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In this study, we report on the prevalence of 19 virulence genes in enteroaggregative Escherichia coli (EAEC) isolates from northern South Africa. Stool samples obtained prospectively from 97 children from 1 to 12 months of age were analyzed, and EAEC isolates were confirmed based on the presence of aaiC or aatA genes. We investigated 177 enteroaggregative Escherichia coli isolates for the prevalence of virulence genes using multiplex polymerase chain reaction. The chromosomal gene aaiC was detected at higher frequency (48.0%) compared with aatA (26.0%). The gene encoding the open reading frame Orf61 was the most prevalent putative virulence trait detected among the isolates (150/177; 84.7%). None of the genes was statistically associated with diarrhea (P > 0.05). Detection rates were higher during 7-12 month of life with an association observed for the pic gene and the age group 7-12 months (P = 0.04). Winter was the season with the highest detection rates. Our data reveal a high prevalence of Orf61, Orf3, and astA in South African EAEC isolates. Specific genes may provide additional markers for the study of disease associations with age and season of sample collection.

Understanding the complex relationship between early childhood infectious diseases, nutritional status, poverty, and cognitive development is significantly hindered by the lack of studies that adequately address confounding between these variables. This study assesses the independent contributions of early childhood diarrhea (ECD) and malnutrition on cognitive impairment in later childhood. A cohort of 131 children from a shantytown community in northeast Brazil was monitored from birth to 24 months for diarrhea and anthropometric status. Cognitive assessments including Test of Nonverbal Intelligence (TONI), coding tasks (WISC-III), and verbal fluency (NEPSY) were completed when children were an average of 8.4 years of age (range = 5.6–12.7 years). Multivariate analysis of variance models were used to assess the individual as well as combined effects of ECD and stunting on later childhood cognitive performance. ECD, height for age (HAZ) at 24 months, and weight for age (WAZ) at 24 months were significant univariate predictors of the studies three cognitive outcomes: TONI, coding, and verbal performance (P < 0.05). Multivariate models showed that ECD remained a significant predictor, after adjusting for the effect of 24 months HAZ and WAZ, for both TONI (HAZ, P = 0.029 and WAZ, P = 0.006) and coding (HAZ, P = 0.025 and WAZ, P = 0.036) scores. WAZ and HAZ were also significant predictors after adjusting for ECD. ECD remained a significant predictor of coding (WISC III) after number of household income was considered (P = 0.006). This study provides evidence that ECD and stunting may have independent effects on children's intellectual function well into later childhood.

Fecal biomarkers have emerged as important tools to assess intestinal inflammation and enteropathy. The aim of this study was to investigate the correlations between the fecal markers, myeloperoxidase (MPO), lactoferrin (FL), calprotectin (FC) and lipocalin-2 (Lcn-2), and to compare differences by breastfeeding status as well as normalization by fecal protein or by fecal weight. Simultaneous, quantitative MPO, FL, FC and Lcn-2, levels were determined in frozen fecal specimens collected from 78 children (mean age 15.2 ± 5.3 months) in a case-control study of childhood malnutrition in Brazil. The biomarker concentrations were measured by enzyme- linked immunosorbent assay. The correlations among all biomarkers were significant (P

Malnutrition results in serious consequences for growth and cognitive development in children. We studied select child and maternal biologic factors, socioeconomic factors, enteric pathogenic burden and gut function biomarkers in 402 children 6-24 months of age in Northeastern Brazil. In this prospective case-control study, not being fed colostrum [odds ratio (OR): 3.29, 95% confidence interval (CI): 1.73-6.26], maternal age ≥18 years (OR: 1.88, 95% CI: 1.10-3.22) and no electric fan (OR: 2.46, 95% CI: 1.22-4.96) or bicycle (OR: 1.80, 95% CI: 1.10-2.95) in the household were positively associated, and higher birth weight (OR: 0.27, 95% CI: 0.19-0.38), larger head circumference (OR: 0.74, 95% CI: 0.66-0.82) and shortness of breath in the last 2 weeks (OR: 0.49, 95% CI: 0.27-0.90) were negatively associated with malnutrition. Subclinical enteric pathogen infections were common, and enteroaggregative Escherichia coli infections were more prevalent in malnourished children (P = 0.045). Biomarkers such as the lactulose-mannitol test, myeloperoxidase, neopterin and calprotectin were highly elevated in both malnourished and nourished children. Nourished children had a better systemic immune response than the malnourished children, as detected by elevated serum amyloid A-1 and soluble cluster of differentiation protein 14 biomarkers (P < 0.001). Serum amyloid A-1 and soluble cluster of differentiation protein 14 were also associated with better nutritional Z scores. Neonatal, maternal and socioeconomic factors were associated with malnutrition in children. There was a substantial subclinical enteric pathogen burden, particularly with enteroaggregative E. coli, in malnourished children.

Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared with the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh). After ranking SNPs by these statistics, we identified the top 10 highly differentiated SNPs in five genome regions in the LSBL tests of Brazilian Amerindian ancestry compared to European and African; and the top 10 SNPs in eight regions comparing their Amerindian component to the closest Asian 1000 Genomes population. We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the genes ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) were most highly differentiated in the Asian comparison. These genes are known to influence immune function, metabolic and anthropometry traits, and embryonic development. These analyses have identified candidate genes for selection within Amerindian ancestry, and by comparison of the two analyses, those for which the differentiation may have arisen during the migration from Asia to the Americas.

We validated a handheld point-of-care lactate (POCL) monitor's ability to measure lactate in cerebrospinal fluid (CSF) and diagnose bacterial meningitis in Uganda. There was a strong linear correspondence between POCL and standard laboratory lactate test results (R2 = 0.86; P < 0.001). For 145 patients with clinical meningitis, the area under the receiver operating characteristic curve for the prediction of bacterial meningitis by CSF POCL was 0.92 (95% confidence interval = 0.85–0.99, P < 0.001). A CSF POCL concentration of 7.7 mmol/L provided 88% sensitivity and 90% specificity for the diagnosis of bacterial meningitis. CSF POCL testing had excellent use in the diagnosis of bacterial meningitis, and it may be useful where CSF analyses are delayed or laboratory infrastructure is limited.

OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

Objectives Deficits in weight gain and linear growth are seen frequently among children in areas where malnutrition and recurrent infections are common. Although both inflammation and malnutrition can result in growth hormone (GH) resistance, the interrelationships of infection, inflammation, and growth deficits in developing areas remain unclear. The aim of this study was to evaluate relationships between low levels of systemic inflammation, growth factors, and anthropometry in a case–control cohort of underweight and normal weight children in northern Brazil. Methods We evaluated data from 147 children ages 6 to 24 mo evaluated in the MAL-ED (Interactions of Malnutrition and Enteric Disease) case–control study following recruitment from a nutrition clinic for impoverished families in Fortaleza, Brazil. We used nonparametric tests and linear regression to evaluate relationships between current symptoms of infections (assessed by questionnaire), systemic inflammation (assessed by high-sensitivity C-reactive protein [hsCRP]), the GH insulin-like growth factor-1 (IGF-1) axis, and measures of anthropometry. All models were adjusted for age and sex. Results Children with recent symptoms of diarrhea, cough, and fever (compared with those without symptoms) had higher hsCRP levels; those with recent diarrhea and fever also had lower IGF-1 and higher GH levels. Stool myeloperoxidase was positively associated with serum hsCRP. hsCRP was in turn positively associated with GH and negatively associated with IGF-1 and IGF-binding protein-3 (IGFBP-3), suggesting a state of GH resistance. After adjustment for hsCRP, IGF-1 and IGFBP-3 were positively and GH was negatively associated with Z scores for height and weight. Conclusions Infection and inflammation were linked to evidence of GH resistance, whereas levels of GH, IGF-1, and IGFBP-3 were associated with growth indices independent of hsCRP. These data implicate complex interrelationships between infection, nutritional status, GH axis, and linear growth in children from a developing area., Highlights • Among children in this developing area, symptoms of illness correlated with high-sensitivity C-reactive protein (hsCRP). • hsCRP correlated positively with growth hormone (GH) and negatively with insulin-like growth factor (IGF)-1 and IGF-binding protein-3 (IGFBP-3). • IGF-1 and IGFBP-3 correlated positively with height. • These data are consistent with a model of inflammation-induced GH resistance.

