The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance

BackgroundHIV-related immune-suppression increases the risk of malaria (infection, disease and treatment failure) and probably the circulating parasite biomass, favoring the emergence of drug resistance parasites.MethodsThe additional malaria parasite biomass related to HIV-1 co-infection in sub-Saharan Africa was estimated by a mathematical model. Parasite biomass was computed as the incidence rate of clinical malaria episodes multiplied by the number of parasites circulating in the peripheral blood of patients at the time symptoms appear. A mathematical model estimated the influence of HIV-1 infection on parasite density in clinical malaria by country and by age group, malaria transmission intensity and urban/rural area. In a multivariate sensitivity analysis, 95% confidence intervals (CIs) were calculated using the Monte Carlo simulation.ResultsThe model shows that in 2005 HIV-1 increased the overall malaria parasite biomass by 18.0% (95%CI: 11.6–26.9). The largest relative increase (134.9–243.9%) was found in southern Africa where HIV-1 prevalence is the highest and malaria transmission unstable. The largest absolute increase was found in Zambia, Malawi, the Central African Republic and Mozambique, where both malaria and HIV are highly endemic. A univariate sensitivity analysis shows that estimates are sensitive to the magnitude of the impact of HIV-1 infection on the malaria incidence rates and associated parasite densities.ConclusionThe HIV-1 epidemic by increasing the malaria parasite biomass in sub-Saharan Africa may also increase the emergence of antimalarial drug resistance, potentially affecting the health of the whole population in countries endemic for both HIV-1 and malaria.

[1]  G. Killeen,et al.  Short report: entomologic inoculation rates and Plasmodium falciparum malaria prevalence in Africa. , 1999, The American journal of tropical medicine and hygiene.

[2]  P. Piot,et al.  Incidence of malaria and efficacy of oral quinine in patients recently infected with human immunodeficiency virus in Kinshasa, Zaire. , 1990, The Journal of infection.

[3]  R. Snow,et al.  Why do some African children develop severe malaria? , 1991, Parasitology today.

[4]  S. Siziya,et al.  Relation between falciparum malaria and HIV seropositivity in Ndola, Zambia. , 1988, BMJ.

[5]  Nicholas J White,et al.  Antimalarial drug resistance. , 2004, The Journal of clinical investigation.

[6]  A. Saah,et al.  Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi. , 1994, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[7]  Robert W. Snow,et al.  The public health burden of Plasmodium falciparum malaria in Africa: deriving the numbers , 2003 .

[8]  O. Müller,et al.  The clinical and parasitological presentation of Plasmodium falciparum malaria in Uganda is unaffected by HIV-1 infection. , 1990, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[9]  U. d’Alessandro,et al.  CD4 T-Cell Count and HIV-1 Infection in Adults With Uncomplicated Malaria , 2006, Journal of acquired immune deficiency syndromes.

[10]  A. Greenberg,et al.  Plasmodium Falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children. , 1991, The New England journal of medicine.

[11]  K. Kain,et al.  HIV immunosuppression and antimalarial efficacy: sulfadoxine-pyrimethamine for the treatment of uncomplicated malaria in HIV-infected adults in Siaya, Kenya. , 2006, The Journal of infectious diseases.

[12]  U. d’Alessandro,et al.  Modelling a predictable disaster: the rise and spread of drug-resistantmalaria. , 2000, Parasitology today.

[13]  J. Breman,et al.  Trends and risk factors for HIV-1 seropositivity among outpatient children, Kinshasa, Zaire. , 1990, AIDS (London).

[14]  R. Snow,et al.  Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population. , 1999, Bulletin of the World Health Organization.

[15]  K. Marsh.  Malaria disaster in Africa , 1998, The Lancet.

[16]  D. Bagenda,et al.  Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children. , 1997, The Pediatric infectious disease journal.

[17]  D. Wolday,et al.  Delayed clearance of Plasmodium falciparum in patients with human immunodeficiency virus co-infection treated with artemisinin. , 2002, Ethiopian medical journal.

[18]  Averill M. Law,et al.  Simulation Modeling and Analysis , 1982 .

[19]  N. French,et al.  HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa , 2004, AIDS.

[20]  U. d’Alessandro,et al.  History, Dynamics, and Public Health Importance of Malaria Parasite Resistance , 2004, Clinical Microbiology Reviews.

[21]  I. Hastings,et al.  Complex dynamics and stability of resistance to antimalarial drugs , 2006, Parasitology.

[22]  L. Chitsulo,et al.  Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1. , 1996, American Journal of Tropical Medicine and Hygiene.

[23]  P. Olliaro,et al.  Averting a malaria disaster , 1999, The Lancet.

[24]  Amanda Ross,et al.  An epidemiologic model of severe morbidity and mortality caused by Plasmodium falciparum. , 2006, The American journal of tropical medicine and hygiene.

[25]  C. Dye,et al.  World Malaria Report, 2008. , 2008 .

[26]  M. Scaglia,et al.  HIV-1 and parasitic infections in rural Tanzania. , 1993, Annals of tropical medicine and parasitology.

[27]  W. Stahel,et al.  Log-normal Distributions across the Sciences: Keys and Clues , 2001 .

[28]  Brian G. Williams,et al.  Malaria Attributable to the HIV-1 Epidemic, Sub-Saharan Africa , 2005, Emerging infectious diseases.

[29]  J. Kublin,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. , 2005, The Journal of infectious diseases.

[30]  J. Vulule,et al.  Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria , 2006, AIDS.

[31]  N. French,et al.  Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence , 2003, The Pediatric infectious disease journal.

[32]  N. White,et al.  The de novo selection of drug–resistant malaria parasites , 2003, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[33]  M. Quigley,et al.  Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study , 2000, The Lancet.

[34]  A. Khasnis,et al.  Human immunodeficiency virus type 1 infection in patients with severe falciparum malaria in urban India. , 2003, Journal of postgraduate medicine.

[35]  N. French,et al.  Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults , 2001, AIDS.

[36]  N. French,et al.  Interactions between HIV and malaria in non-pregnant adults: evidence and implications , 2006, AIDS.

[37]  J. P. Ekwaru,et al.  Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study , 2006, The Lancet.

[38]  R. Quick,et al.  Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda , 2004, The Lancet.

[39]  E. Asamoah-odei,et al.  HIV prevalence and trends in sub-Saharan Africa: no decline and large subregional differences , 2004, The Lancet.

[40]  P. Rosenthal,et al.  Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. , 2006, The Journal of infectious diseases.

[41]  S. P. Kachur,et al.  Preventing Childhood Malaria in Africa by Protecting Adults from Mosquitoes with Insecticide-Treated Nets , 2007, PLoS medicine.

[42]  P. Kazembe,et al.  Increased prevalence of malaria in HIV‐infected pregnant women and its implications for malaria control , 1999, Tropical medicine & international health : TM & IH.

[43]  U. d’Alessandro,et al.  HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults with uncomplicated malaria. , 2006, The Journal of infectious diseases.

[44]  Juno Thomas,et al.  Increased prevalence of severe malaria in HIV-infected adults in South Africa. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[45]  T. Taylor,et al.  Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi. , 2006, The Journal of infectious diseases.

[46]  J. Kublin,et al.  Dual Infection with HIV and Malaria Fuels the Spread of Both Diseases in Sub-Saharan Africa , 2006, Science.

[47]  R. Quick,et al.  Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members , 2005, AIDS.

[48]  P. Brasseur,et al.  Combination therapy for malaria: the way forward? , 2002, Drugs.