Case Report: Co-Infection of Rickettsia rickettsii and Streptococcus pyogenes: Is Fatal Rocky Mountain Spotted Fever Underdiagnosed?

Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A β-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections.     

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

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.     

Absence of Rickettsia rickettsii and Occurrence of Other Spotted Fever Group Rickettsiae in Ticks from Tennessee

Rocky Mountain spotted fever (RMSF) is the most common tick-borne illness in Tennessee. Little is known about the occurrence of R. rickettsii, the causative agent, in ticks in Tennessee. To better understand the prevalence and distribution of rickettsial agents in ticks, we tested 1,265 Amblyomma, Dermacentor, and Ixodes adult and nymphal ticks. Additionally, we tested 231 Amblyomma americanum larvae. Ticks were collected from 49 counties from humans, wild animals, domestic canines, and flannel drags. Spotted fever group rickettsiae (SFGR) DNA was detected by polymerase chain reaction (PCR) in 32% of adult and nymphal ticks. A total minimum infection rate of 85.63 was found in larval pools tested. Three rickettsial species, Rickettsia montana, Rickettsia amblyommii, and Rickettsia cooleyi were identified by molecular analysis. Rickettsia rickettsii was not detected. This study suggests that some RMSF cases reported in Tennessee may be caused by cross-reactivity with other SFGR antigenically related to R. rickettsii.     

Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME)?

Background  

Human monocytic ehrlichiosis (HME) and Rocky Mountain spotted fever (RMSF) are caused by Ehrlichia chaffeensis and Rickettsia rickettsii, respectively. The pathogenesis of RMSF relates to rickettsia-mediated vascular injury, but it is unclear in HME.     

Rocky Mountain Spotted Fever in the United States, 2000–2007: Interpreting Contemporary Increases in Incidence

Rocky Mountain spotted fever (RMSF), a potentially fatal tick-borne infection caused by Rickettsia rickettsii, is considered a notifiable condition in the United States. During 2000 to 2007, the annual reported incidence of RMSF increased from 1.7 to 7 cases per million persons from 2000 to 2007, the highest rate ever recorded. American Indians had a significantly higher incidence than other race groups. Children 5–9 years of age appeared at highest risk for fatal outcome. Enzyme-linked immunosorbent assays became more widely available beginning in 2004 and were used to diagnose 38% of cases during 2005–2007. The proportion of cases classified as confirmed RMSF decreased from 15% in 2000 to 4% in 2007. Concomitantly, case fatality decreased from 2.2% to 0.3%. The decreasing proportion of confirmed cases and cases with fatal outcome suggests that changes in diagnostic and surveillance practices may be influencing the observed increase in reported incidence rates.     

Infection prevalences of common tick-borne pathogens in adult lone star ticks (Amblyomma americanum) and American dog ticks (Dermacentor variabilis) in Kentucky

Rocky Mountain spotted fever, Lyme disease, and ehrlichiosis are tick-borne diseases that are reported annually in Kentucky. We conducted a survey to describe infection prevalence of tick-borne pathogens in Amblyomma americanum and Dermacentor variabilis ticks collected in Kentucky. During 2007-2008, we collected 287 ticks (179 D. variabilis and 108 A. americanum) from canine, feral hog, horse, raccoon, white-tailed deer, and human hosts in six counties in Kentucky. Ticks were screened for Rickettsia spp., Borrelia spp., and Ehrlichia spp. by using polymerase chain reaction. Forty-one (14.3%) ticks (31 A. americanum and 10 D. variabilis) were polymerase chain reaction-positive for a Rickettsia spp. Fourteen (4.9%) ticks (6 A. americanum and 8 D. variabilis) were positive for E. chaffeensis, and 4 A. americanum (1.4%) were positive for E. ewingii. One (0.4%) A. americanum was positive for Borrelia lonestari. Although Rocky Mountain spotted fever is diagnosed in Kentucky, no R. rickettsii was found in ticks in this study.     

Tick-borne diseases in the United States: Rocky Mountain spotted fever and Colorado tick fever. A review.

