Introduction
Scrub typhus is a resurging zoonotic infection prevalent in South Asia with many recent outbreaks in India. It can mimic other tropical infections and the disease spectrum ranges from subclinical illness to life-threatening disease with multiorgan dysfunction. This study was conducted to study the pattern of hepatic and renal injury.
Methods
A retrospective study was done on 176 patients diagnosed by detecting IgM antibodies using an enzyme-linked immunosorbent assay (ELISA) over a period of three years at a tertiary center in Chandigarh, India. They were treated with doxycycline (azithromycin if pregnant) and supportive therapies. The patterns of hepatic and renal functions, along with the need of renal replacement therapy, were recorded and evaluated. The values were expressed as mean ± SD, and p values were calculated to establish statistical significance.
Results
Most of the cases were from the state of Haryana (37.5%), followed by Punjab (33.5%), Himachal Pradesh (13.6%), Uttar Pradesh (10.2%) and Chandigarh (5%). 30% of the study population was engaged in agriculture. The mean age was 32.3 ± 13.5 years with range of 13-65 years. A peak in the incidence was observed during monsoon months. Approximately 13% of the patients died. Urea, creatinine, bilirubin and aspartate transaminase were found to be higher in mortality group with statistical significance (p < 0.05). Alanine transaminase was higher and albumin was lower in the mortality group but without statistical significance. 27.8% had acute kidney injury, 90.9% had liver dysfunction and one patient had acute liver failure. All the pregnant patients had fetal loss.
Conclusion
Renal and liver dysfunctions are common in scrub typhus, and their occurrence adversely affects the outcome.
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Scrub typhus is a tropical infection caused by the rickettsial bacterium
A retrospective study was carried out at a tertiary care hospital in Chandigarh, India, which included 176 patients above the age of 13 years admitted over three years (2016-2018). The diagnosis was confirmed by testing for IgM antibodies against
Out of 280 total cases of scrub typhus, 176 were included in the study after appropriate exclusions. Majority of them were residents of Haryana, followed by Punjab, Himachal Pradesh, Uttar Pradesh and Chandigarh (Figure
Black scab may be seen at the site of bite of the vector. Thorough physical examination should be carried out after stripping the patient.
Urea, creatinine, bilirubin and aspartate transaminase (AST) were found to be higher in the mortality group with statistical significance (p < 0.05). Alanine transaminase (ALT) was higher and albumin was lower in the mortality group but without statistical significance (Table
ALT, alanine transaminase; AST, aspartate transaminase.
Overall (n = 176) | Survivors (n = 153) | Deceased (n = 23) | P value | |
Bilirubin (mg/dl) | 2.61 ± 2.49 | 2.43 ± 2.32 | 3.84 ± 3.24 | 0.0108 |
AST (IU/dl) | 190.69 ± 208.78 | 177.35 ± 207.13 | 279.48 ± 202.04 | 0.0283 |
ALT (IU/dl) | 185.59 ± 240.21 | 175.17 ± 240.10 | 254.91 ± 234.31 | 0.1381 |
Albumin (gm/dl) | 3.36 ± 2.70 | 3.47 ± 2.87 | 2.63 ± 0.46 | 0.1652 |
Urea (mg/dl) | 56.81 ± 30.07 | 53.30 ± 27.90 | 80.13 ± 34.11 | 0.0001 |
Creatinine (mg/dl) | 1.51 ± 0.98 | 1.43 ± 0.93 | 2.01 ± 1.18 | 0.0082 |
The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to stage acute kidney injury (AKI) [
Overall (n = 176) | Survivors (n = 153) | Deceased (n = 23) | |
Stage I | 23 (13%) | 16 (10.4%) | 7 (30.4%) |
Stage II | 20 (11.3%) | 17 (11.1%) | 3 (13%) |
Stage III | 6 (3.4%) | 3 (1.9%) | 3 (13%) |
AST (normal value < 40 IU/ml) elevation was detected in 88.6% (156/176) of the cases and ALT (normal value < 40 IU/ml) elevation in 90.3% (159/176). Clinically detectable hepatomegaly was present in 22% (39/176). All the patients who died had elevated transaminases. Values more than 1,000 IU/ml were present in four patients and one pregnant patient had acute liver failure. The hepatic injury has been graded using the Modified World Health Organization toxicity grade system as depicted in Table
ALT, alanine transaminase; AST, aspartate transaminase; ULN, upper limit of normal.
