Leptospirosis, a zoonosis associated with potentially fatal consequences, has long been a grossly underreported disease in India. There is no accurate estimate of the problem of leptospirosis in non-endemic areas such as north India. In order to understand the clinical spectrum and risk factors associated with leptospirosis, we carried out a retrospective study in patients with acute febrile illness in north India over the last 5 years (January 2004 to December 2008). There was increased incidence of leptospirosis (11.7% in 2004 to 20.5% in 2008) as diagnosed by IgM ELISA and microscopic agglutination titer in paired acute and convalescent sera. The disease showed a peak during the rainy season (August and September). We followed up 86 cases of leptospirosis regarding their epidemiological pattern, clinical features, laboratory parameters, complications, therapy, and outcome. Mean age of patients was 32.6 years (2.5 years to 78 years) and males (57%) outnumbered females (43%). Infestation of dwellings with rats (53.7%), working in farm lands (44.2%), and contact with animals (62.1%) were commonly observed epidemiological risk factors. Outdoor workers including farmers (32.6%), labourers (11.6%), para-military personnel (2.3%), and sweepers (1.2%) were commonly affected. Modified Faine's criteria could diagnose 76 cases (88.3%). Renal failure (60.5%), respiratory failure (20.9%), the neuroleptospirosis (11.6%), and disseminated intravascular coagulation (DIC) (11.6%) were the commonest complications. Five patients died, giving a case fatality rate of 5.9%. There has been a rapid rise in the incidence of leptospirosis in north India. Severe complications such as renal failure, respiratory failure, neuroleptospirosis, and DIC are being seen with increasing frequency. Increased awareness among physicians, and early diagnosis and treatment, may reduce mortality due to leptospirosis. Leptospirosis is often not suspected by physicians in patients with acute febrile illnesses reporting from supposedly “non-endemic areas,” including north India. Clinical manifestations are protean, and complications can affect most organ systems, including liver, kidneys, lungs, and the central nervous system. Timely diagnosis and specific therapy can reduce severity of illness and, in turn, mortality. In this study conducted at a tertiary care center in north India, we find how a much-neglected disease entity has emerged as a major cause of acute febrile illness in a so called “non-endemic area.” Incidence is increasing yearly. The majority of patients were from a rural background, and were farmers or farm labourers. Poor hygiene, contact with animals, rat infestation of houses, and contact with stagnant dirty water are the major determinants of disease. Apart from the usual symptoms of intermittent fever with chill and rigor, hepatosplenomegaly, renal decompensation, muscle pain and tenderness, and conjunctival suffusion, signs and symptoms indicating involvement of the respiratory and central nervous systems were also commonly observed. Severe complications resulting in mortality do occur and is especially due to late suspicion among primary level physicians, and the resulting inappropriate therapy.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern worldwide. It has been recently feared that the bla TEM-1 gene is, via bla TEM-135, evolving into an extended-spectrum β-lactamase (ESBL), which could degrade all cephalosporins including ceftriaxone. The aims of the present study were to characterize the bla TEM genes, types of β-lactamase plasmids, the degradation of ampicillin by TEM-135 compared to TEM-1, and to perform molecular epidemiological typing of β-lactamase-producing N. gonorrhoeae strains internationally. β-lactamase producing N. gonorrhoeae isolates (n = 139) cultured from 2000 to 2011 in 15 countries were examined using antibiograms, bla TEM gene sequencing, β-lactamase plasmid typing, and N. gonorrhoeae multiantigen sequence typing (NG-MAST). Furthermore, the bla TEM gene was sequenced in the first described Toronto plasmid (pJD7), one of the first Asian plasmids (pJD4) and African plasmids (pJD5) isolated in Canada. The degradation of ampicillin by TEM-135 compared to TEM-1 was examined using a MALDI-TOF MS hydrolysis assay. Six different bla TEM sequences were identified (among isolates with 125 different NG-MAST STs), i.e. bla TEM-1 (in 104 isolates), bla TEM-135 (in 30 isolates), and four novel bla TEM sequences (in 5 isolates). The bla TEM-1 allele was only found in the African and Asian plasmids, while all Rio/Toronto plasmids possessed the bla TEM-135 allele. Most interesting, the first described gonococcal Toronto plasmid (pJD7), identified in 1984, also possessed the highly conserved bla TEM-135 allele. The degradation of ampicillin by TEM-135 compared to TEM-1 was indistinguishable in the MALDI-TOF MS hydrolysis assay. bla TEM-135, encoding TEM-135, is predominantly and originally associated with the Rio/Toronto plasmid and prevalent among the β-lactamase producing gonococcal strains circulating globally. bla TEM-135 does not appear, as previously hypothesized, to have recently evolved due to some evolutionary selective pressure, for example, by the extensive use of extended-spectrum cephalosporins worldwide. On the contrary, the present study shows that bla TEM-135 existed in the Toronto plasmid from its discovery and that bla TEM-135 is highly conserved (not further evolved in the past >30 years). Nevertheless, international studies for monitoring the presence of different bla TEM alleles, the possible evolution of the bla TEM-135 allele, and the types of β-lactamase producing plasmids, remain imperative.

