A qualitative assessment of the health systems factors influencing the prevention of malaria in pregnancy using intermittent preventive treatment and insecticide-treated nets in Ghana.

BACKGROUND: Ghana has adopted and implemented intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) and insecticide-treated nets (ITNs) in an antenatal care (ANC) context to prevent malaria among pregnant women. However, the increased ANC attendance and its frequency facilitated by a free maternal health care policy in Ghana does not correspond with the uptake of IPTp-SP and ITN use among pregnant women. This study sought to elucidate the contextual health system factors influencing the delivery of IPTp-SP and ITN from a related quantitative study conducted in Ghana. METHODS: This is the qualitative section of a mixed-methods study design, where audio recorded key informant interviews (KIIs) were conducted with health workers from across health facilities, districts, regional and national health directorates. The KIIs elicited information on health worker knowledge, perceptions, and rationale for the delivery practices of IPTp-SP and ITN revealed in the quantitative findings. The interviews were transcribed and imported into NVivo for analysis. Using the World Health Organization (WHO) Health Systems Framework as the theoretical basis, thematic analysis was conducted under broad themes of the building blocks. Findings are presented in narrative quotes, with a mindmap used to summarize the various health system factors and their interrelated relationship influencing the delivery of IPTp-SP and ITN. RESULTS: Health system factors identified included health staff untrained on malaria delivery directives due to an ineffective trainer of trainer (ToT) system. Additionally, health worker confusion on when to commence SP (at quickening or ≥ 16 weeks) was found to result in delayed start of SP. Stock-outs in facilities due to procurement delays at the national level resulted in missed opportunities to deliver SP to eligible pregnant women at the ANC. Similarly, ITN stock outs led to eligible pregnant women not receiving one at ANC clinics. CONCLUSION: Poor health worker knowledge on policy directives, a consequence of ineffective training strategy led to delayed delivery of IPTp-SP to eligible pregnant women. Supply chain management challenges related to stock of SP and ITN resulted in missed opportunities to deliver the interventions to pregnant women attending ANC.

Prevalence of epilepsy in Ndom Health District (Littoral Region, Cameroon) after long-term ivermectin-based preventive chemotherapy for the control of onchocerciasis.

Assuming the causality relationship between Onchocerca volvulus infection and epilepsy onset, preventive chemotherapy for the control onchocerciasis can result to a significant impact on epilepsy burden. This study aimed at assessing the prevalence of epilepsy in an onchocerciasis endemic area under annual CDTI for 16 years. A cross-sectional survey was conducted in two communities (Kelleng and Nkonkwalla) located in the Ndom Health District (Littoral Region, Cameroon) to assess the prevalence of epilepsy using a standardized questionnaire for non-specialists in tropical areas. Data on the nuisance of onchocerciasis vector and distance of surveyed households to the river were also collected. Epilepsy status was collected from 367 participants (sex ratio (M/F): 1.13). The crude prevalence of epilepsy was estimated at 8.4 % (95 % CI: 5.8-11.8); the highest prevalence was found in females (13.8 %; 95 % CI: 8.8-20.3) compared to males (5.0 %; 95 % CI: 2.4-9.04)) (p-value = 0.02) and in Nkonkwalla (9.0 %; 95 % CI: 5.5-13.6) (p-value = 0.82) compared to Kelleng (7.7 %; 95 % CI: 4.06-13.13). After 16 years of CDTI in Kelleng, crude prevalence of epilepsy decreased from 10.2 % to 7.2 % (p-value = 0.19), whereas the age sex-standardized prevalence dropped from 13.5 % to 7.7 % between 2004 and 2020 (p-value = 0.05). The median age of epilepsy cases shifted from 24 (IQR: 20-30) in 2004 to 28 years (IQR: 23-34) in 2020. The shift in age-specific prevalence over the years suggests a decreasing incidence of epilepsy in areas under long-term CDTI and a significant impact of onchocerciasis control on the prevalence of epilepsy.

Unusual Localization of Blood-Borne Loa loa Microfilariae in the Skin Depends on Microfilarial Density in the Blood: Implications for Onchocerciasis Diagnosis in Coendemic Areas.

