Showing papers by "Soumya Swaminathan published in 2015"

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Abstract: Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Prevalence and risk factors for adult pulmonary tuberculosis in a metropolitan city of South India.

Abstract: BACKGROUND: The present study measured the community prevalence and risk factors of adult pulmonary tuberculosis (PTB) in Chennai city, and also studied geographical distribution and the presence of different M. tuberculosis strains in the survey area. METHODS: A community-based cross sectional survey was carried out from July 2010 to October 2012 in Chennai city. Prevalence of bacteriologically positive PTB was estimated by direct standardization method. Univariate and multivariate analyses were carried out to identify significant risk factors. Drug susceptibility testing and spoligotyping was performed on isolated M. tuberculosis strains. Mapping of PTB cases was done using geographic positioning systems. RESULTS: Of 59,957 eligible people, 55,617 were screened by X-ray and /or TB symptoms and the prevalence of smear, culture, and bacteriologically positive PTB was estimated to be 228 (95% CI 189-265), 259 (95% CI 217-299) and 349 (95% CI 330-428) per 100,000 population, respectively. Prevalence of smear, culture, and bacteriologically positive PTB was highest amongst men aged 55-64 years. Multivariate analysis showed that occurrence of both culture and bacteriologically positive PTB disease was significantly associated with: age >35 years, past history of TB treatment, BMI <18.5 Kgs/m2, solid cooking fuel, and being a male currently consuming alcohol. The most frequent spoligotype family was East African Indian. Spatial distribution showed that a high proportion of patients were clustered in the densely populated north eastern part of the city. CONCLUSION: Our findings demonstrate that TB is a major public health problem in this urban area of south India, and support the use of intensified case finding in high risk groups. Undernutrition, slum dwelling, indoor air pollution and alcohol intake are modifiable risk factors for TB disease.

Safety and tolerability profile of second-line anti-tuberculosis medications.

Abstract: Tuberculosis (TB) remains a major public health problem, representing the second leading cause of death from infectious diseases globally, despite being nearly 100 % curable. Multidrug-resistant (MDR)-TB, a form of TB resistant to isoniazid and rifampicin (rifampin), two of the key first-line TB drugs, is becoming increasingly common. MDR-TB is treated with a combination of drugs that are less effective but more toxic than isoniazid and rifampicin. These drugs include fluoroquinolones, aminoglycosides, ethionamide, cycloserine, aminosalicyclic acid, linezolid and clofazimine among others. Minor adverse effects are quite common and they can be easily managed with symptomatic treatment. However, some adverse effects can be life-threatening, e.g. nephrotoxicity due to aminoglycosides, cardiotoxicity due to fluoroquinolones, gastrointestinal toxicity due to ethionamide or para-aminosalicylic acid, central nervous system toxicity due to cycloserine, etc. Baseline evaluation may help to identify patients who are at increased risk for adverse effects. Regular clinical and laboratory evaluation during treatment is very important to prevent adverse effects from becoming serious. Timely and intensive monitoring for, and management of adverse effects caused by, second-line drugs are essential components of drug-resistant TB control programmes; poor management of adverse effects increases the risk of non-adherence or irregular adherence to treatment, and may result in death or permanent morbidity. Treating physicians should have a thorough knowledge of the adverse effects associated with the use of second-line anti-TB drugs, and routinely monitor the occurrence of adverse drug reactions. In this review, we have compiled safety and tolerability information regarding second-line anti-TB drugs in both adults and children.

Towards early inclusion of children in tuberculosis drugs trials : a consensus statement

Abstract: Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Abstract: Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Plasma interleukin-18 levels are a biomarker of innate immune responses that predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome

Abstract: Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS. Methods: Biomarkers were assayed pre-ART and during TB-IRIS, or equivalent timepoint, in a case‐control study of Malaysian HIV patients with paradoxical or unmasking TB-IRIS (n ¼15), TB no IRIS (n ¼14), and no TB or IRIS (n ¼15). Findings for interleukin18 were verified in another cohort of patients with paradoxical TB-IRIS (n ¼26) and their controls (n ¼22) from India. Results: Interleukin-18 was higher in TB-IRIS patients pre-ART and during the event in bothMalaysianpatients (P <0.0001)andIndian patients (P <0.01). CXCL10 was higher pre-ART (P <0.001), mainly in paradoxical TB-IRIS patients, and during TB-IRIS (P <0.001), whereas CXCL8 was only higher during TB-IRIS (P <0.001). Soluble(s) CD14was increasedin allpatients withHIV/TB coinfectionpre-ARTandduringTB-IRIS or equivalent time-point, compared with patients without TB. In contrast, interferon-g was lower before and during TB-IRIS. By receiver operating curve analysis, CXCL10, and/or interleukin-18 pre-ART were predictive of TB-IRIS. Conclusion: Plasma interleukin-18 levels pre-ART are candidate biomarkers for predicting paradoxical and unmasking TB-IRIS and should be investigated for risk stratification and elucidation of disease pathogenesis.

Pediatric tuberculous meningitis: Model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children.

Abstract: Pediatric tuberculous meningitis (TBM) is a highly morbid, often fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic (PK) and outcomes data from adult TBM trials plus plasma PK data from children. A population PK/pharmacodynamic (PD) model using adult data defined rifampin target exposures (plasma area under the curve (AUC)0-24 = 92 mg*h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously (i.v.). From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19-33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results.

Drug resistance among extrapulmonary TB patients: Six years experience from a supranational reference laboratory

Abstract: Background & objectives: There is limited information available about the drug resistance patterns in extrapulmonary tuberculosis (EPTB), especially from high burden countries. This may be due to difficulty in obtaining extrapulmonary specimens and limited facilities for drug susceptibility testing. This study was undertaken to review and report the first and second-line anti-TB drug susceptibility patterns in extrapulmonary specimens received at the National Institute for Research in Tuberculosis (NIRT), Chennai, India, between 2005 and 2012. Methods: Extrapulmonary specimens received from referring hospitals were decontaminated and cultured using standard procedures. Drug susceptibility testing (DST) for Mycobacterium tuberculosis was done by absolute concentration or resistance ratio methods for the first and the second line anti-TB drugs. Results: Between 2005 and 2012, of the 1295 extrapulmonary specimens, 189 grew M. tuberculosis, 37 (19%) cases were multidrug resistant (MDR) while one was extensively drug resistant (XDR). Specimen-wise MDR prevalence was found to be: CSF-10 per cent, urine-6 per cent, fluids and aspirates-27 per cent, pus-23 per cent, lymph nodes-19 per cent. Resistance to isoniazid and ethionamide was found to be high (31 and 38%, respectively). Interpretation & conclusions: Drug resistance including MDR-TB was observed in a significant proportion of extrapulmonary specimens referred for DST. Access to culture and DST for extrapulmonary specimens should be expanded. Guidelines for MDR-TB management should have explicit sections on extra-pulmonary tuberculosis and training on laboratory techniques is urgently required.

RePORT International: Advancing Tuberculosis Biomarker Research Through Global Collaboration.

Abstract: Progress in tuberculosis clinical research is hampered by a lack of reliable biomarkers that predict progression from latent to active tuberculosis, and subsequent cure, relapse, or failure. Regional Prospective Observational Research in Tuberculosis (RePORT) International represents a consortium of regional cohorts (RePORT India, RePORT Brazil, and RePORT Indonesia) that are linked through the implementation of a Common Protocol for data and specimen collection, and are poised to address this critical research need. Each RePORT network is designed to support local, in-country tuberculosis-specific data and specimen biorepositories, and associated research. Taken together, the expected results include greater global clinical research capacity in high-burden settings, and increased local access to quality data and specimens for members of each network and their domestic and international collaborators. Additional networks are expected to be added, helping to spur tuberculosis treatment and prevention research around the world.

Piloting Upfront Xpert MTB/RIF Testing on Various Specimens under Programmatic Conditions for Diagnosis of TB & DR-TB in Paediatric Population.

