Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-25 (of 25 Records) |
Query Trace: Van Eijk AM[original query] |
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Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis
Unger HW , Hadiprodjo AJ , Gutman JR , Briand V , Fievet N , Valea I , Tinto H , D'Alessandro U , Landis SH , Ter Kuile F , Ouma P , Oneko M , Mwapasa V , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Nahlen B , Desai M , Madanitsa M , Kalilani-Phiri L , Ashorn P , Maleta K , Tshefu-Kitoto A , Mueller I , Stanisic D , Cates J , Van Eijk AM , Ome-Kaius M , Aitken EH , Rogerson SJ . Sci Rep 2023 13 (1) 10310 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 malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy. |
Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis
van Eijk AM , Stepniewska K , Hill J , Taylor SM , Rogerson SJ , Cottrell G , Chico RM , Gutman JR , Tinto H , Unger HW , Yanow SK , Meshnick SR , Ter Kuile FO , Mayor A . Lancet Glob Health 2023 11 (7) e1061-e1074 BACKGROUND: Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD). METHODS: For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342. FINDINGS: The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection. INTERPRETATION: During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections. FUNDING: Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network. |
Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis.
van Eijk AM , Larsen DA , Kayentao K , Koshy G , Slaughter DEC , Roper C , Okell LC , Desai M , Gutman J , Khairallah C , Rogerson SJ , Hopkins Sibley C , Meshnick SR , Taylor SM , Ter Kuile FO . Lancet Infect Dis 2019 19 (5) 546-556 BACKGROUND: Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) in sub-Saharan Africa. We aimed to assess the associations between markers of sulfadoxine-pyrimethamine resistance in P falciparum and the effectiveness of sulfadoxine-pyrimethamine IPTp for malaria-associated outcomes. METHODS: For this systematic review and meta-analysis, we searched databases (from Jan 1, 1990 to March 1, 2018) for clinical studies (aggregated data) or surveys (individual participant data) that reported data on low birthweight (primary outcome) and malaria by sulfadoxine-pyrimethamine IPTp dose, and for studies that reported on molecular markers of sulfadoxine-pyrimethamine resistance. Studies that involved only HIV-infected women or combined interventions were excluded. We did a random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarised dose-response data (relative risk reduction [RRR]) and multivariate meta-regression to explore the modifying effects of sulfadoxine-pyrimethamine resistance (as indicated by Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene). This study is registered with PROSPERO, number 42016035540. FINDINGS: Of 1097 records screened, 57 studies were included in the aggregated-data meta-analysis (including 59 457 births). The RRR for low birthweight declined with increasing prevalence of dhps Lys540Glu (p(trend)=0·0060) but not Ala437Gly (p(trend)=0·35). The RRR was 7% (95% CI 0 to 13) in areas of high resistance to sulfadoxine-pyrimethamine (Lys540Glu ≥90% in east and southern Africa; n=11), 21% (14 to 29) in moderate-resistance areas (Ala437Gly ≥90% [central and west Africa], or Lys540Glu ≥30% to <90% [east and southern Africa]; n=16), and 27% (21 to 33) in low-resistance areas (Ala437Gly <90% [central and west Africa], or Lys540Glu <30% [east and southern Africa]; n=30; p(trend)=0·0054 [univariate], I(2)=69·5%). The overall RRR in all resistance strata was 21% (17 to 25). In the analysis of individual participant data from 13 surveys (42 394 births), sulfadoxine-pyrimethamine IPTp was associated with reduced prevalence of low birthweight in areas with a Lys540Glu prevalence of more than 90% and Ala581Gly prevalence of less than 10% (RRR 10% [7 to 12]), but not in those with an Ala581Gly prevalence of 10% or higher (pooled Ala581Gly prevalence 37% [range 29 to 46]; RRR 0·5% [-16 to 14]; 2326 births). INTERPRETATION: The effectiveness of sulfadoxine-pyrimethamine IPTp is reduced in areas with high resistance to sulfadoxine-pyrimethamine among P falciparum parasites, but remains associated with reductions in low birthweight even in areas where dhps Lys540Glu prevalence exceeds 90% but where the sextuple-mutant parasite (harbouring the additional dhps Ala581Gly mutation) is uncommon. Therapeutic alternatives to sulfadoxine-pyrimethamine IPTp are needed in areas where the prevalence of the sextuple-mutant parasite exceeds 37%. FUNDING: US Centers for Disease Control and Prevention, the Malaria in Pregnancy Consortium (funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine), Worldwide Antimalarial Resistance Network, European and Developing Countries Clinical Trials Partnership. |
Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis
Saito M , McGready R , Tinto H , Rouamba T , Mosha D , Rulisa S , Kariuki S , Desai M , Manyando C , Njunju EM , Sevene E , Vala A , Augusto O , Clerk C , Were E , Mrema S , Kisinza W , Byamugisha J , Kagawa M , Singlovic J , Yore M , van Eijk AM , Mehta U , Stergachis A , Hill J , Stepniewska K , Gomes M , Guérin PJ , Nosten F , Ter Kuile FO , Dellicour S . Lancet 2023 401 (10371) 118-130 BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation. |
Post-discharge morbidity and mortality in children admitted with severe anaemia and other health conditions in malaria-endemic settings in Africa: a systematic review and meta-analysis
