Impact of short-term discontinuation of ivermectin-based chemoprevention on onchocerciasis transmission in endemic settings with long history of mass drug administration.

BACKGROUND: The control of onchocerciasis currently relies on annual distribution of single dose ivermectin. Because ivermectin has minimal effects on the adult parasite, mass drug administration (MDA) campaigns against onchocerciasis require at least 15 years of annual uninterrupted ivermectin distribution. Mathematical models have predicted that short-term disruption of MDA (as was seen during COVID-19) could impacted the microfilaridermia prevalence depending on the pre-control endemicity and the histories of treatment, requiring corrective measures (such as biannual MDA) to mitigate the effect on onchocerciasis elimination. Field evidence supporting this prediction, however, has yet to be gathered. This study aimed to assess the impact of ~2 years disruption of MDA on onchocerciasis transmission indicators. METHODOLOGY: A cross-sectional survey was carried out in 2021 in seven villages of Bafia and Ndikinimeki, two health districts located in the Centre Region, Cameroon, where MDA has been ongoing for two decades, but interrupted in 2020 as a response to the COVID-19 pandemic. Volunteers aged 5 years and above were enrolled for clinical and parasitological examinations for onchocerciasis. Data were compared with pre-COVID-19 prevalence and intensity of infection from the same communities to measure changes over time. PRINCIPAL FINDINGS: A total of 504 volunteers (50.3% males), aged 5-99 years (Median: 38; IQR: 15-54) was enrolled in the two health districts. The overall prevalence of microfilaridermia in 2021 was similar in Ndikinimeki health district (12.4%; 95% CI: 9.7-15.6) and Bafia health district (15.1%; 95% CI: 11.1-19.8) (p-value = 0.16). Microfilaridermia prevalences were either similar between 2018 and 2021 in the communities of Ndikinimeki health district (19.3% vs 12.8% (p = 0.057) for Kiboum 1; and 23.7% vs 21.4% (p = 0.814) for Kiboum 2), or higher in 2019 compared to 2021 in the communities of Bafia health district (33.3% vs 20.0% (p = 0.035) for Biatsota). The mean microfilarial densities in these communities dropped from 5.89 (95% CI: 4.77-7.28) mf/ss to 2.4 (95% CI: 1.68-3.45) mf/ss (p-value < 0.0001), and from 4.81 (95% CI: 2.77-8.31) mf/ss to 4.13 (95% CI: 2.49-6.86) mf/ss (p-value < 0.02) in Bafia and Ndikinimeki health districts, respectively. Community Microfilarial Load (CMFL) dropped from 1.08-1.33 mf/ss in 2019 to 0.052-0.288 mf/ss in 2021 in Bafia health district while remaining stable in the Ndikinimeki health district. CONCLUSION/SIGNIFICANCE: The continued decline in prevalence and CMFL observed ~2 years after MDA disruption is consistent with mathematical predictions (ONCHOSIM) and shows that additional efforts and resources are not needed to mitigate the effects of short-term MDA disruption in highly endemic settings prior to intervention with long treatment histories.

Exposition of Intermediate Hosts of Schistosomes to Niclosamide (Bayluscide WP 70) Revealed Significant Variations in Mortality Rates: Implications for Vector Control.

(1) Background: Schistosomiasis remains a public health issue in Cameroon. Snail control using Niclosamide can prevent schistosome transmission. It is safe to determine lethal concentrations for the population. This study aimed at assessing the toxicity of Niclosamide on different developmental stages of snail populations; (2) Methods: Snails were collected, identified, and reared in the laboratory. Egg masses and adult snails were exposed to Niclosamide, at increasing concentrations (0.06, 0.125, 0.25, 0.5, 1 mg/L for egg embryos and 0.06, 0.08, 0.1, 0.12, 0.14, 0.16, 0.18, 0.2 mg/L for adults). After 24 h exposure, egg masses and snails were removed from Niclosamide solutions, washed with source water and observed; (3) Results: Snail susceptibility was species and population dependent. For egg embryos, Biomphalaria pfeifferi was the most susceptible (LC50: 0.1; LC95: 6.3 mg/L) and Bulinus truncatus the least susceptible (LC50: 4.035; LC95: 228.118 mg/L). However, for adults, B. truncatus was the most susceptible (mortality rate: 100%). The LC50 and LC95 for Bi. camerunensis eggs were 0.171 mg/L and 1.102 mg/L, respectively, and were higher than those obtained for adults (0.0357 mg/L and 0.9634 mg/L); (4) Conclusion: These findings will guide the design of vector control strategies targeting these snail species in Cameroon.

