Query: Hollm-Delgado

title: Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta analysis of 9,153 Patients
abstract: Dick Menzies and colleagues report findings from a collaborative, individual patient level meta analysis of treatment outcomes among patients with multidrug resistant tuberculosis.

title: Resistance to fluoroquinolones and second line injectable drugs: impact on multidrug resistant TB outcomes
abstract: A meta analysis for response to treatment was undertaken using individual data of multidrug resistant tuberculosis (MDR TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR TB patients infected with strains without additional resistance (n=4763; 64% 95% CI 57 72% or with resistance to second line injectable drugs only (n=1130; 56% 95% CI 45 66% than in those having resistance to fluoroquinolones alone (n=426; 48% 95% CI 36 60% or to fluoroquinolones plus second line injectable drugs (extensively drug resistant (XDR) TB) (n=405; 40% 95% CI 27 53% In XDR TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95% CI 1.4 16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95% CI 1.4 26.3) The odds of success in XDR TB patients was maximised when the intensive phase reached 6.6 9.0 months duration and the total duration of treatment 20.1 25.0 months. In XDR TB patients, regimens containing more drugs than those recommended in MDR TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.

title: Drug resistance beyond extensively drug resistant tuberculosis: individual patient data meta analysis
abstract: The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug resistant (XDR) TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR TB outcomes were included in a meta analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR TB patient groups: XDR plus resistance to all the second line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/terizidone or para aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ) Of 405 XDR TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95% CI 0.2 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6 2.8) Patients with additional resistance beyond XDR TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR TB.

title: Acute Lower Respiratory Infection Among Bacille Calmette Guerin (BCG) Vaccinated Children
abstract: To determine whether Bacille Calmette Guerin (BCG) vaccination is linked to the risk of acute lower respiratory infection (ALRI) among children <5 years of age.  Data from Macro International Demographic and Health Surveys and United Nations Children's Fund Multiple Indicator Cluster Surveys were used to identify a primary cohort of 58 021 children in 19 countries (2005 2010) and a secondary cohort of 93 301 children in 18 countries (2000 2007) Information was collected by trained interviewers during home visits using standardized questionnaires, review of vaccination health cards, and measurement of health indicators.  BCG vaccination was associated with a 17% to 37% risk reduction for suspected ALRI in both cohorts. The only vaccine or vitamin supplement to modify the effect of BCG was diphtheria tetanus pertussis (DTP; P .001) The order in which the vaccines were first received was central to this phenomena (BCG before DTP, adjusted/propensity score weighted relative risk [apRR] 0.79, 95% confidence interval [CI] 0.70 0.89; BCG with DTP, apRR: 0.82, 95% CI: 0.71 0.94; and BCG after DTP, apRR: 1.00, 95% CI: 0.87 1.13) but not number of DTP doses received. Other modifiers included vaccine strain used in immunization programs, chlorinating drinking water, using wood burning fuel cook stoves, and owning livestock.  Children vaccinated with BCG had a significantly lower risk of suspected ALRI. Clarification is needed as to whether this is due to reductions in the underlying risk of tuberculosis or ALRI per se.

title: Surgery as an Adjunctive Treatment for Multidrug Resistant Tuberculosis: An Individual Patient Data Metaanalysis.
abstract: Medical treatment for multidrug resistant (MDR) tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR tuberculosis.  Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated.  A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR] 3.0; 95% confidence interval [CI] 1.5 5.9; I(2)R, 11.8% but pneumonectomy was not (aOR, 1.1; 95% CI, .6 2.3; I(2)R, 13.2% Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9 7.1; I(2)R, 0.2% CONCLUSIONS Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

title: Microscopic observation drug susceptibility assay for the diagnosis of TB.
abstract: New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug resistant tuberculosis. Rapid, sensitive detection of tuberculosis and multidrug resistant tuberculosis in sputum has been demonstrated in proof of principle studies of the microscopic observation drug susceptibility (MODS) assay, in which broth cultures are examined microscopically to detect characteristic growth.  In an operational setting in Peru, we investigated the performance of the MODS assay for culture and drug susceptibility testing in three target groups: unselected patients with suspected tuberculosis, prescreened patients at high risk for tuberculosis or multidrug resistant tuberculosis, and unselected hospitalized patients infected with the human immunodeficiency virus. We compared the MODS assay head to head with two reference methods: automated mycobacterial culture and culture on Lowenstein Jensen medium with the proportion method.  Of 3760 sputum samples, 401 (10.7% yielded cultures positive for Mycobacterium tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89.0% for automated mycobacterial culture, and 84.0% for Lowenstein Jensen culture (P<0.001) the median time to culture positivity was 7 days, 13 days, and 26 days, respectively (P<0.001) and the median time to the results of susceptibility tests was 7 days, 22 days, and 68 days, respectively. The incremental benefit of a second MODS culture was minimal, particularly in patients at high risk for tuberculosis or multidrug resistant tuberculosis. Agreement between MODS and the reference standard for susceptibility was 100% for rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined results for multidrug resistance) 95% for ethambutol, and 92% for streptomycin (kappa values, 1.0, 0.89, 0.93, 0.71, and 0.72, respectively)  A single MODS culture of a sputum sample offers more rapid and sensitive detection of tuberculosis and multidrug resistant tuberculosis than the existing gold standard methods used.

