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Scrub typhus

Scrub typhus
Literature review current through: Jan 2024.
This topic last updated: Jan 08, 2024.

INTRODUCTION — Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). Scrub typhus is of greatest public health importance in the rural Asian tropics. The endemic zone of this Asian disease extends as far north as the Kamchatka Peninsula of Russia, as far east as the Solomon Islands, as far south as Queensland, Australia, and as far west as Afghanistan. Scrub typhus is manifested clinically by high fever, cough, intense generalized headache, diffuse myalgias, and, in many patients, rash and an eschar at the site of the insect bite.

This topic will review the epidemiology, clinical manifestations, diagnosis, and treatment of scrub typhus. Detailed discussions of other rickettsial diseases are presented in separate topic reviews. (See "Other spotted fever group rickettsial infections" and "Biology of Rickettsia rickettsii infection" and "Clinical manifestations and diagnosis of Rocky Mountain spotted fever" and "Treatment of Rocky Mountain spotted fever" and "Epidemic typhus".)

MICROBIOLOGY — O. tsutsugamushi is an obligate intracellular, gram-negative coccobacillus that infects a range of host cell types including endothelial cells, monocytes, macrophages, and dendritic cells. It is antigenically distinct from the typhus group rickettsiae and has three primary variants or strains (Karp, Gilliam, and Kato). Infection with one strain does not preclude reinfection with a different strain.

Like all rickettsiae, O. tsutsugamushi cannot be propagated in cell-free media. However, it is unique in that it is released from infected cells by budding from the plasma membrane of host cells. It may then be phagocytosed by adjacent cells while still coated with its original host cell membranes. Rickettsial phospholipase A2 appears to be involved as a mediator of entry into host cells with subsequent release from phagosomes and injury to the host cell [1].

EPIDEMIOLOGY — O. tsutsugamushi is primarily distributed throughout the Asia Pacific rim. Scrub typhus is endemic in Korea, China, Vietnam, Taiwan, Japan, Pakistan, India, Sri Lanka, Thailand, Malaysia, and the tropical (northern) regions of Australia [2,3]. Rare cases of scrub typhus have also been reported in Chile [4,5]. Serologic and molecular evidence of scrub typhus have also been identified in Africa and the Middle East [6,7].

Accurate surveillance data on the incidence of scrub typhus are not usually available because a diagnosis is often unconfirmed, overlooked, or confused with other endemic febrile illnesses. However, it has been estimated that up to 1 million cases occur annually in southeastern Asia [8]. A report summarizing the epidemiological aspects of 27,391 confirmed cases of scrub typhus diagnosed in China from 2006 to 2012 illustrates a number of important epidemiological aspects of scrub typhus in endemic areas [9]:

Agricultural workers with significant outdoor exposure (eg, farmers) accounted for approximately two-thirds of all reported cases

Incidence rates were highest in people aged 40 to 60 years of age, but young children had higher rates of infection than young adults

Approximately 80 percent of cases occurred during summer and autumn (July to November)

Geographic clustering of cases was observed, with a few southeastern Chinese provinces accounting for a large proportion of all reported cases

The incidence of scrub typhus is reportedly increasing in some areas, especially in southeast Asia [10]

Although most cases of scrub typhus occur in rural areas, a number of cases have been acquired in settings such as suburban Bangkok, where the seroprevalence exceeds 20 percent [11], as well as urban areas, such as Beijing and Seoul [9,12].

In addition, the ease of air travel and relatively long incubation period of scrub typhus (up to two weeks) allow the disease to occur in tourists returning to regions where it is not endemic and where clinicians are not familiar with its clinical and epidemiologic features. Cases of scrub typhus have been described in tourists returning to the United States, Canada, and Europe from endemic regions [13-16].

