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Thomas B Nutman - One of the best experts on this subject based on the ideXlab platform.

  • infection associated immune perturbations resolve 1 year following treatment for Loa Loa
    Clinical Infectious Diseases, 2021
    Co-Authors: Amy D Klion, Jesica A Herrick, Michelle Makiya, Nicole Hollandthomas, Thomas B Nutman
    Abstract:

    Background We have previously demonstrated that eosinophil-associated processes underlie some of the differences in clinical presentation among patients with Loa Loa infection prior to therapy and that some posttreatment adverse events appear to be dependent on eosinophil activation. Methods We first conducted a retrospective review of 204 patients (70 microfilaria [MF] positive/134 negative) with Loa Loa both before and following definitive therapy. We then measured filarial-specific antibodies, eosinophil- and Th2-associated cytokines, and eosinophil granule proteins in their banked serum prior to and at 1 year following definitive treatment. We also evaluated the influence of pretreatment corticosteroids and/or apheresis in altering the efficacy of treatment. Results Patients without circulating microfilariae (MF negative) not only had a higher likelihood of peripheral eosinophilia and increased antifilarial antibody levels but also had significantly increased concentrations of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 5, and IL-4 compared with MF-positive patients. However, these differences had all resolved by 1 year after treatment, when all parameters approached the levels seen in uninfected individuals. Neither pretreatment with corticosteroids nor apheresis reduced the efficacy of the diethylcarbamazine used to treat these subjects. Conclusions Our results highlight that, by 1 year following treatment, infection-associated immunologic abnormalities had resolved in nearly all patients treated for loiasis, and pretreatment corticosteroids had no influence on the resolution of the immunologic perturbations nor on the efficacy of diethylcarbamazine as a curative agent in loiasis. Clinical trials registration NCT00001230.

  • feasibility of onchocerciasis elimination using a test and not treat strategy in Loa Loa co endemic areas
    Clinical Infectious Diseases, 2020
    Co-Authors: David J Blok, Joseph Kamgno, Sebastien David Pion, Charles D. Mackenzie, Hugues C Nanadjeunga, Yannick Niamsiemalio, Cedric B Chesnais, Amy D Klion, Daniel A Fletcher, Thomas B Nutman
    Abstract:

    Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa Loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. Loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. Loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. Loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

  • a test and not treat strategy for onchocerciasis elimination in Loa Loa coendemic areas cost analysis of a pilot in the soa health district cameroon
    Clinical Infectious Diseases, 2020
    Co-Authors: Edeltraud J Lenk, Joseph Kamgno, Michel Boussinesq, Hugues C Nanadjeunga, Amy D Klion, Daniel A Fletcher, Henri C Moungui, Christopher Fitzpatrick, Anneclaire Peultier, Thomas B Nutman
    Abstract:

    textabstractBackground. Severe adverse events after treatment with ivermectin in individuals with high levels of Loa Loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. Methods. Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. Results. The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9–$3.6), US$5.2 ($4.5–$8.3), and US$5.4 ($4.6–$8.6), respectively. Conclusions. TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa Loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.

  • Loa Loa microfilariae in skin snips: consequences for onchocerciasis monitoring and evaluation in L. Loa endemic areas
    Clinical Infectious Diseases, 2019
    Co-Authors: Hugues Nana-djeunga, Joseph Kubofcik, Sebastien David Pion, Michel Boussinesq, Thomas B Nutman, Floribert Fossuo-thotchum, Cedric B Chesnais, Amy D Klion, Charles D Mackenzie, Joseph Kamgno
    Abstract:

    The specificity of skin snips for onchocerciasis diagnoses is considered to be almost 100%. Our molecular methods revealed that microfilariae emerging from skin snips collected from highly microfilaremic Loa Loa–infected individuals were largely misidentified as Onchocerca volvulus. This has important implications for onchocerciasis diagnostic testing in Loa-endemic areas.

