Browsing by Author "Mawa, Patrice A."

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    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.
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    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.
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    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.
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    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.
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    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., Elliott
    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 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.
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    The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette–Gue´rin immunization
    (Philosophical Transactions of the Royal Society B: Biological Sciences, 2015) Mawa, Patrice A.; Nkurunungi, Gyaviira; Egesa, Moses; Webb, Emily L.; Smith, Steven G.; Kizindo, Robert; Akello, Mirriam; Lule, Swaib A.; Muwanga, Moses; Dockrell, Hazel M.; Cose, Stephen; Elliott, Alison M.
    Bacille Calmette–Gue´rin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n ¼ 53) and cellular (n ¼ 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml21 [3300–11 050] in cord blood) and sixweeks (0.00 ng ml21 [0–288]). Frequencies of PPD-specific IFN-g-expressing CD4þT cells increased at one week and declined between one and six weeks ( p ¼ 0.031). Frequencies of IL-2- and TNF-a-expressing PPD-specific CD4þT cells increased between one and six weeks ( p ¼ 0.019, p ¼ 0.009, respectively). At one week, the frequency of PPD-specific CD4þT cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses ( p ¼ 0.002) and after adjusting for confounders (mean difference, 95% CI 20.041% (20.082, 20.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCGimmunization. These findings are being explored further in a larger study.