Impact of Climate Change on the Dynamic of Disease

EBV, Cancer, Malaria

and Climate Change : pulling the trigger
Sofia Mubarika Haryana
Faculty of Medicine
Universitas Gadjah Mada
28 29 October 2015

Outline
1.
2.
3.
4.

Post MDGs 2015 SDGs 2030

The effect of climate change to health:
Viral related cancer climate effect
Future works :joint forces to better world

1. Post-2015 SDGs 2030

THE WORLD WE WANT

(status: 20 February 2012)

Equity, accesibility, peace, better life and ecosystem

United Nations Development Programme

Where is health in the SDGs?

SDGs 3: Ensure healthy lives and promote
wellbeing for all at all ages : 9 targets that
cover a wide range of health issues, from
maternal and child health to environmental
health
SDG s 7: greater access to energy , increase
the services hospitals and community health
centers
SDGs 13: climate change that change
ecosystems and increase vector borne
diseases.
SDGs 16: Peace and stability will impact the
mental and physical health of communities

2. Climate Change to Health.....

Heat & cold waves:

5,671
climate

15,000 excess deaths in France, 35,000 elsewhere in Europe, triggered

by two weeks of heatwave. Sixty percent of deaths were >75 years
(IPCC, 2007)

Climate - Vector-borne threats Europe

Disease

Vector

Notes

African horse
sickness,
bluetongue

Biting midges

Europe 1998-2010

Canine
leishmanosis

Sand flies

Belgium 2005
(vectors)

Dengue fever

Asian tiger
mosquito

France 2010

Chikungunya
Fever

Asian tiger
mosquito

Italy 2007

West Nile fever

Culicid
mosquitoes

Mediterranean basin: 1990s to

present

Ticks
Crimean Congo
haemorrhagic fever

Spreading in the Balkans

Vector-borne Disease
What is VBD?
Types of VBD transmission:

Human-vector-human
(Anthroponotic Infections)
Humans
Vector

Vector

Animal-vector-human

Humans

(Zoonotic Infections)
Animals
Vector

Vector
Animals

Humans

Lyme disease
Hantaviral disease
Most arboviral diseases (e.g., WNV)

Malaria
Dengue
Yellow fever

Vector-borne Disease Dynamics

Susceptible
population

Migration (forced)
Vector environment

Vector

Pathogen

Survival, lifespan

Survival

Reproduction/breeding patterns

Transmission

Biting behavior

Replication in host

Direct Effects of Climate Change on Vectorborne Disease

Climate change has the potential to

Increase range or abundance of animal reservoirs
and/or arthropod vectors
(e.g., Malaria, Schistosomiasis, Lyme)

Enhance transmission
(e.g., West Nile virus and other arboviruses)

Increase importation of vectors or pathogens

(e.g., Dengue, Chikungunya, West Nile virus)

Increase animal disease risk and potential human

risk
(e.g., Trypanosomiasis)
Greer et al., 2008

Case Study I: Malaria

Case Study I: Malaria (cont.)

40% world population at risk
500 million severely ill
Climate sensitive disease1

Estimated incidence of clinical malaria episodes (WHO)

No transmission where mosquitoes

cannot survive
Anopheles: optimal adult
development 28-32C
P falciparum transmission: 16-33C

Highland malaria2
Areas on the edges of endemic
regions

Global warming El Nio3

Outbreaks
1 Khasnis

2004

and Nettleman 2005; 2 Patz and Olson 2006; 3 Haines and Patz,

McDonald et al., 1957

Malaria Transmission Map

WHO, 2008b

Climate change and malaria

scenario

Hugo Ahlenius, UNEP/GRID-Arendal, 2005

Summary of Climate Change

Effects
Climate change has the potential to
Increase range or abundance of animal reservoirs
and/or arthropod vectors
Lyme, Malaria, Schistosomiasis

Prolong transmission cycle

Malaria, West Nile virus, and other arboviruses

Increase importation of vectors or animal

reservoirs
Dengue, Chikungunya, West Nile virus

Increase animal disease risk and potential human

risk
African trypanosomiasis

Viral related cancers

1. Epstein Barr Virus (EBV) Nasopharyngeal Cancer,
Lymphoma, Non Hodgkin lymphoma, B Cell
Lymphoma, Gastric carcinoma - SALIVA
2. Human Papilloma Virus (HPV) Cervical Cancer - STD
3. HIV sarcoma - STD
4. Hepatitis B virus ( HBV / HCV) Hepatocellular
carcinoma - SALIVA
5. TB / HPV Lung Cancer - STD

http:/www.med.sc.edu:85/virol/herpes.htm

Globocan 2012 Cancer incidence and mortality

HPV
HPV
EBV + Helicobacter Pylorii
HBV

EBV
EBV

HPV + EBV
HPV + EBV

Cancer Facts Globocan 2012

International Agency for Research on Cancer

> 70% death

Epstein Barr Virus NPC

Infect > 90 % population worldwide - Kissing
disease .
DNA virus ( herpes Virus) once infect will
reside the whole life in the infected individu
Infect Epithel oropharynx through gp 21 ( also
express on B lymphocytes) IgG and IgA
Screening strategy ELISA

Etiology of NPC
Epstein-Barr virus
Diet

Tobacco

100%

(Immuno)genetic
factors

NPC

Gender

Environmental
factors

Ethnicity

Herbal
Drugs/
oils

EBV - Nasopharyngeal carcinoma (NPC)

Tumor arising from the epithelial cells covering nasopharyngeal

surface.
Remarkable geographical incidence; frequently occurs in a welldefined regions.
Absolut association to Epstein-Barr virus (EBV) infection - > 90%
population infected worldwide
Non specific symptoms
http://nasopharyngealcancer.com/images/head.jpg; IARC publication; Chang ET & Adami HO. Cancer Epid Biomarkers Prev. 2006.

