John Ayisi

Ministry of Education

In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malari...

The role of killer cell immunoglobulin-like receptors (KIRs) in the transmission of HIV-1 has not been extensively studied. Here, we investigated the association of KIR gene content polymorphisms with perinatal HIV-1 transmission. The KIR gene family comprising 16 genes was genotyped in 313 HIV-1 positive Kenyan mothers paired with their infants. G...

Background Four studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population. Methods and findings We evaluated the interaction between maternal malaria in...

Assessment of risk of bias for the 13 studies included in the individual participant data meta-analysis. (DOCX)

PRISMA 2009 checklist. (DOC)

Prevalence of low mid-upper arm circumference (MUAC < 23cm) compared to prevalence of low body mass index (BMI < 18.5 kg/m2) among the 13 studies in the Maternal Malaria and Malnutrition (M3) initiative. (DOCX)

Meta-regression results for the effects of malnutrition at enrollment, (a) low mid-upper arm circumference (MUAC < 23 cm) and (b) low BMI (BMI < 18.5 kg/m2), on risk of low birthweight (LBW) and mean birthweight (BW) by time period, study type, location, and malaria prevalence. Median malaria prevalence across studies was 17% at enrollment and 15%...

Descriptions of the scales used to measure birthweight, how gestational age was assessed, and the median gestational age for each of the 13 studies in the Maternal Malaria and Malnutrition (M3) initiative. (DOCX)

Meta-regression results for the effects of malaria infection at enrollment and delivery on risk of low birthweight (LBW) and mean birthweight (BW) by time period, study type, location, and malaria prevalence. Median malaria prevalence across studies was 17% at enrollment and 15% at delivery. RCT = randomized control trial. (DOCX)

Meta-regression results for the multiplicative and additive interaction effects for malaria at enrollment or delivery and low mid-upper arm circumference (MUAC < 23 cm) on risk of low birthweight (LBW) and mean birthweight (BW) by time period, study type, location, and malaria prevalence. Median malaria prevalence across studies was 17% at enrollme...

Characteristics of the 13 individual studies included in the Maternal Malnutrition and Malaria (M3) initiative. (DOCX)

Characteristics of studies not included in the Maternal Malaria and Malnutrition (M3) initiative cohort. (DOCX)

The independent and joint effects of malaria infection at enrollment, malaria infection at delivery, low mid-upper arm circumference (MUAC), and low body mass index (BMI) on the risk of small for gestational age (SGA) and risk of preterm birth among a subset of 9 studies from the Maternal Malaria and Malnutrition (M3) initiative. (DOCX)

Select sensitivity analysis results for the multiplicative interaction effects for malaria and malnutrition on risk of adverse birth outcomes among the 13 studies in the Maternal Malaria and Malnutrition (M3) initiative. Sensitivity analyses varied the definitions of malaria, malnutrition, the outcome of interest, and the approach taken in pooling...

Individual participant data checklist. (DOCX)

Multiple imputation. (DOCX)

Protocol for the individual participant data project. Written 17 November 2014. (DOCX)

Prevalence of malaria infection at delivery among the 13 studies in the Maternal Malaria and Malnutrition (M3) initiative. (DOCX)

Purpose The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria–nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. Participants Data were pooled on 14 635 singleton, live birth pregnancies from women who had p...

In this emerging era of global, fast-paced knowledge-based economy, universities, as major centres of learning and research, are becoming increasingly important as sources of ideas, knowledge, skills, innovation and technological advances. These ideas can be turned into new products, processes and systems needed to drive their respective national e...

Immunoglobulin (Ig) GM and KM allotypes, genetic markers of γ and κ chains, are associated with humoral immune responsiveness. Previous studies have shown the relationships between GM6-carrying haplotypes and susceptibility to malaria infection in children and adults; however, the role of the genetic markers in placental malaria (PM) infection and...

Schistosome and soil-transmitted helminth (STH) infections are recognized as major global public health problems, causing severe and subtle morbidity, including significant educational and nutritional effects in children. Although effective and safe drugs are available, ensuring access to these drugs by all those at risk of schistosomiasis and STHs...

Proportion of SP drug resistant genotypes by HIV status and by study period. A, dhfr genotypes. B, dhps genotypes. C, combined dhfr/dhps genotypes. The figures described the prevalence of dhfr, dhps and the combined dhfr/dhps genotypes between HIV + and HIV- women.

Statistical procedure. The file described the statistical methods used for the descriptive and association analysis.

Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these refer...

