Status of parasitological indicators and morbidity burden of onchocerciasis after years of successive implementation of mass distribution of ivermectin in selected communities of Yeki and Asosa districts, Ethiopia

Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a vector-borne parasitic disease of public health and socio-economic concern in the sub-Sahara Africa. It is transmitted by the bite of infected blackfly of the genus Simulium which breeds in fast-flowing rivers and streams. The adult worm may live up to 18 years inside nodules located in the body of infected persons [1]. The adult female worm produces thousands of microfilariae (mf) per day [2] that migrate under the dermis of the skin to cause skin and eye diseases. Typical cutaneous lesions of onchocerciasis include acute papular dermatitis, chronic papular dermatitis, lichenified onchodermatitis, lymphadenopathy, depigmentation, and atrophy [3].

Onchocerciasis in Ethiopia was first reported from Bonga by Italian investigators in 1939 [4, 5]. Following this case report, several epidemiological studies have been conducted in Ethiopia, and revealed the presence of the disease in different localities in varying level of endemicity [6‐29] According to these studies, the prevalence of the disease ranges from 0% in eastern Ethiopia [28] to as high as 84% in southwest Ethiopia [21]. Consequent rapid epidemiological mappings of onchocerciasis conducted in 1997, 2001, 2004, 2011 and 2012 also proved that the the disease is endemic in several communities in western, southwestern and northwestern Ethiopia [30]. Endemic areas mainly cover the whole Benishangul-Gumuz, portion of Oromia, Amhara, Gambella, and Southern Nations Nationalities Peoples (SNNP) Regions [31]. The clinical picture of the disease is mainly dermal while ocular manifestations are uncommon or absent [4, 6]. It is estimated nearly 5.8 million people are living in highly endemic areas, and over 20 million people are at risk of acquiring infection [32]. The disease has been a major public health problem [21] with socio-economic significance in areas of the country where it is endemic, especially in large-scale coffee plantation enterprises in southwest Ethiopia [11, 16, 17], which are densely populated and vastly covered by forests, with heavy rainfall and numerous perennial rivers and streams [9, 17]. In 2015, onchocerciasis reported to be responsible for 43.9 disability-adjusted life-years lost per 100,000 [33].

As part of the African Program for Onchoceciasis Control (APOC) in sub-Saharan Africa [34, 35], community directed treatment with ivermectin (CDTi) has been the main strategy in the efforts towards the control and elimination of onchocerciasis in Ethiopia [31, 36]. The program was launched in 16 districts of the then Keffa-Sheka Zone of SNNP Region in 2001 [31] and later expanded to other districts where the disease has been reported [32, 36]. Currently, the program is running in 194 endemic districts [37]. As part of the recent renewed interest to eliminate onchocerciasis in Africa, Ethiopia has garnered the concerted efforts of stakeholders in its’ effort to eliminate onchocerciasis.The national elimination program is undertaking 3 major activities: (i) biannual distribution of ivermectin in all CDTi implementation areas, (ii) nationwide mapping of onchocerciasis in untreated areas to detect transmission areas eligible for CDTi and, (iii) post-treatement and post-elimination surveillance activities in CDTi implementation areas that received several rounds of ivermectin treatment. Moreover, the country has also established a committee that provides technical support and decision on the cessation of mass ivermectin treatment, and oversees the overall progress of the elimination program [32, 38, 39].

Control and elimination of onchocerciasis requires regular follow-up and evaluation of program implementation. Then, areas with unsatisfactory progress can be identified quickly [40‐42], and corrective actions can be taken. This involves a coverage verification survey, epidemiological, parasitological, serological and entomological evaluations [39]. It is recommended that parasitological evaluation needs are carried out six years after the commencement of ivermectin distribution to observe the decline in infection level in CDTi implementation areas, and if transmission is still ongoing to undertake similar actions after 3 to 4 years till the elimination breakpoint is achieved [34, 42].