Nasopharyngeal cancer (NPC)

7th

most prevalent cancer in Hong Kong.

Normal nasopharynx

Problems in clinical management of NPC:-

1. Diagnosis at late stage (at stage 3/4)

2. Frequent relapse (>50% for CR
patients)
Nasopharynx with tumor

Tumor on the right

eustachian cushion
Cho WC. Most common cancers in Asia-Pacific region: nasopharyngeal carcinoma.
In: Cancer report of Asian-Pacific region 2010. 284-289.

Nasopharyngeal carcinoma (NPC) in Indonesia:

Sardjito hospital Yogyakarta : the 1st cancer in man

Non-specific symptoms at early stage
70

85% late stage

(III/IV)

60

0%
3%
0%

50

11%

40
30
20

35%

Male
Female
30%

10
0
01- 11- 21- 31- 41- 51- 61- 71- >80
10 20 30 40 50 60 70 80 yrs
yrs yrs yrs yrs yrs yrs yrs yrs

21%
Stage I

Stage II A

Stage II B

Stage III

Stage IV A

Stage IV B

Figure 10-3 part 1 of 3

The complement receptors (CR2/CD21)

are the EBV receptors on B cells

The regulation of B cell activation by complement receptor

Binding of complement proteins (C3d) to antigens directly or via attached antibodies leads to
coligation of antigen receptors (Ig) and complement receptors (CR2, CD21) on antigen-specific
B cells. This enhances the Ig-mediated signal and the subsequent B cell response.

The EBV viral envelope protein gp350/200, which shares a region

of sequence similarity with C3d, can interact with CR2/CD21

Molecular Diversity of
Epstein-Barr virus IgG
and IgA Antibody
Responses in
Nasopharyngeal Carcinoma:
Jajah Fachiroh1, et al.
J.Infect.Dis 189 (15-06-04)

NPC-STAGE II

NPC-STAGE I
MW (kD)

IgG

56

IgA

IgA

IgG

8 9 16 21

8 9 16 21

106.0
81.0

EA-p138 (138 kD)

47.5

EA(d) (47-54 kD)

VCA-p40 (40 kD)
ZEBRA (36+38 kD)

EBNA1 (72 kD)

TK (65 kD)
DNAse (55+57 kD)

35.5
28.2

VCA-p18 (18 kD)

20.8

NPC- STAGE III

IgG
MW (kD) 14 17 34 43 47

106.0
81.0

47.5
35.5

NPC-STAGE IV
IgA

IgG

3 5 11 19 27 31

14 17 34 43 47
EA-p138 (138 kD)
EBNA1 (72 kD)
TK (65 kD)
DNAse (55+57 kD)
EA(d) (47-54 kD)
VCA-p40 (40 kD)
ZEBRA (36+38 kD)

28.2
20.8

Fig.2

VCA-p18 (18 kD)

IgA
3 5 11 19 27 31

Case: Female caucasian (age 16): T4N1M0

Treatment Chemoradiation + IFN-

> 2 years follow-up

R.Mertens et al. Cancer. (1997);80(5):951-9.

Immunoblot
1

9*
BALF2 (138 kD)
BKRF1 (72 kD)
BXLF1 (68 kD)
BGLF5 (58 kD)
BMRF1 (47/54 kD)
BdRF1 (40 kD)
BZLF1 (36+38 kD)

BFRF3 (18 kD)

Date

Days

1: 12-09-2001
2: 03-12-2001
3: 15-03-2002
4: 17-10-2002
5: 16-12-2002
6: 01-05-2003
7: 02-07-2003
8: 05-11-2003
9: 19-11-2003*

1: 0
2: 82
3: 184 CR
4: 400
5: 460
6: 596
7: 658
8: 784
9: 798* Mx

* Lung metastasis (CT/MRI)

EBV IgA ELISA

ELISA OD 450 value

3 ,5
3 ,0

VCA-p18 peptide
2 ,5

EAd-extract
2 ,0
1,5
1,0
0 ,5
0 ,0

Sample number

EBV-serology predictive
at >6 months pre-metastasis
Note: No increased EBV-DNA in circulation

Best practices ....In Taiwan

In year 2002 EBV/ NPC is the highest in
Taiwan and China
In Year 2012 EBV /NPC is very low ( 2nd
lowest ) WHY ??
Taiwan : good hygiene clean water , healthy
life style

Best Practices : To be C oE in EBV Nasopharyngeal carcinoma

diagnosisi, treatment band prevention in Indonesia
Asia Link (EU ) : 2003 2006
KWF : 2006 - now
Ristek Dikti/ PUPT : 2012 - now

IGR

KI

VUMC & AvL

UGM

From Basic to Clinic Advocacy

Multidiscipline & Integrated

translational approach

UNHAS

From bench to precision medicine

USU

UNUD

UNAIR

UI

UNPAD

UNDIP

UB

Future works
EBV cancer - high burden : EBV + Malaria ( Coinfection?
Joint forces muliti and transdiscipiin
Early screening : Dip stick immunohromatography
based - Early Stage
Minimal Invasive : Cancer Biomarkers ( NPC, Breast,
Ovarial, HCC)
Translational reserach From genomic to proteomics
EBV genome Host genome
Clean water , healthy life style are required :
CAMPAIGN

through synergy to better world..........

Merci ...
Kop kun kap...
Thank you ...
Terima kasih...
Matur nuwun...
FM UGM established 5 March 1946
UGM established on 19 December 1949