  • discovery of specific antigens that can predict microfilarial intensity in Loa Loa infection
    Journal of Clinical Microbiology, 2017
    Co-Authors: Papa M Drame, Sasisekhar Bennuru, Thomas B Nutman
    Abstract:

    Antigen-based immunoassays are currently needed for point-of-care quantification of Loa Loa microfilariae (mf). Coupling transcriptomic approaches with bioinformatic analysis, we have identified 11 specific putative proteins (coding mRNAs) with potential utility as biomarkers of patent (mf + ) L. Loa infection. We successfully developed antigen capture immunoassays to quantify 2 (LoaG_14221 and LoaG_15846) of these proteins in individual plasma/serum samples. Of the 2 quantifiable circulating biomarkers, LoaG_14221 showed the highest degree of specificity, particularly with a monoclonal antibody-based immunoassay. Moreover, the levels of LoaG_14221 in L. Loa mf + patients were positively correlated to the mf densities in the corresponding blood samples (r = 0.53 and P = 0.008 for polyclonal assay; r = 0.54 and P = 0.004 for monoclonal assay). Thus, LoaG_14221 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of L. Loa mf densities.

Joseph Kamgno - One of the best experts on this subject based on the ideXlab platform.

  • feasibility of onchocerciasis elimination using a test and not treat strategy in Loa Loa co endemic areas
    Clinical Infectious Diseases, 2020
    Co-Authors: David J Blok, Joseph Kamgno, Sebastien David Pion, Charles D. Mackenzie, Hugues C Nanadjeunga, Yannick Niamsiemalio, Cedric B Chesnais, Amy D Klion, Daniel A Fletcher, Thomas B Nutman
    Abstract:

    Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa Loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. Loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. Loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. Loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

  • individual risk of post ivermectin serious adverse events in subjects infected with Loa Loa
    Social Science Research Network, 2020
    Co-Authors: Cedric B Chesnais, Joseph Kamgno, Sebastien David Pion, Jacques Gardon, N Gardonwendel, Charlotte Boulle, Joel Fokomdomgue, Michel Boussinesq
    Abstract:

    Background: Implementation of onchocerciasis elimination programmes has been delayed in Central Africa because of the risk of ivermectin-related serious adverse events (SAEs) in individuals with high Loa Loa microfilarial densities (MFD). We developed the first statistical models enabling prediction of SAE risk in individuals with a given MFD. Methods: We used individual participant data from two trials conducted in loiasis-onchocerciasis co-endemic areas in Cameroon. Among the 10 506 ivermectin-treated subjects included in the analysis, 38 (0·36 %) developed an ivermectin-related SAE. To predict individual-level risk of SAE, we developed mixed multivariate logistic models including subjects’ sex, age, pre-treatment L Loa and Mansonella perstans MFDs, and study region. Findings: The models predicted that regardless of sex, about 1% of people with 20 000 L Loa microfilariae per milliliter of blood (mf/mL), 10% of people with 50 000 mf/mL and about one third of those with 100 000 mf/mL will develop an SAE. For a given MFD, males have a three-fold higher risk of developing an SAE than females. Interpretation: By enabling the prediction of post-ivermectin SAE risk in communities with known distribution of L Loa MFDs, our results can guide decisions on the choice of ivermectin-based treatment strategies. They also predict that 37 SAEs were prevented in 2015 by using a Test-and-Treat strategy in the Okola District of Cameroon. Funding Statement: UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases; Institut de Recherche pour le Developpement; Mectizan Donation Program; Bill & Melinda Gates Foundation. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: Both studies were approved by the Cameroon National Ethics Committee for Research in Human Health.

  • a test and not treat strategy for onchocerciasis elimination in Loa Loa coendemic areas cost analysis of a pilot in the soa health district cameroon
    Clinical Infectious Diseases, 2020
    Co-Authors: Edeltraud J Lenk, Joseph Kamgno, Michel Boussinesq, Hugues C Nanadjeunga, Amy D Klion, Daniel A Fletcher, Henri C Moungui, Christopher Fitzpatrick, Anneclaire Peultier, Thomas B Nutman
    Abstract:

    textabstractBackground. Severe adverse events after treatment with ivermectin in individuals with high levels of Loa Loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. Methods. Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. Results. The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9–$3.6), US$5.2 ($4.5–$8.3), and US$5.4 ($4.6–$8.6), respectively. Conclusions. TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa Loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.

