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.

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.

Factors associated with repeat visits among clients attending a clinic for sexually transmitted infections in Kisumu, Kenya.

To identify factors associated with repeat visits among patients attending a clinic for sexually transmitted infections (STIs) in Kisumu, Kenya, we examined records of clinic visits from March 2009 to May 2010. Multivariable logistic regression identified factors associated with repeat visits occurring >30 days after the initial visit. Among 1473 clients (1296 single-visit individuals versus 177 individuals with repeat visits), the median age was 24 years, 67% were men and 8.6% self-reported being HIV-positive. In adjusted analyses, men with repeat visits were more likely to report ≥ 2 recent sexual partners (adjusted odds ratio [aOR] = 1.60) and being HIV-positive (aOR = 2.35). They were less likely to have been referred from other health facilities (aOR = 0.14) and more likely to have urethral discharge at their initial visit (aOR = 2.46). Among women, repeat visits were associated with vaginal discharge (aOR = 2.22), but attending the clinic with a partner was protective (aOR = 0.38). The association between sexual risk, HIV positivity and repeat visits among male clients highlights the need to focus intervention efforts on this group. For women, attending with a partner may reflect a decreased risk of re-infection if both partners are treated and counselled together.

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.

Acceptability of male circumcision for prevention of HIV infection in Zambia.

Numerous observational studies and three clinical trials have shown male circumcision (MC) to be partially protective against HIV acquisition in heterosexual men. This has led to consideration of introducing circumcision as an HIV prevention strategy in parts of sub-Saharan Africa. This study assesses the acceptability of male circumcision as an intervention to improve male genital hygiene and reduce sexually transmitted infections, including HIV-1 in Zambia. Thirty-four focus group discussions were conducted - 17 with men and 17 with women - in four districts chosen to represent urban and rural communities where circumcision is and is not traditionally practiced. In communities where circumcision is little practiced, the main facilitators for acceptance were improved genital hygiene, HIV/STI prevention, and low cost. The main barriers were cultural tradition, high cost, pain, and concerns for safety. If MC is proven to reduce risk for HIV and STIs, most participants reported that they would seek circumcision for themselves or their partners or their sons if it was free or at a minimal cost. Acceptability of male circumcision for STI and HIV prevention appears to be high in Zambia.

Acceptability of male circumcision for prevention of HIV/AIDS in sub-Saharan Africa: a review.

Based on epidemiological, clinical and experimental evidence, male circumcision (MC) could have a significant impact on the HIV epidemic in selected areas. We reviewed studies of the acceptability of MC in sub-Saharan Africa to assess factors that will influence uptake of circumcision in traditionally non-circumcising populations. Thirteen studies from nine countries were identified. Across studies, the median proportion of uncircumcised men willing to become circumcised was 65% (range 29-87%). Sixty nine percent (47-79%) of women favored circumcision for their partners, and 71% (50-90%) of men and 81% (70-90%) of women were willing to circumcise their sons. Because the level of acceptability across the nine countries was quite consistent, additional acceptability studies that pose hypothetical questions to participants are unnecessary. We recommend pilot interventions making safe circumcision services available in conjunction with current HIV prevention strategies and evaluating the safety and acceptability of circumcision.

Acceptability of male circumcision and predictors of circumcision preference among men and women in Nyanza Province, Kenya.

Numerous epidemiologic studies report significant associations between lack of male circumcision and HIV-1 infection, leading some to suggest that male circumcision be added to the limited armamentarium of HIV prevention strategies in areas where HIV prevalence is high and the mode of transmission is primarily heterosexual. This cross-sectional survey of 107 men and 110 women in Nyanza Province, Kenya, assesses the attitudes, beliefs, and predictors of circumcision preference among men and women in a traditionally non-circumcising region. Sixty per cent (n=64) of uncircumcised men and 69% (n=68) of women who had uncircumcised regular partners reported that they would prefer to be circumcised or their partners to be circumcised. Men's circumcision preference was associated with the belief that it is easier for uncircumcised men to get penile cancer, sexually transmitted diseases, and HIV/AIDS, and that circumcised men have more feeling in their penises, enjoy sex more, and confer more pleasure to their partners. Women with nine or more years of school were more likely to prefer circumcised partners. Men who preferred to remain uncircumcised were concerned about the pain and cost of the procedure, and pain was a significant deterrent for women to agree to circumcision for their sons. If clinical trials prove circumcision to be efficacious in reducing risk of HIV infection, it is likely that the procedure will be sought by a significant proportion of the population, especially if it is affordable and minimally painful.

Feasibility of medical male circumcision in Nyanza Province, Kenya.

BACKGROUND: Over forty observational studies have reported a protective effect of male circumcision against HIV-I acquisition, leading some to suggest that male circumcision be added to the limited armamentarium of HIV prevention strategies. OBJECTIVES: To evaluate the feasibility and requirements of implementing medical male circumcision in Nyanza Province of Kenya a quasi-experimental design was implemented to assess clinicians' knowledge of male circumcision and to assess the effectiveness of a one day educational intervention in one district. A cross sectional survey assessed the availability of necessary instruments and surgical supplies. RESULTS: None of the participating ten health facilities had all the necessary instruments and supplies to safely perform male circumcisions. Though most clinicians reported training about circumcision, most lacked sufficient knowledge to perform the procedure, and few were familiar with the process of informed consent. We demonstrated that a didactic educational workshop significantly improved providers' knowledge of male circumcision. CONCLUSIONS: Since increasing numbers of young men and parents are requesting male circumcision services in many parts of sub-Saharan Africa, health providers must undergo further training in the performance of the procedure and the process of informed consent. Many health facilities will have to be provided with the instruments and supplies necessary to perform male circumcision safely.

