Yellow fever gains ground / by Thomas P. Monath

Yellow lever gains ground by Thomas P. Monath Or Thomas P. Monath is Director of Vector-Borne Viral Diseases, Centers for Disease Control, U. 5. Department of Health and Human Services, Fort Coffins, USA I n September 1986, doctors at Yahe Lutheran Hospital in the northern part of Cross River State, Nigeria, recognised an un- usual occurrence of illness, jaun- dice and death among villagers in the area. Within a month, health workers were making similar obser- vations in adjacent areas of Benue State. Schools closed down because of deaths among pupils, and school- rooms were converted into treat- ment centres to deal with the expanding epidemic. Serological examinations indi- cated that yellow fever virus was responsible for the outbreak. An immunization campaign started but encountered many difficulties in delivering the vaccine. An inter- national team of virologists, epide- miologists , and entomologists spon- sored by WHO reached the affected area in mid-December, while the epidemic was still in progress. When it subsided in late December, at least 9,800 persons had fallen ill and 5,600 had died. Many people are surprised to learn that yellow fever remains an important public health problem in the 1980s. Despite advances in environmental health, and the dis- covery of vaccines which rendered yellow fever entirely preventable during the first half of this century, the disease continues to appear in epidemic form and threatens to in- vade countries from which it has long been absent. Both 1986 and 1987 witnessed a major resurgence of yellow fever in West Africa, and a reappearance of the disease in cities for the first time in over 40 years. What are the reasons for the continuing spread of this deadly disease? And what can be done to control it? Yellow fever virus is transmitted by the bite of an infected mosquito. Roughly one person among every five who are infected with the virus becomes severely ill , and of these about 20 per cent succumb to the disease. In its most severe form , the disease begins with fever, head- ache, and muscle pains , and pro- gresses within several days to a tox- ic stage, with the appearance of signs of damage to vital organs, in A rapidly deployed information cam- paign helped to contain a yellow fever epidemic in Nigeria two years ago. Photo WHOfT. Monath particular the liver, kidneys , and heart. Patients develop jaundice , kidney failure, bleeding from the stomach and elsewhere, and finally circulatory collapse and coma . At the present time there is no specific drug or treatment , although good supportive care in hospital may pre- vent complications and decrease mortality. Unfortunately, those af- fected by the disease most often live in remote areas served by ex- tremely limited medical resources . Yellow fever was the first infec- tion of humans shown to be due to a virus and the first virus shown to be transmitted by a biting insect , the mosquito Aedes aegypti. From the 18th to the early 20th century, it was one of the great plagues of humankind. From endemic areas of Africa and South America , the disease was introduced by ships into port cities of the Caribbean, Central and North America, and Europe , creating much havoc and social disruption. In 1900 Major Waiter Reed and his colleagues working in Havana obtained proof that the mosquito transmitted the yellow fever virus. This finding led to sanitation cam- paigns against the urban , domestic mosquito , first in Cuba and Pana- ma, and subsequently in other countries in the Americas. These efforts were successful and led to a marked reduction in the frequency of Aedes aegypti-borne epidemics. The last major outbreak in the Americas involving this mosquito vector occurred in Brazil in 1942. Until the 1930s, it was generally accepted that yellow fever was an exclusively human infection, trans- mitted only by Aedes aegypti , which breeds in containers holding water in and around houses. The discov- ery of a jungle cycle of transmission .in South America and Africa , involv- ing passage of the virus between WORLD HEALTH , July 1988 monkeys and tree-hole breeding mosquitos , shattered hopes that the disease could be eradicated . Cities and towns infested by Aedes aegypti would be continuously at peril of re-introduction of yellow fever vi- rus from the jungle cycle. To elimi- nate this threat and to reduce the cost of perpetual aegypti control programmes, Dr Fred L. Soper de- veloped the concept of eradication of this species. Under the aegis of the Pan American Health Organ- ization (PAHO), eradication pro- grammes undertaken in the Ameri- cas between 1940 and 1965 met with some successes. Alas, these suc- cesses have now largely been reversed. Development of the 17D vaccine in 1937 by Dr Max Theiler and Dr Hugh H. Smith of the Rockefeller Foundation was a landmark in the control of yellow fever. Produced in chicken eggs , the 17D vaccine has a remarkable record of safety and efficacy and is now produced in 12 institutes around the world. WHO plays an important role in the international regulation of yellow fever vaccination, granting approv- al of laboratories for manufacture and testing of the vaccine. It may be given to infants as young as nine months (even at six months in situ- ations of high risk), and produces solid immunity lasting at least ten years - the limit recognised for the purposes of international travel - and probably for life. In the Americas, only 50 to 300 cases of yellow fever are officially reported to WHO annually. The true incidence is probably 10 to 20 times greater. Countries reporting the largest number of cases are Bolivia, Brazil, Colombia and Peru. All cases result from exposure to forest mosquitos which have acquired the virus from infected monkeys. So the risk is greatest in young adult males engaged in clearing forests for agriculture , road construction and harvesting timber. Several countries have long-established, systematic programmes of routine immunization , aimed mainly at res- idents of endemic jungle areas. A disquieting problem in recent years has been the reappearance of Aedes aegypti in Brazil, Bolivia, Colombia, Ecuador and Panama, infesting areas from which it had previously been eradicated. The pace of re-infestation of South W ORLD HEALTH , July 1988 Torch in hand, this Nigerian health worker tracks down larvae of the Aedes Aegypti mosquito in a house- hold water jar. Photo WHOfT. Monath America is accelerating inexorably, and epidemics of another aegypti- borne virus - dengue fever- have affected hundreds of thousands of people. These events underscore the increasing risk that yellow fever will again cause urban epidemics in South America, and that the virus will spread to