  • effect of a single standard dose 150 200 μg kg of ivermectin on Loa Loa microfilaremia systematic review and meta analysis
    Open Forum Infectious Diseases, 2019
    Co-Authors: Sebastien David Pion, Joseph Kamgno, Cedric B Chesnais, Jacques Gardon, Jeanphilippe Chippaux, Jules B Tchatchuengmbougua, Stephane Ranque, Jeanchristophe Ernould, Andre Garcia, Michel Boussinesq
    Abstract:

    Background: In central Africa, millions of individuals infected with Loa Loa have received the anthelminthic drug ivermectin (IVM) as part of mass drug administration (MDA) campaigns targeting onchocerciasis control or elimination. Nonetheless, the parasitological surveys that are occasionally conducted to evaluate the impact of IVM treatments on Onchocerca volvulus do not include an assessment of the extra benefits of those MDA campaigns on L. Loa. Methods: We conducted a systematic review of trials on the effect of a single standard (150-200 μg/kg) dose of IVM on L. Loa microfilarial density (MFD). The dynamics of MFD over 365 days of treatment were described using multilevel regression and latent class modeling. Results: IVM brings about a rapid, dramatic, and sustained decrease, with reduction rates of 60%, 75%, 85%, and 90% on day 1 (D1), D2, D7, and D365, respectively. At D365, no participants (0/238) with an initial MFD of <20 000 microfilariae (mf)/mL were at risk of postivermectin severe adverse events, and only 1/57 individuals with an initial MFD of ≥20 000 mf/mL presented with an MFD above this value. The main predictor of post-treatment MFD was the pretreatment value, but this post-treatment value varied little between D8 and D365 regardless of the pretreatment level. Conclusions: A single dose of IVM is very effective at substantially reducing L. Loa MFD for at least a year, irrespective of the initial level of parasitemia. Individuals treated with IVM are probably not any more at risk of severe adverse events when retreated 1 year later.

  • Prevalence and intensity of Loa Loa infection over twenty-three years in three communities of the Mbalmayo health district (Central Cameroon)
    BMC Infectious Diseases, 2019
    Co-Authors: Aude E. Mogoung-wafo, J Bopda, Hugues Nana-djeunga, André Domche, Floribert Fossuo-thotchum, Steve Mbickmen-tchana, Honoré Djomo-kamga, Joseph Kamgno
    Abstract:

    Background Loiasis is a vector-borne parasitic disease due to Loa Loa and transmitted to humans by tabanids of the genus Chrysops . Loiasis has been historically considered as the second or third most common reason for medical consultation after malaria, and a recent study has reported an excess mortality associated with the infection. However, the clinical impact of this filarial disease is yet to be elucidated, and it is still considered a benign disease eliciting very little attention. As a consequence of post-treatment severe adverse events occurring in individuals harboring very high Loa microfilarial Loads, ivermectin is not recommended in onchocerciasis hypo-endemic areas that are co-endemic for loiasis. Without treatment, it is likely that the transmission of the disease and the morbidity associated with the infection will increase over time. This study aimed at investigating the long-term trends in prevalence and intensity of Loa Loa infection in an area where no mass anti-filarial treatment has ever been distributed. Methods A cross-sectional survey was conducted in three communities of the Mbalmayo health district (Central Cameroon). All volunteers, males and females aged five years and above, underwent daytime calibrated thick blood smears (CTBS) to search for L. Loa microfilariae (mf). A structured questionnaire was administered to assess the history of both loiasis related clinical signs and migration of enrollees. Results The prevalence of loiasis was 27.3% (95% CI: 22.3–32.9) in the three surveyed communities, with a mean mf density of 1922.7 (sd: 6623.2) mf/mL. Loa Loa infection rate was higher amongst females than in males ( p  = 0.0001) and was positively associated with age of (OR = 1.018; p  = 0.007). The intensity of infection was higher among males than in females ( p  

Michel Boussinesq - One of the best experts on this subject based on the ideXlab platform.

