Malaria, a tropical disease that has been called one of the most complex health problems facing humanity in the 20th century, is at once a failure, a puzzle, and a serious challenge.

The Failure

One of the main public health programs of the World Health Organization (WHO) in the 1950s was the global malaria eradication program. Between 1955 and 1969, WHO launched a series of campaigns to eradicate malaria by spraying homes with insecticide. In some areas, this worked and halted malaria transmission. But in Latin America and most Asian countries, results varied and the disease persisted. The problems and logistics of malaria control were considered beyond the scope of the vast majority of African countries, and large-scale eradication was never attempted there. Epidemics frequently broke out in Central America and Southeast Asia--culminating in a massive epidemic in 1968 in Sri Lanka, where malaria was thought to have been eradicated. The hope of wiping out the disease finally was abandoned in 1969.

As Dr. Gerald L. Mandell, author of Principles and Practice of Infectious Diseases, dryly noted, "In 1955, the World Health Organization began a worldwide malaria eradication program which continued until 1976, when it was officially declared a failure."

WHO's goal was never achieved for a variety of reasons. First, the mosquitoes that transmit malaria rapidly developed resistance to the main insecticide being used, DDT. Secondly, according to Mandell, "resistance to chloroquine by strains of Plasmodium falciparum [the parasite causing the most serious forms of malaria] severely impaired the WHO Program."

Today, malaria is endemic in 101 member countries and territories: 45 countries in WHO's African Region, 21 in the Americas Region, four in the European Region, 14 in the Eastern Mediterranean Region, eight in the Southeast Asia Region, and nine in the Western Pacific Region.

"We and other groups of economist researchers are trying to determine the consequences of malaria on economic development," said Dr. Jeffrey Sachs, a Harvard University economics professor, in a WHO document on malaria. "Our findings are striking. They point to malaria as a major impediment to economic development."

Roll Back Malaria

In 1998, WHO launched a new global program in partnership with UNICEF, the United Nations Development Program, and the World Bank. Known as "Roll Back Malaria," the program seeks to reduce substantially the human suffering and economic losses due to one of the world's most costly diseases. "Malaria is the Number One health priority of people and leaders in affected communities and countries, but their voices have not been heard," WHO's Director-General, Dr. Gro Harlem Brundtland, said in a press release in launching the program. "The human suffering is unacceptable and so is the economic burden and impediment to progress."

Brundtland stresses that the Roll Back Malaria initiative will be different from previous efforts because it uses new tools to control the disease, strengthen health services, and forge new partnerships. "Above all, it will be a united effort by the four international agencies concerned with malaria and its effects on health and economic development," she notes.

In the Western Hemisphere, Roll Back Malaria seeks to cut deaths from malaria in half by the year 2010, according to Dr. Renato Gusmão, malaria expert for the Pan American Health Organization (PAHO), WHO's Regional Office for the Americas. The plan aims to reduce malaria incidence by controlling transmission, using community health workers to help diagnose and treat the disease.

The Puzzle

New discoveries have led to different approaches for a malaria vaccine, with many of the possibilities already undergoing human trials. However, scientists estimate it could take seven to 15 years before an effective vaccine is ready. Several vaccine candidates using the latest breakthroughs in vaccine technology are in field tests in Asia and Africa and in U.S. volunteers.

On another front, the whole genome--a complete set of hereditary factors--of the malaria parasite is being sequenced. "This will create completely new opportunities," Dr. Harold Varmus, Director of the U.S. National Institutes of Health (NIH), noted in a WHO press release in October 1998. "Malaria is a global concern. We are gearing up our support for research both here and abroad."

A vaccine against malaria would not only benefit vulnerable populations living in malaria-endemic regions but also tourists and military forces in affected areas. In a WHO malaria document, Captain Stephen L. Hoffman of the U.S. Naval Medical Research Institute said: "Malaria vaccine development is the Number One ranked Department of Defense medical research, infectious disease, science, and technology objective, because malaria has been responsible for enormous numbers of casualties during military campaigns."

Vaccines taking advantage of DNA research may provide one of the best hopes. One possibility is being developed by the U.S. Naval Medical Research Institute, the U.S. Agency for Inter-national Development, the U.S. private sector, and partners in Ghana, Australia, and France.

