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Item does not contain fulltext, 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.

Item does not contain fulltext, OBJECTIVES: To estimate the prevalence of nasopharyngeal bacterial colonisation (NPBC) patterns in young Tanzanian HIV-exposed infants and to analyse the influence of maternal NPBC and of the infant's HIV status on the NPBC pattern. METHODS: Longitudinal cohort study of neonates born to HIV-infected mothers visiting Kilimanjaro Christian Medical Centre, Tanzania, between 2005 and 2009. Demographic and clinical data and nasopharyngeal bacterial cultures were obtained at the age of 6 weeks, 3 and 6 months, and at one time point, a paired mother-infant nasopharyngeal swab was taken. RESULTS: Four hundred and twenty-two swabs were taken from 338 eligible infants. At 6 weeks of age, colonisation rates were 66% for Staphylococcus aureus, 56% for Streptococcus pneumoniae, 50% for Moraxella catarrhalis and 14% for Haemophilus influenzae. Colonisation with S. aureus diminished over time and was more common in HIV-infected infants. S. pneumoniae and H. influenzae colonisation rose over time and was more prevalent in HIV-uninfected children. Co-colonisation of S. pneumoniae with H. influenzae or M. catarrhalis was mostly noticed in HIV-infected infants. S. pneumoniae and M.catarrhalis colonisation of the mother was a risk factor for colonisation in HIV-uninfected infants, while maternal S. aureus colonisation was a risk factor for colonisation in HIV-infected infants. Among the 104 S. pneumoniae isolates, 19F was most prevalent, and 57 (55%) displayed capsular serotypes represented in the 13-valent pneumococcal conjugate vaccine. CONCLUSIONS: NPBC was common in Tanzanian HIV-exposed infants. The significant prevalence of pneumococcal vaccine serotypes colonising this paediatric population justifies the use of the 13-valent pneumococcal vaccine to reduce the burden of pneumococcal invasive disease.

Radboud Universiteit Nijmegen, 08 januari 2013, Promotores : Ven, A.J.A.M. van der, Dolmans, W.M.V. Co-promotor : Warris, A., Contains fulltext : 118919.pdf (Publisher’s version ) (Open Access)

Radboud Universiteit Nijmegen, 04 juni 2012, Promotores : Ven, A.J.A.M. van der, Dolmans, W.M.V., Faradz, S.M.H. Co-promotor : Mast, Q. de, Contains fulltext : 109078.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: World Health Organization guidelines recommend zidovudine + lamivudine for 7 days from labor onset in HIV-infected women receiving single-dose nevirapine (sdNVP) to cover prolonged subtherapeutic nevirapine concentrations. Although effective, this is complicated and does not eliminate resistance; alternative strategies could add benefit. METHODS: Antiretroviral-naive HIV-infected pregnant women aged 18-40 years, with CD4 >200 cells per cubic millimeter, able to regularly attend the antenatal clinics in Moshi, Tanzania, were enrolled 1:1 by alternate allocation to receive 200 mg sdNVP alone or in combination with open-label 400-mg single-dose carbamazepine (sdNVP/CBZ) at delivery (ClinicalTrials.gov NCT00294892). The coprimary outcomes were nevirapine plasma concentrations 1 week and nevirapine resistance mutations 6 weeks postpartum. Analyses were based on those still eligible at delivery. RESULTS: Ninety-seven women were assigned to sdNVP and 95 to sdNVP/CBZ during pregnancy, of whom 75 sdNVP and 83 sdNVP/CBZ were still eligible at delivery at study sites. The median (interquartile range) nevirapine plasma concentration was 1.55 (0.88-1.84) mg/L in sdNVP (n = 61) and 1.40 (0.93-1.97) mg/L in sdNVP/CBZ (n = 72) at delivery (P = 0.91), but 1 week later was significantly lower in sdNVP/CBZ [n = 63; 0.09 (0.05-0.20) mg/L] than in sdNVP [n = 52; 0.20 (0.09-0.31) mg/L; rank-sum: P = 0.004] (geometric mean ratio: 0.64, 95% confidence interval: 0.43 to 0.96; P = 0.03). Six weeks postpartum, nevirapine mutations were observed in 11 of 52 (21%) in sdNVP and 6 of 55 (11%) in sdNVP/CBZ (odds ratio = 0.46, 95% confidence interval: 0.16 to 1.34; P = 0.15). CONCLUSIONS: Addition of single-dose carbamazepine to sdNVP at labor onset in HIV-infected, pregnant women did not affect nevirapine plasma concentration at delivery, but significantly reduced it 1 week postpartum, with a trend toward fewer nevirapine resistance mutations.

