Onchocerciasis is diagnosed by detecting microfilariae in skin snips or by detecting OV16 IgG4 antibodies in blood by either enzyme linked immunosorbent assay (ELISA) or a rapid diagnostic test (RDT). Here, we compare the sensitivity and specificity of these three tests in persons with epilepsy living in an onchocerciasis endemic region in the Democratic Republic of Congo. Skin snips and blood samples were collected from 285 individuals for onchocerciasis diagnosis. Three tests were performed: the OV16 RDT (SD Bioline) and the OV16 ELISA both on serum samples, and microscopic detection of microfilariae in skin snips. The sensitivity and specificity of each test was calculated with the combined other tests as a reference. Microfilariae were present in 105 (36.8%) individuals, with a median of 18.5 (6.5–72.0) microfilariae/skin snip. The OV16 RDT and OV16 ELISA were positive in, respectively, 112 (39.3%) and 143 (50.2%) individuals. The OV16 ELISA had the highest sensitivity among the three tests (83%), followed by the OV16 RDT (74.8%) and the skin snip (71.4%). The OV16 RDT had a higher specificity (98.6%) compared to the OV16 ELISA (84.8%). Our study confirms the need to develop more sensitive tests to ensure the accurate detection of ongoing transmission before stopping elimination efforts.
Background: There is anecdotal evidence that ivermectin may decrease seizure frequency in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods: In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy experiencing ≥2 seizures/month were randomly allocated to receive, over a one-year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs. Data was analyzed using multiple logistic regression. Results: We enrolled 197 participants. In an intent-to-treat analysis (data from group 1 and 2 combined), seizure freedom was more likely among OIPWE treated with ivermectin thrice (OR: 5.087, 95% CI: 1.378–19.749; p = 0.018) and twice (OR: 2.471, 95% CI: 0.944–6.769; p = 0.075) than in those treated once. Similarly, >50% seizure reduction was more likely among those treated with ivermectin twice (OR: 4.469, 95% CI: 1.250–16.620) and thrice (OR: 2.693, 95% CI: 1.077–6.998). Absence of microfilariae during the last 4 months increased the odds of seizure freedom (p = 0.027). Conclusions: Increasing the number of ivermectin treatments was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures.
10 February 2019 in Infectious Diseases of Poverty
Onchocerciasis-endemic regions are known to have a high epilepsy prevalence. Limited resources in these areas and poor access to healthcare by persons with epilepsy (PWE) result in a wide anti-epileptic treatment gap, poor seizure control and a high burden of seizure-related complications. Recent community-based surveys highlight the need for epilepsy management strategies suitable for remote onchocerciasis-endemic villages to ensure better health outcomes for PWE. In this paper, we propose a feasible approach to manage PWE in such settings. Improved management of PWE in onchocerciasis-endemic areas may be achieved by decentralizing epilepsy care. Simplified approaches for the diagnosis and treatment of epilepsy may be used by non-physicians, under the supervision of physicians or specialists. To reduce the treatment gap, a regular supply of subsidized anti-epileptic drugs (AED) appropriate for different types of onchocerciasis-associated epilepsy should be instituted. Setting up a community-based epilepsy surveillance system will enable early diagnosis and treatment of PWE thereby preventing complications. Community awareness programs on epilepsy must be implemented to reduce stigma and facilitate the social rehabilitation of PWE. Finally, strengthening onchocerciasis elimination programs by optimizing community-directed treatment with ivermectin (CDTI) and considering alternative treatment strategies might reduce the incidence of epilepsy. A community-based approach with task-shifting of epilepsy care from specialists to non-physician health workers will reduce epilepsy-associated morbidity. Increased advocacy and collaboration with various stakeholders is needed to establish a sustainable, cost-effective chronic care model for epilepsy that will significantly improve the quality of life of PWE in onchocerciasis-endemic regions.
