Current scenario of vbd in india

The ppt highlights types of insecticide resistance, resistance towards antimalarials, rationale of National drug policy for malaria, use of GIS in epidemic predictions for kala azar, malaria, genetically modified mosquitoes and malaria vaccine

1. Current Scenario of Vector Borne Diseases in India Dr Menaal Kaushal Resident Department of Community Medicine S N Medical College Agra

2. The Emergence and Re- Emergence of Vector Borne Diseases Malaria Dengue Chikungunya Japanese Encephalitis Yellow Fever Leishmaniasis

3. Why the Re- emergence? Global Warming Resistance to Insecticidal measures: Physiological Resistance- Triple and Quadrupled Resistance Behavioral Resistance Resistance to Anti parasite measures: Multi drug Resistant M alaria Emergence of Resistant Kala Azar Global Trade& Travel

4. Mosquito: Wiser than what we thought! Mosquitoes are ubiquitous: even found in Arctic In cold climate: the hair around its body can keep and contain the warmth of its body. In warm climate: it remains small and due to comparatively larger surface area it can keep cool The mosquito has become resistant to DDT and other insecticides With about 2 degree C rise in Average Temp (due to Global warming), the Mosquitoes have adapted…

5. Global Warming 2 degree C rise in temp- Shortens extrinsic IP- more infected mosquitos to further spread the disease Delays the hibernation period Quickens the life cycle of the mosquito Shortens the size of the mosquito Rise in temp- mosquito bites more frequently due to “dehydration”- further spreads the VBD

6. Insecticide Resistance Insecticide Resistance can be: Physiological Behavioral Due to Behavioral R esistance: Endophilic , endophagic mosquitoes have become exophilic & exophagus E.g. An. funestus now bites late in the evening rather than at midnight

7. Physiological Insecticide Resistance: At present there are 40 malaria - endemic countries reporting physiological resistance to insecticides, most to pyrethroids In India also, Quadrupled resistance has been detected E.g. A single gene mutation (knock down resistance gene or kdr ) has mutated the Na-K Pump of A. gambiae Multiple gene mutations provide a graded degree of resistance Mutations in Sand-fly has also been recently reported in India, thus providing resistance against DDT.

8. Resistance in Mosquito

9. Are mosquitoes really the curse of the century? Our Ancient ‘Enemy’ The Smart Army An enemy or a friend in disguise: A life without the mosquitoes!

10. So what can we humans do: Anti Mosquito measures? The Strategy to fight the mosquito with our Limited Armamentarium: Anti Adult Measures Mosaic IRS with multi drug rotation Personal Protection LLITN and ITN Anti Larval Measures Battle of the future: Genetically modified mosquitoes

11. Mosaic IRS with Multi Drug Rotation The insecticide resistance is generally restricted to particular target vector species within the geographical confines and appears after a prolonged use in health sector and/or exacerbated by the use of same class of insecticide in the agriculture. Increased Resistance of the mosquitoes to Insecticides is also partly attributed to the Partial Indoor Residual Spraying, in houses with mud walls Rotation policy : Use of unrelated compounds are rotated. Three insecticides are annually rotated which slows down build up of resistance against pyrethroids .

12. Mosaic, Multi Drug Rotation This strategy can be applied to both IRS and ITNs. In case of ITNs, carbamates can be rotated with synthetic pyrethroids or mixture of two unrelated compounds for impregnation can be used. Spraying of different insecticides in a mosaic fashion and their rotation in the adjoining areas is helpful in preventing resistance in vectors.