Kwambai TK , Mori AT , Nevitt S , van Eijk AM , Samuels AM , Robberstad B , Phiri KS , Ter Kuile FO . Lancet Child Adolesc Health 2022 6 (7) 474-483 BACKGROUND: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also remain at increased risk of mortality for several months after hospital discharge. We aimed to compare the risks of morbidity and mortality among children discharged from hospital after recovery from severe anaemia versus other health conditions in malaria-endemic settings in Africa. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and Cochrane Central from inception to Nov 30, 2021, without language restrictions, for prospective or retrospective cohort studies and randomised controlled trials that followed up children younger than 15 years for defined periods after hospital discharge in malaria-endemic countries in Africa. We excluded the intervention groups in trials and studies or subgroups involving children with sickle cell anaemia, malignancies, or surgery or trauma, or those reporting follow-up data that were combined with the in-hospital period. Two independent reviewers extracted the data and assessed the quality and risk of bias using the Newcastle Ottawa Scale or the Cochrane Collaboration's tool. The coprimary outcomes were all-cause death and all-cause readmissions 6 months after discharge. This study is registered with PROSPERO, CRD42017079282. FINDINGS: Of 2930 articles identified in our search, 27 studies were included. For children who were recently discharged following hospital admission with severe anaemia, all-cause mortality by 6 months was higher than during the in-hospital period (n=5 studies; Mantel-Haenszel odds ratio 1·72, 95% CI 1·22-2·44; p=0·0020; I(2)=51·5%) and more than two times higher than children previously admitted without severe anaemia (n=4 studies; relative risk [RR] 2·69, 95% CI 1·59-4·53; p<0·0001; I(2)=69·2%). Readmissions within 6 months of discharge were also more common in children admitted with severe anaemia than in children admitted with other conditions (n=1 study; RR 3·05, 1·12-8·35; p<0·0001). Children admitted with severe acute malnutrition (regardless of severe anaemia) also had a higher 6-month mortality after discharge than those admitted for other reasons (n=2 studies; RR=3·12, 2·02-4·68; p<0·0001; I(2)=54·7%). Other predictors of mortality after discharge included discharge against medical advice, HIV, bacteraemia, and hypoxia. INTERPRETATION: In malaria-endemic settings in Africa, children admitted to hospital with severe anaemia and severe acute malnutrition are at increased risk of mortality in the first 6 months after discharge compared with children admitted with other health conditions. Improved strategies are needed for the management of these high-risk groups during the period after discharge. FUNDING: Research Council of Norway and US Centers for Disease Control and Prevention. |
Use of menstrual cups among school girls: longitudinal observations nested in a randomised controlled feasibility study in rural western Kenya
van Eijk AM , Laserson KF , Nyothach E , Oruko K , Omoto J , Mason L , Alexander K , Oduor C , Mohammed A , Eleveld A , Ngere I , Obor D , Vulule J , Phillips-Howard PA . Reprod Health 2018 15 (1) 139 BACKGROUND: A menstrual cup can be a good solution for menstrual hygiene management in economically challenged settings. As part of a pilot study we assessed uptake and maintenance of cup use among young school girls in Kenya. METHODS: A total of 192 girls between 14 to 16 years were enrolled in 10 schools in Nyanza Province, Western Kenya; these schools were assigned menstrual cups as part of the cluster-randomized pilot study. Girls were provided with menstrual cups in addition to training and guidance on use, puberty education, and instructions for menstrual hygiene. During repeated individual visits with nurses, girls reported use of the menstrual cup and nurses recorded colour change of the cup. RESULTS: Girls were able to keep their cups in good condition, with only 12 cups (6.3%) lost (dropped in toilet, lost or destroyed). Verbally reported cup use increased from 84% in the first 3 months (n = 143) to 96% after 9 months (n = 74). Colour change of the cup, as 'uptake' indicator of use, was detected in 70.8% of 192 participants, with a median time of 5 months (range 1-14 months). Uptake differed by school and was significantly higher among girls who experienced menarche within the past year (adjusted risk ratio 1.29, 95% CI 1.04-1.60), and was faster among girls enrolled in the second study year (hazard ratio 3.93, 95% CI 2.09-7.38). The kappa score comparing self-report and cup colour observation was 0.044 (p = 0.028), indicating that agreement was only slightly higher than by random chance. CONCLUSIONS: Objective evidence through cup colour change suggests school girls in rural Africa can use menstrual cups, with uptake improving with peer group education and over time. TRIAL REGISTRATION: ISRCTN17486946 . Retrospectively registered 09 December 2014. |
Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem
Rogerson SJ , Desai M , Mayor A , Sicuri E , Taylor SM , van Eijk AM . Lancet Infect Dis 2018 18 (4) e107-e118 Over the past 10 years, knowledge of the burden, economic costs, and consequences of malaria in pregnancy has improved, and the prevalence of malaria caused by Plasmodium falciparum has declined substantially in some geographical areas. In particular, studies outside of Africa have increased the evidence base of Plasmodium vivax in pregnancy. Rapid diagnostic tests have been poor at detecting malaria in pregnant women, while PCR has shown a high prevalence of low density infection, the clinical importance of which is unknown. Erythrocytes infected with P falciparum that express the surface protein VAR2CSA accumulate in the placenta, and VAR2CSA is an important target of protective immunity. Clinical trials for a VAR2CSA vaccine are ongoing, but sequence variation needs to be carefully studied. Health system and household costs still limit access to prevention and treatment services. Within the context of malaria elimination, pregnant women could be used to monitor malaria transmission. This Series paper summarises recent progress and highlights unresolved issues related to the burden of malaria in pregnancy. |
Association of maternal KIR gene content polymorphisms with reduction in perinatal transmission of HIV-1.
