Evaluation of the effectiveness of a latrine intervention in the reduction of childhood diarrhoeal health in Nyando District, Kisumu County, Kenya.

Community-led total sanitation (CLTS) is an intervention that strives to end the practice of open defaecation. This study measured the effectiveness of CLTS in Nyando District by examining the association between community open defaecation-free (ODF) status and childhood diarrhoeal illness. A cross-sectional study design was used among households with children ⩽5 years old to ascertain information on acute diarrhoea in the past year (outcome), sanitation and health behaviours. Water testing was conducted to determine Escherichia coli and turbidity levels for 55 water sources. Data were obtained from 210 parents or caregivers from an ODF community and 216 parents or caregivers in a non-ODF community. The non-ODF participants reported a non-significant 16% increased risk of diarrhoea compared with the participants from the ODF community. Children's HIV positivity (adjusted prevalence ratio (aPR) = 2.29; 95% CI 2.07-2.53), unsafe child stool disposal (aPR = 1.92; 95% CI 1.74-2.12) and low household income (aPR = 1.93; 95% CI 1.46-2.56) were associated with diarrhoea, in the non-ODF community. The ODF location had a higher percentage of E. coli in the drinking water compared with the non-ODF location (76.7% vs. 60%). Diarrhoeal disease rates in children ⩽5 years old did not differ by whether a latrine intervention was implemented. Water sampling findings suggest water safety may have decreased the effectiveness of the CLTS' improvement of childhood diarrhoea. Improved water treatment practices, safe stool disposal and education may improve the CLTS intervention in ODF communities and therefore reduced the risk of childhood diarrhoea.

Identification of three novel human leukocyte antigen alleles, HLA-B*58:43, HLA-C*03:190, and HLA-DPA1*01:12, in an East African cohort.

Three novel human leukocyte antigen (HLA) alleles were identified using a sequence-based typing of HLA class I and class II alleles of 1867 participants from a male circumcision cohort in Kenya. The new alleles were first identified by sequencing and then confirmed by cloning the polymerase chain reaction (PCR) products and sequencing multiple clones. HLA-B*58:43 was identical to HLA-B*58:02 with the exception of a nucleotide change at codon 125 in exon 3 (GCC→ACC), and resulted in the amino acid change from Alanine to Threonine. HLA-C*03:190 was identical to HLA-C*03:02:01 with the exception of a nucleotide change at codon 131 in exon 3 (CGC→TGC), and resulted in the amino acid change from Arginine to Cysteine. HLA-DPA1*01:12 was identical to HLA-DPA1*01:03:01:01 with the exception of a nucleotide change at codon 66 in exon 2 (TTG→TCG), and resulted in the amino acid change from Leucine to Serine.

New diagnostics for the spectrum of asymptomatic TB: from infection to subclinical disease.

TB remains a leading cause of morbidity and mortality worldwide. However, most infected immunocompetent individuals are asymptomatic and only 5-10% of these will eventually develop active TB during their lifetime (typically within 2 years after exposure). Therefore, rapid diagnosis and efficient management of asymptomatic infected individuals who are at the highest risk of progression and transmission remain major clinical and public health challenges. In recent years, there has been important scientific progress in our understanding of the spectrum of asymptomatic Mycobacterium tuberculosis (Mtb) infections that not only includes the dynamic state of latent TB infection (LTBI), but also the preclinical state of incipient and subclinical TB. The latter is possibly as prevalent as symptomatically active TB and potentially contributes to global Mtb transmission in various settings. We summarize the latest developments and current challenges of the existing testing tools for LTBI and describe promising biomarkers and diagnostics for the spectrum of asymptomatic TB. Following the negative results of a recent clinical trial for a biomarker-guided preventive therapy approach, we also suggest some treatment options for incipient TB.

Selenium concentrations in greater scaup and dreissenid mussels during winter on Western lake ontario.

