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The value of the "trace" result in Xpert Ultra for diagnosing active tuberculosis (TB) remains unclear. Our study evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) (Cepheid, Sunnyvale, USA) over Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, USA) and mycobacterial culture when compared with a composite reference standard (CRS).A retrospective single-center observational study was conducted in a tertiary care hospital in South India. Over three months, patients (aged ≥15 years) data on Xpert Ultra tests and mycobacterial culture of pulmonary and extrapulmonary samples were extracted from their electronic medical records. Patients were defined as TB cases based on the CRS criteria. Sensitivity, specificity, positive and negative predictive values of diagnostic tests were calculated by comparing them to the CRS.Xpert Ultra was more sensitive (87.8%) than Xpert (72.1%) and culture (44.1%). The specificity of Xpert Ultra was lower (98.1%) than those of Xpert (100%) and culture (100%). The sensitivity (92%) and specificity (100%) of Xpert Ultra were highest when performed on pus samples.Xpert Ultra with the trace category is superior to the conventional Xpert, and mycobacterial culture in identifying TB.

Background The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. Methods Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. Results There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5–85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75–90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98–100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. Conclusion The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Background There have been over 30 million cases of COVID-19 in India and over 430,000 deaths. Transmission rates vary from region to region, and are influenced by many factors including population susceptibility, travel and uptake of preventive measures. To date there have been relatively few studies examining the impact of the pandemic in lower income, rural regions of India. We report on a study examining COVID-19 burden in a rural community in Tamil Nadu. Methods The study was undertaken in a population of approximately 130,000 people, served by the Rural Unit of Health and Social Affairs (RUHSA), a community health center of CMC, Vellore. We established and evaluated a COVID-19 PCR-testing programme for symptomatic patients—testing was offered to 350 individuals, and household members of test-positive cases were offered antibody testing. We also undertook two COVID-19 seroprevalence surveys in the same community, amongst 701 randomly-selected individuals. Results There were 182 positive tests in the symptomatic population (52.0%). Factors associated with test-positivity were older age, male gender, higher socioeconomic status (SES, as determined by occupation, education and housing), a history of diabetes, contact with a confirmed/suspected case and attending a gathering (such as a religious ceremony, festival or extended family gathering). Amongst test-positive cases, 3 (1.6%) died and 16 (8.8%) suffered a severe illness. Amongst 129 household contacts 40 (31.0%) tested positive. The two seroprevalence surveys showed positivity rates of 2.2% (July/Aug 2020) and 22.0% (Nov 2020). 40 tested positive (31.0%, 95% CI: 23.02 − 38.98). Our estimated infection-to-case ratio was 31.7. Conclusions A simple approach using community health workers and a community-based testing clinic can readily identify significant numbers of COVID-19 infections in Indian rural population. There appear, however, to be low rates of death and severe illness, although vulnerable groups may be under-represented in our sample. It’s vital these lower income, rural populations aren’t overlooked in ongoing pandemic monitoring and vaccine roll-out in India.

Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its non-specific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluates the diagnostic performance of various tests. The present study aims at assessing the accuracy of various rapid diagnostic tests, serologic tests, and nucleic acid amplification methods on well-characterized patient samples. Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood, eschar or tissue were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative real time PCR using 47kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil-Felix test(WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT).Among the 316 participants, 158 had confirmed scrub typhus (cases) and 158 were controls. ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies had excellent discriminative potential with sensitivities and specificities of 92%, 94% and 92%, 92% respectively. The sensitivity and specificity of IFA were found to be 95% and 74% respectively. IgM serology had a false positivity rate of 8% with other acute febrile illnesses such as dengue, leptospirosis and spotted fever due to the nonspecific binding of the pentavalent IgM. LAMP assay had 91.7% sensitivity and 77.2% specificity while qPCR provided excellent sensitivity (97%) and perfect specificity. In conclusion, ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies have excellent sensitivity and specificity while the accuracy of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories particularly for diagnosis of early disease with less than 7 days duration. This study provides a comprehensive evaluation of all currently available diagnostic tests for scrub typhus., Author summary Scrub typhus, a life-threatening vector borne rickettsial infection accounts for a million cases annually. While the disease was initially described predominantly in Asia, Northern Australia and islands in the Indian and Pacific Oceans (known as the tsutsugamushi triangle), scrub typhus has now been reported in areas considered previously free of disease like Africa and South America. International travel also accounts for the microbial trafficking of this disease and its presentation to non-endemic areas. The diagnosis of scrub typhus is challenging due to its non-specific symptoms and the lack of sufficient data on the performance of various diagnostic tests. Several tests have been developed for the diagnosis of scrub typhus over the last few decades. However, there exists ambiguity on which tests are most suitable in a given clinical scenario and the apt timing to perform these tests. This study provides further insight into the performance of various serological and molecular tests in the diagnosis of scrub typhus, assists in understanding their discriminatory potential and diagnostic accuracies enabling prompt treatment of the disease.