Contains fulltext : 98478.pdf (publisher's version ) (Closed access), Differential viral recognition by cells bearing Toll-like receptor 4 (TLR4) polymorphisms Asp299Gly and Thr399Ile may influence susceptibility and severity of dengue virus infection. In central Java, Indonesia, we investigated 201 children with dengue hemorrhagic fever (DHF) and 179 healthy controls. Patients and controls were mostly ethnic Javanese. A nearly complete cosegregation of the two mutations was observed. The TLR4 299/399 genotype was found in five patients and four controls. Prevalence of the TLR4 299/399 genotype did not differ significantly between controls and DHF patients or between patients with different severities of DHF. Also, vascular leakage in patients with different TLR4 genotypes did not differ. Thus, the 299/399 TLR4 haplotype has only minor influence on susceptibility and severity of complicated dengue virus infection.

1 december 2011, Contains fulltext : 98003.pdf (publisher's version ) (Closed access), Mortality in children with severe dengue haemorrhagic fever (DHF) in Indonesia is high. The origin of the elevated plasminogen activator inhibitor-1 (PAI-1) levels in these children is unclear. We measured PAI-1, transforming growth factor-beta1 (TGF-beta1), platelet counts, plasma leakage and liver function in 71 children with DHF (3-15 years old) and in 30 healthy children. We found that PAI-1 concentrations in children with DHF were significantly higher on admission than on Day 2. Circulating TGF-beta1 concentrations on admission were significantly lower in DHF than in controls, but on Day 2 increased towards levels in controls. TGF-beta1 and PAI-1 concentrations were not correlated on either day. PAI-1 was correlated with platelet count and serum albumin on admission, and with degree of pleural effusion. Liver function tests were mildly elevated but not correlated with PAI-1. In conclusion, elevated PAI-1 concentrations in DHF were associated with platelet counts and plasma leakage.

Contains fulltext : 87407.pdf (publisher's version ) (Open Access), BACKGROUND: A previous study showed that combination of zinc and vitamin A reduced sputum conversion time in pulmonary tuberculosis (TB) patients. OBJECTIVE: We studied the efficacy of which single micronutrient contributed more to the sputum conversion time. METHODS: In a double-blind randomized community trial, newly sputum smear positive pulmonary TB patients were assigned randomly to receive zinc, vitamin A, zinc + vitamin A or placebo on top of TB treatment. Patients were asked to deliver their sputum on weekly basis to measure positivity of the bacteria. Nutritional status, chest x-ray, hemoglobin, C-reactive protein (CRP), retinol and zinc level were examined prior to, after 2 and 6 months of treatment. RESULTS: Initially, 300 patients were enrolled, and 255 finished the treatment. Most patients were severely malnourished (mean BMI 16.5 +/- 2.2 Kg/m2). Patients in the zinc + vitamin A group showed earlier sputum conversion time (mean 1.9 weeks) compared with that in the other groups; however the difference was not significant. Also, no benefit could be demonstrated of any of the used supplementations on clinical, nutritional, chest x-ray, or laboratory findings. CONCLUSIONS: This study among severely malnourished TB patients, did not confirm that single or combined supplementation of zinc and vitamin A significantly reduced sputum conversion time or had other significant benefit.

