Papers by macklyn kihembo
BMC Infectious Diseases, Sep 2, 2011
Background: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistos... more Background: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown. Methods: In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www. controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy. Results: Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel. Conclusions: Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated.
Public Health Nutrition, Mar 18, 2013
Objective: To assess the associations between maternal HIV infection and growth outcomes of HIV-e... more Objective: To assess the associations between maternal HIV infection and growth outcomes of HIV-exposed but uninfected infants and to identify other predictors for poor growth among this population. Design: Within a trial of de-worming during pregnancy, the cohort of offspring was followed from birth. HIV status of the mothers and their children was investigated and growth data for children were obtained at age 1 year. Lengthfor-age, weight-forage and weight-for-length Z-scores were calculated for each child; Z-scores ,22 were defined as stunting, underweight and wasting, respectively. Setting: The study was conducted in Entebbe municipality and Katabi subcounty, Uganda. Subjects: The sample consisted of 1502 children aged 1 year: HIV-unexposed (n 1380) and HIV-exposed not infected (n 122). Results: Prevalence of stunting, underweight and wasting was 14?2 %, 8?0 % and 3?9 %, respectively. There was evidence for an association between maternal HIV infection and odds of being underweight (adjusted OR 5 2?32; 95 % CI 1?32, 4?09; P 5 0?006) but no evidence for an association with stunting or with wasting. Young maternal age, low maternal education, low birth weight, early weaning and experiencing a higher number of episodes of malaria during infancy were independent predictors for stunting and underweight. A higher number of living children in the family was associated with wasting. Conclusions: Maternal HIV infection was associated with being underweight in HIV-exposed uninfected infants. The success of programmes for prevention of mother-to-child HIV transmission means that an increasing number of infants will be born to HIV-infected women without acquiring HIV. Therefore, viable nutritional interventions need to be identified for this population.
AIDS, Apr 14, 2021
Objective: To determine the impact of virological control on inflammation and cluster of differen... more Objective: To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. Design: Longitudinal cohort study. Methods: In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (IL-6), soluble CD14) and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level viral load or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate the incidence of clinical events. Results: Overall, 42% children experienced viral blips, but these had no significant impact on immune reconstitution or inflammation. Persistent detectable viraemia occurred in one-third of children and prevented further immune reconstitution, but had little impact on inflammatory biomarkers. Virological rebound to !5000 copies/ml was associated with arrested immune reconstitution, rising IL-6 and increased risk of clinical disease progression. Conclusions: As viral load testing becomes more available in sub-Saharan Africa, repeat testing algorithms will be required to identify those with virological rebound, who need switching to prevent disease progression, whilst preventing unnecessary second-line regimen initiation in the majority of children with detectable viraemia who remain at low risk of disease progression.
a<p>The number of mothers with children randomised is lower than the number of children ran... more a<p>The number of mothers with children randomised is lower than the number of children randomised due to 20 sets of twins;</p>b<p>mv: missing values;</p
*<p>Hazard Ratio adjusted for eczema prior to randomisation and maternal hookworm at enrolm... more *<p>Hazard Ratio adjusted for eczema prior to randomisation and maternal hookworm at enrolment.</p
a<p>The number of mothers with children randomised is lower than the number of children ran... more a<p>The number of mothers with children randomised is lower than the number of children randomised due to 20 sets of twins.</p>b<p>mv: missing values.</p>c<p>Household socioeconomic status was scored based on building materials of the home, number of rooms and items owned, “1” representing lowest and “6” representing highest status.</p
<p>Flow of participants through the childhood trial.</p
<p>Kaplan-Meier survival estimates for time to first (or only episode) of (a) malaria, (b) ... more <p>Kaplan-Meier survival estimates for time to first (or only episode) of (a) malaria, (b) diarrhoea and (c) pneumonia during the intervention period, comparing children who received quarterly albendazole with those who received placebo. Numbers shown in the tables are number of events (in brackets) and number of children at risk.</p
