Ooriapadickal Cherian Abraham

Outbreak of Scrub Typhus in Southern India during the Cooler Months

Abstract: Orientia tsutsugamushi, the agent of scrub typhus, is a strict intracellular bacterium which is found in many parts of Asia including India. During the past few years, the number of patients with rickettsial infection and scrub typhus has increased, especially during the cooler months. We report in this study a recent outbreak of scrub typhus recorded during the cooler months (October 2001 to February 2002) in patients admitted to our hospital with acute febrile illness associated with diverse signs and symptoms. Overall, 28 patients were clinically and serologically confirmed to have scrub typhus. Fever for more than one week was the only common manifestation. Myalgias was the next most common feature (52%), and rash was observed in only 22% of the cases. Seventeen patients treated with doxycycline recovered in 1 to 3 days, as well as two patients who received chloramphenicol. In five patients who received ciprofloxacin, fever subsided only after five days. Finally three patients (10.7%) died, including one patient treated with doxycycline. These data indicate that scrub typhus is a reemerging infectious disease in India with a possibility of drug resistance. This reemergence emphasizes the need for further prospective studies to design effective control measures.

Multilocus Genotyping of Cryptosporidium sp. Isolates from Human Immunodeficiency Virus-Infected Individuals in South India

ABSTRACT This study characterized cryptosporidial infections in 48 human immunodeficiency virus-infected individuals in India by multilocus genotyping. Cryptosporidium hominis, C. parvum, C. felis, C. muris, and C. meleagridis were identified. Cpgp40/15 PCR-restriction fragment length polymorphism identified six subgenotypes. Cryptosporidial diarrhea was associated with decreased CD4 counts, below 200 (P = 0.009), but not high viral loads.

Clinical profile and improving mortality trend of scrub typhus in South India

BACKGROUND Scrub typhus, a bacterial zoonosis caused by Orientia tsutsugamushi, may cause multiorgan dysfunction syndrome (MODS) and is associated with significant mortality. This study was undertaken to document the clinical and laboratory manifestations and complications and to study time trends and factors associated with mortality in patients with scrub typhus infection. METHODS This retrospective study, done at a university teaching hospital, included 623 patients admitted between 2005 and 2010 with scrub typhus. The diagnosis was established by a positive IgM ELISA and/or pathognomonic eschar with PCR confirmation where feasible. The clinical and laboratory profile, course in hospital, and outcome were documented. Factors associated with mortality were analyzed using multivariate logistic regression analysis. RESULTS The most common presenting symptoms were fever (100%), nausea/vomiting (54%), shortness of breath (49%), headache (46%), cough (38%), and altered sensorium (26%). An eschar was present in 43.5% of patients. Common laboratory findings included elevated transaminases (87%), thrombocytopenia (79%), and leukocytosis (46%). MODS was seen in 34% of patients. The overall case-fatality rate was 9.0%. Features of acute lung injury were observed in 33.7%, and 29.5% required ventilatory support. On multivariate analysis, shock requiring vasoactive agents (relative risk (RR) 10.5, 95% confidence interval (CI) 4.2-25.7, p<0.001), central nervous system (CNS) dysfunction (RR 5.1, 95% CI 2.4-10.7, p<0.001), and renal failure (RR 3.6, 95% CI 1.7-7.5, p=0.001) were independent predictors of mortality. Over 4 years, a decreasing trend was observed in the mortality rate. CONCLUSIONS Scrub typhus can manifest with potentially life-threatening complications such as lung injury, shock, and meningoencephalitis. MODS occurred in a third of our patients. The overall case-fatality rate was 9%, with shock, renal failure, and CNS associated with a higher mortality.