One hypothesis for the decline of the North American greater (Aythya marila) and lesser (A. affinis) scaup population is that contaminant burdens acquired on wintering or staging areas impair reproduction or cause lethal or sublethal health effects. Recent studies have found increased selenium (Se) concentrations in scaup but have focused on the fall and spring staging periods. From January to March 2006 and December to March 2006 and 2007, we analyzed liver tissues collected from greater scaup wintering in western Lake Ontario for 16 trace elements. We also measured Se concentrations in greater scaup blood and Dreissenid mussel tissue. Se was the only trace element that occurred at increased concentrations (>10 µg/g liver dry weight) in a substantial proportion (99%) of greater scaup livers. We also found that hepatic Se concentrations increased throughout winter and were increased in nearly all birds from January to March, suggesting that accumulation of this trace element occurred soon after their arrival in fall. Se concentrations were similar in male and female birds, but juvenile birds had higher concentrations than did adults. Blood Se concentrations were correlated to liver Se concentrations in 2006 only, suggesting that blood Se concentration is an unreliable predictor of liver concentration. Se in Dreissenid mussels generally decreased with mussel size and did not change throughout winter. Overall, our results suggest that greater scaup wintering on western Lake Ontario acquire sufficiently high Se concentrations to potentially impact their health. Thus, several indicators of health and survival should be examined in relation to Se concentrations in wintering scaup.

Herpes simplex virus type 2 antibody detection performance in Kisumu, Kenya, using the Herpeselect ELISA, Kalon ELISA, Western blot and inhibition testing.

BACKGROUND: In certain parts of Africa, type-specific herpes simplex virus type 2 (HSV-2) ELISAs may have limited specificity. To date, no study has been conducted to validate HerpeSelect and Kalon type-specific HSV-2 ELISAs using both the Western blot and recombinant gG ELISA inhibition testing as reference standards. METHODS: A total of 120 men who were HIV seronegative (aged 18-24 years) provided blood samples. HSV-2 IgG serum antibodies were detected using four different methods: HerpeSelect HSV-2 ELISA (n = 120), Kalon HSV-2 ELISA (n = 120), University of Washington Western blot (n = 101) and a recombinant inhibition test (n = 93). RESULTS: HSV-2 seroprevalence differed significantly by HSV-2 detection method, ranging from 24.8% with the Western blot to 69.8% with the HerpeSelect ELISA. Using the Western blot as the reference standard, the HerpesSelect had the highest sensitivity for HSV-2 antibody detection (100%) yet lowest specificity (40%). Similar results were obtained using the inhibition test as the reference standard. The sensitivity and specificity of the Kalon test versus the Western blot were 92% and 79%, respectively, and 80% and 82% versus the inhibition test. Using the inhibition test as the reference standard, the sensitivity of the Western blot appeared low (49%). CONCLUSIONS: In men in western Kenya who were HIV seronegative, the HerpeSelect and Kalon type-specific ELISAs had high sensitivities yet limited specificities using the Western blot as reference standard. Overall, the Kalon ELISA performed better than the HerpeSelect ELISA in these young men from Kisumu. Further understanding is needed for the interpretation of HSV-2 inhibition or ELISA test positive/ Western blot seronegative results. Before HSV-2 seropositivity may be reliably reported in selected areas of Africa, performance studies of HSV-2 serological assays in individual geographical areas are recommended.

Herpes simplex virus type 2 infection among young uncircumcised men in Kisumu, Kenya.

OBJECTIVES: To identify factors associated with herpes simplex virus type 2 (HSV-2) infection among men aged 18-24 in Kisumu, Kenya. METHODS: Baseline data from a randomised trial of male circumcision were analysed. Participants were interviewed for sociodemographic and behavioural risks. The outcome was HSV-2 by antibody status. Risk factors were considered singly and in combination through logistic regression models. RESULTS: Among 2771 uncircumcised men, 766 (27.6%; 95% confidence interval (CI) 26.0% to 29.3%) tested antibody positive for HSV-2. The median age at first sex was 16 years, and the median number of lifetime sexual partners was four. HSV-2 seroprevalence increased from 19% among 18-year-olds to 43% among 24-year-olds (p<0.001). In multivariable analysis, statistically significant risks for infection were increasing age (adjusted odds ratio (AOR) = 1.22-2.58), being married or having a live-in female partner (AOR = 1.80; 95% CI 1.28 to 2.53), preferring "dry" sex (AOR = 1.39; 95% CI 1.14 to 1.69), reported penile cuts or abrasions during sex (AOR = 1.58; 95% CI 1.32 to 1.91), increasing lifetime sex partners (multiple response categories; AORs ranging from 1.65 to 1.97), and non-student occupation (multiple response categories; AORs ranging from 1.44 to 1.93). Risk decreased with reported condom used at last sex (AOR = 0.82; 95% CI 0.68 to 0.99). CONCLUSION: Primary prevention efforts should be initiated at an early age. The same behavioural interventions used currently for HIV prevention-abstinence, reducing the number of sex partners and increasing condom use-should be effective for HSV-2 prevention.

