Fatal Cases of Rocky Mountain Spotted Fever in Family Clusters—Three States, 2003 FREE

MMWR. 2004;53:407-410

Rocky Mountain spotted fever (RMSF), a tickborne infection caused by Rickettsia rickettsii and characterized by a rash (figure), has a case-fatality rate as high as 30% in certain untreated patients.¹ Even with treatment, hospitalization rates of 72% and case-fatality rates of 4% have been reported.^1-3 This report summarizes the clinical course of three fatal cases of RMSF in children and related illness in family members during the summer of 2003. These cases underscore the importance of (1) prompt diagnosis and appropriate antimicrobial therapy in patients with RMSF to prevent deaths and (2) consideration of RMSF as a diagnosis in family members and contacts who have febrile illness and share environmental exposures with the patient.

Oklahoma. In late May, a female child aged 7 years was taken to an emergency department (ED) with 2 days of fever (102.7°F [39.3°C]), malaise, abdominal pain, nausea, and vomiting. Viral gastroenteritis was diagnosed, and the patient was released. Four days later, the patient reported to a second ED with persistent fever, anorexia, irritability, photophobia, cough, diffuse myalgias, nausea, and vomiting. Physical examination showed hepatosplenomegaly and an erythematous papular rash with scattered petechiae on the trunk, arms, legs, palms, and soles. Laboratory results included an elevated white blood cell (WBC) count of 11.4 × 10⁹ cells/L (normal range: 3.0-9.1 × 10⁹ cells/L), thrombocytopenia (19 × 10⁹ platelets/L [normal range: 150-350 × 10⁹ platelets/L]), elevated aspartate aminotransferase (AST) of 279 U/L (normal: ≤42 U/L), and elevated alanine aminotransferase (ALT) of 77 U/L (normal: ≤48 U/L). In the ED, the patient was treated with intravenous (IV) doxycycline for suspected RMSF and transferred to a pediatric intensive care unit at a tertiary care medical center, where she had declining mental status, metabolic acidosis, and respiratory failure; the patient died 6 days after initially seeking treatment. IgG antibodies reactive with R. rickettsii at a reciprocal titer of 128 were demonstrated by using an indirect immunofluorescence antibody (IFA) assay in a serum specimen collected 2 days before death. Spotted fever group rickettsiae (SFGR) were detected by immunohistochemical (IHC) staining at CDC in autopsy specimens from the brain, skin, heart, lung, spleen, and kidney.

On June 1, the child's sister, aged 3 years, had fever, headache, myalgias, and vomiting; on the following day, she had an erythematous maculopapular rash on the trunk, extremities, palms, and soles. RMSF was diagnosed, and the child was treated with doxycycline; she recovered. Seroconversion of IgG antibodies reactive with R. rickettsii was demonstrated in acute and convalescent phase serum specimens obtained during illness and 5 months later. Both children played frequently in grassy areas near their home. No history of tick bite was reported, although ticks were frequently observed on the family's pet dogs and often were manually removed by members of the household.

Kentucky. In early August, a male child aged 2 years was taken to a pediatrician after 1 day of fever (101.0°F [38.3°C]) with a papular rash on his legs, arms, trunk, and back. An unspecified viral syndrome was diagnosed, and the child was treated with nonsteroidal anti-inflammatory drugs. During the next 2 days, the child continued to have fevers, spiking to 102.0°F–103.0°F (38.9°C–39.4°C), and variable rash. The child was examined in an ED and discharged with a diagnosis of viral infection. Four days after initial treatment, the child was again evaluated by a pediatrician because of lethargy and refusal to walk. Laboratory tests showed thrombocytopenia (42 × 10⁹ platelets/L), a WBC count of 3.3 × 10⁹ cells/L, anemia (hemoglobin 10.4 g/dL [normal range: 13.8-17.2 g/dL]), and hyponatremia (134 mmol sodium/L [normal range: 135-145 mmol sodium/L]). The next day, the child was admitted and treated with IV ceftriaxone and methylprednisolone. Two days later, the child was transferred to a tertiary care hospital. Physical examination at admission revealed a fine petechial rash on the groin, trunk, ankles, and palms. The patient was treated with IV vancomycin, cefotaxime, and doxycycline. His condition continued to deteriorate; 8 days after initial treatment, he died from multiple system failure. A serum specimen collected 2 days earlier tested positive by enzyme immunoassay for IgM antibodies reactive with R. rickettsii at 9.4 index value units (index values >2.0 were considered reactive by the testing laboratory). SFGR were detected by IHC stain in autopsy specimens of the brain, skin, heart, lung, spleen, kidney, lung, and adrenal gland.

The child's mother, aged 40 years, was hospitalized 2 days before her son's death with 2 days of diplopia, dizziness, headache, and fever. Oral doxycycline and IV ceftriaxone were administered; she was discharged after 5 days. Seroconversion of IgG antibodies reactive with R. rickettsii was demonstrated in acute and convalescent phase serum specimens obtained during illness and 2 weeks later. The family lived near a lake with woods. The mother did not recall any recent tick bites, travel, or participation in outdoor activities, by herself or her son prior to illness onset.

