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Background: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment. Objectives: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity. Methods: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival. Results: The 143 patients (104 males [80%], age 54 [42 – 65] years, median [inter-quartile range]) presented 4 (3—7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 – 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 – 165], p value

Background and Aim: Influenza is a disease with varied clinical presentation and varied mortality reported in existing literature. The study aimed to determine the factors associated with mortality in patients hospitalized with influenza infection. Materials and Methods: This was a 5-year nonconcurrent cohort study done in a tertiary care center in Southern India. Patients with laboratory confirmed influenza infection diagnosed between January 2013 and October 2018 were recruited into the study. Results: A total of 130 patients were recruited. Diabetes (45.4%) and chronic obstructive pulmonary disease (COPD) (26.1%) were the most common comorbid illnesses. Thirty-one patients (23.8%) required admission to the intensive care unit (ICU) and 58 patients required ventilation (noninvasive/mechanical ventilation [MV] – 44.6%). Influenza A was the most common isolated strain (46.9%). Univariate analysis demonstrated that a high pneumonia severity index (P < 0.0001), CURB 65 > 2 (P < 0.0001), MV dependency (P < 0.0001), need for ICU stay (P < 0.0001), low PF ratio (P < 0.0001), COPD (P = 0.021), secondary bacterial pneumonia (P < 0.0001), acute respiratory distress syndrome (P = 0.0004), and acute kidney injury (P = 0.0006) were the significant factors associated with in-hospital mortality. Multivariate analysis demonstrated that new onset/worsening renal dysfunction was the only factor significantly associated with in-hospital mortality in patients admitted with influenza. Conclusions: Our study showed a mortality of 12.3% (n= 16) and new onset/worsening renal dysfunction was the only patient factor associated with mortality. Early recognition of complications and appropriate treatment may reduce mortality in patients admitted with severe influenza. We recommend influenza vaccination for at-risk populations to reduce severity and mortality.

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.

ObjectiveLarge data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma.DesignSecondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease.Setting39 public and private hospitals across India during the study period from 22 April to 14 July 2020.ParticipantsOf the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed.Primary outcome measureFactors associated with all-cause mortality at 28 days after enrolment.ResultsThe mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3–7) and non-survivors (4 days; IQR 3–6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p2/FiO2 ratio 10 (9.97, 3.65–27.13, p1.0 mg/L (2.50, 1.14–5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44–4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60–5.45, p=0.001) were significantly associated with death.ConclusionIn this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death.Trial registration numberCTRI/2020/04/024775.

Tuberculosis and cryptococcosis are important opportunistic pathogens causing significant morbidity and mortality in immunocompromised individuals. Concurrent infections of these two agents are rarely reported. We report five cases of culture-proven coinfection of Mycobacterium tuberculosis and Cryptococcus neoformans during inpatient admission at a tertiary care hospital in southern India between 2007 and 2019. Four patients were persons living with HIV infection and one was on immune suppression for chronic renal disease. Maintaining a high degree of clinical suspicion will ensure early diagnosis and appropriate management of coinfections in the immunocompromised individual.

The incidence of (Human immune deficiency) HIV in India has fallen by 58% since the onset of the HIV epidemic. As of 2016 there are 2.1 million people living in India with HIV and only 49% of the adults with HIV are on ART (1). The HIV infected individuals may require intensive care due to various reasons. This study attempts to look at the outcomes of these patients admitted in the intensive care unit and the predictors of these outcomes. Aims: 1. To assess the outcomes of critically ill HIV infected patients admitted in the medical intensive care unit. 2. Assessment of the factors that are likely to influence the outcome. Materials and Methods: it is a retrospective medical review of all the patient records available on our electronic database. The study period was January 2008 – October 2013. Results: in our study cohort the commonest reason for admission into the intensive care unit was sepsis associated with multi organ dysfunction (64%).A low CD 4 count, renal failure acute respiratory distress syndrome, and hypotension and multi organ dysfunction were predictive of a poor outcome in our study. Conclusion: The most common cause of admission of PLHIV in ours study cohort was Infections, ART associated side effects and low CD4 counts, presence of multi organ dysfunction, acute respiratory distress syndrome (ARDS), hypotension were associated with adverse outcomes.