The historical, clinical, ecological, and epidemiological features of Rocky Mountain spotted fever and Colorado tick fever, the two important tick-borne diseases in the United States, are reviewed. Rocky Mountain spotted fever, once considered a disease of the past, has again become a measurable public health problem. Its nationwide incidence has steadily increased since 1960 and has reached record proportions in 1976. The various factors responsible for this trend as well as for the mortality rates, which in spite of availability of effective antibiotics ranges from 5 to 10%, are discussed. Education of the public about ticks and their potential role as vectors of Rickettsia rickettsii and/or Colorado tick fever virus, and about the clinical manifestations of Rocky Mountain spotted fever, is considered the best means for preventing high incidence and mortality from these diseases.     

A fatal urban case of rocky mountain spotted Fever presenting an eschar in san jose, costa rica

Abstract. This study reports the first urban human case of Rocky Mountain spotted fever caused by Rickettsia rickettsii, in Costa Rica. An 8-year-old female who died at the National Children's Hospital 4 days after her admission, and an important and significant observation was the presence of an "eschar" (tache noire), which is typical in some rickettsial infections but not frequent in Rocky Mountain spotted fever cases.     

Investigation ofRickettsia conorii antibodies in the Antalya area

Summary Mediterranean spotted fever, caused byRickettsia conorii, is a tick-borne infection. Serum samples for screeningR. conorii antibodies of professionally exposed persons in the Antalya region, on the Mediterranean coast of Turkey, were analyzed.R. conorii IgG antibodies were detected in 13 of 98 (13.3%) serum samples. Mediterranean spotted fever antibodies were found to be positive in 9.4% of the men and 15.2% of the women (a total of 13 cases). Only three cases had a history of fever and rash.     

High rates of Rickettsia parkeri infection in Gulf Coast ticks (Amblyomma maculatum) and identification of "Candidatus Rickettsia andeanae" from Fairfax County, Virginia

The Gulf Coast tick, Amblyomma maculatum, is a vector of Rickettsia parkeri, a recently identified human pathogen that causes a disease with clinical symptoms that resemble a mild form of Rocky Mountain spotted fever. Because the prevalence of R. parkeri infection in geographically distinct populations of A. maculatum is not fully understood, A. maculatum specimens collected as part of a tick and pathogen surveillance system in Fairfax County, Virginia, were screened to determine pathogen infection rates. Overall, R. parkeri was found in 41.4% of the A. maculatum that were screened. Additionally, the novel spotted fever group Rickettsia sp., tentatively named "Candidatus Rickettsia andeanae," was observed for the first time in Virginia.     

Rocky Mountain spotted fever in Argentina

We describe the first molecular confirmation of Rickettsia rickettsii, the cause of Rocky Mountain spotted fever (RMSF), from a tick vector, Amblyomma cajennense, and from a cluster of fatal spotted fever cases in Argentina. Questing A. cajennense ticks were collected at or near sites of presumed or confirmed cases of spotted fever rickettsiosis in Jujuy Province and evaluated by polymerase chain reaction assays for spotted fever group rickettsiae. DNA of R. rickettsii was amplified from a pool of A. cajennense ticks and from tissues of one of four patients who died during 2003-2004 after illnesses characterized by high fever, severe headache, myalgias, and petechial rash. The diagnosis of spotted fever rickettsiosis was confirmed in the other patients by indirect immunofluorescence antibody and immunohistochemical staining techniques. These findings show the existence of RMSF in Argentina and emphasize the need for clinicians throughout the Americas to consider RMSF in patients with febrile rash illnesses.     

Infection of human vascular endothelial cells by Rickettsia rickettsii

Rocky Mountain spotted fever is caused by Rickettsia rickettsii, an obligate intracellular bacterial parasite. The organism primarily attacks endothelial cells and occasionally attacks smooth-muscle cells of small blood vessels. An effective means of examining host-parasite interaction in Rocky Mountain spotted fever would be to use an in vitro model system with a host-cell type that is similar in structure and function to the putative target cell in human infections. Because human umbilical-vein endothelial cells in culture retain many, if not all, of their characteristic properties in vivo and because they also share many properties of capillary endothelium, the use of this endothelial cell system is appropriate in the study of the interaction between R rickettsii and the cell that is principally parasitized in humans. Uptake by umbilical-vein endothelial-cell cultures of R rickettsii is dose dependent. The organism replicates in both the nucleus and cytoplasm of infected cells and exhibits early cell-to-cell spread without detectable host-cell injury.     