TRANSMISSION — The reservoir and vector of scrub typhus are larval trombiculid mites of the genus Leptotrombidium. These larval mites (also known as chiggers) maintain the infection in successive generations via transovarial transmission. At least eight of the known 60 species of trombiculid mites are capable of transmitting scrub typhus. Organisms disseminate widely after initial inoculation into the skin and have been rapidly detected by staining mononuclear cells in the peripheral blood during acute scrub typhus [17].

Transmission of O. tsutsugamushi may occur in sharply delineated "mite islands" that consist of focal locations of scrub vegetation as small as a few square meters. Mites live on the vegetation, and moisture and temperature conditions are ideal for propagation of chiggers and their small rodent hosts. The risk of disease transmission from chigger bites may be extremely high when humans enter these mite islands. As an example, a classic study performed over 50 years ago found that nearly all Australian soldiers on training exercises in Queensland who camped in a small geographic area developed scrub typhus. In contrast, no soldiers who camped in nearby areas developed the disease [18].

CLINICAL MANIFESTATIONS — In patients with scrub typhus, the clinical manifestations can range from mild signs and symptoms to multiorgan failure and death [8,19,20]. A systematic review, which included a total of 19,644 patients with untreated scrub typhus, reported a median mortality rate of 6 percent (range: 0 to 70 percent) [8]. Mortality rates varied widely by location and were increased in older patients. In addition, the presence of myocarditis, delirium, and pneumonitis were associated with a fatal outcome. There may also be a relationship between the level of rickettsial DNA in blood samples at the time of admission and the risk of mortality [21].

Acute febrile illness — Infection commonly presents as an acute febrile illness about a week after the bite of an infected mite, although clinical onset can range from 6 to 21 days after exposure [21]. (See 'Transmission' above.)

Scrub typhus may begin insidiously with headache, anorexia, and malaise, or start abruptly with chills and fever. As the illness evolves, most patients develop the following symptoms:

Fever, which typically lasts for long periods in untreated patients (median 14.4 days; range 9 to 19) [8]

Intense generalized headache

Diffuse myalgias

Rash, eschar, and other signs and symptoms may also be present. (See 'Rash' below and 'Eschar' below and 'Other signs and symptoms' below.)

Rash — Approximately one-half of all patients develop a characteristically nonpruritic, macular, or maculopapular rash. The rash typically begins on the abdomen and spreads to the extremities. The face is also often involved. Rarely, petechiae may develop.

Eschar — A painless papule often appears at the site of the infecting chigger bite. Subsequent central necrosis then occurs, which in turn leads to the formation of a characteristic eschar with a black crust (picture 1). One or multiple eschars may develop, often before the onset of systemic symptoms. Occasionally, eschars can be atypical and lack a typical black crust [22].

The frequency of eschars in patients with scrub typhus is highly variable. As an example, in one report, eschars developed in 36 of 74 (46 percent) American servicemen in South Vietnam [23]; however, another study found an incidence of 60 to 88 percent [24]. Eschars may be overlooked if a careful clinical exam (including inspection of the genitalia and skin folds under the breast) is not performed.

Other signs and symptoms — Other signs and symptoms may also be seen in scrub typhus:

Lymphadenopathy – Localized, and subsequent generalized lymphadenopathy, occurs in the majority of patients and may be accompanied by inflammation of the lymphatic sinuses, splenomegaly, and portal triaditis.

Gastrointestinal – Nausea, vomiting, and/or diarrhea are prominent findings in approximately one-fourth of patients. Endoscopy was performed in 58 patients with scrub typhus and prominent gastrointestinal symptoms seen at a single Korean center over a five-year period [25]. All patients had one or more endoscopic abnormalities, and 33 patients had changes consisting of superficial ulcers, erosions, or actively bleeding ulcers. Moreover, the presence of endoscopic lesions in the upper gastrointestinal tract was correlated with the occurrence of cutaneous lesions and severity of illness.

