European Journal of Cardiovascular Medicine

Leptospirosis and scrub typhus are two significant zoonotic infections that continue to pose major public health challenges in tropical and subtropical regions, particularly in South and Southeast Asia. Leptospirosis is caused by pathogenic spirochetes of the Leptospira genus, and is typically transmitted to humans through direct or indirect contact with water or soil contaminated with the urine of infected animals, particularly rodents. In contrast, scrub typhus is caused by Orientia tsutsugamushi, an obligate intracellular Gram-negative bacterium transmitted via the bite of larval trombiculid mites (chiggers).1

Both diseases share overlapping clinical manifestations, including high-grade fever, myalgia, headache, gastrointestinal symptoms, hepatic involvement, and thrombocytopenia. This nonspecific symptomatology often poses diagnostic challenges, particularly in resource-limited settings where access to advanced laboratory testing is restricted. As a result, coinfections may remain undiagnosed, contributing to increased morbidity and potentially fatal outcomes if not treated promptly and appropriately.

The north-eastern regions of India, particularly those close to the Himalayan belt, provide an optimal ecological habitat for both Leptospira and O. tsutsugamushi. Factors contributing to this include high humidity, dense vegetation, the presence of animal reservoirs, and increased human exposure through agricultural activities, deforestation, tourism, and expanding peri-urban interfaces. These environmental and socio-economic conditions create unique opportunities for simultaneous transmission of multiple vector- and reservoir-borne diseases.2

This case report aims to present a rare and diagnostically challenging case of concurrent leptospirosis and scrub typhus in a previously healthy adult male. Through detailed clinical evaluation and laboratory investigation, this report emphasizes the need for heightened clinical suspicion of coinfections in endemic regions. A multidisciplinary approach involving early diagnosis and empiric treatment is pivotal to prevent complications and reduce disease burden.

east India   presented to my clinic with a week long history of moderate to high degree continuous fever and severe headache when the temperature became high (>103 degrees Fahrenheit). Associated symptoms included generalized myalgia and fatigue.

Notably, there was no history of rash, conjunctival congestion/redness, cough. Prior to reporting to my clinic he consulted the Nephrology outdoor of a tertiary care hospital as he had sudden rise of serum creatinine to about 8.4mg/dl with no burning micturition or haematuria or features suggestive of Nephrotic syndrome ie, edema, albuminuria. In nephrology OPD of the tertiary care hospital the patient was diagnosed to be a case of AKI with investigations being done to find out the cause of the acute kidney injury. He was suggested to undergo day care haemodialysis which he underwent due to which the serum creatinine level dropped to about 5.6 mg/dl on the third day post dialysis and he began to feel better.

However, his fever continued, in same intensity and calibre and slowly his appetite was decreased as well as his sclera turned yellowish alongwith yellowish colouration of urine there was no itching in the body nor there was any discoloration of his stool. The patient had recent travel history, but there was no sick contact exposure or known comorbidities. On presentation, the patient was alert and oriented with a Glasgow Coma Scale (GCS) score of E4V5M6. Vital signs showed hypotension (BP: 89/61 mmHg), normothermia (temperature: 37.6°C), and a pulse rate of 93 beats per minute.  The respiratory rate was found to be 21 breaths per minute. The SPO₂ was found to be almost consistent in room air with saturation of 98-99% in room air.   On general physical examination –there was pallor, icteric tinge, tongue was coated with no lymphnodes palpable. Systemic examination revealed no focal neurological deficits, and cardiovascular, respiratory, and abdominal examinations were unremarkable.

Laboratory investigations (done earlier during the course of the disease) demonstrated leucocytosis with a total leukocyte count of 12460 cells/cu.mm and neutrophilic predominance (84%). Thrombocytopenia was significant with a platelet count of 1,00,000 cells/cu.mm. Coagulation parameters were within normal limits with an APTT of 37.5 seconds, PT of 13.1 seconds, and INR of 0.99. Inflammatory markers were markedly elevated, with C-reactive protein (CRP) 57 mg/L.

Renal function tests showed marked azotaemia (urea: 77 mg/dL; serum creatinine: 3.2 mg/dL; uric acid: 9.5 mg/dL). Liver function tests revealed hyperbilirubinemia (total bilirubin: 3.5 mg/dL; direct bilirubin: 1.68 mg/dL), and elevated transaminases (AST: 127 U/L; ALT: 245 U/L). Urinalysis showed glycosuria (trace) and microscopic haematuria (8–10 RBCs/hpf).

Arterial blood gas analysis demonstrated a mixed acid-base disturbance: pH 7.3, PaCO₂ 33 mmHg, HCO₃⁻ 17.4 mmol/L, and PaO₂ 46 mmHg with oxygen saturation of 98-99% on ambient air.

Serological testing for dengue (NS1 antigen and IgM) and malarial parasites (thick and thin smears) were negative. Given persistent hypotension and laboratory findings, a diagnosis of septic shock was considered, and the patient was initiated on noradrenaline for hemodynamic support.

