Rocky Mountain spotted fever is a neglected tropical disease in Latin America.

Rocky Mountain spotted fever (RMSF), a severe and extraordinarily lethal infectious disease, has emerged as a widespread public health crisis among predominantly vulnerable populations in several countries of Latin America, particularly evident in northern Mexico. Historically, RMSF has gained less attention than many other tropical infectious diseases, resulting in insufficient allocations of resources and development of capabilities for its prevention and control in endemic regions. We argue that RMSF fulfills accepted criteria for a neglected tropical disease (NTD). The relative neglect of RMSF in most Latin American countries contributes to disparities in morbidity and mortality witnessed in this region. By recognizing RMSF as an NTD, an increased public policy interest, equitable and more appropriate allocation of resources, scientific interest, and social participation can ameliorate the impact of this potentially treatable disease, particularly in vulnerable populations.

The four most frequently diagnosed vector-borne diseases among service member and non-service member beneficiaries in the geographic combatant commands, 2010-2022.

Vector-borne diseases (VBDs) may pose an increased risk for U.S. service members during recurring military training exercises, operations, and response missions, in addition to residence in endemic regions within and outside the continental U.S. Prior MSMR reports address VBD surveillance, described by surveillance data for 23 reportable medical events (RMEs), among active duty and reserve component service members. This report covers a 13-year surveillance period, from January 2010 to December 2022, and provides linear trends of selected VBDs among Armed Forces service and non-service member beneficiaries diagnosed at installations within the Northern Command (NORTHCOM), Africa Command (AFRICOM), Central Command (CENTCOM), European Command (EUCOM), Indo-Pacific Command (INDOPACOM), or Southern Command (SOUTHCOM). Trends of only the 4 mostfrequently reported VBDs were evaluated, as Lyme disease, malaria, Rocky Mountain Spotted Fever (RMSF), and dengue fever comprised 90% (n=5,199) of all 23 VBDs (n=5,750) among Military Health System (MHS) beneficiaries documented as RMEs during the surveillance period.

Case Report: Fatal Rickettsiosis in Pregnancy.

Rocky Mountain spotted fever (RMSF) is a tick-borne infection caused by Rickettsia rickettsii. We present a series of two cases of pregnant patients who showed up at the emergency room of a hospital in Nuevo León, Mexico. Both patients lived in environments where R. rickettsii is endemic and they presented with several days of symptoms, including fever. Both patients developed a rash and had stillbirths during their hospital stay. Treatment with doxycycline was delayed, with fatal results in both patients. Diagnosis of RMSF was confirmed via polymerase chain reaction assay postmortem. The need to link epidemiological clues with clinical data is critical in the diagnosis and early treatment of RMSF to prevent maternal deaths.

Molecular detection of Rickettsia africae from Amblyomma hebraeum ticks in Mafikeng city of North West Province, South Africa.

Rickettsia africae causes zoonotic African tick bite fever, which is a disease of "One Health" importance. There have been reported cases of tourists from Europe and Asia who have been bitten by ticks whilst visiting South Africa's nature reserves, and on their return to their countries, the display African Tick Bite Fever sickness. Hence, the aim of this study was to determine the occurrence of Rickettsia africae in Amblyomma hebraeum ticks infesting livestock in the North West Province. A total of 358 A. hebraeum ticks were collected from 60 ruminants (cattle, sheep and goats) in Mafikeng City of North West Province, South Africa. Ticks were identified morphologically and further confirmed by sequencing of their ITS2 gene. DNA was extracted from 60 pools of ticks which consisted of 5-6 adult ticks that were from the same ruminant host. Infections with Rickettsia spp. were found in 48%, 40%, and 32% of cattle, sheep, and goats, respectively, in amplification by PCR using the ompA gene. The ompA gene sequences showed that the Rickettsia spp. were identified as R. africae. Although the animals from whom the ticks were collected did not exhibit any clinical symptoms, it is well recognised that R. africae is a disease with significant zoonotic potential. Thus, it is important to use the "One Health" approach to formulate prevention and control measures for this pathogen for animal and human health as well as the tourism sector due to the ecotourism importance of the resultant disease.

Evaluation of completeness and timeliness of data in the National Information System for Notifiable Diseases for spotted fever in the state of São Paulo, Brazil, 2007-2017.

