|Year : 2021 | Volume
| Issue : 4 | Page : 359-367
Scrub typhus associated acute kidney injury: An emerging health problem in Odisha, India
Madhusmita Bal1, Chitta Ranjan Kar2, Himanshu K Behera1, Purna Chandra Kar2, Subhojeet Biswas1, Sujata Dixit1, Hemant K Khuntia1, Sanghamitra Pati1, Manoranjan Ranjit1
1 ICMR-Regional Medical Research Center, Chandrasekharpur, Bhubaneswar-751023, Odisha, India
2 Department of Nephrology, SCB Medical College and Hospital, Cuttack, Odisha, India
|Date of Submission||26-Aug-2020|
|Date of Acceptance||09-Dec-2020|
|Date of Web Publication||25-Mar-2022|
Dr Manoranjan Ranjit
ICMR-Regional Medical Research Center, Chandrasekharpur, Bhubaneswar-751023, Odisha
Source of Support: None, Conflict of Interest: None
Background & objectives: Acute kidney injury associated with scrub typhus is an emerging health problem in the tropics including India. This study intended to find out the incidence, clinical outcome, cytokine response and genotypes of Orientia tsutsugamushi associated with AKI patients in Odisha, a state in eastern India. Methods: Acute febrile illness or history of acute fever with various degrees of kidney involvement admitted to SCB Medical College Hospital, Cuttack were included in the study. A detailed demographic characteristics and clinical features were recorded with pre-tested questionnaire at the time of admission. Scrub Typhus was detected by ‘IgM ELISA’ test (OD > 0.5) and PCR. Routine urine, haematological and biochemical tests were performed. Genotyping of the Orientia tsutsugamushi was done using 56-kDa gene for Orientia species and phylogenetic tree by neighbor-joining method. The plasma level of the IFN-γ (pro-inflammatory cytokine) and IL10 (anti-inflammatory) were measured by commercially available ELISA kit. The statistical analysis was performed using Graph Pad Prism software (version 4).
Results: Out of 140 acute febrile illness or history of acute febrile illness patients with AKI admitted to hospital, 32.14% were confirmed to be scrub typhus positive; eschar was seen in 17.8% of them. Of the total scrub typhus positive cases, 24.4% were having multi organ dysfunction. Majority of the AKI patients (60%) were in the “failure” category under RIFLE criteria. The mortality rate was 20.0%. Risk of dialysis requirement and mortality increases with RIFLE classification. “Karp” was the predominant circulating genotype. IFN-γ and IL10 level was high among the scrub typhus associated AKI patients.
Interpretation & conclusion: The study shows a high incidence of scrub typhus associated AKI and high case fatality rate. Hence, emphasis should be given on differential diagnosis. RIFLE classification is applicable with increment risk of dialysis requirement and death. An in-depth study is required to determine the role of O. tsutsugamuchi KARP strain and INF-γ/ IL-10 in disease severity so as to identify a prognostic marker.
Keywords: Scrub typhus; Acute Kidney Injury; Genotype; Cytokine response; Odisha; India
|How to cite this article:|
Bal M, Kar CR, Behera HK, Kar PC, Biswas S, Dixit S, Khuntia HK, Pati S, Ranjit M. Scrub typhus associated acute kidney injury: An emerging health problem in Odisha, India. J Vector Borne Dis 2021;58:359-67
|How to cite this URL:|
Bal M, Kar CR, Behera HK, Kar PC, Biswas S, Dixit S, Khuntia HK, Pati S, Ranjit M. Scrub typhus associated acute kidney injury: An emerging health problem in Odisha, India. J Vector Borne Dis [serial online] 2021 [cited 2022 May 21];58:359-67. Available from: https://www.jvbd.org/text.asp?2021/58/4/359/318318
| Introduction|| |
Scrub typhus caused by Orientia tsutsugamushi, has recently been identified as a re-emerging health problem causing up to 30% deaths in untreated cases in Asia-Pacific region, thus WHO is emphasizing the need for sur- veillance. In the Indian sub-continent during the recent past, several epidemics of scrub typhus have been reported from northern, eastern and southern regions causing a serious public health concern,. Clinically, scrub typhus varies from a self-limiting acute febrile illness to severe course. Based on the involvement of the organ patient could develop pneumonitis, meningoencephalitis, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), myocarditis, septic shock and multiple organ failures.
