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Peter U. Fischer - One of the best experts on this subject based on the ideXlab platform.
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MARCOS AND OTHERS ATYPICAL Microfilariae IN PERU Short Report: Genetic Characterization of Atypical Mansonella (Mansonella) ozzardi Microfilariae in Human Blood Samples from Northeastern Peru
2016Co-Authors: Luis A. Marcos, Nancy Arrospide, Sergio Recuenco, Cesar Cabezas, Gary J. Weil, Peter U. FischerAbstract:DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical Microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical Microfilariae were clustered into the Mansonella group and indistinguishable from M. ozzardi based on these DNA markers. The main filarial species that infect humans in Latin America are Onchocerca volvulus, Wuchereria bancrofti, and two species of Mansonella, M. ozzardi, and M. perstans. The latter are placed in different subgenera, Mansonella and Esslingeria, respectively.1 M. ozzardi is limited to Latin America, whereas the other species also occur in sub-Saharan Africa and were introduced to the new world by the slave trade.2 Atypical Microfilariae (Mf) similar to M. ozzardi have been occasionally reported in Amerindian people from tropical South America. These Mf include Microfilaria bolivarensis in Venezuela,3 a microfilaria sharing characteristics with M. ozzardi and O. volvulus in Brazil,4 and an atypical Mf recently reported from Peru.5 The atypical M
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brugia malayi effects of nitazoxanide and tizoxanide on adult worms and Microfilariae of filarial nematodes
Experimental Parasitology, 2009Co-Authors: Ramakrishna U Rao, Kerstin Fischer, Peter U. Fischer, Yuefang Huang, Gary J. WeilAbstract:Abstract There is an urgent need for safe and effective antifilarials. Prior studies have shown that the nitazoxanide (NTZ) exhibits broad activity against anaerobic bacteria, protozoa, and certain intestinal helminths. We examined the effects of NTZ and tizoxanide (TZ) on Brugia malayi nematodes in vitro and in vivo. In vitro, NTZ and TZ reduced worm motility and viability in a dose-dependent manner. Worm viability was reduced by 50% with both compounds at 2.5 and 20 μg/ml killed adult worms. NTZ or TZ (5 μg/ml) significantly reduced microfilaria release. These compounds blocked worm’s embryogenesis, and decreased microfilarial motility and viability. Treated worms had damaged cuticles and abnormal mitochondria. Wolbachia were not cleared by NTZ or TZ treatment. Neither NTZ nor TZ cleared adult worms or Microfilariae in infected gerbils. These results show that NTZ and TZ have potent effects on B. malayi nematodes in vitro. However, they were not effective in vivo.
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high prevalence of brugia timori infection in the highland of alor island indonesia
American Journal of Tropical Medicine and Hygiene, 2002Co-Authors: Taniawati Supali, Is Suhariah Ismid, Paul Rückert, Herry Wibowo, Kerstin Fischer, Yenny Djuardi, Peter U. FischerAbstract:To identify areas endemic for Brugia timori infection, a field survey was carried out in 2001 on Alor, East Nusa Tenggara Timor, Indonesia. Elephantiasis was reported on this island by villagers as a major health problem. Bancroftian filariasis was detected in four villages in the coastal area, whereas B. timori was identified in four rice-farming villages. No mixed infections with both species were found. In the highland village Mainang (elevation = 880 m), 586 individuals were examined for B. timori infection and 157 (27%) microfilaria carriers were detected. The prevalence of microfilaremic individuals standardized by sex and age was 25%. The geometric mean microfilarial density of microfilaremic individuals was 138 Microfilariae/ml. Among teenagers and adults, males tended to have a higher microfilarial prevalence than females. Microfilaria prevalence increased with age and a maximum was observed in the fifth decade of life. In infected individuals, the microfilarial density increased rapidly and high levels were observed in those individuals 11-20 years old. The highest microfilaria density was found in a 27-year-old woman (6,028 Microfilariae/ml). Brugia timori on Alor was nocturnally periodic, but in patients with high parasite loads, a small number of Microfilariae was also detected in the day blood. The disease rate was high and many persons reported a history of acute filarial attacks. Seventy-seven (13%) individuals showed lymphedema of the leg that occasionally presented severe elephantiasis. No hydrocele or genital lymphedema were observed. This study showed that B. timori infection is not restricted to the lowland and indicated that it might have a wider distribution in the lesser Sunda archipelago than previously assumed.
