1. Christian Medical College, Vellore, India
Scrub typhus in India: emerging insights, and future challenges and opportunities
George M. Varghese, Paul A. Trowbridge, John A. J. Prakash
Department of Infectious Diseases
Christian Medical College, Vellore, India

2. Unusual Acute Febrile Illness in 1990s
Acute febrile illness with multiple organ involvement
Hepatitis with or without jaundice
Pneumonitis ARDS
Aseptic meningitis
Common etiologies ruled out
Eschar in the groin
Varghese et al. CMC Vellore. Scrub typhus in India

3. Initial Report of Re-emergence
In , 28 patients were clinically and serologically confirmed to have scrub typhus
Skin manifestations only in less than a quarter
Multi-organ involvement in almost half
>80% had LFT abnormality
Weil-Felix test neither sensitive nor specific
Testing four different serotypes (Gilliam, Karp, Kato, and Kawasaki) which are antigenically distinct is important
Case fatality 11%
Varghese et al. CMC Vellore. Scrub typhus in India
Mathai EM etal. Ann. N.Y. Acad. Sci.2003

4. Varghese et al. CMC Vellore. Scrub typhus in India
A mite-borne, zoontoic bacterial infection
Causative agent: Orientia tsutsugamushi
Vector: chiggers (larva of trombiculid mite - Leptotrombidium)
Reservoir: chiggers & rats
Normal cycle: rat to mite to rat
Transovarian transmission
Humans incidentally infected
Varghese et al. CMC Vellore. Scrub typhus in India

5. When should scrub typhus be suspected?
Undifferentiated febrile illness with:
Pathognomonic eschar
Evidence of multisystem involvement, especially with:
- Transaminase elevation
- Thrombocytopenia
- Leukocytosis
Varghese et al. J Infection 2006; 52:56–60
Varghese et al. CMC Vellore. Scrub typhus in India

6. Varghese et al. CMC Vellore. Scrub typhus in India
Major Gap & Objectives
Major gap: Grossly under recognized; burden and pattern of scrub typhus have not been adequately documented in India
Objective: Describe the public health risk, spread, and severity of this disease, which can serve as a basis for formulating policy
Varghese et al. CMC Vellore. Scrub typhus in India

7. Varghese et al. CMC Vellore. Scrub typhus in India
Methods
Assessment of disease burden: reviewed medical literature, Integrated Disease Surveillance Programme (IDSP), and rickettsial infection database at CMC, Vellore
Cross-sectional, population-based survey in Vellore district: estimate community seroprevalence of scrub (IgG and IgM)
Case control study: assess risk factors for acquiring the disease in the community
Severity of disease and current management options assessed among patients admitted to CMC
Varghese et al. CMC Vellore. Scrub typhus in India

8. Reported scrub typhus cases: 2010-14
6649 cases of scrub typhus have been documented in 24 states
Tamil Nadu, Karnataka, Himachal Pradesh, Rajasthan and Assam account for at least 300 cases each
Out of 3019 cases from CMC’s database, only 451 are published during this period
Varghese et al. CMC Vellore. Scrub typhus in India

9. Community prevalence of scrub typhus
Clustered sample design
721 participants from Vellore district; 60.6% from rural and 39.4% from semi-urban region
62.6% female, 37.4% male; mean age 50.6 years
Prior scrub typhus exposure in 31.3% using serological tests
IgG + in 30.5% and IgM in 1.9%. Positivity by both in 1.1%
Varghese et al. CMC Vellore. Scrub typhus in India

10. Risk factors & seasonality
Case–control study (128 cases and 132 age- and sex-matched controls from the same village
Agricultural laborers (OR 1.79, 95% CI 1.01–3.15)
Bushes or shrubs around home (OR 1.95, 95% CI 1.08 – 3.53)
Clothing: upper part of the body uncovered (OR 4.23, 95% CI )
Seasonality: highest numbers of cases observed in the cooler months of the year, i.e. September to January
Varghese et al. CMC Vellore. Scrub typhus in India

11. Severity, Complications & Treatment
Multiorgan dysfunction syndrome in 34% majority of whom requiring ventilatory support
Acute respiratory distress syndrome in 33%
Hypotension requiring ionotropic support in 23%
Renal dysfunction in 18%
Case fatality of 9%
Doxycycline is the drug used in majority and is very effective
Unavailability of IV doxycycline until now
Azithromycin is a reasonable alternative used in combination with oral Doxy or alone
Varghese et al. CMC Vellore. Scrub typhus in India

12. Varghese et al. CMC Vellore. Scrub typhus in India
Conclusion
Scrub typhus is a significant public health threat in India, yet it is under-recognised and grossly under-diagnosed
Doxyxcycline is the drug of choice
Azithromycin is a good alternative
Unavailability of IV doxycycline to treat severe infection necessitates urgent advocacy
Information and advocacy are needed for investing in surveillance, prevention and detection, as well as appropriate management strategies
Varghese et al. CMC Vellore. Scrub typhus in India