Leptospirosis in India: a forgotten tropical disease

14 Jul 2021

Leptospirosis, essentially a zoonotic disease that is bacterial in origin, is caused by pathogenic strains of Leptospira and is prevalent worldwide.

However, the problem of the disease has not been wholly addressed globally by governments and health agencies, even though it has been recognised for decades.

The primary reason being that the significant burden of the disease is in poor, developing countries, especially within economically vulnerable populations such as urban slums and rural subsistence farmers.

The global picture

The disease’s primary reservoir host mainly includes infected animals such as rodents, dogs, cattle and pigs. Humans become the accidental hosts through direct or indirect contact with water or soil contaminated by the urine of infected animals.

As a result, people involved in agricultural and livestock farming, who work in underground sewers, meat handlers and veterinarians are at higher risk of getting the disease. Children usually acquire the disease from infected dogs. Thus, contaminated environments, lack of sanitation, stagnant water and rainfall are a few of the crucial epidemiological risk factors responsible for the occurrence of the disease in humans.

In many cases, leptospirosis presents with several non-specific features, including headache, fever and myalgia. However, the spectrum of the disease ranges from a mild icteric form which presents mainly with non-specific symptoms, to a severe icteric form which is potentially fatal and presents with jaundice, renal dysfunction bleeding diathesis and pulmonary manifestations like cough, breathlessness and hemoptysis.

Paucity of evidence

Although the disease can have a high fatality rate and is recognised as the most widespread zoonotic disease, the worldwide burden of morbidity and mortality related to leptospirosis is unknown, meaning that leptospirosis is removed from the public health priority list.

As a result, little is known about the true incidence of leptospirosis. However, it is estimated that 10 or more per 100,000 people are affected by this disease each year in tropical climates.

Owing to this paucity of evidence, the World Health Organization (WHO) recently established the Leptospirosis Burden Epidemiology Reference Group (LERG) to develop accurate estimates of leptospirosis disease burden and inform the identification of modifiable risk factors and preventive interventions.

Disease scenario in India

Outbreaks of leptospirosis have been increasing in India for the past three decades. The positivity rate for the disease is notable in the southern part of India at 25.6%, followed by 8.3%, 3.5%, 3.1%, and 3.3% in northern, western, eastern and central India, respectively.

Moreover, factors like rapid urbanisation, climate change, poor sanitation and improper waste management have resulted in increased reporting of leptospirosis outbreaks in the past few years.

Despite this, the disease remained highly under-reported in India, primarily due to its endemic nature, lack of diagnostic modules, lack of awareness among the treating clinicians, and paucity of literature available on the burden and varied clinical manifestations of this disease in India.

Why is the disease belittled in India?

Acknowledging this information gap, the government of India launched the National Programme for Prevention and Control of Leptospirosis (NPPCL) in 2015 in the endemic states of India (Gujarat, Kerala, Tamil Nadu, Maharashtra, Karnataka and Andaman & Nicobar Islands), intending to reduce the morbidity and mortality associated with leptospirosis.

Several preventive, management and control measures such as limiting exposure to stagnant water, contamination-free drinking water, chemoprophylaxis for high-risk groups, and awareness activities were being implemented through this programme.

However, despite the effort, the country still experiences several outbreaks of leptospirosis across various states. Therefore, in 2019 the Indian Council of Medical Research (ICMR) Expert Committee on leptospirosis reviewed the existing evidence on leptospirosis present in the country in order to prioritise the gaps currently present with respect to the disease.

Misdiagnosis is common

Firstly, leptospirosis mimics other common infectious diseases prevalent in the region because of its protean clinical manifestations, such as dengue, malaria, hepatitis, or other bacterial or viral diseases. Thus often resulting in misdiagnosis, which contributes to a never-ending cycle of underdiagnosis, under-reporting, lack of awareness and neglect.

Secondly, the currently used standard laboratory investigations used, such as polymerase chain reaction (PCR) and multiplex loop-mediated isothermal amplification (m-LAMP used for detecting leptospirosis infections are time-consuming and show poor sensitivity in detecting the disease in the early stages.

However, the traditional serological tests like Immunoglobulin-M(IgM)-based enzyme-linked immunosorbent assay (IgM ELISA) and the microscopic agglutination test (MAT) are used routinely diagnosing leptospirosis; these tests, though they give optimal results, are usually expensive.

Thirdly, there “isn’t much evidence available on individual-level or community-level interventions, community awareness, or the health system’s readiness in terms of outbreak management and availability of essential medicine or diagnostic."

And finally, no human vaccine is available to protect against leptospirosis.

Currently, the vaccine available for animals is an inactive vaccine that is effective against the serovars included in the particular vaccine; further, these vaccines may not prevent infection or develop a carrier state in animals. Thus, vaccinating the animals “doesn’t guarantee defence against disease outbreaks”.

The way forward

With the advancement of technology, newer and more efficient leptospirosis diagnosis methods can aid in the management of disease more effectively.

Recently, biosensors – specifically DNA sensors – have gained importance in disease diagnosis and pathogen detection due to their high sensitivity and specificity. In addition, these sensors only take 30 minutes to detect the pathogen.

Similarly, several new spirocidal agents such as cephalosporins, penicillin compounds, along with certain natural compounds (leaves of Andrographis paniculata Nees; Leaves of Canarium odontophyllum; extract of whole plants of Eclipta alba and Phyllanthus amarus) can be used as a replacement of the existing antibiotics in case of toxicity as these compounds offer better efficacy, least resistance and less toxicity.

Hence, these few recent advances will undoubtedly assist in the easy and efficient diagnosis of leptospirosis and thus will play a significant role in managing the disease in the coming years.

References

1. Torgerson PR, Hagan JE, Costa F, Calcagno J, Kane M, Martinez-Silveira MS, Goris MG, Stein C, Ko AI, Abela-Ridder B. Global burden of leptospirosis: estimated in terms of disability adjusted life years. PLoS Negl Trop Dis. 2015 Oct 2;9(10):e0004122.

2. Moola S, Beri D, Salam A, Jagnoor J, Teja A, Bhaumik S. Leptospirosis prevalence and risk factors in India: Evidence gap maps. Tropical Doctor. 2021 Apr 9:00494755211005203.

3. Holla R, Darshan B, Pandey L, Unnikrishnan B, Kumar N, Thapar R, Mithra P, Kulkarni V. Leptospirosis in Coastal South India: a facility based study. BioMed research international. 2018 Jan 1;2018.

4. Izurieta R, Galwankar S, Clem A. Leptospirosis: The “mysterious” mimic. Journal of emergencies, trauma and Shock. 2008 Jan;1(1):21.

5. Jain L, Kumar V. Leptospirosis a neglected re-emerging zoonoses in India: An overview. Journal of Animal Research. 2020 Dec 1;10(6):853-8.

6. Verma V, Kala D, Gupta S, Kumar H, Kaushal A, Kuča K, Cruz-Martins N, Kumar D. Leptospira interrogans Outer Membrane Protein-Based Nanohybrid Sensor for the Diagnosis of Leptospirosis. Sensors. 2021 Jan;21(7):2552.

7. Gopi C, Sri CS, Krupamai G, Magesh AR, Dhanaraju MD. Recent Progress in the Treatment of Leptospirosis. SN Comprehensive Clinical Medicine. 2021 Feb 27:1-8.

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