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 [1]. 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 [2]. 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40% of all outpatient visits, 25% of all hospital admissions and 14% of all hospital deaths (Uganda Ministry of Health, unpublished).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 [3]. 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premature death was due to malaria and that families spend 25% of their income on malaria (Uganda Ministry of Health, unpublished).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 [4]. 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 [5]. 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 [6].  Second, acute malaria elevates HIV viral load and so may increase the risk of HIV transmission [6].  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 [6].  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 [7].  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 [8] and 10,000 maternal deaths due to anemia each year [9]. 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 [10]. 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 [17]. An estimated 30% of preventable cases of LBW are attributed to malaria [18]. 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 [28].

References:

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2. Organization WH. World Malaria Report, 2005. Geneva, Switzerland: World Health Organization, 2006

3. Lynch KI, Beach R, Asamoa K, Adeya G, Nambooze J and Janowsky E. President's Malaria Initiative, Rapid Assessment Report - Uganda, 2005

4. Lalloo DG, Olukoya P and Olliaro P. Malaria in adolescence: burden of disease, consequences, and opportunities for intervention. Lancet Infect Dis 2006;6:780-93

5. Sachs J, Malaney P. The economic and social burden of malaria. Nature 2002;415:680-5

6.  Achan J, Gasasira AF, Aweeka F, Havlir D, Rosenthal PJ, Kamya MR.  Prophylaxis and treatment of malaria in HIV-infected populations.  Future HIV Therapy.  2008; 2(5), 453-464.

7.  Duffy PE, Fried M. Malaria in the pregnant woman. Curr Top Microbiol Immunol. 2005;295:169-200 

8.  Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. American Journal of Tropical Medicine & Hygiene. 2001;64(1-2 Suppl):28-35.

9.  Guyatt HL, Snow RW. The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. American Journal of Tropical Medicine & Hygiene. 2001;64(1-2 Suppl):36-44.

10. Mbonye AK, Asimwe JB, Kabarangira J, Nanda G, Orinda V. Emergency obstetric care as the priority intervention to reduce maternal mortality in Uganda. Int J Gynaecol Obstet. Mar 2007;96(3):220-225.

11.  Kiwanuka GN. Malaria morbidity and mortality in Uganda. J Vector Borne Dis. Mar-Jun 2003;40(1-2):16-19.

12.  Ndyomugyenyi R, Magnussen P. Anaemia in pregnancy: Plasmodium falciparum infection is an important cause in primigravidae in Hoima district, western Uganda. Ann Trop Med Parasitol. Jul 1999;93(5):457-465.

13.  Ndyomugyenyi R, Magnussen P. Malaria morbidity, mortality and pregnancy outcome in areas with different levels of malaria transmission in Uganda: a hospital record-based study. Trans R Soc Trop Med Hyg. Sep-Oct 2001;95(5):463-468.

14.  Cottrell G, Deloron P, Fievet N, Sow S, Gaye O, Le Hesran JY. Prediction of Plasmodium falciparum placental infection according to the time of infection during pregnancy. Acta Trop. Jul 2006;98(3):255-260.

15.  Ladner J, Leroy V, Simonon A, et al. HIV infection, malaria, and pregnancy: a prospective cohort study in Kigali, Rwanda. Am J Trop Med Hyg. Jan 2002;66(1):56-60.

16.  Briand V, Cottrell G, Massougbodji A, Cot M. Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas. Malar J. Dec 4 2007;6(1):160.

17.  Murphy SC, Breman JG. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. American Journal of Tropical Medicine & Hygiene. 2001;64(1-2 Suppl):57-67.

18.  Steketee RW, Wirima JJ, Campbell CC. Developing effective strategies for malaria prevention programs for pregnant African women. American Journal of Tropical Medicine & Hygiene. 1996;55(1 Suppl):95-100.

19.  Reed SC, Wirima JJ, Steketee RW. Risk factors for anemia in young children in rural Malawi. Am J Trop Med Hyg. Aug 1994;51(2):170-174.

20.  van Eijk AM, Ayisi JG, Ter Kuile FO, et al. Malaria and human immunodeficiency virus infection as risk factors for anemia in infants in Kisumu, western Kenya. Am J Trop Med Hyg. Jul 2002;67(1):44-53.

21.  Cornet M, Le Hesran JY, Fievet N, et al. Prevalence of and risk factors for anemia in young children in southern Cameroon. Am J Trop Med Hyg. May 1998;58(5):606-611.

22.  Cumberland P, Shulman CE, Maple PA, et al. Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya. J Infect Dis. Aug 15 2007;196(4):550-557.

23.  de Moraes-Pinto MI, Verhoeff F, Chimsuku L, et al. Placental antibody transfer: influence of maternal HIV infection and placental malaria. Archives of Disease in Childhood: Fetal & Neonatal Edition. 1998;79(3):F202-205.

24.  Farquhar C, Nduati R, Haigwood N, et al. High maternal HIV-1 viral load during pregnancy is associated with reduced placental transfer of measles IgG antibody. J Acquir Immune Defic Syndr. Dec 1 2005;40(4):494-497.

25.  Scott S, Cumberland P, Shulman CE, et al. Neonatal measles immunity in rural Kenya: the influence of HIV and placental malaria infections on placental transfer of antibodies and levels of antibody in maternal and cord serum samples. J Infect Dis. Jun 1 2005;191(11):1854-1860.

26.  Mount AM, Mwapasa V, Elliott SR, et al. Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection. Lancet. Jun 5 2004;363(9424):1860-1867.

27.  Ned RM, Moore JM, Chaisavaneeyakorn S, Udhayakumar V. Modulation of immune responses during HIV-malaria co-infection in pregnancy. Trends Parasitol. Jun 2005;21(6):284-291.

28.  Antelman G, Msamanga GI, Spiegelman D, et al. Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania. Journal of Nutrition. 2000;130(8):1950-1957.