“Test and Treat” Model Offers New Strategy for Eliminating Malaria

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As researchers work to eliminate malaria worldwide, new strategies are needed to find and treat individuals who have malaria, but show no signs of the disease. The prevalence of asymptomatic or minimally symptomatic malaria can be as high as 35 percent in populations with malaria and these asymptomatic individuals can serve as a reservoir for spreading malaria even in areas where disease transmission has declined.

In a new study, researchers at the Johns Hopkins Malaria Research Institute found that a strategy of actively identifying undiagnosed malaria and then treating those with the disease resulted in significantly lower prevalence of malaria cases compared to a control group. Their findings are published in the February 3, 2012 edition of the journal PLoS ONE.

“New strategies are needed, particularly in areas of declining transmission. One strategy is to screen people for malaria and treat those who are infected, even those who are not sick enough to go to the clinic,” said lead author, Catherine G. Sutcliffe, PhD, an assistant scientist with the Johns Hopkins Bloomberg School of Public Health’s Department of Epidemiology. “Using artemisinin combination therapy can enhance this strategy, as treatment can reduce transmission to mosquitoes. In regions of declining transmission, the burden of malaria could be reduced to such an extent that elimination is achievable.”

The study was conducted in southern Zambia, with colleagues from the Johns Hopkins Malaria Research Institute in Macha. Researchers analyzed data from surveys conducted in 2007 and between 2008 and 2009. In both surveys, households were screened for malaria using rapid diagnostic tests and treated with artemisinin combination therapy when malaria was detected.

According to the new study, a proactive test-and-treat case-detection strategy resulted in a sixfold reduction in prevalence in 2008 and 2009, with the initial parasite prevalence at 4 percent. Test and treat showed a twofold reduction in 2007, when community prevalence was higher at 24 percent.

“Proactive case detection with treatment using artemisinin-combination therapy can reduce transmission and provide indirect protection to household members. If resources permit, this strategy could be targeted to hot spots to achieve further reductions in malaria transmission,” said William J. Moss, MD, senior author of the study and associate professor with the Johns Hopkins Bloomberg School of Public Health.

Worldwide, malaria afflicts more than 225 million people. The disease kills between 800,000 and 1 million people each year, many of whom are children living in Africa.

Authors of “Reduced Risk of Malaria Parastemia Following Household Screening and Treatment: A Cross-Sectional and Longitudinal Cohort Study” include Catherine G. Sutcliffe, PhD; Tamaki Kobayashi, PhD; Harry Hamapumbu; Timothy Shields, MA; Sungano Mharakurwa, PhD; Philip E. Thuma, MD; Thomas A. Louis, PhD; Gregory Glass, PhD; and William J. Moss, MD.

The Johns Hopkins Malaria Research Institute is a state-of-the-art research facility at the Johns Hopkins Bloomberg School of Public Health. It focuses on a broad program of basic science research to treat and control malaria, develop a vaccine and find new drug targets to prevent and cure this deadly disease.

The research was funded by the Johns Hopkins Malaria Research Institute.

Source: Johns Hopkins Bloomberg School of Public Health

Contrasting Patterns of Malaria Drug Resistance Found Between Humans and Mosquitoes

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A recent study has detected contrasting patterns of drug resistance in malaria-causing parasites taken from both humans and mosquitoes in rural Zambia.

Parasites found in human blood samples showed a high prevalence for pyrimethamine-resistance, which was consistent with the class of drugs widely used to treat malaria in the region. However, parasites taken from mosquitoes themselves had very low prevalence of pyrimethamine-resistance and a high prevalence of cycloguanil-resistant mutants indicating resistance to a newer class of antimalaria drug not widely used in Zambia.

The study was conducted by researchers at the Johns Hopkins Malaria Research Institute and their Zambian colleagues and the findings were published November 7, 2011 in the online edition of the journal PNAS.

Surveillance for drug-resistant parasites in human blood is a major effort in malaria control. Malaria in humans is caused by the parasite Plasmodium falciparum, which is spread from person to person through the feeding of the Anopheles mosquito. Over time, through repeated exposure to medications, the parasites can become less susceptible to drugs used to treat malaria infection, limiting their effectiveness.

“This contrast in resistance factors was a big surprise to us,” said Peter Agre, MD, an author of the study and director of the Johns Hopkins Malaria Institute. “The contrast raises many questions, but we suspect that the malaria parasite can bear highly host-specific drug-resistant polymorphisms, most likely reflecting very different selection preferences between humans and mosquitos.”

For the study, Sungano Mharakurwa, PhD, lead author and senior research associate with the Johns Hopkins Malaria Research Institute in Macha, Zambia, conducted a DNA analysis of P. falciparum found in human blood samples to those found in mosquitoes collected inside homes in rural Zambia. In samples taken from human blood, pyrimethamine-resistant mutations were greater than 90 percent and between 30 percent to 80 percent for other polymorphisms. Mutations of cycloguanil-resistance were 13 percent.

For parasites found in the mosquito midgut, cycloguanil-resistant mutants were at 90 percent while pyrimethamine-resistant mutants were detected between 2 percent and 12 percent.

“Our study indicates that mosquitoes exert an independent selection on drug resistant parasites—a finding that has not previously been noticed. If confirmed in other malaria endemic regions, it suggests an explanation for why drug resistance may appear so rapidly,” said Mharakurwa.

Worldwide, malaria afflicts more than 225 million people. Each year, the disease kills approximately 800,000, many of whom are children living in Africa.

Authors of “Malaria antifolate resistance with contrasting Plasmodium falciparum dihydrofolate reductase (DHFR) polymorphisms in humans and Anopheles mosquitoes” are Sungano Mharakurwa, Taida Kumwenda, Mtawa A. P. Mkulama, Mulenga Musapa, Sandra Chishimba, Clive J. Shiff, David J. Sullivan, Philip E. Thuma, Kun Liu and Peter Agre.

The Johns Hopkins Malaria Research Institute is a state-of-the-art research facility at the Johns Hopkins Bloomberg School of Public Health. It focuses on a broad program of basic science research to treat and control malaria, develop a vaccine and find new drug targets to prevent and cure this deadly disease.

Funding was provided by the Johns Hopkins Malaria Research Institute, the Bill & Melinda Gates Foundation and the National Institutes of Health.

Source: Johns Hopkins University