Total lymphocyte count is a good marker for HIV-related mortality and can be used as a tool for starting HIV treatment in a resource-limited setting.

OBJECTIVES: Total lymphocyte counts (TLC) may be used as an alternative for CD4 cell counts to monitor HIV infection in resource-limited settings, where CD4 cell counts are too expensive or not available. METHODS: We used prospectively collected patient data from an urban HIV clinic in Indonesia. Predictors of mortality were identified via Cox regression, and the relation between TLC and CD4 cell counts was calculated by linear regression. Receiver operating characteristics (ROC) curves were used to choose the cut-off values of TLC corresponding with CD4 cell counts <200 and ≤350 cells/µl. Based on these analyses, we designed TLC-based treatment algorithms. RESULTS: Of 889 antiretroviral treatment (ART)-naïve subjects included, 66% had CD4 cell counts <200 and 81% had 350 ≤ cells/µl at baseline. TLC and CD4 cell count were equally strong predictors of mortality in our population, where ART was started based on CD4 cell count criteria. The correlation coefficient (R) between TLC and √CD4 was 0.70. Optimal cut-off values for TLC to identify patients with CD4 cell counts <200 and ≤350 cells/µl were 1500 and 1700 cells/µl, respectively. Treatment algorithms based on a combination of TLC, gender, oral thrush, anaemia and body mass index performed better in terms of predictive value than WHO staging or TLC alone. In our cohort, such an algorithm would on average have saved $14.05 per patient. CONCLUSION: Total lymphocyte counts is a good marker for HIV-associated mortality. Simple algorithms including TLC can prioritize patients for HIV treatment in a resource-limited setting, until affordable CD4 cell counts will be universally available.

Genetic polymorphisms in GSTA1, GSTP1, GSTT1, and GSTM1 and gastric cancer risk in a Vietnamese population.

Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of noxious agents. Genes encoding for GSTA1, GSTP1, GSTT1, and GSTM1 proteins are polymorphic in humans, which can result in (partial) loss of enzyme activity. Previous epidemiologic studies have associated dysfunction of these GST genes with a higher risk of cancer, but this is still controversial. The aim of this study was to investigate the susceptibility to gastric cancer in relation to the above-mentioned GST polymorphisms. Patients visiting the Can Tho General Hospital in Vietnam between January 2004 and August 2004 for upper gastrointestinal endoscopy, who were diagnosed with gastric cancer, were compared with a control group of endoscoped dyspepsia patients with no history of malignancy. Genotypes of the GSTs mentioned above were assessed by multiplex PCR. Fifty-nine patients with gastric cancer (mean age: 63 years, 80% males), and 109 dyspeptic controls (mean age: 46 years, 69% males) were included in this study. The frequencies of the combined heterozygote and homozygote mutant GSTA1 and GSTP1 genotypes were 10% and 48% in patients with gastric cancer versus 28% and 40% in dyspeptic controls, respectively. GSTT1 and GSTM1 were deleted in 42% and 73% of patients with gastric cancer and in 35% and 69% of the controls, respectively. The GSTA1 homozygous wild-type genotype was significantly more often present in patients with gastric cancer compared with controls (odds ratio 4.3, 95% CI 1.2-17), which was even more apparent after adjustment for age, gender, current smoking, current alcohol consumption, and polymorphisms in GSTP1, GSTT1, or GSTM1 (odds ratio 5.0, 95% CI 1.2-25). The present work shows that the homozygous wild-type GSTA1 genotype is associated with gastric cancer in a Vietnamese population, whereas there was no relationship with polymorphisms in GSTP1, GSTT1, or GSTM1.

Optimizing antibiotic usage in adults admitted with fever by a multifaceted intervention in an Indonesian governmental hospital.