Background: Behavioral and geographical factors may play a role in the acquisition of scrub typhus infection. In this prospective case–control study, we studied the factors associated with infection. Patients and Methods: Consecutive adult patients admitted with scrub typhus infection over 10 months were recruited. For every case, a geographical control from the same area and a gender-matched clinical control admitted with acute febrile illness were enrolled. The risk factors, which included sanitation, environment, activity, and protective measures, were compared between cases and controls using univariable and multivariable conditional logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Results: The study cohort (n = 225; 132 female) aged 44 ± 17 years comprised of 75 cases and 150 controls from mid to low socioeconomic background. When compared with clinical controls, on univariable conditional regression analysis, cases were more likely to be involved in farming or gardening and less likely to have a toilet within the house. On multivariate regression analysis, only involvement in farming or gardening was associated with infection (OR: 4.2, 95% CI: 1.5–11.5). When compared with geographical controls, on univariable conditional regression analysis, cases were less likely to change undergarments or clothes before sleeping (OR: 3.5, 95% CI: 1.3–9.5) and more likely to have rodents in their house (OR: 2.5, 95% CI: 1–6.4) and rest on grass/mud without a mat (OR: 2.4, 95% CI: 1.1–5.3). On multivariate regression analysis, not changing undergarments or clothes tended to be associated with infection (OR: 2.7, 95% CI: 0.98–7.3). Conclusion: Certain behavioral factors predisposed our cohort to develop scrub typhus infection. Lifestyle changes may reduce the burden of scrub typhus in South India.

Brucellosis, a common zoonosis, is under reported in India despite its endemicity and increased exposure to livestock among the population. This study was conducted to determine the clinical manifestations, antibiotic susceptibility pattern, treatment and outcome of culture confirmed brucellosis. Adult patients with culture confirmed brucellosis who presented to a large teaching hospital in South India between 2009 and 2015 were included. A diagnosis of brucellosis was confirmed on automated culture. Clinical profile, laboratory parameters, drug susceptibility, treatment and outcome were documented by reviewing the medical records. The cohort comprised of 22 patients with mean ± SD age of 42 ± 13 years. Twenty one (95.5%) was male. Thirteen (59%) patients were from rural area and risk of acquisition of brucellosis including occupational exposure or consumption of unpasteurized milk was evident in 16 (72.7%) patients. The mean duration of symptoms before presentation was 54.5 ± 52 days. The commonest clinical presentation was prolonged fever without a definite focus in 18 patients (82%), whereas 2 (9%) patients had osteoarticular involvement and one patient (4.5%) each had genital involvement and endocarditis. Eighteen patients (82%) with uncomplicated brucellosis were treated with aminoglycoside and doxycycline for 6 weeks. There was no relapse or mortality at 18 ± 9 months of follow up. Brucellosis in this cohort had acute or subacute presentation with prolonged fever and bacteremia. High index of clinical suspicion based on significant epidemiological history along with automated blood culture improves the efficiency of diagnosis. Cure with lack of relapse among these cases suggests a combination therapy with doxycycline and aminoglycoside is highly effective for the treatment.

