An outbreak of scrub typhus in military personnel despite protocols for antibiotic prophylaxis: doxycycline resistance excluded by a quantitative PCR-based susceptibility assay

Abstract

Scrub typhus is caused by the obligate intracellular bacterium Orientia tsutsugamushi and is endemic to many countries in the Asia-Pacific region, including tropical Australia. We describe a recent large outbreak amongst military personnel in north Queensland. A total of 45 clinical cases were identified (36% of all potentially exposed individuals). This occurred despite existing military protocols stipulating the provision of doxycycline prophylaxis. Doxycycline resistance in O. tsutsugamushi has been described in South-East Asia, but not Australia. In one case, O. tsutsugamushi was cultured from eschar tissue and blood. Using quantitative real-time PCR to determine susceptibility to doxycycline for the outbreak strain, a minimum inhibitory concentration (MIC) of ≤0.04 μg/mL was found, indicating susceptibility to this agent. It seems most probable that failure to adhere to adequate prophylaxis over the duration of the military exercise accounted for the large number of cases encountered rather than doxycycline resistance.

A Review of Scrub Typhus (Orientia tsutsugamushi and Related Organisms): Then, Now, and Tomorrow

“…Additionally, the widespread use of Orientia- resistant beta-lactam antimicrobials coincided with the increased incidences of scrub typhus [ 101 ]. In this review, we have documented human outbreaks of scrub typhus from 2007 to the present, 2017 ( Table 1 ) [ 19 , 95 , 99 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ].…”

“…The outbreak investigations used clinical diagnosis coupled with laboratory findings of one or more of the serological diagnostic tests such as Weil-Felix (WF), rapid immunochromatographic test (RICT), immunofluorescence assays, molecular tools such as polymerase chain reaction (PCR), and occasionally, culture of Orientia sp. from the outbreak cases [ 102 ]. For some of the outbreak investigations, other causes of undifferentiated febrile illness, such as dengue, malaria, leptospirosis, and typhoid fevers [ 104 ], were ruled out.…”

“…In a recent outbreak that occurred in Nepal, involving 23 cases, large-scale destruction of human habitation, rendering people homeless, was identified as the risk factor [ 119 ]. In Australia, the most recent outbreak occurred in April 2011, among 124 infantry soldiers and support elements deployed to the Cowley Beach Training Area in northern Queensland, Australia [ 102 ]. The cases were determined by demonstration of a fourfold rise in IgG antibody titer to O. tsutsugamushi by serology, a positive by PCR, or obtaining a positive culture from clinical specimens.…”

Orientia tsutsugamushi Is Highly Susceptible to the RNA Polymerase Switch Region Inhibitor Corallopyronin A In Vitro and In Vivo

“…FISH stains ribosomes, and the absence of a FISH stain indicates absence of significant bacterial metabolic activity. For accurate determination of the MIC, we used the highly sensitive traD quantitative real-time PCR (qPCR) for quantification of O. tsutsugamushi DNA (23), similar to previously published qPCR-based protocols for susceptibility testing of rickettsiae to antimicrobial agents (30,31). The MIC of CorA was 0.0078 g/ml for O. tsutsugamushi.…”

Outer Membrane Protein A Conservation among <em>Orientia tsutsugamushi</em> Isolates Suggests Its Potential as a Protective Antigen and Diagnostic Target

“…Mortality rates range from less than 1.4% to approximately 70%, depending on prior patient immune status, whether proper antibiotic treatment is initiated in a timely manner, and the bacterial strain causing the infection [1,[7][8][9]. Recent outbreaks in the Asia-Pacific [10][11][12][13][14][15][16][17][18][19][20][21][22][23], as well evidence for scrub typhus or scrub typhus-like infections in Cameroon, Kenya, Congo, Djibouti, Tanzania, Chile, and Peru signify these illnesses as both emerging and reemerging global diseases of global importance [24][25][26][27][28][29][30].…”