Science in the time of cholera (and nodding syndrome)

Published online January 11, 2012.

In August 1854 a terrible illness tore through a London neighborhood, killing hundreds in a matter of days. The terrifying disease emptied the body of fluid until vital organs shut down, after which point the petrified soul would succumb to the illness. Death often arrived less than twelve hours after the first signs of an upset stomach. Londoners of the day had a name for this illness, but did not understand its cause. They called it cholera.

Though cholera outbreaks had hit London before the mid-1800s, the Broad Street Pump outbreak of 1854 is now perhaps the best known. It was during this scourge that physician John Snow was able to demonstrate that cholera was not an airborne disease, as was the popular and professional opinion at the time, but rather a waterborne disease. This insight proved critical to improving public health in London and beyond. Londoners had been emptying their waste into the Thames, often just upstream of intake pipes for water companies. Their water and city stunk. But because disease was thought to be airborne, they doused smelly sidewalks in chloride of lime in attempt to purify the air. They made few attempts to purify the water so obviously contaminated with their own waste.

When cholera inevitably struck, they applied all manner of remedies, most of them useless at best. Castor oil, opium, and leeches were all espoused to treat cholera, not just by ordinary folks, but also by doctors. Worse still were treatments such as laxatives or bleeding. The extreme dehydration facilitated by cholera was often “treated” by attempts to further remove fluids from the body.

In hindsight, both the cause and the treatments for cholera are straightforward, if not obvious. Cholera is a waterborne illness that spreads when one person ingests the cholera-infected waste of another person. The treatment for the extreme dehydration that ensues is most fundamentally rehydration – consuming copious amounts of fluid to replace those that are lost. Yet at its emergence, a series of facts and observations did not at first fit together in a single theory about the cause of cholera. When cholera struck a household, sometimes it struck everyone, sometimes just a single person. In a neighborhood, some homes would be hard hit, while others escaped untouched. Whether you survived or not seemed random.

So it is with another illness in our midst – nodding disease. Nodding disease sounds like a folksy and tabloid-inspired syndrome. Its name describes the telltale symptoms of the disease, a rhythmic head nodding in children. The fact that unlike many diseases its name does not betray anything about its likely causes demonstrates just how little we know about its transmission. For example, HIV (human immunodeficiency virus) is named for the virus that causes AIDS. The name malaria comes from the Italian mala aria, meaning “bad air”, so named because the illness we now know is caused by a parasite was originally thought to be airborne.

But despite its odd name, nodding disease is far from folksy or fake. It is often fatal. First reported in Tanzania in 1962, nodding disease has since spread throughout what is now South Sudan, and has been rapidly spreading in northern Uganda as well.

The pattern of incidence of nodding disease and its symptoms are puzzling, as were those of cholera in the early nineteenth century. First, the onset of nodding disease appears to occur almost exclusively in children between the ages of 5 and 15.

Second, nodding is reportedly often triggered by the presence or eating of familiar foods, or when a child becomes cold. Unfamiliar foods, such as chocolate candy bars, do not induce nodding. Third, when untreated, those with nodding syndrome cease developing both physically and mentally. They are often stunted and experience mental retardation. Fourth, most children affected come from very poor families. There are now thousands of children in South Sudan and northern Uganda who experience symptoms of nodding disease, and the incidence of the syndrome appears to be increasing.

Several theories regarding the cause of the syndrome have been mooted, but none proven. For the past several years, teams of experts from the U.S. Centers for Disease Control (CDC) and World Health Organization (WHO) have travelled to South Sudan and northern Uganda in an attempt to better understand the causes of nodding disease, and possible treatments. Their work suggests that nodding disease is a new epilepsy syndrome, and that the characteristic head nodding is caused by seizures that lead to temporary lapses in neck muscle tone.

A vast majority of children experiencing symptoms of nodding disease are also infected with a parasite called Onchocerca volvulus, which causes river blindness. The high prevalence of this parasite in victims of nodding disease means that the most plausible (published) theory about the cause of nodding disease links the syndrome to O. volvulus, but how and why remain unclear. Moreover, there are a number of children both in and outside the region who are infected with the parasite and do not acquire nodding disease, so the link between the two is not straightforward.

So far, therefore, we have accumulated a series of facts about the mysterious syndrome, which have yet to be pieced together in a coherent theory. We have many more tools at our disposal than did the Londoners of the 1800s, but answers to pressing medical and public health questions do not usually come without time and resources. Nodding disease is a terrifying prospect for those living in South Sudan and northern Uganda not only because of the debilitating effect it has on children, but also because families and communities do not understand why their children are falling ill in the first place. A confusing array of facts, theories, and observations are unnerving both to those in the midst of the outbreak, but also those who see its spread as a very serious health issue for the region.

