Clinical Guides
Kala-azar (Visceral Leishmaniasis)
A clinically focused Indian clinical guide to timely kala-azar diagnosis, safe antileishmanial treatment, relapse detection, HIV co-infection care, and surveillance after elimination targets are reached.
MedNext Academy | 15 min read
Kala-azar (Visceral Leishmaniasis)
A clinically focused Indian clinical guide to timely kala-azar diagnosis, safe antileishmanial treatment, relapse detection, HIV co-infection care, and surveillance after elimination targets are reached.
Summary
Kala-azar, or visceral leishmaniasis (VL), is a systemic protozoal infection caused in the Indian subcontinent by Leishmania donovani and transmitted by infected female phlebotomine sandflies. Parasites multiply in macrophages of the reticuloendothelial system. The characteristic syndrome is prolonged fever, progressive splenomegaly, weight loss, weakness and cytopenias in a person with relevant residence or travel. Untreated disease can be fatal, but the early presentation is nonspecific and malaria, tuberculosis, enteric fever, haematological malignancy and other infections remain common competitors.
Diagnosis is clinical plus laboratory, not serology in isolation. In the Indian elimination programme, an rK39 rapid diagnostic test supports a compatible first episode in the correct epidemiological setting. Antibodies can remain detectable for years, so rK39 cannot diagnose relapse or demonstrate cure. Relapse requires parasitological confirmation. Tissue aspiration can confirm infection but has variable sensitivity and procedural risk; splenic aspiration is particularly hazardous outside an experienced, properly equipped service. HIV testing is part of safe care because co-infection changes presentation, regimen, relapse risk and follow-up.
Treatment is geographical, immune-status and programme dependent. India's 2015 operational guideline established single-dose liposomal amphotericin B as first-line programme treatment for uncomplicated primary VL where medicine, cold chain, infusion capacity and trained monitoring are available. Current WHO 2026 guidance updates relapse and post-kala-azar dermal leishmaniasis (PKDL) recommendations for South-East Asia but does not replace the Indian primary-VL programme with an eastern-African regimen. This quarantined draft has been reviewed by the MedNext Clinical Team and does not provide an individual infusion or oral prescription.
How Common Is It?
India has achieved a major fall in kala-azar incidence, but reaching an elimination threshold is not eradication. The programme definition is annual incidence below one case per 10,000 population at block level. A block can meet that target while still detecting cases, and imported or locally imported infection can be diagnosed elsewhere. The 2021 operational definitions distinguish the place of reporting from the place where infection was probably acquired. Therefore current residence, recent and remote travel, seasonal work and care-seeking routes matter when interpreting surveillance data.
Historically, Indian transmission has been concentrated in Bihar, Jharkhand, West Bengal and eastern Uttar Pradesh, with Bihar bearing much of the programme burden. Those distributions are not a permanent diagnostic boundary. Migration, previously silent foci, improved case search and changing vector ecology can produce a confirmed patient in a district with no recent notification. Conversely, fever in a historically endemic village is not automatically VL. Block-level incidence and case-origin investigation are more informative than a state-wide label.
Reported cases underestimate infection because symptoms may be delayed, private diagnoses may not enter the programme promptly and people with poverty or migration barriers may present late. They can also overstate local transmission if the reporting address is mistaken for the place of infection. Serosurveys measure exposure rather than active clinical disease and cannot be added to case counts. Programme status must separate new primary VL, relapse, treatment failure, VL-HIV co-infection, PKDL, imported infection, locally imported infection and locally acquired disease. Monitoring should include diagnostic delay, treatment completion, initial assessment, final assessment at six months, death, relapse, PKDL detection and vector response. A single annual national total cannot describe these clinically different states.
Risk Factors
Risk of infection depends on exposure to Phlebotomus argentipes in an active anthroponotic transmission focus. Residence or overnight stays in endemic rural or peri-rural settings, houses with favourable resting surfaces, proximity to untreated human infection or PKDL, poverty, crowding and limited vector-control coverage can increase exposure. Seasonal migrants may acquire infection in one block and become symptomatic after returning home. Because incubation and recognition can be prolonged, history should cover earlier residences and work rather than only the previous fortnight. Bed nets and indoor residual spraying reduce vector contact but neither proves nor excludes an individual's infection.
Progression from infection to visceral disease is influenced by malnutrition, young or older age, immunosuppression and important co-morbidity. HIV is the clearest risk for atypical presentation, high parasite burden, treatment failure and repeated relapse. Tuberculosis can coexist and may be masked by overlapping fever, weight loss and cytopenias. Corticosteroids, transplantation, malignancy or other immunosuppressive therapy require specialist interpretation. Pregnancy and organ dysfunction alter treatment safety rather than causing infection.