title: Lack of an adverse effect of Giardia intestinalis infection on the health of Peruvian children.
abstract: Giardia intestinalis is a common gastrointestinal protozoan worldwide, but its effects on childhood growth in developing countries are not clearly understood. The authors aimed to describe its effects on child growth. They followed 220 Peruvian children daily for diarrhea, weekly for stool samples, and monthly for anthropometry. The authors modeled the effect of nutritional status on the risk of Giardia infection and the risk of diarrhea attributable to Giardia using negative binomial regression. They modeled the effects of Giardia infection on growth using linear regression, with 85% of children becoming infected with Giardia and 87% of these becoming reinfected. In multivariable analysis, the risk of Giardia infection did not vary with weight for age (relative risk 1.00, 95% confidence interval: 0.89, 1.12) or height for age (relative risk 0.92, 95% confidence interval: 0.82, 1.04) Giardiasis did not affect growth at 1 or 2 months following the first infection at any age interval. The longitudinal prevalence of Giardia between 6 and 24 months of age was not associated with height gain in that interval (p 0.981) Giardia was not associated with an increased risk of diarrhea at any age interval. Study results question the importance of Giardia as a childhood pathogen in developing countries where giardiasis is hyperendemic.

title: Microscopic Observation Drug Susceptibility Assay, a Rapid, Reliable Diagnostic Test for Multidrug Resistant Tuberculosis Suitable for Use in Resource Poor Settings
abstract: There is an urgent need for new tools to improve our ability to diagnose tuberculosis (TB) and multidrug resistant TB (MDR TB) in resource poor settings. In a retrospective analysis undertaken in a region with a high incidence of TB, we evaluated the performance of the microscopic observation drug susceptibility assay (MODS) a novel assay developed in Peru which uses an inverted light microscope and culture in Middlebrook 7H9 broth to detect mycobacterial growth. MODS detected 94.0% of 1,908 positive sputum cultures, whereas Lowenstein Jensen (LJ) culture detected only 86.9% (P 0.001) The median time to culture positivity was 8 days (compared to 16 days for the same 208 samples by LJ culture; P 0.001, Wilcoxon signed rank test) The results obtained by direct susceptibility testing using MODS demonstrated excellent concordance for isoniazid and rifampin and the detection of multidrug resistance with those obtained by indirect colorimetric methods: the microplate Alamar Blue assay (MABA) and the tetrazolium microplate assay (TEMA) (agreement, 95, 98, and 94% kappa values, 0.8, 0.7, and 0.7, respectively) The concordance of the susceptibility testing results for ethambutol and streptomycin was poor. MODS is a novel assay which can detect the organisms responsible for TB and MDR TB directly from sputum inexpensively, rapidly, and effectively. A comprehensive prospective evaluation of MODS is under way in Peru, and independent validation in nonresearch laboratories should be undertaken at the earliest opportunity.

title: Vitamin A supplements, routine immunization, and the subsequent risk of Plasmodium infection among children under 5 years in sub Saharan Africa
abstract: Recent studies, partly based on murine models, suggest childhood immunization and vitamin A supplements may confer protection against malaria infection, although strong evidence to support these theories in humans has so far been lacking. We analyzed national survey data from children aged 6 59 months in four sub Saharan African countries over an 18 month time period, to determine the risk of Plasmodium spp. parasitemia (n=8390) and Plasmodium falciparum HRP 2 (PfHRP 2) related antigenemia (n=6121) following vitamin A supplementation and standard vaccination. Bacille Calmette Guerin vaccinated children were more likely to be PfHRP 2 positive (relative risk [RR]=4.06, 95% confidence interval [CI]=2.00 8.28) No association was identified with parasitemia. Measles and polio vaccination were not associated with malaria. Children receiving vitamin A were less likely to present with parasitemia (RR=0.46, 95% CI=0.39 0.54) and antigenemia (RR=0.23, 95% CI=0.17 0.29) Future studies focusing on climate seasonality, placental malaria and HIV are needed to characterize better the association between vitamin A and malaria infection in different settings.

title: Invasive Group A Streptococcal Infections, Clinical Manifestations and Their Predictors, Montreal, 1995 2002
abstract: Specific clinical manifestations of invasive group A streptococcal infection appear to develop not in response to the pathogen, but rather to host or environmental factors.