Clinical Manifestations and Outcome of Scrub Typhus in Infants From Odisha

research paper

Indian Pediatr 2021;58:367-369

Jyoti Ranjan Behera,¹ Sanjay Kumar Sahu,¹ Niranjan Mohanty,¹ Nirmal Kumar Mohakud¹ and Amos Lal²

From ¹Department of Pediatrics, Kalinga Institute of Medical Sciences, KIIT Deemed University, Bhubaneswar, India; and ²Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, MN, USA.

Correspondence to: Dr Nirmal Kumar Mohakud, Professor, Department of Paediatrics, Kalinga Institute of Medical Sciences, KIIT Deemed to be University, Bhubaneswar, India.
Email: [email protected]

Received: August 10, 2020;
Initial review: August 11, 2020;
Accepted: December 31, 2020.

Objective: To study manifestations and outcome of scrub typhus in infants. Methods: Case record analysis of infants with scrub typhus admitted to a tertiary care hospital, diagnosed by IgM ELISA from January 1, 2016 to December 31, 2019. Results: Out of 374 children diagnosed with scrub typhus, 34 (9%) were infants. Chief presentation were fever 34 (100 %), feeding difficulty 24 (70.6%), lethargy 18 (52.9%) and irritability 15 (44.1%). Clinically, pallor 30 (88.2%), tachycardia 29 (85.3%), tachypnea 24 (70.6%), hepatosplenomegaly 30 (88.2%) and eschar 6 (17.6%) were detected. Significant laboratory parameters were anemia 33 (97.1%), leukocytosis 33 (97.1%), thrombocytopenia 17 (50%) and transaminitis 21 (63.6%). Pneumonia 18 (52.9%) was noticed as the major complication. Infants requiring intensive care 17(50%) had characteristic thrombocytopenia, hypoalbuminemia and transaminitis (P<0.05). They recovered well with doxycycline. Conclusion: Manifestation of scrub typhus in infants tends to be severe with combination of hematologic, pulmonary and hepatic involvement requiring intensive care. The response to doxycycline is good.

Keywords: Doxycycline, Eschar, Intensive care, Rickettsia.

Scrub typhus is an emerging rickettsial infectious disease over the past 8-10 years affecting all age groups and having a wide geographical distribution. Most clinical features mimic common tropical febrile infectious diseases making the diagnosis difficult [1]. Various life-threatening complications resulting from multi-organ dysfunction usually occur in the second week of illness [2]. Eschar is the hallmark of scrub typhus, but the incidence in infants is not known. Ample number of studies are available on different aspects of scrub typhus in children, but not in infants. This study aimed to find out the manifestations and outcome of infants with scrub typhus. The laboratory parameters influencing the need for intensive care were also determined.

METHODS

This was a retrospective observational study conducted in infants with a diagnosis of scrub typhus admitted in the pediatric ward of a tertiary care teaching hospital of Eastern Odisha from January, 2016 to December, 2019. Scrub typhus was suspected in infants who presented with acute fever (>5 days) and confirmed by IgM ELISA using INBIOS kit (In BiOS International Inc., which is 99.9% sensitive and 99.15% specific [3]. Reports with optical density of >0.5 at 450 nm were taken to define case positivity. The difference in manifestation and outcome of infant scrub typhus from older children were considered as the primary outcome and laboratory parameters influencing intensive care requirement as the secondary outcome, respectively.

Data including age, sex, residential area, duration of fever, associated symptoms, vitals with general and systemic examination findings were documented. Complete blood counts, chest X-rays, rapid antigen test for malaria, dengue (NS1 antigen and IgM antibody) test, urine and blood cultures, serum urea and creatinine, C- reactive protein (CRP), liver function tests (LFT), electrolytes and other relevant investigations and treatment provided were collected from the records. Complications, end organ dysfunction, the need for intensive care and mechanical ventilation were also noted. Infants with features of end organ dysfunction were admitted to the pediatric intensive care unit (PICU) [4]. Management of the patients was based on the standard IAP guidelines on ‘Diagnosis and Management of Scrub Typhus in India’. Doxycycline was administered in the dose of 2.2 mg/ kg twice daily till 3 days after subsidence of fever or for a total of 7 days. Severe and/or complicated cases were given 10 days therapy. Alternatively, Azithromycin was used in the dose of 10 mg/kg/day for 5 days [1].

Descriptive statistics were calculated. Laboratory parameters of infants requiring intensive care were compared with those not requiring. The data were analyzed using SPSS version 2.0. P value <0.05 was considered statistically significant. Approval of the institutional ethical committee (IEC) was obtained before initiation of the study.

