A case of acute pulmonary edema in scrub typhus: a rare complication with normal cardiac and renal function – BMC Infectious Diseases

Report on Scrub Typhus: Clinical Manifestations and Alignment with Sustainable Development Goals

Introduction and Pathophysiology

Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, represents a significant public health challenge that directly impacts the achievement of Sustainable Development Goal 3 (Good Health and Well-being). The disease is transmitted through the bite of infected chigger larvae (Leptotrombidium mites), a vector-borne mechanism that underscores the link between environmental health and human well-being.

• Inoculation and Local Replication: Following a bite, the bacteria replicate at the inoculation site, leading to a characteristic papule that ulcerates to form a necrotic eschar.
• Systemic Dissemination: The pathogen spreads systemically, causing bacteraemia approximately 1-3 days before fever onset. The disease process involves perivascular inflammation of small blood vessels, with involvement of endothelial cells and macrophages.
• Multi-Organ Involvement: Dissemination via macrophages can lead to severe, life-threatening complications affecting multiple organs, posing a direct threat to health outcomes targeted by SDG 3.

Clinical Diagnosis and Challenges

Early and accurate diagnosis is critical for effective management and aligns with SDG 3.3, which aims to end epidemics of communicable diseases. However, diagnosis is often complicated by non-specific symptoms and overlooked signs.

Key Diagnostic Indicators

1. Eschar Presence: The eschar is a highly suggestive clinical sign. Its painless nature and location in hidden areas (groin, axilla) mean it is frequently missed, particularly in dark-skinned individuals, leading to diagnostic delays.
2. Lymphadenopathy: Regional lymph node enlargement near the eschar is common, often progressing to generalized lymphadenopathy.
3. Acute Febrile Illness: Patients typically develop an acute fever 8–10 days post-exposure.

In endemic regions like Sri Lanka, clinical identification of the eschar remains a cornerstone of early diagnosis, highlighting the need for robust clinical training and health system capacity, a core component of SDG 3.8 (Universal Health Coverage).

Analysis of Atypical Complications: Noncardiogenic Pulmonary Edema

While pleuropulmonary involvement is documented, noncardiogenic pulmonary edema in the absence of cardiac or renal dysfunction is a rare and severe complication. A case analysis demonstrated a diagnostic pathway to confirm scrub typhus-associated capillary leak syndrome.

• Exclusion of Cardiac Failure: Initial suspicion of myocarditis was refuted by formal echocardiography showing preserved left ventricular function and normal troponin levels. The unavailability of BNP measurement in the reporting center highlights resource gaps that challenge the goals of SDG 3.
• Exclusion of Renal Failure: Normal renal function and adequate urine output ruled out volume overload from renal impairment.
• Distinction from ARDS: The patient did not meet the Berlin criteria for Acute Respiratory Distress Syndrome (ARDS), as the PaO₂/FiO₂ ratio was measured without positive pressure support. The rapid clinical improvement following diuretic therapy further distinguished the condition from ARDS.

This case represents a standalone instance of noncardiogenic pulmonary edema without other multi-organ dysfunction, providing valuable clinical data for managing severe scrub typhus and reducing its mortality rate, thereby contributing to SDG 3.

Treatment and Management Protocols

Timely and appropriate treatment is fundamental to managing scrub typhus and preventing severe outcomes. The management strategy reflects both best practices and resource limitations in endemic settings.

1. First-Line Therapy: Doxycycline is the highly effective, first-line treatment. In the reported case of severe disease, oral doxycycline was administered due to the unavailability of an intravenous formulation, a reality that underscores the challenges in achieving universal access to essential medicines as outlined in SDG 3.
2. Alternative Therapy: Azithromycin serves as an alternative for patients with contraindications to doxycycline, such as pregnant women and young children.
3. Supportive Care: In the case of noncardiogenic pulmonary edema, the cautious administration of low-dose diuretics provided symptomatic relief by mobilizing extravascular lung fluid without compromising hemodynamic stability.

Implications for Sustainable Development Goals (SDGs)

The management of scrub typhus is intrinsically linked to several SDGs, extending beyond immediate health outcomes.