OBJECTIVE: To optimize antimicrobial treatment of patients with fever upon admission to the department of internal medicine of Dr Soetomo Hospital in Surabaya, Indonesia. METHOD: Prospective intervention study. The intervention comprised development of a consensus guideline, an official declaration of the guideline by the head of department, distributing a guideline pocketbook, carrying out blood cultures free of charge, teaching sessions and refresher courses. The outcome was measured with reference to (i) percentage of patients with fever started on antibiotic therapy, (ii) amount of antibiotics used expressed as defined daily doses (DDD)/100 patient-days, (iii) percentage of appropriate prescriptions and of prescriptions without indication as assessed by independent reviewers, (iv) percentage of treatments in accordance with guidelines, (v) percentage of patients in whom blood cultures were taken before starting antimicrobial therapy, (vi) percentage of treatments appropriately stopped on re-evaluation of the patients at 72 h and (vii) mortality. RESULTS: The study involved 501 patients, 95 residents and 60 specialists. After the intervention 17% patients less were treated with antibiotics upon admission and antibiotic use fell from 99.8 to 73 DDD/100 patient-days. The percentage of patients with sepsis and dengue treated in accordance with the guideline increased by 23% and 30%. The percentage of appropriate therapies, therapies without indication and mortality did not change significantly. The percentage of patients for whom a blood culture was taken upon admission increased from 3% to 81%; however, almost all were taken after they commenced antibiotic therapy. Therapy was not adjusted after 72 h in any case. Interrupted time series analysis showed that the start of development of the guideline and the declaration of the guideline were the interventions with the greatest impact. CONCLUSION: The multifaceted intervention had limited success. A very important drawback to the prudent use of antibiotics was the absence of adequate microbiological diagnostics.

Barriers to access to antiretroviral treatment in developing countries: a review.

OBJECTIVE: To present a review of barriers impeding people living with HIV/AIDS in developing countries from accessing treatment, and to make recommendations for further studies. METHODS: Electronic databases, websites of main global agencies and international AIDS conferences were searched for relevant articles published between 1996 and 2007. Articles were reviewed using the Andersen and May framework of access to health services and barriers were categorized as either population-level or health system-level barriers. RESULTS: A total of 19 studies (7 articles and 12 abstracts) in English were reviewed. The barriers most frequently cited at the population level were lack of information about antiretroviral therapy (ART), perceived high costs for ART and stigma. Barriers most frequently cited at the health system level were long distance from home to the health facility, lack of co-ordination across services and limited involvement of the community in the programme planning process. CONCLUSIONS: Dissemination of information about HIV/AIDS and alternative related care, and alternative health financing policies seem to be the most relevant policy measures to remove barriers. In view of the paucity of evidence on barriers to access to ART, research should address the relative importance of barriers, include a mix of qualitative and quantitative research methods and evaluate barriers in different settings.

Short mucin 6 alleles are associated with H pylori infection.

AIM: To investigate the relationship between mucin 6 (MUC6) VNTR length and H pylori infection. METHODS: Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (Pvu II) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by (14)C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (< or = 13.5 kbp) and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)]. RESULTS: 160 patients were studied (mean age 43 years, 36% were males, 58% H pylori positive). MUC6 Pvu II-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6 genotype, 43% (24/56), 57% (25/58) and 76% (11/46) were infected with H pylori, respectively (P = 0.003). CONCLUSION: Short MUC6 alleles are associated with H pylori infection.

A survey of the supply and bacteriologic quality of drinking water and sanitation in Jakarta, Indonesia.

We assessed the water supply, water quality and human waste disposal and their association with diarrheal illness in Jatinegara, East-Jakarta, where part of the area has been involved in the Kampung Improvement Program (KIP). Three hundred seventy-eight households, randomly selected in the study area, were visited and questioned about water source, sanitation and diarrheal illness during the previous 3 months. Microbiological quality of drinking water was assessed. The water sources were boreholes (243; 64%), the water mains (77; 20%), bottled water (45; 12%), and vendors or dug wells (243; 4%). Fecal coliforms were isolated in 56% of the samples [median 23 (IQR 6-240) /100 ml in the contaminated samples]. Only 2 (3%) of the water mains' samples contained >100 fecal coliforms/100 ml, compared to 57 (24%) groundwater samples. Most residents used private toilets with drainage into on-site septic tanks, yet in over one quarter of households human excreta was disposed of into rivers or gutters. KIP areas lagged behind in environmental hygiene. Diarrheal episodes, reported in one third of the households, were significantly associated with water contaminated with >100 fecal coliforms/100 ml [OR 2.4 (95% CI: 1.4-4.2)], but no association with water source or environmental contamination was found. Significantly, all individuals reported boiling water before consumption.

Risk factors for typhoid and paratyphoid fever in Jakarta, Indonesia.

