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Early Diagnosis and Treatment
for Filariasis Elimination by 2030
in India
Dr Rishabh Kumar Rana
MBBS , MD
Assistant Professor ,
Department of PSM
SNMMCH
To Prevent This We Need ……..
Elimination Needs continuous approach..
two-pillar strategy:
Preventive
Chemotherapy
Vector Control
Morbidity
Management
Early Diagnosis and
Treatment
The definition of Elimination of Lymphatic Filariasis
(LF) is to achieve <1% microfilaria rate (Mf rate) in
the endemic areas. The global/India target for
Lymphatic Filariasis is the elimination of the disease
as a public health problem by 2030.
Surveillance
Preventive Strategy
Large-scale treatment (preventive chemotherapy)
• Elimination of lymphatic filariasis is possible by stopping the spread of
the infection through preventive chemotherapy. The WHO
recommended preventive chemotherapy strategy for lymphatic
filariasis elimination is mass drug administration (MDA).
• Ivermectin (200 mcg/kg) together with diethylcarbamazine citrate
(DEC) (6 mg/kg) and albendazole (400 mg)
Vector control
• Mosquito control is a supplemental strategy. It is used to reduce
transmission of lymphatic filariasis and other mosquito-borne
infections.
• Depending on the parasite-vector species, measures such as
insecticide-treated nets, indoor residual spraying or personal
protection measures may help protect people from infection. The use
of insecticide-treated nets in areas where Anopheles is the primary
vector for filariasis enhances the impact on transmission during and
after MDA.
Data
Indicators Jharkhand Dhanbad
Lymphoedema 43550 2259 (5.18%)
Hydrocoele 26854 647 (2.40)
What Can it Mean ?????
Morbidity management
• Morbidity management and disability prevention are vital for improving
public health and are essential services that should be provided by the
health care system to ensure sustainability. Surgery can alleviate most
cases of hydrocele.
• Success in 2030 will be achieved if people affected by lymphatic filariasis
have access to the following essential package of care:
• treatment for episodes of adenolymphangitis (ADL);
• guidance in applying simple measures to manage lymphoedema to prevent
progression of disease and debilitating, inflammatory episodes of ADL;
• surgery for hydrocele;
• treatment for infection
Early Diagnosis !!! Challenges …..
• Manifestations can be protean and classified as:
• 1) Acute – Fever with chills and rigors, lymphedema with pain, lymphadenopathy
(cervical, axillary, inguinal and generalized – Acute Filarial Lymphangitis/Acute
Dermatolymphangioadenitis), chyluria, hematuria, inflammatory granuloma or
abscesses, pain in testes, funiculitis, epididymoorchitis.
2) Chronic - funiculitis, epididymoorchitis, hydrocele, breast edema, elephantiasis.
• 3) Occult- Pulmonary eosinophilia, mono and polyarthritis, tenosynovitis,
glomerulonephropathy, retroperitoneal lymphangitis (acute abdomen), central serous
retinopathy, iridocyclitis, recurrent scleritis and macular oedema, endomyocardial
fibrosis, urticaria, recurrent upper respiratory infections, asthmatic bronchitis. Any lymph
node or any body part can be affected but commonly genital lymphatics are involved in
males.
• 4) Asymptomatic - Endemic normal negative for Mf but positive for antigens (pre-
patency) and
• asymptomatic microfilaremic - presence of microfilaria in peripheral blood during night
but without any overt clinical manifestations of filariasis with or without antigens – also
known as Mf carriers (patency).
Making a Diagnosis !!
• Clinical Diagnosis- (low specificity and sensitivity for acute or
asymptomatic active infections).
• Specific tests include - direct detection of microfilaria on blood
smears, serologic tests, DNA PCR and radiology
• Non Specific Tests - eosinophilia, high IgE levels and
lymphoscintigraphy (that reveal dilated lymph channels or backflow
even in the early stage of infection).
Direct methods
• visualization of microfilaria (or the adult worm) - is made by
microscopic examination of thick film of blood collected between
10:00 PM and 2:00 AM, with or without DEC provocation, stained by
Geimsa or hematoxylineosin for the presence of microfilaria.
• X-ray tests can show calcified adult worms in lymphatics;
ultrasonography can show the ’filarial dance’ .
• Lymph node aspirate and chylus fluid may also yield microfilaria or
worm.
• Direct diagnosis, though definitive, is difficult, because of timing inconvenience of blood collection, long pre-
patency, low patency (<60%) and inadequate sensitivity. Reliance on microfilaria testing may lead to late as well as
under diagnosis;
Seromarkers – Problems
• Early diagnosis of filarial infections is best possible with
• seromarkers. With the entry of the microfilaria there is a natural IgM
response within a few weeks which slowly changes to an IgG response
– initially IgG1 and IgG2 – which changes to IgG4 after some more
time.