We evaluated the association between severity of sepsis and in-hospital mortality in 150 patients with non-surgical sepsis at a regional referral hospital in Uganda. In-hospital mortality occurred in 5 of 52 (9.6%) patients with sepsis, 24 of 71 (33.8%) patients with severe sepsis, and 16 of 27 (59.3%) patients with septic shock. In the multivariate analysis, the identification of severe sepsis (adjusted hazard ratio [AHR] = 2.9, 95% confidence interval [CI] = 1.0–8.2, P = 0.04), septic shock (AHR = 5.7, 95% CI = 1.6–20.3, P = 0.007), and dysfunction of three or more organs (AHR = 2.9, 95% CI = 1.1–7.3, P = 0.03) increased the risk of in-hospital mortality. Adding aggregate organ dysfunction to the multivariate equation that included the sepsis category statistically significantly improved the model, but the opposite did not. Predictors of mortality were easily measurable and could be used to risk stratify critically ill patients in resource-constrained settings.

Dysglycemia during sepsis is associated with poor outcomes in resource-rich settings. In resource-limited settings, hypoglycemia is often diagnosed clinically without the benefit of laboratory support. We studied the utility of point-of-care glucose monitoring to predict mortality in severely septic patients in Uganda.Prospective observational study.One national and two regional referral hospitals in Uganda.We enrolled 532 patients with sepsis at three hospitals in Uganda. The analysis included 418 patients from the three sites with inhospital mortality data, a documented admission blood glucose concentration, and evidence of organ dysfunction at admission (systolic blood pressure≤100 mm Hg, lactate4 mmol/L, platelet number100,000/μL, or altered mental status).None.We evaluated the association between admission point-of-care blood glucose concentration and inhospital mortality. We also assessed the accuracy of altered mental status as a predictor of hypoglycemia. Euglycemia occurred in 33.5% (140 of 418) of patients, whereas 16.3% (68 of 418) of patients were hypoglycemic and 50.2% (210 of 418) were hyperglycemic. Univariate Cox regression analyses comparing in-hospital mortality among hypoglycemic (35.3% [24 of 68], hazard ratio 2.0, 95% confidence interval 1.2-3.6, p=.013) and hyperglycemic (29.5% [62 of 210], hazard ratio 1.5, 95% confidence interval 0.96-2.4, p=.08) patients to euglycemic (19.3% [27 of 140]) patients showed statistically significantly higher rates of inhospital mortality for patients with hypoglycemia. Hypoglycemia (adjusted hazard ratio 1.9, 95% confidence interval 1.1-3.3, p=.03) remained significantly and independently associated with inhospital mortality in the multivariate model. The sensitivity and specificity of altered mental status for hypoglycemia were 25% and 86%, respectively.Hypoglycemia is an independent risk factor for inhospital mortality in patients with severe sepsis and cannot be adequately assessed by clinical examination. Correction of hypoglycemia may improve outcomes of critically ill patients in resource-limited settings.

Prolonged episodes of acute diarrhea (ProD; duration 7-13 days) or persistent diarrhea (PD; duration ≥14 days) are important causes of undernutrition, yet the epidemiology and nutritional impact of ProD are poorly understood.We conducted a 10-year cohort study of 414 children from a Brazilian shantytown who were followed from birth; data were collected on diarrhea, enteric pathogens, and anthropometry.During 1276 child-years of observation, we recorded 3257 diarrheal episodes. ProD was twice as common as PD (12% and 5% of episodes, respectively); ProD and PD together accounted for 50% of all days with diarrhea. ProD was more common in infants whose mothers had not completed primary school (relative risk [RR], 2.1; 95% confidence interval: 1.02-2.78). Early weaning was associated with earlier onset of ProD (Spearman ρ = 0.309; P = .005). Infants with ProD were twice as likely to develop PD in later childhood (log rank, P = .002) compared with infants with only acute diarrhea (AD; duration7 days), even after controlling for confounders. Children's growth was more severely stunted before their first episode of ProD, compared with AD (mean height-for-age Z score (HAZ) -0.81 vs -0.51, respectively, P.05, unpaired t test). Following ProD, HAZ (ΔHAZ = -0.232) and weight-for-age (ΔWAZ = -0.26) significantly decreased (P.005 in paired t tests). ProD was associated with Cryptosporidium and Shigella infections.ProD accounts for significant morbidity and identifies children at risk of a vicious cycle of diarrhea and malnutrition. Further studies are needed to address the recognition and control of ProD and its consequences in resource-limited settings and assess its role in PD pathogenesis.