Despite a long history of community-directed treatment with ivermectin (CDTI), a high ongoing Onchocerca volvulus transmission is observed in certain onchocerciasis-endemic regions in Africa with a high prevalence of epilepsy. We investigated factors associated with higher microfilarial (mf) density after ivermectin treatment. Skin snips were obtained from O. volvulus-infected persons with epilepsy before, and 3 to 5 months after ivermectin treatment. Participants were enrolled from 4 study sites: Maridi (South Sudan); Logo and Aketi (Democratic Republic of Congo); and Mahenge (Tanzania). Of the 329 participants, 105 (31.9%) had a post-treatment mf density >20% of the pre-treatment value. The percentage reduction in the geometric mean mf density ranged from 69.0% (5 months after treatment) to 89.4% (3 months after treatment). A higher pre-treatment mf density was associated with increased probability of a positive skin snip after ivermectin treatment (p = 0.016). For participants with persistent microfiladermia during follow-up, a higher number of previous CDTI rounds increased the odds of having a post-treatment mf density >20% of the pre-treatment value (p = 0.006). In conclusion, the high onchocerciasis transmission in the study sites may be due to initially high infection intensity in some individuals. Whether the decreasing effect of ivermectin with increasing years of CDTI results from sub-optimal response mechanisms warrants further research.
We investigated urinary N-acetyltyramine-O,β-glucuronide (NATOG) levels as a biomarker for active Onchocerca volvulus infection in an onchocerciasis-endemic area in the Democratic Republic of Congo with a high epilepsy prevalence. Urinary NATOG was measured in non-epileptic men with and without O. volvulus infection, and in O. volvulus-infected persons with epilepsy (PWE). Urinary NATOG concentration was positively associated with microfilarial density (p < 0.001). The median urinary NATOG concentration was higher in PWE (3.67 µM) compared to men without epilepsy (1.74 µM), p = 0.017; and was higher in persons with severe (7.62 µM) compared to mild epilepsy (2.16 µM); p = 0.008. Non-epileptic participants with and without O. volvulus infection had similar NATOG levels (2.23 µM and 0.71 µM, p = 0.426). In a receiver operating characteristic curve analysis to investigate the diagnostic value of urinary NATOG, the area under the curve was 0.721 (95% CI: 0.633–0.797). Using the previously proposed cut-off value of 13 µM to distinguish between an active O. volvulus infection and an uninfected state, the sensitivity was 15.9% and the specificity 95.9%. In conclusion, an O. volvulus infection is associated with an increased urinary NATOG concentration, which correlates with the individual parasitic load. However, the NATOG concentration has a low discriminating power to differentiate between infected and uninfected individuals.
In October 2017, a community-based epilepsy treatment program (CBETP) was initiated in the Logo health zone (Ituri province, Democratic Republic of Congo), consisting mainly of community epilepsy education, provision of free antiepileptic drugs (AEDs), and monthly follow-up of persons with epilepsy (PWE). Prior to the implementation of the CBETP, qualitative research had revealed several misconceptions about the cause of epilepsy, major epilepsy-related stigma, and high economic cost for families of PWE mainly because of costly treatment by traditional healers. One year after the implementation of the CBETP, we assessed the perceived effect of this program on the community's perceptions and attitudes regarding epilepsy and on disease costs. Focus group discussions (FGD) and semi-structured in-depth interviews (SSI) were conducted with different target groups. Additionally, the cost associated with epilepsy was evaluated using questionnaires administered to 74 PWE and/or their families. Nine FGDs and 16 SSIs were conducted. There was a notable shift in perceptions and attitudes, as most community members no longer believed that epilepsy is contagious, while acknowledging that this condition can be treated in local health centers. Persons with epilepsy and their family experienced less epilepsy-related stigma and consulted less frequently traditional healers; the latter showed a growing willingness to collaborate with health professionals in the management of PWE. The direct and indirect costs for families caring for a PWE decreased by 95.2% and 95.7%, respectively. The main perceived benefits of the CBETP were the decrease in misconceptions about epilepsy and epilepsy-related stigma. Families with PWE understood the benefit of seeking health care from trained health professionals rather than with traditional healers. The direct and indirect costs for families to take care of a PWE reduced considerably after the program. However, the cost-effectiveness and long-term sustainability of this approach remain to be assessed.