role of papaya in dengue fever, an evidence based answere

Dr.Mohammad Mataro HingorjoResident (IV)

Family Medicine, Aga Khan University Karachi, Sindh 1

Outlines

Patient Scenario

Questions(?)

Brief introduction of Dengue Fever

Brief Introduction of Papaya

Therapeutic Uses of Papaya

Papaya and Dengue

Possible Mechanism of Action of Papaya

Evidence

Critical Analysis

Conclusion

Acknowledgments

2

Scenario

26 years female, @ CHC

◦ Dengue Fever one week back, here with Dengue IgM report

◦ Currently recovering

◦ Platelet count: 110

She is advised to use Papaya leaves’ Juice by one of her relative from Bangladesh

◦ Saying that it increases platelets!

She asked for expert advice regarding papaya use in dengue fever

3

Questions?

Background Question

◦ What is the role of Papaya in Dengue fever?

Foreground Question:

◦ Role of Papaya

Juice/extract/leaves/fruit/seeds in

increasing platelets in patients having

Dengue fever/Dengue hemorrhagic fever

4

Introduction to Dengue Fever

Major international public health problem

Mild febrile illness to a life-threatening shock

syndrome

Early diagnosis and proper handling reduces

complication

50 million dengue infections worldwide every year

Endemic in more than 123 countries

Pakistan first reported an epidemic of dengue fever

in 1994

Endemic in Pakistan, a peak incidence in the post

monsoon period

5

Papaya extract to treat dengue: A novel therapeutic

option? Annals of medicine 2014

Introduction Continued

Platelet count drops in dengue patients

after the first three days

Gradually increases after the 7th day

OR

Drop further with derangement of other

clotting factors to develop into dengue

hemorrhagic state



6

Introduction to Papaya

Scientific Name Carica Papaya

Has been used since ancient times for the

treatment of a number of disease conditions

Ayurvedic literature reveals that papaya

(Carica papaya) leaf extract has hemostatic

and other medicinal properties

Internet communications revealed the

beneficial effects of papaya leaf extract in

Asian patients



7


The chymopapain and papain extracts of the leaves are useful in the treatment of digestive disorders

The extracts from fruits and seeds have bactericidal properties

The fruit juice and leaf extract have been demonstrated to have anticancer, antioxidative, anti-inflammatory, anti-bacterial, nephroprotective, hepatoprotective, hypoglycemic and hypolipidemic effects

Anti-sickling effect in sickle cell diseasePapaya extract to treat dengue: A novel therapeutic


8


The ripe fruit and seeds have been used against ringworm

The green fruit has been used to lower blood pressure

Green fruits are also used for causing abortions

It is also used in the treatment of chronic skin ulcers

The oral administration of C. papaya seed extract can induce reversible male infertility, hence can be used as contraceptive

The leaf extract has also been shown to have larvi-cidal properties against the Aedes aegyptimosquito

Papaya extract to treat dengue: A novel therapeutic option?

Annals of medicine 2014

9

Papaya Use in Dengue

Recently, crude formulations of papaya leaf

have been successfully employed in folk

medicine in Malaysia, Indonesia, Nepal,

India and Pakistan for the treatment of

dengue infections with hemorrhagic

manifestations

10

Papaya leaves extract capsules on platelets count and hematocrit level in dengue fever

patients, International Journal of Medicinal and Aromatic Plants, Vol. 2, No.4, pp. 573-

578, December 2012

Possible Mechanism

C. papaya L. leaf extracts inhibit

heat-induced and hypo tonicity-induced

hemolysis of erythrocytes

The extracts are likely to possess

membrane-stabilizing properties and

protect blood cells against

stress-induced destruction

Papaya extract to treat dengue: A novel

therapeutic option? Annals of medicine 2014

11

Evidence?

12

Search Engines

Pubmed

Google Scholar

Clinical Key

Cochrane library

Medscape

13

Key words

Carica papaya

Leave extracts

Dengue fever

Hematocrit

Platelets

14

Journal/year

of

publication

Study design

and

population

Methods/

Intervention

Results

Journal: Wien Klin

Wochenschr (2009)

121 [Suppl 3]: 19–

22

Topic: Thrombocyte

counts in mice after

the administration

of papaya leaf

suspension

Objective: to

investigate the

effect of C.papaya

crude leaf material

on the thrombocyte

count in an animal

model

Study Design:

Animal study

Study site: Malaysia

Sample size:

15 white male mice

0.405–0.555 ml of

the CPL suspension

in Palm oil, (15

mg/kg) given to five

mice.