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.

Loiasis is endemic in the Ndikinimeki Health District (Centre Region, Cameroon) but does not represent a hindrance to onchocerciasis elimination.

Community-Directed Treatment with Ivermectin (CDTI) is the strategy of choice to fight onchocerciasis in Africa. In areas where loiasis is endemic, onchocerciasis control and/or elimination is hindered by severe adverse events (SAEs) occurring after ivermectin mass treatments. This study aimed at (i) investigating the impact of two decades of CDTI on L. loa clinical and parasitological indicators in the Ndikinimeki Health District, and (ii) assessing the risk of SAEs after this long-term preventive chemotherapy. A cluster-based cross-sectional survey was conducted in the six Health Areas of the Ndikinimeki Health District. All volunteers underwent day-time calibrated thick blood smears to search for L. loa microfilariae, as well as an interview to assess the history of migration of eye worm and Calabar swelling. The overall prevalence of L. loa microfilaraemia was 2.2 % (95% CI: 1.3-3.7%), and the proportions of individuals who had already experienced eye worm and/or Calabar swelling were 1.0% and 0.5%, respectively. The mean microfilarial density was 63.55 (SD: 559.17; maximum: 9220.0) mf/mL. These findings indicate that (i) the long-term ivermectin-based preventive chemotherapy against onchocerciasis significantly reduced L. loa clinical and parasitological indicators, and (ii) the risk of developing neurologic and potentially fatal SAE after ivermectin mass treatment is zero in the Ndikinimeki Health District.

An Integrated Approach to Assess Knowledge/Perceptions and Attitudes/Practices (KAP) Regarding Major Neglected Tropical Diseases Endemic in the Mbengwi Health District, North West Region, Cameroon.

BACKGROUND AND OBJECTIVES: Preventive chemotherapy (PCT) is the main strategy currently used to control and/or eliminate onchocerciasis, lymphatic filariasis (LF) and soil transmitted helminthiasis (STH), and community participation (through implementation or adherence to PCT) is critical. This study aimed at investigating knowledge/perceptions of populations of the Mbengwi health district (North West Region, Cameroon), in relation to their attitudes/practices regarding the most prevalent neglected tropical diseases (NTDs). METHODS: A household-based cross-sectional survey was carried out in the Mbengwi health district (North West Region, Cameroon) using the cluster sampling technique. Clusters were selected using the probability proportionate to estimate size strategy. In each cluster, the random walk technique was used for the selection of households, and a structure questionnaire was administered to 2-3 of its members. RESULTS: A total of 254 households from 26 clusters were visited, and 514 individuals were interviewed. The sex ratio of interviewees (1.08) was unbiased, and their ages ranged between 10 and 99 years old. Though most of the respondents declared having already heard of these NTDs (41.6%, 73.9% and 90.5% for onchocerciasis, LF and STH, respectively), only a minority of them were aware of how they are acquired/transmitted (8.9%, 9.2% and 32.7% for onchocerciasis, LF and STH, respectively), or prevented (23.1%, 18.9% and 47.2% for onchocerciasis, LF and STH, respectively). CONCLUSIONS: This study revealed poor knowledge/perceptions and wrong attitudes/practices of interviewees as regards to these NTDs, and these misconceptions can seriously affect the adherence and contribution of populations to the success of PCTs. It appears compulsory to reinforce information, education, and communication, with a focus on the rationale and importance behind PCTs, to optimize/improve community participation.

Differences in malaria and haematocrit presentation in children living in different settings, North West Region, Cameroon.

BACKGROUND: Malaria continues to be a major cause of morbidity and mortality in Cameroon. With all efforts being made to eliminate malaria, it is imperative to describe the epidemiology of the disease in different parts of the country in order to inform control policies. This study aimed to present the differences in the prevalence and intensity of malaria and the anaemic status of children living in different areas of the North West region of Cameroon. MATERIALS AND METHODS: This study was carried out from April 2016-July 2017. Blood samples were collected from children via finger pricking. Stained thick and thin blood films were examined through microscopy (x100) to detect the presence of parasites and to estimate the geometric mean parasite density (GMPD). Packed cell volume (PCV) values were determined by micro-centrifugation. Data was analysed using SPSS to determine proportions and test for significance levels between these. RESULTS: Overall prevalence of malaria was 45.3%. Awing and Obang recorded the highest prevalence while Mankon and Nkwen recorded the lowest (p=0.01). The GMPD of infection was highly heterogeneous between the different localities (p=0.03). Age significantly affected the prevalence of malaria (p=0.02). Sex did not affect the prevalence nor the GMPD of malaria infection (p>0.05). Overall mean PCV value was 32.9±3.9. Localities in urban settings recorded the highest mean PCV values compared to those in rural settings (p=0.68). Sex and age did not affect mean PCV values (p>0.05). CONCLUSION: Malaria still remains a major problem in the North West region of Cameroon. Malaria control interventions should therefore be based on evident spatial and temporal heterogeneity of Plasmodium species in a particular area so as not to waste resources that would only be of limited effectiveness and value to the populations at risk.

