Background
Onchocerciasis (also known as river blindness) is one of the neglected tropical diseases (NTDs) targeted by the World Health Organization (WHO) for elimination as a public health problem by 2030 [
1]. The disease is caused by the filarial nematode
Onchocerca volvulus, and it is transmitted by
Simulium black flies. Female worms which live in subcutaneous nodules release microfilariae (Mf) that migrate through the skin and are picked up by the vector. Microfilariae are not only crucial for transmission; host inflammatory reactions to Mf cause severe morbidity including visual impairment, blindness, and severe dermatitis which can be disabling and stigmatizing [
2]. Infected persons often experience negative social consequences and economic loss [
3].
Rapid epidemiological mapping of onchocerciasis was carried out in Nigeria between 1994 and 1996 [
4]. This mapping provided estimates of the populations living in high-risk areas and identified villages to be prioritized for ivermectin MDA. Subsequently, MDA commenced in 1997 utilizing local volunteers, known as community drug distributors (CDDs), for the distribution of ivermectin. This strategy has been an effective strategy for drug delivery [
5]. Although ivermectin is effective for clearing Mf from the skin and for interrupting embryogenesis in the female worm, these effects are only temporary, and the treatment has little effect on adult worm viability [
6,
7]. For this reason, repeated treatments are needed to suppress Mf to levels that do not support transmission for the reproductive life span of adult worms (> 10 years).
Nigeria has the largest at-risk population for onchocerciasis of any country in Africa. Historical mapping data showed that all 17 Local Government Areas (LGAs) in Enugu state and eight in Ogun state were endemic for onchocerciasis [
8]. Some endemic foci in these states have received 14 to 26 rounds of ivermectin MDA for onchocerciasis, respectively. Also, since these states are co-endemic for lymphatic filariasis (LF) [
9,
10], ivermectin plus albendazole MDA has been delivered annually in many LGAs since 2000. No data have been published in recent years on the current status of onchocerciasis or progress toward elimination in these states. The data reported here were collected during pilot surveys that were conducted to identify potential sites for clinical trials of new treatments for onchocerciasis, i.e., triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) [
11] (see:
https://dolfproject.wustl.edu/about/ida-for-onchocerciasis-studies/). They provide important information on the persistence of onchocerciasis in some areas of Nigeria that had high baseline endemicity despite the clear beneficial effects of extensive MDA with ivermectin.
Discussion
This study has provided new data on the current status of onchocerciasis in selected LGAs in endemic states in southeast and southwest Nigeria. Although all surveyed villages in Enugu state had received many rounds of ivermectin MDA (26 rounds over more than two decades), our results showed that nodule and skin Mf prevalences were still at meso-endemic levels. In contrast, onchocerciasis infection prevalences in villages surveyed in Ogun state were considerably lower than those in Enugu even though fewer rounds of ivermectin had been distributed in Ogun. This difference may be due to higher baseline infection prevalences and biting rates in Enugu.
Rapid epidemiological mapping of onchocerciasis (REMO) was conducted in 1994 in Enugu state. Some 27 years later, nodule prevalence remained largely unchanged in this setting. This may be because adult
O. volvulus worms can live in subcutaneous nodules for about 15 years, and ivermectin does not kill adult worms [
13,
14], [
15]. The persistence of onchocerciasis in these study areas could be due to suboptimal compliance with MDA or to extremely high
Simulium biting rates.
O. volvulus skin Mf densities are correlated with disease risk [
2]. We do not have access to ivermectin MDA coverage and compliance data for villages in this study, and that is a limitation of our study. However, low skin Mf counts documented in this study are encouraging, because they suggest that MDA coverage and compliance have been high in the recent past in the surveyed villages which were considered by state health officials to be at high risk for persistence of onchocerciasis. They also suggest that ivermectin MDA is working well for disease control in these areas. On the other hand, these results also mean that the surveyed areas did not have enough heavily infected patients to populate our planned clinical trials of new treatments for onchocerciasis. That is good news for Ogun and Enugu states.
We found a statistically significant difference in nodule prevalence rates between males and females in our study population. This is consistent with results from other studies where males had higher nodule prevalences [
16,
17]. These studies suggest that higher infection prevalences in males were due to their higher exposure to bites from the
Simulium vector during outdoor activities such as farming and fishing [
17,
18]. There were no significant differences in Mf prevalence by gender in our study. Differences that may have been present at baseline may have been obscured over time by ivermectin MDA.
The small number of adults sampled per village is a limitation of our study because this results in wide confidence intervals for estimates of infection prevalence by village. Also, the sampling population in this study differed from previous REMO surveys; REMO methodology restricted surveys to a random population of adult males whereas our study did not have any gender restrictions. This difference in sampling population makes it tricky to directly compare our results with results obtained at baseline surveys. Despite these limitations, our results clearly show that these study areas need to continue ivermectin MDA despite the long history of ivermectin distribution in the Enugu study villages and mostly low baseline nodule prevalences in the Ogun study villages. The 2016 WHO onchocerciasis elimination targets require the demonstration of very low infection prevalences in children [
19]. Although we did not include children in our study, the infection rates recorded in adults in our study suggest that these study areas would not meet recommended MDA stopping criteria. Furthermore, mathematical modelling predictions suggest that for an evaluation unit to be considered to have interrupted transmission, skin Mf prevalence should be < 5.0% in 100% of the villages in an implementation unit or < 1.0% in at least 90% of villages [
20].
In conclusion, this study has shown that onchocerciasis persists in the areas surveyed in two states in Nigeria despite many rounds of ivermectin MDA. Although
O. volvulus transmission has been interrupted in some endemic foci in Africa with ivermectin MDA, this intervention is more effective for disease prevention than for elimination. Our results suggest that annual ivermectin alone may not be sufficient to eliminate transmission by 2030 in areas similar to those of our study villages in Enugu. Options to consider include more frequent MDA with ivermectin (with high treatment coverage and compliance), use of a more effective microfilaricide such as moxidectin [
6,
21], distribution of an effective macrofilaricide (not yet available), or addition of vector control to complement mass drug administration.
Acknowledgements
We are grateful to the research team from the Department of Pure and Applied Zoology, Federal University of Agriculture, Abeokuta, and Ogun State NTD control Unit, State Ministry of Health, Abeokuta, Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka; NTD control Unit, Enugu State Ministry of Health, Enugu State; National Arbovirus and Vectors Research Center, Federal Ministry of Health, Enugu, Enugu State. The study also appreciates the kindness of the participants, the chiefs, and the health workers in the surveyed villages for their diverse support.
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