Emergence of human leptospirosis in Meghalaya, India: Clinical evidence from a hilly non-endemic region

Sir,

Leptospirosis is a zoonotic illness caused by the spirochete bacteria, Leptospira. It passes from infected animals to humans through contact with urine or with inoculated soil or water. The disease course often begins with a non-specific prodrome, which can progress to severe complications, such as Weil’s Syndrome, a triad of haemorrhage, jaundice, and acute kidney injury¹. Other syndromes caused by leptospirosis are aseptic meningitis¹, pulmonary hemorrhage², myocarditis³ and more¹. This range of manifestations makes it no surprise that general physicians may not initially suspect leptospirosis and delay initiation of the appropriate treatment⁴.

Although leptospirosis is classically associated with flooding and low-lying coastal environments^5,6, relatively less importance is given to mountainous and non-coastal areas. The dominant feature of Meghalaya State is the Garo-Khasi-Jaintia range (features elevations of 1,200-1,800 m), a low mountain formation nestled in between Assam State and Bangladesh that gives its name to the main tribes and distinct regions of the State. The objective of this study was to provide an overview of risk factors, clinical presentations and disease course in this population as well as estimate the economic burden borne by the affected patients. When diagnosed early, leptospirosis can be managed with oral antibiotics in an uncomplicated and economical manner adds premise to this study as an alert to the presence of leptospirosis in Meghalaya and as a guide to prospective diagnosis for clinicians working here.

Ten patients diagnosed with leptospirosis and tested by IgM ELISA (Bio-Rad Evolis system and the Inbios Leptospira ELISA kit) received treatment between January and December 2023 in a tertiary care, charitable sector hospital in Shillong, the capital city of Meghalaya in the Northeast region of India. The study was initiated after obtaining approval from the Institutional Ethics Committee, Indian Institute of Public Health Shillong. Data was collected retrospectively from patient records and included patient demographics, symptoms, investigatory findings, comorbidities, treatment, clinical outcomes, and expenditure. Using standard operational definitions for critical care⁷, cases with hemodynamic instability or requiring ventilation were classified as severe and compared to those with mild to moderate illness.

This study consisted of one female and nine male patients, with a mean age of 27.1 (SD 7.9) yr. Occupation varied widely across the group, including daily wage labourers, office workers, and a farmer. The case summaries are described in supplementary table.

This study showed a range of syndromic presentations, with one patient presented with only fever and vomiting, while another presented with decreased urine output and altered sensorium in addition to fever. Some patients had notable physical examination findings such as icterus, abdominal tenderness, and bilateral renal angle tenderness. However, the characteristic finding of leptospirosis, conjunctival suffusion, was seen in one case.

Thrombocytopenia and leukopenia with neutrophilic predominance were present in most patients. Biochemical tests were significant for raised creatinine levels in half the cases. Elevated transaminases and markedly increased bilirubin levels accompanied jaundice in two cases, both showing characteristics of conjugated hyperbilirubinemia.

According to the severity criteria, four patients were categorized as severely affected by leptospirosis wherein all four were on inotrope infusions and required mechanical ventilation. The youngest patient was admitted to ICU having, in addition to acute kidney injury and hepatic insufficiency, severe anaemia and thrombocytopenia. Whereas table provides a comparison of the clinical and economic factors. In terms of clinical presentation, the sickest patients all had gastrointestinal manifestations, particularly abdominal pain, which the more moderately affected patients did not have.

All the cases were presented to the hospital between August and December, the months adjacent to the monsoon. Possible exposure to Leptospira bacteria through contact with infected animal urine was specifically noted in only four cases, either through swimming in natural water bodies (1 case), by means of household rodent infestations (2 cases), or both (1 case). The diagnosis in all cases was clinical, and due to the lack of on-site testing capability, the confirmatory test was sent to a laboratory in Mumbai after the empirical initiation of appropriate antibiotics.

Median direct medical expenditure for the study duration was INR 28,110 (334 USD) [interquartile range (IQR) 7,180; 31,961], which included charges for laboratory tests, therapies, and mainly hospital stay, which averaged to 7.4 (SD: 3.7) days in duration. Half of the patients admitted to the hospital had some form of health insurance; however, on an average, only 60 per cent of the total amount was covered. Non-insured patients shouldered a median cost of nearly INR 7,460 (88 USD) (IQR: 3,550; 33,000).

