78 - SECTION 10 Diseases Caused by Rickettsiae, Mycoplasmas, and Chlamydiae

SECTION 10 Diseases Caused by Rickettsiae, Mycoplasmas, and Chlamydiae

■ ■FURTHER READING Arvikar SL, Steere AC: Diagnosis and treatment of Lyme arthritis.

Infect Dis Clin North Am 36:563, 2022. Aucott JN: Posttreatment Lyme disease syndrome. Infect Dis Clin North Am 29:309, 2015. Branda JA, Steere AC: Laboratory diagnosis of Lyme borreliosis. Clin Micro Rev 34:e00018, 2021. Branda JA et al: Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immu­ noassay followed by a VlsE C6 peptide enzyme immunoassay. Clin Infect Dis 53:541, 2011. Klempner MS et al: Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 345:85, 2001. Lantos PM et al: Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology, and the American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis, and treatment of Lyme disease. Clin Infect Dis 72:1, 2021. Lemieux JE et al: Whole genome sequencing of human Borrelia burg­ dorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination. PLoS Pathog 17:e1011243, 2023. Li X et al: Burden and viability of Borrelia burgdorferi in skin or joints of patients with erythema migrans or Lyme arthritis. Arthritis Rheum 63:2238, 2011. Lochhead RB et al: Lyme arthritis, linking infection, inflammation, and autoimmunity. Nat Rev Rheumatol 17:449, 2021. Oschmann P et al: Stages and syndromes of neuroborreliosis. J Neurol PART 5 Infectious Diseases 245:262, 1998. Steere AC: Lyme disease. N Engl J Med 345:115, 2001. Steere AC: Posttreatment Lyme disease syndromes: Distinct pathogenesis caused by maladaptive host responses. J Clin Invest 130:2148, 2020. Steere AC et al: Prospective study of serologic tests for Lyme disease. Clin Infect Dis 47:188, 2008. Steere AC et al: Lyme borreliosis. Nat Rev Dis Primers 2:16090, 2016. Ursinus J et al: Prevalence of persistent symptoms after treatment for Lyme borreliosis: A prospective observational cohort study. Lancet Reg Health Eur 6:100142, 2021. Erratum in: Lancet Reg Health Eur 27:100622, 2023. Section 10 Diseases Caused by Rickettsiae, Mycoplasmas, and Chlamydiae David H. Walker, J. Stephen Dumler,

Lucas S. Blanton, Chantal P. Rovers

Rickettsial Diseases Rickettsiae are a heterogeneous group of small, obligately intracel­ lular, gram-negative coccobacilli and short bacilli, most of which are transmitted by a tick, mite, flea, or louse vector. Except in the case of louse-borne typhus, humans are incidental hosts. Among rickettsiae, Coxiella burnetii, Rickettsia prowazekii, and Rickettsia typhi have the well-documented ability to survive for an extended period outside the reservoir or vector and to be extremely infectious: inhalation of a single Coxiella microorganism can cause pneumonia. High-level infectivity and severe illness after inhalation make R. prowazekii, R. rickettsii, R. typhi, R. conorii, and C. burnetii bioterrorism threats (Chap. S4). Clinical infections with rickettsiae can be classified according to (1) the taxonomy and diverse microbial characteristics of the agents, which

belong to seven genera (Rickettsia, Orientia, Ehrlichia, Anaplasma, Neor­ ickettsia, “Candidatus Neoehrlichia,” and Coxiella); (2) epidemiology; or (3) clinical manifestations. The clinical manifestations of all the acute presentations are similar during the first 5 days: fever, headache, and myalgias with or without nausea, vomiting, and cough. As the course progresses, clinical manifestations—including a macular, maculopapu­ lar, or vesicular rash; eschar; pneumonitis; and meningoencephalitis— vary from one disease to another. Given the many etiologic agents with varied mechanisms of transmission, geographic distributions, and asso­ ciated disease manifestations, the consideration of rickettsial diseases as a single entity poses complex challenges (Table 192-1). Establishing the etiologic diagnosis of rickettsioses is very diffi­ cult during the acute stage of illness, and definitive diagnosis usually requires the examination of serum samples during the acute and con­ valescent phases of illness. Heightened clinical suspicion is based on epidemiologic data, history of exposure to vectors or reservoir animals, travel to endemic locations, clinical manifestations (sometimes includ­ ing rash or eschar), and characteristic laboratory findings (including thrombocytopenia, normal or low white blood cell [WBC] counts, elevated hepatic enzyme levels, and hyponatremia). Such suspicion should prompt empirical treatment. Doxycycline is the empirical drug of choice for most of these infections. Only one agent, C. burnetii, has been documented to cause chronic illness. One other species, R. prowazekii, causes recrudescent illness (Brill-Zinsser disease) when latent infection is reactivated years after resolution of the acute illness. Rickettsial infections dominated by fever may resolve without fur­ ther clinical evolution. However, after nonspecific early manifestations, the illnesses can also evolve along one or more of several principal clinical lines: (1) development of a macular or maculopapular rash; (2) development of an eschar at the site of tick or mite feeding, which can occur during the incubation period; (3) development of a vesicular rash (often in rickettsialpox, R. parkeri infection, and African tick-bite fever); (4) development of pneumonitis with chest radiographic opaci­ ties and/or rales (Q fever and severe cases of Rocky Mountain spotted fever [RMSF], Mediterranean spotted fever [MSF], louse-borne typhus, human monocytotropic ehrlichiosis [HME], human granulocytotropic anaplasmosis [HGA], scrub typhus, and murine typhus); (5) develop­ ment of meningoencephalitis (louse-borne typhus and severe cases of RMSF, scrub typhus, HME, murine typhus, MSF, and [rarely] Q fever); and (6) progressive hypotension and multiorgan failure as seen with sepsis or toxic shock syndromes (RMSF, MSF, louse-borne typhus, murine typhus, scrub typhus, HME, HGA, and neoehrlichiosis). Epidemiologic clues to the transmission of a particular pathogen include (1) environmental exposure to ticks, fleas, or mites during the season of activity of the vector species for the disease in the appropri­ ate geographic region (spotted fever and typhus rickettsioses, scrub typhus, ehrlichiosis, anaplasmosis); (2) travel to or residence in an endemic geographic region during the incubation period (Table 192-1); (3) exposure to parturient ruminants, cats, and dogs (Q fever); (4) exposure to flying squirrels (R. prowazekii infection); and (5) history of previous louse-borne typhus (recrudescent typhus). Clinical laboratory findings such as thrombocytopenia (particularly in spotted fever and typhus rickettsioses, ehrlichiosis, anaplasmosis, and scrub typhus), normal or low WBC counts, mild to moderate serum elevations of hepatic aminotransferases, and hyponatremia sug­ gest some common pathophysiologic mechanisms. Application of these clinical, epidemiologic, and laboratory prin­ ciples requires consideration of a rickettsial diagnosis and knowledge of the individual diseases. TICK-, MITE-, LOUSE-, AND FLEA-BORNE RICKETTSIOSES These diseases, caused by organisms of the genera Rickettsia and Ori­ entia in the family Rickettsiaceae, result from endothelial cell infection and increased vascular permeability. Pathogenic rickettsial species are very closely related, have small genomes (as a result of reductive evolu­ tion, which eliminated many genes for biosynthesis of intracellularly available molecules), and are traditionally separated into typhus and spotted fever groups on the basis of lipopolysaccharide antigens. Some