Clinical features of patients with Rocky Mountain spotted fever, dengue and chikungunya infection.

INTRODUCTION: Clinical distinction between arbovirus infections and those caused by rickettsia is crucial to initiate appropriate medical treatment. OBJECTIVE: To compare the differences between Rocky Mountain spotted fever (RMSF) and other vector-borne diseases (dengue and chikungunya) with similar clinical presentation, and to identify data that could aid rapid diagnosis of these diseases. METHODS: We evaluated sociodemographic, clinical and laboratory data of 399 patients from five hospitals and clinics of Sonora, Mexico, between 2004 and 2016, with laboratory-confirmed diagnosis of RMSF, dengue, or chikungunya. RESULTS: The RMSF group had the highest lethality (49/63 deaths, 77.8 %), followed by the chikungunya group (3/161, 1.9 %) and the dengue group (3/161, 1.9 %). Clinical differences included the presence of rash, edema, and pruritus; in addition, differences in multiple biomarkers such as platelets, hemoglobin, indirect bilirubin, and serum sodium levels were documented. CONCLUSION: Rash on the palms and soles, edema and absence of pruritus, together with high levels of direct bilirubin and severe thrombocytopenia could be useful indicators to differentiate patients at RMSF advanced stages from those with dengue and chikungunya.

INTRODUCCIÓN: La distinción clínica entre infecciones arbovirales y las provocadas por rickettsias es crucial para iniciar el tratamiento médico apropiado. OBJETIVO: Comparar las diferencias entre fiebre manchada de las montañas rocosas (FMMR) y otras enfermedades transmitidas por vector (dengue y chikungunya) con presentación clínica similar e identificar los datos que pudieran ayudar al diagnóstico rápido de esas enfermedades. MÉTODOS: Se evaluaron datos sociodemográficos, clínicos y de laboratorio de 399 pacientes de cinco hospitales y clínicas en Sonora, México, entre 2004 y 2016, con el diagnóstico confirmado por laboratorio de FMMR, dengue o chikungunya. RESULTADOS: El grupo con FMMR presentó la mayor letalidad (49/63 muertes, 77.8 %), seguido por el de chikungunya (3/161, 1.9 %) y el de dengue (3/161, 1.9 %). Las diferencias clínicas consistieron en la presencia de exantema, edema y prurito; además, se documentaron diferencias en múltiples biomarcadores como plaquetas, hemoglobina, bilirrubina indirecta y niveles de sodio sérico. CONCLUSIÓN: El exantema en palmas y plantas, edema y ausencia de prurito, aunados a niveles altos de bilirrubina directa y trombocitopenia severa pudieran ser indicadores útiles para diferenciar a pacientes con FMMR en etapas avanzadas de aquellos con dengue y chikungunya.

Características clínicas de los pacientes con fiebre manchada de las Montañas Rocosas, infección por dengue y chikungunya / Clinical features of patients with Rocky Mountain spotted fever, dengue and chikungunya infection

Resumen Introducción: La distinción clínica entre infecciones arbovirales y las provocadas por rickettsias es crucial para iniciar el tratamiento médico apropiado. Objetivo: Comparar las diferencias entre fiebre manchada de las Montañas Rocosas (FMMR) y otras enfermedades transmitidas por vector (dengue y chikungunya) con presentación clínica similar e identificar los datos que pudieran ayudar al diagnóstico rápido de esas enfermedades. Métodos: Se evaluaron datos sociodemográficos, clínicos y de laboratorio de 399 pacientes de cinco hospitales y clínicas en Sonora, México, entre 2004 y 2016, con el diagnóstico confirmado por laboratorio de FMMR, dengue o chikungunya. Resultados: El grupo con FMMR presentó la mayor letalidad (49/63 muertes, 77.8 %), seguido por el de chikungunya (3/161, 1.9 %) y el de dengue (3/161, 1.9 %). Las diferencias clínicas consistieron en la presencia de exantema, edema y prurito; además, se documentaron diferencias en múltiples biomarcadores como plaquetas, hemoglobina, bilirrubina indirecta y niveles de sodio sérico. Conclusión: El exantema en palmas y plantas, edema y ausencia de prurito, aunados a niveles altos de bilirrubina directa y trombocitopenia severa pudieran ser indicadores útiles para diferenciar a pacientes con FMMR en etapas avanzadas de aquellos con dengue y chikungunya.

