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Entebbe, Uganda

Lule S.A.,Medical Research Council Uganda Virus Research Institute | Webb E.L.,London School of Hygiene and Tropical Medicine | Ndibazza J.,Medical Research Council Uganda Virus Research Institute | Nampijja M.,Medical Research Council Uganda Virus Research Institute | And 5 more authors.
Tropical Medicine and International Health | Year: 2012

Objectives To assess the reliability of maternally recalled birthweight and size in Entebbe, Uganda. Methods The study population comprised 404 mothers, who were participants in the Entebbe Mother and Baby Study (EMaBS). Mothers were recruited to EMaBS during antenatal care, maternal characteristics were recorded during pregnancy, and birthweight was recorded at delivery. Four to seven years after delivery, mothers were asked to recall the child's birthweight and size. Their responses were compared with the birthweight recorded in the EMaBS database. Results Of 404 interviewed mothers, 303 (75%) were able to give an estimate of birthweight and for 265 of these EMaBS data on recorded birthweights were available. Women who were educated and whose children had low birth order were more likely to be able to give an estimate: 37 (14%) recalled the exact recorded birthweight; a further 52 (20%) were accurate to within 0.1kg of the recorded weight. On average, mothers overestimated birthweight by 0.06kg (95% CI: 0.00-0.13kg, P=0.04). Recalled and recorded birthweights showed moderate agreement with an intraclass correlation coefficient of 0.64. Four hundered mothers gave an estimate of birth size: the sensitivity and specificity of recalled birth size for classifying low birthweight were 76% (95% CI: 50-93%) and 70% (95% CI: 65-75%), respectively. Conclusions Mothers' recall of birthweight was not precise but in absence of other data, recall of birthweight and size may have some value in epidemiological studies in these settings. © 2012 Blackwell Publishing Ltd. Source

Elliott A.M.,Uganda Virus Research Institute | Elliott A.M.,London School of Hygiene and Tropical Medicine | Ndibazza J.,Uganda Virus Research Institute | Mpairwe H.,Uganda Virus Research Institute | And 6 more authors.
Parasitology | Year: 2011

In 1994 and 2002, respectively, the World Health Organisation proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunisation was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered. Copyright © 2011 Cambridge University Press. Source

Anderson E.J.,Imperial College London | Anderson E.J.,University of Cardiff | Webb E.L.,London School of Hygiene and Tropical Medicine | Mawa P.A.,MRC UVRI Uganda Research Unit on AIDS | And 5 more authors.
Vaccine | Year: 2012

Background: Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses. Methods: Infants from the Entebbe Mother and Baby Study (ISRCTN32849447) who received BCG-Russia, BCG-Bulgaria or BCG-Denmark at birth, were analysed by BCG strain group. At one year, interferon-gamma (IFN-γ), interleukin (IL)-5, IL-13 and IL-10 responses to mycobacteria-specific antigens (crude culture filtrate proteins and antigen 85) and non-mycobacterial stimuli (tetanus toxoid and phytohaemagglutinin) were measured using ELISA. Cytokine responses, scar frequency, BCG associated adverse event frequency and mortality rates were compared across groups, with adjustments for potential confounders. Results: Both specific and non-specific IFN-γ, IL-13 and IL-10 responses in 1341 infants differed between BCG strain groups including in response to stimulation with tetanus toxoid. BCG-Denmark immunised infants showed the highest cytokine responses. The proportion of infants who scarred differed significantly, with BCG scars occurring in 52.2%, 64.1% and 92.6% of infants immunised with BCG Russia, BCG-Bulgaria and BCG-Denmark, respectively (p< 0.001). Scarred infants had higher IFN-γ and IL-13 responses to mycobacterial antigens only than infants without a scar. The BCG-Denmark group had the highest frequency of adverse events (p= 0.025). Mortality differences were not significant. Conclusions: Both specific and non-specific immune responses to the BCG vaccine differ by strain. Scarring after BCG vaccination is also strain-dependent and is associated with higher IFN-γ and IL-13 responses to mycobacterial antigens. The choice of BCG strain may be an important factor and should be evaluated when testing novel vaccine strategies that employ BCG in prime-boost sequences, or as a vector for other vaccine antigens. © 2012 Elsevier Ltd. Source