Although Meghalaya is known for heavy rainfall, recent spatial analysis has shown that 99 per cent of the land area of the State is classified as low or very low susceptibility for flooding⁸. As stated previously, the main environmental risk factor associated with increased infections is flooding⁹. The floodwater is reportedly contaminated with microbiological organisms, becoming a source of infection and a vector transporting the microbes. On the basis of water saturation levels, pathogenic Leptospira can survive in soils and superficial river sediments at different depths and eventually be carried on to the surface water layer by erosion¹⁰. Elevation also plays an important role, as lower elevations tend to store rainwater, creating conditions favourable for Leptospira survival in freshwater¹¹. With elevations ranging from 4,000 to 6,000 ft (1,220 to 1,830 m), the State of Meghalaya is an upland region characterised by mountainous terrains with rolling grasslands. Recent studies also underscore the fact that an increase in soil moisture brought on by flooding improves Leptospira survival in polluted areas¹². Moist soil with neutral pH and other agroclimatic factors such as high rainfall and high-water table were found as major risk factors for leptospirosis^13,14. Meghalaya is primarily composed of three main types of soil i.e., red loamy soils, lateritic soils, and alluvial soils, which have slightly acidic pH values¹⁵. Given the minimal prevalence of this main environmental risk factor, if leptospirosis is found in this State, it raises the question of previously unknown environmental factors that may predispose to the spread of the disease.

Previous studies have found high seropositivity in animals^16,14 while human cases still remain underreported. Clinical under-recognition or misdiagnosis could be a key factor, as leptospirosis is frequently mistaken due to its non-specific symptoms for other causes of acute-febrile illnesses. In this study, the triad of jaundice, haemorrhage, and acute kidney injury that characterizes Weil’s Syndrome was apparent in at least two of the cases. Therefore, among the study participants, one fifth had features were suggestive of Weil’s Syndrome, whereas published literature shows that this classical 'icteric’ form was known to be found in only 5-10 per cent of leptospirosis cases¹⁷. The study was based on a tertiary hospital, which potentially skewed cases to those with more severe presentation.

This study intended to understand the risk factors, clinical picture and burden of leptospirosis on the affected patients, given the novelty of the disease in this region. Disease burden from a physiological point of view has been discussed; however, the economic burden of the disease also bears impact on the topic being discussed. Given that the National Pharmaceutical Pricing Authority sets the ceiling price for one capsule of 100 mg doxycycline at INR 3.08 (4¢ USD)¹⁸, the total cost of a course of treatment would be just over INR 40 (50¢ USD). Including consultation fees and the price of laboratory tests, the case in this series with the mildest illness only had a direct cost of INR760 (9 USD). Whereas cases needing admission had an average direct expenditure of nearly INR20,000 (240 USD), which excludes the indirect costs, such as for travel, accommodation, etc., considering the fact that many of these patients came referred from outside Shillong city for tertiary care. There is strong evidence that early initiation of antibiotics may prevent the development of major organ system failure, decreasing the severity and, consequently, economic impact of the disease¹.

This study was constrained by the limited number of patients. Additional multicentric studies with a larger sample size are required to improve the generalisability of findings related to severity. Our study setting was a charitable hospital that aims to provide low-cost but high-quality care, further pointing out the challenges of having advanced diagnostic access in resource-limited settings. In this study, patients who presented with an acute febrile illness were subjected to a panel of diagnostic tests for common causes of acute fevers in the region. The patients included in the study were IgM ELISA positive for leptospirosis. PCR and MAT facilities were not available, as this was the first time that leptospirosis was being encountered in the State.

To our knowledge, this study for the first time confirmed the biological presence of Leptospira spp., although there have been no reports of human leptospirosis cases in Meghalaya, possibly due to a low index of suspicion among clinicians in hilly regions, which are historically thought to be non-conducive to leptospiral transmission. The diverse symptomatology observed among just these ten cases, highlights the complexity of diagnosing this potentially fatal infection and the need for inexpensive and rapid diagnostic facilities.

As the climate changes and increasingly frequent flooding besets the urbanized spaces in developing countries, recent studies report on the changing epidemiology of leptospirosis and its growing threat as a global public health concern. However, in the hills of Meghalaya, where floods are rare, there remain undiscovered and uncontrolled risk factors to this emerging zoonosis. This study, in a State without previously reported leptospirosis comes as an alert, seeking to trigger further research into prevalence and risk factors that are specific to hill geographies and raise the index of clinical suspicion among medical practitioners in the region.