Resistance to sulphadoxine-pyrimethamine (SP) in Plasmodium falciparum parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes and has spread worldwide. SP remains the recommended drug for intermittent preventive treatment for malaria in pregnancy (IPTp) and information on population pr...

This cross-sectional study determined the prevalence and distribution of schistosome and soil-transmitted helminth (STH) infections among 1,308 children aged 10-18 years in 34 primary schools in 8 informal urban settlements in Kisumu City, western Kenya. Stool samples were collected and examined for eggs of Schistosoma mansoni and STH (Hookworms, A...

There is increasing importance of trauma not only as a major cause of surgical admissions, but also a significant cause of morbidity, mortality and disability. To document injury-related visits and hospitalization in a provincial hospital, western Kenya. On-site review of records of all patients who visited emergency department (ED) from January 20...

Maternal mortality remains high in developing countries and data to monitor indicators of progress in maternal care is needed. We examined the status of maternal care before and after health care worker (HCW) training in WHO recommended Focused Antenatal Care. An initial cross-sectional survey was conducted in 2002 in Asembo and Gem in western Keny...

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To compare the frequency and etiology of diarrhea in children aged less than 2 years with known HIV status. This was a nested cohort study, whereby children were followed during monthly routine and unscheduled visits. The HIV status of children was determined with PCR. A stool culture was obtained from children with diarrhea. A subset of stool samp...

Geohelminth infections are common in rural western Kenya, but risk factors and effects among pregnant women are not clear. During a community-based cross-sectional survey, pregnant women were interviewed and asked to provide a blood sample and a single fecal sample. Hemoglobin was measured and a blood slide examined for malaria. Geohelminth infecti...

Placental malaria (PM) and maternal infection with human immunodeficiency virus (HIV) type 1 have been shown to affect infant morbidity and immune responses to Plasmodium falciparum. We studied the effects of PM and HIV infection on the antimalarial antibody responses and morbidity outcomes of infants throughout the first year of life. A total of 4...

Sulfadoxine-pyrimethamine (SP) inhibits folate metabolism by the malaria parasite. We investigated the association between folate levels and SP failure in pregnant women. Data from a trial to assess the effect that folate supplementation has on SP failure in 467 pregnant women were analyzed. Plasma folate levels were determined at enrollment and at...

We describe reproductive health issues among pregnant women in a rural area of Kenya with a high coverage of insecticide treated nets (ITNs) and high prevalence of HIV (15%). We conducted a community-based cross-sectional survey among rural pregnant women in western Kenya. A medical, obstetric and reproductive history was obtained. Blood was obtain...

To determine the prevalence of malaria and anaemia among urban and peri-urban women attending their first antenatal clinic (ANC) in an area of perennial malaria transmission. Between November 2003 and May 2004 we screened first ANC attenders for malaria and anaemia in a large urban hospital in Kisumu (western Kenya) and interviewed them to obtain d...

Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy, yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV(+)) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected (HIV(-)) women. We investigated whether this reflects their impair...

In 1998, Kenya adopted intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) for malaria prevention during pregnancy. We conducted a survey in 2002 among women who had recently delivered in the rural neighbouring areas Asembo and Gem and reported coverage of 19% of at least one dose and 7% of two or more doses of SP. Health...

HIV and malaria in sub-Saharan Africa are associated with poor pregnancy outcome and infant survival. We studied the association of placental malaria, infant malaria and anemia, and infant HIV status with postneonatal infant mortality (PNIM) among infants of HIV-seropositive women. During 1996-2001, infants born to 570 HIV-seropositive mothers in K...

Characteristics of Primigravid Participants (Used in Figure 4A) According to HIV Status (12 KB PDF)

Characteristics of Multigravid Participants (Used in Figure 4B) According to HIV Status (12 KB PDF)

Comparison of Phagocytosis of Plasma Opsonized CSA-Binding PEs between Human Monocytes and CD36−/− Murine Macrophages Phagocytic index of CSA-binding PEs opsonized with plasma from non-immune (NI), malaria-exposed PG or malaria-exposed MG women by human monocytes (A) or Cd36−/− murine macrophages (B). The higher baseline phagocytosis observed with...

Plasma Opsonizing Activity of CD36-Binding Parasitized Erythrocytes Is Not Sex-Specific or Parity-Dependent (A) Box (median and IQR) and whisker (range) plot showing phagocytic index of CD36-binding (ITG) PEs opsonized with plasma from malaria-exposed males (M) (n = 12) or malaria-exposed MG women (n = 10). (B) Box (median and IQR) and whisker (ran...

