Breastfeeding reduces risk of malaria in infants with HIV

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In HIV-exposed and HIV-infected infants aged six to 15 months breastfeeding significantly lowered the risks of getting malaria according to Neil Vora and colleagues in a prospective study of infants in Tororo, a high malaria transmission rural area in south eastern Uganda, published in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

However the researchers found that breastfeeding was not protective against malaria in HIV-unexposed and HIV-infected children of 15-24 months of age.

Co-trimoxazole prophylaxis appeared to significantly reduce the risks of malaria when comparing HIV-unexposed infants not taking co-trimoxazole to HIV-infected or exposed infants taking co-trimoxazole. 

Glossary

malaria

A serious disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

inter-quartile range

The spread of values, from the smallest to the largest. The inter-quartile range (IQR) only includes the middle 50% of values and measures the degree of spread of the most common values.

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

confounding

Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 

Breastfeeding is recognised as being one of the most practical and cost-effective ways of providing the best nourishment to infants, of boosting the baby’s immunity by providing protection from infectious disease and reducing diarrhoeal diseases as well as respiratory illnesses. Further evidence has shown that stopping breastfeeding early increases morbidity and mortality rates among children born to HIV-infected mothers.

The World Health Organization (WHO) now recommends that HIV-infected mothers exclusively breastfeed their infants who are HIV-uninfected or of unknown status “for the first six months of life, introducing appropriate complementary foods thereafter, and to continue breastfeeding for the first 12 months of life.”    

WHO also recommends that all HIV-infected and mothers who are nursing take co-trimoxazole prophylaxis  (also known as trimethoprim-sulfamethoxazole or TS, Bactrim, or Septra); for infants born to HIV-infected mothers co-trimoxazole prophylaxis should start at six weeks of age. For children who are breastfeeding prophylaxis should continue until breastfeeding has stopped and HIV negative status is confirmed.

Co-trimoxazole prophylaxis is known to reduce malaria incidence in both HIV-infected adults and children. In vitro studies have shown that breast milk proteins contain antimalarial properties.

Little clinical evidence exists about the effects of breastfeeding on the incidence of malaria in children. Data that does exist does not consider the mother’s HIV status. The high incidence of malaria and HIV in young children across sub-Saharan Africa highlights the importance of understanding the association between breastfeeding and malaria, particularly in the context of the new breastfeeding guidelines.

A cohort of 99 HIV-unexposed children, 202 HIV-exposed children and 45 HIV-infected children enrolled between August 2007 and April 2008 were followed prospectively. All children were given insecticide-treated bednets. Co-trimoxazole prophylaxis was given to both HIV-infected and HIV-exposed infants. A malaria diagnosis was made by the presence of fever and a positive blood smear. Monthly questionnaires were used to determine when breastfeeding stopped.

This study was part of a larger cohort study designed to compare the effectiveness of two different artemisinin-based therapies for treating malaria and to measure the protective efficacy of cotrimoxazole prophylaxis against malaria in HIV-exposed and HIV-infected children.

The median age at enrollment for HIV-exposed children was significantly lower than for HIV-unexposed or HIV-infected, 3.7 (IQR:2.4-6.6), 5.6 (IQR:3.5-7.4) and 4.9 (IQR:3.0-8.3) months, respectively. HIV-infected children were more likely to live in town compared to HIV-unexposed and exposed children (36% compared to 21%, p=0.03).

The authors found that the link between breastfeeding and malaria varied in relation to age and use of cotrimoxazole.

Insufficient data were available for children HIV-unexposed between the ages of six-15 months and not breastfeeding to evaluate an association between breastfeeding and the risk of malaria; the majority of children in this category breastfed for 15 months or more.

No significant difference in the incidence of malaria was seen in this category of children (HIV-unexposed) aged 15-24 months whether they breastfed or not (7.5 compared to 6.67 episodes for each person-year, p=0.21). Following policy guidelines these children did not get co-trimoxazole prophylaxis.

Breastfeeding, however, was associated with a significantly lower malaria incidence rate in HIV-exposed children taking co-trimoxazole aged between 6-15 months (1.36 compared to 2.44 for each person-year p=0.008). Since most children in this category stopped breastfeeding before 15 months of age, in accordance with guidelines, there was insufficient data to evaluate the association between breastfeeding and malaria.

HIV-infected children taking cotrimoxazole showed a greater variation of when breastfeeding stopped compared to the other groups. In those aged between 6-15 months breastfeeding was associated with a significantly lower incidence of malaria (1.13  compared to 3.76 for each person year, p=0.002) whereas in those aged 15-24 months there was no significant difference between those who breastfed and those who did not. Why breastfeeding is protective in the younger age group and not the older is uncertain.

After controlling for age, breastfeeding status and place of residence the risk for malaria in children taking cotrimoxazole prophylaxis (HIV-infected and HIV-exposed) was significantly lower than in those not taking prophylaxis (HIV-unifected) RR =0.42 95% CI: 0.34-0.52, p<0.001.

The authors also found, unlike in adults, no association between HIV and the risk of malaria in children aged 6-15 months of age and taking cotrimoxazole prophylaxis. They suggest this is because of an immature immune system; infants have still to develop partial immunity characteristic of adults after repeated exposure.

Limitations, note the authors, include:

  • Sample sizes were not based on testing the hypothesis that breastfeeding reduces the risk of malaria, so they were unable to analyse all possible associations when disaggregating by age and HIV status.
  • The observational nature of the study meant that analyses were not adjusted for confounding factors, including socio-economic or nutritional status. So breast-feeding could have been a surrogate for time spent outside, or under an insecticide-treated bednet as well as for the nutritional status of the infants. All these factors that would affect the risk of malaria.

The authors conclude that “breastfeeding was protective against malaria in children born to HIV-infected mothers, but this effect faded with age.”

They stress the need for further research to confirm their findings as well as explain how breastfeeding is protective against malaria.

Based on their findings, they recommend that “HIV-infected mothers should be counselled about the importance of breastfeeding and co-trimoxazole prophylaxis to protect their children and themselves against malaria.”

References

 

Vora N et al. Breastfeeding and the risk of malaria in children born to HIV-infected and uninfected mothers in rural Uganda.  J Acquir Immune Defic Syndr, advance online publication, July 28 2010. (Abstract and full text link)