NRU :: Browsing by Author "Webb, Emily L."

Browsing by Author "Webb, Emily L."

Now showing 1 - 20 of 23

Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomized-controlled trial results
(Pediatric Allergy and Immunology, 2011) Mpairwe, Harriet; Webb, Emily L.; Muhangi, Lawrence; Ndibazza, Juliet; Akishule, Denise; Nampijja, Margaret; Ngom-wegi, Sophy; Tumusime, Josephine; Jones, Frances M.; Fitzsimmons, Colin; Dunne, David W.; Muwanga, Moses; Rodrigues, Laura C.; Elliott, Alison M.
Allergy is commoner in developed than in developing countries. Chronic worm infections show inverse associations with allergy, and prenatal exposures may be critical to allergy risk. To determine whether anthelminthic treatment during pregnancy increases the risk of allergy in infancy. A randomized, double-blind, placebo-controlled trial on treatment in pregnancy with albendazole versus placebo and praziquantel versus placebo was conducted in Uganda, with a 2 · 2 factorial design; 2507 women were enrolled; infants’ allergy events were recorded prospectively. The main outcome was doctor-diagnosed infantile eczema.
Assessing the external validity of a randomized controlled trial of anthelminthic in mothers and their children in Entebbe, Uganda
(Trials, 2014) Millard, James D.; Muhangi, Lawrence; Sewankambo, Moses; Ndibazza, Juliet; Elliott, Alison M.; Webb, Emily L.
The ‘external validity’ of randomized controlled trials is an important measure of quality, but is often not formally assessed. Trials concerning mass drug administration for helminth control are likely to guide public health policy and careful interpretation of their context is needed. We aimed to determine how representative participants in one such trial were of their community. We explore implications for trial interpretation and resulting public health recommendations. The trial assessed was the Entebbe Mother and Baby Study (EMaBS), a trial of anthelminthic treatment during pregnancy and early childhood. In a novel approach for assessing external validity, we conducted a two-stage cluster sample community survey within the trial catchment area and compared characteristics of potentially-eligible community children with characteristics of children participating in the trial.
Associations Between Maternal Helminth and Malaria Infections in Pregnancy and Clinical Malaria in the Offspring: A Birth Cohort in Entebbe, Uganda
(The Journal of infectious diseases, 2013) Ndibazza, Juliet; Webb, Emily L.; Lule, Swaib; Mpairwe, Harriet; Akello, Miriam; Oduru, Gloria; Kizza, Moses; Akurut, Helen; Muhangi, Lawrence; Magnussen, Pascal; Vennervald, Birggite; Elliott, Alison
Background. Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood. Methods. In a birth cohort of 2345 mother–child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring. Results. Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10–1.41; aHR, 1.20, 95% CI, 1.05–1.38, respectively). S. mansoni infection had no consistent association with childhood malaria. Conclusions. This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.
BCG-Induced Non-specific Effects on Heterologous Infectious Disease in Ugandan Neonates: an Investigator-blind Randomised Controlled trial
(The Lancet Infectious Diseases, 2021) Prentice, Sarah; Nassanga, Beatrice; Webb, Emily L.; Akello, Florence; Kiwudhu, Fred; Akurut, Hellen; Elliott, Alison M.; Cose, Stephen
Trials done in infants with low birthweight in west Africa suggest that BCG vaccination reduces all-cause mortality in the neonatal period, probably because of heterologous protection against non-tuberculous infections. This study investigated whether BCG alters all-cause infectious disease morbidity in healthy infants in a different high-mortality setting, and explored whether the changes are mediated via trained innate immunity. This was an investigator-blind, randomised, controlled trial done at one hospital in Entebbe, Uganda. Infants who were born unwell (ie, those who were not well enough to be discharged directly home from the labour ward