# Case Report: Murine typhus complicated by symmetrical peripheral gangrene: first report and diagnostic insights from metagenomic next-generation sequencing

**Authors:** Hengling Zhu, Linhui Hu, Zaiming Feng, Zichen Zhang, Hengbao Zhu, Huihua Li

PMC · DOI: 10.3389/fimmu.2025.1746919 · 2026-01-16

## TL;DR

A 69-year-old farmer in South China developed severe murine typhus with gangrene in all four limbs, and metagenomic sequencing helped identify the infection and guide treatment.

## Contribution

First reported case of murine typhus complicated by symmetrical peripheral gangrene, demonstrating the diagnostic value of metagenomic next-generation sequencing.

## Key findings

- Metagenomic next-generation sequencing rapidly identified Rickettsia typhi in a severe case of murine typhus.
- The patient developed life-threatening multiorgan failure and gangrene requiring amputation of all four extremities.
- Timely doxycycline treatment guided by mNGS improved outcomes despite severe complications.

## Abstract

Murine typhus, a flea-borne infection caused by Rickettsia typhi, often presents with nonspecific symptoms that delay diagnosis. While usually self-limiting, it can rarely progress to multiple organ dysfunction syndrome (MODS). We report the first case of murine typhus complicated by symmetrical peripheral gangrene (SPG), in which metagenomic next-generation sequencing (mNGS) enabled rapid diagnosis and guided timely doxycycline therapy.

A 69-year-old female from South China was hospitalized with persistent abdominal pain and low-grade fever. She was a farmer and had suspected animal exposure. Laboratory investigations revealed hypoxia, abnormal coagulation profile, hepatorenal impairment, and thrombocytopenia. Despite empirical antibiotic therapy, her condition deteriorated progressively, manifested as hemodynamic instability, respiratory failure, and the emergence of purpuric-petechial cutaneous eruptions. Immediate interventions were initiated, including administration of vasoactive agents and mechanical ventilation. Based on mNGS, R. typhi was confirmed, she received targeted antibiotic treatment with intravenous doxycycline (100 mg twice daily). On the hospital day 16, gangrene of all four extremities became evident. The patient underwent amputation of all four extremities and survived, with systemic symptoms gradually resolving during 6-months follow-up.

This first reported case of murine typhus complicated by symmetrical peripheral gangrene (SPG) establishes its potential to cause life-threatening multiorgan failure. Metagenomic next-generation sequencing (mNGS) resolved the diagnostic challenge by rapidly identifying Rickettsia typhi, guiding life-saving doxycycline therapy and underscoring its value in severe zoonotic infections.

## Linked entities

- **Chemicals:** doxycycline (PubChem CID 54671203)
- **Diseases:** murine typhus (MONDO:0000330), multiple organ dysfunction syndrome (MONDO:0043726), respiratory failure (MONDO:0021113)
- **Species:** Rickettsia typhi (taxon 785)

## Full-text entities

- **Diseases:** MODS (MESH:D009102), abnormal coagulation profile (MESH:D001778), respiratory failure (MESH:D012131), thrombocytopenia (MESH:D013921), hepatorenal impairment (MESH:D006530), Murine typhus (MESH:D014437), SPG (MESH:D005734), multiorgan failure (MESH:D051437), infection (MESH:D007239), flea- (MESH:D058267), fever (MESH:D005334), abdominal pain (MESH:D015746), hypoxia (MESH:D000860), purpuric-petechial cutaneous eruptions (MESH:C537186)
- **Chemicals:** vasoactive agents (-), doxycycline (MESH:D004318)
- **Species:** Rickettsia typhi (species) [taxon 785], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12855535/full.md

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Source: https://tomesphere.com/paper/PMC12855535