Omosun YO , Blackstock AJ , Williamson J , van Eijk AM , Ayisi J , Otieno J , Lal RB , Ter Kuile FO , Slutsker L , Shi YP . PLoS One 2018 13 (1) e0191733 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. Gene content polymorphisms were presented as presence of individual KIR genes, haplotypes, genotypes and KIR gene concordance. The genetic data were analyzed for associations with perinatal transmission of HIV. There was no association of infant KIR genes with perinatal HIV-1 transmission. After adjustment for gravidity, viral load, and CD4 cell count, there was evidence of an association between reduction in perinatal HIV-1 transmission and the maternal individual KIR genes KIR2DL2 (adjusted OR = 0.50; 95% CI: 0.24-1.02, P = 0.06), KIR2DL5 (adjusted OR = 0.47; 95% CI: 0.23-0.95, P = 0.04) and KIR2DS5 (adjusted OR = 0.39; 95% CI: 0.18-0.80, P = 0.01). Furthermore, these maternal KIR genes were only significantly associated with reduction in perinatal HIV transmission in women with CD4 cell count >/= 350 cells/ mul and viral load <10000 copies/ml. Concordance analysis showed that when both mother and child had KIR2DS2, there was less likelihood of perinatal HIV-1 transmission (adjusted OR = 0.44; 95% CI: 0.20-0.96, P = 0.039). In conclusion, the maternal KIR genes KIR2DL2, KIR2DL5, KIR2DS5, and KIR2DS2 were associated with reduction of HIV-1 transmission from mother to child. Furthermore, maternal immune status is an important factor in the association of KIR with perinatal HIV transmission. |
Malaria, malnutrition, and birthweight: A meta-analysis using individual participant data
Cates JE , Unger HW , Briand V , Fievet N , Valea I , Tinto H , D'Alessandro U , Landis SH , Adu-Afarwuah S , Dewey KG , Ter Kuile FO , Desai M , Dellicour S , Ouma P , Gutman J , Oneko M , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Madanitsa M , Mwapasa V , Ashorn P , Maleta K , Mueller I , Stanisic D , Schmiegelow C , Lusingu JPA , van Eijk AM , Bauserman M , Adair L , Cole SR , Westreich D , Meshnick S , Rogerson S . PLoS Med 2017 14 (8) e1002373 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 infection and maternal anthropometric status on the risk of LBW using pooled data from 14,633 pregnancies from 13 studies (6 cohort studies and 7 randomized controlled trials) conducted in Africa and the Western Pacific from 1996-2015. Studies were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability of treatment-weighted linear and log-binomial regression models and pooled using a random-effects model. The adjusted risk of delivering a baby with LBW was 8.8% among women with malaria infection at antenatal enrollment compared to 7.7% among uninfected women (adjusted risk ratio [aRR] 1.14 [95% confidence interval (CI): 0.91, 1.42]; N = 13,613), 10.5% among women with malaria infection at delivery compared to 7.9% among uninfected women (aRR 1.32 [95% CI: 1.08, 1.62]; N = 11,826), and 15.3% among women with low mid-upper arm circumference (MUAC <23 cm) at enrollment compared to 9.5% among women with MUAC ≥ 23 cm (aRR 1.60 [95% CI: 1.36, 1.87]; N = 9,008). The risk of delivering a baby with LBW was 17.8% among women with both malaria infection and low MUAC at enrollment compared to 8.4% among uninfected women with MUAC ≥ 23 cm (joint aRR 2.13 [95% CI: 1.21, 3.73]; N = 8,152). There was no evidence of synergism (i.e., excess risk due to interaction) between malaria infection and MUAC on the multiplicative (p = 0.5) or additive scale (p = 0.9). Results were similar using body mass index (BMI) as an anthropometric indicator of nutritional status. Meta-regression results indicated that there may be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies. CONCLUSIONS: Pregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only 1 risk factor or none, but malaria and malnutrition do not act synergistically. |
Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific
Unger HW , Cates JE , Gutman J , Briand V , Fievet N , Valea I , Tinto H , d'Alessandro U , Landis SH , Adu-Afarwuah S , Dewey KG , Ter Kuile F , Dellicour S , Ouma P , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Nahlen B , Desai M , Madanitsa M , Kalilani-Phiri L , Ashorn P , Maleta K , Mueller I , Stanisic D , Schmiegelow C , Lusingu J , Westreich D , van Eijk AM , Meshnick S , Rogerson S . BMJ Open 2016 6 (12) e012697 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 participated in 1 of 13 pregnancy studies. The 13 studies cover 8 countries in Africa and Papua New Guinea in the Western Pacific conducted from 1996 to 2015. FINDINGS TO DATE: Data are available at the time of antenatal enrolment of women into their respective parent study and at delivery. The data set comprises essential data such as malaria infection status, anthropometric assessments of maternal nutritional status, presence of anaemia and birth weight, as well as additional variables such gestational age at delivery for a subset of women. Participating studies are described in detail with regard to setting and primary outcome measures, and summarised data are available from each contributing cohort. FUTURE PLANS: This pooled birth cohort is the largest pregnancy data set to date to permit a more definite evaluation of the impact of plausible interactions between poor nutritional status and malaria infection in pregnant women on fetal growth and gestational length. Given the current comparative lack of large pregnancy cohorts in malaria-endemic settings, compilation of suitable pregnancy cohorts is likely to provide adequate statistical power to assess malaria-nutrition interactions, and could point towards settings where such interactions are most relevant. The M3 cohort may thus help to identify pregnant women at high risk of adverse outcomes who may benefit from tailored intensive antenatal care including nutritional supplements and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective. |
