Severe or complicated malaria has not been a feature of reports from regions of stable transmission. This may be because those with a high degree of acquired immunity may be able to sustain sufficient antitoxic immunity to avoid severe disease despite HIV-associated immunosuppression . However, in regions of unstable malaria transmission, HIV-infected adults suffering from malaria are at increased risk of complicated and severe malaria and of death. This is particularly alarming in the light of recent estimates that more than half of the world's malaria is in hypo- and mesoendemic areas , indicating huge numbers of adults at risk of severe malaria and coinfection in regions and cities with generalized HIV epidemics. Studies in South Africa reported a doubling, or more, of the risk of severe or complicated malaria, and a five-fold increased risk of death, among HIV-infected adults compared with those who were uninfected [38,39]. In a study in a rural hospital in Zimbabwe, HIV-infected adults were more likely than uninfected patients to develop malaria complications and were more than twice as likely to die . In a hospital-based study in urban Burkina Faso, where HIV prevalence in adults is reported to be 5–6% [41,42], more than 30% of adults with severe malaria were infected with HIV . However, the number of cases involved was small, and HIV testing was not performed on all patients with severe malaria. Outside Africa, reports include a small study in Mumbai where higher HIV prevalence was found among patients with severe malaria than in the general population , studies demonstrating coinfection with HIV and malaria in injecting drug users in Brazil and Vietnam, and outbreaks of malaria in injecting drug users in previously malaria-free regions owing to needle sharing [45,46].
Generally, malaria is clinically indistinguishable from many other causes of fever in HIV-infected individuals [38,39,43,47]. In many regions, malaria is diagnosed simply on the basis of fever, and drugs are administered without confirmatory testing [48,49]. Consequently, malarial fever may be overestimated and inappropriately treated if diagnosed without blood film examination. A study in 10 Tanzanian hospitals found that only 46% of patients clinically diagnosed with severe malaria had a positive P. falciparum blood slide result, yet 95% were given quinine .
The overdiagnosis of malaria increases the potential for severe outcomes of other causes of fever when incorrect treatment is given . Although rates of clinical malaria increase in HIV-infected adults, the much increased rates of fever as a consequence of HIV infection, and its associated complications, mean that the proportion of fever that is attributable to malaria decreases as immunosuppression progresses [32,35,51]. This reduces further the specificity of a diagnosis of malaria based on febrile symptoms alone.
It can be predicted that responses to antimalarial therapy will be decreased in immunosuppressed individuals coinfected with HIV and malaria living in regions of stable transmission. This may be either because of increased susceptibility to malaria reinfection, or because of recrudescence of infection, since antimalarial therapy is most effective in individuals who already have some acquired immunity. Results of seven studies of response to antimalarial therapy in HIV-infected adults are summarized in Table 2. Early studies did not suggest any impact of HIV on success of therapy with quinine, chloroquine and sulfadoxine–pyrimethamine, which were highly effective in all who were treated [27,52]. A more recent body of evidence suggests treatment failure may be common in HIV-infected individuals. In Ethiopia, parasite and fever clearance times were prolonged in HIV-infected adults treated with artemisinin for uncomplicated malaria . In Kenya, significantly lower rates of parasite clearance at 28 days post-treatment with sulfadoxine–pyrimethamine were noted in patients with CD4 cell counts < 200 cells/μl compared with HIV-uninfected adults . In a randomized controlled trial of artemether–lumefantrine versus sulfadoxine–pyrimethamine for the treatment of uncomplicated adult malaria in Zambia, the frequency of malaria treatment failure, for either therapy increased significantly with advancing immunosuppression . A study in Uganda concluded, on the basis of molecular genotyping, that the increased risk of clinical treatment failure was a result of new infections rather than recrudescence . There are no reports of increased adverse events associated with antimalarial therapy in HIV-infected individuals.