receptive areas of the Caribbean basin , Central and North America. In Africa, the epidemiology of yellow fever stands in stark contrast to that in the Americas. In most countries, surveillance of the dis- ease is rudimentary or non-exis- tent, and sporadic, individual cases such as occur in South America go unrecognised. Instead, explosive epidemics appear at irregular inter- vals, often involving thousands of deaths. Even during epidemics the disease is greatly under-reported , and official notifications , which have numbered only about 3,000 cases between 1965 and 1985, re- flect less than one per cent of the true incidence. Important out- breaks have arisen in Ghana (1977- 1979), Gambia (1978) , Burkina Faso (1983) , Nigeria (1986-1987) , and Mali (1987). Investigations suggest- ed at least 30,000 cases and 10,000 deaths during these episodes. The ecology of yellow fever in Africa is considerably more com- plex than in the Americas. In addition to a jungle transmission cycle (involving tree-hole breeding mosquitos and monkeys) and an " urban" transmission cycle (in- volving domestic Aedes aegypti and humans) , there exists in Africa a " savanna " transmission cycle in- volving tree-hole breeding mosqui- to species and both monkeys and humans. ·Most yellow fever epidem- ics have been of the latter type, oc- curring in relatively remote areas. In Africa , the term "urban" transmission cycle is a misnomer, since A edes aegypti is common in both cities and villages - wherever 21 Yellow fever gains ground people store water in pots and other containers in and Mound the home. In contrast to the Americas , where this domestic mosquito has not been responsible for yellow fe- ver epidemics for decades , Africa has been repeatedly plagued by aegypti-borne outbreaks. The most recent and most fright- ening example of " urbanisation " of yellow fever occurred last year in Nigeria. The 1986 epidemic in Cross River and Benue States oc- curred in a relatively remote area ; but there was considerable move- ment of people in and out of the region. Concern that the virus might thereby spread to densely populated areas, where Aedes ae- gypti was prevalent , was justified by the appearance in March 1987 of a large epidemic in Oyo State, west- ern Nigeria , some 500 kilometers away from the original focus . Mor- bidity in the cities of Ogbomosho and Oyo was high , cases appeared in Ibadan and other localities, and the virus spread subsequently to parts of northern Nigeria. Aedes aegypti populations were exceedingly high , largely due to the breakdown of piped water supplies 22 in the affected towns, with the re- sult that residents were compelled to store water in and around the home. With more than seven mil- lion people at risk in the epidemic areas, the authorities were faced with the need for a mass immuniza- tion campaign that stretched avail- able resources to the limit. Prevention and control Two approaches exist to prevent and control yellow fever: immuni- zation of the population at risk ; and elimination or reduction of the mosquitos responsible for transmit- ting the virus. The 17D vaccine , which provides effective , long-lasting immunity , has been available for 50 years. Yet most countries in Africa have never used the vaccine as a preventive measure (or have discontinued its use), and rely upon emergency mass immunization in response to epidemic spread of the disease. This is invariably initiated too late to effectively combat epidemics. The main obstacle to preventive use of yellow fever vaccine in Afri- ca has been the high cost of large- scale immunization, requmng sup- plies of the vaccine, methods to maintain the live vaccine at low temperatures in the field , and both mobile teams and fixed vaccination centres staffed by trained person- nel. As a long-range strategy, add- ing yellow fever vaccine to the rou- tine schedule of childhood vaccines as part of WHO's Expanded Pro- gramme on Immunization (EPI) may overcome the problems associ- ated with mass immunization. Another aspect of concern to health planners is the limited pro- duction capability and supply of the 17D vaccine. The methods for vac- cine manufacture in eggs, devel- oped in the 1930s, are cumbersome, and some manufacturing institutes have outdated facilities and equip- ment. The increasing threat of Ae- des aegypti-borne epidemics in the Americas ; the potential for similar events in Africa as human popula- tions expand and concentrate in cities; and the possibility of yellow fever virus reaching into Asia all demand a high level of prepared- ness for emergency production of vaccine. Promoted by WHO, efforts are now under way to develop and WORLD HEALTH, July 1988 Left: A deep well not only protects the water supply but also prevents the mosquito breeding. Right : Vaccination by air-gun to counter yellow fever in a Nigerian village. Photos WHOrr. Monath evaluate a new 17D vaccine pro- duced in cell cultures rather than in eggs, and to increase the stocks of seed virus required for rapid manufacture. In the face of an on-going epi- demic, the most effective means of interrupting virus transmission would be to use insecticide sprays to kill the adult, infected mosqui- tos. Unfortunately, this approach is not as easy as it sounds and is of unproven efficacy under the condi- tions faced in most yellow fever epidemics. In the Americas , control or eradication of Aedes aegypti has been successfully used to prevent urban yellow fever. Yet most pro- grammes have suffered set~backs or reversals in the past two decades. To add insult to injury , an exotic mosquito species , Aedes albopictus has recently invaded the Americas from Asia, and threatens to fill a niche similar to those mosquitos in- volved in the savanna transmission cycle in Africa , with an enhanced risk of epidemic spread. Among the factors responsible for the breakdown of the Aedes ae- gypti eradication programme in the Americas are the growth of cities and poor sanitary conditions which encourage breeding sites. The in- creasing rapidity and scale of com- merce and travel allows greater movement of mosquitos and infect- ed persons between countries. The rising cost of vector control , as well as the competition for manpower and funds with other public health and environmental priorities , have led to a diminished commitment to the programmes. As the situation worsens, the pendulum is swinging back toward recognition of the need for effective control and eradication of Aedes aegypti. The next decade will deter- mine whether our fears of expand- ed aegypti-borne epidemics are just, and may witness a rebirth of vector control and immunization programmes in the Americas and in Africa. • W ORLD HEALTH, July 1988 Yellow fever gains ground 23