13. Multi drug Resistant Malaria For P . falciparum, multidrug resistance has been defined as resistance to more than two operational antimalarial compounds belonging to different chemical classes . Emerging multidrug resistance : Areas where there is widespread loss of clinical efficacy of chloroquine and the antifolates along with a potential for emergence of resistance to a third antimalarial MDR Reported in Kamrup district of Assam

14. Drug resistance in Malaria According to WHO standard in vivo test protocol: Resistance refers to therapeutic failure after administration of a standard dose of a drug After ruling out patient compliance, incorrect dosage and duration of treatment So, serum drug concentrations must be measured

15. Detection of Drug R esistance in Malaria Various methods include: In- vitro studies of resistance, Detection of molecular markers of resistance and Therapeutic drug efficacy studies - the Gold Standard. This guides the National Drug Policy for Malaria in most of the countries

16. WARN World Antimalarial Resistance Network ( WARN) : creates a global database for drug resistance in malaria. Various aspects of drug-resistant malaria are dealt with including its distribution and molecular markers of antimalarial resistance It guides antimalarial treatment and prevention policies This network also aims at confirming and characterizing the emergence of new resistance to antimalarial drugs . India Needs to establish its own Antimalarial Resistance Database.

17. So what can we humans do: Anti Parasite measures? The Strategy to fight the Resistant pathogen with our Limited Armamentarium: Malaria Drug Policy 2013 Vaccines against JE and YF The Hope to win the Battle in the Near Future: Malaria Vaccine Newer Drugs under Clinical Trials

18. National Drug Policy for Malaria First formulated in 1982 Has been periodically revised- latest released in 2013 Mainstay: Early diagnosis and Complete Treatment Early Diagnosis by: Microscopy Rapid Diagnostic Test Kits : Till 2012, Pf RDTs have been supplied under NVBDCP. From 2013, Bivalent RDT have been introduced

19. Effective treatment of malaria under the National Drug Policy aims at : Providing complete cure (clinical and parasitological) of malaria cases Prevention of progression of uncomplicated malaria into severe malaria and thereby reduce malaria mortality Prevention of relapses by administration of radical treatment Interruption of transmission of malaria by use of gametocytocidal drugs Preventing drug resistance by rational treatment of malaria cases .

20. Take Home Messages: Ensure treatment with full therapeutic dose with appropriate drug to all confirmed cases- No Role of Presumptive Treatment In cases where parasitological diagnosis is not possible due to non-availability of either timely microscopy or RDT, suspected malaria cases will be treated with full course of chloroquine , till the results of microscopy are received . The private healthcare providers should also follow the National Guidelines according to the Drug Policy 2013

21. Production and sale of Artemisinin monotherapy has been banned in India Resistance should be suspected if in spite of full treatment with no history of vomiting, diarrhoea , patient does not respond within 72 hours , clinically and parasitologically . Such Suspected Resistant cases must be reported to concerned District Malaria /State Malaria Officer/ROHFW for initiation of therapeutic efficacy studies.

22. Different coloured Blister Packs for different age groups, has been introduced P. ovale should be treated as P . vivax and P. malariae should be treated as P. falciparum All cases of mixed infection are to be treated as Pf as per the drug policy applicable in the area plus primaquine for 14 days

23. Chemoprophylaxis Chemoprophylaxis should be administered only in selective groups in high P.falciparum endemic areas. Use of personal protection measures including ITN/LLIN should be encouraged However , for longer stay of Military and Para-military forces in high Pf endemic areas, the practice of chemoprophylaxis should be followed

24. Chemoprophylaxis : Short Term Chemoprophylaxis (Less than 6 weeks): Doxycycline : 100 mg once daily for adults and 1.5 mg/kg once daily for children (contraindicated in children below 8 years). The drug should be started 2 days before travel and continued for 4 weeks after leaving the malarious area . Chemoprophylaxis for longer stay (more than 6 weeks ) Mefloquine : 250 mg weekly for adults and should be administered two weeks before , during and four weeks after exposure

25. Antimalarial drugs that are not recommended for chemoprophylaxis: Ericsson C D et al. Clin Infect Dis. 2001;33:381-385 © 2001 by the Infectious Diseases Society of America

26. J E Vaccination Three type of vaccine available Mouse brain derived ,purified and inactivated vaccine(MBV) Cell culture derived , inactivated JE vaccine based on the Beijing P-3 strain Cell culture derived , live attenuated vaccine based on SA14-14-2 strain Inactivated vaccine and the mouse brain vaccine is now replaced with live attenuated vaccine

27. MBV Schedule - two primary doses 4 wk apart and booster after 1 yrs then at 3 yrs interval. Dose: For < 3yrs- 0.5ml and For >3yrs- 1ml. Protective immunity develop after 1 month of second dose Best used during inter epidemic period.