Abstract: Background India accounts for one-fifth of the global TB incidence. While the exact burden of childhood TB is not known, TB remains one of the leading causes of childhood mortality in India. Bacteriological confirmation of TB in children is challenging due to difficulty in obtaining quality specimens, in the absence of which diagnosis is largely based on clinical judgement. While testing multiple specimens can potentially contribute to higher proportion of laboratory confirmed paediatric TB cases, lack of high sensitivity tests adds to the diagnostic challenge. We describe here our experiences in piloting upfront Xpert MTB/RIF testing, for diagnosis of TB in paediatric population in respiratory and extra pulmonary specimens, as recently recommended by WHO. Method Xpert MTB/RIF testing was offered to all paediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities in the project areas covering 4 cities of India. Results Under this pilot project, 8,370 paediatric presumptive TB & presumptive DR-TB cases were tested between April and–November 2014. Overall, 9,149 specimens were tested, of which 4,445 (48.6%) were non-sputum specimens. Xpert MTB/RIF gave 9,083 (99.2%, CI 99.0–99.4) valid results. Of the 8,143 presumptive TB cases enrolled, 517 (6.3%, CI 5.8–6.9) were bacteriologically confirmed. TB detection rates were two fold higher with Xpert MTB/RIF as compared to smear microscopy. Further, a total of 60 rifampicin resistant TB cases were detected, of which 38 were detected among 512 presumptive TB cases while 22 were detected amongst 227 presumptive DR-TB cases tested under the project. Conclusion Xpert MTB/RIF with advantages of quick turnaround testing-time, high proportion of interpretable results and feasibility of rapid rollout, substantially improved the diagnosis of bacteriologically confirmed TB in children, while simultaneously detecting rifampicin resistance.

Pharmacokinetics of First-Line Antituberculosis Drugs in HIV-Infected Children with Tuberculosis Treated with Intermittent Regimens in India

Abstract: The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (Cmax) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median Cmax and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC0–8]) of INH (Cmax, 2.5 versus 5.1 μg/ml, respectively [P = 0.016]; AUC0–8, 11.1 versus 22.0 μg/ml · h, respectively [P = 0.047[) and PZA (Cmax, 34.1 versus 42.3 μg/ml, respectively [P = 0.055]; AUC0–8, 177.9 versus 221.7 μg/ml · h, respectively [P = 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median Cmax of RMP (1.0 versus 2.8 μg/ml, respectively; P = 0.002) and PZA (31.9 versus 44.4 μg/ml, respectively; P = 0.045) were significantly lower. Among all factors studied, the PZA Cmax influenced TB treatment outcome (P = 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP Cmax. The PZA Cmax significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.

Anemia, diet and therapeutic iron among children living with HIV: a prospective cohort study

Abstract: Children living with HIV have higher-than-normal prevalence of anemia. The beneficial effect of therapeutic iron has been questioned in the setting of high prevalence of infections. This study examines anemia prevalence and effect of standard therapeutic iron on HIV disease progression among children. Perinatally-infected children aged 2–12 years were enrolled at three sites in southern India, and were followed for 1 year with clinical assessments, dietary recall and anthropometry. Laboratory parameters included iron markers (ferritin, soluble transferrin receptor) and other micronutrient levels (vitamin A, B12, folate). Iron was given to anemic children based on WHO guidelines. Statistical analyses including frequency distributions, chi square tests and multivariate logistic regression were performed using Stata v13.0. Among 240 children enrolled (mean age 7.7 years, 54.6 % males), median CD4 was 25 %, 19.2 % had advanced disease, 45.5 % had malnutrition, and 43.3 % were on antiretroviral treatment (ART) at baseline. Anemia was prevalent in 47.1 % (113/240) children. Iron deficiency was present in 65.5 %; vitamin A and vitamin B12 deficiency in 26.6 % and 8.0 % respectively; and anemia of inflammation in 58.4 %. Independent risk factors for anemia were stunting, CD4 < 25 %, detectable viral load ≥400 copies/ml and vitamin A deficiency. Inadequate dietary iron was prominent; 77.9 % obtained less than two-thirds of recommended daily iron. Among clinically anemic children who took iron, overall adherence to iron therapy was good, and only minor self-limiting adverse events were reported. Median hemoglobin rose from 10.4 g/dl to 10.9 mg/dl among those who took iron for 3 months, and peaked at 11.3 mg/dl with iron taken for up to 6 months. Iron was also associated with a greater fall in clinical severity of HIV stage; however when adjusted for use of ART, was not associated with improvement in growth, inflammatory and CD4 parameters. Children living with HIV in India have a high prevalence of anemia mediated by iron deficiency, vitamin A deficiency and chronic inflammation. The use of therapeutic iron for durations up to 6 months appears to be safe in this setting, and is associated with beneficial effects on anemia, iron deficiency and HIV disease progression.

