Why Only 1% of Spotted Fever Cases Are Confirmed: A Look at the Lab Tests, 2010–2015

Summary

• Spotted fever rickettsioses (SFR) — including Rocky Mountain spotted fever (RMSF) — are tickborne bacterial diseases. Reported incidence rose from 1.7 per million people in 2000 to 13.2 in 2016, but how much of that rise is real is uncertain.
• Of 16,807 cases reported to CDC with illness in 2010–2015, only 167 (1.0%) were confirmed; 16,640 (99.0%) were probable.
• Most probable cases rested on one elevated antibody test, which can't distinguish a new infection from a past one. More molecular testing and properly timed paired blood samples would sharpen the picture.

The diseases

SFR are spread by infected ticks and are hard to diagnose early: fever, headache, malaise, a rash and sometimes an eschar are nonspecific, and early tests aren't widely available. Severity varies: Rickettsia parkeri infection is usually milder, while RMSF, caused by R. rickettsii, is the most severe tickborne disease in the U.S., killing an estimated 5%–10% of those infected. Doxycycline is the treatment of choice for all SFR, and delay raises the risk of death. A growing share of cases is thought to be caused by milder species — but routine antibody tests cross-react and can't identify the species.

What counts as confirmed

• Confirmed: a fourfold rise in IgG antibodies by indirect immunofluorescence assay (IFA) between paired samples — one in the first week of illness, another 2–4 weeks later — or detection by PCR, immunohistochemistry or culture.
• Probable: IgG or IgM antibodies by IFA, ELISA, dot-ELISA or latex agglutination.

What the reports showed

Annual reports rose from 1,617 in 2010 to 2,275 in 2015, while the confirmed share fell from 1.9% to 0.7%.

Confirmed cases (167): most by seroconversion, the rest by PCR, immunohistochemistry or culture. The first sample was taken a median 4 days after onset, and in cases with two samples, the second a median 19 days later.

Probable cases (16,640):

A second sample was collected for only 2,942 probable cases (19.7%), and only 1,618 of those were tested by IFA IgG.

Reported SFR cases by case status and laboratory method, 2010–2015. Figure from the CDC report.

Why a single test misleads

IgG antibodies can stay high for months or years after infection. National studies suggest up to 6% of Americans have them, and in some areas where SFR is common, as many as 22%. So one elevated titer — even during a compatible illness — can't prove a new infection. IgM, ELISA and latex agglutination results are weaker still.

What would help

• Clinicians and health departments: recognize the limits of unpaired tests and ask patients to return for a convalescent blood sample.
• Molecular tests: species-specific real-time PCR has been available to qualified state and local labs through CDC's Laboratory Response Network since 2018; using it more would reveal which species cause illness.
• Case definition: dropping tests of limited value as supporting evidence could make species-specific trends clearer.

Limits: surveillance is passive, with uneven investigation and reporting; only cases reported on the supplemental forms were included; and those forms carry limited clinical detail.

Sources

Based on Alison M. Binder, Kristen Nichols Heitman and Naomi A. Drexler, "Diagnostic Methods Used to Classify Confirmed and Probable Cases of Spotted Fever Rickettsioses — United States, 2010–2015," MMWR, Centers for Disease Control and Prevention; a work of the United States government in the public domain. The report's breakdown of confirmed cases by method (102, 66 and one) sums to more than its total of 167; this page leaves the breakdown out.