Relationship between skin snip and Ov16 ELISA: Two diagnostic tools for onchocerciasis in a focus in Cameroon after two decades of ivermectin-based preventive chemotherapy.

BACKGROUND: Onchocerciasis elimination currently relies on repeated ivermectin-based preventive chemotherapy. Current World Health Organization's guidelines strongly recommend, though with low evidence of certainty, the use of Ov16 serology testing in children younger than 10 years old to assess whether mass drugs administration can be safely stopped. Therefore, more evidences are needed to support the use of this marker as sero-evaluation tool. This study aimed at determining the relationship between microfilaridermia and anti-Ov16 IgG4, and their variation according to age, gender and ivermectin intake history. METHODOLOGY: A cross-sectional survey was conducted in an area where ivermectin-based MDA has been implemented since more than 20 years. A questionnaire was used to record ivermectin intake history for the last 5 years. All volunteers aged ≥2 years were tested for microfilaridermia. IgG4 antibodies against Ov16 antigen were determined using the Standard Diagnostic Ov16 IgG4 ELISA kits and the recombinant anti-Ov16 AbD19432 antibodies. Prevalences, microfilaridermia counts and IgG4 concentrations were compared with regards to age, gender and history of ivermectin intake. PRINCIPAL FINDINGS: The prevalence of skin microfilariae was 23.4% (95% CI: 23.4-30.8), whereas Ov16 seroprevalence was 53.2% (95% CI: 47.9-58.4). A moderate positive percentage agreement (50.4%) and a high negative percentage agreement (69.2%) was found between skin snip and Ov16 serology in the whole population, while in children aged <10 years, the agreements were higher (positive percentage agreement: 62.6%; negative percentage agreement: 83.5%). In addition, no associations were found between ivermectin intake, Mf counts and estimated IgG4 concentration of participants. Anti-Ov16 IgG4 were higher in individuals harboring microfilariae than their negative counterparts (p<0.0001), though a negative correlation was found between skin microfilarial counts and anti-Ov16 IgG4 levels (r = -0.2400; p = 0.03). No variation in microfilarial counts according to age and gender was observed. Though positively correlated with age (r = 0.4020; p<0.0001), IgG4 was significantly different between the different age classes (p<0.0001). CONCLUSION/SIGNIFICANCE: Our results revealed moderate positive and negative agreements between parasitological and immunological parameters of onchocerciasis infection after several rounds MDA. Anti-Ov16 IgG4 levels increased with age but decreased with microfilarial counts, suggesting a variation of anti-Ov16 IgG4 as a result of constant exposure and accumulation of infection. This brings evidence sustaining the use of Ov16 serology in children as evaluation tool. However, additional investigations are needed to further reshape the appropriate age range among children aged <10 years old.

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.

Leishmaniasis in Cameroon: what is known and is done so far? A protocol for systematic review.

INTRODUCTION: The first visceral and cutaneous leishmaniasis cases were reported in Cameroon since more than six decades. However, interest in the disease has decreased over time and data on its epidemiology across the country are scanty. This systematic review aims to update data on what is known and done so far on leishmaniasis in Cameroon. METHODS AND ANALYSIS: PubMed/MEDLINE, EMBASE and Web of Science will be searched from inception onwards. Grey literature will be identified through Google Scholar searches, dissertation databases and other relevant documents such as report of the National Control Program. Searches will be conducted between January and February 2021. All studies reporting endemicity, distribution, infecting species, vectors and reservoirs will be eligible. The main outcomes will be epidemiological data (infection rate, distribution, infecting species, vectors and animal reservoir), while the secondary outcomes will be the cases management (diagnostic, treatment, reporting, intervention…). Two reviewers will independently screen eligible papers, and potential conflicts will be resolved by involving a third reviewer as an adjudicator. Methodological quality including bias will be appraised using a methodological quality critical appraisal checklist proposed in the Joanna Briggs Institute systematic review methods manual. A narrative synthesis will describe quality and content of the epidemiological evidence. Data on prevalence and vectors will be used to draw thematic maps of the distribution of leishmaniasis in Cameroon. ETHICS AND DISSEMINATION: This study will not require ethical approval as it will be based on already published or unpublished data. The final report of this review will be published in a peer-reviewed journal, and the outcomes will be used (1) as baseline information to design further studies that will help to better refine the epidemiological situation of leishmaniasis in Cameroon, and (2) to inform both programme managers and policy-makers of the situation of leishmaniasis in the country. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered with the International Prospective Register of Systematic reviews (PROSPERO; registration number: CRD42020211864) database.

