Using metagenomic sequencing, we identified a patient infected with Rickettsia lanei who was initially diagnosed with Rocky Mountain spotted fever (RMSF), a clinically similar disease caused by infection with R. rickettsii. Our investigation highlights the importance of clinical, epidemiologic, and laboratory partnerships to leverage the discovery of novel pathogens.

Murine typhus, a fleaborne disease caused by the bacterium Rickettsia typhi, is found throughout temperate and tropical regions of the world. Transmission of R. typhi to humans involves several species of fleas, and most infections result from direct inoculation of R. typhi-infected flea feces into abrasions in the skin. We describe the transmission of R. typhi from an organ donor in Texas, USA, to 2 kidney transplant recipients. The donor and 1 recipient died from the infection. The occurrence of R. typhi transmission via transplantation is a harbinger for the reemergence of murine typhus in some of the most densely populated metropolitan areas of the United States. Our findings reinforce the need to improve healthcare provider and public awareness of this life-threatening but treatable infection.

BACKGROUND:The disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal-specific IgE (sIgE) antibodies. OBJECTIVE:To evaluate tick exposure as a risk factor for AGS and elevated alpha-gal sIgE level. METHODS:We conducted a case-control study comparing patients with AGS from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tick-borne pathogens. RESULTS:The patients with AGS were more likely to recall finding a tick on themselves (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.97-25.15), live near wooded forest (OR, 2.27; 95% CI, 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR, 5.58; 95% CI, 2.56-12.19). The patients with AGS were also more likely to report 4 or more tick bites (OR, 33.05; 95% CI, 9.92-155.12) and reactions at the site of tick bites (OR, 7.93; 95% CI, 3.74-16.80). Furthermore, elevated alpha-gal sIgE level was observed in 33% of the controls and was associated with tick exposure in the controls (OR, 4.25; 95% CI, 2.21-8.18). CONCLUSION:The results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE level.

Understanding the distribution of pathogens causing acute febrile illness (AFI) is important for clinical management of patients in resource-poor settings. We evaluated the proportion of AFI caused by specific pathogens among outpatients in Bangladesh. During May 2019-March 2020, physicians screened patients aged ≥2 years in outpatient departments of four tertiary level public hospitals. We randomly enrolled patients having measured fever (≥100.4°F) during assessment with onset within the past 14 days. Blood and urine samples were tested at icddr,b through rapid diagnostic tests, bacterial culture, and polymerase chain reaction (PCR). Acute and convalescent samples were sent to the Centers for Disease Control and Prevention (USA) for Rickettsia and Orientia ( R/O ) and Leptospira tests. Among 690 patients, 69 (10%) had enteric fever ( Salmonella enterica serotype Typhi or Salmonella enterica serotype Paratyphi), 51 (7.4%) Escherichia coli , and 28 (4.1%) dengue detected. Of the 441 patients tested for R/O , 39 (8.8%) had rickettsioses. We found 7 (2%) Leptospira cases among the 403 AFI patients tested. Nine patients (1%) were hospitalized, and none died. The highest proportion of enteric fever (15%, 36/231) and rickettsioses (14%, 25/182) was in Rajshahi. Dhaka had the most dengue cases (68%, 19/28). R/O affected older children and young adults (IQR 8–23 years) and was detected more frequently in the 21–25 years age-group (17%, 12/70). R/O was more likely to be found in patients in Rajshahi region than in Sylhet (aOR 2.49, 95% CI 0.85–7.32) between July and December (aOR 2.01, 1.01–5.23), and who had a history of recent animal entry inside their house than not (aOR 2.0, 0.93–4.3). Gram-negative Enterobacteriaceae were the most common bacterial infections, and dengue was the most common viral infection among AFI patients in Bangladeshi hospitals, though there was geographic variability. These results can help guide empiric outpatient AFI management.

Background Since 2000, the reported prevalence of tick-borne spotted fever rickettsiosis has increased considerably. We compared the level of antibody reactivity among healthy blood donors from 2 widely separated regions of the United States and evaluated the impact of antibody prevalence on public health surveillance in one of these regions. Methods Donor serum samples were evaluated by indirect immunofluorescence antibody assay to identify immunoglobulin G (IgG) antibodies reactive with Rickettsia rickettsii. The Georgia Department of Public Health (GDPH) analyzed characteristics of cases from 2016 surveillance data to evaluate the utility of laboratory surveillance for case assessment. Results Of the Georgia donors (n = 1493), 11.1% demonstrated antibody titers reactive with R. rickettsii at titers ≥64, whereas 6.3% of donors from Oregon and Washington (n = 1511) were seropositive. Most seropositive donors had a titer of 64; only 3.1% (n = 93) of all donors had titers ≥128. During 2016, GDPH interviewed 243 seropositive case patients; only 28% (n = 69) met inclusion criteria in the national case definition for spotted fever rickettsiosis. Conclusions These findings suggest that a single IgG antibody titer is an unreliable measure of diagnosis and could inaccurately affect surveillance estimates that define magnitude and clinical characteristics of Rocky Mountain spotted fever and other spotted fever rickettsioses.

Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI.

Rickettsia parkeri rickettsiosis is an emerging, tick-borne disease in the United States (US), transmitted by the bite of Amblyomma maculatum group ticks. Clinical manifestations include fever, headache, myalgia, maculopapular rash, and a characteristic eschar that forms at the site of the tick bite. Arizona's index case of R. parkeri rickettsiosis was reported in 2014. Seven additional confirmed and probable cases were identified during 2016-2017 through routine investigation of electronic laboratory reports and by self-reporting to public health authorities. Serum samples were evaluated for immunoglobulin G antibodies reactive with antigens of Rickettsia rickettsii (the agent of Rocky Mountain spotted fever [RMSF]) and R. parkeri using indirect immunofluorescence antibody tests. Eschar swab specimens were evaluated using Rickettsia genus-specific and R. parkeri-specific real-time PCR assays. Patients (six male, one female) ranged in age from 29 to 69 years (median of 41 years), and became ill between July 2016 and September 2017. Fever (6/7), myalgia (5/7), and arthralgia (5/7) were most commonly reported and 5/7 patients had a documented eschar. All patients reported a tick bite acquired in southern Arizona within 2-8 days before illness onset. Four patients worked as U.S. Border Patrol agents. Antibodies reactive to R. rickettsii, R. parkeri, or to both antigens were detected in all patients. Seroconversions between acute and convalescent-phase samples were identified for two patients and DNA of R. parkeri was identified in eschar swab samples from two patients. R. parkeri rickettsiosis is endemic to a region of the southwestern United States and presents an occupational risk that could be lessened by prevention messaging to Border Patrol agents. RMSF, a closely related and more severe spotted fever rickettsiosis, is also endemic to Arizona. Public health agencies can assist clinicians in distinguishing these two infections clinically through education and accessing species-specific diagnostic assays that can improve surveillance efforts for both diseases.

Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.

Coxiella burnetii is a zoonotic pathogen that causes Q fever in humans and is transmitted primarily from infected goats, sheep, or cows. Q fever typically presents as an acute febrile illness; however, individuals with certain predisposing conditions, including cardiac valvulopathy, are at risk for chronic Q fever, a serious manifestation that may present as endocarditis. In response to a cluster of Q fever cases detected by public health surveillance, we evaluated C. burnetii infection in a community that operates a large-scale cow and goat dairy. A case was defined as an individual linked to the community with a C. burnetii phase II IgG titer ≥ 128. Of 135 participants, 47 (35%) cases were identified. Contact with or close proximity to cows, goats, and their excreta was associated with being a case (relative risk 2.7, 95% confidence interval 1.3-5.3). Cases were also identified among individuals without cow or goat contact and could be related to windborne spread or tracking of C. burnetii on fomites within the community. A history of injection drug use was reported by 26/130 (20%) participants; follow-up for the presence of valvulopathy and monitoring for development of chronic Q fever may be especially important among this population.

In the United States, all previously reported cases of Rickettsia parkeri rickettsiosis have been linked to transmission by the Gulf Coast tick (Amblyomma maculatum). Here we describe 1 confirmed and 1 probable case of R. parkeri rickettsiosis acquired in a mountainous region of southern Arizona, well beyond the recognized geographic range of A. maculatum ticks. The likely vector for these 2 infections was identified as the Amblyomma triste tick, a Neotropical species only recently recognized in the United States. Identification of R. parkeri rickettsiosis in southern Arizona demonstrates a need for local ecologic and epidemiologic assessments to better understand geographic distribution and define public health risk. Education and outreach aimed at persons recreating or working in this region of southern Arizona would improve awareness and promote prevention of tickborne rickettsioses.