No direct evidence has been found to suggest that HIV alters malaria transmission. Investigators have speculated that because HIV infection increases parasitaemia and reduces the response to therapy, it will increase the reservoir of infection in the human population and hence increase transmission [8,57]. In an area with high HIV prevalence (30%), it has been estimated that 20% of malaria infection could be attributable to HIV, assuming gametocytaemia parallels asexual parasitaemia . However, the relationship between asexual parasitaemia and gametocytaemia is not straightforward and the effect of HIV infection on gametocytes remains unclear. The use of sulphonamide preparations, sulfadoxine–pyrimethamine for antimalarial treatment and cotrimoxazole for opportunistic infection prophylaxis, has been shown to increase the production of gametocytes . However, a recent study reports a 38% decline in malaria incidence in household members of HIV-infected persons taking regular cotrimoxazole prophylaxis . Nonetheless there may be an advantage from using effective artemisin-based combination therapy, particularly by rapidly lowering the burden of asexual parasites and transmissible gametocytes [60,61].
A recent study in Uganda in HIV-infected adults found a reduction in febrile parasitaemia of 76% [95% confidence interval (CI), 62–85) associated with cotrimoxazole prophylaxis, of 92% (CI, 83–96%) associated with cotrimoxazole and antiretroviral treatment (ART), and of 95% (CI, 92–97) when insecticide-treated bed nets were added to cotrimoxazole and ART. This study demonstrates that the effects of these three interventions are cumulative, and that malaria infection can be successfully controlled in HIV-infected adults .
Upregulation of HIV viral transcription has been described for coinfection with several pathogens [63–66] and appears to be the case for malaria, as summarized in Table 3. Investigators in Malawi observed nearly a doubling of HIV viral load in 77 subjects following malarial infection and an increase of almost 1 log copies/ml in 13 with CD4 cell count > 300 cells/μl who fulfilled a stricter definition (fever and high parasite density) of clinical malaria . This study confirmed earlier reports from both Malawi  and Uganda  of an acute rise in HIV viral load at the time of malaria infection. In each study, convalescent viral loads generally returned to preinfection levels following malaria treatment.
By contrast, in one small study in rural Guinea-Bissau, mostly involving HIV-2-infected individuals, no increase in viral load was found in HIV-infected patients during the wet (malaria) season compared with the dry season .
No direct evidence has been found to suggest that malaria alters HIV disease progression. Investigators have speculated that transient increases in HIV viral load associated with malaria could accelerate disease progression [8,57]. However, other reports have suggested minimal differences between untreated median survival time in developed (non-malarious) and developing (malarious) countries [69,70]. Evidence to implicate these transient increases in viral load as clinically important is scarce. Indeed, a report from a cohort of HIV-infected individuals and uninfected controls in rural Uganda concluded that there was no strong detrimental effect of malaria on all-cause mortality in HIV-seropositive adults  (Table 3). However, another study in Uganda found significantly faster CD4 cell declines in individuals following episodes of malaria .
Indirect evidence of a possible role for malaria prevention in limiting HIV disease progression comes from studies in Côte d'Ivoire, Uganda and Kenya examining the effect of daily cotrimoxazole as prophylaxis against opportunistic infections, which consistently reported better prognosis and reduced rates of malaria [73–75]. In one study, failure to treat undiagnosed fevers with antimalarial drugs was also associated with death .
Successful ART is expected to reduce the risk of serious opportunistic infections dramatically, and this appears to include clinical malaria . Additionally there are documented in vitro effects of ART on malaria parasites [76,77]. It would be prudent to ensure that malaria surveillance is part of any broader monitoring of ART outcomes in areas where ART use is increasing and HIV and malaria coexist. The potential for interactions between antimalarial and antiretroviral drugs has recently been reviewed .
No direct evidence has been found to suggest that malaria alters HIV transmission in adults. High HIV viral loads have been shown to be associated with increased potential for HIV transmission [79,80], but there is no empiric evidence to implicate the transient increases in HIV viral load associated with malaria infection with increases in HIV transmission .
A primary concern is the transmission of HIV through injections and transfusions for the management of malarial fever or malaria-induced anaemia [9–11]. While this is a documented problem in young children in areas of high malaria transmission , malaria-induced anaemia requiring transfusion is much less common in adults and so may not constitute a major means of HIV transmission.
