Rare nodding syndrome caused by common NTD

CDC scientist conducting consultation in South Sudan. Courtesy CDC.

CDC scientist conducing consultation in South Sudan. Courtesy CDC.

If you’ve been following my blog you know that I recently completed a series highlighting each of the 18 Neglected Tropical Diseases (NTDs). While I like to think I’m a rather knowledgeable public health professional, I can certainly say that I learned quite a bit about many of the NTDs. Perhaps that’s partially the reason they are still neglected, not only do they disproportionately affect poorer individuals but because the global health world isn’t throwing tons of money at them they aren’t getting the publicity they need.

That’s why this¬†NIH (National Institutes of Health) headline, “Rare Disease Mystery: Nodding Syndrome May Be Linked to Parasitic Worm“, caught my eye and prompted this posting. This nodding syndrome they reference is affecting children in remote villages in East Africa, and has been since the 1960s (probably also before then but 1960 is the first recorded occurrence of nodding syndrome). Nodding syndrome mainly affects children ages 5 to 15 and causes progressive neurological symptoms including cognitive dysfunction, neurological deterioration, stunted growth, characteristic nodding of the head, and potentially life-threatening seizures. These symptoms identify nodding syndrome as a form of epilepsy. Many cases occur in clusters in small villages and even within families, leading to a huge burden on communities as the affected kids need a lot of care and attention.

While the burden of nodding syndrome is not well known, various case control studies do suggest an increase in cases of nodding syndrome since the 1950s or 1960s. The CDC and Ugandan Ministry of Health did a study on prevalence of nodding syndrome in Uganda in 2012-2013 and found the prevalence of suspected cases to be 7.2 per 1,000 population and probable cases to be 6.8 per 1,000 population. To put that in perspective, Uganda has a malaria prevalence of 150 cases per 1,000 population, so nodding syndrome is not very common.

So what does nodding syndrome have to do with parasitic worms? Well, up until recently, the etiology of nodding syndrome was unknown. Many scientists from many agencies, including local Ministries of Health, CDC, NIH, etc., have tried to determine the cause of nodding syndrome but were unsuccessful in finding the missing link. Researchers from the NIH noticed that kids who have nodding syndrome also exhibited signs of onchocerciasis, the disease that causes river blindness. Various other researchers had suspected that blackflies and Onchocerca volvulus¬†were somehow involved but there was still that “missing link” connecting onchocerciasis infection with nodding syndrome. The NIH researchers have potentially found that “missing link”.

They found that the human immune system is the key player. Other researchers had suspected nodding syndrome to be an autoimmune issue but their tests came up empty. These NIH researchers suspected the same thing but went with a different approach, using protein chip technology. This technology allowed them to screen for thousands of antibodies at once, comparing pooled samples of kids with nodding syndrome to pooled samples of kids without the disease. What they immediately saw was that kids with nodding syndrome had antibodies that reacted 33,000 times more strongly against a protein called leiomodin-1 compared to the control kids. And these antibodies were present in the cerebrospinal fluid, so they somehow crossed the blood brain barrier into the central nervous system. Further research on this relatively unknown protein demonstrated that it is expressed in neurons and the antibodies from the kids with nodding syndrome could kill neurons in lab dishes.

Onchocerca volvulus. Courtesy WHO.

Onchocerca volvulus. Courtesy WHO.

But what about the worms? Turns out that the worms produce proteins that have a similar structure to leiomodin-1. So some kids who are infected with the worms produce lots of antibodies against the worm protein, and those antibodies accidentally attack the similar-looking human protein as well, causing auto-immune neurological damage.

As with almost all new discoveries, further research is needed to figure out the cause and effect of the infection on nodding syndrome. Research does show that the damage is probably permanent, so preventing onchocerciasis becomes an even more important task.

Leave a Reply

Your email address will not be published. Required fields are marked *