Scrub typhus in South India: clinical and laboratory manifestations, genetic variability, and outcome

OBJECTIVES This study sought to document the clinical and laboratory manifestations, genetic variability, and outcomes of scrub typhus, an often severe infection caused by Orientia tsutsugamushi, in South India. METHODS Patients admitted to a large teaching hospital with IgM ELISA-confirmed scrub typhus were evaluated. Clinical examination with a thorough search for an eschar, laboratory testing, chest X-ray, and outcome were documented and analyzed. Additionally, a 410-bp region of the 56-kDa type-specific antigen gene of O. tsutsugamushi was sequenced and compared with isolates from other regions of Asia. RESULTS Most of the 154 patients evaluated presented with fever and non-specific symptoms. An eschar was found in 86 (55%) patients. Mild hepatic involvement was seen in most, with other organ involvement including respiratory, cardiovascular, and renal. Multi-organ dysfunction was noted in 59 (38.3%), and the fatality rate was 7.8%. Hypotension requiring vasoactive agents was found to be an independent predictor of mortality (p<0.001). The phylogeny of 26 samples showed 17 (65%) clustering with the Kato-like group and eight (31%) with the Karp-like group. CONCLUSIONS The presentation of scrub typhus can be variable, often non-specific, but with potentially severe multi-organ dysfunction. Prompt recognition is key to specific treatment and good outcomes. Further study of the circulating strains is essential for the development of a successful vaccine and sensitive point-of-care testing.

HyPOVITAmINOsIs D AND BONE mINERAl DENsITy IN HumAN ImmuNODEfICIENCy VIRus-INfECTED mEN fROm INDIA, WITH OR WITHOuT ANTIRETROVIRAl THERAPy

OBJECTIVE To study the vitamin D status and bone mineral density (BMD) in men infected with human immunodeficiency virus (HIV) in a tertiary care center from southern India. METHODS We conducted a cross-sectional study of 35 HIV-infected men (between 20 and 50 years old) receiving highly active antiretroviral therapy (HAART) (group 1) in comparison with 35 age- and body mass index-matched HIV-positive antiretroviral therapy-naïve men (group 2) and 35 HIV-negative healthy control subjects (group 3). RESULTS A significantly greater proportion (P = .002) of patients (74%) in the HAART group had vitamin D deficiency (<20 ng/mL) in comparison with the other 2 groups (37% in each group). The mean intact parathyroid hormone level was higher (P<.001) and the mean duration of exposure to sunlight was lower (P = .001) in the HAART group than in the other 2 groups. By logistic regression analysis, HAART was found to be significantly associated with vitamin D deficiency. The BMD in the femoral neck was significantly lower in men with HIV infection who were receiving HAART in comparison with the other 2 groups (P = .006). On multivariate logistic regression, older age, low body mass index, and high parathyroid hormone levels emerged as factors significantly associated with decreased BMD at the femoral neck. CONCLUSION A significant proportion of patients receiving HAART had vitamin D deficiency. The secondary hyperparathyroidism probably due to vitamin D deficiency is an important contributing factor for the observed changes in BMD. Vitamin D deficiency noted in this group is probably multifactorial, and further research is needed to determine whether the effect of HAART on vitamin D metabolism is an additional causative factor and what benefit vitamin D supplementation might confer in these patients.

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.

Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission

Background and Aims: Scrub typhus, a zoonotic rickettsial infection, is an important reason for intensive care unit (ICU) admission in the Indian subcontinent. We describe the clinical profile, organ dysfunction, and predictors of mortality of severe scrub typhus infection. Materials and Methods: Retrospective study of patients admitted with scrub typhus infection to a tertiary care university affiliated teaching hospital in India during a 21-month period. Results: The cohort (n = 116) aged 40.0 ± 15.2 years (mean ± SD), presented 8.5 ± 4.4 days after symptom onset. Common symptoms included fever (100%), breathlessness (68.5%), and altered mental status (25.5%). Forty-seven (41.6%) patients had an eschar. Admission APACHE-II score was 19.6 ± 8.2. Ninety-one (85.2%) patients had dysfunction of 3 or more organ systems. Respiratory (96.6%) and hematological (86.2%) dysfunction were frequent. Mechanical ventilation was required in 102 (87.9%) patients, of whom 14 (12.1%) were solely managed with non-invasive ventilation. Thirteen patients (11.2%) required dialysis. Duration of hospital stay was 10.7 ± 9.7 days. Actual hospital mortality (24.1%) was less than predicted APACHE-II mortality (36%; 95% Confidence interval 32-41). APACHE-II score and duration of fever were independently associated with mortality on logistic regression analysis. Conclusions: In this cohort of severe scrub typhus infection with multi-organ dysfunction, survival was good despite high severity of illness scores. APACHE-II score and duration of fever independently predicted mortality.

