Browsing by Author "Mpairwe, Harriet"
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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 Antibiotic Practices, Perceptions and Self-Medication Among Patients at a National Referral Hospital in Uganda(Infection and drug resistance, 2021) Nabaweesi, Irene; Olum, Ronald; Sekite, Arthur Brian; Tumwesigye Suubi, Willy; Nakiwunga, Prossy; Machali, Aron; Kiyumba, Richard; Kalyango, Peter; Natamba, Allen; Igumba, Yokosofati; Kyeyune, Martin; Mpairwe, Harriet; Katagirya, EricAntimicrobial resistance (AMR) is a major global health concern with increasing reports of microorganisms resistant to most of the available antibiotics. There are limited data on antibiotic practices, perceptions and self-medication among Ugandans, necessitating this study. Methods: A cross-sectional study was conducted among patients at Kiruddu National Referral Hospital, Kampala, Uganda. A pre-tested interviewer administered a questionnaire that was used to collect data after an informed consent. Chi-square tests and logistic regression were used to assess associations between outcome and exposure variables. A P<0.05 was statistically significant. Results: A total of 279 patients (response rate=71%) with a median age of 32 years participated in the study. The majority were females (55.6%, n=155) and from the outpatient department (74.9%, n=209). Overall, 212 (76%) participants had taken an antibiotic in the past 6 months, and some 22.2% (n=47) of the participants had practiced self-medication. Male participants (adjusted odds ratio (aOR)=2.13, 95% confidence intervals (CI): 1.01 to 4.50, P=0.046) and Muslims (aOR=4.37, 96% CI:1.54 to 12.44, P=0.006) were more likely to self-medicate. Employees (aOR=0.06, 95% CI:0.01 to 0.51, P=0.010) and patients with tertiary education (aOR=0.14, 95% CI: 0.02 to 0.81, P=0.028) were less likely to practice self-medication. About 33% (n=70) of the participants had not completed treatment dosage during their last course of antibiotic treatment because of feeling better (60%, n=42), lack of money to purchase the medication (15.7%, n=11) and side effects (10%, n=7). Whereas 169 participants (79.7%) believed that not completing treatment would have an impact on their personal health, only 96 participants (45.3%) believed that this behaviour could affect the health of others. Conclusion: Antibiotic misuse is significant among patients in Uganda. Continuous health education programs aimed at informing the public on antimicrobial resistance, and its dangers are recommended to curtail this challenge.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 Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2017) Muhangi, Lawrence; Woodburna, Patrick; Omara, Mildred; Omoding, Nicholas; Kizito, Dennison; Mpairwe, Harriet; Nabulime, Juliet; Ameke, Christine; Morison, Linda A.; Elliott, Alison M.It is suggested that helminths, particularly hookworm and schistosomiasis, may be important causes of anaemia in pregnancy. We assessed the associations between mildto-moderate anaemia (haemoglobin >8.0 g/dl and HIV among 2507 otherwise healthy pregnant women at enrolment to a trial of deworming in pregnancy in Entebbe, Uganda. The prevalence of anaemia was 39.7%. The prevalence of hookworm was 44.5%, Mansonella perstans 21.3%, Schistosoma mansoni 18.3%, Strongyloides 12.3%, Trichuris 9.1%, Ascaris 2.3%, asymptomatic Plasmodium falciparum parasitaemia 10.9% and HIV 11.9%. Anaemia showed little association with the presence of any helminth, but showed a strong association with malaria (adjusted odds ratio (AOR) 3.22, 95% CI 2.43—4.26) and HIV (AOR 2.46, 95% CI 1.90—3.19). There was a weak association between anaemia and increasing hookworm infection intensity. Thus, although highly prevalent, helminths showed little association with mild-to-moderate anaemia in this population, but HIV and malaria both showed a strong association. This result may relate to relatively good nutrition and low helminth infection intensity. These findings are pertinent to estimating the disease burden of helminths and other infections in pregnancy. [Clinical Trial No. ISRCTN32849447]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 A Description of Congenital Anomalies Among Infants in Entebbe, Uganda(Clinical and Molecular Teratology, 2011) Juliet, Ndibazza,; Lule, Swaib; Nampijja, Margaret; Mpairwe, Harriet; Oduru, Gloria; Kiggundu, Molly; Akello, Miriam; Muhangi, Lawrence; Elliott, Alison M.BACKGROUND: 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. METHODS: 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. CONCLUSION: 