Point prevalence mapping reveals hotspot for onchocerciasis transmission in the Ndikinimeki Health District, Centre Region, Cameroon.

BACKGROUND: Ivermectin-based preventive chemotherapy (PC) is distributed annually to all at-risk populations eligible for ivermectin treatment to control and/or eliminate onchocerciasis. Information on the impact of mass ivermectin administration on onchocerciasis transmission is scanty, and it is tricky to appreciate the progress towards elimination and engage corrective measures. To fill that gap in the Centre Region in Cameroon, the current onchocerciasis endemicity level in the Ndikinimeki Health District after about two decades of mass treatments was assessed. METHODS: A cluster-based cross-sectional survey was carried out in the Ndikinimeki Health District and all volunteers aged ≥ 5 years were (i) interviewed on their compliance to ivermectin over the past five years and (ii) underwent clinical (nodule palpation and visual search for onchocercal lesions) and parasitological examinations (skin snip) for onchocerciasis. RESULTS: The overall Onchocerca volvulus prevalence was 7.0% (95% CI: 5.2-9.3%). The prevalence of the disease was significantly higher in the communities Kiboum 1 and Kiboum 2 compared to the other communities (highest prevalence in Makénéné Town Water: 8.5%; 95% CI: 2.3-20.4%) (χ2 = 51.314, df = 11, P = 0.0001). The proportion of systematic non-compliers to ivermectin was 23.3% (95% CI: 19.9-27.1%) among individuals interviewed. In the sentinel sites (Kiboum communities), onchocerciasis prevalence decreased from 95.2% (95% CI: 88.3-98.1%) to 23.7% (95% CI: 14.7-36.0%). CONCLUSIONS: This study has revealed that the Ndikinimeki Health District is hypo-endemic for onchocerciasis after about two decades of preventive chemotherapy. However, transmission is ongoing, with potential hotspots in the Kiboum 1 and Kiboum 2 communities, which are known as first-line communities (closest to the breeding sites of the vector). Alternative or complementary strategies to annual ivermectin appear compulsory to accelerate the momentum towards onchocerciasis elimination.

Identifying thresholds for classifying moderate-to-heavy soil-transmitted helminth intensity infections for FECPAKG2, McMaster, Mini-FLOTAC and qPCR.

The World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworm and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings.

Evaluation of circulating cathodic antigen (CCA) urine-tests for diagnosis of Schistosoma mansoni infection in Cameroon.

BACKGROUND: The Kato-Katz is the most common diagnostic method for Schistosoma mansoni infection. However, the day-to-day variability in host egg-excretion and its low detection sensitivity are major limits for its use in low transmission zones and after widespread chemotherapy. We evaluated the accuracy of circulating cathodic antigen (CCA) urine-assay as a diagnostic tool of S. mansoni. In comparison, a low sensitive CCA test (CCA-L) was assessed. METHODOLOGY: THE STUDY WAS CONDUCTED IN THREE SETTINGS: two foci with single S. mansoni infections (settings A and B), and one mixed S. mansoni - S. haematobium focus (setting C). Stool and urine samples were collected from school-children on three consecutive days. Triplicate Kato-Katz readings were performed per stool sample. Each urine sample was tested with one CCA and only the first urine sample was subjected to CCA-L. Urine samples were also examined for S. haematobium eggs using the filtration method and for microhaematuria using urine reagent strips. Overall, 625 children provided three stool and three urine samples. PRINCIPAL FINDINGS: Considering nine Kato-Katz thick smears as 'reference' diagnostic test, the prevalence of S. mansoni was 36.2%, 71.8% and 64.0% in settings A, B and C, respectively. The prevalence of S. haematobium in setting C was 12.0%. The sensitivities of single Kato-Katz, CCA and CCA-L from the first stool or urine samples were 58%, 82% and 46% in setting A, 56.8%, 82.4% and 68.8% in setting B, and 49.0%, 87.7% and 55.5% in setting C. The respective specificities were 100%, 64.7% and 100%; 100%, 62.3% and 91.3%; and 100%, 42.5% and 92.0%. Mixed infection with S. haematobium did not influence the CCA test results for S. mansoni diagnosis. CONCLUSIONS/SIGNIFICANCE: Urine CCA revealed higher sensitivity than CCA-L and triplicate Kato-Katz, and produced similar prevalence as nine Kato-Katz. It seems an attractive method for S. mansoni diagnosis.