• Cannot distinguish current infection from past infection or exposure
• to other parasite , Cross reactivity _____ poor specificity (~40%).
Antibody Based diagnostic assays
• Antibody-based diagnostic assays using four recombinant antigens,
Bm14, WbSXP, BmSXP and BmR1 are there .
• The BmR1 ELISA as well as dipstick (Brugia Rapid
immunochromatography based) antibody tests have very high
sensitivity for Brugia malayi (~100%), Bm14 ELISA is sensitive for both
Wuchereria bancrofti and Brugia malayi
• (~91%-96%), and WbSXP was predominantly sensitive for Wuchereria
bancrofti (91%) and somewhat less for Brugia malayi (40%). BmSXP is
another recombinant antigen having high sensitivity for Wuchereria
bancrofti (95%).
Antigen Tests
• Filarial Antigen tests, available commercially, are better than antibody
tests. They show little 24 hour variation in their positivity can detect
active infection (better specificity). Can monitor therapy
• Immunochromatographic test (ICT) is a highly sensitive and specific
circulating filarial antigen (CFA) detection assay, both as card test
(AD-12.1 antibody) and in ELISA based format (Og4C3 antibody–
‘Tropbio’)
• Circulating filarial antigen (CFA) detection test the ‘gold standard’ for
diagnosing Wuchereria bancrofti infections.
DNA Probes
• DNA probes using Real-Time Polymerase Chain Reaction (RT-PCR) are
of high specificity and sensitivity, but are not cost effective.
For NTDs hard to Expect
Treatment
Diethylcarbamazine (DEC)
12-day course of DEC (6 mg/kg/day). Micro + Macro
21 days regime also used ,
although albendazole (400 mg twice daily by
mouth for 21 days) also has demonstrated macrofilaricidal
efficacy.
A 4- to 6-week course of oral doxycycline (targeting the
intracellular Wolbachia) also has significant macrofilaricidal
activity, as does DEC/albendazole used daily for 7 days.
Caution Those belonging to onchocerciasis or loiasis co-
endemic areas must not be prescribed DEC as it can result in a
fatal adverse reaction.
Mazzotti reaction
Doxycycline and ivermectin or albendazole is the
recommended combination in these individuals.
References
• Lahariya C, Tomar SS. How Endemic Countries can Accelerate Lymphatic Filariasis Elimination? An Analytic Review to Identify Strategic and
Programmatic Interventions. J Vector Borne Dis 2011; 48:1-6.
• Sabesan S, Vanamail P, Raju KHK, Jambulingam P. Lymphatic Filariasis in India: Epidemiology and control measures. J Postgrad Med 2010; 56:232-8.
• Bjerum CM, Ouattara AF, Aboulaye M, Kouadio O, Marius VK, Andersen BJ, Weil GJ, Koudou BG, King CL. Efficacy and Safety of a Single Dose of
Ivermectin, Diethylcarbamazine, and Albendazole for Treatment of Lymphatic Filariasis in Côte d'Ivoire: An Open-label Randomized Controlled
Trial. Clin Infect Dis. 2020 Oct 23;71(7):e68-e75. [PMC free article] [PubMed]
• Taylor MJ, Hoerauf A, Bockarie M. Lymphatic filariasis and onchocerciasis. Lancet. 2010 Oct 02;376(9747):1175-85. [PubMed]
• Kalyanasundaram R, Khatri V, Chauhan N. Advances in Vaccine Development for Human Lymphatic Filariasis. Trends Parasitol. 2020 Feb;36(2):195-
205. [PMC free article] [PubMed]
• Stocks ME, Freeman MC, Addiss DG. The Effect of Hygiene-Based Lymphedema Management in Lymphatic Filariasis-Endemic Areas: A Systematic
Review and Meta-analysis. PLoS Negl Trop Dis. 2015 Oct;9(10):e0004171. [PMC free article] [PubMed]
• Gardon J, Gardon-Wendel N, Demanga-Ngangue, Kamgno J, Chippaux JP, Boussinesq M. Serious reactions after mass treatment of onchocerciasis with
ivermectin in an area endemic for Loa loa infection. Lancet. 1997 Jul 05;350(9070):18-22. [PubMed]
• Andersen BJ, Rosa BA, Kupritz J, Meite A, Serge T, Hertz MI, Curtis K, King CL, Mitreva M, Fischer PU, Weil GJ. Systems analysis-based assessment of
post-treatment adverse events in lymphatic filariasis. PLoS Negl Trop Dis. 2019 Sep;13(9):e0007697.

