Anugrah Chrispal

Scrub typhus: an unrecognized threat in South India - clinical profile and predictors of mortality.

Summary Scrub typhus is an important cause of acute undifferentiated febrile illnesses in the Indian subcontinent. Delay in diagnosis and in the initiation of appropriate treatment can result in severe complications such as acute respiratory distress syndrome (ARDS), septic shock and multisystem organ failure culminating in death. We conducted a prospective, observational study to delineate the clinical profile and predictors of mortality in scrub typhus in adults admitted to the medical wards of a tertiary care, referral hospital in South India over a one-year period. The case fatality rate in this study was 12.2%. Metabolic acidosis (odds ratio [OR] 6.1), ARDS (OR 3.6), altered sensorium (OR 3.6) and shock (OR 3.1) were independent predictors of mortality. It appears that scrub typhus has four possible overlapping clinical presentations: mild disease; respiratory predominant disease; central nervous system predominant disease (meningoencephalitis); or sepsis syndrome. Given the telltale presence of an eschar (evident in 45.5%), the characteristic clinical profile and the dramatic therapeutic response to a cheap, yet effective, drug such as doxycycline, medical practitioners in the region should have ample opportunity to reach an early diagnosis and initiate treatment which could, potentially, reduce the mortality and morbidity associated with scrub typhus.

Acute undifferentiated febrile illness in adult hospitalized patients: the disease spectrum and diagnostic predictors – an experience from a tertiary care hospital in South India

Local prevalences of individual diseases influence the prioritization of the differential diagnoses of a clinical syndrome of acute undifferentiated febrile illness (AFI). This study was conducted in order to delineate the aetiology of AFI that present to a tertiary hospital in southern India and to describe disease-specific clinical profiles. An 1-year prospective, observational study was conducted in adults (age >16 years) who presented with an undifferentiated febrile illness of duration 5–21 days, requiring hospitalization. Blood cultures, malarial parasites and febrile serology (acute and convalescent), in addition to clinical evaluations and basic investigations were performed. Comparisons were made between each disease and the other AFIs. A total of 398 AFI patients were diagnosed with: scrub typhus (47.5%); malaria (17.1%); enteric fever (8.0%); dengue (7.0%); leptospirosis (3.0%); spotted fever rickettsiosis (1.8%); Hantavirus (0.3%); alternate diagnosis (7.3%); and unclear diagnoses (8.0%). Leucocytosis, acute respiratory distress syndrome, aseptic meningitis, mild serum transaminase elevation and hypoalbuminaemia were independently associated with scrub typhus. Normal leukocyte counts, moderate to severe thrombocytopenia, renal failure, splenomegaly and hyperbilirubinaemia with mildly elevated serum transaminases were associated with malaria. Rash, overt bleeding manifestations, normal to low leukocyte counts, moderate to severe thrombocytopenia and significantly elevated hepatic transaminases were associated with dengue. Enteric fever was associated with loose stools, normal to low leukocyte counts and normal platelet counts. It is imperative to maintain a sound epidemiological database of AFIs so that evidence-based diagnostic criteria and treatment guidelines can be developed.

Acute kidney injury in tropical acute febrile illness in a tertiary care centre—RIFLE criteria validation

BACKGROUND Acute febrile illnesses are a common cause of tropical acute kidney injury (AKI). The incidence and severity of AKI in tropical febrile illnesses and validity of RIFLE classification are unclear. METHODS Consecutive adult inpatients of a tertiary hospital in southern India with tropical acute febrile illness between January 2007 and January 2008 were prospectively studied for the incidence and severity of AKI based on RIFLE classification and its association with mortality and dialysis requirement. RESULTS The 367 patients (mean age 39.7±16.9 years; 60% males) with tropical acute febrile illness due to scrub typhus (51.2%), falciparum malaria (10.4%), enteric fever (8.7%), dengue (7.6%), mixed malaria (6.5%), leptospirosis (3.3%), undifferentiated acute febrile illness (8.4%) and others (3.8%) (spotted fever, vivax malaria and Hantaan virus infection) had an overall mortality rate of 12.3%. The incidence of AKI was 41.1%; of which, 17.4%, 9.3% and 14.4% were in the Risk, Injury and Failure classes, respectively. Of the patients, 7.9% required dialysis. Among the Risk, Injury and Failure groups, there was an incremental risk of mortality (OR 6.9, 20.2 and 25.6; P<0.001) and dialysis requirement (OR 3.4, 28.8 and 178.8; P<0.001). CONCLUSIONS The incidence of AKI in the common tropical acute febrile illnesses in our study such as scrub typhus, falciparum malaria, enteric fever, dengue and leptospirosis is 41.1%. RIFLE classification is valid and applicable in AKI related to tropical acute febrile illnesses, with an incremental risk of mortality and dialysis requirement.

Hair dye poisoning - an emerging problem in the tropics: an experience from a tertiary care hospital in South India

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.

Clinical profile and outcome of patients hospitalized with dimethyl and diethyl organophosphate poisoning.