28. Live attenuated vaccine It provide long term protection It is included in UIP in all endemic district schedule Vaccine not recommended for infant less than 6 month Two doses, 1 st and 2 nd at an interval of 1 yr give about > 99% protection For travelers, two doses – at one month interval or three doses at 0,7,28 days should be offered with booster every 3yrs

29. Till September 2013 vaccine was procured from abroad (China) but since October 2013 the vaccine is being manufactured in India with PPP scheme with Bharat Biotech &ICMR with name JENVAC ,cost reduced to 160 INR per dose Vaccination of swine is extremely important but it is difficult to maintain because the population is rapidly renewed.

30. Resistant Kala Azar For more than 60 years, treatment of leishmaniasis has centered around pentavalent antimonials ( Sb v ). Widespread misuse has led to the emergence of Sb v resistance in the hyperendemic areas of North Bihar The HIV/ visceral leishmaniasis (VL) coinfected patients are another potential source for the emergence of drug resistance

31. Resistant Kala Azar Kala Azar treatment failure is now as high as 65% in some parts of India Glycan found on the surface of Leishmania : makes human host cells expel antimony-based drugs Areas where drug resistance has escalated up to 70% include Brazil and Sudan

32. Strategies to Combat Drug Resistant Kala Azar Monitoring therapy Free distribution of drugs Combination therapy Monitoring drug resistance Management of HIV/VL Co-infection

33. Surveillance Techniques: GIS& RS Geographical Information System and Remote Sensing translate the satellite pictures to detailed information of the land use factors, associated with the vector borne diseases The remotely sensed environmental variables (temperature, humidity, rainfall) can be obtained in real time. This helps in stratifying the prone areas and predicting the epidemics Thus Preventive strategies can be timely channelized to such high risk areas, before the epidemic emerges

34. Use of GIS and RS for VBD analysis in India The Technology has been used to study patterns of malaria, filaria and kala azar Stratification thus is at 2 levels: Macro Level: Studies the Land use Pattern, Ecological patterns (Soil type, altitude, forest cover, temperature& rainfall) of the remote and distant areas Micro Level: Longitude& latitude of the houses, Health centers and vector breeding sites can be obtained by Global Positioning System (GPS)

35. The Future: Near and Distant

36. Malaria Vaccines Are in the Phase III Trial in Africa 2015 will see development of a first- generation malaria vaccine that has a protective efficacy of more than 50% against severe disease and death and lasts longer than one year. By 2025 , Aim is to develop and license a malaria vaccine that has a protective efficacy of more than 80% against clinical disease and lasts longer than four years.

37. Pre erythrocytic: RTS, S Ag Vaccine The RTS,S antigen , produced in S. cerevisiae , consists of the two proteins RTS and S that intracellularly and spontaneously assemble into mixed polymeric particulate structures that are each estimated to contain, on average, 100 polypeptides. Antigen : RTS,S consists of sequences of the circumsporozoite protein and the hepatitis B surface antigen ( HBsAg ) . Project initiation : October 2005. Project end date : December 2014. Biological rationale : Targets the pre-erythrocytic stages of Plasmodium falciparum

38. Mechanism of Action: The vaccine would elicit a strong neutralizing humoral immune response directed against surface-exposed sporozoite proteins, through opsonization and destruction of the invading parasites by macrophages An efficient pre-erythrocytic vaccine should also elicit Cell Mediated Immune (CMI) responses of the CD8+ and CD4+ Th1 type. The vaccine should therefore be capable of inducing appropriate subsets of memory T and B cells , specific for epitopes derived from parasite proteins.