  • individual risk of post ivermectin serious adverse events in subjects infected with Loa Loa
    Social Science Research Network, 2020
    Co-Authors: Cedric B Chesnais, Joseph Kamgno, Sebastien David Pion, Jacques Gardon, N Gardonwendel, Charlotte Boulle, Joel Fokomdomgue, Michel Boussinesq
    Abstract:

    Background: Implementation of onchocerciasis elimination programmes has been delayed in Central Africa because of the risk of ivermectin-related serious adverse events (SAEs) in individuals with high Loa Loa microfilarial densities (MFD). We developed the first statistical models enabling prediction of SAE risk in individuals with a given MFD. Methods: We used individual participant data from two trials conducted in loiasis-onchocerciasis co-endemic areas in Cameroon. Among the 10 506 ivermectin-treated subjects included in the analysis, 38 (0·36 %) developed an ivermectin-related SAE. To predict individual-level risk of SAE, we developed mixed multivariate logistic models including subjects’ sex, age, pre-treatment L Loa and Mansonella perstans MFDs, and study region. Findings: The models predicted that regardless of sex, about 1% of people with 20 000 L Loa microfilariae per milliliter of blood (mf/mL), 10% of people with 50 000 mf/mL and about one third of those with 100 000 mf/mL will develop an SAE. For a given MFD, males have a three-fold higher risk of developing an SAE than females. Interpretation: By enabling the prediction of post-ivermectin SAE risk in communities with known distribution of L Loa MFDs, our results can guide decisions on the choice of ivermectin-based treatment strategies. They also predict that 37 SAEs were prevented in 2015 by using a Test-and-Treat strategy in the Okola District of Cameroon. Funding Statement: UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases; Institut de Recherche pour le Developpement; Mectizan Donation Program; Bill & Melinda Gates Foundation. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: Both studies were approved by the Cameroon National Ethics Committee for Research in Human Health.

  • a test and not treat strategy for onchocerciasis elimination in Loa Loa coendemic areas cost analysis of a pilot in the soa health district cameroon
    Clinical Infectious Diseases, 2020
    Co-Authors: Edeltraud J Lenk, Joseph Kamgno, Michel Boussinesq, Hugues C Nanadjeunga, Amy D Klion, Daniel A Fletcher, Henri C Moungui, Christopher Fitzpatrick, Anneclaire Peultier, Thomas B Nutman
    Abstract:

    textabstractBackground. Severe adverse events after treatment with ivermectin in individuals with high levels of Loa Loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. Methods. Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. Results. The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9–$3.6), US$5.2 ($4.5–$8.3), and US$5.4 ($4.6–$8.6), respectively. Conclusions. TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa Loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.

  • effect of a single standard dose 150 200 μg kg of ivermectin on Loa Loa microfilaremia systematic review and meta analysis
    Open Forum Infectious Diseases, 2019
    Co-Authors: Sebastien David Pion, Joseph Kamgno, Cedric B Chesnais, Jacques Gardon, Jeanphilippe Chippaux, Jules B Tchatchuengmbougua, Stephane Ranque, Jeanchristophe Ernould, Andre Garcia, Michel Boussinesq
    Abstract:

    Background: In central Africa, millions of individuals infected with Loa Loa have received the anthelminthic drug ivermectin (IVM) as part of mass drug administration (MDA) campaigns targeting onchocerciasis control or elimination. Nonetheless, the parasitological surveys that are occasionally conducted to evaluate the impact of IVM treatments on Onchocerca volvulus do not include an assessment of the extra benefits of those MDA campaigns on L. Loa. Methods: We conducted a systematic review of trials on the effect of a single standard (150-200 μg/kg) dose of IVM on L. Loa microfilarial density (MFD). The dynamics of MFD over 365 days of treatment were described using multilevel regression and latent class modeling. Results: IVM brings about a rapid, dramatic, and sustained decrease, with reduction rates of 60%, 75%, 85%, and 90% on day 1 (D1), D2, D7, and D365, respectively. At D365, no participants (0/238) with an initial MFD of <20 000 microfilariae (mf)/mL were at risk of postivermectin severe adverse events, and only 1/57 individuals with an initial MFD of ≥20 000 mf/mL presented with an MFD above this value. The main predictor of post-treatment MFD was the pretreatment value, but this post-treatment value varied little between D8 and D365 regardless of the pretreatment level. Conclusions: A single dose of IVM is very effective at substantially reducing L. Loa MFD for at least a year, irrespective of the initial level of parasitemia. Individuals treated with IVM are probably not any more at risk of severe adverse events when retreated 1 year later.

