroesophageal junction. We attempted an endoscopic reduction, but it was unsuccessful. The patient got laparoscopic anterior gastropexy. Based on our result, laparoscopic gastropexy can be considered as a good choice of the treatment for gastric volvulus. PMID:26161290
Senior, Andrew; Hari, Churunal
Gastric volvulus is a rare condition with two forms of presentation, either acute or chronic. Since its discovery, there have been no cases of acute on chronic volvulus discussed in the literature. Its vague presentation makes diagnosis and subsequent management difficult. The diagnosis of acute gastric volvulus is made on clinical grounds via Borchardt's triad; however, barium swallow and oesophagogastroduodenoscopy have been shown to play a role. We describe a case of a 95-year-old Caucasian woman who presented with worsening dysphagia, epigastric pain, retching without vomiting and hiccups of 5 months. Initially diagnosed as a hiatus hernia, the patient subsequently died following an acute on chronic gastric volvulus. This rare, life-threatening diagnosis provides an opportunity to discuss characteristics of gastric volvulus and the difficulties in management.
Machado, Norman O; Machado, Lovina S M
Sigmoid volvulus is an extremely rare cause of intestinal obstruction in pregnancy. The rarity of the condition and the fact that pregnancy itself clouds the clinical picture invariably leads to a delay in diagnosis with an increased risk of gangrene of the gut. The majority of these patients would then require resection and colostomy. However, an early diagnosis and intervention as in our patient, which would require a high index of clinical suspicion, could significantly improve the outcome of the foetus and the mother. A case of sigmoid volvulus in pregnancy is reported which was managed by resection and primary anastomosis. A review of literature revealed no previous reports of sigmoid volvulus in pregnancy managed by primary anastomosis following resection of the sigmoid volvulus. The literature is also reviewed regarding predisposing factors, management options and the outcome of sigmoid volvulus complicating pregnancy.
Inaba, Kazuki; Sakurai, Yoichi; Isogaki, Jun; Komori, Yoshiyuki; Uyama, Ichiro
Although mesenterioaxial gastric volvulus is an uncommon entity characterized by rotation at the transverse axis of the stomach, laparoscopic repair procedures have still been controversial. We reported a case of mesenterioaxial intrathoracic gastric volvulus, which was successfully treated with laparoscopic repair of the diaphragmatic hiatal defect using a polytetrafluoroethylene mesh associated with Toupet fundoplication. A 70-year-old Japanese woman was admitted to our hospital because of sudden onset of upper abdominal pain. An upper gastrointestinal series revealed an incarcerated intrathoracic mesenterioaxial volvulus of the distal portion of the stomach and the duodenum. The complete laparoscopic approach was used to repair the volvulus. The laparoscopic procedures involved the repair of the hiatal hernia using polytetrafluoroethylene mesh and Toupet fundoplication. This case highlights the feasibility and effectiveness of the laparoscopic procedure, and laparoscopic repair of the hiatal defect using a polytetrafluoroethylene mesh associated with Toupet fundoplication may be useful for preventing postoperative recurrence of hiatal hernia, volvulus, and gastroesophageal reflux.
Uni, Shigehiko; Fukuda, Masako; Agatsuma, Takeshi; Bain, Odile; Otsuka, Yasushi; Nakatani, Jun; Matsubayashi, Makoto; Harada, Masashi; Omar, Hasmahzaiti; Ramli, Rosli; Hashim, Rosli; Azirun, Mohd Sofian; Takaoka, Hiroyuki
Human zoonotic onchocercosis is caused by Onchocerca dewittei japonica, parasitic in wild boars (Sus scrofa leucomystax) in Japan. Previously, microfilariae longer than those of Onchocerca dewittei japonica were observed in skin snips from wild boars during the study of O. dewittei japonica. Moreover, the third-stage larvae (L3) of these longer microfilariae were obtained from the blackfly Simulium bidentatum after experimental injections. Based on morphometric and molecular studies, similar L3 were found in blackflies during fieldwork in Oita, Japan. However, except for O. dewittei japonica, adult worms of Onchocerca have not been found in wild boars. In this study, we discovered adult females of a novel Onchocerca species in the skin of a wild boar in Oita, and named it Onchocerca takaokai n. sp. Females of this new species had longer microfilariae and differed from O. dewittei japonica in terms of their morphological characteristics and parasitic location. The molecular characteristics of the cytochrome c oxidase subunit 1 and 12S rRNA genes of the new species were identical to those of the longer microfilariae and L3 previously detected, but they differed from those of O. dewittei japonica at the species level. However, both species indicated a close affinity among their congeners and Onchocerca ramachandrini, parasitic in the warthog in Africa, was basal in the Suidae cluster of the 12S rRNA tree.
Relationship between oral declaration on adherence to ivermectin treatment and parasitological indicators of onchocerciasis in an area of persistent transmission despite a decade of mass drug administration in Cameroon.
Wanji, Samuel; Kengne-Ouafo, Jonas A; Esum, Mathias E; Chounna, Patrick W N; Adzemye, Bridget F; Eyong, Joan E E; Jato, Isaac; Datchoua-Poutcheu, Fabrice R; Abong, Raphael A; Enyong, Peter; Taylor, David W
Onchocerciasis control for years has been based on mass drug administration (MDA) with ivermectin (IVM). Adherence to IVM repeated treatment has recently been shown to be a confounding factor for onchocerciasis elimination precisely in rain forest areas where transmission continues and Loa loa co-exists with Onchocerca volvulus. In this study, participants' oral declarations were used as proxy to determine the relationship between adherence to IVM treatment and parasitological indicators of onchocerciasis in the rain forest area of Cameroon with more than a decade of MDA. Participants were recruited based on their IVM intake profile with the aid of a semi-structured questionnaire. Parasitological examinations (skin sniping and nodule palpation) were done on eligible candidates. Parasitological indicators were calculated and correlated to IVM intake profile. Of 2,364 people examined, 15.5% had never taken IVM. The majority (40.4%) had taken the drug 1-3 times while only 18% had taken ≥ 7 times. Mf and nodule prevalence rates were still high at 47%, 95% CI [44.9-49.0%] and 36.4%, 95% CI [34.4-38.3%] respectively. There was a treatment-dependent reduction in microfilaria prevalence (rs =-0.986, P = 0.01) and intensity (rs =-0.96, P = 0.01). The highest mf prevalence (59.7%) was found in the zero treatment group and the lowest (33.9%) in the ≥ 7 times treatment group (OR = 2.8; 95% CI [2.09-3.74]; P < 0.001). Adults with ≥ 7 times IVM intake were 2.99 times more likely to have individuals with no microfilaria compared to the zero treatment group (OR = 2.99; 95% CI [2.19-4.08], P < 0.0001). There was no clear correlation between treatment and nodule prevalence and intensity. Adherence to ivermectin treatment is not adequate in this rain forest area where L. loa co-exists with O. volvulus. The prevalence and intensity of onchocerciasis remained high in individuals with zero IVM intake after more than a decade of MDA. Our
Hartin, Charles W.; Ozgediz, Doruk E.
Introduction: Most foreign bodies that a child ingests pass harmlessly through the gastrointestinal tract. However, ingesting multiple magnets places a child at risk for serious viscus injury. Case Description: A 16-y-old boy swallowed multiple magnets and presented with abdominal pain and emesis. Upon laparoscopy, the boy was found to have malrotation with volvulus caused by a cecal magnet attracted to a gastric magnet, resulting in a gastrocecal fistula. Discussion: We review the management of magnet ingestion with an emphasis on a high index of suspicion and the use of laparoscopy for diagnosis, as well as the consequences of a coexisting rotational anomaly. PMID:23484578
Jabbour, Gaby; Afifi, Ibrahim; Ellabib, Mohamed; El-Menyar, Ayman; Al-Thani, Hassan
Patient: Male, 23 Final Diagnosis: Acute spontaneous gastric volvulus Symptoms: — Medication: — Clinical Procedure: Laparotomy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Acute gastric volvulus is a surgical emergency that requires early recognition and treatment. Acute idiopathic mesenteroaxial gastric volvulus is a rare sub-type and there are few cases reported in children and there are even fewer reports in adults. Case Report: We report a rare case of a 23-year-old man who presented with a 1-day history of vomiting, epigastric pain, distention, and constipation. The diagnosis for mesenteroaxial type gastric volvulus was confirmed by abdominal radiography and computed tomography. The patient was successfully treated by laparotomy with resection of the ischemic stomach wall and anastomosis. Acute spontaneous mesenteroaxial gastric volvulus is rare in adults and early diagnosis is challenging due to non-specific symptoms. A missed or delayed diagnosis may result in serious complications due to gastric obstruction. Conclusions: A patient presenting with severe epigastric pain and clinical evidence of gastric outlet obstruction should be considered as a surgical emergency to rule out gastric volvulus. High index of suspicion, early diagnosis and prompt surgical management are important for favorable outcome in patients with acute spontaneous gastric volvulus. PMID:27112797
Marine, Megan B; Cooper, Matthew L; Delaney, Lisa R; Jennings, Samuel Gregory; Rescorla, Frederick J; Karmazyn, Boaz
Colonic volvulus is rare in children and associated with colonic dysmotility. Diagnosis of colonic volvulus on radiographs in these patients can be challenging. The purpose of the study was to identify the accuracy of abdominal radiographs and findings suggestive of colonic volvulus. A retrospective (2003- 2014) study of all children with colonic volvulus proven surgically or endoscopically reviewed their medical charts for underlying disease and clinical presentation as well as their original radiograph reports. Two pediatric radiologists (reader 1 and reader 2) independently reviewed the radiographs. The kappa test was used to evaluate interobserver variability. There were 19 cases of colonic volvulus in 18 patients (11 males) a mean age 14 years. Cecal volvulus was the most common finding at 14/19 cases (74%). Sixteen of 18 (89%) patients had neurological impairment and 10 of 18 (56%) had intestinal dysmotility. The most common presentation was abdominal distension (14/19 [74%]) and pain (11/19 [58%]). Colonic volvulus was diagnosed in only 7/16 (44%) of the abdominal radiographs. The specific finding of a coffee-bean sign was retrospectively observed only by reader 2 in two cases. Absence of rectal gas and focal colonic loop dilation were the most common findings by the readers (average 73.5% and 87%, respectively) with Kappa values of 0.3 and 0.38, respectively. Diagnosis of colonic volvulus in children can be challenging. Radiologists should be alerted to the possibility of colonic volvulus when there is focal colonic loop distention or absent rectal gas.
Titanji, V P; Barla, E; Anyangwe, S; Ngu, J L
A single dose of promethazine or of betamethazone, either alone or compounded with dexchloropheniramine, was found to inhibit skin wheal formation in onchocerciasis patients challenged with Onchocerca supernatants. The mean wheal diameter developing 24 hours after drug administration ranged between 40-60% less than the original pre-treatment diameter but this effect had been abolished or was significantly less by 48 hours. Diethycarbamazinecitrate had only a 20% inhibitory effect on the wheal diameter of the skin reaction. It is concluded that antihistamines and corticosteroid derivates may interfere with the immunodiagnostic skin test for onchocerciasis based on skin reactivity to Onchocerca supernatants, unless measures are taken to ensure that these drugs are not consumed within the 48 hours preceding the skin test.
Esterson, Yonah B; Villani, Robert; Dela Cruz, Ronald A; Friedman, Barak; Grimaldi, Gregory M
Here we report the case of a pregnant 28-year-old who presented with acute upper abdominal pain. CT demonstrated midgut volvulus with short segment occlusion of the superior mesenteric artery (SMA). Emergent detorsion of the small bowel was performed, at which time underlying intestinal malrotation was discovered. Following detorsion, the SMA had a bounding pulse and did not require thrombectomy or revascularization. Fewer than 25 cases of midgut volvulus during pregnancy have been reported over the past 20years. To our knowledge, this is the first report of maternal midgut volvulus in which imaging captures the resultant occlusion of the SMA.
Morshedi, Mehdi; Baradaran Jamili, Mohammad; Shafizadeh Barmi, Fatemeh
Symptomatic intestinal malrotation first presenting in the adults is rare. Midgut volvulus is the most common complication of malrotation in the adults. Because of more differential diagnosis, Computed Tomography (CT) scan can play an important role in the evaluation of patients with this abnormality. The whirl pattern around the superior mesenteric artery found on CT scan in patients with midgut volvulus is pathognomonic and diagnostic. We describe a case of intestinal malrotation complicated by midgut volvulus in an adult patient. The preoperative CT findings were pathognomonic. PMID:28182093
Fan, H-L; Chen, T-W; Hong, Z-J; Hsieh, C-B; Chan, D-C; Chen, C-J; Liu, Y-C; Yu, J-C
Mesenteric cyst is a rare intra-abdominal lesion. Most patients with mesenteric cysts are asymptomatic. Symptomatic mesenteric cysts are associated with cyst size, cyst location, and complications, including infection, rupture, hemorrhage, and intestinal obstruction. Volvulus is a rare complication of mesenteric cyst. We report a 50-year-old woman with colicky epigastric pain for three days. The symptoms exacerbated in the supine position and were relieved in the sitting position. Computed tomography of her abdomen revealed a huge cystic lesion with a whirl sign of mesentery vessels. She had the history of gastro-esophageal reflux disease. Segmental resection of the small intestine with end-to-end anastomosis was performed. Histology indicated a hemorrhagic pseudocyst. The patient recovered well after surgery. Mesenteric pseudocyst rarely results in volvulus of small intestine. Our case is the eleventh case reported in the English literature. Atypical presentation of epigastric pain while lying down may lead to mis-diagnosis. This case reminds the clinicians this rare complication.
Mohi, Rommel Singh; Moudgil, Ashish; Bhatia, Suresh Kumar; Seth, Kaushal; Kaur, Tajinder
The incidence of the diverticulum of the small bowel varies from 0.2-1.3% in autopsy studies to 2.3% when assessed on enteroclysis. It occurs mostly in patients in the 6th decade of their life. Of all the small bowel diverticuli, jejunal diverticulum is the most common type. This rare entity is usually asymptomatic. However, they may cause chronic non-specific symptoms for a long period of time like dyspepsia, chronic postprandial pain, nausea, vomiting, borborgymi, alternating diarrhoea and constipation, weight loss, anaemia, steatorrhea or rarely lead to complications like haemorrhage, obstruction, perforation. Obstruction can be due to enterolith, adhesions, intussusception, and volvulus. The condition is difficult to diagnose because patients are generally presented with symptoms that mimic other diseases. It is important for clinicians to have awareness of this entity. Here, we present a case of multiple jejunal diverticuli with a history of repeated attacks of diverticulitis over past 20 years, which were misdiagnosed and now presented with intestinal obstruction due to volvulus of the involved segment along with mesentery around its axis. Resection of the diverticuli segment of jejunum was done with end-to-end jejuno-jejunal anastomosis. The patient is asymptomatic since 10 months of follow-up. PMID:27853337
Uni, S; Bain, O; Takaoka, H; Miyashita, M; Suzuki, Y
We describe Onchocerca dewittei japonica n. subsp. from the Japanese wild boar, Sus scrofa leucomystax, in Oita, Kyushu Island, where all seven animals examined were found to be infected. This study began with efforts to identify the causative species in a recent case of zoonotic onchocerciasis. Compared with Onchocerca dewittei dewittei from Sus scrofa jubatus in Malaysia, which was reexamined here, our new subspecies has much greater space between the ridges on the females. In addition, its microfilariae (from uteri) are shorter (192-210 microns compared with 228-247 microns), and only the posterior third of the microfilarial body is coiled, instead of the entire body. The Onchocerca species parasitic in suids (these two subspecies and O. ramachandrini from the warthog in the Ethiopian region) form a group sharing several characters. Among the most unusual characters are the body swellings (a specialized apparatus for mating, known in only a few other genera). In addition, longitudinal cuticular crests were found on males of both subspecies from wild boar and on females of O. ramachandrini.
Phytochemical analysis and in vitro anthelmintic activity of Lophira lanceolata (Ochnaceae) on the bovine parasite Onchocerca ochengi and on drug resistant strains of the free-living nematode Caenorhabditis elegans.
Kalmobé, Justin; Ndjonka, Dieudonné; Boursou, Djafsia; Vildina, Jacqueline Dikti; Liebau, Eva
Onchocerciasis is one of the tropical neglected diseases (NTDs) caused by the nematode Onchocerca volvulus. Control strategies currently in use rely on mass administration of ivermectin, which has marked activity against microfilariae. Furthermore, the development of resistance to ivermectin was observed. Since vaccine and safe macrofilaricidal treatment against onchocerciasis are still lacking, there is an urgent need to discover novel drugs. This study was undertaken to investigate the anthelmintic activity of Lophira lanceolata on the cattle parasite Onchocerca ochengi and the anthelmintic drug resistant strains of the free living nematode Caenorhabditis elegans and to determine the phytochemical profiles of the extracts and fractions of the plants. Plant was extracted in ethanol or methanol-methylene chloride. O. ochengi, C. elegans wild-type and C. elegans drug resistant strains were cultured in RPMI-1640 and NGM-agar respectively. Drugs diluted in dimethylsulphoxide/RPMI or M9-Buffer were added in assays and monitored at 48 h and 72 h. Worm viability was determined by using the MTT/formazan colorimetric method. Polyphenol, tannin and flavonoid contents were determined by dosage of gallic acid and rutin. Acute oral toxicity was evaluated using Swiss albino mice. Ethanolic and methanolic-methylene chloride extracts killed O. ochengi with LC50 values of 9.76, 8.05, 6.39 μg/mL and 9.45, 7.95, 6.39 μg/mL respectively for leaves, trunk bark and root bark after 72 h. The lowest concentrations required to kill 50% of the wild-type of C. elegans were 1200 and 1890 μg/mL with ethanolic crude extract, 1000 and 2030 μg/mL with MeOH-CH2Cl2 for root bark and trunk bark of L. lanceolata, respectively after 72 h. Leave extracts of L. lanceolata are lethal to albendazole and ivermectin resistant strains of C. elegans after 72 h. Methanol/methylene chloride extracted more metabolites. Additionally, extracts could be considered relatively safe. Ethanolic and
Flores-Ríos, Enrique; Méndez-Díaz, Cristina; Rodríguez-García, Esther; Pérez-Ramos, Tania
Wandering spleen is a rare condition, characterized by a mobile spleen that is attached only by an elongated vascular pedicle, allowing it to migrate to any part of the abdomen or pelvis. Mesenteroaxial gastric volvulus usually occurs in children and may be associated with wandering spleen. Both entities result from abnormal laxity or absence of the peritoneal attachments due to abnormal fusion of the peritoneal mesenteries. Pancreatic volvulus is a very rare anomaly, with only a few isolated case reports described in association with wandering spleen. Anomalous right sided descending and sigmoid colon is a very rare entity and its association with wandering spleen has not been previously reported. We report a case of wandering spleen associated with mesenteroaxial gastric volvulus, pancreatic volvulus and rightward shift of the splenic flexure of the colon and right sided descending and sigmoid colon in a young female. PMID:26629290
Flores-Ríos, Enrique; Méndez-Díaz, Cristina; Rodríguez-García, Esther; Pérez-Ramos, Tania
Wandering spleen is a rare condition, characterized by a mobile spleen that is attached only by an elongated vascular pedicle, allowing it to migrate to any part of the abdomen or pelvis. Mesenteroaxial gastric volvulus usually occurs in children and may be associated with wandering spleen. Both entities result from abnormal laxity or absence of the peritoneal attachments due to abnormal fusion of the peritoneal mesenteries. Pancreatic volvulus is a very rare anomaly, with only a few isolated case reports described in association with wandering spleen. Anomalous right sided descending and sigmoid colon is a very rare entity and its association with wandering spleen has not been previously reported. We report a case of wandering spleen associated with mesenteroaxial gastric volvulus, pancreatic volvulus and rightward shift of the splenic flexure of the colon and right sided descending and sigmoid colon in a young female.
Gupta, Rahul Amreesh; Das, Rinki; Verma, Ganga Ram
We report an extremely rare case of recurrent gastric volvulus after open splenectomy for hereditary spherocytosis. The initial episode was managed by endoscopic derotation. Later, for recurrent symptoms, she was successfully managed by laparoscopic anterior gastropexy. PMID:28281486
Gastric volvulus is a rare and life-threatening condition that involves the abnormal rotation of the stomach around its axis by more than 180°. The association between acute gastric volvulus and atrial fibrillation with rapid ventricular response is rare with only few cases that have been reported. Our patient was an 86-year-old female who presented with upper abdominal pain, distension, nausea, and shortness of breath. Clinical and laboratory workup revealed acute gastric volvulus with diaphragmatic hernia. On presentation, she was also in atrial fibrillation with rapid ventricular response. She was successfully treated by laparotomy with reduction of the gastric volvulus and repair of the diaphragmatic hernia, with significant improvement. PMID:28373916
Cong, Qing; Li, Xilian; Ye, Xuping; Sun, Li; Jiang, Wei; Han, Zhigang; Lu, Weiqi; Xu, Huan
Volvulus in pregnancy is rare and difficult to diagnose. Delayed diagnosis would result in high maternal and fetal mortality. Here we present an unusual case of small bowel volvulus in late pregnancy timely managed by emergency Cesarean section and derotation with excellent maternal and fetal outcomes. Volvulus should be considered in patients complaining ongoing abdominal pain, nausea, vomiting, constipation even diarrhea. Imaging is essential for early and precise diagnosis, including plain abdominal film, MRI and/or ultrasound. Once highly suspected or diagnosed of volvulus or ileus, emergency laparotomy should be performed immediately to avoid catastrophic outcomes, because the maternal and fetal prognosis is dependent on the interval from volvulus to operation apart from the degree of volvulus. PMID:25550984
Knafo, S Emmanuelle; Rosenblatt, Alana J; Morrisey, James K; Flanders, James A; Thompson, Margret S; Knapp-Hoch, Heather M
An 8-year-old male red kangaroo (Macropus rufus) was evaluated with a 2-week history of vomiting and anorexia. Four days prior, the patient became refractory to medical management. The kangaroo was admitted for diagnostic testing and treatment including whole body CT, blood work, and emergency laparotomy. CT findings of a severely enlarged stomach, splenic displacement, and a whirl sign were indicative of mesenteric volvulus with gastric dilatation-volvulus (GDV). Contrast enhancement of abdominal viscera suggested intact arterial blood supply; however, compression of the caudal vena cava and portal vein indicated venous obstruction. Results of preoperative blood work suggested biliary stasis without evidence of inflammation. Additionally, a tooth root abscess was diagnosed on the basis of results of CT. Exploratory laparotomy confirmed the diagnosis of mesenteric volvulus and GDV. The volvuli were corrected by clockwise derotation, and a gastropexy was performed. Tissue samples were obtained from the spleen and liver for evaluation. The kangaroo recovered from surgery, and the abscessed tooth was extracted 6 days later. Eight days after initial evaluation, the kangaroo was discharged. In the present report, the CT whirl sign was used to diagnose volvulus of the abdominal viscera, which suggests that this diagnostic indicator has utility in veterinary patients. Mesenteric volvulus with GDV was successfully treated in a nondomestic species. The tooth root abscess, a common condition in macropods, may explain the historic episodes of anorexia reported by the owner and may have contributed to the development of mesenteric volvulus and GDV in this kangaroo.
Choi, Byung Jo; Jeong, Won Jun; Kim, Say-June; Lee, Sang Chul
AIM: To report our experience with single-port laparoscopic surgery (SPLS) for sigmoid volvulus (SV). METHODS: Between October 2009 and April 2013, 10 patients underwent SPLS for SV. SPLS was performed transumbilically or through a predetermined stoma site. Conventional straight and rigid-type laparoscopic instruments were used. After intracorporeal, segmental resection of the affected sigmoid colon, the specimen was extracted through the single-incision site. Patient demographics and perioperative data were analyzed. RESULTS: SPLS for SV was successful in all 10 patients (4, resection and primary anastomosis; 6, Hartmann’s procedure). The median operative time and postoperative hospitalization period were 168 (range, 85-315) min and 6.5 (range, 4-29) d, respectively. No intraoperative complications were noted; there were 2 postoperative complications, including 1 anastomotic leak. CONCLUSION: SPLS was a safe and feasible therapeutic approach for SV, when performed by a surgeon experienced in conventional laparoscopic surgery. PMID:25741145
Schlanser, Justin R; Agnew, Dalen; Paperd, Deborah W; Harrison, Tara M
A 10-year-old male red panda presented acutely with symptoms of shock due to acute abdominal distress and respiratory compromise. Abdominal ultrasound confirmed a severely distended stomach for which passage of an orogastric tube for relief was unsuccessful. Intra-operatively, the stomach was found to be distended and torsed around its long axis supporting the diagnosis of Gastric dilitation-volvulus (GDV). The animal arrested and died intra-operatively and was submitted for necropsy with lesions supportive of the diagnosis of GDV. No risk factors for GDV were found to correlate between the panda and those described in domestic dogs. This case suggests that red pandas can be susceptible to this condition in captive settings.
SCHLANSER, Justin R.; AGNEW, Dalen; PAPERD, Deborah W.; HARRISON, Tara M.
ABSTRACT A 10-year-old male red panda presented acutely with symptoms of shock due to acute abdominal distress and respiratory compromise. Abdominal ultrasound confirmed a severely distended stomach for which passage of an orogastric tube for relief was unsuccessful. Intra-operatively, the stomach was found to be distended and torsed around its long axis supporting the diagnosis of Gastric dilitation-volvulus (GDV). The animal arrested and died intra-operatively and was submitted for necropsy with lesions supportive of the diagnosis of GDV. No risk factors for GDV were found to correlate between the panda and those described in domestic dogs. This case suggests that red pandas can be susceptible to this condition in captive settings. PMID:24521795
Collobert, C; Bernard, N; Lamidey, C
The umbilical skin and ligamentum nuchae of 368 horses were examined post mortem for Onchocerca species. Only four of the horses were infected and pathological changes were observed on the skin of two of them. Thelazia lacrimalis was recovered from 38 (10.3 per cent) of the horses, and animals aged six months to two years were more frequently infected. No ocular lesions were observed. The prevalences of these two nematodes were low when compared with the infection rates reported in the United Kingdom and North America.
Giannelli, Alessio; Cantacessi, Cinzia; Graves, Patricia; Becker, Luke; Campbell, Bronwyn Evelyn; Dantas-Torres, Filipe; Otranto, Domenico
Onchocerca lupi is a neglected filarioid causing nodular lesions associated with acute or chronic ocular disease in dogs. Despite the recent appraisal of its zoonotic potential, human cases are increasingly reported in the Old and New Worlds. Therefore, the development of accurate tools for the rapid diagnosis of O. lupi infections in dogs is becoming a priority. In this study, we conducted a preliminary investigation aimed at evaluating the usefulness of a commercially available ELISA test for the detection of O. lupi antigens in canine sera. The potential use of this tool for larger epidemiological studies of canine onchocerciasis is discussed.
Like other ambrosia beetles, Xyleborus volvulus Fabricius (Coleoptera: Curculionidae) lives in a mutualistic symbiotic relationship with fungi that serve as food source. Until recently, X. volvulus was not considered a pest, and none of its symbionts were considered plant pathogens. However, recent ...
Batirel, Hasan Fevzi; Uygur-Bayramicli, Oya; Guler, Sevgi; Yildizeli, Bedrettin; Yuksel, Mustafa
Gastric volvulus is an extremely rare late complication of pneumonectomy. We report the case of a 61-year-old man who presented with a 1-year history of progressive intolerance of solids and weight loss 33 years after a left pneumonectomy. Preoperative examinations showed a mesenteroaxial gastric volvulus. We performed a laparoscopic Toupet fundoplication and anterior gastropexy, following which his symptoms disappeared.
Tampakis, Athanasios; Droeser, Raoul A; Tampaki, Ekaterini Christina; von Holzen, Urs; Delko, Tarik
Cecal volvulus and ogilvie syndrome are two entities which may display similar clinical presentation but require different treatment approaches. An 84-year old male patient admitted for conservative treatment of a pelvis fracture, complained of abdominal cramps and flatulence on the third hospitalization day. Abdominal radiographs arose suspicion of cecal volvulus. The diagnosis was ruled out on the CT scan but however was later confirmed by an exploratory laparotomy. The management of cecal volvulus requires prompt (emergency) surgical intervention while Ogilvie syndrome can be principally managed with conservative treatment. Our patient's profile was typical for both entities. The absence of air throughout all colonic segments including the rectosigmoid on plain abdominal radiographs seems to be the most important sign in the exclusion of the Ogilvie syndrome diagnosis. Cecal volvulus and Ogilvie syndrome display overlapping clinical features at their time of presentation and need to be carefully distinguished. By uncertainty, an exploratory laparotomy should always be performed, in view of the reported high mortality rate of cecal volvulus if surgery is delayed.
