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Antimicrobial resistance (AMR) has emerged as a significant threat to global health security and threatens the achievements of modern medicine. Research and successful development of new antibiotics, especially those with novel mechanisms of action vital to combat resistance, has slowed dramatically since the 1980s. Surveillance for AMR is highly variable globally with significant limitations in many countries impeding the ability to fully characterize the problem. Global efforts to control tuberculosis, malaria and HIV are facing increasing difficulties from the emergence of resistance. Similarly, bacteria causing some of the most common infections in communities or in hospitals such as Escherichia coli and Klebsiella pneumoniae have shown high levels of resistance to third generation cephalosporins requiring treatment with expensive carbapenems as last-resort. Additionally, Streptococcus pneumoniae has shown reduced susceptibility to penicillin in many regions, exceeding 50% in some settings. The cost in lives from AMR over the next 40 years could go as high as 10 million per year with the cost to economic development as high as $3 trillion per year if current trends continue. In addition to ensuring appropriate use of antibiotics and development of novel classes with new or enhanced mechanisms of action, many plans for the global response call for new vaccines as integral to the fight against AMR. Vaccines and antibiotics should be used together to produce synergistic gains in public health, and ultimately, vaccines will extend the clinical utility of antibiotics. The decrease in cases of invasive pneumococcal disease and decrease in prescriptions for antibiotics in some settings resulting from the introduction of broad access to, and utilization of conjugate vaccines for Streptococcus pneumoniae exemplifies the synergy that can be achieved in the fight against AMR. [ABSTRACT FROM AUTHOR]

Randomized clinical trials are the most reliable approaches to evaluating the effects of new treatments and vaccines. During the 2014-2015 West African Ebola epidemic, many argued that such trials were neither ethical nor feasible in an environment of limited health infrastructure and severe disease with a high fatality rate. Consensus among the numerous organizations providing help to the affected areas was never achieved, resulting in fragmented collaboration, delayed study initiation and ultimately failure to provide definitive evidence on the efficacy of treatments and vaccines. Randomized trials were in fact approved by local ethics boards and initiated, demonstrating that randomized trials, even in such difficult circumstances, are feasible. Improved planning and collaboration among research and humanitarian organizations, and affected communities, in the interepidemic periods are needed to ensure that questions regarding the efficacy of vaccines and treatments can be definitively answered during future public health emergencies. [ABSTRACT FROM AUTHOR]

Background: Of the 9.2 million new TB cases occurring each year, about 10% are in children. Because childhood TB is usually non-infectious and non-fatal, national programs do not prioritize childhood TB diagnosis and treatment. We reviewed data from a demonstration project to learn more about the epidemiology of childhood TB in Thailand. Methods: In four Thai provinces and one national hospital, we contacted healthcare facilities monthly to record data about persons diagnosed with TB, assist with patient care, provide HIV counseling and testing, and obtain sputum for culture and susceptibility testing. We analyzed clinical and treatment outcome data for patients age < 15 years old registered in 2005 and 2006. Results: Only 279 (2%) of 14,487 total cases occurred in children. The median age of children was 8 years (range: 4 months, 14 years). Of 197 children with pulmonary TB, 63 (32%) were bacteriologically-confirmed: 56 (28%) were smear-positive and 7 (4%) were smear-negative, but culture-positive. One was diagnosed with multi-drug resistant TB. HIV infection was documented in 75 (27%). Thirteen (17%) of 75 HIV-infected children died during TB treatment compared with 4 (2%) of 204 not known to be HIV-infected (p < 0.01). Conclusion: Childhood TB is infrequently diagnosed in Thailand. Understanding whether this is due to absence of disease or diagnostic effort requires further research. HIV contributes substantially to the childhood TB burden in Thailand and is associated with high mortality. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis strains that are resistant to an increasing number of second-line drugs used to treat multidrug-resistant tuberculosis (MDR TB) are becoming a threat to public health worldwide. We surveyed the Network of Supranational Reference Laboratories for M. tuberculosis isolates that were resistant to second-line anti-TB drugs during 2000-2004. We defined extensively drug-resistant TB (XDR TB) as MDR TB with further resistance to >3 of the 6 classes of second-line drugs. Of 23 eligible laboratories, 14 (61%) contributed data on 17,690 isolates, which reflected drug susceptibility results from 48 countries. Of 3,520 (19.9%) MDR TB isolates, 347 (9.9%) met criteria for XDR TB. Further investigation of population-based trends and expanded efforts to prevent drug resistance and effectively treat patients with MDR TB are crucial for protection of public health and control of TB. [ABSTRACT FROM AUTHOR]

Summary Background Latvia has one of the highest rates of multidrug-resistant tuberculosis (MDRTB). Our aim was to assess treatment outcomes for the first full cohort of MDRTB patients treated under Latvia's DOTS-Plus strategy following WHO guidelines. Methods We retrospectively reviewed all civilian patients who began treatment with individualised treatment regimens for pulmonary MDRTB in Latvia between Jan 1, and Dec 31, 2000. We applied treatment outcome definitions for MDRTB, developed by an international expert consensus group,and assessed treatment effectiveness and risk factors associated with poor outcome. Findings Of the 204 patients assessed, 55 (27%) had been newly diagnosed with MDRTB, and 149 (73%) had earlier been treated with first-line or second-line drugs for this disease. Assessment of treatment outcomes showed that 135 (66%) patients were cured or completed therapy, 14 (7%) died, 26 (13%) defaulted, and treatment failed in 29 (14%). Of the 178 adherent patients,135 (76%) achieved cure or treatment completion. In a multivariate Cox proportional-hazards model of these patients, independent predictors of poor outcome (death and treatment failure) included having previously received treatment for MDRTB (hazard ratio 5 ·7,95%CI 1·9--6·16), the use of five or fewer drugs for 3 months or more (3·2,1·1--9·6), resistance to ofloxacin (2·6,1 ·2 --5·4), and body-mass index less than 18·5 at start of treatment (2·3,1·1--4·9). Interpretation The DOTS-Plus strategy of identifying and treating patients with MDRTB can be effectivelyimplemented on a nationwide scale in a setting of limited resources. [ABSTRACT FROM AUTHOR]

India has a third of the world's tuberculosis cases. Large-scale expansion of a national programme in 1998 has allowed for population-based analyses of data from tuberculosis registries. We assessed seasonal trends using quarterly reports from districts with stable tuberculosis control programmes (population 115 million). In northern India, tuberculosis diagnoses peaked between April and June, and reached a nadir between October and December, whereas no seasonality was reported in the south. Overall, rates of new smear-positive tuberculosis cases were 57 per 100 000 population in peak seasons versus 46 per 100 000 in trough seasons. General health-seeking behaviour artifact was ruled out. Seasonality was highest in paediatric cases, suggesting variation in recent transmission. [ABSTRACT FROM AUTHOR]