Arizona. In mid-August, a male child aged 14 months was taken to a community health clinic after 1 day of fever (103.7°F [39.8°C]), with a maculopapular rash, including the palms and soles, and thick white exudates on the tongue. Chest radiographic evaluation showed a possible right lower lobe infiltrate. The child was treated with intramuscular cefotaxime, acetominophen, and antifungal medication for presumptive thrush. The next day, the child visited the clinic with nausea, vomiting, anorexia, and dehydration. The patient was transferred to a referral hospital for treatment of pneumonia, roseola infantum, and thrush; on admission, the patient had a temperature of 105.7°F (41°C). After 3 days, he was transferred to a tertiary care hospital with a diagnosis of sepsis and disseminated intravascular coagulopathy. The patient was treated with IV ceftazidime and vancomycin. Laboratory findings included an elevated WBC count (16.2 × 10⁹ cells/L), thrombocytopenia (46 × 10⁹ platelets/L), and elevated levels of AST (291 U/L) and ALT (99 U/L). Six days after initial treatment, the child died of pulmonary hemorrhage; an autopsy was not performed. A serum specimen obtained 5 days before the child's death tested negative by IFA for IgM and IgG antibodies reactive with R. rickettsii; however, R. rickettsii DNA was amplified from serum by polymerase chain reaction (PCR) assay. A serum specimen obtained from a brother, aged 5 years, showed IgM and IgG antibodies reactive to R. rickettsii, indicating recent exposure. The children lived in a rural environment with low shrubs and grasses and frequently interacted with free-roaming dogs with ticks; however, neither child had a history of recent tick bite.

C Levy, MS, J Burnside, MS, T Tso, Arizona Dept of Health Svcs. S Englender, MD, M Auslander, DVM, S Billings, DVM, Div of Epidemiology and Health Planning, Kentucky Dept for Public Health. K Bradley, DVM, J Bos, MPH, L Burnsed, MPH, Div Communicable Diseases, Oklahoma Dept of Health. J Brown, MD, D Mahoney, MD, K Chamberlain, M Porter, C Duncan, B Johnson, R Ethelbah, K Robinson, M Wessel, S Savoia, MD, C Garcia, J Dickson, D Kvamme, D Yost, MD, M Traeger, MD, Indian Health Svc. J Krebs, MS, C Paddock, MD, W Shieh, MD, J Guarner, MD, S Zaki, MD, D Swerdlow, MD, J McQuiston, DVM, WL Nicholson, PhD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; L Demma, PhD, EIS Officer, CDC.

RMSF is the most commonly fatal tickborne illness in the United States. Characterized by fever and a macular rash in its early stages, untreated RMSF can result in severe systemic manifestations, including pneumonitis, myocarditis, hepatitis, acute renal failure, encephalitis, gangrene, and death. An estimated 612 deaths were attributable to RMSF in the United States during 1983-1998, and approximately 12% of reported deaths occurred in children aged <10 years.⁴ Family clusters of infection are a well-recognized feature of RMSF because of shared residence and risks for vector exposure.⁵

In its early stages, RMSF can resemble many other infectious and noninfectious conditions and can be difficult to diagnose (Box), even for physicians familiar with the disease. ^3,6 The majority of patients do not have the classic RMSF triad of fever, rash, and history of tick bite on their first visit for medical care; often the rash appears several days after onset of fever and can evolve to become petechial. The absence of known tick bite is common and should not dissuade clinicians from suspecting RMSF. None of the patients in this report recalled a tick bite before illness onset, although all lived near wooded or grassy areas where ticks might have been present.

The infection can have a rapid course; 50% of RMSF deaths occur within 9 days of illness onset.^1,2 Doxycycline therapy is considered the best treatment for RMSF in both adults and pediatric patients and is most successful when initiated within 5 days of illness onset.^1,7 Delay of doxycycline therapy can increase the risk for severe or fatal outcomes; treatment should never be delayed pending laboratory confirmation.

Criteria for diagnosis* of a confirmed infection include the presence of a clinically compatible illness, plus at least one of the following: (1) serologic evidence of a significant change (fourfold increase or greater) in antibody titer reactive with R. rickettsii antigens between paired serum specimens, as measured by a standardized assay conducted in a commercial, state, or reference laboratory; (2) demonstration of R. rickettsii antigen by IHC in a clinical specimen such as skin biopsy or other tissue; (3) detection of R. rickettsii DNA by PCR in a clinical specimen, such as whole blood or tissue; or (4) isolation of R. rickettsii from a clinical specimen in cell culture. Probable cases have a clinically compatible illness and serologic evidence of antibodies reactive with R. rickettsii in a single serum sample at a titer considered indicative of current or past infection (cutoff titers are determined by individual laboratories). At CDC, reciprocal IFA IgG titers of ≥64 are considered to be evidence of current or past infection.

The most effective measures to reduce the risk for RMSF (particularly in children) are to (1) limit exposure to ticks during periods of peak tick activity (i.e., April-September); (2) inspect the head, body, and clothes for ticks thoroughly after being in wooded or grassy areas, especially along the edges of trails, roads, or yards; and (3) remove attached ticks immediately by grasping them with tweezers or forceps close to the skin and pulling gently with steady pressure. Because rapid laboratory confirmation of RMSF infection is not available, clinicians should consider initiating empiric therapy in patients with a compatible clinical presentation (e.g., fever usually with subsequent development of a macular or petechial rash) and epidemiologic circumstance (e.g., recent recreational or occupational activities during spring and summer months that could have exposed persons to ticks) to reduce morbidity and mortality resulting from delayed diagnosis.^3,6 As a nationally notifiable disease, all RMSF cases should be reported to state health departments. Additional information about RMSF is available at http://www.cdc.gov/ncidod/dvrd/rmsf/index.htm.

References: 7 available

*A case definition for RMSF is available at http://www.cste.org/ps/2003pdfs/2003finalpdf/03-id-08revised.pdf.