Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model

ABSTRACT In sub-Saharan Africa, HIV-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, Mycobacterium tuberculosis and malaria parasites. The consequences are often devastating, resulting in enhanced morbidity and mortality. Due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (SIV)-malaria coinfection. In sub-Saharan Africa, Plasmodium falciparum is the most common malaria parasite and is responsible for most malaria-induced deaths. The simian malaria parasite Plasmodium fragile can induce clinical symptoms, including cerebral malaria in rhesus macaques, that resemble those of P. falciparum infection in humans. Thus, based on the well-characterized rhesus macaque model of SIV infection, this study reports the development of a novel rhesus macaque SIV-P. fragile coinfection model to study human HIV-P. falciparum coinfection. Using this model, we show that coinfection is associated with an increased, although transient, risk of both HIV and malaria transmission. Specifically, SIV-P. fragile coinfected macaques experienced an increase in SIV viremia that was temporarily associated with an increase in potential SIV target cells and systemic immune activation during acute parasitemia. Conversely, primary parasitemia in SIV-P. fragile coinfected animals resulted in higher gametocytemia that subsequently translated into higher oocyst development in mosquitoes. To our knowledge, this is the first animal model able to recapitulate the increased transmission risk of both HIV and malaria in coinfected humans. Therefore, this model could serve as an essential tool to elucidate distinct immunological, virological, and/or parasitological parameters underlying disease exacerbation in HIV-malaria coinfected people.

[1]  P. Earl,et al.  Partial efficacy of a VSV-SIV/MVA-SIV vaccine regimen against oral SIV challenge in infant macaques. , 2011, Vaccine.

[2]  P. Earl,et al.  Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV. , 2010, Vaccine.

[3]  Michael W. Bolton,et al.  Altered Immune Responses in Rhesus Macaques Co-Infected with SIV and Plasmodium cynomolgi: An Animal Model for Coincident AIDS and Relapsing Malaria , 2009, PloS one.

[4]  U. d’Alessandro,et al.  Impact of HIV-1 Infection on the Hematological Recovery After Clinical Malaria , 2009, Journal of acquired immune deficiency syndromes.

[5]  Umberto D'Alessandro,et al.  The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance , 2008, Malaria Journal.

[6]  M. Wahlgren,et al.  METHODS IN MALARIA RESEARCH , 2008 .

[7]  R. Koup,et al.  SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. , 2007, Blood.

[8]  S. Barratt-Boyes,et al.  Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS1 , 2007, The Journal of Immunology.

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

[10]  J. Barnwell,et al.  STUDIES ON SPOROZOITE-INDUCED AND CHRONIC INFECTIONS WITH PLASMODIUM FRAGILE IN MACACA MULATTA AND NEW WORLD MONKEYS , 2006, The Journal of parasitology.

[11]  C. Drakeley,et al.  The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. , 2006, Trends in parasitology.

[12]  K. Abel,et al.  Rapid Virus Dissemination in Infant Macaques after Oral Simian Immunodeficiency Virus Exposure in the Presence of Local Innate Immune Responses , 2006, Journal of Virology.

[13]  J. Brewer,et al.  Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function , 2006, Journal of biology.

[14]  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.

[15]  J. Lifson,et al.  Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS , 2005, Journal of medical primatology.

[16]  David M. Rocke,et al.  Temporal and Anatomic Relationship between Virus Replication and Cytokine Gene Expression after Vaginal Simian Immunodeficiency Virus Infection , 2005, Journal of Virology.

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

[18]  J. Kublin,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 , 2005, The Lancet.

[19]  Petra Schneider,et al.  Real-Time Nucleic Acid Sequence-Based Amplification Is More Convenient than Real-Time PCR for Quantification of Plasmodium falciparum , 2005, Journal of Clinical Microbiology.

[20]  M. Molyneux,et al.  Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection , 2004, The Lancet.

[21]  Andrew J Tatem,et al.  The global distribution and population at risk of malaria: past, present, and future. , 2004, The Lancet. Infectious diseases.

[22]  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.

[23]  K. Stanecki,et al.  AIDS epidemic update December 2004. , 2004 .

[24]  B. Gazzard,et al.  Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. , 2003, Blood.

[25]  C. M. Owens,et al.  Human and Simian Immunodeficiency Virus Capsid Proteins Are Major Viral Determinants of Early, Postentry Replication Blocks in Simian Cells , 2003, Journal of Virology.

[26]  S. Herrera,et al.  REPRODUCIBLE INFECTION OF INTACT AOTUS LEMURINUS GRISEIMEMBRA MONKEYS BY PLASMODIUM FALCIPARUM SPOROZOITE INOCULATION , 2002, The Journal of parasitology.

