RESUMO
BACKGROUND: 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. 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 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 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. 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. FUNDING: Wellcome Trust.
Assuntos
Anti-Helmínticos/administração & dosagem , Doenças Transmissíveis/imunologia , Infecções por HIV/imunologia , Complicações Parasitárias na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adulto , Albendazol/administração & dosagem , Albendazol/efeitos adversos , Anti-Helmínticos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Praziquantel/administração & dosagem , Praziquantel/efeitos adversos , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Vacinação , Adulto JovemRESUMO
Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study. We analyzed TB incidence in 462 members of this cohort who were screened for filarial infections, gastrointestinal nematodes, and schistosomiasis. Progression to TB was not associated with gastrointestinal nematodes (rate ratio [RR], 1.18; confidence intervals [CIs], 0.66-2.10) or Mansonella perstans (RR, 0.42; CI, 0.13-1.34). A weak association between Schistosoma mansoni infection and TB was found (RR, 1.42; CI, 0.86-2.34); after adjusting for potential explanatory variables and using more stringent diagnostic criteria, the association was strengthened (RR, 2.31; 1.00-5.33). This analysis suggests an effect of S. mansoni infection on progression to active TB among HIV-1-infected Ugandans.
Assuntos
Infecções por HIV/complicações , HIV-1 , Esquistossomose mansoni/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Animais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/sangue , Esquistossomose mansoni/complicações , Esquistossomose mansoni/patologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Análise de Sobrevida , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/mortalidade , Tuberculose Pulmonar/patologia , Uganda/epidemiologiaRESUMO
BACKGROUND: Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown. METHODS: In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-gamma) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using chi2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests. RESULTS: Maternal hookworm was associated with reduced maternal IFN-gamma responses to CFP (adjusted odds ratio for IFN-gamma > median response: 0.14 (95% confidence interval 0.02-0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-gamma responses in their one-year-old infants (adjusted OR 17.65 (1.20-258.66; p = 0.013)). Maternal albendazole tended to reduce these effects. CONCLUSION: Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-gamma responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.
Assuntos
Albendazol/farmacologia , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Infecções por Uncinaria/imunologia , Mycobacterium tuberculosis/imunologia , Complicações Parasitárias na Gravidez/imunologia , Adulto , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Animais , Método Duplo-Cego , Feminino , Helmintos/imunologia , Infecções por Uncinaria/tratamento farmacológico , Humanos , Lactente , Interferon gama/imunologia , Interferon gama/metabolismo , Mycobacterium tuberculosis/metabolismo , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológicoRESUMO
OBJECTIVES: To describe the progression times of HIV-1 infection from seroconversion to AIDS and to death, and time from first developing AIDS to death in rural Uganda. Also, to describe the proportion of individuals within the cohort dying with AIDS and the CD4 lymphocyte count before death. DESIGN: A prospective, longitudinal, population-based cohort. METHODS: Since 1990, 107 HIV-prevalent cases, 168 incident cases and 235 HIV-seronegative controls have been recruited into a cohort in rural Uganda. Participants are recruited from the general population and they are reviewed routinely every 3 months and at other times when ill. RESULTS: The median time from seroconversion to death was 9.8 years. Age over 40 years at seroconversion was associated with more rapid progression (P < 0.001, log rank test). For the first 4 years of the study, HIV contributed little to the death rates in the HIV incident cases, but after 5 years, the contribution of HIV became greater and was particularly marked in the oldest age group. Survival rates in the cohort were similar to those in the general population. The median time from seroconversion to AIDS was 9.4 years and from AIDS to death was 9.2 months. Of those infected with HIV-1, 80% died with AIDS and 20% had a CD4 count < 10 x 106 cells/l. CONCLUSIONS: Survival with HIV-1 infection is similar in Africa to industrialized countries before the use of antiretroviral therapy; when they do die, many of those in Africa are severely immunosuppressed and most have clinical features of AIDS.
