Phylogeography of Rickettsia rickettsii Genotypes Associated with Fatal Rocky Mountain Spotted Fever

Abstract

Abstract. Rocky Mountain spotted fever (RMSF), a tick-borne zoonosis caused by Rickettsia rickettsii, is among the deadliest of all infectious diseases. To identify the distribution of various genotypes of R. rickettsii associated with fatal RMSF, we applied molecular typing methods to samples of DNA extracted from formalin-fixed, paraffin-embedded tissue specimens obtained at autopsy from 103 case-patients from seven countries who died of RMSF. Complete sequences of one or more intergenic regions were amplified from tissues of 30 (29%) case-patients and revealed a distribution of genotypes consisting of four distinct clades, including the Hlp clade, regarded previously as a non-pathogenic strain of R. rickettsii. Distinct phylogeographic patterns were identified when composite case-patient and reference strain data were mapped to the state and country of origin. The phylogeography of R. rickettsii is likely determined by ecological and environmental factors that exist independently of the distribution of a particular tick vector.

Genetic Identification of Rickettsial Isolates from Fatal Cases of Brazilian Spotted Fever and Comparison with Rickettsia rickettsii Isolates from the American Continents

“…While our results of no polymorphisms among Central/ South American isolates was biased because most of these isolates were derived from fatal cases, a recent study reported the same clade distribution as shown in our Fig. 1 when analyzing the intergenic regions of R. rickettsii derived from fatal cases from the United States, Mexico, and Central/South America (21).…”

“…A more divergent clade was composed of North American isolates that have been ecologically associated with the ticks Dermacentor variabilis and R. sanguineus. As reported in previous studies (10,(19)(20)(21), the North American isolates of R. rickettsii presented relatively high polymorphism compared to that of the Central/South American isolates. Our concatenated analysis showed the formation of 3 North American haplotypes (A, B, and C), each associated with a different tick species (Fig.…”

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States

“…The acquisition and evaluation of clinical samples previously believed suboptimal for a particular molecular method are now more frequently being considered as important sources of diagnostic information. For example, improved nucleic acid extraction technology has facilitated recovery of rickettsial DNA from some types of formalin-fixed, paraffin-embedded skin biopsies or autopsy tissues to allow species-specific PCR and sequence analysis (292,293). Testing of CSF by PCR assays has successfully identified E. chaffeensis (135,159,294).…”

“…In cases of ehrlichiosis or anaplasmosis in which bone marrow biopsies are performed as part of the investigation of cytopenias, immunostaining of bone marrow biopsy specimens can reveal the diagnosis (156,160). Immunostaining can be particularly useful for diagnosing fatal tickborne rickettsial diseases in tissue specimens from patients who had not developed diagnostic levels of antibodies before death (16,141,293,300). Immunostaining methods are most likely to reveal organisms in patients before or within the first 48 hours after initiating appropriate antibacterial therapy.…”

Febre maculosa no Brasil: estudo da mortalidade para a vigilância epidemiológica

“…Atualmente, o método mais utilizado no diagnóstico é a sorologia, apesar de os anticorpos IgM e IgG aparecerem somente após 7-10 dias do início da doença 19,20 . Existem estudos demonstrando a existência de variações intergênicas entre diferentes isolados de R. rickettsii associadas à virulência 21 , reforçando a importância não somente da identificação mas também da caracterização para o entendimento da doença.…”