Leptospirosis: A commonly misdiagnosed disease
M3 India Newsdesk Jul 26, 2022
Leptospirosis, a zoonotic illness of bacterial origin, is caused by pathogenic strains of leptospira and is widespread across the globe. The prevalence of leptospirosis in India, its diagnosis and clinical management are penned down in this article.
Leptospirosis is a bacterial illness transmitted by water that is more frequent during monsoon. Leptospirosis is caused by the bacteria of the genus Leptospira, of which more than 250 pathogenic serotypes are recognised. Leptospira colonises the kidneys of infected mammals and is discharged into the environment via urine, where it may persist for weeks. Direct contact with infected animals, including rodents, wildlife, cattle, and pets, or contact with soil or water polluted by the urine of infected animals causes infection in humans. Infection risk variables are influenced by interactions among people, animals, and the environment.
The Indian disease picture
In India, leptospirosis outbreaks have increased during the previous three decades. The rate of positive for the illness is highest in the southern region of India at 25.6%, followed by 8.3%, 3.5%, 3.1%, and 3.3% in northern, western, eastern, and central India, respectively.
In addition, factors such as fast urbanisation, climate change, inadequate sanitation, and incorrect waste management have led to a rise in the number of leptospirosis outbreaks reported in recent years.
Why is it downplayed in India?
Even so, the disease wasn't talked about much in India. This was mostly because it was endemic, there weren't any diagnostic modules, doctors weren't aware of it, and there wasn't much written about how common it was and how it showed up in different ways.
Leptospirosis is an emerging infectious disease with a growing incidence, increasing frequency and severity of outbreaks, and altering climatic, sociodemographic, and environmental transmission factors worldwide. Recent outbreaks have been unusual because of the combined effects of climate change, floods, population increase, and urbanisation (typically associated with poverty and slums in developing countries).
- Variable clinical course is characteristic of leptospirosis. The vast majority of instances are mild and self-limiting or asymptomatic, although a few are severe and possibly fatal.
- Following an incubation period of two to twenty-six days, fever, rigours, myalgias, and headache often manifest in 75 to 100 per cent of patients. (average 10 days).
- Conjunctival suffusion, characterised by conjunctiva redness, is an important but frequently overlooked sign. This is not a common finding in other infectious diseases, and its presence in a patient with a nonspecific febrile illness should raise the possibility of leptospirosis. Subconjhaemorrhagesmorrhages also occur.
- In 25% to 35% of instances, nonproductive cough is seen.
- Approximately 50% of patients experience nausea, vomiting and diarrhoea.
- 7 to 40 per cent of patients exhibit muscular tenderness, splenomegaly, lymphadenopathy, pharyngitis, hepatomegaly, muscle stiffness, abnormal respiratory auscultation, or skin rash.
- Arthralgias, bone pain, sore throat, and stomach discomfort are uncommon symptoms.
Leptospirosis has been characterised as a biphasic disease.
- The first phase consists of a two-to-nine-day acute febrile bacteremic phase, followed by a period with little or no fever and apparent recovery.
- The second phase is an "immune" phase marked by a return of fever and the emergence of problems. Leptospires are missing from the blood during the immunological phase but may be present in the urine. Clinically, the two periods may overlap, especially in cases of severe illness.
If cerebrospinal fluid (CSF) is analysed seven days after the onset of sickness, 50 to 85% of individuals are found to have aseptic meningitis. In general, this observation has been ascribed to the immunological reaction of the host to the organism, as opposed to direct infection.
Leptospirosis may be worsened by jaundice and renal failure (sometimes known as "Weil's disease"), pulmonary bleeding, acute respiratory distress syndrome (ARDS), uveitis, optic neuritis, peripheral neuropathy, myocarditis, and rhabdomyolysis.
- Standard laboratory testing may not be very specific. White blood cell (WBC) levels are typically less than 10,000/microL but may vary from 3,000 to 26,000/microL; around two-thirds of patients exhibit a left shift. Thrombocytopenia is possible.
- Hyponatremia is typical in cases of severe leptospirosis. Leptospirosis can act directly on electrolyte transport pathways, causing sodium and potassium imbalances.
- Urinalysis often reveals proteinuria, pyuria, granular casts, and seldom microscopic hematuria.
- Approximately forty per cent of individuals had modest to moderate hepatic transaminase increases.
- The cerebrospinal fluid (CSF) may exhibit lymphocytic or neutrophilic pleocytosis with little to moderately increased protein concentrations and normal glucose content.
- Radiographs of the chest may reveal tiny nodular densities that proceed to confluent consolidation or a ground-glass look.
Features with unfavourable outcomes: Oliguria, a WBC count > 12,900/mm3, repolarisation abnormalities on the ECG, and alveolar infiltrates on chest radiography are related to unfavourable outcomes.