because they required medical intervention), with major congenital malformations, to mothers with HIV, into families with known or suspected tuberculosis, or for whom cord blood samples could not be taken, were excluded from the study. Any other infant well enough to be discharged directly from the labour ward was eligible for inclusion, with no limitation on gestational age or birthweight. Participants were recruited at birth and randomly assigned (1:1) to receive standard dose BCG 1331 (BCG-Danish) on the day of birth or at age 6 weeks (computer-generated randomisation, block sizes of 24, stratified by sex). Investigators and clinicians were masked to group assignment; parents were not masked. Participants were clinically followed up to age 10 weeks and contributed blood samples to one of three immunological substudies. The primary clinical outcome was physician-diagnosed non-tuberculous infectious disease incidence. Primary immunological outcomes were histone trimethylation at the promoter region of TNF, IL6, and IL1B; ex-vivo production of TNF, IL-6, IL-1β, IL-10, and IFNγ after heterologous stimulation; and transferrin saturation and hepcidin levels. All outcomes were analysed in the modified intention-to-treat population of all randomly assigned participants except those whose for whom consent was withdrawn. This trial is registered with the International Standard Randomised Controlled Trial Number registry (#59683017). Between Sept 25, 2014, and July 31, 2015, 560 participants were enrolled and randomly assigned to receive BCG at birth (n=280) or age 6 weeks (n=280). 12 participants assigned to receive BCG at birth and 11 participants assigned to receive BCG at age 6 weeks were withdrawn from the study by their parents shortly after randomisation and were not included in analyses. During the first 6 weeks of life before the infants in the delayed vaccination group received BCG vaccination, physician-diagnosed non-tuberculous infectious disease incidence was lower in infants in the BCG at birth group than in the delayed group (98 presentations in the BCG at birth group vs 129 in the delayed BCG group; hazard ratio [HR] 0·71 [95% CI 0·53–0·95], p=0·023). After BCG in the delayed group (ie, during the age 6–10 weeks follow-up), there was no significant difference in non-tuberculous infectious disease incidence between the groups (88 presentations vs 76 presentations; HR 1·10 [0·87–1·40], p=0·62). BCG at birth inhibited the increase in histone trimethylation at the TNF promoter in peripheral blood mononuclear cells occurring in the first 6 weeks of life. H3K4me3 geometric mean fold-increases were 3·1 times lower at the TNF promoter (p=0·018), 2·5 times lower at the IL6 promoter (p=0·20), and 3·1 times lower at the IL1B promoter (p=0·082) and H3K9me3 geometric mean fold-increases were 8·9 times lower at the TNF promoter (p=0·0046), 1·2 times lower at the IL6 promoter (p=0·75), and 4·6 times lower at the IL1B promoter (p=0·068), in BCG-vaccinated (BCG at birth group) versus BCG-naive (delayed BCG group) infants. No clear effect of BCG on ex-vivo production of TNF, IL-6, IL-1β, IL-10, and IFNγ after heterologous stimulation, or transferrin saturation and hepcidin concentration, was detected (geometric mean ratios between 0·68 and 1·68; p≥0·038 for all comparisons). BCG vaccination protects against non-tuberculous infectious disease during the neonatal period, in addition to having tuberculosis-specific effects. Prioritisation of BCG on the first day of life in high-mortality settings might have significant public-health benefits through reductions in all-cause infectious morbidity and mortality.
Contrasting Impact of Rural, Versus Urban, Living on Glucose Metabolism and Blood Pressure in Uganda
(Wellcome open research, 2020) Sanya, Richard E.; Biraro, Irene Andia; Nampijja, Margaret; Zziwa, Christopher; Nanyunja, Carol; Nsubuga, Denis; Kiwanuka, Samuel; Tumusiime, Josephine; Walusimbi, Bridgious; Cose, Stephen; Ocama, Ponsiano; Grencis, Richard K.; Elliott, Alison M.; Webb, Emily L.