Relapse risk is not the same as acquisition risk. Prior VL, incomplete or interrupted therapy, immunosuppression, inadequate drug exposure and failure to attend follow-up increase concern when symptoms recur. WHO's 2026 guideline notes a measurable relapse burden among apparently immunocompetent South-East Asian cohorts and supports parasitologically confirmed relapse pathways. PKDL may follow treated VL or occur without a recalled visceral episode; its lesions can maintain human-to-sandfly transmission. Drug access introduces further risk: liposomal amphotericin B requires verified product, storage, reconstitution, infusion and observation capacity; miltefosine requires adherence, reproductive precautions and ocular safety monitoring. These system conditions should be documented rather than misclassified as patient behaviour.
Diagnosis
History
Ask about fever duration and pattern, appetite, weight, weakness, abdominal fullness, bleeding, infection symptoms and previous antimalarial or antibiotic response. Record current and former village, block, district, migration and nights spent in endemic areas. Seek any previous VL, treatment drug and dates, completion, six-month outcome, PKDL rash and household cases. Ask about HIV status and testing, tuberculosis exposure, immunosuppressants, pregnancy possibility and co-morbidity. Recurrence after initial cure is not diagnosed by repeating rK39.
Examination
Assess airway, circulation, mental state, temperature, hydration and bleeding. Look for pallor, wasting, oedema, jaundice, petechiae and infection. Measure spleen and liver consistently; splenomegaly may be massive, but absence in advanced HIV or an early presentation does not absolutely exclude VL. Check nodes, skin and mucosa, including symmetrical hypopigmented, erythematous, papular or nodular lesions that could be PKDL. Evaluate focal signs suggesting malaria, tuberculosis, enteric infection, endocarditis or malignancy.
Investigations
Obtain CBC with differential and platelets, liver and renal function, glucose, electrolytes and tests guided by severity. Pancytopenia, hypergammaglobulinaemia and low albumin can support the syndrome but are nonspecific. In a compatible first episode from an endemic setting, a quality-assured rK39 RDT supports programme diagnosis; a positive result without the clinical case definition may be past antibody or false positivity. A negative result is less reliable in HIV and does not end a high-suspicion work-up. Demonstrating amastigotes in tissue confirms disease. Bone-marrow aspiration is safer but less sensitive than splenic aspiration; the latter belongs only in a trained referral centre with bleeding-risk screening and rescue capacity. PCR may help selected difficult cases but availability and standardisation vary. Relapse requires parasitological confirmation because rK39 persists. Test every diagnosed patient for HIV with consent under the national algorithm and investigate tuberculosis or other opportunistic disease where indicated.
Differential Diagnosis
The differential for prolonged fever with splenomegaly in India is broad. Malaria, especially partially treated or chronic infection, enteric fever, tuberculosis, brucellosis, viral infections, bacterial endocarditis and disseminated fungal disease can resemble VL. Scrub typhus and other rickettsial disease may be relevant by geography and acute severity. Haematological causes include lymphoma, leukaemia, myelofibrosis, haemolytic anaemia and haemophagocytic lymphohistiocytosis. Portal hypertension and chronic liver disease can enlarge the spleen without the same febrile syndrome. More than one diagnosis may coexist, particularly tuberculosis or opportunistic infection in a person with HIV.
A positive rK39 does not close this differential. Antibodies persist after cure, and false positivity is more likely when the clinical definition is ignored. Previous VL with recurrent fever could represent parasitologically confirmed relapse, reinfection that cannot routinely be distinguished programmatically, tuberculosis, malaria or another illness. Persistent symptoms immediately after treatment may represent treatment failure, infusion complication or an unrelated diagnosis. Bone marrow morphology and cultures may disclose malignancy or infection but sampling error remains possible.
PKDL must be distinguished from leprosy, vitiligo, pityriasis versicolor, post-inflammatory hypopigmentation, sarcoidosis, lupus and other dermatoses. Preserved sensation over typical PKDL lesions helps but does not replace confirmation; macular lesions can be rK39-negative. The 2021 programme definition requires a compatible pattern and parasitological confirmation by PCR, slit-skin smear or biopsy for a confirmed case. Isolated hepatomegaly, focal nodes or absence of splenic enlargement should widen the differential rather than trigger automatic exclusion. When epidemiology, examination and tests disagree, revisit exposure and sampling, involve an infectious-disease or haematology service and avoid empiric toxic antileishmanial therapy without a defensible plan.