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detection of dna of nocturnally periodic brugia malayi in night and day blood samples by a polymerase chain reaction elisa based method using an internal control dna
American Journal of Tropical Medicine and Hygiene, 2000Co-Authors: Peter U. Fischer, Taniawati Supali, Heri Wibowo, Insa Bonow, Steven A WilliamsAbstract:An internal control was used in a polymerase chain reaction (PCR)-ELISA-based technique to detect the Hha I repeat of the filarial parasite Brugia malayi. A single microfilaria added to 200 microl of blood was reliably detected. The assay was evaluated on field samples from persons living in an area endemic for Anopheles-transmitted, nocturnally periodic B. malayi in central Sulawesi, Indonesia. Examination of night blood of 138 individuals for the presence of Microfilariae by filtration revealed 44 microfilaria carriers. All microfilaria carriers were also positive in the PCR-ELISA and, in addition, 14 more samples were proven to contain parasite DNA. The sensitivity of both methods was compared on night and on day blood samples collected from 113 persons. Whereas 37 microfilaria carriers were identified by filtration of night blood, no Microfilariae were observed in the corresponding day blood samples. The PCR-ELISA result was positive in all 37 night blood samples of microfilaria carriers and in an additional 13 night blood samples without Microfilariae. Parasite DNA was detected in 31 day blood samples of microfilaria carriers and in 3 day blood samples of amicrofilaremic persons. Assuming a sensitivity of the PCR-ELISA on night blood of 100%, the sensitivity of night blood filtration is 74% and that of the PCR-ELISA on day blood is 68%. These data suggest that the described PCR-ELISA method is capable of detecting infections with nocturnally periodic B. malayi in day blood samples. Therefore, this method may facilitate both the identification of endemic areas and the monitoring of control programs.
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long term suppression of mansonella stveptocevca Microfilariae after treatment with ivermectin
The Journal of Infectious Diseases, 1999Co-Authors: Peter U. Fischer, Ephraim Tukesiga, Dietrich W ButtnerAbstract:The long-term effect of a single oral dose of 150 microg/kg of body weight of ivermectin on Mansonella streptocerca Microfilariae was studied in western Uganda. Before treatment, the geometric mean microfilaria density (mf) in 93 infected persons was 2.4 mf/mg of skin (range, 0.1-42.6). One year after treatment, 43 persons (46%) were microfilaria-negative, and the geometric mean in the remaining persons dropped significantly, to 0.7 mf/mg (range, 0.1-6.9). Thus, ivermectin is highly effective against M. streptocerca, and a single dose leads to a sustained suppression of Microfilariae in skin. In Africa, ivermectin is used for mass treatment to control Onchocerca volvulus and Wuchereria bancrofti. Because these filarial parasites are often coendemic with M. streptocerca, the treated population may receive the additional benefit of suppression of M. streptocerca Microfilariae.
Michel Boussinesq - One of the best experts on this subject based on the ideXlab platform.
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dynamics of onchocerca volvulus microfilarial densities after ivermectin treatment in an ivermectin naive and a multiply treated population from cameroon
PLOS Neglected Tropical Diseases, 2013Co-Authors: Sebastien D S Pion, Joseph Kamgno, Hugues C Nanadjeunga, Roger K Prichard, Nicholas Tendongfor, Samuel Wanji, Flobert Njiokou, Michel BoussinesqAbstract: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-naive 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-naive 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-naive 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 worms as previously described.