Growth hormone induces resistance to the mitogenic action of insulin through local IGF-I. Studies in normal and Pygmy T-cell lines.

Growth hormone (GH) and insulin have both mitogenic and metabolic actions. The growth-promoting effects of GH in vivo are thought to be mediated by insulin-like growth factor-I (IGF-I), whereas the metabolic effects of GH are thought to be either direct or mediated by factors other than IGF-I. In previous studies using HTLV-II-transformed T-lymphoblast cell lines established from normal individuals, we have shown that GH preincubation induces resistance to the growth-promoting (mitogenic) action of insulin. In this study, using T-cell lines from 3 American control subjects, 1 African control subject, and 1 African Pygmy (the latter previously shown to be resistant to the growth-promoting actions of both IGF-I and GH), we examined the role of local IGF-I in the mediation of GH-induced resistance to the mitogenic action of insulin. In these studies, we quantified the stimulation of T-cell colony formation in response to insulin in the presence and absence of either GH or IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor I resistance in immortalized T cell lines from African Efe Pygmies.

Previous investigations suggested that resistance to GH was the cause of short stature of African Pygmies. Because many of the actions of GH are mediated by insulin-like growth factor I (IGF-I), we sought to determine whether Pygmy tissue was responsive to IGF-I. An initial effort to obtain HTLV-II-transformed T lymphoblast cell lines resulted in a single cell line that showed complete resistance to both IGF-I and GH in a clonal proliferation assay as well as decreased IGF-I binding. In the current study, we examined T cell lines from seven Efe Pygmy subjects, three neighboring Lese farmers, and six American controls and quantified clonal responses to IGF-I, GH, and insulin. The T cell lines from the Efe Pygmies were all completely resistant to the growth-promoting actions of IGF-I concentrations less than 250 micrograms/L and GH concentrations less than 500 micrograms/L. The Lese population, with whom there is admixture with the Efe population, showed heights and clonal responses to IGF-I and GH intermediate between those of Pygmies and American controls. The Pygmy T cell lines showed reduced clonal proliferation in response to high insulin concentrations known to act through the IGF-I receptor. These findings indicate that genetic IGF-I resistance is present in the T cell lines of Efe Pygmies and suggest that unresponsiveness to IGF-I may be responsible for their short stature.

Decreased insulin-like growth factor I receptor expression and function in immortalized African Pygmy T cells.

Efe Pygmies of northeast Zaire have the shortest mean adult stature of any population on earth. Although various alterations in the GH/insulin-like growth factor I (IGF-I) axis have been suggested, the basis for short stature in the Pygmy is unknown. We previously described IGF-I unresponsiveness in a T lymphoblast cell line derived from an Efe Pygmy, and studies in five additional lines have confirmed severe IGF-I resistance in these cells. We have now performed experiments to determine the molecular basis for the IGF-I resistance in these cells. We found markedly decreased cell surface expression of IGF-I receptors with normal ligand binding affinity. The Pygmy IGF-I receptors were not autophosphorylated and did not transmit a signal in response to physiological concentrations of IGF-I. There was a substantially decreased level of IGF-I receptor messenger ribonucleic acid in the Pygmy cells with a normal messenger ribonucleic acid half-life. The nucleotide sequence of the full-length IGF receptor complementary DNA in Pygmy 1 showed no significant variation. These results indicate decreased IGF-I receptor gene transcription and IGF-I receptor signaling as the primary variation in the Pygmy cell lines. The findings point to the IGF-I receptor as the locus governing short stature in the African Pygmy and suggest that human stature may be genetically controlled by expression of the IGF-I receptor.

Male circumcision and HIV prevention: current knowledge and future research directions.

