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Patients with suspected enteric (typhoid and paratyphoid) fever are predominantly managed as outpatients in endemic regions. Nonspecific clinical presentation, lack of accurate diagnostic tools, and widespread antimicrobial resistance makes management challenging. Resistance has been described for all antimicrobials including chloramphenicol, amoxycillin, trimethoprim-sulfamethoxazole, ciprofloxacin, ceftriaxone, and azithromycin. No significant differences have been demonstrated between these antimicrobials in their ability to treat enteric fever in systematic reviews of randomized controlled trials (RCTs). Antimicrobial choice should be guided by local resistance patterns and national guidance. Extensively drug-resistant typhoid isolates require treatment with azithromycin and/or meropenem. Combining antimicrobials that target intracellular and extracellular typhoid bacteria is a strategy being explored in the Azithromycin and Cefixime in Typhoid Fever (ACT-SA) RCT, in progress in South Asia. Alternative antimicrobials, such as the oral carbapenem, tebipenem, need clinical evaluation. There is a paucity of evidence to guide the antimicrobial management of chronic fecal carriers. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention.Methods: We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance.Findings: We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified.Interpretation: Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice.Trial Registration: PROSPERO CRD42018029432. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains the most common cause of infectious disease deaths worldwide. What is perhaps less appreciated is that the caseload of tuberculosis patients in South Asia is staggering. South Asia has almost 40% of the global TB burden with 4,028,165 cases in 2015. This region also has a disproportionate share of TB deaths (681,975 deaths, 38% of the global burden). Worldwide just 12.5% of TB cases are in HIV positive individuals, but much research and investment has focused on HIV-associated TB. Only 3.5% of patients with tuberculosis in South Asia have HIV co-infection. Not surprisingly with such a huge burden of disease, this region has an estimated 184,336 multi drug resistant (MDR) cases among notified TB cases which accounts for a third of global MDR burden. Crucially, at least 70% of the estimated MDR cases remain untreated in this region and MDR treatment success ranged from only 46% for India to 88% for Sri Lanka in the 2012 cohort that received treatment. This region represents many of the drivers of the modern TB epidemic: rapid urbanization and high density populations with dramatically rising incidence of diabetes, a burgeoning and largely unregulated private sector with escalating drug resistance and high air pollution both outdoor and household. Conclusion: From bacterial biochemistry to policy implementation, we suggest ways in which South Asia can seize the opportunity lead global TB elimination by demonstrating feasibility in some of the world's most densely populated cities and remotest reaches of the Himalayas. Clearly political will is essential, but we cannot defeat TB without understanding how to eliminate it in South Asia. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about general medical knowledge in South Asia, with an example of Harrison's "Principles of Internal Medicine,' not having an entry for altitude sickness.

Presents an editorial on the cardiovascular and infectious diseases in South Asia. Need for innovation, political commitment and new partnerships in order to combat the problems associated with disease; Risk factors for disease including unprotected sex, poor sanitation, tobacco use and unsafe water; Changes in lifestyle and work patterns, resulting in less physical activity and more obesity and tobacco use; What can be done to reduce the number of communicable and non-communicable diseases; Lack of public awareness of the link between lifestyle and health.

The GeneXpert MTB/RIF assay (Xpert) is a novel automated diagnostic tool for tuberculosis but its optimal placement in the healthcare system has not been determined. The objective of this study was to determine the possibility of additional case detection for pulmonary tuberculosis (PTB) by offering Xpert to smear-negative patients in a low-HIV burden setting with no Mycobacterium tuberculosis (M.tb.) culture facilities. Patients routinely presenting with symptoms suggestive of PTB with negative smears were offered single Xpert test on a fee-paying basis. Data were retrospectively reviewed to determine case detection in patients tested from February to December 2013. Symptoms associated with a positive test were analysed to determine if refinement of clinical criteria would reduce unnecessary testing. 258 smear-negative patients were included and M.tb. was detected in 55 (21.32%, n=55/258). Using standard clinical assessment for selection, testing 5 patients detected one case of smear-negative PTB. These results demonstrate that fee-paying Xpert service in low-income setting can increase TB case confirmation substantially and further systematic studies of health economic implications should be conducted to determine optimal implementation models to increase access to Xpert in low- and middle-income countries. [ABSTRACT FROM AUTHOR]