Publications by authors named "Indu Malhotra"

Dengue virus (DENV) is the most common arbovirus globally, with its incidence growing dramatically in recent decades. Although the effects of DENV infection during pregnancy are unclear, reported associations with adverse health outcomes include miscarriage, prematurity, and low birth weight. In this study, we used an IgG ELISA to identify mothers exposed to DENV during pregnancy by testing samples obtained from a previous study that followed a cohort of pregnant women in Kenya to investigate parasitic infections during pregnancy.

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Background: Vaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.

Methods: In this study, the 10-valent pneumococcal conjugate vaccine (Synflorix® or PCV10) was administered to a child cohort (5-7 years old, = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status.

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Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Two groups of baboons ( = 8 each), were infected with Schistosoma mansoni cercariae to establish chronic infections.

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Iron deficiency may impair adaptive immunity and is common among African infants at time of vaccination. Whether iron deficiency impairs vaccine response and whether iron supplementation improves humoral vaccine response is uncertain. We performed two studies in southern coastal Kenya.

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Background: Prevention and treatment of malaria during pregnancy is crucial in dealing with maternal mortality and adverse fetal outcomes. The World Health Organization recommendation to treat all pregnant women with sulfadoxine-pyrimethamine (SP) through antenatal care structures was implemented in Kenya in the year 1998, but concerns about its effectiveness in preventing malaria in pregnancy has arisen due to the spread of SP resistant parasites. This study aimed to determine the prevalence of SP resistance markers in Plasmodium falciparum parasites isolated from pregnant women seeking antenatal care at Msambweni County Referral Hospital, located in coastal Kenya, between the year 2013 and 2015.

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Background: Chronic malnutrition, often measured as stunted growth, is an understudied global health problem. Though poor nutritional intake has been linked to stunted growth, there is evidence suggesting environmental exposures may have a significant role in its occurrence. Here, we characterize the non-nutritional prenatal and postnatal factors that contribute to early childhood stunted growth in rural coastal Kenya.

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Anemia is known to impact a child's growth and development, but not all anemias are caused by iron deficiency, and the CDC and WHO have emphasized investigating other contributors to anemia. This cross-sectional sub-study of a 2012-2016 maternal-child cohort in coastal Kenya evaluated 244 children and found 185 (76%) to have been anemic on at least one time point since birth. At the time of assessment in 2016, evaluation included a complete blood count, nutritional assessment, and testing for parasitic infections, focusing on the primary outcome of anemia, defined as hemoglobin (Hb) < 11 g/dL.

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Background: Globally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment.

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Infections during pregnancy can expose the fetus to microbial Ags, leading to inflammation that affects B cell development. Prenatal fetal immune priming may have an important role in infant acquisition of pathogen-specific immunity. We examined plasma proinflammatory biomarkers, the proportions of various B cell subsets, and fetal priming to tetanus vaccination in cord blood from human United States and Kenyan neonates.

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(SP) is a leading cause of child mortality globally, killing around half a million children aged 5 years and less per year. Nasopharyngeal carriage of SP is a prerequisite to disease, and the prevalence of colonization reaches 100% within the first few years of life. Serotype prevalence varies geographically, impacting the serotype coverage of pneumococcal vaccines, and serotype prevalence data are limited from large regions of the world, including sub-Saharan Africa.

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Background: Antenatal exposure to parasites can affect infants' subsequent responses to vaccination. The present study investigated how maternal prenatal infections and newborns' antiparasite cytokine profiles relate to immunoglobulin G (IgG) responses to standard vaccination during infancy.

Methods: A total of 450 Kenyan women were tested for parasitic infections during pregnancy.

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The study of antigenic targets of naturally-acquired immunity is essential to identify and prioritize antigens for further functional characterization. We measured total IgG antibodies to 38 antigens, investigating their relationship with prospective risk of malaria in a cohort of 1-3 years old Papua New Guinean children. Using simulated annealing algorithms, the potential protective efficacy of antibodies to multiple antigen-combinations, and the antibody thresholds associated with protection were investigated for the first time.