Over the past decade, numerous epidemiological studies have reported a significant association between lack of male circumcision and risk for HIV infection, leading to recommendations for male circumcision to be added to the armamentarium of effective HIV prevention strategies. We review the epidemiological data from studies that have investigated this association, including ecological, cross-sectional/case-control, and prospective studies. We discuss problematic issues in interpreting the epidemiological data, including the presence of other sexually transmitted infections, age of circumcision, and potential confounders such as religion, cultural practices, and genital hygiene. In addition, we review studies of biological mechanisms by which the presence of the foreskin may increase HIV susceptibility, data on risks associated with the circumcision procedure, and available data on the acceptability and feasibility of introducing male circumcision in societies where it is traditionally not practised. Although the evidence in support of male circumcision as an effective HIV prevention measure is compelling, residual confounding in observational studies cannot be excluded. Taken together with concerns over the potential disinhibiting effect of male circumcision on risk behaviour, and safety of the circumcision procedure, randomised trials of male circumcision to prevent HIV infection are recommended. An individual's choice to undergo male circumcision or a community's decision to promote the practice should be made in the light of the best available scientific evidence. More knowledge is required to assist individuals and communities in making those decisions. We conclude with recommendations for future research.

Computations for a best match strategy for kidney transplantation.

In some cases success or failure of a proposed innovation in transplantation may be better judged if we consider the average survival time of the graft rather than the actuarial survival at a point in time. It is suggested that HLA matching may be an example of such a case and that the possible clinical benefits of modest improvements in matching may have been underestimated. Calculations are made that show that transplanting to the best match available in a pool of 100 patients might increase the expected graft survival time by more than 1 year.

A proposal for the analysis of kidney graft survival.

A survival analysis using a model provides numerous advantages over other approaches. The effectiveness of concomitant variables in describing the data can be evaluated whether the variables are continuous or dichotomized. We can evaluate the effectiveness of such variables in describing either short- or long-term components of the risk. The expected life span of the graft may be computed with the model and complements the insight obtained from the more commonly displayed survival curves.

Assessment of prognostic factors and projection of outcomes in renal transplantation.

Analysis of data on renal transplantation collected in two large multicenter observational studies resulted in the concordant identification of five factors that correlated highly and at a substantial level of statistical significance with the outcome of unrelated cadaveric donor transplantation (i.e., they were associated with differences in one-year graft survivals of 0.07-0.21 and P values less than 0.05). These factors were: blood transfusions prior to the transplant, race of the recipient (white or black), prior failure in transplantation, level of sensitization to lymphocyte alloantigens, and diabetes as the cause of end-stage renal failure. Multivariate analysis with a mathematical survival model confirmed the importance and independence of these prognostic factors. Matching of HLA antigens appeared to be beneficial in both studies, but failed to attain high statistical significance in one. Systematic differences in the use of pretransplant splenectomy and, probably, in the nature of the antilymphocyte serum or globulin led to discordance in assessment of the importance of these factors in the two studies. Although advanced age (greater than 45 years) of the recipient was associated with reduced graft survival in both studies, analysis by means of the model failed to detect a significant correlation between the recipient's age and the outcome in one of the studies because the relation was not monotonic. In an illustration of their utility in the detailed assessment of performance, the prognostic factors were found to substantially account for the markedly superior results at one center and partly for lower graft survivals at another. These prognostic factors may be used to predict probable outcomes for populations and for individual patients subjected to particular arrays of conditioning strategies.

Effects of acidification on metal availability to aquatic biota, with special reference to filamentous algae.

A survey of 34 shield lakes in Ontario and Quebec, pH 4.4 to 7.1, was made to evaluate which metals should be considered of concern as a risk to aquatic biota or consumers when lakes are acid stressed. A set of predictions, concerning the mobilization by man, the mobility, the chemical speciation, and the toxicity or bioaccumulation of metals in acid-stressed waters, were used as a basis for designing the study and organizing the results. Attached algae were used as biomonitors to assess metal bioavailability. The study concluded that zinc, lead, aluminum, and mercury were of concern in acid-stressed lakes, while the situation for manganese was unresolved, and cadmium was not studied. Nickel and copper were of concern only when a point source was involved. The study also concluded that the attached algal community had some value as a biomonitor, for metals in acid-stressed as well as metal-polluted surface waters.