A control group (n =

5) was given the

vehicle(palm oil)

alone.

Another five mice

received

physiological saline

at the same dose

volume

blood were drawn at

0 hr. and thereafter

at 1,

2, 4, 8, 10, 12, 24, 48,

and 72 hours after

dosing in all

animals.

Saline Group: no

Significant

improvement

Palm oil group: Same

progress as saline

CPLJ group:

statistically

significant rise in PLT

with a peak at 4 hours

Conclusion: Results

are significant in

comparison reaching p

values as low as

0.000002, indicating a

potential of papaya

leaf formulations in the

treatment of

Dengue/ITP

15

Journal/year of

publication

Study design

and population

Methods/

Intervention

Results

Journal:Ann Med

Health Sci Res.

2014 May-Jun;

Topic: Papaya

Extract to Treat

Dengue: A Novel

Therapeutic

Option?

Objective:

There is conflicting

reports on the

effectiveness of this

extract in the

treatment of

dengue. A brief

review of available

literature

regarding the use

of the papaya leaf

extract is presented

here

Study Design:

Systemic Review

Study site:

Department of

Pharmacology, Sri

Devaraj Urs

Medical College and

Academy of Higher

Education and

Research, Tamaka,

Kolar, Karnataka,

India

Sample Size:

352

The search was

done independently

by the two authors

using PubMed,

Google and the

library database

and included

relevant articles of

the last 10 years. A

total of 7 studies

were included in

this review, which

were one animal

study, one case

report, three case

series and two

randomized

controlled trials

Papaya extract no

doubt offers a cheap

and possibly effective

treatment for dengue.

However, currently, it

is also necessary

not to rely entirely on

the leaf extract and

ignore standard

treatment for dengue

until the benefits are

established

16

Journal/year of

publication

Study design

and population

Methods/

Intervention

Results

Journal: Evidence-

Based

Complementary and

AlternativeMedicine

Volume 2013

Topic: Carica

papaya Leaves Juice

Significantly

Accelerates the Rate

of Increase in

Platelet Count

among Patients

with DF & DHF

Objective: to

investigate the

platelet

increasing

property of CPLJ

in patients with

dengue fever

Study Design:

Randomized

controlled trial

Sample size: 228

Setting: Infectious

Disease Research

Center, Institute

for Medical

Research, Jalan

Pahang, 50588

Kuala Lumpur,

Malaysia

Half the

inpatients

received juice,

for 3 consecutive

days .

Controls received

the standard

management.

FBC ,monitored

Q8H for 48

hours.

The mean

increase in

platelet counts

were compared

in both groups

Significant increase in

mean platelet count

observed in the

intervention group (𝑃< 0.001) but not in

the control group 40

hours since the first

dose of CPLJ.

Mean platelet count in

intervention group was

significantly higher

than control group

after 40 and 48 hours of

admission (𝑃 < 0.01).

Conclusion: It was

concluded that CPLJ

does significantly

increase the platelet

count in patients with

DF and DHF.

17

Journal/year of

publication

Study design

and population

Methods/

Intervention

Results

Journal: International Journal

of Medicinal and

Aromatic Plants,

Vol. 2, No.4, pp.

573-578, December

2012

Topic:The effect of Carica

papaya leaves

extract capsules on

platelets count and

hematocrit level in

dengue fever

patients

Objective: to

determine the effect

of C-pappaya

leaves extract

capsules in dengue

fever patients.

Study Design:

Randomized

controlled trial

Study site:

Indonesia

Duration: From

November 2011 to

April 2012

Sample size: 80

Subjects

randomized in two

groups

Intervention

Group: 40

Controls:40

550mg CPC,

containing 70%

ethanol extract of

CP leaves.

