Rickettsioses are emerging, and re-emerging diseases caused by obligate intracellular arthropod-borne bacteria that infect humans and animals worldwide. Various rickettsiae such as Orientia, Rickettsia, Anaplasma and Ehrlichia have been circulated in companion, domesticated and wild animals through bites of infected ticks, fleas, lice or mites. This review summarizes the infections of rickettsiae, including the newly discovered regional species Rickettsia thailandii, Candidatus Rickettsia sepangensis, Candidatus Rickettsia johorensis, Candidatus Rickettsia laoensis, Candidatus Rickettsia mahosotii, Candidatus Rickettsia khammouanensis, Candidatus Anaplasma pangolinii, and other novel genotypes in vectors, humans and animals in Southeast Asia. Issues on some unidentified rickettsiae that elicit immune responses and production of antibodies that are cross-reactive with the antigens used are discussed. Knowledge gaps which required attention are also identified in this review.
Rickettsia felis (Rickettsiales: Rickettsiaceae) is an emergent human pathogen that causes febrile illnesses in various parts of the world. This study describes the identification and growth characteristics of a R. felis-like organism (designated as Rickettsia sp. TH2014) cultured from Ctenocephalides orientis fleas in rural Malaysia. In this study, culturing of rickettsiae from filtered triturated flea lysates was performed in Aedes albopictus C6/36 cells. Cytopathic effects were observed from one of the samples 4 d post-inoculation. Electron microscopy revealed actively replicating intracytosolic coccobacillary organisms in the rickettsia-infected cells. Sequence analysis of amplified citrate synthase (gltA) gene fragment shows complete match of the rickettsia with Rickettsia sp. Rf31 in Southeast Asia, and 'Candidatus Rickettsia senegalensis' strain PU01-02 in Africa. The whole-genome sequence of Rickettsia sp. TH2014 was determined and assembled. The estimated genome size and guanine + cytosine content of the rickettsia are 1.37 Mb and 32.9%, respectively. The high values of average nucleotide identity and tetra-nucleotide signature correlation index obtained from pairwise genome comparison study suggest the identification of the rickettsia as R. felis. The whole-genome single-nucleotide polymorphism analysis demonstrates close genetic relatedness of the rickettsia with R. felis and Rickettsia asemboensis. However, based on sequence analyses of rickettsial genes (16S rDNA, gltA, ompB, and sca4), Rickettsia sp. TH2014 is found to be distinct from R. felis and R. asemboensis. The sequence analyses reveal that Rickettsia sp. TH2014 is highly similar to 'Ca. Rickettsia senegalensis' detected in fleas from Africa, Asia, and North America. Further investigation to provide insights on pathogenic potential and transmission dynamics of the rickettsia is warranted.
Matched MeSH terms: Rickettsia/classification*; Rickettsia/genetics; Rickettsia/growth & development
Orientia tsutsugamushi, spotted fever group rickettsioses, and typhus group rickettsioses (TGR) are reemerging causes of acute febrile illness (AFI) in Southeast Asia. To further delineate extent, we enrolled patients >4 weeks of age with nonmalarial AFI in Sabah, Malaysia, during 2013-2015. We confirmed rickettsioses (past or acute, IgG titer >160) in 126/354 (36%) patients. We confirmed acute rickettsioses (paired 4-fold IgG titer rise to >160) in 38/145 (26%) patients: 23 O. tsutsugamushi, 9 spotted fever group, 4 TGR, 1 O. tsutsugamushi/spotted fever group, and 1 O. tsutsugamushi/TGR. PCR results were positive in 11/319 (3%) patients. Confirmed rickettsioses were more common in male adults; agricultural/plantation work and recent forest exposure were risk factors. Dizziness and acute hearing loss but not eschars were reported more often with acute rickettsioses. Only 2 patients were treated with doxycycline. Acute rickettsioses are common (>26%), underrecognized, and untreated etiologies of AFI in East Malaysia; empirical doxycycline treatment should be considered.
1. The Proteus strain XL, isolated by Dr. LIMA in the endemic area at Sao Paulo, represents the serological type of Proteus which corresponds to the local variety of typhus virus. 2. The Proteus strain "Muar", isolated in the Federated Malay States and described by MARTIN, antigenically corresponds to the virus of the local variety of tropical typhus (type XK). 3. The agglutinins for the two types OX19 and OX2, present in the serum from cases of "fie`vre boutonneuse" of the Mediterranean, are of the order of group agglutinins and are due to group antigens present in the virus. 4. It is suggested that the type of the main antigen of the virus of "fie`vre boutonneuse" will remain unknown until the corresponding type of Proteus has been isolated. 5. The relationship between the agglutinogenic and the immunogenic properties of different varieties of typhus virus is discussed. The established facts indicate that cross-immunity between typhus viruses is accompanied by identity of the serum reactions to Proteus X whereas failure to obtain cross-immunity coincides with dissimilarity in agglutination reactions. 6. The present knowledge of serological varieties of typhus, based on the occurrence in the patients' serum of main and group agglutinins for various types of Proteus X is presented in tabular form. It is suggested that serological methods, using various types of Proteus, are indispensable in the experimental study of the typhus group of viruses. 7. The technique of the agglutination reaction with Proteus X strains is discussed. The use of O variants and of the new Oxford standard suspension are recommended. 8. The isolation of Proteus X strains and the hypothesis of the transformation of Rickettsia into Proteus X are discussed and some technical details of the methods of cultivation are described. c 1933.
1. The results of the Weil-Felix reactions of sera from rabbits and monkeys inoculated with human virus or virus of laboratory strains of rural typhus, urban typhus or the tsutsugamushi disease are reported and discussed; as also are corresponding results in rabbits inoculated with the virus of two strains of tropical typhus recovered from wild rats.
