In 2008, 22.4 million of the 33.4 million people infected with HIV resided in sub-Saharan Africa1. Women, the majority of who are in their prime reproductive years account for about 60% of these infections1.
Two hundred and fifty thousand African women die each year during pregnancy, delivery or shortly after having given birth2. A two-year study in Zambia showed that the majority of maternal deaths were in fact caused by non-obstetric causes, most of which were infections including malaria, tuberculosis (TB), respiratory infections and other HIV-associated opportunistic infections3. Malaria and AIDS-associated tuberculosis along with other unspecified 'chronic respiratory illnesses' are now major causes of maternal death in Zambia3. Similarly, in Mozambique, it was shown that 56% of maternal deaths were the result of HIV/AIDS-related infections, lung sepsis, meningitis, malaria and TB2. "Major increases in TB-associated maternal deaths, and TB in pregnancy, are now occurring in Africa."2
Malaria is endemic to most of sub-Saharan Africa and 70% of all TB patients are also infected with HIV2,4. Both of these opportunistic infections have marked negative effects on the health of both pregnant women and their unborn or newly-born children.
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Due to the stress of pregnancy, especially in correlation with HIV which compromises the immune system, TB may flare up during pregnancy5.
Being co-infected with TB and HIV does not only heighten the risk of maternal mortality, but also increases the risk of the infant contracting these two diseases5.
Pregnant women with advanced TB and HIV show an increased risk of abortion, of babies born prematurely and low birth weights5.
Treatment for TB
The WHO recommends that TB is treated similarly in pregnant and nonpregnant women. Treatment is standard therapy for 6 months and 9 months for those who are infected with HIV as well. The first-line regimen of INH, RIF, ethambutol and pyrazinamide are easily absorbed across the placenta to treat the unborn child also5.
Patients co-infected with HIV and TB, who are at WHO clinical stage III and IV, are eligible for combination antiretroviral treatment (cART) regardless of their CD4 count5.
Because of its high endemic rate in sub-Saharan Africa, and the damage it causes to the placenta, malaria causes high numbers of stillbirths4. It is estimated that about 1 million pregnancies in sub-Saharan Africa are complicated by the co-infection of HIV and malaria6. Malaria during pregnancy can infect the placenta which has numerous distressing consequences for both mother and baby. These include: maternal anaemia, fetal distress, intrauterine growth retardation, perinatal mortality, abortion, stillbirth, premature delivery, low birth weight, congenital malaria and neonatal or maternal deaths6,7. With HIV co-infection the risk of these adverse pregnancy outcomes is exacerbated. The risk for post-neonatal death is increased 3-8x for children born to mothers infected by both diseases compared to those born to mothers with only one of the two.6
Malaria and HIV aggravate each other: the placental damage caused by malaria, increases the placental viral load which in turn increases the risk of transmission from mother to child. On the other hand, women with HIV have reduced immunity to malaria and show higher prevalence rates for the disease.6
In countries of low and middle-income where malaria is endemic, a high percentage of women have placental malaria, which doubles their risk of stillbirth. This makes malaria one of the most crucial preventable causes of stillbirth4.
Treatment for malaria
The WHO recommends intermittent preventative treatment with sulfadoxine-pyrimethamine (SP) in areas where malaria is endemic. Certain studies have indicated that women who received monthly doses of SP, rather than intermittent ones were better protected against the incidence of placental malaria, but others have shown no benefit, thus highlighting the need for further studies in this area6,8.
As an alternative to intermittent preventative treatment with SP, the WHO has also recommended daily treatment with co-trimoxazole (trimethoprim and sulfamethoxazole) for all adults who are HIV positive, including pregnant women6.
Other antimalarial drugs which have shown antiretroviral activity are chloroquine and hydroxyl-chloroquine. Chloroquine has also shown in vitro activity against a number of AIDS-related opportunistic infections. Chloroquine is well-documented to be safe for use in pregnancy and both chloroquine and hydoxy-chloroquine have been suggested as potentially valuable elements as part of antiretroviral treatment in resource-limited countries6.
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It has been shown that the growth of Plasmodium falciparum, the organism responsible for causing malaria, can be inhibited by certain retroviral protease inhibitors. Protease inhibitors may also prevent patients from contracting malaria by inhibiting the CD36-meditated cytoadherence of P. falciparum-infected erythrocytes6.
There is however, a serious lack of research on the interactions between antimalarials and antiretrovirals and it is imperative that this is addressed6.
Although it is not the preferred prophylaxis for malaria, co-trimoxazole (trimethoprim-sulfamethoxazole) is a drug which is used in resource-limited settings to treat other infections. This widely available and low-cost antibiotic has also shown some antimalarial activity9.
Although the study did not include pregnant women, it has been suggested that the use of co-trimoxazole prophylaxis used in combination with cART for at least 72 weeks significantly reduced mortality rates 9.
It is well-known that in many resource-limited countries, prenatal care is used when it is available, sometimes as their only contact with health services2,6. Mbonye et al8 suggest the integration of antenatal care and malaria prevention in the private health sector - especially in Uganda, where the co-infection of malaria and HIV is the leading cause of death.
The high incidence of HIV, TB and malaria in sub-Saharan Africa and the severe negative effect the combination of HIV with either TB or malaria has on maternal and infant well-being brings to the fore the need to create integrated programmes in the region to prevent and treat malaria, TB, bacterial sepsis and HIV/AIDS2. It is crucial to screen for these infections at antenatal healthcare centres in order to prevent maternal mortality2 and to make sure that WHO-recommended antenatal care is provided which includes the prevention and treatment of HIV and malaria6.