Monday, January 21, 2008

Reservoir Dogs

Outbreak
One morning, just before Christmas, I was startled by the banner headlines of my local newspaper, which read, ‘Uganda Hit By Epidemics!’ Closer inspection revealed that apart from the ‘usual suspects’, cholera and meningococcal meningitis which have plagued the parts of country recently, two new pestilences are stalking the land, Bubonic Plague in Nebbi, West Nile and Ebola in Bundibugyo, western Uganda.

The outbreak of Bubonic Plague is the latest in a series of epidemics of yersinia pestis that periodically afflicts the border between northwestern Uganda and eastern Democratic Republic of Congo (DRC). The catalyst is exceptionally heavy rains; this past year has seen widespread flooding of the region. The rats, the primary reservoir, meal-ticket and main means of transport for the fleas, the key vector, move into human habitation to avoid drowning. The disease kills the rats, the fleas jump hosts and off we go; ‘The Black Death’ on a miniature scale. As usual, the local health service’s reactions were slow, medicines in short supply and a few hundred caught the disease; about 20, mainly women, have died to date.

The outbreak has been contained in the major towns along the Border but has certainly not been extinguished. It is hardly surprising; the populations are huge, over-crowded and grindingly poor. Healthcare resources are minimal and it’s a long way from Kampala. Central government’s attitude to the epidemic is exemplified by the statements made to the press by the Minister of State for Primary Healthcare, Dr Otaala and the Director General of Health Services, Dr Zaramba. At the press conference Dr Otaala attributed, “the recurrence of [P]lague in Nebbi…….is due to the primitive culture of indigenous people, where men sleep in beds and women on the floor. The people mainly affected are women because in Nebbi women only come up on the bed for sex.” Dr Zaramba, obviously seeking to clarify his Boss’s offensively patronizing statement elaborated, “The flea that causes the Plague can only jump six inches high, if everybody was sleeping on a bed, there would be no Plague in the country.” Now why didn’t someone in CDC think of that!

Ebola
‘The Plague’ has deep historical connotations for many but it no longer frightens the way it did our forefathers. Not so Ebola Hemorrhagic Fever (EHF). Thanks to Richard Preston’s not-bad account of Ebola-Reston in a government laboratory and the hysterical film ‘Outbreak’ in 1995, Ebola has a truly frightening global reputation; to be fair, not without cause. It has an impressive mortality rate of between 50% and 80%. The last time it visited Uganda was 2000/1; it sickened about 450 people in three towns, spread across the north and west, and killed 250. This time it seems to be contained in western Uganda, in a region surrounded by national parks. To date over one hundred people have been diagnosed with EHF and about 40 have died.

What makes this outbreak as interesting as it is scary, is its relatively slow progression. The estimate is it began in September 2007 and was not officially recognized until December. This may in part be to the paucity of healthcare resources in the region but skeptics also suggest that the Government kept it quiet because they did not want to frighten away the Commonwealth Heads of Government Meeting, a huge international junket held in Kampala in late November. The disease became international news in early December.

The second issue is the relatively low mortality of this outbreak compared to others. It seems that the pathogen is a new subtype (the three known to date are Ebola Sudan, Ebola Zaire and Ebola Reston). Paradoxically, the slow progression and low mortality could be very bad for us humans. Scientific opinion holds that humans are ‘dead-end hosts’ for EHF and the speed at which the virus kills us limits its ability to propagate; slowing down the process may enable it to spread more efficiently.

Finally, the so-called index case, the first known casualty, seems to have been a hunter who killed and ate a monkey (primates of all types are common food source in the region). The Government and wildlife organizations are warning locals not to eat monkeys (or chimpanzees or gorillas) which is good for the primate population but primates are just as susceptible to the disease as humans, an outbreak in 2000 in DRC is estimated to have killed 5,000 lowland gorillas. They [primates] are not the reservoir host, which normally carries the disease asymptomatically. The monkey that was killed was probably sick, this week a number of dead monkeys were found in the nearby national park.

