Descriptive Epidemiology
According to media reports and assessments from local officials, there may be as many as 3,000–8,000 cases of nodding syndrome in the districts of Kitgum, Pader, and Lamwo in northern Uganda, and Western and Central Equatoria States in South Sudan. In March 2012, the Uganda government actively sought to register cases for the purpose of providing services and recorded >3,000 names, although a standardized and consistently applied case definition was not used. Detailed investigations that used consistently applied case definitions and active community outreach have identified ≥224 cases across Kitgum District in Uganda and 260 cases in Western Equatoria State in South Sudan; complete ascertainment of all cases was not the primary objective in either investigation. Widespread registration of cases has not been completed in Tanzania, but in a study conducted in 2005, a total of 62 cases were documented and investigated in detail. What seems clear is that there are at least several hundred affected children currently in the 3 geographic areas, and the actual numbers might be much higher. In July 2012 a standard set of case definitions (Table 2) was developed during an international meeting on nodding syndrome in Kampala, Uganda, and applied in an extensive community survey across affected districts of northern Uganda.
Deaths among nodding syndrome patients also are commonly reported but incompletely ascertained. A Uganda news report in May 2012 listed the number of deaths at 205, but the Ministry of Health could not confirm that all of these deaths were a result of nodding disease. Anecdotal reports of deaths from drowning, burns, and other causes among nodding syndrome patients are common, but a collaborative effort between the Uganda Ministry of Health and CDC to register deaths and obtain autopsy specimens resulted in 1 autopsy over an 18-month period during 2011–2012. A 2009 follow-up investigation of 62 patients with nodding syndrome in Tanzania first evaluated in 2005 identified 2 deaths that occurred in the interim. A follow-up investigation of 12 patients in Uganda evaluated in 2009 and 2010 identified interval worsening in 6 patients, improvement in none, and no deaths. Although the mortality rate associated with nodding syndrome remains to be accurately defined, media reports from affected communities imply that this rate is high, and long-term studies of childhood epilepsy also suggest that it will probably increase.
On the basis of reports for Uganda and probably for South Sudan, the incidence of nodding syndrome appears to be increasing (Figure 2). The earliest cases among the 224 documented patients in Uganda occurred in 2000, except for 1 possible onset in 1997, and there was a steady increase in cases identified through the study in 2009. In South Sudan, the earliest cases recognized were in 1991 in Mundri County and 1995 in Lui Township. Community reports from a village administrator in Sudan and focus groups in Uganda indicated that previous generations had not been affected by this disease. In contrast, reports of head nodding in Tanzania date back >50 years, and it is not clear from available reports whether the incidence has increased.
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Figure 2.
Epidemic curve of nodding syndrome cases in Kitgum District, Uganda, by year of onset. Modified from Foltz et al. (6).
The disease appears to be localized in 3 noncontiguous areas in South Sudan, Uganda, and Tanzania (Figure 3). Although head nodding as 1 feature of seizure disorders has been reported from Liberia, Taiwan, and elsewhere, clustering of hundreds of cases of this syndrome and the same manifestations has not been described elsewhere. Although onchocerciasis is endemic to all 3 areas, the distribution of this parasitic disease is much wider, extending to across much of eastern and western Africa and Central and South America, which are huge areas with populations apparently unaffected by nodding syndrome (Figure 3).
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Figure 3.
Countries in the former Onchocerciasis Control Programme in western Africa in which onchocerciasis was eliminated as a public health problem through vector control (green); countries in the African Programme for Onchocerciasis Control in which onchocerciasis control is ongoing through annual mass treatment with ivermectin (beige); and areas in Southern Sudan, northern Uganda, and southern Tanzania in which nodding syndrome has been reported (red circles).
Most of the populations affected by nodding syndrome were internally displaced; in Uganda and Sudan, the conflict with the Lord's Resistance Army during the 1990s resulted in dependence on refugee camps and in widespread food shortages during the years preceding nodding syndrome. In Tanzania, most (58/62) of the described patients with nodding syndrome were members of the Pogoro tribe. Although the Pogoro were not recently internally displaced refugees, they are among the poorest of the region, and therefore susceptible to food shortages. Potential associations of nodding syndrome with hunger, specific micronutrient malnutrition, or ingestion of toxic substances or contaminated relief foods have been explored in 4 case–control studies, as detailed below.
The distinctive age distribution (tight clustering among persons 5–15 years of age) is a consistent feature of nodding syndrome (Figure 4). Caregivers report that the children were unaffected as infants and had apparently normal growth; most of these children achieved their developmental milestones until the onset of nodding. Although persons of other ages with onset of nodding are occasionally identified, the disease is rare among younger children or adults. Onset in late childhood or early adolescence is seen in certain epilepsy syndromes, autoimmune diseases such as juvenile idiopathic arthritis, Sydenham chorea and other complications of group A streptococcal infections, and some nutritional toxicities such as konzo and neurolathyrism. Many epidemic infectious diseases predispose the very young or elderly, but some clustering of infections among persons 5–15 years of age are occasionally seen in neurologic infections such as meningococcal meningitis, parasitic infections such as urinary schistosomiasis, or epidemic viral infections such as mumps.
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Figure 4.
Age distribution of patients at onset of nodding syndrome, Kitgum District, Uganda. For nodding syndrome elsewhere, age distribution tightly clusters in persons 5–15 years of age. Modified from Foltz et et al. (6).