Pregnancy Outcome in Relation to Treatment of Murine Typhus and Scrub Typhus Infection: A Fever Cohort and a Case Series Analysis

Abstract

BackgroundThere is a paucity of published reports on pregnancy outcome following scrub and murine typhus despite these infections being leading causes of undifferentiated fever in Asia. This study aimed to relate pregnancy outcome with treatment of typhus.Methodology/Principal FindingsData were analyzed from: i) pregnant women with a diagnosis of scrub and/or murine typhus from a fever cohort studies; ii) case series of published studies in PubMed using the search terms “scrub typhus” (ST), “murine typhus” (MT), “Orientia tsutsugamushi”, “Rickettsia tsutsugamushi”, “Rickettsia typhi”, “rickettsiae”, “typhus”, or “rickettsiosis”; and “pregnancy”, until February 2014 and iii) an unpublished case series. Fever clearance time (FCT) and pregnancy outcome (miscarriage and delivery) were compared to treatment. Poor neonatal outcome was a composite measure for pregnancies sustained to 28 weeks or more of gestation ending in stillbirth, preterm birth, or delivery of a growth restricted or low birth weight newborn.ResultsThere were 26 women in the fever cohort. MT and ST were clinically indistinguishable apart from two ST patients with eschars. FCTs (median [range] hours) were 25 [16–42] for azithromycin (n = 5), 34 [20–53] for antimalarials (n = 5) and 92 [6–260] for other antibiotics/supportive therapy (n = 16). There were 36.4% (8/22) with a poor neonatal outcome.In 18 years, 97 pregnancies were collated, 82 with known outcomes, including two maternal deaths. Proportions of miscarriage 17.3% (14/81) and poor neonatal outcomes 41.8% (28/67) were high, increasing with longer FCTs (p = 0.050, linear trend). Use of azithromycin was not significantly associated with improved neonatal outcomes (p = 0.610)ConclusionThe published ST and MT world literature amounts to less than 100 pregnancies due to under recognition and under diagnosis. Evidence supporting the most commonly used treatment, azithromycin, is weak. Collaborative, prospective clinical trials in pregnant women are urgently required to reduce the burden of adverse maternal and newborn outcomes and to determine the safety and efficacy of antimicrobial treatment.

Rickettsial Diseases: Not Uncommon Causes of Acute Febrile Illness in India

“…Mane et al detected higher SFG IgM positivity in females and higher IgM seropositivity for TG rickettsiae in housewives [13]. Clinically, McGready et al reported that scrub typhus and murine typhus are indistinguishable with a poor neonatal outcome in 36% of patients [16].…”

Underrecognized Arthropod-Borne and Zoonotic Pathogens in Northern and Northwestern Thailand: Serological Evidence and Opportunities for Awareness

“…Recent studies have established the impact of scrub typhus and murine typhus as causes of acute febrile illness in Thailand (Blacksell et al 2008, Thitivichianlert et al 2009, Ruang-Areerate et al 2011) and adjacent countries (Phongmany et al 2006, Chheng et al 2013, Mayxay et al 2013, McGready et al 2014). Although pathogens like Orientia tsutsugamushi and Rickettsia typhi are well described, only limited evidence is available for other zoonotic pathogens contributing to the burden of undifferentiated febrile illness.…”

Rocky Mountain Spotted Fever and Pregnancy: Four Cases from Sonora, Mexico

“…From a series of scrub typhus in 11 pregnant women, investigators noted an abortion rate of 18% that likely resulted from circulatory impairment relating to thrombotic occlusion or coagulopathy initiated from endothelial infection with Orientia tsutsugamushi. 25 However, thrombotic occlusive events are rare in RMSF, 26 and it is more likely that hypotensive shock could led to placental ischemia and fetal loss. In our series, infection with R. rickettsii precipitated the death of the fetus in for each of the three patients infected during the first trimester of pregnancy.…”