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Background: In this follow-up study, we aimed to establish the cut-off values of the volume, conductivity and scatter (VCS) parameters of leucocytes that significantly differ in dengue fever, malaria, scrub typhus and enteric fever, as described in our pilot study., Methods: A prospective observational case-control study was undertaken on patients with an established diagnosis of acute malaria (n=476), dengue fever (n=927), scrub typhus (n=425), bacterial sepsis (n=1598) or enteric fever (n=885) and the haematological and VCS data obtained by the Coulter LH 750 analyser were compared with controls., Results: Malaria significantly altered the platelet count and plateletcrit. The cut-offs for the monocyte volume, lymphocyte volume, neutrophil volume, neutrophil volume distribution width, lymphocyte volume distribution width, monocyte volume distribution width and neutrophil conductivity distribution width had 90% negative predictive values (NPVs) for malaria. Except for the proportion of monocytes, lymphocyte scatter distribution width and platelet distribution width, a >70% positive (PPV) and negative predictive value (NPV) for dengue was noted in all the haematological and VCS parameters analysed. While the cut-offs determined in scrub typhus had a good (>80%) PPV and NPV, a significant difference was seen in neutrophil, monocyte and lymphocyte conductivities, but with low sensitivity, specificity, PPV and NPV in enteric fever., Conclusions: Aetiology-specific changes occur both in numbers as well as in VCS properties in acute fevers. Formulae and/or algorithms need to be utilized to realize the full potential of the VCS technology.

Background & Objectives: Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India., Methods: Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA., Results: A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death., Interpretation & Conclusions: The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

Background: A single diagnostic test for acute undifferentiated febrile illnesses (AUFI) is elusive. This pilot study was undertaken on the premise that leucocytes, being the main cells of defence, undergo quantitative, structural and functional changes in AUFI. We evaluated the potential of volume, conductivity and scatter (VCS) parameters of leucocytes, generated with the haemogram report by the Coulter auto-analyzer, in differentiating the common etiologies of AUFI., Methods: The haematological and VCS data obtained from 800 controls and 200 cases of AUFI (50 cases each of acute malaria, dengue, scrub typhus and enteric fever) were retrieved for analysis., Results: The cases and controls differed significantly with respect to relative numbers and the VCS parameters of neutrophils, lymphocytes and monocytes (p<0.05). The neutrophil and lymphocyte were significantly voluminous in acute malaria and scrub typhus as compared to dengue and enteric fevers (p<0.05). Enteric fever significantly enhanced the conductivity of neutrophils as compared to other subgroups while lymphocyte conductivity significantly differed from dengue and scrub typhus. Lymphocyte and neutrophil scatter values in malaria and scrub typhus were comparable but differed significantly from that in enteric fever., Conclusions: Etiology-specific changes occur in leucocytes, both in numbers and their VCS properties which can be identified without additional cost., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Acute encephalitis syndrome (AES) has a diverse etiology and Japanese encephalitis virus (JE) is the most common etiological agent implicated in its causation. However, AES in different geographical locations have distinct etiological agents that may have seasonal variability, miscellaneous presentations and outcome. We wished to study the demographical profile, etiology and clinical parameters of AES in a tertiary referral center of Uttarakhand as data from this newly created state is lacking. An observational cross-sectional study was conducted where various demographic and clinical profile, etiology and laboratory parameters in 111 patients of AES were studied and comparison was made between the two outcome groups (improved and expired). In the present study, tuberculous meningo-encephalitis was the most common etiology (22.5 %) of AES followed by scrub typhus (19.8 %). Statistically significant (p-value < 0.05) difference was Observed between patients who expired from those who improved in terms of hematological parameters (mean leucocyte and platelet counts), renal function (mean creatinine, pH, bicarbonate) and liver functions (liver enzymes and albumin levels).This study highlights the fact that AES can have different etiologies depending upon various factors like difference in geographic location, season, agent and vector prevalence. Identification of the specific etiological agent is important for management, understanding the prognosis, instituting timely prophylaxis and public health interventions. [ABSTRACT FROM AUTHOR]

Objective: To study the clinical profile and complications of childhood scrub typhus. Methods: Prospective observational study of 66 children with scrub typhus, admitted to a tertiary hospital in north India, during the period between January 2011 and December 2012. The diagnosis was confirmed by serology. Findings: All children presented with fever. Other common symptoms were vomiting (56%), facial swelling (52%), cough (35%), abdominal pain (33%), breathlessness (29%) and decreased urine output (29%). High grade fever (>101 oF) was recorded in 91% of children. Other common signs were hepatomegaly, splenomegaly, edema, tender lymphadenopathy and hypotension, observed in 82%, 59%, 39%, 38% and 36% of cases, respectively. An eschar and a maculopapular rash each were observed in 20% of patients. Meningoencephalitis (30.3%), severe thrombocytopenia (27.2%), shock (25.8%), acute kidney injury (16.7%) and hepatitis (13.6%) were the most common complications observed in these children. Other common complications were acute respiratory distress syndrome, respiratory failure requiring ventilation, bronchopneumonia and myocarditis. Ninety percent of children became afebrile within 48 hours of initiating an appropriate antibiotic. Median time to defervescence was 22 hours. The overall mortality rate was 7.5%. Causes of death were refractory shock, meningoencephalitis, acute respiratory distress syndrome, bronchopneumonia, acute kidney injury and myocarditis. Conclusion: Pediatricians should keep a high index of suspicion for scrub typhus in any febrile child having a maculopapular rash, hepatosplenomegaly, tender lymphadenopathy, thrombocytopenia and features suggestive of capillary leak. Pending serological confirmation, empirical therapy with doxycycline or azithromycin should be started, as delay in treatment would result in life threatening complications. [ABSTRACT FROM AUTHOR]

