Nationwide prevalence of Rickettsia felis infections in patients with febrile illness in Bangladesh.

From July 2015 to December 2016, the presence of rickettsial pathogens was investigated for 414 patients with unknown fever in eight places in all the divisions of Bangladesh. Rickettsia felis was identified in blood samples from all the regions (overall detection rate, 19.6%), suggesting nationwide prevalence of R. felis infections.

Rickettsia felis is an obligate intracellular bacterium belonging to the transitional group Rickettsiae, and causes febrile disease known as cat-flea typhus [1], [2], [3]. Transmission of R. felis to humans is mediated by cat fleas from an unknown reservoir; mosquitoes are also suspected of being potential vectors [2], [4]. Since the first report in the USA in 1994 [5], R. felis infection has been spreading as an emerging infectious disease globally, but frequencies of genetically confirmed cases were very low in Asian countries [1], [2], [6]. However, in our previous studies in central-northern Bangladesh (Mymensingh), R. felis DNA was identified in blood samples from febrile patients at a high rate (46% in 2012/13 [7], 42% in 2013/14 [8]), which indicated the significance of studying the prevalence of R. felis infections in other parts of Bangladesh. Hence, we conducted an extended cross-sectional study covering all regions in Bangladesh, to determine the overall prevalence of R. felis infection, and to explore any difference in its prevalence depending on region.

A total of 414 blood samples from febrile patients (sex ratio, 0.89; age range, 7 months to 73 years) (see Supplementary material, Tables S1 and S2) were obtained in the collaborative medical institutions located in all eight divisions in Bangladesh (Dhaka, Rangpur, Rajshahi, Mymensingh, Sylhet, Khulna, Barisal and Chittagong) (Fig. 1) during a period from July 2015 to December 2016. Inclusion criteria for patients were the same as that employed in our previous study [7], including the positive Weil–Felix test (≥1: 160 titre) (see Supplementary material, Table S3). This study was approved by the Institutional Review Board, and informed consent was taken from individual patients (or guardians). Through nested PCR and sequencing of the PCR product as described previously [5], [7], the 17-kDa antigen gene of R. felis (strain URRWXCa12, GenBank Accession no. CP000053) was identified in 81 samples, representing an overall detection rate of 19.6%. Among them, 26 and 15 samples were PCR positive for 16S rRNA gene and gltA, respectively, showing identical sequences to those of R. felis strain URRWXCa12. Detection rates of R. felis were different depending on the study site: Dhaka, 24%; Rangpur, 36%; Rajshahi, 30%; Mymensingh, 20%; Sylhet, 5%; Khulna, 3%; Barisal, 24%; Chittagong, 10% (Fig. 1). Rickettsia typhi was identified in only one sample, from Barisal, and had 17 kDa antigen gene, 16S rRNA gene and gltA sequences identical to those of R. typhi strain Wilmington (GenBank Accession no. AE017197). Among all the Rickettsia-positive patients (age and sex distribution; see Supplementary material, Tables S4 and S5), OX-2 showed the highest positive rate (74%; solely OX-2-positive, 50%) in the Weil–Felix test (see Supplementary material, Table S6). None of these patients had malaria, typhoid fever or brucellosis, whereas dengue and chikungunya had not been tested.

Fig. 1

Geographical locations of the eight study sites in Bangladesh. Height of filled bar represents relative value of Rickettsia felis positive rate (%) as shown. Numbers of R. felis positive samples / total samples examined are indicated in parentheses.

The present study revealed the nationwide prevalence of R. felis infections in Bangladesh. It was noted that higher detection rates of R. felis were observed in central regions including Dhaka, and northwest regions (Rangpur and Rajshahi), although sufficient numbers of samples were not available in some study sites. Recent serological studies in Bangladesh also described higher prevalence of R. typhi in Dhaka and Comilla (eastern district) [9], and spotted fever group rickettsiosis and scrub typhus in Rajshahi [10]. Accordingly, it is suggested that the geographical distribution of R. felis in Bangladesh may be similar to those of other rickettsial pathogens. Apparent difference in the prevalence of R. felis by study site may be related to number of cats/dogs associated with population and its density in individual divisions, although a definite reservoir of this Rickettsia has not yet been established. Recently, detection of R. felis DNA was reported in the Anopheles gambiae mosquito [4], and also in blood and skin of healthy individuals [6], [11], [12], suggesting a capability of R. felis to colonize or infect various living organisms. Therefore, further studies are necessary to determine definite pathogenic significance of R. felis DNA in humans, and also to explore the potential reservoir and vector of this bacterium, in a putative endemic area such as Bangladesh.

Transparency declaration

The authors have no conflicts of interest to declare.