Tampakis, Athanasios; Droeser, Raoul A.; Tampaki, Ekaterini Christina; von Holzen, Urs; Delko, Tarik
Introduction Cecal volvulus and ogilvie syndrome are two entities which may display similar clinical presentation but require different treatment approaches. Presentation of case An 84-year old male patient admitted for conservative treatment of a pelvis fracture, complained of abdominal cramps and flatulence on the third hospitalization day. Abdominal radiographs arose suspicion of cecal volvulus. The diagnosis was ruled out on the CT scan but however was later confirmed by an exploratory laparotomy. Discussion The management of cecal volvulus requires prompt (emergency) surgical intervention while Ogilvie syndrome can be principally managed with conservative treatment. Our patient's profile was typical for both entities. The absence of air throughout all colonic segments including the rectosigmoid on plain abdominal radiographs seems to be the most important sign in the exclusion of the Ogilvie syndrome diagnosis. Conclusion Cecal volvulus and Ogilvie syndrome display overlapping clinical features at their time of presentation and need to be carefully distinguished. By uncertainty, an exploratory laparotomy should always be performed, in view of the reported high mortality rate of cecal volvulus if surgery is delayed. PMID:27054035
Söker, Gökhan; Yılmaz, Cengiz; Karateke, Faruk; Gülek, Bozkurt
The most important complication of intestinal malrotation is midgut volvulus because it may lead to intestinal ischaemia and necrosis. A 29-year-old male patient was admitted to the emergency department with abdominal pain. Ultrasonography (US), colour Doppler ultrasonography (CDUS), CT and barium studies were carried out. On US and CDUS, twisting of intestinal segments around the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) and alteration of the SMA–SMV relationship were detected. CT demonstrated that the small intestine was making a rotation around the SMA and SMV, which amounted to more than 360°. The upper gastrointestinal barium series revealed a corkscrew appearance of the duodenum and proximal jejunum, which is a pathognomonic finding of midgut volvulus. Prior knowledge of characteristic imaging findings of midgut volvulus is essential in order to reach proper diagnosis and establish proper treatment before the development of intestinal ischaemia and necrosis. PMID:24811563
León Valdivies, Yusbiel José; Saínz Menéndez, Benito; Fernández García, Sergio; Osés Herrera, Liliana
The gastric volvulus is a not very frequent entity that can show up in acute form or chronic. The acute volvulus can show up with the triad of Borchardt, the chronic one can be asymptomatic and its diagnosis is usually incidental. We present shows a case of an airplane pilot that presents dyspnea to the medium efforts with cough related with episodes of gastric acidity mainly after profuse foods. The diagnostic confirmation was carried out by means of radiological simple and contrasted studies. A surgical intervention was performed and the symptoms disappeared without other alterations in a period of pursuit of one year.
El Azzouzi, Driss
Intrathoracic gastric volvulus in the neonatal period is a rare surgical emergency. Delays in diagnosis and treatment are life-threatening due to progressive deterioration of the gastric walls. Presentation in this period can be confused with the possibility of esophageal atresia or esophageal web. The upper gastrointestinal tract contrast study is diagnostic in this disease. The authors report a case of acute intrathoracic gastric volvulus diagnosis by radiologic-contrast-study in 1-day-old girl that was confirmed at surgery. The physiopathology, classification and different presentations of this entity are briefly reviewed. PMID:25309661
Gastric volvulus (GV) is a rare condition that presents with epigastric pain, retching and at times, vomiting. There are two types of GV: organoaxial and mesenteroaxial. We report the case of a 49-year-old woman with chronic mesenteroaxial volvulus with left-sided diaphragmatic defect. She presented with significant weight loss over a period of two years, with nonspecific symptoms of heartburn, occasional mild epigastric pain and anorexia. The patient was diagnosed with barium meal and contrast-enhanced computed tomography imaging. She was treated with open repair of diaphragmatic defect and anterior gastropexy. She was asymptomatic and had gained weight at the six-month follow-up.
Forsyth, K P; Mitchell, G F; Copeman, D B
Monoclonal antibodies directed to stage-specific surface antigens of Onchocerca gibsoni eggs were used in immunoradiometric assays to detect antigens in the sera of cattle infected with O. gibsoni. Two monoclonal antibodies detected antigens, presumably of egg origin, in sera. The target antigens appeared to be carbohydrate in nature and of variable molecular weights. Significant increases in levels of circulating egg antigens were found after treatment of infected cattle with benzimidazole compounds. These drugs cause disruption of embryogenesis and accelerated loss of worm uterine contents. In contrast, administration of either macrofilaricides or microfilaricides to infected cattle did not alter pretreatment levels of circulating egg antigens. Measurement of changes in levels of circulating antigens by immunoradiometric assays with stage-specific monoclonal antibodies provides a new means of assessing the efficacy of drugs and their site of action in onchocerciasis.
Hassan, Hassan K; Bolcen, Shanna; Kubofcik, Joseph; Nutman, Thomas B; Eberhard, Mark L; Middleton, Kelly; Wekesa, Joseph Wakoli; Ruedas, Gimena; Nelson, Kimberly J; Dubielzig, Richard; De Lombaert, Melissa; Silverman, Bruce; Schorling, Jamie J; Adler, Peter H; Unnasch, Thomas R; Beeler, Emily S
In southern California, ocular infections caused by Onchocerca lupi were diagnosed in 3 dogs (1 in 2006, 2 in 2012). The infectious agent was confirmed through morphologic analysis of fixed parasites in tissues and by PCR and sequencing of amplicons derived from 2 mitochondrially encoded genes and 1 nuclear-encoded gene. A nested PCR based on the sequence of the cytochrome oxidase subunit 1 gene of the parasite was developed and used to screen Simulium black flies collected from southern California for O. lupi DNA. Six (2.8%; 95% CI 0.6%-5.0%) of 213 black flies contained O. lupi DNA. Partial mitochondrial16S rRNA gene sequences from the infected flies matched sequences derived from black fly larvae cytotaxonomically identified as Simulium tribulatum. These data implicate S. tribulatum flies as a putative vector for O. lupi in southern California.
Hassan, Hassan K.; Bolcen, Shanna; Kubofcik, Joseph; Nutman, Thomas B.; Eberhard, Mark L.; Middleton, Kelly; Wekesa, Joseph Wakoli; Ruedas, Gimena; Nelson, Kimberly J.; Dubielzig, Richard; De Lombaert, Melissa; Silverman, Bruce; Schorling, Jamie J.; Adler, Peter H.; Beeler, Emily S.
In southern California, ocular infections caused by Onchocerca lupi were diagnosed in 3 dogs (1 in 2006, 2 in 2012). The infectious agent was confirmed through morphologic analysis of fixed parasites in tissues and by PCR and sequencing of amplicons derived from 2 mitochondrially encoded genes and 1 nuclear-encoded gene. A nested PCR based on the sequence of the cytochrome oxidase subunit 1 gene of the parasite was developed and used to screen Simulium black flies collected from southern California for O. lupi DNA. Six (2.8%; 95% CI 0.6%–5.0%) of 213 black flies contained O. lupi DNA. Partial mitochondrial16S rRNA gene sequences from the infected flies matched sequences derived from black fly larvae cytotaxonomically identified as Simulium tribulatum. These data implicate S. tribulatum flies as a putative vector for O. lupi in southern California. PMID:25897954
Tudor, Poliana; Turcitu, Mihai; Mateescu, Cosmin; Dantas-Torres, Filipe; Tudor, Niculae; Bărbuceanu, Florica; Ciuca, Lavinia; Burcoveanu, Ioana; Acatrinei, Dumitru; Rinaldi, Laura; Mateescu, Romanița; Bădicu, Adina; Ionașcu, Iuliana; Otranto, Domenico
Onchocerca lupi is a filarial nematode, which infects the scleral conjunctival tissue of dogs, wolves and cats. Whilst adult nematodes localize in the conjunctive tissue of sclera or in the retrobulbar, microfilariae are found in the skin, and they are rarely diagnosed in asymptomatic animals. Since the first report of human ocular infection 5 years ago, up to 10 zoonotic cases have been identified in patients worldwide. We report, for the first time in Romania, three cases of canine ocular onchocercosis in dogs. Fragments of the harvested worms were characterized morphologically and molecularly. This article expands knowledge on the distribution of this parasite in Eastern Europe and sounds an alarm bell for ophthalmologists about the possible occurrence of human cases of O. lupi infection.
Otranto, Domenico; Sakru, Nermin; Testini, Gabriella; Gürlü, Vuslat P.; Yakar, Konuralp; Lia, Riccardo P.; Dantas-Torres, Filipe; Bain, Odile
In the past decades, cases of canine ocular onchocercosis have been reported worldwide, particularly in the United States and Europe. Onchocerca lupi, originally described from a wolf, has been implicated in some of these cases, and its zoonotic role has been hypothesized on the basis of the reexamination of two cases of human ocular onchocerciasis. In the present study, we describe, for the first time, the occurrence of O. lupi in the subconjunctival region of the human eye in a patient from Turkey. The nematode was identified as O. lupi based on its morphology and molecular phylogenetic analysis of partial cox1 and 12S ribosomal DNA genes. The results suggest that O. lupi should be considered in the differential diagnosis of other eye parasitic infections in humans. The role of dogs as natural hosts of O. lupi and the vectors of this zoonotic parasite need to be investigated. PMID:21212202
Wang, Jing; Tricoche, Nancy; Du, Lanying; Hunter, Meredith; Zhan, Bin; Goud, Gaddam; Didier, Elizabeth S; Liu, Jing; Lu, Lu; Marx, Preston A; Jiang, Shibo; Lustigman, Sara
Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.
Wang, Jing; Tricoche, Nancy; Du, Lanying; Hunter, Meredith; Zhan, Bin; Goud, Gaddam; Didier, Elizabeth S.; Liu, Jing; Lu, Lu; Marx, Preston A.; Jiang, Shibo; Lustigman, Sara
Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant. PMID
Cantone, Noemi; Gulia, Caterina; Miele, Vittorio; Trinci, Margherita; Briganti, Vito
Wandering spleen and gastric volvulus are two rare entities that have been described in association with congenital diaphragmatic hernia. The diagnosis is difficult and any delay can result in ischemia and necrosis of both organs. We present a case of a 13-year-old girl, previously operated on for anterior diaphragmatic hernia and intrathoracic gastric volvulus, that presented to our service for a subdiaphragmatic gastric volvulus recurrence associated with a wandering spleen. In this report we reviewed the literature, analyzing the clinical presentation, diagnostic assessment, and treatment options of both conditions, in particular in the case associated with diaphragmatic hernia.
Gulia, Caterina; Miele, Vittorio; Trinci, Margherita; Briganti, Vito
Wandering spleen and gastric volvulus are two rare entities that have been described in association with congenital diaphragmatic hernia. The diagnosis is difficult and any delay can result in ischemia and necrosis of both organs. We present a case of a 13-year-old girl, previously operated on for anterior diaphragmatic hernia and intrathoracic gastric volvulus, that presented to our service for a subdiaphragmatic gastric volvulus recurrence associated with a wandering spleen. In this report we reviewed the literature, analyzing the clinical presentation, diagnostic assessment, and treatment options of both conditions, in particular in the case associated with diaphragmatic hernia. PMID:27703832
Coban, Sacid; Yilmaz, Mehmet; Terzi, Alpaslan; Yildiz, Fahrettin; Ozgor, Dincer; Ara, Cengiz; Yologlu, Saim; Kirimlioglu, Vedat
AIM: To evaluate the efficacy of resection and primary anastomosis (RPA) and RPA with modified blow-hole colostomy for sigmoid volvulus. METHODS: From March 2000 to September 2007, 77 patients with acute sigmoid volvulus were treated. A total of 47 patients underwent RPA or RPA with modified blow-hole colostomy. Twenty-five patients received RPA (Group A), and the remaining 22 patients had RPA with modified blow-hole colostomy (Group B). The clinical course and postoperative complications of the two groups were compared. RESULTS: The mean hospital stay, wound infection and mortality did not differ significantly between the groups. Superficial wound infection rate was higher in group A (32% vs 9.1%). Anastomotic leakage was observed only in group A, with a rate of 6.3%. The difference was numerically impressive but was statistically not significant. CONCLUSION: RPA with modified blow-hole colostomy provides satisfactory results. It is easy to perform and may become a method of choice in patients with sigmoid volvulus. Further studies are required to further establish its role in the treatment of sigmoid volvulus. PMID:18810779
Ba, P A; Diop, B; Soumah, S A
The aim of this study is to report our experience in the management of sigmoid volvulus in a tropical environment. This retrospective study covers the period from June 1, 2010, to December 31, 2013, in the department of emergency surgery at the regional hospital of Thiés: 40 patients were admitted with sigmoid volvulus: 36 men and 4 women, with a mean age of 45 years (20-89 years). Twelve had chronic constipation. All four signs of occlusion were present in 72.5% of cases. Abdominal radiography confirmed the diagnosis in all cases. The volvulus resolved spontaneously in one patient, while the other 39 required laparotomy: 25 had a one-stage colectomy, and 11 patients a sigmoidectomy with a temporary colostomy. Two patients underwent a sigmoidopexy, one with a simple closure of a perforated duodenal ulcer. The morbidity rate was 7.5%, due mainly to complications of infection. The mortality rate was 10%. After a mean follow-up of 2.77 months (range: 15 days-12 months), no recurrences were observed. Sigmoid volvulus is a common condition in Africa especially in younger patients. The diagnosis is easy, based on clinical and abdominal radiography findings. Several procedures have been described but the one-stage colectomy remains the method of choice, especially in tropical areas where socioeconomic conditions are difficult.
Olaoye, Iyiade Olatunde; Adesina, Micheal Dapo
Small intestinal volvulus is rare in adults and rarely caused by string adhesions between the liver and the diaphragm. Similar adhesions were described in Fitz-Hugh-Curtis syndrome. We report a 45-year-old lady with small intestinal volvulus from entrapment of a loop in string adhesions between the liver and the diaphragm. Her plain radiographs showed a significant shadow of the trapped loop. PMID:28003317
Okolo, C A; Afolabi, A O; Sahabi, S M
A 31 year-old Nigerian man with jejuno-jejunal intussusception with the lead point being an adenocarcinoma complicated by small intestinal volvulus is presented. The subtle clinical features of an underlying small bowel malignancy were masked by the overwhelming clinical and radiological features of intussusception. rare case is reported to remind clinicians to have an increased index of suspicion of malignancy in patients who present with the usual features of chronic anemia, weight loss and loss of appetite with an intra-abdominal mass. The presentation of acute intestinal obstruction, with mesenteric vein thrombosis probably due to intussusception or volvulus should not however lower the suspicion. Histological evaluation of surgical biopsies is of immense importance.
Diouf, Cheikh; Kane, Ahmed; Ndoye, Ndeye Aby; Ndour, Oumar; Faye-Fall, Aimé Lakh; Fall, Mbaye; Alumeti, Désiré Munyali; Ngom, Gabriel
We report an exceptional case of a 7 year-old patient with necrotic small bowel volvulus due to adult ascaris lumbricoides. At the admission, the child had intestinal obstruction evolving since two days with alteration of general state. Abdominal radiography without preparation showed small bowel air-fluid levels and tiger-stripe appearance evoking the diagnosis of acute intestinal obstruction associated with abdominal mass. After resuscitation, the surgical treatment consisted of laparotomy which showed necrotic volvulus of the terminal ileum containing adult ascaris lumbricoides. The patient underwent small bowel resection, approximately one meter of affected section was removed and then an ileostomy was performed. The evolution was favorable. The patient underwent ileorectal anastomosis four weeks later. After a 2 year follow-up period the child had no symptoms.
Aslanian, M E; Sharp, C R; Garneau, M S
A brachycephalic dog was presented with an acute onset of retching and abdominal discomfort. The dog had a chronic history of stertor and exercise intolerance suggestive of brachycephalic airway obstructive syndrome. Radiographs were consistent with a Type II hiatal hernia. The dog was referred and within hours of admission became acutely painful and developed tympanic abdominal distension. A right lateral abdominal radiograph confirmed gastric dilatation and volvulus with herniation of the pylorus through the hiatus. An emergency exploratory coeliotomy was performed, during which the stomach was derotated, and an incisional gastropexy, herniorrhaphy and splenectomy were performed. A staphylectomy was performed immediately following the exploratory coeliotomy. The dog recovered uneventfully. Gastric dilatation and volvulus is a potentially life-threatening complication that can occur in dogs with Type II hiatal hernia and should be considered a surgical emergency. © 2014 British Small Animal Veterinary Association.
Abdelilah, Mouhsine; Jihad, Anzaoui; Rachid, Bouchentouf
Le volvulus gastrique est une rotation anormale de l'estomac autour de son axe. La forme aiguë constitue une urgence chirurgicale. Le diagnostic est souvent retardé en raison d'une symptomatologie fréquemment non spécifique. Des signes respiratoires tels la dyspnée et le hoquet peuvent révéler cette pathologie. Les auteurs rapportent une nouvelle observation de volvulus gastrique aigu chez un adolescent de 17 ans, diagnostiqué par la tomodensitométrie, et confirmé par une intervention chirurgicale. Le traitement est chirurgical et consiste à détordre et fixer l'estomac pour prévenir la récidive. PMID:23503200
Tandian, Foulaké; Cissé, Mamadou; Touré, Alpha Oumar; Seck, Mamadou; Thiam, Ousmane; Guèye, Mohamadou Lamine
Le volvulus de la vésicule biliaire (VVB) est une affection rare et de diagnostic difficile; le plus souvent per opératoire. Nous rapportons 1 cas de VVB avec gangrène de la vésicule biliaire chez un enfant de 10 ans. Le diagnostic a été porté à l'exploration chirurgicale réalisée en urgence pour un syndrome occlusif fébrile. Il s'agissait d'un volvulus total de la vésicule biliaire. A cette occasion, nous rappelons les aspects diagnostiques et thérapeutiques de cette affection. PMID:26140071
Díaz Plasencia, J; Huaynalaya, E; Rodríguez, F; Rebaza, H
This retrospective study evaluated predisposing factors, clinical picture and the methods of treatment related to morbidity and mortality of 19 small bowel volvulus (SBV) who underwent operation at Belen Hospital (Trujillo-Peru) during the last 26 years (1966-1992). The SBV was 1.6% of all cases of intestinal obstruction in this period and 10.8% of all intestinal volvulus. The median age was of 43 +/- 20.5 years (range, 6 to 78 years) and the majority of them were between 41 and 60 years. Sixteen cases (84.2%) were men from Indian and Spanish extraction and most of them were farmers and came from the Sierra of the Department of La Libertad. Two cases (10.5%) had non-related antecedents previous surgery. In six patients (31.6%) the volvulus was less than seven day's duration and in thirty (68.4%) it was more eight day's duration with previous attacks of obstruction (median: 19.3 days, range: 17 hours to 94 days). Pain, vomiting and distention were present in almost all of these cases. The most frequent abdominal finding was distention. The location of the volvulus was: ileum, 12 cases (63.2%), root of mesentery, 4 cases (21%) and jejunum, 3 cases (15.8%). Gangrenous bowel was present in six patients (31.5) and gangrenous intestine with perforation in two cases (10.5%) who underwent resection of the involved segment with primary anastomosis. In this group one patient (5.2%) died of sepsis and the wound infection rate was of 37.5%. There was no statistically significant correlation with the duration of illness and the presence of gangrenous loops or the mortality rate (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
An 8-year-old crossbreed dog presented after one episode of acute collapse due to rupture of a splenic haemangiosarcoma. Following splenectomy the dog recovered well. Two days after discharge the dog re-presented because of gastric dilatation-volvulus (GDV) that eventually led to his death. Splenectomy to remove a voluminous splenic tumour may predispose to GDV and dogs may benefit from concurrent prophylactic gastropexy.
George, Dafnomilis; Apostolos, Pappas V.; Athanasios, Panoutsopoulos; Emmanuel, Lagoudianakis E.; Nikolaos, Koronakis E.; Nikolaos, Panagiotopoulos; Charalampos, Seretis; George, Karanikas; Andreas, Manouras J.
Type IV hiatal hernias are characterized by herniation of the stomach along with associated viscera such as the spleen, colon, small bowel, and pancreas through the esophageal hiatus. They are relatively rare, representing only about 5%–7% of all hernias, and can be associated with severe complications. We report a 71-year-old veteran wrestler who presented to our department with a type IV paraesophageal hernia containing a gastric volvulus and treated successfully with emergency operation. PMID:20981251
Chang, Chih-Jung; Hsieh, Tsung-Hung; Tsai, Kuang-Chau; Fan, Chieh-Min
Volvulus of the sigmoid colon is a potentially life-threatening condition rarely seen in younger age groups and is male predominant. We report a previously healthy young woman with the triad of constipation, progressive abdominal distension, and severe abdominal pain, with plain-film x-ray studies mimicking stool impaction and computed tomography disclosing the typical findings of sigmoid volvulus. The case reminds Emergency Physicians to consider sigmoid volvulus if mechanical obstruction is suspected, even in a young patient. A 33-year-old woman had the triad of symptoms for 3 days. Physical examination did not show peritoneal signs. Digital rectal examination disclosed neither palpable mass nor stool in rectum. Computed tomography revealed "coffee bean" sign and "whirl" sign. Laparoscopy demonstrated redundant sigmoid colon and she was treated with detorsion with colopexy uneventfully. Sigmoid volvulus is rarely seen in developed countries. Clinical manifestations vary with disease progression, but it typically presents with a triad of constipation, progressive abdominal distension, and severe abdominal pain. Plain-film x-ray studies can demonstrate a coffee bean or "omega loop" (inverted-U sigmoid) sign in <60% cases, but it was reported as high as 86% in computed tomography. The whirl sign on computed tomography might also be observed. The cause is multifactorial and colonic length is the most important predisposing factor. Flexible colon fiberscopic decompression followed by elective definitive surgery is the treatment choice, but exploratory laparotomy is mandatory if any complicated entity occurs. The mortality rate is still >50% when bowel gangrene develops. Copyright © 2013 Elsevier Inc. All rights reserved.
Miró, Guadalupe; Montoya, Ana; Checa, Rocío; Gálvez, Rosa; Mínguez, Juan José; Marino, Valentina; Otranto, Domenico
Onchocerca lupi causes ocular pathology of varying severity in dogs from south-western United States, western Europe and northern Asia. This filarioid has also been recognized as a zoonotic agent in Tunisia, Turkey, Iran and the USA, though the information about the biology and epidemiology of this infection is largely unknown. In Europe, O. lupi has been reported in dogs from Germany, Greece, Hungary, Portugal and Romania and in a cat from Portugal. The present study was designed to establish the occurrence of O. lupi in dogs in southwestern Spain. In the present study a total of 104 dogs of different breed, sex, and age living in a shelter in Huelva (SW Spain) were examined. Skin snip samples were collected using a disposable scalpel in the forehead and inter-scapular regions and stored as aliquots in saline solution (0.5 ml) before light microscopy observation of individual sediments (20 μl) and molecular examination. Of the 104 dogs examined, 5 (4.8 %) were skin snip-positive for O. lupi: two by microscopy and three by PCR. One of the O. lupi infected dogs showed neurological signs but ocular ultrasonography and/or MRI detected no abnormalities. This first report of O. lupi infection in dogs in southern Spain expands the range of geographical distribution of this parasite and sounds an alarm bell for practitioners and physicians working in that area.
Chen, Tsinsue; Moon, Karam; deMello, Daphne E; Feiz-Erfan, Iman; Theodore, Nicholas; Bhardwaj, Ratan D
A 13-year-old boy presented with fever and neck pain and stiffness, which was initially misdiagnosed as culture-negative meningitis. Magnetic resonance images of the brain and cervical spine demonstrated what appeared to be an intradural extramedullary mass at the C1-3 level, resulting in moderate cord compression, and a Chiari Type I malformation. The patient underwent a suboccipital craniectomy and a C1-3 laminectomy with intradural exploration for excisional biopsy and resection. The lesion containing the parasite was extradural, extending laterally through the C2-3 foramina. Inflammatory tissue secondary to Onchocerca lupi infection was identified, and treatment with steroids and doxycycline was initiated. At the 6-month follow-up, the patient remained asymptomatic, with MR images demonstrating a significant reduction in lesional size. However, 10 weeks postoperatively, the infection recurred, necessitating a second operation. The patient was treated with an additional course of doxycycline and is currently maintained on ivermectin therapy. This is the second reported case of cervical O. lupi infection in a human. In the authors' experience, oral doxycycline alone was insufficient in controlling the disease, and the addition of ivermectin therapy was necessary.
Grácio, António J Santos; Richter, Joachim; Komnenou, Anastasia Th; Grácio, Maria Amélia
Globalization has increased circulation of people, their food, livestock and pets in the world, and changes in the environment, climate and human behaviour have led to the rapid expansion of emerging infections throughout the world. One of the reasons of a new pathogen affecting humans is the passage from an animal to a human being. Onchocerca (O.) lupi, a filarial worm first described in a wolf in 1967, is an emerging pathogen which has been incriminated as the etiological agent for 205 canine, 2 feline and 18 human infections in Europe, Tunisia, Turkey, Iran and the USA. Most frequent findings in animals and humans are monolateral or asymmetrical variably painful subconjunctival swellings and nodules containing immature or mature worms affecting the eye and/or adjacent tissues accompanied by conjunctival hyperemia. Occasionally, subcutaneous nodules and masses affecting the spinal cord have been observed in humans. Diagnosis of O. lupi is achieved by microscopy of excised adult female worms which exhibit a particular cuticular structure and molecular analysis. Treatment consists in worm removal accompanied by antihelminthic, antibiotic and anti-inflammatory therapy.
Lachhab, Imad; Traoré, Boubacar Zan; Saoud, Omar; Khedid, Yahia Zain Al Abidine; Zouaidia, Fouad; Echarrab, Mahjoub; Chkoff, Mohamed Rachid
The primary malignant tumors of the small bowel are rare, representing 1 to 1.4% of all gastrointestinal tumors. We report a case of a 33 year-old women, admitted to our emergency department of visceral surgery for acute abdomen. The clinical examination revealed diffuse abdominal distension, defenseless, the hernia orifices were free and the rectal examination was normal. The biological test showed no hydro electrolytic disorders with normal hemoglobin and normal renal function. The abdominal CT-Scan showed signs of bowel obstruction due to a volvulus with intussusception without ischemia. The patient was operated urgently; the exploration has revealed a small bowel obstruction in the ileum with volvulus, an intussusceptum associated with a retractile mesenteritis, and the hepatic exploration found no metastases. The patient underwent a bowel resection taking away the intussusceptum with the infiltrated mesentery. The postoperative course was uneventful. The pathological result has proved a well-differentiated neuroendocrine tumor with five free nodes. Through this observation, we aim to highlight that an obstruction of small bowel with volvulus and intussusception could be exceptionally due to a neuroendocrine tumor, this complication has enabled a relatively early diagnosis in the absence of metastases and a 6-month follow-up without recurrence is a demonstration.
Ramírez-Ramírez, Moisés Marino; Villanueva-Sáenz, Eduardo; Ramírez-Wiella-Schwuchow, Gustavo
Caecal volvulus is an uncommon cause of intestinal obstruction. Its clinical presentation is non-specific, with the diagnosis usually confirmed by barium enema and abdominal computed tomography. Treatment depends on many factors, and minimally invasive approaches are becoming the treatment of choice. A 54 years old female, admitted to the Emergency Department with clinical symptoms of intestinal obstruction. On physical examination she had a palpable, firm, and tympanitic mass in the right abdomen, with peritoneal irritation. The radiographs of the abdomen, barium enema and abdominal computed tomography showed caecal volvulus. As she showed a full remission after the barium enema, with no clinical or biochemical data of systemic inflammatory response syndrome or peritoneal irritation, she was discharged to her home. Two weeks later, a laparoscopic right hemicolectomy was performed with an ileo-transverse extracorporeal anastomosis. Her progress was satisfactory, and she was discharged 4 days after surgery due to improvement. Caecal volvulus is a rare cause of intestinal obstruction, with high mortality rates, and is caused by excessive mobility of the caecum. Its incidence is increasing. Treatment depends on many factors. Early non-surgical untwisting, followed by an elective laparoscopic surgical procedure offers several advantages and reduces mortality. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.
Inayat, Faisal; Hurairah, Abu; Shaikh, Faiq
The Marfan syndrome (MFS) is a pleiotropic, autosomal dominant disorder of connective tissue with highly variable clinical manifestations. It primarily involves the skeletal, cardiovascular, and ocular systems; however, gastrointestinal complications are rare. Herein, we describe the case of a 31-year-old male who initially presented with acute abdominal pain for one day. His imaging features revealed a dilated sigmoid colon, consistent with sigmoid volvulus that was immediately decompressed. Surgical resection was recommended to treat the sigmoid volvulus. Preceding the treatment, the patient underwent an extensive workup, including an echocardiography that revealed aortic root dilatation. His clinical history, physical exam, and echocardiographic findings raised the suspicion for MFS. Subsequently, the diagnosis of MFS was confirmed on genetic testing. This is a case that highlights the multidisciplinary (clinical, radiological, endoscopic, molecular/genetic) approach to diagnose a patient with MFS who presented with symptomatic sigmoid volvulus. As this presentation may be a harbinger of more severe manifestations of MFS, it is important to identify it as such in order to accomodate for timely management.
Yang, Chao; Wang, Shan; Zhang, Jun; Kong, Xiang Ru; Zhao, Zhenzhen; Li, Chang Chun
Volvulus caused by mesenteric masses is rare and may result in serious consequences. This study aimed to better characterize volvulus caused by mesenteric masses in children. A retrospective study was conducted in 24 patients who underwent surgical treatment between January 1994 and January 2014 in one single institution. There were 10 boys and 14 girls. The most frequent findings were abdominal pain (100%), emesis (91.7%) and nausea (83.3%). Physical examination showed positive ileus signs in majority cases, and palpable mass was found in half of the patients. Ultrasound and CT scans revealed mesenteric masses in 21 and 24 patients, and 'whirlpool sign' was observed in 19 and 22 patients, respectively. Emergency laparotomy was performed in all patients. Histological examination revealed that 18 cystic masses were lymphangioma, 5 solid cases were lipoma and the remaining one was lipoblastoma. The postoperative course was uneventful in 22 patients, and postoperative obstruction and incision infection occurred in 2 patients. There was no evidence of recurrence at follow-up. Volvulus caused by mesenteric masses is a rare but potentially life-threatening cause of abdominal pain, which should be considered in the differential diagnosis of paediatric acute abdominal pain.
