Screening utility, local perceptions, and care-seeking for reported jaundeesh among respondents lacking signs of icterus in rural Bangladesh.

In rural Bangladesh, acute viral hepatitis presents a significant burden on the public-health system. As part of the formative work for a large epidemiologic study of hepatitis E in rural Bangladesh, we sought to identify local terms that could be used for population-based screening of acute viral hepatitis. Exploration of the local term jaundeesh for screening utility identified a high burden of reported jaundeesh among individuals without symptoms of icterus. Recognizing that local perceptions of illness may differ from biomedical definitions of disease, we also sought to characterize the perceived aetiology, care-seeking patterns, diagnostic symptoms, and treatments for reported jaundeesh in the absence of icteric symptoms to inform future population-based studies on reported morbidities. We conducted a cross-sectional survey among 1,441 randomly-selected subjects to identify the prevalence of reported jaundeesh and to test the validity of this local term to detect signs of icterus. To characterize the perceived aetiology and care-seeking patterns for jaundeesh among the majority of respondents, we conducted in-depth interviews with 100 respondents who self-reported jaundeesh but lacked clinical signs of icterus. To describe diagnostic symptoms and treatments, in-depth interviews were also performed with 25 kabirajs or traditional faith healers commonly visited for jaundeesh. Of the 1,441 randomly-selected participants, one-fourth (n=361) reported jaundeesh, with only a third (n=122) reporting yellow eyes or skin, representative of icterus; Jaundeesh had a positive predictive value of 34% for detection of yellow eyes or skin. Anicteric patients with reported jaundeesh perceived their illnesses to result from humoral imbalances, most commonly treated by amulets, ritual handwashing, and bathing with herbal medicines. Jaundeesh patients primarily sought folk and spiritual remedies from informal care providers, with only 19% visiting allopathic care providers. Although the local term jaundeesh appeared to have limited epidemiologic utility to screen for acute symptomatic viral hepatitis, this term described a syndrome perceived to occur frequently in this population. Future population-based studies conducting surveillance for acute hepatitis should use caution in the use and interpretation of self-reported jaundeesh. Further study of jaundeesh may provide insight into the appropriate public-health response to this syndrome.

Selective cell cycle arrest and induction of apoptosis in human prostate cancer cells by a polyphenol-rich extract of Solanum nigrum.

Progression of prostate cancer is associated with escape of tumor cells from cell cycle arrest and apoptosis. Agents capable of selectively eliminating cancer cells by cell cycle arrest and/or induction of apoptosis offer a highly desirable approach. Here we demonstrate that a polyphenolic extract derived from ripe berries of Solanum nigrum (SN) differentially causes cell cycle arrest and apoptosis in various human prostate cancer cells without affecting normal prostate epithelial cells. Virally transformed normal human prostate epithelial PZ-HPV-7 cells and their cancer counterpart CA-HPV-10 cells, were used to evaluate the growth-inhibitory effects of the SN extract. SN treatment (5-20 µg/ml) of PZ-HPV-7 cells resulted in growth inhibitory responses of low magnitude. In sharp contrast, SN treatment of CA-HPV-10 cells increased cytotoxicity, decreased cell viability and induced apoptosis. Similar results were noted in the human prostate cancer LNCaP, 22Rv1, DU145 and PC-3 cell lines, where significant reductions in cell viability and induction of apoptosis was observed in all these cells, an effect independent of disease stage and androgen association. Cell cycle analysis revealed that SN treatment (5-20 µg/ml) resulted in a dose-dependent G2/M phase arrest and subG1 accumulation in the CA-HPV-10 but not in the PZ-HPV-7 cell line. Our results, for the first time, demonstrate that the SN extract is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. SN may be developed as a promising therapeutic and/or preventive agent against prostate cancer.

Effectiveness of an integrated approach to reduce perinatal mortality: recent experiences from Matlab, Bangladesh.

