Current Scenario of Vector Borne

Diseases in India

Dr Menaal KaushalResident

Department of Community MedicineS N Medical College

Agra

The Emergence and Re- Emergence of Vector Borne

Diseases

Malaria

Dengue

Chikungunya

Japanese Encephalitis

Yellow Fever

Leishmaniasis

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

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!

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

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.

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.

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

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

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

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.

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

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

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.

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

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.

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

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

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

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

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

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

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.

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 patients are another potential

source for the emergence of drug resistance

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

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

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)

The Future: Near and Distant

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.

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

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.

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.

Genetically Modified Mosquito

Transposon- based mechanism

Aims either at :

Population Suppression Techniques

Population Replacement Techniques

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.

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

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

Thank you