RESULTS

Infants constituted 34 (9.1%) of the 374 cases of scrub typhus cases admitted during the study period of 3 years. Out of these, 18 (52.95%) were under 6 months, and 16 (47.05%) were between 7 months to 1 year of age. The mean (SD) age of infants was 6.4 (3.6) months, the youngest being 38 days old. There was a male 23 (67.7%) predominance. Majority of infants 25 (73.53%) were from rural background.

Common clinical symptoms were fever 34 (100%), poor feeding 24 (70.59%), lethargy 18 (52.94%), respiratory symptoms 16 (47.07%), irritability 15 (44.12%), seizure 8 (23.53%) and rash 6 (17.65%). On examination, the key findings were pallor 30 (88.24%), hepatosplenomegaly 30 (88.26%), tachycardia 29 (85.29%), tachypnea 24 (70.57%) and meningeal signs 4 (11.76%). Eschar was found in 6 (17.65%) infants. Characteristic laboratory findings were anemia (Hb <10.5 gm%), leukocytosis (TLC >14000/mm3) and raised C Reactive Protein (CRP>6 mg/dL) in 33 (97.06%) infants. Transaminitis (AST & ALT >2 times) 21 (63.63%), thrombocytopenia (<1.5 lacs/mm3) 17 (50%), hypo-natremia (<135 meq/L) 13 (39.39%), hypoalbuminemia (<2.5 gm/dL) 9 (27.27%) were other significant lab findings. Common complications seen were, pneumonia 18 (52.94%) and meningoencephalitis 7 (20.58%). Acute respiratory distress syndrome (ARDS), septic shock and multi organ dysfunction syndrome (MODS) were found in 4 (11.76%) cases each whereas Haemophagocytic Lymphohistiocytosis (HLH) was seen in 1(2.9%) patient.

Intensive care (ICU) was needed in 17 (50%) infants, of which 5 (14.71%) required mechanical ventilation. Table I compares laboratory parameters among infants of PICU and non-PICU group. Significant parameter were hypoalbuminemia (P=0.001), transaminitis (P=0.03) and thrombocytopenia (P<0.001). The mean value of scrub typhus IgM in PICU admitted infants was 1.89 as compared to non PICU admitted infants which was 1.11 (P=0.003). Of note, mean (SD) CRP of the infants admitted in PICU was 80.03 (42.55) mg/dL compared to the non PICU group was 59.49 (29.14) mg/dL (P=0.08).

Table I Laboratory Parameters Among Infants With Scrub Typhus With or Without Need of Intensive Care

Parameter	Non-PICU group, n=17	PICU group, n=17
Anemia	17 (100)	16 (94.1)
Leucocytosis	17 (100)	1694.11
Thrombocytopeniaa	4 (23.52)	13 (76.5)
Hypoalbuminemiaa	1 (5.9)	8 (47.0)
Hyponatremia	5 (29.4)	8 (47.0)
Transaminitisb	7 (41.2)	14 (82.3)
High c-reactive protein	16 (94.1)	17 (100)
Values in no. (%). PICU-Pediatric intensive care unit; blevels greater than twice normal.aP<0.001.

Along with supportive treatment, doxycycline was administered to 30 (88.23%), Azithromycin to 3 (8.82%) and both Doxycycline and Azithromycin were administered to 1 (2.94%) case. All ICU patients received IV/oral doxycycline. No adverse events were noticed following doxycycline administration in infants. The mean (SD) for defervescence was 2.23 (1.72) days. The median (IQR) hospital stay was 7 (5-8) days with a range of 4 to 20 days. Out of 34 infants, 33 (97%) were discharged and one left against medical advice. There was no mortality.

DISCUSSION

Our study focuses on different aspects of scrub typhus in infants. Major clinical findings observed in our study like fever, lethargy, poor feeding, tachycardia, tachypnea and hepatoslenomegaly are similar to malaria, dengue, enteric fever and sepsis in this age group. Hence scrub typhus should be an important differential diagnosis in febrile infants. Various studies in older children have documented eschar in 40-90% of cases [5,6]. Age-wise distribution of eschar observed by Rose, et al. [6] were 54.5%, 31.9% and 13.6% in <5, 6-10 and 11-15 years age group, respectively. However, no exclusive data is available for infants [6]. One report from Odisha has observed 17.9% of older children with scrub typhus had eschar [7]. Similarly, our study has found eschar in 17.65% of infants with scrub typhus. Due to its uncommon occurrence in the infants, the diagnosis should however not be discarded in the absence of eschar.

