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

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 Malaria
 Emergence of Resistant Kala Azar
 Global Trade& Travel

4. 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!

5. 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

6. 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.

7. 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.

8. 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

9. 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

10. Detection of Drug
Resistance 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

11. 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.

12. 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

13. 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

14. 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.

15. 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

16.  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

17.  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

18. 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

19. 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

20. 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

21. 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

22. 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, 1st and 2nd 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

23.  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.

25. Resistant Kala Azar
 For more than 60 years, treatment of
leishmaniasis has centered around pentavalent
antimonials (Sbv).
 Widespread misuse has led to the emergence of
Sbv resistance in the hyperendemic areas of North
Bihar
 The HIV/ visceral leishmaniasis (VL) coinfected

26. 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

27. 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

28. 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)

29. The Future: Near and
Distant

30. 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.

31. 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

32. 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.

33. Newer Anti Malarial Drugs
 Drugs targeting the following are being tested:
 Chromatin-modifying enzymes,
 Parasitic metabolic pathways (e.g. the coenzyme A
pathway),
 Parasite transporters and
 Mitochondrial enzymes
 Phytomedicine: From the Plant Argemone mexicana
 Resistance Reversal Approaches: Verapamil (an Anti-
hypertensive) and Desipramine (An Anti depressant) have
shown reversal of parasitic resistance in vitro.

34. Genetically Modified
Mosquito
Transposon- based mechanism
Aims either at :
 Population Suppression Techniques
 Population Replacement Techniques

35. Population Suppression
Techniques:
 Sterile Insect Technique (SIT):
 The sterile males compete with the wild males for female
insects.
 If a female mates with a sterile male then it will have no
offspring, thus reducing the next generationʼs population.
 Genetics rather than radiation: Wild female mosquitoes mate
released engineered ʻsterileʼ male, progeny will inherit the
lethal gene and die.
 Furthermore, the sterile males actively seek out wild females
to mate.

36. Population Replacement
Techniques
 This includes 2 steps:
 Develop a modified strain of vector mosquito that is unable to
transmit the pathogen of interest (or with greatly reduced
ability to transmit relative to wild mosquitoes)
 Introgress (i.e. spread) this ‘refractoriness gene’ or genetic
system into the target population
 A ‘gene drive system’ or ‘gene driver’ is needed in the
environment

37. Some Questions to be
Reflected upon:
 Is partial IRS coverage in Kutcha houses a solution or a
problem for the near future?
 Almost every year a new Drug policy for Malaria is being
launched, but How many of our Practitioners are actively
updated regularly?
 Of these updated Medical Practitioners, how many are
fairly practicing according to the Policy?
 How well is our Resistance Reporting System among the
Private practitioners?
 Can we really survive without our age old enemy- the
Mosquito

38. Thank you