What is filariasis due to Brugia malayi in a patient from Southeast Asia or India?

Filariasis Due to Brugia malayi

Overview and Geographic Distribution

Filariasis due to Brugia malayi is a mosquito-transmitted parasitic infection causing lymphatic damage that is endemic primarily in Southeast Asia and parts of India, with B. malayi and B. timori being the predominant species in this region. 1

The infection is transmitted by mosquito vectors including Aedes, Anopheles, and Culex species, with B. malayi having a prepatent period of approximately 2 months before microfilariae appear in the blood. 1 The disease is endemic in countries including Indonesia, Thailand, Malaysia, India, and other Southeast Asian nations, with approximately 15 million people affected in Southeast Asia alone. 2

Clinical Presentation

Acute Phase

• Most infections are initially asymptomatic but cause progressive lymphatic damage nevertheless. 1
• Acute presentations include fever with localized skin inflammation, lymphadenitis, and lymphangitis. 1
• The incubation period from infection to clinical symptoms is highly variable, ranging from 4 weeks to 16 months. 1

Chronic Manifestations

• Chronic lymphoedema (historically termed elephantiasis) develops as the disease progresses. 1
• Scrotal oedema and hydrocoele occur in male patients. 1

Tropical Pulmonary Eosinophilia (TPE)

• Non-immune travelers from endemic regions may present with fever and respiratory symptoms representing a hypersensitivity reaction to B. malayi. 1
• TPE presents with fever, dry cough, wheeze, and breathlessness, often initially misdiagnosed as asthma. 1, 3
• Eosinophil counts typically exceed 3 × 10⁹/L, and IgE levels are markedly elevated. 1, 3
• Chest radiograph shows interstitial shadowing, reticulonodular or miliary infiltrates in 80% of cases. 1, 3
• Filarial serology is strongly positive, but microfilariae are NOT detected on blood film microscopy, distinguishing TPE from other forms of filariasis. 1, 3

Diagnostic Approach

Blood Microscopy

Nocturnal blood microscopy collected between 10 pm and 2 am is the gold standard for diagnosis, as microfilariae of B. malayi circulate nocturnally. 1, 4

• Collect 20 ml total volume in 4 citrated blood bottles (not to be refrigerated). 1
• Examine Giemsa-stained thick and thin blood films. 1
• Examination of concentrated blood specimens (Knott, Nuclepore filtered blood, or buffy coat) increases sensitivity in cases of low parasitemia. 1
• Repeat examinations may be necessary due to low parasitemia. 1

Serology

• Serology is available but does not differentiate between filarial species (Wuchereria, Brugia, Mansonella). 1
• In TPE, filarial serology is strongly positive while blood microscopy remains negative. 1, 3

Treatment Algorithm

Critical Pre-Treatment Screening

Before initiating treatment, you must exclude co-infections with Onchocerca volvulus (onchocerciasis) and Loa loa (loiasis) to prevent life-threatening complications including fatal encephalopathy and severe neurological reactions. 1, 4, 5

Screening Protocol:

1. For onchocerciasis exclusion: Obtain skin snips for microscopy and perform slit lamp examination if the patient has traveled to co-endemic areas (sub-Saharan Africa, Yemen, parts of South America). 1, 4

   • If unavailable, administer a test dose of DEC 50 mg to precipitate a mild Mazzotti reaction if onchocerciasis is present. 4

2. For loiasis exclusion: Obtain daytime blood microscopy if the patient has traveled to loiasis-endemic areas (Central/West Africa). 1, 4

   • If Loa loa microfilariae are detected with counts >1000 mf/ml, treat first with prednisolone and albendazole 200 mg twice daily for 21 days to reduce microfilarial load before definitive treatment. 1, 4

Primary Treatment Regimen for Lymphatic Filariasis

The recommended treatment is diethylcarbamazine (DEC) 6 mg/kg in 3 divided doses for 14 days plus doxycycline 200 mg daily for 6 weeks, after excluding onchocerciasis and loiasis co-infection. 1, 4, 5

Alternative Regimen:

• In onchocerciasis co-endemic areas where DEC is contraindicated: ivermectin 200 μg/kg single dose plus albendazole 400 mg single dose. 4, 5

Triple-Drug Therapy:

• Recent evidence supports ivermectin, DEC, and albendazole (IDA) triple therapy as highly effective, with 94% of treated patients clearing all microfilariae at one year. 6

Treatment for Tropical Pulmonary Eosinophilia

Diethylcarbamazine is the definitive treatment for TPE, and prompt initiation is critical to prevent progression to irreversible pulmonary fibrosis. 1, 3

• Standard DEC dosing: 6 mg/kg in 3 divided doses for 14 days. 1
• Symptoms typically resolve rapidly following treatment. 1
• Corticosteroids (prednisolone 20 mg/day initially) may be beneficial for ongoing alveolitis and to prevent pulmonary fibrosis, particularly in patients with delayed diagnosis. 3
• Always exclude strongyloidiasis before initiating steroids, as corticosteroids can precipitate fatal hyperinfection syndrome. 3
• Approximately 20% of TPE patients relapse and require re-treatment with a second course of DEC. 1, 3

Special Populations

Pregnancy and Lactation

• Avoid DEC in pregnancy and seek expert consultation. 4, 5
• Ivermectin can be used in second and third trimesters with no observed teratogenicity in limited human data. 4, 5
• Ivermectin is excreted in very low levels in breast milk and is likely compatible with breastfeeding. 4, 5

Pediatric Patients

• Children aged 12-24 months should be discussed with an expert before treatment. 4, 5
• Children over 24 months can receive standard dosing. 4, 5

Monitoring Requirements

• Monitor full blood counts and liver function tests every 2 weeks for 3 months, then monthly if within normal range for prolonged courses. 4, 5
• Monitor for adverse reactions including fever, lymphadenitis, and lymphangitis during DEC and doxycycline treatment. 4, 5
• Repeat blood microscopy at 6 and 12 months after last negative sample to monitor for relapse. 4
• When using DEC with microfilaraemia present, prednisolone is usually given alongside to reduce inflammatory reactions. 5

Critical Pitfalls and Drug Interactions

• DEC can cause fatal encephalopathy in patients with high Loa loa microfilarial loads (>1000/ml). 1, 4
• DEC can cause severe Mazzotti reactions including blindness, hypotension, pruritus, and erythema in patients co-infected with onchocerciasis. 4
• Azithromycin significantly increases serum ivermectin concentrations; use caution with co-administration. 4, 5
• Ivermectin should be taken with food, as bioavailability increases 2.5 times with high-fat meals. 5
• Albendazole should be taken with or after food. 5
• Alcohol may worsen side effects. 4, 5

Reservoir Hosts and Transmission Considerations

• Domestic cats serve as the major reservoir host for B. malayi in endemic areas such as southern Thailand. 7
• Recent evidence demonstrates that dogs can also harbor B. malayi infection, with 20% of microfilarial-positive dogs showing sheathed microfilariae confirmed as B. malayi. 7
• Post-treatment surveillance in the community may be needed to detect potential parasite reservoirs in adults, as most infections persist in individuals over 21 years of age. 6