Webb E.L.,London School of Hygiene and Tropical Medicine | Kyosiimire-Lugemwa J.,Uganda Virus Research Institute | Kizito D.,Uganda Virus Research Institute | Nkurunziza P.,Uganda Virus Research Institute | And 6 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2012

Background: To investigate the effect of helminth infections and their treatment during pregnancy on HIV load, we conducted a 2 × 2 factorial randomized controlled trial of albendazole versus placebo and praziquantel versus placebo in pregnant women in Entebbe, Uganda. Methods: Two hundred sixty-four HIV-infected pregnant women from the Entebbe Mother and Baby Study (ISRCTN 32849447) were included in this analysis. Women were tested for helminth infections at enrollment, and mean HIV load was compared between infected and uninfected groups. The effect of anthelmintic treatment on HIV load was evaluated at 6 weeks after treatment and at delivery using linear regression and adjusting for enrollment viral load. Results: Hookworm and Trichuris infections were associated with higher mean viral load at enrollment [adjusted mean difference 0.24 log10 copies/mL, 95% confidence interval (CI): 0.01 to 0.47, P = 0.03, and 0.37 log10 copies/mL, 95% CI: 0.00 to 0.74, P = 0.05, respectively]. There were no associations between viral load and other helminth species. There was some evidence that albendazole reduced viral load at 6 weeks after treatment (adjusted mean difference-0.17, 95% CI:-0.36 to 0.01, P = 0.07); however, this effect did not differ according to mother's hookworm infection status and had diminished at delivery (adjusted mean difference-0.11, 95% CI:-0.28 to 0.07, P = 0.23). There was no effect of praziquantel treatment on HIV load at any time point. Conclusions: Infection with some soil-transmitted helminth species is associated with increased HIV load in pregnancy. Treatment with albendazole causes a small decrease in HIV load; however, this may not represent a direct effect of worm removal. © 2012 Lippincott Williams & Wilkins. Source

Lule S.A.,MRC UVRI Uganda Research Unit on AIDS | Mawa P.A.,MRC UVRI Uganda Research Unit on AIDS | Nkurunungi G.,MRC UVRI Uganda Research Unit on AIDS | Nampijja M.,MRC UVRI Uganda Research Unit on AIDS | And 6 more authors.
Vaccine | Year: 2015

Background: BCG is used widely as the sole licensed vaccine against tuberculosis, but it has variable efficacy and the reasons for this are still unclear. No reliable biomarkers to predict future protection against, or acquisition of, TB infection following immunisation have been identified. Lessons from BCG could be valuable in the development of effective tuberculosis vaccines. Objectives: Within the Entebbe Mother and Baby Study birth cohort in Uganda, infants received BCG at birth. We investigated factors associated with latent tuberculosis infection (LTBI) and with cytokine response to mycobacterial antigen at age five years. We also investigated whether cytokine responses at one year were associated with LTBI at five years of age. Methods: Blood samples from age one and five years were stimulated using crude culture filtrates of Mycobacterium tuberculosis in a six-day whole blood assay. IFN-γ, IL-5, IL-13 and IL-10 production was measured. LTBI at five years was determined using T-SPOT. TB® assay. Associations with LTBI at five years were assessed using multivariable logistic regression. Multiple linear regression with bootstrapping was used to determine factors associated with cytokine responses at age five years. Results: LTBI prevalence was 9% at age five years. Only urban residence and history of TB contact/disease were positively associated with LTBI. BCG vaccine strain, LTBI, HIV infection, asymptomatic malaria, growth z-scores, childhood anthelminthic treatment and maternal BCG scar were associated with cytokine responses at age five. Cytokine responses at one year were not associated with acquisition of LTBI by five years of age. Conclusion: Although multiple factors influenced anti-myocbacterial immune responses at age five, factors likely to be associated with exposure to infectious cases (history of household contact, and urban residence) dominated the risk of LTBI. © 2014 The Authors. Source

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