Context: Relative risk of non-Hodgkin lymphoma (NHL) in people living with HIV is 60–200 times that of normal population. This is the largest series from India on lymphomas arising in HIV-infected individuals including workup for Epstein–Barr virus (EBV) and human herpesvirus-8 (HHV-8). Aims: This study aims to ascertain the distribution and detailed clinicopathologic features of lymphoma arising in HIV-infected persons in India. Settings and Design: The study was done during the period of 2007–2011 in the pathology department of a tertiary care center in South India. Subjects and Methods: All cases diagnosed as lymphoma in the department of pathology during the study period were identified, and patients with HIV positive by serology were included in the study. Clinical details were obtained from electronic records, slides were reviewed and tissue blocks retrieved, and immunohistochemistry for HHV-8 and in situ hybridization for EBV-encoded RNA was done. Statistical Analysis Used: Descriptive statistics were done using SPSS software. Kaplan–Meier curves were used to do survival analysis. Results: Of 3346 patients diagnosed with lymphoma, 73 (2%) were diagnosed to be positive for HIV. About 87.6% of the cases were NHL, of which diffuse large B-cell lymphoma was the most common and plasmablastic lymphoma was the second common subtype. Survival was uniformly poor in 36% of the cases where follow-up was available. Conclusions: The striking differences from world literature included higher frequency of plasmablastic lymphomas, lack of primary central nervous system lymphomas, and low association with HHV8.

Background The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen, Author summary Snakebite is a neglected tropical disease and responsible for an estimated 130,000 deaths per year. Coagulopathy is the commonest clinical manifestation of systemic snakebite envenoming and is indicative of a need for antivenom. The 20WBCT is a simple, cheap and quick bedside clotting test devised to detect coagulopathy after snakebite. The test is used widely and is incorporated in multiple national and WHO guidelines. However, following a publication questioning its diagnostic accuracy, there is a lack of consensus regarding its diagnostic accuracy and utility. In this review, we conclude that the 20WBCT is capable of detecting coagulopathy following snakebite with high specificity and acceptable sensitivity. Diagnostic test accuracy of the 20WBCT is improved when assessing for the presence of severe coagulopathy. Inclusion of data in this analysis from a variety of countries, make the findings widely applicable. However, the heterogeneity in study findings indicates the need for local assessment of external validity. The results of this study support the WHO guidelines that recommend its continued use in the absence of conventional laboratory clotting assays. Urgent efforts are required to identify an optimal method of detecting systemic snakebite envenoming and the response to treatment through pharmacokinetic and pharmacodynamic studies of venom and antivenom.

It is unclear if the clinical presentation of poisoning with type 1 and type 2 pyrethroid compounds is different. This study was undertaken to detail the clinical profile and outcome of patients presenting with pyrethroid poisoning and to quantify serum pyrethroid levels. In this prospective study, patients were categorised as poisoning with type 1 pyrethroids or type 2 pyrethroids. Blood samples were sent for compound identification and quantification. Clinical features and outcomes were compared between the two groups. Factors associated with moderate and severe toxicity were explored using univariate logistic regression analysis and presented as odds ratio (OR) and 95% confidence intervals (CI). Type 1 pyrethroids were implicated in 16 patients and type 2 in 43 patients. The incidence of nausea and vomiting (81.2% vs. 81.3%) and tremor (37.5% vs. 32.6%) were similar in type 1 and type 2 poisoning; paraesthesia (6.2% vs. 32.6%, p = 0.04), hypersalivation (0% vs. 20.9%, p = 0.04), seizures (0% vs. 7%, p = 0.29) and depressed sensorium (0% vs. 18.6%, p = 0.03.) were observed more frequently in type 2 pyrethroid poisoning. Pyrethroids were detected in the serum samples of 24 patients; quantification was possible in 22 patients in whom serum levels ranged from 1.1 to 453 ��g/ml. The compounds were undetectable in 35 patients. Two patients (lambda-cyhalothrin poisoning and cypermethrin poisoning) required intubation for low sensorium and respiratory distress. The median (interquartile range) duration of hospitalization was 12 (12���24) hours. All patients survived. Factors associated with moderate and severe toxicity included ingestion of a type 2 pyrethroid, lambda-cyhalothrin (OR 7.81, 95%CI 1.55���39.37, p = 0.01) and volume ingested (OR 1.01, 95%CI 1.00���1.02, p = 0.02). Patients with pyrethroid poisoning present predominantly with mild to moderate symptoms. Paraesthesia and hypersalivation are more frequent in type 2 poisoning. A favourable outcome can be expected.

