Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America.

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.

Beneficial effects of the n-3 long-chain polyunsaturated fatty acids in surgical patients: updating the evidence.

The use of n-3 polyunsaturated fatty acids in surgical patients has risen by the fact that this may attenuate systemic and acute inflammatory responses secondary to surgical trauma through modulation of inflammatory mediators and cell membrane interactions. Moreover, the inclusion of n-3 fatty acids in clinical trials as part of the therapy in patients, who expect to undergo a surgical stress, suggests benefits on clinical progress. Therefore, the objective of this article is to review data from n-3 polyunsaturated fatty acid effects on biochemical parameters and on reduced length of hospitalization, number of infections, and mortality as main clinical outcomes in human surgical patients.

Fluoroquinolone resistance in clinical and environmental isolates of Escherichia coli in Mexico City.

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.

Neonatal outcome of children born to women with tuberculosis.

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.

Bacteriospermia and male infertility: a method for increasing the sensitivity of semen culture.

OBJECTIVE: To test a method for increasing the sensitivity of semen culture. Design-Prospective and transverse. Setting-Andrology clinic at a tertiary care health institution in Mexico City. PATIENTS: 65 infertile patients with abnormal semen, bacteriospermia detected on Gram stain and at least two previous negative semen cultures (<3 months) were included to test routine semen culture and a method including centrifugation of semen at 10,00 rpm for 20 minutes. Localization cultures were also carried out in all patients. MAIN OUTCOME MEASURE: Bacterial isolation in semen samples. RESULTS: Routine semen culture was positive in 22% of patients, while centrifuged aliquots of the same semen sample were positive in 52% of patients (chi2 = 6.60, P < .01). Enterococcus was isolated in 43% of patients, E. coli in 24%, coagulase-negative Staphylococcus in 19%, and U. urealyticum in 14%. Ninety percent of isolates corresponded to specimens from the urethra and the prostato-vesicular region. CONCLUSION: Sensitivity of semen culture increased with centrifugation of semen samples. Localization pattern and type of isolates suggest that these patients had chronic prostatitis and that episodic elimination of bacteria might also explain false negative semen cultures in patients with chronic asymptomatic infection of the accessory sex glands.

Amniotic fluid interleukin-6 and the risk of early-onset sepsis among preterm infants.

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.

[The outcome of pregnancies complicated by rubella, 1990-1997]. / Resultado de los embarazos complicados con rubéola, 1990-1997.

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.

Pregnancy and tuberculosis: influence of treatment on perinatal outcome.

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.

[AIDS and pregnancy]. / SIDA y embarazo.

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.

Assessment of the functional capacity for intracellular death and phagocytosis of polymorphonuclear cells in healthy neonates.

The objective of this study was to assess the functional capacity for intracellular death (ID) and/or phagocytic index (PI) of polymorphonuclear cells of 24-h-old healthy newborns with respect to the PMN cells of adults using the same standard exogenous source of opsonins. The ID and PI techniques were standardized and 2-3 ml of blood were used. No differences were found in the percentages of ID, P, PI among the PMNs of the newborns and those of the adults: 43.95 +/- 15.70 vs. 44.56 +/- 8.43 for ID; 38.96 +/- 14.34 vs. 39.00 +/- 14.54 for P; 1.71 +/- 0.54 vs. 1.73 0.45 for PI, respectively. It was concluded that the PMNs of 24-h newborns have an ID, P, PI functionality comparable to adult PMNs; differences observed in PMN function in newborns may be due to humoral deficiencies (opsonins).

Infection of pregnant women with hepatitis B and C viruses and risks for vertical transmission.

Pregnant women infected with hepatitis B and C viruses pose a risk for infecting their newborn infants by vertical transmission. We studied 6,253 pregnant women aged 12-49 years for infection with hepatitis B (HBV) and C (HCV) viruses. Infection was diagnosed by measuring IgG antibodies against HBc, HBs, HBe, as well as IgM-HBc and HCV viral antigens with commercially available immunoassay kits. HBV infection was detected in 113 cases (1.8%), and prevalence was significantly higher (2.4%) in a group of women with a high-risk pregnancy who were attending a perinatology hospital than in healthy pregnant women (1.67%, p < 0.05). Infection with HBV was significantly higher in women older than 30 years old (p < 0.05). HBsAg was found in blood, colostrum and vaginal exudate of two pregnant women; HBsAg was detected in the gastric aspirate but not in the blood of the two newborn infants. HBeAg and IgM-HBc were not detected in any of the samples. DNA-HBV was detected in serum of seven women, and DNA-HBV was detected in the gastric aspirate of only one of the newborns. HCV infection was diagnosed in three out of 111 women with markers for HBV infection (2.7%), and in 6 out of 1,000 women without these markers (0.6%). Anti-HCV antibodies were found in the serum of six of their infants during up to six months of age. Infants were monitored for one year and none of them developed any sign of hepatic disease. These results suggest that special attention should be paid to women older than 30 years and with a high-risk pregnancy, as they are at a higher risk of HBV and HCV infections.

Perinatal outcome of pregnancies complicated with varicella infection during the first 20 weeks of gestation.

