Concurrent Scrub Typhus and Cytomegalovirus Encephalitis in an Immunosuppressed Patient: A Rare Case Report

Vidhya N¹, Durga Devi G², Shenbaga Lalitha S³, Swetha N B⁴

This study shows a rare co-infection of scrub typhus and CMV encephalitis in immunosuppressed patients, underscoring diagnostic challenges and treatment strategies.

Abstract

Background: Scrub typhus, a zoonotic infection caused by Orientia tsutsugamushi, is highly endemic in South East Asia and has emerged as a significant public health concern due to increasing urbanization. The disease commonly presents with nonspecific symptoms such as fever, headache, and myalgia, but can lead to severe complications like encephalitis, particularly in immunocompromised patients. Concurrent infections, such as with cytomegalovirus (CMV), are rare but can complicate the clinical presentation and management. Methods: We present a case of a 53-year-old female with rheumatoid arthritis on immunosuppressive therapy who developed encephalitis. The patient was evaluated with a comprehensive diagnostic approach, including cerebrospinal fluid (CSF) analysis, serological testing, and brain imaging. Initial broad-spectrum antimicrobial therapy was started empirically, and further testing was performed to identify potential tropical infections. Results: CSF analysis revealed elevated protein levels and lymphocytic pleocytosis, suggesting a viral or rickettsial etiology. Radiological imaging indicated nonspecific findings of encephalitis. Serological testing confirmed a dual infection with scrub typhus and CMV. The patient’s treatment regimen was adjusted to include doxycycline for scrub typhus and valganciclovir for CMV encephalitis. Following the modified therapy, the patient showed significant clinical improvement, with normalization of her Glasgow Coma Scale (GCS) score and resolution of neurological symptoms. Conclusion: This case highlights the complexity of diagnosing and managing co-infections in immunocompromised patients presenting with encephalitis in endemic regions. It underscores the need for a high index of suspicion for multiple pathogens, comprehensive diagnostic evaluations, and prompt initiation of appropriate therapies to improve patient outcomes. Early recognition of atypical manifestations and co-infections is crucial in reducing morbidity and mortality associated with tropical infections.

Keywords: Scrub typhus, Cytomegalovirus (CMV) infection, Encephalitis, Immunosuppressive therapy, Co-infection

References

Ahmad, S., Srivastava, S., Verma, S. K., Puri, P., Shirazi, N., & Khare, S. (2010). Prevalence of scrub typhus in different regions of India: A prospective cohort study. Journal of Infectious Diseases, 61(2), 125-130.

Anitharaj, V., & Pradeep, A. (2014). Scrub typhus in South India: A review of 200 cases. International Journal of Infectious Diseases, 20, 87-91.

Bithu, R., Kanodia, V., & Maheshwari, R. K. (2014). Possibility of scrub typhus as an emerging threat in North India: A hospital-based study. Journal of Vector Borne Diseases, 51(2), 100-101.

Chrispal, A., Boorugu, H., Gopinath, K. G., Prakash, J. A. J., Chandy, S., Abraham, O. C., & Thomas, K. (2010). Scrub typhus: An unrecognized threat in South India—Clinical profile and predictors of mortality. Tropical Doctor, 40(3), 129-133.

Dhooria, A., Bansal, A., Mehta, S., & Suri, V. (2016). Scrub typhus during pregnancy: A case series and review of literature. International Journal of Infectious Diseases, 45, 442-445.

Fang, Y., Huang, Z., Zhang, H., Cao, Y., & Yan, J. (2015). Epidemiological analysis of scrub typhus in Fujian Province, China, from 2006 to 2012. American Journal of Tropical Medicine and Hygiene, 92(5), 1040-1044.

Gurung, S., Pradhan, J., & Bhutia, P. Y. (2013). Outbreak of scrub typhus in the North East Himalayan region—Sikkim: An emerging threat. Indian Journal of Medical Microbiology, 31(1), 72-74.

Huang, C. T., Chi, H., Lee, H. C., Chiu, N. C., & Huang, F. Y. (2009). Scrub typhus in children in a teaching hospital in eastern Taiwan, 2000–2005. Southeast Asian Journal of Tropical Medicine and Public Health, 40(4), 789-794.

Ittyachen, A. M. (2009). Emerging infections in Kerala: A case of scrub typhus. National Medical Journal of India, 22(6), 333-334.

Ittyachen, A. M., Ramachandran, R., & John, P. (2017). Scrub typhus: A retrospective study from a tertiary care hospital in South India. Journal of Global Infectious Diseases, 9(3), 119-121.

Kamarasu, K., Malathi, M., Rajagopal, V., Subramani, K., Jagadeeshramasamy, D., & Mathai, E. (2007). Serological evidence for wide distribution of spotted fevers & typhus fever in Tamil Nadu. Indian Journal of Medical Research, 126(2), 128-130. https://doi.org/10.4103/0971-5916.33075

Kelly, D. J., Fuerst, P. A., Ching, W. M., & Richards, A. L. (2009). Scrub typhus: The geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clinical Infectious Diseases, 48(Suppl 3), S203-S230.

Kim, D. M., Kang, D. W., Kim, J. O., & Kim, H. L. (2017). Clinical and epidemiological characteristics of scrub typhus in South Korea, 2001–2013. Infection and Chemotherapy, 49(3), 188-193.

Kim, S. J., Chung, I. K., Koh, Y. S., Kim, S. Y., Park, C. G., Shin, H. S., & Lee, M. H. (2006). Clinical and laboratory findings associated with severe scrub typhus. BMC Infectious Diseases, 6(1), 108.

