Leonardo Martinez

The Epidemiology and Geographic Distribution of Nontuberculous Mycobacteria Clinical Isolates from Sputum Samples in the Eastern Region of China

Background Nontuberculous mycobacteria (NTM) have been reported to be increasing worldwide and its geographic distribution differs by region. The aim of this study was to describe the epidemiology and distribution of NTM in the eastern part of China. Methods Sputum samples were collected from 30 surveillance sites for tuberculosis drug resistance test from May 1, 2008 to December 31, 2008. Identification was performed using a biochemical test, multiplex PCR and GenoType Mycobacterium CM/AS assay. Results A total of 1779 smear positive clinical isolates were obtained, of which 60 (3.37%) were NTM. Five species/complex of NTM were identified; M. intracellulare was the predominated species (68.33%), followed by M. abscessus-M. immunogenum (13.33%), Mycobacterium spec. (10.00%), M. Kansasii (6.67%) and M. peregrinum-M. alvei-M. septicum (1.67%). Conclusion M. intracellulare was the main species of NTM in the eastern part of China and clinical physicians should pay more attention to NTM induced pulmonary disease.

Changes in tuberculin skin test positivity over 20 years in periurban shantytowns in Lima, Peru

A cross-sectional, community-based study was performed in 2012 with 428 residents of periurban shantytowns in Lima, Peru to study risk factors for and changes in latent tuberculosis infection in age-stratified groups compared with our data from the same region in 1990 (N = 219) and 2005 (N = 103). Tuberculin skin test positivity in these communities was highly prevalent at 52% overall, increased with age (P < 0.01) and was similar to 2005 (53%) and 1990 (48%). From 1990 to 2012, the prevalence of tuberculin positivity decreased in 5-14 and 15-24 year old groups (to 17% and 34%, respectively, both P < 0.05). However, this may be explained by cessation of Bacille Calmette-Guérin revaccination during this period, because Bacille Calmette-Guérin revaccination doubled tuberculin positivity. Over the same 22-year period, tuberculin positivity in the ≥ 25 year old group remained high (71%, P = 0.3), suggesting that prevalent latent tuberculosis infection persists in the adult population despite improving medical care and socioeconomic development in this region.

Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV–tuberculosis co-infected patients on combination antiretroviral therapy

BACKGROUND Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status. METHODS This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants. RESULTS cART was associated with a monthly rise of 15.7 cells/μl (p<0.001). Overall, age was not associated with CD4+ T-cell recovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age <40 vs. ≥40 years predicted superior absolute CD4+ T-cell recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p<0.001). CONCLUSIONS TB-infected HIV-positive patients aged ≥40 years have a slower rate of immune restoration given cART, particularly if BMI is >18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART.

Cutaneous Leishmaniasis “Chiclero's Ulcer” in Subtropical Ecuador

An 18-year-old female presented with a severe ulcerative lesion on her right ear of 6 weeks duration. Her right ear was edematous and erythematous with a large, painless ulcerative lesion covering a third of the pinna and satellite papular lesions on the posterior. She was diagnosed with chicleros ulcer. A skin smear stained with Diff-quik showed abundant Leishmania parasites. Chicleros ulcer is a rare clinical presentation and is typically severe and difficult to treat. Physicians in Ecuador recommend administering prolonged intramuscular Glucantime. Side effects are common and can be severe resulting in low patient compliance. Because of preferences of the patient and the large volume needed for her weight, we recommended topical treatment with a lotion of Glucantime mixed half and half with white Merthiolate. After applying this lotion to the lesion 3 to 4 times a day for 6 weeks, the lesion healed.

Time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis: a prospective cohort study from urban China

Sputum culture plays an important role in monitoring treatment response in patients with multidrug-resistant tuberculosis (MDR-TB), and sputum culture conversion is a clinical tool used to predict therapeutic efficacy [1]. Monthly culture monitoring is essential for earlier detection of treatment failure in patients with MDR-TB. More sensitive signals of nonresponse would further avoid adverse outcomes [2]. The timing of testing for culture conversion has potential as a marker of MDR-TB treatment success http://ow.ly/borO308pPXg

Free-Ranging Chickens in Households in a Periurban Shantytown in Peru—Attitudes and Practices 10 Years after a Community-Based Intervention Project

Free-ranging chickens are often found in periurban communities in developing countries, and their feces can pose a significant public health sanitation problem. Corralling chickens raised in these periurban areas in chicken coops has been proposed previously as an intervention to address this problem. Aims of this study were to revisit households in a corralling intervention study conducted in 2000-2001 to compare poultry-raising practices and investigate current attitudes regarding the impact of raising chickens in a periurban environment. Sociobehavioral questionnaires were given sequentially to all study participants; 30 families (58%) ceased raising poultry of any kind, whereas 42 (81%) do not raise chickens in their home. This finding indicates a significant reduction in poultry-raising in our study population since 2000-2001, possibly because of acculturation and/or change in socioeconomic status. However, attitudes about corral use for raising poultry were overwhelmingly positive, and the most common reason cited was cleanliness of the home.