Collateral Impact of Community-Directed Treatment with Ivermectin (CDTI) for Onchocerciasis on Parasitological Indicators of Loa loa Infection.

Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. IVM-based preventive chemotherapies (PCs), so-called community-directed treatment with ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. A cross-sectional study was conducted in the Yabassi Health District where CDTI have been implemented since 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf). The prevalence of loiasis was 3.7% (95% CI: 2.2-6.2), significantly lower than its baseline prevalence (12.4%; 95% CI: 10.1-15.2; Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline microfilarial density (mean = 839.3 mf/mL; SD = 6447.1; max = 130,840; Wilcoxon W = 179,904.5; p < 0.0001). This study revealed that the endemicity level of loiasis was significantly low compared to its baseline value, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.

Serious limitations of the current strategy to control Soil-Transmitted Helminths and added value of Ivermectin/Albendazole mass administration: A population-based observational study in Cameroon.

BACKGROUND: Soil-transmitted helminth (STH) infections remain a public health concern in sub-Saharan Africa. School-based mass drug administration (MDA) using the anthelminthic drug Mebendazole/Albendazole have succeeded in controlling morbidity associated to these diseases but failed to interrupt their transmission. In areas were filarial diseases are co-endemic, another anthelminthic drug (Ivermectin) is distributed to almost the entire population, following the community-directed treatment with ivermectin (CDTI) strategy. Since Ivermectin is a broad spectrum anthelmintic known to be effective against STH, we conducted cross-sectional surveys in two health districts with very contrasting histories of Ivermectin/Albendazole-based PC in order to investigate whether CDTI might have contributed in STH transmission interruption. METHODOLOGY: Cross-sectional surveys were conducted in two health districts with similar socio-environmental patterns but with very contrasting CDTI histories (Akonolinga health district where CDTI was yet to be implemented vs. Yabassi health district where CDTI has been ongoing for two decades). Stool samples were collected from all volunteers aged >2 years old and analyzed using the Kato-Katz technique. Infections by different STH species were compared between Akonolinga and Yabassi health districts to decipher the impact of Ivermectin/Albendazole-based MDA on STH transmission. PRINCIPAL FINDINGS: A total of 610 and 584 participants aged 2-90 years old were enrolled in Akonolinga and Yabassi health districts, respectively. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found, with prevalence significantly higher in Akonolinga health district (43.3%; 95% CI: 38.1-46.6) compared to Yabassi health district (2.5%; 95% CI: 1.1-5.1) (chi-square: 90.8; df: 1; p < 0.001). CONCLUSION/SIGNIFICANCE: These findings (i) suggest that Mebendazole- or Albendazole-based MDA alone distributed only to at-risk populations might not be enough to eliminate STH, (ii) support the collateral impact of Ivermectin/Albendazole MDA on A. lumbricoides and T. trichiura infections, and (iii) suggest that Ivermectin/Albendazole-based PC could accelerate STH transmission interruption.

Impact of 19 years of mass drug administration with ivermectin on epilepsy burden in a hyperendemic onchocerciasis area in Cameroon.

