Taking on malaria in the Amazon
2010; Elsevier BV; Volume: 376; Issue: 9747 Linguagem: Inglês
10.1016/s0140-6736(10)61522-x
ISSN1474-547X
Autores Tópico(s)Mosquito-borne diseases and control
ResumoMining and logging are increasing the spread of malarial mosquitoes throughout the Amazon. Barbara Fraser reports on a unique collobarative effort to eliminate the disease from the region.At the end of a muddy path in the rain forest in southeastern Peru, two men stripped to their shorts are waist deep in muddy water at the bottom of a 20-foot-deep pit the size of two football fields. One blasts away earth at the side of the pit with a high-pressure water stream, while another clears debris from a suction hose leading to a sluice that separates gold-bearing sediment from cobbles and debris. The two men, who have moved to the tropical lowlands from the Andean highlands, will work around the clock, finally taking home their day's wages in a tiny lump of gold.Mining and logging camps and new farming settlements are increasingly common sights around the Amazonian region, but they are also perfect breeding grounds for the anopheles mosquitoes that transmit malaria. Their proliferation helps explain why the disease remains a stubborn problem in the region, even though malaria morbidity and mortality rates in Latin America are far below those of Africa.“If you look at a map of rural settlement, malaria incidence and deforestation, they're almost a perfect match”, says Monica da Silva-Nunes, a researcher at the Federal University of Acre in Brazil, who has been studying malaria among small farmers who are clearing new land on the country's western frontier.da Silva-Nunes is part of an interdisciplinary team of researchers from the USA, Peru, and Brazil that is planning a multi-pronged attack on malaria with a study that will probe mosquito ecology, the molecular biology of the parasite, epidemiological factors, and the demographics of workers who move around the region. Their goal is to develop a vaccine to block malaria transmission.The US$12·5 million project, funded by a multiproject grant awarded in July by the US National Institutes of Health, will target “the science behind the eradication of malaria on the South American continent”, according to programme leader Joseph Vinetz, professor of medicine at the University of California in San Diego, who has studied malaria in the Loreto region in northeastern Peru for the past 5 years. Researchers will work in Brazil, the Latin American country with the highest incidence of malaria, and Peru.Although endemic in 21 countries in the Americas, from Mexico to Argentina, as well as the Caribbean nations of Haiti and the Dominican Republic, malaria is less severe in Latin America than in Africa, with only about 1 million cases reported annually.In the Peruvian Amazon, vector control had largely eliminated malaria by the 1960s, but cases spiked in the 1990s. Other countries saw a similar increase after DDT use was curbed or scrapped, while some that had eliminated the disease saw it reintroduced by travellers.Drug resistance also contributed to the resurgence of the disease, which led the Pan American Health Organization (PAHO) to set a “roll back malaria” goal of cutting the number of cases in half by 2010—a target reached by last year in all the region's countries except Panama, Peru, French Guiana, Venezuela, the Dominican Republic, and Haiti. Some showed marked improvement. In El Salvador, for example, the number of cases dropped from more than 100 000 a year in the 1980s to 20 in 2009, according to Keith Carter, PAHO's regional adviser on malaria in the Americas.The Millennium Development Goals built on the roll-back target, by calling for a 75% reduction by 2015. Carter is optimistic about meeting the goal, but notes that unless countries commit to funding control efforts even after the target is reached, the number of cases could rise again.“One of the main challenges is that, having reduced the malaria burden, some countries may try to reduce expenditure”, Carter says. Effective control depends on “a mix of methods”, he says, including prompt diagnosis and treatment, vector control, and environmental sanitation and control of mosquito breeding sites.Unlike Africa, where Plasmodium falciparum causes most malaria cases, the main culprit in the Amazon region is the less-studied Plasmodium vivax. The region is also characterised by low rates of infection, rather than the high rates seen in Africa. Although mortality rates are low, the disease still takes a public health toll and is associated with anaemia in pregnant women and low birthweight in newborns.In the Amazon region, where provision of health-care services to remote communities is often difficult, malaria control is complicated by human mobility. In malaria-free areas, adults, especially men, can become infected when they leave home temporarily to work in logging or mining camps or oil fields, gather Brazil nuts, or clear new farm land. Returning home, they infect local mosquitoes, which then spread the disease locally.Studies in Brazil have shown that a large proportion of infected people are asymptomatic, according to Marcelo Ferreira of the