Abstract Introduction: Clinical distinction between arbovirus infections and those caused by rickettsia is crucial to initiate appropriate medical treatment. Objective: To compare the differences between Rocky Mountain spotted fever (RMSF) and other vector-borne diseases (dengue and chikungunya) with similar clinical presentation, and to identify data that could aid rapid diagnosis of these diseases. Methods: Sociodemographic, clinical and laboratory data of 399 patients from five hospitals and clinics of Sonora, Mexico, with laboratory-confirmed diagnosis of RMSF, dengue, or chikungunya between 2004 and 2016 were evaluated. Results: The RMSF group had the highest lethality (49/63 deaths, 77.8 %), followed by the chikungunya group (3/161, 1.9 %) and the dengue group (3/161, 1.9 %). Clinical differences included the presence of rash, edema, and pruritus; in addition, differences in multiple biomarkers such as platelets, hemoglobin, indirect bilirubin, and serum sodium levels were documented. Conclusion: Rash on the palms and soles, edema and absence of pruritus, together with high levels of direct bilirubin and severe thrombocytopenia could be useful indicators to differentiate patients at RMSF advanced stages from those with dengue and chikungunya.

Epidemiology and Clinical Features of Rocky Mountain Spotted Fever from Enhanced Surveillance, Sonora, Mexico: 2015-2018.

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is a severe and potentially fatal tick-borne disease. In 2015, Mexico issued a declaration of epidemiologic emergency in response to ongoing outbreaks of RMSF in northern Mexico. Sonora state is one of the most heavily impacted states in Mexico, with historic case fatality rates (CFRs) of 18%. We summarized data from enhanced surveillance to understand demographic, clinical, and treatment factors associated with the high mortality. We conducted a retrospective review of confirmed and probable RMSF cases reported to the General Directorate of Health Promotion and Disease Prevention in Sonora. A case of RMSF is defined as fever (> 38.5°C), plus two symptoms, and epidemiologic criteria. A confirmed case requires laboratory evidence. During 2015-2018, a total of 510 cases of RMSF were reported; 252 (49%) were in persons aged ≤ 18 years. Case fatality rate was 44% (n = 222). Older age and being confirmed by PCR were associated with fatal outcome (P-value < 0.01). The mean time from onset of symptoms to treatment with doxycycline was 7.9 days (SD ± 5.5). Hot spot analysis revealed neither areas of inordinately high nor low incidence, rather clusters of disease in population centers. The CFR for RMSF in Sonora remains high, and a large proportion of cases are seen in persons aged ≤ 18 years. Whereas previously children experienced a disproportionately high CFR, interventions have reversed this trend. Disease clusters in urban nuclei, but location remains a predictor of fatal outcome.

Molecular Confirmation of Rocky Mountain Spotted Fever Epidemic Agent in Mexicali, Mexico.

Since 2008, a large epidemic of Rocky Mountain spotted fever has been emerging among humans and dogs in Mexicali, adjacent to the United States in Baja California, Mexico. We molecularly confirmed the causative agent; this information can be used to study the origin and dynamics of the epidemic.

Predictive Factors for Fatal Tick-Borne Spotted Fever in Brazil.

