Aggregatibacter actinomycetemcomitans as the Aetiological Cause of Rheumatoid Arthritis: What Are the Unsolved Puzzles?

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host's immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA.

Leptospirosis: Increasing importance in developing countries.

Leptospirosis is a zoonotic disease caused by the pathogenic helical spirochetes, Leptospira. Symptoms include sudden-onset fever, severe headaches, muscle pain, nausea and chills. Leptospirosis is endemic in developing countries such as Malaysia, India, Sri Lanka, and Brazil where thousands of cases are reported annually. The disease risk factors include the high population of reservoirs, environmental factors, recreational factors, and occupational factors. To end the endemicity of leptospirosis, these factors need to be tackled. The management of leptospirosis needs to be refined. Early diagnosis remains a challenge due to a lack of clinical suspicion among physicians, its non-specific symptoms and a limited availability of rapid point-of-care diagnostic tests. The purpose of this review is to provide insight into the status of leptospirosis in developing countries focusing on the risk factors and to propose methods for the improved management of the disease.