BACKGROUND: Improving perinatal health is the key to achieving the Millennium Development Goal for child survival. Recently, several reviews suggest that scaling up available effective perinatal interventions in an integrated approach can substantially reduce the stillbirth and neonatal death rates worldwide. We evaluated the effect of packaged interventions given in pregnancy, delivery and post-partum periods through integration of community- and facility-based services on perinatal mortality. METHODS: This study took advantage of an ongoing health and demographic surveillance system (HDSS) and a new Maternal, Neonatal and Child Health (MNCH) Project initiated in 2007 in Matlab, Bangladesh in half (intervention area) of the HDSS area. In the other half, women received usual care through the government health system (comparison area). The MNCH Project strengthened ongoing maternal and child health services as well as added new services. The intervention followed a continuum of care model for pregnancy, intrapartum, and post-natal periods by improving established links between community- and facility-based services. With a separate pre-post samples design, we compared the perinatal mortality rates between two periods--before (2005-2006) and after (2008-2009) implementation of MNCH interventions. We also evaluated the difference-of-differences in perinatal mortality between intervention and comparison areas. RESULTS: Antenatal coverage, facility delivery and cesarean section rates were significantly higher in the post- intervention period in comparison with the period before intervention. In the intervention area, the odds of perinatal mortality decreased by 36% between the pre-intervention and post-intervention periods (odds ratio: 0.64; 95% confidence intervals: 0.52-0.78). The reduction in the intervention area was also significant relative to the reduction in the comparison area (OR 0.73, 95% CI: 0.56-0.95; P = 0.018). CONCLUSION: The continuum of care approach provided through the integration of service delivery modes decreased the perinatal mortality rate within a short period of time. Further testing of this model is warranted within the government health system in Bangladesh and other low-income countries.

Zinc treatment for 5 or 10 days is equally efficacious in preventing diarrhea in the subsequent 3 months among Bangladeshi children.

We conducted a randomized, double-blind placebo controlled, community trial in rural Bangladesh in children 4-59 mo of age to compare the efficacy of a 5- and 10-d course of zinc therapy on the incidence and duration of diarrhea over the subsequent 90-d follow-up after initial treatment for an acute childhood diarrheal (ACD) episode. Children (n = 1622) with ACD were randomly allocated to either 5 or 10 d of zinc treatment. Female field workers visited each child daily, supervised the administration of zinc, recorded the duration of current episode, and the occurrence and duration of diarrhea over the subsequent 3 mo. The incidence of diarrhea over the 90 d of follow-up did not differ between the 5-d (1.08 ± 1.38 episodes) and 10-d (1.02 ± 1.35 episodes) groups (P = 0.35). Children in both groups experienced a comparable duration of diarrheal episodes (3.1 ± 5.6 d vs. 2.9 ± 5.6 d, 5-d vs. 10-d, respectively; P = 0.64) with a mean difference between groups within the defined range of equivalence. Time to onset of the first episode and the proportion children experiencing diarrhea during the 90-d follow-up also did not differ between groups. These findings suggest that among Bangladeshi children, a 5-d zinc treatment for ACD is as efficacious as 10 d in preventing diarrhea in the subsequent 3 mo.

Zinc supplementation and serum zinc during diarrhea.

OBJECTIVE: Zinc deficiency is very common in developing countries and is more pronounced during an episode of diarrhea. Supplementation with zinc improves diarrhea and might correct zinc deficiency in both the short and longer term. METHOD: We conducted a nested study within a cluster randomized treatment trial. Fifty children with diarrhea living in the zinc treated clusters, 50 children with diarrhea living in control clusters, and 50 healthy children living in the control clusters were enrolled. We assessed serum zinc at the start of the diarrhea episode, which was 1-3 days after supplementation began in zinc treated children, and again one week after the diarrhea ended and supplementation ceased. Baseline characteristics and serum zinc concentration were assessed. RESULTS: Serum zinc was low in 44% of healthy children at the first blood draw. Compared to healthy controls, serum zinc was 3.1 mmol/L higher among children with diarrhea who were supplemented with zinc at first blood draw and 1.3 mmol/L higher 3 weeks later. CONCLUSION: Zinc supplementation enhances serum zinc concentration when given as a treatment for diarrhea and helps children maintain a more adequate zinc status during the convalescent period.

Zinc therapy for diarrhoea increased the use of oral rehydration therapy and reduced the use of antibiotics in Bangladeshi children.