Bats
“At this point you are entitled to ask: Damn, what is it about bats?’ David Quammen .
This outbreak comes at a key moment in the study of Ebola and growing array of viruses such as Marburg, Hendra, Nipah and the corona-viruses of SARS, which are producing new and frighteningly lethal human diseases. Virologists collaborating on international research have strong scientific evidence the reservoirs for these and other pathogens, are bats. This should come as no surprise. They have been around a long time, are hugely adaptable and can be found almost everywhere on the planet. It seems the reservoir for Ebola might be a fruit bat. There are lots of them in the forests of western Uganda and the DRC. Moreover, as human population pressure mounts, people increasingly encroach on the natural habitat of the bat and every other wild animal.

Zoonoses
This brings me to the point of my argument. Both of ‘Uganda’s Epidemics’ are zoonotic diseases: Infectious diseases that can be transmitted from animals, wild and domestic, to humans. The really surprising issue (for me at least) is how many zoonotic diseases there are and the burden of disease for which they are responsible. A recent study by the University of Edinburgh calculates that of the 1,710 pathogens afflicting humans, 832 are zoonotic (49%). Among the so-called new and emerging diseases 75% occurred first in animals.

A cursory ‘Google’ produces a veritable avalanche of information on Zoonoses. To study zoonotic disease is to study the path of human history. A couple of examples might serve to illustrate. Yellow Fever, the scourge of the New World for much of the 18th, 19th and early 20th Centuries, that almost stopped the building of the Panama Canal, probably originated in west Africa and traveled to the Americas in the mosquito larvae living in the water barrels of slave ships.


West Nile Virus, a mosquito-borne virus, appeared in the USA in 1999 attacking and killing birds, horses and humans and is now considered enzootic/endemic to the USA. It was first identified in West Nile District Uganda, the setting of my Bubonic Plague story, in 1937. How it got from Nebbi to Nebraska in 70 years is a mystery almost certainly as related to human movement as the migration of Yellow Fever.

Sleeping Sickness or Trypanosomiasis is another disease with an odious reputation. There are two types. African Trypanosomiasis is transmitted by the tse-tse fly from wild animals to domestic cattle and dogs and humans. Data on the disease is sparse; it affects mainly the rural poor who are ill-served by modern healthcare and is an appalling way to die. New World Trypanosomiasis or Chagas Disease is transmitted the Reduviid or “kissing bug”. Chagas Disease infects about 18m people every year in Central and South America, about 50,000 die. Charles Darwin is believed to have succumbed to the disease. The principal reservoir for Chagas is the domestic dog. A recent study found that people could significantly reduce the risk of infection by excluding dogs from bedrooms.

Reservoir Dogs
It seems that ‘man’s best friend’ is a reservoir for a significant number of zoonotic diseases. ‘Fido’ is host to an array of worms, which regularly infest our children, sometimes with awful results like Ocular Larva Migrans, where worms migrate to the child’s eye, and to adults, particularly a tapeworm, which migrates to the liver and causes chronic inflammation known as Hydatid Disease. In Sudan, the domestic dog is the principal reservoir for a terrible disease known as Kala Azar or Visceral Leishmaniasis. Domestic dogs are also the principal reservoir for rabies, in Africa. About 55,000 people, mainly children, die of Rabies every year.

Adapted to Travel
Despite Ebola’s fearsome reputation, it and other exotically-named viruses are seen as diseases of primitive far away places, unlikely to be encountered in the average American ER. That may be true today, Ebola has not yet adapted to distant travel, but if history is any judge, it will soon, and the results could be ghastly. Consider the evolution of the perfectly adapted virus, HIV. It almost certainly jumped to humans from primates in the same way as Ebola and probably the same part of the world. But it kills so slowly it has managed to become a global pandemic, killing millions within 50 years. Even more worrying SARS, a corona-virus which probably spilled over from horseshoe bats and which infected many thousands and killed over 700 people on its first world tour, has disappeared from our radar but will probably return with a vengeance soon, its vector, the international traveler. Finally, there is Avian Influenza, the boogey man of the infectious diseases. One of its ancestors scythed the human race less than one hundred years ago, when the world’s population was much smaller and travel slower. I shudder to think what havoc it would reap in over-crowded poverty stricken Africa or Latin America.