Rickettsia parkeri, a newly recognized tick-borne pathogen of humans in the Americas, is a confirmed cause of spotted fever group rickettsiosis in Argentina. Until recently, almost all cases of R. parkeri rickettsiosis in Argentina have originated from the Paraná River Delta, where entomological surveys have identified populations of R. parkeri-infected Amblyomma triste ticks. In this report, we describe confirmed cases of R. parkeri rickettsiosis from Córdoba and La Rioja provinces, which are located several hundred kilometers inland, and in a more arid ecological region, where A. triste ticks do not occur. Additionally, we identified questing A. tigrinum ticks naturally infected with R. parkeri in Córdoba province. These data provide evidence that another human-biting tick species serves as a potential vector of R. parkeri in Argentina and possibly, other countries of South America.

Among 13 suspected Rocky Mountain spotted fever (RMSF) cases identified through an enhanced surveillance program in Tennessee, antibodies to Rickettsia rickettsii were detected in 10 (77%) patients using a standard indirect immunofluorescent antibody (IFA) assay. Immunoglobulin M (IgM) antibodies were observed for 6 of 13 patients (46%) without a corresponding development of IgG, and for 3 of 10 patients (30%) at least 1 year post-onset. However, recent infection with a spotted fever group rickettsiae could not be confirmed for any patient, based on a lack of rising antibody titers in properly timed acute and convalescent serologic specimens, and negative findings by polymerase chain reaction testing. Case definitions used in national surveillance programs lack specificity and may capture cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other spotted fever group rickettsiae in the United States.

Ehrlichiosis is a tick-borne disease that ranges in severity from asymptomatic infection to fatal sepsis. Ehrlichiosis acquired from transfusion of blood products has not been documented in the literature to date. A case of Ehrlichia ewingii infection likely transmitted by transfusion of leukoreduced platelets is described, and public health implications are discussed.

Several spotted fever group rickettsiae (SFGR) previously believed to be nonpathogenic are speculated to contribute to infections commonly misdiagnosed as Rocky Mountain spotted fever (RMSF) in the United States, but confirmation is difficult in cases with mild or absent systemic symptoms. We report an afebrile rash illness occurring in a patient 4 days after being bitten by a Rickettsia montanensis-positive Dermacentor variabilis tick. The patient's serological profile was consistent with confirmed SFGR infection.

Recrudescent Rickettsia prowazekii infection, also known as Brill-Zinsser disease, can manifest decades after untreated primary infection but is rare in contemporary settings. We report the first known case of Brill-Zinsser disease in a patient originally infected with a zoonotic strain of R. prowazekii acquired from flying squirrels.

Q fever was diagnosed in a previously healthy man who had recently traveled to the East Coast of Australia. The patient experienced fever and headache accompanied by lymphopenia and elevated liver enzymes but not pneumonia. He had no known direct exposures to animals, exhibited IgM and IgG seroconversion to phase II antigen of Coxiella burnetii and IgM only to phase I antigen, and responded to doxycycline treatment. This case serves as a reminder to clinicians to consider Q fever in the differential diagnosis of acute febrile illness in travelers returning from endemic areas.

The increasing popularity of foreign travel and ecotourism places travelers at increased risk for certain tick-borne diseases. From 1999 through 2002, 31 cases of imported spotted fever-group rickettsioses (SFGR) in United States residents reporting travel to Africa were confirmed by laboratory testing at the Centers for Disease Control and Prevention. Nineteen patients (61%) reported visiting South Africa prior to illness onset. Most patients reported fever and one or more eschars; rash was reported for only 26% of the patients. Twelve patients had an initial non-reactive acute-phase serum sample obtained a median of three days after illness onset, and were confirmed by testing a second convalescent-phase serum sample obtained a median of 32 days after illness onset. Five patients were confirmed positive through immunohistochemical staining of skin biopsies, including three patients with acute-phase serum samples that tested negative for SFGR. This study emphasizes the importance of evaluating convalescent-phase serum specimens 28 days or more after illness onset or examining skin biopsies by immunohistochemical staining during early infection to confirm a diagnosis of imported SFGR.

Serum samples from people exposed to sheep at a research facility were evaluated by a commercial laboratory and resulted in an overall Coxiella burnetii seroprevalence of 75%. We interviewed individuals to determine exposure history and compatible illness, and retested their sera. Analysis indicated that the commercial laboratory was misinterpreting its results; when corrected, the seroprevalence dropped to 27%. Test kits of the brand used by the commercial laboratory gave equivalent results to the in-house CDC assay when tested in parallel at CDC. Upon final analysis, only the attending veterinarian was confirmed as a Q fever case. This event resulted in increased risk reduction protocols at the research facility and improved public health communication among health authorities. This pseudoepidemic resulted from a lapse in laboratory quality control for testing. Similar errors can be avoided through standardization and improved review of laboratory procedures.