Dr,Mohammad Mataro Hingorjo Resident Family Medicine Aga Khan University Karachi Sindh Pakistan

1. Dr.Mohammad Mataro Hingorjo
Resident (IV)
Family Medicine, Aga Khan University Karachi, Sindh 1

2. 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

3. 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

4. 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

5. 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

6. 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
Papaya extract to treat dengue: A novel therapeutic
option? Annals of medicine 2014
6

7. 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
Papaya extract to treat dengue: A novel therapeutic
option? Annals of medicine 2014
7

8. Therapeutic Uses of Papaya
 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 disease
Papaya extract to treat dengue: A novel therapeutic
option? Annals of medicine 2014
8

9. Therapeutic Uses of Papaya
 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 aegypti
mosquito
Papaya extract to treat dengue: A novel therapeutic option?
Annals of medicine 2014
9

10. 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

11. 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

12. Evidence?
12

13. Search Engines
 Pubmed
 Google Scholar
 Clinical Key
 Cochrane library
 Medscape
13

14. Key words
 Carica papaya
 Leave extracts
 Dengue fever
 Hematocrit
 Platelets
14

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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 study
Objective:
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

21. 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

22. 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

23. 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

24. 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

25. Conclusion
25

26. 26