Misunderstanding the causes of nodding disease can have disastrous consequences, as was the case with cholera some 150 years ago. So far, anti-epilepsy treatments appear to be helping children experiencing nodding disease, but supplies of these treatments are often scarce, and determining the ultimate cause of epilepsy in these children should be a high priority for health officials. Cases of epilepsy are often documented at high rates in hospitals in the region, and there is thought to be a link between epilepsy and cerebral malaria as well. In Arua Regional Referral Hospital, in northwestern Uganda at the border with Sudan and DRC, 7 percent of all outpatient children over age 5 in April 2009 were diagnosed with epilepsy. In 2004/05, 74 percent (nearly 4500) of all cases in the Mental Ward were diagnosed as epilepsy.

Clearly, epilepsy, whether nodding disease or otherwise, is a condition that deserves the utmost attention from public health and medical professionals. The sooner we understand the causes of this new breed of epileptic seizures, the sooner we can take steps to both treat it and prevent its spread. In the absence of a compelling theory about its cause, however, fear and futile treatments are likely to ensue.

Researching Nodding Disease

Nodding disease is a syndrome that was first reported in Tanzania in 1962, has been spreading in South Sudan and Uganda more recently. The number of cases in northern Uganda appear to have increased at a particularly fast clip in the last year. Nodding disease sounds made-up, but it is very real and often fatal, and is becoming a growing problem in the region. Most problematic is that the causes of nodding disease are still unclear, although there appears to be a connection with a parasitic infection from Onchocerca Volvulus, which causes river blindness.

Adult Onchocerca volvulus worms (WHO)

The Daily Monitor ran a story on December 23, 2011, quoting director of health services in Uganda, Dr. Jane Achieng, as saying that there are around 2,200 reported cases of nodding disease in Uganda (most in Acholi sub-region) and that the first case in the area had been reported in 2009.

A letter to the Daily Monitor written by Dr. Ddungu, of the Uganda Programme on Cancer and Infectious Diseases, notes that a similar phenomenon was studied in Kyarusozi sub-county as early as 1991. A 1992 study by E. Ovuga et al. on this topic was published in the East African Medical Journal.

Nodding disease appears to afflict children between the ages of 5 and 15 and is usually diagnosed by the characteristic nodding it produces in children. The head nodding (HN) is often triggered by eating or seeing familiar foods, or when a child becomes cold. Winkler et al. (2008) write:

HN represents a repetitive short loss of neck muscle tone resulting in a nodding of the head, sometimes associated with a short loss of muscle tone of the upper extremities. Loss or impairment of consciousness may be present, but not always. To date HN is not mentioned in any classification and it remains unclear whether it represents a seizure disorder and if so, whether it belongs to the group of generalized or partial seizures.

Nodding disease appears to be a growing problem that warrants serious attention from the government. The CDC and WHO have been involved in investigating its causes, but there has been relatively little information available to the public about this illness. I’ll be posting information on the published medical literature on nodding disease, as well as news updates and commentary as they become available.

Why Don’t We Have a Global Fund for Maternal Health?

Well, cause someone would steal the money anyway. No? Ok, how about because the international community is preoccupied (is obsessed too strong a word?) by the much more exotic sounding tropical and infectious diseases (a virus that turns your insides to mush = exciting/terrifying, bleeding to death giving birth = boring). Not everyone gets Ebola or HIV or malaria, but most people either give birth or are the direct cause of someone else giving birth (and if nothing else, at least someone once gave birth to them). So maternal health is ordinary, banal, and just plain not-sexy. That is, unless it is tied to something exotic (see Prevention of Mother-to-Child Transmission of HIV — PMTCT)…

The wards described in the article of the Tanzanian hospital are not different from those in Uganda. In Mugalo Hospital, around 80 to 100 babies are delivered every day, and there are certainly not enough beds for all the mothers. One medical student working in the labour ward described to me how the “fluids” from one mother giving birth flowed into the ears of another mother who was sharing her mattress one night during his shift.

I don’t know what the solution is to the neglect of maternal health. In Uganda, maternal mortality statistics have barely budged in the past 20 years. The 2006 Uganda Demographic and Health Survey (depressingly) discusses the lack of improvement with regard to maternal mortality:

At first glance, it would appear that the maternal mortality ratio has declined significantly
over the last five years, from 527 maternal deaths per 100,000 live births for the ten-year period prior to the 1995 UDHS to 505 for the ten-year period before the 2000-01 UDHS, and to 435 for the ten- year period before the 2006 UDHS. However, the methodology used and the sample sizes implemented in these three surveys do not allow for precise estimates of maternal mortality. The sampling errors around each of the estimates are large and, consequently, the estimates are not significantly different; thus, it is impossible to say with confidence that maternal mortality has declined. Moreover, a decline in the maternal mortality ratio is not supported by the trends in related indicators, such as antenatal care coverage, delivery in health facilities, and medical assistance at delivery, all of which have increased only marginally over the last ten years.