Acute kidney injury is a common disorder that is strongly linked to short- and long-term morbidity and mortality. More timely diagnosis is essential for early intervention to improve patient outcomes. Scrub typhus associated acute kidney injury previously considered to be rare has now been reported in different endemic countries. In India, which witnessed rising cases of acute kidney injury mostly associated with multiple organ dysfunction (MOD) during the last few years reported 21% to 43% of scrub typhus in acute kidney injury (AKI) cases in southern and northern part of the country,,. But no data is available on scrub typhus associated AKI from Odisha, an eastern Indian state known to be endemic for P. falciparum malaria. Also, frequent outbreaks of dengue and lepotospira have been reported which are the other most common causes of community acquired acute kidney injury in tropical countries. Hence, we have made an attempt in the present study to explore the incidence and genotypes of O. tsutsugamushi associated with acute kidney injury. We aim to summarise the clinical outcomes and describe the immune response of scrub typhus associated AKI patients in this geographical part of the country. This is crucial for promotion of awareness and generation of adequate resources for timely diagnosis and management of the disease.
| Material & Methods|| |
Study settings and patients
This prospective study was carried out on patients admitted to the Department of Nephrology, SCB Medical College and Hospital, Cuttack, one of the largest tertiary care referral hospitals of Odisha state. All AKI patients reporting to the outpatient department or admitted to Nephrology Department from August 2018 to August 2019, with acute fever and varying degrees of kidney involvement or history of acute fever during/after onset of kidney problem were included in the study. After detailed clinical examinations, patients were diagnosed for O. tsutsugamushi using IgM ELISA (InBios International, USA) as per the manufacturer’s instructions. Test was considered positive when the optical density (OD) found to be >0.5. Confirmation of diagnosis was checked by PCR analysis. All patients were also tested for malaria by RDT (Standard Q Malaria Pf /PAN Ag Test, SD Biosensor), dengue (NS1 antigen/IgM antibody) and leptospira (IgM antibody).
At the time of admission, the demographic and treatment details were recorded. A detailed physical examination was done in all patients to specifically look for eschar, rash, hepatomegaly, splenomegaly and lymphadenopathy. Further routine haematological investigations using automatic hematological analyzer (MS Laboratories Ltd, France) and biochemical profiles by semi-automatic chemistry analyser (TransAsia Bio-Medicals Ltd) were performed upon admission and during follow-up. Urine was tested using dipstick for albumin and sugar, and microscopic examination of freshly voided urine specimen was performed in all patients. Hourly urine output and serum creatinine was monitored after every 24 hours during entire period of hospital stay.
A confirmed case of scrub typhus was defined as the one with positive for O. tsutsugamushi with IgM ELISA. Shock was defined as systolic blood pressure <90 mm Hg; oliguriaas urine output of less than 400 milliliters (mL) per day in adult; anuria as urine output of less than 100 milliliters (mL) per day in adult; impaired consciousness defined as decreased or impaired response to external stimuli, hepatic dysfunction as elevated serum aspartate aminotransferase (40 U/L); elevated serum alanine aminotransferase (40 U/L) and elevated serum alkaline phosphatase (130 U/L), gastrointestinal dysfunction includes constipation and irritable bowel syndrome (IBS) , diarrhea (loose, watery stools three or more times a day), anemia as hemoglobin <9 g/dL; leukocytosis as total leukocyte count. 11000 cells/mL; leukopenia as total leukocyte count, 4000 cells/mL; thrombocytopenia as platelet count, 100000 cells/mL; hypoalbuminemia as serum albumin, 3.5 g/dL; hyperbilirubinemia as serum total bilirubin,1.2 mg/dL.
AKI was defined and classified based on the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Complications were noted and appropriate treatment was provided by the hospital to all patients.
Genomic DNA was extracted from eschar/blood samples using QIAamp DNA Mini Kit (QIAGEN, USA) following the manufacturer’s instructions and used as template for PCR assay. PCR amplification targeting a ~ 410 bp region of 56Kd protein of O. tsutsugamushi was carried out in the thermal cycler (G-Storm, UK) using the genus specific primer and temperature profile as described Varghese et al.2013. PCR amplification was carried out in 25μl of final reaction volume containing 1X reaction buffer (Fermentas, USA), 0.2 mM dNTPs (Fermentas, USA), 0.40 μM of each primers and 1.25U Taq polymerase (Fermentas, USA). DNA from known isolates of O. tsutsugamushi was used as positive control and reaction mixture with 5μl of distilled water was used as a negative control. Amplified PCR products were electrophoresed on ethidium bromide containing 1.5% agarose gel and visualized under a Gel documentation system (Syngene, USA).
