Sunday, July 27, 2014

Recent advances in the Diagnosis and treatment of Lymphatic Filariasis.

Recent advances in the Diagnosis and treatment of Lymphatic Filariasis.
                                             Dr. Dwijesh Kumar Panda, M.D, Ph.D(Medicine-Filaria)
Introduction;
  • Caused by nematodes those  inhabit the lymphatics and subcutaneous tissues.
  • Species are Wuchereria bancrofti  (95%), Brugia malayi, and Brugia timori.
  • It is usually acquired in early childhood.
  • Major cause of disfigurement and disability.
  • More than 120 million people worldwide are affected.
  • India accounts for 40% of global prevalence. (Map)
  • Transmitted by mosquito vectors. Humans are definitive host. (Fig 1-Life cycle)
  • Adult worms live for 5-7 years.
  • More than $ 840 million is lost each year.
Lymphatic Pathology:  In chronic lymphedema, lymph flow is stifled. Macromolecular protein deposition increases. Fibroblasts accumulate in interstitium. Fibrovascular proliferation results in worsening brawny edema. Obliteration of elastic fibers. Increased collagen deposition and fibrosis. Fig.
Clinical presentations:
Diagnosis:
  • Definite diagnosis by (a) detecting circulating filarial antigen. Og4C3 test procedure chart.
  • Demonstration of microfilariae in the blood- rarely seen after an attack of lymphangitis due death of adult worm. Picture
  • Filarial DNA in the blood. (PCR) Polymerase chain reaction used as a research tool to detect filarial infection in humans. Not commercially available. One pg of W. bancrofti genomic DNA added to 100 microliters of human blood.
  • Adult worms in the lymphatics- rarely detected.
  • Peripheral blood Eosinophilia- may exceed 3000/micro L. Other helminth infections frequently coexist- may increase eosinophils in the blood.
  • Tropical Eosinophilia- Confused with Tuberculosis, Asthma, Round worm infestation. Leads to progressive interstitial fibrosis, Hypersensitive immunological process. Total eosinophil count more than 3000/micro L.  Fig
Nonspecific diagnosis: Elevated serum IgE. Microscopic hematuria, Proteinuria and chyluria. Picture.
  • OG4C3 Test:   .
Detection of circulating adult filarial antigen in the blood. Positive even in amicrofilaremic          individuala.
The assay has excellent specificity and better sensitivity than microscopy.
The filarial antigens become undetectable in treated or “burned out” infection.
The quantitative OG4C3 test is useful in following patients after treatment as antigen levels decline with treatment.
Imaging:
  • Ultrasound techniques used to detect presence of adult worms in lymphatic vessels.
  • Living worms in continuous motion is described as “filarial dance” sign. Movie
  • Worms can be visualized in breast and scrotal lymphatic.
  • Lymphoscintigraphic technique:  Useful for assessing the extent of lymphatic damage in the regional lymphatic prior to development of clinical symptoms. Massive lymphatic dilation observed surrounding adult worms. The images cannot provide high resolution anatomical details. A small amount of radio isotope labeled colloidal substance is injected intra-dermally.
Treatment:
  • Medical:
  • Treatment of choice- Diethyl carbamazine (DEC) – Dose: 6mg/kg for 12 days alone or in combination with Albendazole- 400mg-once.
  • Ivermectin- It has microfilaricidal activity. No precedence over DEC in Bancroftian filariasis.
  • Benzopyrones and Flavonoids improve lymphedema through protein resorption and proteolysis.
  • Diuretics have no effect.
  • Antibiotics reserved for bouts of cellulitis.
  • Asymptomatic phase:  Due to the Cytokine IL-4 suppressing the activity of TH1 cells of immune system. This occurs for years until inflammatory reaction rises again.
  • Restriction of long chain triglycerides have some benefit.
  • Surgical:        
  • Largely disappointing.  
  • MLVA- Microlymphatic-venous anastomosis- encouraging in early stages of lymphedema.
  • Overall result disappointing in long-term edema.

                                                    THANK YOU.

Homage to Dr(Prof) L.N.Mohapatra, my Ph. D guide.