Hurairah, Abu; Shaikh, Faiq
The Marfan syndrome (MFS) is a pleiotropic, autosomal dominant disorder of connective tissue with highly variable clinical manifestations. It primarily involves the skeletal, cardiovascular, and ocular systems; however, gastrointestinal complications are rare. Herein, we describe the case of a 31-year-old male who initially presented with acute abdominal pain for one day. His imaging features revealed a dilated sigmoid colon, consistent with sigmoid volvulus that was immediately decompressed. Surgical resection was recommended to treat the sigmoid volvulus. Preceding the treatment, the patient underwent an extensive workup, including an echocardiography that revealed aortic root dilatation. His clinical history, physical exam, and echocardiographic findings raised the suspicion for MFS. Subsequently, the diagnosis of MFS was confirmed on genetic testing. This is a case that highlights the multidisciplinary (clinical, radiological, endoscopic, molecular/genetic) approach to diagnose a patient with MFS who presented with symptomatic sigmoid volvulus. As this presentation may be a harbinger of more severe manifestations of MFS, it is important to identify it as such in order to accomodate for timely management. PMID:27382527
Gonzalez, L. M.; Fogle, C. A.; Baker, W. T.; Hughes, F. E.; Law, J. M.; Motsinger-Reif, A. A.; Blikslager, A. T.
Summary Reasons for performing the study There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus. Objectives To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus. Study Design Retrospective cohort study Methods Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson & Smith and Chino Valley Equine Hospitals between 2006–2013 undergoing an exploratory celiotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitial: crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital). Results Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitial: crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be significantly associated with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified haemorrhage area measurement strengthened the association of haemorrhage with non-survival in cases of large colon volvulus. Conclusions Histomorphometric measurements of interstitial: crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study
Pollack, R J; Lok, J B; Donnelly, J J
Reduced glutathione (GSH), but not its oxidized form (GSSG), stimulated development of Onchocerca lienalis microfilariae to the late first-larval stage in vitro. The degree and frequency of development was dose-related with a peak of activity at 15 mM, a concentration that is similar to known intracellular levels of GSH. To determine the mode(s) of action of this multifunctional compound, other reducing agents (L-cysteine, dithiothreitol), cysteine delivery agents (N-acetyl-L-cysteine, L-thiazolidine-4-carboxylic acid, L-2-oxothiazolidine-4-carboxylic acid), cysteine analogues (S-methyl-L-cysteine, D-glucose-L-cysteine, cysteine ethyl ester), free-component amino acids of GSH (glutamic acid, cysteine, and glycine), a specific metabolic inhibitor of gamma-glutamyl synthetase (buthionine sulfoximine), and an inhibitor of gamma-glutamyl transpeptidase (gamma-glutamyl glutamic acid) were also tested at concentrations of 0.01-50 mM in this system. N-acetyl-L-cysteine at 1-5 mM and D-glucose-L-cysteine at 2.5-10 mM significantly enhanced development. In contrast to those worms maintained in GSH-supplemented medium, microfilariae exposed to GSH for only the first 24 hr showed no enhancement by day 7 in culture. Neither buthionine sulfoximine nor gamma-glutamyl glutamic acid at 0.01-35 mM inhibited the effects of 15 mM GSH or 1 mM N-acetyl-L-cysteine. Results indicate that GSH or other cysteine analogues possessing a free sulfhydryl group must be present in the extranematodal environment to support microfilarial differentiation in vitro.
Onchocerca cervipedis is a filarioid nematode of cervids reported from Central America to boreal regions of North America. It is found primarily in subcutaneous tissues of the legs, and is popularly known as ‘legworm’. Blackflies are intermediate hosts and transmit larvae to ungulates when they bloo...
François-Fiquet, Caroline; Belouadah, Mohamed; Chauvet, Philippe; Lefebvre, Francis; Lefort, Gérard; Poli-Merol, Marie Laurence
A 2.5-year-old boy was referred to the emergency room for a sudden onset of diffuse and increasing abdominal pain with lethargy, abdominal distension, and vomiting, all in the past 24 hours. A plain abdominal X-ray showed gastric distension. Two liters of gastric contents were evacuated by suction. The abdominal sonogram showed an unusual position of the spleen in the left-lower quadrant, with no splenic ischemia. The diagnosis of gastric volvulus associated with a wandering spleen was then evoked. Laparoscopic exploration revealed a nonischemic spleen, absence of normal supporting ligaments for the spleen, and gastric distension with flaccid gastric walls. The spleen was then easily moved in the left-under quadrant. A parietal peritoneal posterolateral incision was made, opposite the large gastric curve, up to the diaphragm (7 cm). This delimitated a sharp demarcation zone between the two edges of the incised peritoneum. The stomach was fixed to the peritoneal incision, covering and anchoring the spleen in a good position. Recovery was uneventful, and an abdominal sonogram performed 4 years after the surgery shows a viable spleen in its correct location. The rarity of gastric volvulus associated with a wandering spleen and its fast clinical improvement with medical treatment often delays the diagnosis and the surgical treatment. Laparoscopy in this case has a dual relevance: diagnosis and therapeutic management (splenectomy or gastropexy). Laparoscopic gastropexy for the treatment of gastric volvulus associated with a wandering spleen is an easy procedure and combines the advantages of all the surgical techniques previously described.
Dème, Hamidou; Badji, Nfally; Akpo, Léra Géraud; Touré, Mouhamed Hamine; Draha, Ronald; Niang, Fallou Gallas; Diop, Abdoulaye Dione; Niang, El Hadj
Nous rapportons le cas d'une patiente de 7 ans qui a consulté pour une douleur abdominale aigue paroxystique siégeant au niveau de l'épigastre associée à des vomissements sans arrêt des matières et des gaz. L'examen clinique ainsi que le bilan biologique étaient sans particularité. L'échographie abdominale demandée en première intention a montré une masse du flanc et de la fosse iliaque droite échogène, homogène à contours réguliers sans signal vasculaire au Doppler associée à un signe du tourbillon des vaisseaux mésentériques. A la tomodensitométrie cette masse correspondait à une formation lipomateuse, bien limitée, exerçant un effet de masse sur le cœcum avec volvulus du mésentère au contact. La disposition des vaisseaux mésentériques à leur origine était normale. Le diagnostic de volvulus du mésentère sur lipome a été retenu. La prise en charge chirurgicale et l'analyse anatomopathologique de la pièce opératoire a confirmé le diagnostic. Nous allons à travers ce cas clinique revoir l'apport de l'échographie et du scanner dans le diagnostic de volvulus du mésentère. PMID:28250879
Joung, Hae Soo; Guerrero, Alexandra Leon; Tomita, Sandra; Kuenzler, Keith A
Anorectal malformations (ARMs) commonly co-occur with other congenital anomalies, particularly VACTERL (vertebral, anorectal, cardiac, tracheal, esophageal, renal, limb, and duodenal) associations. However, this collection of associations is not comprehensive, and other concurrent anomalies may exist that can be missed during the standard work-up of patients with ARMs. We present a rare case of a neonate with a low ARM with concurrent jejuno-ileal atresia that was diagnosed after the correction of the ARM when the patient developed segmental volvulus. This case illustrates the importance of having a high index of suspicion when deviation from a classic presentation occurs.
Watanabe, Toshihiko; Nakano, Miwako; Yamazawa, Kazuki; Maeyama, Katsuhiro; Endo, Masao
Situs ambiguus is a rare lateralization anomaly that is frequently associated with other malformations, including preduodenal portal vein (PDPV), intestinal malrotation, and cardiovascular anomalies. This is a case report on a newborn that was clinically diagnosed with situs ambiguus and midgut volvulus. During surgery the patient was found to have intestinal malrotation, Meckel's diverticulum, and PDPV that was not a direct cause of duodenal obstruction. The patient was treated with Ladd's procedure and resection of Meckel's diverticulum. It is important to be familiar with the spectrum of situs anomalies to prevent trauma to the portal vein with serious complications during surgery.
Joung, Hae Soo; Guerrero, Alexandra Leon; Tomita, Sandra; Kuenzler, Keith A.
Anorectal malformations (ARMs) commonly co-occur with other congenital anomalies, particularly VACTERL (vertebral, anorectal, cardiac, tracheal, esophageal, renal, limb, and duodenal) associations. However, this collection of associations is not comprehensive, and other concurrent anomalies may exist that can be missed during the standard work-up of patients with ARMs. We present a rare case of a neonate with a low ARM with concurrent jejuno-ileal atresia that was diagnosed after the correction of the ARM when the patient developed segmental volvulus. This case illustrates the importance of having a high index of suspicion when deviation from a classic presentation occurs. PMID:27896167
Tepas, J J; MacLean, W C; Kolbach, S; Shermeta, D W
Absorption studies in rats have shown that intestinal adaptation after catastrophic injury can be stimulated by early enteral feeding. Using this concept, we have devised a technique of early initiation and advancement of oral feedings that begins with Cho-Free and Polycose and gradually adds sucrose and MCT in increasing proportions. The increasing complexity and caloric density of this diet provide sufficient nutrition to allow weaning from total parenteral alimentation within 2--3 wk. Our preliminary experience in babies with midgut volvulus, necrotizing enterocolitis, and gastroschisis has been successful and uncomplicated. These patients have demonstrated consistent weight gain and have been spared the complications associated with prolonged parenteral alimentation.
Diouf, Cheikh; Kane, Ahmed; Ndoye, Ndeye Aby; Ndour, Oumar; Faye-Fall, Aimé Lakh; Fall, Mbaye; Alumeti, Désiré Munyali; Ngom, Gabriel
Nous rapportons un cas exceptionnel de volvulus nécrosé de l'intestin grêle dû à des ascaris adultes chez un enfant de 7 ans. A l'admission, l'enfant présentait le tableau d'occlusion intestinale qui évoluait depuis deux jours avec altération de l'état général. La radiographie de l'abdomen sans préparation retrouvait des niveaux hydroaériques de type grêlique et un aspect tigré évoquant le diagnostic d'une occlusion intestinale haute sur masse abdominale. Après la réanimation, le traitement chirurgical consistait en une laparotomie qui avait retrouvé un volvulus nécrosé de l'iléon terminale contenant des ascaris adultes. Une résection du grêle sur environ un mètre emportant le segment nécrosé suivie d'une iléostomie était réalisée. L'évolution a été favorable, l'anastomose iléo-colique fut réalisée quatre semaines plus tard. Au recul de deux ans l'enfant est indemne de tout symptôme. PMID:27795803
Coe, Taylor M; Chang, David C; Sicklick, Jason K
Small bowel volvulus is a rare entity in Western adults. Greater insight into epidemiology and outcomes may be gained from a national database inquiry. The Nationwide Inpatient Sample (1998 to 2010), a 20% stratified sample of United States hospitals, was retrospectively reviewed for small bowel volvulus cases (International Classification of Diseases, 9th Edition [ICD-9] code 560.2 excluding gastric/colonic procedures) in patients greater than or equal to 18 years old. There were 2,065,599 hospitalizations for bowel obstruction (ICD-9 560.x). Of those, there were 20,680 (1.00%) small bowel volvulus cases; 169 were attributable to intestinal malrotation. Most cases presented emergently (89.24%) and operative management was employed more frequently than nonoperative (65.21% vs 34.79%, P < .0001). Predictors of mortality included age greater than 50 years, Charlson comorbidity index greater than or equal to 1, emergent admission, peritonitis, acute vascular insufficiency, coagulopathy, and nonoperative management (P < .0001). As the first population-based epidemiological study of small bowel volvulus, our findings provide a robust representation of this rare cause of small bowel obstruction in American adults. Copyright © 2015 Elsevier Inc. All rights reserved.
Younan, George; Schumm, Max
Introduction. Gallbladder volvulus is a rare, potentially fatal condition unless diagnosed and treated early. Choledochal cysts are rare congenital malformations of the biliary tree predisposing to different pathologies and posing the risk of degradation into cholangiocarcinoma and gallbladder cancer. Dealing with both diseases at once has not been published yet in the literature. Presentation of Case. We report a case of gallbladder volvulus in an elderly female who happened to have a concomitant type I choledochal cyst. Treatment was achieved with a cholecystectomy and observation and follow-up of the choledochal cyst. Discussion. Prompt diagnosis and surgical management of gallbladder volvulus is important to avoid the morbidity and mortality of gangrenous cholecystitis and biliary peritonitis in a frail old population of patients. Precise clinical diagnosis, supplemented with specific imaging clues, helps in the diagnosis. Management of choledochal cysts is also surgical; however the timing of surgery is still a matter of debate. Conclusion. We describe in this report the first case of gallbladder volvulus in a patient with a choledochal cyst and propose a management algorithm of a very rare biliary tree pathology combination. PMID:27747125
Uni, Shigehiko; Fukuda, Masako; Ogawa, Kou; Lim, Yvonne Ai-Lian; Agatsuma, Takeshi; Bunchom, Naruemon; Saijuntha, Weerachai; Otsuka, Yasushi; Bhassu, Subha; Mat Udin, Ahmad Syihan; Zainuri, Nur Afiqah; Omar, Hasmahzaiti; Nakatani, Jun; Matsubayashi, Makoto; Maruyama, Haruhiko; Ramli, Rosli; Azirun, Mohd Sofian; Takaoka, Hiroyuki
An 11-year-old boy living in Otsu City, Shiga Prefecture, Kansai Region, Western Honshu, Japan had zoonotic onchocercosis. The patient developed a painful swelling on the little finger of his left hand. The worm detected in the excised mass had external transverse ridges but did not have inner striae in the cuticle. On the basis of the parasite's histopathological characteristics, the causative agent was identified as a female Onchocerca dewittei japonica (Spirurida: Onchocercidae). The species of the filarial parasite was confirmed by sequencing the cox1 gene of the parasite. The Japanese wild boar Sus scrofa leucomystax is a definitive host for O. dewittei japonica, which is then transmitted by blackflies as the vector to humans. The current case described occurred in the Kansai Region, Western Honshu, where such infections were previously not reported. Copyright © 2017 Elsevier B.V. All rights reserved.
Vogel, Susan R; Nichols, Sylvain; Buczinski, Sébastien; Desrochers, André; Babkine, Marie; Veillette, Manon; Francoz, David; Doré, Elizabeth; Fecteau, Gilles; Bélanger, Anne-Marie; Badillo, Mauricio
To characterize duodenal sigmoid flexure volvulus (DSFV) and determine the prognosis for affected cattle undergoing surgery. Retrospective case series. 29 dairy cattle. The medical records were analyzed for history, signalment, clinical signs, medical management, surgical findings, and outcome. 29 cattle were determined to have DSFV between December 2006 and August 2010. Twenty cattle had had an omentopexy or pyloropexy performed 1 day to 2 years before initial evaluation. Cattle were afebrile, tachycardic, and moderately dehydrated, with a small zone of percussion with a ping at the 10th to 12th right intercostal spaces and associated succussion. Biochemical changes were a severe hypokalemic (mean ± SD, 2.9 ± 0.5 mmol/L; median, 3.1 mmol/L; range, 2.08 to 3.92 mmol/L), hypochloremic (mean, 69.7 ± 11.1 mmol/L; median, 71.7 mmol/L; range, 49.1 to 94.1 mmol/L) metabolic alkalosis (mean total CO(2), 44.5 ± 7.4 mmol/L; median, 45.3 mmol/L; range, 31.5 to 59.6 mmol/L) and hyperbilirubinemia (mean, 32.4 ± 29.0 μmol/L; median, 20.5 μmol/L; range, 7.8 to 107 μmol/L). Surgical findings for DSFV included an empty descending duodenum adjacent to a dorsally displaced and dilated cranial segment of the duodenum, distended abomasum and gallbladder, and a tight volvulus at the base of the duodenal sigmoid flexure. Manual reduction was considered successful if the descending duodenum filled after cranial duodenal massage. Twenty-two patients were successfully treated; the remaining 7 died or were euthanized within 4 days after surgery. A condition clinically resembling abomasal volvulus but affecting the duodenal sigmoid flexure has been recognized in dairy cattle. When a focal, dorsal right-sided ping and succussion are present combined with severe hypokalemic, hypochloremic metabolic alkalosis and high bilirubin concentration, DSFV should be suspected, especially when there is a history of prior abomasal fixation. After surgical correction, the prognosis is fair to good.
Remes-Troche, J M; Pérez-Martínez, C; Rembis, V; Arch Ferrer, J; Ayala González, M; Takahashi, T
To analyze morbidity-mortality and results of surgical treatment for colonic volvulus. Retrospective review of 33 patients who underwent surgical treatment for colonic volvulus from 1986 through 1996. Mean age was 62 +/- 20 years (SD) with predominance of female sex (2:1). There were 25 cases of sigmoid volvulus (76%), 7 in the cecum (21%) and 1 in the transverse colon (3%). Colonic necrosis and/or perforation were most frequently seen in the right and transverse colon (50%) than in the sigmoid (4%) (P < 0.002). Operative morbidity was 45% with mortality of 21%. Age was the only variable statistically significant for operative morbidity (52 +/- 23 years in patients without morbidity vs 71 +/- 17 years in patients with morbidity, P = 0.02). Surgical procedures for sigmoid volvulus were resection in 13 and fixation in 12. Recurrence after fixation was 38% to 12 months and 69% to 24 months (Kaplan-Meier), with associated mortality of 50%. There was no recurrence after resections. Treatment for cecal volvulus was cecopexy in 4 cases, with one recurrence; and right hemicolectomy without recurrence. The results should encourage resective procedures in sigmoid volvulus because the risk of recurrence after fixation is high and the morbidity-mortality is similar. Elderly patients are more susceptible to complications.
Justin L, Regner Angela, Lomas
An 86 year-old woman with a past medical history significant for abdominal hernia and Alzheimer dementia presented to the Emergency Department with a 24 hour history of acute right upper quadrant pain associated with nausea and non-bilious emesis. Physical exam revealed right sided abdominal tenderness with associated mass. All laboratory values were within normal ranges. Both abdominal ultrasound and computed tomography of the abdomen/pelvis revealed a large distended gallbladder with wall thickening and gallstones. Based on presentation and radiologic findings, the emergency general surgery service was consulted for suspected acute cholecystitis. The patient was then admitted for intravenous antibiotics and scheduled for laparoscopic cholecystectomy the following day. Intra-operative findings revealed volvulus with acute necrosis of the entire gallbladder. The gallbladder had a long pedunculated cystic duct and artery that was detorsed before proceeding with resection. Postoperatively, the patient did well and was discharged a few days later tolerating a regular diet.
Hadjittofi, Christopher; Matter, Ibrahim; Eyal, Ori; Slijper, Nadav
An otherwise healthy 17-year-old boy presented to the paediatric emergency department with acute severe epigastric pain. An admission abdominal radiograph demonstrated gastric dilation, associated with an elevated left hemidiaphragm. Subsequent barium contrast imaging confirmed the diagnosis of organoaxial acute gastric volvulus (AGV). Emergent exploratory laparoscopy revealed AGV with migration of the stomach, spleen, pancreatic tail, splenic flexure, left kidney and adrenal through a left-sided Bochdalek diaphragmatic hernia. Following careful mobilisation of the displaced structures, a mesh closure of the diaphragmatic defect was performed. The patient's postoperative chest radiograph was unremarkable, and he was discharged on the sixth postoperative day after an uneventful recovery. At 2 months the patient was well and asymptomatic, with normal barium contrast imaging results. PMID:23519514
Rivier, Pablo; Furneaux, Rob; Viguier, Eric
This prospective study describes a simple method of combining laparoscopic ovariectomy and laparoscopic-assisted prophylactic gastropexy and determines the duration of surgery, complications, and long-term outcome including prevention of gastric dilatation-volvulus (GDV). Laparoscopic ovariectomy and laparoscopic-assisted gastropexy were performed on 26 sexually intact female dogs susceptible to GDV. The mean surgery time was 60.8 ± 12.4 min. No GDV episode was seen during the study period (mean follow-up: 5.2 ± 1.4 y). All dogs had an intact gastropexy attachment assessed by ultrasonography at 1 y. Post-operative complications were minor and owners were satisfied with the procedure. Combined laparoscopic ovariectomy and laparoscopic- assisted gastropexy appears to be a successful and low morbidity alternative procedure to both ovariectomy/ovariohysterectomy and gastropexy via open ventral-midline laparotomy. PMID:21461209
Amstrup, Steven C.; Nielsen, Carol A.
A large, adult male polar bear (Ursus maritimus) was found dead on a barrier island north of Prudhoe Bay, Alaska (USA), in June 1987. There were no external signs of trauma. A twisted distended stomach, distinctive parenchymal and fascial congestion, and significant difficulty in repositioning the anterior abdominal organs, indicated that gastric dilatation-volvulus (GDV) was the proximate cause of death. Polar bears frequently consume large quantities of food at one time and have large stomachs that are well adapted to periodic gorging. The scarcity of food in winter and early spring, combined with voluntary fasting and protracted vigorous activity during the breeding season in late spring may have predisposed this bear to GDV. The relationship between GDV and postprandial exercise emphasizes the need for a better understanding of how the present human invasion of arctic habitats may influence polar bear activities.
Olczak, Mieszko; Skrzypek, Ewa
An 8-year boy was admitted to the ER of one of Warsaw's pediatric hospitals with a history of having bloody vomiting the day before. During admission the boy collapsed and lost consciousness. CPR was unsuccessful. On medico-legal autopsy, two foreign objects (small magnetic spheres--0.5 cm in diameter) were found in two different places in the small and large intestines and were notably attracted magnetically one to another. A loop of approximately 1-m length with features of small intestinal hemorrhagic necrosis and small intestinal mechanical obstruction was found. The cause of death was intestinal volvulus and small intestinal mechanical obstruction caused by ingestion of foreign objects (two neodymium magnets). Most likely these small magnetic spheres were part of a popular toy, the safety of which, lately, has been widely discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Richard-Lenoble, D; Kombila, M; Rupp, E A; Pappayliou, E S; Gaxotte, P; Nguiri, C; Aziz, M A
Two clinical studies were carried out in Gabon, Africa to evaluate the efficacy, safety, and tolerability of ivermectin in the treatment of patients with Loa loa infection. In the first study, 35 patients received single oral doses of ivermectin, 5-200 mcg/kg body weight. Blood microfilariae levels did not decrease after a single oral 5, 10, 30, or 50 mcg/kg dose of ivermectin, but levels did decrease after doses of 100, 150, and 200 mcg/kg. The most efficacious dose was 200 mcg/kg; mean blood microfilariae levels decreased to 12% of mean pretreatment values by day 15 and remained decreased for 28 days. A second study evaluated the safety and efficacy of ivermectin in patients with multifilarial infections. All 17 patients had concomitant Loa loa and O. volvulus infection. M. perstans affected 5 of the patients. Sixteen patients also had infections due to intestinal nematodes. The patients each received single oral doses of 200 mcg/kg ivermectin. Ten days later, the mean Loa loa blood microfilariae level had decreased to 20% of the mean pretreatment level. O. volvulus dermal microfilariae densities were reduced to 2% of the pretreatment levels. A minimal increase in blood microfilaria levels was observed on day 28. In contrast, dermal microfilariae levels remained near zero for the duration of the study. Intestinal infection due to Ascaris was eradicated in all of the affected patients by day 23; efficacy against Trichuris and hookworm infections, however, was poor. All patients tolerated ivermectin well including those with multiple infections.
Mbaye, Papa Alassane; Faye, Aime Lakh; Sagna, Aloise; Ndoye, Ndeye Aby; Seck, Ndeye Fatou; Ndour, Oumar; Ngom, Gabriel
Nous rapportons l'observation d'une fillette âgée de 7ans qui reçue dans un tableau de syndrome sub-occlusif avec une douleur abdominale aigue paroxystique siégeant au niveau de l'épigastre associée à des vomissements et un arrêt des matières. L'examen physique mettait en évidence une sensibilité à la palpation de l'épigastre. L'échographie abdominale a montré une formation tissulaire intra péritonéale mal limitée sans caractère vasculaire au doppler, exerçant un effet de masse sur les structures de voisinage ; les vaisseaux mésentériques étaient en position normale. A la tomodensitométrie cette masse correspondait à une formation lipomateuse bien limitée exerçant un effet de masse sur le caecum avec un volvulus du grêle. Le diagnostic de volvulus du grêle sur lipome mésentérique a été retenu. L'exploration chirurgicale confirmait ce diagnostic. Une détorsion grélique et une énucléation lipomateuse étaient réalisées. Les suites opératoires étaient simples après un recul de 6 mois. L'examen anatomopathologique confirmait la nature lipomateuse de la masse. PMID:28819497
... in the abdomen Nausea or vomiting Shock Vomiting green material Symptoms are very often severe. The infant in such cases is taken to the emergency room. Early treatment can be critical for survival.
Al Maksoud, Ahmed M.; Barsoum, Adel K.; Moneer, Mohamed M.
Introduction Sigmoid volvulus is a rare cause of intestinal obstruction during pregnancy associated with high maternal and foetal mortality. Effective management represents a challenge due to delayed presentation, obstructive symptoms regarded as pregnancy-related and hesitation in using radiological evaluation. Presentation of case We report a case of a lady, pregnant for 26 weeks and with a 5 day history of abdominal pain and constipation. She underwent concomitant caesarean section and laparotomy for intestinal obstruction. Intra-operatively, the sigmoid colon was extensively dilated and gangrenous. The ischemic colon was resected and a Hartmann’s procedure was performed. A preterm male child was delivered and admitted to neonatal intensive care. The post operative course was uneventful and the patient was discharged home on the 9th post-operative day. Six months later she underwent an uneventful reversal of the Hartmann’s procedure. Discussion Sigmoid volvulus is the most common cause of bowel obstruction during pregnancy, accounting for up to 44% of reported cases. We have reviewed the available literature on this topic and present another case managed at our institution. Conclusion Diagnosis of sigmoid volvulus in pregnancy is a challenge, but a delay in diagnosis increases the rates of feto-maternal mortality. A high incidence of clinical suspicion and timely surgical intervention are the key to a favourable outcome. PMID:26551555
Kaba, Metin; Oksuzoglu, Aysegul; Kaba, Gokcen; Timur, Hakan; Akbaba, Eren; Turgut, Kadriye
A midgut volvulus rarely occurs in a fetus; however, when it does, it requires an immediate diagnosis and surgery. Thirty-week pregnant was referred to our clinic with a diagnosis of a fetal abdominal cystic mass and preterm labor. The initial ultrasound examination revealed a female fetus with a 55 × 50 mm cystic mass in the lower abdomen, which was preliminarily diagnosed as an ovarian cyst. There was a sinusoidal rhythm on cardiography. The middle cerebral artery peak systolic velocity was 60.4 cm/sec, compatible with 1.49 MoMs that suggested fetal anemia on Doppler examination. Uterine contractions were observed with tocography and maternal hydration was administered for tocolytic treatment. Despite hydration, uterine contractions continued and the infant was delivered. A newborn ultrasonographic evaluation revealed a 6 cm abdominal cyst, and plain abdominal radiographs revealed distended loops of the small bowel on the left side. Emergency surgery was performed. A midgut volvulus leading to dilatation and necrosis of the small bowel without anatomical causes was observed during laparotomy. The necrotic bowel loop was resected and an end-to-end anastomosis was performed. The newborn died due to multiorgan failure. Obstetricians should be familiar with the appropriate diagnosis and management of a fetal volvulus. PMID:26779358
Nelson, G. S.; Pester, F. R. N.