This case-control study examines whether chronic diarrhea at initiation of antiretroviral therapy (ART) affects survival of human immunodefiency virus–infected patients. Cases (288) were treatment-naive, non-pregnant, adults with self report of frequent loose stool for > 3 weeks at the time ART was initiated. One-third of patients had an enteric pathogen identified including Cryptosporidium spp., Giardia spp., Isospora belli, Cyclospora cayetanensis, and Entamoeba histolytica. Control patients (400) did not have diarrhea when initiating ART. At six weeks, mortality was 10% in the patients with diarrhea and 5% in the patients without diarrhea (P = 0.009). Chronic diarrhea in patients requesting ART in Haiti is associated with increased early mortality.

We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sep- sis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with neg- ative malaria smears ( N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortal- ity among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank χ 2 = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores ≤ 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank χ 2 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility.

Purpose: This article reviews the relevant literature on treatment-induced alopecia in women with cancer and describes the development of a computer-assisted intervention to reduce distress associated with this side effect. Description of program: Alopecia has been cited as the most disturbing anticipated side effect by up to 58% of women preparing for chemotherapy, with 8% being at risk for avoiding treatment. Women with cancer who experience alopecia as a side effect, compared with women with cancer and no alopecia, report lower self-esteem, poorer body image, and lower quality of life. Although physicians' recommendations are the most influential factor on cancer treatment choice, body image and effects on sexuality are the next most influential factors. A study of a computer-imaging intervention, based on concepts related to guided imagery and anticipatory grief, has been launched in an effort to aid women in coping with anticipated treatment-related alopecia. Results: While we are still waiting for final data collection and analysis from the computer intervention study, the feedback thus far has been positive. Clinical implications: The intervention described here may prove to be effective in desensitizing women with cancer to hair loss and facilitating an adjustment to self-acceptance. As such, a higher quality of life during the difficult time of coping may be maintained. The development of a computer-imaging intervention offers an opportunity to integrate a standard psychosocial intervention, personalized for each patient, into the routine patient care in the oncology setting.

Prediction of mortality may improve management and outcomes of patients with sepsis in resource-limited settings. Therefore, we evaluated the ability of a hand-held portable whole-blood lactate (PWBL) analyzer to predict mortality of patients who are admitted to the hospital with severe sepsis.A prospective observational study enrolled 253 patients at a national referral hospital in Uganda. Inclusion criteria required (1)or=2 systemic inflammatory response syndrome criteria or thermodysregulation, (2) hypotension, and (3) suspected infection. A subset of 72 patients had PWBL and standard laboratory serum lactate measured. The primary measured outcome was in-hospital mortality.Fifty-nine (81.9%) of 72 evaluated patients were infected with human immunodeficiency virus type 1. The in-hospital mortality rate was 25.7% (18 of 70), and the in- and outpatient mortality at 30 days was 41.6% (30 of 72). PWBL was positively associated with in-hospital but not outpatient mortality (P=.001). The receiver operating characteristic area under the curve for PWBL was 0.81 (P=.081). The optimal PWBL concentration for predicting in-hospital mortality (sensitivity, 88.3%; specificity, 71.2%) wasor=4.0 mmol/L. Patients with a PWBL concentrationor=4.0 mmol/L died while in the hospital substantially more often (50.0%) than did those with a PWBL concentration4.0 mmol/L (7.5%) (odds ratio, 12.3; 95% confidence interval, 3.5-48.9; [P=.001). Standard laboratory serum lactate results were inconsistent and less predictive of mortality than were those of PWBL in a multiple logistic regression model.A PWBL concentrationor=4.0 mmol/L predicts with 81% accuracy a 7-fold higher mortality of patients with sepsis than does a PWBL concentration4.0 mmol/L. PWBL testing would be useful in places where clinical decisions are limited by lack of laboratory infrastructure and poor reliability.