Pulmonary tuberculosis among tribals in India: A systematic review & meta-analysis

Abstract: Results: The pooled estimate, based on the random effects model, was 703 per 100,000 population with a 95 % CI of 386-1011. The associated heterogeneity measures in terms of Cochran’s Q was significant (p=0.08 <0.1) and I 2 was moderate at 48 per cent. Interpretation & conclusions: The meta-analysis demonstrated a large variability in pulmonary TB prevalence estimates among the different studies with poor representation of the various tribal groups. The moderate level of heterogeneity found across the studies suggests that the pooled-estimate needs to be treated with caution. Our findings also highlight the need to assess the pulmonary TB burden in India.

High rates of ofloxacin resistance in Mycobacterium tuberculosis among both new and previously treated patients in Tamil Nadu, South India.

Abstract: Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis (TB) control measures. The present study determines the prevalence of drug resistance among new sputum smear positive (NSP) and previously treated (PT) pulmonary TB patients, diagnosed at public sector designated microscopy centers (DMCs) in the state of Tamil Nadu, India. In this single-stage cluster-sampling prevalence survey, 70 of 700 DMCs were randomly selected using a probability-proportional to size method. A cluster size of 24 for NSP and a varying size of 0 to 99 for PT cases were fixed for each selected DMC. Culture and drug susceptibility testing was done on Lowenstein-Jensen medium using the economic variant of proportion sensitivity test for isoniazid (INH), rifampicin (RMP), ofloxacin (OFX) and kanamycin (KAN). Human Immunodeficiency Virus (HIV) status was collected from patient records. From June 2011 to August 2012, 1524 NSP and 901 PT patients were enrolled. Any RMP resistance and any INH resistance were observed in 2.6% and 15.1%, and in 10.4% and 30% respectively in NSP and PT cases. Among PT patients, multi drug resistant TB (MDR-TB) was highest in the treatment failure (35%) group, followed by relapse (13%) and treatment after default (10%) groups. Extensively drug resistant TB (XDRTB) was seen in 4.3% of MDR-TB cases. Any OFX resistance was seen in 10.4% of NSP, 13.9% of PT and 29% of PT MDR-TB patients. The HIV status of the patient had no impact on drug resistance levels. RMP resistance was present in 2.6% of new and 15.1% of previously treated patients in Tamil Nadu. Rates of OFX resistance were high among NSP and PT patients, especially among those with MDR-TB, a matter of concern for development of new treatment regimens for TB.

Challenges in childhood tuberculosis.

Abstract: While tuberculosis (TB) typically causes respiratory disease in adults, the spectrum of disease is different in children, ranging from paucibacillary lymphadenitis or limited intrathoracic disease to severe disseminated disease. Diagnosing pediatric TB and monitoring treatment response is challenging, as collecting respiratory specimens is difficult in children and disease may be extrapulmonary. While basic principles of treatment are similar to adults, developmental differences in pharmacokinetics and pharmacodynamics require that drug dosages in children be adjusted for body weight and age.

The Usefulness and Feasibility of Mobile Interface in Tuberculosis Notification (MITUN) Voice Based System for Notification of Tuberculosis by Private Medical Practitioners--A Pilot Project.

Abstract: Introduction Tuberculosis (TB) is a notifiable disease and health care providers are required to notify every TB case to local authorities. We conducted a pilot study to determine the usefulness and feasibility of mobile interface in TB notification (MITUN) voice based system for notification of TB cases by private medical practitioners. Methodology The study was conducted during September 2013 to October 2014 in three zones of Chennai, an urban setting in South India. Private clinics wherein services are provided by single private medical practitioners were approached. The steps involved in MITUN included: Registration of the practitioners and notification of TB cases by them through voice interactions. Pre and post-intervention questionnaires were administered to collect information on TB notification practices and feasibility of MITUN after an implementation period of 6 months. Results A total of 266 private medical practitioners were approached for the study. Of them, 184 (69%) participated in the study; of whom 11 (6%) practitioners used MITUN for TB notification. Reasons for not using MITUN include lack of time, referral of patients to government facility, issues related to patient confidentiality and technical problems. Suggestions for making mobile phone based TB notification process user-friendly included reducing call duration, including only crucial questions and using missed call or SMS options. Conclusion The performance (feasibility and usefulness) of MITUN voice based system for TB notification in the present format was sub-optimal. Perceived problems, logistical and practical issues preclude scale–up of notification of TB by private practitioners.