Current prevention and control programmes for HIV and malaria are defined and separate from one another, despite having a number of common features and goals. There may be substantial overlap in risk population groups, with common infrastructure needs. Many control efforts utilize the same health personnel and sites for service delivery, often with common intervention tools, programme and resource mechanisms. The overlapping characteristics of these programmes are shown in Table 4. In areas where both infections are common, specific coordinated prevention and treatment measures for adults that would have immediate impact on both diseases include:
* encouraging all identified HIV-infected persons (and especially those under HIV care and treatment programmes) to sleep under an insecticide-treated bed net  and use other malaria-prevention measures (indoor residual spraying, other personal protection measures) as appropriate
* providing all HIV-infected persons with highly effective antimalarial drugs for the treatment of any malaria illness
* providing all symptomatic HIV-infected persons with cotrimoxazole as prophylaxis for opportunistic infections; this is also likely to prevent malaria infection [62,73–75]
* providing voluntary counselling and testing sites for persons with unknown HIV status at places where malaria interventions, such as free or highly subsidized insecticide-treated bed nets, might be distributed, thus serving as an incentive for many to attend
* including interventions for both infections for pregnant women, and anaemia prevention and safe use of blood products for young children , as part of a comprehensive strategy for the two diseases.
HIV and malaria coexist in regions with the most poorly developed health surveillance systems, making the public health scale of any interaction difficult to determine. In general, the national malaria estimates by the World Health Organization and the UNAIDS national HIV estimates are derived with much extrapolation from limited data and thus the estimates are imprecise [2,36,83–87]. Large sections of the populations of countries with generalized HIV epidemics (> 1% HIV prevalence in the general population) and a high malaria burden are at particular risk of coinfection. In low-level and concentrated HIV epidemics (< 1% HIV prevalence in the general population), specific population subgroups are likely to be most at risk of coinfection by virtue of their behaviour. For example, expanding HIV epidemics are being fuelled by injecting drug use and heroin trafficking in malaria-endemic areas in Asia and Latin America [88,89] and increasing incidence of coinfections are to be expected in the future.
The two diseases have the greatest overlap in subSaharan Africa, where 70% of the global burden of P. falciparum infections  and 60% of HIV infections occur  in an area with only 12% of the world's population. However, HIV is predominantly a disease of sexually active adults, worse in urban environments and in southern Africa, while malaria is predominantly a disease of young children and pregnant women, with the greatest burden in rural areas and in west and eastern Africa . This will reduce the actual infection overlap; indeed a recent modelling study estimated that the HIV-1 epidemic has increased the incidence of clinical malaria by only 1.3%, and malaria deaths by 4.9% in subSaharan Africa as a whole . However, in regions of unstable malaria transmission, where adults are affected by both diseases, and especially in southern Africa, the HIV-attributable increase in clinical malaria incidence may rise up to 28%, and for malaria deaths up to 114%. However, more work is needed at subnational level to obtain an accurate estimate of the impact of each infection on the other.
There is increasing clarity on the spectrum of interaction between HIV and malaria in non-pregnant adults (Table 5). The HIV–malaria biological interaction is apparently driven by substantial immune compromise, which contributes to more malaria infection, somewhat higher parasite density, more malaria clinical illness, and possibly a diminishing response to treatment when drugs may be starting to fail. More severe malaria disease and death are seen specifically among persons with little or no acquired immunity. The effect of malaria on HIV is less clear. Malaria contributes to transient HIV viral load increases, but these are reversible with effective therapy. Much remains to be discovered about the interaction between HIV and malaria, and some of the most important gaps in our knowledge are priorities for research:
* the effect of HIV infection on malarial infection and disease across the full range of malaria transmission settings
* the clinical effect of acute malaria episodes on HIV prognosis and transmission
* details at subnational level of HIV and malaria distribution to identify geographical and age and sex group overlaps
* the contribution of inaccurate malaria case definition and diagnosis to the overuse of drugs and clinical outcome
* the effects of ART and cotrimoxazole on malaria diagnosis, rates of clinical disease and the development of drug resistance in different settings
* the effect of intermittent presumptive treatment of malaria for HIV-infected individuals
* the contribution of HIV to overestimates of malaria-attributable mortality.