Sequence homology analysis and construction of phylogenetic tree
Amplified DNA bands (~410bp in length) were cut out from the agarose gel and purified using QIA quick Gel Extraction Kit (QIAGEN, USA) as per the manufacturer’s instructions. Sequencing of the purified DNA was done commercially (Eurofins, India) and nucleotide sequences thus obtained were edited using FinchTV (Geospiza Inc.). Homology of nucleotide sequences of O. tsutsugamushi (n=11) were searched using NCBI BLAST platform (NCBI, USA). The NCBI Gene Bank accession numbers of the sequences were MH182744 to MH182754. Phylogenetic analysis was performed using O. tsutsugamushi (Karp, Kato, Gilliam and Kawasaki) reference sequences available in NCBI databank (http://www.ncbi.nlm.nih. gov/ pubmed) by CLUSTAL W alignment programme within MEGA6 programme and phylogenetic tree was reconstructed with the neighbor-joining method with 1000 bootstrap replicates using Kimura two-parameter distance algorithm. The distances were calculated using the maximum composite likelihood method.
IFN-γ and IL-10 cytokine assay
IFN-γ and IL-10 levels in plasma were detected by using commercially available ELISA kits (E-Bioscience San Diego, CA, USA.) and expressed in pg/mL as per the manufacturers’ instruction. Briefly, 100 μl of plasma and standards were added to each well of the antibody coated ELISA plate followed by incubation for 2 hours with 50 μl Biotin conjugate at room temperature (18 to 25°C). Then plates were washed with PBST (PBS with 1% Tween 20) for 3 times and incubated with 100 μl of Streptavidin- HRP for 1 hour at room temperature. Thereafter, plates were washed for 3 times and incubated with 100μl of TMB substrate for 10 min at room temperature. Finally, the optical density (OD) was read at 450 nm using an ELISA plate reader after addition of 100 μl of stop solution to each well.
Graph Pad Prism software (version 4) was used for statistical analysis of data. Categorical variables are presented as percentage and continuous data are expressed as means ±SD, and the means of the two study groups were compared using an unpaired t test. Mann-Whitney test was used to analyze the difference between two groups of unpaired data. P-values <0.05 were considered statistically significant.
The Institutional Ethics committee of ICMR-Regional Medical Research Center, Bhubaneswar, India has approved this study. Informed consent from all participants in vernacular language has been obtained before enrollment in the study.
| Results|| |
From August 2018 to August 2019, a total number of 140 acute kidney injury (AKI) patients with acute febrile illness or histories of acute febrile illness were admitted to the Department of Nephrology. Out of them 45 (32.14%) cases were confirmed to be scrub typhus positive and 4 of them were co-infected with malaria. While the non-scrub typhus AKI patients (n=95, 67.9%) were found to be infected with either malaria (n=12, 8.6%), dengue (n=6, 4.3%), leptospira (n= 12, ,8.6%), malaria + dengue (n=6,4.3%), malaria+leptospira (n=8, 5,6%), urinary tract infection (n=14,10.0%), lower respiratory tract infection including pneumonia (n=9, 6.4%), skin and soft tissue infection (n= 4, 2.9%) or with infection of unknown origin (n= 20, 14.3%). The median age of the scrub typhus associated-AKI (SAKI) patients was 47 years (interquartile range: 34.5-60 years), while other infection related -AKI (OAKI) patients was 45.0 years (interquartile range: 35-55 years). Male preponderance of cases has been observed in both SAKI (66.7 %) and OAKI (62. 1%). The socio-demographic data of SAKI reflects that prevalence of disease is high amongst the people living in rural areas (84.4%), with low level of education (55.5%) and with low income (77.7%). When occupation was considered farmers and laborers constituted around 68.9% (n=31) of the cases.