2. Instances are given of a change in type of antibody response; in particular, an experience is described in which the agglutinogenic properties of a virus of a tropical typhus strain underwent a temporary change, while the immunogenic properties remained unchanged.
(1) Two strains of tropical typhus have been isolated from wild rats trapped in endemic areas.
(2) Both were isolated and maintained in guinea-pigs.
(3) One could be isolated in rabbits by the intra-ocular inoculation of virus, and maintained thus indefinitely. The features of this infection appeared to be identical with corresponding infections obtained with the viruses of rural typhus and the tsutsugamushi disease of human origin. Repeated attempts to isolate the other rat strain in rabbits in the same manner failed.
(4) Rickettsia were found with ease and in abundance in infected material from guinea-pigs infected with either strain, and from rabbits infected with the one-strain.
(5) The sera of rabbits infected with the two rat strains gave positive Weil-Felix reactions of significant titre.
(6) Cross-immunity tests in rabbits between one rat strain and six strains of huinan origin of rural typhus and tsutsugamushi showed a cross-immunity to exist, complete in five strains and partial in the sixth strain.
(7) A concomitant infection with sodoku was present in the guinea-pigs of botlh strains ; although this may have modified the clinical signs, the infection by a typhus virus could be determined by four decisive criteria.
(8) The conclusion is drawn that the murine origin of the virus of the rural typhus-tsutsugamuslhi group of diseases is now firmly established.
Limited information is available on the etiological agents of rickettsioses in southeast Asia. Herein, we report the molecular investigation of rickettsioses in four patients attending a teaching hospital in Malaysia. DNA of Rickettsia sp. RF2125, Rickettsia typhi, and a rickettsia closely related to Rickettsia raoultii was detected in the blood samples of the patients. Spotted fever group rickettsioses and murine typhus should be considered in the diagnosis of patients with nonspecific febrile illness in this region.
Fleas of the genus Ctenocephalides serve as vectors for a number of rickettsial zoonoses, including Rickettsia felis. There are currently no published reports of the presence and distribution of R. felis in India, however, the ubiquitous distribution of its vector Ctenocephalides felis, makes it possible that the pathogen is endemic to the region. This study investigates the occurrence of Rickettsia spp. infection in various subspecies of C. felis infesting dogs from urban areas of Mumbai, Delhi and Rajasthan in India.
Rickettsioses are emerging zoonotic diseases reported worldwide. In spite of the serological evidence of spotted fever group rickettsioses in febrile patients in Malaysia, limited studies have been conducted to identify the animal reservoirs and vectors of rickettsioses. This study investigated the presence of rickettsiae in the tissue homogenates of 95 wild rats and 589 animal ectoparasites. Using PCR assays targeting the citrate synthase gene (gltA), rickettsial DNA was detected in the tissue homogenates of 13 (13.7%) wild rats. Sequence analysis of the gltA amplicons showed 98.6-100% similarity with those of Rickettsia honei/R. conorii/R. raoultii (Rickettsiales: Rickettsiaceae). Sequence analysis of outer membrane protein A gene (ompA) identified Rickettsia sp. TCM1 strain from two rats. No rickettsia was detected from Laelaps mites, Rhipicephalus sanguineus and Haemaphysalis bispinosa ticks, and Felicola subrostratus lice in this study. R. felis was identified from 32.2% of 177 Ctenocephalides felis fleas. Sequence analysis of the gltA amplicons revealed two genotypes of R. felis (Rf31 and RF2125) in the fleas. As wild rats and cat fleas play an important role in the enzoonotic maintenance of rickettsiae, control of rodent and flea populations may be able to reduce transmission of rickettsioses in the local setting.
Isolation of rickettsiae from patients' blood samples and organ samples of wild rodents from areas with high seroprevalence of rickettsial infections was attempted using cell culture assay and animal passages. L929 mouse fibroblast cells grown in 24 well tissue culture plate were inoculated with buffy coat of febrile patients and examined for the growth of rickettsiae by Giemsa, Gimenez staining and direct immunofluorescence assay. No rickettsiae were isolated from 48 patients' blood samples. No symptomatic infections were noted in mice or guinea pigs infected with 50 organ samples of wild rodents. There was no rickettsial DNA amplified from these samples using various PCR detection systems for Orientia tsutsugamushi, typhus and spotted fever group rickettsiae.
1. A strain of the urban form of tropical typhus has been established in guinea-pigs, and maintained in them for more than one hundred generations. The history and characteristics of the strain are given. The clinical criteria of infection are febrile and scrotal reactions.
2. Methods of demonstration of Rickettsia in material from infected guinea-pigs and rabbits are described. In morphology, distribution and staining characteristics these Rickettsia do not appear to differ from R. prowazeki.
3. The infection of rabbits by intra-ocular inoculation of virus has met with only partial success ; the strains rapidly lose virulence, and do not survive beyond the third generation. The results are closely similar to those reported by Nagayo et al., in corresponding infections of rabbits with the virus of typhus exanthematicus, and to those obtained by the authors in corresponding infections with a strain of Rocky Mountain spotted fever.
4. Infection of white rats has been readily secured, and has been of the "inapparente" form.
5. Two monkeys, inoculated intradermally with infected material, showed a mild general reaction only; no lesion developed at the site of inoculation.
6. The results of the Weil-Felix reactions of sera from rabbits and monkeys convalescent from the infection are summarized. Agglutination is of the OX19 type of Proteus X strains, never of the OXK type.
7. The experimental data obtained indicate that the guinea-pig is the laboratory animal of choice for the study of the urban form of tropical typhus.