Assuntos
Países Desenvolvidos , Infecções por HIV/mortalidade , HIV-1 , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Adolescente , Adulto , Progressão da Doença , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/imunologia , Soropositividade para HIV/mortalidade , Soropositividade para HIV/fisiopatologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , População Rural , Fatores de Tempo , Uganda/epidemiologiaRESUMO
23-Valent pneumococcal polysaccharide vaccine was previously reported to be ineffective in HIV-infected Ugandan adults. Prolonged follow-up of trial participants confirmed persistent excess of all-cause pneumonia in vaccine recipients [hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.0-2.4], but surprisingly a survival advantage favouring vaccination (HR 0.84; CI 0.7-1.0). An explanation for the improvement in survival in the face of excess morbid events is lacking; a role for vaccine in HIV care in Africa remains unlikely.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções por HIV/complicações , Vacinas Pneumocócicas , Pneumonia Viral/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Estudos de Coortes , Seguimentos , Infecções por HIV/mortalidade , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Uganda/epidemiologiaRESUMO
OBJECTIVE: Changing behaviour is an important method for preventing HIV infection. We examined why a community randomized trial of a behavioural intervention found no significant effect of this on HIV incidence in rural Uganda. DESIGN: An individual-level analysis of a community randomized trial. METHODS: All sexually active, initially HIV-seronegative individuals with data on sexual behaviour were included (1558 men and 1836 women). Uptake of the intervention was measured using self-reported attendance at meetings, videos, dramas, and interactions with community educators in the past year. Sexual behaviour was assessed using self-reported condom use and the number of sexual partners in the past year. RESULTS: Overall, 81% of individuals in the intervention communities and 9% in the comparison communities reported attending at least one of the intervention activities in the past year. Attendance was lower in women, in those aged 55 years or older, and in the widowed. There was a lower HIV incidence in those who reported attending at least one intervention activity compared with those who attended none, and in women this effect was statistically significant (in women, adjusted rate ratio 0.41, 95% CI 0.19-0.89, P = 0.024; in men, adjusted rate ratio 0.66, 95% CI 0.25-1.79, P = 0.42). Reported behaviour change did not differ markedly between those who did and did not report attending any intervention activities. CONCLUSION: Although the intervention had no significant benefit in the communities as a whole, it resulted in a reduced risk of HIV acquisition in women who attended it. The methodological implications for future trials are discussed.
Assuntos
Terapia Comportamental/métodos , Infecções por HIV/prevenção & controle , Adolescente , Adulto , Idoso , Feminino , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Uganda/epidemiologiaRESUMO
OBJECTIVE: Despite the recognition of Cryptococcus neoformans as a major cause of meningitis in HIV-infected adults in sub-Saharan Africa, little is known about the relative importance of this potentially preventable infection as a cause of mortality and suffering in HIV-infected adults in this region. DESIGN: A cohort study of 1372 HIV-1-infected adults, enrolled and followed up between October 1995 and January 1999 at two community clinics in Entebbe, Uganda. METHODS: Systematic and standardized assessment of illness episodes to describe cryptococcal disease and death rates. RESULTS: Cryptococcal disease was diagnosed in 77 individuals (rate 40.4/1000 person-years) and was associated with 17% of all deaths (77 out of 444) in the cohort. Risk of infection was strongly associated with CD4 T cell counts < 200 x 10(6) cells/l(75 patients) and World Health Organization (WHO) clinical stage 3 and 4 (68 patients). Meningism was present infrequently on presentation (18%). Clinical findings had limited discriminatory diagnostic value. Serum cryptococcal antigen testing was the most sensitive and robust diagnostic test. Cryptococcal antigenaemia preceded symptoms by a median of 22 days (> 100 days in 11% of patients). Survival following diagnosis was poor (median survival 26 days; range 0-138). CONCLUSIONS: Cryptococcal infection is an important contributor to mortality and suffering in HIV-infected Ugandans. Improvements in access to effective therapy of established disease are necessary. In addition, prevention strategies, in particular chemoprophylaxis, should be evaluated while awaiting the outcome of initiatives to make antiretroviral therapy more widely available.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Criptococose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Adolescente , Adulto , Antígenos de Fungos/sangue , Estudos de Coortes , Criptococose/etiologia , Cryptococcus neoformans/imunologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/etiologia , Pessoa de Meia-Idade , Vacinas Pneumocócicas , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Soroepidemiológicos , Análise de Sobrevida , Uganda/epidemiologiaRESUMO