  • Loa Loa microfilariae in skin snips: consequences for onchocerciasis monitoring and evaluation in L. Loa endemic areas
    Clinical Infectious Diseases, 2019
    Co-Authors: Hugues Nana-djeunga, Joseph Kubofcik, Sebastien David Pion, Michel Boussinesq, Thomas B Nutman, Floribert Fossuo-thotchum, Cedric B Chesnais, Amy D Klion, Charles D Mackenzie, Joseph Kamgno
    Abstract:

    The specificity of skin snips for onchocerciasis diagnoses is considered to be almost 100%. Our molecular methods revealed that microfilariae emerging from skin snips collected from highly microfilaremic Loa Loa–infected individuals were largely misidentified as Onchocerca volvulus. This has important implications for onchocerciasis diagnostic testing in Loa-endemic areas.

  • confirmation of no influence of Loa Loa and mansonella perstans on the card agglutination test for trypanosomosis used for serological screening of human african trypanosomosis
    Journal of Tropical Diseases & Public Health, 2017
    Co-Authors: Sebastien David Pion, Flobert Njiokou, Michel Boussinesq, Gustave Simo, Philippe Truc
    Abstract:

    In central Africa, the geographical distribution of human African trypanosomosis (HAT) due to Trypanosoma brucei gambiense overlaps that of Loa Loa and Mansonella perstans filariases. This study investigated whether the presence of blood borne M. perstans and L. Loa microfilariae interferes with the agglutination reaction of CATT (Card Agglutination Test for Trypanosomosis), used for mass screening of HAT. 146 CATT positive participants and 146 age and sex matched CATT negative subjects were recruited in three sites in Cameroon and one in the Republic of Congo. CATT positive persons were not more frequently infected by L. Loa and M. perstans than CATT negative ones. This unique matched case-control study confirmed a previous study and does not bring any evidence of the influence of L. Loa or M. perstans on serodiagnosis of HAT in the field using CATT/ T. b. gambiense LiTat 1.3. HAT screening activities can be performed without controlling for filariasis at the same time.

Amy D Klion - One of the best experts on this subject based on the ideXlab platform.

  • infection associated immune perturbations resolve 1 year following treatment for Loa Loa
    Clinical Infectious Diseases, 2021
    Co-Authors: Amy D Klion, Jesica A Herrick, Michelle Makiya, Nicole Hollandthomas, Thomas B Nutman
    Abstract:

    Background We have previously demonstrated that eosinophil-associated processes underlie some of the differences in clinical presentation among patients with Loa Loa infection prior to therapy and that some posttreatment adverse events appear to be dependent on eosinophil activation. Methods We first conducted a retrospective review of 204 patients (70 microfilaria [MF] positive/134 negative) with Loa Loa both before and following definitive therapy. We then measured filarial-specific antibodies, eosinophil- and Th2-associated cytokines, and eosinophil granule proteins in their banked serum prior to and at 1 year following definitive treatment. We also evaluated the influence of pretreatment corticosteroids and/or apheresis in altering the efficacy of treatment. Results Patients without circulating microfilariae (MF negative) not only had a higher likelihood of peripheral eosinophilia and increased antifilarial antibody levels but also had significantly increased concentrations of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 5, and IL-4 compared with MF-positive patients. However, these differences had all resolved by 1 year after treatment, when all parameters approached the levels seen in uninfected individuals. Neither pretreatment with corticosteroids nor apheresis reduced the efficacy of the diethylcarbamazine used to treat these subjects. Conclusions Our results highlight that, by 1 year following treatment, infection-associated immunologic abnormalities had resolved in nearly all patients treated for loiasis, and pretreatment corticosteroids had no influence on the resolution of the immunologic perturbations nor on the efficacy of diethylcarbamazine as a curative agent in loiasis. Clinical trials registration NCT00001230.

