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.

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.

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.

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.

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.

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.

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.

[Gynecologic and obstetric infections caused by aerobic bacteria]. / Infecciones ginecoobstétricas por bacterias anaerobias.

The anaerobic bacteria (AB) are between the most numerous microorganisms (mo) that constitute the flora of the female genital tract, so they can participate in the etiology of obstetric and gynecologic infections (OGI). The objective of this study was to investigate the frequency of AB isolations and the clinical characteristics of the anaerobic infections (AI) in patients of the National Institute of Perinatology, from January 1st, 1988 to May 31, 1991. AB were isolated from 117 patients who developed 163 infections; 167 anaerobic and 83 aerobic bacteria were recovered from these infections. The 99.2% were obstetric patients. The 85.5% of the isolations of AB were done from patients with endometritis, and 8.5% from postsurgical wound abscesses. Most of the AI were polymicrobial with a mean of 2.1 mo by infection. Peptostreptococcus, Clostridium and Bacteroids were the AB most frequent recovered. The majority of the patients had resolution of the infection within the first 5 days of antimicrobial treatment. There was no mortality in this group. We concluded that the AB have an important role in the etiology of OGI, then it is necessary that the treatment of these infections include antibiotics that cover AB.

[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.

[Current concepts in the pathogenesis and treatment of abortion and septic shock. II. The physiopathological bases and outlook in the management of septic shock]. / Conceptos actuales en la patogénesis y tratamiento del aborto y el choque séptico. Parte II. Bases fisiopatológicas y perspectivas en el manejo del choque séptico.

The septic shock has a low frequency in the gynecologic-obstetric patients, nevertheless several obstetric conditions like: septic abortion, chorioamnionitis or puerperal infections can be complicated with this syndrome. The infections cause near 20% of the maternal deaths. Because the high morbidity and mortality of the patients with septic shock is necessary to have an actual knowledge of its pathogenesis and treatment. Any person can be infected but only few of them will develop a septic shock, the response of the host to the microorganisms is the critical point for the develop of this syndrome. Many studies had showed the importance of the bacterial endotoxin and the tumoral necrosis factor as mediators of septic shock. The treatment include: control of the infectious process, restoration of tissue perfusion pressure, restoration of blood volume, use of inotropic agents and general support measures. The role of monoclonal antibodies against endotoxin in the management of Gram-negative sepsis is still ignored, but there are several studies that support its use.

[Current concepts in the pathogenesis and treatment of abortion and septic shock I. The epidemiology, pathogenesis and management of septic abortion]. / Conceptos actuales en la patogénesis y tratamiento del aborto y el choque séptico. Parte I. Epidemiología, patogénesis y manejo del aborto séptico.

In view of the illegal status induced abortion, it is difficult to determine the degree to which it is practiced. In our country there are a great inconsistency in the statistics on the number of abortions and the number of maternal deaths due to this cause. The principal complication of the illegal induced abortion is the septic abortion, with an uncontrolled bacterial infection and systemic complications that dominate the clinical picture. The mortality of the septic abortion is elevated, in the majority of cases due to septic shock. The treatment consist on antimicrobial agents and early surgery. A reduction on the number of illegal abortions will decrease significantly the number of septic abortion's cases.

[Tuberculosis in the pregnant woman]. / Tuberculosis en la mujer embarazada.

The prevalence of tuberculosis (TB) in Mexico as in the rest of the developing countries is high and no reduction has been noted in the past years. This article describe the clinical features of the disease during the gestational period. We studied 15 cases of TB and pregnancy treated at the Infectious Diseases Department of the Instituto Nacional de Perinatología, from January 1990 to June 1991. At our Institute the incidence was 1.54 cases by 1000 obstetric patients discharged, with a lethality rate of 6.6 deaths by 100 infected patients. We treated 15 women, nine had pulmonary TB, three renal TB, two TB of the cervical lymph node and one cutaneous TB. In seven patients the diagnosis was made before pregnancy, other seven were diagnosed during gestation, and one during puerperium. All patients were treated with antituberculous drugs; the most frequent combination was isoniazid, ethambutol and rifampin. Twelve women had no complications, one died, another developed preeclampsia, and in one case the patient had a low birth weight neonate. No cases of congenital TB were identified and none of the neonates had abnormalities at birth.