RU Radboud Universiteit Nijmegen, 02 december 2009, Promotores : Jansen, J.B.M.J., Dolmans, W.M.V. Co-promotores : Janssen, M.J.R., Laheij, R.J.F., Contains fulltext : 79644.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Plasma zinc and vitamin A concentrations have been reported to be low in tuberculosis (TB) patients in some studies, although it is not clear whether this constitutes a risk for a more severe clinical presentation among TB patients. The acute phase reaction may also deplete zinc and vitamin A in the plasma. Therefore, we further studied these associations. METHODS: We carried out a cross-sectional study among newly diagnosed sputum smear-positive TB patients in East Nusa Tenggara. The patients were categorized as either mild TB when Karnofsky Score (KS) > or =80 or severe TB (KS <80). Body mass index (BMI), mid upper arm circumference (MUAC), chest radiograph, and the results of hemoglobin, erythrocyte sedimentation rate, albumin, C-reactive protein (CRP), zinc and vitamin A in plasma were correlated with TB category. RESULTS: A total of 300 TB patients participated in the study (63% male and 37% female), and were categorized as mild TB (53%) or severe TB (47%). Vitamin A, hemoglobin and plasma albumin were significantly lower, and CRP was significantly higher, in severe TB than in mild TB, and the active lesion area on the chest radiograph was greater among severe TB patients. In a multiple regression analysis, after adjustment for CRP, low vitamin A (beta=3.2, 95%CI (confidence interval) 1.6-4.9, P=0.000) but not zinc, correlated with the severity of TB. MUAC was better than BMI as a predictor of TB severity (beta=1.3, 95%CI 0.6-6.2, P=0.000). CONCLUSIONS: Severe TB was associated with vitamin A deficiency. MUAC can be applied as a measure of TB severity.

RU Radboud Universiteit Nijmegen, 15 april 2009, Promotores : Meer, J.W.M. van der, Velden, J. van der, Dolmans, W.M.V. Co-promotor : Karyadi, E., Contains fulltext : 74395.pdf (publisher's version ) (Open Access)

Contains fulltext : 80762.pdf (publisher's version ) (Open Access), Aim: to investigate which recent infection could have caused the present dengue-like symptoms, in adult patients clinically fulfilling the WHO criteria for dengue, in which serologically were not confirmed for dengue virus infections. Methods: prospective study. During an outbreak of dengue (between May 1995 and May 1996) 118 consecutive adults (>13 years) suspected by the WHO 1997 case definition of DF or DHF were investigated. Patients were examined for history of illness, physical and laboratory findings consisting of full blood counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), liver function (bilirubin, ASAT, ALAT), renal function (creatinine), and serological assays included dengue, hantavirus, chikungunya, R. typhi, R. tsutsugamuchi, rubella virus, influenza A virus, and leptospira. Results: in 58 of the total 118 patients, recent dengue virus infection was serologically confirmed. In 20 of the remaining 60 patients, we found serological evidence of another recent infection: hantavirus (5), chikungunya virus (2), R. typhi (5), R. tsutsugamuchi (2), rubella virus (3), influenza A virus (1), and leptospira (2). No evidence for recent infection with any of the mentioned agents was detected in the remaining 40 specimens. Conclusion: we conclude that based on clinical characteristics alone, it is not easy to diagnose dengue. Specific laboratory tests to differentiate dengue from other febrile illnesses are needed. Among these, in Indonesia hantavirus infection should be considered as well.

RU Radboud Universiteit Nijmegen, 27 juni 2007, Promotores : Dolmans, W.M.V., Shao, J.F. Co-promotor : Ven, A.J.A.M. van der, Item does not contain fulltext

Contains fulltext : 52739.pdf (publisher's version ) (Closed access)