In Brazil, two pathogenic Rickettsia species have been identified causing tick-borne spotted fever (SF). The aetiological agent Rickettsia rickettsii causes serious illness, particularly in the south-eastern region of the country. Moreover, the Rickettsia sp. strain Atlantic Rainforest cause milder clinical manifestations in south-eastern, south and north-east regions. This study has sought to analyse predictive factors for fatal SF. A case-control study was performed using disease notification records in Brazil. The cases included were individuals with laboratory confirmation and fatal progression of SF, while the controls included individuals with SF who were cured. A total of 386 cases and 415 controls were identified (1 : 1.1), and the cases and controls were similar in age. The factors identified as being protective against death were reported presence of ticks (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.41-0.88), residing in urban areas (OR, 0.47, 95% CI, 0.31-0.74) and presenting lymphadenopathy (OR, 0.43; 95% CI, 0.23-0.82). Males exhibited a greater chance of death (OR, 1.57; 95% CI, 1.13-2.18), as did patients who were hospitalized (OR, 10.82; 95% CI, 6.38-18.35) and who presented hypotension or shock (OR, 10.80; 95% CI, 7.33-15.93), seizures (OR, 11.24; 95% CI, 6.49-19.45) and coma (OR of 15.16; 95% CI, 8.51-27.02). The study demonstrates the severity profile of the SF cases, defined either as the frequency of hospitalization (even in cases that were cured) or as the increased frequency of the clinical complications typically found in critical patients. Opportune clinical diagnosis, a careful evaluation of the epidemiological aspects of the disease and adequate care for patients are determining factors for reducing SF fatality rates.

Retrospective Study of Rocky Mountain Spotted Fever in Children.

BACKGROUND/OBJECTIVES: Rocky Mountain spotted fever (RMSF), a lethal tick-borne illness, is prevalent in the south central United States. Children younger than 10 years old have the greatest risk of fatal outcome from RMSF. The objective of the current study was to review pediatric cases of RMSF seen in the dermatology consult service and to evaluate dermatology's role in the diagnosis and management of this disease. METHODS: A retrospective review was performed of inpatient dermatology consultations at a tertiary care center in North Carolina from 2001 to 2011. Data collected included patient demographic characteristics, symptoms, pre- and postconsultation diagnoses, diagnostic procedures, length of hospital stay, and outcome. RESULTS: A total of 3,912 consultations were conducted in the dermatology service over 10 years. Six patients with RMSF, ranging in age from 22 months to 10 years (mean 5.1 years), were evaluated during April, May, and June. All preconsultation diagnoses included RMSF in the differential diagnosis. All patients underwent skin biopsies, and a culture was obtained in one case. Fifty percent of patients died within 4 days of hospitalization. CONCLUSIONS: Variables associated with mortality from RMSF are delayed diagnosis and initiation of antirickettsial therapy. Physicians should consider RMSF in children presenting with fever and rash during the summer months. Dermatology consultation is useful in evaluating patients with suspicious clinical features of RMSF with skin findings.

[Complications and cause of death in mexican children with rocky mountain spotted fever]. / Complicaciones y causa de muerte en niños mexicanos con fiebre manchada de las Montañas Rocosas (FMMR).

BACKGROUND: Rocky Mountain spotted fever is a life threatening disease caused by Rickettsia rickettsia, characterized by multisystem involvement. METHODS: We studied 19 dead children with Rocky Mountain spotted fever. All children who were suspected of having rickettsial infections were defined as having Rocky Mountain spotted fever by serology test and clinical features. Through the analysis of each case, we identified the clinical profile and complications associated to the death of a patient. RESULTS: In nine (69.2%) of 13 cases that died in the first three days of admission, the associated condition was septic shock. Others complications included respiratory distress causes by non-cardiogenic pulmonary edema, renal impairment, and multiple organ damage. CONCLUSIONS: The main cause of death in this study was septic shock. The fatality rate from Rocky Mountain spotted fever can be related to the severity of the infection, delay in diagnosis, and delay in initiation of antibiotic therapy. Pulmonary edema and cerebral edema can be usually precipitated by administration of excess intravenous fluids.

[Rocky Mountain spotted fever in Mexican children: Clinical and mortality factors]. / Fiebre maculosa de las Montañas Rocosas en niños y adolescentes mexicanos: cuadro clínico y factores de mortalidad.

