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Seeking an End to the Terror of Rabies in Madagascar

Local boys rejoice over their newly rabies-vaccinated pups in Serengeti District, Tanzania. May 2014. Photo by Malavika Rajeev.
Local boys rejoice over their newly rabies-vaccinated pups in Serengeti District, Tanzania. Mass dog vaccination campaigns have been shown to be the most effective way to control canid rabies globally. Photo by Malavika Rajeev

“Haromotana,” nods the nurse in the remote health clinic in western Madagascar.

She’s only seen one case in her lifetime, but she remembers the incident from five years prior as though it happened only yesterday. She shudders slightly as she recalls the raving man who staggered into her clinic, mouth foaming, limbs thrashing, only further agitated by attempts to calm his nerves and slake his thirst. “Tena natahotra ny rano izy,” she recollects. He was so afraid of water. 

Haromotana is a Malagasy word which translates roughly to “twisted in fury.”  In French, we know the disease better as la rage, in Italian la rabbia, in Spanish la rabia—all derived from a Latin root meaning “to rave with madness.” In English, we call it rabies.

An Ancient Disease

Rabies is perhaps the oldest known infectious disease afflicting humans, with accounts dating back as far as 2300 B.C. when the Babylonian Eshnunna code documented fines assigned to dog owners whose animals had bitten people. Today, we think that rabies originated in vampire bats in Latin America, but most human cases we see result from a virus that has jumped the species barrier and is now independently maintained in dogs; human infection with bat rabies is comparatively rare. Bats appear relatively resilient to the disease (as they seem with many viruses!), but rabies is almost universally fatal for both dogs and humans.

Rabies is a curious beast that we still don’t understand well—incubation periods (that’s how long the pathogen circulates in a host before that host shows symptoms) can range from days to months to possibly years, depending on the location of the bite. The pathogen appears to hide out for a while, then slowly works its way through the central nervous system to attack the brain, and by the time people begin to show symptoms, it is usually far too late for effective treatment. Rabies manifests itself so violently that witnesses, like our nurse in remote Andavadoaka, Madagascar, tend to remember a single case for years after the incident. And one of its most notable symptoms is that which she recalls best—the telltale fear of water. Rabies is transmitted via saliva, and in a clever manipulation on the part of the pathogen, the disease causes infected persons to eschew water, thus resulting in extreme thirst and heightened production of virus-ridden saliva in an infected individual’s mouth.

Investigating New Research Questions

As part of my PhD studies at Princeton University, I’ve been researching bat-borne zoonotic diseases (including rabies-related lyssaviruses) in Madagascar for much of the past four years. This trip, however, I am joined by classmate Malavika Rajeev, a first year student in Professor Jessica Metcalf’s lab at Princeton, who is launching a new project attempting to understand the dynamics of rabies persistence and transmission in domestic dogs in Madagascar. Previously, Mal worked on a project under the supervision of University of Glasgow Professor Katie Hampson (a Princeton alum), using contact tracing methods adopted from the public health field to track chains of rabies transmission in the Serengeti District of Tanzania.

The first case of human rabies in Madagascar was reported in 1896 and, just two years later, inspired the formation of Institut Pasteur de Madagascar (IPM), an epidemiological research institute still active to this day. Originally, IPM was launched to attempt to understand and combat rabies, though today, scientists and doctors at IPM (myself included) busy themselves with studies of a whole host of human and wildlife afflictions. IPM also provides free post-exposure prophylaxis (PEP) treatment for people who have been bitten by a potentially rabid animal at anti-rabies centers distributed all across the island of Madagascar.

If post-exposure vaccines with long-term, anti-rabies antibodies are sought immediately after an individual is bitten by a rabid dog, the disease can usually be halted before it ever progresses to the symptomatic stage. Thus, rabies deaths are preventable—but they still happen with terrifying frequency; such is often the case among the so-called “neglected tropical diseases.”

A Plan for Elimination

Disease ecologists like to quote a figure called “R∅,” or the basic reproduction number, which describes the number of infections resulting from one initial infection in a population. A disease spreads when R∅ is greater than 1, meaning the infection can more than replace itself.

Typically, we estimate R∅ using complex statistical techniques, but Katie Hampson has actually been able to measure R∅ on the ground by conducting interviews in places where dog bites have recently occurred and quantifying the average number of new infections resulting from one rabid dog in a community.

People line up for dog vaccination. Serengeti District, 2015. Photo by Katie Hampson.
People lined up for dog vaccination in Serengeti District, Tanzania, 2015. Photo by Katie Hampson

Katie’s estimates of rabies R∅ from contact tracing methods are consistent with those previously reported using other methods, and all suggest that rabies R∅ is just over 1, meaning that relatively minor interventions should be able to push R∅ below 1 and force the pathogen along the road to eradication. Typically, those interventions appear in the form of mass dog vaccination campaigns—but such an intervention is hard to maintain in a region like the Serengeti with porous, transnational borders. In Madagascar, however, an isolated, island nation—the Eighth Continent, if you will—such a goal should be more tractable, though difficult still.

The Challenge Ahead

“Misy haromontana rehetra eto Madagascar!” There is rabies everywhere in Madagascar, says Dr. Glenn Edosoa, Coordinator of the Anti-Rabies Program at the Ministry of Public Health, Madagascar. And, indeed, it seems to be so. Mal and I traipse across the island—from the Center to the South to the East to the West: Moramanga, Toliara, Andavadoaka, Ranomafana, Mananjary, Mahajanga. We inspect notebooks full of bite reports, chat with doctors and veterinarians and families, and everyone has stories about rabies. For over a hundred years it has been raging on this island, and it looks as though it shows no signs of stopping soon.

“Hoviana hiverina?” When are you coming back? asks Dr. Glenn of Mal, who is still in the planning stages of her research.

“Amin’ny juillet,” she says. In July, picking up her first few words of Malagasy quickly. “That’s when we’ll really get started.” And I see in her eyes the fear and excitement of a new project, a new challenge ahead.

Malavika Rajeev contemplates rabies dynamics near Ambatondrajaka, one of the most rabies-afflicated regions of Madagascar, according to Dr. Glenn Edosoa at the Ministry of Public Health. February 2016. Photo by Cara Brook.
Malavika Rajeev contemplates rabies dynamics near Ambatondrajaka, Madagascar, one of the highest-reporting vaccine distribution centers on the island. Photo by Cara Brook

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