Pre-control epidemiological studies showed that onchocerciasis was highly endemic in communities of Yeki district [17, 21, 23, 24]. The district is endowed with rapidly flowing perennial rivers, streams, and vegetation cover that provide suitable habitats for the vector. CDTi distribution started in Yeki in 2001 and continued to the present day as part of the national efforts to control the disease in highly endemic areas (Fig. 1). Subsequent parasitological evaluations have shown transmission of the disease was ongoing [34, 43]. Similarly, previous studies indicated that onchocerciasis is endemic in several communities of Asosa [18] and its surroundings [12, 15]. CDTi has been running in this area since 2013 (Fig. 2). However, hitherto, no study was conducted to investigate the impact of the program and to assess the epidemiological status of the disease. The aim of this study was to assess the current status of onchocerciasis in selected communities of Asosa and Yeki districts after 5 and 15 years of successive CDTi program, respectively, and to evaluate the impact of ongoing CDTi activities in reducing the prevalence, intensity of infection and morbidity of onchocerciasis in communities of respective districts that have baseline epidemiological data collected prior to the launch of mass ivermectin distribution.

This study encompasses the evaluation of phase one onchocerciasis elimination program using a skin-snip microscopy and morbidity assessment survey. We assessed the prevalence, intensity of infection and morbidity of onchocerciasis in selected communities of Yeki and Asosa districts in Ethiopia after 15 and 5 years of successive ivermectin distribution, respectively. We also measured the decline in infection and morbidity of onchocerciasis in communities against pre-control epidemiological data collected before initiation of ivermectin distribution. We also compared our findings with results of previous impact evaluation studies of comparably similar duration of intervention from elsewhere in Africa and Latin America endemic areas.

Before the launch of the CDTi intervention, onchocerciasis was highly endemic in Yeki district. It was a serious public health and socioeconomic problem in this area, particularly in those working in coffee plantation enterprises [17]. The highest pre-control mean mf intensity of infection was reported from this area [17, 23]. This study showed that 15 years of continuous CDTi has brought the prevalence of infection to zero. The skin mf reservoir available to the local vector population in the area might have gradually decreased after the long term treatment [48], and ultimately with possible interruption of active parasite transmission [49]. We believe that the switch from annual to biannual CDTi in 2015 might have contributed to bringing the prevalence and intensity of infection status to zero level. Similar findings were reported from other endemic areas where at least 14 rounds of MDA was carried out in Africa [45, 49‐54] and Latin America [55]. In contrast, irrespective of long term CDTi, considerably higher prevalences than the present finding were reported from other CDTi implementation areas in Africa [29, 56‐62]. Several factors may have contributed to the differences in the impact of CDTi. Among these include variations in program implementation in the areas (variation in treatment coverage [34, 58, 63, 64]; treatment non-compliance rate [48, 61, 63, 65]; differences in vector species [50, 64], densities [55, 56, 60, 62, 63, 65], biting rates [64], vectorial capacities [64], vector competences [50, 64, 66, 67], vector migration [68‐71]; ecological conditions [58, 59, 64, 72]; transmission pattern [50]; parasite susceptibility to ivermectin [73, 74]; human migration [64, 65], and difference in time after community-wide treatment and parasitological assessment). Another possible explanation is that variation in pre-control endemicity level could influence the long term impact of ivermectin on prevalence of infection [34, 50, 51, 57, 64, 75, 76]. In low pre-control endemicity areas, a break in O. volvulus infection transmission may be achieved within 6–8 years of treatment [42, 77]. A very good example of this is in Rio Géba hypoendemic focus of Guinea-Bissau where onchocerciasis had been eliminated only after seven years of biannual CDTi [63]. While, in high pre-control endemicity areas, many years of ivermectin treatment may be required to achieve disease elimination [34]. Katabarwa et al. [57] for example refers to Toubouro holoendemic focus of north Cameroon where the highest pre-control endemicity level of onchocerciasis was ever recorded [66], and even 21 years annual CDTi with good coverage had not interrupted transmission of infection [34].