Background: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analyzed the factors associated with mortality in a cohort of moderately ill COVID-19 patients enrolled in a multicentre randomized trial on convalescent plasma. Methods: Demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic records. Factors associated with mortality were explored using univariate and multivariable Cox regression analysis and expressed as hazard ratio (HR) with 95% confidence intervals (CI). Findings: The mean (SD) age of the cohort (n=451) was 51±12·4 years; 76·7% were male. Admission SOFA score was 2·4±1·1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98·9%, 8·4% and 4·0% respectively. The 28 day all-cause mortality was 14·4%. Median time from symptom onset to hospital admission was similar (p=1.0) in survivors (4 days; IQR 3-7) and non survivors (4 days; IQR 3-6). Patients with two or more co-morbidities had 2·25 (95%CI:1·17–4·32, p=0·014) times risk of death. When compared with survivors, admission IL-6 levels were higher (p 10 (9·38, 3·67-24·0,p 1·0mg/l (2·51,1·14-5·51,p=0·022), ferritin>500ng/ml (2·66,1·46-4·85,p=0·001) and LDH≥450 IU/L (2·96,1·61-5·45,p=0·001) were significantly associated with death. Interpretation: In this cohort of moderately ill COVID-19 patients, severity of illness, underlying co-morbidities and higher levels of inflammatory markers were significantly associated with death. Trial Registration: The trial protocol was registered with the Clinical Trial Registry of India (CTRI/2020/04/024775). Funding: This study was funded by Indian Council of Medical Research, an autonomous government funded medical research council. Declaration of Interests: No other author has any competing financial or non-financial interest. Ethics Approval Statement: Ethical approval was obtained from the ICMR Central Ethics Committee on Human Research 326 (CECHR-002/2020) as well as from the Institutional Review Boards (IRB) /Institutional Ethics 327 Committees of all the participating hospitals.

Introduction: Varicella zoster virus is an exclusively human neurotrophic virus. The primary infection with the virus causes varicella. The virus remains latent in nervous tissue and upon secondary activation causes a variety of syndromes involving the central nervous system (CNS) including meningoencephalitis and cerebellitis. Materials and Methods: In this study, we looked at the epidemiology, clinical and laboratory features, and outcomes of patients who were admitted with varicella zoster of the CNS from 2005 to 2014. Results: There were 17 patients. Fever was present in 13 patients, seizures in 9 patients and headache and vomiting in 4 patients each. A generalized varicella rash was present in 8 out of 17 patients. A single dermatomal herpes zoster was present in seven patients. Two patients had no rash. Varicella zoster polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) was done in 5 patients of which 4 were positive and 1 was negative. Nine patients had diabetes with an average glycated hemoglobin of 8.6%. Total number of deaths was five. Conclusions: Patients with diabetes who develop varicella or herpes zoster may be at risk for CNS complications. The diagnosis of varicella encephalitis has to rest on a combination of clinical findings and CSF PCR, as neither the rash nor the PCR is sensitive enough to diagnose all the cases with varicella encephalitis.