OBJECTIVE: Characterize clinical manifestations and predictors of mortality in children hospitalized for spotted fever. MATERIALS AND METHODS: Cross-sectional study in 210 subjects with a diagnosis of Rocky Mountain spotted fever (RMSF) in a pediatric hospital in Sonora, from January 1st, 2004 to June 30th, 2015. Data were analyzed using descriptive statistics and multivariate logistic regression. RESULTS: An upward trend was observed in RMSF morbidity and mortality. Fatality rate was 30%.Three predictors were associated with risk of death: delay ≥ 5 days at the start of doxycycline (ORa= 2.95, 95% CI 1.10-7.95), acute renal failure ((ORa= 8.79, 95% CI 3.46-22.33) and severe sepsis (ORa= 3.71, 95% CI 1.44-9.58). CONCLUSIONS: RMSF causes high mortality in children, which can be avoided with timely initiation of doxycycline. Acute renal failure and severe sepsis are two independent predictors of death in children with RMSF.

Fiebre maculosa de las Montañas Rocosas en niños y adolescentes mexicanos: cuadro clínico y factores de mortalidad / Rocky Mountain spotted fever in Mexican children: Clinical and mortality factors

Resumen: Objetivo: Caracterizar las manifestaciones clínicas y predictores de mortalidad en niños hospitalizados por fiebre maculosa de las Montañas Rocosas (FMMR). Material y métodos: Estudio transversal en 210 sujetos hospitalizados por FMMR en un hospital pediátrico de Sonora, entre el 1 de enero de 2004 y el 30 de junio de 2015. El análisis se sustentó en estadística descriptiva y regresión logística multivariada. Resultados: Se apreció un incremento en la incidencia y mortalidad en los casos hospitalizados por FMMR, con una letalidad de 30%.Tres variables se asociaron con el riesgo de muerte: retraso ≥ 5 días en el inicio del uso de doxiciclina (RMa=2.95, IC95% 1.10-7.95), falla renal aguda (RMa=8.79, IC95% 3.46-22.33) y sepsis severa (RMa=3.71, IC95% 1.449.58). Conclusión: La FMMR provoca resultados fatales en niños, que puede evitarse con la administración oportuna de doxiciclina. La falla renal aguda y la sepsis severa son dos predictores de muerte en niños con FMMR.

Abstract: Objective: Characterize clinical manifestations and predictors of mortality in children hospitalized for spotted fever. Materials and methods: Cross-sectional study in 210 subjects with a diagnosis of Rocky Mountain spotted fever (RMSF) in a pediatric hospital in Sonora, from January 1st, 2004 to June 30th, 2015. Data were analyzed using descriptive statistics and multivariate logistic regression. Results: An upward trend was observed in RMSF morbidity and mortality. Fatality rate was 30%.Three predictors were associated with risk of death: delay ≥ 5 days at the start of doxycycline (ORa= 2.95, 95% CI 1.10-7.95), acute renal failure ((ORa= 8.79, 95% CI 3.46-22.33) and severe sepsis (ORa= 3.71, 95% CI 1.44-9.58). Conclusions: RMSF causes high mortality in children, which can be avoided with timely initiation of doxycycline. Acute renal failure and severe sepsis are two independent predictors of death in children with RMSF.

Clinical profile and predictors of fatal Rocky Mountain spotted fever in children from Sonora, Mexico.

