Global research is focussing on understanding the genetic determinants of the pathogen. There are lessons for India

In the summer and rainy seasons of 2015, leptospirosis, a dangerous, neglected tropical disease, struck in multiple cities of India. In Mumbai, the toll was high — at least 18 people reportedly succumbed to the zoonotic disease, also known colloquially as “rat fever” for its association with the urine of rodents among several host species.

Given its position as one of the most congested hubs of urban activity along India’s 8,129-km-long coastline, Mumbai was always particularly vulnerable to the outbreaks of such a disease. Typically, Leptospira interrogans spreads under conditions of stagnant water, flood water, humidity, and proximity between man and beast.

The outbreak that year escalated to the point where the Brihanmumbai Municipal Corporation had to lodge 171 FIRs against owners of goshalas, or cattle shelters, who had until then not complied with the health department’s guidelines to avoid discharging cow dung or cattle urine into a common drainage outlet, and to give the cattle two oxytetracycline injections in a span of 10 days to protect against four Leptospira strains.

In 2016 leptospirosis cases were reported even before the onset of the monsoon. In the Udipi area of Karnataka four people died and even more were infected. With 2017 facing the prospect of erratic monsoons and no major improvements nationwide in waste-water and flood-water management, what will the leptospirosis toll be?

Understanding genomes

It is precisely to improve the odds of controlling this disease by understanding the genetic determinants of Leptospira pathogenesis that researchers at the Yale School of Public Health (YSPH) and the J. Craig Venter Institute have collaborated in a major genome-sequencing effort for 20 Leptospira species.

One accomplishment of the effort is the development of a pangenomic signalling (Two Component System) database by Haritha Adhikarla, associate research scientist in epidemiology at YSPH. This has enabled researchers to explore the molecular mechanisms and regulatory pathways underlying Leptospira virulence, she explains, adding that the results, which were published in the journal PLOS Neglected Tropical Diseases (2016), revealed novel adaptations and traits in infectious species of Leptospira and opened new avenues for preventive and treatment approaches.

Similarly, a YSPH study using high-density proteome arrays in the characterisation of antibody signatures against several infectious agents of human and veterinary importance identified the first comprehensive profile of the human antibody response against L. interrogans serovar Copenhageni proteins, the serovar associated with more than 90% of the urban leptospirosis cases in Salvador, Brazil. In turn, this translational study has led to the identification of promising candidates for the development of therapeutic diagnostic tests and sub-unit vaccines.

 The ‘One Health’ approach

At the heart of these efforts is the focus on a “One Health” approach, which integrates efforts to predict and control a disease at the human-animal-ecosystem interface, and this collaborative approach appears to be the key to defeating re-emerging zoonotic diseases such as leptospirosis.

Dr. Adhikarla notes that there is enough scientific evidence internationally to state that the infection of humans and animals and environmental pathogen loads were lower in villages that used environmental interventions based on the One Health approach than in villages that used the usual disease control measures.

In terms of approach specifics, there is a recognition that leptospirosis is a complex disease with multifactorial transmission, and so efforts should focus on identifying transmission sources, stratify disease risk and prioritise prevention in the resource-poor settings of Indian slums, Dr. Adhikarla says, pointing out that changes in climatic conditions and population drift from rural to semi-urban and urban areas of India are also contributing to the increase in the magnitude and severity of leptospirosis outbreaks.

PHC conundrum

Research at Yale also highlights the fact that across Primary Health Centres in India, rapid diagnostic tests often replace serological tests due to lack of adequate trained personnel. These rapid tests may not reach the optimal sensitivity until at least a week after onset of fever, and as the sensitivity of the tests is low during the acute visit, these rapid diagnostic tests should be used with caution to rule out leptospirosis.

Otherwise, the frequently observed underreporting and the misdiagnosis of leptospirosis may lead to an inaccurate determination of the real impact of the disease in the Indian subcontinent.

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