Ecological study of Rocky Mountain spotted fever in Costa Rica

Since Rocky Mountain spotted fever (RMSF) was recognized in Costa Rica, ecological studies have been undertaken to discern its distribution and the natural cycle of Rickettsia rickettsii. The population of ticks parasitizing animals and vegetation was scarce. Rickettsiae were not isolated from pools of ticks nor from spleens of the animals studied. However, the active circulation of rickettsiae was evidenced through the demonstration of spotted fever group antibodies in humans, dogs, and wild rabbits. These findings concur with those in a number of fatal human cases as well as with the isolation of R. rickettsii from wild rabbit ticks.     

Rickettsia rickettsii and Rickettsia montana from Ixodid ticks in Connecticut

Dermacentor variabilis, infected with spotted fever group rickettsiae, parasitized 8 of 70 raccoons captured in Newtown, Connecticut. The spotted fever agent, Rickettsia rickettsii, was isolated and identified from 4 adult D. variabilis and from 1 nymphal Ixodes texanus removed from raccoons. This verifies the presence of this etiologic agent in ticks in an area where 6 people had clinical signs and symptoms of Rocky Mountain spotted fever (RMSF) and antibodies to R. rickettsii. These are the first isolations of R. rickettsii from D. variabilis in southern New England and the first identified rickettsiae from I. texanus. No rickettsiae were isolated from Ixodes muris or I. cookei. Rickettsia montana was recovered in Vero cell culture from a D. variabilis collected in East Haddam, Connecticut where RMSF is not known to be prevalent.     

Detection of Rickettsia parkeri and Candidatus Rickettsia andeanae in Amblyomma maculatum Gulf Coast ticks collected from humans in the United States

Rickettsia parkeri, a spotted fever group (SFG) rickettsia recently found to be pathogenic to humans, causes an eschar-associated febrile illness. The R. parkeri rickettsiosis, Tidewater spotted fever, has been misdiagnosed as Rocky Mountain spotted fever due to serologic cross reactivity and the lack of specific diagnostic methods. Candidatus Rickettsia andeanae, also a SFG rickettsia, is a recently described agent of unknown pathogenicity originally identified in ticks collected from domestic animals during a fever outbreak investigation in northern Peru. Among 37 Amblyomma maculatum (collected from humans (n=35) and questing (n=2)) obtained from the southern United States during 2000-2009, nine and four A. maculatum nucleic acid preparations were found positive for R. parkeri and Candidatus R. andeanae, respectively, by newly developed genus- and species-specific quantitative real-time polymerase chain reaction assays. In addition Rickettsia felis was found in two A. maculatum nucleic acid preparations.     

Reactogenicity, immunogenicity, and efficacy of a chick embryo cell-derived vaccine for Rocky Mountain spotted fever

A new formalin-inactivated vaccine prepared by sucrose density gradient centrifugation of tissue culture-grown Rickettsia rickettsii was evaluated for safety and immunogenicity in a placebo-controlled, double-blind study. Most of the 52 seronegative adult vaccinees, 88% after the first and 66% after the second dose, experienced brief, mild (mostly local) reactions, but only 50% exhibited a systemic immune response to vaccination. Six unvaccinated volunteers (controls) and 16 of these vaccinees were challenged with R rickettsii one month after vaccination. Vaccine efficacy was 25%; all six controls and 12 of 16 vaccinees developed typical Rocky Mountain spotted fever. The incubation period was longer, the duration of constitutional symptoms shorter, and the height of fever lower in ill vaccinees than in controls. The vaccine provided only partial protection against Rocky Mountain spotted fever but ameliorated the illness.     

A method for specific diagnosis of Rocky Mountain spotted fever on fixed, paraffin-embedded tissue by immunofluorescence.