Effectiveness of WHO's pragmatic screening algorithm for child contacts of tuberculosis cases in resource-constrained settings: A prospective cohort study in Uganda

BACKGROUND Tuberculosis is a leading cause of global childhood mortality; however, interventions to detect undiagnosed tuberculosis in children are underused. Child contact tracing has been widely recommended but poorly implemented in resource-constrained settings. WHO has proposed a pragmatic screening approach for managing child contacts. We assessed the effectiveness of this screening approach and alternative symptom-based algorithms in identifying secondary tuberculosis in a prospectively followed cohort of Ugandan child contacts. METHODS We identified index patients aged at least 18 years with microbiologically confirmed pulmonary tuberculosis at Old Mulago Hospital (Kampala, Uganda) between Oct 1, 1995, and Dec 31, 2008. Households of index patients were visited by fieldworkers within 2 weeks of diagnosis. Coprevalent and incident tuberculosis were assessed in household contacts through clinical, radiographical, and microbiological examinations for 2 years. Disease rates were compared among children younger than 16 years with and without symptoms included in the WHO pragmatic guideline (presence of haemoptysis, fever, chronic cough, weight loss, night sweats, and poor appetite). Symptoms could be of any duration, except cough (>21 days) and fever (>14 days). A modified WHO decision-tree designed to detect high-risk asymptomatic child contacts was also assessed, in which all asymptomatic contacts were classified as high risk (children younger than 3 years or immunocompromised [HIV-infected]) or low risk (aged 3 years or older and immunocompetent [HIV-negative]). We also assessed a more restrictive algorithm (ie, assessing only children with presence of chronic cough and one other tuberculosis-related symptom). FINDINGS Of 1718 household child contacts, 126 (7%) had coprevalent tuberculosis and 24 (1%) developed incident tuberculosis, diagnosed over the 2-year study period. Of these 150 cases of tuberculosis, 95 (63%) were microbiologically confirmed with a positive sputum culture. Using the WHO approach, 364 (21%) of 1718 child contacts had at least one tuberculosis-related symptom and 85 (23%) were identified as having coprevalent tuberculosis, 67% of all coprevalent cases detected (diagnostic odds ratio 9·8, 95% CI 6·8-14·5; p<0·0001). 1354 (79%) of 1718 child contacts had no symptoms, of whom 41 (3%) had coprevalent tuberculosis. The WHO approach was effective in contacts younger than 5 years: 70 (33%) of 211 symptomatic contacts had coprevalent disease compared with 23 (6%) of 367 asymptomatic contacts (p<0·0001). This approach was also effective in contacts aged 5 years and older: 15 (10%) of 153 symptomatic contacts had coprevalent disease compared with 18 (2%) of 987 asymptomatic contacts (p<0·0001). More coprevalent disease was detected in child contacts recommended for screening when the study population was restricted by HIV-serostatus (11 [48%] of 23 symptomatic HIV-seropositive child contacts vs two [7%] of 31 asymptomatic HIV-seropositive child contacts) or to only culture-confirmed cases (47 [13%] culture confirmed cases of 364 symptomatic child contacts vs 29 [2%] culture confirmed cases of 1354 asymptomatic child contacts). In the modified algorithm, high-risk asymptomatic child contacts were at increased risk for coprevalent disease versus low-risk asymptomatic contacts (14 [6%] of 224 vs 27 [2%] of 1130; p=0·0021). The presence of tuberculosis infection did not predict incident disease in either symptomatic or asymptomatic child contacts: in symptomatic contacts, eight (5%) of 169 infected contacts and six (5%) of 111 uninfected contacts developed incident tuberculosis (p=0·80). Among asymptomatic contacts, incident tuberculosis occurred in six (<1%) of 795 contacts infected at baseline versus four (<1%) of 518 contacts uninfected at baseline, respectively (p=1·00). INTERPRETATION WHOs pragmatic, symptom-based algorithm was an effective case-finding tool, especially in children younger than 5 years. A modified decision-tree identified 6% of asymptomatic child contacts at high risk for subclinical disease. Increasing the feasibility of child-contact tracing using these approaches should be encouraged to decrease tuberculosis-related paediatric mortality in high-burden settings, but this should be partnered with increasing access to microbiological point-of-care testing. FUNDING National Institutes of Health, Tuberculosis Research Unit, AIDS International Training and Research Program of the Fogarty International Center, and the Center for AIDS Research.

Cognitive deficits and educational loss in children with schistosome infection—A systematic review and meta-analysis

Background By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. Methodology/Principal findings This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design. Conclusion/Significance Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits. Trial registration ClinicalTrials.gov CRD42016040052

Glycemic Control and the Prevalence of Tuberculosis Infection: A Population-based Observational Study

Background Several cohort studies demonstrate that diabetics are at increased risk for active tuberculosis, and poor glycemic control may exacerbate this risk. A higher prevalence of tuberculosis infection at baseline among diabetics may partially explain these results; however, no population-based studies have investigated this association. Furthermore, whether glycemic control modifies the relationship between diabetes and tuberculosis infection, as it does with active tuberculosis, is unknown. Methods Diabetics were diagnosed through physician evaluation and using 3 laboratory tests including hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), or 2-hour plasma glucose (PG). Tuberculosis infection was diagnosed through tuberculin skin tests, and glycemic control was assessed linearly and categorically using recommended targets. Results Among 4215 participants, the prevalence of tuberculosis infection was 4.1%, 5.5%, and 7.6% in nondiabetic, prediabetic, and diabetic participants (Ptrend = .012). In multivariate analysis, diabetes was associated with tuberculosis infection (adjusted odds ratio [AOR], 1.5; 95% confidence interval [CI], 1.0-2.2). Compared to nondiabetics, diabetics who were undiagnosed (AOR, 2.2 and 1.2 in diagnosed diabetics), FPG >130 mg/dL (AOR, 2.6 and 1.3 in diabetics with FPG ≤130 mg/dL), or not on insulin (AOR, 1.7 and 0.8 in diabetics on insulin) had elevated tuberculosis infection rates. In a linear dose-response analysis, increasing values of FPG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.03), PG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.04), and HbA1C (AOR, 1.13 per 1%; 95% CI, 1.04-1.22) all predicted tuberculosis infection. Conclusions Our results suggest glycemic control may modify the relationship between tuberculosis infection and diabetes.

Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

ABSTRACT The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.