Lee, Y. H., Kim, D. M., Yun, N. R., Kim, S. W., Park, K. H., Song, H. J., & Oh, W. S. (2012). A case of scrub typhus presenting with meningoencephalitis and acute hearing loss. American Journal of Tropical Medicine and Hygiene, 87(5), 1012-1015.

Luce-Fedrow, A., Mullins, K., Kostik, N., Stenos, J., Jiang, J., & Richards, A. L. (2018). Strategies for detecting and identifying Orientia tsutsugamushi: A systematic review. Vector-Borne and Zoonotic Diseases, 18(2), 75-89.

Lyu, Y., Tian, L., Zhang, L., Dou, X., Wang, X., Li, W., et al. (2013). A case-control study of risk factors associated with scrub typhus infection in Beijing, China. PLoS ONE, 8(6), e63668. https://doi.org/10.1371/journal.pone.0063668

Mahajan, S. K. (2005). Scrub typhus. Journal of the Association of Physicians of India, 53, 954-958.

Mahajan, S. K., Rolain, J. M., Sankhyan, N., Kaushal, R. K., & Raoult, D. (2008). Pediatric scrub typhus in Indian Himalayas. Indian Journal of Pediatrics, 75(10), 947-949. https://doi.org/10.1007/s12098-008-0198-z

Mave, V., Mishra, A., Samant, R., Gupte, N., Deshpande, P., & Rodrigues, C. (2017). Scrub typhus in India: Risk factors and clinical profile. American Journal of Tropical Medicine and Hygiene, 97(1), 116-120.

Mittal, V., Thangaraj, J. W. V., Rose, W., & Verghese, V. P. (2012). Acute encephalitis syndrome complicating scrub typhus in a pediatric patient. Indian Pediatrics, 49(6), 487-488.

Narvencar, K. P., Rodrigues, S., Nevrekar, R. P., Dias, L., Dias, A., Vaz, M., & Mascarenhas, J. (2012). Scrub typhus in patients reporting with acute febrile illness at a tertiary health care institution in Goa. Indian Journal of Medical Research, 136(6), 1020-1024.

Omashekar, H. R., Moses, P. D., Pavithran, S., Mathew, L. G., Agarwal, I., Rolain, J. M., et al. (2006). Magnitude and features of scrub typhus and spotted fever in children in India. Journal of Tropical Pediatrics, 52(4), 228-229. https://doi.org/10.1093/tropej/fmi096

Prakash, J. A., Kavitha, M. L., Kumar, N. S., & Abraham, O. C. (2006). Scrub typhus: Clinical spectrum and diagnostic challenges in the tropics. Journal of Vector Borne Diseases, 43(3), 195-202.

Premaratna, R., Rajapakse, R. P. V. J., Chandrasena, T. G. A. N., Bandara, N. W. N. M. R., & de Silva, H. J. (2008). Scrub typhus among pediatric patients in Sri Lanka: Clinical presentation and diagnostic challenges. Transactions of the Royal Society of Tropical Medicine and Hygiene, 102(9), 868-870.

Rathi, N., & Rathi, A. (2010). Rickettsial infections: Indian perspective. Indian Pediatrics, 47(2), 157-164.

Rvencar, K. P., Rodrigues, S., Nevrekar, R. P., Dias, L., Dias, A., Vaz, M., et al. (2012). Scrub typhus in patients reporting with acute febrile illness at a tertiary health care institution in Goa. Indian Journal of Medical Research, 136(6), 1020-1024. https://doi.org/10.4103/0971-5916.200974

Sharma, A., Mahajan, S. K., Gupta, M. L., Kanga, A., & Sharma, V. (2005). Investigation of an outbreak of scrub typhus in the Himalayan region of India. Japanese Journal of Infectious Diseases, 58(4), 208-210.

Sharma, A., Mahajan, S. K., Gupta, M. L., Kanga, A., & Sharma, V. (2005). Investigation of an outbreak of scrub typhus in the Himalayan region of India. Japanese Journal of Infectious Diseases, 58(4), 208-210. https://doi.org/10.7883/yoken.58.208

Thai, E., Lloyd, G., Cherian, T., Abraham, O. C., & Cherian, A. M. (2001). Serological evidence for the continued presence of human rickettsioses in southern India. Annals of Tropical Medicine and Parasitology, 95(4), 395-398. https://doi.org/10.1080/00034983.2001.11813652

Trickman, D., Sheer, T., Salata, K., Hershey, J., Dasch, G., Kelly, D., et al. (1995). In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus. Antimicrobial Agents and Chemotherapy, 39(11), 2406-2410. https://doi.org/10.1128/AAC.39.11.2406

Varghese, G. M., Abraham, O. C., Mathai, D., Thomas, K., Aaron, R., Kavitha, M. L., et al. (2006). Scrub typhus among hospitalized patients with febrile illness in South India: Magnitude and clinical predictors. Journal of Infection, 52(1), 56-60. https://doi.org/10.1016/j.jinf.2005.02.001

Vivekanandan, M., Mani, A., Priya, Y. S., Singh, A. P., Jayakumar, S., & Purty, S. (2010). Outbreak of scrub typhus in Pondicherry. Journal of the Association of Physicians of India, 58, 24-28.

Xu, G., Walker, D. H., Jupiter, D., Melby, P. C., & Arcari, C. M. (2017). A review of the global epidemiology of scrub typhus. PLoS Neglected Tropical Diseases, 11(11), e0006062.

Zhang, M., Wang, X., Zhao, Z., & Chen, Y. (2016). Clinical characteristics and risk factors for severe scrub typhus in Shandong, Northern China. International Journal of Infectious Diseases, 43, 37-42.