Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi

Mwapasa, Victor; Rogerson, Stephen J.; Kwiek, Jesse J.; Wilson, Philip; Milner, Danny A.; Molyneux, Malcolm E.; Kamwendo, Deborah; Tadesse, Eyob; Chaluluka, Ebbie; Meshnick, Steven R.

doi:10.1097/01.aids.0000244206.41500.27

Cited by 116 publications

(111 citation statements)

References 22 publications

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“…Assessment of other risk factors associated with MTCT confirmed high maternal HIV RNA viral load, as reported by others, to be an independent risk factor for perinatal MTCT [6][7][8]. Anaemia was also found to be associated with perinatal MTCT after adjusting for treatment group and HIV RNA viral load.…”

Section: Discussionsupporting

confidence: 70%

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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Section: Discussionsupporting

confidence: 70%

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

et al. 2008

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“…Plasma samples were collected as part of the Malaria and HIV-1 in Pregnancy (MHP) prospective cohort (17,29,30,38,39). The MHP study was approved by both the Malawi College of Medicine Research Committee and the Institutional Review Board at the University of North Carolina at Chapel Hill.…”

Section: Methodsmentioning

confidence: 99%

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

Russell¹,

Kwiek

Keys

et al. 2011

J Virol

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Subtype C human immunodeficiency virus type 1 (HIV-1C) continues to cause the majority of new cases of mother-to-child transmission (MTCT), and yet there are limited data on HIV-1C transmission. We amplified env from plasma RNA for 19 HIV-1C MTCT pairs, 10 transmitting in utero (IU) and 9 transmitting intrapartum (IP). There was a strong genetic bottleneck between all mother-infant pairs, with a majority of transmission events involving the transmission of a single virus. env genes of viruses transmitted to infants IP, but not IU, encoded Env proteins that were shorter and had fewer putative N-linked glycosylation sites in the V1-V5 region than matched maternal sequences. Viruses pseudotyped with env clones representative of each maternal and infant population were tested for neutralization sensitivity. The 50% inhibitory concentration of autologous serum was similar against both transmitted (infant) and nontransmitted (maternal) viruses in a paired analysis. Mother and infant Env proteins were also similar in sensitivity to soluble CD4, to a panel of monoclonal antibodies, and to heterologous HIV-1C sera. In addition, there was no difference in the breadth or potency of neutralizing antibodies between sera from 50 nontransmitting and 23 IU and 23 IP transmitting HIV-1C-infected women against four Env proteins from heterologous viruses. Thus, while a strong genetic bottleneck was detected during MCTC, with viruses of shorter and fewer glycosylation sites in env present in IP transmission, our data do not support this bottleneck being driven by selective resistance to antibodies.

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“…The Malaria and HIV in Pregnancy Study (MHP) patient samples originated from a study of pregnant women attending Queen Elizabeth Central Hospital, an urban hospital in Blantyre. The complete characteristics of the cohort and study design have been described elsewhere (10). The Mpemba and Madziabango (MM) patient samples were also collected from pregnant women as part of a pilot randomized, open-label, effi cacy study of intermittent preventive treatment in pregnancy at rural health clinics.…”

Section: Study Samplesmentioning

confidence: 99%

Minority-Variant pfcrt K76T Mutations and Chloroquine Resistance, Malawi

Juliano

Kwiek

Cappell

et al. 2007

Emerg. Infect. Dis.

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Genotyping of the chloroquine-resistance biomarker pfcrt (Plasmodium falciparum chloroquine resistance transporter gene) suggests that, in the absence of chloroquine pressure, Plasmodium falciparum parasites in Malawi have reverted to chloroquine sensitivity. However, malaria infections in Africa are commonly polyclonal, and standard PCRs cannot detect minority genotypes if present in <20% of the parasites in an individual host. We have developed a multiple site-specifi c heteroduplex tracking assay (MSS-HTA) that can detect pfcrt 76T mutant parasites consisting of as little as 1% of the parasite population. In clinical samples, no pfcrt 76T was detected in 87 pregnant Malawian women by standard PCR. However, 22 (25%) contained minority-variant resistant genotypes detected by the MSS-HTA. These results were confi rmed by subcloning and sequencing. This fi nding suggests that the chloroquine-resistant genotype remains common in Malawians and that PCR-undetectable drug-resistant genotypes may be present in disease-endemic populations. Surveillance for minority-variant drugresistant mutations may be useful in making antimalarial drug policy. D rug-resistant Plasmodium falciparum malaria continues to be a growing health problem throughout most of the world (1). To combat this threat, governments and aid agencies need accurate drug resistance surveillance data. The World Health Organization has stressed the need for methods of detecting molecular markers of drug resistance that will be useful in predicting responses to both clinical and public health interventions (2). This has been diffi cult in highly malaria-endemic areas, where infections are almost always polyclonal (3,4). In patients with polyclonal infections, small drug-resistant parasite populations (minority variants) may be masked by larger drug-sensitive populations because standard PCRs are relatively insensitive to minority variants (2). Therefore, new methods capable of detecting these subpopulations may lead to better drug resistance surveillance and provide a better tool to predict outcome.We describe a new multiple site-specifi c heteroduplex tracking assay (MSS-HTA) for detecting the pfcrt (Plasmodium falciparum chloroquine resistance transporter gene) K76T mutation. This mutation in a putative transporter gene is well-associated with chloroquine resistance in P. falciparum (5). The MSS-HTA was compared with a standard allele-restricted PCR (ARPCR) in clinical samples from Malawi, a country where standard PCR analyses and a recent clinical trial have suggested that chloroquine-resistant malaria has disappeared (6-9). Materials and Methods Study SamplesInformed consent, as approved by the ethics committees of the University of North Carolina and the Malawi College of Medicine/Ministry of Health, was obtained from all participants in this research study. The Malaria and HIV in Pregnancy Study (MHP) patient samples originated from a study of pregnant women attending Queen Elizabeth Central Hospital, an urban hospital in Blantyre. The complete characte...

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Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi

Abstract: Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections.

Cited by 116 publications

References 22 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^*

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

Minority-Variant pfcrt K76T Mutations and Chloroquine Resistance, Malawi

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Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi

Abstract: Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections.

Cited by 116 publications

References 22 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*

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

Minority-Variant pfcrt K76T Mutations and Chloroquine Resistance, Malawi

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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^*