Scrub typhus, or tsutsugamushi disease, is an obligate intracellular bacterium zoonotic infection caused by Orientia tsutsugamushi. It is conveyed to human beings by the bites of infected larval trombiculid mites that inhabit rodents. The disease is endemic in most regions of Asia and is largely reported in the "Tsutsugamushi Triangle," which runs from north to east Russia and Japan to Australia in the south and Afghanistan in the west. Although scrub typhus was hitherto considered to be restricted to the Himalayan belt and the Indian peninsula in the south, recent findings report a growing number of cases from other areas as well, which points towards its increasing geographic spread.

Despite increasing awareness, scrub typhus continues to be underdiagnosed owing to its nonspecific clinical manifestations. The disease ranges from mild febrile illness to extreme, life-threatening complications. Early classical signs and symptoms involve fever, rash, lymphadenopathy, and the distinctive eschar at the mite bite site. However, in more severe forms of the disease, multi-organ involvement is present, involving the respiratory, cardiovascular, renal, and nervous systems. Pulmonary complications, more specifically, have been increasingly being noted as an important cause of morbidity and mortality among patients with scrub typhus. Complications may vary from mild interstitial pneumonia to extreme acute respiratory distress syndrome (ARDS), requiring critical medical treatment.

Serological analysis is the ideal diagnostic tool for scrub typhus, and the indirect immunofluorescence assay (IFA) has been regarded as the gold standard. Early diagnosis and accuracy are important to avert complications and institute proper antibiotic therapy. With the rising cases of scrub typhus and its possible manifestation of severe lung involvement, it is the focus of this investigation to examine and identify the disease's clinical and respiratory manifestations. Through enhanced insights into these complications, more optimal diagnostic and management approaches can be established to decline the disease load and enhance outcomes in patients.

Study Design and Setting

The present study was an observational hospital-based study carried out over a period of one year from October 2023 to October 2024. The study was done in the General Medicine, Respiratory Medicine Departments, and Intensive Care Unit of a tertiary care center. The purpose of the study was to assess the clinical profile and pulmonary presentations of patients with scrub typhus.

Study Population

The study included 100 patients who were admitted with definite scrub typhus infection. A case of scrub typhus was suspected if a patient had undifferentiated fever, with or without other features such as eschar, rash, headache, lymphadenopathy, or multi-organ dysfunction. The final analysis included only those patients who had laboratory-confirmed scrub typhus. Dengue, typhoid, malaria, and leptospirosis cases were excluded prior to enrollment for diagnostic specificity.

Data Collection and Clinical Evaluation

Clinical, epidemiologic, and lab information was ascertained using a standardized questionnaire. Demographic information, present symptoms, and systemic involvement information were noted down. All of the patients went through a full clinical assessment that included a systematic history and a physical examination aimed at evaluating overall and respiratory complaints. The pulmonary involvement in cases of scrub typhus was specifically evaluated under this study.

Laboratory Diagnosis

For serological diagnosis, a 2 ml blood sample was taken from every suspected case at the acute stage of illness. Serum was separated and tested with the gold-standard IgM immunofluorescence assay (IFA) supplied by Fuller Laboratories, USA. The assay involved four Orientia tsutsugamushi strains—Karp, Kato, Gilliam, and Boryong—grown in L292 cells. Patient serum samples were diluted and left to react with antigen-coated IFA slides to allow antigen-antibody interaction. The use of a fluorescence conjugate to identify the antigen-antibody complexes and then observe it under a fluorescent microscope was practiced. A positive test was marked by the identification of fluorescent rod shapes against counterstained red cells.

Radiological and Pulmonary Evaluation

All the patients with scrub typhus were thoroughly evaluated for pulmonary involvement to assess the degree of respiratory impairment. High-resolution computed tomography of the thorax was done to assess lung pathology. Imaging results were examined to reveal pulmonary manifestations from interstitial pneumonia to acute respiratory distress syndrome (ARDS). Other investigations like arterial blood gas analysis and pulmonary function tests were done when clinically relevant.

Data Analysis

Prevalence of scrub typhus among undifferentiated febrile illness-presenting patients was ascertained, and clinical presentations, including pulmonary presentations, were quantitated in percentages. Data were collected systematically in order to review the range of respiratory complications for scrub typhus.

During the study period, 100 patients were diagnosed with scrub typhus using IgM IFA. Among these, 37 patients (37%) were found to have abnormal chest roentgenograms.