OBJECTIVE: to evaluate the completeness and timeliness of notifications of cases of spotted fever (SF) held on the Notifiable Health Conditions Information System (SINAN) in São Paulo State, Brazil, from 2007 to 2017. METHODS: this was a descriptive and ecological study of confirmed human cases of SF regarding completeness and timeliness of ten fields of the notification form (good if ≥ 90% for most variables); time series analysis was performed using the Prais-Winsten technique. RESULTS: we analyzed 736 records; among essential fields, only "Discharge date" showed poor completeness (68.5%). Timeliness was good for the "Investigation" and "Closure" fields; other time lapses were not adequate. CONCLUSION: in São Paulo state, data completeness was good for most variables, whereas timeliness was not adequate (except for "Closure" and "Investigation"), pointing to the need for health education and communication actions about SF.

Serologic Testing for Rocky Mountain Spotted Fever in a Low-Incidence Region.

BACKGROUND: Tick-borne diseases have grown in incidence over recent decades. As a result, diagnostic testing has become more common, often performed as broad antibody-based panels for multiple tick-transmitted pathogens. Rocky Mountain spotted fever (RMSF) is rare in our region yet may cause severe morbidity, leading to diagnostic screening in low-risk patients. We sought to describe trends in RMSF diagnostic testing, rate of IgG seropositivity, and clinical features of those tested. METHODS: We performed a retrospective chart review of patients ≤21 years old undergoing testing for RMSF and/or with an ICD-9/10 code for RMSF. Patients were categorized by infection likelihood based on clinical and laboratory criteria adapted from Centers for Disease Control and Prevention's (CDC) case definition of spotted fever rickettsioses. Clinical data were collected and analyzed with descriptive statistics. RESULTS: One hundred and seventy patients were included. 5.8% met CDC criteria for rickettsial infection, 6.5% had an elevated IgG titer but lacked suggestive symptoms, and 87.6% had a negative IgG titer. Many patients tested were unlikely to have RMSF, including 50% lacking fever, 20% lacking any RMSF "classic triad" symptoms, 13% without acute illness, and 22% tested during months with low tick activity. Convalescent serology was performed in 7.6% of patients and none underwent Rickettsia rickettsii polymerase chain reaction (PCR) testing. CONCLUSIONS: Diagnostic testing was frequently performed in patients unlikely to have RMSF. We identified many opportunities for improving test utilization. Reserving testing for those with higher pretest probability, performing convalescent serology, and utilizing PCR may improve the accuracy of RMSF diagnosis and reduce clinical challenges stemming from inappropriate testing.

Wide distribution of Mediterranean and African spotted fever agents and the first identification of Israeli spotted fever agent in ticks in Uganda.

Rickettsia microorganisms are causative agents of several neglected emerging infectious diseases in humans transmitted by arthropods including ticks. In this study, ticks were collected from four geographical regions of Uganda and pooled in sizes of 1-179 ticks based on location, tick species, life stage, host, and time of collection. Then, they were tested by real-time PCR for Rickettsia species with primers targeting gltA, 17kDa and ompA genes, followed by Sanger sequencing of the 17kDa and ompA genes. Of the 471 tick pools tested, 116 (24.6%) were positive for Rickettsia spp. by the gltA primers. The prevalence of Rickettsia varied by district with Gulu recording the highest (30.1%) followed by Luwero (28.1%) and Kasese had the lowest (14%). Tick pools from livestock (cattle, goats, sheep, and pigs) had the highest positivity rate, 26.9%, followed by vegetation, 23.1%, and pets (dogs and cats), 19.7%. Of 116 gltA-positive tick pools, 86 pools were positive using 17kDa primers of which 48 purified PCR products were successfully sequenced. The predominant Rickettsia spp. identified was R. africae (n = 15) in four tick species, followed by R. conorii (n = 5) in three tick species (Haemaphysalis elliptica, Rhipicephalus appendiculatus, and Rh. decoloratus). Rickettsia conorii subsp. israelensis was detected in one tick pool. These findings indicate that multiple Rickettsia spp. capable of causing human illness are circulating in the four diverse geographical regions of Uganda including new strains previously known to occur in the Mediterranean region. Physicians should be informed about Rickettsia spp. as potential causes of acute febrile illnesses in these regions. Continued and expanded surveillance is essential to further identify and locate potential hotspots with Rickettsia spp. of concern.

Identification of common sequence motifs shared exclusively among selectively packed exosomal pathogenic microRNAs during rickettsial infections.