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dynamics of onchocerca volvulus microfilarial densities after ivermectin treatment in an ivermectin naive and a multiply treated population from cameroon
PLOS Neglected Tropical Diseases, 2013Co-Authors: Sebastien D S Pion, Joseph Kamgno, Hugues C Nanadjeunga, Roger K Prichard, Nicholas Tendongfor, Samuel Wanji, Flobert Njiokou, Michel BoussinesqAbstract: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-naive 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-naive 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-naive 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 worms as previously described.
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effect of single dose ivermectin on onchocerca volvulus a systematic review and meta analysis
Lancet Infectious Diseases, 2008Co-Authors: Mariagloria Basanez, Sebastien D S Pion, Eve Boakes, Joao A N Filipe, Thomas S Churcher, Michel BoussinesqAbstract:Summary 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 μg/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.
Gerusa Dreyer - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the og4c3 elisa in wuchereria bancrofti infection infected persons with undetectable or ultra low microfilarial densities
Tropical Medicine & International Health, 2007Co-Authors: Abraham Rocha, David G. Addiss, M E Ribeiro, J Norotes, M Baliza, Zulma Medeiros, Gerusa DreyerAbstract:The recently developed Og4C3 ELISA, which detects circulating Wuchereria bancrofti antigen, appears promising for use in epidemiological surveys, but its sensitivity is unknown in persons with ultra-low microfilarial densities. We used the Og4C3 to test the sera of 282 persons who were microfilaria-positive in 1-16 ml of blood, 18 persons who were microfilaria-negative but who had ultrasonographic or biopsy evidence of adult W. bancrofti infection, and 63 lifelong residents of a non-endemic area of Brazil. A total of 276 (97.9%) persons with detectable microfilaraemia tested positive (optical density >0.033). At microfilarial densities of 30 Microfilariae per ml of blood, the sensitivity of the Og4C3 was 72.2, 97.6 and 100%, respectively (X 2 -test for trend, P<10 -6 ). The assay was positive in 66.7% of amicrofilaraemic persons with evidence of adult worm infection and in one (1.6%) of 63 residents of the non-endemic area (specificity, 98.4%). Our findings support the increasingly widespread use of the Og4C3 for field investigations and epidemiological assessments. However, the sensitivity of the assay may be low in persons who are microfilaria-negative or with densities of
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evaluation of the og4c3 elisa in wuchereria bancrofti infection infected persons with undetectable or ultra low microfilarial densities
Tropical Medicine & International Health, 2007Co-Authors: Abraham Rocha, David G. Addiss, M E Ribeiro, M Baliza, Zulma Medeiros, Joaquim Noroes, Gerusa DreyerAbstract:The recently developed Og4C3 ELISA, which detects circulating Wuchereria bancrofti antigen, appears promising for use in epidemiological surveys, but its sensitivity is unknown in persons with ultra-low microfilarial densities. We used the Og4C3 to test the sera of 282 persons who were microfilaria-positive in 1-16 ml of blood, 18 persons who were microfilaria-negative but who had ultrasonographic or biopsy evidence of adult W. bancrofti infection, and 63 lifelong residents of a non-endemic area of Brazil. A total of 276 (97.9%) persons with detectable microfilaraemia tested positive (optical density > 0.033). At microfilarial densities of 30 Microfilariae per ml of blood, the sensitivity of the Og4C3 was 72.2, 97.6 and 100%, respectively (chi 2-test for trend, P < 10(-6)). The assay was positive in 66.7% of amicrofilaraemic persons with evidence of adult worm infection and in one (1.6%) of 63 residents of the non-endemic area (specificity, 98.4%). Our findings support the increasingly widespread use of the Og4C3 for field investigations and epidemiological assessments. However, the sensitivity of the assay may be low in persons who are microfilaria-negative or with densities of < 1 microfilaria per ml.