<p>Malaria parasitaemia results were missing for 39, 53, 52 and 38 children at ages 2, 3, 4... more <p>Malaria parasitaemia results were missing for 39, 53, 52 and 38 children at ages 2, 3, 4 and 5 years, respectively; haemoglobin results were missing for 17, 28, 658<sup>b</sup> and 13 children at ages 2, 3, 4 and 5 years, respectively; weight-for-age z-scores were missing for 2, 0, 1 and 4 children at ages 2, 3, 4 and 5 years, respectively; height-for-age z-scores were missing for 12, 2, 9 and 12 children at ages 2, 3, 4 and 5 years, respectively; weight-for-height z-scores were missing for 16, 4, 11 and 184<sup>c</sup> children at ages 2, 3, 4 and 5 years, respectively.</p>a<p>The effect of quarterly albendazole on asymptomatic malaria parasitaemia changed with time (interaction p = 0.02), therefore the overall effect of the intervention on this outcome is not presented.</p>b<p>Haemoglobin was not measured for four-year olds from 22<sup>nd</sup> January 2009 onwards due to budget constraints.</p>c<p>Weight-for-height z-scores could not be calculated using WHO Anthro software for children who were aged >5 years and 1 month.</p
<p>cCFP: crude culture filtrate proteins of <i>Mycobacterium tuberculosis</i>.&... more <p>cCFP: crude culture filtrate proteins of <i>Mycobacterium tuberculosis</i>.</p>a<p>geometric mean of response concentration +1;</p>b<p>bias-corrected accelerated confidence intervals computed by bootstrapping.</p
<p>Kaplan-Meier survival estimates for time to first (or only episode) of eczema (a) compar... more <p>Kaplan-Meier survival estimates for time to first (or only episode) of eczema (a) comparing children whose mothers received albendazole during pregnancy with those whose mothers received albendazole-placebo (b) comparing children whose mothers received praziquantel during pregnancy with those whose mothers received praziquantel-placebo. Numbers shown in the tables are number of events (in brackets) and number of children at risk.</p
<p>The effect of maternal anthelminthic treatment on childhood disease incidence by materna... more <p>The effect of maternal anthelminthic treatment on childhood disease incidence by maternal helminth status (from birth to 5 years).</p
We are also grateful to the help provided by Andrew Balyeku in geo-coding health facilities in Ju... more We are also grateful to the help provided by Andrew Balyeku in geo-coding health facilities in July 2013, Didas Namanya of the ministry of health, planning department for help with administrative unit information, the WHO country office-mTRAC project for parts of the health facility inventory, and Catherine Linard for assistance on modelling human population settlement. We are grateful to the technical leadership of the Uganda Ministry of Health for agreeing to sign the MoU that facilitated this collaborative work. We acknowledge in particular all those who have generously provided unpublished data, helped locate information or the geo-coordinates of data necessary to complete the analysis of malaria risk across Uganda:
AIDS, 2021
OBJECTIVE To determine the impact of virological control on inflammation and cluster of different... more OBJECTIVE To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. DESIGN Longitudinal cohort study. METHODS In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads, inflammatory biomarkers (C-reactive protein, tumour necrosis factor alpha, interleukin 6 (IL-6), soluble CD14) and (Uganda only) whole blood immunophenotype by flow cytometry in 311 Zimbabwean and Ugandan children followed for median 3.5 years on first-line ART. We classified each viral load measurement as consistent suppression, blip/post-blip, persistent low-level viral load or rebound. We used multi-level models to estimate rates of increase or decrease in laboratory markers, and Poisson regression to estimate the incidence of clinical events. RESULTS Overall, 42% children experienced viral blips, but these had no significant impact on immune ...
mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results... more mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial
The Journal of infectious diseases, Jul 18, 2016
Identifying determinants of morbidity and mortality may help target future interventions for hum... more Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)-infected children. CD4(+) T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART. There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4-11.4 years) and 5.8 years (IQR, 2.3-9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%-9%) and 13% (IQR, 8%-18%), respectiv...
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Papers by macklyn kihembo