The burden of cardiometabolic diseases, including cardiovascular diseases and diabetes, is increasing in sub-Saharan Africa and this has been linked to urbanisation. Helminths, through their immunomodulatory properties, may protect against these disorders. We hypothesised that the rural environment protects against cardiometabolic diseases and that helminths may influence rural-urban disparity of cardiometabolic disease risk.We compared metabolic parameters of individuals aged ≥10 years living in rural, high-helminth-transmission and urban, lower-helminth-transmission settings in Uganda. Cross-sectional surveys were conducted in rural Lake Victoria island fishing communities and in urban sub-wards in Entebbe municipality. Helminth infection and outcomes, including insulin resistance (computed using the homeostatic model assessment of insulin resistance [HOMA-IR]), fasting blood glucose, fasting blood lipids, blood pressure, body mass index (BMI), waist and hip circumference, were assessed.We analysed 1,898 rural and 930 urban participants. Adjusting for BMI, exercise, smoking, alcohol intake, age and sex, urban residents had lower mean fasting glucose (adjusted mean difference [95%CI] 0.18 [-0.32, -0.05] p=0.01) and HOMA-IR (-0.26 [-0.40, -0.11] p=0.001) but higher blood pressure (systolic, 5.45 [3.75, 7.15] p<0.001; diastolic, 1.93 [0.57, 3.29] p=0.006). Current helminth infection did not explain the observed differences.In the Ugandan context, living in rural fishing communities may protect against hypertension but worsen glucose metabolism.
The Effect of Helminth Infections and Their Treatment on Metabolic Outcomes: Results of a Cluster-Randomized Trial
(Clinical infectious diseases, 2020) Sanya, Richard E.; Webb, Emily L.; Zziwa, Christopher; Kizindo, Robert; Sewankambo, Moses; Tumusiime, Josephine; Nakazibwe, Esther; Oduru, Gloria; Niwagaba, Emmanuel; Nakawungu, Prossy Kabuubi; Kabagenyi, Joyce; Nassuuna, Jacent; Walusimbi, Bridgious; Andia-Biraro, Irene; Elliot, Alison M.
Helminths may protect against cardiometabolic risk through effects on inflammation and metabolism; their treatment may be detrimental to metabolic outcomes. In a cluster-randomized trial in 26 Ugandan fishing communities we investigated effects of community-wide intensive (quarterly single-dose praziquantel, triple-dose albendazole) vs standard (annual single-dose praziquantel, biannual single-dose albendazole) anthelminthic treatment on metabolic outcomes, and observational associations between helminths and metabolic outcomes. The primary outcome, homeostatic model assessment of insulin resistance (HOMA-IR), and secondary outcomes (including blood pressure, fasting blood glucose, lipids) were assessed after 4 years' intervention among individuals aged ≥10 years. We analyzed 1898 participants. Intensive treatment had no effect on HOMA-IR (adjusted geometric mean ratio, 0.96 [95% confidence interval {CI}, .86–1.07]; P = .42) but resulted in higher mean low-density lipoprotein cholesterol (LDL-c) (2.86 vs 2.60 mmol/L; adjusted mean difference, 0.26 [95% CI, −.03 to .56]; P = .08). Lower LDL-c levels were associated with Schistosoma mansoni (2.37 vs 2.80 mmol/L; −0.25 [95% CI, −.49 to −.02]; P = .04) or Strongyloides (2.34 vs 2.69 mmol/L; −0.32 [95% CI, −.53 to −.12]; P = .003) infection. Schistosoma mansoni was associated with lower total cholesterol (4.24 vs 4.64 mmol/L; −0.25 [95% CI, −.44 to −.07]; P = .01) and moderate to heavy S. mansoni infection with lower triglycerides, LDL-c, and diastolic blood pressure. Helminth infections improve lipid profiles and may lower blood pressure. Studies to confirm causality and investigate mechanisms may contribute to understanding the epidemiological transition and suggest new approaches to prevent cardiometabolic disease.
Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled tria
(The Lancet, 2011) Webb, Emily L.; Mawa, Patrice A; Ndibazza, Juliet; Kizito, Dennison; Nanteza, Bridget; Nampijja, Margaret; Muhangi, Lawrence
Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections. In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447.
Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial
(The Lancet,, 2011) Webb, Emily L.; Mawa, Patrice A.; Ndibazza, Juliet; Kizito, Dennison; Namatovu, Alice; Kyosiimire-Lugemwa, Jacqueline; Nanteza, Bridget; Nampijja, Margaret; Muhangi, Lawrence; Woodburn, Patrick W; Akurut, Hellen; Mpairwe, Harriet; Akello, Miriam; Lyadda, Nancy; Bukusuba, Joseph; Kihembo, Macklyn; Kizza, Moses; Kizindo, Robert; Nabulime, Juliet; Ameke, Christine; Namujju, Proscovia B.; Tweyongyere, Robert; Muwanga, Moses; Whitworth, James A. G.; Elliott, Alison M.
Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections.In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447.Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30–0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34–0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3–43·7), of diarrhoea was 134·1 (129·2–139·2), and of pneumonia was 22·3 (20·4–24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79–1.14], diarrhoea [1·06, 0·96–1·16], pneumonia [1·11, 0·90–1·38]) or praziquantel treatment (malaria [1·00, 0·84–1·20], diarrhoea [1·07, 0·98–1·18], pneumonia [1·00, 0·80–1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35–1·42) or praziquantel (0·60, 0·29–1·23) treatment.These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed.
Effects of Maternal and Infant Co-infections, and of Maternal Immunization, on the Infant Response to BCG and Tetanus Immunization
(Vaccine, 2010) Kizzaa, Moses; Elliott, Alison M.; Mawa, Patrice A.; Webb, Emily L.; Nampijja, Margaret; Lyadd, Nancy; Bukusuba, Joseph; Kizzaa, Moses; Namujju, Proscovia B.; Nabulime, Juliet; Ndibazza, Juliet; Muwanga, Moses; Whitworth, James A. G.
Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigated factors that might influence responses to BCG and tetanus immunisation. Whole blood assay responses to crude culture filtrate proteins of Mycobacterium tuberculosis (cCFP)) and tetanus toxoid (TT) were examined among 1506 and 1433 one-year-olds, respectively. Maternal Mansonella perstans infection was associated with higher interleukin (IL)-10 responses to both immunogens but no reduction in gamma interferon (IFN- ), IL-5 and IL-13 responses; other maternal helminth infections showed little effect. Tetanus immunization during pregnancy was associated with higher infant responses to TT; maternal BCG scar (from past immunization) with lower infant IL-5 and IL-13 responses to cCFP. IFN- , IL-5 and IL-13 to TT were reduced in HIV-exposed-uninfected infants; infant malaria and HIV were associated with lower IFN- , IL-5 and IL-13 responses to both immunogens. We conclude that maternal helminth infections are unlikely to explain poor vaccine efficacy in the tropics. Effects of maternal immunization on infant responses to vaccines should be explored. Prevention of infant malaria and HIV could contribute to effectiveness of immunization programmes.
Factors affecting the infant antibody response to measles immunisation in Entebbe-Uganda
(BMC public health,, 2013) Kizito, Dennison; Tweyongyere, Robert; Namatovu, Alice; Webb, Emily L.; Muhangi, Lawrence; Lule, Swaib A.; Bukenya, Henry; Cose, Stephen; Elliott, Alison M.
Background: Vaccine failure is an important concern in the tropics with many contributing elements. Among them, it has been suggested that exposure to natural infections might contribute to vaccine failure and recurrent disease outbreaks. We tested this hypothesis by examining the influence of co-infections on maternal and infant measles-specific IgG levels. Methods: We conducted an observational analysis using samples and data that had been collected during a larger randomised controlled trial, the Entebbe Mother and Baby Study (ISRCTN32849447). For the present study, 711 pregnant women and their offspring were considered. Helminth infections including hookworm, Schistosoma mansoni and Mansonella perstans, along with HIV, malaria, and other potential confounding factors were determined in mothers during pregnancy and in their infants at age one year. Infants received their measles immunisation at age nine months. Levels of total IgG against measles were measured in mothers during pregnancy and at delivery, as well as in cord blood and from infants at age one year. Results: Among the 711 pregnant women studied, 66% had at least one helminth infection at enrolment, 41% had hookworm, 20% M. perstans and 19% S. mansoni. Asymptomatic malaria and HIV prevalence was 8% and 10% respectively. At enrolment, 96% of the women had measles-specific IgG levels considered protective (median 4274 mIU/ml (IQR 1784, 7767)). IgG levels in cord blood were positively correlated to maternal measles-specific IgG levels at delivery (r = 0.81, p < 0.0001). Among the infants at one year of age, median measles-specific IgG levels were markedly lower than in maternal and cord blood (median 370 mIU/ml (IQR 198, 656) p < 0.0001). In addition, only 75% of the infants had measles-specific IgG levels considered to be protective. In a multivariate regression analysis, factors associated with reduced measles-specific antibody levels in infancy were maternal malaria infection, infant malaria parasitaemia, infant HIV and infant wasting. There was no association with maternal helminth infection. Conclusion: Malaria and HIV infection in mothers during pregnancy, and in their infants, along with infant malnutrition, may result in reduction of the antibody response to measles immunisation in infancy. This re-emphasises the importance of malaria and HIV control, and support for infant nutrition, as these interventions may have benefits for vaccine efficacy in tropical settings.