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tolerance of diethylcarbamazine by microfilaraemic and amicrofilaraemic individuals in an endemic area of bancroftian filariasis recife brazil
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1994Co-Authors: Gerusa Dreyer, Zulma Medeiros, Joaquim Noroes, Maria Luiza Pires, Luiz Dias De Andrade, Edmundo Pessoa De Almeida Lopes, Jocelene Tenorio, Amaury Coutinho, Jose FigueredosilvaAbstract:To determine the tolerance to diethylcarbamazine (DEC) treatment of patients with Bancroftian filariasis, 193 individuals (138 asymptomatic microfilaraemic, 30 amicrofilaraemic diseased patients and 25 asymptomatic amicrofilaraemic endemic residents) were enrolled in a prospective trial with different dose schedules, in a hospital and outpatient clinic setting in Brazil. Systemic adverse reactions, localized adverse reactions, and side effects, related to Microfilariae, adult worms and the drug itself, were evaluated. Systemic reactions occurred irrespective of the DEC dose and schedule in about 40% of the Microfilariae carriers, but not in amicrofilaraemic diseased patients or residents; they usually consisted of microscopic haematuria, followed by fever and malaise. Localized reactions were manifested by the appearance of inflammatory reactions, mainly in the scrotal area. Nodules containing degenerating adult worms developed mainly in the scrotal lymphatics of microfilaraemic patients, diseased amicrofilaraemic patients, and residents. Drowsiness, which increased with higher doses of DEC, was the most common side effect in both microfilaraemic and amicrofilaraemic individuals, followed by nausea and gastric upset. The results indicate that the occurrence of systemic and local adverse reactions was unrelated to either the dose of DEC or the pretreatment microfilarial density. The severity of systemic reactions was proportional to the microfilarial density. Side effects were dependent on the drug dosage irrespective of infection status.
Sebastien D S Pion - One of the best experts on this subject based on the ideXlab platform.
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implications for annual retesting after a test and not treat strategy for onchocerciasis elimination in areas co endemic with loa loa infection an observational cohort study
Lancet Infectious Diseases, 2020Co-Authors: Sebastien D S Pion, Charles D. Mackenzie, Hugues C Nanadjeunga, Cedric B Chesnais, Amy D Klion, Hugo Deléglise, Yannick Niamsiemalio, Wilma A Stolk, Daniel A Fletcher, Thomas B NutmanAbstract:Summary Background A test-and-not-treat (TaNT) strategy has been developed to prevent people with high concentrations of circulating Loa loa Microfilariae (>20 000 Microfilariae per mL) developing serious adverse events after ivermectin treatment during mass drug administration to eliminate onchocerciasis. An important question related to cost and programmatic issues is whether annual retesting is required for everyone. We therefore aimed to investigate changes in L loa microfilarial densities during TaNT campaigns run 18 months apart. Methods In this observational cohort study, we assessed the participants of two TaNT campaigns for onchocerciasis. These campaigns, which were run by a research team, together with personnel from the Ministry of Health and community health workers, were done in six health areas (in 89 communities) in Okola health district (Cameroon); the first campaign was run between Aug 10, and Oct 29, 2015, and the second was run between March 7, and May 26, 2017. All individuals aged 5 years and older were invited to be screened for Loa loa microfilaraemia before being offered ivermectin (unless contraindicated). L loa microfilarial density was measured at the point of care using the LoaScope. All those with a L loa microfilarial density of 20 000 Microfilariae per mL or less were offered treatment; in the first 2 weeks of the 2015 campaign, a higher exclusion threshold of 26 000 Microfilariae per mL or less was used. At both rounds of the intervention, participants were registered with a paper form, in which personal information were collected. In 2017, we also recorded whether each individual reported participation in the 2015 campaign. The primary outcome, assessed in all participants, was whether L loa microfilarial density was above or below the exclusion threshold (ie, the criteria that guided the decision to treat). Findings In the 2015 TaNT campaign, 26 415 people were censused versus 29 587 people in the 2017 TaNT campaign. All individuals aged 5 years and older without other contraindications to treatment (22 842 people in 2015 and 25 421 people in 2017) were invited to be screened for L loa microfilaraemia before being offered ivermectin. In 2015, 16 182 individuals were examined with the LoaScope, versus 18 697 individuals in the same communities in 2017. 344 (2·1%) individuals were excluded from ivermectin treatment because of a high L loa microfilarial density in 2015, versus 283 (1·5%) individuals in 2017 (p 99·9%) of 6983 individuals treated with ivermectin in 2015 had L loa Microfilariae density below the level associated with neurological serious adverse events. Interpretation Individuals treated with ivermectin do not need to be retested for L loa microfilaraemia before the next treatment, provided that they can be re-identified. This adjusted approach will enable substantial cost savings and facilitate reaching programmatic goals for elimination of onchocerciasis in areas that are co-endemic for loiasis. Funding Bill & Melinda Gates Foundation, Division of Intramural Research (National Institute of Allergy and Infectious Diseases, US National Institutes of Health).
