What is the initial workup and management for an infant presenting with fever and hepatosplenomegaly in the Indian subtropics?

Initial Workup for Fever with Hepatosplenomegaly in an Infant in the Indian Subtropics

In an infant presenting with fever and hepatosplenomegaly in the Indian subtropics, immediately obtain blood cultures, complete blood count with differential, peripheral blood smear, liver function tests, and serum ferritin, while simultaneously evaluating for life-threatening conditions including acute leukemia, visceral leishmaniasis, and hemophagocytic lymphohistiocytosis. 1

Immediate Life-Threatening Conditions to Rule Out

Acute Leukemia

• Bone marrow aspiration and biopsy must be performed urgently when fever, hepatosplenomegaly, and pancytopenia (anemia, thrombocytopenia, neutropenia) are present together. 1
• Flow cytometry and cytogenetic testing are essential to identify acute lymphoblastic leukemia or myelodysplastic syndromes 1
• Delaying bone marrow examination when organomegaly is present can delay diagnosis of life-threatening malignancies 1

Hemophagocytic Lymphohistiocytosis (HLH)

• Consider HLH when persistent fever continues beyond expected viral illness course, especially with hepatosplenomegaly and progressive cytopenias 2, 3
• Cardinal diagnostic features include: prolonged fever, cytopenias affecting 2-3 lineages, hepatosplenomegaly, and elevated ferritin (>3000 ng/mL suggests HLH) 3, 4
• Additional laboratory markers: hypertriglyceridemia (>314 mg/dL), hypofibrinogenemia, and elevated LDH 2, 4
• Bone marrow biopsy showing hemophagocytosis confirms diagnosis, though absence does not exclude HLH 4
• HLH is fatal without treatment; initiate dexamethasone 10 mg/m²/day if diagnostic criteria are met 2

Geographic-Specific Infectious Workup for Indian Subtropics

Visceral Leishmaniasis (Kala-azar)

• This is a critical diagnosis in the Indian subcontinent (Bihar, Nepal, Bangladesh regions) presenting with fever, hepatosplenomegaly, weight loss, and pancytopenia 5
• Obtain leishmaniasis serology and bone marrow aspiration for parasite detection 5, 6
• Neurological signs (diminished tone, tremors) may be the first manifestation 6

Dengue Hemorrhagic Fever

• Obtain dengue PCR (days 1-8 post-symptom onset) and dengue serology 5
• Monitor daily complete blood count for rising hematocrit and falling platelets indicating plasma leakage 5
• Ultrasound abdomen to detect plasma leakage (pleural effusion, ascites) 2
• Persistent fever beyond the critical phase (days 5-7) with ongoing cytopenias should trigger evaluation for secondary HLH 2

Enteric Fever (Typhoid/Paratyphoid)

• Blood cultures are essential; Salmonella species account for 4.7-5.4% of bacteremia in febrile children 5
• Fever with hepatosplenomegaly, constipation or diarrhea, and relative bradycardia suggest enteric fever 5
• Complications (gastrointestinal bleeding, perforation, encephalopathy) occur in 10-15% if duration exceeds 2 weeks 5

Malaria

• Thick and thin blood smears must be obtained immediately and repeated every 12-24 hours if initially negative 5
• Malaria remains the most common cause of fever in travelers from sub-Saharan Africa and South Asia 5

Other Endemic Infections

• Leptospirosis: obtain blood culture within first 5 days; CSF if meningeal signs present 5
• Brucellosis: extended blood culture and serology if livestock contact or unpasteurized milk consumption 5
• Acute schistosomiasis (Katayama syndrome): consider if freshwater exposure 2-9 weeks prior with fever, rash, eosinophilia 5

Age-Specific Considerations for Infants <3 Months

If the infant is under 3 months of age:

• Hospitalization with empirical parenteral antibiotics is mandatory due to 8-13% risk of invasive bacterial infection 7
• Obtain urine analysis (catheterized specimen), blood culture, and inflammatory markers immediately 7
• Lumbar puncture should be performed based on risk stratification 7
• Initiate ceftriaxone 50 mg/kg IV/IM daily pending culture results 5, 8
• Never rely solely on clinical appearance: only 58% of infants with bacteremia or meningitis appear clinically ill 7

Essential Initial Laboratory Panel

Mandatory First-Line Tests

• Complete blood count with differential and peripheral blood smear examination by hematologist/pathologist 1
• Blood cultures from all lumens if central venous catheter present 5
• Liver function tests (transaminases, bilirubin, albumin) 5
• Serum ferritin (>3000 ng/mL highly suggestive of HLH) 2, 3
• Triglycerides and fibrinogen (for HLH evaluation) 3
• Lactate dehydrogenase 4

Second-Tier Investigations Based on Initial Results

• Bone marrow aspiration and biopsy if pancytopenia or abnormal peripheral smear 1
• Ultrasound abdomen to assess organomegaly extent and detect fluid collections 2
• Chest radiograph if respiratory symptoms present 5

Critical Pitfalls to Avoid

• Do not assume viral infection excludes bacterial infection: coexistence is common in infants 7
• Physical examination showing hepatosplenomegaly mandates bone marrow examination; this is not primary immune thrombocytopenia 1
• Do not delay bone marrow examination when systemic symptoms or organomegaly are present 1
• Recent antipyretic use can mask fever severity and disease progression 7
• HLH may initially masquerade as normal infection; maintain high suspicion when fever persists beyond expected course with progressive cytopenias 3
• In HIV-exposed infants, do not overlook congenital infections 1

Empirical Treatment Considerations

• For infants 28-89 days meeting low-risk criteria: ceftriaxone 50 mg/kg IM with strict 24-hour follow-up is acceptable alternative to hospitalization 8
• For high-risk or ill-appearing infants: immediate hospitalization with broad-spectrum parenteral antibiotics 5, 7
• If HLH suspected based on diagnostic criteria: initiate dexamethasone 10 mg/m²/day without delay 2
• If visceral leishmaniasis confirmed: specific anti-leishmanial therapy 5
• Treatment duration for confirmed bacterial infections: minimum 48-72 hours beyond symptom resolution or bacterial eradication 7