Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis.

BACKGROUND: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. METHODS AND FINDINGS: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%-19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%-48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15-20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0-8.3, p = 0.041 and aOR 5.9, 95% CI 1.7-20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias. CONCLUSIONS: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated.

Morphological and molecular characterization of Strongyloides ophidiae (Nematoda, Strongyloididae).

The aim of the present study is to report morphological data from parasitic female, rhabditoid and filarioid larvae, free-living female worms and eggs of Strongyloides ophidiae (Nematoda, Strongyloididae). In addition, a molecular DNA analysis was carried out using a pool of eight S. ophidiae parasitic females. Samples were obtained from the small intestine of Oxyrhopus guibei (Serpentes, Colubridae) collected in the municipality of Lençóis Paulista, State of São Paulo, Brazil. DNA amplification by polymerase chain reaction (PCR) resulted in a 350 bp band for samples containing S. ophidiae and Strongyloides venezuelensis DNA. Strongyloides ophidiae nucleotide sequence analysis showed 98% similarity with Strongyloides procyonis and 97% with Strongyloides cebus, Strongyloides stercoralis, Strongyloides fuelleborni and Strongyloides sp. from snakes.

Comparative RH maps of the river buffalo and bovine Y chromosomes.

Radiation hybrid maps were constructed for river buffalo and cattle Y chromosomes. A total of 41 cattle-derived Y-chromosome molecular markers were selected and tested with 2 previously described 5,000-rad whole-genome radiation hybrid (RH) panels (river buffalo - BBURH(5000) and cattle - BTARH(5000)) for generation of maps. Among the initial 41 selected markers, a subset of 26 markers generated PCR products suitable for scoring with the BBURH(5000) panel. Of these, 19 markers (73%) were distributed in 1 linkage group spanning 341.3 cR. Retention frequencies (RF) for individual markers ranged from 17.8% for SMCY to 56.7% for BTY1, with an average RF of 37.6%. From the selected markers, 37 generated reliable scores using the BTARH(5000) panel. The newly constructed BTAY RH map contains 28 markers distributed within 1 linkage group. Twenty-four of these markers had been previously mapped on BTAY using a 7,000-rad cattle-hamster WG-RH panel and 4 markers were mapped for the first time (ZFY, SeqRep, RepSeqS4 and BTY1). The length of the BTAY RH map was estimated to be 602.4 cR. Retention frequencies for individual mapped markers ranged from 10% (INRA126) to 63.3% (SeqRep), with an average RF of 35.3%. RH marker positions along the Y chromosome were compared between BBUY and BTAY, which revealed differences in the order of some of the markers. The BBUY pseudoautosomal region (PAR) is delineated by 3 BTAY PAR markers (MAF45, TGLA325 and UMN2008). These markers are telomeric in both species but are not found in the same order. Here we have demonstrated the effective use of bovine Y chromosome markers for the development of the first BBUY RH map. Likewise, these set of markers can be used for comparative assessment of Y chromosomes in other members of the Bovidae family.

Vertical migration of Haemonchus contortus third stage larvae on Brachiaria decumbens grass.

The present study aimed at evaluating the vertical migration of Haemonchus contortus third stage larvae (L3) on Brachiaria decumbens grass, as well as at verifying whether larval numbers on pasture varies over the day due to climatic conditions. Feces containing H. contortus L3 were deposited on the soil in the middle of herbage which was initially 30 cm high. Seven days later, samples of different herbage strata (0-10, 10-20 and >20 cm), remaining feces and a layer of approximately 1cm soil were collected. Tests were carried out in four periods: September 2006, December 2006, March 2007, and June 2007. Samples were collected at sunrise, mid-day, sunset, and mid-night. The humidity and temperature conditions observed in different months influenced larval migration from the feces to the grass. In September, December and March, it rained after fecal deposition on pasture, which favored migration of larvae from the feces to the herbage. Conversely, in June 2007, when there was no rainfall after fecal deposition and temperatures were lower, L3 were mainly recovered from feces. As regards the vertical migration of larvae, the numbers of H. contortus L3 in the forage strata remained relatively constant over the day. This indicates there is not a determined period in which sheep on pasture are at higher risk of infection. Finally, in all collection periods a considerable amount of third stage larvae was observed on the herbage top, which is the first plant part consumed by sheep.

Salmonella typhi endocarditis: a case report.

Salmonella are a rare cause of infective endocarditis. This report describes a case where Salmonella typhi was isolated from the blood and urine of a patient with echocardiographically documented aortic valve disease and endocarditis. The patient was treated with two weeks of ceftriaxone (3 g/day) and amikacin (15 mg/kg/day), followed by a further two weeks of ceftriaxone (3 g/day) alone. He made a complete recovery.

Gujjar lung: a disease mimicking miliary tuberculosis.

Gujjar lung is a chronic lung disease caused due to the long-term exposure to pinewood smoke inhalation in Gujjar community and the people residing at the hilly regions of the Indian sub-continent. This is characterized clinically by progressive cough and dyspnea, distinct radiological patterns and pathological features of anthracotic nodules and fibrosis. A typical case with miliary mottling on chest radiograph is presented and the relevant literature reviewed.

Seroprevalence of brucellosis in Kashmir (India) among patients with pyrexia of unknown origin.

Over a period of 5 years from 1992 to 1997 a total of 3,532 patients of pyrexia of unknown origin (PUO) were subjected to Wright's tube agglutination test for brucellosis. Of the 3,532 patients tested, 28 (0.8%) were found seropositive for brucellosis. Males outnumbered females by a ratio of 3:1. Whereas the seroprevalence among males clearly was age-related, the seroprevalence among women was not. The highest number (43%) of positive males belonged to the age group 21-30 years. The majority of patients had titres of 1:160 or 1:256, high titres of 1:512 and 1:1024 were found in 21.4% patients.