Impact of Anthelminthic Treatment in Pregnancy and Childhood on Immunisations, Infections and Eczema in Childhood: A Randomised Controlled Trial
(PloS one, 2012) Ndibazza, Juliet; Mpairwe, Harriet; Webb, Emily L.; Mawa, Patrice A.; Nampijja, Margaret; Muhangi, Lawrence; Kihembo, Macklyn; Lule, Swaib A.; Rutebarika, Diana; Apule, Barbara; Akello, Florence; Akurut, Hellen; Oduru, Gloria; Naniima, Peter; Kizito, Dennison; Kizza, Moses; Kizindo, Robert; Tweyongere, Robert; Alcock, Katherine J.; Muwanga, Moses; Alison M., Elliott
Helminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects. A randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly singledose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15–2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73–0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome. Routine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic. Given the low helminth prevalence in our children, the effect of albendazole on malaria is likely to be direct.
The Impact of Intensive Versus Standard Anthelminthic Treatment on Allergy-related Outcomes, Helminth Infection Intensity, and Helminth-related Morbidity in Lake Victoria Fishing Communities, Uganda: Results From the LaVIISWA Cluster-randomized Trial
(Clinical infectious diseases, 2019) Sanya, Richard E.; Nkurunungi, Gyaviira; Hoek Spaans, Remy; Nampijja, Margaret; O’Hara, Geraldine; Kizindo, Robert; Oduru, Gloria; Kabuubi Nakawungu, Prossy; Niwagaba, Emmanuel; Abayo, Elson; Kabagenyi, Joyce; Zziwa, Christopher; Tumusiime, Josephine; Nakazibwe, Esther; Kaweesa, James; Muwonge Kakooza, Fred; Akello, Mirriam; Lubyayi, Lawrence; Verweij, Jaco; Nash, Stephen; Ree, Ronald van; Mpairwe, Harriet; Tukahebwa, Edridah; Webb, Emily L.; Elliott, Alison M.
The prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity. Methods. In an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly. Results. The outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio [RR] 1.11, 95% confidence interval [CI] 0.64–1.93), SPT (RR 1.10, 95% CI 0.85–1.42), or asIgE (RR 0.96, 95% CI 0.82–1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55–0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31–1.00). There were no differences in anemia or hepatospenomegaly between trial arms. Conclusions. Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy- related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis- transmission fishing communities, in the absence of other interventions.
The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette–Gue´rin immunization
(Philosophical Transactions of the Royal Society B: Biological Sciences, 2015) Mawa, Patrice A.; Nkurunungi, Gyaviira; Egesa, Moses; Webb, Emily L.; Smith, Steven G.; Kizindo, Robert; Akello, Mirriam; Lule, Swaib A.; Muwanga, Moses; Dockrell, Hazel M.; Cose, Stephen; Elliott, Alison M.
Bacille Calmette–Gue´rin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n ¼ 53) and cellular (n ¼ 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml21 [3300–11 050] in cord blood) and sixweeks (0.00 ng ml21 [0–288]). Frequencies of PPD-specific IFN-g-expressing CD4þT cells increased at one week and declined between one and six weeks ( p ¼ 0.031). Frequencies of IL-2- and TNF-a-expressing PPD-specific CD4þT cells increased between one and six weeks ( p ¼ 0.019, p ¼ 0.009, respectively). At one week, the frequency of PPD-specific CD4þT cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses ( p ¼ 0.002) and after adjusting for confounders (mean difference, 95% CI 20.041% (20.082, 20.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCGimmunization. These findings are being explored further in a larger study.
The Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA): Study Protocol for a Randomised Controlled Trial
(Trials, 2015) Nampijja, Margaret; Webb, Emily L.; Kaweesa, James; Kizindo, Robert; Namutebi, Milly; Nakazibwe, Esther; Oduru, Gloria; Kabuubi, Prossy; Kabagenyi, Joyce; Kizito, Dennison; Muhangi, Lawrence; Akello, Mirriam; Verweij, Jaco J.; Nerima, Barbara; Tukahebwa, Edridah; Elliott, Alison M.
The Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes.
Maternal HIV infection and other factors associated with growth outcomes of HIV-uninfected infants in Entebbe, Uganda
(Public health nutrition, 2013) Muhangi, Lawrence; Lule, Swaib A.; Mpairwe, Harriet; Ndibazza, Juliet; Kizza, Moses; Nampijja, Margaret; Nakazibwe, Esther; Kihembo, Macklyn; Elliott, Alison M.; Webb, Emily L.
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. 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-for-age 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% and3?9%, respectively. There was evidence for an association between maternal HIV infection and odds of being underweight (adjusted OR52?32; 95% CI 1?32, 4?09; P50?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.
Maternal hookworm modifies risk factors for childhood eczema: results from a birth cohort in Uganda
(Pediatric Allergy and Immunology, 2014) Mpairwe, Harriet; Ndibazza, Juliet; Webb, Emily L.; Nampijja, Margaret; Muhangi, Lawrence; Apule, Barbara; Akurut, Hellen; Kizito, Dennison; Kakande, Mohammed; Jones, Frances M.; Fitzsimmons, Colin M.; Muwanga, Moses; Rodrigues, Laura C.; Dunne, David W.; Elliott, Alison M.
Worms may protect against allergy. Early-life worm exposure may be critical, but this has not been fully investigated. Objectives: To investigate whether worms in pregnancy and in early childhood are associated with childhood eczema incidence. The Entebbe Mother and Baby Study, an anthelminthic treatment trial, enrolled pregnant women between 2003 and 2005 in Uganda. Mothers were investigated for worms during pregnancy and children annually. Eczema was doctor-diagnosed from birth to age five years. A planned observational analysis was conducted within the trial cohort to investigate associations between worms and eczema. Data for 2345 live-born children were analysed. Hookworm was the most prevalent maternal worm (45%). Childhood worms were less prevalent. Eczema incidence was 4.68/100 person-years. Maternal hookworm was associated with reduced eczema incidence [adjusted hazard ratio (95% confidence interval), p-value: 0.71(0.51–0.99), 0.04] and modified effects of known risk factors for eczema: Dermatophagoides-specific IgE in children was positively associated with eczema incidence if the mother had no hookworm [2.72(1.11–6.63), 0.03], but not if the mother had hookworm [0.41(0.10–1.69), 0.22], interaction p-value = 0.03. Similar interactions were seen for maternal history of eczema {[2.87(1.31–6.27, 0.008) vs. [0.73(0.23–2.30), 0.60], interaction p-value = 0.05}, female gender {[1.82(1.22–2.73), 0.004 vs. [0.96 (0.60–1.53), 0.87], interaction p-value = 0.04} and allergen-specific IgE. Childhood Trichuris trichiura and hookworm were inversely associated with eczema. Maternal hookworm modifies effects of known risk factors for eczema. Mechanisms by which early-life worm exposures influence allergy need investigation. Worms or worm products, and intervention during pregnancy have potential for primary prevention of allergy.
Maternal Recall of Birthweight and Birth Size in Entebbe, Uganda
(Tropical medicine & international health, 2012) Lule, Swaib A.; Webb, Emily L.; Ndibazza, Juliet; Nampijja, Margaret; Muhangi, Lawrence; Akello, Florence; Kakande, Muhammed; Kizindo, Robert; Elliott, Alison M.
To assess the reliability of maternally recalled birthweight and size in Entebbe, Uganda. 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. 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 0.1 kg of the recorded weight. On average, mothers overestimated birthweight by 0.06 kg (95% CI: 0.00–0.13 kg, P = 0.04). Recalled and recorded birthweights showed moderate agreement with an intraclass correlation coefficient of 0.64. Four hundred 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. 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.