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dynamics of onchocerca volvulus microfilarial densities after ivermectin treatment in an ivermectin naive and a multiply treated population from cameroon
PLOS Neglected Tropical Diseases, 2013Co-Authors: Sebastien D S Pion, Joseph Kamgno, Hugues C Nanadjeunga, Roger K Prichard, Nicholas Tendongfor, Samuel Wanji, Flobert Njiokou, Michel BoussinesqAbstract: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-naive 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-naive 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-naive 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 worms as previously described.
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dynamics of onchocerca volvulus microfilarial densities after ivermectin treatment in an ivermectin naive and a multiply treated population from cameroon
PLOS Neglected Tropical Diseases, 2013Co-Authors: Sebastien D S Pion, Joseph Kamgno, Hugues C Nanadjeunga, Roger K Prichard, Nicholas Tendongfor, Samuel Wanji, Flobert Njiokou, Michel BoussinesqAbstract: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-naive 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-naive 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-naive 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 worms as previously described.
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effect of single dose ivermectin on onchocerca volvulus a systematic review and meta analysis
Lancet Infectious Diseases, 2008Co-Authors: Mariagloria Basanez, Sebastien D S Pion, Eve Boakes, Joao A N Filipe, Thomas S Churcher, Michel BoussinesqAbstract:Summary 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 μg/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.
Hugues C Nanadjeunga - One of the best experts on this subject based on the ideXlab platform.
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implications for annual retesting after a test and not treat strategy for onchocerciasis elimination in areas co endemic with loa loa infection an observational cohort study
Lancet Infectious Diseases, 2020Co-Authors: Sebastien D S Pion, Charles D. Mackenzie, Hugues C Nanadjeunga, Cedric B Chesnais, Amy D Klion, Hugo Deléglise, Yannick Niamsiemalio, Wilma A Stolk, Daniel A Fletcher, Thomas B NutmanAbstract:Summary Background A test-and-not-treat (TaNT) strategy has been developed to prevent people with high concentrations of circulating Loa loa Microfilariae (>20 000 Microfilariae per mL) developing serious adverse events after ivermectin treatment during mass drug administration to eliminate onchocerciasis. An important question related to cost and programmatic issues is whether annual retesting is required for everyone. We therefore aimed to investigate changes in L loa microfilarial densities during TaNT campaigns run 18 months apart. Methods In this observational cohort study, we assessed the participants of two TaNT campaigns for onchocerciasis. These campaigns, which were run by a research team, together with personnel from the Ministry of Health and community health workers, were done in six health areas (in 89 communities) in Okola health district (Cameroon); the first campaign was run between Aug 10, and Oct 29, 2015, and the second was run between March 7, and May 26, 2017. All individuals aged 5 years and older were invited to be screened for Loa loa microfilaraemia before being offered ivermectin (unless contraindicated). L loa microfilarial density was measured at the point of care using the LoaScope. All those with a L loa microfilarial density of 20 000 Microfilariae per mL or less were offered treatment; in the first 2 weeks of the 2015 campaign, a higher exclusion threshold of 26 000 Microfilariae per mL or less was used. At both rounds of the intervention, participants were registered with a paper form, in which personal information were collected. In 2017, we also recorded whether each individual reported participation in the 2015 campaign. The primary outcome, assessed in all participants, was whether L loa microfilarial density was above or below the exclusion threshold (ie, the criteria that guided the decision to treat). Findings In the 2015 TaNT campaign, 26 415 people were censused versus 29 587 people in the 2017 TaNT campaign. All individuals aged 5 years and older without other contraindications to treatment (22 842 people in 2015 and 25 421 people in 2017) were invited to be screened for L loa microfilaraemia before being offered ivermectin. In 2015, 16 182 individuals were examined with the LoaScope, versus 18 697 individuals in the same communities in 2017. 