[27]  D. Torre,et al.  Role of nitric oxide in HIV-1 infection: friend or foe? , 2002, The Lancet. Infectious diseases.

[28]  Mathieu Nacher,et al.  DECREASED HEMOGLOBIN CONCENTRATIONS, HYPERPARASITEMIA, AND SEVERE MALARIA ARE ASSOCIATED WITH INCREASED PLASMODIUM FALCIPARUM GAMETOCYTE CARRIAGE , 2002, The Journal of parasitology.

[29]  K. Reimann,et al.  Variability of Viral Load in Plasma of Rhesus Monkeys Inoculated with Simian Immunodeficiency Virus or Simian-Human Immunodeficiency Virus: Implications for Using Nonhuman Primate AIDS Models To Test Vaccines and Therapeutics , 2001, Journal of Virology.

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

[31]  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.

[32]  J. Sodroski,et al.  Species-Specific, Postentry Barriers to Primate Immunodeficiency Virus Infection , 1999, Journal of Virology.

[33]  A. Pain,et al.  Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells , 1999, Nature.

[34]  H. Whittle,et al.  Plasma HIV viral load in relation to season and to Plasmodium falciparum parasitaemia. , 1999, AIDS.

[35]  M. Molyneux,et al.  The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration. , 1999, AIDS.

[36]  R. Nagel,et al.  Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte-rich blood. , 1999, Experimental parasitology.

[37]  D. Chandramohan,et al.  Is there an interaction between human immunodeficiency virus and Plasmodium falciparum? , 1998, International journal of epidemiology.

[38]  D. Dormont,et al.  Nitric oxide synthesis during acute SIVmac251 infection of macaques , 1998 .

[39]  R. Lal,et al.  Plasmodium falciparum antigen-induced human immunodeficiency virus type 1 replication is mediated through induction of tumor necrosis factor-alpha. , 1998, The Journal of infectious diseases.

[40]  R. Vishwakarma,et al.  Plasmodium fragile:Efficacy of Arteether (α/β) against Cerebral Malaria Model , 1997 .

[41]  R. Vishwakarma,et al.  Plasmodium fragile: efficacy of arteether (alpha/beta) against cerebral malaria model. , 1997, Experimental parasitology.

[42]  D. Torre,et al.  Immunological aspects of nitric oxide in HIV-1 infection. , 1996, Medical hypotheses.

[43]  A. Lal,et al.  Phylogenetic relationship among the malaria parasites based on small subunit rRNA gene sequences: monophyletic nature of the human malaria parasite, Plasmodium falciparum. , 1996, Molecular phylogenetics and evolution.

[44]  R. Coppel,et al.  Protective immunity induced in squirrel monkeys with recombinant apical membrane antigen-1 of Plasmodium fragile. , 1994, The American journal of tropical medicine and hygiene.

[45]  Y. Ito,et al.  A nonhuman primate model for human cerebral malaria: rhesus monkeys experimentally infected with Plasmodium fragile. , 1994, Experimental parasitology.

[46]  T. McCutchan,et al.  Evolutionary relatedness of some primate models of Plasmodium. , 1993, Molecular biology and evolution.

[47]  M. Ramírez,et al.  Detection of toxigenic Vibrio cholerae 01 using polymerase chain reaction. , 1992, Memorias do Instituto Oswaldo Cruz.

[48]  W. Trager,et al.  Enhanced gametocyte formation in young erythrocytes by Plasmodium falciparum in vitro. , 1992, The Journal of protozoology.

[49]  H. Webster,et al.  Plasmodium coatneyi-infected rhesus monkeys: a primate model for human cerebral malaria. , 1992, Memorias do Instituto Oswaldo Cruz.

[50]  W. Collins,et al.  Plasmodium fragile and Macaca mulatta monkeys as a model system for the study of malaria vaccines. , 1979, The American journal of tropical medicine and hygiene.

[51]  W. Collins,et al.  The continuous cultivation of Plasmodium fragile by the method of Trager-Jensen. , 1979, The American journal of tropical medicine and hygiene.

[52]  W. Collins,et al.  The exoerythrocytic stages of Plasmodium fragile in Macaca mulatta monkeys. , 1977, The Journal of parasitology.

[53]  W. Collins,et al.  Primate malarias. , 1974, Advances in veterinary science and comparative medicine.

[54]  D. Eyles A stain for malarial oocysts in temporary preparations. , 1950, The Journal of parasitology.