Malaria
Malaria and HIV co-infection is a critical public health problem that may fuel the spread of both diseases in countries where both diseases are endemic. Malaria seems to be more common for people living with HIV and in areas of unstable malaria transmission, people living with HIV face increased risk of death (Mermin et al., 2006). Men and women living with HIV with CD4 counts below 300 cells per cubic mm have both a higher risk of experiencing early treatment failure for malaria and a recurrence of malaria symptoms than HIV-positive people with CD4 counts over 300 or HIV-negative people (Van Geertruyden et al., 2006). Clinical malaria has also been associated with an increase in HIV viral load and a fall in CD4 cell count, potentially worsening the clinical outlook for people living with HIV. Repeated and transient increases in HIV viral load resulting from co-infection can amplify HIV prevalence, suggesting that malaria may be an important factor in the rapid spread of HIV infection in sub-Saharan Africa (Abu-Raddad et. al., 2006 cited in Sepulveda et al., 2007).
In areas where malaria occurs, malaria prevention should be part of basic HIV care (Whitworth et al., 2005 cited in Mermin et al., 2006). The U.S. President's Malaria Initiative and other donors are working to integrate HIV/malaria co-infection activities, especially for pregnant women (PMI, 2012).
Malaria and HIV Co-Infection is of Special Concern to Pregnant Women
"Approximately one million pregnancies per year are complicated by co-infection of malaria and HIV in sub-Saharan Africa" (WHO, 2004 cited in Uneke and Ogbonna, 2009).Malaria during pregnancy can result in maternal death, anemia, miscarriage and premature birth, as well as other adverse effects for the infant. The first pregnancies are the most critical, as women develop pregnancy-specific immunity against placental parasites over successive pregnancies as a consequence of repeated exposure (Fried et al., 1998 cited in Gamble et al., 2007). However, available evidence suggests that women who are living with HIV have the same low immunity to malaria in subsequent pregnancies as they do in their first pregnancy and are twice as susceptible to clinical malaria, which can increase the risk of adverse outcomes (Van Eijk et al., 2003 cited in Brentlinger et al., 2006; Flateau et al., 2011). Co-infection increases women's risk of developing severe anemia. It can also restrict fetal growth, reduce the transfer of maternal immunities to other infectious diseases from mother to child, and is associated with pre-term delivery and low birth weight.
Pregnant women with both HIV and malaria who do not have access to antiretroviral therapy may have higher viral loads, which both increases their risk for vertical transmission to their babies and for adverse health effects. A longitudinal study of 1,066 HIV-positive pregnant women, conducted in Dar es Salaam, Tanzania exploring the relationship between malaria parasitemia, CD4 count and viral load of women without access to treatment found that women with low levels of parasitemia at baseline had, on average, a 67% increase in viral load compared to those without parasitemia. Baseline parasitemia itself was not a predictor of AIDS-related death, however, women with a baseline CD4 count greater than or equal to 500 cells/cubic mm, who also had parasitemia, were 2.6 times more likely to be classified with an AIDS-related death (Franke et al., 2010).
There is recent evidence that shows a link between HIV and malaria co-infection in pregnant women and low birth weight newborns. Low birth weight infants have also been shown to have significantly higher risks of mother-to-child transmission of HIV compared with infants of normal birth weight. However, studies evaluating the impact of HIV and malaria co-infection on mother-to-child transmission of HIV have revealed mixed results, with some showing greater risk, and others reporting no change (Ter Kuile et al., 2004; Kublin et al., 2005 cited in Brentlinger et al., 2006; Desai et al., 2007; WHO, 2005; UNICEF, 2003a; WHO, 2008c; UNICEF, 2009).
Significant gaps remain in how to treat women living with HIV who are sick with malaria, especially during pregnancy. "Studies of the synergy or antagonism between antiretrovirals and antimalarials are... essential to ensure effective and safe malaria case management... and HIV treatment for pregnant women" (Ward et al., 2008: 141). Further evidence on malaria and pregnancy is available at: www.mip-consortium.org.
The Interactions between HIV and Malaria Are Not Well Understood
"Although the consequences of co-infection with HIV and malaria parasites are not fully understood, available evidence suggests that the infections act synergistically and together result in worse outcomes" (Skinner-Adams et al., 2008: 264). "Despite the wide prevalence of malaria and HIV in many parts of the tropics, knowledge of how these two important diseases interact is still hampered by lack of knowledge in many key areas... drug interactions form only a very small part of the potentially massive number of ways in which HIV and malaria interact to the detriment of human health" (Khoo et al., 2005).