We previously reported that microRNA (miR)23a and miR30b are selectively sorted into exosomes derived from rickettsia-infected endothelial cells (R-ECExos). Yet, the mechanism remains unknown. Cases of spotted fever rickettsioses have been increasing, and infections with these bacteria cause life-threatening diseases by targeting brain and lung tissues. Therefore, the goal of the present study is to further dissect the molecular mechanism underlying R-ECExos-induced barrier dysfunction of normal recipient microvascular endothelial cells (MECs), depending on their exosomal RNA cargos. Infected ticks transmit the rickettsiae to human hosts following a bite and injections of the bacteria into the skin. In the present study, we demonstrate that treatment with R-ECExos, which were derived from spotted fever group R parkeri infected human dermal MECs, induced disruptions of the paracellular adherens junctional protein VE-cadherin, and breached the paracellular barrier function in recipient pulmonary MECs (PMECs) in an exosomal RNA-dependent manner. We did not detect different levels of miRs in parent dermal MECs following rickettsial infections. However, we demonstrated that the microvasculopathy-relevant miR23a-27a-24 cluster and miR30b are selectively enriched in R-ECExos. Bioinformatic analysis revealed that common sequence motifs are shared exclusively among the exosomal, selectively-enriched miR23a cluster and miR30b at different levels. Taken together, these data warrant further functional identification and characterization of a monopartition, bipartition, or tripartition among ACA, UCA, and CAG motifs that guide recognition of microvasculopathy-relevant miR23a-27a-24 and miR30b, and subsequently results in their selective enrichments in R-ECExos.

Spotted Fever and Typhus Group Rickettsiae in Dogs and Humans, Mexico, 2022.

We found serologic evidence of spotted fever group Rickettsia in humans and dogs and typhus group Rickettsia in dogs in Reynosa, Mexico. Our investigation revealed serologic samples reactive to spotted fever group Rickettsia in 5 community members, which highlights a potential rickettsial transmission scenario in this region.

Evaluation of tetracycline and fluoroquinolone therapy against Japanese spotted fever: Analysis based on individual data from case reports and case series.

OBJECTIVES: Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not yet been standardised. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful instances of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, the antipyretic effect of TC+FQ was evaluated in this study. METHODS: A comprehensive search of published JSF case reports was conducted to extract individual patient data. In cases where it was possible to extract temperature data, after homogenising patient characteristics, time-dependent changes in fever type from the date of the first visit was evaluated for the TC and TC+FQ groups. RESULTS: The primary search yielded 182 cases, with individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group) that included temperature data. The TC+FQ group had significantly lower body temperature compared with the TC group from Days 3 to 4. CONCLUSIONS: Although TC monotherapy for JSF can eventually result in defervescence, the duration of fever is longer compared with other rickettsial infections such as scrub typhus. The results suggest that the antipyretic effect of TC+FQ was more effective, with a potential shortening of the duration that patients suffer from febrile symptoms.

Alerta epidemiológico: alerta acerca do registro de casos de febre maculosa no Estado de São Paulo / Epidemiological alert: alert about the record of cases of spotted fever in the State of São Paulo

Alerta emitido pela Coordenação de Zoonoses da Gerência de Vigilância Epidemiológica de Doenças Transmissíveis (GVEDT) e o Centro de Informações Estratégicas e Resposta em Vigilância (CIEVS Goiás) da Gerência de Emergências em Saúde Pública (GESP) da Superintendência de Vigilância em Saúde (SUVISA) com o objetivo de alertar os profissionais de saúde quanto aos sinais e sintomas devido aos casos recentes de febre maculosa (FM) registrados no estado de São Paulo

Alert issued by the Zoonoses Coordination of the Communicable Diseases Epidemiological Surveillance Management (GVEDT) and the Center for Strategic Information and Surveillance Response (CIEVS Goiás) of the Public Health Emergencies Management (GESP) of the Health Surveillance Superintendence (SUVISA) in order to alert health professionals about the signs and symptoms due to recent cases of spotted fever (FM) registered in the state of São Paulo

[Simultaneous detection of 7 important Rickettsiales pathogens by TaqMan-probe quantitative real-time PCR].

Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R2 >0.990 0), the minimum detection limit was 10 copies/µl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.

Spotted fever rickettsioses. Study of cases reported in a secondary care pediatric hospital of northeastern Mexico, 2012-2022.

