Placental and infant malaria protect HIV-infected infants against early childhood deaths, according to the findings of a longitudinal study published in the July 1st edition of The Journal of Infectious Diseases. But the study found that infant anaemia was a significant risk factor for postneonatal infant mortality (PNIM) in HIV-negative children of HIV-positive women.
HIV and malaria are co-endemic in sub-Saharan Africa and appear to impact on each other’s clinical course. HIV significantly increases the risk of malaria in pregnant women. Malaria increases HIV viral load and is a risk factor for mother-to-child transmission (MTCT). However, the impact of placental malaria on MTCT is controversial; some studies have demonstrated a significant association while others have shown a protective effect against transmission.
PNIM in HIV-positive and HIV-negative children born to HIV-infected mothers is more frequent than in children born to HIV-negative women. A Malawian study suggested that placental malaria was a risk factor for PNIM. This suggested that placental malaria either increased MTCT or accelerated HIV disease progression in infected infants. A team of Dutch, US and Kenyan researchers undertook an HIV vertical transmission study to address these possibilities.
The study took place at the Nyanza Provincial General Hospital in Kisumu, Western Kenya. The study participants were HIV-positive mothers and their infants. Enrolment lasted from June 1996 to August 2000 and infant follow up ended in August 2001.
Healthy pregnant women (32 weeks’ gestation) were tested for HIV after informed consent and counselling, received antenatal care, and were encouraged to deliver at the hospital. Women who gave birth at the hospital had placental blood smears prepared and peripheral blood collected for haemoglobin and viral load measurements. Infants were weighed and their gestational age assessed within 24 hours of birth.
All HIV-seropositive mothers and their normal live born infants were followed up. A month after delivery, maternal blood was collected for CD4 cell counts. Infants were seen every month until the age of one or death. Routine infant visits entailed taking the health history for the preceding month and collecting finger-prick blood samples for laboratory analyses. Home visits were made in case of missed infant visits. Verbal autopsies were carried out in case of deaths.
PNIM was defined as death between 29 and 364 days of delivery. HIV-positive infants were infants of HIV-positive mothers who had two consecutive positive PCR tests with the first positive PCR test at age of four months. HIV-negative infants were infants of HIV-seropositive mothers who had two consecutive negative PCR tests and for whom the PCR test at the last visit was negative.
Infant malaria was defined as the presence of asexual blood stage parasites in thick smears. Infant anaemia was a haemoglobin level < 8 g/dl. Infant malaria was treated with sulfadoxine-pyrimethamine or amodiaquine; anaemia and other complaints were treated accordingly.
Placental malaria was detected in 24.7 % of the women with Plasmodium falciparum constituting the majority of the infections; mixed infections with P. malariae were rare. During follow up, 13 % of blood smears were positive. Moderate to severe anaemia was seen in 5.2 % of routine visits.
PNIM was significantly more common among HIV-positive infants than in HIV-negative infants. Thirty-nine deaths occurred among 112 HIV-positive infants (420/1000 live births) and 36 occurred among 458 HIV-negative infants (99/1000 live births) (P < 0.001).
Placental malaria was protective against PNIM in HIV-positive infants. The frequency of placental malaria among dead infants was lower in HIV-positive infants by comparison with HIV-negative infants (7.7 % versus 30.6 %). HIV-positive infants born to mothers with placental malaria were more likely to survive by comparison with those born to mothers without placental malaria. Placental malaria was not associated with PNIM in HIV-negative infants.
Infant malaria also appeared to be protective against PNIM among HIV-infected and HIV-uninfected infants. Survival was longer in infants with at least one episode of malaria by comparison with those without any episode of malaria (274 days versus 134 days in HIV-positive children, P < 0.01; and 263 days versus 160 days in HIV-negative infants, P = 0.08). This protective effect was not due to age, placental malaria, anaemia, or SP treatment.
In HIV-negative infants, PNIM was associated with infant anaemia (AHR, 5.03 [95% CI, 1.97–12.81]) but not with placental malaria (AHR, 1.29 [95% CI, 0.62–2.66]) or infant malaria (AHR, 0.35 [95% CI, 0.10–1.21]). Among HIV-positive infants, neither placental malaria (AHR, 0.34 [95% CI, 0.11–1.11]), infant malaria (AHR, 0.31 [95% CI, 0.07–1.33]), nor anaemia (AHR, 1.07 [95% CI, 0.32–3.61]) was significantly associated with PNIM.
Infant HIV infection and death were associated with a significantly higher viral load. While placental malaria was not associated with a significantly higher maternal viral load, those who transmitted HIV to their infants had significantly higher viral loads when placental malaria was present.
The geometric mean maternal viral load of 14 survivors of mothers with placental malaria was significantly higher than that of 54 survivors whose mothers did not have placental malaria (16,846 copies /ml versus 3849 copies /ml; P = 0.02) and comparable to that of 31 infants who died and whose mothers did not have placental malaria (16,846 copies /ml versus 8561 copies /ml; P = 0.4).
The data of van Eijk et al. demonstrate that in this Kenyan population placental and infant malaria were protective factors for PNIM among infants of HIV-seropositive women and that anaemia was an important risk factor for death in HIV-negative children of HIV-positive mothers.
These findings add further fuel to the controversy about the impact of malaria on MTCT and PNIM. The authors proposed some plausible mechanisms, based on recent published data, which might explain the protective effect of malaria.
The main policy implication, say the authors, is that the prevention of infant anaemia might improve survival in HIV-negative infants of HIV-positive women.
van Eijk AM et al. HIV, malaria, and infant anaemia as risk factors for postneonatal infant mortality among HIV-seropositive women in Kisumu, Kenya. Journal of Infectious Diseases 196: 30 - 37, 2007.