[Comparative study of the placenta from HIV+ mothers. Ultrastructural analysis]. / Estudio comparativo de la placenta de madres seropositivas a VIH. Análisis ultraestructural.

Perinatal vertical transmission has increased in all the world; it is considered that at the present time there are about one million of children with HIV. Variation goes from 12 to 40%, at different countries. During the last years antiretroviral drugs as AZT, ddI and others have been used to diminish the virus passage via transplacentary. Eighteen placentaes from HIV seropositive women, three corresponded to first trimester, and 15 to the third trimester of gestation; in four cases they were treated with AZT in weeks fourteen (two patients), 26 and 35 of gestation; and one patient received AZT and ddI at week 28. Control group was with ten normal placentaes. Ultraestructural analysis and immuno-peroxidase and immuno-oro with antibody anti gp 41, were done. Ultraestructurally there were different localizations of HIV virus, at sincitiotrophoblast, decidual cells and umbilical vessels (six cases). In 13 cases there was hyperplasia and hypertrophy of macrophages containing a great amount of lysosomes. In one case, where a girl was seropositive many viriones HIV, were identified in macrophages. With immuno-oro viral proteins were seen in cytoplasm an plasmatic membrane, in endothelium of fetal capillars and trophoblast. With immunoperoxidase, four cases were positive. Placentaes with antiretroviral treatment since week 14, trophoblast was more dense by philaments increment. Placentaes with treatment during the third trimester, showed normal morphology with slight increase of philaments. In the cases treated with AZT and ddI, there were not macrophages hyperplasia and hypertrophy, nor viral particles. It is concluded that in seropositive mothers without treatment, the virus may be present in any part of chorionic villi, and in patients with treatment, virus is not identified, but a viral proteins synthesis.

[Use of antibiotics in pregnancy. I]. / El uso de antibióticos en el embarazo. Parte I.

The use of antibiotics during pregnancy have particularly risk, choosing an antibiotic requires consideration of the effects on both the mother and the unborn child. Some antimicrobial agents are safe for use throughout pregnancy, while other are completely contraindicated. Pregnant women need treatment for serious infections, in this cases antibiotics must be used nevertheless the adverse effects of the antimicrobial agent, we must choose the antibiotic with more antimicrobial activity and less risk for the mother and the fetus.

[Usefulness of two tests for rapid diagnosis of urinary infections in pregnancy]. / Utilidad de dos pruebas para el diagnóstico presuntivo rápido en infección de vías urinarias y embarazo.

Sixty pregnant women with symptoms of UTI, who assisted to the Emergency Room of the INPer, were submitted to urine culture and rapid urine tests for the detection of nitrites and leukocytes with the "Multistix 10 SG" (R) stripes. A control group was integrated of 20 pregnant women without symptoms of UTI submitted to the same methodology. In the first group, 34 urine cultures were reported as negative, 9 were as contaminated and 17 were positive. The sensitivity and specificity of the nitrite test was 94%. For the leukocyte test, the sensitivity was 64% and the specificity was 100%. In the control group, 13 urine cultures were negative, two were contaminated and five were positive. In this group, the sensitivity of the nitrite test was 100% and the specificity was 92%; while the sensitivity of the leukocyte test was 40% and the specificity was 100%.

[AIDS and the gynecologist-obstetrician]. / El SIDA y el ginecoobstetra.