Furthermore, our study demonstrated an overall prevalence and intensity of infection of 1.6% and 0.02 mf/mg skin snip, respectively in Asosa. Interestingly, no mf was detected in the study participants from 21 of the 23 communities (including from all of the study participants of evaluation communities where the disease was reported in the pre-control period). The current prevalence in Asosa was recorded only from two communities; Mugufudie and Dabus-Atinbaqo. This could be due to the presence of a nearby fast-flowing rivers, Dabus, Tumed, Tasa, Gemedie and Andil rivers which serve as conducive sites for blackfly breeding. The residents of Dabus-Atinbaqo and Mugufudie communities predominantly rely on these rivers for their livelihood; and practice irrigation, fishing, crop farming and gold mining on day-to-day basis so that they are frequently exposed to blackfly bites. The study participants from both communities complained that blackfly nuisance and biting is a problem in the environs of their village. The biting rate is reported by residents to be intense especially near to the Dabus River. Relatively higher prevalence of infection than this was reported in other studies after similar years of intervention [43, 49, 65‐67, 78‐83].

Our study also investigated the magnitude of onchocerciasis associated morbidities in both study areas. Unlike other previous study [78], the observed prevalences of onchocerciasis morbidity were low. Among the observed prevalences, a relatively higher prevalence of papular dermatitis was observed in Asosa. Nonetheless, all the dermatitis might not be caused by onchocerciasis. It could be by other etiologic agents like dermatophytes, contact allergens and insect bites [79, 80]. The findings of this study has revealed the decline to low levels in the magnitude of the morbidities following the CDTi intervention in both study areas. This suggests that repeated and prolonged CDTi could have an impact on the morbidity of onchocerciasis through reducing the progress of existing lesions [81] and preventing the occurrence of new lesions [79].

The findings of this study should be interpreted with the below-mentioned caveats in mind. First, the parasitological evaluation to detect active O. volvulus infection is not sensitive enough to detect low levels of O. volvulus infection [42, 82, 83] following multiple rounds of treatment [63]. It is also an invasive procedure and there is high refusal in communities participating in the study especially those systematic non-compliers might not be represented in the study [51]. Thus, the findings could be biased [50] and might not exactly signify the exact levels of infection in the communities of the two districts. Second, pre-control epidemiological data were not available for most of the communities in Yeki and Asosa so that it was not possible to observe and compare the impact of mass ivermectin intervention on the epidemiology of the disease at community level. Third, our study began few i.e. two months after the second biannual mass ivermectin distribution. The time gap between treatment and mf assessment has been short (especially in communities of Asosa where the survey started). This may affect the estimates of infection and inturn partly impact informativeness of the study in the progress to disease elimination. Last but not least, there was a long time gap in between the collection of baseline pre-control data and the start of the initiation of ivermectin distribution in Asosa. Thus, it could be possible that the epidemiology of the disease might have been partly changed in the area in the earlier years due to causes other than ivermectin intervention. For instance; this could be supplemented by vectors related factors due to environmental modifications caused by land-use and land-cover changes which inturn might have affected the vector breeding sites. This phenomenon was seen in the Humera area of northwestern Ethiopia where presence of onchocerciasis was reported in 1981 [10], yet repeated evaluation survey in 2009 confirmed the absence of infection without ivermectin intervention [26]. The study participants in Asosa also complained that much of the forest and vegetation has been cleared for crop farming during the resettlement and villagization program.

Fifteen years of successive CDTi intervention transformed the epidemiological situation of onchocerciasis in Yeki. It brought the mf infection from highly endemic to zero. The fact that no single skin snip positive person was detected suggests that interruption of infection might have been achieved, and the CDTi program is well underway to meet the goal of interrupting parasite transmission in the area. This observation might give clues on the possibilities that interruption of transmission might also have been achieved in other onchocerciasis endemic areas of Ethiopia currently under CDTi intervention. However, thorough entomological and serological evaluations are recommended to ensure whether complete interruption of parasite transmission has been achieved, and for an evidence-based CDTi cessation. Moreover, 5 years of CDTi in Asosa significantly reduced the prevalence, intensity of infection and morbidity of onchocerciasis to very low level.

It is tempting to declare that onchocerciasis is no longer a public health problem in Yeki, and possibly in Asosa. From the elimination point of view, however, there is still ongoing transmission of infection in two communities. We, hereby, recommend biannual CDTi need to continue in Asosa and its surroundings until the transmission of infection is fully interrupted.