BACKGROUND: Western blot (WB) criteria in epidemiological studies in Africa exhibit an unacceptably high proportion of indeterminate results. New diagnostic criteria are urgently needed. METHODS: From 1989 to 1998, WB confirmatory tests were performed after weakly positive or discordant results of two enzyme immunoassays in a large Ugandan population. Enzyme immunoassays (EIA) on new sera taken prospectively from the same individuals one year later were used to assess the human immunodeficiency virus (HIV) status of these people. A logistic model was used to determine which set of WB bands was the most predictive of HIV status. Diagnostic criteria were then established, based on the likely HIV status determined using the predictive values and the intensity of the bands. RESULTS: Using 1109 WB tests, the best diagnostic criteria were based on only two bands (gp160 and p31). These criteria were validated on an independent sample of 587 WB tests, giving a high sensitivity and specificity (90.3% and 97.0%, respectively) and few indeterminate results (2.7%). These criteria classified correctly 96.3% of the sera. CONCLUSION: Our diagnostic criteria gave far better results in our population than the existing published criteria. This suggests that new criteria could be developed to improve WB interpretation in African settings.
Assuntos
Western Blotting/métodos , Infecções por HIV/diagnóstico , HIV-1 , África/epidemiologia , Anticorpos Antivirais/sangue , Antígenos HIV/sangue , Proteína gp160 do Envelope de HIV/sangue , Infecções por HIV/epidemiologia , HIV-1/imunologia , Humanos , Técnicas Imunoenzimáticas , Modelos Logísticos , Valor Preditivo dos Testes , ProbabilidadeRESUMO
It has been suggested that type 1 immune responses protect against tuberculosis (TB), while type 2 responses, such as those induced by helminths, may suppress protective responses and increase susceptibility to TB. Factors associated with progression to active TB were investigated in a cohort of HIV-1-infected Ugandan adults, a group at high risk of TB. High rates of subsequent progression to active TB were associated with eosinophil counts > or = 0.4 x 10(9)/L at enrolment. Eosinophilia at enrolment was associated with male gender, low socio-economic status, high CD4+ T cell counts, and schistosomiasis, but adjusting for these factors did not explain the association of eosinophilia with progression to active TB (adjusted rate ratio = 2.76, P = 0.004). Eosinophilia is most likely to be indicative of a type 2 immune response induced by helminth infection in this Ugandan cohort, but the mechanism of the observed association between eosinophilia and risk of TB remains to be determined.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Eosinofilia/complicações , Infecções por HIV/complicações , HIV-1 , Tuberculose/complicações , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Fatores de Risco , Esquistossomose/complicações , Classe SocialRESUMO
Identifying correlates of immunity or susceptibility to disease promotes understanding of pathogenesis and development of diagnostic tools, treatments, and vaccines. There is evidence that type 1 cytokine responses are associated with protection against tuberculosis, and suppression of type 1, or switching to type 2 responses, with susceptibility, but this has not been studied prospectively. We studied a cohort of 631 HIV-1-infected Ugandan adults. At enrollment we performed whole blood cultures for type 1 (interferon [IFN]-gamma, interleukin [IL]-2) and type 2/immunosuppressive (IL-5, IL-10) responses to mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). The incidence of tuberculosis was not associated with IFN-gamma responses, but was higher among participants with IL-2 responses (adjusted rate ratios [RR]: PPD 3.48; CFP 3.99; P < 0.001). For tuberculin skin test-positive participants, high incidence was also associated with an IL-10 response to PPD (adjusted RR 6.24, P = 0.03); for those with a BCG scar, high incidence was associated with positive IL-5 responses (adjusted RRs: PPD 3.64, P = 0.006; CFP 3.44, P = 0.04). The association with IL-2 production may reflect a response to tuberculous infection or to activating disease; the associations with IL-10 and IL-5 are in keeping with the expected role of immunosuppressive or type 2 cytokines.
