Browsing by Author "Ndibazza, Juliet"
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Item 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.Item 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.Item Association between malaria exposure and Kaposi’s sarcoma-associated herpes virus seropositivity in Uganda(Tropical medicine & international health, 2015) Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Miley, Wendell; Ndibazza, Juliet; Drakeley, Christopher; Elliott, Alison; Whitby, Denise; Newton, RobertUnlike other herpes viruses, Kaposi’s sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparumapical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. results Kaposi’s sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP- 1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti- ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. conclusion The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation.Item 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, AlisonBackground. 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.Item A Description of Congenital Anomalies Among Infants in Entebbe, Uganda(Clinical and Molecular Teratology,, 2011) Ndibazza, Juliet; Lule, Swaib; Nampijja, Margaret; Mpairwe, Harriet; Oduru, Gloria; Kiggundu, Molly; Akello, Miriam; Muhangi, Lawrence; Elliott, Alison M.Data on congenital anomalies from developing countries of the sub-Saharan region are scarce. However, it is important to have comprehensive and reliable data on the description and prevalence of congenital anomalies to allow surveillance and the implementation of appropriate public health strategies for prevention and management. In this study, we describe the profile of congenital anomalies seen in a birth cohort in Entebbe, Uganda. Congenital anomalies were defined as any structural defect present at birth. Pregnant women were recruited to the cohort between 2003 and 2005. Defects present at birth were recorded by the midwife at delivery and by physicians at the routine six-week postnatal visit and at illness-related visits until 1 year of life. The anomalies were classified by organ system according to the 10th version of the World Health Organization International Classification of Diseases (ICD-10). RESULTS: There were 180 infants with a congenital anomaly among 2365 births. The most commonly affected systems were the musculoskeletal (42.7 per 1000 births) and skin (16.1 per 1000 births). The prevalence of major anomalies was 20.3 per 1000 births; 1.7 per 1000 births for cardiac anomalies and 1.3 per 1000 births for neural system anomalies. Forty (22%) of the congenital anomalies were identified at birth, 131 (73%) at the 6- week postnatal visit, and nine (5%) at illness-related visits. Congenital anomalies are common in developing countries. Establishment of comprehensive databases for surveillance would be helpful for surveillance of effects of new exposures, for prevention, management, and health care planning. Birth Defects Research (Part A) 91:857–861, 2011. 2011 Wiley-Liss, Inc.Item Effect of Praziquantel Treatment during Pregnancy on Cytokine Responses to Schistosome Antigens: Results of a Randomized, Placebo-Controlled Trial(The Journal of infectious diseases, 2008) Tweyongyere, Robert; Mawa, Patrice A.; Ngom-wegi, Sophy; Ndibazza, Juliet; Duong, Trinh; Vennervald, Birgitte J.; Dunne, David W.; Katunguka-Rwakishaya, Eli; Elliott, Alison M.Praziquantel treatment of schistosomiasis boosts antischistosome responses, with type 2 helper T cell bias that may contribute to immunologically mediated killing and to protection against reinfection. Praziquantel treatment during pregnancy was recommended in 2002, but the immunological effects of the treatment had not been investigated.A cohort of 387 Schistosoma mansoni-infected women were recruited from a larger trial of deworming during pregnancy. Women were randomized to receive either praziquantel or placebo during pregnancy. Six weeks after delivery, all women received praziquantel. Cytokine responses to S. mansoni worm and egg antigens were measured in whole blood culture before and 6 weeks after each treatment.Schistosome-specific cytokine responses were suppressed during pregnancy. Praziquantel treatment during pregnancy caused significant boosts in interferon-γ (IFN-γ), interleukin (IL)-2, IL-4, IL-5, IL-13, and IL-10 responses to schistosome worm antigen and in IFN-γ, IL-5, and IL-13 responses to schistosome egg antigen, but these boosts were not as substantial as those seen for women treated after delivery.Pregnancy suppresses a potentially beneficial boost in cytokine responses associated with praziquantel treatment. Further studies are needed on the long-term effects that treatment of schistosomiasis during pregnancy have on morbidity and resistance to reinfection among treated women and their offspring.Item 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, LawrenceHelminth 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.Item 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.Item Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunization and on susceptibility to infectious diseases in infancy: a randomized, 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 MHelminth infections aff ect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections aff ects development of an infant’s immune response to immunisations and unrelated infections. Methods 