Institute of Tropical Medicine Antwerp

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    Prenatal food supplementation fortified with multiple micronutrients increases birth length: a randomized controlled trial in rural Burkina Faso

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    BACKGROUND: Prenatal multiple micronutrient (MMN) or balanced energy and protein supplementation has a limited effect on birth size of the offspring. OBJECTIVE: The objective was to determine whether a prenatal MMN-fortified food supplement (FFS) improves anthropometric measures at birth compared with supplementation with an MMN pill alone. DESIGN: We conducted a nonblinded, individually randomized controlled trial in 1296 pregnant women in 2 villages in rural Burkina Faso. Supplements were provided on a daily basis, and compliance was closely verified by using a community-based network of home visitors. RESULTS: Anthropometric measures at birth were available for analysis for 87% of the 1175 live singleton deliveries enrolled. After adjustment for gestational age at birth, the FFS group had a significantly higher birth length (+4.6 mm; P = 0.001). FFS supplementation resulted in a modestly higher birth weight (+31 g; P = 0.197). Subgroup analyses showed clinically important treatment effects on birth length (+12.0 mm; P = 0.005) and on birth weight (+111 g; P = 0.133) for underweight [body mass index (in kg/m(2)) <18.5] pregnant women. Women with early pregnancy anemia who received FFS gave birth to longer newborns (+7.3 mm; P = 0.002) than did those who received MMN supplementation. CONCLUSIONS: The provision of FFS to pregnant women resulted in higher birth length than did MMN supplementation. For women with a suboptimal prepregnancy nutritional status, MMN supplementation should be complemented with a balanced energy and protein supplement to produce a clinical effect on birth size. The trial was registered at clinicaltrials.gov as NCT00909974

    Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis

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    BACKGROUND: Human African trypanosomiasis, caused by Trypanosoma brucei, involves an early hemolymphatic stage followed by a late encephalitic stage. METHODS: We studied the expression of chemokines with use of microarray and enzyme-linked immunosorbent assay in T. brucei brucei-infected mice and in patients with human African trypanosomiasis and examined their role in controlling brain accumulation of T cells and parasites. RESULTS: The messenger RNAs (mRNAs) encoding CXCR3 ligands CXCL9 and CXCL10 demonstrated the greatest increases among chemokines in brain specimens of infected mice, as determined by microarray. CXCL9 and CXCL10 mRNA accumulation was interferon (IFN)-gamma-dependent. Expression of CXCL10 was predominantly observed in astrocytes. Weight loss was registered in wild-type but not in CXCL10(-/-) and CXCR3(-/-) infected mice. Infected CXCL10(-/-) or CXCR3(-/-) mice demonstrated reduced accumulation of trypanosomes and T cells in the brain parenchyma but similar parasitemia levels, compared with wild-type mice. CXCL10 and IFN-gamma levels were increased in the cerebrospinal fluid of patients with late stage but not early stage human African trypanosomiasis. Levels of CXCL10 in patients with late stage human African trypanosomiasis were associated with somnolence, low body weight, and trypanosomes in the cerebrospinal fluid. CONCLUSION: IFN-gamma-dependent CXCL10 is critical for accumulation of T cells and trypanosomes in the brain during experimental African trypanosomiasis. Data suggest CXCL10 as a candidate marker for late stage human African trypanosomiasis

    The prevalence of Mycobacterium bovis-infection and atypical mycobacterioses in cattle in and around Morogoro, Tanzania

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    A study was conducted to determine the prevalence of Mycobacterium bovis-infection and atypical mycobacterioses in different cattle herd management systems in and around Morogoro, Tanzania. Between April and June 2005, a total of 728 bovines from 49 herds were tested for M. bovis-infection and atypical mycobacterioses. Milk samples were taken from tuberculin positive animals and analysed for the presence of mycobacteria. Total prevalences of 2.5% and 10.1% were found for M. bovis-infection and atypical mycobacterioses respectively, with more M. bovis-infection in cattle in the extensive management system and more atypical mycobacterioses in cattle in the intensive management system. From 8 out of 42 milk samples (19%) atypical mycobacteria were cultured. A higher prevalence of M. bovis-infection in the extensive sector could be due to several factors. In addition, such high prevalence puts herd owners and their families at risk for BTB. Therefore control of BTB, as well as education of cattle owners is important, especially in the extensive sector