Eschar, a typical pathognomonic sign of scrub typhus was seen in 17.8% of SAKI. Fever (86.7%) / history of acute fever (13.3%), nausea/ vomiting (75.5%), pedal oedema (55.5%), breathlessness (53.3%), jaundice (51.1%), anaemia (51.1%), hepatomegaly (42.2%), splenomegaly (40.0%), lymphadenopathy (35.5%), dry cough (24.4%), impaired consciousness (22.2%), maculopapular rash (13.3%) and seizures (11.1%) were the predominant clinical features. Multi organ dysfunction (MOD) was seen in 24.4% (n=11) of cases. Out of the 45 patients 15.5% presented with anuria, while 51.1% with oliguria. The complication such as shock was seen in one (2.2%) and ARDS in eight (17.8%) patients associated with scrub typhus, while in 2 (2.1%) patients associated with other infections. Prevalence of most of the clinical signs and symptoms were similar in both group of patients, but maculopapular rash (13.3% vs 3.1%, P= 0.0215, 95% CI= 1.13% to 23.20%), jaundice (51.1% vs 27.3%, P = 0.0060, 95% CI= 6.68% to 39.84%), lymphadenopathy (35.5% vs 6.6%, P=0.0079, 95% CI= 14.79% to 43.92%), hepatomegaly (42.2% vs 29.4%, P = 0.1354, 95% CI= 3.69% to 29.44%) and splenomegaly (40.0% vs 21.05%, P = 0.0224, 95% CI=2.55% to 34.67%) were significantly more prevalent among SAKI group than OAKI group of patient [Table 1].
|Table 1: Clinical characteristics of the AKI patients with Scrub Typhus (SAKI) and Other infections (OAKI).|
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When classified on the basis of RIFLE criteria majority of the patients were found to be under “F” category (60%, n= 27) followed by “I” (13.3%, n=6), “R” (11.1%, n=5) and “E” (4.4%, n=4). None of the patients was under the “L” category. When compared between two groups (SAKI vs OAKI) no statistical difference (P>0.05) was observed in frequency of distribution of patients in different category of RIFLE criteria [Figure 1].
|Figure 1: Frequency of AKI patients with Scrub Typhus (SAKI) and other infections (OAKI) in different category of RIFLE criteria.|
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The average haemoglobin level (g/dl) of the patients was 9.80 ±2.83, while blood urea nitrogen (BUN)(mg/ dl) was 111.8 ±38.45 and serum creatinine (mg/dl) was 6.50 ±2.94. Almost 80% of the patients had increased level of liver enzymes (AST: > 40 IU/L, ALT: > 40 IU/L and ALP: 130 IU/L). Around 60.0% (n=27) of them had thrombocytopenia and one third (n=9, 20 %) of these patients had a platelet count <100 000 per μ1. While 20.0% (n=9) had leucocytosis. The total leukocyte count (cells/ mm3)/platelet counts (lakh cells/mm3) was significantly low (P=0.0414/ P=0.0094) in SAKI (9114.29 ±2236.02 / 1.08 ± 6.2) compared to OAKI (10112.94 ± 2864.67 / 2.85 ± 3.4) patients. While no statistical significant difference was observed in Hb, blood urea nitrogen, serum creatinine and liver enzyme (AST, ALT and ALP) levels between SAKI and OAKI group of patients [Table 2].
|Table 2: Haematological and biochemical results of the AKI patients with scrub typhus (SAKI) and other infections (OAKI)|
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All the scrub typhus cases were treated with doxycycline (2.2 mg/kg/dose intravenous, maximum 200 mg/ day for 7–10 days. Around 80.0% (n=36) of the cases recovered and 20.0% (n=9) died in the SAKI group because of late reporting/diagnosis in spite of best treatment support, while five patients (5.3%) died and 90 (94.7%) patients recovered who were diagnosed with other infections (OAKI). The average days of fever clearance was 2.30 ±0.84 (range 1–4 days), while mean days of hospital stay of the recovered patient was 8.52 ±6.07 (range 3–15 days). The average number of dialysis sessions attended by the recovered patient was 2.79 ±3.39 (range 1-7). The frequency of dialysis session was low in “failure” (range: 1–7) compared to “end” (range: 3–10) stage patients and no dialysis was instituted in “risk” and “injury” stage. No statistical difference was seen between average days of fever clearance, average number of dialysis sessions and mean days of hospital stay of scrub associated AKI patients and AKI patients associated with other infections [Table 3].