Excessive use of antibiotics for diarrhoea is a major contributing factor towards increasing rates of antimicrobial resistance in developing countries. Zinc therapy for diarrhoea has been shown to be beneficial in controlled efficacy trials, and it is of interest to determine if availability of zinc syrup for treatment of diarrhoea would satisfy the demand for a 'medicine' for diarrhoea, thus reducing the use of antibiotics, without competing with the use of oral rehydration therapy (ORT). This community-based controlled trial was conducted from November 1998 to October 2000, and all children aged 3-59 months in the study area were included. In this trial, the availability of zinc supplements, along with ORT and appropriate education programmes, was associated with significantly higher use of ORT and lower use of antibiotics.

Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants.

Given the high prevalence of micronutrient deficiencies and infectious diseases in infants in developing countries, an evaluation of the efficacy of different micronutrient formulations on infant morbidity is a priority. The efficacy of weekly supplementation of four different micronutrient formulations on diarrhea and acute lower respiratory infection (ALRI) morbidity was evaluated in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 799 infants aged 6 mo were randomly assigned to one of the following 5 groups: 1) 20 mg elemental iron with 1 mg riboflavin, 2) 20 mg elemental zinc with 1 mg riboflavin, 3) 20 mg iron and 20 mg zinc with 1 mg riboflavin, 4) a micronutrient mix (MM) containing 20 mg iron, 20 mg zinc, 1 mg riboflavin along with other minerals and vitamins and 5) a control treatment, 1 mg riboflavin only. Health workers visited each infant weekly until age 12 mo to feed the supplement and to collect data on diarrhea and ALRI morbidity. Hemoglobin, serum ferritin and serum zinc levels of a sample of infants were measured at 6 and 12 mo. Compared with the control group, at 12 mo, serum ferritin levels were higher in the iron + zinc group, and serum zinc levels were higher in the zinc and iron + zinc groups. Simultaneous supplementation with iron + zinc was associated with lower risk of severe diarrhea, 19% lower in all infants and 30% lower in less well-nourished infants with weight-for-age Z-score below -1. Iron + zinc supplementation was also associated with 40% lower risk of severe ALRI in less well-nourished infants. MM supplementation was associated with a 15% higher risk of diarrhea in all infants and 22% higher risk in less well-nourished infants. Intermittent simultaneous supplementation with iron + zinc seems promising; it will be useful to determine whether higher doses would provide greater benefits.

Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial.

OBJECTIVE: To evaluate the effect on morbidity and mortality of providing daily zinc for 14 days to children with diarrhoea. DESIGN: Cluster randomised comparison. SETTING: Matlab field site of International Center for Diarrhoeal Disease Research, Bangladesh. PARTICIPANTS: 8070 children aged 3-59 months contributed 11 881 child years of observation during a two year period. INTERVENTION: Children with diarrhoea in the intervention clusters were treated with zinc (20 mg per day for 14 days); all children with diarrhoea were treated with oral rehydration therapy. MAIN OUTCOME MEASURES: Duration of episode of diarrhoea, incidence of diarrhoea and acute lower respiratory infections, admission to hospital for diarrhoea or acute lower respiratory infections, and child mortality. RESULTS: About 40% (399/1007) of diarrhoeal episodes were treated with zinc in the first four months of the trial; the rate rose to 67% (350/526) in month 5 and to >80% (364/434) in month 7 and was sustained at that level. Children from the intervention cluster received zinc for about seven days on average during each episode of diarrhoea. They had a shorter duration (hazard ratio 0.76, 95% confidence interval 0.65 to 0.90) and lower incidence of diarrhoea (rate ratio 0.85, 0.76 to 0.96) than children in the comparison group. Incidence of acute lower respiratory infection was reduced in the intervention group but not in the comparison group. Admission to hospital of children with diarrhoea was lower in the intervention group than in the comparison group (0.76, 0.59 to 0.98). Admission for acute lower respiratory infection was lower in the intervention group, but this was not statistically significant (0.81, 0.53 to 1.23). The rate of non-injury deaths in the intervention clusters was considerably lower (0.49, 0.25 to 0.94). CONCLUSIONS: The lower rates of child morbidity and mortality with zinc treatment represent substantial benefits from a simple and inexpensive intervention that can be incorporated in existing efforts to control diarrhoeal disease.