Enteric infections, enteropathy and undernutrition in early childhood are preventable risk factors for child deaths, impaired neurodevelopment and later life metabolic diseases. However, the mechanisms linking these exposures and outcomes remain to be elucidated, as do biomarkers for identifying children at risk. By examining the urinary metabolic phenotypes of nourished and undernourished children participating in a case-control study in Semi-Arid Brazil, we identified key differences with potential relevance to mechanisms, biomarkers and outcomes. Undernutrition was found to perturb several biochemical pathways, including choline and tryptophan metabolism, while also increasing the proteolytic activity of the gut microbiome. Furthermore, a metabolic adaptation was observed in the undernourished children to reduce energy expenditure, reflected by increased N-methylnicotinamide and reduced β-aminoisobutyric acid excretion. Interestingly, accelerated catch-up growth was observed in those undernourished children displaying a more robust metabolic adaptation several months earlier. Hence, urinary N-methylnicotinamide and β-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls. These findings have important implications for understanding contributors to long-term sequelae of early undernutrition, including cognitive, growth and metabolic functions.

The objectives were to compare first, second and third year medical students on self-perceived sexual health knowledge, comfort in addressing sexual health problems, and attitudes towards the importance of addressing sexual health issues with patients as part of a sexual health medical curriculum enhancement project. A paper-and-pencil questionnaire survey was designed and administered to first and second year medical students at the start of the fall semester, resulting in high participation rates for both years (98% and 86%, respectively). Third year students were surveyed through an on-line version of the questionnaire yielding a lower response rate (52%). Multivariate statistical analyses were used to compare knowledge, comfort and attitudes by year in medical school. Results were as follows: As might be expected, sexual health knowledge and comfort in addressing sexual health problems increased linearly from first to third year (P

Studies of extensive, full-time child care in infancy and early childhood have shown negative, positive and no effects on children's social-emotional development. The current study explored the prediction of children's behavioral adjustment 4 years after assessments of daycare center quality (e.g. caregiver-child interactions, caregiver-to-child ratios) and of the home and family environment (e.g. parental stress, discipline). Participants included 141 school-age children (73 girls) and their employed mothers (91% Euro-American) who had made use of full-time child care when the children were toddlers or preschoolers. Home environment factors and earlier behaviors were predictive of individual differences in adjustment 4 years later, particularly for maternal ratings of child behaviors. By contrast, indicators of center quality were generally unrelated to mother and teacher ratings of behavioral adjustment.

For HIV-infected patients, experiencing multiple traumas is associated with AIDS-related and all-cause mortality, increased opportunistic infections, progression to AIDS, and decreased adherence to therapy. The impact of intimate partner violence (IPV) on adherence and HIV outcomes is unknown. HIV-infected patients recruited from a public HIV clinic participated in this observational cohort study (n=251). Participants completed interviews evaluating IPV and covariates. CD4 count

Background Diarrhea is a leading cause of morbidity among children under 5 years of age in low- and middle-income countries yet the additional effects and sequelae, such as cognitive impairment associated with diarrhea, have not been quantified. Methods We quantified the association between diarrhea prevalence and cognitive outcomes while controlling for linear growth in 4 study populations. Cognition was assessed using different methods across sites and was expressed in standardized units. We built linear regression models for each study with standardized cognitive score as the outcome and diarrhea prevalence as the main predictor variable. We then conducted meta-analyses of the regression coefficients to generate pooled estimates of the association between diarrhea prevalence and cognition whilst controlling for anthropometric status and other covariates. Results Diarrhea was not a significant predictor of cognitive score in any site in the regression models or in the meta-analyses (Coefficient = 0.07; 95% CI: −0.1, 0.2). The length for age Z- score was negatively related to cognition in all sites (0.18; 95% CI: 0.14, 0.21), with coefficients remarkably similar across sites (Coefficient Range: 0.168–0.186). Conclusions We did not demonstrate an association between diarrhea and cognition with stunting included in the model. The links between diarrhea, stunting, and cognition provide additional rationale for accelerating interventions to reduce diarrhea.