The HIV–malaria programme interaction is extensive and driven by the common features of the clinical illnesses, the similar sites and health staff involved, and the similarity in services that must be provided, resourced and coordinated. Effective prevention and management of HIV and malaria, and indeed of tuberculosis, will jointly reduce their impact [62,92,93]. Malaria interventions are relatively inexpensive (insecticide-treated bed nets cost US$2.50–5.00 for quality products; antimalarial adult curative treatment doses are less than US$2.00) and have been shown to be highly cost effective ; this will be particularly true for the HIV-infected community. Collaboration in joint programming is often not achieved, but in this case and particularly for the benefit of the HIV-infected populations, joint advocacy and receptivity to combined service delivery will improve survival and the quality of many lives.
1. UNAIDS Joint United Nations Programme on HIV/AIDS. AIDS Epidemic Update
. Geneva: UNAIDS; December 2005.
2. World Health Organization Roll Back Malaria Partnership. World Malaria Report
. Geneva: World Health Organization; 2005.
3. Good MF, Doolan DL. Immune effector mechanisms in malaria. Curr Opin Immunol 1999; 11:412–419.
4. Xiao L, Owen SM, Rudolph DL, Lal RB, Lal AA. Plasmodium falciparum
antigen-induced human immunodeficiency virus type 1 replication is mediated through induction of tumour necrosis factor-alpha. J Infect Dis 1998; 177:437–445.
5. Froebel J, Howard W, Schafer JR, Howie F, Whitworth J, Kaleebu P, et al
. Activation by malaria antigens renders mononuclear cells susceptible to HIV infection and re-activates replication of endogenous HIV in cells from HIV-infected adults. Parasite Immunol 2004; 26:213–217.
6. Vlahov D, Graham N, Hoover D, Flynn C, Bartlett JG, Margolick JB, et al
. Prognostic markers for AIDS and infectious disease death in HIV-1 infected injection drug users: plasma viral load and CD4+ cell count. JAMA 1998; 279:35–40.
7. Graziosi C, Soudeyns H, Rizzardi GP, Bart P-A, Chapuis A, Pantaleo G. Immunopathogenesis of HIV infection. AIDS Res Hum Retroviruses 1998; 14:S135–S142.
8. Kublin J, Jere C, Miller W, Hoffman N, Chimbiya N, Pendame R, et al
. Effect of Plasmodium falciparum
malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet 2005; 365:233–240.
9. Greenberg AE, Nguyen-Dinh P, Mann JM, Kabote N, Colebunders RL, Francis H, et al
. The association between malaria, blood transfusions, and HIV seropositivity in a paediatric population in Kinshasa, Zaire. JAMA 1988; 259:545–549.
10. Moore A, Herrera G, Nyamongo J, Lackritz E, Granade T, Nahlen B, et al
. Estimated risk of HIV transmission by blood transfusion in Kenya. Lancet 2002; 358:657–660.
11. Snow RW, Omumbo JA. Malaria mortality in sub-Saharan Africa
. In: Disease and Mortality in sub-Saharan Africa.
Edited by Bos E, Jamison D, Baingana F. Oxford: World Bank Publications; in press.
12. ter Kuile FO, Parise ME, Verhoeff FH, Udhayakumar V, Newman RD, van Eijk AM, et al
. The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-Saharan Africa. Am J Trop Med Hyg 2004; 71(Suppl 2):41–54.
13. Steketee RW, Wirima JJ, Slutsker L, Roberts JM, Khoromana CO, Heymann DL. Malaria parasite infection during pregnancy and at delivery in mother, placenta and newborn: efficacy of chloroquine and mefloquine in rural Malawi. Am J Trop Med Hyg 1996; 55(Suppl 1):24–32.
14. Steketee RW, Nahlen BD, Ayisi J, van Eijk A, Misore A. HIV and malaria overlap and do interact in sub-Saharan African pregnant women
. XII International Conference on AIDS
. Geneva, June 1998 [abstract 145].
15. Verhoeff FH, Brabin BJ, Hart CA, Chimsuku L, Kazembe P, Broadhead RL. Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control. Trop Med Int Health 1999; 4:5–12.
16. Parise ME, Ayisi JG, Nahlen BL, Schultz LJ, Roberts JM, Misore A, et al
. Efficacy of sulfadoxine–pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection. Am J Trop Med Hyg 1998; 59:813–822.
17. Ayisi JG, van Eijk AM, ter Kuile FO, Kolczak MS, Otieno JA, Misore AO, et al
. The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya. AIDS 2003; 17:585–594.