BACKGROUND: Rocky Mountain spotted fever (RMSF) is an increasingly important cause of preventable mortality in children in Sonora, Mexico. Although early treatment with tetracycline has shown to prevent fatal outcome, the disease remains a life-threatening condition, particularly for children. This study describes the clinical factors associated with pediatric mortality due to RMSF in Sonora, in order to guide healthcare practices. METHODS: This is a retrospective analysis of 104 children consecutively hospitalized at the major pediatric hospital of Sonora, diagnosed with RMSF between January 2004 and December 2013. Descriptive statistics and multiple logistic regression were used to identify risk factors for fatal outcome. RESULTS: The case fatality ratio in this cohort was 20.2%. Children were hospitalized after a median of 6 days from onset of symptoms including fever (100%), rash involving palms and soles (88.5%) and headache (79.8%); 90.4% of fatal cases had low platelet counts (<50,000/µL) and 33.3% showed serum creatinine concentrations above the normal value. Acute kidney injury increased mortality, odds ratio (OR(adj)) = 4.84, 95% confidence interval (CI): 1.2-16.2, as well as delay in treatment (≥ 5th day from onset) with doxycycline, OR(adj) = 2.62, 95% CI: 1.24-5.52 and hemorrhage, OR(adj) = 6.11, 95% CI: 1.89-19.69. CONCLUSIONS: RMSF is a public health problem in Sonora. Clinically, fatal cases differ from non-fatal cases in renal function and hemorrhagic manifestations, although these findings may occur too late for a timely intervention. First-line providers must be educated to harbor a timely suspicion of RMSF, and should provide empiric treatment with doxycycline when febrile patients first present for care.

Feeding period required by Amblyomma aureolatum ticks for transmission of Rickettsia rickettsii to vertebrate hosts.

Rocky Mountain spotted fever is endemic to the São Paulo metropolitan area, Brazil, where the etiologic agent, Rickettsia rickettsii, is transmitted to humans by adult Amblyomma aureolatum ticks. We determined the minimal feeding period required by A. aureolatum nymphs and adults to transmit R. rickettsii to guinea pigs. Unfed nymphs and unfed adult ticks had to be attached to the host for >10 hours to transmit R. rickettsii. In contrast, fed ticks needed a minimum of 10 minutes of attachment to transmit R. rickettsii to hosts. Most confirmed infections of Rocky Mountain spotted fever in humans in the São Paulo metropolitan area have been associated with contact with domestic dogs, the main host of A. aureolatum adult ticks. The typical expectation that transmission of tickborne bacteria to humans as well as to dogs requires ≥2 hours of tick attachment may discourage persons from immediately removing them and result in transmission of this lethal bacterium.

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.

Self-reported treatment practices by healthcare providers could lead to death from Rocky Mountain spotted fever.

Among 2012 Docstyle survey respondents, 80% identified doxycycline as the appropriate treatment for Rocky Mountain spotted fever in patients ≥ 8 years old, but only 35% correctly chose doxycycline in patients <8 years old. These findings raise concerns about the higher pediatric case-fatality rate of Rocky Mountain spotted fever observed nationally. Targeted education efforts are needed.

Investigation of an outbreak of rickettsial febrile illness in Guatemala, 2007.

OBJECTIVES: We describe an outbreak of spotted fever group (SFG) rickettsiosis that occurred in 2007 in a farming community in southeastern Guatemala. We identified 17 cases of an acute febrile illness, among which 10, including two fatalities, were confirmed or probable cases of rickettsial disease (case-fatality proportion 12%). METHODS: PCR, a microimmunofluorescence assay (IFA), and Western blotting were performed on patient samples, and PCR was performed on ticks. RESULTS: Using an indirect IFA, seven of 16 (44%) ill persons tested had both IgM and IgG antibodies reacting with one or more Rickettsia spp antigens; the other nine (56%) had only IgM titers or were seronegative. Antibodies to SFG protein and lipopolysaccharide were detected by Western blotting with antigens of Rickettsia typhi, Rickettsia rickettsii, and Rickettsia akari. Only one sample, from an ill person who died, tested positive by PCR for a SFG Rickettsia. PCR analysis of Amblyomma cajennense ticks from domestic animals in the area detected the presence of SFG Rickettsia DNA in one of 12 ticks collected. CONCLUSIONS: Further studies in Guatemala are warranted to establish the prevalence of rickettsioses and to fully characterize the identity of the etiologic agents and vectors.

Fatal Rocky Mountain spotted fever in the United States, 1999-2007.