To explore the genetic components of susceptibility to early childhood diarrhea (ECD), we used a quantitative genetic approach to estimate the heritability of ECD among children from two Brazilian favelas. Shared environment was used to model common exposure to environmental factors. Genetic relatedness was determined from pedigree information collected by screening household participants (n = 3,267) from two geographically related favelas located in Fortaleza, Brazil. There were 277 children within these pedigrees for whom diarrheal episodes in the first two years of life were recorded. Data on environmental exposure and pedigree relationship were combined to quantitatively partition phenotypic variance in ECD into environmental and genetic components by using a variance components approach as implemented in Sequential Oligogenic Linkage Analysis Routines program. Heritability accounted for 54% of variance in ECD and proximity of residence effect accounted for 21% (P < 0.0001). These findings suggest a substantial genetic component to ECD susceptibility and the potential importance of future genetics studies.

This case-control study examines whether chronic diarrhea at initiation of antiretroviral therapy (ART) affects survival of human immunodefiency virus–infected patients. Cases (288) were treatment-naive, non-pregnant, adults with self report of frequent loose stool for > 3 weeks at the time ART was initiated. One-third of patients had an enteric pathogen identified including Cryptosporidium spp., Giardia spp., Isospora belli, Cyclospora cayetanensis, and Entamoeba histolytica. Control patients (400) did not have diarrhea when initiating ART. At six weeks, mortality was 10% in the patients with diarrhea and 5% in the patients without diarrhea (P = 0.009). Chronic diarrhea in patients requesting ART in Haiti is associated with increased early mortality.

We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sepsis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank chi(2) = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scoresor= 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank chi(2) 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility.

Data on the relationship between the two genotypes of Giardia duodenalis that infect humans, assemblages A and B, their clinical presentation and intestinal inflammation are limited. We analyzed 108 stool samples previously collected for a diarrhoeal study among Brazilian children, representing 71 infections in 47 children. Assemblage B was most prevalent, accounting for 43/58 (74.1%) infections, while assemblage A accounted for 9/58 (15.5%) infections and 6/58 (10.3%) infections were mixed (contained both assemblage A and B). There was no significant difference in diarrhoeal symptoms experienced during assemblage A, B or mixed infections. Children with assemblage B demonstrated greater variability in G. duodenalis cyst shedding but at an overall greater level (n=43, mean 3.6 x 10(5), range 5.3 x 10(2)-2.5 x 10(6)cysts/ml) than children infected with assemblage A (n=9, mean 1.4 x 10(5), range 1.5 x 10(4)-4.6 x 10(5)cysts/ml; P=0.009). Children with mixed infections shed more cysts (mean 8.3 x 10(5), range 3.1 x 10(4)-2.8 x 10(6)cysts/ml) than children with assemblage A or B alone (P=0.069 and P=0.046 respectively). This higher rate of cyst shedding in children with assemblage B may promote its spread, accounting for its increased incidence. Additionally, second and third infections had decreasing faecal lactoferrin, suggesting some protection against severity, albeit not against infection, by prior infection.

Cryptosporidium parvum is a leading pathogen in children in developing countries. To investigate whether early postnatal malnutrition leads to heavier C. parvum infections, we assessed intestinal adaptation and parasite load in suckling mice during the first 2 wk of life, analogous to the first postnatal yr in humans. Undernutrition was induced by daily C57BL6J pup separation from lactating dams. Half of the pups were separated daily, for 4 hr on day 4, 8 hr on day 5, and for 12 hr from day 6 until day 14. On day 6, each pup received an oral inoculum of 10(5) to 10(7) parasites in 10-25 microl of PBS. Littermate controls received PBS alone. Stools were assessed from days 8, 11, and 14 for oocyst counts. Mice were killed on day 14, 8 days postinoculation, at the peak of the infection. Ileal and colon segments were obtained for histology, real-time and reverse transcriptase PCR, and immunoassays. Villus and crypt lengths and cross-sectional areas were also measured. Undernourished and nourished mice infected with excysted 10(6) or 10(7) oocysts exhibited the poorest growth outcomes compared with their uninfected controls. Nourished 10(6)-infected mice had comparable weight decrements to uninfected undernourished mice. Body weight and villi were additively affected by malnutrition and cryptosporidiosis. Hyperplastic crypts and heavier inflammatory responses were found in the ilea of infected malnourished mice. Undernourished infected mice exhibited greater oocyst shedding, TNF-alpha and IFN-gamma intestinal levels, and mRNA expression compared to nourished mice infected with either 10(5) or 10(6) oocysts. Taken together, these findings show that Cryptosporidium infection can cause undernutrition and, conversely, that weanling undernutrition intensifies infection and mucosal damage.

