4.5 Article

Nodding syndrome, a case-control study in Mahenge, Tanzania: Onchocerca volvulus and not Mansonella perstans as a risk factor

Journal

PLOS NEGLECTED TROPICAL DISEASES
Volume 17, Issue 6, Pages -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pntd.0011434

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Epidemiological studies suggest that onchocerciasis may be one of the causes of nodding syndrome (NS), but other causes have been considered. A study in Mahenge found that a probable Mansonella perstans infection was associated with a higher epilepsy rate, but onchocerciasis and onchocerciasis-associated skin lesions were stronger risk factors. Therefore, onchocerciasis remains the most likely main risk factor for NS.
Author summaryNodding syndrome (NS) is a rare and severe form of epilepsy that mainly affects children. The syndrome has only been found in onchocerciasis-endemic areas, and epidemiological studies suggest that it may be one of the forms of onchocerciasis-associated epilepsy caused by the parasite Onchocerca volvulus. Nevertheless, other causes have been considered, such as an infection with Mansonella perstans. To identify a main causal factor for NS, it needs to be present in all sites where the syndrome is found. Hence, our team explored 113 people with epilepsy and 132 healthy controls in Mahenge, Tanzania, to determine if M. perstans could be behind the epidemic of NS in the area. Over a third of the epilepsy cases in the study met the criteria for probable NS. None of the participants was diagnosed with an M. perstans infection. However, those exposed to onchocerciasis and with onchocerciasis-associated skin lesions were more likely to have epilepsy, including probable NS. In conclusion, onchocerciasis remains the most likely main risk factor for NS. BackgroundNodding syndrome (NS) has been consistently associated with onchocerciasis. Nevertheless, a positive association between NS and a Mansonella perstans infection was found in South Sudan. We aimed to determine whether the latter parasite could be a risk factor for NS in Mahenge. MethodsCases of epilepsy were identified in villages affected by NS in Mahenge, Tanzania, and matched with controls without epilepsy of the same sex, age and village. We examined blood films of cases and controls to identify M. perstans infections. The participants were also asked for sociodemographic and epilepsy information, examined for palpable onchocercal nodules and onchocerciasis-related skin lesions and tested for anti-Onchocerca volvulus antibodies (Ov16 IgG4) by ELISA. Clinical characteristics of cases and controls, O. volvulus exposure status and relevant sociodemographic variables were assessed by a conditional logistic regression model for NS and epilepsy status matched for age, sex and village. ResultsA total of 113 epilepsy cases and 132 controls were enrolled, of which, respectively, 56 (49.6%) and 64 (48.5%) were men. The median age in cases and controls was 28.0 (IQR: 22.0-35.0) and 27.0 (IQR: 21.0-33.3) years. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria and 106 (93.8%) had onchocerciasis-associated epilepsy (OAE). M. perstans infection was absent in all participants, while Ov16 seroprevalence was positively associated with probable NS (odds ratio (OR): 5.05, 95%CI: 1.79-14.27) and overall epilepsy (OR: 2.03, 95%CI: 1-07-3.86). Moreover, onchocerciasis-related skin manifestations were only found in the cases (n = 7, p = 0.0040), including persons with probable NS (n = 4, p = 0.0033). Residing longer in the village and having a family history of seizures were positively correlated with Ov16 status and made persons at higher odds for epilepsy, including probable NS. ConclusionIn contrast to O. volvulus, M. perstans is most likely not endemic to Mahenge and, therefore, cannot be a co-factor for NS in the area. Hence, this filaria is unlikely to be the primary and sole causal factor in the development of NS. The main risk factor for NS remains onchocerciasis.

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