The Nodding Syndrome Epidemic: An International Medical Mystery

Ugandan researchers, along with the rest of the world, tackle this unexplained syndrome through the diagnostic process of elimination.

by Cristina Deptula

From Dr. Oz to House M.D., medical mysteries fascinate us. Along with the practical need to avoid suffering and health risks, many of us seek answers to unexplained puzzles as a way to make sense of our world.

In real life, matters are often complicated, and not always solved in an hour by one charismatic, maverick researcher. Still, though, the hard work and ingenuity of a dedicated scientific team can bring positive results in tough situations.

One real-world challenge for international medical professionals is the outbreak of ‘nodding syndrome’ in eastern Africa. First documented in Tanzania in the 1960s, nodding syndrome is a debilitating and usually deadly neurological disorder currently affecting nearly 7,000 children between the ages of 5-15, causing seizures, stunted growth, and progressively worsening brain damage. Named for the distinctive nodding motion of its victims’ heads during seizures, the disease kills patients indirectly by leaving them weak and vulnerable to accidents or through malnutrition since the children experience seizures while eating.

According to Dr. Abubakar of the World Health Organization, scientists have classified nodding syndrome as a new medical condition since its etiology – how it affects patients and develops over time – differs from that of normal epilepsy or narcolepsy.

“The symptoms and signs of nodding syndrome are very unique, and cannot be linked to any other illness,” Abubakar explains. “Nodding Syndrome is believed to be different from other regular epilepsy since [the] majority of the patients are without any [congenital] brain damage or focal neurological signs.”

Formerly also called ‘nodding disease,’ the condition’s now termed ‘nodding syndrome’ since no one knows what’s causing it. Health professionals can only diagnose it by noticing the presence of certain symptoms that tend to occur together in affected patients.

As SEED Media Group science writer Tara C. Smith explains in her March 27 entry in her blog Aetiology on nodding syndrome, a ‘new’ disease does not necessarily mean that a new infectious organism or toxic substance has appeared. It could simply mean that the conditions have finally become right for something already present to affect enough people to get noticed by medical science.

Physicians and health workers in southern Sudan and northern Uganda continue to diagnose new cases of nodding syndrome, and cannot offer many treatments or preventive measures. So, the CDC, the Ugandan Ministry of Health, Gulu Hope and other private Ugandan and Western charities and nongovernmental organizations and the WHO have joined forces to carry out comprehensive medical research and to provide support to the families of sick children.

Dr. Suzanne Gazda, a physician with Gulu Hope, a large and widely recognized medical and development charity in Uganda, says that nodding syndrome seems to occur in areas already hard-hit by war. This would include the locations of the most recent observed outbreaks: Tanzania in the sixties, South Sudan during and after the civil conflict there, and now northern Uganda as people return home from refugee camps a few years after fighting raged in the region.

Gazda further points out, “According to a study by the Centers for Disease Control (CDC), we do not believe that nodding syndrome is contagious. Without any insights to the cause, however, there is no way to know if there could be worldwide implications due to other random outbreaks. Not knowing the cause of the disease poses the biggest threat at this time.”

 

Current Directions in Treatment

Gulu Hope is building treatment centers for children with nodding syndrome around northern Uganda, known as Havens of Hope. Currently medical treatment for the disorder is limited to antiseizure drugs, which can only treat symptoms and slow the condition’s progress, and which are often in short supply in poor rural areas. But the centers also offer food and day care for those who often cannot be left alone safely, offering some relief to impoverished farmers with sick children while collecting epidemiologic data on affected families to assist with medical research.

Community health workers survey families receiving care from the Havens, and other public and private treatment facilities, to see if any patterns emerge among the sick: similar life experiences, locations, etc that might provide a clue as to the disease’s origin. Through epidemiology – the statistical study of how medical conditions affect populations – scientists can see what groups of people seem most vulnerable to a disease and thus deduce possible risk factors.

Donations to [Havens of Hope] will provide funds towards these care centers and research efforts. Donations can be made at http://www.guluhope.org/donate/.

Uganda’s governmental Ministry of Health has also undertaken a public education campaign to teach public and private community health workers to identify and track cases of nodding syndrome. They also encourage the public to take part in the international epidemiological research studies.

 

Preliminary Investigations

Most diseases presently known to medical science have causes that fall into one or more major categories: infection (from a virus, bacteria, fungi or other parasite), environment (from exposure to a toxic substance), nutritional deficiency, genetic, or autoimmune (caused by the immune system’s mistakenly targeting the body’s own cells).