Diarrhea is a leading cause of mortality worldwide; however, its long-term morbidity is poorly understood. Recently, early childhood diarrhea (ECD) has been associated with impaired physical fitness, growth and cognitive function 6 to 9 years later. We studied the effects of ECD on school functioning in a shantytown in northeastern Brazil.We administered 77 educational surveys. Complete diarrhea surveillance (ie,90%) in the first 2 years of life and demographic and anthropometric information were available for 73 children. Age at starting school was calculated for 62 children, whereas age appropriateness for the current grade (AFG) was calculated for all 73 children who were6 years old. Stepwise regression was used to examine the independent effect of ECD on school functioning after controlling for socioeconomic factors, maternal education, breast feeding, growth and cognitive functioning.ECD correlated with age at starting school (r = 0.55, P = 0.0005) and remained a significant predictor even after controlling for family demographics, days of breast feeding, early growth and TONI-3 test of nonverbal intelligence. This was true despite significant correlations of ECD with growth shortfalls and impaired cognitive functioning. ECD also correlated with AFG (r = 0.38, P = 0.001). Only TONI-3 test scores explained this association, suggesting that ECD may hinder school performance, but only in part school readiness, by impairing cognitive function as measured by performance on the TONI-3 nonverbal intelligence test.These findings document effects of early childhood diarrhea on later school readiness and performance and hence potential long-term human and economic costs of ECD, which warrant further attention and far greater investment for the control of ECD and its consequences.

Cryptosporidium is an important cause of infectious diarrhoea worldwide, but little is known about the course of illness when infected with different species. Over a period of 5 years, Cryptosporidium was identified in the stools of 58 of 157 children prospectively followed from birth in an urban slum (favela) in northeast Brazil. Forty isolates were available for quantification and 42 for speciation (24 Cryptosporidium hominis and 18 C. parvum). Children with C. hominis shed significantly more oocysts/ml of stool (3.5 x 10(6) vs. 1.7 x 10(6)perml; P=0.001), and oocyst counts were higher among symptomatic children (P=0.002). Heavier C. parvum shedding was significantly associated with symptoms (P=0.004), and symptomatic C. parvum-infected children were significantly more likely than asymptomatic children to be lactoferrin-positive (P=0.004). Height-for-age (HAZ) Z-scores showed significant declines within 3 months of infection for children infected with either C. hominis (P=0.028) or C. parvum (P=0.001). However, in the 3-6 month period following infection, only C. hominis-infected children continued to demonstrate declining HAZ score and asymptomatic children showed even greater decline (P=0.01). Cryptosporidium hominis is more common than C. parvum in favela children and is associated with heavier infections and greater growth shortfalls, even in the absence of symptoms.

We report the results of a 10-year follow-up recidivism study of two sex offender treatment programs for incarcerated juvenile sex offenders (JSOs) in Virginia. The programs vary in environment and intensity. The more intense JSO program ("self-contained") operates in specialized living units that are separate from those of the general juvenile incarcerated population. In the less intense program ( "prescriptive" ), JSOs remain housed with the general population of juvenile offenders. Arrest and incarceration data through January 2003 were obtained for 261 male JSOs released between 1992 and 2001. The inclusion of adult incarceration data allowed for a more accurate assessment of the actual time at risk for sexual re-offending. Outcomes are re-arrest rates, length of time to re-arrest and type of offense (property, nonsexual assault, sexual) on re-arrest, with analyses using survival curve functions. For both groups, actual re-arrest is most likely to be for a nonsexual person offense (31 and 47%, respectively) and least likely to be for a sexual offense (