    High level of cross-resistance between kanamycin, amikacin, and capreomycin among Mycobacterium tuberculosis isolates from Georgia and a close relation with mutations in the rrs gene

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    The aminoglycosides kanamycin and amikacin and the macrocyclic peptide capreomycin are key drugs for the treatment of multidrug-resistant tuberculosis (MDR-TB). The increasing rates of resistance to these drugs and the possible cross-resistance between them are concerns for MDR-TB therapy. Mutations in the 16S rRNA gene (rrs) have been associated with resistance to each of the drugs, and mutations of the tlyA gene, which encodes a putative rRNA methyltransferase, are thought to confer capreomycin resistance in Mycobacterium tuberculosis bacteria. Studies of possible cross-resistance have shown variable results. In this study, the MICs of these drugs for 145 clinical isolates from Georgia and the sequences of the rrs and tlyA genes of the isolates were determined. Of 78 kanamycin-resistant strains, 9 (11.5%) were susceptible to amikacin and 16 (20.5%) were susceptible to capreomycin. Four strains were resistant to capreomycin but were susceptible to the other drugs, whereas all amikacin-resistant isolates were resistant to kanamycin. Sequencing revealed six types of mutations in the rrs gene (A514C, C517T, A1401G, C1402T, C1443G, T1521C) but no mutations in the tlyA gene. The A514C, C517T, C1443G, and T1521C mutations showed no association with resistance to any of the drugs. The A1401G and C1402T mutations were observed in 65 kanamycin-resistant isolates and the 4 capreomycin-resistant isolates, respectively, whereas none of the susceptible isolates showed either of those mutations. The four mutants with the C1402T mutations showed high levels of resistance to capreomycin but no resistance to kanamycin and amikacin. Detection of the A1401G mutation appeared to be 100% specific for the detection of resistance to kanamycin and amikacin, while the sensitivities reached 85.9% and 94.2%, respectively

    Nicht-tuberkulöse mykobakterielle Infektionen an Hand und Handgelenk: eine retrospektive Analyse von fünf Fällen

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    Purpose: A suggestion for a graduated diagnostic and therapeutic approach for patients with a suspected infection with non-tuberculous mycobacteria (NTM) of the hand and wrist is made. Patients and Methods: Between March 2003 and February 2007, 2 women and 3 men with an average age of 64 years were treated for an NTM infection of the hand and wrist. 4 patients had a tenosynovitis of the wrist. In 1 patient both wrists were involved. 1 patient had a granuloma of the index finger. The patients' charts, the operation reports, histological and bacteriological findings and the antibiogram were evaluated. Results: An inoculating trauma was identified in four patients. Intraoperatively rice bodies were present in the 4 patients with a tenosynovitis of the wrist. Histological findings showed acid-fast bacilli in 2 patients and chronic inflammatory reaction with/without granuloma (3/2) in 5 patients. Species identification was based on PCR and microbiological culture and revealed in three patients slow growing species (M. malmoense, M. nonchromogenicum, M. szulgai) and in two patients M. marinum (intermediate growth rate). Therapy consisted of immediate postoperative empirical combined drug treatment followed by antibiogram-based therapy. All patients showed healing of the infection at the final follow-up at an average of 25.2 months (range: 15-44 months) postoperatively. Conclusion: Consideration of non-tuberculous mycobacteria in the differential diagnosis in cases of localised tenosynovitis is paramount for diagnosis. Treatment based on graduated diagnostic steps, surgery and drugs (empirical followed by directed drugs) can achieve favourable clinical outcomes

    Pathogenetic mechanisms of the intracellular parasite Mycobacterium ulcerans leading to Buruli ulcer