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Many factors can influence maternal placental antibody transfer to the fetus, which confers important immune protection to the newborn infant. However, little is known about the effect of maternal parasitic infection on placental antibody transfer. To investigate this, we selected from a parent study of 576 pregnant Kenyan women four groups of women with term deliveries (≥37 weeks), including uninfected women ( = 30) and women with solo infections with malaria ( = 30), hookworm ( = 30), or schistosomiasis ( = 10).

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Background And Objective: is a leading cause of mortality before age 5, but few studies examine details of childhood response to pneumococcal vaccine in less-developed settings. Although malnutrition, HIV, and concurrent infections can impair response, evidence suggests that chronic parasitic infections can also contribute to poor vaccination results. The objective of this study was to determine whether response to pneumococcal vaccine varied among children either exposed to parasitic infections in utero, previously infected in infancy, or infected at the time of immunization.

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There has been an increasing concern with the safety of genetically modified (GM) crops. An important modification of GM crops is the expression of (Bt) protein, Cry1Ab. Animal exposure to Cry1Ab indicates that the protein is safe, but that it is immunogenic.

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Article Synopsis
  • Chronic schistosomiasis (S. mansoni) is shown to affect the severity of malaria by potentially enhancing the immune response, with baboons used in a controlled study to examine this interaction.
  • The study found that 81% of baboons with chronic schistosomiasis survived malaria infection, compared to only 25% of those infected with malaria alone.
  • Results indicated that schistosomiasis-infected baboons had lower malaria parasite levels and experienced less severe anemia, suggesting that chronic schistosomiasis may improve innate immunity against malaria.
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IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age.

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Background: Parasitic infections, which are among the most common infections worldwide, disproportionately affect children; however, little is known about the impact of parasitic disease on growth in very early childhood. Our objective was to document the prevalence of parasitic infections and examine their association with growth during the first three years of life among children in coastal Kenya.

Methodology/principal Findings: Children enrolled in a maternal-child cohort were tested for soil transmitted helminths (STHs: Ascaris, Trichuris, hookworm, Strongyloides), protozoa (malaria, Entamoeba histolytica and Giardia lamblia), filaria, and Schistosoma infection every six months from birth until age three years.

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In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (anti-soluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10.

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Background: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT).

Methods And Findings: 450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy.

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Background: Relative contribution of these infections on anemia in pregnancy is not certain. While measures to protect pregnant women against malaria have been scaling up, interventions against helminthes have received much less attention. In this study, we determine the relative impact of helminthes and malaria on maternal anemia.

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To better delineate the impact of parasitic coinfection in coastal Kenya, we developed a novel specimen-sparing bead assay using multiplex flow immunoassay (MFI) technology to simultaneously measure serum or plasma immunoglobulin G4 (IgG4) against Brugia malayi antigen (BMA) and Schistosoma haematobium soluble worm antigen (SWAP). Properties of the bead assay were estimated by latent class analysis using data from S. haematobium egg counts/filarial rapid diagnostic cards (RDTs), parasite-specific enzyme-linked immunosorbent assays (ELISAs), and the multichannel IgG4 assay.

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Article Synopsis
  • Expanded malaria control in Kenya since the early 2000s has led to fewer hospital admissions and a significant decrease in malaria infection rates among pregnant women and their children.
  • Blood samples from pregnant women and their children in Kwale District showed a drop in Plasmodium falciparum prevalence from 40% to 1% between 2000 and 2010, linked to increased use of bed nets and malaria prevention treatments.
  • The risk of Plasmodium falciparum infection in children under three years also decreased sharply, from nearly 100% in 1996-1999 to 15% in 2006-2010, indicating a major reduction in malaria transmission in the region.
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Transplacental transfer of antibodies from clinically malaria immune pregnant women to their fetuses is thought to provide passive protection against malaria during infancy. However, the presences and duration of functional antibodies against Plasmodium falciparum (Pf) in newborns has not been described. We used growth inhibition assays (GIA) to measure total anti-malaria functional antibodies present at birth and over the following year.

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Results of studies on the associations of maternal helminth infection and malaria-helminth co-infection on birth outcomes have been mixed. A group of 696 pregnant women from the Kwale district in Kenya were recruited and tested for malaria and helminth infection at delivery. Birthweight was documented for 664 infants.

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