18. Ned R, Moore J, Chaisavaneeyakorn S, Udhayakumar V. Modulation of immune responses during HIV-malaria co-infection in pregnancy. Trends Parasitol 2005; 21:284–291.
19. van Eijk AM, Ayisi JG, ter Kuile FO, Misore AO, Otieno JA, Rosen DH, et al
. HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya. AIDS 2003; 17:595–603.
20. Inion I, Mwanyumba F, Gaillard P, Chohan V, Verhofstede C, Claeys P, et al
. Placental malaria and perinatal transmission of human immunodeficiency virus type 1. J Infect Dis 2003; 188:1675–1678.
21. Mwapasa V, Rogerson SJ, Molyneux ME, Abrams ET, Kamwendo DD, Lema VM, et al
. The effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA concentrations in pregnant Malawian women. AIDS 2004; 18:1051–1059.
22. Brahmbhatt H, Kigozi G, Wabwire-Mangen F, Serwadda D, Sewankambo N, Lutalo T, et al
. The effects of placental malaria on mother-to-child HIV transmission in Rakai, Uganda. AIDS 2003; 17:2539–2541.
23. Ayouba A, Nerrienet E, Menu E, Monny Lobé M, Thonnon J, Leke RJI, et al
. Mother-to-child transmission of human immunodeficiency virus type 1 in relation to the season in Yaounde, Cameroon. Am J Trop Med Hyg 2003; 69:447–449.
24. Greenberg AE. HIV and malaria. In: Mann JM, Tarantola DJM, Netter TW, editors. AIDS in the World. Cambridge, MA: Harvard University Press; 1992. pp. 143–148.
25. Chandramohan D, Greenwood BM. Is there an interaction between human immunodeficiency virus and Plasmodium falciparum
? Int J Epidemiol 1998; 27:296–301.
26. French N, Gilks CF. Royal Society of Tropical Medicine and Hygiene Meeting at Manson House, London, 18 March 1999 Fresh from the field: some controversies in tropical medicine and hygiene HIV and malaria, do they interact? Trans R Soc Trop Med Hyg 2000; 94:233–237.
27. Colebunders R, Bahwe Y, Nekwei W, Ryder R, Perriens J, Nsimba K, et al
. Incidence of malaria and efficacy of oral quinine in patients recently infected with human immunodeficiency virus in Kinshasa, Zaire. J Infect 1990; 21:167–173.
28. Atzori C, Bruno A, Chichino G, Cevini C, Bernuzzi AM, Gatti S, et al
. HIV-1 and parasitic infections in rural Tanzania. Ann Trop Med Parasitol 1993; 87:585–593.
29. Niyongabo T, Deloron P, Aubry, Ndarugirire F, Manirakiza F, Muhirwa G, et al
. Prognostic indicators in adult cerebral malaria; a study in Burundi, an area of high prevalence of HIV infection
. Acta Trop
30. Leaver RJ, Haile Z, Watters DA. HIV and cerebral malaria. Trans R Soc Trop Med Hyg 1990; 84:201.
31. Whitworth J, Quigley M, Smith A, Mayanja B, Eotu H, Omoding N, et al
. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 2000; 356:1051–1056.
32. French N, Nakiyingi J, Lugada E, Watera C, Whitworth J, Gilks C. Increasing rates of malarial fever with deteriorating immune status in HIV-1 infected Ugandan adults. AIDS 2001; 15:899–906.
33. Francesconi P, Fabiani M, Dente M, Lukwiya M, Okwey R, Ouma J, et al
. HIV, malaria parasites, and acute febrile episodes in Ugandan adults: a case–control study. AIDS 2001; 15:2445–2450.
34. Patnaik P, Jere C, Miller W, Hoffman I, Wirima J, Pendame R, et al
. Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi. J Infect Dis 2005; 192:984–991.
35. Laufer MK, van Oosterhaut JJG, Thesing PC, Thumba F, Zijlastra EE, Graham SM. Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi. J Infect Dis 2006; 193:872–878.
36. Butcher GA. T-cell depletion and immunity to malaria in HIV-infections. Parasitology 2005; 130:140–150.
37. Hay S, Guerra C, Tatem A, Noor A, Snow R. The global distribution and population at risk of malaria: past, present, and future. Lancet Infect Dis 2004; 4:327–336.
