|Year : 2021 | Volume
| Issue : 1 | Page : 94-96
Scrub typhus: A rare cause of secondary nephrotic syndrome
Ankur Singh1, Akansha Anjali1, Rajniti Prasad1, Pradyot Prakash2, Om Prakash Mishra1
1 Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Microbiology, Institute Of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
|Date of Submission||17-May-2020|
|Date of Acceptance||28-Aug-2020|
|Date of Web Publication||18-Nov-2021|
Dr Ankur Singh
Associate Professor, Department of Pediatrics, Institute Of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005
Source of Support: None, Conflict of Interest: None
Scrub typhus is an important etiological agent in acute febrile illness in the post-monsoon season in tropical countries. It leads to dreaded complications if left untreated. Acute kidney injury is one such complication. Malaria, syphilis, and HIV have been associated with secondary nephrotic syndrome in pediatric age group. Scrub typhus has been reported only once with nephrotic syndrome. We report a case of scrub typhus-associated nephrotic syndrome with acute kidney injury in a five-year-old female with uneventful outcome
Keywords: Scrub typhus; Nephrotic syndrome; Acute kidney injury
|How to cite this article:|
Singh A, Anjali A, Prasad R, Prakash P, Mishra OP. Scrub typhus: A rare cause of secondary nephrotic syndrome. J Vector Borne Dis 2021;58:94-6
|How to cite this URL:|
Singh A, Anjali A, Prasad R, Prakash P, Mishra OP. Scrub typhus: A rare cause of secondary nephrotic syndrome. J Vector Borne Dis [serial online] 2021 [cited 2021 Nov 27];58:94-6. Available from: https://www.jvbd.org/text.asp?2021/58/1/94/321744
| Introduction|| |
Scrub typhus is an important emerging cause of fever in the post-monsoon season. It is caused by Orientia tsutsugamushi, an obligate intracellular gram-negative bacterium and is transmitted by the bite of infected mite vectors. The global burden of this disease is high. There is a lack of population-based data on the incidence and prevalence of the disease in India. It is a systemic disease with a high mortality rate if left untreated. Bonnel et al have reported mortality rates of 6 % (median range: 0–70%) in untreated scrub typhus and 1.4 % (range: 0–33.3 %) for treated scrub typhus,. Acute kidney injury (AKI) is an important complication of the disease with varying degrees of frequency in Indian pediatric studies (20 % versus 12 %),. Secondary nephrotic syndrome has been associated with malaria, HIV, syphilis, hepatitis B, hepatitis C, and toxoplasmosis. Scrub typhus has been reported only once as a cause of secondary nephrotic syndrome in a 72-year-old female by Lee et al in 2013. We report a case of secondary nephrotic syndrome due to scrub typhus with an uneventful recovery. We emphasize that clinicians should keep in mind scrub typhus as a causative agent of secondary nephrotic syndrome in a clinical setting of rickettsiosis.
A five-year-old female child presented with complaints of fever for 15 days, abdominal distention, generalized body edema, and decreased urine output for 5 days. There was no history of rash, joint swelling, boils, pustules, yellowish discoloration of eyes and urine, red-colored urine, convulsions, headache, vomiting, or bleeding manifestations. There was no prior history of chronic illness or drug intake.
Examination revealed normal vitals. Pallor with generalized edema was present. There were red erythematous rashes over the face. Hepatosplenomegaly, with a palpable liver of 4cm (liver span -9cm) and a spleen of 2cm were observed. There was no eschar. The rest of the systemic examination was normal.
Investigations revealed: low hemoglobin (Hb: 7.4 g/dL); high total leucocyte count (32660/μL) with a differential of (neutrophils 58%, lymphocytes 26%, monocytes14% and eosinophils 2%); platelet count: 175,000/ μL; urea: 234.7 mg/dL; creatinine: 6.4 mg/dL, sodium:124.0 mmol/L; potassium: 5.5 mmol/L; total protein: 5.5 g/dL; serum albumin: 1.5 g/dL; serum cholesterol: 265 mg/dL; urine protein creatinine ratio 4.66; scrub typhus IgM ELISA [0.67 OD (positive >0.5)]. Urine microscopy examination revealed bland urinary sediments and only proteinuria (3+). Rest of Investigations (liver function test, chest x ray) were normal. USG of KUB region was normal with right kidney size 6.5 cm and left kidney size 7 cm. Test for malaria, dengue, leptospirosis, typhoid were normal.
The child was managed symptomatically with two sessions of peritoneal dialysis (each session was of 72 cycles with each cycle of 60 min duration) and intravenous doxycycline (5 mg/kg/day in two divided doses) for seven days. She responded well to treatment. Her urine output improved on day 5 of treatment, and the renal function began normalizing (urea 58mg/dL and creatinine: 1.2 mg/dL by day7 of hospital stay). Renal parameters for nephrotic syndrome also improved during follow up.
| Discussion|| |
Nephrotic syndrome is a common disease of childhood and it affects 5 per 100,000 children in age group of 1–18 years with varying prevalence in different ethnic groups. Pathogenesis of Nephrotic syndrome has evolved in stages over time: direct injury, immune-mediated injury, systemic circulating factors, podocytopathy. Recent evidence suggests that podocytes are final target of infection-associated or immune-mediated injury to glomerulus. All injury pathways merge together and hit functional unit of slit diaphragm and cytoskeleton of foot processes. This leads to disruption of multiprotein complex and proteinuria. Tropical infections (malaria, dengue, rickettisiae, leptospirosis) can involve kidneys with multiple mechanisms: direct parenchymal injury, immune complex deposition (post-infectious glomerulonephritis), interstitial injury and acute tubular necrosis. Rickettsia can involve the kidneys either by direct injury to endothelial cells leading to acute tubular necrosis or immune-mediated glomerulonephritis.