BACKGROUND: Spotted fever rickettsiosis is a serious disease with a high mortality rate if not timely detected. OBJECTIVE: To describe the characteristics of patients hospitalized for spotted fever rickettsiosis, as well as the risk factors associated with poor prognosis. MATERIAL AND METHODS: Data from medical records of patients hospitalized between August 2012 and July 2022 were collected. Variables were analyzed using Mann-Whitney's U-test, Fisher's exact test, and univariate or multivariate logistic regression analysis. RESULTS: Twenty-six patients were analyzed, among which a mortality of 57.6% was identified. In the between-group comparison, platelet count was lower in non-survivors (16.0 × 103/µL vs. 25.9 × 103/µL, p = 0.031). The percentage of surviving patients who received treatment more than 72 hours after fever onset was 45.5% (five patients) vs. 86.7% of non-survivors (13 patients) (p = 0.034). Receiving treatment 72 hours after fever onset increased by 7.09 times the probability of a fatal outcome (OR = 8.09, 95% CI = 1.1-55.8, p = 0.034). CONCLUSIONS: Starting adequate treatment 72 hours after the onset of fever may be an important risk factor for mortality, hence the importance of timely diagnosis and appropriate treatment of this disease.

ANTECEDENTES: La rickettsiosis de fiebre manchada es una enfermedad grave y con alta tasa de letalidad si no se identifica oportunamente. OBJETIVO: Describir las características de los pacientes hospitalizados por rickettsiosis de fiebre manchada, así como los factores de riesgo asociados a mal pronóstico. MATERIAL Y MÉTODOS: Se recabaron los datos del expediente clínico de pacientes hospitalizados entre agosto de 2012 y julio de 2022. Las variables se analizaron mediante prueba U de Mann-Whitney, prueba exacta de Fisher y regresión logística univariada y multivariada. RESULTADOS: Se analizaron 26 pacientes, en quienes se identificó una mortalidad de 57.6 %. En la comparación entre grupos, el número de plaquetas fue menor en los no supervivientes (16.0 × 103/µL versus 25.9 × 103/µL, p = 0.031). El porcentaje de pacientes supervivientes que recibieron tratamiento más de 72 horas después del inicio de la fiebre fue 45.5 % (cinco pacientes) versus 86.7 % de los no supervivientes (13 pacientes), p = 0.034. Recibir tratamiento después de 72 horas del inicio de la fiebre incrementó 7.09 veces la probabilidad de desenlace fatal (RM = 8.09, IC 95 % = 1.1-55.8, p = 0.034). CONCLUSIONES: Iniciar tratamiento adecuado posterior a 72 horas del inicio de la fiebre podría ser un factor de riesgo de mortalidad, de ahí que la importancia del diagnóstico oportuno y tratamiento adecuado de esta enfermedad.

Serological cross-reactivity between spotted fever and typhus groups of rickettsia infection in Japan.

OBJECTIVES: We examined the frequency of cross-reactions to Rickettsia typhi in patients with Japanese spotted fever (JSF) and evaluated the differences between two rickettsiae using antibody endpoint titers. METHODS: Patients' immunoglobulin (Ig)M and IgG titers against Rickettsia japonica and Rickettsia typhi in two phases were measured using an indirect immunoperoxidase assay at two reference centers for rickettsiosis in Japan. Cross-reaction was defined as a higher titer against R. typhi in convalescent sera than in acute sera among patients fulfilling the criteria for JSF diagnosis. The frequencies of IgM and IgG were also evaluated. RESULTS: Approximately 20% of cases showed positive cross-reactions. A comparison of antibody titers revealed the difficulty in identifying some positive cases. CONCLUSION: Cross-reactions of 20% in serodiagnosis may lead to the misclassification of rickettsial diseases. However, with the exception of some cases, we were able to successfully differentiate JSF from murine typhus using each endpoint titer.

Imported rickettsial infections to the United Kingdom, 2015-2020.

OBJECTIVE: The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national reference laboratory between 2015 and 2022. METHODS: Samples testing positive for spotted fever group, typhus group, and scrub typhus IgG/IgM on acute and convalescent blood samples, and/or PCR on tissue/blood were categorized as suspected, confirmed or past infection. RESULTS: 220 patients had rickettsioses, and the commonest import was acute spotted fever group infection (61%, 125/205), 54% (62/114) from South Africa. In acute typhus group cases, 60% (40/67) were from Southeast Asia. One patient with Rickettsia typhi bacteremia died. Scrub typhus group infections (5%, 10/205) were exclusively from Asia and the Western Pacific regions. Overall, 43% of confirmed cases (39/91) had not received doxycycline prior to results. CONCLUSIONS: Rickettsial infections are important and under-recognized causes of imported fever in the UK. Thorough history, examination, and timely treatment with doxycycline should be considered if there is suspicion of Rickettsia infection before testing.

Clinical manifestations of Rickettsia rickettsii in a familial outbreak in Panama.