One Medicine
When I began examining the issue of zoonotic disease what puzzled me the most was why, given that zoonoses contribute hugely to the burden of disease and the very clear and intimate relationship between human health, animal health and the ecosystem in which both exist; their respective sciences are so stove-piped. I am not sure they always were. Where we are now seems to be the result of the narrowing of our scientific viewpoints and the specialization of our professions, driven partly by the sheer volume of what we have to know. The history of human health is replete with accounts of men and women who took a broader view of human health than simply the absence of disease; individuals who described, promoted and practiced what has been called ‘One Medicine’ or latterly ‘One Health’.

Amongst the most famous proponents of ‘One Health’, three deserve special mention. Rudolph Virchow, a 19th Century German physician and statesman, often cited as the Founder of Modern Medicine, wrote extensively about the link between human and animal diseases and coined the term zoonosis. William Osler, a Canadian physician and former pupil of Virchow who became one of the four ‘Founding Fathers’ of Johns Hopkins School of Medicine, began his scientific life as a veterinarian and is credited with creating the term ‘One Medicine’. Ironically, whilst at Oxford in 1919, Osler fell victim to the great zoonotic disease of the era, the Influenza Pandemic. Finally, no account of the One Medicine movement would be complete without mention of Calvin Schwabe, the legendry epidemiologist from UC Davis School of Veterinary Medicine, who until his death in 2006, was the leading proponent of a unified approach to human and animal health. His monograph, ‘Veterinary Medicine and Human Health’ remains a classic.

One Health Now and the Future
So where are we now? ‘One Medicine’ is unquestionably a resurgent concept, growing in strength as the public and the scientific communities become increasingly aware of global ecological disturbance directly attributable to human population pressure. The growth of One Medicine ( I prefer One Health) is evinced by the creation of organizations like the Consortium of Conservation Medicine (see www.conservationmedicine.org) and One World, One Health (see www.oneworldonehealth.org) The most recent conference, the Fifth Annual ‘One Medicine’ Symposium, held at the University of North Carolina In December 2007, provided clear directions for future collaboration between scientists involved in the entire spectrum of human, animal and ecological health. I also strongly recommend the excellent article I quoted by David Quammen in National Geographic October 2007.

One Health and the Community
I confess to some reservations regarding how ‘One Health’ is developing, essentially as the academic pursuit of elite scientists. I believe there is an urgent need to include the ‘foot soldiers’ of human and animal healthcare in the debate and in the action, particularly in the developing world where most of the action and interaction is taking place. My experience in Africa and Latin America leads me to believe that the community healthcare workers, who form the backbone of healthcare in most developing countries, know little about zoonotic disease, the inter-relationship between human and animal health, (their domestic animals or wildlife) and even less about their environment and ecology. Yet, as the Ebola story indicates, it is the community healthcare worker who comes first in contact with infectious disease outbreaks, ancient or emerging. Invariably community healthcare providers are so ill-prepared they are amongst the first victims.

I am advocating a fundamental review of what is taught and practiced as community health and healthcare in the developing world. I believe I have illustrated the vital importance of zoonotic disease in the health of people, particularly the rural poor. Most rural peoples are agriculturalists and own domestic animals; healthy animals add to the wealth of their owners, sick animals increase their poverty. The more rural people encroach upon wildlife habitats, the greater the risk that diseases which live relatively innocuously in the wild, will spill over into domestic animals and humans, Uganda’s Ebola outbreak is a good example. I offer an idea. Train two types of community healthcare worker under the same roof; one in human health and one in veterinary health and deploy them to work in teams together in the community. Maybe that’s a concept worthy of a trial project somewhere in Latin America, soon.

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