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 computergenerated 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. Findings 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 aff ected 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 eff ect 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.Item 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.Item Helminth Infection During Pregnancy and Development of Infantile Eczema(American Medical Association, 2005) Elliott, Alison M.; Mpairwe, Harriet; Quigley, Maria A.; Nampijja, Margaret; Muhangi, Lawrence; Oweka-Onyee, James; Muwanga, Moses; Ndibazza, Juliet; Whitworth, James A. G.The burden of atopic and inflammatory disease is escalating in developed countries, in inverse relation to infectious diseases.1 Mechanisms by which exposure to infections may promote balanced immunological development are being explored2 and trials of therapeutic helminth parasites have been initiated for asthma and inflammatory bowel disease.3,4 In developing countries, advocacy for deworming is increasing, and treatment with anthelmintics targeting hookworm anemia is recommended after the first trimester of pregnancy.5-7 During a trial8 to determine the effects of deworming during pregnancy on immune responses and infectious disease incidence in infants, we noted an unexpectedly high incidence of infantile eczema. Therefore, we examined associations between maternal helminth parasites and deworming and infantile eczema.Item 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., ElliottHelminth 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.Item The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447](Clinical trials, 2007) Elliotta, Alison M.; Kizza, Moses; Quigley, Maria A.; Ndibazza, Juliet; Nampijja, Margaret; Muhangi, Lawrence; Morison, Linda; Namujju, Proscovia B.; Muwanga, Moses; Kabatereine, Narcis; Whitworth, James A. G.Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects “spill-over”, altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life. Purpose To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood.Item 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.Item 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.Item 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.Item 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, RobertImmune 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.Item Participation in Clinical Research Could Modify Background Risk for Trial Outcome Measures(AIDS Research and Human Retroviruses, 2014) Abaasa, Andrew M.; Asiki, Gershim; Levin, Jonathan; Bahemuka, Ubaldo; Ruzagira, Eugene; Kibengo, Freddie M.; Mulondo, Jerry; Ndibazza, Juliet; Price, Matthew A.; Fast, Pat; Kamali, AnatoliData on HIV incidence and retention are needed to inform study design of efficacy trials. However, the selection criteria and interventions during an actual clinical trial could reduce HIV incidence and thus affect the statistical power. We investigated the effect of inclusion and participation in a simulated vaccine efficacy trial (SiVET) on HIV and pregnancy incidence in a fisherfolk cohort in SW Uganda.Item Risk Factors for Helminth, Malaria, and HIV Infection in Pregnancy in Entebbe, Uganda(PLoS Negl Trop Dis, 2009) Woodburn, Patrick William; Muhangi, Lawrence; Hillier, Stephen; Ndibazza, Juliet; Bazanya Namujju, Proscovia; Kizza, Moses; Ameke, Christine; Emojong Omoding, Nicolas; Booth, Mark; Mary Elliott, AlisonInfections during pregnancy may have serious consequences for both mother and baby. Assessment of risk factors for infections informs planning of interventions and analysis of the impact of infections on health outcomes. To describe risk factors for helminths, malaria and HIV in pregnant Ugandan women before intervention in a trial of de-worming in pregnancy. The trial recruited 2,507 pregnant women between April 2003 and November 2005. Participants were interviewed and blood and stool samples obtained; location of residence at enrolment was mapped. Demographic, socioeconomic, behavioral and other risk factors were modelled using logistic regression. There was a high prevalence of helminth, malaria and HIV infection, as previously reported. All helminths and malaria parasitemia were more common in younger women, and education was protective against every infection. Place of birth and/or tribe affected all helminths in a pattern consistent with the geographical distribution of helminth infections in Uganda. Four different geohelminths (hookworm, Trichuris, Ascaris and Trichostrongylus) showed a downwards trend in prevalence during the enrolment period. There was a negative association between hookworm and HIV, and between hookworm and low CD4 count among HIV-positive women. Locally, high prevalence of schistosomiasis and HIV occurred in lakeshore communities. Interventions for helminths, malaria and HIV need to target young women both in and out of school. Antenatal interventions for malaria and HIV infection must continue to be promoted. Women originating from a high risk area for a helminth infection remain at high risk after migration to a lower-risk area, and vice versa, but overall, geohelminths seem to be becoming less common in this population. High risk populations, such as fishing communities, require directed effort against schistosomiasis and HIV infection.Item 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.