Demographic and Clinical Characteristics

The age of the patients varied between 18 and 92 years, with a mean age of 51.91 years. The pattern of cases in various age groups was as follows: 4 patients (10.81%) belonged to the 18-29 years age group, 10 patients (27.02%) to the 30-49 years age group, 13 patients (35.13%) to the 50-69 years age group, and 10 patients (27.02%) to the 70-92 years age group. In 37 patients whose chest imaging were abnormal, the male gender involved 24 patients (64.86%), with 13 female patients (35.13%) being the others.

Fever was a pervasive symptom (100%) in each of the patients. Fever alone was the sole chief complaint among only 13 patients (35.13%) but was noticed in other signs such as in 19 patients (51.3%) being cough and shortness of breath in 11 patients (29.7%), although shortness of breath never appeared as a single complaint alone.

Acute kidney injury, as evidenced by elevated levels of urea and creatinine, was seen in 16 patients (43.2%).

Hematological abnormalities that were common among the cases were anemia in 15 patients (40.5%), leukocytosis in 7 patients (18.9%), and transaminitis in 14 patients (37.8%).

Electrolyte imbalance was also common, with hyponatremia (serum sodium <135 mEq/L) being seen in 26 patients (70.2%) and hypokalemia (serum potassium <3.5 mEq/L) in 8 patients (21.6%).

The average CRP (C-reactive protein) value was 155.39 mg/L, ranging from 26.9 to 387.71 mg/L. Likewise, the average ESR (Erythrocyte Sedimentation Rate) was 49 mm/hr, ranging from 10 to 130 mm/hr.

Radiological Findings

Among the 37 patients with abnormal imaging, 11 patients (29.7%) had a normal chest X-ray.

The most frequent chest X-ray finding was bilateral pleural effusion in 14 patients (37.8%). Consolidation was present in 8 patients (21.6%), and bilateral reticular opacities were present in 4 patients (10.8%).

On CT Thorax, there were abnormalities in 25 (67.5%) patients. The most common abnormality was bilateral pleural effusion in 25 (67.5%) patients, with 14 (37.8%) patients having pleural effusion as the sole abnormality.

Bilateral ground glass opacities (GGO) were observed in 15 patients (40.5%), and consolidation in 9 patients (24.3%). Among them, bilateral consolidation was in 6 patients (16.2%), right-sided consolidation in 2 patients (5.4%), and left-sided consolidation in 1 patient (2.7%).

Other findings included tree-in-bud nodules in 1 patient (2.7%) and interlobular septal thickening in 4 patients (10.8%).

Table 1: Demographic Distribution of Patients with Abnormal Chest Imaging

Table 2: Distribution of Radiological Abnormalities in Scrub Typhus Patients

Figure 1: Age Distribution of Patients with Abnormal Chest Imaging (Bar Graph)

Figure 2: Proportion of Different Radiological Findings in Scrub Typhus Patients (Pie Chart)

Figure 3: Frequency of Common Symptoms in Scrub Typhus Patients (Bar Graph)

These observations underscore the fact that a high percentage of scrub typhus patients demonstrate chest imaging abnormalities, and the most common observed features are bilateral pleural effusion and ground glass opacities. This underlines the need for prompt imaging in cases suspected of scrub typhus to identify pulmonary complications.

Scrub typhus is a significant zoonotic infection caused by Orientia tsutsugamushi, with a wide spectrum of clinical manifestations. In our retrospective study spanning one year, we analyzed 100 patients diagnosed with scrub typhus using IgM IFA. Among them, 37% had abnormal chest imaging, highlighting the significant pulmonary involvement in the disease course. The pulmonary manifestations that were observed in our study, such as bilateral pleural effusion, consolidation, and ground-glass opacities, are consistent with findings in previous studies (Abhilash et al., 2016; Charoensak et al., 2006) [7, 8].

Cough (51.3%) and shortness of breath (29.7%) were the most common respiratory symptoms in our patients. Our results contrast with Gupta et al. (18.2%) and Kashyap et al. (31.2%), who had lower percentages of respiratory symptoms in scrub typhus patients. The difference could be due to variation in sample size, geographical differences, or variations in disease severity at presentation. Interestingly, none of the patients in our research had mediastinal lymphadenopathy, which is in contrast to Kashyap et al., in which 47.37% of patients who received CT thorax had this characteristic. Rather, pleural effusion (67.5%) was the most frequent pulmonary abnormality among our patients, which is in line with that of Wu et al., in which pleural effusion was the most common abnormality among patients with scrub typhus.