Respiratory – Respiratory complaints occur in up to two-thirds of cases, with symptoms ranging from mild cough to overt acute respiratory distress syndrome (ARDS) [23]. Radiographic abnormalities are often present, the most commonly reported abnormality being bilateral reticular opacities [26].

Cardiovascular – Relative bradycardia occurs in up to two-thirds of patients with scrub typhus [27-29]. Relative bradycardia has been defined as a median increase in heart rate <10 beats/min per 1ºC increase in temperature [27].

Myocarditis has been reported to occur [30-32]. Clinical pericarditis is not common but has also been reported. In one case, the organism was demonstrated by indirect immunofluorescence of pericardial fluid [33]. Pericardial effusions have been described in autopsy series [34].

Central nervous system – Involvement of blood vessels in the central nervous system may produce meningitis, meningoencephalitis, seizures, and strokes, especially in children and older adults [35,36]. Altered sensorium is particularly common in older patients. Acute hearing loss or tinnitus has also been reported [37] and may be a useful clue to the diagnosis of scrub typhus when present [38].

Renal – Acute kidney injury has been reported in those with severe disease [39]. In one report, of 116 patients with severe disease, 13 percent required dialysis [40].

Elderly patients are more likely to have severe illness and complications compared with younger patients. As an example, a retrospective study from a single medical center evaluated 615 Korean patients >16 years of age with scrub typhus [39]. Forty-six percent of patients >65 years developed one or more complications compared with 23 percent of younger patients. Acute kidney injury, mental confusion, and dyspnea were more common in older patients, whereas the frequency of fever, rash, and eschars were similar in both groups. Delays in therapy were also associated with a higher risk of complications. The average time from onset of illness to effective therapy was modestly greater in patients with complications compared with those without complications (approximately seven versus six days).

Laboratory findings — Most patients with severe illness develop thrombocytopenia. Elevations in hepatic enzymes, bilirubin, and creatinine may also be present. Leukopenia or leukocytosis can occur, but most have a normal white blood cell count

DIAGNOSIS

Approach to diagnosis — In most cases, an initial diagnosis of scrub typhus is made presumptively, based on compatible clinical signs, symptoms, and laboratory features as well as epidemiologic clues (eg, recent exposure to environments in which chiggers are known or suspected to be present). (See 'Clinical manifestations' above and 'Epidemiology' above.)

Treatment should be initiated immediately when the diagnosis is suspected. A rapid response to empiric treatment can also be used to support the diagnosis, although response times >48 hours have been reported [41]. (See 'Treatment' below.)

Serologic testing should be performed to help support the diagnosis in patients with suspected disease. For most institutions, serology is the most accessible diagnostic assay. (See 'Serology' below.)

Although biopsy of the eschar or polymerase chain reaction (PCR) can also be used to help with the diagnosis, it is not usually needed. (See 'Biopsy of an eschar or generalized rash' below and 'Polymerase chain reaction' below.)

Diagnostic tests

Serology — The indirect fluorescent antibody (IFA) test remains the mainstay of serologic diagnosis. A battery of antigens from common strains of O. tsutsugamushi are typically used to detect convalescent antibodies because of the organism's antigenic heterogeneity. In the United States, the IFA is available through most state health laboratories, which can send the specimens to the Centers for Disease Control and Prevention.

A diagnosis of scrub typhus is supported by:

A fourfold or greater increase in immunoglobulin (Ig)G titer in paired samples drawn at least 14 days apart [42,43].

Detectable IgM antibodies when combined with an appropriate clinical syndrome and epidemiology. This approach to serologic testing is often used to make a presumptive diagnosis in many resource-limited settings worldwide [44].

An elevated single timepoint IgG titer may also be suggestive of acute scrub typhus when the clinical and epidemiologic features strongly suggest the diagnosis and standard acute and convalescent titers cannot be obtained [42]. In travelers from nonendemic areas who have recently traveled to areas where scrub typhus is prevalent, we typically consider a titer of >1:128 to be consistent with a diagnosis of scrub typhus [45]. However, there is not a broadly generalizable cutoff value given the variety of IFA methodologies and reagents in use as well as the variation in baseline IgG titers across populations from endemic and nonendemic regions.

