Conference Coverage

In the reemergence of typhus, the challenge is early diagnosis



– Typhus in many forms, particularly scrub typhus, has reemerged worldwide, but none of these rickettsial infections poses a significant public health threat if promptly diagnosed, according to an update presented at an annual scientific meeting on infectious diseases.

Scrub typhus, which is spread by several species of trombiculid mites or chiggers, poses a large threat in regard to typhus epidemics, particularly in Asia, but sporadic cases of different types of typhus are being seen everywhere, including in the United States, according to George M. Varghese, MD, department of infectious diseases, Christian Medical College, Vellore, India.

“The typhus diseases are clinically similar but epidemiologically and etiologically distinct,” reported Dr. Varghese, “but doxycycline is the drug of choice for almost all of the rickettsial infections.”

Dr. George Varghese, department of infectious diseases, Christian Medical College, Vellore, India

Dr. George Varghese

The bacteria responsible for scrub typhus is Orientia tsutsugamushi, which is no longer included in the genus Rickettsia, but Dr. Varghese, who has published frequently on the epidemiology of scrub typhus, said that it is still appropriately grouped among rickettsial infections. It shares many features with the other rickettsioses, which were considered to be fading but are now resurging after the large epidemics that occurred prior to the introduction of antibiotics.

In the World Wars, Rickettsia prowazekii – which is carried and spread by body lice – was the most well known typhus threat. According to Dr. Varghese, this bacterium may have killed more soldiers in these conflicts than did firearms. Although R. prowazekii has not disappeared as a source of typhus outbreaks, particularly in South America and Africa, there are current epidemics produced from rickettsial infections carried by fleas, such as R. typhi, or ticks, like R. rickettsii, or mice, like R. felis.

For clinical detection of these forms of typhus, there are differences. Although all are associated with a rapid onset of fever, headache, and myalgia, subtle signs can be helpful in making a diagnosis while waiting for laboratory confirmation. For example, scrub typhus, unlike Rocky Mountain Fever, which is caused by tick bites, does not generally include a rash. Rather, eschars, which are small patches of necrotic skin, are far more characteristic.

“Serological tests are the most common diagnostic tool for typhus, but serology may not allow early diagnosis. You can obtain a false positive in the early stages of disease,” Dr. Varghese warned. To speed the diagnosis, he said that looking for the clinical clues characteristic of the suspected form of typhus, such as the scrub typhus-associated eschar, “is valuable.” However, he also emphasized that even with positive serology results, “good epidemiology and history is helpful for laboratory interpretation.”

A variety of serological tests can identify typhus pathogens, but ELISA is now the most widely used, according to Dr. Varghese, noting that this test offers a sensitivity of 93% and a specificity of 91%. Both are higher than those provided by alternatives. As a result of improved sensitivity of diagnostic tests, prevalence rates of some forms of typhus have proved to be unexpectedly high. For example, in a study undertaken in his region of India, the seroprevalence of scrub typhus was 31.8% (Trop Med Int Health. 2017;22:576-82. doi: 10.1111/tmi.12853).

Of unmet needs in the clinical management of typhus, Dr. Varghese listed better strategies for point-of-care diagnosis and treatment and better data on how to manage patients who are severely ill. Advanced disease, which is common to rural areas with limited access to health care, is the source of almost all typhus mortality, according to Dr. Varghese. He described a trial now being initiated in severe disease that will compare intravenous doxycycline to IV azithromycin and to a combination of both IV doxycycline and azithromycin.

Although Dr. Varghese cautioned that reports of resistant typhus infections, particularly in Thailand, might prove to be the next big clinical challenge in typhus, he said that progress is being made toward reducing the burden of this disease in his area of the world. In a disease associated with a mortality of 50% if left untreated, he attributes gains to earlier diagnosis and prompt treatment.

At his medical center, “we have been working with this disease for a decade and a half,” he said, referring to scrub typhus. “When we started off, the mortality was around 15% after diagnosis. Today, the mortality is about 5%-7%.”

Dr. Varghese reported that he has no financial relationships relevant to this topic. The event was the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

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