Hrishikesh Chakraborty

Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.

ObjectiveTo develop a model to predict transmission of HIV-1 from men to women. DesignHIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to develop a probabilistic model. SettingsSemen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois. ParticipantsEighty-six men (not receiving antireroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined. Main outcome measuresPrediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume × HIV RNA copies/ml seminal plasma). ResultsThe model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse. ConclusionsThis model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.

Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial

BACKGROUND Postpartum haemorrhage is a major cause of maternal mortality in the developing world. Although effective methods for prevention and treatment of such haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in resource-poor settings where many births occur at home. We aimed to investigate whether oral misoprostol, a potential alternative to oxytocin, could prevent postpartum haemorrhage in a community home-birth setting. METHODS In a placebo-controlled trial undertaken between September, 2002, and December, 2005, 1620 women in rural India were randomised to receive oral misoprostol (n=812) or placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss. The primary outcome was the incidence of acute postpartum haemorrhage (defined as > or =500 mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The trial was registered with the US clinical trials database (http://www. clinicaltrials.gov) as number NCT00097123. FINDINGS Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91]. One case of postpartum haemorrhage was prevented for every 18 women treated. Misoprostol was also associated with a decrease in mean postpartum blood loss (262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group. Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control. INTERPRETATION Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss. The drugs low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings.

Trichomonas vaginalis as a cause of urethritis in Malawian men.

BACKGROUND AND OBJECTIVES Trichomonas vaginalis is one of the most common sexually transmitted infections. In Malawi, rates of trichomoniasis in women are high. The prevalence of T. vaginalis infection in men is expected to be high but has not previously been documented. GOALS We sought to determine the prevalence of trichomoniasis in Malawian men with and without urethritis, to evaluate a polymerase chain reaction detection assay for T. vaginalis in urethral swabs and to examine the effect of T. vaginalis infection on excretion of human immunodeficiency virus (HIV) in semen. STUDY DESIGN Men presenting at the Sexually Transmitted Diseases (STD) and Dermatology Clinics in Malawi were enrolled in a cross-sectional study. We compared a polymerase chain reaction-based test for T. vaginalis detection with wet-mount microscopy and culture of urethral swabs. HIV serology was determined by enzyme-linked immunosorbent assay (ELISA), and HIV-1 RNA concentrations in semen were measured by quantitative nucleic acid sequence-based analysis. RESULTS T. vaginalis was detected in 51 of 293 men. The estimated prevalence among symptomatic men was 20.8% and among asymptomatic men, 12.2%. Polymerase chain reaction performed with a sensitivity of 0.82 (95% CI: 0.66-0.92) and specificity of 0.95 (95% CI: 0.91-0.97) compared to wet-mount microscopy and culture. There was no difference in the rate of HIV seropositivity in men with and without T. vaginalis infection. However, in men with symptomatic urethritis, the median HIV RNA concentration in seminal plasma from men with T. vaginalis was significantly higher that in seminal plasma from HIV-positive men without trichomonas.

Effects of genital tract inflammation on human immunodeficiency virus type 1 V3 populations in blood and semen.

ABSTRACT We have examined cell-free viral populations in the blood plasma and seminal plasma compartments of men infected with subtype C human immunodeficiency virus type 1 (HIV-1) using the V3-specific heteroduplex tracking assay (V3-HTA). We studied two cohorts of subjects who had visited either a sexually transmitted disease (STD) clinic for genital tract inflammation in the form of urethritis (n = 43) or a dermatology clinic (controls,n = 14) in Malawi. We have previously shown that the presence of urethritis is associated with an eightfold increase in virus load in the seminal plasma compartment (M. S. Cohen et al., Lancet 349:1868–1873, 1997). The purpose of this study was to determine whether genital tract inflammation and its treatment caused genetic instability in cell-free HIV-1 populations. In a cross-sectional analysis at study entry, three-fourths of the STD and control subjects had multiple V3 populations in their blood while 60% of the STD subjects and 79% of the control subjects had multiple V3 populations in their semen. Overall, one-fourth of all of the subjects showed discordance between results with blood and semen specimens when samples were compared for the presence and absence of subpopulations. When differences in the relative levels of abundance of bands were also taken into account, two-fifths of all of the subjects showed discordance between the compartments. Among the subset of subjects in whom multiple virus populations could be detected, half showed discordance between the compartments. There were no differences between STD and control cohorts for these comparisons of the compartments in this cross-sectional analysis at study entry. Longitudinal analysis of the viral populations from two separate clinic visits over 1 to 4 weeks showed that the complexity of each V3 population as measured by Shannon entropy was different in blood and semen at the two time points, indicating that the blood and semen constitute different compartments for HIV-1. The seminal plasma compartment was more dynamic than the blood plasma compartment for the STD subjects who were treated for urethritis, with changes being noted in the presence or absence of V3-HTA bands in the semen of 29% of these subjects but in the blood of only 9% of these subjects. However, the changes were generally small. Overall, our results suggest that 40% of male subjects show discordance between seminal and blood viral populations and that the complexity of each V3 population was different between the two compartments. Both of these results point to the partial independence of the seminal compartment as a viral niche within the body.