  • feasibility of onchocerciasis elimination using a test and not treat strategy in Loa Loa co endemic areas
    Clinical Infectious Diseases, 2020
    Co-Authors: David J Blok, Joseph Kamgno, Sebastien David Pion, Charles D. Mackenzie, Hugues C Nanadjeunga, Yannick Niamsiemalio, Cedric B Chesnais, Amy D Klion, Daniel A Fletcher, Thomas B Nutman
    Abstract:

    Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa Loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. Loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. Loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. Loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

  • a test and not treat strategy for onchocerciasis elimination in Loa Loa coendemic areas cost analysis of a pilot in the soa health district cameroon
    Clinical Infectious Diseases, 2020
    Co-Authors: Edeltraud J Lenk, Joseph Kamgno, Michel Boussinesq, Hugues C Nanadjeunga, Amy D Klion, Daniel A Fletcher, Henri C Moungui, Christopher Fitzpatrick, Anneclaire Peultier, Thomas B Nutman
    Abstract:

    textabstractBackground. Severe adverse events after treatment with ivermectin in individuals with high levels of Loa Loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. Methods. Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. Results. The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9–$3.6), US$5.2 ($4.5–$8.3), and US$5.4 ($4.6–$8.6), respectively. Conclusions. TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa Loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.

  • 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
    The Lancet Infectious Diseases, 2020
    Co-Authors: Sebastien David Pion, Cedric B Chesnais, Amy D Klion, Charles D Mackenzie, Hugues Nana-djeunga, Yannick Niamsi-emalio, Hugo Deléglise, Wilma Stolk, Daniel Fletcher, Thomas Nutman
    Abstract:

    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 (p99·9%) 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.

  • Loa Loa microfilariae in skin snips: consequences for onchocerciasis monitoring and evaluation in L. Loa endemic areas
    Clinical Infectious Diseases, 2019
    Co-Authors: Hugues Nana-djeunga, Joseph Kubofcik, Sebastien David Pion, Michel Boussinesq, Thomas B Nutman, Floribert Fossuo-thotchum, Cedric B Chesnais, Amy D Klion, Charles D Mackenzie, Joseph Kamgno
    Abstract:

    The specificity of skin snips for onchocerciasis diagnoses is considered to be almost 100%. Our molecular methods revealed that microfilariae emerging from skin snips collected from highly microfilaremic Loa Loa–infected individuals were largely misidentified as Onchocerca volvulus. This has important implications for onchocerciasis diagnostic testing in Loa-endemic areas.

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  • Heterogeneity in the in vitro susceptibility of Loa Loa microfilariae to drugs commonly used in parasitological infections
    Parasites & Vectors, 2018
    Co-Authors: Abdel Jelil Njouendou, Fanny F. Fombad, Maeghan O’neill, Denis Zofou, Chuck Nutting, Patrick C. Ndongmo, Arnaud J. Kengne-ouafo, Timothy G. Geary, Charles D. Mackenzie, Samuel Wanji
    Abstract:

    Background Co-infection with loiasis remains a potential problem in control programs targeting filarial infections. The effects of many anti-parasitic drugs often administered to Loa Loa infected people are not well documented. This study compared the in vitro activity of several of these drugs on the viability of L. Loa microfilariae (mf). Methods Human strain L. Loa mf were isolated from baboon blood using iso-osmotic Percoll gradient, and cultured in RPMI 1640/10% FBS with antimalarial drugs (mefloquine, amodiaquine, artesunate, chloroquine and quinine), anthelmintics (ivermectin, praziquantel, flubendazole and its reduced and hydrolyzed metabolites), two potential trypanocidal agents (fexinidazole and Scynexis-7158) and the anticancer drug imatinib. The drug concentrations used varied between 0.156 μg/ml and 10 μg/ml. Mf motility (CR_50 = 50% immotility) and a metabolic viability assay (MTT) were used to assess the effects of these drugs on the parasites. Results Mf in control cultures showed only a slight reduction in motility after 5 days of culture. Active inhibition of Loa Loa motility was seen with mefloquine and amodiaquine (CR_50 values of 3.87 and 4.05 μg/ml, respectively), immobilizing > 90% mf within the first 24 hours: mefloquine killed the mf after 24 hours of culture at concentrations ≥ 5 μg/ml. SCYX-7158 also induced a concentration-dependent reduction in mf motility, with > 50% reduction in mf motility seen after 5 days at 10 μg/ml. The anticancer drug imatinib reduced mf motility at 10 μg/ml from the first day of incubation to 55% by day 5, and the reduction in motility was concentration-dependent. Praziquantel and fexinidazole were inactive, and FLBZ and its metabolites, as well as ivermectin at concentrations > 5 μg/ml, had very minimal effects on mf motility over the first 4 days of culture. Conclusions The considerable action of the anti-malarial drugs mefloquine and amodiaquine on Loa mf in vitro highlights the possibility of repurposing the existing anti-infectious agents for the development of drugs against loiasis. The heterogeneity in the activity of anti-parasitic agents on Loa Loa mf supports the need for further investigation using animal models of loiasis.

