Intermittent malaria prophylaxis for infants effective, should be integrated into child health programmes

Intermittent prophylactic treatment with anti-malaria drugs given three times during the first year of life cuts the risk of clinical malaria by over one-third in children up to the age of two, and should be considered for integration into child health programmes, say researchers from the London School of Hygiene and Tropical Medicine working in Tanzania.

The findings are published in the April 23^rd edition of The Lancet

Infant malaria

Infection with the parasite Plasmodium falciparum kills about a million African children every year. Using malaria drugs regularly can protect children from malaria episodes and death. However, stopping this treatment can be followed by increased risk of malaria, suggesting that it interferes with the development of antimalarial immunity.

The study

Following a trial involving 700 children in Tanzania, David Schellenberg (Ifakara Health Research and Development Centre, Kilombero, Tanzania and London School of Hygiene & Tropical Medicine, UK) and colleagues, reported that the anti-malarial drug sulfadoxine-pyrimethamine delivered just three times, at the time of routine vaccinations (2, 3 and 9 months of age), reduced the incidence of malaria by 59% in the first year of life when compared with a placebo. (See Lancet 2001; 357: 1471-77) In their latest study they extended follow-up to two years to see if the risk of malaria increased during this period. They found the opposite: the rate of clinical malaria was 36% lower in recipients of sulfadoxine-pyrimethamine than placebo recipients.

Dr Schellenberg states: "We have shown a continuing reduction in the risk of first or only episodes of clinical malaria in children aged 10 months to 2 years from intermittent preventative malarial treatment for infants. This finding increases the potential public-health benefits of such treatment."

Implementation

In an accompanying editorial, Imelda Bates of Liverpool’s School of Tropical Medicine comments: “Intermittent presumptive treatment (IPT) in infants follows in the footsteps of IPT during pregnancy. There is clear evidence that IPT during pregnancy reduces anaemia and improves fetal growth, which is impaired by malaria infection of the placenta.”

“The IPT strategies during pregnancy and in infants are both built on existing systems rather than being set up as new parallel programmes. This approach is recognised to be key to achieving successful and sustainable implementation of new interventions.”

Malaria and HIV

The editorial does not comment on the importance of these findings for programmes seeking to introduce antiretroviral therapy into settings where maternal and infant care is already provided. However, malaria is an important co-infection in HIV-positive women and their children (regardless of HIV status):

• Malaria increases HIV viral load
• HIV/malaria coinfection increases the risk of complications during pregnancy, and the risk of mother to child transmission.
• Malaria causes anaemia, increasing the risk of severe anaemia and treatment intolerance in women or infants receiving AZT (zidovudine) either as part of combination therapy or as prophylaxis against mother to child transmission after birth (infants may receive AZT prophylaxis for some weeks after birth, and studies are testing its suitability as prophylaxis against infection through breastfeeding for up to six months after birth).
• However, a complicating factor is that the regimen used in this study, sulfadoxine/pyramethamine, may be less effective if infants have already been exposed to co-trimoxazole (which may be given prophylactically to all infants of HIV-positive mothers until the child’s own HIV status can be established, and which is recommended for all children with HIV-related symptoms). Co-trimoxazole can cause malaria parasites to develop resistance to the sulfadoxine component of the malaria prophylaxis.

The Schellenberg study first delivered malaria prophylaxis two months after birth, at the time of the first immunization visit. In children of HIV-positive mothers, regardless of the child’s HIV status, research is clearly needed to determine the appropriate intervals of presumptive malaria treatment and the appropriate regimen in settings where co-trimoxazole prophylaxis or treatment is already being implemented.