BACKGROUND: The diagnostic gold standard for onchocerciasis relies on identification and enumeration of (skin-dwelling) Onchocerca volvulus microfilariae (mf) using the skin snip technique (SST). In a recent study, blood-borne Loa loa mf were found by SST in individuals heavily infected with L. loa, and microscopically misidentified as O. volvulus due to their superficially similar morphology. This study investigates the relationship between L. loa microfilarial density (Loa MFD) and the probability of testing SST positive. METHODS: A total of 1053 participants from the (onchocerciasis and loiasis coendemic) East Region in Cameroon were tested for (1) Loa MFD in blood samples, (2) O. volvulus presence by SST, and (3) Immunoglobulin (Ig) G4 antibody positivity to Ov16 by rapid diagnostic test (RDT). A Classification and Regression Tree (CART) model was used to perform a supervised classification of SST status and identify a Loa MFD threshold above which it is highly likely to find L. loa mf in skin snips. RESULTS: Of 1011 Ov16-negative individuals, 28 (2.8%) tested SST positive and 150 (14.8%) were L. loa positive. The range of Loa MFD was 0-85 200 mf/mL. The CART model subdivided the sample into 2 Loa MFD classes with a discrimination threshold of 4080 (95% CI, 2180-12 240) mf/mL. The probability of being SST positive exceeded 27% when Loa MFD was >4080 mf/mL. CONCLUSIONS: The probability of finding L. loa mf by SST increases significantly with Loa MFD. Skin-snip polymerase chain reaction would be useful when monitoring onchocerciasis prevalence by SST in onchocerciasis-loiasis coendemic areas.

Feasibility of Onchocerciasis Elimination Using a "Test-and-not-treat" Strategy in Loa loa Co-endemic Areas.

BACKGROUND: Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is 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 precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from 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% to 40% precontrol 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 nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 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.

Assessing health system factors affecting access and delivery of IPTp-SP and ITN to pregnant women attending ANC clinics in Ghana.

INTRODUCTION: Malaria interventions including use of Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment (IPTp-SP) and distribution of Insecticide Treated Nets (ITNs) have been implemented through ante-natal clinic (ANC) services in Ghana. Yet, the high ANC attendance is not commensurate with the uptake of these interventions, with missed opportunities to deliver the interventions. This study sought to assess the health system factors affecting access and delivery of IPTp-SP and ITN as defined by the Ghana Malaria Policy Guideline to eligible pregnant women attending ANC clinic sessions. METHODS: A quantitative cross-sectional study was conducted in the Volta Region of Ghana, with data collected across three levels of health care delivery facilities, including hospitals, health centres and Community-Based Health Planning Service (CHPS) compounds. Data collection included structured observation checklists to document the communication and interaction between the ANC health staff and pregnant women. Additionally, structured questionnaires were used to elicit information on cadre, trainings attended, knowledge and delivery practices of health workers on IPTp-SP and ITN. Stata 16 was used for data analysis, and a defined delivery algorithm was used to compute appropriate and inappropriate delivery practices, using the Ghana policy directive as a guide. Predictors of appropriate delivery were determined using logistic regression analysis. RESULTS: Approximately 97% of the 680 ANC observations had complete information for analysis. Of these, 78% (511/657) were eligible for IPTp-SP after excluding women who have less than 16 weeks of gestation, G6PD deficient, malaria positive and have taken 5 doses of IPTp-SP prior to day of observation. Appropriate delivery of IPTp-SP was 76% (390/511). Despite the availability of SP, 15% (75/511) of all eligible women were not offered the medication and 37% (44/119) of inappropriate delivery was recorded during periods of stock out. ITNs were appropriately delivered to 59% (139) out of 237 eligible women. Thirty-two percent (77/237) of eligible women, mostly continuing ANC clients, were not given ITN despite stock availability. CONCLUSIONS: IPTp-SP was appropriately delivered to most of the eligible pregnant women compared to ITN. While stock out of both intervention could account for inappropriate delivery, despite stock availability, IPTp-SP and ITN were not delivered to some eligible women.

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.

BACKGROUND: 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.

A Test-and-Not-Treat Strategy for Onchocerciasis in Loa loa-Endemic Areas.

BACKGROUND: Implementation 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. METHODS: A 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 for posttreatment adverse events was performed daily for 6 days. RESULTS: From August through October 2015, a total of 16,259 of 22,842 persons 5 years of age or older (71.2% of the target population) were tested for L. loa microfilaremia. Among the participants who underwent testing, a total of 15,522 (95.5%) received ivermectin, 340 (2.1%) were excluded from ivermectin distribution because of an L. loa microfilarial density above the risk threshold, and 397 (2.4%) were excluded because of pregnancy or illness. No serious adverse events were observed. Nonserious adverse events were recorded in 934 participants, most of whom (67.5%) had no detectable L. loa microfilariae. CONCLUSIONS: The LoaScope-based test-and-not-treat strategy enabled the reimplementation of community-wide ivermectin distribution in a heretofore "off limits" health district in Cameroon and is a potentially practical approach to larger-scale ivermectin treatment for lymphatic filariasis and onchocerciasis in areas where L. loa infection is endemic. (Funded by the Bill and Melinda Gates Foundation and others.).