  • Identification and characterization of Loa Loa antigens responsible for cross-reactivity with rapid diagnostic tests for lymphatic filariasis
    2018
    Co-Authors: Marla I. Hertz, Joseph Kamgno, Samuel Wanji, Hugues Nana-djeunga, Abdel Jelil Njouendou, Valerine Chawa Chunda, Amy Rush, Peter U. Fischer, Gary J. Weil, Philip J. Budge
    Abstract:

    The Global Program to Eliminate Lymphatic Filariasis (LF) relies on rapid diagnostic tests (RDTs) to determine where annual mass drug administration for LF is required and when it can be stopped. These tests detect a Wuchereria bancrofti glycoprotein in the blood of infected persons via a carbohydrate moiety recognized by the monoclonal antibodies AD12 and DH6.5. Loiasis cross-reactivity with LF RDTs has recently been recognized as a serious obstacle to LF elimination in loiasis-endemic areas. To better understand the nature of this cross-reactivity, we used the DH6.5 antibody to immunoaffinity purify Loa Loa antigens from the sera of individuals with a positive RDT due to loiasis. Immunoblot analysis revealed many circulating AD12/DH6.5-reactive antigens, and proteomic analysis identified multiple L. Loa proteins in LF RDT-positive loiasis sera. These included both secreted and somatic proteins, suggesting that they may be released by dying L. Loa adult worms and/or microfilariae. Unlike the single high molecular weight W. bancrofti circulating filarial antigen that is reliably present in the blood of persons with bancroftian filariasis, reactive L. Loa antigens appeared to be only transiently present in the blood of a subset of persons with loiasis. These key differences between the circulating antigens of W. bancrofti and L. Loa can be used to differentiate positive results generated by both species and may lead to improved diagnostic tests for LF and loiasis.

  • positivity of antigen tests used for diagnosis of lymphatic filariasis in individuals without wuchereria bancrofti infection but with high Loa Loa microfilaremia
    American Journal of Tropical Medicine and Hygiene, 2016
    Co-Authors: Sebastien David Pion, Joseph Kamgno, Samuel Wanji, Celine Montavon, Thomas B Nutman, Cedric B Chesnais, Amy D Klion, Michel Boussinesq
    Abstract:

    Abstract Since the mid-2000s, the immunochromatographic card test (ICT), a point-of-care test for detecting Wuchereria bancrofti circulating filarial antigens (CFAs), has been the backbone for mapping and monitoring lymphatic filariasis (LF) worldwide. Recently, there have been instances in which CFA positivity has been associated with Loa Loa microfilaremia. Here, we examined the association, at both the community and individual levels, between L. Loa and CFA using additional diagnostic tools (quantitative polymerase chain reaction [qPCR], Og4C3 enzyme-linked immunosorbent assay, and IgG4 antibodies to Wb123 assays) to demonstrate the relationship between L. Loa microfilaremia and ICT positivity. In May 2013, peripheral blood was collected during the day from 1,812 individuals living in southern Cameroon. ICT tests were done on the spot, and positive individuals were resampled at night. Results of qPCR and Wb123 assays concurred proving the absence of W. bancrofti infection. Og4C3 assays indicate a quantitative relationship between the level of L. Loa microfilaremia and that of CFA. This was confirmed by epidemiological analyses, which reveal a strong association between L. Loa microfilaremia and ICT positivity, with 50% of ICT reacting to L. Loa when its microfilarial density exceeds 30,000 microfilariae/mL. At the community level, the proportion of positive ICT would exceed 2% when the prevalence of L. Loa microfilaremia in the total population is above 20%. This has significant implications in terms of mapping and control of LF caused by W. bancrofti in Loa-endemic areas. Cross-reactivity of ICT with L. Loa has to be considered in the context of both individual and community diagnostics.