We have compared several parameters from different studies of scrub typhus in children above 1 year from various parts of Indian subcontinent with the present study. Anemia and leucocytosis were the key haematological abnormalities, which were significantly higher than those observed by others. However, the incidence of thrombocytopenia was comparable [2,8]. Transaminitis denotes hepatic involvement and its incidence was higher in our study when compared to scrub typhus in older children [9,10]. More than half of infants (52.94%) developed pneumonia, However the incidence in older children has been reported to be around 11%; thus signifying pulmonary predilection in infants. Pathak, et al. [11] found very high incidence AKI (65.8%) and myocarditis (75.4%) in 1-16 years age group but these findings were negligible in infants as in the present study. HLH, a rare complication was observed in only 1 case which also recovered on treatment of the underlying disease. Intensive care was required in 50% infants which was higher as compared to older children [9,11]

Thrombocytopenia, transaminitis, hypoalbuminemia and higher IgM titer by ELISA were significant findings while comparing PICU and non PICU infants (P value<0.05). Hence these parameters may be considered as markers of severity in infant with scrub typhus. Although CRP values were not found statistically significant in these two groups, there was a trend towards higher CRP in the intensive care groups. The mean (SD) defervescence period and median (IQR) hospital stay were similar to other studies in older children [13,14].There was no mortality in our study, whereas mortality in older children ranged from 9-12% in literature [10,15]. Smaller sample size and retrospective nature were the major limitations of this study. Scrub typhus should be considered as a differential diagnosis for unremitting fever in infants. Significant hepatic, pulmonary and hematological involvement would indicate the requirement of intensive care in infants. Eschar, the hallmark of the disease may not be always present in infants. Hence increase awareness of early diagnosis and treatment will significantly help in decreasing the mortality and improving the prognosis in this vulnerable age group.

Ethical clearance: Institutional ethics committee of KIMS; No. : KIIT/KIMS/IEC/339/2020, dated July 28, 2020.

Acknowledgement: Dr Mona Pathak, statistician, for her help in analysis of the data. Dr Mirabai Das for her help in grammatical correction.

Contributors: NM, NKM: conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript; JB, AL and SS: designed the data collection instruments, collected data, carried out the initial analyses, reviewed and revised the manuscript. All authors approved the final manuscript.

Funding: None; Competing interests: None stated.

WHAT THIS STUDY ADDS?

• Infants with scrub typhus have predominant hepatic, pulmonary and hematological involvement.

REFERENCES

1. Rathi N, Kulkarni A, Yewale V; For Indian Academy of Pediatrics Guidelines on Rickettsial Diseases in Children Committee. IAP Guidelines on Rickettsial Diseases in Children. Indian Pediatr. 2017;54:223-9.

2. 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;5:82-8.

3. Pote K, Narang R, Deshmukh P. Diagnostic performance of serological tests to detect antibodies against acute scrub typhus infection in central India. Indian J Med Microbiol. 2018;36:108-12.

4. Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics. Pediatr Crit Care Med. 2005;6:2-8.

5. Pradeepan JA, Ketheesan N, Murugananthan K. Emerging scrub typhus infection in the northern region of Sri Lanka. BMC Res Notes. 2014;7:1-4.

6. Rose W, Rajan RJ, Punnen A, Ghosh U. Distribution of eschar in pediatric scrub typhus. J Trop Pediatr. 2016;62:415-20.

7. Bal M, Mohanta MP, Sahu S, Dwibedi B, Pati S, Ranjit M. Profile of pediatric scrub typhus in Odisha, India. Indian Pediatr. 2019;56:304-6.

8. Kumar Bhat N, Dhar M, Mittal G, et al. Scrub typhus in children at a tertiary hospital in north India: Clinical profile and complications. Iran J Pediatr. 2014;24:387-92.

9. Ganesh R, Suresh N, Pratyusha LL, Janakiraman L, Manickam M, Andal A. Clinical profile and outcome of children with scrub typhus from Chennai, South India. Eur J Pediatr. 2018;177:887-90.

10. Nallasamy K, Gupta S, Bansal A, et al. Clinical profile and predictors of intensive care unit admission in pediatric scrub typhus: A retrospective observational study from north India. Indian J Crit Care Med. 2020;24:445-50.

11. Pathak S, Chaudhary N, Dhakal P, et al. Clinical profile, complications and outcome of scrub typhus in children: A hospital based observational study in central Nepal. PLoS One. 2019;14:e0220905.　

12. Henter JI, Horne A, Arico M, et al. HLH-2004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis. Pediatr Blood Cancer. 2007;48: 124-31.

13. Basu S, Saha A, Sarkar S, et al. Clinical profile and therapeutic response of scrub typhus in children: A recent trend from Eastern India. J Trop Pediatr. 2019;65:139-46.

14. Das P, Singh D, Das M, Nayak RK, Mohakud NK. Epidemiological and clinical features of scrub typhus in Odisha, Eastern India. Medical Journal of Dr. DY Patil Vidyapeeth. 2019;12:419-23.

15. Palanivel S, Nedunchelian K, Poovazhagi V, Raghunadan R, Ramachandran P. Clinical profile of scrub typhus in children. Indian J Pediatr. 2012;79:1459-62.