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.Item Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial(BMC Infectious Diseases, 2009) Tweyongyere, Robert; Mawa, Patrice A.; Emojong, Nicholas O.; Mpairwe, Harriet; Jones, Frances M.; Duong, Trinh; Dunne, David W.; Vennervald, Birgitte J.; Katunguka-Rwakishaya, Eli; Elliott, Alison M.Praziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery.A nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1–99 eggs per gram (epg)), moderate (100–399 epg) or heavy (≥400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery.At enrolment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens.S mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed during pregnancy, but this was not associated with major reduction in the efficacy of praziquantel. Long-term implications of these findings in relation to resistance to re-infection remain to be explored.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 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 Helminth therapy or elimination: epidemiological, immunological, and clinical considerations(The Lancet Infectious Diseases, 2014) Wammes, Linda J; Mpairwe, Harriet; Elliott, Alison M; Yazdanbakhsh, MariaDeworming is rightly advocated to prevent helminth-induced morbidity. Nevertheless, in affluent countries, the deliberate infection of patients with worms is being explored as a possible treatment for inflammatory diseases. Several clinical trials are currently registered, for example, to assess the safety or efficacy of Trichuris suis ova in allergies, inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, and autism, and the Necator americanus larvae for allergic rhinitis, asthma, coeliac disease, and multiple sclerosis. Studies in animals provide strong evidence that helminths can not only downregulate parasite-specific immune responses, but also modulate autoimmune and allergic inflammatory responses and improve metabolic homoeostasis. This finding suggests that deworming could lead to the emergence of inflammatory and metabolic conditions in countries that are not prepared for these new epidemics. Further studies in endemic countries are needed to assess this risk and to enhance understanding of how helminths modulate inflammatory and metabolic pathways. Studies are similarly needed in non-endemic countries to move helminth-related interventions that show promise in animals, and in phase 1 and 2 studies in human beings, into the therapeutic development pipeline.Item HIV Risk Perception and Prevalence in a Program for Prevention of Mother-to-Child HIV Transmission Comparison of Women Who Accept Voluntary Counseling and Testing and Those Tested Anonymously(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2005) Mpairwe, Harriet; Muhangi, Lawrence; Namujju, Proscovia B.; Kisitu, Andrew; Tumusiime, Alex; Muwanga, Moses; Whitworth, James A. G.; Onyango, Saul; Biryahwaho, Benon; Elliott, Alison M.To determine whether data from voluntary counseling and testing (VCT)/prevention of mother-to-child transmission (PMTCT) programs can be used for HIV surveillance. Women attending an antenatal clinic at the district hospital in Entebbe, Uganda, from May 2002 to April 2003 were offered counseling and HIV testing with same-day results (VCT) and nevirapine for PMTCT was provided for HIV-positive women and their babies. Those who declined VCT were tested for HIV anonymous Overall, 2635 women accepted VCT; 883 were tested anonymously. HIV prevalence was higher in VCT than in anonymously tested women in the first month of the program (20% vs. 11%, P = 0.05) and in months with <70% VCT uptake (17% vs. 8%, P < 0.001) but was similar in months with high uptake. Uptake of VCT was higher in women who had risk factors for HIV, especially those who believed themselves to have been exposed (84% vs. 73%, P < 0.001). There was a bias to accepting VCT in women with HIV, or risk factors for HIV infection, the former most apparent when there was low coverage. Data from VCT/PMTCT programs cannot replace anonymous surveillance for monitoring of HIV epidemic trends where coverage is incomplete within clinics or communities.