|Table 3: Treatment response pattern of AKI patients with scrub typhus (SAKI) and other infections (OAKI)|
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Molecular typing of O. tsutsugamushi
Molecular analysis of 11 samples from the eschar (n=8) and buffy coat (n=3) using targets specific protein (56kDa gene for Orientia species) could be amplified. Phylogenetic tree reconstructions placed all 11 O. tsutsugamushi sp. in genotype “Karp” [Figure 2] and sequence homology shared more than 94% similarity to the previously identified strains O. tsutsugamushi of Vietnam, Laos and India [Table 4].
|Figure 2: Phylogenetic tree generated using the neighbour-joining method based on the 56-kD gene for Orientia species. Numbers at nodes represent bootstrap percentages based on 1000 samplings. The scale bars represent 0.02 substitutions per site.|
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|Table 4: NCBI Accession Number, sequence homology and origin of O. tsutsugamushi isolates of Odisha|
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A variety of cytokines of inflammatory (IFN-γ) and anti-inflammatory cytokines (IL-10) can regulate the pathogenesis of AKI. Here we have measured the plasma levels of IFN-γ and IL-10 cytokines in 45SAKI and 45. IFN-γ was significantly higher (P<0.0001) in SAKI in comparison to OAKI patient. The level of IL-10 also significantly higher in SAKI but the level of significance is less as compared to IFN-γ as shown in [Figure 3].
|Figure 3: Plasma levels of IFN-γ (A) and IL-10 (B) in AKI patients with and without scrub typhus. Significantly elevated levels of IFN-γ and IL-10 were observed in AKI patients infected with scrub typhus compared to scrub typhus negative AKI. The number of subjects in each group was represented by a single dot. Bars represent mean value. SAKI: AKI patients positive for Scrub typhus (n=45), OAKI: AKI patients negative for scrub typhus but had other infection (n=45).|
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| Discussion|| |
Scrub typhus, an emerging infection in Asia-Pacific including India have been demonstrated to be one of the important differentials to be considered in patients presenting with fever and AKI,. In this prospective study from a tertiary care hospital in eastern India, we have observed that 32.4 % of acute febrile illness patients with AKI are due to scrub typhus and the mortality rate is around 20.0%. The study also shown that O. tsutsugamushi Karp is the predominant circulating genotype and increased level of IFN-γ and IL10 associated of with the clinical manifestation of acute kidney injury in scrub typhus.
The causes of AKI in tropical countries can be due to infections, animal and plant toxins, drugs/poisons, or obstetric complications. Scrub typhus is recently being emerged as one of the causes of mild simple urinary abnormalities to AKI that ultimately leads to complications. Though scrub typhus has been reported from different parts of India, clinicians usually do not consider it as differential diagnosis. In part, the reason might be inability to make an accurate diagnosis on clinical grounds because of similarity of the clinical presentations of the various forms of infection-associated AKI and second non-availability of an accurate diagnostic test. Out of all available supporting test, a single point IgM ELISA has been found to be used by most of the studies as confirmatory diagnosis. A major limiting factor in this test is the use of cutoff in absence of the local sero prevalence data. Since, sero prevalence data in Indian population is not available, we have considered test to be positive when the optical density (OD) found to be >0.5 as defined by the manufacturer. The high proportion (45 out of 140) cases with scrub-typhus among the AKI patients with/history of acute fever in the present study indicates that scrub typhus is grossly under-diagnosed and under-reported from Odisha. Similar to our finding the incidence of AKI associated with scrub typhus has been reported to be 19-42% from South India, , 24-34% from North India, , 35.8% in Nepal and 35.9% in South Korea. But the incidence was comparatively low in Meghalaya (5.51%) and Taiwan (6.6-8.3 %). Seasonal occurrence of scrub typhus is seen and varies with the climate in different countries. Usually, the epidemic period is influenced by the activities of the infected mite. In the same season, farmers are involved in harvesting activity in the fields, where there is every possibility of exposure to the bites of larval mites. This might be the reason of high incidence of scrub typhus infection among the farmers and laborers living in the rural areas in the present study.
Our study reveals that compared to other infection (malaria, dengue, leptospira, urinary tract infection and lower respiratory tract infection including pneumonia) related AKI group, significantly large portions of scrub typhus AKI patients were presenting with high grade fever, nausea/vomiting, eschar, maculopapular rash, jaundice, lymphadenopathy, hepatomegaly, splenomegaly suggesting usefulness of these markers as differential diagnosis. Similar to our observation, thrombocytopenia appears to be a consistent para clinical feature,, and hence can be used as a predictor of acute renal damage in patients with scrub typhus. Whether earlier diagnosis and treatment in patients with the above risk factors reduce the incidence and severity of AKI deserves to be investigated.