The acceptability of male circumcision to reduce HIV infections in Nyanza Province, Kenya.

Compelling epidemiological evidence showing a significant association between lack of male circumcision and HIV infection has prompted calls for consideration of male circumcision interventions as a strategy for reducing HIV prevalence in highly affected areas where circumcision is little practiced and transmission is predominantly heterosexual. Little is known about whether male circumcision interventions would be acceptable or feasible in traditionally non-circumcisng areas of Africa. This study assesses the acceptability of male circumcision in the Luo, a large, traditionally non-circumcising ethnic group in western Kenya. Separate focused group discussions with adult Luo men and women and semi-structured interviews with clinicians were conducted in Nyanza Province, Kenya. The primary barriers to acceptance of male circumcision were cultural identification, fear of pain and excessive bleeding and cost. The main facilitators were association of male circumcision with better hygiene and reduced risk of infection. Both men and women were eager for promotion of genital hygiene and male circumcision, and they desired availability of circumcision clinical services in the Province's health facilities. Clinicians lacked the knowledge and resources to offer safe circumcision counselling and services. If results from this study are valid for other areas of sub-Saharan Africa, acceptability of male circumcision as a means to reduce STDs and HIV is higher than previously suspected. Further studies are needed in other regions to assess the feasibility of introducing acceptable male circumcision information and services to reduce HIV transmission.

Eight hundred-year-old human remains from the Ituri tropical forest, Democratic Republic of Congo: the rock shelter site of Matangai Turu Northwest.

Little is known about human prehistory in the central African lowland tropical forest due to a paucity of archaeological evidence. Here we report results from our archaeological investigations of a late Holocene site in the northeast Congo Basin, with emphasis on a single skeleton from the rock shelter site of Matangai Turu Northwest, in the Ituri Forest, Democratic Republic of Congo. The skeleton dates from approximately 810 BP (1235 calibrated AD) and is associated with Later Stone Age lithics, animal bone and shell remains from wild taxa, fruit endocarps from forest trees, phytoliths from tropical forest plants, Late Iron Age ceramics, and a single iron artifact. Phytolith analysis indicates that the habitat was dense tropical forest, without evidence of domesticated food.

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.

Complications of tube thoracostomy in trauma.

OBJECTIVE: To assess the complication rate of tube thoracostomy in trauma. To consider whether this rate is high enough to support a selective reduction in the indications for tube thoracostomy in trauma. METHODS: A retrospective case series of all trauma patients who underwent tube thoracostomy during a 12 month period at a large UK teaching hospital with an accident and emergency (A&E) department seeing in excess of 125,000 new patients/year. These patients were identified using the hospital audit department computerised retrieval system supplemented by a hand search of both the data collected for the Major Trauma Outcome Study and the A&E admission unit log book. The notes were assessed with regard to the incidence of complications, which were divided into insertional, infective, and positional. RESULTS: Fifty seven chest drains were placed in 47 patients over the 12 month period. Seven patients who died within 48 hours of drain insertion were excluded. The commonest indications for tube thoracostomy were pneumothorax (54%) and haemothorax (20%); 90% of tubes were placed as a result of blunt trauma. The overall complication rate of the procedure was 30%. There were no insertional complications and only one (2%) major complication, which was empyema thoracis. CONCLUSION: This study reveals no persuasive evidence to support a selective reduction in the indications for tube thoracostomy in trauma. A larger study to confirm or refute these findings must be performed before any change in established safe practice.

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.

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.

Sexual behaviors and other HIV risk factors in circumcised and uncircumcised men in Uganda.

OBJECTIVE: To study the differences in sexual practices, hygienic behaviors, and other HIV risk factors between circumcised and uncircumcised men. DESIGN: A cross-sectional study of men >17 years of age selected by single stage cluster sampling in the Industrial Borough, Mbale, Uganda. METHODS: Using a structured questionnaire, 188 circumcised and 177 uncircumcised consenting Ugandan men were interviewed in one of four native languages during April and May, 1997. RESULTS: Among non-Muslims, circumcised men had a higher risk profile than uncircumcised men in that they were more likely to drink alcohol in conjunction with sex (odds ratio [OR], 1.86: 95% confidence interval [CI], 1.09-3.16), to have sexual contacts with women on the first day of meeting (OR, 2.37; 95% CI, 1.39-4.04), to have had sexual contacts in exchange for money or gifts (OR, 2.08; 95% CI, 1.21-3.09), to have experienced episodes of pain on urination or to have experienced penile discharge (OR, 1.68; 95% CI, 1.07-2.64), had an earlier age at sexual debut (15.7 versus 16.9 years), and had more extramarital sex partners in the last year (1.13 versus 0.62). Circumcised men also reported a preference for nonwet sex. Muslims generally had a lower risk profile than other circumcised men except they were less likely to have ever used a condom (OR, 0.34; 95% CI, 0.15-0.78) or to have used a condom during the last sex encounter (OR, 0.37; 95% CI, 0.14-0.87). CONCLUSIONS: These results suggest that differences between circumcised and uncircumcised men in their sex practices and hygienic behaviors do not account for the higher risk of HIV infection found among uncircumcised men. Further consideration should be given to male circumcision as a prevention strategy in areas of high prevalence of HIV and other sexually transmitted diseases. Studies of the feasibility and acceptability of male circumcision in traditionally noncircumcising societies are warranted.