Management
Stabilise severe illness first. Treat shock, hypoglycaemia, bleeding, severe anaemia, bacterial sepsis and organ dysfunction while arranging definitive VL care. Confirm the episode category: primary immunocompetent VL, treatment failure, parasitologically confirmed relapse, VL-HIV co-infection, pregnancy, severe co-morbidity or PKDL. Each has a different evidence pathway. Record baseline weight, spleen size, temperature, blood counts, renal and hepatic indices, electrolytes, HIV status, pregnancy status where relevant, previous drug exposure and the probable place of infection. Notify and link the case through the state programme.
For uncomplicated primary VL in the Indian elimination programme, single-dose liposomal amphotericin B remains the preferred national regimen when quality-assured medicine, cold chain, infusion preparation, trained staff and observation are assured. Alternative combination or multidose regimens are specialist and programme decisions when first-line delivery is unsuitable or unavailable. Do not substitute the 2026 eastern-African primary-VL recommendations; parasite epidemiology and evidence setting differ. Provide nutrition, hydration and treatment of confirmed co-infection, but avoid routine transfusion or antibiotics without indication.
Assess initial clinical response and document programme outcome. Fever resolution, appetite or weight recovery and spleen regression support initial cure, but final cure requires remaining symptom-free at the six-month assessment under the operational definitions. Recurrent symptoms after initial cure need parasitological confirmation. WHO 2026 provides current South-East Asian options for confirmed relapse in HIV-negative patients; use them through an experienced centre and current national policy. VL-HIV care requires the separate 2022 WHO guidance, antiretroviral coordination and longer relapse surveillance. Examine for PKDL during and after follow-up, counsel that skin disease is treatable and relevant to transmission, and arrange confirmatory dermatology or programme assessment rather than stigma or isolation.
Prescribing Information
Liposomal amphotericin B is not interchangeable with amphotericin B deoxycholate. Verify formulation, batch, storage history and reconstitution instructions before prescribing. Baseline assessment should include renal function, potassium, magnesium, liver profile, CBC, pregnancy status and infusion risk. Monitor observations during and after infusion and have a plan for fever, rigors, hypotension, bronchospasm or anaphylaxis. Even the less nephrotoxic liposomal formulation can affect renal function and electrolytes. The Indian 2015 programme uses a single total 10 mg/kg infusion for eligible uncomplicated primary VL, but the bedside order must come from the current programme protocol and product label.
Miltefosine is oral but not simple. It is teratogenic, has prolonged elimination and requires strict pregnancy avoidance according to the current regimen and label. The 2026 WHO guideline adds weight-band allometric dosing and ocular adverse-event precautions. Ask about baseline eye symptoms, explain prompt reporting of pain, photophobia or visual change, and ensure access to examination if symptoms occur. Gastrointestinal toxicity can reduce adherence and exposure. Do not copy older 28-day or 12-week schedules into relapse or PKDL care without checking the updated indication-specific recommendation.
Paromomycin can cause injection-site toxicity, ototoxicity and renal effects and should be used only in a validated combination or programme regimen. Amphotericin B deoxycholate requires repeated infusions and more intensive renal, electrolyte and infusion monitoring. Antimonial regimens have region-specific resistance and cardiac, hepatic and pancreatic toxicity; they are not default Indian primary care. Treatment of VL-HIV, relapse, PKDL, pregnancy, severe malnutrition, kidney disease and treatment failure belongs to a referral service. Drug stock, brand substitution and cold-chain failure can invalidate an otherwise correct plan. This guide deliberately does not calculate a patient dose or contraception interval; confirm the current national circular, WHO indication, CDSCO label and institutional protocol at the time of care.
When to Refer
Urgently refer a suspected VL patient with haemodynamic instability, severe anaemia or bleeding, jaundice, renal dysfunction, altered consciousness, bacterial sepsis, respiratory compromise, pregnancy complication or inability to maintain hydration. Children, older adults and people with severe malnutrition can deteriorate quickly. Arrange transfer to a centre that can both confirm the diagnosis and deliver monitored antileishmanial treatment; an rK39 result without infusion capacity is not completion of care. Communicate previous drugs, allergies, organ function and likely place of infection.