After the first case of HIV infection in a pregnant woman in our hospital, we thought on the need to review the medical literature about HIV infection and pregnancy and bring up to date the knowledge of this topic to the obstetricians and neonatologists. HIV infection is caused by a retrovirus. It selectively infects helper/inducer lymphocytes after binding to a glycoprotein receptor on their surface, named CD4. This depletion is slow and gradual, and by time is characterized by the presence of opportunistic infections and some class of tumors. Homosexual men are by now the group most affected by this virus. In Mexico, until August 1988, there were reported 1,628. One hundred forty one of these were women that is 8.6%; that mean that we have a significant female fertile population with an increased risk of perinatal transmission of HIV. The risk calculated to be infected by the HIV for obstetricians and other health care workers is less than 0.5%. However they had to take some measures to avoid contamination with body fluids and blood during the performance of a cesarean section or during delivery. We review briefly the measures that had to be taken by the neonatologist and the obstetrician in the attention of a pregnant woman since the prenatal care until the postpartum period. Among the measures that are reviewed are the use of gloves, gown, mask, glasses and the precautions that had to be taken with the use of sharp instruments during the performance of surgery.

[Efficacy and safety of azithromycin in the treatment of female genital Chlamydia trachomatis infections]. / Eficacia y seguridad de azitromicina en el tratamiento de la infección genital femenina por Chlamydia trachomatis.

Genital tract infections by Chlamydia trachomatis associated to sterility and infertility problems as well as perinatal complications have become increasingly frequent. Azithromycin is a new macrolide with a lower activity spectrum than erythromycin and a longer half life as well as less secondary effects. The objective of the study was to evaluate the safety and efficiency of Azithromycin on genital tract infection by C. trachomatis. MATERIAL AND METHODOLOGY. A total of 30 nonpregnant women between the ages of 19 and 35 were studied; 70% had only one sexual partner. In order to insure the presence of C. trachomatis as unique pathogen, cervicovaginal sampling, clinical evaluation and gynecologic exploration were undertaken. One dose of 1 g orally of Azithromycin was administered evaluating microbiologic and clinical remission at days 7-10, 12-16 and 33-37 after treatment. RESULTS. Two patients abandoned the study; global criteria of the evaluation were good to excellent in 17 cases; moderate to sufficient in six and poor in five. None of the cases reported secondary reactions. Results showed that Azithromycin treatment of cervicitis by C. trachomatis is useful with the advantage of unique dose administration.

[Antibiotic use in pregnancy. II]. / El uso de antibióticos en el embarazo. Parte II.

Tetracyclines are antimicrobial agents that must be avoided during pregnancy. Metronidazole has showed to be carcinogenic in animals like mouse, but in humans this effect has not been proved. In developing countries the tuberculosis has a high prevalence, so tuberculosis in pregnant women isn't a rare event, all of this patient must receive antituberculosis agents. Of the extensive group of antiviral agents only few has proved clinical efficiency, of this acyclovir can be used during pregnancy with caution. At his moment there aren't sufficient information about the utility of zidovudine in pregnant women.

[Clinico-microbiological profile of urinary Staphylococcus infection in gynecologico-obstetric patients]. / Perfil clínico-microbiológico de la infección urinaria por Staphylococcus en pacientes ginecoobstétricas.

The Enterobacteriaceae are the major cause of urinary tract infections (UTI). The Gram-positive Cocci also produce UTI, of these Staphylococcus saprophyticus are the most frequent reported. To know the clinical and microbiological characteristics of the UTI caused by Staphylococcus in the gyneco-obstetric patients, we made a prospective study of the case identified at the Instituto Nacional de Perinatología during the period from January to July 1992. There were 32 cases, 19 cystourethritis, 12 asymptomatic bacteriuria, and one pyelonephritis. Twenty nine of the Staphylococcus isolated were coagulase-negative (SCN), of them Staphylococcus epidermidis was the most regained. The 82.7% of the SCN isolated had a positive slime test. The antimicrobial susceptibility tests showed a low percent of resistance to the majority of the antimicrobial agents proved excepting penicillin and gentamicin.