Grade I (1.25-3.0 X ULN) | Grade II (3.1-5.0 X ULN) | Grade III (5.1-10 X ULN) | Grade IV ( >10 X ULN) | |
Bilirubin (ULN = 2 mg/dl) | 46 (26.1%) | 8 (4.5%) | 3 (1.7%) | 0 |
AST (ULN = 40 IU/L) | 50 (28.4%) | 29 (16.4%) | 31 (17.6%) | 24 (13.6%) |
ALT (ULN = 40 IU/L) | 59 (33.5%) | 28 (15.9%) | 28 (15.9%) | 17 (9.6%) |
Four pregnant patients were part of the study group. One of them, who was in the third trimester, developed acute liver failure with seizures and died due to multiorgan dysfunction. The other three were in the second trimester and all of them had an abortion. Grade I hepatic injury was noted in all of them, and none had AKI.
The recent increase in the prevalence of scrub typhus in India is a cause of concern. This may be partly attributed to earlier under-reporting or misdiagnosis owing to inadequate awareness among the health professionals. The role of urbanization of rural areas and the ease of traveling due to economic development and better transportation facilities need to be explored. Patients from any state presenting with fever and liver or renal dysfunction should be investigated for scrub typhus, especially in post-monsoon season. The economic impact of the disease is compounded by the fact that the disease inflicts the working population preferentially, who spend time outdoors.
Earlier scrub typhus was considered to occur mostly in rural areas; however, now India as a whole has been shown to be endemic for it with outbreaks reported even from the metropolitans [
The pathogenesis involves systemic dissemination of the bacterium from the site of inoculation, and infection of the endothelial cells with consequent vasculitic injury that culminates in organ dysfunctions [
Bhargava et al. found creatinine and albumin to predict mortality [
Scrub typhus has been reported to be an important infectious cause of acute liver failure in India, along with dengue, viral hepatitis, malaria and amoebic liver abscess [
The clinical profile of pregnant patients with scrub typhus has been found to be similar to those who are not pregnant [
In contrast to scrub typhus, where organ damage results from vasculitis, liver injury in dengue has been documented to be a consequence of entry of the virus into hepatocytes, either directly or via a receptor [
Leptospirosis is particularly prevalent in areas with poor sanitation. In a multicentric retrospective study with mortality of 5%, elevated AST was seen in 33.3% and AKI in 82% of the patients [
In acute viral hepatitis, patients have a marked elevation in bilirubin preceded by a prodrome of fever, nausea, anorexia and malaise. The transaminases rise by at least 10-fold and extreme elevations to more than 100-fold are not uncommon, and acute liver failure is more common than in scrub typhus [
Liver involvement in enteric fever is almost universal and generally mild. AST and ALT elevations have been reported in 100% and 91%, respectively [
The liver involvement has been found to be similar in falciparum and non-falciparum malaria, and less common than in scrub typhus [
Hepatic and renal dysfunctions are common in scrub typhus, and both adversely affect the outcome. Liver injury can range from mild transaminitis to acute liver failure. It can sometimes mimic acute viral hepatitis and other tropical infections. AKI can be severe enough to require renal replacement therapy, and if the patient survives, recovery is quick. It is imperative to sensitize health workers about the disease to enable early diagnosis and treatment. Lack of diagnostic facility at peripheral centers should not be a deterrent, and the use of empirical therapy is justified in endemic regions until the diagnosis is ruled out.
The authors have declared that no competing interests exist.
Consent was obtained by all participants in this study
We would like to thank the Department of Microbiology and Department of Obstetrics and Gynecology, Government Medical College and Hospital, Chandigarh for their cooperation.