Researchers work through the process of elimination to uncover the cause(s) of any new conditions.

As mentioned before, researchers do not believe that nodding syndrome is contagious from person to person, making some types of infection unlikely as a cause. As for  parasites, likely candidates, such as the native black fly-transmitted worm Onchocheria Volvulus, which causes river blindness, have been hypothesized, but no one has found solid evidence for a causal link to nodding syndrome. Currently the CDC, in collaboration with Ugandan authorities, is spraying to eliminate the black fly from the country’s affected northern regions to see if that produces a beneficial effect.

Dr. Abubakar explained that World Health Organization (WHO)  researchers had conducted skin snips (taken skin samples) from children with nodding syndrome in three different Ugandan communities. Most affected children had antibodies for O. volvulus infection, but the worm’s prevalent in many other areas of Africa where nodding syndrome is rare or nonexistent, so the conditions could be unrelated.

A German research paper published in the December 2008 issue of the scientific journal Epilepsia discusses a prospective study of 62 children with nodding syndrome in Tanzania. Many children had signs of O.volvulus in their skin (skin PCR positivity) but did not show any of the expected diagnostic signs that the infection had spread to their brain. However, the sick children did seem to have hippocampal sclerosis (damage to certain areas of the brain) brought about by an unknown mechanism.

As for environmental or toxic exposure, a CDC study tested nodding syndrome patients through urinalysis for signs of mercury and arsenic, both of which could cause relevant symptoms. However, the urine samples from all the children in the study had low levels of these toxins. Researchers are presently testing for evidence of exposure to other damaging substances.

Some studies suggest children with nodding syndrome have low levels of vitamin b6, a substance important for many body functions, including oxygen transport, protein digestion, and immune function. However, the children’s seizures make eating difficult, so many become malnourished as a result of the disease. So it is unclear whether the vitamin deficiency functions as a cause or risk factor for developing nodding syndrome or if it is simply another symptom. The CDC will soon carry out a vitamin b6 trial to see if supplementing children’s diets in affected areas with the nutrient reduces the incidence and/or severity of the disease.

A genetic or autoimmune component to nodding syndrome could be possible, but would not explain why the condition tends to break out in small, localized regions. If this condition has nothing to do with the environment, then why does it affect many children in certain rural villages, rather than being dispersed randomly through the population? Some researchers have observed that cases of epilepsy and related conditions tend to cluster within certain families. So it could be that some people are genetically predisposed to be more vulnerable to whatever’s causing nodding syndrome.

Nodding syndrome could also arise from the interaction of multiple environmental or lifestyle risk factors.   For example, children already weakened by a nutritional deficiency might be more vulnerable to a certain parasite, or vice versa. Or people whose bodies were already stressed in some way by armed conflict could be more affected by whatever causes nodding syndrome than others.

Perhaps factors associated with poverty and/or war in the affected African regions contribute to this syndrome? The disease does seem more common in poorer rural areas. However, nodding syndrome only became prevalent in northern Uganda after the nation’s civil war ended and most people left the crowded, unsanitary refugee camps and returned home to the countryside. So scientists do not believe it is directly connected to camp conditions.

 

World Health Organization Conference in Uganda: Time to Strategize

The World Health Organization, together with the Ugandan Ministry of Health and the CDC, just hosted the first scientific conference on nodding syndrome, in Kampala from July 30th-August 2^nd, with hundreds of leading researchers in attendance.

According to Dr. Abubakar, the conference’s goal was to bring together experts, researchers, and officials from universities, the WHO, CDC, international development agency USAID, and other partners. Together, they set the agenda for future collaborative nodding syndrome research and agreed on recommended clinical definitions, procedures and treatments.

Researchers are looking into several possible factors to see if they have any relevance to nodding syndrome. These include environmental toxins, local food and imported food aid, genetics, O. volvulus infection, African swine fever virus, autoimmune reactions to O.volvulus, malnutrition and B complex vitamin deficiencies, and chronic carbon disulfate intoxication. Scientists also would like to learn more about what causes the brain atrophy of many nodding syndrome patients.

The CDC and the Ugandan Ministry of Health also will undertake a small clinical trial in the next few weeks to determine the efficacy of antiseizure medications, currently the best available treatment for the syndrome.