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 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.Item Lack of effectiveness of syndromic management in targeting vaginal infections in pregnancy in Entebbe, Uganda(MRC/UVRI, 2006) Tann, C J; Mpairwe, Harriet; Morison, L; Nassimu, K; Hughes, P; Omara, M; Mabey, D; Muwanga, M; Grosskurth, H; Elliott, A MTo measure the prevalence of reproductive tract infections (RTIs) during pregnancy in Entebbe, Uganda, and to evaluate the current syndromic diagnosis and management approach in effectively targeting infections, such as bacterial vaginosis (BV) and trichomoniasis, that are associated with low birth weight and prematurity among newborns. We enrolled 250 antenatal clinic attenders. Vaginal swabs and diagnostic tests were performed for BV, Trichomonas vaginalis (TV), candida, Neisseria gonorrhoeae, Chlamydia trachomatis and for HIV-1 and active (TPHA+/RPR+) syphilis infection. Same day treatment was offered for symptoms according to syndromic management guidelines. The treatment actually provided by healthcare workers was documented. Sensitivity, specificity, positive and negative predictive values were used to assess the effectiveness of syndromic management guidelines and practice. The prevalence of infections were: BV 47.7%, TV 17.3%, candida 60.6%, gonorrhoea 4.3%, chlamydia 5.9%, syphilis 1.6%, and HIV 13.1%. In total, 39.7% of women with BV and 30.2% of those with TV were asymptomatic. The sensitivity of syndromic management as applied by health workers in targeting BV and TV was 50.0% and 66.7%, respectively. This would have increased to 60.3% (BV) and 69.8% (TV) had the algorithm been followed exactly. The prevalence of BV and TV seen in this and other African populations is high. High rates of asymptomatic infection and a tendency of healthcare workers to deviate from management guidelines by following their own personal clinical judgment imply that many vaginal infections remain untreated. Alternative strategies, such as presumptive treatment of BV and TV in pregnancy, should be considered.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 Risk factors for asthma among schoolchildren who participated in a casecontrol study in urban Uganda(Elife, 8,, 2019) Mpairwe, Harriet; Namutebi, Milly; Nkurunungi, Gyaviira; Tumwesige, Pius; Nambuya, Irene; Mukasa, Mike; Onen, Caroline; Nnaluwooza, Marble; Apule, Barbara; Katongole, Tonny; Oduru, Gloria; Kahwa, Joseph; Webb, Emily L; Lubyayi, Lawrence; Pearce, Neil; Elliott, Alison MData on asthma aetiology in Africa are scarce. We investigated the risk factors for asthma among schoolchildren (5–17 years) in urban Uganda. We conducted a case-control study, among 555 cases and 1115 controls. Asthma was diagnosed by study clinicians. The main risk factors for asthma were tertiary education for fathers (adjusted OR (95% CI); 2.32 (1.71–3.16)) and mothers (1.85 (1.38–2.48)); area of residence at birth, with children born in a small town or in the city having an increased asthma risk compared to schoolchildren born in rural areas (2.16 (1.60–2.92)) and (2.79 (1.79–4.35)), respectively; father’s and mother’s history of asthma; children’s own allergic conditions; atopy; and cooking on gas/electricity. In conclusion, asthma was associated with a strong rural-town-city risk gradient, higher parental socio-economic status and urbanicity. This work provides the basis for future studies to identify specific environmental/lifestyle factors responsible for increasing asthma risk among children in urban areas in LMICs.Item Skin prick test reactivity to common allergens among women in Entebbe, Uganda(Royal Society of Tropical Medicine and Hygiene, 2008) Mpairwe, Harriet; Muhangi, Lawrence; Ndibazza, Juliet; Tumusiime, Josephine; Muwanga, Moses; Rodrigues, Laura C.; Elliott, Alison 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 in Entebbe, Uganda, and to determine risk factors for atopic sensitization among those with and without a history of asthma or eczema. A case—control study was conducted within a trial of deworming in pregnancy, approximately 2 years after the intervention. Skin prick test reactivity was assessed among 20 women with a history of asthma, 25 with history of eczema and 95 controls. Overall prevalence of reactivity was estimated by adjusting for the prevalence of asthma in the whole cohort. Overall skin prick test prevalence was: any allergen 30.7%, Blomia tropicalis 10.9%, Dermatophagoides mix 16.8%, cockroach 15.8%. The prevalence of a positive skin 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 with Mansonella perstans had 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 (adjusted odds ratio 0.24, 95% CI 0.07—0.81) but this association was weaker for women with a history of eczema. [Clinical Trial No. ISRCTN32849447]Item Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child?(Parasitology, 2011) Elliott, Alison M.; Ndibazza, Juliet; Mpairwe, Harriet; Muhangi, Lawrence; Webb, Emily L.; Kizito, Dennison; Mawa, Patrice; Tweyongyere, Robert; Muwanga, MosesIn 1994 and 2002, respectively, the World Health Organization 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 immunization 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.