Mapping of schistosomiasis and soil-transmitted helminthiasis in the regions of centre, East and West Cameroon.

BACKGROUND: Schistosomiasis and soil-transmitted helminthiasis (STH) are widely distributed in Cameroon. Although mass drug administration (MDA) of mebendazole is implemented nationwide, treatment with praziquantel was so far limited to the three northern regions and few health districts in the southern part of Cameroon, based on previous mapping conducted 25 years ago. To update the disease distribution map and determine where treatment with praziquantel should be extended, mapping surveys were conducted in three of the seven southern regions of Cameroon, i.e. Centre, East and West. METHODOLOGY: Parasitological surveys were conducted in April-May 2010 in selected schools in all 63 health districts of the three targeted regions, using appropriate research methodologies, i.e. Kato-Katz and urine filtration. PRINCIPAL FINDINGS: The results showed significant variation of schistosomiasis and STH prevalence between schools, villages, districts and regions. Schistosoma mansoni was the most prevalent schistosome species, with an overall prevalence of 5.53%, followed by S. haematobium (1.72%) and S. guineensis (0.14%). The overall prevalence of schistosomiasis across the three regions was 7.31% (95% CI: 6.86-7.77%). The prevalence for Ascaris lumbricoides was 11.48 (95% CI: 10.93-12.04%), Trichuris trichiura 18.22% (95% CI: 17.56-18.90%) and hookworms 1.55% (95% CI: 1.35-1.78%), with an overall STH prevalence of 24.10% (95% CI: 23.36-24.85%) across the three regions. STH was more prevalent in the East region (46.57%; 95% CI: 44.41-48.75%) in comparison to the Centre (25.12; 95% CI: 24.10-26.17%) and West (10.49%; 95% CI: 9.57-11.51%) regions. CONCLUSIONS/SIGNIFICANCE: In comparison to previous data, the results showed an increase of schistosomiasis transmission in several health districts, whereas there was a significant decline of STH infections. Based on the prevalence data, the continuation of annual or bi-annual MDA for STH is recommended, as well as an extension of praziquantel in identified moderate and high risk communities for schistosomiasis.

Assessment of the anthelmintic efficacy of albendazole in school children in seven countries where soil-transmitted helminths are endemic.

BACKGROUND: The three major soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are among the most widespread parasites worldwide. Despite the global expansion of preventive anthelmintic treatment, standard operating procedures to monitor anthelmintic drug efficacy are lacking. The objective of this study, therefore, was to define the efficacy of a single 400 milligram dose of albendazole (ALB) against these three STH using a standardized protocol. METHODOLOGY/PRINCIPAL FINDINGS: Seven trials were undertaken among school children in Brazil, Cameroon, Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the McMaster egg counting technique to determine fecal egg counts (FEC). Overall, the highest CRs were observed for A. lumbricoides (98.2%) followed by hookworms (87.8%) and T. trichiura (46.6%). There was considerable variation in the CR for the three parasites across trials (country), by age or the pre-intervention FEC (pre-treatment). The latter is probably the most important as it had a considerable effect on the CR of all three STH. Therapeutic efficacies, as reflected by the FECRs, were very high for A. lumbricoides (99.5%) and hookworms (94.8%) but significantly lower for T. trichiura (50.8%), and were affected to different extents among the 3 species by the pre-intervention FEC counts and trial (country), but not by sex or age. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that a FECR (based on arithmetic means) of >95% for A. lumbricoides and >90% for hookworms should be the expected minimum in all future surveys, and that therapeutic efficacy below this level following a single dose of ALB should be viewed with concern in light of potential drug resistance. A standard threshold for efficacy against T. trichiura has yet to be established, as a single-dose of ALB is unlikely to be satisfactory for this parasite. TRIAL REGISTRATION: ClinicalTrials.gov NCT01087099.