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Volume 29, Number 4—April 2023
Synopsis

Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India

Tina DamodarComments to Author , Bhagteshwar Singh, Namratha Prabhu1, Srilatha Marate1, Vykuntaraju K. Gowda, A.V. Lalitha, Fulton Sebastian Dsouza, Sushma Veeranna Sajjan, Mallesh Kariyappa, Uddhava V. Kinhal, P.V. Prathyusha, Anita Desai, Kandavel Thennarasu, Tom Solomon, Vasanthapuram Ravi, and Ravi YadavComments to Author 
Author affiliations: National Institute of Mental Health and Neurosciences, Bangalore, India (T. Damodar, N. Prabhu, S. Marate, P.V. Prathyusha, A. Desai, K. Thennarasu, V. Ravi, R. Yadav); Christian Medical College, Vellore, India (B. Singh); University of Liverpool, Liverpool, UK (B. Singh, T. Solomon); Liverpool University Hospitals NHS Foundation Trust, Liverpool (B. Singh, T. Solomon); Indira Gandhi Institute of Child Health, Bangalore (V.K. Gowda, U.V. Kinhal); St. John’s Medical College and Hospital, Bangalore (A.V. Lalitha, F.S. Dsouza); Vani Vilas Women and Children’s Hospital, Bangalore Medical College and Research Institute, Bangalore (S.V. Sajjan, M. Kariyappa); The Walton Centre NHS Foundation Trust, Liverpool (T. Solomon); The Pandemic Institute, Liverpool (T. Solomon)

Main Article

Table 2

Definitions used for diagnostic association of AES with scrub typhus, ME, and scrub typhus ME in study of association of AES with scrub typhus in children, southern India*

Condition Definition
Diagnostic association of AES with scrub typhus Confirmed: Detection of Orientia tsutsugamushi DNA by PCR in CSF or blood
Probable (single): Positive serum IgM ELISA with or without positive CSF IgM ELISA for Orientia tsutsugamushi and no other explanatory pathogen or cause
Probable (co-positive): Positive serum IgM ELISA and positive CSF IgM ELISA for Orientia tsutsugamushi with evidence of another pathogen(s)
Possible: Positive serum IgM ELISA and negative CSF IgM ELISA for Orientia tsutsugamushi with evidence of another pathogen(s)
Meningoencephalitis (22)
 Presence of >1 of the following findings: CSF pleocytosis, meningeal enhancement or parenchymal inflammation on contrast enhanced CT or MRI of brain, positive real time PCR in CSF
Scrub typhus ME Patients with meningoencephalitis AND positive real-time PCR or serum IgM ELISA for Orientia tsutsugamushi (and no other explanatory pathogen or cause) (i.e, patients with confirmed or probable [single] diagnostic association of AES with scrub typhus)

*AES, acute encephalitis syndrome; CSF, cerebrospinal fluid; CT, computed tomography; ME, meningoencephalitis; MRI, magnetic resonance imaging.