Empiric antimicrobial therapy with intravenous meropenem (1 g every 8 hours) and oral doxycycline (100 mg twice daily) was commenced, considering the regional prevalence of tropical infections. Intravenous hydrocortisone (50 mg every 6 hours) was introduced as an adjunctive measure for refractory hypotension. Despite medical therapy, the patient developed progressive renal dysfunction, with serum creatinine rising to 7.2 mg/dL and urea to 178 mg/dL.  Given declining urine output, diuretics were initiated, followed by hemodialysis.³

After 5 days of hospitalisation in tertiary care center, chest radiography was repeated thinking it to be in line with Covid -19 infection as the person was took only a single dose of covid vaccine -Covishield & the chest radiography revealed bilateral pulmonary infiltrates, suggestive of acute respiratory distress syndrome (ARDS).⁴ Rapid test for Covid-19 was done and it came out negative.  He was supported initially with oxygen via nasal prongs as his saturation in room air dropped from 98% to 82% and later with non-invasive ventilation due to deteriorating oxygenation. Blood and urine cultures remained sterile.

Serological assays using ELISA on day 7 revealed positive IgM antibodies for both Orientia tsutsugamushi and Leptospira spp., confirming a dual infection with scrub typhus and leptospirosis. Based on these findings, antibiotic therapy was de-escalated to intravenous cefotaxime (1Gm-12 hourly, IV), while doxycycline was continued to complete the course of treatment.

Following haemodialysis, the patient demonstrated improved renal function and increasing urine output. Respiratory parameters stabilized, and oxygen requirements decreased, allowing for discontinuation of non-invasive ventilatory support.

 Haematological parameters, including platelet count, showed significant recovery (from 72,000 to 196,000 cells/cu.mm). Serum creatinine levels demonstrated a downward trend (from 6.6 to 2.4 mg/dL), consistent with renal recovery.

By day 14 of hospitalization, the patient showed marked clinical improvement and was able to maintain normal oxygen saturation in room air. He was discharged in a stable condition with appropriate follow-up and counselling.

Table 1. Investigation result during hospital stay.

Image:  Chest X ray of the patient.

The clinical presentation of this patient, marked by non-specific symptoms such as high-grade fever, malaise, headache, and myalgia, is consistent with the overlap seen in several endemic febrile illnesses, including leptospirosis and scrub typhus. Both these zoonotic infections are known to present with multisystem involvement, potentially affecting the hematologic, hepatic, renal, and pulmonary systems.

In this case, the development of thrombocytopenia, elevated liver enzymes, acute kidney injury, and respiratory compromise underscored the severity and diagnostic complexity of the illness. The patient demonstrated favourable clinical response following early empiric administration of doxycycline and broad-spectrum antibiotic coverage with meropenem and then injectable cefotaxime(1Gm) along with meticulous supportive care.

Leptospirosis and scrub typhus are frequently underdiagnosed tropical diseases, often due to their overlapping clinical manifestations and shared seasonal prevalence. Monsoonal patterns significantly influence their incidence—leptospirosis increases following heavy rainfall and flooding due to exposure to water contaminated with the urine of infected rodents, while scrub typhus typically peaks with the proliferation of trombiculid mites in areas of dense scrub vegetation during and after the rainy season. These common epidemiological drivers, along with similar clinical features, facilitate the potential for co-infection in endemic areas, particularly in South and Southeast Asia.⁵

Despite this epidemiological plausibility, confirmed cases of coinfection with Leptospira spp. and Orientia tsutsugamushi remain relatively infrequent in published Indian literature compared to countries such as Thailand and Taiwan. Reports from India are limited, though a few studies do acknowledge their concurrent occurrence. The overlap in symptomatology such as high-grade fever, headache, malaise, and organ dysfunction complicates early clinical differentiation. Characteristic clinical signs, when present, can help narrow the diagnosis; for instance, conjunctival congestion and calf muscle tenderness favour leptospirosis, while the presence of an eschar remains the most pathognomonic sign of scrub typhus. Unfortunately, such hallmark signs are frequently absent, as observed in this case, which prolongs the diagnostic process and may delay targeted treatment.

Both infections can progress to severe disease, manifesting as thrombocytopenia, acute liver injury, renal dysfunction, and acute respiratory distress syndrome (ARDS). While both pathogens can cause renal impairment, it tends to be more pronounced in leptospirosis due to direct spirochaetal invasion and immune-mediated tubular injury. In the presented case, the presence of significant azotaemia and subsequent requirement for haemodialysis suggested predominant renal involvement attributable to leptospirosis.