38. Cohen C, Karstaedt A, Frean J, Thomas J, Govender N, Prentice E, et al
. Increased prevalence of severe malaria in HIV-infected adults in South Africa. Clin Infect Dis 2005; 41:1631–1637.
39. Grimwade K, French N, Mbatha D, Zungu D, Dedicoat M, Gilks C. HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa. AIDS 2004; 18:547–554.
40. Chirenda J, Siziya S, Tshimanga M. Association of HIV infection with the development of severe and complicated malaria cases at a rural hospital in Zimbabwe. Cent Afr J Med 2000; 46:5–9.
41. Lagarde E, Congo Z, Meda N, Baya B, Yaro S, Sangli G, et al
. Epidemiology of HIV infection in urban Burkina Faso. Int J STD AIDS 2004; 15:395–402.
42. Nagot N, Meda N, Ouangre A, Ouedraogo A, Yaro S, Sombie I, et al
. Review of STI and HIV epidemiological data from 1990 to 2001 in urban Burkina Faso: implications for STI and HIV control. Sex Transm Infect 2004; 80:124–129.
43. Diallo A, Zerbo G, Sawadogo A, Guiguemide T. Paludisme grave et infection á vih chez l'adulte á Bobo-Dioulasso, Burkina Faso. Méd Trop 2004; 64:1–6.
44. Khasnis AA, Karnad D. Human immunodeficiency virus type 1 infection in patients with severe falciparum malaria in urban India. J Postgrad Med 2003; 49:114–117.
45. Bastos F, Barcellos C, Lowndes C, Friedman S. Co-infection with malaria and HIV in injecting drug users in Brazil: a new challenge to public health? Addiction 1999; 94:1165–1174.
46. Chau T, Mai N, Phu N, Luxemburger C, Chuong L, Loc P, et al
. Malaria in injection drug abusers in Vietnam. Clin Infect Dis 2002; 34:1317–1322.
47. Nwanyanwu OC, Kumwenda N, Kazembe PN, Jemu S, Ziba C, Nkhoma WC, et al
. Malaria and human immunodeficiency virus infection among male employees of a sugar estate in Malawi. Trans R Soc Trop Med Hyg 1997; 91:567–569.
48. Makani J, Matuja W, Liyombo E, Snow R, Marsh K, Warrell D. Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description. Q J Med 2003; 96:355–362.
49. Petti CA, Polage CR, Quinn TC, Ronald AR, Sande MA. Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis 2006; 42:377–382.
50. Reyburn H, Mbatia R, Drakeley C, Carneiro I, Mwakasungula E, Mwerinde O, et al
. Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study. Br Med J 2004; 329:1212–1215.
51. Anglaret X, Dakoury Dogbo N, Bonard D, Toure S, Combe P, Ouasse T, et al
. Causes and empirical treatment of fever in HIV-infected adult outpatients, Abidjan, Côte d'Ivoire. AIDS 2002; 16:909–918.
52. Muller O, Moser R. The clinical and parasitological presentation of Plasmodium falciparum
malaria in Uganda is unaffected by HIV-1 infection. Trans R Soc Trop Med Hyg 1990; 84:336–338.
53. Birku Y, Mekonnen E, Bjorkman A, Wolday D. Delayed clearance of Plasmodium falciparum in patients with human immunodeficiency virus co-infection treated with artemisinin. Ethiop Med J 2002; 40(Suppl 1):17–26.
54. Shah S, Smith E, Obonyo C, Bloland P, Slutsker L, Hamel M. The effect of HIV-infection on antimalarial treatment response: preliminary results of a 28-day drug efficacy trial in HIV-infected and HIV-uninfected adults in Siaya, Kenya [53rd Annual Meeting of the American Society of Tropical Medicine and Hygiene Florida]. Am J Trop Med Hyg 2004; 71:318.
55. van Geertruyden JP, Mwananyanda L, Chalwe V, Moerman F, Chilengi R, Kestens L, et al
. Higher risk of antimalarial treatment failure in HIV positive than in HIV negative individuals with clinical malaria. [53rd Annual Meeting of the American Society of Tropical Medicine and Hygiene Florida 2004.]. Am J Trop Med Hyg 2004; 71:315.