24 capsules were

given BID to

intervention group

PLT and HCT

were checked twice

daily

Results: There was

accelerated platelet

growth and shortened

hospital stay noted in

intervention group (p

value <0.005)

Conclusion:

CPC could be used as

an additional or

complementary drug in

the management of

Dengue fever

18

Journal/yea

r of

publication

Study

design and

population

Methods/

Intervention

Results

Journal: Kala,

Med Aromat

Plants 2012, 1:6

Topic: Leaf Juice

of Carica papaya

Leaves: A Remedy

of Dengue Fever

Objective: To

investigate the role

of CPLJ in

potentiating

platelet growth in

Dengue fever

patients

Study Design:

Case Series

Setting: Faculty

of Public Health

Sciences ,

University of

Indonesia

Sample size: 05

Home made CPLJ

given two tablespoons

three times a day to 05

patients

Samples before and

after ingestion of juice

taken

The increase in number

of platelets varied from

patients to patients that

ranged from 8000 to

11000. The

dengue patients had

reiterated that there

was a significant

improvement

in their health within

24 hrs. of taking

papaya leaf juice

Conclusion: The juice

of papaya leaves is an

effective herbal therapy

for curing the dengue

fever

19

Journal/year of

publication

Study design

and

population

Methods/

Intervention

Results

Journal: Sri Lankan

Family Physician,

2008, 29, 17-19

Topic: Salutary

effects of Carica

papaya leaf

extract in dengue

fever patients

– a pilot studyObjective:

Find out whether

carica papaya leaf

extract had any

effect on increasing

the lowered platelet

count.

Study Design:

Case Series

Setting:

Family

Physician’s Clinic,

Maharagama Siri

Lanka

Sample size:12

Study included patients

with clinically or

biochemically proven

dengue fever who were

managed as outpatients

They were given a

drink of papaya leaf

extract 5ml doses at an

8 hour interval for

adults and 2.5 ml doses

at an 8 hour interval for

children

<10 years.

PLT, WBC,PCV,ALT

were checked before

and after the intake of

CPLJ ,Samples

repeated second day

too, Patients were

monitored for two

weeks for adverse

effects

12 patients’ platelet and

WBC count improved

Clinical condition

improved. 08 patients

did not have significant

improvement in PCV

and SGPT, 04 patients

had 1/3 reduction in

SGPT, 05 patients with

PLT < 100000 had

itching hemorrhagic

skin rash which

disappeared within two

days of treatment with,

papaya leaf juice

Conclusion:

This pilot study has

shown the effects of

papaya leaf

juice in dengue patients

of elevating the total

white cell counts,

platelet counts and

recovery without

hospital admission. 20

Journal/year of

publication

Study design and

population

Methods/

Intervention

Results

Journal: Asian

Pacific Journal of

Tropical

Biomedicine 2011

Topic: Dengue

fever treatment

with Carica

papaya leaves

extracts

Objectives: to

investigate the

potential of Carica

papaya leaves

againist Dengue

fever in 45 year old

patient bitten by

carrier mosquitoes

Study Design:

Case Report

Setting: Lady

Reading Hospital,

Peshawar Pakistan

Sample size: 01

Age: 45 years

Intervention:

25ml of aqueous

extract Q12H, for

five days

Blood samples

before and after

the extract

administration

taken and

compared

(WBC,PLT)

PLTs increased

from 55 to 168

WBC from 3.7 to 7.7

(After 72 hours)

Conclusion: From

patient feeling and

lab reports it is

appeared that

Carica Papaya

leaves extract

exhibited potential

activity against

dengue fever

21

Critical Analysis

Scientific literature reveals that C. papaya L. leaf extract does have beneficial properties in dengue

Rapid rise in platelets could be attributed to presumed membrane stabilizing properity of Papaya leaves’ extract

One study found that the leaves of papaya plant are rich in several minerals may balance the mineral deficiency caused by the virus and strengthen the immune cells against it

22

Critical Analysis continued:

Picture is not entirely cleared

In most of studies dengue fever is diagnosed on the basis of thrombocytopenia only

Proper diagnosis is mandatory for more convincing evidence

Most of the patients were given crude leave extracts and amount given also differs

The active principle needs to be identified and the dosage standardized to conduct clinical studies on it to prove its efficacy in dengue beyond doubt

23

Critical Analysis Continued

Pharmacokinetic studies need to be conducted

Cheap and possibly effective treatment for dengue

It is necessary not to rely entirely on the leaf extract and ignore standard treatment

Large scale randomized clinical trials in dengue-confirmed patients is necessary to establish their usefulness and safety

Papaya plant also appears to be effective against the Aedes mosquito, so could be used for “Prevention” also

24

Conclusion

25

role of papaya in dengue fever, an evidence based answere

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