Assuntos
Citocinas/imunologia , Infecções por HIV/imunologia , HIV-1 , Tuberculose/imunologia , Adolescente , Adulto , Antígenos de Bactérias/imunologia , Vacina BCG/uso terapêutico , Contagem de Linfócito CD4 , Citocinas/sangue , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Humanos , Incidência , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-2/sangue , Interleucina-2/imunologia , Interleucina-5/sangue , Interleucina-5/imunologia , Masculino , Estudos Prospectivos , Tuberculose/sangue , Tuberculose/epidemiologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/imunologia , Uganda/epidemiologiaRESUMO
Recent debate about the evaluation of community based, HIV/AIDS behavioural interventions has focused on the appropriateness of the randomised controlled trial (RCT) design, and the difficulty of obtaining reliable outcome measures. A community based HIV AIDS behavioural change RCT, recently conducted in rural Uganda, used HIV incidence as the principal outcome measure. This paper examines the acceptability of the trial from the community perspective. It asks whether, in a rural African setting, it is possible to implement a scientifically rigorous evaluation without compromising acceptability of the trial to the community. Opinions of the trial held by community members working as trial field workers were collected by semi-structured interview (n = 37), and focus group discussions (4) Community opinions of the trial were ascertained through 10 focus groups. For both field workers and the community, the sero-survey was more salient than the intervention, and the source of many rumours and disputes. Despite intensive mobilisation and close monitoring of field workers, it was impossible to ensure the veracity of explanations about the survey at ground level, and to protect each individual from coercion. The community expected a reward in return on their blood. Although the introduction of incentives at the final survey round increased the acceptability of the trial, they not only created jealousies and tensions, but also led to expectations of greater rewards in future. We conclude that RCTs in poor, rural communities are feasible, but the challenges involved should not be underestimated. Obtaining community support for the trial, respecting established hierarchies, and close supervision of field workers are all essential, but even then, controversies should be anticipated. There is an urgent need for relevant guidelines to help researchers navigate the complex ethical issues involved.
Assuntos
Infecções por HIV/prevenção & controle , Soroprevalência de HIV , Conhecimentos, Atitudes e Prática em Saúde , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Saúde da População Rural , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Coerção , Agentes Comunitários de Saúde/psicologia , Participação da Comunidade/psicologia , Ética , Grupos Focais , Guias como Assunto , Infecções por HIV/epidemiologia , Humanos , Incidência , Entrevistas como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Reprodutibilidade dos Testes , Uganda/epidemiologiaRESUMO
Investigators need, both for ethical and methodological reasons, to consider the acceptability of their intervention to the study population. We explored the response to a community-based randomized controlled trial (RCT) of an HIV/AIDS behavioral change intervention in rural Uganda. The views of field-workers, trial community, nongovernment organization representatives, and religious leaders were explored via focus groups (13) and interviews (45). The results suggest that the components of the intervention valued by the community are not necessarily those prioritised by trial implementers. Specifically, prevention activities appear to be valued less than material assistance. Furthermore, universal acceptance of the trial is probably unattainable. For these reasons, sensitive mobilization, respect for community members and their appointed leaders, and ongoing communication is essential. We suggest that evaluations of process be regarded as essential to the conduct of community-based RCTs and highlight the need for appropriate evaluation indicators to facilitate this.
