From the Guidelines
The Jarisch-Herxheimer reaction in leptospirosis is caused by the rapid killing of Leptospira bacteria following antibiotic treatment, leading to a massive release of bacterial toxins and inflammatory mediators. This reaction typically occurs within 1-2 hours after starting antibiotics, especially penicillin or doxycycline, and manifests as a temporary worsening of symptoms including fever, chills, headache, myalgia, and sometimes hypotension 1. The reaction happens because the dying bacteria release endotoxins and other cellular components that trigger an intense immune response with cytokine release, particularly tumor necrosis factor-alpha, interleukin-6, and interleukin-8. This inflammatory cascade can exacerbate symptoms before improvement begins. The reaction is self-limiting, usually resolving within 24 hours, and can be managed with supportive care including antipyretics, adequate hydration, and close monitoring. In severe cases with significant hypotension, careful fluid management and sometimes corticosteroids may be needed. Despite this potential reaction, antibiotic therapy should not be delayed or discontinued as it remains essential for treating the underlying leptospirosis infection. Some key points to consider in the management of leptospirosis include:
- Early mild disease is generally self-limiting; penicillin and tetracycline antibiotics are thought to be effective during the bacteraemic phase 1
- Patients presenting with classical symptoms and signs of Weils disease such as jaundice can become very unwell despite therapy and may require renal or liver support 1
- A systematic review of antibiotic effectiveness in established leptospirosis showed no benefit for antibiotic treatment based on three trials, however, pending further evidence most infectious disease specialists continue to recommend antibiotics, whilst accepting that severe disease is probably immunologically mediated 1
From the Research
Jarisch Herxheimer Reaction in Leptospirosis
The Jarisch Herxheimer reaction (JHR) is a potential complication of leptospirosis treatment, characterized by a temporary worsening of symptoms after antibiotic administration 2, 3, 4, 5, 6.
Causes and Risk Factors
- The exact causes of JHR in leptospirosis are not fully understood, but it is thought to be related to the release of endotoxins and other pro-inflammatory substances after the death of Leptospira bacteria 5, 6.
- Risk factors for JHR in leptospirosis include the infecting strain of Leptospira, with Leptospira interrogans serogroup Australis being associated with a higher risk of JHR 4.
- Delays of less than 3 days between the onset of symptoms and the initiation of antibiotic therapy have also been identified as a risk factor for JHR 4.
Clinical Presentation
- JHR can manifest with a range of symptoms, including shaking chills, fever, and intensification of skin rashes 6.
- In severe cases, JHR can lead to more serious complications, such as acute respiratory distress syndrome, myocardial injury, and hypotension 6.
Incidence and Awareness
- The true incidence of JHR in leptospirosis is unknown, but it is estimated to occur in around 21% of patients treated with amoxicillin 4.
- Awareness of JHR among clinicians is considered insufficient, and it is recommended that leptospirosis guidelines and protocols emphasize the importance of monitoring for JHR after antibiotic administration 2.