CONTEXT: The proportion of paratyphoid fever cases to typhoid fever cases may change due to urbanization and increased dependency on food purchased from street vendors. For containment of paratyphoid a different strategy may be needed than for typhoid, because risk factors for disease may not coincide and current typhoid vaccines do not protect against paratyphoid fever. OBJECTIVE: To determine risk factors for typhoid and paratyphoid fever in an endemic area. DESIGN, SETTING, AND PARTICIPANTS: Community-based case-control study conducted from June 2001 to February 2003 in hospitals and outpatient health centers in Jatinegara district, Jakarta, Indonesia. Enrolled participants were 1019 consecutive patients with fever lasting 3 or more days, from which 69 blood culture-confirmed typhoid cases, 24 confirmed paratyphoid cases, and 289 control patients with fever but without Salmonella bacteremia were interviewed, plus 378 randomly selected community controls. MAIN OUTCOME MEASURES: Blood culture-confirmed typhoid or paratyphoid fever; risk factors for both diseases. RESULTS: In 1019 fever patients we identified 88 (9%) Salmonella typhi and 26 (3%) Salmonella paratyphi A infections. Paratyphoid fever among cases was independently associated with consumption of food from street vendors (comparison with community controls: odds ratio [OR], 3.34; 95% confidence interval [CI], 1.41-7.91; with fever controls: OR, 5.17; 95% CI, 2.12-12.60) and flooding (comparison with community controls: OR, 4.52; 95% CI, 1.90-10.73; with fever controls: OR, 3.25; 95% CI, 1.31-8.02). By contrast, independent risk factors for typhoid fever using the community control group were mostly related to the household, ie, to recent typhoid fever in the household (OR, 2.38; 95% CI, 1.03-5.48); no use of soap for handwashing (OR, 1.91; 95% CI, 1.06-3.46); sharing food from the same plate (OR, 1.93; 95% CI, 1.10-3.37), and no toilet in the household (OR, 2.20; 95% CI, 1.06-4.55). Also, typhoid fever was associated with young age in years (OR, 0.96; 95% CI, 0.94-0.98). In comparison with fever controls, risk factors for typhoid fever were use of ice cubes (OR, 2.27; 95% CI, 1.31-3.93) and female sex (OR, 1.79; 95% CI, 1.04-3.06). Fecal contamination of drinking water was not associated with typhoid or paratyphoid fever. We did not detect fecal carriers among food handlers in the households. CONCLUSIONS: In Jakarta, typhoid and paratyphoid fever are associated with distinct routes of transmission, with the risk factors for disease either mainly within the household (typhoid) or outside the household (paratyphoid).

Prevalence of lipodystrophy in HIV-infected children in Tanzania on highly active antiretroviral therapy.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has been associated with lipodystrophy (LD) in adults but data are more limited for children. The purpose of this study was to determine the prevalence of and risk factors for LD in Tanzanian children receiving HAART by clinical assessment and to compare the results with anthropometric data. DESIGN AND METHODS: A cross-sectional study was performed in a cohort of HIV-infected children aged 1-18 years receiving HAART in a single center in Moshi, Tanzania. Age, gender, past and current medication regimens and anthropometric measurements were recorded. A clinical scoring method was used to assess LD. Backward binary multivariate logistic regression was used to determine relationships between anthropometric measurements and the presence of clinical LD. RESULTS: Among 210 HIV-infected children, the prevalence of LD was 30% (95% confidence interval [CI]: 23.8-36.2) overall, 19% (95% CI: 13.7-24.3) for lipoatrophy only, 3.8% (95% CI: 1.2-6.4) for lipohypertrophy only and 7.1% (95% CI: 3.6-10.6) for the mixed type. Most cases were mild. Older age and use of stavudine increased the risk of LD. Overall, the study population was stunted but not underweight. In children with relatively lower weight-for-height (<1), only the mid-upper arm circumference was found to be associated with lipoatrophy, while nearly all anthropometric measurements were associated with lipoatrophy in the well-nourished (weight-for-height ≥1) children. CONCLUSIONS: Our findings demonstrate that LD is a significant problem among Tanzanian HIV-infected children receiving HAART. Anthropometric measurements predicted LD in well-nourished children but generally failed to do so in relatively wasted children. Our findings support current efforts to avoid stavudine use in children.