56. Kamya M, Gasasira AF, Yeka A, Bakyaita N, Nsobya SL, Francis D, et al
. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. J Infect Dis 2006; 193:9–15.
57. Hoffman I, Jere C, Taylor T, Munthali P, Dyer J, Wirima J, et al
. The effect of Plasmodium falciparum
malaria on HIV-1 RNA blood plasma concentration. AIDS 1999; 13:487–494.
58. Sowunmi A, Adedeji A, Fehintola F, Fateye B, Gbotosho O, Happi C. Effects of antifolates, co-trimoxazole and pyrimethamine-sulfadoxine on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum
malaria [53rd Annual Meeting of the American Society of Tropical Medicine and Hygiene Florida 2004]. Am J Trop Med Hyg 2004; 71:288.
59. Mermin J, Lule J, Ekwaru J, Downing R, Hughes P, Bunnell R, et al
. Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members. AIDS 2005; 19:1035–1042.
60. Sutherland C, Ord R, Hallett R, Alexander N, Dunyo S, Drakeley C, et al
. Artemisinin-based combination therapy drastically reduces infectiousness of Gambian children with Plasmodium falciparum
malaria, and reduces transmission of resistant parasites. [53rd Annual Meeting of the American Society of Tropical Medicine and Hygiene Florida 2004.]. Am J Trop Med Hyg 2004; 71:565.
61. Targett G, Drakeley C, Jawara M, von Seidlein L, Coleman R, Deen J, et al
. Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum
to Anopheles gambiae
. J Infect Dis 2001; 183:1254–1259.
62. Mermin J, Ekwaru JP, Liechty CA, Were W, Downing R, Ransom R, et al
. Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bed nets on the incidence of malaria among HIV-infected adults in Uganda. Lancet 2006; 367:1256–1261.
63. Lawn SD, Butera ST, Folks TM. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev 2001; 14:753–777.
64. Seage GR III, Losina E, Goldie SJ, Paltiel D, Kimmel AD, Freedberg KA. The relationship of preventable opportunistic infections, HIV-1 RNA and CD4 cell counts to chronic mortality. J Acquir Imm Def Syndr 2002; 30:421–428.
65. Whalen CC, Nsubuga P, Okwera A, Johnson J, Hom D, Michael N, et al
. Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda. AIDS 2000; 14:1219–1228.
66. Mellors JW, Munoz J, Giorgi JV, Margolick J, Tassoni C, Gupta P, et al
. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997; 126:946–954.
67. French N. Pneumococcal disease and its prevention by vaccination in HIV-infected Ugandan adults. PhD thesis, University of Liverpool; 2004:181–191.
68. Ariyoshi K, van der Loeff M Schim, Berry N, Jaffar S, Whittle H. Plasma HIV viral load in relation to season and to Plasmodium falciparum
parasitaemia. AIDS 1999; 13
69. Morgan D, Mahe C, Mayanja B, Whitworth JA. Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: prospective cohort study. Br Med J 2002; 324:193–196.
70. UNAIDS Reference Group on Estimates, Modeling and Projections. Improved methods and assumptions for estimation of the HIV/AIDS epidemic and its impact. Recommendations of the UNAIDS Reference Group on Estimates, Modelling and Projections. AIDS 2002; 16
71. Quigley M, Hewitt K, Mayanja B, Morgan D, Eotu H, Ojwiya A, et al
. The effect of malaria on mortality in a cohort of HIV-infected Ugandan adults. Trop Med Int Health 2005; 10:894–900.
72. Mermin J, Lule J, Ekwaru J. Association between malaria and CD4 cell count decline among persons with HIV. J Acquir Immun Def Syndr 2006; 41:129–130.
73. Anglaret X, Chene G, Attia A, Toure S, Lafont S, Combe P, et al
. Early chemoprophylaxis with trimethoprim–sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999; 353:1463–1468.
74. Hamel M, Greene C, Chiller T, Ouma P, Polyak C, Ping Shi Y, et al
. A prospective study of daily cotrimoxazole prophylaxis in Kenyan HIV-infected adults and the development of antimicrobial resistance. [53rd Annual Meeting of the American Society of Tropical Medicine and Hygiene Florida 2004.]. Am J Trop Med Hyg 2004; 71:906.