Menstrual cups and sanitary pads to reduce school attrition, and sexually transmitted and reproductive tract infections: A cluster randomised controlled feasibility study in rural Western Kenya
Phillips-Howard PA , Nyothach E , Ter Kuile FO , Omoto J , Wang D , Zeh C , Onyango C , Mason L , Alexander KT , Odhiambo FO , Eleveld A , Mohammed A , van Eijk AM , Edwards RT , Vulule J , Faragher B , Laserson KF . BMJ Open 2016 6 (11) e013229 OBJECTIVES: Conduct a feasibility study on the effect of menstrual hygiene on schoolgirls' school and health (reproductive/sexual) outcomes. DESIGN: 3-arm single-site open cluster randomised controlled pilot study. SETTING: 30 primary schools in rural western Kenya, within a Health and Demographic Surveillance System. PARTICIPANTS: Primary schoolgirls 14-16 years, experienced 3 menses, no precluding disability, and resident in the study area. INTERVENTIONS: 1 insertable menstrual cup, or monthly sanitary pads, against 'usual practice' control. All participants received puberty education preintervention, and hand wash soap during intervention. Schools received hand wash soap. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary: school attrition (drop-out, absence); secondary: sexually transmitted infection (STI) (Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoea), reproductive tract infection (RTI) (bacterial vaginosis, Candida albicans); safety: toxic shock syndrome, vaginal Staphylococcus aureus. RESULTS: Of 751 girls enrolled 644 were followed-up for a median of 10.9 months. Cups or pads did not reduce school dropout risk (control=8.0%, cups=11.2%, pads=10.2%). Self-reported absence was rarely reported and not assessable. Prevalence of STIs in the end-of-study survey among controls was 7.7% versus 4.2% in the cups arm (adjusted prevalence ratio (aPR) 0.48, 0.24 to 0.96, p=0.039), 4.5% with pads (aPR=0.62; 0.37 to 1.03, p=0.063), and 4.3% with cups and pads pooled (aPR=0.54, 0.34 to 0.87, p=0.012). RTI prevalence was 21.5%, 28.5% and 26.9% among cup, pad and control arms, 71% of which were bacterial vaginosis, with a prevalence of 14.6%, 19.8% and 20.5%, per arm, respectively. Bacterial vaginosis was less prevalent in the cups (12.9%) compared with pads (20.3%, aPR=0.65, 0.44 to 0.97, p=0.034) and control (19.2%, aPR=0.67, 0.43 to 1.04, p=0.075) arm girls enrolled for 9 months or longer. No adverse events were identified. CONCLUSIONS: Provision of menstrual cups and sanitary pads for approximately 1 school-year was associated with a lower STI risk, and cups with a lower bacterial vaginosis risk, but there was no association with school dropout. A large-scale trial on menstrual cups is warranted. TRIAL REGISTRATION: ISRCTN17486946; Results. |
Menstrual hygiene management among adolescent girls in India: A systematic review and meta-analysis
van Eijk AM , Sivakami M , Thakkar MB , Bauman A , Laserson KF , Coates S , Phillips-Howard PA . BMJ Open 2016 6 (3) e010290 OBJECTIVES: To assess the status of menstrual hygiene management (MHM) among adolescent girls in India to determine unmet needs. DESIGN: Systematic review and meta-analysis. We searched PubMed, The Global Health Database, Google Scholar and references for studies published from 2000 to September 2015 on girls' MHM. SETTING: India. PARTICIPANTS: Adolescent girls. OUTCOME MEASURES: Information on menarche awareness, type of absorbent used, disposal, hygiene, restrictions and school absenteeism was extracted from eligible materials; a quality score was applied. Meta-analysis was used to estimate pooled prevalence (PP), and meta-regression to examine the effect of setting, region and time. RESULTS: Data from 138 studies involving 193 subpopulations and 97 070 girls were extracted. In 88 studies, half of the girls reported being informed prior to menarche (PP 48%, 95% CI 43% to 53%, I(2) 98.6%). Commercial pad use was more common among urban (PP 67%, 57% to 76%, I(2) 99.3%, n=38) than rural girls (PP 32%, 25% to 38%, I(2) 98.6%, n=56, p<0.0001), with use increasing over time (p<0.0001). Inappropriate disposal was common (PP 23%, 16% to 31%, I(2) 99.0%, n=34). Menstruating girls experienced many restrictions, especially for religious activities (PP 0.77, 0.71 to 0.83, I(2) 99.1%, n=67). A quarter (PP 24%, 19% to 30%, I(2) 98.5%, n=64) reported missing school during periods. A lower prevalence of absenteeism was associated with higher commercial pad use in univariate (p=0.023) but not in multivariate analysis when adjusted for region (p=0.232, n=53). Approximately a third of girls changed their absorbents in school facilities (PP 37%, 29% to 46%, I(2) 97.8%, n=17). Half of the girls' homes had a toilet (PP 51%, 36% to 67%, I(2) 99.4%, n=21). The quality of studies imposed limitations on analyses and the interpretation of results (mean score 3 on a scale of 0-7). CONCLUSIONS: Strengthening of MHM programmes in India is needed. Education on awareness, access to hygienic absorbents and disposal of MHM items need to be addressed. TRIAL REGISTRATION NUMBER: CRD42015019197. |
Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data
Fernandes S , Sicuri E , Kayentao K , van Eijk AM , Hill J , Webster J , Were V , Akazili J , Madanitsa M , Ter Kuile FO , Hanson K . Lancet Glob Health 2015 3 (3) e143-53 BACKGROUND: In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of a cost-effectiveness analysis to lend support to the decision of policy makers. We therefore estimated the incremental cost-effectiveness of IPTp with three or more (IPTp-SP3+) versus two doses of sulfadoxine-pyrimethamine (IPTp-SP2). METHODS: For this analysis, we used data from a 2013 meta-analysis of seven studies in sub-Saharan Africa. We developed a decision tree model with a lifetime horizon. We analysed the base case from a societal perspective. We did deterministic and probabilistic sensitivity analyses with appropriate parameter ranges and distributions for settings with low, moderate, and high background risk of low birthweight, and did a separate analysis for HIV-negative women. Parameters in the model were obtained for all countries included in the original meta-analysis. We did simulations in hypothetical cohorts of 1000 pregnant women receiving either IPTp-SP3+ or IPTp-SP2. We calculated disability-adjusted life-years (DALYs) for low birthweight, severe to moderate anaemia, and clinical malaria. We calculated cost estimates from data obtained in observational studies, exit surveys, and from public procurement databases. We give financial and economic costs in constant 2012 US$. The main outcome measure was the incremental cost per DALY averted. FINDINGS: The delivery of IPTp-SP3+ to 1000 pregnant women averted 113.4 DALYs at an incremental cost of $825.67 producing an incremental cost-effectiveness ratio (ICER) of $7.28 per DALY averted. The results remained robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analyses, the ICER was $7.7 per DALY averted for moderate risk of low birthweight, $19.4 per DALY averted for low risk, and $4.0 per DALY averted for high risk. The ICER for HIV-negative women was $6.2 per DALY averted. INTERPRETATION: Our findings lend strong support to the WHO guidelines that recommend a monthly dose of IPTp-SP from the second trimester onwards. FUNDING: Malaria in Pregnancy Consortium and the Bill & Melinda Gates Foundation. |
Deaths ascribed to non-communicable diseases among rural Kenyan adults are proportionately increasing: evidence from a health and demographic surveillance system, 2003-2010
Phillips-Howard PA , Laserson KF , Amek N , Beynon CM , Angell SY , Khagayi S , Byass P , Hamel MJ , van Eijk AM , Zielinski-Gutierrez E , Slutsker L , De Cock KM , Vulule J , Odhiambo FO . PLoS One 2014 9 (11) e114010 BACKGROUND: Non-communicable diseases (NCDs) result in more deaths globally than other causes. Monitoring systems require strengthening to attribute the NCD burden and deaths in low and middle-income countries (LMICs). Data from health and demographic surveillance systems (HDSS) can contribute towards this goal. METHODS AND FINDINGS: Between 2003 and 2010, 15,228 deaths in adults aged 15 years (y) and older were identified retrospectively using the HDSS census and verbal autopsy in rural western Kenya, attributed into broad categories using InterVA-4 computer algorithms; 37% were ascribed to NCDs, 60% to communicable diseases (CDs), 3% to injuries, and <1% maternal causes. Median age at death for NCDs was 66y and 71y for females and males, respectively, with 43% (39% male, 48% female) of NCD deaths occurring prematurely among adults aged below 65y. NCD deaths were mainly attributed to cancers (35%) and cardio-vascular diseases (CVDs; 29%). The proportionate mortality from NCDs rose from 35% in 2003 to 45% in 2010 (chi2 linear trend 93.4; p<0.001). While overall annual mortality rates (MRs) for NCDs fell, cancer-specific MRs rose from 200 to 262 per 100,000 population, mainly due to increasing deaths in adults aged 65y and older, and to respiratory neoplasms in all age groups. The substantial fall in CD MRs resulted in similar MRs for CDs and NCDs among all adult females by 2010. NCD MRs for adults aged 15y to <65y fell from 409 to 183 per 100,000 among females and from 517 to 283 per 100,000 population among males. NCD MRs were higher among males than females aged both below, and at or above, 65y. CONCLUSIONS: NCDs constitute a significant proportion of deaths in rural western Kenya. Evidence of the increasing contribution of NCDs to overall mortality supports international recommendations to introduce or enhance prevention, screening, diagnosis and treatment programmes in LMICs. |
HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites
Streatfield PK , Khan WA , Bhuiya A , Hanifi SM , Alam N , Millogo O , Sie A , Zabre P , Rossier C , Soura AB , Bonfoh B , Kone S , Ngoran EK , Utzinger J , Abera SF , Melaku YA , Weldearegawi B , Gomez P , Jasseh M , Ansah P , Azongo D , Kondayire F , Oduro A , Amu A , Gyapong M , Kwarteng O , Kant S , Pandav CS , Rai SK , Juvekar S , Muralidharan V , Wahab A , Wilopo S , Bauni E , Mochamah G , Ndila C , Williams TN , Khagayi S , Laserson KF , Nyaguara A , Van Eijk AM , Ezeh A , Kyobutungi C , Wamukoya M , Chihana M , Crampin A , Price A , Delaunay V , Diallo A , Douillot L , Sokhna C , Gómez-Olivé FX , Mee P , Tollman SM , Herbst K , Mossong J , Chuc NT , Arthur SS , Sankoh OA , Byass P . Glob Health Action 2014 7 25370 BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS. |