Varicella-Zoster (V-Z) virus infection during pregnancy is uncommon. Nevertheless, it has importance due to the risk of vertical transmission of the infection and also because of a higher morbidity rate among pregnant women. The cases of varicella infection that occur in the first and second trimesters of pregnancy are occasionally associated to the development of congenital varicella syndrome. We studied 22 women whose pregnancy was complicated with varicella during the first 20 weeks of gestation. The average age of these patients was 20 +/- 3.6 years with a range of 16 to 20 years. None of the patients presented complications due to the V-Z virus infection. Two pregnancies finalized in preterm labor. None of the newborns had congenital anormalies; one presented microcephaly, and another low birth weight. There was no significant difference between the infants of women with varicella and those of the controls in birth weight, size, and head circumference. We concluded that varicella infection during the first 20 weeks of gestation was not associated with serious maternal morbidity, and has low repercussion in the pregnancy outcome and the fetus.

[Prevalence of serologic markers of hepatitis A, B, C, and D viruses in pregnant women]. / Prevalencia de marcadores serológicos de los virus de la hepatitis A, B, C y D en embarazadas.

OBJECTIVE: To determine the seroprevalence of hepatitis A, B, C and D virus infection among pregnant women attending a perinatal care hospital. MATERIAL AND METHODS: A prospective study was carried out to determine the seroprevalence of hepatitis A virus IgG antibodies (anti-HAV), hepatitis B virus markers (anti-HBcAg and HBsAg) and hepatitis C virus antibodies (anti-HCV) in pregnant women. In HBsAg positive cases. HBeAg and hepatitis D virus antibodies (anti-HDV) were investigated. All analyses were performed with the ELISA technique. RESULTS: Of the 1500 pregnant women studied. 93.3% were positive for anti-HAV IgG. The HBsAg seroprevalence was 0.26% and anti-HCV seroprevalence was 0.53%. There were no patients with HBeAg or anti-HDV. CONCLUSIONS: A higher seroprevalence of HBsAg was found in this study than in other studies of pregnant Mexican women. We propose that HBsAg screening become a routine prenatal test.

Tuberculosis of the female reproductive tract: effect on function.

OBJECTIVE: To discuss the clinical presentation and consequences of genital tuberculosis (GTB), a known cause of infertility. Although it appears to be a rare entity, usually secondary to a primary site of infection by Mycobacterium tuberculosis, its true incidence is not known owing, in part, to inadequate diagnostic procedures, particularly in less developed areas of the world. PATIENTS AND METHODS: We present our experience with 25 cases of genital TB. Of these woman, 21 were seen for infertility; 3 were postmenopausal with uterine hemorrhage, and 1 was admitted with an acute abdomen. All women were treated medically and/or surgically. RESULTS: Only five women were found to be suitable for artificial insemination. Two of the women became pregnant but aborted. CONCLUSIONS: The incidence of genital TB may be higher than one might imagine, based on the lack of reports in the literature, and may account for a significant amount of female infertility.

PIP: During 1988-93, in Mexico City, the National Institute of Perinatology diagnosed 25 cases of female genital tuberculosis. Their age ranged from 21 to 42 years. The diagnostic procedures used to detect these cases included laparoscopy, PPD skin test reaction, hysterosalpingography (HSG), culture of tissue and fluid samples, and histopathological examination of tissue biopsies. 16% had a history of tuberculosis. 39.1% had a history of contact with a relative with tuberculosis. Three women were postmenopausal and suffered from uterine bleeding; they underwent a hysterectomy. 17 of 21 women who went on to infertility studies had suffered infertility for 2-14 years. HSG revealed abnormalities in 95.2%, especially bilateral tubal occlusion (57.1%) and deformity of the uterine cavity (54.5%). Mycobacterium tuberculosis was isolated in 4 women, all of whom had fluid in the pelvic cavity. 14 of the 16 patients who underwent the PPD skin test had an induration larger than 10 mm in diameter. 68% of the 19 patients who underwent endometrial biopsy had granulomas consistent with tuberculosis. All the women received antibiotics to treat female genital tuberculosis. Five of the 17 patients referred for infertility evaluation underwent in vitro fertilization and embryo transfer. Two of these women became pregnant but later suffered a spontaneous abortion. The other 3 women never conceived. These findings indicate that the incidence of female genital tuberculosis may be higher than expected and may be responsible for a substantial amount of female infertility. Pregnancy occurs when female genital tuberculosis is detected at an early stage and when no irreversible anatomical pathology is evident. Thus, it is important to determine the existence of tuberculosis early in cases of infertility and to begin therapy immediately.

[Comparison of the therapeutic efficacy of the piperacillin/tazobactame combination vs. ampicillin and gentamycin in in the management of post-cesarean endometritis]. / Comparación de la eficacia terapéutica de piperacilina/tazobactam vs ampicilina más gentamicina en el tratamiento de endometritis poscesárea.

Traditionally obstetric infections have been treated with combination antimicrobial agents that provide coverage against aerobic and anaerobic bacteria commonly found in these infections. New antibiotics may be a monotherapy alternative for this type of infections. The objective of the study was to compare the efficacy of the agent piperacillin/tazobactam against ampicillin plus gentamicin in the treatment of postcesarean endometritis. By randomized way 14 patients were enrolled in the piperacillin/tazobactam group and 42 in the ampicillin-gentamicin group. A favorable clinical response occurred in 78.6% of piperacillin/tazobactam patients and 88.1% of ampicillin and gentamicin patients (p = NS). There was no statistically significant difference in the times to recovery and days of hospitalization between the two groups. The combination piperacillin/tazobactam did not show advantage towards the standard treatment, so combination antimicrobial agent continue been the optimal approach to the management of obstetric infection.