Browsing by Author "Kizza Moses"

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Associations Between Maternal Helminth and Malaria Infections in Pregnancy and Clinical Malaria in the Offspring: A Birth Cohort in Entebbe, Uganda
(Oxford University Press on behalf of the Infectious Diseases Society of America, 2013) Ndibazza Juliet; Webb Emily L; Lule Swaib; Mpairwe Harriet; Akello Miriam; Oduru Gloria; Kizza Moses; Akurut Helen; Muhangi Lawrence; Magnussen Pascal; Vennervald Birgitte J.; Elliott Alison M
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.
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
(2011) Ndibazza Juliet ; Maw Patrice A. ; Webb Emily L. ; 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. ; Elliot Alison M.
Helminth 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 toimmunisations and unrelated infections.Methods In this randomised, doubleblind, 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.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 interleukin13 (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.Interpretation 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
(2012) Ndibazza Juliet; Muwanga Moses; Whitworth James A. G.; Elliotta Alison M.; Mawaa Patrice A.; Webb Emily L.; Nampijja Margaret; Lyadda Nancy; Bukusuba Joseph; Kizza Moses; Namujju Proscovia B.; Nabulime Juliet
Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigatedfactors that might influence responses to BCG and tetanus immunisation. Whole blood assay responsesto crude culture filtrate proteins ofMycobacterium tuberculosis(cCFP)) and tetanus toxoid (TT) wereexamined among 1506 and 1433 one-year-olds, respectively. MaternalMansonella perstansinfection wasassociated with higher interleukin (IL)-10 responses to both immunogens but no reduction in gammainterferon (IFN-), IL-5 and IL-13 responses; other maternal helminth infections showed little effect.Tetanus immunisation during pregnancy was associated with higher infant responses to TT; maternalBCG scar (from past immunisation) with lower infant IL-5 and IL-13 responses to cCFP. IFN-, IL-5 andIL-13 to TT were reduced in HIVexposed-uninfected infants; infant malaria and HIV were associatedwith lower IFN-, IL-5 and IL13 responses to both immunogens. We conclude that maternal helminthinfections are unlikely to explain poor vaccine efficacy in the tropics. Effects of maternal immunisation oninfant responses to vaccines should be explored. Prevention of infant malaria and HIV could contributeto effectiveness of immunisation programmes.
Impact of Anthelminthic Treatment in Pregnancy and Childhood on Immunisations, Infections and Eczema in Childhood: A Randomised Controlled Trial
(Uganda Martyrs University, 2012) Ndibazza Juliet; Mpairwe Harriet; Webb Emily L.; Mawa Patrice A; Nampijja Margaret; Muhang 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; Elliott Alison M
Background: 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 wherehelminths 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 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]
(Society for Clinical Trials, 2007) Elliott Alison M; Kizza Moses; Quigley Maria A; Ndibazza Juliet; Nampijja Margaret; Muhangi Lawrence; Morison Linda; Namujju Proscovia B; Muwanga Moses; Kabatereine Narcis; Whitworth James AG
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. Methods The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 _ 2(_2) factorial design. Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed. Conclusion This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy.
Risk Factors for Helminth, Malaria, and HIV Infection in Pregnancy in Entebbe, Uganda
(Uganda Martyrs University, 2009) Ndibazza Juliet; Bazanya Proscovia Namujju; Kizza Moses; Ameke Christine; Omoding Nicolas Emojong; Booth Mark; Elliott Alison Mary; Woodburn Patrick William; Muhangi Lawrence; Hillier Stephen
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. Results: 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. Conclusions: 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.