June’s passing

She just bought two pairs of new shoes.

This is the refrain my brain keeps returning to, as if that will make the outcome any different. She hardly ever bought new shoes, or clothes, and especially furniture. Yet in the past year, as she decided she’d go on dialysis and stick around awhile, she purchased all of that. The shoes were just mere weeks ago. So she can’t really be gone.

My Grandma had been preparing for her death for literally decades. She’d occasionally show me things–knick knacks, collectibles, heirlooms, etc.–that she’d tagged with a sticker on the bottom bearing my name. She’d been methodically going through her belongings and identifying who should get what in order to minimize any issues after her passing. She and Grandpa bought their cemetery plots long ago, just a few blocks from their house, and joked that any other moves they made would be to their plots there.

She taught me how to bake, and made the best desserts ever. She was way more precise with her recipes than I am; I tend to dump flour and sugar and use “rounded” everything for measurements; she always meticulously scraped the extra flour off the top of a measuring cup, and laid down spoons as counting devices for large recipes to keep track of how many cups she’d already added. She knew where to go for the “best lard” in the area. She used to make her own strawberry jam and keep a garden; as kids, we’d snap beans at her house and watch the hummingbirds at her backyard feeders.

She was immensely patient. We stayed at her house quite a bit as children when my mom was in the hospital. One day she was making breakfast for myself and my siblings, including my younger brother, who was maybe 4 years old at the time. He wanted “dipping eggs”– basically made over-easy. Every egg she made, she cracked the yolk and he refused to eat it. Finally one came out unbroken–and she said she “could have killed him” when the first thing my brother did was take a piece of toast and break the yolk.

She was a fan of both sports and politics. She loved the Buckeyes and the Indians, and was disappointed when hometown hero Ben Roethlisberger kept screwing up his charmed life. Though she’d never gotten a driver’s license and had only been employed a few weeks out of her life, she was progressive and couldn’t stand the right-wing mouthpieces. She routinely clipped newspaper articles on MRSA and other infectious diseases to mail to me. She still used words like “oleo” and “davenport.” She would have been 86 in just a few weeks, and we were already planning a party for her and my Grandpa’s 65th wedding anniversary in June. Though she was also obsessive about sending everyone birthday and anniversary cards (always written in her neat, small cursive) but I didn’t know until just a few weeks ago that she’d never gotten a card for Grandpa. She figured 65 years was enough time to wait, and just bought him his first birthday card. It was on the mantle yesterday when my sister went over to visit.

She seemed, in many ways, both fragile and invincible. Over the past 20 years, she’d survived breast cancer, Clostridium difficile, a heart attack (and ~5 minutes of death in 2008), and “The E. Coli” as she called it, like it was a person rather than a bacterium. The E. Coli put her in the hospital with hemolytic uremic syndrome. It was this foe, with its subsequent reduction in kidney function, that necessitated her dialysis. She started the latter in late summer of 2011, after feeling incredibly tired for much of that season. Initially she fought it–she “didn’t want to trouble anyone” and there were no transportation options for seniors going to and from dialysis in her county–but after a family intervention (“you need this or you WILL die, and soon”) she decided she wanted to stick around for awhile. Indeed, she’d mentioned more than once that she felt better in the past 6 months than she had in quite awhile. She’d lost 50 pounds, some of it fluid due to the dialysis, and some due to better eating via a “meals on wheels” program she started with Grandpa–and was confident enough to make some purchases, like the shoes and a new sofa.

Two days ago, Grandma June was unable to do dialysis at her clinic as a clot was identified. Yesterday, my aunt took her to a hospital facility to have it checked out and receive dialysis there. I’m not yet sure of all the details; sounds like she had another heart attack (due to the clot?) but this time, there wasn’t any coming back, new shoes and sofa be damned.

The emergence of “nodding disease”

The emergence of “new” diseases is a complicated issue. “New” diseases often just means “new to biomedical science.” Viruses like Ebola and HIV were certainly circulating in Africa in animal reservoirs for decades, and probably millenia, before they came to the attention of physicians via human infections. Hantavirus in the American southwest has likely infected many people, causing pneumonia of unknown origin, before the Four Corners outbreak led to the eventual identification of the Sin Nombre virus. Encroachment of humans into new areas can bring them into contact with novel infectious agents acquired via their food or water, or by exposure to new disease vectors such as mosquitoes or ticks. Occasionally, emerging diseases may be truly “new”–such as recombinant influenza viruses that resulted from a mixture of viruses from different host species to form a unique variant, different from either parent virus.

Nodding disease is one of those that has only recently appeared on the radar of those of us in public health, although it is not truly a “new” disease. It was first described 40 years ago, but this syndrome has been sufficiently rare as to not merit significant medical attention until 2010. Outbreaks of nodding disease have now occurred in South Sudan, Tanzania, and Uganda, affecting thousands of children. The disease first presents as cognitive difficulties; then the nodding starts, especially when children are provided food. They experience further cognitive decline, and ultimately regress to an almost infantile stage, where parents cannot leave them unattended for fear they may wander off or injure themselves by accident. Death appears to often be a result of such accidents: (drowning, falling into a cookfire) or starvation, as the seizures in the late stages of the disease seem to make it virtually impossible for the child to eat. No one is known to have recovered from the disease.

While the cause(s) still remain mysterious, studies have been done trying to determine risk factors for disease development. A recent CDC-assisted study, for example, was carried out in the new country of South Sudan. This examined 38 matched cases and controls and examined dietary as well as infectious disease factors, looking at issues such as vitamin deficiencies, a history of hunger, and current infection with the parasite Onchocerca volvulus.