Posaconazole has significant activity against the Mucormycetes. However, data are limited on the clinical efficacy of posaconazole for treating rhino-orbito-cerebral mucormycosis (ROCM). The aim of this study is to assess the efficacy and safety of posaconazole in patients with ROCM. We included 12 consecutive adult patients admitted with ROCM and treated with posaconazole between January 2010 and February 2015. The main outcome of the study was the overall success rate (i.e. either complete or partial response) at the end of treatment. We also assessed serum posaconazole concentrations in a subgroup of patients. Of the 12 patients who received posaconazole, eight patients (66.6%) had complete resolution with median follow-up of 6.5 months (range 2-24 months). Two patients (16.6%) had significant reduction of disease and two (16.6%) had marked residual disease on follow-up. Uncontrolled diabetes was the predisposing factor in all except one patient. One patient developed diarrhoea on posaconazole, which settled without discontinuation of the drug. Posaconazole appears to be a safe and effective antifungal agent in diabetic patients with ROCM, especially in those who have toxicity with polyene therapy.

Introduction: The National Aids Control Organization (NACO) has been providing free Antiretroviral Therapy (ART) in India since 2004. Several concerns exist regarding functional outcome, possible low rates of treatment adherence, treatment failure, mortality and high drug toxicity with the provision of large scale free ART. Aim: This study was done to evaluate the outcomes of ability to return to work, lost to follow up rates, treatment failure and drug toxicity requiring regimen change from the ART centre located in Christian Medical College, Vellore, Tamil Nadu, India, which is a large tertiary care centre attached to an academic Infectious Disease and medical unit in Southern India. Materials and Methods: A prospective longitudinal follow up study on patients enrolled in the NACO ART centre at a large tertiary care hospital in Southern India between April 2008 and April 2012 were followed up for a minimum of two years. Outcomes assessed were WHO clinical stage and functional status at the end of the follow up period, rate of lost to follow up, failure of ART, mortality rate and drug toxicity requiring change of regimen. Results: There were 963 patients included in the study with a mean follow up period of 39.78 months (SD 11.34). At the end of the follow up period, 914 (94.9%) of the patients were asymptomatic (WHO clinical stage 1T) and 92.3% of all patients on treatment were able to return to work after ART initiation. We found low rates of lost to follow up (3.2%), drug toxicity and mortality (5.8%) compared to data from other centres in India. A total of 136 adverse events were recorded, the most common being Zidovudine induced anaemia (7.2%). There was also a very low rate of treatment failure in our cohort. Conclusion: This data shows the overall success of the program and the feasibility of having low rates of lost to follow up because of rigorous methods used in follow up of patients and support offered by attachment to an academic infectious disease unit.

We studied the association between admission serum 25-hydroxy vitamin D3 level and in-hospital mortality in a prospective cohort of critically ill patients admitted to the medical intensive care unit of a tertiary care referral center. Of the 180 patients enrolled, 129 were included. Vitamin D3 deficiency was observed in 37 % (n = 48) and supra-physiological levels (≥250 nmol/L) in 15.5 % (n = 20). Patients with supraphysiological vitamin D3 levels were grouped as outliers. There was no difference in mortality (p = 0.41) between vitamin D3 deficient (21/48) and non-deficient (36/81) patients in analysis with and without outliers. Patients with vitamin D3 ≥250 nmol/L had a significantly higher (p = 0.02) Simplified Acute Physiology Score (SAPS) II and mortality (p = 0.003) [mean (SD) 60.1 ± 17.1 and 75 % (15/20), respectively] when compared with the rest [45.6 ± 18 and 38.5 % (42/109), respectively]. The sensitivity, specificity and SAPS II independent odds ratio to predict mortality in patients with supraphysiological vitamin D3 levels were 26.3, 93.1 and 3.7 % (95 % confidence interval 1.2–11.4; p = 0.03), respectively. In conclusion, vitamin D3 deficiency in our cohort was not associated with mortality. A patient subset with supra-physiological vitamin D levels had higher illness severity scores and mortality. Extrinsic factors interfering with test results were ruled out. A biological hypothesis to explain this observation is proposed. Further clarification of mechanisms leading to this observation is warranted.