Determinants and coverage of vaccination in children in Western Kenya from a 2003 cross-sectional survey
Calhoun LM , van Eijk AM , Lindblade KA , Odhiambo FO , Wilson ML , Winterbauer E , Slutsker L , Hamel MJ . Am J Trop Med Hyg 2013 90 (2) 234-41 This study assesses full and timely vaccination coverage and factors associated with full vaccination in children ages 12-23 months in Gem, Nyanza Province, Kenya in 2003. A simple random sample of 1,769 households was selected, and guardians were invited to bring children under 5 years of age to participate in a survey. Full vaccination coverage was 31.1% among 244 children. Only 2.2% received all vaccinations in the target month for each vaccination. In multivariate logistic regression, children of mothers of higher parity (odds ratio [OR] = 0.27, 95% confidence interval [95% CI] = 0.13-0.65, P ≤ 0.01), children of mothers with lower maternal education (OR = 0.35, 95% CI = 0.13-0.97, P ≤ 0.05), or children in households with the spouse absent versus present (OR = 0.40, 95% CI = 0.17-0.91, P ≤ 0.05) were less likely to be fully vaccinated. These data serve as a baseline from which changes in vaccination coverage will be measured as interventions to improve vaccination timeliness are introduced. |
Health care seeking for childhood diarrhea in developing countries: evidence from seven sites in Africa and Asia
Nasrin D , Wu Y , Blackwelder WC , Farag TH , Saha D , Sow SO , Alonso PL , Breiman RF , Sur D , Faruque AS , Zaidi AK , Biswas K , Van Eijk AM , Levine MM , Kotloff KL . Am J Trop Med Hyg 2013 89 3-12 We performed serial healthcare use surveys among caretakers of children ages 0-59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0-11 months of age), from 0.4% to 4.7% for toddlers (12-23 months of age), and from 0.3% to 2.4% for preschoolers (24-59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15-56%, 17-64%, and 7-33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking behavior outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial healthcare use surveys as an invaluable tool for optimizing operational and methodological issues related to the performance of a large case control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings. |
Health-seeking behavior during childhood diarrheal illness: results of healthcare use and attitude surveys of caretakers in western Kenya, 2007-2010
Omore R , O'Reilly CE , Williamson J , Moke F , Were V , Farag TH , van Eijk AM , Kotloff KL , Levine MM , Obor D , Odhiambo F , Vulule J , Laserson KF , Mintz ED , Breiman RF . Am J Trop Med Hyg 2013 89 29-40 We interviewed caretakers of 1,043 children < 5 years old in a baseline cross-sectional survey (April to May 2007) and > 20,000 children on five separate subsequent occasions (May of 2009 to December 31, 2010) to assess healthcare seeking patterns for diarrhea. Diarrhea prevalence during the preceding 2 weeks ranged from 26% at baseline to 4-11% during 2009-2010. Caretakers were less likely to seek healthcare outside the home for infants (versus older children) with diarrhea (adjusted odds ratio [aOR] = 0.33, confidence interval [CI] = 0.12-0.87). Caretakers of children with reduced food intake (aOR = 3.42, CI = 1.37-8.53) and sunken eyes during their diarrheal episode were more likely to seek care outside home (aOR = 4.76, CI = 1.13-8.89). Caretakers with formal education were more likely to provide oral rehydration solution (aOR = 3.01, CI = 1.41-6.42) and visit a healthcare facility (aOR = 3.32, CI = 1.56-7.07). Studies calculating diarrheal incidence and healthcare seeking should account for seasonal trends. Improving caretakers' knowledge of home management could prevent severe diarrhea. |
Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis
Kayentao K , Garner P , van Eijk AM , Naidoo I , Roper C , Mulokozi A , MacArthur JR , Luntamo M , Ashorn P , Doumbo OK , ter Kuile FO . JAMA 2013 309 (6) 594-604 IMPORTANCE: Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. OBJECTIVE: To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. DATA SOURCES AND STUDY SELECTION: ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. DATA EXTRACTION: Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. RESULTS: Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2 = 0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I 2 = 0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat = 31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I 2 = 0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2 = 20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events. CONCLUSIONS AND RELEVANCE: Among pregnant women in sub-Saharan Africa, intermittent preventive therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of intermittent preventive therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester. |
Association between immunoglobulin GM and KM genotypes and placental malaria in HIV-1 negative and positive women in western Kenya.