Although it is recognized that the presence of animal filariae can lead to confusion in the interpretation of infection rates in mosquito vectors of filariasis, the filariae found in man-biting simuliids are usually assumed to be Onchocerca volvulus. The authors of this paper emphasize that it is unwise to calculate transmission indices from infection rates in man-biting simuliids unless there is confidence in the identification of the filarial larvae. In this respect they cite their observations on Mount Elgon in Uganda which show that the majority of the filarial larvae in Simulium neavei—the local vector of onchocerciasis—are of species that do not affect man. To assist in the correct interpretation of infection rates in the vectors the authors made a detailed study of the morphological character of O. volvulus infective larvae and established criteria for distinguishing O. volvulus from other filariae known to be transmitted by simuliids. PMID:13938041
Baldacchino, Frédéric; Muenworn, Vithee; Desquesnes, Marc; Desoli, Florian; Charoenviriyaphap, Theeraphap; Duvallet, Gérard
Stomoxys flies are mechanical vectors of pathogens present in the blood and skin of their animal hosts, especially livestock, but occasionally humans. In livestock, their direct effects are disturbance, skin lesions, reduction of food intake, stress, blood loss, and a global immunosuppressive effect. They also induce the gathering of animals for mutual protection; meanwhile they favor development of pathogens in the hosts and their transmission. Their indirect effect is the mechanical transmission of pathogens. In case of interrupted feeding, Stomoxys can re-start their blood meal on another host. When injecting saliva prior to blood-sucking, they can inoculate some infected blood remaining on their mouthparts. Beside this immediate transmission, it was observed that Stomoxys may keep some blood in their crop, which offers a friendly environment for pathogens that could be regurgitated during the next blood meal; thus a delayed transmission by Stomoxys seems possible. Such a mechanism has a considerable epidemiological impact since it allows inter-herd transmission of pathogens. Equine infectious anemia, African swine fever, West Nile, and Rift Valley viruses are known to be transmitted by Stomoxys, while others are suspected. Rickettsia (Anaplasma, Coxiella), other bacteria and parasites (Trypanosoma spp., Besnoitia spp.) are also transmitted by Stomoxys. Finally, Stomoxys was also found to act as an intermediate host of the helminth Habronema microstoma and may be involved in the transmission of some Onchocerca and Dirofilaria species. Being cosmopolite, Stomoxys calcitrans might have a worldwide and greater impact than previously thought on animal and human pathogen transmission. PMID:23985165
Sickinger, M; Doll, K; Roloff, N C; Halekoh, U
A randomized clinical trial was conducted to compare the efficacy of rapid intravenous (IV) infusion of a 7.2% hypertonic saline solution with that of continuous application of an isotonic solution in stabilizing the circulation of cows with abomasal volvulus. Cattle treated with hypertonic saline had a significantly greater reduction in volume deficit within the first 10 min of therapy than cows treated with isotonic saline (from 5.9 ± 4.8 to 2.1 ± 4.4 L/100 kg vs. 7.0 ± 4.5 to 4.9 ± 3.8 L/100 kg, respectively). The central venous pressure (CVP) of the cows given the hypertonic saline rose within the first 10 min of therapy from 7.3 ± 3.5 to 10.8 ± 3.4 cm H2O, while the CVP of the cattle treated with isotonic saline did not increase significantly during this time. Sixty minutes after the start of the infusion, the CVP of the isotonic group was still significantly lower than that of the hypertonic group (9.5 ± 2.1 vs. 10.3 ± 3.3 cm H2O, respectively). Within the first 60 min, the base excess decreased from 5.5 ± 6.9 to 4.7 ± 6.2 mmol/L in the hypertonic group whereas it increased from 5.6 ± 5.7 to 6.8 ± 5.4 mmol/L in the isotonic group. These results suggest that for cows with abomasal volvulus, IV therapy with hypertonic saline may improve the haemodynamic and circulatory situation considerably faster and more effectively than continuous infusion with isotonic saline. Copyright © 2014 Elsevier Ltd. All rights reserved.
deC Bronsvoort, Barend M; Renz, Alfons; Tchakouté, Virginia; Tanya, Vincent N; Ekale, David; Trees, Alexander J
Background Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin (Ivomec®, Merck and Co. Inc.) at 500 μg/kg or doramectin (Dectamax®, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion These results have important implications for
Moore, George E.; Levine, Michael; Anderson, Johnna D.; Trapp, Robert J.
Gastric dilatation-volvulus (GDV) is a life-threatening condition in dogs and other species in which the stomach dilates and rotates on itself. The etiology of the disease is multi-factorial, but explicit precipitating causes are unknown. This study sought to determine if there was a significant association between changes in hourly-measured temperature and/or atmospheric pressure and the occurrence of GDV in the population of high-risk working dogs in Texas. The odds of a day being a GDV day, given certain temperature and atmospheric pressure conditions for that day or the day before, was estimated using logistic regression models. There were 57 days in which GDV(s) occurred, representing 2.60% of the days in the 6-year study period. The months of November, December, and January collectively accounted for almost half (47%) of all cases. Disease risk was negatively associated with daily maximum temperature. An increased risk of GDV was weakly associated with the occurrence of large hourly drops in temperature that day and of higher minimum barometric pressure that day and the day before GDV occurrence, but extreme changes were not predictive of the disease.
Davidson, J R; Lantz, G C; Salisbury, S K; Kazacos, E A; Bottoms, G D
Gastric dilatation-volvulus (GDV) was created experimentally and maintained for 90 minutes in 16 anesthetized, mixed-breed dogs. After the GDV was corrected, normal saline solution (0.044 mL/kg intravenously [IV]) was administered to eight dogs (controls), and flunixin meglumine (2.2 mg/kg IV) was administered to eight dogs. Microspheres labeled with radioactive cobalt, scandium, tin, or niobium were injected intravenously at baseline (before GDV) and minutes 90, 100, and 270, respectively, to determine tissue blood flows. Plasma endotoxin and prostacyclin were measured at the same intervals. Electrocardiogram, mean arterial pressure, portal pressure, and cardiac output were recorded continuously. Dogs were euthanatized at minute 270 and necropsied. There was no significant difference between treatment groups for any measured variable at any time. Endotoxin levels increased significantly during GDV. Prostacyclin levels were lower in dogs treated with flunixin meglumine than in controls at minutes 210 and 270. Histopathologic findings were similar for all dogs and consistent with those associated with endotoxemia. Flunixin meglumine treatment did not alter cardiac indices or tissue blood flows significantly. However, elevation of prostacyclin was inhibited by flunixin meglumine, which suggested that continued effects of endotoxic damage might be attenuated or inhibited.
Sharp, Claire R; Rozanski, Elizabeth A
Gastric dilatation and volvulus (GDV) is a common emergency condition in large and giant breed dogs that is associated with high morbidity and mortality. Dogs with GDV classically fulfill the criteria for the systemic inflammatory response syndrome (SIRS) and can go on to develop multiple organ dysfunction syndrome (MODS). Previously reported organ dysfunctions in dogs with GDV include cardiovascular, respiratory, gastrointestinal, coagulation and renal dysfunction. Cardiovascular manifestations of GDV include shock, cardiac arrhythmias and myocardial dysfunction. Respiratory dysfunction is also multifactorial, with contributory factors including decreased respiratory excursion due to gastric dilatation, decreased pulmonary perfusion and aspiration pneumonia. Gastrointestinal dysfunction includes gastric necrosis and post-operative gastrointestinal upset such as regurgitation, vomiting, and ileus. Coagulation dysfunction is another common feature of MODS in dogs with GDV. Disseminated intravascular coagulation can occur, putting them at risk of complications associated with thrombosis in the early hypercoagulable state and hemorrhage in the subsequent hypocoagulable state. Acute kidney injury, acid-base and electrolyte disturbances are also reported in dogs with GDV. Understanding the potential for systemic effects of GDV allows the clinician to monitor patients astutely and detect such complications early, facilitating early intervention to maximize the chance of successful management.
Delgado-Lecaroz, R; Warnick, L D; Guard, C L; Smith, M C; Barry, D A
The objective of this study was to evaluate serum mineral and electrolyte concentrations at the time of on-farm diagnosis of left displaced abomasum, right displaced abomasum, or abomasal volvulus in dairy cows. Data were collected from 104 affected cows and 96 control cows matched with cases, based on herd, parity, and stage of lactation. Cows with abomasal displacement or volvulus had significantly lower calcium, phosphorous, magnesium, potassium, and chloride concentrations and increased anion gap at the time of diagnosis compared with control cows from the same herds. The percentages of cases and controls with total serum calcium concentrations below the lower limit of the laboratory reference range (2.08 mmol/L [8.3 mg/dL]) were 70% and 23%, respectively. Based on the large percentage of cases with hypocalcemia, administering calcium salts at the time of treatment of field cases of abomasal displacement or volvulus may be beneficial. PMID:10769767
Hidalgo, M R; Martínez, A; Carreño, R A; González, S; Ferreras, M C; Díez, N
Between 2005 and 2007, the presence of Onchocerca flexuosa (Wedl, 1856) was discovered and investigated in 110 red deer (Cervus elaphus) shot in the Riaño Regional Hunting Reserve, in the province of León (north-western Spain). Nodules containing O. flexuosa were located in the dorsal region and flanks of the deer. These were collected and measured, and some adult parasites were extracted from the nodules and identified by morphology and by obtaining mitochondrial 12S rDNA sequences, which were identical to those of previously published sequences for O. flexuosa. Some nodules were prepared for histology, embedded in paraffin, sectioned and stained with haematoxylin-eosin. Histologically, the worms were found in several compartments separated by an infiltrated fibrous tissue. These compartments were inhabited by several females and males, surrounded by a fibrous capsule. A total of 85.45% (95% confidence interval (CI): 78.86-92.04%) of red deer were parasitized, with a mean intensity of 9.53 ± 12.27 nodules/host, ranging between 1 and 74 nodules/deer. Significant differences in prevalence and intensity of infection were found between young and adult red deer, and also between seasons. However, no significant differences between males and females were observed. Five hundred and ninety-seven nodules were measured (15.81 ± 3.94 mm) and classified by sizes into small ( < 10 mm), medium (10-20 mm) and large (>20 mm). No relation was found between the size of the nodules and the time of infection. The high values found in the studied parameters show that northern Spain is an area of high-intensity infection for deer.
Omata, Jiro; Utsunomiya, Katsuyuki; Kajiwara, Yoshiki; Takahata, Risa; Miyasaka, Nobuo; Sugasawa, Hidekazu; Sakamoto, Naoko; Yamagishi, Yoji; Fukumura, Makiko; Kitagawa, Daiki; Konno, Mitsuhiko; Okusa, Yasushi; Murayama, Michinori
A 43-year-old female was referred to our hospital for sudden onset of abdominal pain, fullness, and vomiting. Physical examination revealed abdominal distension with mild epigastric tenderness. Abdominal radiography showed massive gastric distension and plain computed tomography (CT) a markedly enlarged stomach filled with gas and fluid. A large volume of gastric contents was suctioned out via a nasogastric (NG) tube. Contrast-enhanced CT showed a grossly distended stomach with displacement of the antrum above the gastroesophageal junction, and the spleen was dislocated inferiorly. Upper gastrointestinal (GI) series showed the greater curvature to be elevated and the gastric fundus to be lower than normal. Acute mesenteroaxial gastric volvulus was diagnosed. GI endoscopy showed a distortion of the gastric anatomy with difficulty intubating the pylorus. Various endoscopic maneuvers were required to reposition the stomach, and the symptoms showed immediate and complete solution. GI fluoroscopy was performed 3 days later. Initially, most of the contrast medium accumulated in the fundus, which was drawn prominently downward, and then began flowing into the duodenum with anteflexion. Elective laparoscopic surgery was performed 1 month later. The stomach was in its normal position, but the fundus was folded posteroinferiorly. The spleen attached to the fundus was normal in size but extremely mobile. We diagnosed a wandering spleen based on the operative findings. Gastropexy was performed for the treatment of gastric volvulus and wandering spleen. The patient remained asymptomatic, and there was no evidence of recurrence during a follow-up period of 24 months. This report describes a rare adult case of acute gastric volvulus associated with wandering spleen. Because delay in treatment can result in lethal complications, it is critical to provide a prompt and correct diagnosis and surgical intervention. We advocate laparoscopic surgery after endoscopic reduction because
O'Neill, D G; Case, J; Boag, A K; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C
To report prevalence, risk factors and clinical outcomes for presumptive gastric dilation-volvulus diagnosed among an emergency-care population of UK dogs. The study used a cross-sectional design using emergency-care veterinary clinical records from the VetCompass Programme spanning September 1, 2012 to February 28, 2014 and risk factor analysis using multivariable logistic regression modelling. The study population comprised 77,088 dogs attending 50 Vets Now clinics. Overall, 492 dogs had presumptive gastric dilation-volvulus diagnoses, giving a prevalence of 0·64% (95% Confidence interval: 0·58 to 0·70%). Compared with cross-bred dogs, breeds with the highest odds ratios for the diagnosis of presumptive gastric dilation-volvulus were the great Dane (odds ratio: 114·3, 95% Confidence interval 55·1 to 237·1, P<0·001), akita (odds ratio: 84·4, 95% Confidence interval 33·6 to 211·9, P<0·001) and dogue de Bordeaux (odds ratio: 82·9, 95% Confidence interval 39·0 to 176·3, P<0·001). Odds increased as dogs aged up to 12 years and neutered male dogs had 1·3 (95% Confidence interval 1·0 to 1·8, P=0·041) times the odds compared with entire females. Of the cases that were presented alive, 49·7% survived to discharge overall, but 79·3% of surgical cases survived to discharge. Approximately 80% of surgically managed cases survived to discharge. Certain large breeds were highly predisposed. © 2017 British Small Animal Veterinary Association.
Pipan, Marko; Brown, Dorothy Cimino; Battaglia, Carmelo L; Otto, Cynthia M
To evaluate risk factors for gastric dilatation-volvulus (GDV) in a large number of privately owned dogs across a wide geographic area. Internet-based, cross-sectional study. 2,551 privately owned dogs. A questionnaire addressed dog-specific, management, environmental, and personality-associated risk factors for GDV in dogs. Respondents were recruited through the posting of the electronic link to the questionnaire on websites for dog owners; the information was also disseminated at meetings of dog owners and via newsletters, e-mail lists for dog owners and breeders, owner-oriented dog publications, and e-mails forwarded by participants. Descriptive statistics and logistic regression analysis were performed. Factors significantly associated with an increased risk of GDV were being fed dry kibble, anxiety, residence in the United Kingdom, being born in the 1990s, being a family pet, and spending at least 5 hours a day with the owner. Factors associated with a decreased risk of GDV were playing with other dogs and running the fence after meals, fish and egg dietary supplements, and spending equal time indoors and outdoors. A significant interaction between sex and neuter status was observed, with sexually intact females having the highest risk for GDV. In dogs with a high risk of GDV, regular moderate daily and postprandial activity appeared to be beneficial. Feeding only commercial dry dog food may not be the best choice for dogs at risk; however, supplements with fish or eggs may reduced this risk. The effect of neuter status on GDV risk requires further characterization.
Yan, Suqi; Xiong, Xiaoli; Wan, Qi; Liu, Fan; Tang, Jianqiao; Jiang, Zhixia; Zhou, Lishan; Yuan, Kai; Xie, Dong
To study the preventative effects of massage on gastric volvulus (GV) in infants with gastroesophageal reflux (GER)-induced pneumonia. One-hundred and eighty GV with GER-induced pneumonia inpatients were divided randomly into four groups: basic treatment 1 (n = 60), basic treatment 2 (n = 30), massage treatment 1 (n = 60) and massage treatment 2 (n = 30). Clinical examinations selected between groups 1 and 2 were different. Radiography of the upper gastrointestinal tract using iodine-containing contrast was assessed in group 1 before and after treatment, whereas 24-h pH monitoring of the distal esophagus was assessed in group 2 before and after treatment. Symptom scores and chest radiography were assessed in all groups upon hospital admission and after procedures. Clinical effects were estimated after procedures in all groups. The prevalence of severe pneumonia among the four groups was compared. Massage treatment groups showed a significantly higher percentage of cure and total effect (P < 0.05, P < 0.01) and a lower prevalence of recurrence (but with no statistic difference, P > 0.05) than basic treatment groups. Furthermore, massage treatment groups had remarkably lower scores for symptoms and signs (P < 0.05, P < 0.01), especially for choking on milk, than basic treatment groups. There was significant attenuation of chest inflammation (P < 0.05, P < 0.01), GV (P < 0.05, P < 0.01) and GER (P < 0.05, P < 0.01) in massage treatment groups compared with those in basic treatment groups. Finally, massage treatment groups demonstrated a lower prevalence of severe pneumonia than basic treatment groups (P < 0.05). Massage treatment can prevent GV with GER-induced pneumonia in infants by timely correction of stomach rotation and subsequent attenuation of GER.
Tubby, Kurtis G
Postmortem examination of a 7-year-old German shepherd dog which had gastric dilatation/volvulus and splenectomy 2 months earlier revealed that the right middle and quadrate liver lobes were diffusely congested and torsed. The gall bladder was grossly distended and torsed along its long axis and there was evidence of bile peritonitis.
Nyuwi, Kuotho T; Singh, Chabungbam Gyan; Sangtam, Ty Apila; Varte, Lalhruaitluanga
Enteric Duplication Cysts (EDC) is a rare congenital malformation, usually found in mesenteric side of Gastrointestinal (GI) tract. Generally patients present with non-specific symptoms depending on size and location of the cyst in GI tract. EDC presenting as small bowel volvulus is a rare clinical entity. Herein, we are reporting a 16-year-old adolescent girl who presented to Emergency Department (ED) with the features of acute bowel obstruction with septicemia. Patient underwent exploratory laparotomy which revealed dilated, twisted, gangrenous bowel due to a cystic lesion adjacent to the mesenteric side. Resection of the cystic lesion along with the affected gangrenous segment of bowel with an end to end anastomosis performed. PMID:28208934
Bouassria, Abdesslam; Mazine, Khalid; Elbouhaddouti, Hicham; Mouaqit, Ouadii; Ousadden, Abdelmalek; Mazaz, Khalid; Benjelloun, Elbachir; Taleb, Khalid Ait
L'hydatidose péritonéale peut être primitive, hématogène ou hétérotopique, comme elle peut être secondaire et résulte de la fissuration d'un kyste hydatique, le plus souvent hépatique. Cliniquement polymorphe, elle peut se révéler par des douleurs abdominales ou par la palpation d'une masse abdominale. Nous rapportons le cas d'une patiente chez qui l'hydatidose péritonéale était révélée par un accident occlusif: un volvulus grêlique dû à un volumineux kyste hydatique mésentérique. Le traitement de l'hydatidose péritonéale est chirurgical, couplé à un traitement médical à base d'albendazole. PMID:25400846
Madiba, T E; Haffajee, M R
Sigmoid volvulus demonstrates geographical, racial, and gender variation. This autopsy study was undertaken to establish morphological differences of the sigmoid colon and its mesocolon in which the length and other characteristics were assessed. A total of 590 cadavers were examined (403 African, 91 Indian, and 96 White). Length and height of the sigmoid colon and mesocolon were significantly longer in Africans, and mesocolon root was significantly narrower in Africans. Mesocolic ratio for Africans, Indians, and Whites was 1.1 ± 0.8, 1.8 ± 0.7, and 1.9 ± 1.0, respectively. Africans had a significantly high incidence of redundant sigmoid colon with the long-narrow type and suprapelvic position predominating (P = 0.003); the opposite applied to the classic type. There was no difference in sigmoid colon length, mesocolon height, and width between males and females in all population groups. Among Africans, the long-narrow type was more common in males, and the classic and long-broad types were more common in females. Splaying of teniae coli and thickening of the mesentery were more common in Africans. Tethering of the sigmoid colon to the posterior abdominal wall was less common in Africans compared with other population groups. In conclusion, the sigmoid colon was longer, and the sigmoid mesocolon root was narrower in Africans compared with the other population groups, and the sigmoid colon had a suprapelvic disposition among Africans. In Africans, the sigmoid colon was longer in males with a long-narrow shape. These differences may explain geographical and racial differences in sigmoid volvulus.
Abstract The objective of the study was to determine whether nitric oxide (NO) is present in clinically healthy horses (control) under basal conditions, and if it increases secondary to naturally acquired strangulating large colon volvulus (affected). Eleven affected horses and 10 controls were studied. Jugular venous blood, abdominal fluid, and urine were collected. The NO concentrations were standardized to the creatinine concentration in the respective samples. A biopsy specimen collected from the large colon pelvic flexure at surgery was divided into subsections for processing for inducible nitric synthase (iNOS) and nitrotyrosine (NT) immunohistochemical staining and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical staining. There were no significant differences in plasma, abdominal fluid, or urine NO concentrations between affected and control horses. There was a significant decrease in submucosal arteriolar and venular endothelium, submucosal plexus, mucosal leukocyte, mucosal and musclaris vasculature, and myenteric plexus NADPH diaphorase staining in affected versus control horses. There was a significant increase in iNOS staining in mucosal leukocytes and vasculature in affected versus control horses. Other than a greater number of positively stained mucosal leukocytes in affected horses, there were no significant differences between affected and control horses for NT staining. The presence of NADPH diaphorase staining in the endothelium and submucosal neurons suggests endothelial and neuronal NOS are present under basal conditions in the large colon of horses. Increased iNOS and NT staining in mucosal leukocytes of affected horses suggests involvement of the NO pathway in large colon volvulus. The reasons for the lack of a significant difference in plasma, abdominal fluid, and urine NO concentrations between affected and control horses are unknown. PMID:15971674
Baldacchino, Frédéric; Muenworn, Vithee; Desquesnes, Marc; Desoli, Florian; Charoenviriyaphap, Theeraphap; Duvallet, Gérard
Stomoxys flies are mechanical vectors of pathogens present in the blood and skin of their animal hosts, especially livestock, but occasionally humans. In livestock, their direct effects are disturbance, skin lesions, reduction of food intake, stress, blood loss, and a global immunosuppressive effect. They also induce the gathering of animals for mutual protection; meanwhile they favor development of pathogens in the hosts and their transmission. Their indirect effect is the mechanical transmission of pathogens. In case of interrupted feeding, Stomoxys can re-start their blood meal on another host. When injecting saliva prior to blood-sucking, they can inoculate some infected blood remaining on their mouthparts. Beside this immediate transmission, it was observed that Stomoxys may keep some blood in their crop, which offers a friendly environment for pathogens that could be regurgitated during the next blood meal; thus a delayed transmission by Stomoxys seems possible. Such a mechanism has a considerable epidemiological impact since it allows inter-herd transmission of pathogens. Equine infectious anemia, African swine fever, West Nile, and Rift Valley viruses are known to be transmitted by Stomoxys, while others are suspected. Rickettsia (Anaplasma, Coxiella), other bacteria and parasites (Trypanosoma spp., Besnoitia spp.) are also transmitted by Stomoxys. Finally, Stomoxys was also found to act as an intermediate host of the helminth Habronema microstoma and may be involved in the transmission of some Onchocerca and Dirofilaria species. Being cosmopolite, Stomoxys calcitrans might have a worldwide and greater impact than previously thought on animal and human pathogen transmission. © F. Baldacchino et al., published by EDP Sciences, 2013.
Guèye, Mohamadou Lamine; Touré, Alpha Oumar; Thiam, Ousmane; Seck, Mamadou; Cissé, Mamadou; Kâ, Ousmane; Dieng, Madieng; Touré, Cheikh Tidiane
Le volvulus gastrique aigu sur éventration diaphragmatique est une affection rare et une urgence diagnostique et thérapeutique. Sa présentation clinique est peu spécifique et la tomodensitométrie abdominale permet de confirmer le diagnostic. Nous rapportons le cas d'un patient de 22 ans qui présentaitun syndrome occlusif et une voussure épigastrique. A la radiographie de l'Abdomen Sans Préparation, on notait 2 niveaux hydro-aériques sous la coupole diaphragmatique gauche qui était surélevée. Une dévolvulation et une gastrectomie atypique ont été réalisées devant un volvulus gastrique aigu avec nécrose du fundus mis en évidence à la laparotomie. Les suites opératoires ont été simples. PMID:26161223
Iso, Yukihiro; Tagaya, Nobumi; Nemoto, Takehiko; Kita, Junji; Sawada, Tokihiko; Kubota, Keiichi
An 86-year-old woman was admitted to the hospital to undergo an examination for tarry stools. Laboratory tests showed hypoproteinemia and renal dysfunction. Upper gastrointestinal endoscopy demonstrated a type 5 tumor located in the upper body of the stomach. An upper gastrointestinal series and computed tomography revealed an organoaxial gastric volvulus and the dislocation of the proximal stomach through an esophageal hiatal hernia. The preoperative diagnosis was the incarceration of a gastric carcinoma arising from the proximal stomach with an organoaxial gastric volvulus through an esophageal hiatal hernia. A total gastrectomy and hernia repair were performed. A microscopic examination of the surgical specimen revealed a gastric large cell neuroendocrine carcinoma (GLCNEC). The patient was discharged 22 days after the surgery. Although the prognosis of GLCNEC is significantly worse than that of a conventional adenocarcinoma, the patient was doing well without recurrence at 15 months after surgery. The details of this case are reported with some bibliographical comments.
Toé, Laurent D; Koala, Lassane; Burkett-Cadena, Nathan D; Traoré, Bizini M; Sanfo, Moussa; Kambiré, Sié Roger; Cupp, Eddie W; Traoré, Soungalo; Yameogo, Laurent; Boakye, Daniel; Rodríguez-Pérez, Mario A; Unnasch, Thomas R
A simple inexpensive trap (Esperanza window trap) was shown recently to collect significant numbers of Simulium ochraceum sensu lato, a major vector of Onchocerca volvulus in Mesoamerica. Here, we report studies optimizing this trap for the collection of Simulium damnosum s.l., the major vector of O. volvulus in Africa. A shortened, blue and black striped version of the Esperanza window trap, when baited with a combination of CO2 and worn trousers, rivalled human landing collections in the number of S. damnosum s.l. females collected. Traps baited with a commercially available human skin lure and CO2 resulted in collections that were not significantly different than those obtained from traps baited with worn trousers and CO2. This suggests that the Esperanza window trap may offer a replacement for human landing collections for monitoring onchocerciasis transmission in Africa.
Cakoni, Fioralba; Haddar, Houssem
In inverse scattering theory, transmission eigenvalues can be seen as the extension of the notion of resonant frequencies for impenetrable objects to the case of penetrable dielectrics. The transmission eigenvalue problem is a relatively late arrival to the spectral theory of partial differential equations. Its first appearance was in 1986 in a paper by Kirsch who was investigating the denseness of far-field patterns for scattering solutions of the Helmholtz equation or, in more modern terminology, the injectivity of the far-field operator . The paper of Kirsch was soon followed by a more systematic study by Colton and Monk in the context of developing the dual space method for solving the inverse scattering problem for acoustic waves in an inhomogeneous medium . In this paper they showed that for a spherically stratified media transmission eigenvalues existed and formed a discrete set. Numerical examples were also given showing that in principle transmission eigenvalues could be determined from the far-field data. This first period of interest in transmission eigenvalues was concluded with papers by Colton et al in 1989  and Rynne and Sleeman in 1991  showing that for an inhomogeneous medium (not necessarily spherically stratified) transmission eigenvalues, if they existed, formed a discrete set. For the next seventeen years transmission eigenvalues were ignored. This was mainly due to the fact that, with the introduction of various sampling methods to determine the shape of an inhomogeneous medium from far-field data, transmission eigenvalues were something to be avoided and hence the fact that transmission eigenvalues formed at most a discrete set was deemed to be sufficient. In addition, questions related to the existence of transmission eigenvalues or the structure of associated eigenvectors were recognized as being particularly difficult due to the nonlinearity of the eigenvalue problem and the special structure of the associated transmission
Evaluation of groundwater resources requires the knowledge of the capacity of aquifers to store and transmit ground water. This requires estimates of key hydraulic parameters, such as the transmissivity, among others. The transmissivity T (m2/sec) is a hydrauli...
Miura, M.; Aoki, H.
An automatic transmission is described comprising: an automatic transmission mechanism portion comprising a single planetary gear unit and a dual planetary gear unit; carriers of both of the planetary gear units that are integral with one another; an input means for inputting torque to the automatic transmission mechanism, clutches for operatively connecting predetermined ones of planetary gear elements of both of the planetary gear units to the input means and braking means for restricting the rotation of predetermined ones of planetary gear elements of both of the planetary gear units. The clutches are disposed adjacent one another at an end portion of the transmission for defining a clutch portion of the transmission; a first clutch portion which is attachable to the automatic transmission mechanism portion for comprising the clutch portion when attached thereto; a second clutch portion that is attachable to the automatic transmission mechanism portion in place of the first clutch portion for comprising the clutch portion when so attached. The first clutch portion comprising first clutch for operatively connecting the input means to a ring gear of the single planetary gear unit and a second clutch for operatively connecting the input means to a single gear of the automatic transmission mechanism portion. The second clutch portion comprising a the first clutch, the second clutch, and a third clutch for operatively connecting the input member to a ring gear of the dual planetary gear unit.
Evaluation of groundwater resources requires the knowledge of the capacity of aquifers to store and transmit ground water. This requires estimates of key hydraulic parameters, such as the transmissivity, among others. The transmissivity T (m2/sec) is a hydrauli...