The effects of heavy burdens of diarrhea in the first 2 years of life on specific executive control function like verbal fluency are not well understood. In previous studies, we have shown associations of early childhood diarrhea (ECD) with nonverbal intelligence and school functioning. Therefore, we postulated that ECD might affect early neuropsychological development leading to long-term deficits in normal cognitive development. Based on our extensive 14-year prospective cohort studies of early childhood diarrheal illnesses in a Brazilian shantytown community, we examined ECD correlations between specific impairments of higher mental function and executive skills in shantytown children 5-10 years later (now at 6-12) years of age. Specifically we examined whether heavy diarrheal illnesses correlate with reduced performance on selected tests of executive function. Our study, for the first time, suggests a disproportional impairment in semantic but not phonetic fluency in a subset of children with heavy burdens of diarrhea in their first 2 years of life even when controlling for maternal education, breastfeeding, and child schooling. Similar semantic decrements have been associated with impaired recovery from brain injury. These exploratory studies suggest the importance of verbal fluency tests to assess executive functioning in children challenged by poor nutrition and diarrhea in early life. In addition, our unique findings show the potential influences of early childhood diarrhea on language development that is so critical to productive adulthood and potentially set a foundation for new neuropsychological approaches, which assess early burdens of enteric illnesses on childhood development.

Objective This study reports the results of a placebo-controlled, double-blind comparison of bupropion sustained release (SR) as an antidote for sexual dysfunction versus placebo in 42 patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. Exploratory analyses of the association of testosterone and sexual functioning in women in the study were also performed. Method Patients with DSM-IV major depression who experienced a therapeutic response to any SSRI and were experiencing medication-induced global or phase-specific sexual dysfunction, as measured by the Changes in Sexual Functioning Questionnaire (CSFQ), were randomly assigned to receive either bupropion SR 150 mg b.i.d. or placebo for 4 weeks in addition to the SSRI. Total testosterone levels were assessed at baseline and week 4. Results The difference in global sexual functioning, based on the total CSFQ score, was not statistically significant between the 2 groups at week 4, nor were differences in orgasm, desire/ interest as measured by sexual thoughts, or self-reported arousal. There was a statistically significant difference between the 2 groups at week 4 in desire as measured by self-report feelings of desire and frequency of sexual activity. Desire/ frequency showed a significantly greater improvement among those patients receiving bupropion SR compared with placebo (Wilk's F = 5.47, df = 1, p =.024). Frequency was significantly correlated to total testosterone level at baseline (r = 0.36, p =.027) and at week 4 (r = 0.41, p =.025). Conclusions Bupropion SR, as an effective antidote to SSRI-induced sexual dysfunction, produced an increase in desire to engage in sexual activity and frequency of engaging in sexual activity compared with placebo. A larger study is needed to further investigate this finding.

Background: We examine changes in sexual functioning and depressive symptoms in patients' transition from a selective serotonin reuptake inhibitor (SSRI), which induced both a therapeutic response and sexual dysfunction, to bupropion sustained release (SR) over the course of an 8-week trial. Method: The study included 11 adults (8 women and 3 men) who had a DSM-IV diagnosis of major depressive disorder in remission (Hamilton Rating Scale for Depression [HAM-D] score < 11) and were receiving an SSRI. Depression (using the HAM-D) and sexual dysfunction (using the Changes in Sexual Functioning Questionnaire) were assessed at baseline, 2 weeks after bupropion SR was added to the current antidepressant (combined treatment), 2 weeks after taper of the SSRI was initiated and completed, and after 4 weeks of bupropion SR monotherapy. T tests were performed to assess changes in depression and sexual function. Results: Patient participation dropped from the initial group of 11 at week 2 to 9 at week 4 and to 6 by week 8. Sexual functioning improved from week 0 (baseline) to week 2 and from week 2 to week 4. The patients showed no significant change in mean HAM-D scores in weekly comparisons during the study period; 55% of patients completed the substitution without significant adverse events or recurrence of depressive symptoms. Conclusion: Bupropion SR as a treatment for depression also alleviates sexual dysfunction due to SSRI treatment. Results show that sexual functioning improves after the addition of bupropion SR to SSRI treatment and continues to improve, after discontinuation of the SSRI, with bupropion SR treatment alone.