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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 Recent cohort studies have proven the association between sleep deprivation and adverse glycemic control (GC). The aim of this study was to assess the prevalence of excessive daytime sleepiness (EDS), a subjective measure of sleep deprivation, among type 2 diabetic mellitus (T2DM) patients and its association with GC. METHODS This cross-sectional study was conducted between July 2015 and June 2016 in five diabetes clinics in the district of Erode, Tamil Nadu, India. An equal number of consenting patients with T2DM was recruited consecutively from each of the centers, and EDS was measured subjectively using the Epworth sleepiness scale (ESS), whereas GC was assessed using HbA1c levels. RESULTS In all, 126 patients were screened and 102 were found eligible for the study. The prevalence of EDS was 17.5% (95% confidence interval 10.13-24.87). The association between ESS scores and HbA1c levels was analyzed using linear regression after adjusting for age, dietary intake, inflammatory markers (erythrocyte sedimentation rate), depression (Patient Health Questionnaire-9 score) and stress (Perceived Stress Scale score): for every unit increase in the ESS score, HbA1c increased by 0.143 g/dL (P < 0.001). CONCLUSION Subjective EDS was seen in approximately one-quarter of patients with diabetes in our population. There was a positive association between EDS and glycemic control. Screening of patients with diabetes for EDS should be part of routine diabetes management.

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: Ross syndrome is diagnosed by the presence of segmental anhidrosis, areflexia, and tonic pupils. Fewer than 60 cases have been described in literature so far. There have been reports of presence of antibodies in such patients, suggesting an autoimmune pathogenesis. Methods: We describe the clinical profile in this case series of 11 patients with Ross syndrome and discuss the current status of autoimmunity in its pathogenesis and the management. Results: Of the 11 patients with Ross syndrome there was an almost equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset of symptoms was 26 years. Patients took an average of 6 years to present to a tertiary center. Sixty-three percent of the patients presented with complaints of excessive sweating, whereas only 27% had complaints of decreased sweating over a particular area of the body. Only 45% of the patients had the complete triad of Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent reflexes. Eighty-nine percent of the patients had documented absent sympathetic skin response on electromyography. The various markers of autoimmunity were negative in all patients who were investigated for the same in this series. Ninety percent of the patients were managed conservatively. Conclusions: These findings suggest that, in Ross syndrome, generalized injury to ganglion cells or their projections are not purely autoimmune-mediated.

There is limited information on extrapyramidal symptoms in acute organophosphate (OP) poisoning. We describe the course and outcome of severely poisoned patients who develop extrapyramidal manifestations.In this prospective observational study, spanning 8 months (Apr-Nov 2013) adult patients (18 years) admitted with OP poisoning were enrolled. Patients on anti-psychotic therapy, those refusing consent or presenting with co-ingestions were excluded. Treatment included atropine and supportive care (e.g. ventilation and inotropes as indicated); oximes were not administered. The presence of rigidity, tremors, dystonia and chorea were assessed daily till discharge using modifications of the Unified Parkinson's Disease rating scale and the Tremor rating scale. The presence of extrapyramidal manifestations was correlated with length of ventilation and hospital stay and mortality.Of the 77 patients admitted with OP poisoning, 32 were enrolled; 17 (53.1%) developed extrapyramidal manifestations which included rigidity (94.1%), tremors (58.8%) and dystonia (58.8%). None developed chorea. The median (inter-quartile range) time of symptom onset was 8 (5-11) days; extrapyramidal features resolved in 11 (6-17) days. The median duration of intensive care stay in patients not developing extrapyramidal symptoms was 6 (2-8) days, indicating that most of these patients had recovered even before symptom onset in patients who developed extrapyramidal manifestations. Overall, 27/32 (84%) were ventilated. Hospital mortality was 6.25% (2/32). When compared with patients not developing extrapyramidal signs, those with extrapyramidal manifestations had significantly prolonged ventilation (5 versus 16 median days; p = 0.001) and hospitalization (8 versus 21 days; p 0.001), reduced ventilator-free days (23 versus 12 days; p = 0.023) and increased infections (p = 0.03). The need for ventilation and mortality were not significantly different (p 0.6). Extrapyramidal symptoms were not observed in non-OP poisoned patients with prolonged ICU stay.In this small series of acute OP poisoning, extrapyramidal manifestations were common after 1 week of intensive care but self-limiting. They are significantly associated with longer duration of ventilation and hospital stay.

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 Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.

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%.