University of São Paulo, who is working with Vinetz, coordinating the research in Brazil. That means infection rates could be under-reported, because health-care workers could miss people who show no symptoms. Brazilian researchers are also using molecular analysis to determine whether some asymptomatic cases persist at such a low rate that the parasite does not even show up on smears.According to Ferreira, in some Brazilian communities where malaria is present, as many as two-thirds of infected people are asymptomatic. A substantial amount of asymptomatic parasitemia has also been found around Iquitos, in the Loreto region of northeastern Peru, bordering Brazil, Vinetz says. Researchers do not know why, nor do they know how long people remain asymptomatic, the rate at which they could infect mosquitoes, or the effect of the low rate of infection on the carriers. “We don't know the mechanisms,” Vinetz says. “How can people become clinically immune?”Adding to the puzzle are questions about how the parasite passes from infected people to the Anopheles darlingi mosquito, generally believed to be the main vector for P vivax in the Amazon region. “Not everyone infects mosquitoes — we just don't know why. We think it's an immune factor”, says Vinetz, whose team has found that only about half the mosquitoes fed infected blood became infected themselves.Possible explanations include interleukins, the stage of maturation of the gametocytes when the mosquito fed, and differences in protein profiles between transmitters and non-transmitters, according to Raul Chuquiyauri of Peru's Cayetano Heredia National University, who is studying the mosquitoes in Iquitos. Vinetz and his colleagues will explore those questions, along with factors related to severe P vivax infection and the interplay between mosquito ecology and human demographics.Entomologist Jan Conn of the New York State Health Department's Wadsworth Center will head a study of the mosquitoes to identify the vectors for P vivax and P falciparum, understand population dynamics and biting rates, look for genetic changes, and determine susceptibility to insecticides. Based on earlier research in Brazil, Conn said, species other than A darlingi might be vectors for malaria in parts of Peru.Peruvian researchers Dionicia Gamboa and Alejandro Llanos will head the research to assess whether there is a difference between parasites that cause initial cases and reinfection, correlate parasite genotypes with clinical symptoms, and understand genetic mutations in P falciparum that have made rapid diagnostic tests unreliable.The multifaceted study, with research sites in areas affected by logging, mining, and clearing of farmland in the northern and southern Peruvian Amazon region and western Brazil, should result in the most comprehensive body of information so far about malaria in the Amazon region and lay the groundwork for better control.Various methods have been used to control malaria, and new means are being studied. Insecticide-impregnated bednets can be effective, but health departments might be reluctant or unable to make the continued investment. Residual spraying, another key vector-control method, might be inconsistent or might not be done properly. Eliminating malaria by vector control alone is not feasible. “You can't just kill the species”, Vinetz says. “The cost to the environment would be incredible.”In recent years, there have been efforts to genetically engineer a malaria-resistant mosquito, but Vinetz says replacing the natural vector in the wild is also impractical. The RTS,S vaccine currently in phase 3 trials in Africa has been shown to be effective for at least 18 months, reducing malaria by 35% and severe malaria by 49%. Given the pattern of malaria in the Amazon—low rates of infection often spread by workers who move around the region—Vinetz believes a transmission-blocking vaccine that would prevent infected people from transmitting the parasite to mosquitoes holds the greatest promise for eliminating malaria in the region.PAHO's Carter says public health officials need to use a range of measures, which could include vaccines, vector control, and release of sterile mosquitoes. Most important, he says, is access to free diagnosis and treatment. Patients, in turn, must complete the treatment regimen. People who seek treatment for P vivax symptoms often stop treatment after a few days, allowing the parasite to remain untreated in the phase in which it infects the liver, he says.Because of the environmental factors in the spread of malaria in the Amazon region, control might require policies that go beyond public health. In Brazil, malaria cases increase sharply when farmers begin clearing forested land, but drop to near zero once an area is completely deforested and replaced by pasture, according to da Silva-Nunes. The lesson, she says, is not that deforestation is good, but that settlers in the Amazon region need farming methods or alternative income sources that allow them to make a living without having to clear new land every few years. Ideally, she says, “government policy would take into account the epidemiology of malaria in rural settlements and help people (make a sustainable