This particular agent is interesting, as the nematode already causes a well-known disease, river blindness. Like many parasites, the life cycle of O. volvulus is fascinating and complicated. Humans are the main host, who are initially infected via the bite of the black fly, which was herself infected with O. volvulus from a previous human meal. After inoculation, the nematode larvae migrate to the subcutaneous tissue of their human host, where they multiply and mature over the course of 6-12 months, eventually mating and producing microfilariae–little baby worms, up to 3000 per day per female nematode. It’s this life stage that are then ingested by black flies during a daytime meal, when the microfilariae migrate to the host’s skin. Within the fly, they will mature through three larval stages, ready to infect another human host.

How then do these worms cause blindness, if they live mainly in the subcutaneous tissues and, sporadically, the skin? The microfilariae also migrate to the surface of the cornea, and when these organisms die, they cause an intense immune response. Interestingly, this response seems to be due not to the worms themselves, but to their Wolbachia symbionts–bacteria species notorious for infecting parasites (and insects) and causing all sorts of weird things to happen. Repeated episodes of this inflammation can lead to keratitis, and the cornea eventually becomes opaque. O. volvulus can also cause intense skin itching, leaving dead and discolored patches of skin in addition to the characteristic blindness. In all, it’s a nasty disease but one that is relatively simple to treat if caught early, either with antiparasitic drugs or even with antibiotics such as tetracycline to kill the Wolbachia. The disease can also be prevented by fly mitigation and preventative doses of anti-parasitic medicines.

Testing for O. volvulus is relatively simple. The MMWR study used a “skin snip”–just as it sounds, taking a small piece of skin from the patient and examining it for microfilariae. However, this has the limitation that it may miss early infections (where microfilariae have not yet developed and spread) or mild infections (where there are fewer organisms per square millimeter of skin sample). They note that they also took blood samples to examine antibody responses, but those data were not yet available.

What they found was interesting. In one village, Maridi, they found a matched odds ratio of 9.3 (with the cases being more likely to be currently infected with O. volvulus than the controls), which agrees with an earlier study done in Tanzania which found high levels of infections in cases. However, no healthy controls were tested for comparison in that publication. Furthermore, in the South Sudan study, no statistically significant difference in parasite infection was found between cases and controls in the second village, Witto. Why the dramatic difference between the two locations in the same country? Don’t know. It could simply be related to small sizes (only 25 pairs were examined in Maridi, a “semi-urban” area, and 13 in Witto, described as rural). We also don’t know anything about temporality–were the patients affected before they developed nodding disease, or subsequent to the start of symptoms? Even though many questions remain, the Ugandan government is taking steps that look as if they believe a cause of nodding disease has been found, and that O. volvulus is that cause. While additional measures to stop the spread of the parasite are probably a good idea in any case (reducing river blindness is also good), I certainly wouldn’t call this case closed, and neither did the individuals speaking on this issue recently at ICEID, where this outbreak was discussed in at least two sessions I attended.

There is biologic plausibility for O. volvulus to cause a seizure disorder. Several other types of parasites can cause epileptic conditions, including the tapeworm Taenia solium, which can originate in beef or pork products. Could it be that O. volvulus is getting into the brain and causing pathology, leading to seizures? The 2008 Tanzanian study suggests no, as the cerebral spinal fluid was tested in 42 patients and found to be negative for O. volvulus DNA in all patients.

With some emerging diseases, there is the risk that the incidence of a disease is increasing due only to awareness of an illness–the more doctors that recognize it, the more cases they will diagnose. However, there is anecdotal evidence that this isn’t the case with nodding disease:

Dr. Abubakar said in an interview that while the syndrome is known to have existed for some time in South Sudan, the recent spike in reported cases could only partially be explained by wider awareness and better surveillance. “It’s not only local authorities but local NGOs saying more children have been affected,” he said. Particularly striking, he said, is that in South Sudan “there are a number of displaced people from another location who did not have nodding. But after the displacement, when they moved to affected areas, after 2 years the children started developing the syndrome.”

Additional studies and more thorough surveillance are needed to confirm that this is true, which would suggest a localized focus of disease in multiple different areas (which does seem to be the case at this point in time).

The migration aspect is intriguing, suggesting some sort of environmental exposure–if it was simple genetics, where the children were living shouldn’t matter. However, this puts us back almost as square one, examining what is present in the local environment–both infectious and non-infectious agents including heavy metals and various toxins.

The work investigating nodding disease is still in its infancy, but already “nodding disease” has affected more individuals than all of the recorded cases of Ebola. Now that there is recognition of the disease, and some international support for research into its causes, hopefully better treatment and prevention efforts will follow.

Works cited

WInkler et al, 2008. The head nodding syndrome–clinical classification and possible causes. Epilepsia. 49(12):2008-15. Link.

CDC. 2012. Nodding Syndrome — South Sudan, 2011. MMWR. 61(03);52-54. Link.

Great Plains Emerging Infectious Diseases Conference–Registration Open

I mentioned last month that we are planning an Emerging Diseases conference here in April. Things are moving quickly and registration is now open (here). Abstract submission is also up and running here.

The details:

Oral and poster presentation research abstracts are due by 5:00pm on March 23, 2012. Individuals may submit up to two research abstracts. Abstracts must not exceed 250 words in length. There are a limited number of spots available for those interested in providing a 15-minute oral presentation. Abstracts submitted for oral presentations that are not selected for a talk will automatically be considered for the poster session. Please do not submit an abstract if your attendance is questionable. Confirmation of participation must be received no later than April 1, 2012.

Monetary awards will be conferred upon the top three student presentations (oral or poster).

Authors will be notified of the review committee’s decision by April 2, 2012.

If you have any questions regarding the conference, registration, or abstract submission, drop me a line or visit the conference website. We’re also still accepting ideas for breakout sessions in an unconference format, so feel free to contact me about thoughts for those as well. Hope to see some of you there!