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OBJECTIVE: Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. METHODS: The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. RESULTS: Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. CONCLUSIONS: The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.

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AIMS: To assess the different phenotypes and mechanisms of fluoroquinolone (FQ) resistance in clinical and environmental isolates of Escherichia coli. METHODS AND RESULTS: We compared FQ-resistant E. coli isolates, measuring minimal inhibitory concentrations (MIC) of ciprofloxacin, along with susceptibility to other antibiotics. We also searched for the presence of efflux pumps, using efflux inhibitors, and for plasmid-borne FQ-resistance by PCR. We found that, aside from the higher FQ-resistance prevalence among clinical strains, environmental ones resist much lower concentrations of ciprofloxacin. Efflux pumps mediate fluoroquinolone resistance as frequently among environmental isolates than in clinical strains. Plasmid-borne qnrA genes were not detected in any resistant strain. CONCLUSIONS: Environmental FQ-resistant strains may have a nonclinical origin and/or a selective pressure different from the clinical use of FQs. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of the source of low-level FQ-resistant strains (ciprofloxacin MIC c. 8 microg ml(-1)) in the environment could be important to curb the rapid emergence and spread of FQ-resistance in clinical settings, as these strains can easily become fully resistant to FQ concentrations achievable in fluids and tissues during therapy.

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BACKGROUND: As the incidence of tuberculosis (TB) has increased worldwide, it is expected that pregnant women will acquire this infection more frequently. Mycobacterium tuberculosis infection during pregnancy may represent a risk for maternal and neonatal complications. METHODS: We studied the perinatal events of 35 consecutive pregnancies complicated by TB from March 1990 to June 1998; 105 apparently healthy pregnant women were included as controls, matched in age, gestational age upon arrival at the Institute, and socioeconomic status. Frequency and type of neonatal complications were recorded. Relative risk (RR) with 95% confidence interval (CI) was calculated. To control potentially confounding variables, a stratified analysis was performed. RESULTS: Seventeen (48.5%) tuberculous mothers had a pulmonary infection and 18 (51.5%), an extrapulmonar localization of the TB. The neonatal morbidity rate in children born to women with TB was 23% against 3.8% of the children of the control cohort (p <0.05). Average weight of newborn infants of tuberculous mothers was 2,859 +/- 78.5 g, while average weight at birth of control neonates was 3,099 +/- 484 g (p = 0.03). Newborns of women with TB had a higher risk of prematurity (RR 2.1; 95% CI 1-4.3), perinatal death (RR 3.1; 95% CI 1.6-6), and weight at birth less than 2,500 g (RR 2.2; 95% CI 1.1-4.9). Pulmonary localization of the TB and late start of the treatment in the mothers increase the risk of perinatal death and neonatal morbidity. CONCLUSIONS: Children born to women with TB have an increased risk of morbidity and mortality in the neonatal period.

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BACKGROUND: High concentrations of interleukin-6 (IL-6) have been demonstrated in amniotic fluid (AF) from women with intra-amniotic infection. Recent studies have reported that IL-6 levels in AF were related to an increase in neonatal morbidity; moreover, higher IL-6 plasma levels have been observed in neonates with sepsis. METHODS: A cohort study was carried out at the National Institute of Perinatology in Mexico City. Inclusion criteria were the following: 1) preterm singleton pregnancy; 2) intact membranes at time of enrollment, and 3) written informed consent. Women with other complications of pregnancy were excluded. Newborn sepsis during the first 72 h was defined as early-onset sepsis. Amniotic fluid was obtained at the moment of delivery. Amniotic fluid IL-6 (AF IL-6) was determined by enzyme-linked immunoassays. RESULTS: Ninety-three women met the criteria for enrollment in the study and 31 (33%) of their newborns had early-onset neonatal sepsis. The mean AF IL-6 in mothers of septic newborns was 5779 +/- 2804 pg/ml compared to 729 +/- 382 pg/ml in mothers with non-infected neonates (p < 0.001). AF IL-6 concentrations higher than 1250 pg/ml were significantly associated with early-onset sepsis (OR 33.3; 95% CI 9.4-117.3) (p < 0.001). Gestational age under 32 weeks was also associated with neonatal sepsis (OR 2.56; 95% CI 1.2-9) (p = 0.002). Women whose infants developed neonatal sepsis had a higher frequency of clinical chorioamnionitis (p = 0.02). CONCLUSIONS: IL-6 determination in AF may be a useful indicator to identify neonates with higher risk of in utero bacterial infection.

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OBJECTIVE: To describe the experience of management of pregnant women complicated with rubella and to evaluate the perinatal outcome. MATERIAL AND METHODS: A total of 67 pregnant women with positive IgM test for rubella were studied in the period from January 1st, 1990 to October 31st, 1997. Sixty-six of these women were followed until the end of gestation, in 4 patients an elective abortion was performed and 1 patient had a molar pregnancy. The effects of rubella on gestation and on the product were evaluated in sixty-one of the patients. Anti-rubella IgM was determined at birth and positive infants were subjected to evaluation by echocardiogram, brainstem auditory evoked potentials (BAEP) and ophthalmological study. RESULTS: Mean age of the patients was 24.7 +/- 5.5 years; 28 patients were primigravidae. Pregnancies were normal showing no complications due to the rubella episode. In 35 cases (52.2%), the viral infection occurred during the first trimester of pregnancy, in 23 cases (34.5%) during the second and in 9 (13.3%) during the third. Seventy-one percent of infants born to mothers infected during the first trimester of pregnancy were also infected, and 51.6% developed congenital rubella syndrome. The most frequent manifestations of CRS were: prematurity, low birth weight and alterations of the BAEP. CONCLUSIONS: In Mexico, rubella is still a cause of fetal damage, which shows the need for preventive strategies, such as universal vaccination, to avoid rubella infection during pregnancy.

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The objective of this article is to evaluate the impact of tuberculosis (TB) on perinatal outcome in a cohort of 25 pregnant women with TB treated at the National Institute of Perinatology (Mexico, City) from March 1990 to September 1995. They were compared with a cohort of normal pregnant women; both cohorts were matched by age, gestational age, and socioeconomic status. For purposes of analysis, patients with TB were further stratified into two groups: one included 9 women who started treatment either before or at the beginning of pregnancy, and the other constituted 16 women who started treatment in either the second or third trimester of gestation. Thirteen women (52%) had pulmonary TB, 7 (28%) had renal infection, and the rest of patients had diverse extrapulmonary localization of the infection. Obstetrical morbidity and neonatal mortality were significantly higher in pregnant women with TB who started treatment late in pregnancy. Perinatal morbidity was similar in pregnant women receiving antituberculous drugs early during pregnancy to that in uninfected women. We conclude that TB represents a risk factor for pregnancy. Early treatment of the disease during gestation reverts its negative impact on perinatal outcome.

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Near 70 per cent of Mexican women infected by the Human Immunodeficiency virus (HIV) are between 15 and 44 years old, in this women sexual transmission are the most frequent route of infection. The objective of this article was to describe the obstetric course and perinatal repercussion of the HIV-Positive pregnant women with medical care at the Instituto Nacional de Perinatología, Mexico city between January 1994 to December 1996. Nineteen women were studied, sexual transmission was the route of infection in 16 of them. One had diagnostic criteria for AIDS, the others 18 had HIV asymptomatic infection. At delivery 18 a term products were born. The mean of the newborn weight was 3159 g. At moment of this report 4 children (22%) have been diagnosed as HIV infected, all of them dead during their first year of life.

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