75. Mermin J, Lule J, Ekwaru J, Malamba S, Downing R, Ransom R, et al
. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 2004; 364:1428–1434.
76. Nathoo S, Serghides L, Kain KC. Effect of HIV-1 antiretroviral drugs on cytoadherence and phagocytic clearance of Plasmodium falciparum
-parasitised erythrocytes. Lancet 2003; 362:1039–1041.
77. Skinner-Adams TS, McCarthy JS, Gardiner DL, Hilton PM, Andrews KT. Antiretrovirals as antimalarial agents. J Infect Dis 2004; 190:1998–2000.
78. Khoo S, Back D, Winstanely P. The potential for interactions between antimalarial and antiretroviral drugs. AIDS 2005; 19:995–1005.
79. Gray R, Wawer M, Brookmeyer R, Sewankambo N, Serwadda D, Wabwire-Mangen F, et al
. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1 discordant couples in Rakai, Uganda. Lancet 2001; 357:1149–1153.
80. Quinn T, Wawer M, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, et al
. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000; 342:921–929.
81. Whitworth J, Hewitt K. What effect does malaria have on HIV-1 progression? Lancet 2005; 365:196–197.
82. Berkley JA, Maitland K, Mwangi I, Ngetsa C, Mwarumba S, Lowe BS, et al
. Use of clinical syndromes to target antibiotic prescribing in seriously ill children in malaria endemic area: observational study. Br Med J 2005; 330:995.
83. Craig MH, Snow RW, le Sueur D. A climate-based distribution model of malaria transmission in sub-Saharan Africa. Parasitol Today 1999; 15:105–111.
84. Korenromp E, Williams B, Gouws E, Dye C, Snow R. Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy. Lancet Infec Dis 2003; 3:349–358.
85. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum
malaria. Nature 2005; 434:214–217.
86. Boerma J, Ghys P, Walker N. HIV estimates from population-based surveys: a new gold standard for surveillance systems? Lancet 2003; 362:1929–1931.
87. Walker N, Grassly N, Garnett G, Stanecki K, Ghys P. Estimating the global burden of HIV/AIDS: what do we really know about the HIV pandemic? Lancet 2004; 363:2180–2185.
88. Beyrer C, Razak MH, Lisam K, Chen J, Lui W, Yu XF. Overland heroin trafficking routes and HIV-1 spread in south and south-east Asia. AIDS 2000; 14:75–83.
89. Aceijas C, Stimson GV, Hickman M, Rhodes T. United Nations Reference Group on HIV/AIDS Prevention and Care among IDU in Developing and Transitional Countries Global overview of injecting drug use and HIV infection among injecting drug users. AIDS 2004; 18:2295–2303.
90. Hay SI, Guerra CA, Tatem AJ, Atkinson PM, Snow RW. Urbanization, malaria transmission and disease burden in Africa. Nat Rev Microbiol 2005; 3:81–90.
91. Korenromp E, Williams BG, de Vlas S, Gouws E, Gilks C, Ghys P, et al
. Malaria attributable to the HIV-1 epidemic, sub-Saharan Africa. Emerg Infect Dis 2005; 9:1410–1419.
92. Corbett EL, Marston B, Churchyard GJ, de Cock KM. Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment. Lancet 2006; 367:926–937.
93. Brentlinger PE, Behrens CB, Micek MA. Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa. Lancet Infect Dis 2006; 6:100–111.
94. Goodman CA, Coleman PG, Mills A. Cost-effectiveness of malaria control in sub-Saharan Africa. Lancet 1999; 354:378–385.
95. Greenberg AE, Nsa W, Ryder RW, Medi M, Nzeza M, Kitadi N, et al
. Plasmodium falciparum
malaria and perinatally acquired immunodeficiency virus type 1 infection in Kinshasa, Zaire. N Engl J Med 1991; 325:105–109.
96. Fleming AF, Menendez C. Blood. In: Parry E, Godfrey R, Mabey D, Gill G, editors. Principles of Medicine in Africa. 3rd edn. Cambridge: Cambridge University Press; 2004. pp. 924–970.