A number of other enzyme-linked immunosorbent assays and passive hemagglutination assays have also been developed for the diagnosis of scrub typhus [46,47]. A dot blot immunoassay dipstick, which is undergoing clinical evaluation, may permit rapid diagnosis of scrub typhus [48].

The Weil Felix test is neither specific nor sensitive and should not be used. This test is based upon a fortuitously discovered cross reaction between anti-rickettsial antibodies and Proteus antigens (OX2 and OX19).

Biopsy of an eschar or generalized rash — In challenging cases, biopsy of the eschar is an additional diagnostic option. The pathological hallmark of scrub typhus is a lymphohistiocytic vasculitis.

Damage to endothelial cells occurs early in infection, leading to widespread vascular dysfunction. This endothelial injury causes a loss of vascular integrity, egress of plasma and plasma proteins, and microscopic and macroscopic hemorrhages. Thus, the histologic changes in biopsies of eschars include focal areas of cutaneous necrosis surrounded by a zone of intense vasculitis, with perivascular collections of lymphocytes and macrophages. Thrombosis of small blood vessels can also occur.

Demonstration of these typical vasculitic changes can be diagnostic, even when rickettsiae are not demonstrable by fluorescent antibody conjugates. PCR testing of the eschar can be performed as well. (See 'Polymerase chain reaction' below.)

Polymerase chain reaction — PCR testing of blood samples from patients with scrub typhus can definitively establish the diagnosis of scrub typhus, even in the minority of patients who lack IgM antibodies early in the course of infection [49-52]. However, similar to other rickettsial diseases, PCR assays on blood have generally demonstrated lower sensitivity than specificity and are not reliable for ruling out disease [51,52]. Metagenomic sequencing and direct from blood multiplex PCR panels have also shown some ability to detect O. tsutsugamushi, but data defining test performance for these platforms are lacking [53].

PCR testing of eschar samples can also be performed and appears to be a sensitive and specific means to identify scrub typhus despite prior antibiotic treatment [54]. However, this type of testing is typically available only in specialized centers that have access to the required testing elements and laboratory facilities.

Culture — Culture of this organism is available in only a few specialized laboratory centers with rigorous quality control and appropriate laboratory safety measures, as rare lab-associated exposures have occurred [55].

Differential diagnosis — Scrub typhus may be confused with a number of different infectious illnesses.

Malaria and dengue – Malaria and dengue share some common clinical features (eg, acute febrile illness) and similar endemic patterns with scrub typhus. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children" and "Dengue virus infection: Clinical manifestations and diagnosis".)

Leptospirosis – Leptospirosis is a common disease in some tropical regions where scrub typhus also occurs. Rarely, coinfection with scrub typhus and leptospirosis may occur. In one study of 296 febrile Thai patients, 69 patients (23 percent) had leptospirosis; 57 patients (19 percent) had scrub typhus; and 11 patients (4 percent) had evidence of coinfection with leptospira and O. tsutsugamushi [56]. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Salmonella Typhi – Scrub typhus may mimic infection with Salmonella Typhi in areas of the tropics where typhoid fever is common. This confusion is particularly true in patients who lack a rash or localized eschar and in whom gastrointestinal symptoms are prominent. (See "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

Other rickettsial diseases – The clinical manifestations of infections due to the spotted fever group of rickettsiae (eg, Rickettsia australis, Rickettsia japonica, and Rickettsia sibirica) may mimic scrub typhus. Infection with R. australis, R honei, and R. sibirica may even be associated with a localized eschar at the site of the infecting tick bite. These diseases can be almost identical, particularly when there is no history of tick bite. Fortunately, the treatment for these other rickettsial diseases is identical to that for scrub typhus. (See "Other spotted fever group rickettsial infections".)