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    The necrotising skin infection Buruli ulcer is at present the third most common human mycobacteriosis worldwide, after tuberculosis and leprosy. Buruli ulcer is an emergent disease that is predominantly found in humid tropical regions. There is no vaccine against Buruli ulcer and its treatment is difficult. In addition to the huge social effect, Buruli ulcer is of great scientific interest because of the unique characteristics of its causative organism, Mycobacterium ulcerans. This pathogen is genetically very close to the typical intracellular parasites Mycobacterium marinum and Mycobacterium tuberculosis. We review data supporting the interpretation that M ulcerans has the essential hallmarks of an intracellular parasite, producing infections associated with immunologically relevant inflammatory responses, cell-mediated immunity, and delayed-type hypersensitivity. This interpretation judges that whereas M ulcerans behaves like the other pathogenic mycobacteria, it represents an extreme in the biodiversity of this family of pathogens because of its higher cytotoxicity due to the secretion of the exotoxin mycolactone. The acceptance of the interpretation that Buruli ulcer is caused by an intracellular parasite has relevant prophylactic and therapeutic implications, rather than representing the mere attribution of a label with academic interest, because it prompts the development of vaccines that boost cell-mediated immunity and the use of chemotherapeutic protocols that include intracellularly active antibiotics

    Five-year experience with scaling-up access to antiretroviral treatment in an HIV care programme in Cambodia

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    OBJECTIVES: To evaluate a 5-year HIV care programme (2003-2007) in the Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia. METHODS: Analysis of routine programme indicators per year: number of new patients, active patients, antiretroviral therapy (ART) coverage in the cohort, mortality and loss to follow-up. Comparison of mortality before and after the start of ART using Kaplan-Meier survival curves. Analysis of risk factors using Cox regression for the combined endpoint of mortality and loss to follow-up in patients on ART. RESULTS: 3844 patients were registered in the hospital between March 2003 and December 2007. The mortality and loss to follow-up rate fell and paralleled the rise of ART coverage from 23% in 2003 to 90% in 2007. The mortality and the loss to follow-up rate was significantly higher in patients not on ART but eligible (Log rank P < 0.001). The combined endpoint of mortality and loss to follow-up was 48.7% after one year in patients who were waiting for ART. 1667 patients were started on ART. The combined endpoint (mortality and loss to follow-up) in this group was 11.5% at 12 months and 14.2% at 24 months. Risk factors for mortality in the ART group were male sex, CD4 count <50 cells/microl, BMI <18 and haemoglobin levels <10 g/dl. CONCLUSION: Better access to ART is associated with lower mortality and fewer losses to follow-up. Pre-ART attrition remains significant. Strategies are needed to enable an earlier start of ART and to promote retention in care

    Reducing costs and operational constraints of dengue vector control by targeting productive breeding places: a multi-country non-inferiority cluster randomized trial

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    OBJECTIVES: To test the non-inferiority hypothesis that a vector control approach targeting only the most productive water container types gives the same or greater reduction of the vector population as a non-targeted approach in different ecological settings and to analyse whether the targeted intervention is less costly. METHODS: Cluster randomized trial in eight study sites (Venezuela, Mexico, Peru, Kenya, Thailand, Myanmar, Vietnam, Philippines), with each study area divided into 18-20 clusters (sectors or neighbourhoods) of approximately 50-100 households each. Using a baseline pupal-demographic survey, the most productive container types were identified which produced >or=55% of all Ae. aegypti pupae. Clusters were then paired based on similar pupae per person indices. One cluster from each pair was randomly allocated to receive the targeted vector control intervention; the other received the 'blanket' (non-targeted) intervention attempting to reach all water holding containers. RESULTS: The pupal-demographic baseline survey showed a large variation of productive container types across all study sites. In four sites the vector control interventions in both study arms were insecticidal and in the other four sites, non-insecticidal (environmental management and/or biological control methods). Both approaches were associated with a reduction of outcome indicators in the targeted and non-targeted intervention arm of the six study sites where the follow up study was conducted (PPI, Pupae per Person Index and BI, Breteau Index). Targeted interventions were as effective as non-targeted ones in terms of PPI. The direct costs per house reached were lower in targeted intervention clusters than in non-targeted intervention clusters with only one exception, where the targeted intervention was delivered through staff-intensive social mobilization. CONCLUSIONS: Targeting only the most productive water container types (roughly half of all water holding container types) was as effective in lowering entomological indices as targeting all water holding containers at lower implementation costs. Further research is required to establish the most efficacious method or combination of methods for targeted dengue vector interventions

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