living) from their land without increasing deforestation.” Mining and logging are increasing the spread of malarial mosquitoes throughout the Amazon. Barbara Fraser reports on a unique collobarative effort to eliminate the disease from the region. At the end of a muddy path in the rain forest in southeastern Peru, two men stripped to their shorts are waist deep in muddy water at the bottom of a 20-foot-deep pit the size of two football fields. One blasts away earth at the side of the pit with a high-pressure water stream, while another clears debris from a suction hose leading to a sluice that separates gold-bearing sediment from cobbles and debris. The two men, who have moved to the tropical lowlands from the Andean highlands, will work around the clock, finally taking home their day's wages in a tiny lump of gold. Mining and logging camps and new farming settlements are increasingly common sights around the Amazonian region, but they are also perfect breeding grounds for the anopheles mosquitoes that transmit malaria. Their proliferation helps explain why the disease remains a stubborn problem in the region, even though malaria morbidity and mortality rates in Latin America are far below those of Africa. “If you look at a map of rural settlement, malaria incidence and deforestation, they're almost a perfect match”, says Monica da Silva-Nunes, a researcher at the Federal University of Acre in Brazil, who has been studying malaria among small farmers who are clearing new land on the country's western frontier. da Silva-Nunes is part of an interdisciplinary team of researchers from the USA, Peru, and Brazil that is planning a multi-pronged attack on malaria with a study that will probe mosquito ecology, the molecular biology of the parasite, epidemiological factors, and the demographics of workers who move around the region. Their goal is to develop a vaccine to block malaria transmission. The US$12·5 million project, funded by a multiproject grant awarded in July by the US National Institutes of Health, will target “the science behind the eradication of malaria on the South American continent”, according to programme leader Joseph Vinetz, professor of medicine at the University of California in San Diego, who has studied malaria in the Loreto region in northeastern Peru for the past 5 years. Researchers will work in Brazil, the Latin American country with the highest incidence of malaria, and Peru. Although endemic in 21 countries in the Americas, from Mexico to Argentina, as well as the Caribbean nations of Haiti and the Dominican Republic, malaria is less severe in Latin America than in Africa, with only about 1 million cases reported annually. In the Peruvian Amazon, vector control had largely eliminated malaria by the 1960s, but cases spiked in the 1990s. Other countries saw a similar increase after DDT use was curbed or scrapped, while some that had eliminated the disease saw it reintroduced by travellers. Drug resistance also contributed to the resurgence of the disease, which led the Pan American Health Organization (PAHO) to set a “roll back malaria” goal of cutting the number of cases in half by 2010—a target reached by last year in all the region's countries except Panama, Peru, French Guiana, Venezuela, the Dominican Republic, and Haiti. Some showed marked improvement. In El Salvador, for example, the number of cases dropped from more than 100 000 a year in the 1980s to 20 in 2009, according to Keith Carter, PAHO's regional adviser on malaria in the Americas. The Millennium Development Goals built on the roll-back target, by calling for a 75% reduction by 2015. Carter is optimistic about meeting the goal, but notes that unless countries commit to funding control efforts even after the target is reached, the number of cases could rise again. “One of the main challenges is that, having reduced the malaria burden, some countries may try to reduce expenditure”, Carter says. Effective control depends on “a mix of methods”, he says, including prompt diagnosis and treatment, vector control, and environmental sanitation and control of mosquito breeding sites. Unlike Africa, where Plasmodium falciparum causes most malaria cases, the main culprit in the Amazon region is the less-studied Plasmodium vivax. The region is also characterised by low rates of infection, rather than the high rates seen in Africa. Although mortality rates are low, the disease still takes a public health toll and is associated with anaemia in pregnant women and low birthweight in newborns. In the Amazon region, where provision of health-care services to remote communities is often difficult, malaria control is complicated by human mobility. In malaria-free areas, adults, especially men, can become infected when they leave home temporarily to work in logging or mining camps or oil fields, gather Brazil nuts, or clear new farm land. Returning home, they infect local mosquitoes, which then spread the disease locally. Studies in Brazil have shown that a large proportion of infected people are asymptomatic, according to Marcelo Ferreira of the University of São Paulo, who is working with Vinetz, coordinating the research in Brazil. That means infection rates could be