Single-nucleotide polymorphisms in Toll-like receptor (TLR)-2, TLR4 and heat shock protein 70 genes and susceptibility to scrub typhus

Scrub typhus is a highly prevalent bacterial infection in India and South Asia that is caused by Orientia tsutsugamushi. The innate immune response to infections is modulated by Toll-like receptors (TLRs) and heat shock proteins (HSPs). This study was done to assess the prevalence and possible association of TLR and HSP polymorphisms in scrub typhus. TLR4 Asp299Gly, TLR4 Thr399Ile, TLR2 Arg753Gln and HSP70-2 A1267G are single-nucleotide polymorphisms (SNPs) that may modulate their activities, and these SNPs were assessed in 137 scrub typhus patients and 134 controls by PCR restriction fragment length polymorphism. We found that the two TLR4 mutations, TLR4 D299G and TLR4T399I, were present in 19.5% and 22% of the study population, respectively, and was in significant linkage disequilibrium with a D’ of 0.8. The TLR2 mutation was found to be rare, whereas the HSP A>G mutation was very common (77.5%). Compared with the controls, the prevalence of heterozygous genotype of the TLR4D299G SNP, but not any of the other SNPs, was significantly higher among scrub typhus patients. Further studies using a larger sample size and more candidate genes may better enable in determining the role of these associations in susceptibility and severity of scrub typhus.

Kikuchi-Fujimoto disease: Clinical and laboratory characteristics and outcome

Introduction: Kikuchi-Fujimoto disease is an uncommon disorder with worldwide distribution, characterized by fever and benign enlargement of the lymph nodes, primarily affecting young adults. Awareness about this disorder may help prevent misdiagnosis and inappropriate investigations and treatment. The objective of the study was to evaluate the clinical and laboratory characteristics of histopathologically confirmed cases of Kikuchis disease from a tertiary care center in southern India. Materials and Methods: Retrospective analysis of all adult patients with histopathologically confirmed Kikuchis disease from January 2007 to December 2011 in a 2700-bed teaching hospital in South India was done. The clinical and laboratory characteristics and outcome were analyzed. Results: There were 22 histopathologically confirmed cases of Kikuchis disease over the 5-year period of this study. The mean age of the subjects’ was 29.7 years (SD 8.11) and majority were women (Male: female- 1:3.4). Apart from enlarged cervical lymph nodes, prolonged fever was the most common presenting complaint (77.3%). The major laboratory features included anemia (54.5%), increased erythrocyte sedimentation rate (31.8%), elevated alanine aminotransferase (27.2%) and elevated lactate dehydrogenase (LDH) (31.8%). Conclusion: Even though rare, Kikuchis disease should be considered in the differential diagnosis of young individuals, especially women, presenting with lymphadenopathy and prolonged fever. Establishing the diagnosis histopathologically is essential to avoid inappropriate investigations and therapy.

The Twin Epidemics of Tuberculosis and HIV.

The deadly combination of tuberculosis (TB) and human immunodeficiency virus (HIV) currently ravaging the world, taking a toll of about 0.35 million people every year, is one of the major public health crises of the decade. Throughout the course of HIV infection, the risk of acquisition, reactivation, and reinfection of TB keeps increasing substantially as the immune deficiency progresses. TB coinfected patients inadvertently facilitate HIV infection by release of the proinflammatory cytokines and overexpression of coreceptors CXCR4 and CCR5; thereby, the progression of each is facilitated. The difficulties in diagnosing active tuberculosis in HIV-infected individuals poses a great challenge that is further complicated by the challenges in identification of latent TB infection, creating a setback to preventive therapy. Furthermore, prescribing antituberculous therapy and antiretroviral therapy together poses several management challenges, including drug interactions, added toxicities, and TB immune reconstitution inflammatory syndrome. The current approach to diagnosis, prevention, and treatment strategies in TB and HIV coinfected individuals, along with epidemiology and overview of pathogenetic interplay of both microbes, is reviewed here.