Safety of high-dose ivermectin: a systematic review and meta-analysis.

BACKGROUND: Ivermectin is a key anthelmintic for the control of neglected tropical diseases. The main indications for population-level control with ivermectin through mass drug administration are onchocerciasis and lymphatic filariasis; however, there is interest in using higher, fixed-dose regimens for the control of scabies, soil-transmitted helminths and malaria. Safety data for these higher-dose regimens are needed. METHODS: A systematic literature review and meta-analysis on the safety and doses of ivermectin was conducted. Eligible studies reported patient-level data and, for the meta-analysis, clinical trials reporting data on doses ≥200 and ≥400 µg/kg were included. Incidence ratios were used to compare adverse events by severity and organ system affected. RESULTS: The systematic search identified six studies for inclusion, revealing no differences in the number of individuals experiencing adverse events. A descriptive analysis of these clinical trials for a variety of indications showed no difference in the severity of the adverse events between standard (up to 400 µg/kg) and higher doses of ivermectin. Organ system involvement only showed an increase in ocular events in the higher-dose group in one trial for the treatment of onchocerciasis, all of them transient and mild to moderate in intensity. CONCLUSIONS: Although within this review the safety of high-dose ivermectin appears to be comparable to standard doses, there are not enough data to support a recommendation for its use in higher-than-approved doses. Ocular adverse events, despite being transient, are of concern in onchocerciasis patients. These data can inform programme managers and guide operational research activities as new approaches for the use of ivermectin are evaluated.

Community-based door to door census of suspected people living with epilepsy: empowering community drug distributors to improve the provision of care to rural communities in Cameroon.

BACKGROUND: Epilepsy is a severe neurological disorder with huge psychological, social, and economic consequences, including premature deaths and loss of productivity. Sub-Saharan Africa carries the highest burden of epilepsy. The management of epilepsy in Cameroon remains unsatisfactory due to poor identification of cases and a limited knowledge of the distribution of the disease. The objective of this study was to determine whether community drug distributors (CDDs) - volunteers selected by their communities to distribute ivermectin against onchocerciasis and who have been proven efficient to deliver other health interventions such as insecticide-treated bed nets to prevent malaria, vitamin A tablets, and albendazole to treat soil transmitted helminthiasis - can be used to reliably identify people living with epilepsy to promote better management of cases. METHODS: This study was carried out in three health Districts in Cameroon. An exhaustive house to house census was carried out by trained CDDs under the supervision of local nurses. In each household, all suspected cases of epilepsy were identified. In each health district, five communities were randomly selected for a second census by trained health personnel (research team). The results of the two censuses were compared for verification purposes. RESULTS: A total of 53,005 people was registered in the 190 communities surveyed with 794 (1.4%) individuals identified as suspected cases of epilepsy (SCE) by the CDDs. In the 15 communities where the SCE census was verified, the average ratio between the number of suspected cases of epilepsy reported in a community by the research team and that reported by the CDDs was 1.1; this ratio was < 0.8 and > 1.2 in 6 communities. CONCLUSIONS: The results of this study suggest that CDDs, who are present in about 200,000 communities in 31 Sub Saharan African countries where onchocerciasis is endemic, can be successfully used to assess epilepsy prevalence, and therefore map epilepsy in many African countries.

Loa loa Microfilariae in Skin Snips: Consequences for Onchocerciasis Monitoring and Evaluation in L. loa-Endemic Areas.

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.

Prevalence and intensity of Loa loa infection over twenty-three years in three communities of the Mbalmayo health district (Central Cameroon).

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 < 0.0001), and displayed a convex in form trends with age groups. The follow up over 23 years revealed that both the rate and intensity of infection were similar to baseline. CONCLUSIONS: The prevalence and intensity of Loa loa infection 23 years on is stable over time, indicating that this filarial disease might be noncumulative as regarded till now.

High snakebite underreporting rate in the Centre Region of Cameroon: an observational study.