Verocai, Guilherme G; Lejeune, Manigandan; Beckmen, Kimberlee B; Kashivakura, Cyntia K; Veitch, Alasdair M; Popko, Richard A; Fuentealba, Carmen; Hoberg, Eric P; Kutz, Susan J
Onchocerca cervipedis is a filarioid nematode of cervids reported from Central America to boreal regions of North America. It is found primarily in subcutaneous tissues of the legs, and is more commonly known as 'legworm'. Blackflies are intermediate hosts and transmit larvae to ungulates when they blood-feed. In this article we report the first records of O. cervipedis from high latitudes of North America and its occurrence in previously unrecognized host subspecies including the Yukon-Alaska moose (Alces americanus gigas) and the Grant's caribou (Rangifer tarandus granti). We examined the subcutaneous connective tissues of the metacarpi and/or metatarsi of 34 moose and one caribou for parasitic lesions. Samples were collected from animals killed by subsistence hunters or animals found dead in the Northwest Territories (NT), Canada and Alaska (AK), USA from 2005 to 2012. Genomic DNA lysate was prepared from nematode fragments collected from two moose. The nd5 region of the mitochondrial DNA was amplified by PCR and sequenced. Subcutaneous nodules were found in 12 moose from the NT and AK, and one caribou from AK. Nematodes dissected from the lesions were identified as Onchocerca cervipedis based on morphology of female and male specimens. Histopathological findings in moose included cavitating lesions with multifocal granulomatous cellulitis containing intralesional microfilariae and adults, often necrotic and partially mineralized. Lesions in the caribou included periosteitis with chronic cellulitis, eosinophilic and lymphoplasmacytic infiltrate, and abundant granulation associated with intralesional adult nematodes and larvae. Sequences of the nd5 region (471bp), the first generated for this species, were deposited with Genbank (JN580791 and JN580792). Representative voucher specimens were deposited in the archives of the United States National Parasite Collection. The geographic range of O. cervipedis is broader than previously thought, and extends into
Background Onchocerca cervipedis is a filarioid nematode of cervids reported from Central America to boreal regions of North America. It is found primarily in subcutaneous tissues of the legs, and is more commonly known as ‘legworm’. Blackflies are intermediate hosts and transmit larvae to ungulates when they blood-feed. In this article we report the first records of O. cervipedis from high latitudes of North America and its occurrence in previously unrecognized host subspecies including the Yukon-Alaska moose (Alces americanus gigas) and the Grant’s caribou (Rangifer tarandus granti). Methods We examined the subcutaneous connective tissues of the metacarpi and/or metatarsi of 34 moose and one caribou for parasitic lesions. Samples were collected from animals killed by subsistence hunters or animals found dead in the Northwest Territories (NT), Canada and Alaska (AK), USA from 2005 to 2012. Genomic DNA lysate was prepared from nematode fragments collected from two moose. The nd5 region of the mitochondrial DNA was amplified by PCR and sequenced. Results Subcutaneous nodules were found in 12 moose from the NT and AK, and one caribou from AK. Nematodes dissected from the lesions were identified as Onchocerca cervipedis based on morphology of female and male specimens. Histopathological findings in moose included cavitating lesions with multifocal granulomatous cellulitis containing intralesional microfilariae and adults, often necrotic and partially mineralized. Lesions in the caribou included periosteitis with chronic cellulitis, eosinophilic and lymphoplasmacytic infiltrate, and abundant granulation associated with intralesional adult nematodes and larvae. Sequences of the nd5 region (471bp), the first generated for this species, were deposited with Genbank (JN580791 and JN580792). Representative voucher specimens were deposited in the archives of the United States National Parasite Collection. Conclusions The geographic range of O. cervipedis is broader than
Transmissibility is the defining characteristic of infectious diseases. Quantifying transmission matters for understanding infectious disease epidemiology and designing evidence-based disease control programs. Tracing individual transmission events can be achieved by epidemiological investigation coupled with pathogen typing or genome sequencing. Individual infectiousness can be estimated by measuring pathogen loads, but few studies have directly estimated the ability of infected hosts to transmit to uninfected hosts. Individuals' opportunities to transmit infection are dependent on behavioral and other risk factors relevant given the transmission route of the pathogen concerned. Transmission at the population level can be quantified through knowledge of risk factors in the population or phylogeographic analysis of pathogen sequence data. Mathematical model-based approaches require estimation of the per capita transmission rate and basic reproduction number, obtained by fitting models to case data and/or analysis of pathogen sequence data. Heterogeneities in infectiousness, contact behavior, and susceptibility can have substantial effects on the epidemiology of an infectious disease, so estimates of only mean values may be insufficient. For some pathogens, super-shedders (infected individuals who are highly infectious) and super-spreaders (individuals with more opportunities to transmit infection) may be important. Future work on quantifying transmission should involve integrated analyses of multiple data sources.
Wills, Sarah; Beaufrère, Hugues; Watrous, Gwyneth; Oblak, Michelle L; Smith, Dale A
CASE DESCRIPTION A 13-year-old female green iguana (Iguana iguana) was examined because of a 6-day history of vomiting, anorexia, and lethargy and a 4-day history of decreased fecal and urate output. CLINICAL FINDINGS Physical examination revealed a distended abdomen, signs of depression, pallor, tachycardia, harsh lung sounds, and vomiting. Abdominal radiographs revealed gas distention of the stomach and small intestine with fluid lines evident on the lateral view. Plasma biochemical analysis indicated hypochloremic metabolic alkalosis, hyperglycemia, and hyperuricemia. TREATMENT AND OUTCOME Exploratory laparotomy confirmed a diagnosis of small intestinal entrapment and 170° volvulus involving approximately 80% (20 to 30 cm) of the small intestine. The portion of the small intestine extending from the middle portion of the duodenum to the caudal extent of the ileum was resected, and end-to-end anastomosis of the remaining small intestine was performed. The iguana recovered without apparent complications and was reportedly doing well 1 year after surgery. CLINICAL RELEVANCE Findings suggested that iguanas, as hindgut fermenters, may tolerate > 70% resection of the small intestine with a good outcome and no clinical evidence of residual gastrointestinal dysfunction.
Schmitz, S; Jansen, N; Failing, K; Neiger, R
The aim of the study was to assess solid phase gastric emptying via non-invasive 13C-sodium acetate breath test in large breed dogs with or without gastric dilatation-volvulus (GDV). Dogs were recruited into one of the following groups: group 1 = healthy large breed dogs with no history of GDV, group 2 = dogs that underwent elective abdominal surgery for reasons unrelated to the gastrointestinal tract, and group 3 = dogs that underwent laparotomy and gastropexy to correct GDV. The dogs were fed a test meal containing 100 mg 13C-sodium acetate (for group 2 and 3, this was < 48 hours post-operatively). Breath samples were obtained at baseline and every 30 minutes for 3 hours, then every hour for a total of 7 hours. 12CO2/13CO2 ratio was measured for each breath sample via non-dispersive infrared spectroscopy and 25%, 50% and 75% gastric emptying times were calculated and compared between groups. Gastric emptying times were significantly prolonged in dogs undergoing surgery (group 2) compared to group 1 and 3. Also, gastric emptying times of dogs with GDV were significantly prolonged compared to controls, but not to the same extent as dogs in group 2. There was a significant effect of abdominal surgery on gastric emptying times. Surprisingly, dogs after GDV surgery and gastropexy had shorter gastric emptying times than dogs undergoing laparotomy for reasons other than GDV, but still prolonged compared to healthy controls. The reason for these differences requires further study.
This patent describes a power transmission. It comprises: in combination, a master gear having at least one annular tooth set, means for drivingly engaging the master gear with a power source, driven shaft, a yoke member attached to the shaft and including a screw pump housing extending radially with respect to the shaft with a pair of ports in spaced relation, a pump screw rotatable in the housing and a pump gear attached to the screw and engaging the annular tooth set, and a casing for transmission fluid. The pump housing being located for immersion in the fluid.
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Leahy, E R; Holcombe, S J; Hackett, E S; Scoggin, C F; Embertson, R M
Limited data exist describing broodmare longevity and reproductive efficiency after surgical correction of ≥360 degree large colon volvulus (° LCV). Compare career duration and foals delivered for broodmares before and after ≥360° LCV surgery. Retrospective case series. Broodmares registered with The Jockey Club that had surgical correction of ≥360° LCV and survived to hospital discharge at Rood and Riddle Equine Hospital from 1 January 2000 to 31 December 2015 were included. Information was collected from the hospital's medical data base and The Jockey Club produce records about the mares' reproductive careers. Data were evaluated using parametric and nonparametric tests, P≤0.05. Mares that were bred but never foaled prior to surgery (n = 19) had shorter careers (mean ± standard deviation [s.d.]), 4.4 ± 4.5 years, and fewer foals, 3.1 ± 3.3, compared with mares that delivered ≥1 foal before surgery (n = 565), 10.4 ± 4.5 years and 7.4 ± 3.4 foals, respectively, P<0.001. Broodmares that delivered foals before surgery produced more foals in the years before surgery, 4.8 ± 3.0, than after surgery, 2.6 ± 2.4, P<0.001, and had longer breeding careers, 5.9 ± 3.8 vs. 4.5 ± 3.3 years before compared with after surgery, P<0.001. No significant differences in career length or number of foals delivered were detected for mares with a single compared with multiple LCV surgeries. Mares that were 3-11 years old at the time of surgery had significantly more foals after surgery compared with mares ≥12 years old, P<0.001, as expected. Retrospective collection of data. Broodmares had productive careers following surgery for ≥360° LCV that were largely influenced by the mares' age at the time of surgery. © 2017 EVJ Ltd.
Coy, John J.
The NASA Lewis Research Center and the U.S. Army Aviation Systems Command share an interest in advancing the technology for helicopter propulsion systems. In particular, this presentation outlines that portion of the program that applies to the drive train and its various mechanical components. The major goals of the program are to increase the life, reliability, and maintainability; reduce the weight, noise, and vibration; and maintain the relatively high mechanical efficiency of the gear train. The current activity emphasizes noise reduction technology and analytical code development followed by experimental verification. Selected significant advances in technology for transmissions are reviewed, including advanced configurations and new analytical tools. Finally, the plan for transmission research in the future is presented.
This patent describes an automatic transmission including a fluid torque converter, a first gear unit having three forward-speed gears and a single reverse gear, a second gear unit having a low-speed gear and a high-speed gear, and a hydraulic control system, the hydraulic control system comprising: a source of pressurized fluid; a first shift valve for controlling the shifting between the first-speed gear and the second-speed gear of the first gear unit; a second shift valve for controlling the shifting between the second-speed gear and the third-speed gear of the first gear unit; a third shift valve equipped with a spool having two positions for controlling the shifting between the low-speed gear and the high-speed gear of the second gear unit; a manual selector valve having a plurality of shift positions for distributing the pressurized fluid supply from the source of pressurized fluid to the first, second and third shift valves respectively; first, second and third solenoid valves corresponding to the first, second and third shift valves, respectively for independently controlling the operation of the respective shift valves, thereby establishing a six forward-speed automatic transmission by combining the low-speed gear and the high-speed gear of the second gear unit with each of the first-speed gear, the second speed gear and the third-speed gear of the first gear unit; and means to fixedly position the spool of the third shift valve at one of the two positions by supplying the pressurized fluid to the third shift valve when the manual selector valve is shifted to a particular shift position, thereby locking the second gear unit in one of low-speed gear and the high-speed gear, whereby the six forward-speed automatic transmission is converted to a three forward-speed automatic transmission when the manual selector valve is shifted to the particular shift position.
An automatic transmission is described combining a stator reversing type torque converter and speed changer having first and second sun gears comprising: (a) a planetary gear train composed of first and second planetary gears sharing one planetary carrier in common; (b) a clutch and requisite brakes to control the planetary gear train; and (c) a speed-increasing or speed-decreasing mechanism is installed both in between a turbine shaft coupled to a turbine of the stator reversing type torque converter and the first sun gear of the speed changer, and in between a stator shaft coupled to a reversing stator and the second sun gear of the speed changer.
This primer highlights recent trends in transmission investment, summarizes the division of jurisdictional authority over transmission, and presents four alternative models for transmission ownership. (author)
An automatic transmission is described, comprising: a torque converter including an impeller having a connected member, a turbine having an input member and a reactor; and an automatic transmission mechanism having first to third clutches and plural gear units including a single planetary gear unit with a ring gear and a dual planetary gear unit with a ring gear. The single and dual planetary gear units have respective carriers integrally coupled with each other and respective sun gears integrally coupled with each other, the input member of the turbine being coupled with the ring gear of the single planetary gear unit through the first clutch, and being coupled with the sun gear through the second clutch. The connected member of the impeller is coupled with the ring gear of the dual planetary gear of the dual planetary gear unit is made to be and ring gear of the dual planetary gear unit is made to be restrained as required, and the carrier is coupled with an output member.
This patent describes a vented transmission. It comprises: a housing; a rotary input to the housing; a rotary output from the housing; transmission means within the housing interconnecting the input and the output and including a hollow, rotary shaft journaled within the housing; a vent tube having a first end extending into one end of the hollow shaft and a second end in fluid communication with the exterior of the housing; a shoulder within the hollow shaft and intermediate the ends of the vent tube and defining of relatively smaller diameter section near the first end of the vent tube that is within the hollow shaft and a relatively large diameter section nearer the second end of the vent tube; at least one aperture extending through the hollow shaft from the large diameter section immediately adjacent the shoulder; and a labyrinth seal at the interface of the vent tube and the large diameter section at a location between the aperture (s) and the second end of the vent tube.
A gear transmission is provided with a first rotary shaft, a first non-circular gear fixed thereto, a second rotary shaft, and a second non-circular gear fixed thereto, the first non-circular gear and the second non-circular gear being continuously engageably rotated, thereby transmitting a rotational driving force between the first rotary shaft and the second rotary shaft. The gear transmission is characterized in that when the absolute value vertical bar..omega..2/..omega..1vertical bar of a ratio of an angular velocity of ..omega..2 of the second rotary shaft with respect to an angular velocity of ..omega..1 of the first rotary shaft is represented by F(theta) as the function of the angular displacement theta of the first rotary shaft, an engageably rotary portion where a differential value K given in a differential equation as to the angular displacement thetaK=d log F(theta)/dtheta presents a positive or negative constant value in continuation is provided in the shape of intermeshing pitch curves of the first non-circular gear and the second non-circular gear.
An automatic transmission is described comprising wheel members each having discs defining an inner space therebetween; turnable blades and vane members located in the inner space between the discs of at least one of the wheel members, the turnable blades being mechanically connected with the vane members. Each of the turnable blades has an inner surface and an outer surface formed by circular cylindrical surfaces having a common axis, each of the turnable blades being turnable about the common axis of the circular cylindrical surfaces forming the inner and outer surfaces of the respective blade; levers turnable about the axes and supporting the blades; the discs having openings extending coaxially with the surfaces which describe the blades. The blades are partially received in the openings of the discs; and a housing accommodating the wheel members and the turnable blades and the vane members.
Hamane, M.; Ohri, H.
This patent describes an automatic transmission connected between a drive shaft and a driven shaft and comprising: a planetary gear mechanism including a first gear driven by the drive shaft, a second gear operatively engaged with the first gear to transmit speed change output to the driven shaft, and a third gear operatively engaged with the second gear to control the operation thereof; centrifugally operated clutch means for driving the first gear and the second gear. It also includes a ratchet type one-way clutch for permitting rotation of the third gear in the same direction as that of the drive shaft but preventing rotation in the reverse direction; the clutch means comprising a ratchet pawl supporting plate coaxially disposed relative to the drive shaft and integrally connected to the third gear, the ratchet pawl supporting plate including outwardly projection radial projections united with one another at base portions thereof.
Nerstad, K.A.; Windish, W.E.
A planetary transmission is described comprising: an input shaft; a first planetary gear set having a first sun gear driven by the input shaft, a first planet carrier serving as the output, a first ring gear, and first brake means for selectively holding the fist ring gear stationary; a second planetary gear set having a second sun gear driven by the input shaft, a second planet carrier connected for joint rotation to the first ring gear, a second ring gear, and second brake means for selectively holding the second ring gear stationary; a third planetary gear set having a third sun gear connected for joint rotation to the second planet carrier, a third planet carrier connected for joint rotation to the second ring gear, a third ring gear, and third brake means for selectively holding the third ring gear stationary; and clutch means for connecting the third sun gear to the input shaft and providing a direct drive mode of operation.
This patent describes an overdrive transmission device for use with a motor vehicle. It consists of: a housing; a driving shaft rotatably mounted within the housing; a planetary gear-train; a driven shaft rotatably mounted in the housing and driven by the planetary gear train; and, a device for selectively connecting the planetary gear carrier to the housing or to the driven shaft for rotation; a hydraulically actuated piston adapted to forcibly contact the clutch friction members of the second clutch; a source of working fluid; a pump in fluid flow communication with the source of working fluid; a first valve downstream of the pump and in fluid flow communication with the pump and the hydraulically activated piston.
Himmelein, M.K.; Haaser, J.D.
This patent describes a mechanical power transmission. It comprises a pair of axially aligned rotatable shaft members, a motor member, having a motor housing of thin axial width located within the central housing, fixed to one of the shaft members and axially aligned to rotate wherewith, and a harmonic drive member of thin axial width positioned within the central housing in axial alignment between the motor member and the remaining shaft member, a circular spline fixed to the motor housing for rotation therewith, a flex spline engaged with the dynamic spline and the circular spline, and a wave generator in communication with the flex spline and a wave generator in communication with the flex spline and engaged with the center shaft of the motor member.
Orshansky, Jr. deceased, Elias; Weseloh, William E.
A power transmission having three planetary assemblies, each having its own carrier and its own planet, sun, and ring gears. A speed-varying module is connected in driving relation to the input shaft and in driving relationship to the three sun gears, all of which are connected together. The speed-varying means may comprise a pair of hydraulic units hydraulically interconnected so that one serves as a pump while the other serves as a motor and vice versa, one of the units having a variable stroke and being connected in driving relation to the input shaft, the other unit, which may have a fixed stroke, being connected in driving relation to the sun gears. The input shaft also drives the carrier of the third planetary assembly. A brake grounds the first carrier in the first range and in reverse and causes drive to be delivered to the output through the first ring gear in a hydrostatic mode. The carrier of the third planetary assembly drives the ring gear of the second planetary assembly, and a first clutching means connects the second carrier with the output in a second range, the brake for grounding the first carrier then being released. A second clutching means enables the third ring gear to drive the output shaft in a third range.
Coulibaly, Mahamadoun; Boukatta, Brahim; Derkaoui, Ali; Sbai, Hicham; Ousadden, Abdelmalek; Kanjaa, Nabil
Le mésentère commun résulte d'une anomalie de rotation du tube digestif. Il est caractérisé par la persistance d'une disposition anatomique embryonnaire secondaire à une anomalie de rotation de l'anse ombilicale primitive, constituant ainsi un méso commun à toute l'anse intestinale et une racine du mésentère extrêmement courte. Cette insuffisance de rotation est le plus souvent associée à un défaut d'accolement. Ces anomalies de rotation intestinale peuvent aboutir à des complications redoutables parfois mortelles, qui surviennent généralement au cours de la période néonatale où à l’âge pédiatrique. On estime que la prévalence de ces malformations congénitales à l’âge adulte est de l'ordre de 0,2% à 0,5% âge auquel elles demeurent très souvent asymptomatiques et donc non diagnostiquées. Le diagnostic de volvulus total du grêle peut se faire dans des circonstances très variées: en urgence devant un tableau d'occlusion intestinale aiguë, voire un état de choc pouvant conduire au décès, devant un tableau de douleurs abdominales répétées plus ou moins associées à des troubles du transit. Nous rapportons l'observation d'un patient de 18 ans admis pour volvulus total du grêle sur mésentère commun incomplet chez qui l’évolution était favorable. PMID:26113900
Ordo, J.P.; Raszkowski, J.A.; Klemen, D.
This patent describes a transmission. It comprises a housing having first and second end covers; an input shaft rotatably mounted in the first end cover; an output shaft rotatably supported on the input shaft and in the second end cover; first and second countershafts rotatably supported in the end covers for rotation on respective axis parallel with the input shaft and the output shaft; a first head gear continuously rotatable with the input shaft; second and third head gears meshing with the first head gear and continuously rotatable with the first and second countershafts respectively; ratio gears rotatably supported on each of the countershafts including a first ratio gear on the first countershaft and a second ratio gear on the second countershaft; reverse gear means including a first ratio gear on the first countershaft and a second ratio gear on the second countershaft; reverse gear means including a first member rotatable with the first ratio gear means including a first member rotatable with the first ratio gear and a second member rotatably supported on the second countershaft; synchronizer clutch means selectively and alternatively connectible with the second ratio gear and the second member of the reverse gear means; output gear means drivingly connected with the output shaft and including a first ratio output gear meshing with the second ratio gear; first selectively engageable friction clutch means for connecting the first ratio gear with the first countershaft for completing a low forward drive ratio between the input and output shafts; and second selectively engageable friction clutch means for selectively connecting the synchronizer clutch means to the second countershaft and cooperating therewith to selectively alternatively complete a reverse drive ratio between the input shaft and the output shaft and another forward drive ratio between the input and output shafts.
Miura, M.; Inuzuka, T.
1. An automatic transmission with four forward speeds and one reverse position, is described which consists of: an input shaft; an output member; first and second planetary gear sets each having a sun gear, a ring gear and a carrier supporting a pinion in mesh with the sun gear and ring gear; the carrier of the first gear set, the ring gear of the second gear set and the output member all being connected; the ring gear of the first gear set connected to the carrier of the second gear set; a first clutch means for selectively connecting the input shaft to the sun gear of the first gear set, including friction elements, a piston selectively engaging the friction elements and a fluid servo in which hydraulic fluid is selectively supplied to the piston; a second clutch means for selectively connecting the input shaft to the sun gear of the second gear set a third clutch means for selectively connecting the input shaft to the carrier of the second gear set including friction elements, a piston selectively engaging the friction elements and a fluid servo in which hydraulic fluid is selectively supplied to the piston; a first drive-establishing means for selectively preventing rotation of the ring gear of the first gear set and the carrier of the second gear set in only one direction and, alternatively, in any direction; a second drive-establishing means for selectively preventing rotation of the sun gear of the second gear set; and a drum being open to the first planetary gear set, with a cylindrical intermediate wall, an inner peripheral wall and outer peripheral wall and forming the hydraulic servos of the first and third clutch means between the intermediate wall and the inner peripheral wall and between the intermediate wall and the outer peripheral wall respectively.
Ojurongbe, Olusola; Akindele, Akeem Abiodun; Adeleke, Monsuru Adebayo; Oyedeji, Matthew Oyebode; Adedokun, Samuel Adeyinka; Ojo, Josephine Folashade; Akinleye, Callistus Adewale; Bolaji, Oloyede Samuel; Adefioye, Olusegun Adelowo; Adeyeba, Oluwaseyi Adegboyega
Background Loiasis is currently receiving attention as a disease of public health importance because of the possibility of increased risk of developing neurologic serious adverse event following mass ivermectin treatment against onchocerciasis in individual co-infected with Onchocerca volvulus and Loa loa. Methodology/Principal Findings Rapid assessment procedure for loiasis (RAPLOA) was conducted in 12 communities covering the 3 senatorial districts of Osun State, Nigeria. A total of 960 people were interviewed for history of eye worm using the WHO guidelines for rapid assessment. The survey confirmed the presence of loiasis in all the 12 communities with 4 in Osun East/Ife south senatorial district being at high risk with a prevalence of over 40%. Based on the RAPLOA results, communities within Osun East/Ife south senatorial district were selected for microfilaraemic assessment of L. loa and O. volvulus. A total of 1115 and 1091 individuals were screened for L. loa and O. volvulus microfilaria worms respectively. 160 (14.3%) had L. loa microfilaria detected in their blood with 8 (5.0%) individuals having L. loa loads above 8000 mf/ml. 166 (15.2%) subjects had O. volvulus microfilaria (range 4-504 mf/ml) detected in their skin snip. 30 (2.69%) subjects were co-infected with both L. loa and O. volvulus. There was a significant variation in the prevalence (2.1% to 33.3%) of onchocerciasis in the communities studied (p = 0.001). Five (41.7%) of the studied communities had a prevalence that is equal to or greater than 20%. Conclusions/Significance Low prevalence of onchocerciasis and loiasis co-infection in this study suggests that loiasis may not pose a serious epidemiological threat to the continuous distribution and sustainability of ivermectin for the treatment of onchocerciasis. Evaluation of the interruption of onchocerciasis transmissions in this region using all the indicators set forth by WHO is therefore suggested. PMID:25812086
Amano, Hizuru; Uchida, Hiroo; Kawashima, Hiroshi; Tanaka, Yujiro; Kishimoto, Hiroshi
Midgut volvulus is a highly life-threatening condition that carries a high risk of short gut syndrome. We report a case of catastrophic neonatal midgut volvulus in which second-look laparotomy revealed apparently non-viable remnant small intestine but with a moderate blood supply. Full-thickness small intestine necrosis was distributed in a patchy fashion, with non-viable and necrotic areas distributed so widely that no portion of the intestine could be resected. A section of full-thickness necrotic intestine preserved at surgery was able to regenerate, and normal function was restored over a period of 1 month. This case indicated that intestinal resumption may be dependent on blood flow. Even when intestinal viability is questionable, preservation enables the chance of regeneration if moderate blood flow is present.
Egwang, T G; Nguiri, C; Kombila, M; Duong, T H; Richard-Lenoble, D
Immunologic analyses of sera from 47 selected individuals living in a mixed filariasis transmission zone in Gabon were carried out. Onchocerca volvulus, Loa loa, Mansonella streptocerca, and M. perstans are transmitted in this region. Based on parasitologic findings and age, the 47 individuals were stratified into four groups: microfilaria negative (Mf-) children (3-15 years old), Mf- adults (> 15 years old), microfilaria positive (Mf+) children and Mf+ adults. For descriptive purposes, the term microfilaria positive refers to individuals with skin and blood microfilariae. Antifilarial antibody titers were determined using an enzyme-linked immunosorbent assay with Dipetalonema viteae antigens. In general, children had higher titers of IgG antibodies than adults. For the IgG1, IgG2, and IgG3 subclass responses, both age and microfilarial status appeared to be important variables since Mf- children consistently had the highest titers whereas Mf- adults had the lowest titers. For the IgG4 antifilarial response, only the microfilarial status was an important variable. All Mf+ individuals had significantly higher levels of IgG4 antibody than Mf- individuals. Pooled sera of Mf- and Mf+ individuals reacted with similar O. volvulus antigens on Western blots. Control sera of individuals who did not reside in the study area, but who had single infections with L. loa or M. perstans, did not react with any O. volvulus antigens.
Fink, S.; Porter, K.; Mudd, C.; Rogers, J.
The report presents transmission cost allocation methodologies for reliability transmission projects, generation interconnection, and economic transmission projects for all Regional Transmission Organizations.
Pettengill, Matthew A.; Lam, Verissa W.; Ollawa, Ikechukwu; Marques-da-Silva, Camila; Ojcius, David M.
Ivermectin is currently approved for treatment of both clinical and veterinary infections by nematodes, including Onchocerca cervicalis in horses and Onchocerca volvulus in humans. However, ivermectin has never been shown to be effective against bacterial pathogens. Here we show that ivermectin also inhibits infection of epithelial cells by the bacterial pathogen, Chlamydia trachomatis, at doses that could be envisioned clinically for sexually-transmitted or ocular infections by Chlamydia. PMID:23119027
Filser, Joerg; Reibetanz, Joachim; Krajinovic, Katica; Germer, Christoph-Thomas; Dietz, Ulrich Andreas; Seyfried, Florian
Transabdominal preperitoneal endoscopic hernia repair (TAPP) is part of primary surgical health care. While both, the reported recurrence rate and procedure specific morbidity are consistently low, rare serious complications occur. A 36-year-old male patient developed bowel obstruction three days after both-sided TAPP for inguinal hernia repair. A computer tomography scan of the abdomen revealed a small bowel volvulus in the right lower quadrant of the abdomen requiring urgent revisional surgery. Intraoperatively, the small bowel and its mesenterial vessels were found to be twisted around a 5cm long V-Loc™ barbed absorbable suturing wire. After successful laparoscopic adhesiolysis, removal of the wire and detorquing of the bowel conglomerate, resection of small intestine was not necessary. The patient's further postoperative recovery was uneventful. Due to the barbed configuration of the V-Loc™ wire, a gapless continuous suturing of the peritoneum without laparoscopic knotting is easily and fast to accomplish. In this case the recommendation of the manufacturer to shorten the wire was not strictly followed and neither had the suture stump been extraperitonealized in order to avoid such rare complications. Surgeons need to be aware of relevant "tricks and traps" of routinely performed procedures and have to know all tools and material they use very well. This case may therefore increase our attention when it comes to little things which actually do matter. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
This patent describes a vehicular transmission of the type in which a manual transmission has two parallel shafts. One shaft is connected through a transmission clutch to an engine in which manual transmission is connected in series to an auxiliary transmission having high and low speed transmission lines. The auxiliary transmission has a high speed transmission line equipped with a hydraulic clutch and a low speed transmission line equipped with a one-way clutch for allowing the overrun of the output side of the low speed transmission line so that the low speed transmission line is established when the hydraulic clutch is released. The high speed transmission is established when the hydraulic clutch is applied. A sleeve shaft is on one of the two shafts. A transmission gear mechanism connects the sleeve shaft to the other shaft. One shaft has an extension with a fixed gear. A coacting gear is fixed on the sleeve shaft, the hydraulic clutch and coacting gear positioned on the extension of one shaft, an idle gear mechanism in meshing engagement with both the coacting gear and the fixed gear. The idle gear mechanism has a low speed transmission line one-way clutch, and the hydraulic clutch is operable to connect and disconnect the sleeve shaft to and from the one shaft.
Cupp, E W; Cupp, M S
When blood-feeding, black flies introduce secretions into the feeding lesion that act in a coordinated manner on the 3 arms of the vertebrate hemostatic system (platelet aggregation, coagulation, and vasoconstriction). Apyrase activity inhibits platelet aggregation and is ubiquitous in the saliva of black flies, although activity per gland varies by species and has a positive association with anthropophagy. Anticoagulants target components in the final common pathway of the coagulation cascade, including factors V, Xa, and II (thrombin). The antithrombin salivary protein may exert a redundant effect by inhibiting the role of thrombin in platelet aggregation. Antithrombin presence and activity also varies among black fly species, and exhibits a positive correlation with zoophagy. Vasodilation of capillaries to increase blood supply to the feeding wound appears to be an important requirement for Simulium spp., because substantial erythema-inducing activity, has been demonstrated in salivary glands of all New World species examined. Salivary glands of Simulium ochraceum (Walker), a highly anthropophilic vector of Onchocerca volvulus (Leuckhart), contain greater vasodilator activity than several other species, including S. metallicum Bellardi, a secondary zoophagic vector of human onchocerciasis. Simulium vittatum Zetterstedt saliva affects immune cell responses and cytokine production. The ability of the saliva to modulate components of the host immune system provides an opportunity for enhancing transmission of pathogens during bloodfeeding. Thus, the likely possibility that effective pathogen transmission relies on vector saliva may complement present efforts aimed at target epitopes of O. volvulus or identify additional molecules to be investigated as part of a "river blindness" vaccine cocktail. Components in saliva also may enhance the transmission of other microbial agents either by a cofeeding process similar to that observed in ixodid ticks or through rupture
... Address What's this? Submit What's this? Submit Button Zika and Sexual Transmission Language: English EspaÃ±ol PortuguÃªs ... 1 page] Portuguese [PDF - 1 page] Basics of Zika Virus and Sex Transmission Zika can be passed ...