Contains fulltext : 53004.pdf (publisher's version ) (Open Access), BACKGROUND: Tuberculosis (TB) is a major health problem and HIV is the major cause of the increase in TB. Sub-Saharan Africa is endemic for both TB and HIV infection. Determination of the prevalence of M. tuberculosis strains and their drug susceptibility is important for TB control.TB positive culture, BAL fluid or sputum samples from 130 patients were collected and genotyped. The spoligotypes were correlated with anti-tuberculous drug susceptibility in HIV-infected and non-HIV patients from Tanzania. RESULTS: One-third of patients were TB/HIV co-infected. Forty-seven spoligotypes were identified.Fourteen isolates (10.8%) had new and unique spoligotypes while 116 isolates (89.2%) belonged to 33 known spoligotypes. The major spoligotypes contained nine clusters: CAS1-Kili 30.0%, LAM11- ZWE 14.6%, ND 9.2%, EAI 6.2%, Beijing 5.4%, T-undefined 4.6%, CAS1-Delhi 3.8%, T1 3.8% and LAM9 3.8%. Twelve (10.8%) of the 111 phenotypically tested strains were resistant to anti-TB drugs. Eight (7.2%) were monoresistant strains: 7 to isoniazid (INH) and one to streptomycin. Four strains (3.5%) were resistant to multiple drugs: one (0.9%) was resistant to INH and streptomycin and the other three (2.7%) were MDR strains: one was resistant to INH, rifampicin and ethambutol and two were resistant to all four anti-TB drugs. Mutation in the katG gene codon 315 and the rpoB hotspot region showed a low and high sensitivity, respectively, as predictor of phenotypic drug resistance. CONCLUSION: CAS1-Kili and LAM11-ZWE were the most common families. Strains of the Beijing family and CAS1-Kili were not or least often associated with resistance, respectively. HIV status was not associated with spoligotypes, resistance or previous TB treatment.

Contains fulltext : 51582.pdf (publisher's version ) (Closed access), Macrophage migration inhibitory factor (MIF) activates macrophages, promotes delayed-type hypersensitivity reaction, and regulates Th1/Th2 balance in inflammatory response. Serum MIF concentration is high in patients with pulmonary tuberculosis (PTB). Higher MIF levels are associated with high mortality. No study has addressed MIF levels and its role in PTB/HIV-co infection. We determined serum and BAL MIF levels in Tanzanian HIV-infected patients with and without PTB, and correlated the levels with 1-month outcome. We compared with serum MIF levels of HIV seronegative patients with PTB and of healthy controls. All HIV-infected patients irrespective of PTB infection had significantly higher serum MIF levels than HIV-seronegative patients with PTB, and than healthy controls. In HIV seropositive patients low serum MIF levels were associated with high 1-month mortality. In conclusion, HIV infection was associated with elevated serum MIF levels regardless of PTB. Low serum MIF levels were associated with high mortality.

Contains fulltext : 49877.pdf (publisher's version ) (Closed access), Few data exist on the current capacity of Tanzanian health-care facilities to deliver antiretroviral therapy (ART). We evaluated this capacity among Northern Zone facilities in 2004 using a questionnaire that addressed human resources, clinical facilities and services, and laboratory capacity. Of 19 facilities surveyed, nine (47%) had staff trained to manage ART and three (16%) prescribed ART. Two (11%) offered CD4 counts, five (26%) offered liver function tests, 16 (84%) offered chest radiography, and 18 (95%) offered acid-fast sputum staining. Of 12 (67%) facilities offering outpatient HIV/AIDS services, 12 (100%) provided co-trimoxazole to outpatients and six (50%) provided isoniazid (INH). All 19 (100%) facilities offered rapid HIV tests and full blood pictures. Overall in 2004, facilities needed strengthening to increase staff training in ART management and to implement INH for treatment of latent tuberculosis. Laboratory facilities for ART monitoring were inadequate, and outpatient ART was limited.