The two major classes of organophosphate compounds, dimethyl and diethyl organophosphates, have different toxicokinetic properties. This study evaluated the clinical profile and outcomes in patients admitted with poisoning with these two classes of organophosphates. Methods. This retrospective study spanned 6 years (2002–2007). Patients were treated with atropine and supportive care including ventilation, as required, and followed up until death or hospital discharge. Oximes were not administered. Of the 422 charts retrieved, 396 fulfilled inclusion criteria. Data on the clinical profile, ventilation, length of hospital stay, incidence of intermediate syndrome and mortality were extracted. Results. The mean (±standard deviation) age was 31.4 ± 12.7 years with a male preponderance (2.6:1). The median (interquartile range (IQR)) admission pseudocholinesterase level of 317 (222–635) U/L indicated significant inhibition of cholinesterase activity. The median lag-time to presentation to our hospital was 5 (IQR 3–8.5) hours. Oximes were administered at a primary center in 33 patients (8.3%). Dimethyl organophosphate was ingested by 141 patients, diethyl organophosphate by 108, S-alkyl organophosphate by 2, and an un-identified organophosphate by 145 patients. Ventilation was required in 260 patients (65.7%); the median duration of ventilation being 7.5 (IQR 3–12) days. Overall mortality was 13.1%. There was a significant difference between dimethyl and diethyl organophosphate compounds in ventilatory requirement (76% vs. 56%, adjusted odds ratio (OR) 2.37, 95% CI 1.01–5.57, p = 0.047), duration of ventilation (11 (4–15) vs. 5 (2–9) days, adjusted OR 1.12, 95%CI 1.04–1.21, p = 0.002) and incidence of intermediate syndrome (72/125 (58%) vs. 24/92 (26%), adjusted OR 2.84, 95%CI 1.38–5.86, p = 0.004). Mortality was similar in the two groups (20/141 (14%) vs. 7/108 (6%), dimethyl vs. diethyl organophosphate, adjusted OR 1.29, 95%CI 0.43–3.94, p = 0.65). Conclusions. Patients admitted with dimethyl organophosphate poisoning have a worse outcome compared with diethyl organophosphate poisoning for clinically relevant patient outcomes.

Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia.

Aminoglycoside-induced renal toxicity is well known and may manifest with nonoliguric renal failure or renal tubular dysfunction. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome, or distal renal tubular acidosis. We discuss a patient who developed severe renal tubular dysfunction secondary to short-term therapy with Amikacin, resulting in refractory hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, and polyuria. This constellation of biochemical abnormalities mimic Type 5 Bartters syndrome, where there is activating mutation of the calcium sensing receptor in the thick ascending loop of Henle and the distal tubule. In this case this activation of the calcium sensing receptor was triggered by amikacin. This phenomenon has been described with gentamicin though never with amikacin. Recovery of the tubular dysfunction took 15 days following cessation of the offending drug, Amikacin.

Acute febrile illness caused by hantavirus: serological and molecular evidence from India

Study of hantavirus infections in India is in its early stages. As early symptoms of hantavirus disease can be non-specific and the diagnosis confirmed only by laboratory testing, use of appropriate diagnostic tools is important. To improve the diagnosis of hantavirus infections in India, commercial ELISA systems followed by indirect immunofluorescence assays were used to detect anti-hantavirus IgM and IgG in samples from patients with acute febrile illness. Of 347 patients tested, 5.2% showed serological evidence of hantavirus infection. Sequences obtained from patients showing molecular evidence of hantavirus infection were related to Hantaan virus. In the absence of mu-capture ELISA, we recommend the use of combination testing systems in areas non-endemic for hantavirus infections. In India there is an increased risk of rodent-borne infections and the differential diagnosis of undifferentiated febrile illness should include hantavirus infection.

A clinical study of renal tubular dysfunction in Cleistanthus collinus (Oduvanthalai) poisoning

Introduction. 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. Methods. 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. Results. 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. Conclusions. 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.

Cleistanthus collinus poisoning

Cleistanthus collinus, a toxic shrub, is used for deliberate self-harm in rural South India. MEDLINE (PUBMED) and Google were searched for published papers using the search/ MeSH terms “Cleistanthus collinus,” “Euphorbiaceae,” “Diphyllin,” “Cleistanthin A,” Cleistanthin B” and “Oduvanthalai.” Non-indexed journals and abstracts were searched by tracing citations in published papers. The toxic principles in the leaf include arylnaphthalene lignan lactones — Diphyllin and its glycoside derivatives Cleistanthin A and B. Toxin effect in animal models demonstrate neuromuscular blockade with muscle weakness, distal renal tubular acidosis (dRTA) and type 2 respiratory failure with conflicting evidence of cardiac involvement. Studies suggest a likely inhibition of thiol/thiol enzymes by the lignan-lactones, depletion of glutathione and ATPases in tissues. V-type H+ ATPase inhibition in the renal tubule has been demonstrated. Mortality occurs in up to 40% of C. collinus poisonings. Human toxicity results in renal tubular dysfunction, commonly dRTA, with resultant hypokalemia and normal anion gap metabolic acidosis. Aggressive management of these metabolic derangements is crucial. Acute respiratory distress syndrome (ARDS) is seen in severe cases. Cardiac rhythm abnormalities have been demonstrated in a number of clinical studies, though the role of temporary cardiac pacemakers in reducing mortality is uncertain. Consumption of decoctions of C. collinus leaves, hypokalemia, renal failure, severe metabolic acidosis, ARDS and cardiac arrhythmias occur in severe poisonings and predict mortality. Further study is essential to delineate mechanisms of organ injury and interventions, including antidotes, which will reduce mortality.

Central nervous system involvement in scrub typhus.

Scrub typhus is an emerging infectious disease in India. Among its protean clinical manifestations, central nervous system involvement is common. In this prospective observational study, altered sensorium, headache, seizures and aseptic meningitis were found to be common central nervous system manifestations. Prompt treatment with doxycycline reduces morbidity and mortality.