Newborn Care Training of Midwives and Neonatal and Perinatal Mortality Rates in a Developing Country

OBJECTIVE: This study was designed to test the hypothesis that 2 training programs would reduce incrementally 7-day neonatal mortality rates for low-risk institutional deliveries. METHODS: Using a train-the-trainer model, certified research midwives sequentially trained the midwives who performed deliveries in low-risk, first-level, urban, community health clinics in 2 cities in Zambia in the protocol and data collection, in the World Health Organization Essential Newborn Care (ENC) course (universal precautions and cleanliness, routine neonatal care, resuscitation, thermoregulation, breastfeeding, kangaroo care, care of small infants, and common illnesses), and in the American Academy of Pediatrics Neonatal Resuscitation Program (in-depth basic resuscitation). Data were collected during 3 periods, after implementation of each training course. RESULTS: A total of 71 689 neonates were enrolled in the 3 study periods. All-cause, 7-day neonatal mortality rates decreased from 11.5 deaths per 1000 live births to 6.8 deaths per 1000 live births after ENC training (relative risk: 0.59 [95% confidence interval: 0.48–0.77]; P < .001), because of decreases in rates of deaths attributable to birth asphyxia and infection. Perinatal mortality rates but not stillbirth rates decreased. The 7-day neonatal mortality rate was decreased further after Neonatal Resuscitation Program training, after correction for loss to follow-up monitoring. CONCLUSIONS: ENC training for midwives reduced 7-day neonatal mortality rates in low-risk clinics. Additional in-depth basic training in neonatal resuscitation may reduce mortality rates further.

Effect of WHO newborn care training on neonatal mortality by education

BACKGROUND Ninety-nine percent of the 4 million neonatal deaths per year occur in developing countries. The World Health Organization (WHO) Essential Newborn Care (ENC) course sets the minimum accepted standard for training midwives on aspects of infant care (neonatal resuscitation, breastfeeding, kangaroo care, small baby care, and thermoregulation), many of which are provided by the mother. OBJECTIVE The aim of this study was to determine the association of ENC with all-cause 7-day (early) neonatal mortality among infants of less educated mothers compared with those of mothers with more education. METHODS Protocol- and ENC-certified research nurses trained all 123 college-educated midwives from 18 low-risk, first-level urban community health centers (Zambia) in data collection (1 week) and ENC (1 week) as part of a controlled study to test the clinical impact of ENC implementation. The mothers were categorized into 2 groups, those who had completed 7 years of school education (primary education) and those with 8 or more years of education. RESULTS ENC training is associated with decreases in early neonatal mortality; rates decreased from 11.2 per 1000 live births pre-ENC to 6.2 per 1000 following ENC implementation (P < .001). Prenatal care, birth weight, race, and gender did not differ between the groups. Mortality for infants of mothers with 7 years of education decreased from 12.4 to 6.0 per 1000 (P < .0001) but did not change significantly for those with 8 or more years of education (8.7 to 6.3 per 1000, P = .14). CONCLUSIONS ENC training decreases early neonatal mortality, and the impact is larger in infants of mothers without secondary education. The impact of ENC may be optimized by training health care workers who treat women with less formal education.