Mycoplasma genitalium is one of the important causes of non-gonococcal urethritis. Rising incidence and emerging antimicrobial resistance are a major concern these days. The poor clinical outcomes with doxycycline therapy led to the use of azithromycin as the primary drug of choice. Single-dose azithromycin regimen over a period of time was changed to extended regimen following studies showing better clinical cures and less risk of resistance development. However, emerging macrolide resistance, either due to transmission of resistance or drug pressure has further worsened the management of this infection. The issues of drug resistance and treatment failures also exist in cases of M. genitalium infection. At present, the emergence of multidrug-resistant (MDR) M. genitalium strains is an alarming sign for its treatment and the associated public health impact due to its complications. However, newer drugs like pristinamycin, solithromycin, sitafloxacin, and others have shown a hope for the clinical cure, but need further clinical trials to optimize the therapeutic dosing schedules and formulate appropriate treatment regimens. Rampant and inappropriate use of these newer drugs will further sabotage future attempts to manage MDR strains. There is currently a need to formulate diagnostic algorithms and etiology-based treatment regimens rather than the syndromic approach, preferably using combination therapy instead of a monotherapy. Awareness about the current guidelines and recommended treatment regimens among clinicians and local practitioners is of utmost importance. Antimicrobial resistance testing and global surveillance are required to assess the efficacy of current treatment regimens and for guiding future research for the early detection and management of MDR M. genitalium infections.

Multidrug resistant (MDR) and extensively-drug resistant (XDR) tuberculosis (TB) are a serious threat to the national TB control programs of developing countries, and the situation is further worsened by the human immunodeficiency virus (HIV) pandemic. The literature regarding MDR/XDR-TB is, however, scanty from most parts of India. We carried out this study to assess the prevalence of MDR/XDR-TB in new and previously treated cases of pulmonary TB and in HIV seropositive and seronegative patients.

A tertiary care hospital in North India. Tuberculosis (TB) remains a major public health problem in developing countries. The diagnosis of tuberculosis is still challenging in primary care settings in endemic countries like India. WHO has endorsed loop mediated isothermal amplification assay (LAMP) for TB as a replacement for smear microscopy for peripheral settings, however, more data is required to establish the specificity of this modality for the diagnosis of TB. In this study we aim to determine the diagnostic accuracy of the TB-LAMP assay in pulmonary tuberculosis. A total of 236 patients (117 cases suspected of TB and 119 patients with non-TB pulmonary disease) were enrolled between February to July, 2018. Microbiological workups consisting of mycobacterial smear microscopy, culture, Xpert MTB/Rif and TB-LAMP were performed. From 236 samples, 18 (7.6%) were excluded from the study. TB-LAMP and Xpert MTB/RIF were positive in 46 (21.1%) and 49 (22.5%) of the samples, respectively. The sensitivity of Xpert MTB/RIF and TB-LAMP, when culture was taken as a reference standard, was 90% (95%CI: 78.2-96.7) and 82% (95%CI: 68.6-91.4), respectively. The specificity, positive predictive value (PPV), and negative predictive value (NPV) of TB-LAMP assay were 96.8% (95%CI: 92.8-98.9), 89.1% (95%CI: 77.4-95.2), and 94.4% (95%CI: 90.4-96.5), respectively. The TB-LAMP assay showed a good specificity and sensitivity for detection ofM. tuberculosis in adults, however, for programmatic implementation, more studies are required to be conducted at peripheral level healthcare settings.

Scrub typhus is re-emerging in India. We describe an outbreak of 45 cases from our tertiary care center in north India. This outbreak included city dwellers who had no history of travel to hilly areas. The classical feature of scrub typhus, the eschar, was also noted rarely in these patients. The changing epidemiology of scrub typhus should be kept in mind while attending patients with acute febrile illness.