ESSENTIALS OF DIAGNOSIS
Exposure to tick bite in an endemic area.
Influenza-like prodrome followed by fever, severe headache, and myalgias; occasionally, delirium and coma.
Red macular rash appears between days 2 and 6 of fever, first on the wrists and ankles and then spreading centrally; it may become petechial.
Mortality over 70% in untreated patients.
Serial serologic examinations by indirect fluorescent antibody confirm the diagnosis retrospectively.
Despite its name, most cases of Rocky Mountain spotted fever (RMSF) occur outside the Rocky Mountain area. More than half of the cases are from five states: North Carolina, Tennessee, Oklahoma, Missouri, and Arkansas (eFigure 32–6). RMSF is endemic in Central and South America with a small fatal familial cluster reported from Panama (Table 32–3). Native Americans are at high risk for infection. The causative agent, R rickettsii, is transmitted to humans by the bite of ticks, including the Rocky Mountain wood tick, Dermacentor andersoni, in the western United States, and the American dog tick, D variabilis, in the eastern United States. Several hours of contact between the tick and the human host are required for transmission. The brown dog tick, Rhipicephalus sanguineus, is a vector in eastern Arizona and responsible for many Native American cases. Epidemic RMSF, as described in Arizona and Mexico, is associated with massive local infestations of the brown dog tick in domestic dogs, which may explain why the incidence of RMSF in the three most highly affected communities in an Arizona epidemic from 2003 to 2012 was 150 times the US national average. Recent studies show that the seroprevalence for dogs on the Arizona Mexican border is lower than anticipated at about 5% seroprevalence for spotted fever group rickettsial antibodies.
Other hard-bodied ticks transmit the organism in the southern United States and in Central and South America and are responsible for transmitting it among rodents, dogs, porcupines, and other animals. Human cases reemerged in Mexico in 2008 after decades of quiescence (since the 1940s). As of 2018, northern Mexico reported nearly 4000 RMSF cases.
There are 25 genotypes of R rickettsii in four different groups, and potential genomic-clinical correlations are underway. Several other rickettsial species cause mild, nonlethal infections in the United States, including R parkeri, R phillipi, and R massiliae. These are discussed in the “tick typhus” section.
In the United States, the estimated annual incidence of RMSF is as high as seven cases per million persons (primarily occurring from April through September), with a higher incidence among children and men. Better diagnostic capacity and improved surveillance are thought responsible for the changing epidemiology.
A Brazilian spotted fever with higher mortality than RMSF is thought to be due to a virulent strain of R rickettsii. A host of spotted fever species have been identified from human patients over the last 20 years throughout the world including species from China (Rickettsia sp. XY99), Slovakia (R slovaca), Morocco (R aeschlimannii), Sicily (R massiiliae), China, and Egypt (R sibirica monolitimonae). Capybaras are a highly mobile vector for the Brazilian disease.
RMSF can cause severe multiorgan dysfunction and fatality rates of up to 73% if left untreated, making it the most serious rickettsial disease. Two to 14 days (mean, 7 days) after the bite of an infectious tick, symptoms begin with the abrupt onset of high fever, chills, headache, nausea and vomiting, myalgias, restlessness, insomnia, and irritability. The characteristic rash (faint macules that progress to maculopapules and then petechiae) appears between days 2 and 6 of fever. It initially involves the wrists and ankles, spreading centrally to the arms, legs, and trunk over the next 2–3 days. Involvement of the palms and soles is characteristic. Eschars are more suggestive of rickettsial fevers. Facial flushing, conjunctival injection, and hard palate lesions (Figure 32–7) may occur. In about 10% of cases, however, no rash or only a minimal rash is seen. Cough and pneumonitis may develop, and delirium, lethargy, seizures, stupor, and coma may also appear in more severe cases. Splenomegaly, hepatomegaly, jaundice, myocarditis (which may mimic an acute coronary syndrome), adrenal hemorrhage, polyarticular arthritis, or uremia is occasionally present. ARDS and necrotizing vasculitis, when present, are of greatest concern.
Hard palate lesion caused by Rocky Mountain spotted fever. (Public Health Image Library, CDC.)
In Sonora, Mexico during 2015–2016, spontaneous abortions were reported in three of four pregnant women with RMSF.
Thrombocytopenia, hyponatremia, elevated aminotransferases, and hyperbilirubinemia are common. CSF may show hypoglycorrhachia and mild pleocytosis. Disseminated intravascular coagulation is observed in severe cases. Diagnosis during the acute phase of the illness can be made by immunohistologic or PCR demonstration of R rickettsii in skin biopsy specimens (or cutaneous swabs of eschars or skin lesions). Performing such studies as soon as skin lesions become apparent and before antibiotics commence maximizes sensitivity. Isolation of the organism using the shell-vial technique is available in some laboratories but is hazardous.
Serologic studies confirm the diagnosis, but most patients do not mount an antibody response until the second week of illness. The indirect fluorescent antibody test is most commonly used.
Diagnosis is most commonly made serologically and 99% of cases are diagnosed with probable disease. It is important that paired sera (acute and convalescent) be used when possible to establish an acute infection.
The diagnosis is challenging because early symptoms resemble those of many other infections. The classic triad of fever, rash, and tick bite is rarely recognized, with up to 40% of patients not recalling a tick bite. Moreover, the rash may be confused with that of measles, typhoid, and ehrlichiosis, or—most importantly—meningococcemia. Blood cultures and examination of CSF establish the latter. Coinfections may mask the diagnosis. Some spotted fever rickettsioses may also mimic RMSF but will not be detected by routine serologic testing for RMSF.
Treatment with doxycycline at similar doses and duration as for epidemic typhus (100 mg orally twice daily for 4–10 days) is recommended. Similarly, chloramphenicol (50–100 mg/kg/day in four divided doses, orally or intravenously for 4–10 days) is the preferred alternative during pregnancy. Patients usually defervesce within 48–72 hours, and therapy should be continued for at least 3 days after defervescence occurs.
The reported mortality rate for treated patients in the United States is about 3–5%. The following features are associated with increased mortality: (1) infection in older adults or Native Americans; (2) the presence of atypical clinical features (absence of headache, no history of tick attachment, gastrointestinal symptoms) and underlying chronic diseases; and (3) a delay in initiation of appropriate antibiotic therapy. The usual cause of death is pneumonitis with respiratory or cardiac failure. A fulminant form of RMSF can be seen in patients with glucose-6-phosphate dehydrogenase deficiency. Sequelae may include seizures, encephalopathy, peripheral neuropathy, paraparesis, bowel and bladder incontinence, cerebellar and vestibular dysfunction, hearing loss, and motor deficits; these sequelae are reported to last for years after the initial infection.
Unfavorable prognostic factors for mortality from a 2017 Brazilian series of spotted fever cases included male sex, shock, seizures, and hypotension, and favorable prognostic factors were urban exposure, recognition of a tick, and lymphadenopathy. Cases reported from Mexico in 2017 were more severe among children under 10 years of age and among the very poor.
Protective clothing, tick-repellent chemicals, and the removal of ticks at frequent intervals are helpful measures. The effectiveness of aggressive campaigns to decrease ticks in the community is under investigation in communities with high RMSF attack rates. Prophylactic therapy after a tick bite is not recommended.
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