Main Article

References
  1. Jiang  J, Richards  AL. Scrub typhus: no longer restricted to the tsutsugamushi triangle. Trop Med Infect Dis. 2018;3:11. DOIPubMedGoogle Scholar
  2. Devasagayam  E, Dayanand  D, Kundu  D, Kamath  MS, Kirubakaran  R, Varghese  GM. The burden of scrub typhus in India: A systematic review. PLoS Negl Trop Dis. 2021;15:e0009619. DOIPubMedGoogle Scholar
  3. Garg  D, Manesh  A. Neurological facets of scrub typhus: a comprehensive narrative review. Ann Indian Acad Neurol. 2021;24:849–64. DOIPubMedGoogle Scholar
  4. Varghese  GM, Trowbridge  P, Janardhanan  J, Thomas  K, Peter  JV, Mathews  P, et al. Clinical profile and improving mortality trend of scrub typhus in South India. Int J Infect Dis. 2014;23:39–43. DOIPubMedGoogle Scholar
  5. Ravi  V, Hameed  SKS, Desai  A, Mani  RS, Reddy  V, Velayudhan  A, et al. An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study. Lancet Glob Health. 2022;10:e685–93. DOIPubMedGoogle Scholar
  6. Murhekar  MV, Vivian Thangaraj  JW, Sadanandane  C, Mittal  M, Gupta  N, Rose  W, et al. Investigations of seasonal outbreaks of acute encephalitis syndrome due to Orientia tsutsugamushi in Gorakhpur region, India: A One Health case study. Indian J Med Res. 2021;153:375–81. DOIPubMedGoogle Scholar
  7. Jain  P, Prakash  S, Tripathi  PK, Chauhan  A, Gupta  S, Sharma  U, et al. Emergence of Orientia tsutsugamushi as an important cause of Acute Encephalitis Syndrome in India. PLoS Negl Trop Dis. 2018;12:e0006346. DOIPubMedGoogle Scholar
  8. Sen  PK, Dhariwal  AC, Jaiswal  RK, Lal  S, Raina  VK, Rastogi  A. Epidemiology of acute encephalitis syndrome in India: changing paradigm and implication for control. J Commun Dis. 2014;46:4–11.
  9. Government of India. Guidelines for surveillance of acute encephalitis syndrome (with special reference to Japanese encephalitis). November 2006 [cited 2022 Jul 1]. http://nvbdcp.gov.in/WriteReadData/l892s/AES_guidelines.pdf
  10. John  TJ, Verghese  VP, Arunkumar  G, Gupta  N, Swaminathan  S. The syndrome of acute encephalitis in children in India: Need for new thinking. Indian J Med Res. 2017;146:158–61. DOIPubMedGoogle Scholar
  11. Granerod  J, Cunningham  R, Zuckerman  M, Mutton  K, Davies  NWS, Walsh  AL, et al. Causality in acute encephalitis: defining aetiologies. Epidemiol Infect. 2010;138:783–800. DOIPubMedGoogle Scholar
  12. Venkatesan  A, Geocadin  RG. Diagnosis and management of acute encephalitis: A practical approach. Neurol Clin Pract. 2014;4:206–15. DOIPubMedGoogle Scholar
  13. Misra  UK, Kalita  J, Mani  VE. Neurological manifestations of scrub typhus. J Neurol Neurosurg Psychiatry. 2015;86:761–6. DOIPubMedGoogle Scholar
  14. Kannan  K, John  R, Kundu  D, Dayanand  D, Abhilash  KPP, Mathuram  AJ, et al. Performance of molecular and serologic tests for the diagnosis of scrub typhus. PLoS Negl Trop Dis. 2020;14:e0008747. DOIPubMedGoogle Scholar
  15. Varghese  GM, Rajagopal  VM, Trowbridge  P, Purushothaman  D, Martin  SJ. Kinetics of IgM and IgG antibodies after scrub typhus infection and the clinical implications. Int J Infect Dis. 2018;71:53–5. DOIPubMedGoogle Scholar
  16. Koh  GC, Maude  RJ, Paris  DH, Newton  PN, Blacksell  SD. Diagnosis of scrub typhus. Am J Trop Med Hyg. 2010;82:368–70. DOIPubMedGoogle Scholar
  17. Pommier  JD, Gorman  C, Crabol  Y, Bleakley  K, Sothy  H, Santy  K, et al.; SEAe Consortium. Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study. Lancet Glob Health. 2022;10:e989–1002. DOIPubMedGoogle Scholar
  18. Lo Stanley  F. Reference intervals for laboratory tests and procedures. In: Kleigman RM, Behrman RE, Jenson HB, Stanton BP, editors. Nelson textbook of pediatrics. 20th ed. Philadelphia: Saunders Elsevier; 2011. p. 3464–3472.
  19. 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. DOIPubMedGoogle Scholar
  20. Jiang  J, Chan  TC, Temenak  JJ, Dasch  GA, Ching  WM, Richards  AL. Development of a quantitative real-time polymerase chain reaction assay specific for Orientia tsutsugamushi. Am J Trop Med Hyg. 2004;70:351–6. DOIPubMedGoogle Scholar
  21. Behera  B, Satapathy  AK, Ranjan  J, Chandrasekar  S, Patel  S, Mishra  B, et al. Profile of scrub typhus meningitis/meningoencephalitis in children with and without scrub typhus IgM antibody in CSF. J Neurosci Rural Pract. 2021;12:786–91. DOIPubMedGoogle Scholar
  22. Granerod  J, Ambrose  HE, Davies  NW, Clewley  JP, Walsh  AL, Morgan  D, et al.; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10:835–44. DOIPubMedGoogle Scholar
  23. Jaijakul  S, Salazar  L, Wootton  SH, Aguilera  E, Hasbun  R. The clinical significance of neutrophilic pleocytosis in cerebrospinal fluid in patients with viral central nervous system infections. Int J Infect Dis. 2017;59:77–81. DOIPubMedGoogle Scholar
  24. 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:e0005838. DOIPubMedGoogle Scholar