Countries with Unstable Rates of Malaria Transmission Require Special Attention
In areas where malaria occurs at regular intervals, those who survive repeated malarial infections acquire partial immunity by the age of five and carry it into their adult lives. Adults in areas with uncomplicated malaria usually experience mild illness. However in areas where malaria transmission is low and unstable, adults may not have acquired immunity. This means that all age groups are susceptible to severe malaria and its sequelae. Countries with high HIV prevalence and unstable malaria transmission include: Botswana, Namibia, South Africa, Swaziland and Zimbabwe (Idemyor, 2007). In a study of an area of South Africa with unstable malaria transmission, HIV-positive adults with malaria were significantly more likely to die (Grimwade et al., 2004 cited in Slutsker and Marston, 2007). "Unfortunately, the link between the current prevention and control programs for HIV is weak... All those involved in control activities for malaria and HIV... should approach the control of these two diseases in a more integrated way" (Van Geertruyden and D'Alessandro, 2007: 467). Blood-smear microscopy is the most common approach to diagnosing malaria. However, low-sensitivity and specificity increases the risk of misdiagnosis and failure to receive treatment. Recent research has found that polymerase chain reaction (PCR) has a higher-sensitivity for diagnosing malaria among HIV-positive and HIV-negative pregnant women. Additional research is needed to determine the feasibility and acceptability of use in resource poor settings, as PCR is not readily available due to cost.
Bednets and Indoor Spraying Can Dramatically Reduce Malaria Transmission
Effective interventions exist which can dramatically reduce the prevalence and incidence of malaria among both women living with HIV and women who are HIV-negative. A critical intervention is insecticide-treated bednets (ITNs). To be effective, ITNs should be distributed to whole communities in order to achieve area-wide reductions in malaria transmission. In sub-Saharan Africa, the number of households owning at least one ITN increased from 3% in 2000 to 50% in 2011 and surveys indicate that a substantial proportion of people with access to an ITN actually use it (WHO, 2011g). Others estimate that ITN use, defined as "having slept under an ITN the night before" is 60-80% (Slutsker, 2012). Long-lasting insecticidal nets have been developed in response to low re-treatment rates of conventional ITNs. These are pre-treated nets that require no further re-treatment during their optimal lifespan of one and a half to three years (Slutsker, 2012).
The method and timing of providing bednets should be considered. ITNs distributed through outpatient HIV care programs can result in greater use. However, ITNs distributed only to people living with HIV may become stigmatizing. In addition, because approximately 65% of African women do not present for antenatal care until the second or third trimester, distributing ITNs through antenatal care is not sufficient to protect women in the first or early second trimester before they present to ANC, when malaria can still have deleterious effects on the developing fetus programs may not be effective, as malaria parasites may be well established by the time the woman presents for antenatal care (Brentlinger et al., 2006). ITNs are as effective as indoor residual spraying (Yartey, 2006), as long as ITNs are used consistently and appropriately (Robson, 2009).
Indoor residual spraying (IRS) is another vector control option that involves the application of insecticide to the interior walls of dwellings. Mosquito survival is shortened by exposure to the insecticide thus resulting in overall reduction in malaria transmission. The effectiveness of indoor residual spraying depends on coverage in the community and the level of acceptance. The World Health Organization recommends 12 insecticides for the use of indoor residual spraying, including DDT. DDT is one of the most widely used pesticides as it is the most affordable (Robson, 2009). However, resistance is developing to DDT and new pesticides are needed for indoor residual spraying (Feachem, 2009; Robson, 2009).
In addition, a review of 494 peer reviewed studies from 2005 to 2008 on the health impacts of DDT found that "...exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion and impaired neurodevelopment in children" (Eskenazi et al., 2009). A recent study of DDT and breast cancer found that pre-pubertal and pubertal years are critical periods of exposure to DDT that may result in increased risk for breast cancer, requiring longitudinal studies of many years (Cohn et al., 2007 cited in Eskenazi et al., 2009). Studies found that indoor residual spraying results in high DDT exposure in humans, including pregnant women and fetuses (Eskenazi et al., 2009). However, no data were found on use of indoor residual spraying for HIV-positive women who are at risk for malaria and on the impact of DDT on immunocompromised women. "Additional research is needed to understand the effects of DDT/E on the immune system and associated diseases, especially since DDT is used in areas where there are often high rates of HIV" (Eskenazi et al., 2009: 25). According to WHO, "new information published since 2000 was evaluated by a WHO Expert Consultation held in December 2010. This information included new epidemiological studies, up-to-date reported levels in human milk, and new information on exposures to DDT occurring as a result of IRS. A detailed exposure assessment was undertaken, including potential exposure to both residents in IRS-treated homes as well as to spray operators. The WHO Expert Consultation concluded that in general, levels of exposure reported in studies were below levels of concern for human health. In order to ensure that all exposures are below levels of concern, best application practices must be strictly followed to protect both residents and workers. Based on the most recent information, WHO has no reason to change its current recommendations on the safety of DDT for disease vector control. However, WHO's position on the safety and use of DDT will be revised if new information on the potential hazards of DDT becomes available justifying such a revision" (WHO, 2011h: 3).
Intermittent Preventive Treatment Is an Important Strategy in Reducing Malaria in Pregnant Women
A Cochrane review of six trials involving 2,495 pregnant women having their first or second babies found that antimalarial medications given routinely to women in their first or second pregnancy reduced parasite prevalence and placental malaria. The treatment also had positive effects on birth weight and possibly on perinatal death (Garner and Gulmezoglu, 2006). More research is also needed on the potential interactions of intermittent preventive treatment and antiretroviral medications, particularly during pregnancy (Uneke and Ogbonna, 2009).