Parasite infection is associated with Kaposi’s sarcoma associated herpesvirus (KSHV) in Ugandan women
(Infectious Agents and Cancer, 2011) Wakeham, Katie; Webb, Emily L.; Sebina, Ismail; Muhangi, Lawrence; Miley, Wendell; Johnson, W. Thomas; Ndibazza, Juliet; Elliott, Alison M.; Whitby, Denise; Newton, Robert
Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods) and antibodies against Kaposi’s sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001[trend]). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education. Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.
Profiles of Inflammatory Markers and their Association With Cardiometabolic Parameters in Rural and Urban Uganda
(Wellcome Open Research, 2021) Sanya, Richard E.; Nalwoga, Angela; Grencis, Richard K.; Elliott, Alison M.; Webb, Emily L.; Biraro, Irene Andia
Inflammation may be one of the pathways explaining differences in cardiometabolic risk between urban and rural residents. We investigated associations of inflammatory markers with rural versus urban residence, and with selected cardiometabolic parameters previously observed to differ between rural and urban residents: homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), blood pressure (BP) and body mass index (BMI).From two community surveys conducted in Uganda, 313 healthy individuals aged ≥ 10 years were selected by age- and sex-stratified random sampling (rural Lake Victoria island communities, 212; urban Entebbe municipality, 101). Fluorescence intensities of plasma cytokines and chemokines were measured using a bead-based multiplex immunoassay. We used linear regression to examine associations between the analytes and rural-urban residence and principal component analysis (PCA) to further investigate patterns in the relationships. Correlations between analytes and metabolic parameters were assessed using Pearson’s correlation coefficient.The urban setting had higher mean levels of IL-5 (3.27 vs 3.14, adjusted mean difference [95% confidence interval] 0.12[0.01,0.23] p=0.04), IFN-⍺ (26.80 vs 20.52, 6.30[2.18,10.41] p=0.003), EGF (5.67 vs 5.07, 0.60[0.32,0.98] p<0.00001), VEGF (3.68 vs 3.28, 0.40[0.25,0.56] p<0.00001), CD40 Ligand (4.82 vs 4.51, 0.31[0.12, 0.50] p=0.001) and Serpin-E1 (9.57 vs 9.46, 0.11[0.05,0.17] p<0.00001), but lower levels of GMCSF (2.94 vs 3.05, -0.10[-0.19,-0.02] p=0.02), CCL2 (2.82 vs 3.10, -0.45[-0.70,-0.21] p<0.00001) and CXCL10 (5.48 vs 5.96, -0.49[-0.71,-0.27] p<0.00001), compared to the rural setting. In PCA, the urban setting had lower representation of some classical inflammatory mediators but higher representation of various chemoattractants and vasoactive peptides. HOMA-IR, FBG, BP and BMI were positively correlated with several principal components characterised by pro-inflammatory analytes.In developing countries, immunological profiles differ between rural and urban environments. Differential expression of certain pro-inflammatory mediators may have important health consequences including contributing to increased cardiometabolic risk observed in the urban environment.
Risk Factors for Seropositivity to Kaposi Sarcoma–Associated Herpesvirus Among Children in Uganda
(Journal of acquired immune deficiency syndromes, 2013) Wakeham, Katie; Webb, Emily L.; Sebina, Ismail; Nalwoga, Angela; Muhangi, Lawrence; Miley, Wendell; Johnston, W. Thomas; Ndibazza, Juliet; Whitby, Denise; Newton, Robert; Elliott, Alison M.
Determinants of Kaposi sarcoma–associated herpesvirus (KSHV) seropositivity among children living in sub-Saharan African populations where infection is endemic are not well understood. Local environmental factors, including other infectious agents, may be key. Within the context of a well-characterized birth cohort, we examined associations between various factors and antibodies against KSHV, measured in stored plasma samples from 1823 mother–child pairs in Entebbe, Uganda.

Browsing by Author "Webb, Emily L."

Results Per Page

Sort Options