Modulation of immune responses during HIV–malaria co-infection in pregnancy

Ned, Renée M.; Moore, Julie M.; Chaisavaneeyakorn, Sujittra; Udhayakumar, Venkatachalam

doi:10.1016/j.pt.2005.04.010

Cited by 54 publications

(56 citation statements)

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“…The detrimental effects of this interaction may be especially relevant during pregnancy, with adverse outcomes for both the mother and the infant [2,3].…”

Section: Introductionmentioning

confidence: 99%

Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria^*

et al. 2008

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Malaria infection may impact on mother-to-child transmission (MTCT) of HIV-1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV-1 MTCT in southern Mozambique. MethodsA total of 207 HIV-positive Mozambican pregnant women were enrolled in the study as part of a randomized placebo-controlled trial of two-dose sulfadoxine-pyrimethamine (SP) IPTp in women receiving single-dose nevirapine to prevent MTCT of HIV. HIV RNA viral load, maternal anaemia and peripheral and placental malaria were assessed at delivery. Infant HIV status was determined by DNA polymerase chain reaction (PCR) at 1 month of age. ResultsThere were 19 transmissions of HIV in 153 mother-infant pairs. IPTp with SP did not have a significant impact on MTCT (11.8% in the SP group vs. 13.2% in the placebo group; P 5 0.784) or on maternal HIV RNA viral load [16 312 (interquartile range {IQR} 4076-69 296) HIV-1 RNA copies/mL in the SP group vs. 18 274 (IQR 5471-74 104) copies/mL in the placebo group; P 5 0.715]. In multivariate analysis, maternal HIV RNA viral load [adjusted odds ratio (AOR) 19.9; 95% confidence interval (CI) 2.3-172; P 5 0.006] and anaemia (haematocrit o33%; AOR 7.5; 95% CI 1.7-32.4; P 5 0.007) were independent risk factors for MTCT. Placental malaria was associated with a decrease in MTCT (AOR 0.23; 95% CI 0.06-0.89; P 5 0.034). ConclusionsIPTp with SP was not associated with a significant impact on MTCT of HIV. Maternal anaemia was an independent risk factor for MTCT.Keywords: anaemia, intermittent preventive treatment, mother-to-child transmission, placental malaria, pregnancy Received: 18 February 2008, accepted 15 May 2008 Introduction HIV/AIDS and malaria infections are two of the most important global health problems of our time, and strongly overlap in sub-Saharan Africa [1]. The detrimental effects of this interaction may be especially relevant during pregnancy, with adverse outcomes for both the mother and the infant [2,3].Vertical transmission of HIV occurs at an approximate rate of 25-40% in untreated breast feeding populations [4,5]. Maternal RNA viral load [2,6,7] [6,7,11], it has been suggested that malaria, by increasing the replication of HIV, may increase the risk of MTCT [2,6]. However, studies assessing the impact of placental malaria (PM) on MTCT have produced conflicting results, suggesting either that PM could increase MTCT or that low-density PM parasitaemia could decrease MTCT [6,7,17,18]. Pregnant women are especially susceptible to malaria infection, which is associated with considerable maternal and infant morbidity and mortality. The World Health Organization recommends that pregnant women in stable transmission areas receive intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) and sleep under insecticide-treated nets (ITNs). However, the efficacy of the concomitant use of these two interventions has not been evaluated. IPTp consists of the provision of two doses, at le...

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“…The detrimental effects of this interaction may be especially relevant during pregnancy, with adverse outcomes for both the mother and the infant [2,3].…”

Section: Introductionmentioning

confidence: 99%

Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria^*

et al. 2008

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“…Such conditions are mutually aggravating, resulting in more severe clinical outcomes. Since the emergence of HIV, there have been increasing concerns about pregnant women infected with both malaria and HIV [82]. In sub-Saharan Africa the prevalence of HIV in pregnant women can be as high as 40% [83], with up to 65% of pregnant women affected by malaria [3].…”

Section: Co-morbidity and Implications For Vaccinationmentioning

confidence: 99%

“…During HIV infection the adaptive immune response becomes compromised, weakening the defence against malaria infection [82]. In 2004, Mount et al, [85] demonstrated that anti-VSAPAM antibodies were reduced in co-infected women, thereby impairing host defence against placental binding of the parasite to CSA in the placenta.…”