Extremely Low Birth Weight and Infant Mortality Rates in the United States

OBJECTIVE: Infant mortality rates (IMR) and neonatal mortality rates (NMR) in the United States have not decreased recently. The purpose of this study was to determine the contributions of birth weight and gestational age subgroups to the IMR and NMR in the United States. METHODS: We used the most recent (1983–2005) US linked birth and infant death data and simple regression analysis to determine the contributions of specific birth weight and gestational age subgroups to trends in IMR and NMR. RESULTS: IMR and NMR decreased between 1983 and 2005 for all birth weight and gestational age subgroups. There was an increase in births of very low birth weight infants from 1.2% to 1.5% (P < .001) over this period. The proportion of very low birth weight–infant deaths increased from 42.9% to 54.8%, resulting in recent nonsignificant declines in IMR and NMR. The proportion of live-birth infants <500 g increased from 0.12% to 0.18% (P < .001). The adjusted IMR and NMR over time (excluding infants <500 g) have steeper declining trends than the ones including infants <500 g. The changes in overall IMR and NMR in recent years (2000–2005) are not statistically significant. However, the adjusted IMR and NMR trends during this time are highly significant. CONCLUSIONS: The increased proportions of infants <500 g and other low birth weight infants contribute greatly to the lack of a decrease in IMR and NMR from 2000 to 2005, although birth weight– and gestational age–specific IMR and NMR continue to decrease.

Trends of Gonorrhea and Chlamydial Infection during 1985–1996 among Active-Duty Soldiers at a United States Army Installation

High rates of sexually transmitted diseases (STDs) have been reported in military populations. However, it remains uncertain whether the incidence of STDs is higher among military personnel than in the civilian population. The annual incidence of gonorrhea and chlamydia from 1985 through 1996 at Fort Bragg, North Carolina, was determined by use of a clinic database and demographic information for the entire installation. A direct standardization for age, sex, and race/ethnicity was performed, and the adjusted annual rates among active duty soldiers were compared with rates among men and women in North Carolina and the United States. Results showed that the adjusted incidence of gonorrhea and chlamydia among Fort Bragg soldiers remained higher overall than comparable state and national rates during the period of analyses. The 1996 adjusted chlamydia rates for male and female active duty soldiers were 3-fold to 6-fold higher than rates for males and females in North Carolina and in the United States as a whole. STDs continue to lead to significant morbidity in this representative military population.

Causes of community stillbirths and early neonatal deaths in low-income countries using verbal autopsy: an International Multicenter Study.

Objective:Six million stillbirths (SB) and early neonatal deaths (END) occur annually worldwide, mostly in rural settings distant from health facilities. We used verbal autopsy (VA), to understand causes of non-hospital, community-based SB and END from four low-income countries.Study Design:This prospective observational study utilized the train-the-trainer method. VA interviewers conducted standardized interviews; in each country data were reviewed by two local physicians who assigned an underlying causes of deaths (COD).Result:There were 252 perinatal deaths (118 END; 134 SB) studied from pooled data. Almost half (45%) the END occurred on postnatal day 1, 19% on the second day and 16% the third day. Major early neonatal COD were infections (49%), birth asphyxia (26%), prematurity (17%) and congenital malformations (3%). Major causes of SB were infection (37%), prolonged labor (11%), antepartum hemorrhage (10%), preterm delivery (7%), cord complications (6%) and accidents (5%).Conclusion:Many of these SB and END were from easily preventable causes. Over 80% of END occurred during the first 3 days of postnatal life, and >90% were due to infection, birth asphyxia and prematurity. The causes of SB were more varied, and maternal infections were the most common cause. Increased attention should be targeting at interventions that reduce maternal and neonatal infections and prevent END, particularly during the first 3 days of life.

Side effects of oral misoprostol for the prevention of postpartum hemorrhage: Results of a community-based randomised controlled trial in rural India

Objective. To investigate the side effects of 600 μg oral misoprostol given for the mother and the newborn to prevent postpartum hemorrhage (PPH). Methods. One thousand six hundred twenty women delivering at home or subcentres in rural India were randomised to receive misoprostol or placebo in the third stage of labour. Women were evaluated for shivering, fever, nausea, vomiting and diarrhea at 2 and 24 h postpartum. Newborns were evaluated within 24 h for diarrhea, vomiting and fever. Symptoms were graded as absent, mild-to-moderate or severe. Results. Women who received misoprostol had a significantly greater incidence of shivering (52%vs. 17%, p < 0.001) and fever (4.2%vs. 1.1%, p < 0.001) at 2 h postpartum compared with women who received placebo. At 24 h, women in the misoprostol group experienced significantly more shivering (4.6%vs. 1.4%, p < 0.001) and fever (1.4%vs. 0.4%, p < 0.03). There were no differences in nausea, vomiting or diarrhea between the two groups. There were no differences in the incidence of vomiting, diarrhea or fever for newborns. Conclusions. Misoprostol is associated with a significant increase in postpartum maternal shivering and fever with no side effects for the newborn. Given its proven efficacy for the prevention of PPH, the benefits of misoprostol are greater than the associated risks.