Estimating the burden of scrub typhus: A systematic review

Abstract

BackgroundScrub typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub typhus remains poorly known.MethodsWe systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub typhus since the year 2000.FindingsIn prospective fever studies from Asia, scrub typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%–27.9% (median 22.2% IQR 18.6–25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub typhus. Limited evidence suggests high mortality in complicated scrub typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes.InterpretationScrub typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8–10 years from countries with an established surveillance system. A wider distribution of scrub typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches.

Confirmation of local transmission of Orientia tsutsugamushi during scrub typhus outbreaks in Nepal

“…Despite the high fatality (6%) observed during the first wave of scrub typhus in Nepal in 2015, CFR successfully declined to approximately 1% in 2017 which is quite encouraging for the disease control program. This rate is within the wide range of reported fatality (median, 6% and 1.4% for untreated and treated cases, respectively) [1]. The government initiatives that perhaps lowered down the CFR [10,11] include distribution of guidelines, public awareness, and training and orientation of physicians/ health workers for prompt treatment of scrub typhus with the available drugs (doxycycline, azithromycin, chloramphenicol and ciprofloxacin or their appropriate combinations).…”

“…Our study shows scrub typhus as an emerging public health problem in Nepal with several outbreaks since 2015. Scrub typhus is a severely understudied neglected tropical disease and a leading cause of undifferentiated treatable fever in Asia [1,16]. This study uncovered a firmly This has resulted in a significant lack of understanding when it comes to epidemiological features, treatment response and severity, and its ecological niche.…”

“…The government initiatives that perhaps lowered down the CFR [10,11] include distribution of guidelines, public awareness, and training and orientation of physicians/ health workers for prompt treatment of scrub typhus with the available drugs (doxycycline, azithromycin, chloramphenicol and ciprofloxacin or their appropriate combinations). Infection with resistant or reduced drugsusceptible O. tsutsugamushi strains often yield very high mortality (up to 24%), miscarriage and poor neonatal outcomes [1]; it may be speculated that these strains are yet to emerge in Nepal. Since there was no definitive evidence for this, a careful monitoring for drug resistance (including potential resistance genes) should be in place.…”

“…Scrub typhus is a vector-borne acute febrile illness caused by Orientia tsutsugamushi and transmitted to humans and rodents by infected chigger mites (larval stage of Trombiculidae mites) [1,2]. Historically, scrub typhus was endemic in Asia, Australia and islands in the Indian and Pacific Oceans known as the "tsutsugamushi triangle" [1]. However, there have been recent reports of scrub typhus from Africa, France, the Middle East, and South America suggesting the disease is no longer restricted to this triangle [2].…”

Assessment and initial management of acute undifferentiated fever in tropical and subtropical regions

“…Untreated, case fatality ratios range from 2.49% in enteric fever,75 0-39.7% in icteric leptospirosis,76 and 0-33% in scrub typhus 77…”