We report an isolated outbreak of Rickettsia rickettsii in the Ngäbe-Buglé indigenous region, located 750 m (tropical wet) above sea level, in a jungle and mountainous area of Western Panama. Seven members of a family were infected simultaneously, resulting in four deaths. Family outbreaks have been previously described and are responsible for 4-8% of the cases described [1-4]. The simultaneous onset of symptoms in the affected population group is extremely unusual [1,5], but it should not dissuade the clinician from considering the possibility of Rickettsia rickettsii infection.

The inoculation eschar of Rickettsia parkeri rickettsiosis in Brazil: Importance and cautions.

Two well characterized tick-borne rickettsioses occur in Brazil. Rickettsia rickettsii caused spotted-fever, transmitted by Amblyomma sculptum and Amblyomma aureolatum, is a severe disease with a high case-fatality rate in the southeastern region of the country. Rickettsia parkeri strain Atlantic rainforest infections transmitted by adult Amblyomma ovale ticks cause a milder non-lethal febrile disease with an eschar (necrosis) at the tick bite site. Clinical diagnosis of rickettsiosis is challenging, particularly during the early stages of the illness when signs and symptoms are non-specific. Since eschar at the tick bite site has emerged as the main clinical feature of mild R. parkeri infections and used to differentiate it from severe R. rickettsii infection, its proper recognition, distinction from other tick bite lesions, and boundaries as a clinical tool must be highlighted. Of importance, eschars induced by Rickettsia must be differentiated from dermatoses caused by other tick-borne skin infections as well from lesions caused by the tick bite itself. We herein highlight information on eschar in rickettsial diseases in Brazil and discuss the need for further research on its clinical relevance and application in the diagnosis of spotted fever caused by R. parkeri strain Atlantic rainforest. In particular, we draw attention to diagnosis of other febrile diseases in the presence of concomitant tick bites.

Emerging tick-borne spotted fever group rickettsioses in the Balkans.

The impact of tick-borne pathogens (TBPs) on human health has increased in the last decades, since the incidence of emerging and re-emerging infectious and zoonotic tick-borne diseases has increased worldwide. Tick-borne rickettsiae of the Spotted Fever group (SFGR) are considered as emerging pathogens that can infect humans and cause a variety of non-specific clinical symptoms. Here, we report nine cases of atypical tick-borne diseases (9/460; 1.95%) that occurred over a period of four months (from 15 April 2021 to 16 August 2021) in Serbia, from which five cases were classified as confirmed SFGR infection, two cases as probable SFGR infection and two cases as suspected SFGR infection. Within cases of confirmed SFGR infection, R. helvetica was detected as the causative agent in two cases. The most common clinical finding was non-expanding persistent circular redness, followed by eschar and enlargement of regional lymph nodes, and pain at lesion site. Rickettsia outer membrane protein B (ompB) and citrate synthase (gltA) gene fragments were amplified from clinical samples and ticks attached to patients and IgG reacting with Rickettsia conorii antigen were detected in sera samples of patients, which are highly suggestive of exposure to SFGR. Surveillance and monitoring of rickettsial diseases in Serbia should continue and extended to new areas due to the increasing trend of clinical infections caused by SFGR in the country.

Mapping the global distribution of spotted fever group rickettsiae: a systematic review with modelling analysis.

BACKGROUND: Emerging and re-emerging spotted fever group (SFG) rickettsioses are increasingly recognised worldwide as threats to public health, yet their global distribution and associated risk burden remain poorly understood. METHODS: In this systematic review and modelling analysis, we mapped global distributions of all confirmed species of SFG rickettsiae (SFGR) detected in animals, vectors, and human beings, using data collected from the literature. We assessed ecological drivers for the distributions of 17 major SFGR species using machine learning algorithms, and mapped model-predicted risks. FINDINGS: Between Jan 1, 1906, and March 31, 2021, we found reports of 48 confirmed SFGR species, with 66 133 human infections worldwide, with a large spatial variation across the continents. 198 vector species were detected to carry 47 of these Rickettsia spp. (146 ticks, 24 fleas, 15 mosquitoes, six mites, four lice, two keds, and one bug). Based on model-predicted global distributions of the 17 major SFGR species, we found five spatial clusters aggregated by ecological similarity in terms of environmental and ecoclimatic features. Rickettsia felis is the leading SFGR species to which 4·4 billion (95% CI 3·8-5·3 billion) people are at risk, followed by Rickettsia conorii (3·7 billion) and Rickettsia africae (3·6 billion). INTERPRETATION: The wide spectrum of vectors is contributing substantially to the increasing incidence of SFGR infections among humans. Awareness, diagnosis, and surveillance of SFGR infections should be improved in the high-risk regions, especially in areas where human infections are underreported. FUNDING: National Key Research and Development Program of China.