A 28-year-old man diagnosed with diabetes mellitus and systemic hypertension presented with a medical history of sudden onset retrosternal discomfort followed by loss of consciousness and generalised tonic clonic seizures. Examination revealed obesity, polysyndactyly and retinal pigment dystrophy. He was diagnosed to have acute myocardial infarction and left posterior watershed infarct. He was also diagnosed to have Bardet-Biedl syndrome based on clinical features. He was managed symptomatically and is currently doing well on regular follow-up in the outpatient clinic.

Background. Acute kidney injury (AKI) is a common complication of snake envenomation. However, the long-term renal outcomes of such patients are not well defined. We aimed to determine the proportion of patients who developed AKI, characterize the presenting syndromes and ascertain the long-term resolution of AKI. Methods. We did a cohort study with prospective follow- up from two centres in southern India. All admitted patients >15 years of age with snake envenomation and serum creatinine ≥1.5 mg/dl over the past 10 years were identified through their discharge summaries. These patients were prospectively contacted, interviewed telephonically and requested to come for a hospital review. Results. Of the 866 patients screened, 1 84 developed AKI (21.2%). Among these, 53% had combined renal, haematological and neurological manifestations; 33.6% required admission to the intensive care unit and 38% were dialysed. On follow-up of hospital records the creatinine of 49% of patients had normalized. Of those admitted, 36% were contacted and none had a known renal disease or were on dialysis. Among these, 16 patients came to the hospital for review and only 2 had an elevated creatinine. The total mortality was 1 4. Conclusion. AKI is an important cause of morbidity with snake envenomation and a proportion will require dialysis. The mortality in our study was low and long-term renal outcomes were relatively good.

Acute organophosphate pesticide poisoning is a common medical emergency with high fatality in agricultural communities of Asia. Organophosphate compounds inhibit acetylcholinesterase and prolonged neuromuscular weakness is a major cause of morbidity and mortality of poisoning. Organophosphate pesticide induced muscle weakness may not only arise from inhibition of acetylcholinesterase but also from non-cholinergic pathomechanisms, particularly mitochondrial dysfunction, affecting the production of sufficient ATP for muscle function. This study examined whether muscle weakness in rats subject to monocrotophos toxicity (0.8LD 50 ) was caused by inhibition of ATP synthesis, by oxidative phosphorylation and glycolysis, in addition to inhibition of muscle acetylcholinesterase. Severe muscle weakness in rats following monocrotophos administration was associated with inhibition of muscle acetylcholinesterase (30–60%) but not with reduced ATP production. The rats rapidly recovered muscle strength with no treatment. The ability of rats to spontaneously reactivate dimethyoxy phosphorylated acetylcholinesterase and efficiently detoxify organophosphates may prevent severe inhibition of muscle acetylcholinesterase following acute severe monocrotophos poisoning. This may protect rodents against the development of prolonged muscle weakness induced by organophosphates.

Organophosphate (OP) poisoning results in significant toxicity while pyrethroid poisoning is associated with extremely low fatality. OPs can inhibit the detoxification of pyrethroid and increase the toxicity of the combination. We assessed whether mixed OP-pyrethroid poisoning impacted outcome in human poisoning.Patients were identified from a prospectively collected institutional poisoning database that incorporates demographic and outcome data of patients presenting with poisoning.Of the 1177 poisoned patients admitted over 2 years, 32 presented with OP-pyrethroid (50% chlorpyrifos-5% cypermethrin mixture) poisoning (Group 1), 26 consumed 20% chlorpyrifos (Group 2), and 32 took 15% cypermethrin (Group 3). Seizures occurred in 15.6% (n = 5) with chlorpyrifos-cypermethrin poisoning, 18.8% (n = 6) with cypermethrin poisoning, and 3.9% (n = 1) with chlorpyrifos poisoning. Ventilatory requirements were 53.5% (17/32), 42.3% (11/26), and 15.7% (5/32) in Groups 1-3, respectively. Ventilator-free days (Mean ± SD) was significantly lower (p0.006) in Group 1 (20.9 ± 9.3 days) than those in Group 2 (26.1 ± 4.4 days) or 3 (27.8 ± 0.6). The median (inter-quartile range) hospital stay was 5.5 (4-19.5), 5 (5-6), and 1 (0.65-1.5) days, respectively, in the three groups. Four patients died in Group 1 (13%). None died in the other groups.Although confounded by the varying quantity of chlorpyrifos and cypermethrin in the different formulations, patients with mixed poisoning appear to have shorter ventilator-free days than patients poisoned by either of the pesticides alone. Further studies are required comparing patients poisoned by formulations with similar quantities of OP and pyrethroid or with analysis of blood pesticide concentration on admission.