Death from Rocky Mountain spotted fever (RMSF) is preventable with prompt, appropriate treatment. Data from two independent sources were analyzed to estimate the burden of fatal RMSF and identify risk factors for fatal RMSF in the United States during 1999-2007. Despite increased reporting of RMSF cases to the Centers for Disease Control and Prevention, no significant changes in the estimated number of annual fatal RMSF cases were found. American Indians were at higher risk of fatal RMSF relative to whites (relative risk [RR] = 3.9), and children less than 10 years of age (RR=5.1) [corrected] and adults ≥ 70 years of age (RR = 3.0) were also at increased risk relative to other ages. Persons with cases of RMSF with an immunosuppressive condition were at increased risk of death (RR = 4.4). Delaying treatment of RMSF was also associated with increased deaths. These results may indicate a gap between recommendations and practice.

Epidemiological characteristics of Brazilian spotted fever in Minas Gerais State, Brazil, 2000-2008.

Brazilian spotted fever is the most common rickettsiosis in Brazil, most prevalent in the States of São Paulo and Minas Gerais. The aim of this study was to describe the epidemiological characteristics of Brazilian spotted fever in Minas Gerais from 2000 to 2008. Of the 132 cases of Brazilian spotted fever, 53 patients died, representing a case-fatality rate of 40.2%. Males predominated, with 78.8% of confirmed cases, and median age was 26.5 years. Absence of rash was associated with increased risk of death (p = 0.005). Greater Metropolitan Belo Horizonte, Rio Doce Valley, and Zona da Mata accounted for 70.6% of the cases, which occurred mainly from May to November. There was an increase in the number of cases, which could suggest an expansion of the disease, but probably resulted from an increase in the health system's diagnostic capacity and sensitivity. Despite this improvement, the case-fatality rate remains high and with no apparent tendency to decrease, thus indicating the need for improved prevention and patient care.

Epidemiological characteristics of Brazilian spotted fever in Minas Gerais State, Brazil, 2000-2008 / Aspectos epidemiológicos dos casos de febre maculosa brasileira ocorridos em Minas Gerais, Brasil, 2000 a 2008

Brazilian spotted fever is the most common rickettsiosis in Brazil, most prevalent in the States of São Paulo and Minas Gerais. The aim of this study was to describe the epidemiological characteristics of Brazilian spotted fever in Minas Gerais from 2000 to 2008. Of the 132 cases of Brazilian spotted fever, 53 patients died, representing a case-fatality rate of 40.2 percent. Males predominated, with 78.8 percent of confirmed cases, and median age was 26.5 years. Absence of rash was associated with increased risk of death (p = 0.005). Greater Metropolitan Belo Horizonte, Rio Doce Valley, and Zona da Mata accounted for 70.6 percent of the cases, which occurred mainly from May to November. There was an increase in the number of cases, which could suggest an expansion of the disease, but probably resulted from an increase in the health system's diagnostic capacity and sensitivity. Despite this improvement, the case-fatality rate remains high and with no apparent tendency to decrease, thus indicating the need for improved prevention and patient care.

A febre maculosa brasileira é a rickettsiose mais comum do território nacional, com maior importância nos estados de São Paulo e Minas Gerais. O objetivo deste estudo foi descrever os aspectos epidemiológicos dos casos de febre maculosa brasileira ocorridos em Minas Gerais no período de 2000 a 2008. Dos 132 casos confirmados, 53 evoluíram para óbito, representando uma letalidade de 40,2 por cento. O sexo masculino foi o mais acometido com 78,8 por cento dos casos confirmados, e mediana de idade de 26,5 anos. Entre os fatores de risco determinantes do óbito, a ausência de exantema apresentou associação significativa (p = 0,005). A Região Metropolitana de Belo Horizonte, o Vale do Rio Doce e a Zona da Mata responderam por 70,6 por cento dos casos, que ocorreram principalmente entre os meses de maio e novembro. Houve crescimento no número de casos, que apesar de sugerir expansão da doença, provavelmente decorreu do aumento da capacidade diagnóstica e sensibilidade do sistema de saúde. Apesar dessa melhora, a letalidade permaneceu alta e sem tendências à diminuição, o que implica a necessidade de medidas preventivas e assistenciais.