Scrub typhus is caused by Orientia tsutsugamushi, an obligate intracellular bacterium transmitted by the larvae of trombiculid mites, commonly called chiggers. The disease is endemic across a vast swath of the Asia-Pacific region, stretching from Japan and Korea to northern Australia and from the Indian subcontinent to the Pacific islands, an area that puts an estimated one billion people at risk and produces roughly one million cases each year. Once the bacterium enters the body, it triggers a systemic vasculitis marked by inflammation around blood vessels, dysfunction of the endothelial cells that line them, and leakage of fluid from the circulation. About one-third of patients develop organ dysfunction, which can include respiratory failure, shock, kidney or liver impairment, involvement of the central nervous system, and blood abnormalities. Although mild cases generally resolve well, mortality among severe cases with multi-organ failure can reach 24 percent, and historical data from China have reported an overall death rate of 13.8 percent in untreated patients.

The diagnostic trap that the Guangzhou team documents arises because scrub typhus and Kawasaki disease share a strikingly similar clinical face. Kawasaki disease is an acute vasculitis that predominantly strikes children under five years of age, characterized by prolonged fever, rash, conjunctivitis, inflamed lips and mouth, swollen cervical lymph nodes, and changes in the hands and feet. Roughly 20 percent of untreated patients develop coronary artery aneurysms, making Kawasaki disease the leading cause of acquired heart disease in children in developed countries. Its cause remains incompletely understood, but accumulating evidence points to infectious triggers that provoke a dysregulated immune response in genetically susceptible children. Because scrub typhus also produces fever, rash, lymphadenopathy and, as the new study shows, coronary artery involvement, the two conditions can be almost indistinguishable at the bedside, particularly in regions where both circulate.

The retrospective analysis covered seven patients, two boys and five girls, aged 11 months to 8 years, with a median age of 3 years, all admitted between January 2020 and May 2026 and all long-term residents of Guangdong Province. Six of the seven had plausible exposures: two reported mosquito bites and four described outdoor activity in grass or vegetable fields. Illness onset clustered in the warm months, with four cases beginning in June, consistent with the April-to-September epidemic season of scrub typhus in China. Every child presented with fever, with peak temperatures ranging from 39.1 to 42.0 degrees Celsius, and every child had a rash. Crucially, six of the seven displayed the eschar, the painless black necrotic lesion at the site of the chigger bite that is pathognomonic for scrub typhus. Six children also had bilateral cervical lymphadenopathy, five had enlargement of the liver or spleen, and three developed conjunctival injection or red lips during their illness, features that pushed clinicians toward a Kawasaki diagnosis.

Laboratory testing revealed a profound hyperinflammatory state. C-reactive protein was elevated in all seven children, with values from 32 to 147 milligrams per liter, and serum ferritin, a marker of macrophage activation, was strikingly high in all six patients tested, reaching up to 11,705 nanograms per milliliter. Liver enzymes were mildly to moderately elevated and serum albumin was reduced in every patient. In the three children whose immune cells were profiled, CD8-positive cytotoxic T cells were markedly expanded while the CD4-to-CD8 ratio fell to between 0.30 and 0.50, a pattern suggesting a dominant cytotoxic immune response. Bone marrow examination in four patients revealed hemophagocytosis, the engulfing of blood cells by macrophages, a hallmark of the immune activation syndrome hemophagocytic lymphohistiocytosis, which was clinically diagnosed in two of the children. Complications across the cohort were severe: five had pneumonia, three of them severe; three developed respiratory failure; three went into septic shock; and single patients experienced coagulopathy, pulmonary hemorrhage and encephalopathy.