The temporal profile of butyrylcholinesterase (BuChE) and in vitro pralidoxime-reactivated BuChE was studied in a cohort of 25 organophosphate-poisoned patients to examine their relationship to the development of intermediate syndrome and to understand reasons for lack of efficacy of oxime treatment. The clinical severity of poisoning (assessed by the Namba Scale) correlated significantly with the severity of intermediate syndrome. BuChE activity increased significantly over time and showed significant relationship to muscle power. The temporal profile of the enzyme was correlated to the clinical severity of poisoning. Reactivation potentials of BuChE (the difference between oxime-reactivated and-unreactivated enzyme activity) declined significantly with time after organophosphate ingestion. The reactivation potential of the enzyme at admission decreased significantly with increasing severity of poisoning and was lower in patients who developed intermediate syndrome. Patients who received oxime prior to hospitalization had a higher rate of intermediate syndrome and lower levels of BuChE at admission than those who had not. The study suggests that (i) BuChE reflects the clinical course of poisoning, confirming earlier studies; (ii) intermediate syndrome may be associated with a persistent inhibition of BuChE; and (iii) the lack of oxime efficacy in our patients maybe due to their severity of poisoning and the timing of oxime treatment.

Four cases of the rare disorder, inherited degenerative chondropathy have been previously reported (Kurien et al., 1989). A five-year follow-up of these patients and two additional cases are presented in this report. The progress of this disease appears to be arrested after regulardapsone therapy and there was no other organ involvement noted during the follow-up period.

Self-poisoning through the ingestion of Oduvanthalai is common in South India. Mortality may occur because of arrhythmias, renal failure, shock, and respiratory distress. The mechanisms of toxicity are unclear. This prospective, clinical study was designed to assess renal tubular dysfunction because of Oduvanthalai poisoning.Thirty-two consecutive patients admitted with Oduvanthalai poisoning at a tertiary care hospital in South India, from June 2007 to August 2009 (26 months), were evaluated through history, physical examination, and laboratory studies. Following an interim analysis, additional studies of renal tubular function were performed on a subcohort of eight patients. These included the following: (1) urinary pH, daily serum, and urine anion gap; (2) 24-h urine protein and potassium; and (3) assessment of urine hexosaminidase and amino acid levels.Metabolic acidosis (100%), which persisted at discharge (65.6%), hypokalemia (62.5%), and renal failure (15.6%), was apparent in the total cohort. Tests of renal tubular function on the subcohort revealed a normal anion gap, hyperchloremic, metabolic acidosis of renal etiology, defective urinary acidification, and hypokalemia with kaliuresis, indicative of distal renal tubular acidosis in six patients. Urinary hexosaminidase and amino acid levels, markers of proximal tubular dysfunction, were elevated in seven and two patients, respectively.Distal renal tubular acidosis is an important feature of Oduvanthalai poisoning. Proximal tubular injury and, in more severe forms, global tubular dysfunction with diminished glomerular filtration rate may occur.