 

Various Challenges, Ways to Move Forward

So far there has not been any international organizational funding directed specifically and exclusively towards nodding syndrome treatment or research. The participating organizations have been tackling the condition out of their regular, limited budgets.

Gazda and others with Gulu Hope say one of the most challenging aspects of addressing nodding syndrome is the lack of a systematic strategy for medication distribution and patient follow-up.

Some of these difficulties stem from patients’ living in remote areas with few medical resources. Uganda’s Ministry of Health press releases highlight food, medicine and resources directed towards affected people in northern areas, but many families of children with the syndrome have said there are not enough medical supplies at their local clinics. When there are antiseizure medicines available, patients must take whatever drugs their clinic has to offer, making it difficult to track and compare the efficacy of various medications. People in remote rural areas also cannot always afford transportation to medical care, even when it is available.

Researchers hope to surmount some of these obstacles by raising worldwide awareness of the scope of nodding syndrome. Tara Smith reminds us there are already more diagnosed cases of this condition than total ever-reported incidences of Ebola virus.

Ugandan media campaigns are drawing more public attention to the matter. One member of Parliament, Beatrice Anywar, who hails from a district where the condition is prevalent, continually advocates for attention to research and patient care.

Other members of Uganda’s government have responded, although more slowly. Recently, in response to public pressure, the country’s parliament sent a fact-finding mission to affected regions to ‘determine whether nodding syndrome was really a problem.’

Most professionals working on nodding syndrome say that recruiting qualified researchers, and having a plan in place to implement their recommendations, could help ensure funds are used effectively. Dr. Abubakar considers bringing more scientific expertise to the table even more important than fundraising at this stage in the research effort.

 

Hope, Determination, and Dignity

Despite the scientific and logistical difficulties, researchers remain determined to develop treatments, cures, and preventive measures.

According to Dr. Gazda, “a recent [scientific] article suggests that medication, nutrition, and vitamins may help many [sick] children live more normally.” She sees this sign of hope as further motivation to continue conducting and promoting research.

After first learning of nodding syndrome in December 2011, she immediately felt compelled to help tackle the issue.

As she explains, “We are humbled by and honored to work with the Acholi people [an ethnic group affected by nodding syndrome.] By their strength, resilience, love for their families, determination to survive and will to go on. And we hope to help the children live longer and with restored dignity.”

It may not be possible to teleport famed television diagnostician Dr. Gregory House to northern Uganda, southern Sudan or Tanzania to get to the bottom of this mysterious condition. But, hopefully, harnessing the intellectual power, resources, and diagnostic procedures of the world’s medical scientists will lead to more insights into the nature of the syndrome and more effective treatments.

 

References:

Dr. Suzanne Gazda. Personal interview, July and August 2012.

Dr. Abdinasir Abubakar, Personal interview, July 2012.

Smith, Tara C. “The emergence of “nodding syndrome.” Aetiology, Ed. Seed Media Group, March 27, 2012. Seed Media Group, accessed May 2012, http://scienceblogs.com/aetiology/2012/03/27/the-emergence-of-nodding-disea/

Winkler, Andrea S., Friedrich Katrine., Konig Rebekka., Meindl Michael., Helbok, Raimund., Unterberger, Iris., Gotwald, Thaddaeus, Jaffer, Dharsee., Velicheti, Sandeep., Kidunda, Aslam., Jilek-Aall, Louise., Matuja, William., Schmutzhard, Erik. “The head nodding syndrome: clinical classification and possible causes.” Epilepsia Volume 49, Issue 12, pages 2008–2015, December 2008. Wiley Online Library, accessed July 2012. http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2008.01671.x/full

Flock, Elizabeth. “Forget Joseph Kony, what Ugandan children fear is the nodding syndrome.” Washington Post Blogs, Ed. Washington Post,  March  03/13/ 2012. Accessed June 2012,    http://www.washingtonpost.com/blogs/blogpost/post/forget-joseph-kony-what-ugandan-children-fear-is-the-nodding-disease/2012/03/13/gIQA4Cif9R_blog.html

MacKinnon, Rebecca. “Uganda: nodding syndrome Denying Children Their Future.” Global Voices, July 11, 2012. Global Voices Foundation, accessed July 2012, www.globalvoices.org

 

Cristina Deptula is a writer from San Leandro, California. She can be reached at cedeptula@sbcglobal.net.