Introduction: Acute undifferentiated febrile illness (AUFI) is a common clinical entity in most of the hospitals. The fever can be potentially fatal if the aetiology is not recognized and appropriately treated early. Aim: To describe the aetiology of fever among patients in a tertiary care hospital in Northern India. Materials and Methods: A one-year retro-prospective, observational study was conducted in adults (age>18years) presenting with undifferentiated febrile illness (of duration 5-14 days). Diagnosis was confirmed by suitable laboratory tests after exhaustive clinical examination. Results: A total of 2547 patients with AUFI were evaluated. Of these, 1663 (65.3%) were males and 884 (34.7%) were females. Dengue (37.54%); enteric fever (16.5%); scrub typhus (14.42%); bacterial sepsis (10.3%); malaria (6.8%); hepatitis A (1.9%); hepatitis E (1.4%); leptospirosis (0.14%); were the main infections while no specific diagnosis could be delineated in 11%. Mixed infections were noted in 48 (1.9%) patients. Conclusion: A good clinical acumen supported by the basic investigations can help diagnose the cause of fever with reasonable certainty. [ABSTRACT FROM AUTHOR]

Scrub typhus is a commonly encountered rickettsial disease of the Indian subcontinent. In India, scrub typhus is being now reported from several areas where it was previously unknown. We report clinical profile and complications of an outbreak of scrub typhus in children from the north Indian state of Uttarakhand. a region not previously known to have endemic disease. We describe the results of a prospective observational study of children with scrub typhus, at a tertiary hospital during the year 2013. The diagnosis was confirmed serologically by an IgM ELISA test. Sixty-two children were diagnosed with scrub typhus. All presented with fever. Other common symptoms were vomiting (59%), facial swelling (53%), cough (24%), abdominal pain (35%), breathlessness (26%) and decreased urine output (21 %). High grade fever (> 101 °F) was recorded in 95% of the children. Other common signs observed in cases of scrub typhus were hepatomegaly (77%), splenomegaly (63%), edema (37%). tender lymphadenopathy (42%) and hypotension (35%). An eschar was observed in 23% of patients. Meningoencephalitis (30.6%), severe thrombocytopenia (27.4%), shock (17.7%), hepatitis (16.1%) and acute kidney injury (11.3%) were the most commonly encountered complications. Eighty-seven percent of children became afebrile within 48 hours of initiating an appropriate antibiotic. Median time to defervescence was 24 hours. The overall mortality rate was 6.4%. Pediatricians should keep a high index of suspicion for scrub typhus in any febrile child having a maculopapular rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and features suggestive of capillary leak. Pending serological confirmation, early empirical therapy with doxycycline or azithromycin should be started, as delay in treatment would result in life threatening complications. [ABSTRACT FROM AUTHOR]

Neurologic involvement in scrub typhus in the form of meningitis or meningoencephalitis, and its differentiation from other forms of bacterial and viral meningitis, has not been extensively studied in pediatric population. We compared the clinical and laboratory profiles of children with scrub typhus meningitis (STM) and acute bacterial meningitis (ABM) at a university teaching hospital in North India. Twenty-seven children were diagnosed with acute meningitis over 12 months. Meningitis was diagnosed based on clinical features and abnormal cerebrospinal fluid (CSF) analysis, with either a positive IgM ELISA for scrub typhus (n = 19) or isolation of bacteria known to cause ABM from CSF (n = 8). The children with STM were significantly older (7.8 ± 4.9 vs. 4.5 ± 4.9 years; p = 0.029), had longer duration of fever (7.9 ± 2.7 vs. 3.4 ± 2.1 days; p < 0.001), and were more likely to have multisystem involvement compared with ABM group. The STM group had CSF pleocytosis of lessermagnitude (99.2±103.4 vs. 1770 ±3,333 cells/mm3; p < 0.001), a higher proportion of lymphocytes in CSF (74 ± 16 vs. 12 ± 6.8%; p < 0.001), lesser degree of protein elevation (108.4 ± 43.9 vs. 639.0 ± 546.3 mg%; p < 0.001), and higher CSF sugar level (60.8 ± 13.1 vs. 21.6 ± 11.6 mg%; p < 0.001) as compared with ABM group. Time to defervescence in children with STM was shorter. In conclusion, compared with ABM children, STM children tended to be older, usually had multisystem involvement, and had longer duration of fever but more rapid defervescence in response to appropriate antibiotics. Typical CSF findings included lymphocytic pleocytosis, moderate protein elevation, and a normal glucose concentration. [ABSTRACT FROM AUTHOR]