Iriemenam NC , Pandey JP , Williamson J , Blackstock AJ , Yesupriya A , Namboodiri AM , Rocca KM , van Eijk AM , Ayisi J , Oteino J , Lal RB , Ter Kuile FO , Steketee R , Nahlen B , Slutsker L , Shi YP . PLoS One 2013 8 (1) e53948 Immunoglobulin (Ig) GM and KM allotypes, genetic markers of gamma and kappa 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 PM with HIV co-infection during pregnancy has not been investigated. We examined the relationship between the gene polymorphisms of Ig GM6 and KM allotypes and the risk of PM infection in pregnant women with known HIV status. DNA samples from 728 pregnant women were genotyped for GM6 and KM alleles using polymerase chain reaction-restriction fragment length polymorphism method. Individual GM6 and KM genotypes and the combined GM6 and KM genotypes were assessed in relation to PM in HIV-1 negative and positive women, respectively. There was no significant effect of individual GM6 and KM genotypes on the risk of PM infection in HIV-1 negative and positive women. However, the combination of homozygosity for GM6(+) and KM3 was associated with decreased risk of PM (adjusted OR, 0.25; 95% CI, 0.08-0.8; P = 0.019) in HIV-1 negative women while in HIV-1 positive women the combination of GM6(+/-) with either KM1-3 or KM1 was associated with increased risk of PM infection (adjusted OR, 2.10; 95% CI, 1.18-3.73; P = 0.011). Hardy-Weinberg Equilibrium (HWE) tests further showed an overall significant positive F(is) (indication of deficit in heterozygotes) for GM6 while there was no deviation for KM genotype frequency from HWE in the same population. These findings suggest that the combination of homozygous GM6(+) and KM3 may protect against PM in HIV-1 negative women while the HIV-1 positive women with heterozygous GM6(+/-) combined with KM1-3 or KM1 may be more susceptible to PM infection. The deficit in heterozygotes for GM6 further suggests that GM6 could be under selection likely by malaria infection. |
Mortality trends from 2003 to 2009 among adolescents and young adults in rural western Kenya using a health and demographic surveillance system
Phillips-Howard PA , Odhiambo FO , Hamel M , Adazu K , Ackers M , van Eijk AM , Orimba V , Hoog AV , Beynon C , Vulule J , Bellis MA , Slutsker L , de Cock K , Breiman R , Laserson KF . PLoS One 2012 7 (11) e47017 BACKGROUND: Targeted global efforts to improve survival of young adults need information on mortality trends; contributions from health and demographic surveillance system (HDSS) are required. METHODS AND FINDINGS: This study aimed to explore changing trends in deaths among adolescents (15-19 years) and young adults (20-24 years), using census and verbal autopsy data in rural western Kenya using a HDSS. Mid-year population estimates were used to generate all-cause mortality rates per 100,000 population by age and gender, by communicable (CD) and non-communicable disease (NCD) causes. Linear trends from 2003 to 2009 were examined. In 2003, all-cause mortality rates of adolescents and young adults were 403 and 1,613 per 100,000 population, respectively, among females; and 217 and 716 per 100,000, respectively, among males. CD mortality rates among females and males 15-24 years were 500 and 191 per 100,000 (relative risk [RR] 2.6; 95% confidence intervals [CI] 1.7-4.0; p<0.001). NCD mortality rates in same aged females and males were similar (141 and 128 per 100,000, respectively; p = 0.76). By 2009, young adult female all-cause mortality rates fell 53% (chi(2) for linear trend 30.4; p<0.001) and 61.5% among adolescent females (chi(2) for linear trend 11.9; p<0.001). No significant CD mortality reductions occurred among males or for NCD mortality in either gender. By 2009, all-cause, CD, and NCD mortality rates were not significantly different between males and females, and among males, injuries equalled HIV as the top cause of death. CONCLUSIONS: This study found significant reductions in adolescent and young adult female mortality rates, evidencing the effects of targeted public health programmes, however, all-cause and CD mortality rates among females remain alarmingly high. These data underscore the need to strengthen programmes and target strategies to reach both males and females, and to promote NCD as well as CD initiatives to reduce the mortality burden amongst both gender. |
Profile: The KEMRI/CDC Health and Demographic Surveillance System--Western Kenya
Odhiambo FO , Laserson KF , Sewe M , Hamel MJ , Feikin DR , Adazu K , Ogwang S , Obor D , Amek N , Bayoh N , Ombok M , Lindblade K , Desai M , Ter Kuile F , Phillips-Howard P , van Eijk AM , Rosen D , Hightower A , Ofware P , Muttai H , Nahlen B , Decock K , Slutsker L , Breiman RF , Vulule JM . Int J Epidemiol 2012 41 (4) 977-87 The KEMRI/Centers for Disease Control and Prevention (CDC) Health and Demographic Surveillance System (HDSS) is located in Rarieda, Siaya and Gem Districts (Siaya County), lying northeast of Lake Victoria in Nyanza Province, western Kenya. The KEMRI/CDC HDSS, with approximately 220 000 inhabitants, has been the foundation for a variety of studies, including evaluations of insecticide-treated bed nets, burden of diarrhoeal disease and tuberculosis, malaria parasitaemia and anaemia, treatment strategies and immunological correlates of malaria infection, and numerous HIV, tuberculosis, malaria and diarrhoeal disease treatment and vaccine efficacy and effectiveness trials for more than a decade. Current studies include operations research to measure the uptake and effectiveness of the programmatic implementation of integrated malaria control strategies, HIV services, newly introduced vaccines and clinical trials. The HDSS provides general demographic and health information (such as population age structure and density, fertility rates, birth and death rates, in- and out-migrations, patterns of health care access and utilization and the local economics of health care) as well as disease- or intervention-specific information. The HDSS also collects verbal autopsy information on all deaths. Studies take advantage of the sampling frame inherent in the HDSS, whether at individual, household/compound or neighbourhood level. |
Differential association of gene content polymorphisms of killer cell immunoglobulin-like receptors with placental malaria in HIV- and HIV+ mothers.