Growth of children according to maternal and child HIV, immunological and disease characteristics: a prospective cohort study in Kinshasa, Democratic Republic of Congo.

BACKGROUND: Most HIV-infection in children occurs in sub-Saharan Africa where antiretroviral therapy is seldom available. This study compares the growth progression and retardation of HIV-infected and uninfected children in the Democratic Republic of Congo (formerly Zaire). It estimates the risk for child growth retardation according to child and maternal immunological factors, severity of maternal and child illness, and maternal socioeconomic and marital status. METHODS: In a prospective cohort study of 258 children born to HIV seropositive mothers and 256 children of seronegative mothers in Kinshasa, Congo, the growth in length, weight, and weight-for-length of infected children (n = 68), uninfected children born to seropositive mothers (n = 190), and uninfected children born to uninfected mothers (n = 256) was compared. Serological, anthropometric and other clinical measures were collected monthly from 3-12 months and bi-monthly during the second year of life. Polymerase chain reaction for HIV was performed on bloods drawn at 2 days and 3 months post partum. Length-for-age, weight-for-age, and weight-for-length mean z-scores against National Center for Health Statistics (NCHS) reference data were calculated, and Cox proportional hazards models were used to estimate the risk of falling below -2.00 z-scores as a function of child and maternal immunological, clinical and sociodemographic variables. RESULTS: There was no difference in mean length-for-age at birth between HIV-infected (Group 1) children, uninfected children of infected mothers (Group 2) or Control children, but by 3 months old, HIV-infected children were shorter than both Group 2 and Controls. In weight-for-age and weight-for-length, Group 1 infants were lighter and more wasted at birth and onwards. Group 2 newborns were lighter than Controls at birth, but by three months they had caught up to Controls in both length and weight and remained the same as Controls thereafter. The odds of falling below -2.00 z-scores by 20 months for length, weight, and weight-for-length for HIV-infected children compared to uninfected children were 2.10, 2.84, and 2.56 respectively. Both HIV-infection and associated illnesses were factors associated with child stunting, underweight and wasting. The mother's age, socioeconomic status, presence of father, stage of illness and immune status had no detectable effect on the child's growth in the first two years of life. CONCLUSION: The HIV-infected children in Congo with no access to antiretroviral therapy were stunted, underweight, and wasted compared to same age uninfected children. Both HIV infection and HIV-associated signs and symptoms, not maternal immunological or socioeconomic circumstances, placed children at risk for growth retardation.

Long-term d-amphetamine in rats: lack of change in post-synaptic dopamine receptor sensitivity.

Treatment of rats with d-amphetamine (5 mg/kg) once daily for 25 days did not change locomotor responses, on day 7 of withdrawal, to dopamine (DA) or d-amphetamine into the nucleus accumbens. Nor was there a change in 3H-spiperone binding of caudate nucleus membranes. There was no effect of treatment on the locomotor response of rats to 1.0, 1.5 or 2.0 mg/kg d-amphetamine IP. However, d-amphetamine-treated rats were significantly less sensitive to 0.5 mg d-amphetamine. Although 1, 2 or 3 mg/kg apomorphine produced in same degree of stereotypy in both treatment groups, there was a significant difference in the response of the two groups to 0.5 mg apomorphine, d-amphetamine-treated animals being less sensitive than vehicle-treated animals. No change was found in brain DA levels with or without synthesis inhibition. The present data do not support the hypothesis that chronic treatment of rats with d-amphetamine can produce supersensitive post-synaptic DA receptors.

Evaluation of the HCFA model for the analysis of mortality following hospitalization.

