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Leptospirosis

Pathogen:Bacteria →Gram-negative spirochaetes →Leptospira interrogans
Transmission:Exposure to infected animals, mainly through urine
Geographical range:Worldwide; most prevalent in tropical regions
Incidence:Up to 1 million infections per year (estimated)

Case history

A 41-year-old Indonesian man has been suffering from an intermittent fever for several days. Five days after the onset of the fever, he is admitted to hospital and his physician reports his symptoms as a headache and pain in the eyes, muscles and major joints. The physician also observes abundant petechiae and immediately orders a full blood count including WBC differential and reticulocyte count in order to differentially diagnose the man’s condition and subsequently start the appropriate treatment.

Leptospirosis pathophysiology and diagnostics

Leptospirosis is an infectious disease caused by pathogenic bacteria belonging to the genus Leptospira, which are transmitted directly or indirectly from animals to humans. Typical animals that spread the disease are rodents. Humans are infected by water, food or soil containing urine from infected animals. The infection can also come from swallowing contaminated food or water, but also through skin contact. In the developing world, the disease is common among farmers and poor city-dwellers. In the developed world, leptospirosis is quite common amongst water-sport enthusiasts in certain areas, because a prolonged stay in water facilitates the leptospirosis infection. It is estimated that 7 to 10 million people are infected by leptospirosis annually (1). One million cases of severe leptospirosis occur each year and lead to around 60,000 deaths.

Typical signs and symptoms are usually mild, such as headaches, muscle pain and fever, but severe bleeding can also occur.

In a susceptible host, virulent bacteria rapidly enter the bloodstream and spread to all organs, particularly to the liver and kidney. The incubation period is typically 5 to 14 days, but is generally described as 3 to 30 days. Research mainly suggests endotoxins, haemolysins and lipases as possible sources of pathogenicity, but the true mechanism of host tissue injury remains unclear.

The common pathologic finding in leptospirosis is vasculitis of capillaries manifested by endothelial oedema, necrosis and lymphocytic infiltration. Capillary vasculitis is found in affected organs. The resulting loss of RBC and fluids causes secondary tissue injury and accounts for many of the clinical findings. The damage to the vascular system can result in capillary leakage, hypovolemia and shock. Patients may develop disseminated intravascular coagulation, haemolytic uremic syndrome or thrombotic thrombocytopenic purpura. Thrombocytopenia indicates severe disease (2).

Following acute infection, multiplication of the bacteria persists until opsonizing immunoglobulin develops in the plasma followed by rapid immune clearance. Although the systemic immune response may eliminate the organism from the body, it may also lead to a symptomatic inflammatory reaction that can produce secondary end-organ injury.

Early diagnosis of leptospirosis is important, because antibiotic treatment is most effective when initiated early in the course of the disease. Bacterial cell culture and microscopic agglutination tests are gold-standard methods for leptospirosis diagnosis, but are not useful for early diagnosis. Rapid bacterial serological tests demonstrate low sensitivity to early-phase leptospirosis and PCR-based techniques are often unavailable in developing countries.

Laboratory results

 

Case interpretation

The XN results shows severe thrombocytopenia, leukocytosis and mild anaemia. The WDF channel reveals severe neutrophilia and lymphopenia and a very high ratio between the neutrophil and lymphocyte count (NEUT#/LYMPH# = 31). Furthermore, the WDF scattergram shows the activation of neutrophils (NEUT-RI = 61.1 FI) and monocytes (MONO-SFL = 150.1 FI) indicated by their increased fluorescence intensity.

The PLT count from the PLT-F channel is very low (PLT = 9 x 109/L) and correlates with the bleeding and petechiae observed on the patient. The normal value of the immature platelet fraction (IPF% = 1.7%) suggests that the cause of thrombocytopenia is decreased production in the bone marrow, which is also indicated by the low value of IPF# and is common during infectious processes.

The RET channel reveals that erythropoiesis is also affected, because the RET count is slightly decreased and the Delta-He is negative (- 4.2 pg). This strong negative value is indicative of an acute infection and sequestration of available iron in the macrophages. Iron sequestration by ferritin in macrophages restricts iron availability for extracellularly occurring pathogens for inhibiting pathogen growth. However, this mechanism also suppresses iron availability to the erythropoietic progenitor cells. This leads to a decrease in the RET-He value and a negative Delta-He value.

This blood cell response profile is typical for an early innate immune reaction to an extracellularly located bacterial pathogen. The very high neutrophil/lymphocyte ratio and low total lymphocyte count could likely exclude a viral infection. High neutrophilia and low cellular lymphocyte immune response (Re-LYMP) also excludes intracellular pathogen as a possible cause of infection.

A positive IgM anti-leptospira ELISA test performed a day after the XN results were received diagnosed the patient’s leptospirosis infection.

References

  1. UK NHS on Leptospirosis
    http://www.nhs.uk/conditions/Leptospirosis/Pages/Introduction.aspx
  2. Chierakul W, Tientadakul P, Suputtamongkol Y, Wuthiekanun V, Phimda K, Limpaiboon R (2008): Activation of the coagulation cascade in patients with leptospirosis. Clin. Infect Dis. Jan 15. 46(2):254-60.

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