"Our work in relationship to World Health Organization objectives is focused on producing multi-gene DNA vaccines designed to reduce morbidity and mortality of malaria in young children in sub-Saharan Africa," says Hoffman, who recently published the first proof of the principle that DNA vaccines can produce immunity in normal, healthy humans. On 30 April 1998, physicians conducting the first human trial of a DNA vaccine against malaria reported that it was well tolerated and safe. The next phase of clinical testing will include assessment of protective efficacy against malaria. Vical Inc. and Pasteur Merieux Connaught sponsored the trial.

Other promising vaccine candidates are under development. One is a recombinant protein vaccine developed by SmithKline Biologicals that would prevent the malaria parasite in its infectious stage from entering or developing within liver cells of human beings, thus blocking the severe and life-threatening consequences of malaria in non-immune individuals. Another is a transmission-blocking vaccine being developed by NIH scientists. Meanwhile, in Colombia, Dr. Manuel Elkin Patarroyo has developed a synthetic peptide vaccine called Spf66 that has undergone field trials in South America, Africa, and Southeast Asia. It only has been partially effective to date, and Patarroyo is working to improve its potency.

The Challenge

As roads are built, forests cut down, and new mining areas opened up, mosquito habitats expand, and malaria continues to sicken and kill people in underdeveloped tropical areas where inadequate health care services and poor socioeconomic conditions make it hard to control.

Renato Gusmão at PAHO says two main problems influence the malaria situation in the Americas. One is the settlement of primitive jungle areas by people in search of economic opportunities, and the other is a lack of health care coverage among large population groups, both in rural areas and in poor outskirts around the large cities.

"The key priority in malaria control is early diagnosis of malaria cases and immediate treatment," says Gusmão. "In a matter of 12 hours, a person with a fever can succumb and die from malaria. A person who is stricken by severe malaria can go into a coma and require intensive care, which is extremely costly. And each case of malaria, on the average, results in an average of two months of lost income."

Gusmão says several things must be done to reduce death and disease from malaria. Apart from the key responses of early diagnosis and rapid treatment, measures to prevent transmission include mosquito control, environmental clean-up, and better housing offering more protection from mosquitoes. Effective control programs must take into account local conditions and engage the community at large with improvements and access to basic health services.

Drastic budget cuts are an obstacle, along with the outdated perception that insecticide spraying is the main way to control malaria, according to a PAHO Regional Overview of Malaria Control published in 1998. Also, the risk of exposure to malaria varies widely from area to area, depending on population movement, social stability, and the level of community actions to prevent malaria and protect against mosquitoes.

In the Americas, Gusmão says, resource networks are being set up to improve collaboration, communicate lessons learned, prevent and control epidemics, provide anti-malaria drugs, and monitor resistance to drugs and insecticides. PAHO has launched a revolving fund to buy drugs and insecticides with a grant from the Government of Brazil. But more financing is needed, says Gusm‹o, "in order to roll back malaria in the Region of the Americas."

Bad Air, Old Remedies

The symptoms of malaria have been known for ages, although the actual causes remained a mystery. "Marsh miasma," the invisible mists and vapors emanating from swamps and decaying organic matter, was thought for many years to cause the disease. In fact, the word "malaria" comes from the Italian mal aria, meaning "harmful air." In Africa, fossils of mosquitoes indicate that the vector, or carrier, for malaria was present some 30 million years ago.

Some ancient treatments for malaria were remarkably effective. Qinghao (Artemisia annva) has been used in China for the last 2,000 years, even though its active ingredient qinghaosu (artemisinin) was only recently identified. Artemisinin and its derivatives are now considered "the most rapidly acting antimalarial drugs and are effective against falciparum malaria, including multidrug resistant infections," according to a group of experts who met in June 1998 at WHO's Geneva Headquarters to consider the drug.

In Peru, pre-Columbian populations knew the anti-fever properties of the bitter bark of the cinchona tree (Cinchona ledgeriana). Quinine, which has been used to treat and cure millions of malaria sufferers, was first isolated in 1820 and comes from this same dried bark. The effectiveness of nets and other protective barriers against mosquito bites were cited by the ancient Greek historian Herodotus, indicating their use for more than 2,400 years.