Stich, R.L.; Neal, W.D.
This patent describes, in a four-wheel-drive vehicle apparatus having a power train including an automatic transmission and a transfer case, an automatic transmission adapter kit for installation of a replacement automatic transmission of shorter length than an original automatic transmission in the four-wheel-drive vehicle. The adapter kit comprises: an extension housing interposed between the replacement automatic transmission and the transfer case; an output shaft, having a first end which engages the replacement automatic transmission and a second end which engages the transfer case; first sealing means for sealing between the extension housing and the replacement automatic transmission; second sealing means for sealing between the extension housing and the transfer case; and fastening means for connecting the extension housing between the replacement automatic transmission and the transfer case.
Duke, B O; Vincelette, J; Moore, P J
Microfilariae of Onchocerca volvulus were found in the cerebrospinal fluid (CSF) of 5/8 heavily infected onchocerciasis patients. During treatment with diethylcarbamazine citrate 10/11 patients showed increased numbers of 0. volvulus microfilariae in the CSF. Patients with concentrations of 8-31 mf/ml CSF developed severe vertigo, and some other neurological manifestations, during treatment. A hypothesis is put forward to account for this clinical piciture, and its importance in relation to the treatment of onchocerciasis is discussed.
BROWN, A W
It has become possible to control or even eradicate the Simulium fly vectors of Onchocerca volvulus, the causative organism of onchocerciasis. There are two vectors in Africa-namely, S. damnosum, characteristic of the rivers of West Africa, and S. neavei, which breeds on the carapaces of crabs in the streams of East Africa. The use of DDT applied to the water at a concentration as low as 0.1 p.p.m. for 30 minutes eliminates the larvae of Simulium. Such larvicidal methods have eradicated S. neavei from western Kenya and virtually eradicated S. damnosum from the Victoria Nile in Uganda. Excellent control sufficient to render the transmission of onchocerciasis almost negligible has been obtained at Léopoldville (Republic of the Congo) and in circumscribed areas in southern Chad, Northern Nigeria, and Sierra Leone. The following survey describes operational research on Simulium control carried out in Kenya, Uganda, the Congo, Chad, Nigeria, Ghana, Upper Volta and Sierra Leone.
Darge, K; Lucius, R; Monson, M H; Behrendsen, J; Büttner, D W
Microfilariae were studied in skin and lymph node biopsies from Liberian patients with generalised onchocerciasis 12-78 hours after administration of a single dose of 150 micrograms/kg body weight using histology, transmission electron microscopy and immunocytological staining with antibodies against an immunodominant antigen of Onchocerca volvulus. Most microfilariae in the skin appeared morphologically intact and beginning signs of degeneration were seen only on the ultrastructural level. The densities of microfilariae in the lymph nodes were about thousandfold higher in ivermectin treated patients. More than 90% of the microfilariae in the lymph nodes showed distinct signs of degeneration. Early changes were seen in the muscle cells. The disintegrating microfilariae in the lymph nodes were always encircled by eosinophils or macrophages or both cells. Immunohistological staining with antifilarial antibodies increased the detection of small and disintegrating pieces of microfilariae considerably.
Oguttu, David; Byamukama, Edson; Katholi, Charles R; Habomugisha, Peace; Nahabwe, Christine; Ngabirano, Monica; Hassan, Hassan K; Lakwo, Thomson; Katabarwa, Moses; Richards, Frank O; Unnasch, Thomas R
Uganda is the only African country whose onchocerciasis elimination program uses a two-pronged approach of vector control and mass drug distribution. The Ugandan program relies heavily upon the use of serosurveys of children to monitor progress toward elimination. The program has tested over 39,000 individuals from 11 foci for Onchocerca volvulus exposure, using the Ov16 ELISA test. The data show that the Ov16 ELISA is a useful operational tool to monitor onchocerciasis transmission interruption in Africa at the World Health Organization (WHO) recommended threshold of < 0.1% in children. The Ugandan experience has also resulted in a re-examination of the statistical methods used to estimate the boundary of the upper 95% confidence interval for the WHO prevalence threshold when all samples tested are negative. This has resulted in the development of Bayesian and hypergeometric statistical methods that reduce the number of individuals who must be tested to meet the WHO criterion.
Well over 20 million people in the world are infected with Onchocerca volvulus and it is probable that 200 000-500 000 people are blind as a result of this infection, which is the most important cause of blindness in certain areas of Africa and Latin America. Treatment of the disease is difficult and often produces serious adverse reactions in the patient. Combined use of diethylcarbamazine citrate and suramin is still the most suitable form of treatment. Screening for the early detection of cases at high risk of ocular manifestations must be organized, and their treatment undertaken, if blindness is to be avoided. Prevention of ocular onchocerciasis is feasible, using vector control methods to reduce transmission, but the procedures are costly and may have to be maintained for many years. Research is needed to improve treatment and to find a chemoprophylactic agent or a preventive vaccine. PMID:307448
Southgate, B A
The descriptive epidemiology of onchocerciasis is well understood in the major foci of infection; a great stimulus to epidemiological research has been the implementation of the first control programme, which led to the eradication of infection in Kenya and, more recently, the vast Onchocerciasis Control Programme in the Volta River Basin of West Africa. However, there are still significant gaps in epidemiological knowledge which hamper the planning of future control programmes and the evaluation of current programmes. The four most important unsolved problems are: the refinement of field diagnostic techniques to identify skin microfilariae at the ultra-low densities that will become common in the late stages of vector-control campaigns; the definitive identification of Onchocerca volvulus infective larvae in Simulium species; strain analysis in the field of microfilariae from humans and of developing stages from Simulium, to determine their potential for ocular pathogenicity; determination of the lifespan, or maximum fecundity span, of adult female O. volvulus after the interruption of transmission. Three other unsolved problems are of enormous interest epidemiologically, although less urgent in practical importance. They are the identification of factors causing severe disease as opposed to heavy infection; the effects of seasonal as opposed to perennial transmission; and the importance of transplacental transmission of microfilariae or soluble antigens.
Udonsi, J K
In a cross-sectional, epidemiological and parasitological study of human filariasis, 845 individuals were examined in settlements along the Igwun Basin, Imo State, Nigeria. Four different filarial nematode species were identified. Two hundred and fifty-six (30.3%) of the individuals examined were positive for Onchocerca volvulus, 113 (13.4%) for Mansonella perstans, 76 (9.6%) for Wuchereria bancrofti and 77 (9.1%) for Loa loa. Microfilarial rates increased with age of individuals and showed a tendency towards higher prevalence rates in males than in females. The intensity of O. volvulus infection was high, with the highest microfilarial density of 44 mf mg-1 snip which occurred in the 40-49-year-old individuals. In W. bancrofti and L. loa infections, infections of over 1000 mf 20 ml-1 blood were recorded in 15.8% and 19.5% of individuals, respectively. Observed clinical signs were associated with inflammatory, lympho-obstructive and ocular manifestations. In M. perstans infections all clinical cases were inflammatory. In W. bancrofti, 44.4% of clinical cases were inflammatory, and lympho-obstructive manifestations consisted of 23.8% chyluria, 12.7% hydrocele and 19.1% elephantiasis. In L. loa infections all clinical cases were inflammatory with indications of Calabar swellings. In O. volvulus infections 23.5% of clinical cases were inflammatory, while 76.5% showed ocular manifestations. The absence of blindness despite high O. volvulus infection rates was remarkable. The presence of potential insect vectors and the occurrence of clinical signs are indications of active transmissions.
Lawrie, Robert E.; Reed, Jr., Richard G.; Bernier, David R.
A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.
Trainor, Elizabeth A; Nicholson, Tracy L; Merkel, Tod J
Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission.
Makepeace, Benjamin L.; Jensen, Siv Aina; Laney, Sandra J.; Nfon, Charles K.; Njongmeta, Leo M.; Tanya, Vincent N.; Williams, Steven A.; Bianco, Albert E.; Trees, Alexander J.
Human onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is controlled almost exclusively by the drug ivermectin, which prevents pathology by targeting the microfilariae. However, this reliance on a single control tool has led to interest in vaccination as a potentially complementary strategy. Here, we describe the results of a trial in West Africa to evaluate a multivalent, subunit vaccine for onchocerciasis in the naturally evolved host-parasite relationship of Onchocerca ochengi in cattle. Naïve calves, reared in fly-proof accommodation, were immunised with eight recombinant antigens of O. ochengi, administered separately with either Freund's adjuvant or alum. The selected antigens were orthologues of O. volvulus recombinant proteins that had previously been shown to confer protection against filarial larvae in rodent models and, in some cases, were recognised by serum antibodies from putatively immune humans. The vaccine was highly immunogenic, eliciting a mixed IgG isotype response. Four weeks after the final immunisation, vaccinated and adjuvant-treated control calves were exposed to natural parasite transmission by the blackfly vectors in an area of Cameroon hyperendemic for O. ochengi. After 22 months, all the control animals had patent infections (i.e., microfilaridermia), compared with only 58% of vaccinated cattle (P = 0.015). This study indicates that vaccination to prevent patent infection may be an achievable goal in onchocerciasis, reducing both the pathology and transmissibility of the infection. The cattle model has also demonstrated its utility for preclinical vaccine discovery, although much research will be required to achieve the requisite target product profile of a clinical candidate. PMID:19901988
Developed to solve specific problem: Assist transmission planning for regional transfers in interconnected power systems. This work was originated in a study for the U.S. Department of State, to recommend transmission reinforcements for the Central American regional system that interconnects 6 countries. Transmission planning analysis is currently performed by engineers with domainspecific and systemspecific knowledge without a unique methodology. The software codes of this disclosure assists engineers by defining systematic analysis procedures to help identify weak points and make decisions on transmission planning of regional interconnected power systems. Transmission Planning Analysis Tool groups PSS/E results of multiple AC contingency analysis and voltage stability analysis and QV analysis of many scenarios of study and arrange them in a systematic way to aid power system planning engineers or transmission operators in effective decision]making process or in the off]line study environment.
Buckles, Robert A.; Booth, Rex; Yen, Boris T.
A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.
Judson, Seth; Prescott, Joseph; Munster, Vincent
An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus. PMID:25654239
Judson, Seth; Prescott, Joseph; Munster, Vincent
An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus.
Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea
Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Over the period 1990-2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries.
Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea
Background Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. Methods A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Results Over the period 1990–2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. Conclusion The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries. PMID:17521449
Wu, Yang; Preston, Gillian; Bianco, Albert E.
Chitinase expression in microfilariae of the parasitic nematode Brugia malayi (B. malayi, Bm) is coincidental with the onset of their infectivity to mosquitoes. An antibody raised to Onchocerca volvulus (O. volvulus, Ov) infective-stage larval chitinase (Ov-CHI-1) was specifically reactive against B. malayi microfilarial chitinase and was used to study the localization of chitinase in B. malayi during microfilarial development and transmission to the insect vector. Immuno-electron microscopy (IEM) was used to demonstrate that the chitinase was confined to the inner body of the microfilariae and furthermore that chitinase was only present in sheathed microfilarial species, although the inner body is present in all species. Observation using the IEM implicates two distinct routes of chitinase secretion from the inner body, via either the pharyngeal thread, or during transmission of the microfilariae to the vector, contained in vesicle-like structures. Many morphological studies have described the structure of the inner body, but no function has been assigned to it as of yet. Although it has been commented that the cells surrounding the inner body and pharyngeal thread are those destined to become the intestine and pharynx and that the inner body represents a store of material. Our studies suggest that chitinase is one such product stored in the inner body and that it is secreted during the exsheathment of the microfilaria in the mosquito. PMID:18611418
Rodríguez-Pérez, Mario A.; Adeleke, Monsuru A.; Burkett-Cadena, Nathan D.; Garza-Hernández, Javier A.; Reyes-Villanueva, Filiberto; Cupp, Eddie W.; Toé, Laurent; Salinas-Carmona, Mario C.; Rodríguez-Ramírez, Américo D.; Katholi, Charles R.; Unnasch, Thomas R.
Background Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America. Methodology/Principal Findings Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the “Esperanza window trap” showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components) a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors. Conclusions/Significance The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus. PMID:24116169
Comparative efficacy of moxidectin 2% equine oral gel and ivermectin 2% equine oral paste against Onchocerca cervicalis (Railliet and Henry, 1910) microfilariae in horses with naturally acquired infections in Formosa (Argentina).
Mancebo, O A; Verdi, J H; Bulman, G M
On the basis of positive skin snips for Onchocerca cervicalis microfilariae (MF), 45 horses were chosen from 48 in a total of 257 screened on 12 locations in the northeast Province of Formosa (Argentina), and randomly assigned to two treatment groups of 20 horses each, and a nontreated control group of five horses. On Day 14 post-treatment (PT), skin snip samples in the ivermectin-treated (0.2 mg/kg) group were negative for normal viable microfilariae (MF), while horses in the control group maintained their pretreatment level of infection. On the same Day in the moxidectin-treated (0.4 mg/kg) group, 18 horses were negative for MF, but the remaining two had a total of 1 and 2 MF, respectively (equivalent to 10 and 20 MF/g of skin), but all three parasites showed marked cuticular and structural damage. Both horses were negative in a repeat biopsy on Day 21. From Day 3 PT, one ivermectin-treated horse (5%) evidenced an approximate 15 x 2 x 3 cm-sized, apparently nonpainful, oedematous swelling on the ventral midline, 20 cm in front of the navel, which remained unchanged on Day 14 PT. Adverse reactions were not observed in the moxidectin-treated group. Parasitaemia was found in 18.7% of sampled horses (48 of 257), and the number of MF varied between 10-1820/g of skin snip (mean 172). Similar prevalence and total counts had been described previously in 1985 and 1986 in cattle-farm horses in the same area of Argentina; in surveys in Texas (1974) and Louisiana (1995) in the USA, infection rates were also similar, but total counts much higher. It is concluded that moxidectin 2% equine oral gel and ivermectin 2% equine oral paste, were equally 100% effective in the control of O. cervicalis MF. Contrary to ivermectin, moxidectin did not cause post-treatment dermal reactions.
The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.
The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.
Introduces some basic concepts related to the transmission of data from a computer to its peripherals to help distance educators make decisions regarding computer equipment purchases for their institutions. The following data transmission concepts are described: cables, serial and parallel, synchronous and asynchronous, bandwidth, and analog and…
This book is organized under the following headings. The Mercedes-Benz 5-speed automatic transmission targets and comparison of concepts. 1991 model year Chrysler mini-van all wheel drive vehicle. Mesh stiffness and transmission error of spur and helical gears. High precision cutting tool system for the manufacture of world class powertrain components.
Hasegawa, H.; Ishiguro, T.
This patent describes a method of controlling an automatic transmission of an automotive vehicle. The transmission has a gear train which includes a brake for establishing a first lowest speed of the transmission, the brake acting directly on a ring gear which meshes with a pinion, the pinion meshing with a sun gear in a planetary gear train, the ring gear connected with an output member, the sun gear being engageable and disengageable with an input member of the transmission by means of a clutch. The method comprises the steps of: detecting that a shift position of the automatic transmission has been shifted to a neutral range; thereafter introducing hydraulic pressure to the brake if present vehicle velocity is below a predetermined value, whereby the brake is engaged to establish the first lowest speed; and exhausting hydraulic pressure from the brake if present vehicle velocity is higher than a predetermined value, whereby the brake is disengaged.
American Association for Agricultural Engineering and Vocational Agriculture, Athens, GA.
The manual was developed as a reference for teaching students about transmissions in farm tractors. The manual is divided into five sections: (1) transmission history, (2) gears and bearings in transmission, (3) sliding-gear transmissions, (4) planetary gearing, and (5) glossary. The working principles of the sliding-gear transmission, the most…
Nasvytis, A. L.; White, G.
The basic configuration of geared traction drives, geometric and structural factors to be considered in their construction, and current work on hybrid helicopter transmissions rated at 500 and 3000 hp are discussed.
Hall, David R.; Hall, Jr., H. Tracy
A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. The electrically conducting coil comprises at least two generally fractional loops. In the preferred embodiment, the transmission elements are connected by an electrical conductor. Preferably, the electrical conductor is a coaxial cable. Preferably, the MCEI trough comprises ferrite. In the preferred embodiment, the fractional loops are connected by a connecting cable. In one aspect of the present invention, the connecting cable is a pair of twisted wires. In one embodiment the connecting cable is a shielded pair of twisted wires. In another aspect of the present invention, the connecting cable is a coaxial cable. The connecting cable may be disposed outside of the MCEI circular trough.
Hall, David R [Provo, UT; Fox, Joe [Spanish Fork, UT
A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. An electrical conductor connects both the transmission elements. The electrical conductor comprises at least three electrically conductive elements insulated from each other. In the preferred embodiment the electrical conductor comprises an electrically conducting outer shield, an electrically conducting inner shield and an electrical conducting core. In some embodiments of the present invention, the electrical conductor comprises an electrically insulating jacket. In other embodiments, the electrical conductor comprises a pair of twisted wires. In some embodiments, the electrical conductor comprises semi-conductive material.
According to a June 1998 report from UNAIDS, the majority of children infected with HIV acquired it from their mothers during or near birth. One way to prevent perinatal transmission of HIV is to increase prevention efforts for women. Other ways to prevent perinatal transmission include using AZT treatment, avoiding breastfeeding, and choosing a C-section delivery instead of a vaginal delivery. One important study, called the Thai study, promoted a shorter course of AZT therapy that was less expensive, more accessible, and still prevented transmission in many cases. Several reasons are cited for why some women continue breastfeeding, despite the increased risk of transmitting HIV to their babies. An important factor in preventing perinatal transmission is the overall health of the mother, and her ability to maintain her health and treatment regimen while caring for a newborn.
Reed, W. R.
Time-multiplexing system enables several cameras to share a single commercial television transmission channel. This system is useful in industries for visually monitoring several operating areas or instrument panels from a remote location.
Grana, D. C.
Chain slides along two cones, in novel transmission concept. Transmission includes chain drive between two splined shafts. Chain sprockets follow surfaces of two cones. As one chain sprocket moves toward smaller diameter other chain sprocket moves toward larger diameter, thereby changing "gear" ratio. Movement initiated by tension applied to chain by planetary gear mechanism. Device positive, simple, and efficient over wide range of speed ratios.
Chambers, J. P.
The BBC Datacast service allows one-way transmission of general data services for public service data broadcasting or for commercial purposes using the existing teletext system as the carrier. Such uses were anticipated when the 1976 UK teletext specification was written, so Datacast can co-exist with the normal teletext service (Ceefax) without problems. This Report provides a detailed specification of the Datacast transmission standard.
... Energy Regulatory Commission Zephyr Power Transmission, LLC; Pathfinder Power Transmission, LLC; Duke-American Transmission Company, LLC; Notice of Petition for Declaratory Order Take notice that on January 30... (Commission), 18 CFR 381.302, Zephyr Power Transmission, LLC (Zephyr), Pathfinder Power Transmission, LLC...
A multistate transmission is described having an input shaft and an output shaft comprising: a. planetary gear train means having a ring gear, planetary gears with planetary gear carrier, and a sun gear, the planetary gear train means connected to the output shaft; b. first bypass means connecting the input shaft to the planetary gear train means; c. differential transmission means for receiving its input from the input shaft and having means to adjust the torque and speed output infinitely variable over its range of operation for each state of the transmission; d. power return means for receiving the output of the differential transmission means; e. means including clutch operated speed reversing means for interconnecting the sun gear in the planetary gear train means with the power return means; f. the power return means including a first gear to receive the output of the differential transmission means; g. first multispeed transmission means connecting the means for supporting the carrier shaft to the first bypass means.
The National Energy Policy Plan directed the U.S. Department of Energy (DOE) to conduct a study to examine the benefits of establishing a national electricity transmission grid and to identify transmission bottlenecks and measures to address them. DOE began by conducting an independent analysis of U.S. electricity markets and identifying transmission system bottlenecks using DOE’s Policy Office Electricity Modeling System (POEMS). DOE’s analysis, presented in Section 2, confirms the central role of the nation’s transmission system in lowering costs to consumers through increased trade. More importantly, DOE’s analysis also confirms the results of previous studies, which show that transmission bottlenecks and related transmission system market practices are adding hundreds of millions of dollars to consumers’ electricity bills each year. A more detailed technical overview of the use of POEMS is provided in Appendix A. DOE led an extensive, open, public input process and heard a wide range of comments and recommendations that have all been considered.1 More than 150 participants registered for three public workshops held in Detroit, MI (September 24, 2001); Atlanta, GA (September 26, 2001); and Phoenix, AZ (September 28, 2001).
The Onchocerciasis Control Programme in West Africa (OCP) started operations in 1975. Its main objectives were to eliminate human onchocerciasis, as a disease of public-health importance and an obstacle to socio-economic development, from the Programme area. By the end of 2002, the OCP covered 11 West African countries, and had introduced large-scale Mectizan (ivermectin) distribution to about 10 million people, through the communitydirected treatment approach, with treatment coverages ranging from 51%-81%. Research on large-scale Mectizan use illustrated the importance of evidence-based results, the power of multicountry studies, the need for social science in community-driven endeavours and operations research, and the value of empowering communities as allies in disease control. The generous donation of Mectizan by Merck & Co., Inc., has increased general interest in health-related public-private partnerships and generated the momentum for other donations to tackle other diseases. The vector control on which the OCP was initially based successfully interrupted the transmission of the parasite causing human onchocerciasis, Onchocerca volvulus, in many areas. The introduction of Mectizan led to the decline in anterior-segment lesions in the eye and the arrest of posterior-segment lesions. The drug continues to be highly effective in morbidity control, although recently there have been reports of sub-optimal responses in some adult O. volvulus, albeit in a few, very small and isolated foci.
Wagner, Karen S.; Soumbey-Alley, Edoh W.; Boatin, Boakye A.; Basáñez, María-Gloria
Background The parasite Onchocerca volvulus has, until recently, been regarded as the cause of a chronic yet non-fatal condition. Recent analyses, however, have indicated that in addition to blindness, the parasite can also be directly associated with human mortality. Such analyses also suggested that the relationship between microfilarial load and excess mortality might be non-linear. Determining the functional form of such relationship would contribute to quantify the population impact of mass microfilaricidal treatment. Methodology/Principal Findings Data from the Onchocerciasis Control Programme in West Africa (OCP) collected from 1974 through 2001 were used to determine functional relationships between microfilarial load and excess mortality of the human host. The goodness-of-fit of three candidate functional forms (a (log-) linear model and two saturating functions) were explored and a saturating (log-) sigmoid function was deemed to be statistically the best fit. The excess mortality associated with microfilarial load was also found to be greater in younger hosts. The attributable mortality risk due to onchocerciasis was estimated to be 5.9%. Conclusions/Significance Incorporation of this non-linear functional relationship between microfilarial load and excess mortality into mathematical models for the transmission and control of onchocerciasis will have important implications for our understanding of the population biology of O. volvulus, its impact on human populations, the global burden of disease due to onchocerciasis, and the projected benefits of control programmes in both human and economic terms. PMID:22479660
Filipe, João A. N.; Boussinesq, Michel; Renz, Alfons; Collins, Richard C.; Vivas-Martinez, Sarai; Grillet, María-Eugenia; Little, Mark P.; Basáñez, María-Gloria
Here we analyze patterns of human infection with Onchocerca volvulus (the cause of river blindness) in different continents and ecologies. In contrast with some geohelminths and schistosome parasites whose worm burdens typically exhibit a humped pattern with host age, patterns of O. volvulus infection vary markedly with locality. To test the hypothesis that such differences are partly due to heterogeneity in exposure to vector bites, we develop an age- and sex-structured model for intensity of infection, with parasite regulation within humans and vectors. The model is fitted to microfilarial data from savannah villages of northern Cameroon, coffee fincas of central Guatemala, and forest-dwelling communities of southern Venezuela that were recorded before introducing ivermectin treatment. Estimates of transmission and infection loads are compared with entomological and epidemiological field data. Host age- and sex-heterogeneous exposure largely explains locale-specific infection patterns in onchocerciasis (whereas acquired protective immunity has been invoked for other helminth infections). The basic reproductive number,R0, ranges from 5 to 8, which is slightly above estimates for other helminth parasites but well below previously presented values. PMID:16217028
A steering transmission is described comprising: first and second drive units each driven at a substantially constant speed for producing respective first and second unidirectional, continuous outputs infinitely variable between a minimum speed and a maximum speed; a first output planetary gear drivingly connected to a first transmission output; a second output planetary gear set drivingly connected to a second transmission output; an input gear set; means interconnecting the first and second output planetary gear sets; means connecting the first drive unit to the first output planetary gear set; means applying the second drive unit output to the second output planetary gear set; means applying a substantially constant speed input to the input gear set; means for selectively conditioning the input gear set to drive the one output planetary gear set at a speed having a first predetermined fixed ratio to the constant speed input, whereby to operate the transmission in one speed range; and means for selectively applying the first drive unit output to second output planetary gear set, whereby to operate the transmission in another speed range different from the one speed range.
This patent describes an infinitely variable transmission of inline configuration for interconnecting a primer mover with a load for clutch free operation in a range of speed including hydraulic neutral comprising: a. planetary gear train means having a ring gear, planetary gears supported by a planetary gear carrier, and a sun gear, the sun gear being connected mechanically to the load, output shaft means for joining the sun gear to the load; b. variable torque feedback means comprising (i) a variable displacement hydraulic motor whose rotor shaft is in line with the output shaft means and drivingly connected to the prime mover and the planetary gear carrier during the full range of operation of the transmission, and (ii) a fixed displacement hydraulic pump connected hydraulically to the motor, the rotor shaft of the pump being connected mechanically to the ring gear and being axially displaced from the output shaft means; c. means for adjusting the displacement volume within the hydraulic motor for controlling the torque feedback in the transmission to provide infinitely variable coupling between the prime mover and the load over the full range of the transmission including hydraulic neutral; d. a speed reducer between the primer mover and the motor rotor shaft and a speed multiplier between the sun gear and the load; and e. mechanical transmission assembly means between the speed multiplier and the load in line with the motor rotor shaft and the output shaft means for providing selection of drive, reverse, park, and neutral.
Winchester, L. W., Jr.; Gimmestad, G. G.; Jackovich, J. E.
While the propagation of visible and infrared radiation in adverse weather has been studied by many investigators, the effect of rain on contrast transmission or visual range have received little attention. A theoretical and experimental program examining contrast transmission in adverse weather will be described in this paper. Measurements of contrast transmission were made using bar targets consisting of parallel flourescent light bulbs. The bulb spacing is four times the bulb diameter. Data is obtained by photographing the target from a distance of two hundred meters using a camera fitted with an eight-hundred millimeter lens under both clear and obscured conditions. The negatives are then analyzed using a microdensitometer and contrast is defined by C = (I MAX - i MAX + i MIN)-1 where I-MAX and I-MIN are the intensity maximum and minimum, respectively. In addition to contrast measurements, simultaneous measurements of atmospheric transmission, snow particle phase function, and all relevant weather parameters are made. A computer model, based on scattering theory, has been developed for predicting contrast transmission. The model computes zero, first and second order scattering contributions in a three-dimensional atmosphere using phase function computations based on Mie theory.
Bujold, M. P.
The testing of a Mercury Lynx automatic transmission is reported. The transmission was tested in accordance with a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these conditions, the transmission attained maximum efficiencies in the mid-ninety percent range both for drive performance test and coast performance tests. The torque, speed, and efficiency curves are presented, which provide the complete performance characteristics for the Mercury Lynx automatic transmission.
Bujold, M. P.
The small passenger car transmission test was initiated to supply electric vehicle manufacturers with technical information regarding the performance of commercially available transmissions. This transmission was tested in accordance with a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the mid eighty percent range for both drive performance test and coast performance tests.
Samper, Juan C; Tibary, Ahmed
Bacterial, viral and protozoal infections may cause severe reproductive losses. The present paper reviews the risk factors, clinical signs and preventive measures for the most important venereal or potential sexually transmitted diseases in horses. The stallion and use of semen for artificial insemination represent major risk factors for the transmission of bacterial contaminants of the penis, including Streptococcus equi subspecies zooepidemicus, Pseudomonas aeruginosa and Klebsiella pneumoniae, known to cause endometritis and infertility in the mare. The role of the stallion in disease transmission is also due to the non-clinical manifestation of diseases such as contagious equine metritis and equine viral arteritis. Dourine has been eradicated from many countries, but continues to be a problem in other areas of the globe. Strategies for the prevention of introduction and transmission of diseases in breeding operation are discussed.
Mekibib, Berhanu; Ariën, Kevin K
Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo (formerly Zaire) and Sudan, the 2013-2015 western African Ebola virus disease (EVD) outbreak is the largest, both by number of cases and geographical extension, and deadliest, recorded so far in medical history. The source of ebolaviruses for human index case(s) in most outbreaks is presumptively associated with handling of bush meat or contact with fruit bats. Transmission among humans occurs easily when a person comes in contact with contaminated body fluids of patients, but our understanding of other transmission routes is still fragmentary. This review deals with the controversial issue of aerosol transmission of filoviruses.
Yen, F.Y.; Ardayfio, D.D.
This patent describes a system for converting a manual multi-speed transmission to operate as an automatic-manual transmission, the system being disposed within a vehicle, the transmission having a conventional gearshift lever and a clutch pedal. It comprises: a gearshift position selection panel, the panel being located apart from the gearshift lever, the panel enabling a driver to select the desired gear position of the gearshift lever by manipulating the panel without the necessity of the driver handling the gearshift lever; a controller which transforms the gearshift selection of the driver to an output signal, the signal corresponding to the gearshift position selected by the driver; and actuating means for mechanically repositioning the gearshift lever automatically in accordance with the output signal.