Infections are a major cause of secondary renal involvement, and scrub typhus is a significant cause of infection-associated renal involvement. Common causes of AKI presenting to our centre are diarrhea, malaria, dengue, rickettsiosis, leptospirosis, staphylococcal disease in post neonatal age group. Indian studies in the pediatric population have also highlighted the problem of scrub typhus-related acute kidney injury (AKI) which have ranged from 3.7% to 20%,. Pathak et al reported the prevalence of acute kidney injury in scrub typhus as high as 65.8 % in a tertiary center from central Nepal. The mechanism of AKI in scrub typhus is mainly believed to be impaired renal perfusion due to volume depletion or increased vascular permeability. Other potential mechanisms include direct tubular toxicity leading to acute tubular necrosis, interstitial nephritis, pigment nephropathy due to rhabdomyolysis, and thrombotic microangiopathy secondary to disseminated intravascular coagulation.
Secondary nephrotic syndrome following scrub typhus infection has been reported only once, by Lee et al in a 72-year-old female in 2013. Since the development of nephrotic syndrome in scrub typhus is rare phenomena, the pathophysiology is yet to be understood. The likely pathogenesis of nephrotic syndrome in our case may be partially explained by mechanism of molecular mimicry between the 47-kDa protein of Orientia tsutsugamushi and Human serine protease HtrA1 (hHtrA1), as previously demonstrated by Chen et al. Molecular mimicry is elicited with pathogen shares amino-acid sequence to host body and elicits auto-immune response. Newer research has showed podocyte injury is central to mechanism of proteinuria in glomerular diseases. Boehlke et al had showed proteinuria and effacement of podocyte foot processes following Hantavirus infection. They further showed that proteinuria and foot process effacement was resolved few weeks after infection. Although we could not demonstrate podocyte foot process effacement during the disease course, this could be another likely mechanism of proteinuria in our case as previously demonstrated in Hantavirus infection. There is another possibility of the child having a primary nephrotic syndrome, with secondary infection with scrub typhus. But the child went into remission with the treatment of scrub typhus and there was no reoccurrence of nephrotic syndrome in the six months of follow up. However, we cannot rule out the existence of primary nephrotic syndrome in the disease-free state. Renal biopsy was not performed as the parents refused consent for the procedure.
In conclusion, this report highlights the importance of keeping scrub typhus in mind as an etiology for infection-associated acute kidney injury in tropical countries. Scrub typhus can cause nephrotic syndrome-like features like malaria does.
Conflict of interest: None
| References|| |
Traub R, Wisseman CL Jr. The ecology of chigger-borne rickettsiosis (scrub typhus). J Med Entomol
. 1974; 11(3):
Taylor AJ, Paris DH, Newton PN. A Systematic Review of Mortality from Untreated Scrub Typhus (Orientia tsutsugamushi). PLoS Negl Trop Dis
2015; 9(8): e0003971.
Bonell A, Lubell Y, Newton PN, Crump JA, Paris DH. Estimating the burden of scrub typhus: A systematic review. PLoS Negl Trop Dis
2017; 11(9): e0005838.
Kumar M, Krishnamurthy S, Delhikumar CG, Narayanan P, Biswal N, Srinivasan S. Scrub typhus in children at a tertiary hospital in southern India: clinical profile and complications. J Infect Public Health
2012; 5(1): 82–8.
Narayanasamy DK, Arunagirinathan AK, Kumar RK, Raghavendran VD. Clinico - Laboratory Profile of Scrub Typhus - An Emerging Rickettsiosis in India. Indian J Pediatr
Andolino TP, Reid-Adam J. Nephrotic syndrome. Pediatr Rev
Lee JH, Lee MJ, Shin DH, Kang SW, Choi KH, Yoo TH. A case of Tsutsugamushi disease presenting with nephrotic syndrome. Korean J Intern Med
Banh TH, Hussain-Shamsy N, Patel V, Vasilevska-Ristovska J, Borges K, Sibbald C, et al
. Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome. Clin J Am Soc Nephrol
Müller-Deile J, Schiffer M. Podocyte directed therapy of nephrotic syndrome-can we bring the inside out? Pediatr Nephrol
Kamath N, Iyengar A. Infections and the kidney: a tale from the tropics. Pediatr Nephrol
2018; 33(8): 1317–26.
Prasad N, Patel MR. Infection-Induced Kidney Diseases. Front Med (Lausanne)
2018; 5: 327.
Pathak S, Chaudhary N, Dhakal P, Shakya D, Dhungel P, Neupane G, et al
. Clinical profile, complications and outcome of scrub typhus in children: A hospital based observational study in central Nepal. PLoS One
2019; 14(8): e0220905
Kim DM, Kang DW, Kim JO, Chung JH, Kim HL, Park CY, et al
. Acute renal failure due to acute tubular necrosis caused by direct invasion of Orientia tsutsugamushi. J Clin Microbiol
Chen HW, Zhang Z, Huber E, Chao CC, Wang H, Dasch GA, et al
. Identification of cross-reactive epitopes on the conserved 47-kilodalton antigen of Orientia tsutsugamushi and human serine protease. Infect Immunol
2009; 77(6): 2311–9.
Cusick MF, Libbey JE, Fujinami RS. Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allergy Immunol
Boehlke C, Hartleben B, Huber TB, Hopfer H, Walz G, Neumann-Haefelin E. Hantavirus infection with severe proteinuria and podocyte foot-process effacement. Am J Kidney Dis