Systematic malaria control began after French army surgeon Charles Alphonse Laveran discovered the malaria parasite in 1880, and Sir Ronald Ross, a British military physician, successfully demonstrated in 1897 that mosquitoes were the carriers of malaria, for which he won the Nobel prize in 1902. These findings quickly led to control strategies and, with the discovery during World War II of DDT's powerful insecticidal effects, the notion of global eradication. Effective and inexpensive antimalarial drugs of the chloroquine group were synthesized during this period.

Recognizing Malaria

Malaria is an extremely debilitating disease, leaving people suffering from chills, fever, headaches, and fatigue. It is also hard to diagnose. "The ability of malaria to masquerade as other diseases is well known and frequently results in delays in establishing the correct diagnosis," notes Gerald Mandell in his book on infectious disease.

In endemic areas, most people who have malaria parasites in their blood are not ill. Others develop mild malaria. A few will suffer severe, complicated malaria that may be fatal if treatment is delayed or not available. Because malaria cannot be diagnosed accurately on the basis of signs and symptoms alone, and blood films to confirm malaria are not always available, health workers cannot always be sure whether a child has malaria. Depending on national guidelines in endemic areas, they are advised to treat all children who have fever for malaria, even if other illnesses are present and are also being treated.

Malaria is caused by four types of Plasmodium parasites, of which Plasmodium falciparum is the most dangerous; if left untreated, it can lead to fatal cerebral malaria. In endemic regions, where the disease freely circulates, people are continuously infected and over time develop immunity. Children, until they develop the necessary immunity, are particularly vulnerable. Pregnant women are also highly susceptible since the natural defense mechanisms are reduced during pregnancy.

Malaria Situation:Is It Better, Worse, or the Same?

Dr. Keith Carter, who headed Guyana's malaria program before moving to work for PAHO in Guayaquil, Ecuador, says: "On the whole, we could probably state that slight progress has been made through increasing diagnostic and treatment facilities and in preventing the number of complicated cases and deaths. I think we need to bear in mind the fact that the disease is endemic in the Region and that there are no efforts to eradicate it. I think that the test will be on the capacity to prevent and control epidemics in the Region. If we look at the early 1980s, we can cite Guyana as an example of an increase as a result of movement of non-immune persons from the coastal area to the interior in search of gold, together with poor housing and inaccessibility to health facilities. Brazil and Venezuela are other examples in Rondônia and Bolivar States. That critical period has been overcome."

Carter says that "Hurricane Mitch will also present a challenge to the health services' capacity to deal with potential outbreaks of malaria. The destruction of health facilities, destroyed housing, displaced persons with varied immune status, and flooding (increased breeding sites) favor increased transmission of the disease. If we do not hear of uncontrolled epidemics in the post-Mitch period, then we could probably conclude that there has been progress in the response capability by the health services in dealing with malaria."

In Guyana, where Carter frequently took trips by Jeep, ferry, and canoe into the country's interior searching out malaria cases and supervising his malaria staff, the malaria situation has been deteriorating, largely because populations with different immunity levels are constantly mixing and moving around. "The fact is that communities or groups of miners spring up in an unpredictable manner in virgin territory where gold prospecting is occurring faster than facilities for diagnosis and treatment can be established, with precarious housing and human behavior, which does nothing to help reduce man-vector contact," Carter says.

Bed nets have been touted as one solution in the prevention of malaria transmission, especially if they are treated with insecticides. But getting people to use them may be difficult, Carter says. "If people normally use bed nets, they do so at night. If the malaria vector's peak biting period is at night when people are most likely under the nets, these will help reduce man-vector contact and theoretically reduce transmission."

"In that situation," he says, "... mosquito nets can help, then if people do not normally use nets, or feel uncomfortable after one try due to heat or claustrophobia, getting them to change their behavior will be the question. What we have to do is to show that bed nets would in fact reduce transmission in the Region."

As is the case with AIDS and other diseases that threaten public health, progress toward a solution depends more on changes in human behavior than on medical advances.

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Daniel Epstein is a Washington, D.C.-based journalist in charge of media relations for PAHO's Office of Public Information.