Additional considerations – The eschar in patients with scrub typhus can be confused with the skin lesions seen in patients with anthrax and with a spider bite. (See "Clinical manifestations and diagnosis of anthrax" and "Diagnostic approach to the patient with a suspected spider bite: An overview".)

TREATMENT

Indications — All patients with suspected or confirmed scrub typhus should be treated with antimicrobial therapy. Treatment should be initiated as soon as possible. Delayed administration of antibiotics has been independently associated with the development of major organ dysfunction (OR 1.2; CI 1.0-1.5) and hospitalization for >10 days (OR 1.4; CI 1.1-1.9) [57].

Determining disease severity — The approach to treatment depends upon the severity of disease. We typically classify patients having mild to moderate or severe disease.

Mild to moderate disease – Patients with mild to moderate disease typically present with fever, myalgia, and headache as well as a rash (with or without eschar) and/or cough.

Severe – Patients with severe disease typically present with the findings above in combination with clinical or laboratory manifestations that indicate end-organ damage. These include hyperbilirubinemia, renal failure, cardiovascular collapse (hypotension/shock), acute respiratory distress syndrome (ARDS), and meningoencephalitis.

Preferred antimicrobial regimens — The choice of regimen depends on the severity of disease and if the patient is pregnant.

Persons with mild to moderate disease — For patients with presumed mild to moderate scrub typhus, we suggest monotherapy with doxycycline or azithromycin.

For most patients, we favor doxycycline (100 mg orally or intravenously twice daily) due to extensive experience with this agent, including its use in published studies [24,58]. In addition, it has broad activity against other organisms that may cause similar clinical syndromes (eg, other rickettsial diseases); this is important since the diagnosis is often not confirmed at the time of initial treatment. (See 'Differential diagnosis' above.)

However, azithromycin (500 mg orally or intravenously daily) is also a reasonable choice when the diagnosis of scrub typhus is strongly suspected or supported by serologic evidence. An increasing number of clinical trials have shown that azithromycin offers similar efficacy to doxycycline across a wide array of relevant outcomes (eg, time to defervescence, risk of complications, length of hospitalization) [41,56,59,60].

Specific considerations for regimen selection in persons who are pregnant are discussed below. (See 'Considerations during pregnancy' below.)

Persons with severe disease — For most patients with severe disease, we suggest monotherapy with doxycycline. In this setting, we administer 200 mg of doxycycline twice daily on day one, followed by 100 mg twice daily for a total duration of seven days. Doxycycline has been the historical standard of care for patients with severe scrub typhus. In addition, in a recent randomized trial of 794 patients with scrub typhus who had complications requiring intravenous therapy, those who received monotherapy with doxycycline had a nonsignificant but lower absolute mortality than those who received combination therapy with doxycycline and azithromycin (11 versus 13 percent, respectively) [60]. In this trial, the need for mechanical ventilation, the duration of ventilation, the length of stay in the ICU, and the overall hospital length of stay were also similar between the groups.

However, combination therapy with doxycycline and azithromycin may be considered on a case-by-case basis. In the randomized trial above, those who received combination therapy had a lower incidence of a composite primary outcome (death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5) than those who received monotherapy with doxycycline (33 versus 47 percent; risk difference of −13.3 percent, 95% CI, −21.6 to −5.1) or azithromycin (33 versus 48 percent; risk difference −14.8 percent, 95% CI, −23.1 to −6.5) [60]. This difference was due primarily to a reduction in persistence of certain complications at day 7 (eg, the need for supplemental oxygen, resolution of hyperbilirubinemia [T. bili >2], and resolution of elevated creatinine). Thus, combination therapy may offer more rapid resolution of some secondary outcomes and laboratory abnormalities and may be reasonable in patients if this is deemed to be a priority.