BACKGROUND: In Cameroon, since the first epidemiological week held in 2015, snakebites have been registered among Potential Epidemic Diseases (PED). In the Centre Region, the most densely populated of the country, weekly reports of snakebites are generated at health districts level for monthly data updates. METHODS: To contribute to the better management of snakebite cases, an observational study was conducted to assess the snakebite reporting rate in the Centre Region of Cameroon. The results of this retro-prospective survey were confronted to those of the weekly epidemiological surveillance system, recorded in the PED regional data base. RESULTS: The incidence of bites was relatively high (36.6 bites per 100,000 inhabitants), as well as the general attack rate (about 49 envenomations per 100 victims). The lethality recorded was 2.5% and the mortality was about 1 death per 100,000 inhabitants a year. The sex ratio was largely female biased (61.6%). The bites occurred mostly during the rainy season (73.0%). Bitten victims were mainly farmers (47.4%), and agriculture was the main risk factor. The comparative analysis of the data suggested a high non-reporting rate of snakebite cases (67.8%). CONCLUSION: Snakebite is an endemic condition in the Centre Region of Cameroon. Because of the high rate of non-reporting of cases, the collection of information from the registers of the health facilities only appears not enough to assess the real importance of envenomation in this Region.

Familial Aggregation and Heritability of Loa loa Microfilaremia.

Background: For a given prevalence of Loa loa microfilaremia, the proportion of people with high densities varies significantly between communities. We hypothesized that this variation is related to the existence of familial clusters of hypermicrofilaremic individuals that would be the consequence of a genetic predisposition to present high L. loa microfilarial densities. Methods: A familial study was performed in 10 villages in the Okola Health District of Cameroon. Intrafamilial correlation coefficients and heritability estimates were assessed for both the presence of L. loa microfilaremia and individual microfilarial densities by controlling for age, sex, Mansonella perstans coinfection, and household effects. Results: Pedigrees were constructed for 1126 individuals. A significant familial susceptibility to be microfilaremic for L. loa was found for first-degree relatives (ρ = 0.08, P < .05; heritability = 0.23). Regarding individual microfilarial densities, a significant familial aggregation was demonstrated (ρ = 0.36 for first-degree and 0.27 for second-degree relatives). For first-degree relatives, the highest coefficient was found between mothers and daughters (ρ = 0.57). The overall heritability estimate for L. loa microfilarial density was 0.24 (P = .003). Conclusions: A significant genetic component governs L. loa microfilarial density. This supports the hypothesis that a genetic predisposition to be hypermicrofilaremic exists, leading to the presence of familial clusters of individuals at risk for postivermectin severe adverse events. This finding should be taken into account while developing sampling strategies (including a household-level sampling) to identify villages where community-directed treatment with ivermectin cannot be applied.

Macrofilaricidal Efficacy of Repeated Doses of Ivermectin for the Treatment of River Blindness.

BACKGROUND: Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques. METHODS: Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon. RESULTS: Multiple doses of ivermectin have a partial macrofilaricidal and a modest permanent sterilizing effect after 4 or more consecutive treatments, even at routine MDA doses (150 µg/kg) and frequencies (annual). The life expectancy of adult O. volvulus is reduced by approximately 50% and 70% after 3 years of annual or 3-monthly (quarterly) exposures to ivermectin. CONCLUSIONS: Our quantification of macrofilaricidal and sterilizing effects of ivermectin should be incorporated into transmission models to inform onchocerciasis elimination efforts in Africa and residual foci in Latin America. It also provides a framework to assess macrofilaricidal candidate drugs currently under development.

Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection.

Background: Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology. Methods: Twelve patients with loiasis and microfilarial counts <2000 mf/mL were randomized to receive single-dose DEC (8 mg/kg) or IVM (200 µg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment. Results: Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups. Conclusions: Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology. Clinical Trials Registration: NCT01593722.

Loss of sensitivity of immunochromatographic test (ICT) for lymphatic filariasis diagnosis in low prevalence settings: consequence in the monitoring and evaluation procedures.