The literature on co-infection with scrub typhus and leptospirosis remains sparse. While several studies have analyzed co-infection patterns involving scrub typhus and other tropical diseases such as dengue or malaria, limited data exist comparing clinical and biochemical markers between scrub typhus-leptospirosis coinfections and mono infections. A seroprevalence study conducted in Uttar Pradesh, India, reported a coinfection rate of 8.4% among febrile outpatients; however, this study relied solely on serologic criteria without incorporating standardized clinical definitions, potentially leading to overestimation of coinfection rates. Another study identified that patients with leptospirosis-scrub typhus coinfections may exhibit lower bilirubin and creatinine levels and higher platelet counts compared to those with isolated leptospirosis. Such laboratory profiles, while potentially useful in identifying coinfection trends at a population level, require cautious extrapolation to clinical settings given inter-individual variability.⁶

The empiric initiation of doxycycline, a tetracycline-class antibiotic with proven efficacy against both Leptospira and O. tsutsugamushi, is both logical and widely recommended in endemic regions. The concurrent use of a broad-spectrum agent such as meropenem further enhances coverage, particularly in cases initially presenting with suspected septic shock. Timely de-escalation of antibiotics based on clinical response and serological confirmation, as executed here, aligns with antimicrobial stewardship principles.

Diagnosis based solely on serological assays such as IgM ELISA has limitations. Serological cross-reactivity, delayed seroconversion, and persistence of IgM antibodies may lead to false positives or misinterpretation. While polymerase chain reaction (PCR)-based molecular diagnostics offer greater specificity and reliability, their routine use in clinical practice within low-resource settings remains limited due to cost and accessibility constraints. Thus, in practice, clinical acumen complemented by serological evidence continues to remain essential for prompt recognition and management of such co-infections.

 This case highlights the importance of considering dual infections in the differential diagnosis of acute febrile illnesses, especially in tropical areas where multiple vector- and water-borne infections are highly prevalent.

 General practitioners and hospital-based clinicians should be aware of the high likelihood of coinfections during and following the monsoon season, especially in rural or agricultural communities. Early empiric therapy with doxycycline in patients with undifferentiated febrile illness, coupled with supportive interventions and judicious use of diagnostics, can significantly improve clinical outcomes and reduce the risk of severe complications or mortality.

Although coinfections with leptospirosis and scrub typhus are infrequently reported from other parts of India but they are very rare in north-eastern part of India, they may be under recognized due to overlapping clinical features and limited diagnostic resources. Both diseases are endemic in this region, particularly during the monsoon season, and can present with non-specific febrile illness accompanied by severe complications such as sepsis, septic shock, multi-organ dysfunction, and acute respiratory distress syndrome (ARDS). In such clinical scenarios, especially in endemic rural settings, clinicians should maintain a high index of suspicion for concurrent infections.

Empirical treatment that includes coverage for both Leptospira and Orientia tsutsugamushi, such as doxycycline, is prudent while awaiting definitive diagnostic confirmation. Prompt recognition and timely initiation of appropriate therapy are crucial for improving clinical outcomes and preventing high morbidity or mortality associated with delayed or missed diagnoses.

This case underscores the importance of improved diagnostic accessibility and increased clinical vigilance for co-infections in regions with favourable ecological conditions for both pathogens. Furthermore, there is a pressing need for comprehensive epidemiological studies to better understand the prevalence, risk factors, and public health implications of such coinfections in north eastern India. Proactive surveillance and clinician education are key to enhancing early diagnosis and management in endemic settings.

Funding: Self-Funding

Conflict of Interest: The author declares no conflict of interest with any person or organisation.

Human Ethics: Consent was obtained from the patient.

1. Coinfection with leptospirosis and scrub typhus in Taiwanese patients. Lee CH, Liu JW. https://pubmed.ncbi.nlm.nih.gov/17827372/Am J Trop Med Hyg. 2007;77:525–527. [PubMed] [Google Scholar]
2. Scrub typhus and leptospirosis co-infection in Himalayan region. Mahajan SK, Babu S, Singh D, Kanga A, Kaushal SS. Trop Doct. 2012;42:176–177. doi: 10.1258/td.2012.120041. [DOI] [PubMed] [Google Scholar]
3. Clinical and laboratory characteristics of dengue-orientia tsutsugamushi co-infection from a tertiary care center in South India. Basheer A, Iqbal N, Mookkappan S, Anitha P, Nair S, Kanungo R, Kandasamy R. Mediterr J Hematol Infect Dis. 2016;8:0. doi: 10.4084/MJHID.2016.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
4. Scrub typhus and its co-infection with Leptospirosis at a tertiary care hospital in Uttar Pradesh. Husain U, Kalyan RK, Jahan A, Gupta KK, Verma SK. Trop Doct. 2022;52:302–303. doi: 10.1177/00494755221077744. [DOI] [PubMed] [Google Scholar]
5. Leptospirosis and coinfection: should we be concerned? Md-Lasim A, Mohd-Taib FS, Abdul-Halim M, Mohd-Ngesom AM, Nathan S, Md-Nor S. Int J Environ Res Public Health. 2021;18 doi: 10.3390/ijerph18179411. [DOI] [PMC free article] [PubMed] [Google Scholar]
6. Molecular confirmation of co-infection by pathogenic Leptospira spp. and Orientia tsutsugamushi in patients with acute febrile illness in Thailand. Sonthayanon P, Chierakul W, Wuthiekanun V, et al. https://www.tropicalmedicine.ox.ac.uk/gram/publications/421056. Am J Trop Med Hyg. 2013;89:797–799. doi: 10.4269/ajtmh.13-0402. [DOI] [PMC free article] [PubMed] [Google Scholar]