• SDG 3 (Good Health and Well-being): Scrub typhus is a communicable disease whose control is essential for Target 3.3. The challenges in diagnosis (e.g., missed eschars) and treatment (e.g., lack of IV formulations or diagnostic tools) highlight the need to strengthen health systems and work towards universal health coverage (Target 3.8).
• SDG 1 (No Poverty): As a disease prevalent in rural and endemic regions, scrub typhus disproportionately affects vulnerable populations. The illness can lead to loss of income and catastrophic health expenditures, hindering progress towards poverty eradication.
• SDG 17 (Partnerships for the Goals): The reliance on global research and clinical guidelines (e.g., UpToDate) for management demonstrates the importance of international collaboration. Sharing knowledge and building capacity in endemic regions are critical for improving health outcomes and advancing global health equity.

Analysis of Sustainable Development Goals in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

The article primarily addresses issues related to SDG 3: Good Health and Well-being. The entire text is a medical case report focusing on the diagnosis, complications, and management of scrub typhus, a communicable disease. The discussion revolves around ensuring healthy lives and promoting well-being by improving the understanding and treatment of this infectious disease.

• SDG 3: Good Health and Well-being: The core of the article is the detailed clinical analysis of a patient with scrub typhus, an infectious disease endemic in regions like Sri Lanka. It explores diagnostic challenges, treatment protocols, and patient outcomes, all of which are central to the goal of ensuring good health.

2. What specific targets under those SDGs can be identified based on the article’s content?

Based on the focus on infectious disease management and healthcare system capacity, the following specific targets under SDG 3 can be identified:

1. Target 3.3: By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.
   • Explanation: The article is entirely focused on scrub typhus, a vector-borne communicable disease. By detailing the clinical presentation, diagnostic process (“serological confirmation”), and effective treatment (“Doxycycline is the first-line treatment”), the article contributes to the body of knowledge needed to combat and manage outbreaks of such diseases in endemic areas.
2. Target 3.8: Achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all.
   • Explanation: The article implicitly points to challenges in achieving universal health coverage. It mentions limitations in the healthcare facility, such as the unavailability of a specific diagnostic test (“BNP measurement, which can help differentiate cardiogenic from noncardiogenic pulmonary edema, was not available in our center”) and a specific formulation of an essential medicine (“oral doxycycline was initiated as intravenous formulation was not available”). This highlights gaps in access to quality essential healthcare services and medicines.
3. Target 3.d: Strengthen the capacity of all countries, in particular developing countries, for early warning, risk reduction and management of national and global health risks.
   • Explanation: The article emphasizes the importance of early diagnosis for managing the health risk posed by scrub typhus. It states, “In endemic regions such as Sri Lanka, the identification of an eschar remains vital for early diagnosis.” This focus on recognizing early clinical signs is a key component of strengthening the capacity for risk reduction and management at the clinical level. The case report itself serves as a tool to educate and strengthen the capacity of healthcare professionals to handle complex presentations of the disease.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

Yes, the article mentions or implies several indicators that can be used to measure progress:

1. For Target 3.3 (End epidemics of communicable diseases):
   • Implied Indicator – Rate of early and accurate diagnosis: The article stresses the importance of identifying the eschar for “early diagnosis.” Progress could be measured by tracking the percentage of scrub typhus cases diagnosed early based on clinical signs and confirmed by methods like “serological confirmation.”
   • Implied Indicator – Treatment efficacy and patient outcomes: The article notes that the “patient showed a favorable response to doxycycline, with marked clinical improvement within 48 h.” This suggests that treatment success rates and the time to clinical improvement are key indicators for measuring the effectiveness of interventions against the disease.
2. For Target 3.8 (Universal health coverage):
   • Indicator – Availability of essential diagnostics: The text explicitly states that “BNP measurement… was not available in our center.” This points to a measurable indicator: the proportion of healthcare facilities in a region that have access to specific essential diagnostic tests.
   • Indicator – Availability of essential medicines: The article mentions that the “intravenous formulation [of doxycycline] was not available.” The availability of different formulations of first-line, essential medicines in health centers is a direct indicator of access to quality healthcare services.
3. For Target 3.d (Strengthen capacity for health risks):
   • Implied Indicator – Clinical capacity for disease recognition: The emphasis on identifying the eschar, which is “often overlooked,” implies that the capacity of healthcare workers to recognize key diagnostic signs of endemic diseases is a crucial indicator of a health system’s preparedness and early warning capabilities.

4. Summary Table of SDGs, Targets, and Indicators

Source: bmcinfectdis.biomedcentral.com