BACKGROUND: Diagnostic tools for lymphatic filariasis (LF) elimination programs are useful in mapping the distribution of the disease, delineating areas where mass drug administrations (MDA) are required, and determining when to stop MDA. The prevalence and burden of LF have been drastically reduced following mass treatments, and the evaluation of the performance of circulating filarial antigen (CFA)-based assays was acknowledged to be of high interest in areas with low residual LF endemicity rates after multiple rounds of MDA. The objective of this study was therefore to evaluate the immunochromatographic test (ICT) sensitivity in low endemicity settings and, specifically, in individuals with low intensity of lymphatic filariasis infection. METHODS: To perform this study, calibrated thick blood smears, ICT and Og4C3 enzyme-linked immunosorbent assay (ELISA) were carried out by night to identify Wuchereria bancrofti microfilarial and circulating filarial antigen carriers. A threshold determination assay regarding ICT and ELISA was performed using serial plasma dilutions from individuals with positive microfilarial counts. RESULTS: All individuals harbouring microfilariae (positive blood films) were detected by ICT and ELISA, but among individuals positive for ELISA, only 35.7 % of them were detected using ICT (Chi square: 4.57; p-value = 0.03), indicating a moderate agreement between both tests (kappa statistics = 0.49). Threshold determination analyses showed that ELISA was still positive at the last plasma dilution with negative ICT result. CONCLUSIONS: These findings suggest a loss of sensitivity for ICT in low endemicity settings, especially in people exhibiting low levels of circulating filarial antigen, raising serious concern regarding the monitoring and evaluation procedures in the framework of LF elimination program.

Loop-mediated isothermal amplification for rapid and semiquantitative detection of Loa loa infection.

Rapid and accurate tests are currently needed to identify individuals with high levels of Loa loa microfilaria (mf), so that these individuals may be excluded from mass ivermectin administration campaigns against onchocerciasis and lymphatic filariasis being conducted in areas where Onchocerca volvulus, Wuchereria bancrofti, and L. loa are coendemic. To address this need, colorimetric loop-mediated isothermal amplification (LAMP) assays targeting the L. loa-specific gene sequences LLMF72 and LLMF342 were developed for the detection and quantification of L. loa microfilaremia. Both LAMP assays were highly specific (100%) for L. loa infection compared to the absence of infection or infection with related filarial pathogens. The LLMF72-based LAMP assay showed greater analytic sensitivity (limit of detection, 0.1 pg/ml of genomic DNA [gDNA] and/or 5 mf/ml) than the LLMF342-based LAMP assay (10 pg/ml of gDNA and/or 50 mf/ml), and its analytic sensitivity was similar to that of LLMF72-based quantitative PCR (qPCR). A high level of correlation was observed between microfilaria counts as determined by LLMF72-based qPCR and time to positivity by the LAMP assay, and performance measures of sensitivity, specificity, and positive and negative predictive values were similar for both assays when applied to field-collected clinical samples. By simply varying the run time, the LAMP assay was able to accurately distinguish individuals at risk for serious adverse events (SAEs) after exposure to ivermectin, using thresholds of >5,000 mf/ml and >30,000 mf/ml as indicators of increasing levels of risk. In summary, LLMF72 LAMP represents a new molecular diagnostic tool that is readily applicable as a point-of-care method for L. loa microfilarial detection and quantification in resource-limited countries where L. loa infection is endemic.

Significant reduction of blackfly densities in persistent onchocerciasis area following pilot implementation of an environment friendly approach (Slash and Clear).

The effectiveness of the "Slash and Clear" method in reducing blackfly populations in low transmission areas is established, but its impact in high transmission settings with large rivers and dense vectors is yet to be proven. A community-based intervention study was conducted in the Mbam Valley, Centre Cameroon, involving two sites: Bayomen (control) and Biatsota (intervention). In each arm, baseline blackfly densities were collected over one year using the human landing method. The intervention consisted of destroying the trailing vegetation where blackflies breed. Blackfly densities were collected post-intervention to assess the impact of the intervention. Post-intervention data showed a 50.8% reduction in blackfly density in Biatsota (mean number of collected blackflies from 1936 to 953), while a reduction of 26.7% was observed in Bayomen (mean number of collected blackflies from 2418 to 1774). The reduction rate attributable to the intervention was 32.9%. Statistical analysis confirmed that the reduction in blackfly density was significantly greater in the intervention site. This study demonstrates the feasibility and significant impact of the "Slash and Clear" method in high transmission areas. However, further research is required to assess its long-term effects and determine how this strategy can be scaled up and sustained until onchocerciasis elimination is achieved.

Correction: Ivermectin and doxycycline treatments against Onchocerciasis: Adaptations and impact among semi-nomadic population in Massangam Health District, Cameroon.

[This corrects the article DOI: 10.1371/journal.pntd.0011463.].