Background: Acute undifferentiated febrile illness (AUFI) may have similar clinical presentation, and the etiology is varied and region specific. Materials and Methods: This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3-14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed. Results: The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9%) followed by dengue (30.6%), malaria (10.4%), enteric fever (3.7%), and leptospirosis (0.6%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days) and scrub typhus (8.2 [3.2] days). Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%), scrub typhus (4.2%), and malaria (4.6%). The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6%) followed by dengue fever (2.3%). Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38-7.3), total whole blood cell count >10,000 cells/mm 3 (OR: 2.31; 95% CI: 1.64-3.24), serum albumin

Background Tuberculosis (TB) is still a significant health problem worldwide. Central nervous system TB amounts to 10% of all cases of TB. Despite advances in the pharmacological management of TB, the overall outcomes remain poor with significant mortality and morbidity. There are no predictors for neurological outcomes in tuberculosis meningitis (TBM). In this study, we aimed to evaluate the role of cerebrospinal fluid (CSF) C-reactive protein (CRP) in predicting mortality and neurological outcome in TBM. Method: In this observational study, all patients with TBM were recruited prospectively over a 12-month duration. Baseline demographic data, laboratory parameters, and Imaging findings were collected. CSF CRP was obtained on the CSF sample collected at the time of diagnosis. Patients were followed up at 3 months to assess neurological status and mortality. Results Seventy-one patients with TBM were recruited in this study. The overall mortality in this study was 22.5% of patients. The primary composite outcome of mortality and adverse neurological outcome occurred in 40.8%. The CSF CRP levels ranged between 0.1 and 4.8 mg/dl, and the mean CSF CRP level was 1.11 mg/dl. The Relative risk for a patient with high CSF CRP to develop adverse outcome was 1.84 (P = 0.038). CSF CRP was a good predictor of mortality with a relative risk of 2.92 (P = 0.027). Stroke in TBM had a high incidence of 47.9% and a relative risk of 3.42 for an adverse neurological outcome. CSF CRP did not predict the occurrence of stroke. Hydrocephalus and elevated intracranial pressure were good predictors of stroke. Conclusion TBM is a disease with significant mortality and morbidity. CRP level in the CSF can be measured, but a highly sensitive scale may be needed as the mean values were much lower compared to the serum values. CSF CRP Levels showed significant associations with adverse outcomes and mortality.

Background Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its nonspecific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluated the diagnostic performance of various tests. Methods Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood or eschar were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative PCR using 47 kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil–Felix test (WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT). Results Among the 302 participants, 152 had confirmed scrub typhus (cases) and 150 were controls. ELISA and RDT detecting IgM antibodies had excellent discriminative potential with sensitivities and specificities of 94%, 93% and 92%, 93%, respectively. False-positive IgM serology was observed with spotted fever and leptospirosis. The sensitivity and specificity of IFA were found to be 80% and 85%, respectively. qPCR exhibited excellent sensitivity (96%) and perfect specificity. Conclusion ELISA and RDT detecting IgM antibodies have excellent sensitivity and specificity while the sensitivity of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories. Disclosures All authors: No reported disclosures.

Thirty-seven patients with severe organophosphorus poisoning (OPP) presented to the emergency ward of BP Koirala Institute of Health Sciences between January 1995 and December 1996. The mean age of patients was 26.9 years. There were 17 (46%) males and 20 (54%) females, with male: female ratio being 1:1.2. Twenty-three (62%) patients were unmarried with 16 (46%) of them students. The most common reason for poisoning was suicide − 32 patients (86.5%). The most commonly involved compound was Metacid (methyl-parathion) − 23 (62%) patients. Ninety per cent of the patients presented within 2 h of ingestion. All patients were managed with intravenous atropine. Pralidoxime was given to patients with nicotinic symptoms and mechanical ventilation initiated in patients with respiratory distress. The mean dose of atropine used in the first 24 h and during the hospital stay was 30.6 mg and 136.7 mg, respectively. The mean duration of treatment was 5.5 days (range 2–20 days). Two patients developed intermediate syndrome and the overall mortality among hospitalized patients was 8%.

Envenoming from snake bite is an important medical condition, frequently encountered at the emergency department of BPKIHS hospital (Dharan, Nepal). This is a retrospective study of 52 cases of suspected snake bite who presented at the department from August 1993 to November 1994. Analysis of the data showed that snake bite was more frequent between the ages of 11 to 20 years (36.7%) and 2.5 times more common in males. Fifty-seven per cent of the bites occurred between 1600 h and midnight with highest incidence (51%) occurring during the monsoon (August–October). Twenty per cent of the patients were able to identify the snake species as venomous and 90% of them presented to the hospital within 3 h of being bitten. Sixty per cent of the bites were in the lower limb. Neurotoxicity due to envenoming was recorded in nine patients (17%). No case of coagulopathy was recorded. The overall case fatality was 3.8% but mortality amongst those exhibiting signs of neurotoxicity was 22%.