Specialist referral is mandatory for previous VL with recurrent symptoms, suspected treatment failure, HIV infection or unknown HIV status with atypical disease, tuberculosis co-infection, organ transplantation, immunosuppressive therapy, pregnancy, renal or hepatic impairment and suspected PKDL. Relapse needs tissue or validated parasitological confirmation, not a repeat antibody test. Splenic aspiration should be undertaken only by an experienced team with appropriate patient selection, laboratory support and emergency capability. Dermatology or a designated kala-azar service should evaluate possible PKDL, especially macular disease with negative rK39 or leprosy in the differential.
Refer when fever persists despite a correctly delivered regimen, spleen size fails to regress, cytopenias worsen, a new focal infection appears or initial cure is followed by recurrent illness. A person who cannot return for outcome assessment needs proactive programme tracing rather than being silently labelled default. Include block, village, travel and migration information so surveillance can determine likely place of infection and investigate a possible new focus or outbreak. After tertiary care, the discharge plan should name the six-month assessment, HIV and TB follow-up, PKDL warning signs, responsible facility and transport route. Referral quality is measured by completed linkage and outcome, not by issuing a paper slip.
Red Flags
Shock, confusion, severe weakness, active bleeding, rapidly worsening pallor, dyspnoea, oliguria, jaundice, persistent vomiting or hypoglycaemia indicate complicated illness and require hospital care. Profound thrombocytopenia can make invasive sampling dangerous. A spleen that is massively enlarged is vulnerable to trauma; acute abdominal pain, shoulder-tip pain or collapse raises splenic rupture and demands emergency assessment. Do not perform splenic aspiration in a routine clinic or when trained personnel and rescue resources are absent.
During amphotericin infusion, hypotension, bronchospasm, chest pain, severe rigors, rash or altered consciousness requires immediate treatment and reassessment. Rising creatinine, falling potassium or magnesium, arrhythmia or worsening anaemia can signal drug toxicity. New eye pain, photophobia, reduced vision or other ocular symptoms during miltefosine requires prompt interruption decisions by the treating service and ophthalmic assessment under current guidance. Pregnancy during or soon after a miltefosine course is a high-stakes exposure requiring specialist counselling, not blame.
Recurrent fever or splenomegaly after apparent cure may be relapse and must not be diagnosed with rK39. It may also be malaria, tuberculosis, sepsis or malignancy. HIV co-infection increases relapse and mortality risk; missing HIV testing is a safety failure. New hypopigmented, erythematous, papular or nodular skin lesions after VL can be PKDL and warrant confirmation. Severe malnutrition, inability to swallow oral therapy, missed infusions, drug stock interruption or loss to follow-up are treatment threats requiring programme escalation. In a supposedly non-endemic area, one locally acquired confirmed case can be epidemiologically important; ensure notification and place-of-infection assessment rather than assuming clerical error.
Indian Clinical Context
The kala-azar programme is built around early diagnosis and complete treatment, case and PKDL surveillance, vector control, outbreak response and verification at block level. Elimination as a public-health problem is defined as fewer than one annual case per 10,000 population at block level. That threshold should never be marketed as zero transmission. The 2021 definitions require outcome assessment after treatment and again at six months, and they distinguish relapse, treatment failure, default, loss to follow-up, imported, locally imported and locally infected cases. These categories determine both care and public-health response.
Programme geography is dynamic. The 2015 guideline described 54 endemic districts across Bihar, Jharkhand, West Bengal and Uttar Pradesh, but that historical count is not a 2026 prevalence statement. Current case-origin investigation must account for travel and migration. A case reported at a tertiary hospital may belong epidemiologically to another block, while the reporting block still owns timely notification and care. Case search should include PKDL because people with skin-only disease can act as a parasite reservoir and may not seek care. Leprosy programmes and dermatology services are important partners.
Access determines whether a theoretical regimen is executable. Liposomal amphotericin B depends on reliable procurement, cold chain, sterile reconstitution, infusion observation and management of adverse reactions. rK39 stock, tissue diagnostics, HIV testing, TB services and pharmacovigilance may sit at different facilities. A plan must name the actual referral centre and available drug rather than assume universal supply. WHO's July 2026 guidance is newer for immunocompetent relapse and PKDL, while primary uncomplicated Indian VL still requires current national-programme confirmation; the guideline itself directs countries to adapt and update national policy. Evidence remains limited for repeated relapse, pregnancy, severe organ disease, children at weight extremes, HIV co-infection and delivery in under-resourced settings. These limitations should be visible in counselling and audit.