Super-Vasmol, a cheap, freely-available hair dye is emerging as a major cause of suicidal poisoning in India. It contains potential toxins including paraphenylene diamine, resorcinol, sodium ethylenediaminetetraacetic acid and propylene glycol which can result in multiorgan dysfunction. A retrospective study was conducted over 3.5 years (January 2006 – July 2009) of 13 consecutive patients with Super-Vasmol poisoning admitted to a tertiary care, referral hospital in South India. A chart review including records of clinical presentations, laboratory findings and treatment details was carried out. Eleven of the patients were women and the mean age was 27.2 years. The predominant clinical features were cervico-facial oedema and pain, cola-coloured urine and oliguria. Laboratory investigations revealed elevated hepatic transaminases (100%), leucocytosis (92.3%), elevated creatinine phosphokinase (92.3%), metabolic acidosis (84.6%), hypocalcaemia (61.5%), hyperphosphataemia (46.2%) and renal failure (38.5%). Eight of the patients were discharged with complete recovery. Trends towards a poor outcome were evident among the following patients: late presentation at our centre; when no gastric lavage was done at the primary-care centre; those requiring tracheostomy/intubation at the primary centre; presentation with a low Glasgow Coma Score or seizures; established renal failure; and those who subsequently require dialysis, mechanical ventilation or intensive care. Hair dye poisoning classically presents with cervico-facial oedema, severe rhabdomyolysis and renal failure. Early therapy with tracheostomy and aggressive forced diuresis are essential in order to prevent the high mortality associated with this toxin. It is imperative to raise public awareness of the potential toxicity of the dye as well as to educate physicians about the need for aggressive and early treatment.

Organophosphate poisoning is a common method of deliberate self-harm in countries where the pesticides are readily available. The severity of neuroparalysis and myopathy occurring in acute organophosphate poisoned patients is determined by the severity of poisoning and is associated with morbidity and mortality. Molecular mechanisms that underlie severe paralysis are not well delineated but are essential to know to improve treatment. In this study rats were subjected to increasing doses (0.25 to 0.8 LD(50)) of monocrotophos, and cell membrane lipid profiles, particularly those of myofibril membranes, were examined in relation to neuromuscular weakness occurring in poisoning. Increasing doses of monocrotophos inhibited brain and RBC acetylcholinesterase/=60% early in the poisoning. RBC acetylcholinesterase levels recovered to 70% to 80% of normal while brain acetylcholinesterase remained 44% to 67% inhibited 1 week after poisoning. Increasing severity of poisoning led to significant changes in myofibril membrane lipid composition with cholesterol to phospholipid ratios increasing from 0.029 +/- 0.008 in controls to 0.063 +/- 0.023 in severe poisoning (p0.05). These changes were associated with neuromuscular weakness in the first day of poisoning. Membrane changes were reversible and rats recovered muscle strength in 1 week with no treatment. Lipid compositions of the intestine, brain, and muscle mitochondrial membranes were not affected by monocrotophos. The study indicated that neuromuscular weakness was associated with muscle membrane disorganization early in the course of acute organophosphate poisoning and that subclinical neurotoxicity of long duration may be a consequence of acute organophosphate poisoning. Controlling the severity of poisoning early in the course of acute organophosphate poisoning appears to be important for clinical recovery.

Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD(50)) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-N(G) Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure.

and immune studies were negative. Chest x-ray showed right hilar enlargement. Serum ACE levels and serum calcium were normal. The biopsy from the purpura yielded a histological diagnosis of leukocytoclastic vasculitis and direct immunofluorescence (DIF) was negative. Computed tomography (CT) disclosed significant mediastinal lymphadenopathy and matted lymph nodes in the lesser sac. Montoux test was highly positive. In view of high ESR, lymphadenopathy and positive montoux test, antitubercular treatment (ATT) was started. After oneweek of starting ATT, the skin lesions and fever completely resolved. CT chest and abdomen repeated after 2 months showed significant regression of lymphadenopathy. ATT continued for 6 months. Complete resolution of the lymphadenopathy was noted on Magnetic Resonance Imaging of chest and abdomen done 1 year later. Conclusion: Although incidence is rare, tuberculosis should be considered the possible underlying cause of vasculitis.