Plasma Heat Inactivation Does Not Affect Opsonizing Activity Phagocytosis of CSA-binding PEs opsonized with malaria-exposed MG plasma by Cd36−/− murine macrophages. Solid bars indicated non-heat inactivated plasma and hatched bars indicate heat-inactivated plasma. Data are means with SD of triplicates. Plasma was heat inactivated for 1 h at 56 °C p...

Correlation between Levels of VSA-PAM-Specific Total IgG and Plasma Opsonizing Activity Plasma levels of total IgG specific for VSA expressed by CS2 PEs measured by flow cytometry were compared with their corresponding phagocytic index. Open squares represent plasma from HIV-negative MG women (n = 23), and solid triangles represent plasma from HIV-...

Characteristics of Participants (Used in Figure 1) According to Parity (12 KB PDF)

Primigravid (PG) women are at risk for pregnancy-associated malaria (PAM). Multigravid (MG) women acquire protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG specific for variant surface antigens (VSA-PAM) expressed by chondroitin sulfate A (CSA)-adhering p...

To evaluate the effect of routine antenatal haematinic supplementation programmes and intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) in Kenya. Anaemia [haemoglobin (Hb) <11 g/dl), severe anaemia (Hb <8 g/dl) and placental malaria were compared among women with known HIV status who delivered at a provincial hospital aft...

Improving maternal health is one of the UN Millennium Development Goals. We assessed provision and use of antenatal services and delivery care among women in rural Kenya to determine whether women were receiving appropriate care. Population-based cross-sectional survey among women who had recently delivered. Of 635 participants, 90% visited the ant...

Recent resurgence of malaria in the highlands of Western Kenya has called for a more comprehensive understanding of the previously neglected complex highland vector ecology. Besides other drivers of malaria epidemiology, topography is likely to have a major effect on spatial vector and parasite distribution. The aim of this study was to determine t...

Sulfadoxine-pyrimethamine (SP) is an antimalarial drug that acts on the folate metabolism of the malaria parasite. We investigated whether folate (FA) supplementation in a high or a low dose affects the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. This was a randomized, placebo-controlled, double-blind trial. The tri...

Kenya established intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) for malaria in pregnancy as national policy in 1998. We assessed the coverage of IPT among women who had recently delivered in a rural area of western Kenya with perennial malaria transmission and high coverage with insecticide treated nets (ITNs) through...

To determine the effect of placental malaria (PM) infection on the development of antibody responses to malaria in infants, we measured immunoglobulin G levels to seven different Plasmodium falciparum epitopes by using plasma samples collected at monthly intervals from infants born to mothers with and without PM. Overall, PM was associated with dim...

Genetic polymorphism of the Fc receptor IIa for immunoglobulin (Ig) G (Fc gamma RIIa) determines IgG subclass binding. Previous studies have shown that individuals with the IgG1/3-binding Fc gamma RIIa-Arg/Arg131 genotype are relatively protected against high-density malaria, whereas individuals with the IgG2-binding Fc gamma RIIa-His/His131 genoty...

The high genetic diversity of HIV-1 continues to complicate effective vaccine development. To better understand the extent of genetic diversity, intersubtype recombinants and their relative contribution to the HIV epidemic in Kenya, we undertook a detailed molecular epidemiological investigation on HIV-1-infected women attending an antenatal clinic...

To evaluate the effect of polymorphism of the Fc gamma receptor IIa, which is associated with differential human IgG subclass binding, on perinatal HIV-1 transmission. Fc gamma RIIa genotype was tested in 448 HIV-seropositive mothers and their infants from a cohort study designed to assess the effect of placental malaria on HIV vertical transmissio...

In 1998, the Kenyan Ministry of Health introduced intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), one treatment dose in the second trimester (16-27 weeks) and one treatment dose between 28 and 34 weeks of gestational age, for the control of malaria in pregnancy. We evaluated the coverage and determinants of receipt of...

Objective: To evaluate the effect of polymorphism of the Fcgamma receptor IIa, which is associated with differential human IgG subclass binding, on perinatal HIV-1 transmission. Methods: FcgammaRIIa genotype was tested in 448 HIV-seropositive mothers and their infants from a cohort study designed to assess the effect of placental malaria on HIV ver...

To monitor the effectiveness of intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) for the control of malaria in pregnancy at delivery in the Provincial Hospital in Kisumu, Kenya, and to assess the effect of IPT in participants in a cohort study. Between June 1999 and June 2000, information on IPT and birth outcome was col...