NMC Competency Mapping
Kala-azar connects microbiology, pathology, community medicine, internal medicine, paediatrics, dermatology and pharmacology. The Indian medical graduate should explain the Leishmania life cycle, sandfly transmission, amastigotes in human macrophages and promastigotes in the vector. They should relate reticuloendothelial infection to fever, splenomegaly, cytopenias and wasting, and understand why PKDL matters to anthroponotic transmission. Community-medicine learning includes case definitions, block-level elimination thresholds, notification, active and passive case search, place-of-infection classification, indoor residual spraying and outcome surveillance. Exact competency numbering must be verified against the 2024 NMC curriculum before formal publication.
Clinical competence includes a geographic and migration history, systematic fever assessment, safe spleen and skin examination, interpretation of CBC and organ function, and rational use of rK39. A learner must state that rK39 supports a compatible primary episode but cannot establish relapse or cure. They should recognise when parasitological confirmation is needed, why splenic aspiration is restricted, and when HIV and tuberculosis testing alter management. Counselling should explain six-month follow-up and PKDL without stigma.
Prescribing competence is bounded. Memorising a liposomal amphotericin dose does not authorise unsupervised reconstitution, infusion, electrolyte management or substitution with deoxycholate. Students should compare formulation toxicity, recognise miltefosine reproductive and ocular hazards and identify specialist groups: relapse, HIV, pregnancy, organ failure and PKDL. A useful assessment case asks the learner to distinguish new VL from relapse in an rK39-positive patient, stabilise red flags, choose confirmatory testing and notify the programme. High-quality answers make the regimen conditional on episode type, current Indian policy, drug availability and monitoring capacity rather than offering a context-free drug list.
Key Exam Pearls for NEET PG
Indian kala-azar is caused by Leishmania donovani and transmitted by the female Phlebotomus argentipes sandfly. Humans harbour intracellular amastigotes, classically called Leishman-Donovan bodies, within macrophages; the sandfly carries promastigotes. The usual syndrome combines prolonged irregular fever, massive splenomegaly, weight loss, hyperpigmentation in some patients and pancytopenia. Hypergammaglobulinaemia with hypoalbuminaemia may occur. Splenic aspirate has high sensitivity but greater haemorrhagic risk; bone marrow is safer but less sensitive.
rK39 detects antibody and is useful for a compatible first episode in an endemic setting. It can stay positive for months or years after successful treatment, so it cannot diagnose relapse or confirm cure. Parasitological confirmation is essential for relapse. HIV can reduce serological sensitivity and produces atypical disease, treatment failure and repeated relapse. PKDL presents with symmetrical macular, papular, plaque or nodular lesions, usually with preserved sensation; it may follow VL or occur without a known visceral episode and can sustain transmission. Differentiate it from leprosy.
The Indian programme's classic first-line regimen for uncomplicated primary VL is single-dose liposomal amphotericin B, not amphotericin B deoxycholate. Formulations are not interchangeable. Miltefosine is oral but teratogenic, adherence-dependent and now carries explicit ocular-safety precautions. WHO 2026 updates South-East Asian relapse and PKDL regimens, not the eastern-African primary-VL schedule for India. Initial clinical cure is followed by final outcome assessment at six months. The elimination target is fewer than one case per 10,000 population annually at block level; it does not mean zero cases, zero reservoirs or permission to stop surveillance.
Frequently Asked Questions
Can a positive rK39 test prove kala-azar relapse?
No. Antileishmanial antibodies can remain detectable long after successful treatment, so rK39 cannot distinguish relapse, reinfection or past exposure. Recurrent compatible symptoms after initial cure require parasitological confirmation in an experienced service while malaria, tuberculosis, bacterial infection, malignancy and other causes are assessed.
Does meeting the kala-azar elimination target mean transmission has ended?
No. The programme target is annual incidence below one case per 10,000 population at block level. Cases, imported infections, relapse and PKDL can still occur. Continued case detection, place-of-infection investigation, treatment outcome follow-up, vector action and surveillance are necessary after the threshold is reached.
Why must liposomal amphotericin B not be substituted with ordinary amphotericin B?
They are different formulations with different dosing, infusion schedules and toxicity. Amphotericin B deoxycholate generally requires repeated administration and more intensive renal, electrolyte and infusion monitoring. Any substitution must be an explicit specialist and programme decision using the correct product label, not a pharmacy-level name match.
What skin change after kala-azar should prompt assessment for PKDL?
New symmetrical hypopigmented, erythematous, papular, plaque-like or nodular lesions should prompt assessment, even without fever or a recalled past VL episode. Sensation is often preserved, but leprosy and other dermatoses remain important alternatives. Confirmation uses programme-approved parasitology such as PCR, slit-skin smear or biopsy.
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