ABSTRACT
BACKGROUND: Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. METHODS: This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. RESULTS: 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (p<0.001) in the vaccine group compared to 1.6 (p<0.14) in the placebo group. Among the 16 vaccinees,14 vaccinees (87.5%) had seroconversion compared to 1 of 16 placebo recipients (6.3%). V. cholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. CONCLUSION: Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults.
Subject(s)
Cholera Vaccines/adverse effects , Cholera Vaccines/immunology , Cholera/prevention & control , HIV Infections/complications , Administration, Oral , Adolescent , Adult , Antibodies, Bacterial/blood , Cholera Vaccines/administration & dosage , Double-Blind Method , Female , HIV Infections/immunology , Humans , Male , Middle Aged , Placebos/administration & dosage , Thailand , Treatment Outcome , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology , Young AdultABSTRACT
En 1995, el Programa Mundial de Vacunas e Immunización de la OMS estableció un registro para ensayos con vacunas. En septiembre de 1996, este registro contenía 50 ensayos de vacunación patrocinados por la OMS, de los cuales 25 (50 por cien) eran estudios ya terminados. Las vacunas que se habían estudiado con mayor frecuencia fueron las de sarampión (9 ensayos), poliovirus (8 ensayos), cólera (8 ensayos), Escherichia coli enterotoxígena (4 ensayos) y neumococo (4 ensayos). Casi 80 por cien de estos ensayos se llevaron a cabo en países en desarrollo, principalmente en el Africa. En los 25 ensayos ya terminados, los resultados investigados fueron la respuesta inmunitaria (24 ensayos), las reacciones adversas (13 ensayos), la morbilidad (4 ensayos) y la mortalidad (1 ensayo). La OMS contribuyó a estos ensayos con el aporte indirecto de fondos, ayuda con el diseño metodológico, visitas a las localidades, el análisis de los datos, la adquisición de vacunas y la investigación de su potencia
Subject(s)
Clinical Trials as Topic , World Health OrganizationABSTRACT
STUDY OBJECTIVE: To measure the association between the development of air leak (pneumothorax or pulmonary interstitial emphysema) during the first 27 postnatal days and neonatal death or chronic lung disease, as determined on day 28, among very low birth weight infants who required mechanical ventilation from the first day of life. DESIGN: Prospective, multicenter cohort study. PATIENTS: Two hundred sixty inborn, very low birth weight (501 to 1500 gm) infants given ventilatory support from the first day of life. RESULTS: The risk of an adverse outcome (death or chronic lung disease) changed with postnatal age at the time of diagnosis of the air leak. The association between air leak and an adverse outcome, as measured by gestational age-adjusted odds ratio (95% confidence interval), was 13.9 (1.7 to 114.6) for those in whom an air leak developed on day 0 or 1 (early), decreased to 1.7 (0.7 to 4.1) for those whose air leak developed on day 2 or 3 (intermediate), and increased to 16.6 (2.1 to 130.4) for those whose air leak developed on days 4 to 27 (late). The association with neonatal death showed even more striking fluctuations with postnatal age at occurrence of an air leak, ranging from an odds ratio of 40.3 (3.5 to 464.8) for the early group to 7.5 (2.3 to 25.0) for the intermediate group and 78.3 (6.9 to 889.5) for the late group. CONCLUSIONS: Air leak in newborn infants requiring mechanical ventilation is associated with increased risks of death or future morbidity, but the magnitude of these risks changes with postnatal age at the time of diagnosis of the air leak. Failure to consider the age at which the air leak is detected may miss changes in its prognostic implications and may partly explain inconsistent results in previous studies.