To determine whether maternal placental malaria is associated with an increased risk for perinatal mother-to-child HIV transmission (MTCT), we studied HIV-positive women in western Kenya. We enrolled 512 mother-infant pairs; 128 (25.0%) women had placental malaria, and 102 (19.9%) infants acquired HIV perinatally. Log10 HIV viral load and episiotom...

A short pregnancy interval (PI) has been associated with increased child mortality, but mechanisms are unclear. We studied factors associated with PI and the effect of PI on birthweight and haemoglobin. Information was analysed from 2218 multigravidae who were recruited at the prenatal clinic (1758) or in the labour ward (460) of the Provincial Hos...

Little is known about the impact of HIV-1 group M subtypes on mother-to-child transmission (MTCT) of HIV-1 in African settings where multiple HIV-1 group M subtypes are co-circulating. To assess the role of subtype variation on MTCT. HIV-1-infected women attending an antenatal clinic in western Kenya were enrolled for a prospective study (1996-2000...

Background: Little is known about the impact of HIV-1 group M subtypes on mother-to-child transmission (MTCT) of HIV-1 in African settings where multiple HIV-1 group M subtypes are co-circulating. Objective: To assess the role of subtype variation on MTCT. Methods: HIV-1-infected women attending an antenatal clinic in western Kenya were enrolled fo...

HIV-seropositive pregnant women are more susceptible to malaria than HIV-seronegative women. We assessed whether HIV infection alters maternal and cord plasma malarial antibody responses and the mother-to-infant transfer of malaria antibodies. We determined plasma levels of maternal and cord antibodies [Immunoglobulin (IgG)] to recombinant malarial...

To determine the effect of dual infection with HIV and malaria on birth outcomes and maternal anaemia among women delivering at a large public hospital in Kisumu, western Kenya. Data on obstetric and neonatal characteristics, maternal and placental parasitaemia, and postpartum haemoglobin levels were collected from women enrolled in a cohort study...

To study the importance of HIV infection for malaria in pregnancy in Kisumu, Kenya. Healthy women with an uncomplicated pregnancy of 32 weeks or more attending the prenatal clinic in the Provincial Hospital between June 1996 and March 1999 were tested for HIV and malaria after consent had been obtained. For participating women who delivered in the...

To develop a rapid field assessment methodology to address the burden of malaria during pregnancy and the options for intervening within the existing antenatal care system in Kenya. Surveys consisting of questionnaires, sampling of blood for parasitaemia and anaemia, and birth outcome assessment were conducted in antenatal clinics, delivery units,...

To assess risk factors for malaria in pregnancy in Kisumu, western Kenya, we studied healthy women with an uncomplicated pregnancy of ⩾32 weeks attending the antenatal clinic in the Provincial Hospital. Between June 1996 and March 1999, malaria and human immunodeficiency virus (HIV) infection were examined in 5093 pregnant women: 20·1% of the women...

The role of maternal and pediatric infection with human immunodeficiency virus type 1 (HIV-1) and malaria as risk factors for anemia was determined in a birth cohort of infants born to mothers participating in a study of the interaction between placental malaria and HIV infection, in Kisumu, Kenya. Between June 1996 and April 2000, 661 infants born...

To assess risk factors for anemia in late pregnancy, we studied healthy pregnant women with a singleton uncomplicated pregnancy of > or = 32 weeks attending the prenatal clinic in the Provincial Hospital in Kisumu, Kenya. Between June 1996 and December 1998, 4,608 pregnant women had a blood sample collected for hemoglobin (Hb) measurement, malaria...

Prevention of placental malaria through administration of antimalarial medications to pregnant women in disease-endemic areas decreases the risk of delivery of low birth weight (LBW) infants. In areas of high Plasmodium falciparum transmission, two intermittent presumptive treatment doses of sulfadoxine-pyrimethamine (SP) during the second and thir...

An association was demonstrated recently between elevated in vitro production of interferon (IFN)—γ by intervillous blood mononuclear cells (IVBMCs) and protection against placental malaria (PM). Because human immunodeficiency virus (HIV)—infected pregnant women have increased susceptibility to PM, loss of the IFN-γ response in these women may impa...

Our objective was to evaluate HIV prevalence and identify risk factors for HIV infection among women attending the antenatal clinic (ANC) at a large public hospital in Kisumu town, western Kenya. Between June 1996 and November 1997, in the context of a study to determine the effect of placental malaria on mother-to-child transmission of HIV in west...