Contains fulltext : 48952.pdf (publisher's version ) (Closed access), BACKGROUND: Single-dose nevirapine is a highly cost-effective strategy to reduce perinatal HIV-1 transmission. Its major disadvantage is the selection of nevirapine resistance in 20% to 30% of women, probably attributable to the long elimination half-life of nevirapine. To develop intervention strategies, it is important to know the interpatient variability in nevirapine half-life in women receiving a single dose of nevirapine. METHODS: HIV-negative, healthy, nonpregnant Dutch women were eligible for this study. After administration of a single 200-mg dose of nevirapine to the subjects, blood was sampled for measurement of nevirapine twice a week for a total of 21 days. Nevirapine plasma levels were determined by a validated high-performance liquid chromatography method with a lower limit of quantification of 0.15 mg/L. The primary end point was the first sample with an undetectable nevirapine concentration. RESULTS: Forty-four subjects participated. The median age, height, and body weight (interquartile range) were 26 (21-33) years, 1.72 (1.68-1.75) m, and 64 (59-75) kg, respectively. The median elimination half-life of nevirapine was 56.7 hours, with a range of 25.6 to 164 hours. The time to the first undetectable nevirapine plasma concentration was 10 days in 4 subjects, 14 days in 12 subjects, 17 days in 12 subjects, and 21 days in 9 subjects. In the remaining 7 subjects, nevirapine was still detectable on day 21, the last day of sampling. Time to an undetectable nevirapine plasma concentration was influenced by oral contraceptive use but not by age, height, body weight, body surface area, alcohol use, or smoking. CONCLUSIONS: Most women who received a single 200-mg nevirapine dose still had detectable plasma concentrations of nevirapine after more than 2 weeks. This information is valuable for designing intervention studies to prevent the development of nevirapine resistance.

Contains fulltext : 58840.pdf (publisher's version ) (Closed access), BACKGROUND: Workers in informal small-scale industries (SSI) in developing countries involved in welding, spray painting, woodwork and metalwork are exposed to various hazards with consequent risk to health. Aim To assess occupational exposure and health problems in SSI in Dar es Salaam, Tanzania. METHODS: Focused group discussions (FGD) were conducted among SSI workers. Participants were assessed for exposure to occupational and environmental hazards, the use of protective equipment and health complaints by interview. The findings were discussed with participants and potential interventions identified. RESULTS: Three hundred and ten workers were interviewed (response rate 98%). There was a high level (>90%) of self-reported exposure to either dust, fumes, noise or sunlight in certain occupational groups. There was low reported use of personal protective equipment. There was a high level of self-reported occupational health problems, particularly amongst welders and metalworkers. Workers reported their needs as permanent workplaces, information on work related hazards, water and sanitation, and legislation for SSI. CONCLUSIONS: In SSI in Tanzania, our study suggests that workers have high levels of exposure to multiple health hazards and that use of protective equipment is poor. This group of workers warrants improved occupational health and safety provision.

Contains fulltext : 58496.pdf (publisher's version ) (Closed access), Workers in small-scale wood industries (SSWI) have increased risks of developing asthma and other respiratory diseases. Wood dust and microbial agents have both been suggested to play a role, but few studies have measured endotoxin exposure in SSWI in Africa. We assessed inhalable dust levels in 281 samples from 115 workers and bacterial endotoxins levels in 157 samples from 136 workers from SSWI in Dar es Salaam, Tanzania. The overall geometric mean of personal exposure was 3.3 mg/m(3); geometric standard deviation (GSD) 2.5; range 0.45-67.0 mg/m(3)) and 91 EU/m(3) (GSD 3.7; range 9-4914.8 EU/m(3)) for wood dust and endotoxins, respectively. Dust and endotoxin levels were weakly correlated (r = 0.44, n = 157, P < 0.0001). Between- and within-worker variances and percentages explained by the differences among job titles and seasons were 0.31 (9%) and 0.35 (30%), respectively, for wood dust exposure, and 0.35 (0%) and 0.35 (38%) for endotoxin exposure. Higher dust and endotoxin exposure levels were observed in the dry compared to the wet season, after correcting for differences in exposure between jobs. Carving and manual cleaning were associated with the highest dust exposures. Sewing seat covers and manual cleaning were associated with the highest endotoxin exposures. Dust and endotoxin exposure levels in SSWI are high and appropriate control measures are necessary.

Contains fulltext : 58700.pdf (publisher's version ) (Closed access)