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Early Diagnosis and Treatment Key for India's 2030 Filariasis Goal

  • 1. Early Diagnosis and Treatment for Filariasis Elimination by 2030 in India Dr Rishabh Kumar Rana MBBS , MD Assistant Professor , Department of PSM SNMMCH
  • 2. To Prevent This We Need ……..
  • 3. Elimination Needs continuous approach.. two-pillar strategy: Preventive Chemotherapy Vector Control Morbidity Management Early Diagnosis and Treatment The definition of Elimination of Lymphatic Filariasis (LF) is to achieve <1% microfilaria rate (Mf rate) in the endemic areas. The global/India target for Lymphatic Filariasis is the elimination of the disease as a public health problem by 2030. Surveillance
  • 4. Preventive Strategy Large-scale treatment (preventive chemotherapy) • Elimination of lymphatic filariasis is possible by stopping the spread of the infection through preventive chemotherapy. The WHO recommended preventive chemotherapy strategy for lymphatic filariasis elimination is mass drug administration (MDA). • Ivermectin (200 mcg/kg) together with diethylcarbamazine citrate (DEC) (6 mg/kg) and albendazole (400 mg)
  • 5. Vector control • Mosquito control is a supplemental strategy. It is used to reduce transmission of lymphatic filariasis and other mosquito-borne infections. • Depending on the parasite-vector species, measures such as insecticide-treated nets, indoor residual spraying or personal protection measures may help protect people from infection. The use of insecticide-treated nets in areas where Anopheles is the primary vector for filariasis enhances the impact on transmission during and after MDA.
  • 6. Data Indicators Jharkhand Dhanbad Lymphoedema 43550 2259 (5.18%) Hydrocoele 26854 647 (2.40) What Can it Mean ?????
  • 7. Morbidity management • Morbidity management and disability prevention are vital for improving public health and are essential services that should be provided by the health care system to ensure sustainability. Surgery can alleviate most cases of hydrocele. • Success in 2030 will be achieved if people affected by lymphatic filariasis have access to the following essential package of care: • treatment for episodes of adenolymphangitis (ADL); • guidance in applying simple measures to manage lymphoedema to prevent progression of disease and debilitating, inflammatory episodes of ADL; • surgery for hydrocele; • treatment for infection
  • 8. Early Diagnosis !!! Challenges ….. • Manifestations can be protean and classified as: • 1) Acute – Fever with chills and rigors, lymphedema with pain, lymphadenopathy (cervical, axillary, inguinal and generalized – Acute Filarial Lymphangitis/Acute Dermatolymphangioadenitis), chyluria, hematuria, inflammatory granuloma or abscesses, pain in testes, funiculitis, epididymoorchitis. 2) Chronic - funiculitis, epididymoorchitis, hydrocele, breast edema, elephantiasis. • 3) Occult- Pulmonary eosinophilia, mono and polyarthritis, tenosynovitis, glomerulonephropathy, retroperitoneal lymphangitis (acute abdomen), central serous retinopathy, iridocyclitis, recurrent scleritis and macular oedema, endomyocardial fibrosis, urticaria, recurrent upper respiratory infections, asthmatic bronchitis. Any lymph node or any body part can be affected but commonly genital lymphatics are involved in males. • 4) Asymptomatic - Endemic normal negative for Mf but positive for antigens (pre- patency) and • asymptomatic microfilaremic - presence of microfilaria in peripheral blood during night but without any overt clinical manifestations of filariasis with or without antigens – also known as Mf carriers (patency).
  • 9. Making a Diagnosis !! • Clinical Diagnosis- (low specificity and sensitivity for acute or asymptomatic active infections). • Specific tests include - direct detection of microfilaria on blood smears, serologic tests, DNA PCR and radiology • Non Specific Tests - eosinophilia, high IgE levels and lymphoscintigraphy (that reveal dilated lymph channels or backflow even in the early stage of infection).
  • 10. Direct methods • visualization of microfilaria (or the adult worm) - is made by microscopic examination of thick film of blood collected between 10:00 PM and 2:00 AM, with or without DEC provocation, stained by Geimsa or hematoxylineosin for the presence of microfilaria. • X-ray tests can show calcified adult worms in lymphatics; ultrasonography can show the ’filarial dance’ . • Lymph node aspirate and chylus fluid may also yield microfilaria or worm. • Direct diagnosis, though definitive, is difficult, because of timing inconvenience of blood collection, long pre- patency, low patency (<60%) and inadequate sensitivity. Reliance on microfilaria testing may lead to late as well as under diagnosis;
  • 11. Seromarkers – Problems • Early diagnosis of filarial infections is best possible with • seromarkers. With the entry of the microfilaria there is a natural IgM response within a few weeks which slowly changes to an IgG response – initially IgG1 and IgG2 – which changes to IgG4 after some more time. • Cannot distinguish current infection from past infection or exposure • to other parasite , Cross reactivity _____ poor specificity (~40%).
