The Paradox of the Chicken and the Egg: Lack of Actionable Diagnostics Prevents Global Burden of Disease Assessment and Deployment of Public Health Preventive Measures

Leptospirosis, a bacterial zoonosis, is a globally important emerging infectious disease. The magnitude of its public health importance in most regions and countries remains unknown, both in terms of clinical diagnosis and overall burden of disease, which supports the designation of leptospirosis as a neglected tropical disease. Indeed, the Director of the World Health Organization formally appointed an advisory council, the Leptospirosis Epidemiology Reference Group (LERG), to assess the global burden of leptospirosis. (www.who.int/zoonoses/diseases/lerg/en/index.html). The work of LERG has been preliminarily reported (1). An essential finding from the LERG reports is that systematic data to assess the global burden of disease are lacking. The lack of clinically responsive diagnostic tests combined with insufficient systematic study of affected human populations remains a major impediment to understanding the impact of leptospirosis on affected human populations at the clinical, public health and policy levels. This difficulty in diagnosis leads to a paucity of data so that leptospirosis is usually not recognized as a public health threat. Hence, public health approaches to prevent and ameliorate this disease through environmental remediation of hot spots of transmission or novel vaccine or other preventive interventions do not receive programmatic priority by governmental and private research funding organizations or by public health agencies. This story is typical of neglected tropical diseases. However, in the case of leptospirosis, which has the capability of causing explosive epidemics (and predictably and regularly does so around the world) of acute febrile illness, jaundice, renal failure, pulmonary hemorrhage, refractory shock and death, the stakes are too high not to develop new ways to identify, treat, and prevent this disease. The overall strategy of any global research effort to develop new, globally applicable leptospirosis diagnostic tools has to based on organizing epidemiology and clinical research groups in a diversity of leptospirosis-endemic setting. The current state of diagnostic testing for leptospirosis is poor and relies primarily on decades-old testing methods that are inexact, slow, and not useful at the point of care, hence leading to delayed or missed opportunities for timely clinical care and public health interventions. In the developing world, reference laboratories are generally based at government-supported entities; in the industrialized world, reference laboratories are far removed from the field setting where the burden of disease is highest. Leptospirosis has sporadic,(2,3,4) highly endemic(5, 6, 7, 8) and explosively epidemic patterns of disease,(9, 10, 11) which are related to how humans interact with the environment around them and the diversity of Leptospiradue to the presence of mammalian reservoir hosts such as rodents, dogs and livestock. Sporadic leptospirosis occurs dramatically in the context of intermittent activities in which people come into contact with Leptospira-contaminated environmental surface waters and wet soils, for example during the EcoChallenge Sabah in 2000(12) or other adventure traveler events such as triathlons.(13) Progress in addressing the global threat of leptospirosis rests on the premise that the development of new clinically timely diagnostics for acute leptospirosis is an essential tool for controlling this disease. Major efforts need to be Vinetz JM 1*