  25. Horwood  PF, Duong  V, Laurent  D, Mey  C, Sothy  H, Santy  K, et al. Aetiology of acute meningoencephalitis in Cambodian children, 2010-2013. Emerg Microbes Infect. 2017;6:e35. DOIPubMedGoogle Scholar
  26. Olsen  SJ, Campbell  AP, Supawat  K, Liamsuwan  S, Chotpitayasunondh  T, Laptikulthum  S, et al.; Thailand Encephalitis Surveillance Team. Infectious causes of encephalitis and meningoencephalitis in Thailand, 2003-2005. Emerg Infect Dis. 2015;21:280–9. DOIPubMedGoogle Scholar
  27. Dittrich  S, Rattanavong  S, Lee  SJ, Panyanivong  P, Craig  SB, Tulsiani  SM, et al. Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study. Lancet Glob Health. 2015;3:e104–12. DOIPubMedGoogle Scholar
  28. Dubot-Pérès  A, Mayxay  M, Phetsouvanh  R, Lee  SJ, Rattanavong  S, Vongsouvath  M, et al. Management of central nervous system infections, Vientiane, Laos, 2003–2011. Emerg Infect Dis. 2019;25:898–910. DOIPubMedGoogle Scholar
  29. Dinesh Kumar  N, Arun Babu  T, Vijayadevagaran  V, Ananthakrishnan  S, Kittu  D. Clinical profile of scrub typhus meningoencephalitis among South Indian children. J Trop Pediatr. 2018;64:472–8.PubMedGoogle Scholar
  30. Viswanathan  S, Muthu  V, Iqbal  N, Remalayam  B, George  T. Scrub typhus meningitis in South India—a retrospective study. PLoS One. 2013;8:e66595. DOIPubMedGoogle Scholar
  31. Subbalaxmi  MV, Madisetty  MK, Prasad  AK, Teja  VD, Swaroopa  K, Chandra  N, et al. Outbreak of scrub typhus in Andhra Pradesh—experience at a tertiary care hospital. J Assoc Physicians India. 2014;62:490–6.PubMedGoogle Scholar
  32. Usha  K, Kumar  E, Kalawat  U, Kumar  BS, Chaudhury  A, Gopal  DV. Molecular characterization of Orientia tsutsugamushi serotypes causing scrub typhus outbreak in southern region of Andhra Pradesh, India. Indian J Med Res. 2016;144:597–603.PubMedGoogle Scholar
  33. Mørch  K, Manoharan  A, Chandy  S, Chacko  N, Alvarez-Uria  G, Patil  S, et al. Acute undifferentiated fever in India: a multicentre study of aetiology and diagnostic accuracy. BMC Infect Dis. 2017;17:665. DOIPubMedGoogle Scholar
  34. Khan  SA, Bora  T, Laskar  B, Khan  AM, Dutta  P. Scrub typhus leading to acute encephalitis syndrome, Assam, India. Emerg Infect Dis. 2017;23:148–50. DOIPubMedGoogle Scholar
  35. Gupte  MD, Gupte  M, Kamble  S, Mane  A, Sane  S, Bondre  V, et al. Detection of immunoglobulin m and immunoglobulin g antibodies against Orientia tsutsugamushi for scrub typhus diagnosis and serosurvey in endemic regions. Indian Pediatr. 2020;57:1131–4. DOIPubMedGoogle Scholar
  36. Kim  DM, Chung  JH, Yun  NR, Kim  SW, Lee  JY, Han  MA, et al. Scrub typhus meningitis or meningoencephalitis. Am J Trop Med Hyg. 2013;89:1206–11. DOIPubMedGoogle Scholar
  37. Peter  JV, Sudarsan  TI, Prakash  JA, Varghese  GM. Severe scrub typhus infection: Clinical features, diagnostic challenges and management. World J Crit Care Med. 2015;4:244–50. DOIPubMedGoogle Scholar
  38. Varghese  GM, Mathew  A, Kumar  S, Abraham  OC, Trowbridge  P, Mathai  E. Differential diagnosis of scrub typhus meningitis from bacterial meningitis using clinical and laboratory features. Neurol India. 2013;61:17–20. DOIPubMedGoogle Scholar
  39. Pan  S, Islam  K, Datta  A. Orientia tsutsugamushi: an emerging major cause of acute encephalitis syndrome in south Asian children. In: Abstracts of the British Paediatric Allergy Immunity and Infection Group; 2021. Abstract 989. Archives of Disease in Childhood, 2021 [cited 2022 Jul 1]. https://adc.bmj.com/content/archdischild/106/Suppl_1/A185.full.pdf
  40. Kaur  P, Jain  R, Kumar  P, Randev  S, Guglani  V. Clinical spectrum and outcome of acute encephalitis syndrome in children with scrub typhus: a series of eight cases from India. Indian J Crit Care Med. 2020;24:885–7. DOIPubMedGoogle Scholar
  41. Ralph  R, Prabhakar  AT, Sathyendra  S, Carey  R, Jude  J, Varghese  GM. Scrub typhus-associated opsoclonus: clinical course and longitudinal outcomes in an Indian cohort. Ann Indian Acad Neurol. 2019;22:153–8.PubMedGoogle Scholar
  42. Saini  L, Dhawan  SR, Madaan  P, Suthar  R, Saini  AG, Sahu  JK, et al. Infection-associated opsoclonus: a retrospective case record analysis and review of literature. J Child Neurol. 2020;35:480–4. DOIPubMedGoogle Scholar
  43. Nandi  M, Maity  D. Opsoclonus myoclonus syndrome: a presenting feature of scrub typhus in a child. The Child and Newborn. 2018;22:8–9.
  44. Cho  HJ, Choi  JH, Sung  SM, Jung  DS, Choi  KD. Bilateral optic neuritis associated with scrub typhus. Eur J Neurol. 2013;20:e129–30. DOIPubMedGoogle Scholar
  45. Jessani  LG, Gopalakrishnan  R, Kumaran  M, Devaraj  V, Vishwanathan  L. Scrub typhus causing unilateral optic neuritis. Indian J Pediatr. 2016;83:1359–60. DOIPubMedGoogle Scholar
  46. Sood  AK, Chauhan  L, Gupta  H. CNS manifestations in Orientia tsutsugamushi disease (scrub typhus) in North India. Indian J Pediatr. 2016;83:634–9. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

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