Echocardiography, performed between days 9 and 14 of illness, defined the coronary pathology. Two children had true aneurysms, one of the right coronary artery and one of the left anterior descending artery, defined by a Z-score of 2.5 or greater. Two had coronary dilatation, with Z-scores between 2.0 and 2.5, and three had intimal thickening, an abnormal buildup of the inner vessel lining exceeding age-adjusted limits. All seven children were initially suspected of having Kawasaki disease, and four formally met the diagnostic criteria for complete or incomplete Kawasaki disease. Six received intravenous immunoglobulin at standard doses, mostly 2 grams per kilogram, the mainstay of Kawasaki therapy, and one child remained febrile even after two full courses. Yet every one of the immunoglobulin-treated children failed to respond, with high fevers recurring for days, sometimes accompanied by falling platelet counts.

The therapeutic turning point came only when antimicrobial therapy targeted at scrub typhus was started, between days 9 and 15 of illness. Two older children, aged 6 and 8, received doxycycline for 7 to 10 days, while five received azithromycin, given intravenously or orally, for one to three courses. All seven children, including the one who never received immunoglobulin, defervesced within one to three days of starting the antibiotics, a speed of response that the authors argue is itself diagnostic. Meta-analytic evidence indicates azithromycin is non-inferior to doxycycline for pediatric scrub typhus, and doxycycline use in young children has not been associated with demonstrable dental enamel defects, addressing a long-standing prescribing concern. Hospital stays ranged from 8 to 29 days, four children required intensive care, and supportive measures ranged from mechanical ventilation to transfusions, albumin, fibrinogen replacement and corticosteroids.

Follow-up imaging offered reassurance. Five of the children with available echocardiography showed complete normalization of their coronary arteries within one week to three months. One child with a right coronary aneurysm received three months of the antiplatelet drug clopidogrel until the vessel healed, and remained normal on repeat imaging after the drug was stopped. Another, with a left anterior descending aneurysm, still had residual dilatation and mild intimal thickening at two months. One patient was lost to echocardiographic follow-up, and the authors acknowledge that the long-term cardiovascular outlook for these children remains unknown, a gap they flag alongside the inherent limits of a small, single-center, retrospective series.

The broader significance of the report lies in what it reveals about infection-driven vascular injury. The authors situate their findings within a growing family of Kawasaki-like syndromes triggered by pathogens, from the Kawasaki-like disease seen in adults with advanced HIV to multisystem inflammatory syndrome in children after SARS-CoV-2 infection, both of which demonstrate that immune dysregulation can precipitate coronary vasculitis. A 2014 Taiwanese cohort study found that adults with scrub typhus had a 37 percent increased risk of acute coronary syndrome within a year of infection, hinting that the cardiovascular consequences of the bacterium extend well beyond childhood. The Guangzhou team also underscores the diagnostic bottleneck: the Weil-Felix test, the most widely used assay at their institution, has a reported sensitivity of only about 16 percent, and three of their patients had repeatedly negative results. Because a diagnosis delayed beyond day 8 of illness is associated with increased mortality, the authors recommend early metagenomic next-generation sequencing, which detected the bacterium in two of their patients, for children with suggestive illness who lack an eschar. Their bottom line for clinicians is unambiguous: in any child with coronary artery lesions and a poor response to immunoglobulin, search the skin for a chigger’s calling card, take a careful exposure history, and treat the pathogen, not just the inflammation.

Subject of Research: Coronary artery lesions associated with pediatric scrub typhus infection

Article Title: Coronary artery lesions in pediatrichus scrub typhus: A case series from Guangzhou, China

Article References: Liu, S., Wang, Q., Gong, Y., Li, X., Zeng, F., & Xu, Y. (2026). Coronary artery lesions in pediatrichus scrub typhus: A case series from Guangzhou, China. PLOS Neglected Tropical Diseases, 20(10), e0014784. https://doi.org/10.1371/journal.pntd.0014784

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014784

Keywords: scrub typhus, Orientia tsutsugamushi, coronary artery lesions, Kawasaki disease, children, intravenous immunoglobulin, doxycycline, azithromycin, chiggers, Guangzhou, PLOS Neglected Tropical Diseases, vasculitis