Browsing by Author "Muwanga, Moses"

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Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised-controlled trial results
(John Wiley & Sons A/S, 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
Background: 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. Objective: To determine whether anthelminthic treatment during pregnancy increases the risk of allergy in infancy. Methods: A randomised, 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 Results: Worms were detected in 68% of women before treatment. Doctor-diagnosed infantile eczema incidence was 10.4/100 infant years. Maternal albendazole treatment was associated with a significantly increased risk of eczema [Cox HR (95% CI), p: 1.82 (1.26–2.64), 0.002]; this effect was slightly stronger among infants whose mothers had no albendazole-susceptible worms than among infants whose mothers had such worms, although this difference was not statistically significant. Praziquantel showed no effect overall but was associated with increased risk among infants of mothers with Schistosoma mansoni [2.65 (1.16–6.08), interaction p = 0.02]. In a sample of infants, skin prick test reactivity and allergen-specific IgE were both associated with doctor-diagnosed eczema, indicating atopic aetiology. Albendazole was also strongly associated with reported recurrent wheeze [1.58 (1.13–2.22), 0.008]; praziquantel showed no effect. Conclusions: The detrimental effects of treatment suggest that exposure to maternal worm infections in utero may protect against eczema and wheeze in infancy. The results for albendazole are also consistent with a direct drug effect. Further studies are required to investigate mechanisms of these effects, possible benefits of worms or worm products in primary prevention of allergy, and the possibility that routine deworming during pregnancy may promote allergic disease in the offspring.
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.
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, Matti
Background 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.
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 M
Background: 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.
Risk of Being Seropositive for Multiple Human Papillomavirus Types Among Finnish and Ugandan Women
(Informa Healthcare, Taylor & Francis, 2010-02-24) Namujju, Bazanya Proscovia; Surcel, Heljä-Marja; Kirnbauer, Reinhard; Kaasila, Marjo; Banura, Cecily; Byaruhanga, Romano; Muwanga, Moses; Mbidde, Katongole Edward; Koskela, Pentti; Lehtinen, Matti
Although infections with multiple human papillomavirus (HPV) types have been reported widely, more information is needed on the occurrence of the different types. We determined the distribution of seroprevalences to multiple HPV types in Finland and Uganda to compare the epidemiology of the different HPV types in the 2 populations. Serum samples were obtained from 2784 Finnish and 1964 Ugandan women (mean ages 22 y and 25 y, respectively) of whom 44% and 57%, respectively, had antibodies to at least 1 of the 7 HPV types (6, 11, 16, 18, 31, 33, 45) tested ( p 0.001). Multiple HPV antibody positivity was common. HPV45-seropositive Finns had a higher risk of having antibodies to other high-risk HPV types: HPV18 (odds ratio (OR) 10.9), HPV31 (OR 6.1), HPV33 (OR 12.2), than their Ugandan counterparts: HPV18 (OR 3.4), HPV31 (OR 2.2), HPV33 (OR 3.3). Increased estimates for being double antibody-positive were also noted among HPV18- and HPV16- seropositive women, but there were no major differences between HPV16-seropositive Finns and Ugandans. In addition to biological and behavioural factors, iatrogenic and societal factors (screening vs no screening) may also result in the different occurrence of infections with the high-risk HPV types in Finland and Uganda.
Skin Prick Test Reactivity to Common Allergens Among Women in Entebbe, Uganda
(2008) Mpairwe, Harriet; Muhangi, Lawrence; Ndibazza, Juliet; Tumusiime, Josephine; Muwanga, Moses; Laura, Rodrigues C.; Alison, Elliott M.
The objectives of this study were to estimate the prevalence of atopic sensitization,and to identify common aeroallergens associated with atopic sensitization among women inEntebbe, Uganda, and to determine risk factors for atopic sensitization among those with andwithout a history of asthma or eczema. A case—control study was conducted within a trial ofdeworming in pregnancy, approximately 2 years after the intervention. Skin prick test reactivitywas assessed among 20 women with a history of asthma, 25 with history of eczema and 95controls. Overall prevalence of reactivity was estimated by adjusting for the prevalence ofasthma in the whole cohort. Overall skin prick test prevalence was: any allergen 30.7%,Blomiatropicalis10.9%,Dermatophagoidesmix 16.8%, cockroach 15.8%. The prevalence of a positiveskin prick test was significantly associated with a history of asthma (70% to any allergen vs.32%,P= 0.002) but not with a history of eczema (44% vs. 36%,P= 0.49). Women withMansonellaperstanshad significantly reduced odds for atopic sensitization (adjusted odds ratio 0.14, 95%CI 0.03—0.69); women with a history of asthma were less likely to have hookworm (adjustedodds ratio 0.24, 95% CI 0.07—0.81) but this association was weaker for women with a history ofeczema. [Clinical Trial No. ISRCTN32849447]
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, Moses
In 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.