Mekibib, Berhanu; Ariën, Kevin K.
Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo (formerly Zaire) and Sudan, the 2013–2015 western African Ebola virus disease (EVD) outbreak is the largest, both by number of cases and geographical extension, and deadliest, recorded so far in medical history. The source of ebolaviruses for human index case(s) in most outbreaks is presumptively associated with handling of bush meat or contact with fruit bats. Transmission among humans occurs easily when a person comes in contact with contaminated body fluids of patients, but our understanding of other transmission routes is still fragmentary. This review deals with the controversial issue of aerosol transmission of filoviruses. PMID:27223296
Hughes, K.R.; Brown, D.R.
The displacement or deferral of conventional AC transmission line installation is a key benefit associated with several technologies being developed with the support of the U.S. Department of Energy`s Office of Energy Management (OEM). Previous benefits assessments conducted within OEM have been based on significantly different assumptions for the average cost per mile of AC transmission line. In response to this uncertainty, an investigation of transmission line capital cost data was initiated. The objective of this study was to develop a database for preparing preliminary estimates of transmission line costs. An extensive search of potential data sources identified databases maintained by the Bonneville Power Administration (BPA) and the Western Area Power Administration (WAPA) as superior sources of transmission line cost data. The BPA and WAPA data were adjusted to a common basis and combined together. The composite database covers voltage levels from 13.8 to 765 W, with cost estimates for a given voltage level varying depending on conductor size, tower material type, tower frame type, and number of circuits. Reported transmission line costs vary significantly, even for a given voltage level. This can usually be explained by variation in the design factors noted above and variation in environmental and land (right-of-way) costs, which are extremely site-specific. Cost estimates prepared from the composite database were compared to cost data collected by the Federal Energy Regulatory Commission (FERC) for investor-owned utilities from across the United States. The comparison was hampered because the only design specifications included with the FERC data were voltage level and line length. Working within this limitation, the FERC data were not found to differ significantly from the composite database. Therefore, the composite database was judged to be a reasonable proxy for estimating national average costs.
Johnson, A M; Laga, M
Recent developments concerning heterosexual transmission of HIV (review of 1988 literature only) suggest improved understanding of the pattern of spread and role of risk behaviors and biological cofactors in its transmission. 3 distinct patterns if HIV infection are known: heterosexual spread in sub-Saharan Africa and the Caribbean, spread primarily among homosexuals and injecting drug users in Europe, North American and much of Latin America and Australia, and both homosexual and heterosexual transmission in Asia, the Pacific, the Middle East and Eastern Europe, where prevalence is low. In Africa an estimated 80% of cases are acquired heterosexually. Important risk factors are number of sex partners, sex with prostitutes, being a prostitute, being a sex partner of an infected person, and having a history of other sexually transmitted diseases. Prevalence rates have risen rapidly in Zaire and Kenya. In Africa, acquisition of HIV is related to sexual activity only. In contrast, in the U.S., heterosexual cases make up only 4% of all cases, and in Europe only 6%. Data on types of sexual transmission of HIV are mounting, in aggregate suggestive of a marked heterogeneity in infectivity and possibly susceptibility between individuals. Among couples where the man is positive, in some places individuals appear to be highly infective, notably those from Kinshasa, Zaire and Haiti, while other series of discordant couples the receptive partner remained seronegative for several years. Transmission from women to men appears to be less efficient than from men to women, as has been observed with other STDs such as gonorrhea. Biological cofactors implicated in enhanced HIV transmission appear to be advanced CDC Stage IV AIDS disease, with low T-helper lymphocyte counts and high antigenemia; concomitant STDS, especially those with genital ulceration; lack of circumcision; oral contraceptive use; practice of anal intercourse; inconsistent or no use of condoms. Theoretical models for
Bill, Robert C.
The Advanced Rotorcraft Transmission (ART) program is an Army-funded, joint Army/NASA program to develop and demonstrate lightweight, quiet, durable drivetrain systems for next generation rotorcraft. ART addresses the drivetrain requirements of two distinct next generation aircraft classes: Future Air Attack Vehicle, a 10,000 to 20,000 lb. aircraft capable of undertaking tactical support and air-to-air missions; and Advanced Cargo Aircraft, a 60,000 to 80,000 lb. aircraft capable of heavy life field support operations. Both tiltrotor and more conventional helicopter configurations are included in the ART program. Specific objectives of ART include reduction of drivetrain weight by 25 percent compared to baseline state-of-the-art drive systems configured and sized for the next generation aircraft, reduction of noise level at the transmission source by 10 dB relative to a suitably sized and configured baseline, and attainment of at least a 5000 hr mean-time-between-removal. The technical approach for achieving the ART goals includes application of the latest available component, material, and lubrication technology to advanced concept drivetrains that utilize new ideas in gear configuration, transmission layout, and airframe/drivetrain integration. To date, candidate drivetrain systems were carried to a conceptual design stage, and tradeoff studies were conducted resulting in selection of an ART transmission configuration for each of the four contractors. The final selection was based on comparative weight, noise, and reliability studies. A description of each of the selected ART designs is included. Preliminary design of each of the four selected ART transmission was completed, as have mission impact studies wherein comparisons of aircraft mission performance and life cycle costs are undertaken for the next generation aircraft with ART and with the baseline transmission.
Burleigh, Scott C.; Krupiarz, Chris
This software is an implementation of the Licklider Transmission Protocol (LTP), a communications protocol intended to support the Bundle Protocol in Delay-Tolerant Network (DTN) operations. LTP is designed to provide retransmission-based reliability over links characterized by extremely long message round-trip times and/or frequent interruptions in connectivity. Communication in interplanetary space is the most prominent example of this sort of environment, and LTP is principally aimed at supporting long-haul reliable transmission over deep-space RF links. Like any reliable transport service employing ARQ (Automatic Repeat re-Quests), LTP is stateful. In order to assure the reception of a block of data it has sent, LTP must retain for possible retransmission all portions of that block which might not have been received yet. In order to do so, it must keep track of which portions of the block are known to have been received so far, and which are not, together with any additional information needed for purposes of retransmitting part, or all, of the block. Long round-trip times mean substantial delay between the transmission of a block of data and the reception of an acknowledgement from the block s destination, signaling arrival of the block. If LTP postponed transmission of additional blocks of data until it received acknowledgement of the arrival of all prior blocks, valuable opportunities to use what little deep space transmission bandwidth is available would be forever lost. For this reason, LTP is based in part on a notion of massive state retention. Any number of requested transmission conversations (sessions) may be concurrently in flight at various displacements along the link between two LTP engines, and the LTP engines must necessarily retain transmission status and retransmission resources for all of them. Moreover, if any of the data of a given block are lost en route, it will be necessary to retain the state of that transmission during an additional
Ikezi, Hiroyuki; Lin-Liu, Yuh-Ren; DeGrassie, John S.
A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other.
Ikezi, H.; Lin-Liu, Y.R.; DeGrassie, J.S.
A printed circuit dispersive transmission line structure is disclosed comprising an insulator, a ground plane formed on one surface of the insulator, a first transmission line formed on a second surface of the insulator, and a second transmission line also formed on the second surface of the insulator and of longer length than the first transmission line and periodically intersecting the first transmission line. In a preferred embodiment, the transmission line structure exhibits highly dispersive characteristics by designing the length of one of the transmission line between two adjacent periodic intersections to be longer than the other. 5 figures.
Four drivers sustained severe injuries when run down by their own automatic cars while adjusting the carburettor or throttle linkages. The transmission had been left in the “Drive” position and the engine was idling. This accident is easily avoidable. PMID:4695693
Dong, Jun; Zhang, Jing
Though China is well along in restructuring its power markets, it still has some way to travel before economic considerations receive adequate weight in transmission planning decisions. Adoption of more sophisticated tools such as multi-agent modeling will help China continue in its progress in achieving this. (author)
Lucy Green's (2008) "Music, Informal Learning, and the School: A New Classroom Pedagogy" gives rise to an interesting corollary. Does the manner of music's transmission inform one's understanding of a musical category? While categories of music can be difficult to define according to strict musical characteristics, a better understanding of…
A autonomous borehole data transmission apparatus is described for transmitting measurement data from measuring instruments at the downhole end of a drill string by generating pressure pulses utilizing a transducer longitudinally responsive to magnetic field pulses caused by electrical pulses corresponding to the measured downhole parameters. 4 figs.
transmettre les cartes tactiques et les compte rendu de situation. La presente note technique expose les 6lements nec~ssaires A la transmission de t~l6copies...Group MI machines introduced digital scanning techniques in which the single photoelectric cell was replaced with a Charged Coupled Device (CCD) array
Itoh, H.; Okada, M.
This patent describes a continuously variable transmission for transmitting a torque from an engine to a final reduction gear, comprising: an input shaft connected with the engine at one end thereof; a continuously variable transmission means having a driving pulley with a fixed member and a movable member, the movable member being actuated by an hydraulic cylinder to form a V-shaped opening between the fixed member and movable member, a driven pulley with another fixed member and another movable member. The other movable member is similarly actuated by another hydraulic cylinder to form another V-shaped opening between the other fixed member and the other movable member, and a belt member spanning the pulleys provides for a continuously variable transmission ratio; a planetary gear unit including a sun gear, a plurality of pinion gears which mesh with the sun gear and are connected with the driven pulley and a ring gear which meshes with the plurality of pinion gears; and a rotation transmitting means for transmitting rotation of the input shaft to the planetary gear unit. The rotation transmitting means is provided between the input shaft and the planetary gear unit and includes a shaft connected with the sun gear of the planetary gear unit and a first gear connected with the input shaft. The first gear is located between the engine and the continuously variable transmission means.
Conway, Edmund J.
An overview of previous studies related to laser power transmission is presented. Particular attention is given to the use of solar pumped lasers for space power applications. Three general laser mechanisms are addressed: photodissociation lasing driven by sunlight, photoexcitation lasing driven directly by sunlight, and photoexcitation lasing driven by thermal radiation.
Parsons, W. E.; Richards, L. O.
Monitor improves complex network reliability in computer data links and command transmission lines. System evaluates circuit performance against preselected criteria, identifies and stores data indicating out-of-tolerance conditions, conducts closed loop testing, and provides for operation under command of digital computer that determines restoration priorities.
Kotlyar, Oleg M.
A autonomous borehole data transmission apparatus for transmitting measurement data from measuring instruments at the downhole end of a drill string by generating pressure pulses utilizing a transducer longitudinally responsive to magnetic field pulses caused by electrical pulses corresponding to the measured downhole parameters.
Lucy Green's (2008) "Music, Informal Learning, and the School: A New Classroom Pedagogy" gives rise to an interesting corollary. Does the manner of music's transmission inform one's understanding of a musical category? While categories of music can be difficult to define according to strict musical characteristics, a better understanding of…
The fundamental problem of the 21st century is that in the modern civilization "the transmission of values is not stable." There is nothing, except for the natural sense of justice and some legal traditions, which would exercise selective power on social behavior. At a critical time in 1949 Albert Szent-Györgyi drew the attention to the…
Hadden, G. B.; Dyba, G. J.; Ragen, M. A.; Kleckner, R. J.; Sheynin, L.
PLANETSYS simulates thermomechanical performance of multistage planetary performance of multistage planetary power transmission. Two versions of code developed, SKF version and NASA version. Major function of program: compute performance characteristics of planet bearing for any of six kinematic inversions. PLANETSYS solves heat-balance equations for either steadystate or transient thermal conditions, and produces temperature maps for mechanical system.
A borehole data transmission apparatus is described whereby a centrifugal pump impeller(s) is used to provide a turbine stage having substantial pressure characteristics in response to changing rotational speed of a shaft for the pressure pulsing of data from the borehole through the drilling mud to the surface of the earth.
Kotlyar, Oleg M.
A borehole data transmission apparatus whereby a centrifugal pump impeller(s) is used to provide a turbine stage having substantial pressure characteristics in response to changing rotational speed of a shaft for the pressure pulsing of data from the borehole through the drilling mud to the surface of the earth.
This work provides an overview of current knowledge of AIDS transmission and attitudes toward prevention in France. Most HIV infections are transmitted sexually. AIDS became established in the homosexual community in California because of mutual infection by members of the community with large numbers of sexual partners. The possibility of heterosexual transmission was not immediately recognized by all observers. Different publications estimate the risk of seroconversion after 1 episode of heterosexual coitus at between 1:100 and 1:1000/ Heterosexual transmission is bidirectional, but male-female transmission appears easier. Factors favoring transmission identified in AFrican studies include multiple partners, sexually transmitted diseases, anal penetration, relations during menstruation, and age. No epidemiologic study has concluded that kissing with mutual salivary contact can lead to infection, but oral-genital sex may pose a risk. As of October 1991, 966 cases of posttransfusion AIDS had been diagnosed in France, and an estimated 6000-9000 HIV seropositive persons were infected through transfusion. 239 AIDS cases were reported in hemophiliacs and others with coagulation disorders. 1200 of 3500 French hemophiliacs receiving transfusions before 1985 are seropositive. The risk of developing AIDS from a transfusions in France is currently estimated at 1/250,000. HIV transmission among drug addicts results from sharing contaminated needles and syringes. The risk of infection for health workers treating those who are HIV positive appears small; only about 30 documented cases have been reported worldwide, including 3 of 10,000 cases in France. The risk that an infected mother will have a seropositive baby is estimated at 25% in France. The number of seropositive women in the world is estimated at over 3 million, with 80% in sub-Saharan Africa. As of October 1991, 16,0000-36,000 seropositive women and 1500 seropositive children were estimated to live in France
Young, Ryan M.; Burkett-Cadena, Nathan D.; McGaha, Tommy W.; Rodriguez-Perez, Mario A.; Toé, Laurent D.; Adeleke, Monsuru A.; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R.; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L.; Salinas-Carmona, Mario C.; Baker, Bill; Unnasch, Thomas R.; Cupp, Eddie W.
Background Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Methodology/Principal Findings Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. Conclusions/Significance The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa. PMID:25569240
Tamarozzi, Francesca; Tendongfor, Nicholas; Enyong, Peter A; Esum, Mathias; Faragher, Brian; Wanji, Samuel; Taylor, Mark J
Anti-Wolbachia treatment with doxycycline is effective in sterilising and killing adult Onchocerca volvulus nematodes, proving superior to ivermectin and of great potential as an alternative approach for the treatment and control of onchocerciasis, particularly in areas of Loa loa co-endemicity. Nevertheless, the length of the required treatment poses potential logistical problems and risk of poor compliance, raising a barrier to the use of doxycycline in Mass Drug Administration (MDA) strategies. In 2007 and 2008 a feasibility trial of community-directed treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The current study evaluated the effectiveness of this community-directed delivery of doxycycline four years after delivery. Infection with O. volvulus was evaluated by skin biopsy and nodule palpation. Of the 507 subjects recruited, 375 had completed the treatment with doxycycline followed by one or two rounds of annual ivermectin MDA and 132 received one or two rounds of annual ivermectin MDA alone. Statistically significant lower microfilarial prevalence (17.0% [doxycycline plus ivermectin group], 27.0% [ivermectin only group], p = 0.014) and load (p = 0.012) were found in people that had received doxycycline followed by ivermectin compared to those who received ivermectin only. This study demonstrates the long-term effectiveness of doxycycline treatment delivered with a community-directed strategy even when evaluated four years after delivery in an area of ongoing transmission. This finding shows that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its implementation to compliment existing control strategies
Background Anti-Wolbachia treatment with doxycycline is effective in sterilising and killing adult Onchocerca volvulus nematodes, proving superior to ivermectin and of great potential as an alternative approach for the treatment and control of onchocerciasis, particularly in areas of Loa loa co-endemicity. Nevertheless, the length of the required treatment poses potential logistical problems and risk of poor compliance, raising a barrier to the use of doxycycline in Mass Drug Administration (MDA) strategies. In 2007 and 2008 a feasibility trial of community-directed treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The current study evaluated the effectiveness of this community-directed delivery of doxycycline four years after delivery. Findings Infection with O. volvulus was evaluated by skin biopsy and nodule palpation. Of the 507 subjects recruited, 375 had completed the treatment with doxycycline followed by one or two rounds of annual ivermectin MDA and 132 received one or two rounds of annual ivermectin MDA alone. Statistically significant lower microfilarial prevalence (17.0% [doxycycline plus ivermectin group], 27.0% [ivermectin only group], p = 0.014) and load (p = 0.012) were found in people that had received doxycycline followed by ivermectin compared to those who received ivermectin only. Conclusions This study demonstrates the long-term effectiveness of doxycycline treatment delivered with a community-directed strategy even when evaluated four years after delivery in an area of ongoing transmission. This finding shows that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its implementation to
Akuffo, H; Maasho, K; Lavebratt, C; Engström, K; Britton, S
Onchocerciasis is associated with blindness and gross skin changes, believed to be a consequence of the immune response to antigens released from the offspring of the female worm of Onchocerca volvulus, the microfilariae (mf). An effective microfilaricidal drug is now available which quickly reduces the mf burden without affecting the adult worm. There exist foci in onchocerciasis endemic areas where some of the patients have many mf in their skin but relatively few clinical symptoms. This state of hyposensitivity is believed to be due to immunosuppression. The aim of this study was to address the question of the basis of, and the effect of ivermectin treatment on this immunosuppression. Female adult worms of O. volvulus were used as whole or fractionated antigens to stimulate peripheral blood mononuclear cells. Microfilariae are found in the reproduction tract of the female worms, and thus an antigen preparation of the female adult O. volvulus contains both exclusive adult antigens as well as antigens from microfilariae. Cells were obtained from onchocerciasis patients, individuals of similar socio-economic status living in the same Ghanaian village, but who showed no parasitological or clinical evidence of onchocerciasis (exposed endemic controls), healthy Ghanaians living in areas where transmission of onchocerciasis does not seem to occur (non-exposed endemic controls) and unexposed healthy Swedish donors. As a group, cells from onchocerciasis patients proliferated to a lesser degree than cells from the exposed endemic control and the non-exposed endemic control groups to the whole worm antigen, whereas the phytohaemagglutinin (PHA) response was strongest in the patients. Proliferative responses of above 1000 ct/min to fractions of the worm extract were only evident in the cells from a few individuals in each of the various groups. However, 28 days following ivermectin treatment, cells from all onchocerciasis patients were able to mount significantly enhanced
Coy, John J.; Bill, Robert C.
The NASA Lewis Research Center and the U.S. Army Aviation Systems Command share an interest in advancing the technology for helicopter propulsion systems. In particular, this paper presents highlights from that portion of the program in drive train technology and the related mechanical components. The major goals of the program are to increase the life, reliability, and maintainability; reduce the weight, noise, and vibration; and maintain the relatively high mechanical efficiency of the gear train. The current activity emphasizes noise reduction technology and analytical code development followed by experimental verification. Selected significant advances in technology for transmissions are reviewed, including advanced configurations and new analytical tools. Finally, the plan for future transmission research is presented.
A task order was written by the High Resolution, High Frame Rate Video Technology (HHVT) project engineers to investigate data compression techniques that could be applied to the HHVT system, and both existing and planned downlink/uplink capabilities of the Space Shuttle and Space Station Freedom. The following tasks were included: (1) Investigate signal channel availability and determine both the maximum possible data rate and the average data rate; (2) Identify time blocks for HHVT video transmission assuming time sharing and interruptions in the communication links; (3) Determine the bit error rates to be expected; and (4) Define the transmit and receive interfaces. A summary chart of the data transmission capabilities for Tracking and Data Relay Satellite System (TDRSS), the Space Shuttle, Space Station Freedom, Spacelab, and USLab are also presented.
Tatara, Y.; Okawa, S.; Matsui, H.; Nakawaki, Y.
A continuously variable transmission means is described for motor vehicles including a driving pulley with a fixed member and a movable member. The movable member is actuated by a hydraulic cylinder to form a V-shaped opening, a driven pulley with another fixed member and another movable member. Another movable member is actuated by another hydraulic cylinder to form another V-shaped opening, and a flexible endless member spans the driving and driven pulleys. The continuously variable transmission means comprises such items as: a first output shaft; a first gear; a second gear; a reverse gear; a second output shaft; a third gear; a jaw clutch mounted; a first one-way clutch; a fourth gear; a hydraulic clutch means; and a second one-way clutch.
Hall, David R.; Hall, Jr., H. Tracy; Pixton, David S.; Bradford, Kline; Fox, Joe
A transmission line assembly for transmitting information along a downhole tool comprising a pin end, a box end, and a central bore traveling between the pin end and the box end, is disclosed in one embodiment of the invention as including a protective conduit. A transmission line is routed through the protective conduit. The protective conduit is routed through the central bore and the ends of the protective conduit are routed through channels formed in the pin end and box end of the downhole tool. The protective conduit is elastically forced into a spiral or other non-linear path along the interior surface of the central bore by compressing the protective conduit to a length within the downhole tool shorter than the protective conduit.
This patent describes a transmission. It includes a transmission housing; a first shaft rotatably mounted in the housing and having a third gear fixed for rotation therewith and fourth and fifth gears rotatably mounted thereto, the fourth and fifth gears meshing with the first and second gears, respectively; first and second clutch means for selectively fixing the fourth and fifth gears, respectively, for rotation with the second shaft; a third shaft rotatably mounted in the housing and having a sixth gear fixed for rotation therewith and seventh and eighth gears rotatably mounted thereto, the seventh and eighth gears meshing with the first and second gears, respectively; third and fourth clutch means for selectively fixing the seventh and eighth gears respectively, for rotation with the third shaft.
Bill, Robert C.
The U.S. Army/NASA Advanced Rotorcraft Transmission (ART) program is charged with developing and demonstrating a light, quiet, and durable drivetrain for next-generation rotorcraft in two classes: a 10,000-20,000 Future Attack Air Vehicle capable of both tactical ground support and air-to-air missions, and a 60,000-80,000 lb Advanced Cargo Aircraft, for heavy-lift field-support operations. Specific ART objectives encompass a 25-percent reduction in drivetrain weight, a 10-dB noise level reduction at the transmission source, and the achievement of a 5000-hr MTBF. Four candidate drivetrain systems have been carried to a conceptual design stage, together with projections of their mission performance and life-cycle costs.
Marsh, M. R.
This invention provides apparatus for use in a drive transmission system comprising a pump adapted to perform work on a medium and means repetitively and automatically to unload the pump. When connected with a flywheel driven by a prime mover an embodiment alternately performs work and then is unloaded to permit acceleration of the flywheel. In use in a driven transmission system there is provided a flywheel driven by an engine, a pump driven by the flywheel, powered by the pump, and means repetitively to unload the pump permitting the engine to accelerate the flywheel and compensation means to power the hydraulic motor while the pump is unloaded. The pump is preferably a rotary positive displacement pump having relief galleries eliminating the seal between pumping elements driving each cycle.
Bujold, M. P.
A 1978 Chevrolet LUV manual transmission tested per the applicable portions of a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the upper ninety percent range for both drive performance tests and coast performance tests. The major results of this test (torque, speed, and efficiency curves) are presented. Graphs map the complete performance characteristics for the Chevrolet LUV transmission.
Bujold, M. P.
A 1979 Ford C4 automatic transmission was tested per a passenger car automatic transmission test code (SAE J651b) which required drive performance, coast performance, and no load test conditions. Under these test conditions, the transmission attained maximum efficiencies in the mid-eighty percent range for both drive performance tests and coast performance tests. The major results of this test (torque, speed, and efficiency curves) are presented. Graphs map the complete performance characteristics for the Ford C4 transmission.
Mudry, Andrew; Poulin, Brad
Modern tactical communications systems are becoming increasingly compatible with existing civilian systems. This compatibility allows the military to take advantage of the equipment available commercially and spare the expense of developing costly customized systems. It also increases the interoperability of various communications systems employed by allies involved in multinational operations. Finally, the compatibility allows the military to augment its telecommunications assets with existing commercial equipment and networks during times of conflict. One civilian communication standard that has recently been adopted by the military for tactical communications is that of facsimile. Facsimile is now commonly used on the battlefield for the transmission of tactical maps and situation reports. This technical note examines the requirements for facsimile transmission. An overview of the various facsimile standards are given, followed by a detailed description of the most commonly used standard; CCITT Group III. The Group III specifications are a composite of various CCITT modulation and encoding standards. These consist of V.21, V.27ter, and V.29 modulations, as well as T.4 image encoding standards, and T.30 signalling specifications. Each of these standards is described in the context of facsimile transmissions. A complete description of the handshaking which occurs between the facsimile transmitter and receiver is given.
Iwanaga, K.; Yamaguchi, T.
A change speed transmission is described comprising: a stationary part; an input member; an output member; first and second planetary gear sets; clutch and brake means for selectively controlling the first and second planetary gear sets to provide a plurality of forward speed rations and a reverse speed ratio between the input and output member; the clutch and brake means including a first clutch, a first one-way clutch, and a second one-way clutch which, when the first clutch is engaged, provide a path of transmission of reaction to the stationary part thereby establishing a path of transmission of torque through at least a part of the first and second planetary gear sets to achieve a predetermined one speed ratio of the forward speed ratios; the clutch and brake means including also a brake and a second slutch which, when both of the brake and the second clutch are engaged, hinder the action of the second one-way clutch and that of the first one-way clutch, respectively, thereby providing engine braking during running with the predetermined one speed ratio; the first clutch including means forming a drum-shaped member disposed radially outwardly of and receiving at least one of the first and second planetary gear sets, and an actuating piston of the first clutch; and the second clutch including an actuating piston slidably disposed within the actuating piston of the first clutch.
Explored the effect of "transmission belts" (conditions favorable to cultural transmission within particular socioeconomic and cultural contexts) on the similarity of values between Turkish fathers and their sons. Data from father-son dyads in Germany indicated that transmission of values related to the collective value categories of…
In an engine driven vehicle having an engine extending transversely with respect to the vehicle at one end thereof, a pair of wheels at the same end of the vehicle, and automatic drive transmission means connecting the engine to the wheels, the automatic drive transmission means includes a housing attached to the vehicle. The housing has a torque converter section, a speed change section adjacent the torque converter section, and a differential and transfer section; the engine having a crankshaft, a torque converter in the torque converter section of the housing rotatable on the same axis as the crankshaft and adapted to be driven by the engine crankshaft, the torque converter drivingly connected to one outer end of a transmission input shaft, the input shaft having its other inner end located about midway through the speed change section, a speed change section output shaft mounted coaxial with the input shaft in the speed change section with its inner end adjacent the input shaft inner end and its outer free end extending beyond the speed change section, an output gear having peripheral teeth formed thereon, the output gear connected on the output shaft outer free end such that the output shaft and the output gear rotate on the input shaft axis, a transfer shaft having a transfer gear engaged with the output gear, the output shaft having a bore extending axially therethrough, the improvement wherein; a speed sensor shaft having a speed sensor wheel with peripheral teeth formed thereon fixed on the free outer end thereof, means journally supporting the speed shaft concentrically within the output shaft bore such that the speed wheel is axially spaced closely adjacent to the output gear.
Lewicki, David G. (Technical Monitor); Samuel, Paul D.; Conroy, Joseph K.; Pines, Darryll J.
This report presents a methodology for detecting and diagnosing gear faults in the planetary stage of a helicopter transmission. This diagnostic technique is based on the constrained adaptive lifting algorithm. The lifting scheme, developed by Wim Sweldens of Bell Labs, is a time domain, prediction-error realization of the wavelet transform that allows for greater flexibility in the construction of wavelet bases. Classic lifting analyzes a given signal using wavelets derived from a single fundamental basis function. A number of researchers have proposed techniques for adding adaptivity to the lifting scheme, allowing the transform to choose from a set of fundamental bases the basis that best fits the signal. This characteristic is desirable for gear diagnostics as it allows the technique to tailor itself to a specific transmission by selecting a set of wavelets that best represent vibration signals obtained while the gearbox is operating under healthy-state conditions. However, constraints on certain basis characteristics are necessary to enhance the detection of local wave-form changes caused by certain types of gear damage. The proposed methodology analyzes individual tooth-mesh waveforms from a healthy-state gearbox vibration signal that was generated using the vibration separation (synchronous signal-averaging) algorithm. Each waveform is separated into analysis domains using zeros of its slope and curvature. The bases selected in each analysis domain are chosen to minimize the prediction error, and constrained to have the same-sign local slope and curvature as the original signal. The resulting set of bases is used to analyze future-state vibration signals and the lifting prediction error is inspected. The constraints allow the transform to effectively adapt to global amplitude changes, yielding small prediction errors. However, local wave-form changes associated with certain types of gear damage are poorly adapted, causing a significant change in the
Retrieval of image data from a centralized database may be subject to bandwidth limitations, whether due to a low-bandwidth communications link or to contention from simultaneous accesses over a high-bandwidth link. Progressive transmission can alleviate this problem by encoding image data so that any prefix of the data stream approximates the complete image at a coarse level of resolution. The longer the prefix, the finer the resolution. In many cases, as little at 1 percent of the image data may be sufficient to decide whether to discard the image, to permit the retrieval to continue, or to restrict retrieval to a subsection of the image. Our approach treats resolution not as a fixed attribute of the image, but rather as a resource which may be allocated to portions of the image at the direction of a user-specified priority function. The default priority function minimizes error by allocating more resolution to regions of high variance. The user may also point to regions of interest requesting priority transmission. More advanced target recognition strategies may be incorporated at the user's discretion. Multispectral imagery is supported. The user engineering implications are profounded. There is immediate response to a query that might otherwise take minutes to complete. The data is transmitted in small increments so that no single user dominates the communications bandwidth. The user-directed improvement means that bandwidth is focused on interesting information. The user may continue working with the first coarse approximations while further image data is still arriving. The algorithm has been implemented in C on Sun, Silicon Graphics, and NeXT workstations, and in Lisp on a Symbolics. Transmission speeds reach as high as 60,000 baud using a Sparc or 68040 processor when storing data to memory; somewhat less if also updating a graphical display. The memory requirements are roughly five bytes per image pixel. Both computational and memory costs may be reduced
Winey, Mark; Meehl, Janet B.; O'Toole, Eileen T.; Giddings, Thomas H.