Assuntos
Atitude do Pessoal de Saúde , Redes Comunitárias/organização & administração , Infecções por HIV/prevenção & controle , Serviços Preventivos de Saúde/organização & administração , Saúde da População Rural , Grupos Focais , Humanos , Entrevistas como Assunto , Aceitação pelo Paciente de Cuidados de Saúde , Valores Sociais , UgandaRESUMO
OBJECTIVES: To estimate the rate of progression from seroconversion to symptomatic disease in adults infected with HIV-1, and to establish whether the background level of signs and symptoms commonly associated with HIV-1 in uninfected controls are likely to affect progression rates. DESIGN: Longitudinal, prospective cohort study of people infected with HIV-1 and randomly selected subjects negative for HIV-1 antibodies identified during population studies. SETTING: Study clinic with basic medical care in rural Uganda. SUBJECTS: 275 patients infected with HIV-1 (107 prevalent cases and 168 incident cases) and 246 controls negative for HIV-1 antibodies. MAIN OUTCOME MEASURES: Signs and symptoms of HIV disease, as determined by stages 2 and 3 of the World Health Organization clinical staging system. RESULTS: The median time from seroconversion to WHO stage 2 was 25.4 months and to stage 3 was 45.5 months. 43% of the participants infected with HIV-1 had signs or symptoms by two years after seroconversion. The most common clinical conditions used to define progression of disease were weight loss, mucocutaneous manifestations, bacterial infections, chronic fever, and chronic diarrhoea. Although the rates of these conditions (apart from minor weight loss) were significantly higher in the participants infected with HIV-1, they were also relatively frequent in the control group. Herpes zoster, oral candidiasis, and pulmonary tuberculosis were not common events in the control group and therefore were more indicative of infection with HIV-1. CONCLUSIONS: Disease progression associated with infection with HIV-1 seems to be rapid in rural Uganda. This is most likely due to the high prevalence of conditions in the general population that could be taken as symptoms and signs of infection with HIV-1.
Assuntos
Países em Desenvolvimento , Infecções por HIV/patologia , HIV-1 , Saúde da População Rural , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Progressão da Doença , Feminino , Seguimentos , Infecções por HIV/complicações , Soropositividade para HIV/complicações , Soropositividade para HIV/patologia , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , UgandaAssuntos
Infecções por HIV/virologia , HIV-1 , Malária Falciparum/complicações , Progressão da Doença , Feminino , Infecções por HIV/complicações , Infecções por HIV/transmissão , HIV-1/isolamento & purificação , Humanos , Gravidez , Complicações Infecciosas na Gravidez/virologia , Complicações Parasitárias na Gravidez , RNA Viral/análise , Fatores de Risco , Carga ViralAssuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Eczema/epidemiologia , Helmintíase/tratamento farmacológico , Helmintíase/imunologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/imunologia , Eczema/imunologia , Feminino , Humanos , Lactente , Recém-Nascido , Distribuição de Poisson , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , RiscoRESUMO
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-γ), 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; maternal BCG scar (from past immunisation) with lower infant IL-5 and IL-13 responses to cCFP. IFN-γ, IL-5 and IL-13 to TT were reduced in HIV-exposed-uninfected infants; infant malaria and HIV were associated with lower IFN-γ, 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 immunisation on infant responses to vaccines should be explored. Prevention of infant malaria and HIV could contribute to effectiveness of immunisation programmes.
Assuntos
Vacina BCG/imunologia , Toxoide Tetânico/imunologia , Adulto , Anticorpos Antibacterianos/sangue , Estudos de Coortes , Citocinas/metabolismo , Feminino , Infecções por HIV/imunologia , Humanos , Lactente , Recém-Nascido , Linfócitos/imunologia , Malária/imunologia , Masculino , Mansonelose/imunologia , Mycobacterium tuberculosis/imunologia , Gravidez , UgandaRESUMO
OBJECTIVES: To determine the probable route of transmission of HIV to children aged 12 years or younger in a rural area of Uganda from 1999 through 2000 and to examine associations between HIV infection and health care-related variables. METHODS: The HIV infections status for 6991 children was determined from 1 round of an ongoing population surveillance system, and the reported numbers of injections in the past year and blood transfusions were determined for 5922 of these children based on a medical questionnaire. Data from the surveillance system and from an additional survey were used to assess the potential for vertical infection from a mother to her child. RESULTS: The HIV prevalence among children was 0.4%. Of 23 definite and 4 probable cases of HIV infection in children, vertical transmission was not possible for 1 case, not likely for another case, and possibly not vertical for another case. The population-attributable fraction for vertical transmission was between 90% and 94%. Large numbers of injections in the past year and ever having a blood transfusion were only associated with HIV infection in children exposed to vertical transmission. CONCLUSIONS: Up to 10% of HIV infections in children in the study area were not attributable to vertical transmission, and thus were possibly attributable to iatrogenic transmission. Associations seen between health care-related variables and HIV were likely to be attributable to treatment for AIDS-related illness in children infected vertically.