  • using community level prevalence of Loa Loa infection to predict the proportion of highly infected individuals statistical modelling to support lymphatic filariasis and onchocerciasis elimination programs
    PLOS Neglected Tropical Diseases, 2016
    Co-Authors: Daniela K Schluter, Samuel Wanji, Innocent Takougang, Martial L Ndeffombah, Tony Ukety, Alison P Galvani, Peter J Diggle
    Abstract:

    Lymphatic Filariasis and Onchocerciasis (river blindness) constitute pressing public health issues in tropical regions. Global elimination programs, involving mass drug administration (MDA), have been launched by the World Health Organisation. Although the drugs used are generally well tolerated, individuals who are highly co-infected with Loa Loa are at risk of experiencing serious adverse events. Highly infected individuals are more likely to be found in communities with high prevalence. An understanding of the relationship between individual infection and population-level prevalence can therefore inform decisions on whether MDA can be safely administered in an endemic community. Based on Loa Loa infection intensity data from individuals in Cameroon, the Republic of the Congo and the Democratic Republic of the Congo we develop a statistical model for the distribution of infection levels in communities. We then use this model to make predictive inferences regarding the proportion of individuals whose parasite count exceeds policy-relevant levels. In particular we show how to exploit the positive correlation between community-level prevalence and intensity of infection in order to predict the proportion of highly infected individuals in a community given only prevalence data from the community in question. The resulting prediction intervals are not substantially wider, and in some cases narrower, than the corresponding binomial confidence intervals obtained from data that include measurements of individual infection levels. Therefore the model developed here facilitates the estimation of the proportion of individuals highly infected with Loa Loa using only estimated community level prevalence. It can be used to assess the risk of rolling out MDA in a specific community, or to guide policy decisions.

  • parasitological hematological and biochemical characteristics of a model of hyper microfilariaemic loiasis Loa Loa in the baboon papio anubis
    PLOS Neglected Tropical Diseases, 2015
    Co-Authors: Samuel Wanji, Nicholas Tendongfor, Peter Enyong, Ebanga Joan E Eyong, Che Julius Ngwa, Elive N Esuka, Arnaud J Kengneouafo, Fabrice R Datchouapoutcheu, Adrian Hopkins, Charles D. Mackenzie
    Abstract:

    Background Loiasis, a filarial infection caused by Loa Loa usually thought to cause relatively minor morbidity, can cause serious and often fatal reactions in patients carrying very high levels of circulating Loa Loa microfilariae (mf) following administration of microfilaricidal drugs. An experimental model of this condition would greatly aid the definition of the optimal management of this important clinical presentation. Methodology/Principle Findings Fifteen baboons (Papio anubis) were infected with 600 infective larvae (L3) isolated from Chrysops vector flies. Animals were observed for any clinical changes; blood samples were collected every 1–2 months for 22 months, and analysed for parasitological, hematological and biochemical profiles using standard techniques. All animals became patent but remained clinically normal throughout the study. The parasitological pre-patent period was between 4–8 months, with a majority (60%) of animals becoming patent by 5 months post infection (MPI); all animals were patent by 8 MPI. Microfilarial Loads increased steadily in all animals and reached a peak at 18 MPI. By 10 MPI >70% of animals had mf >8,000 mf/mL, and at 18 MPI >70% of animals had mf >30,000mf/mL with 50% of these animals with mf >50,000mf/mL. Absolute eosinophil, creatinine, Ca2+ and K+ levels were generally above normal values (NV). Positive associations were seen between microfilariaemia and eosinophilia, Hb, Ca2+, and gamma-GT values, whilst significant negative associations were seen between microfilariaemia and potassium, glucose and mononuclear leukocyte levels. Conclusions Infection of splenectomised baboons with L. Loa can induce levels of circulating microfilariae, and corresponding haematological profiles, which parallel those seen in those humans in danger of the severe post-microfilariacide clinical responses. Utilization of this experimental model could contribute to the improved management of the loiasis related adverse responses in humans.