344 (2·1%) individuals were excluded from ivermectin treatment because of a high L loa microfilarial density in 2015, versus 283 (1·5%) individuals in 2017 (p 99·9%) of 6983 individuals treated with ivermectin in 2015 had L loa Microfilariae density below the level associated with neurological serious adverse events. Interpretation Individuals treated with ivermectin do not need to be retested for L loa microfilaraemia before the next treatment, provided that they can be re-identified. This adjusted approach will enable substantial cost savings and facilitate reaching programmatic goals for elimination of onchocerciasis in areas that are co-endemic for loiasis. Funding Bill & Melinda Gates Foundation, Division of Intramural Research (National Institute of Allergy and Infectious Diseases, US National Institutes of Health).
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a test and not treat strategy for onchocerciasis in loa loa endemic areas
The New England Journal of Medicine, 2017Co-Authors: Joseph Kamgno, Sebastien David Pion, Charles D. Mackenzie, Hugues C Nanadjeunga, Cedric B Chesnais, Matthew H Bakalar, Michael V Dambrosio, Raceline Gounouekamkumo, Guyroger Njitchouang, Philippe NwaneAbstract:BackgroundImplementation of an ivermectin-based community treatment strategy for the elimination of onchocerciasis or lymphatic filariasis has been delayed in Central Africa because of the occurrence of serious adverse events, including death, in persons with high levels of circulating Loa loa Microfilariae. The LoaScope, a field-friendly diagnostic tool to quantify L. loa Microfilariae in peripheral blood, enables rapid, point-of-care identification of persons at risk for serious adverse events. MethodsA test-and-not-treat strategy was used in the approach to ivermectin treatment in the Okola health district in Cameroon, where the distribution of ivermectin was halted in 1999 after the occurrence of fatal events related to L. loa infection. The LoaScope was used to identify persons with an L. loa microfilarial density greater than 20,000 Microfilariae per milliliter of blood, who were considered to be at risk for serious adverse events, and exclude them from ivermectin distribution. Active surveillance f...
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dynamics of onchocerca volvulus microfilarial densities after ivermectin treatment in an ivermectin naive and a multiply treated population from cameroon
PLOS Neglected Tropical Diseases, 2013Co-Authors: Sebastien D S Pion, Joseph Kamgno, Hugues C Nanadjeunga, Roger K Prichard, Nicholas Tendongfor, Samuel Wanji, Flobert Njiokou, Michel BoussinesqAbstract: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-naive 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-naive 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-naive 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 worms as previously described.
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dynamics of onchocerca volvulus microfilarial densities after ivermectin treatment in an ivermectin naive and a multiply treated population from cameroon
PLOS Neglected Tropical Diseases, 2013Co-Authors: Sebastien D S Pion, Joseph Kamgno, Hugues C Nanadjeunga, Roger K Prichard, Nicholas Tendongfor, Samuel Wanji, Flobert Njiokou, Michel BoussinesqAbstract: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-naive 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-naive 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-naive 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 worms as previously described.