Section: Co-morbidity and Implications For Vaccinationmentioning

confidence: 99%

“…Unsurprisingly, HIV-infected women with the lowest CD4 + T cell counts had the most reduced levels of anti-VSAPAM antibodies [85]. HIV also induces the down-regulation of some cytokines of the cellular immune response, such as IL-12 and IFN-and causes destruction of memory T cells, leading to reduced ability to clear the parasite from the placenta [82]. HIV infection appears to impair the normal acquisition of immunity to PAM.…”

Section: Co-morbidity and Implications For Vaccinationmentioning

confidence: 99%

“…HIV infection appears to impair the normal acquisition of immunity to PAM. Therefore, the effects of this dual association are most marked in the multigravidae, unlike cases in which malaria infection occurs in isolation [82].…”

Section: Co-morbidity and Implications For Vaccinationmentioning

confidence: 99%

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Understanding How Plasmodium falciparum Binds to the Placenta and Produces Pathology Provides a Rationale for Pregnancy-Associated Malaria Vaccine Development

Morley¹

2012

TOVACJ

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By adulthood repeated exposure to Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, can induce semi-immunity to clinical infection. During pregnancy, however, there is a striking recurrence of severe disease, a syndrome described as pregnancy-associated malaria (PAM). This is caused by P. falciparum-infected erythrocytes binding to receptors on the placental endothelium that are expressed uniquely during pregnancy. This subset of parasites binds by virtue of expressing a cell surface antigen that is the ligand for the corresponding endothelial receptor, thereby providing a selective pressure for its clonal expansion. The antigen also triggers a protective antibody-mediated immune response. With subsequent pregnancies and further exposure to these variant parasites, antibodies develop earlier and women may experience milder infections. Women with PAM exhibit more severe malaria infections than do non-gravid women, with 2,500-10,000 deaths each year due to haemolytic anaemia. PAM also has a detrimental effect on the foetus, increasing the risk of low birth weight, which causes 60,000-200,000 infant deaths annually in sub-Saharan Africa. Current research aims to produce a vaccine to stimulate development of antibodies which would be protective against infection with wild-type parasites. This is hampered by significant diversity in variant surface antigens and available vaccine candidates may only protect women living in malaria-endemic areas. While placental-parasite interactions are not sufficiently understood, incremental progress is being made towards producing an effective vaccine. This review focuses on the molecular structures involved in binding to consider the prospects for a vaccine mimicking naturally-acquired immunity to PAM.

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Humoral immune responses to Plasmodium falciparum among HIV‐1‐infected Kenyan adults

Nnedu

O’Leary

Mutua

et al. 2011

Proteomics Clinical Apps

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Introduction Humoral immune responses play a pivotal role in naturally acquired immunity to malaria. Understanding which humoral responses are impaired among individuals at higher risk for malaria may improve our understanding of malaria immune control and contribute to vaccine development. Methods We compared humoral responses with 483 Plasmodium falciparum antigens between adults in, Kisumu (high, year-long malaria transmission leading to partial immunity), and adults in Kisii (low, seasonal malaria transmission). Then within each site, we compared malaria-specific humoral responses between those at higher risk for malaria (CD4+ ≤ 500) and those at lower risk for malaria (CD4+>500). A protein microarray chip containing 483 P. falciparum antigens and 71 HIV antigens was used. Benjamini–Hochberg adjustments were made to control for multiple comparisons. Results Fifty-seven antigens including CSP, MSP1, LSA1 and AMA1 were identified as significantly more reactive in Kisumu than in Kisii. Ten of these antigens had been identified as protective in an earlier study. CD4+ T-cell count did not significantly impact humoral responses. Conclusion Protein microarrays are a useful method to screen multiple humoral responses simultaneously. This study provides useful clues for potential vaccine candidates. Modest decreases in CD4 counts may not significantly impact malaria-specific humoral immunity.

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Modulation of immune responses during HIV–malaria co-infection in pregnancy

Cited by 54 publications

References 73 publications

Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria^*

Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria^*

Understanding How Plasmodium falciparum Binds to the Placenta and Produces Pathology Provides a Rationale for Pregnancy-Associated Malaria Vaccine Development

Humoral immune responses to Plasmodium falciparum among HIV‐1‐infected Kenyan adults

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Modulation of immune responses during HIV–malaria co-infection in pregnancy

Cited by 54 publications

References 73 publications

Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria*

Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria*

Understanding How Plasmodium falciparum Binds to the Placenta and Produces Pathology Provides a Rationale for Pregnancy-Associated Malaria Vaccine Development

Humoral immune responses to Plasmodium falciparum among HIV‐1‐infected Kenyan adults

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Product

Resources

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Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria^*

Mother‐to‐child transmission of HIV‐1: association with malaria prevention, anaemia and placental malaria^*