Browsing by Author "Kizito, Dennison"
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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(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.Item 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.Item Low Avidity of Human Papillomavirus (HPV) Type 16 Antibodies is Associated with Increased Risk of Low-Risk but not High-Risk HPV Type Prevalence(BioMed Central, 2011-06-06) Namujju, B. Proscovia; Hedman, Lea; Hedman, Klaus; Banura, Cecily; Mbidde, K Edward; Kizito, Dennison; Byaruhanga, Romano; Muwanga, Moses; Kirnbauer, Reinhard; Surcel, Heljä-Marja; Lehtinen, MattiBackground Low avidity of antibodies against viral, bacterial and parasitic agents has been used for differential diagnosis of acute versus recent/past infections. The low-avidity antibodies may however, persist for a longer period in some individuals. Findings We studied the association of human papillomavirus (HPV) type 16 antibody avidity with seroprevalence to HPV types 6/11/18/31/33/45. Antibody avidity was analysed for 365 HPV16 seropositive pregnant Finnish and Ugandan women using a modified ELISA. Low avidity of HPV16 antibodies was found in 15% of Finnish and 26% of Ugandan women. Ugandan women with low-avidity HPV16 antibodies had an increased risk estimate for HPV6/11 (odds ratio, OR 2.9; 95%CI 1.01-8.4) seropositivity but not to high-risk HPV types 18/31/33/45. Conclusion Association of the low avidity HPV16 antibody "phenotype" with possible susceptibility to infections with other HPV types warrants investigation.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; Lule, Swaib; Akurut, Helen; Kizito, Dennison; Kakande, Mohammed; Jones, Frances M; Fitzsimmons, Colin M.; Muwanga, Moses; Rodrigues, Laura C.; Dunne, David W; Elliott, Alison MBackground: 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. Methods: 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. Results: 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. Conclusions: 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 Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child?(Cambridge University Press, 2011) Elliott, Alison M; Ndibazza, Juliet; Mpairwe, Harriet; Muhangi, Lawrence; Webb, Emily L; Kizito, Dennison; Mawa, Patrice A; Tweyongyere, Robert; Muwanga, MosesIn 1994 and 2002, respectively, theWorld 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.