BackgroundThe “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients.Methods and FindingsThis 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases.A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting.ConclusionsThe low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.

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MDRT induced a substantial antiviral response in this heavily pretreated group of patients despite extensive phenotypic resistance at baseline. Adverse effects were frequent but generally manageable. Our data suggest that relying exclusively on historical, clinical and laboratory evidence may not be sufficient to rule out a possible antiviral response when multiple drug regimens are used in this heavily pretreated patient population.

BackgroundThe comparison of Mycobacterium tuberculosis bacterial genotypes with phenotypic, demographic, geospatial and clinical data improves our understanding of how strain lineage influences the development of drug-resistance and the spread of tuberculosis.MethodsTo investigate the association of Mycobacterium tuberculosis bacterial genotype with drug-resistance. Drug susceptibility testing together with genotyping using both 15-loci MIRU-typing and spoligotyping, was performed on 2,139 culture positive isolates, each from a different patient in Lima, Peru. Demographic, geospatial and socio-economic data were collected using questionnaires, global positioning equipment and the latest national census.ResultsThe Latin American Mediterranean (LAM) clade (OR 2.4, p<0.001) was significantly associated with drug-resistance and alone accounted for more than half of all drug resistance in the region. Previously treated patients, prisoners and genetically clustered cases were also significantly associated with drug-resistance (OR's 2.5, 2.4 and 1.8, p<0.001, p<0.05, p<0.001 respectively).ConclusionsTuberculosis disease caused by the LAM clade was more likely to be drug resistant independent of important clinical, genetic and socio-economic confounding factors. Explanations for this include; the preferential co-evolution of LAM strains in a Latin American population, a LAM strain bacterial genetic background that favors drug-resistance or the "founder effect" from pre-existing LAM strains disproportionately exposed to drugs.

BackgroundSymptoms of anxiety and depression are among the major mental health problems in cancer patients. These symptoms affect the quality of life and treatment adherence, and are associated with other symptoms and longer hospital stays. Valid and reliable screening instruments such as the Hospital Anxiety and Depression Scale (HADS), have made possible the detection of possible cases of depression and anxiety in medically ill patients. However, the psychometric properties of this instrument have not been documented in different types of cancer diagnoses in the Mexican population.

Adherence to highly active antiretroviral therapy (HAART) is necessary to achieve long-term effectiveness. The impact of HIV/AIDS-specific pharmacy services on patient adherence and HIV viral suppression is currently not well described. This study aimed to compare the impact of differing levels of HIV-pharmacy care on adherence and time to HIV viral suppression among participants on HAART enrolled in a population-based HIV/AIDS drug treatment programme in British Columbia. We performed a retrospective observational study of 788 treatment-naïve patients who started HAART between August 1997 and July 2000 and were followed until 31 March 2002. The degree of outpatient pharmacy care was defined according to pharmacy dispensing site for the participants' first prescription of HAART: highest at the AIDS-tertiary care hospital outpatient pharmacies, intermediate at HIV/AIDS drug treatment programme funded off-site pharmacies and lowest at family physician's offices. Cox-proportional hazard models examined the independent effect of pharmacy dispensing site on time to two consecutive HIV viral suppressions controlling for other prognostic factors including physicians' experience, age, gender, injection drug use, use of therapy containing NNRTI versus PI, adherence >90%, AIDS diagnosis at baseline, baseline CD4 cell count and HIV viral load. The median time on antiretrovirals was 28 months (IQR=14-38). There were 489 (62.1%) participants who obtained their medications from the AIDS-tertiary care outpatient pharmacies; 98 (12.4%) from off-site pharmacies and 201 (25.5%) from their physicians' offices. The proportion of patients exhibiting >90% adherence to treatment was observed to be higher among patients receiving their HAART at the AIDS-tertiary care pharmacies compared to off-site pharmacies and to physicians' offices (70.4, 59.2 and 55.7%, respectively; p=0.0001). After adjusting for other prognostic factors, subjects who were first dispensed medications from the AIDS-tertiary care pharmacy were 1.42 times (CI: 1.10-1.84) more likely to achieve HIV viral suppression than those getting their medications from off-site pharmacies and physicians' offices. Providing regular outpatient pharmacy care is independently associated with improved HIV viral load response through enhanced adherence to HAART. Standardization of pharmacy practices for dispensing HAART may improve outcomes for patients who receive their HIV medications from other non-tertiary care pharmacy sites.

BackgroundThe emergence of multidrug-resistant strains is a major health problem especially for countries with high TB incidence such as Peru. In this study, we evaluated High Resolution Melting (HRM) assay in Peruvian isolates for the detection of mutations within rpoB, katG genes and promoter region inhA to determine isoniazid and rifampicin resistance in Mycobacterium tuberculosis (Mtb).MethodsDNA samples extracted from a total of 167 clinical isolates of Mtb, 89 drug-sensitive and 78 multidrug-resistant, were blindly analyzed by HRM analysis and verified by DNA sequencing.ResultsThe HRM analysis generated patterns that were specific to distinguish between sensitive and resistance isolates. The sensitivity and specificity of the HRM assays in comparison with drug susceptibility testing (DST) for detection of rifampicin resistance were 98.7 % and 97.5 %, and for isoniazid resistance were 98.7 % and 100 %.ConclusionThis study suggests that HRM Analysis could help with rapid diagnosis of MDR-TB cases in Peru.

ResumenLa sintomatología ansiosa es uno de los principales problemas psicológicos en pacientes oncológicos. La Escala de Ansiedad de Beck (BAI) ha demostrado ser un instrumento válido y confiable. Sin embargo, hasta ahora no se había documentado su comportamiento psicométrico en población oncológica en México.Objetivo: Determinar las propiedades psicométricas de la Escala de Ansiedad de Beck (BAI) en una muestra de pacientes con cáncer.Material y Método: participaron 250 pacientes del Instituto Nacional de Cancerología, de los cuales 138 eran mujeres (55,2%) y 112 eran hombres (44,8%); la edad promedio fue de 46,6 ± 14,3 años. Los participantes contestaron además del BAI, la Subescala de ansiedad de la Escala de Ansiedad y Depresión (HADS-A).Resultados: El análisis factorial varimax con 21 reactivos presentó una estructura con 4 factores: Subjetivo, Neurofisiológico, Autonómi-co y Síntomas vasomotores que explicaron el 46,38% de la varianza. La consistencia interna de la escala global mostró un índice satisfactorio (α=0,82). La validez por medio de correlación con el HADS-A mostraron resultados significativos (r de Pearson Conclusions: The BAI in Mexican population with cancer showed adequate psychometric characteristics. Detection of anxiety symp-