Browsing by Author "Whitworth, James A. G."

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    Breastfeeding practices and attitudes relevant to the vertical transmission of HIV in rural south-west Uganda
    (Annals of tropical paediatrics, 2001) Nyanzi, Stella; Pool, Robert; Whitworth, James A. G.
    Breastfeeding has been associated with a doubling of the risk of HIV transmission. In developed countries, it is recommended that HIV-positive women do not breastfeed, but this is not a feasible option in most of Africa. It is therefore important to know the extent to which breastfeeding practices are amenable to change. To study this, we carried out 24 focus group discussions with 208 women attending maternity clinics in three rural sites in rural south-west Uganda. Breastfeeding starts from a few minutes to a few days after delivery; most women reported starting after 2 days. The main reason for delay is lack of milk or that the breasts are ‘blocked’. Most women thought that this delay was good for the baby, or at least not harmful. Almost all women reported giving the child a soup made of boiled mushrooms before starting to breastfeed. Once they have started breastfeeding, various supplementary foods are gradually introduced at 4–6 months. Women thought that ideally breastfeeding should last for 2–3 years, but in practice most stopped after 18 months. The father and his female relatives generally decide when the child should be weaned. The women thought that commercial milk formula foods were good but could not use them because they are too expensive and anyway unavailable in rural areas. Most women were unaware that HIV could be passed to the child through breastfeeding. Various practices identi ed as potentially risky are common in this population. Arti cial feeding is not a viable option in this area, and although women were prepared to make sacri ces to prevent vertical transmission of HIV, practices are deeply ingrained in traditional culture and will need to be addressed in future interventions. Male partners will also need to be involved.
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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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    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.
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    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.
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    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]
    (Clinical trials, 2007) Elliotta, Alison M.; Kizza, Moses; Quigley, Maria A.; Ndibazza, Juliet; Nampijja, Margaret; Muhangi, Lawrence; Morison, Linda; Namujju, Proscovia B.; Muwanga, Moses; Kabatereine, Narcis; Whitworth, James A. G.
    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.
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    Relation Between Chemokine Receptor Use, Disease Stage, and HIV-1 Subtypes A and D Results From a Rural Ugandan Cohort
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2007) Kaleebu, Pontiano; Nankya, Immaculate L.; Yirrell, David L.; Shafer, Leigh Anne; Kyosiimire-Lugemwa, Jacqueline; Lule, Daniel B.; Morgan, Dilys; Beddows, Simon; Weber, Jonathan; Whitworth, James A. G.
    To determine whether there are differences in coreceptor use in subjects infected with HIV-1 envelope subtypes A and D that could explain the differences in progression rates between these subtypes in a rural Ugandan cohort. HIV-1 was subtyped in env by V3 sequencing or heteroduplex mobility assay. Coreceptor use was determined by the ability of the isolates to replicate in U87 CD4+ cells expressing different coreceptors. The Fisher exact test was used to examine the relation between coreceptor use and subtype, clinical stage, and V3 charge. The Kruskall-Wallis nonparametric test was used to examine the association between median CD4 cell counts, coreceptor use, and subtype. Logistic regression was used to examine predicted coreceptor use at different CD4 groupings. Isolates from 66 participants were analyzed. Thirty-one were infected with subtype A, and 35 were infected with subtype D. Although this work was based on a small sample size, we found statistically significant differences. The probability of having an X4 virus was higher in subtype D infections than in subtype A infections among those with a non-AIDS clinical status (Fisher exact test, P = 0.040). Logistic regression analysis, in which we predicted X4 use by subtype and stratified by CD4 group, confirmed these findings among those with a CD4 count .200 cells/mL (likelihood ratio test, P = 0.003). R5 viruses were associated with higher median CD4 cell counts than X4 or X4/R5 (Kruskall-Wallis test, P = 0.0045). AV3 charge of +5 and greater was highly associated with X4 virus (Fisher exact test, P = 0.006). These subtype differences in coreceptor use may partially explain the faster progression rates we have previously