BACKGROUND: Surveys conducted in 1991-1992 in the Mbam Valley (Cameroon) revealed that onchocerciasis was highly endemic, with community microfilarial loads (CMFL) > 100 microfilariae/snip in some villages. Also in 1991-1992, a survey of suspected cases of epilepsy (SCE) found 746 SCE using a questionnaire administered to individuals identified by key informants, with prevalences reaching 13.6% in some communities. From 1998, annual community-directed treatment with ivermectin (CDTI) was implemented to control onchocerciasis. In 2017, a door-to-door household survey was conducted in three of the villages visited in 1991-1992, using a standardized 5-item epilepsy screening questionnaire. RESULTS: In 2017, a total of 2286 individuals living in 324 households were screened (582 in Bayomen, 553 in Ngongol and 1151 in Nyamongo) and 112 SCE were identified (4.9%). Neurologists examined 92 of these SCE and confirmed the diagnosis of epilepsy for 81 of them (3.5%). Between the surveys in 1991-1992 and 2017, the prevalence of SCE decreased from 13.6% to 2.5% in Bayomen (P = 0.001), from 8.7% to 6.6% in Ngongol (P = 0.205) and from 6.4% to 5.4% in Nyamongo (P = 0.282). The median age of SCE shifted from 20 (IQR: 12-23) to 29 years (IQR: 18-33; P = 0.018) in Bayomen, from 16 (IQR: 12-21) to 26 years (IQR: 21-39; P < 0.001) in Ngongol and from 16 (IQR: 13-19) to 24 years (IQR: 19-32; P < 0.001) in Nyamongo. The proportions of SCE aged < 10, 10-19, 20-29 and ≥ 30 years shifted from 9.5, 58.3, 25.0 and 7.1% in 1991-1992 to 2.7, 20.5, 39.3 and 37.5% in 2017, respectively. CONCLUSIONS: SCE prevalence decreased overall between 1991-1992 and 2017. The age shift observed is probably due to a decrease in the number of new cases of epilepsy resulting from the dramatic reduction of Onchocerca volvulus transmission after 19 years of CDTI.

The temporal relationship between onchocerciasis and epilepsy: a population-based cohort study.

BACKGROUND: Many studies have suggested that onchocerciasis might be associated with epilepsy. Therefore, we did a cohort study to assess the incidence of epilepsy relative to Onchocerca volvulus skin microfilarial density (MFD) measured during childhood and to assess the possibility of a temporal relationship. METHODS: During onchocerciasis surveys undertaken in 25 villages in Cameroon during 1991-93, we measured MFD in individuals aged 5 years or older. In 2017, we revisited seven of these villages. With a standardised five-item questionnaire, we collected information on the occurrence of epilepsy in 856 individuals who were aged 5-10 years in 1991-93, and had MFD determined during the original surveys. We did multivariable analyses to assess the overall incidence and incidence ratios taking into account age, sex, individual MFD in 1991-93, and onchocerciasis endemicity level in the village. FINDINGS: In 2017, we obtained data on the history of epilepsy for 85% (729 of 856) of individuals. Among these individuals, we classified 60 as being suspected cases of epilepsy. The overall incidence of epilepsy was 350 per 100 000 person-years (95% CI 270-450). The adjusted incidence ratio for developing epilepsy was 7·07 (95% CI 0·98-51·26; p=0·0530) in individuals with initial MFD of one to five microfilariae per skin snip (mf per snip), 11·26 (2·73-46·43) in individuals with six to 20 mf per snip, 12·90 (4·40-37·83) in individuals with 21-50 mf per snip, 20·00 (3·71-108·00) in individuals with 51-100 mf per snip, 22·58 (3·21-158·56) in individuals with 101-200 mf per snip, and 28·50 (95% CI 3·84-211·27; p=0·0010) in individuals with more than 200 mf per snip, compared with that of individuals without detectable densities of skin microfilariae. INTERPRETATION: Individual O volvulus MFD in childhood was associated with the risk of either seizures or epilepsy in an onchocerciasis focus in Cameroon. This temporal relationship suggests a potential causal link between onchocerciasis and epilepsy. FUNDING: European Research Council, NSETHIO Project.