Challenges in the early diagnosis of HIV infection in infants: Experience from Tamil Nadu, India

Abstract: Objectives To analyze critical steps in the testing algorithm of the National Early Infant Diagnosis (EID) program in India

Setting priorities for a research agenda to combat drug-resistant tuberculosis in children.

Abstract: Setting: Numerous knowledge gaps hamper the prevention and treatment of childhood drug-resistant tuberculosis (TB). Identifying research priorities is vital to inform and develop strategies to address this neglected problem. Objective: To systematically identify and rank research priorities in childhood drug-resistant TB. Design: Adapting the Child Health and Nutrition Research Initiative (CHNRI) methodology, we compiled 53 research questions in four research areas, then classified the questions into three research types. We invited experts in childhood drug-resistant TB to score these questions through an online survey. Results: A total of 81 respondents participated in the survey. The top-ranked research question was to identify the best combination of existing diagnostic tools for early diagnosis. Highly ranked treatment-related questions centred on the reasons for and interventions to improve treatment outcomes, adverse effects of drugs and optimal treatment duration. The prevalence of drug-resistant TB was the highest-ranked question in the epidemiology area. The development type questions that ranked highest focused on interventions for optimal diagnosis, treatment and modalities for treatment delivery. Conclusion: This is the first effort to identify and rank research priorities for childhood drug-resistant TB. The result is a resource to guide research to improve prevention and treatment of drug-resistant TB in children.

Outcome of Prevention of Parent-to-Child Transmission of HIV in an Urban Population in Southern India.

Abstract: Objective To analyze the outcomes of Prevention of Parent to Child Transmission (PPTCT) of HIV program in an urban Southern Indian setting.

Treatment of W. bancrofti (Wb) in HIV/Wb coinfections in South India.

Abstract: Background The disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coincident infections.

Does effect of BCG vaccine decrease with time since vaccination and increase tuberculin skin test reaction

Abstract: The protective efficacy of BCG was studied for over 15 years, from 1968, in South India. A secondary analysis of data was performed to investigate the relationship between Bacille Calmette-Guerin (BCG) and tuberculosis (TB) disease and between BCG and positive tuberculin skin test for different time periods among children aged less than 10 years. A randomized controlled trial was conducted, where 281,161 persons were allocated to receive BCG 0.1mg, BCG 0.01mg or placebo. Tuberculin skin test was performed at baseline and at 4 years after BCG vaccination. Surveys were conducted every 2.5 years to detect all new cases of culture-positive/smear-positive TB occurring in the community over a 15-year period. Relative risk (RR) was obtained from the ratio of incidence among the vaccinated and the placebo groups. Among those children vaccinated with 0.1mg of BCG, the RR for TB was 0.56 (95% CI: 0.32-0.87, P=0.01) at 12.5 years but increased to 0.73 later. Similar pattern was seen with 0.01mg. The increase in the number of skin test positives with 0.1mg of BCG was 57.8%, 49.4% and 34% for cut-off points at ≥10mm, ≥12mm and ≥15mm, respectively. The study suggests that the effect of BCG may decrease since vaccination and the tuberculin positive was higher at post-vaccination test period due to BCG.

RMP exposure is lower in HIV-infected TB patients receiving intermittent than daily anti-tuberculosis treatment.

Abstract: We compared the pharmacokinetics of rifampicin (RMP) during daily and intermittent (thrice weekly) anti-tuberculosis treatment in human immunodeficiency virus infected tuberculosis patients. Patients treated with a thrice-weekly regimen had significantly lower plasma peak concentration, area under the time concentration curve from 0 to 24 h and higher oral clearance of RMP than those treated with the daily regimen. The median values were respectively 3.7 and 6.4 μg/ml (P < 0.001), 20.7 and 29.4 μg/ml.h (P = 0.03) and 21.7 and 15.3 ml/min (P = 0.03).

Hiccups as an unusual manifestation of tuberculosis-associated immune reconstitution inflammatory syndrome.

Abstract: Andrade, Bruno de Bezerril “Documento produzido em parceria ou por autor vinculado a Fiocruz, mas nao consta a informacao no documento”.