Nodding syndrome in Uganda: field observations, challenges and research agenda.

This article summarizes observations made in Northern Uganda and a lecture given at the Nodding Syndrome Workshop in Nagasaki September 2013. The objective of the manuscript is to summarize the current knowledge on nodding syndrome and to provide an agenda for investigations into the epidemiology, pathophysiology, diagnosis and care management of nodding syndrome in Uganda.

Historical Aspects

In the 1950s the Norwegian psychiatrist Louise Jilek-Aall reported an hitherto unknown neurologic disease while working in the southern part of Tanzania in an area inhabited by the Pogoro people [1]. She noticed a peculiar form of epilepsy that started with nodding of the head and in later stages of the disease was accompanied by impaired cognitive functions.

In the mid-1990s health providers from the Equatoria States of the Sudan (an area near to the Ugandan border) reported an increasing number of children with nodding syndrome to the Ministry of Health (MOH) in Khartoum. However, only in 2001 Sudanese health officials notified the emerging epidemic to WHO.

Similarly, in the mid-2000s health workers and local NGOs from the Northern District of Uganda reported increasing numbers of children with nodding syndrome to the MOH in Kampala. Only in 2011 the MOH sent a team to the area to collect data on the occurrence of nodding syndrome in Kitgum, Lamwo and Pader district.

Disease Occurrence

Almost all cases of nodding syndrome notified so far occurred in the Northern Districts of Uganda (Fig. 1) and in several counties of the Western, Central and Eastern Equatoria States of South Sudan (a new nation independent since 2011).

Fig. 1.

Area affected by nodding syndrome in Northern Uganda

The area is inhabited by the Acholi people. Reliable data on disease occurrence do not exist and only estimates are at hand (Table 1).

Table 1.

Dimension of the problem

The heterogeneous spatial distribution of patients with nodding syndrome within the endemic area is striking (Table 2).

Table 2.

Heterogenous distribution of cases with foci and clusters in Uganda

There is a considerable spatial overlap between nodding syndrome and epilepsy sui generis (Table 3).

Table 3.

Nodding Syndrome and Epilepsy in Pader District

Supposedly, part of the cases recorded as epilepsy are the patients with nodding syndrome in whom the disease started with (grand mal or other type) seizures and who had not yet developed nodding attacks. Since 2000, notifications have increased considerably (Fig. 2a, b, c).

Fig. 2.

Trend of detected cases in Northern Uganda between 1997 and 2010

No data are available beyond 2010. Incidence data (i.e. onset of disease per 10,000 children per year) are not available.

The age of onset peaks between 8 and 15 years (Fig. 3). 95% of the patients developed the disease between 5 and 16 years.

Fig. 3.

Number of cases according to age [3]

Clinical Neurology

In about half of the patients the disease starts with the characteristic nodding of the head (Table 4).

Table 4.

Nodding is a particular manifestation of atonic seizures

About one third of the parents note an abnormal behavior of the child as a first sign. The remaining cases begin with classical epilepsy. Nodding may be accompanied by drooling of saliva, urine incontinence and other neurological symptoms. Cognitive function impairment develops over time. In a small case series generalized cerebral atrophy was detected in MRI (Table 5) [2].

Table 5.

Clinical, neurological, and eloctrophysiological features of nodding syndrome in Kitgum, Uganda: an observational case series

Hitherto, no longitudinal studies have been performed and the natural history of the disease remains enigmatic. How many patients die, and why death occurs are not known (Table 6).

Table 6.

Putative causes of death

Social and Economic Implications

Nodding syndrome has a devastating effect on families and communities (Table 7).

Table 7.

Nodding syndrome has a devastating effect on families and communities

Children with nodding syndrome have to be under continuous observation. Those in an advanced stage have to be nursed. Patients and their caretakers are stigmatized. Social exclusion will be the consequence. The situation is aggravated by the fact that the disease often affects several children within one family.

Several categories of causes have been proposed. Recently, Dowell et al. (3) summarized the four small case control studies hitherto performed (Table 9).

Table 9.

Causes of Nodding Syndrome

The authors came to the conclusion that nodding syndrome is an epidemic epilepsy for which the cause remains enigmatic.

Several authors have observed an association between onchocerciasis and nodding syndrome. However, it is difficult to envisage that the infection with Onchocerca volvulus could cause nodding syndrome: onchocerciasis is endemic in many countries of West, Central and East Africa and occurs since a hundred of years. However, nodding syndrome is a recent disease and occurs only in a geographically limited area. We suggest that the nodding syndrome increases the exposure to O. volvulus: since the patients become autistic and rather immobile when the disease progresses, the chances to be bitten by black flies are higher than in healthy children. Hence, nodding syndrome could be the cause of an increased frequency of onchocerciasis in patients with nodding syndrome.

In the interviews conducted by one of our authors (HF), mothers of children with nodding syndrome mentioned trauma experienced during the civil war and the existence of bad spirits as the causes of the disease. However, disease concepts rooted in the history and culture of Acholi people are only imperfectly understood.

Mothers consented that nodding syndrome is linked to their presence in IDP (internally displaced persons) camps into which the Acholi were forced to stray during the civil war (1986–2008) (Table 10).

Table 10.

Perceived Causes

Hunger was constant in the camps and people had to eat rotten food and pesticide-impregnated seeds (foreseen to be planted and not to be eaten!). However, a rationale how the ingestion of toxic substances, such as fungal toxins or pesticides or heavy metal, by the mother can lead to development of nodding syndrome in their children is lacking.

There seems to be a relationship between children conceived/born in camps and the later development of nodding syndrome: out of 64 children seen in May 2013, 11 were born in a IDP camp (or shortly later) and developed nodding syndrome when they were between one and nine years old. Four out of the 15 patients, though, were born in the village before parents moved to a camp (Table 11).

Table 11.

Interrogation of 8 families in 4 villages

Treatment

Since the pathophysiology of nodding syndrome is not understood, there is no causal treatment. According to the guidelines of the MOH of Uganda, patients are treated with simultaneously seven anti-epileptic drugs, plus vitamin B6 (Fig. 4). Despite the multidrug treatment mothers report that children still develop seizures.

Fig. 4.

Anti-epileptic drugs and vitamin B6 used in Uganda

Research Agenda

In order to understand the natural history of the disease, to identify the cause(s) and to develop an effective case management the following steps are suggested (Table 12):

Table 12.

Research Agenda 1–4

description of the epidemic

description of the natural history of the disease

identification of the cause(s) and understanding of the pathophysiology of nodding syndrome

personalized treatment and support for affected families and communities

Obviously, nodding syndrome is a complex health issue and can only be solved through a transdisciplinary approach (Fig. 5).

Fig. 5.

Transdisciplinary approach to understand and control nodding syndrome

Table 8.

The search for cause(s)