The clinical outcome of AKI according to the RIFLE classification associated with scrub typhus has not been well documented but several authors have described that it is a valid indicator of AKI in acute febrile diseases, including scrub typhus, and can predict renal replacement therapy and the risk ofmortality,. The incidence of AKI associated with scrub typhus was low (34.5%) compared the report from South India (51.2%) but almost equal to South Korea (35.9%). But the severity of AKI was greater in our population compared to South India/South Korea: ‘risk’ (11.1% vs 20.2% / 25.9%), ‘injury’ (13.3% vs 11.2% / 7.3%), ‘failure’ (60% vs 11.2% / 2.7%) and ‘end’ (4.4% vs 0.0/0.0). Around 46.7% (21 out of 45) of the patients underwent dialysis and average number of dialysis session undertaken was 2.79 ±3.39 for recovery of the patients. The mortality rate was significantly high (20.0%) compared to South India (13.3%) and South Korea (14.8%). In our study the risk of mortality and number of dialysis requirement was found to be correlated with the severity according to RIFLE classification. The average days of hospital stay of the SAKI patients was 8.52 ±6.07.
More than 20 prototype strains of Orientia tsutsugamushi have been identified from different parts of the tsutsugamushi triangle by sequencing the 56 kDa gene. In India studies conducted mostly in the north, south and extreme north-east part, have however documented Karp-like and Gilliam-like strains to be the predominant types,,. In this study we have detected Karp-like strains as the most prevalent type associated with associated AKI in the eastern part of India not reported earlier, even though our study has limitations being undertaken in a tertiary care hospital where generally referral patients get treatment. Karp-like strains also reported predominantly in northeastern part of India. This indicates that distribution of O. tsutsugamushi varies from region to region.
Endothelial cells are one of the primary cellular targets of O. tsutsugamushi during systemic infection and its activation can be triggered directly via pathogen replication or indirectly via inflammatory cytokines. In combination with endothelial adhesiveness, inflammatory mediators act in concert to promote inflammation in a positive feedback loop promoting kidney injury. The pro-inflammatory cytokine IFN-γ is a potent macrophage activator that plays a central role in host defense against intracellular pathogens has been demonstrated to be closely associated with the development of immunity against O. tsutsugamushi. We have measured the inflammatory and anti-inflammatory cytokine in both groups of AKI patients and observed significantly high level of IFNγ and IL-10 in AKI patients with scrub typhus emphasizing its key role in the pathogenesis. But some other studies have shown IFN-γ as read-out cytokine in scrub typhus patients as well as experimental animals (during the acute phase) indicates it’s protective against O. tsutsugamuchi infection. Significantly increased serum levels of IFN-γ in the SAKI patients was consistent with a Th1 immune pattern as shown in mice infected with O. tsutsugamushi and in patients with acute phase of scrub typhus. Besides pro-inflammatory cytokine, the increased level of antiinflammatory cytokine (IL-10) in SAKI patients emphasizes an additional counterbalancing mechanism to ensure homeostasis within the host. The antagonistic effect of IL-10 against pro-inflammatory cytokine production that potentially prevents further pathological tissue alterations is well documented. This could be institution of treatment because of severe manifestation of the disease. However, more studies are needed to shed light on delineating the mechanism how these molecules contribute to the disease progression will help in developing an effective management strategy.
| Conclusion|| |
Scrub typhus has emerged as an important cause of acute kidney injury in eastern India and emphasis should be given on differential diagnosis in patients with acute febrile illness and AKI. The case fatality rate is more in scrub typhus compared to other community acquired AKI. RIFLE classification is applicable with increment risk of dialysis requirement and death. Thrombocytopenia may be considered as predictors of acute renal damage in patients with scrub typhus. An in-depth study is required to determine the virulence factor of O. tsutsugamuchi KARP strain and role of INF-γ and IL-10 in disease severity so as to identify a prognostic marker.
Conflict of interest: None
| Acknowledgements|| |
We are grateful to all the patients for their sincere cooperation throughout this study. We express our gratitude to the staff of Department of Nephrology, SCB medical College & Hospital, Cuttack, Odisha for their support during the study. We thankfully acknowledge the technical assistants rendered by Mr Minaketan Barik, Mr KC Parichha of the institute during the study.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]