ARDS is a deadly and potentially life-threatening complication of scrub typhus. In our study, 13.5% of patients presented with chest radiographic abnormalities consistent with ARDS, and all of them died regardless of prompt initiation of doxycycline. This result is consistent with the range published in earlier literature, wherein ARDS incidence in scrub typhus ranged from 6% to 25%, with mortality rate of 25% (Dinesh Bhanushali et al., 2024) [12]. The precise pathophysiology of ARDS in scrub typhus is still not known, but endothelial dysfunction, diffuse alveolar injury, and microvascular leakage causing pulmonary edema have been suggested as etiological factors. Although vasculitis is a characteristic feature of scrub typhus, ARDS seems to be due to diffuse alveolar damage rather than to direct inflammation of the vessels (Thap et al., 2002) [11].

Renal involvement in scrub typhus is established, with the reported rates of acute kidney injury (AKI) varying between 18% and 66.4% (Varghese et al., 2014) [15]. In our study, AKI was observed in 43.2% of the cases, which is within this range. Renal dysfunction in scrub typhus would be multifactorial, with direct endothelial damage, vasculitis leading to ischemic injury, and systemic inflammation as contributing factors. In parallel, hepatic involvement manifested by mild hepatitis and transaminitis in 37.8% of our patients is also a result confirmed by previous studies (Sivarajan et al., 2016) [14].

Inflammatory parameters like CRP and ESR are common findings in elevated levels in scrub typhus as a measure of the body's inflammatory reaction. Our case was found with an average of CRP value at 155.39 mg/L, in which 37.8% of the cases presented with CRP >150 mg/L. This is significantly higher than the 10.8% Lin et al. found in rickettsial disease and may indicate a more severe inflammatory response in our population. ESR was also raised, with a mean of 49 mm/hr. It is important to note early detection of systemic inflammation, as increased CRP has been shown to be indicative of more severe scrub typhus courses (Yun et al., 2019) [9].

Chest imaging abnormalities were present in 37% of our patients, with pleural effusion (67.5%) being the most prevalent radiological abnormality on CT scans. Bilateral pleural effusion was the only abnormality in 37.8% of cases. Ground-glass opacities (40.5%) and consolidation (24.3%) were also common occurrences. These findings are consistent with earlier studies, where the most prevalent pulmonary abnormality was bilateral reticulonodular opacities (Choi et al., 2006). Remarkably, interlobular septal thickening and tree-in-bud nodules were noted in a minority of patients, previously rarely reported manifestations in scrub typhus.

The management of scrub typhus is mostly with doxycycline, which was started in all our cases. Azithromycin can be used as an alternative in pregnant women and children, but doxycycline is the drug of choice because of its quicker resolution of symptoms (Jo et al., 2012) [10]. Even with early treatment initiation, 13.5% of patients died of ARDS, highlighting the severity of respiratory complications in scrub typhus.

The nonspecific nature of scrub typhus requires a high suspicion level, particularly in endemic regions. Classic features of rash, lymphadenopathy, and eschar may not always be evident, and thus diagnosis would be tricky. The need for early diagnosis and treatment is stressed through our observation that severe complications like ARDS and multiorgan dysfunction can quickly set in. More studies are required to improve the understanding of the pathogenesis of ARDS in scrub typhus and investigate possible adjunctive treatments apart from doxycycline (Qu Y. 2000) [13].

Our research reaffirms the important pulmonary, renal, and hepatic involvement in scrub typhus. The strong presence of pleural effusion, ground-glass opacities, and ARDS underscores the importance of early imaging among patients presenting with respiratory complaints. Considering the mortality noted in the cases of ARDS with prompt treatment, clinicians must be alert to early respiratory distress signs among scrub typhus patients and initiate intensive supportive therapy when the need arises.

Scrub typhus continues to be a serious seasonal febrile disease, with involvement of the lung playing a significant role in morbidity and mortality. The illness frequently poses with nonspecific signs and symptoms, which make early diagnosis difficult, particularly in areas where other vector-borne conditions like malaria and dengue occur. The prevalence of high pleural effusion, ground-glass opacities, and ARDS highlights the importance of early recognition and treatment of respiratory complications. Rise in CRP during the acute phase can be a valuable indicator of disease severity and response to treatment. With more patients presenting with atypical presentations, enhanced clinical suspicion and better diagnosis are the need of the hour. With limited information on scrub typhus in the Indian subcontinent, additional studies are essential to formulate improved management strategies and decrease disease burden.

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