Omosun YO , Blackstock AJ , Gatei W , Hightower A , van Eijk AM , Ayisi J , Otieno J , Lal RB , Steketee R , Nahlen B , Ter Kuile FO , Slutsker L , Shi YP . PLoS One 2012 7 (6) e38617 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 references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes. |
Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya.
Iriemenam NC , Shah M , Gatei W , van Eijk AM , Ayisi J , Kariuki S , Vanden Eng J , Owino SO , Lal AA , Omosun YO , Otieno K , Desai M , Ter Kuile FO , Nahlen B , Moore J , Hamel MJ , Ouma P , Slutsker L , Shi YP . Malar J 2012 11 (1) 134 BACKGROUND: 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 prevalence of the SP resistance molecular markers in pregnant women is limited. METHODS: Temporal trends of SP resistance molecular markers were investigated in 489 parasite samples collected from pregnant women at delivery from three different observational studies between 1996 and 2009 in Kenya, where SP was adopted for both IPTp and case treatment policies in 1998. Using real-time polymerase chain reaction, pyrosequencing and direct sequencing, 10 single-nucleotide polymorphisms (SNPs) of SP resistance molecular markers were assayed. RESULTS: The prevalence of quintuple mutant (dhfr N51I/C59R/S108N and dhps A437G/K540E combined genotype) increased from 7 % in the first study (1996-2000) to 88 % in the third study (2008-2009). When further stratified by sample collection year and adoption of IPTp policy, the prevalence of the quintuple mutant increased from 2.4 % in 1998 to 44.4 % three years after IPTp policy adoption, seemingly in parallel with the increase in percentage of SP use in pregnancy. However, in the 1996-2000 study, more mutations in the combined dhfr/dhps genotype were associated with SP use during pregnancy only in univariable analysis and no associations were detected in the 2002-2008 and 2008-2009 studies. In addition, in the 2008- 2009 study, 5.3 % of the parasite samples carried the dhps triple mutant (A437G/K540E/A581G). There were no differences in the prevalence of SP mutant genotypes between the parasite samples from HIV + and HIV- women over time and between paired peripheral and placental samples. CONCLUSIONS: There was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype containing dhps 581 in the parasites from pregnant women in western Kenya over 13 years. IPTp adoption and SP use in pregnancy only played a minor role in the increased drug resistant parasites in the pregnant women over time. Most likely, other major factors, such as the high prevalence of resistant parasites selected by the use of SP for case management in large non-pregnant population, might have contributed to the temporally increased prevalence of SP resistant parasites in pregnant women. Further investigations are needed to determine the linkage between SP drug resistance markers and efficacy of IPTp-SP. |
Diarrhea in children less than two years of age with known HIV status in Kisumu, Kenya
van Eijk AM , Brooks JT , Adcock PM , Garrett V , Eberhard M , Rosen DH , Ayisi JG , Ochieng JB , Kumar L , Gentsch JR , Nahlen BL , Mintz ED , Slutsker L . Int J Infect Dis 2010 14 (3) e220-5 OBJECTIVE: To compare the frequency and etiology of diarrhea in children aged less than 2 years with known HIV status. METHODS: 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 samples was examined for parasites and tested for rotavirus. RESULTS: Between 1997 and 2001, 682 children (51.0% male) contributed observation periods with a mean of 47 weeks. Overall there were 198 episodes of diarrhea per 100 child-years of observation (CYO); diarrhea was more common among HIV-positive children than among HIV-negative children (321 vs. 183 episodes/100 CYO, respectively, p<0.01) and was not statistically different for HIV-negative children born to HIV-positive compared with HIV-negative mothers (182 vs. 187 episodes/100 CYO, respectively, p=0.36). For 66.5% of the acute episodes a stool culture was obtained; 27.8% of stool cultures yielded a bacterial pathogen. A positive stool culture was less likely among HIV-positive children compared to children of HIV-negative mothers (20.5% vs. 34.3%, p=0.01). Susceptibility of Salmonella and Shigella to commonly used antibiotics was low. Rotavirus was detected in 13.9% of 202 examined stool samples, and a stool parasite in 3.8% of 394 samples. Diarrhea was associated with 37.8% of child deaths. CONCLUSIONS: Diarrhea was more common among HIV-infected children, but was not associated with specific bacterial pathogens. Measures that reduce diarrhea will benefit all children, but may benefit HIV-infected children in particular. |
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