Burden of malaria in Uganda
Malaria is Africa’s leading cause of mortality in children underfive years of age. There are several reasons why Africa bears a large proportion of the world's malaria burden. First, most malaria infections in sub-Saharan Africa are due to Plasmodium falciparum, the cause of the most difficult to treat and severe form of the disease. Second, this region is home to the most efficient malaria mosquito vectors. Third, most African countries are "the poorest of the poor", lacking the basic infrastructure and resources necessary to mount sustainable malaria control efforts. Uganda is emblematic of the immense problem that malaria poses for African countries. Malaria is endemic in over 95% of the country, with the highest malaria transmission intensities reported in the world . According to a recent report from the World Health Organization, Uganda has the world’s highest malaria incidence, with a rate of 478 cases per 1000 population per year . Malaria is the leading cause of morbidity and mortality in Uganda and is responsible for up to 40% of all outpatient visits, 25% of all hospital admissions and 14% of all hospital deaths (Uganda Ministry of Health, unpublished). The overall malaria-specific mortality is estimated to be between 70,000 and 100,000 child deaths annually in Uganda, a death toll that far exceeds that of HIV/AIDS . A 1995 Burden of Disease study indicated that 15% of life years lost to premature death was due to malaria and that families spend 25% of their income on malaria (Uganda Ministry of Health, unpublished). Poor school performance and absenteeism due to malaria reduce chances of escaping from poverty . Poor people tend to live in environments conducive to mosquito breeding and malaria transmission. Thus malaria enhances poverty, which in turn causes poor disease management, locking people in a malaria-poverty trap . Despite the overwhelming burden imposed by malaria in Africa, there is increasing optimism that the tide can be turned through the establishment of several recent large-scale initiatives. The United States government recently launched the President’s Malaria Initiative (PMI), with the goal of reducing malaria-related deaths in selected countries, including Uganda, by 50% within five years. Through PMI and other large funding sources, such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, Uganda and other Africa countries have an unprecedented opportunity to reduce malaria associated morbidity and mortality on a national scale. Innovative approaches to malaria control targeting high-risk populations are urgently needed to achieve these goals.
Malaria and HIV
Malaria and HIV infection are two of the most important infectious disease worldwide, accounting for a combined 4 million deaths annually. Several interactions between malaria and HIV infection have been established. First, an HIV infection disrupts the acquired immune response to malaria, increasing the incidence and severity of malaria . Second, acute malaria elevates HIV viral load and so may increase the risk of HIV transmission . Thus, malaria co-infection in HIV-infected individuals could play an important role in promoting the spread of HIV in Africa. Third, HIV infection may be associated with reduced efficacy of antimalarial treatment. Finally, therapies for each infection may interact, leading to unanticipated effects on drug efficacy or toxicity . These interactions remain a major public health concern in most areas affected by the two diseases. Increased incidence and severity of malaria has been well documented in HIV-infected populations, with resulting increased morbidity and mortality. This information suggests that malaria is a particular risk for those with HIV infection and call for the strengthening of programs for the prevention of malaria in this population.
Malaria and pregnancy
Malaria during pregnancy is associated with poor maternal, obstetrical and infant outcomes. Malaria affects pregnant women living in both low and high transmission areas. In low transmission areas, primigravid and multigravid women are both at risk for severe and complicated malaria, but in high transmission areas, primigravida experience the most severe episodes. Malaria causes significant maternal anemia and poor infant outcomes . In pregnant women living in high transmission areas, malaria magnifies the risk of anemia, contributing indirectly or directly to significant morbidity and mortality. In sub-Saharan Africa, malaria is estimated to account for 2-15% of cases of maternal anemia  and 10,000 maternal deaths due to anemia each year . In a recent survey of 553 Ugandan health care facilities with an overall maternal mortality rate of 67.1/10,000 live births, malaria was attributed as a direct or indirect cause of maternal mortality in 65% of cases . Moreover, it is estimated that malaria may account for up to 60% of spontaneous abortions in Uganda [11-13].
In addition to its effects on pregnant women, malaria infection during pregnancy has severe consequences for the fetus and infant. Malaria infection appears to have the most significant effect on LBW and poor fetal outcomes during the third trimester, but infections earlier in pregnancy may also contribute [14-16]. LBW is the strongest risk factor for neonatal and infant death, and malaria is thought to be responsible for 62,000-363,000 infant deaths associated with LBW yearly . An estimated 30% of preventable cases of LBW are attributed to malaria . In addition, infants born to women with malaria have approximately 2-3 fold increased risk of anemia [19-21]. Lastly, maternal P. falciparum infection also appears to have an adverse effect on neonatal immunity [22-25].
HIV magnifies the effect of malaria among pregnant women and their infants.HIV-infected pregnant women have significant alterations in both cellular and humoral immunity to malaria [26-27]. As a result, HIV-infected women, regardless of parity, are at greater risk of clinical and placental malaria and experience greater rates of anemia and adverse birth outcomes than HIV-uninfected women. They are also at greater risk of increased malaria parasite density as compared to HIV-negative women and this, in turn, is associated with worse anemia .
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