Researchers have used transmission electron microscopy (TEM) to make contributions to cell biology for well over 50 years, and TEM continues to be an important technology in our field. We briefly present for the neophyte the components of a TEM-based study, beginning with sample preparation through imaging of the samples. We point out the limitations of TEM and issues to be considered during experimental design. Advanced electron microscopy techniques are listed as well. Finally, we point potential new users of TEM to resources to help launch their project. PMID:24482357
Korban, J.F.; Korban, N.F.
This patent describes an infinitely variable speed transmission. It comprises: an input shaft; a drive plate having a plurality of radial slots therein, the drive plate fixed to the input shaft; an output shaft parallel to the input shaft; a bevel gear fixed to the output shaft; a plurality if independently rotatable sprocketed pinions freely rotatable about and meshing with the bevel gear. The pinions also engaging the drive plate by projections from the pinions slidably mounted in the radial slots in the drive plate; and clutching means for selectively locking and unlocking the pinions in sequence to effect driving of the bevel gear.
This report describes measurements to determine transmission losses in S-band (2.60-3.95 GHz) waveguide sections due to misalignment of the sections relative to each other. The experiments were performed in support of the Hydrostar program to determine the feasibility of using deployable waveguide sections in a large space radiometer. The waveguide sections would possibly be hinged and folded for launch, then deployed in space to form long sections of waveguide. Since very low losses are required for radiometer applications, the effects of potential misalignment after deployment of the waveguide sections may be significant. These measurements were performed in the Electromagnetic Properties Measurement Laboratory in the Electromagnetics Research Branch.
Cakoni, Fioralba; Colton, David; Rezac, Jacob D.
In this paper we study the distribution of transmission eigenvalues in the complex plane for obstacles whose contrast is small in magnitude. We use a first order approximation of the refractive index to derive and study an approximate interior transmission problem. In the case of spherically stratified media, we prove existence and discreteness of transmission eigenvalues and derive a condition under which the complex part of transmission eigenvalues cannot lie in a strip parallel to the real axis. For obstacles with general shape, we demonstrate that if transmission eigenvalues exist then they form a discrete set.
Tsang, Tim K; Lau, Lincoln L H; Cauchemez, Simon; Cowling, Benjamin J
Human influenza viruses cause regular epidemics and occasional pandemics with a substantial public health burden. Household transmission studies have provided valuable information on the dynamics of influenza transmission. We reviewed published studies and found that once one household member is infected with influenza, the risk of infection in a household contact can be up to 38%, and the delay between onset in index and secondary cases is around 3 days. Younger age was associated with higher susceptibility. In the future, household transmission studies will provide information on transmission dynamics, including the correlation of virus shedding and symptoms with transmission, and the correlation of new measures of immunity with protection against infection.
Toso M, Alberto; Vial U, Felipe; Galanti, Norbel
The traditional transmission pathways of Chagas' disease are vectorial, transfusional, transplacental and organ transplantation. However, oral transmission is gaining importance. The first evidence of oral transmission was reported in Brazil in 1965. Nowadays the oral route is the transmission mode in 50% of cases in the Amazon river zone. Oral infection is produced by the ingestion of infected triatomine bugs or their feces, undercooked meat from infested host animals and food contaminated with urine or anal secretion of infected marsupials. Therefore travelers to those zones should be advised about care to be taken with ingested food. In Chile, this new mode of transmission should be considered in public health policies.
Lawrie, Robert E.; Reed, Jr., Richard G.; Rausen, David J.
A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.
Zehner, Richard E.
Citation Information: Originator: Earth Science &Observation Center (ESOC), CIRES, University of Colorado at Boulder Originator: Xcel Energy Publication Date: 2012 Title: Colorado XcelEnergy NonXcel Transmission Network Edition: First Publication Information: Publication Place: Earth Science & Observation Center, Cooperative Institute for Research in Environmental Science (CIRES), University of Colorado, Boulder Publisher: Earth Science &Observation Center (ESOC), CIRES, University of Colorado at Boulder Description: This layer contains transmission network of Colorado Spatial Domain: Extent: Top: 4540689.017558 m Left: 160606.141934 m Right: 758715.946645 m Bottom: 4098910.893397m Contact Information: Contact Organization: Earth Science &Observation Center (ESOC), CIRES, University of Colorado at Boulder Contact Person: Khalid Hussein Address: CIRES, Ekeley Building Earth Science & Observation Center (ESOC) 216 UCB City: Boulder State: CO Postal Code: 80309-0216 Country: USA Contact Telephone: 303-492-6782 Spatial Reference Information: Coordinate System: Universal Transverse Mercator (UTM) WGS’1984 Zone 13N False Easting: 500000.00000000 False Northing: 0.00000000 Central Meridian: -105.00000000 Scale Factor: 0.99960000 Latitude of Origin: 0.00000000 Linear Unit: Meter Datum: World Geodetic System ’1984 (WGS ’1984) Prime Meridian: Greenwich Angular Unit: Degree Digital Form: Format Name: Shapefile
Kimberlin, R H
Scrapie in sheep and goats is the best known of the transmissible encephalopathies of animals. The combination of maternal transmission of infection and long incubation periods effectively maintains the infection in flocks. A single sheep gene (Sip) controls both experimental and natural scrapie and the discovery of allelic markers could enable the use of sire selection in the control of the natural disease. Studies of experimental rodent scrapie show that neuroinvasion occurs by spread of infection from visceral lymphoreticular tissues along nerve fibers to mid-thoracic cord. The slowness of scrapie is due to restrictions on replication and cell-to-cell spread of infection affecting neuroinvasion and subsequent neuropathogenesis. Probably both stages in mice are controlled by Sinc gene, the murine equivalent of Sip. The glycoprotein PrP may be the normal product of Sinc gene. Posttranslationally modified PrP forms the disease specific "scrapie associated fibrils" and may also be a constituent of the infectious agent. Scrapie-like diseases have been reported in mink and several species of ruminants including cattle. All of them may be caused by the recycling of scrapie infected sheep material in animal feed. The human health implications are discussed. PMID:2407328
This patent describes a mechanism for selecting the gear of an automatic transmission in a vehicle. The mechanism consists of: a pressure source; a gear selection valve having an inlet means for receiving fluid from the pressure source, first outlet ports, and second outlet ports; a manual override means for opening and blocking communication between the pressure source and the first ports and for simultaneously opening and blocking communication between the pressure source and the second outlet ports; a port selector means within the valve for controlling flow through the second ports, the port selector means being movable to a plurality of positions, each position permitting a selected second outlet port to open; a selector control mans for moving the port selector means from one position to another, the selector control means including a planetary gear set connected by an input shaft to the transmission and connected to a vehicle load by an output shaft, the planetary gear set having a ring gear whose angular position is a function of reaction torque imposed by the load on the output shaft, the selector control means further including an arm assembly connected between the ring gear and the port selector means so that the position of the port selector means is a function of the reaction torque on the output shaft.
A multi-speed transmission is described for transferring power between a first shaft and a second shaft, the transmission comprising: a compound planetary assembly including a sun gear, a ring gear concentric with the sun gear, a reaction gear concentric with the ring gear, a planetary gear carrier rotatably supporting first and second sets of planet gears, the first planet gear set intermeshing with the ring gear. The sun gear and the second planet gear set intermesh with the first planet gear set and the reaction gear, means for selectively coupling the first shaft with the sun gear and the reaction gear, and means for selectively preventing rotation of the ring gear, and reaction gear and the planetary carrier; a simple planetary assembly comprising a sun gear component concentric with the sun gear of the compound planetary assembly, a ring gear component concentric with both of the sun gears, and a planetary gear carrier component rotatably supporting a set of planet gears, the planet gear set meshing with the sun gear and the ring gear of the simple planetary.
Iwase, Y.; Morisawa, K.
An automatic transmission is described comprising: an output shaft of the transmission including a stepped portion; a parking gear spline-connected with the output shaft on a first side of the stepped portion; a plurality of governor values mounted on a rear side of the parking gear and radially disposed around the output shaft on the first side of the stepped portion; a speed meter drive gear spline-connected with the output shaft on a second side of the stepped portion and on a rear side of the governor valves; and an annular spacer fitted on the output shaft on the second side of the stepped portion between the governor valves and the speed meter drive gear to abut on each of the governor valves and the speed meter drive gear. The annular member is constructed separately from the speed meter drive gear and has an outer diameter larger than an outer diameter of the speed meter drive gear thereby resulting in a contact area between the annular space and the speed meter drive gear which is smaller than a contact area between the annular spacer and the rear side of the governor valves; the drive gear being axially secured relative to the output shaft by a bearing thereby enabling a fixed axial positioning of the annular spacer on the output shaft.
Hagen, Wilfred R
EPR spectroscopy employs a resonator operating at a single microwave frequency and phase-sensitive detection using modulation of the magnetic field. The X-band spectrometer is the general standard with a frequency in the 9-10 GHz range. Most (bio)molecular EPR spectra are determined by a combination of the frequency-dependent electronic Zeeman interaction and a number of frequency-independent interactions, notably, electron spin - nuclear spin interactions and electron spin - electron spin interactions, and unambiguous analysis requires data collection at different frequencies. Extant and long-standing practice is to use a different spectrometer for each frequency. We explore the alternative of replacing the narrow-band source plus single-mode resonator with a continuously tunable microwave source plus a non-resonant coaxial transmission cell in an unmodulated external field. Our source is an arbitrary wave digital signal generator producing an amplitude-modulated sinusoidal microwave in combination with a broadband amplifier for 0.8-2.7 GHz. Theory is developed for coaxial transmission with EPR detection as a function of cell dimensions and materials. We explore examples of a doublet system, a high-spin system, and an integer-spin system. Long, straigth, helical, and helico-toroidal cells are developed and tested with dilute aqueous solutions of spin label hydroxy-tempo. A detection limit of circa 5 µM HO-tempo in water at 800 MHz is obtained for the present setup, and possibilities for future improvement are discussed.
This patent describes a transmission shift control assembly mounted on a steering column having a longitudinal axis comprising: bracket means secured to the steering column; transmission shift cable means having a portion secured to the bracket means and a portion linearly movable relative to the secured portion; mounting means on the bracket cable drive arm means having an axis and being rotatably mounted on the rotary axis on the mounting means oblique to the longitudinal axis and including a cable connecting portion secured to the movable portion of the cable means and lever mounting means adjacent the mounting means; operator control means including lever means, pin means for pivotally mounting the lever means on the lever mounting means on an axis substantially perpendicular to the rotary axis and positioning arm means formed on the lever means and extending from the pin means; and detent gate means disposed on the bracket means in position to abut the positioning arm means for limiting the extent of pivotal movement of the lever means.
Filser, Joerg; Reibetanz, Joachim; Krajinovic, Katica; Germer, Christoph-Thomas; Dietz, Ulrich Andreas; Seyfried, Florian
Introduction Transabdominal preperitoneal endoscopic hernia repair (TAPP) is part of primary surgical health care. While both, the reported recurrence rate and procedure specific morbidity are consistently low, rare serious complications occur. Presentiation of case A 36-year-old male patient developed bowel obstruction three days after both-sided TAPP for inguinal hernia repair. A computer tomography scan of the abdomen revealed a small bowel volvulus in the right lower quadrant of the abdomen requiring urgent revisional surgery. Intraoperatively, the small bowel and its mesenterial vessels were found to be twisted around a 5 cm long V-Loc™ barbed absorbable suturing wire. After successful laparoscopic adhesiolysis, removal of the wire and detorquing of the bowel conglomerate, resection of small intestine was not necessary. The patient's further postoperative recovery was uneventful. Discussion Due to the barbed configuration of the V-Loc™ wire, a gapless continuous suturing of the peritoneum without laparoscopic knotting is easily and fast to accomplish. In this case the recommendation of the manufacturer to shorten the wire was not strictly followed and neither had the suture stump been extraperitonealized in order to avoid such rare complications. Conclusion Surgeons need to be aware of relevant “tricks and traps” of routinely performed procedures and have to know all tools and material they use very well. This case may therefore increase our attention when it comes to little things which actually do matter. PMID:25704567
Bujold, M P
The small passenger car transmission test was initiated to supply electric vehicle manufacturers with technical information regarding the performance of commercially available transmissions. This information would enable EV manufacturers to design a more energy efficient vehicle. With this information the manufacturers would be able to estimate vehicle driving range as well as speed and torque requirements for specific road load performance characteristics. This report covers the 1981 Mercury Lynx ATX transaxle. This transmission was tested per a passenger car automatic transmission test code (SAE J65lb) which required drive performance, coast performance, and no load test conditions. Under these test conditions the transmission attained maximum efficiencies in the 93% range for drive performance tests. The major results of this test are the torque, speed and efficiency curves which are located in the data section of this report. These graphs map performance characteristics for the Mercury Lynx ATX transmission.
Bujold, M. P.
The small passenger car transmission was tested to supply electric vehicle manufacturers with technical information regarding the performance of commerically available transmissions which would enable them to design a more energy efficient vehicle. With this information the manufacturers could estimate vehicle driving range as well as speed and torque requirements for specific road load performance characteristics. A 1979 Chevrolet Model 200 automatic transmission was tested per a passenger car automatic transmission test code (SAE J651b) which required drive performance, coast performance, and no load test conditions. The transmission attained maximum efficiencies in the mid-eighty percent range for both drive performance tests and coast performance tests. Torque, speed and efficiency curves map the complete performance characteristics for Chevrolet Model 200 transmission.
Inoue, Y.; Satoh, S.
A technique for automated command transmission (ACT) to GEO-stationed satellites is presented. The system is intended for easing the command center workload. The ACT system determines the relation of the commands to on-board units, connects the telemetry with on-board units, defines the control path on the spacecraft, identifies the correspondence of back-up units to primary units, and ascertains sunlight or eclipse conditions. The system also has the address of satellite and command decoders, the ID and content for the mission command sequence, group and inhibit codes, a listing of all available commands, and restricts the data to a command sequence. Telemetry supplies data for automated problem correction. All other missions operations are terminated during system recovery data processing after a crash. The ACT system is intended for use with the GMS spacecraft.
The VKP-7990 Multistage Depressed Collector (MDC) Klystron is a result of cooperative development by Varian Associates, Inc., the National Association of Broadcasters, Lewis Research Center, the Public Broadcasting System and TV transmitter manufacturers. The effort was initiated to make power amplifying devices with efficiencies comparable to VHF available to UHF operators. The klystron is a vacuum tube used to generate and amplify ultrahigh frequencies but at low efficiencies because most of the energy is dissipated as waste heat. Lewis had earlier developed the MDC to enhance the efficiency of communications satellite transmissions. Varian Microwave Power Tube Products, which has since become Communications and Power Industries, and Lewis combined the MDC and the klystron, resulting in a product which increases efficiency by recovering some of the residual energy that normally would be lost as heat. The MDC klystron cuts the electric power consumption of UHF-TV transmitters in half; there are 90 units in operation in 36 UHF-TV stations.
An experimental evaluation was performed on a high-speed (72.9 m/s, 14,349 ft/min) transmission seal of the synergistic type. During testing of the seal, oil leakage occurred at positive bearing cavity pressures. Modifications were made in an attempt to eliminate the leakage but none were completely successful. Leakage appears to be the result of questionable positioning of the sealing elements resulting in inadequate shaft contact by the oil side sealing element. This condition may be related to the nonsymmetrical shape of the elastomeric retainer and to dimensional changes caused by swelling of the elastomeric retainer from exposure to the sealed fluid. Indications of a speed dependent leakage characteristic were also observed.
Bitensky, I. S.; Sigmund, P.
General expressions have been derived for the nonlinear yield of transmission sputtering for an incident polyatomic ion under the assumption that the molecule breaks up on entering the target and that sputter yields are enhanced due to proximity of atomic trajectories. Special attention is given to the case of negligible Coulomb explosion where projectile atoms penetrate independently. For weakly overlapping trajectories, the yield enhancement factor of a polyatomic molecule can be expressed by that of a diatom, amended with a correction for triple correlations if necessary. This expression is in good agreement with recent experimental findings on phenylalanine targets. Pertinent results on multiple scattering of atomic ions are reviewed and applied to independently-moving fragment atoms. The merits of measurements at variable layer thickness in addition to variable projectile energy are mentioned.
A recent experimental study shows that astrocytes, a subtype of glia, are able to influence the spontaneous activity in the brain via calcium dependent glutamate release. We model the coupling mechanism between an astrocyte and a neuron based on experimental data. This coupling is dynamic and bi-directional, such that the modulations in intracellular calcium concentrations in astrocytes affect neuronal excitability and vice versa via a glutamatergic pathway. We demonstrate through simple neural-glial circuits that increases in the intracellular calcium concentration in astrocytes nearby can enhance spontaneous activity in a neuron, a significant mechanism said to be involved in plasticity and learning. The pattern of this marked increase in spontaneous firing rate in our model quantitatively follows that observed in the experiment. Further, depending on the type of synaptic connections diverging from the neuron, it can either inhibit or excite the ensuing dynamics and potentiate synaptic transmission, thus reinstating the integral role played by astrocytes in normal neuronal dynamics.
In a preferred embodiment, the flywheel electric transmission system is made up of three electric machines and a flywheel and is adapted for use in an automobile. The first electric machine is driven or energized by a prime mover such as a heat engine and is selectively clutched to the second machine. The flywheel and the armatures for both the first and second machines rotate as a unit. The third machine is connected to the second machine through gearing and, under the control of a computer, supplies excess electrical power to or consumes excess electrical power from the first and second machines that are functioning as either a motor or generator as required. In a second embodiment, the energy source is a battery pack.
Hagen, Wilfred R.
EPR spectroscopy employs a resonator operating at a single microwave frequency and phase-sensitive detection using modulation of the magnetic field. The X-band spectrometer is the general standard with a frequency in the 9–10 GHz range. Most (bio)molecular EPR spectra are determined by a combination of the frequency-dependent electronic Zeeman interaction and a number of frequency-independent interactions, notably, electron spin – nuclear spin interactions and electron spin – electron spin interactions, and unambiguous analysis requires data collection at different frequencies. Extant and long-standing practice is to use a different spectrometer for each frequency. We explore the alternative of replacing the narrow-band source plus single-mode resonator with a continuously tunable microwave source plus a non-resonant coaxial transmission cell in an unmodulated external field. Our source is an arbitrary wave digital signal generator producing an amplitude-modulated sinusoidal microwave in combination with a broadband amplifier for 0.8–2.7 GHz. Theory is developed for coaxial transmission with EPR detection as a function of cell dimensions and materials. We explore examples of a doublet system, a high-spin system, and an integer-spin system. Long, straigth, helical, and helico-toroidal cells are developed and tested with dilute aqueous solutions of spin label hydroxy-tempo. A detection limit of circa 5 µM HO-tempo in water at 800 MHz is obtained for the present setup, and possibilities for future improvement are discussed. PMID:23555819
Mocenter, Michael M.
Imagery and other visual information have become a critical element in planning and performing modern military operations. The effectiveness of this imagery information is often directly tied to the time it takes to get from the collector of this imagery to the user of the imagery. Hard copy distribution of annotated imagery to the tactical commander is hampered by the lack of effective communications paths, and the tactical use of hand held imagery is restricted by the lack of film processing facilities. The military has begun to rely on electronic imagery and digital communications technology for answers, with some success. The new obstacles created by applied electronic imagery are interoperability standards and effective use of communications bandwidth in a tactical environment. New technological developments in computer hardware/software have changed this situation by allowing for the gathering, dissemination, and transfer of near-real-time information to various intelligence audiences at any location. The Naval Air Development Center (NAVAIRDEVCEN) has coupled commercial-off-the-shelf (COTS) technology with National Image Transmission Formats (NITF) Standards to develop a Secondary Imagery Dissemination System (SIDS) package that is designed to meet the flexibility challenge of the tactical military environment. This tailorable SIDS package is called Laptop Image Transmission Equipment (LITE). The LITE system is an extension of the Navy's existing Fleet Imagery Support Terminal (FIST) into the man-portable tactical environment. As such, LITE development is focused on developing flexible imagery input (from sources such as filmless cameras) and connectivity to tactical communications paths and ruggedization/miniaturization issues. The LITE system, in prototype form, has already found application through operational use in special operations, counter narcotics operations, and classic air/ground/sea military operations. This paper provides an overview of the
Cupp, E W; Sauerbrey, M; Richards, F
We review and analyze approaches over a 65 year period that have proven successful for onchocerciasis control in several different epidemiological settings. These include vector control with the goal of transmission interruption versus the use of mass drug administration using ivermectin (Mectizan(®)) monotherapy. Ivermectin has proven exceedingly effective because it is highly efficacious against Onchocerca volvulus microfilariae, the etiological agent of onchocercal skin and ocular disease and the infective stage for the vector. For these reasons, the drug was donated by the Merck Company for regional control programs in Africa and the Americas. Recurrent treatment with ivermectin at semi-annual intervals also impacts adult worms and result in loss of fecundity and increased mortality. Using a strategy of 6-monthly treatments with high coverage rates, the Onchocerciasis Elimination Program for the Americas has interrupted transmission in seven of the thirteen foci in the Americas and is on track to eliminate onchocerciasis in the region by 2015. Treatments given annually or semi-annually for 15-17 years in three hyperendemic onchocerciasis foci in Mali and Senegal also have resulted in a few infections in the human population with transmission levels below thresholds postulated for elimination. Follow-up evaluations did not detect any recrudescence of infection or transmission, suggesting that onchocerciasis elimination could be feasible with Mectizan(®) treatment in some endemic foci in Africa.
Lee, S J; Francis, H L; Awadzi, K; Ottesen, E A; Nutman, T B
To define the changes in antibody response to Onchocerca volvulus antigens after treatment of patients with onchocerciasis, IgG and IgE antibodies were examined quantitatively and qualitatively in 21 patients and 3 control individuals before and sequentially for 14 days after treatment with diethylcarbamazine. The quantitative levels of IgE and IgG responses (both polyclonal and O. volvulus-specific) remained essentially unchanged for all patients, but 9 of the 21 patients showed intensified responses to one or more parasite-specific antigens, and 8 of 21 developed antibodies to previously undetected antigens. There was a significant correlation between the intensities of infection and the development of newly recognized anti-O. volvulus antibodies. These studies demonstrate that O. volvulus-specific IgE and IgG antibody responses are, at least transiently, enhanced by treatment with diethylcarbamazine and that after treatment, parasites possibly release antigens previously hidden from the host's immune response.
Lu, Honggang; Hu, Chunsheng; Wang, Xingshu; Gao, Yang
It often needs transfer a reference from one place to another place in aerospace and guided missile launching. At first, principles of several typical optical azimuth transmission methods are presented. Several typical methods are introduced, such as Theodolite (including gyro-theodolite) collimation method, Camera series method, Optical apparatus for azimuth method and polarization modulated light transmission method. For these typical azimuth transmission methods, their essential theories are elaborated. Then the devices, the application fields and limitations of these typical methods' are presented. Theodolite (including gyro-theodolite) collimation method is used in the ground assembly of spacecraft. Camera series method and optical apparatus for azimuth method are used in azimuth transmission between different decks of ship. Polarization modulated light transmission method is used in azimuth transmission of rocket and guided missile. At the last, the further developments of these methods are discussed.
Technical Paper 3. DATES COVERED (From - To) 2011 4. TITLE AND SUBTITLE Dielectric Nonlinear Transmission Line (POSTPRINT) 5a. CONTRACT NUMBER...14. ABSTRACT A parallel plate nonlinear transmission line (NLTL) was constructed. Periodic loading of nonlinear dielectric slabs provides the...846-9101 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. 239.18 Dielectric Nonlinear Transmission Line David M. French, Brad W. Hoff
Allen, Judith E.; Adjei, Ohene; Bain, Odile; Hoerauf, Achim; Hoffmann, Wolfgang H.; Makepeace, Benjamin L.; Schulz-Key, Hartwig; Tanya, Vincent N.; Trees, Alexander J.; Wanji, Samuel; Taylor, David W.
River blindness is a seriously debilitating disease caused by the filarial parasite Onchocerca volvulus, which infects millions in Africa as well as in South and Central America. Research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. This review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. Experimental findings with Litomosoides sigmodontis in mice and Onchocerca ochengi in cattle are placed in the context of how these models can advance our ability to control the human disease. PMID:18446236
This patent describes a multi-speed powershift transmission for connection to a driven power shift. The transmission comprising: a speed transmission assembly including a speed input section connectable to the power shaft for selectively producing either of at least two forward input speed ratios having a relatively small speed ratio differential therebetween; a speed output section for selectively producing any one of at least three equally different forward output speed ratios and at least one reverse speed ratio. The input section comprising a pair of clutch operated drive gears mounted on a speed input shaft and hydraulically actuated in an alternative manner. The output section comprising a plurality of driven gears including a reverse gear mounted on a common speed output shaft, each driven gear having a hydraulically actuated clutch for connecting a selected driven gear to the speed output shaft; and a cluster gear assembly interconnecting the input and output section. The cluster gear assembly being selectively driven by either of the clutch operated drive gears, and a range transmission assembly for selectively producing any one of at least three equally different forward speed ranges. The range transmission assembly including a range input shaft which is operably coupled to the speed output shaft of the speed transmission assembly, a transmission output shaft, and a plurality of hydraulic clutch actuated gears interposed between the range input shaft and the transmissions output shaft and a master clutch assembly selectively interconnecting the speed and range transmission assemblies.
Warfel, Jason M; Beren, Joel; Merkel, Tod J
Pertussis is a contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis. Although it is widely believed that transmission of B. pertussis occurs via aerosolized respiratory droplets, no controlled study has ever documented airborne transmission of pertussis. We set out to determine if airborne transmission occurs between infected and naive animals, utilizing the baboon model of pertussis. Our results showed that 100% of exposed naive animals became infected even when physical contact was prevented, demonstrating that pertussis transmission occurs via aerosolized respiratory droplets.
Kutyrev, A. S.; Moseley, H. S.; Fettig, R. K.; Kuhn, J. L.; Woodgate, B. E.; Kimble, R. A.; Orloff, J. H.
We report further progress on the development of a two-dimensional array of microshutters, which can be used as a high efficiency, high contrast field selection device for a multi-object spectrometer for the Next Generation Space Telescope (NGST). The device is a close packed array of shutters, with a typical size of 100 microns square and an area filling factor of up to 80%. Each shutter, made of single crystal silicon or silicon nitride with an appropriate optical coating, pivots on a torsion flexure along one edge. Each of the shutters is individually selectable. Although these devices can be used as reflection devices, their primary mode of operation is in transmission, which provides the minimum possible level of scattered light. An original double-shutter mechanism is employed for actuation. Small shutter arrays have been built using a Focus Ion Beam milling machine is a 3 x 3 double shutter actuation with a micro-manipulator under electron microscope observation has been demonstrated. An important aspect of this study has been to demonstrate the reliability of the structures over its expected lifetime. We analyzed stiffness, strength and fatigue issues of two good candidate materials, single crystal silicon and silicon nitride. Both appear to be suitable from the mechanical point of view. This project is supported by NASA grants.
Showen, Charles R.
The Geological Survey, Water Resources Division, established a pilot project to evaluate equipment that would transmit date recorded on 16-channel paper tapes over voice-grade telephone lines from field offices to the Washington, D.C., Automatic Data Processing Unit (A.D.P. Unit). Such equipment would allow computer-processed data for current-purpose hydrologic data stations to be made available in a more timely manner. The specifications for the equipment were prepared in March 1970; invitations to bid were solicited, a contract was awarded and the equipment was delivered in November 1970. The equipment included two reader/transmitter units, and one receiver/recorder unit. The reader/transmitter units transmit manually entered fixed information, i.e. station number, beginning date and time, and ending date and time, and photoelectrically read and transmit the 16-channel paper tape data. The receiver/recorder unit records the transmitted information on IBM-compatible magnetic tape. This report summarizes the information gained from a year of pilot operation of the equipment, with and without a computer terminal at the field level, and makes recommendations for establishing a data-transmission system in the Water Resources Division.
Ashikawa, N.; Nakayama, H.; Sumi, M.
This patent describes a multi-speed transmission having forward speed gear trains and at least one reverse speed gear train, comprising, a pair of parallel fork shafts, one the shaft being fixed, the other the shaft being slidable along its axial direction, means to selectively engage the gear trains and means to retain the selective engagement means in the selected position. The means selectively engages the gear trains including a first shift fork connected to the fixed fork shaft so as to slide to either side of its disengaged neutral position, a second shift fork connected to the slideable fork shaft so as to slide to either side of its disengaged neutral position, and a third shift fork connected to the slidable fork shaft so as to slide in one direction by motion of the slideable fork shaft to only one side of its disengaged neutral position. Also included is a reverse shift fork connected to the slideable fork shaft and adapted to be actuated by motion of the slideable fork shaft in a direction opposite to the direction of the motion which engages the third shift fork.