under-reported, because health-care workers could miss people who show no symptoms. Brazilian researchers are also using molecular analysis to determine whether some asymptomatic cases persist at such a low rate that the parasite does not even show up on smears. According to Ferreira, in some Brazilian communities where malaria is present, as many as two-thirds of infected people are asymptomatic. A substantial amount of asymptomatic parasitemia has also been found around Iquitos, in the Loreto region of northeastern Peru, bordering Brazil, Vinetz says. Researchers do not know why, nor do they know how long people remain asymptomatic, the rate at which they could infect mosquitoes, or the effect of the low rate of infection on the carriers. “We don't know the mechanisms,” Vinetz says. “How can people become clinically immune?” Adding to the puzzle are questions about how the parasite passes from infected people to the Anopheles darlingi mosquito, generally believed to be the main vector for P vivax in the Amazon region. “Not everyone infects mosquitoes — we just don't know why. We think it's an immune factor”, says Vinetz, whose team has found that only about half the mosquitoes fed infected blood became infected themselves. Possible explanations include interleukins, the stage of maturation of the gametocytes when the mosquito fed, and differences in protein profiles between transmitters and non-transmitters, according to Raul Chuquiyauri of Peru's Cayetano Heredia National University, who is studying the mosquitoes in Iquitos. Vinetz and his colleagues will explore those questions, along with factors related to severe P vivax infection and the interplay between mosquito ecology and human demographics. Entomologist Jan Conn of the New York State Health Department's Wadsworth Center will head a study of the mosquitoes to identify the vectors for P vivax and P falciparum, understand population dynamics and biting rates, look for genetic changes, and determine susceptibility to insecticides. Based on earlier research in Brazil, Conn said, species other than A darlingi might be vectors for malaria in parts of Peru. Peruvian researchers Dionicia Gamboa and Alejandro Llanos will head the research to assess whether there is a difference between parasites that cause initial cases and reinfection, correlate parasite genotypes with clinical symptoms, and understand genetic mutations in P falciparum that have made rapid diagnostic tests unreliable. The multifaceted study, with research sites in areas affected by logging, mining, and clearing of farmland in the northern and southern Peruvian Amazon region and western Brazil, should result in the most comprehensive body of information so far about malaria in the Amazon region and lay the groundwork for better control. Various methods have been used to control malaria, and new means are being studied. Insecticide-impregnated bednets can be effective, but health departments might be reluctant or unable to make the continued investment. Residual spraying, another key vector-control method, might be inconsistent or might not be done properly. Eliminating malaria by vector control alone is not feasible. “You can't just kill the species”, Vinetz says. “The cost to the environment would be incredible.” In recent years, there have been efforts to genetically engineer a malaria-resistant mosquito, but Vinetz says replacing the natural vector in the wild is also impractical. The RTS,S vaccine currently in phase 3 trials in Africa has been shown to be effective for at least 18 months, reducing malaria by 35% and severe malaria by 49%. Given the pattern of malaria in the Amazon—low rates of infection often spread by workers who move around the region—Vinetz believes a transmission-blocking vaccine that would prevent infected people from transmitting the parasite to mosquitoes holds the greatest promise for eliminating malaria in the region. PAHO's Carter says public health officials need to use a range of measures, which could include vaccines, vector control, and release of sterile mosquitoes. Most important, he says, is access to free diagnosis and treatment. Patients, in turn, must complete the treatment regimen. People who seek treatment for P vivax symptoms often stop treatment after a few days, allowing the parasite to remain untreated in the phase in which it infects the liver, he says. Because of the environmental factors in the spread of malaria in the Amazon region, control might require policies that go beyond public health. In Brazil, malaria cases increase sharply when farmers begin clearing forested land, but drop to near zero once an area is completely deforested and replaced by pasture, according to da Silva-Nunes. The lesson, she says, is not that deforestation is good, but that settlers in the Amazon region need farming methods or alternative income sources that allow them to make a living without having to clear new land every few years. Ideally, she says, “government policy would take into account the epidemiology of malaria in rural settlements and help people (make a sustainable living) from their land without increasing deforestation.”
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