Misdiagnosis is common. The diagnostic methods for the detection of leptospirosis are as follows:
- Clinical strategy: In acute infections, clinical and laboratory data are often vague, therefore a high threshold of suspicion is necessary to establish a diagnosis based on epidemiologic exposure and clinical presentations. In the bacteremic phase of infection, nucleic acid detection is most sensitive, while antibodies become detectable by serologic techniques after one week. Consequently, a combined serologic/molecular diagnostics method is widely adopted for prompt identification of patients with suspected leptospirosis.
- Molecular tests: Leptospirosis has been diagnosed using molecular methods such as real-time polymerase chain reaction (PCR) and loop-mediated isothermal amplification.
- Serology: Most often, serologic tests are utilised to diagnose leptospirosis. Assays include the microagglutination test (MAT), the macroagglutination test, indirect hemagglutination, and the enzyme-linked immunosorbent assay (ELISA).
- Culture: Leptospirosis can be confirmed by culture of the organism from clinical specimens in appropriate media if antibiotic therapy has not been administered before samples are taken. Blood and CSF specimens are generally positive during the first 10 days of the illness.
- Antigen detection: A monoclonal anti-LipL32 antibody-based antigen capture ELISA has been developed for blood antigen detection.
1. General principles: In the absence of antibiotic treatment, the majority of cases of leptospirosis are self-limiting; nonetheless, some individuals develop sequelae with severe morbidity and death. In general, if the disease is severe enough to warrant clinical care and the diagnosis is made, antibiotic treatment should be offered to decrease the duration of the illness and limit the shedding of organisms in the urine.
Leptospirosis antibiotic treatment may cause a Jarisch Herxheimer reaction, which is an immediate inflammatory response to spirochete clearance from the blood and is clinically characterised by fever, rigours and hypotension.
2. Mild disease:
For outpatients with mild disease-
- Adults: 100 mg orally twice daily for 7 days
- Children: 2 mg/kg per day in two equally divided doses [not to exceed 200 mg daily] for 7 days)
- Adults: 500 mg orally once daily for three days;
- Children: 10 mg/kg orally on day 1 [maximum dose 500 mg/day] followed by 5 mg/kg/day orally once daily on subsequent days [maximum dose 250 mg/day]).
Rickettsial illness, which is sometimes mistaken for leptospirosis, is likewise susceptible to these drugs' actions.
3. For pregnant women:
- Azithromycin (500 mg orally once daily for three days) or amoxicillin (25 to 50 mg/kg in three equally divided doses [maximum 500 mg/dose] for seven days).
- Azithromycin is preferred over amoxicillin if the differential diagnosis includes rickettsial infection.
4. Severe disease:
For hospitalised adults with severe disease,
- Treatment with penicillin (1.5 million units intravenously [IV] every six hours),
- Doxycycline (100 mg IV twice daily),
- ceftriaxone (1 to 2 g IV once daily),
- Cefotaxime (1 g IV every six hours).
The duration of treatment for severe disease is usually seven days.
5. For hospitalised children with severe disease:
- Treatment with penicillin (250,000 to 400,000 units/kg IV per day in four to six divided doses [maximum dose 6 to 12 million units daily]),
- Doxycycline (4 mg/kg IV per day in two equally divided doses [maximum dose 200 mg/day]), Ceftriaxone (80 to 100 mg/kg IV once daily [maximum dose 2 g daily]), or
- Cefotaxime (100 to 150 mg/kg IV per day in three to four equally divided doses).
- For children who cannot tolerate the above agents, azithromycin is an acceptable alternative agent (10 mg/kg IV on day 1 [maximum dose 500 mg/day], followed by 5 mg/kg/day IV once daily on subsequent days [maximum dose 250 mg/day]).
The duration of treatment for severe disease is usually seven days.
6. Pregnant women with severe leptospirosis:
Treatment with penicillin, ceftriaxone, cefotaxime, or azithromycin. Doxycycline appears to be safer in pregnancy than other tetracyclines; it should be considered if the diagnosis of leptospirosis is not certain.
There have been many human vaccines created; each one is serovar-specific and made for a particular epidemiologic situation. None is readily accessible. Avoiding possible sources of infection, administering prophylaxis to persons at high risk of exposure, and vaccinating animals are all preventative strategies.
Avoiding probable sources of infection, such as stagnant water and animal farm water runoff, controlling rodents, and protecting food from animal contamination are the most significant management techniques for preventing human leptospirosis.
Chemoprophylaxis may be recommended for those who have a high risk of exposure to potentially contaminated sources (such as farmers, soldiers, rescue teams and those who are involved in adventurous sports). For prophylaxis, it is suggested that 200 mg of doxycycline be taken orally once a week for the duration of exposure.
The prognosis for leptospirosis is dependent on the disease's severity and related consequences. The prognosis for anicteric leptospirosis is typically favourable. The condition is virtually seldom deadly in the absence of jaundice; nonetheless, severe pulmonary haemorrhage and myocarditis have sometimes been documented in anicteric patients. The case fatality rate for Weil's illness ranges from 15 to 40% and is greater in individuals older than 60 years. 26 In one of our investigations including 33 patients with icteric leptospirosis, we found a death rate of 39.3% (13 individuals).
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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.
The author is a practising super specialist from New Delhi.
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