  • 12. Antibody Based diagnostic assays • Antibody-based diagnostic assays using four recombinant antigens, Bm14, WbSXP, BmSXP and BmR1 are there . • The BmR1 ELISA as well as dipstick (Brugia Rapid immunochromatography based) antibody tests have very high sensitivity for Brugia malayi (~100%), Bm14 ELISA is sensitive for both Wuchereria bancrofti and Brugia malayi • (~91%-96%), and WbSXP was predominantly sensitive for Wuchereria bancrofti (91%) and somewhat less for Brugia malayi (40%). BmSXP is another recombinant antigen having high sensitivity for Wuchereria bancrofti (95%).
  • 13. Antigen Tests • Filarial Antigen tests, available commercially, are better than antibody tests. They show little 24 hour variation in their positivity can detect active infection (better specificity). Can monitor therapy • Immunochromatographic test (ICT) is a highly sensitive and specific circulating filarial antigen (CFA) detection assay, both as card test (AD-12.1 antibody) and in ELISA based format (Og4C3 antibody– ‘Tropbio’) • Circulating filarial antigen (CFA) detection test the ‘gold standard’ for diagnosing Wuchereria bancrofti infections.
  • 14. DNA Probes • DNA probes using Real-Time Polymerase Chain Reaction (RT-PCR) are of high specificity and sensitivity, but are not cost effective. For NTDs hard to Expect
  • 15. Treatment Diethylcarbamazine (DEC) 12-day course of DEC (6 mg/kg/day). Micro + Macro 21 days regime also used , although albendazole (400 mg twice daily by mouth for 21 days) also has demonstrated macrofilaricidal efficacy. A 4- to 6-week course of oral doxycycline (targeting the intracellular Wolbachia) also has significant macrofilaricidal activity, as does DEC/albendazole used daily for 7 days. Caution Those belonging to onchocerciasis or loiasis co- endemic areas must not be prescribed DEC as it can result in a fatal adverse reaction. Mazzotti reaction Doxycycline and ivermectin or albendazole is the recommended combination in these individuals.
  • 16. References • Lahariya C, Tomar SS. How Endemic Countries can Accelerate Lymphatic Filariasis Elimination? An Analytic Review to Identify Strategic and Programmatic Interventions. J Vector Borne Dis 2011; 48:1-6. • Sabesan S, Vanamail P, Raju KHK, Jambulingam P. Lymphatic Filariasis in India: Epidemiology and control measures. J Postgrad Med 2010; 56:232-8. • Bjerum CM, Ouattara AF, Aboulaye M, Kouadio O, Marius VK, Andersen BJ, Weil GJ, Koudou BG, King CL. Efficacy and Safety of a Single Dose of Ivermectin, Diethylcarbamazine, and Albendazole for Treatment of Lymphatic Filariasis in Côte d'Ivoire: An Open-label Randomized Controlled Trial. Clin Infect Dis. 2020 Oct 23;71(7):e68-e75. [PMC free article] [PubMed] • Taylor MJ, Hoerauf A, Bockarie M. Lymphatic filariasis and onchocerciasis. Lancet. 2010 Oct 02;376(9747):1175-85. [PubMed] • Kalyanasundaram R, Khatri V, Chauhan N. Advances in Vaccine Development for Human Lymphatic Filariasis. Trends Parasitol. 2020 Feb;36(2):195- 205. [PMC free article] [PubMed] • Stocks ME, Freeman MC, Addiss DG. The Effect of Hygiene-Based Lymphedema Management in Lymphatic Filariasis-Endemic Areas: A Systematic Review and Meta-analysis. PLoS Negl Trop Dis. 2015 Oct;9(10):e0004171. [PMC free article] [PubMed] • Gardon J, Gardon-Wendel N, Demanga-Ngangue, Kamgno J, Chippaux JP, Boussinesq M. Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection. Lancet. 1997 Jul 05;350(9070):18-22. [PubMed] • Andersen BJ, Rosa BA, Kupritz J, Meite A, Serge T, Hertz MI, Curtis K, King CL, Mitreva M, Fischer PU, Weil GJ. Systems analysis-based assessment of post-treatment adverse events in lymphatic filariasis. PLoS Negl Trop Dis. 2019 Sep;13(9):e0007697.