Prevalence and incidence of nodding syndrome and other forms of epilepsy in onchocerciasis-endemic areas in northern Uganda after the implementation of onchocerciasis control measures

Abstract

Background: Around 2007, a nodding syndrome (NS) epidemic appeared in onchocerciasis-endemic districts of northern Uganda, where ivermectin mass distribution had never been implemented. This study evaluated the effect of community-directed treatment with ivermectin (CDTI) and ground larviciding of rivers initiated after 2009 and 2012 respectively, on the epidemiology of NS and other forms of epilepsy (OFE) in some districts of northern Uganda. Methods: In 2012, a population-based community survey of NS/epilepsy was carried out by the Ugandan Ministry of Health in Kitgum and Pader districts. In August 2017, we conducted a new survey in selected villages of these districts and compared our findings with the 2012 data. In addition, two villages in Moyo district (where CDTI was ongoing since 1993) served as comparative onchocerciasis-endemic sites in which larviciding had never been implemented. The comparison between 2012 and 2017 prevalence and cumulative incidence were done using the Fisher's and Pearson's Chi-square tests at 95% level of significance. Results: A total of 2138 individuals in 390 households were interviewed. In the selected villages of Kitgum and Pader, there was no significant decrease in prevalence of NS and OFE between 2012 and 2017. However, the cumulative incidence of all forms of epilepsy decreased from 1165 to 130 per 100 000 persons per year (P = 0.002); that of NS decreased from 490 to 43 per 100 000 persons per year (P = 0.037); and for OFE from 675 to 87 per 100 000 persons per year (P = 0.024). The median age of affected persons (NS and OFE) shifted from 13.5 (IQR: 11.0-15.0) years in 2012 to 18.0 (IQR: 15.0-20.3) years in 2017; P < 0.001. The age-standardized prevalence of OFE in Moyo in 2017 was 4.6%, similar to 4.5% in Kitgum and Pader. Conclusions: Our findings support the growing evidence of a relationship between infection by Onchocerca volvulus and some types of childhood epilepsy, and suggest that a combination of biannual mass distribution of ivermectin and ground larviciding of rivers is an effective strategy to prevent NS and OFE in onchocerciasis-hyperendemic areas.

The Role of the Maridi Dam in Causing an Onchocerciasis-Associated Epilepsy Epidemic in Maridi, South Sudan: An Epidemiological, Sociological, and Entomological Study

“…In 1986, when 300,000 cows were stolen from the Acholi, 1.8 million people were lodged in internally displaced persons (IDP) camps, several located close to rivers with blackfly breeding sites, and the absence of an ivermectin MDA program may have been the main reason why an OAE epidemic appeared in northern Uganda during that period [22]. Upon strengthening onchocerciasis elimination efforts in this area from 2012, the burden of OAE and nodding syndrome was drastically reduced [26].…”

Zoonotic Implications of Onchocerca Species on Human Health

“…Onchocerca infections may have been underestimated, particularly in wildlife, where infected animals are easier to be preyed upon, especially when the Onchocerca nodules are found in the joints, making movement difficult [7]. However, Onchocerca control in wildlife is difficult because of the ubiquity of the adult insect vectors [8], the need of larviciding of vector breeding sites [6], and the migratory patterns of some hosts, leading to the expansion of Onchocerca species [9]. The most common Onchocerca species identified so far, related to their main vectors, hosts, and geographical distribution, are described in Table 1.…”

“…The mechanism through which O. volvulus causes epilepsy remains unknown [6]. One of the most important challenges to study OAE etiology is the need to perform autopsies for subsequent histopathological analysis, which can be extremely difficult in most rural African regions.…”

“…Each larva stays as a single male or female and grows until it becomes a mature worm, which remains separated in the skin or collected together in subcutaneous fibrous nodules because of the immunological reaction of the host; females produce microfilariae, which invade the skin, travel in it, and very often reach the eye [1,5]. As a result, onchocerciasis usually causes dermatitis and ocular damages, but epilepsy has also been reported in humans [6]. In recent years, Onchocerca species infecting animals were found in human tissues.…”

Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial

“…Accumulating evidence is suggesting a protective effect of ivermectin in the development of OAE. After the introduction of biannual mass treatment with ivermectin and ground larviciding of blackfly-infested rivers in 2012 in northern Uganda, no new nodding syndrome cases have been observed and the number of persons developing other forms of epilepsy also decreased [8]. In two age-and village-matched case control studies in the Democratic Republic of Congo (DRC), ivermectin coverage among persons with epilepsy (PWE) prior to seizure onset, was lower compared to healthy controls in the same time period [9,10].…”