For specific demonstration of Rickettsia rickettsii in fixed, paraffin-embedded tissues, the technique of trypsin digestion of deparaffinized, rehydrated sections was investigated. It was determined that 3.5 hr of digestion was optimal for achieving discrete, bright, green immunofluorescence of rickettsiae. At autopsy kidneys from seven of 10 cases of probably Rocky Mountain spotted fever contained structures that were specifically stained and that had the size and shape of rickettsiae. These structures were strictly limited to the endothelium and vascular walls of renal capillaries, veins, and arteries. Results from controls indicated that specificity of the immunofluorescence. R. rickettsii may be demonstrated by this method with greater sensitivity and specificity than by current histological methods. The technique allows retrospective analysis of certain organs for pathogenesis of involvement in Rocky Moutain spotted fever and offers a specific diagnostic test.     

A focus of dogs and Rickettsia massiliae-infected Rhipicephalus sanguineus in California

A recurrent focus of Rhipicephalus sanguineus infestation was investigated in a suburban area of southern California after reports of suspected Rocky Mountain spotted fever in two dogs on the same property. Abundant quantities of Rh. sanguineus were collected on the property and repeatedly from each dog, and Rickettsia massiliae DNA was detected by polymerase chain reaction (PCR). Whole blood and serum samples from four dogs were tested by using PCR and microimmunofluorescent assay for antibodies against spotted fever group rickettsiae. Serum samples from all four dogs contained antibodies reactive with R. massiliae, R. rhipicephali, R. rickettsii, and 364D Rickettsia but no rickettsial DNA was detected by PCR of blood samples. Serum cross-absorption and Western blot assays implicated R. massiliae as the most likely spotted fever group rickettsiae responsible for seropositivity. To our knowledge, this is the first detection of R. massiliae in ticks in California.     

Studies of the coagulation and complement systems during experimental Rocky Mountain spotted fever in rhesus monkeys.

We studied the coagulation and complement systems during Rocky Mountain spotted fever in Macaca mulatta experimentally infected with Rickettsia rickettsii. Ninety-one percent of monkeys infected intravenously with a high dose (10(6) plaque-forming units [pfu]) and 56% of monkeys infected with low doses (10(-1)-10(2) pfu) of R. rickettsii died after two to four days of illness. With the onset of fever and rickettsemia, animals developed hyperfibrinogenemia, mild thrombocytopenia, prolonged prothrombin and activated thromboplastin times, and increased serum fibrin/fibrinogen degradation products (FDP). Rickettsemia, thrombocytopenia, and FDP were greater in fatally ill monkeys than in survivors. Hemolytic titers of the second and third components of complement were not depressed except in a single surviving monkey that developed peripheral gangrenous ecchymoses at a time when both rickettsemia and agglutinating antibody were present. Thus, although activation and consumption of complement may occur during Rocky Mountain spotted fever, the hemostatic disturbances in fulminant infections seem to be a direct effect of the infectious vasculitis.     

Multispacer Typing (MST) of Spotted Fever Group Rickettsiae Isolated from Humans and Rats in Chengmai County,Hainan Province,China

Spotted fever caused by spotted fever group rickettsiae (SFGR) is found throughout China. During 2007–2008, 28 human SFGR isolates and 34 rat SFGR isolates including 15 isolates from Rattus fulvescens, 5 isolates from R. edwardsi, 7 isolates from Callosciurus erythraeus roberti and 7 isolates from Dremomys rufigenis) were obtained from L929 cell culture. Previous research indicated that the 62 strains of SFGR mentioned above shared not only the same serophenotype but also 100% of identity sequences of 16S rRNA, gltA, ompA, groEL and 17KD, which enabled us to apply multispacer typing (MST) to the 62 SFGR isolates in the study. Six primer pairs, which were used for typing of Rickettsia rickettsii and Rickettsia conorii, were chosen, and the results exhibited greater nucleotide polymorphisms among the 62 isolates tested. A total of 48 distinct genotypes were identified. The dominant genotype, represented by h3 isolates, accounted for 21.7% (13/60) of the isolates tested, and the remaining 47 genotypes were all unique. Phylogenetic analysis showed that all the 48 genotypes could be classified in the same clade, while the genetically related strain, R. heilongjiangensis, was close but not the same as the cluster. We concluded that the genetically diverse of spotted fever group rickettsiae strains are endemic in Chengmai County, Hainan Province, China.