Duration — The optimal duration of treatment remains uncertain. When doxycycline is used, we typically favor seven days of therapy, although published trials have utilized a variety of regimens. For azithromycin we administer therapy for five to seven days for most patients, reserving shorter durations for milder cases. In the randomized study discussed above, seven days of doxycycline, azithromycin, or combination therapy was associated with high rates of cure in those with severe disease [60]. Patients who initiate intravenous therapy can switch to oral therapy as soon as they are clinically stable.

Although regimens as short as one day of doxycycline (400 mg given in two divided doses) have been advocated for the therapy of scrub typhus [61], short courses of doxycycline have been associated with an increased risk of relapse. In one study evaluating a three-day course of therapy, relapse occurred in three of seven patients treated with chloramphenicol and three of six treated with doxycycline; in comparison, no relapses were noted in 37 patients treated with either regimen for five days or longer [24]. Given that treatment is often given while the diagnosis remains unconfirmed, another benefit of a standard seven-day course of doxycycline is its overlap with regimens used for similar infectious syndromes.

For azithromycin monotherapy, a variety of durations (ranging from one to seven days) have been studied, although not comparatively. We favor the five to seven day duration given the heterogeneity of lengths of therapy in published studies and the suggestion from some that shorter courses may be associated with prolonged duration of fever [41,56,59,60].

Alternate antimicrobial regimens — Given the efficacy and safety of doxycycline and azithromycin, the use of alternative agents for treatment of scrub typhus is generally not warranted, even though available data suggest they may be effective. However, on occasion, a patient may have contraindications to doxycycline and azithromycin, and in this setting, one of the following agents can be considered:

Rifampin – Rifampin is an option for treatment of scrub typhus when there are contraindications to doxycycline and azithromycin (the preferred agents). While a generally effective option, rifampin creates challenges with its many drug-drug interactions. This, combined with the overall greater body of published evidence supporting doxycycline and azithromycin, relegates rifampin to third-line therapy in most situations. (See 'Preferred antimicrobial regimens' above.)

When compared to doxycycline, rifampin (600 mg once daily for five days) therapy cured all patients who received it (n=119) and showed no difference in time to resolution of fever, myalgias, headache, or rash [62].

Combination therapy with doxycycline plus rifampin has also been studied, but given the efficacy and safety of other regimens, this combination is rarely indicated. A randomized trial performed in an area of northern Thailand compared the efficacy of doxycycline alone to the combination of doxycycline and rifampin in 86 patients with mild scrub typhus infection [63]. The median duration of fever was significantly shorter in the 24 patients treated with daily doses of 900 and 600 mg of rifampin (mean fever clearance times 22.5 and 27.5 hours, respectively) than in 52 patients treated with doxycycline therapy alone (mean fever clearance time 52 hours).

Fluoroquinolones – Fluoroquinolones (FQ) have shown efficacy for the treatment of scrub typhus, particularly in mild/moderate disease. However, use of FQ for scrub typhus has also been shown to be associated with delayed time to resolution and higher mortality compared to doxycycline or minocycline [64].

Chloramphenicol – Chloramphenicol (250 to 500 mg orally or intravenously every six hours) was the first drug shown to be effective for the treatment of scrub typhus, and an analysis that included three treatment trials found no significant differences in time to resolution of fever and incidence of relapse in patients treated with doxycycline or chloramphenicol [65]. However, given the toxicity of this drug and difficulty obtaining it in most countries, chloramphenicol should be reserved for situations when other options are not available.

Considerations during pregnancy — Scrub typhus may cause spontaneous abortions or stillbirths in pregnant persons [66-68]. As an example, a literature review that included information on 55 pregnant persons with scrub typhus (including three who had both scrub typhus and malaria) found that 24 out of 55 patients (44 percent) had a poor neonatal outcome, defined as stillbirths, preterm birth, or low birth weight [67].

For such patients we typically administer azithromycin (500 mg daily) for seven days, as this regimen has the greatest amount of published data supporting its use in pregnancy [66,69].

