Figure 3: Repeat Pure Tone Audiometry at 12 weeks postpartum
Discussion
This is a case of scrub typhus in pregnancy with respiratory and possible meningoencephalitis complications. The diagnosis of scrub typhus in our case was delayed due to predominant respiratory symptoms, absence of eschar and the initial false negative serology result with SD Bioline Tsutsugamushi RDT (Standard Diagnostics Inc, Korea). 8 The appearance of audiological symptoms such as hearing loss in acute undifferentiated febrile illness should raise suspicion for scrub typhus infection.2 Audiological symptoms were present in almost 30% of the cases. 2 A hospital based review of records of 33 pregnant women with scrub typhus infection reported 4.5% incidence although none of the cases reported hearing loss. 9Similar to non pregnant patients, the severity of disease is associated with delayed diagnosis and treatment leading to multiorgan failure. It is associated with poor obstetric outcome such as maternal admission to intensive care unit, miscarriage, fetal demise and preterm birth especially in 3rd trimester in atleast 50% of the cases. 9,10 Consistent with other studies, maternal, fetal and neonatal outcomes were favorable in our case as there was no multi organ dysfunction. There are also few case reports on vertical transmission. 11 However the baby’s serology in our case came negative for scrub typhus infection. Case series reported by Premaratna et al have shown objective improvement in hearing loss in those who recovered without any complications. 2 All cases except one responded to course of tetracycline/chloramphenicol. One patient died due to myocarditis and meningoencephalitis due to delayed diagnosis. As a result of delayed diagnosis, our case developed clinical features suggestive of meningoencephalitis. The permanent loss of hearing might have been a sequela to this complication. A hypothetic explaination on rarity of literature on permanent hearing loss due to scrub typhus in pregnancy may be due to shift in Th 1 to Th 2 immune modulation.12 Possibly, neuroinflammation may be less pronounced due to the Th1 to Th2 shift in early stage of infection followed by overwhelming infection at later stage leading to more generalized meningoencephalitis. A reasonable postpartum time period of 3 months was allowed to recover from pregnancy associated hearing loss as seen in some healthy women. 13 Telephonic follow up with spouse at 6 months revealed no subjective improvement in hearing.
This case report is probably the first of its kind in describing the permanent hearing loss following scrub typhus in pregnancy. Although no cause effect relationship can be deduced from this report, we still generate a hypothesis based on hormonal mediated immunomodulation and permanent hearing loss in scrub typhus infection.
Conclusion
As clinicians, we need to be vigilant about these rare and atypical presentations given the endemic nature of scrub typhus in southern belt of the country. Timely diagnosis and appropriate treatment is the key aspect to prevent further complications. Possibly, hearing loss in pregnancy due to scrub typhus could be permanent due to synergistic effect of hormone induced changes in immunomodulation and meningoencephalitis.
Acknowledgement: We would like to thank Mr. Sangay Tshering, Audiologist at the JDWNRH, Thimphu for the providing the results of Pure Tone Audiometry in digital form.
Conflict of interest: There is no conflict of interest in publication of this article.
Funding: None.
Ethical approval: Ethical approval is not needed for case report in de-identified patients.
List of abbreviations
PTA: Pure Tone Audiometry
ABR: Auditory Brainstem Response
Authors contribution
ST was involved in conception and design, acquisition of data, analysis and interpretation of data, revising it critically for important intellectual content, final approval of the version to be published and agreed to be accountable for all aspects of the work.
ND was involved in conception and design, acquisition of data, revising it critically for important intellectual content, final approval of the version to be published and agreed to be accountable for all aspects of the work.
DD was involved in conception and design, acquisition of data, interpretation of data, revising it critically for important intellectual content, final approval of the version to be published and agreed to be accountable for all aspects of the work.
TO was involved in conception and design, acquisition of data, interpretation of data, revising it critically for important intellectual content, final approval of the version to be published and agreed to be accountable for all aspects of the work.
References
1. Dorji K, Phuentshok Y, Zangpo T, Dorjee S, Dorjee C, Jolly P, et al. Clinical and Epidemiological Patterns of Scrub Typhus, an Emerging Disease in Bhutan. Trop Med Infect Dis. 2019 Mar;4(2).
2. Premaratna R, Chandrasena TG, Dassayake AS, Loftis AD, Dasch GA, de Silva HJ. Acute hearing loss due to scrub typhus: a forgotten complication of a reemerging disease. Clin Infect Dis. 2006;42(1):6–8.
3. Kang JI, Kim DM, Lee J. Acute sensorineural hearing loss and severe otalgia due to scrub typhus. BMC Infect Dis. 2009;9:173.
4. Soong L. Dysregulated Th1 Immune and Vascular Responses in Scrub Typhus Pathogenesis. J Immunol. 2018;200(4):1233–40.
5. Peter JV, Sudarsan TI, Prakash JAJ, Varghese GM. Severe scrub typhus infection: Clinical features, diagnostic challenges and management. World J Crit care Med. 2015 Aug;4(3):244–50.
6. 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.
7. Kim D-M, Kim SW, Choi S-H, Yun NR. Clinical and laboratory findings associated with severe scrub typhus. BMC Infect Dis. 2010 Apr;10:108.
8. 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(1):108–12.
9. Rajan SJ, Sathyendra S, Mathuram AJ. Scrub typhus in pregnancy: Maternal and fetal outcomes. Obstet Med. 2016;9(4):164–6.
10. Kumar R, Thakur S, Bhawani R, Kanga A, Ranjan A. Clinical Profile of Scrub Typhus in Pregnancy in Sub-Himalayan Region. J Obstet Gynecol India. 2016;66:82–7.
11. Suntharasaj T, Janjindamai W, Krisanapan S. Pregnancy with scrub typhus and vertical transmission: a case report. J Obstet Gynaecol Res. 1997 Feb;23(1):75–8.
12. Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J. T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells. Front Immunol. 2020;11(August):1–14.
13. Sharma K, Sharma S, Chander D. Evaluation of Audio-Rhinological Changes During Pregnancy. Indian J Otolaryngol Head Neck Surg. 2011;63(1):74–8.