From 1987 through 1990, the Health Care Financing Administration (HCFA) evaluated variations in the mortality rates experienced by patients admitted to hospitals participating in the Medicare program. This study was conducted to evaluate the adequacy of the model used for that purpose. Detailed clinical data were gathered on 42,773 patients admitted to 84 statistically selected hospitals. The effect of risk adjustment using the HCFA model, which is based on claims data, was compared to a risk-adjustment model based on physiologic and clinical data. Models that include claims data were markedly superior to those containing only demographic characteristics in predicting the probability of patient death, and the addition of clinical data resulted in further improvement. The correlation of ranks of hospitals based on a model that uses only the claims data and on one that uses, in addition, clinical data, was .91. As a screen for the identification of "high (mortality) outlier" hospitals, the claims model had moderate sensitivity (81 percent) and specificity (79 percent), a high negative predictive value (90 percent), and a low positive predictive value (64 percent) when compared to the clinical model. The two mortality models gave similar results when used to determine which structural characteristics of hospitals were related to mortality rates: hospitals with a higher proportion of registered nurses or board-certified physician specialists, or with a greater level of access to high-technology equipment had lower risk-adjusted mortality rates. These data suggest that the current claims-based risk-adjustment procedure may satisfactorily be used to characterize variations in mortality rates associated with hospitalization. The procedure could also be used as a basis for further epidemiological analyses of factors that affect the probability of patient death. However, it does not positively identify outlier hospitals as providers of problematic care.

Women's strategies to alleviate nutritional stress in a rural African society.

Many agricultural populations are subject to chronic or seasonal undernutrition, reproductive women and children often being most vulnerable. This paper presents quantitative and qualitative data on food consumption, food distribution practices, food taboos, garden sizes and work effort to show how Lese horticulturalist women living in the Ituri Forest of northeast Democratic Republic of Congo attempt to alleviate nutritional stress. The Lese experience an annual hunger season when approximately one quarter of the population suffer from energy deficiency. Nutritional intake is also compromised by a complex system of food taboos against meat from wild forest animals. Anthropometric data collected over several years suggest that Lese women suffer from nutritional stress more than men during the hunger season. They also have more food taboos particularly during pregnancy and lactation. Their low fertility is compounded by nutritional stress. Despite these inequities, Lese women use several strategies to improve their food intake. Since they are responsible for all household cooking, they manipulate food portions. During the hunger season, they snack frequently, and increase their consumption of palliative foods. Women with more food taboos plant larger gardens to supplement their diet with vegetable foods. Although this results in their consumption of more daily protein, they work harder compared to women with smaller gardens. Women cheat in their adherence to specific food taboos by actively discounting them, or by eating prophylactic plants that supposedly prevent the consequences (usually illness) of eating tabooed foods. In addition, women resort to subterfuge to access desirable resources. Lese women do not reduce work effort during the hunger season, but adapt physiologically by reducing resting metabolic rates during periods of weight loss. These results point to the ability of Lese women to minimize the ecological and cultural constraints on their nutrition. More data, however, are required to assess the long-term effectiveness of these strategies.

The level and tempo of children's physical activities: an observational study.

We develop an observation system that quantifies the duration, intensity, and frequency of children's physical activities. We use this system to assess the level and tempo of energy expenditure under free-ranging, natural conditions experienced by 15 children aged 6-10 yr in southern California. Observations were recorded every 3 s during 4-h time blocks from 8:00 a.m.-8:00 p.m. Agreement among observers using the coding system was 91%. Using indirect calorimetry, calibration studies in the laboratory determined VO2 (ml.min-1.min-1) during each coded activity, and activities were categorized by intensity (low, medium, or high). Subjects were found to engage in activities of low intensity 77.1% of time and activities of high intensity 3.1% of time. The median duration of low and medium intensity activities was 6 s, of high intensity activities only 3 s with 95% lasting less than 15 s. Children engaged in very short bursts of intense physical activity interspersed with varying intervals of low and moderate intensity. These findings may be important for discovering how children's activity patterns under natural conditions influence physiological processes leading to growth and development. This study demonstrates the advantages of using an observational system that captures more than the intensity and frequency of children's activities to include duration and the length of intervals between activities of varying intensity.

Design and application of a low-temperature Peltier-cooling microscope stage.

A light microscopy system has been designed for freezing and lyophilization studies of protein pharmaceuticals. The system consists of a cascade of four Peltier thermoelectric modules in the lyophilization cell to freeze samples to -60 degrees C, controllers to regulate temperature and pressure conditions, and a video camera to record the events under study. Specific demonstration of the system was conducted using recombinant CD4-IgG and human growth hormone (hGH) as model proteins. Observations of recrystallization during warming of frozen CD4-IgG solution and lyophilization of hGH solution are discussed. These examples demonstrate that the system is a useful tool for the fundamental understanding of freezing and lyophilization of protein pharmaceuticals.