There is suggestion in the literature that shorter regimens (ranging one to five days) of azithromycin may also be effective in pregnancy, but the data supporting any specific regimen in this population remain sparse, and reports of slower resolution of fever and other clinical signs with shorter courses of azithromycin also suggest caution when selecting regimens of shorter duration [60,70]. (See 'Duration' above.)

PREVENTION — Prevention of scrub typhus consists of avoiding exposure to mites. No vaccine is available to prevent the transmission of scrub typhus, and the antigenic heterogeneity of O. tsutsugamushi suggests that the prospect of future vaccine development will be a difficult undertaking [71].

SUMMARY AND RECOMMENDATIONS

Etiology – Scrub typhus is caused by Orientia tsutsugamushi, an obligate intracellular, gram-negative coccobacillus. It is antigenically distinct from the typhus group rickettsiae.

O. tsutsugamushi is primarily distributed throughout the Asia Pacific rim. Scrub typhus is endemic in Korea, China, Vietnam, Taiwan, Japan, Pakistan, India, Sri Lanka, Thailand, Malaysia, and the tropical (northern) regions of Australia. The reservoir and vector of scrub typhus are larval trombiculid mites. (See 'Microbiology' above and 'Epidemiology' above and 'Transmission' above.)

Clinical manifestations – Infection commonly presents as an acute febrile illness 7 to 10 days after the bite of an infected mite. Most patients develop an intense generalized headache and diffuse myalgias. (See 'Acute febrile illness' above.)

A macular or maculopapular rash, an eschar (picture 1), and/or other signs and symptoms may also be present. These include lymphadenopathy; nausea, vomiting, and diarrhea; cough and shortness of breath; relative bradycardia; meningoencephalitis; and acute kidney injury. (See 'Rash' above and 'Eschar' above and 'Other signs and symptoms' above.)

Diagnosis – In most cases, an initial diagnosis of scrub typhus is made presumptively, based on compatible clinical signs, symptoms, and laboratory features in the setting of epidemiologic clues (eg, recent exposure to environments in which chiggers are known or suspected to be present). (See 'Approach to diagnosis' above.)

Serologic testing should be performed to help support the diagnosis in patients with suspected disease. Scrub typhus may be confused with a number of different infectious illnesses (eg, malaria, dengue, leptospirosis, other rickettsial diseases). Although biopsy of the eschar or polymerase chain reaction (PCR) can also be used to help with the diagnosis, it is not usually needed. (See 'Diagnostic tests' above and 'Differential diagnosis' above.)

Treatment – All patients with suspected or confirmed scrub typhus should be treated with antimicrobial therapy. Treatment should be initiated as soon as possible. Delayed administration of antibiotics has been associated with the development of major organ dysfunction. (See 'Indications' above and 'Determining disease severity' above.)

For nonpregnant patients, we suggest monotherapy with doxycycline (Grade 2B). For patients with mild to moderate disease, we administer doxycycline (100 mg orally/intravenously twice daily) for seven days. For those with severe disease, we administer doxycycline (200 mg orally/intravenously twice daily) on day one, followed by 100 mg orally/intravenously twice daily for the remainder of the seven-day course. (See 'Preferred antimicrobial regimens' above.)

We prefer doxycycline rather than other regimens given extensive clinical experience with this agent. In addition, doxycycline has broad activity against other organisms that cause similar clinical syndromes, which is beneficial since the diagnosis is often not confirmed when treatment is initiated.

Azithromycin (500 mg daily for five to seven days) is a good alternative to doxycycline for persons with mild to moderate disease. In addition, it is preferred for treatment during pregnancy. (See 'Persons with mild to moderate disease' above and 'Considerations during pregnancy' above.)

Prevention – Prevention of scrub typhus consists of avoiding exposure to mites. No vaccine is available to prevent the transmission of scrub typhus. (See 'Prevention' above.)

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Topic 7911 Version 9.0

References

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