SITI ZUBAIDAH BINTI RAMANOON DVM (UPM), MSC (GUELPH · 2016. 8. 2. · 2.1 Foot and mouth disease 9 2.2 Foot and mouth disease virus 10 2.3 Host range and pathogenesis 13 2.4 Clinical

THE EPIDEMIOLOGY OF FOOT AND MOUTH DISEASE IN MALAYSIA

SITI ZUBAIDAH BINTI RAMANOON

DVM (UPM), MSC. (GUELPH)

THIS THESIS IS PRESENTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY OF

MURDOCH UNIVERSITY, 2016

ii

I declare that this thesis is my own account of my research and contains

as its main content work which has not previously been submitted for

a degree at any tertiary education institution.

Siti Zubaidah Binti Ramanoon

iii

Dedication

This thesis is dedicated to my husband Adriandy Lubis Saparno for his

love and support, and for sharing the pain and joy throughout this

special journey in Australia (and in life); to my beloved son Akasha

Rosman Ehsan as the source of encouragement, inspiration, motivation

and my sweetheart forever.

iv

ABSTRACT

The objectives of the present study were to determine the prevalence of foot and

mouth disease (FMD) and the serotypes of foot and mouth disease virus (FMDV) in

Malaysia; to describe the temporal and spatial distribution of FMD in Malaysia; to

evaluate the risk of the introduction of FMD to Malaysia; to evaluate the effectiveness

of mitigation strategies adopted in Malaysia during outbreaks of FMD; and ultimately

to give recommendations on FMD control to the Malaysia-Thailand-Myanmar (MTM)

Tri-state Commission and Zoning Working Groups.

The first documented outbreak of FMD in Peninsular Malaysia was in the 1860s

and, although there have been periods where no outbreaks have been reported, the

disease is now endemic in Peninsular Malaysia. Serotypes A, O and Asia 1 have been

involved in the outbreaks of FMD in Peninsular Malaysia. In contrast the states of

Sabah and Sarawak, located on Borneo have never had a reported outbreak of FMD.

The virus strains involved in outbreaks in Peninsular Malaysia are closely related to

those in southern Thailand and outbreaks have occurred in both countries at similar

times.

A total of 622 outbreaks of FMD were reported between 2001 and 2011 in

Peninsular Malaysia. Serotype O was responsible for 92% of the 253 outbreaks

serotyped and A in 8%. The number of outbreaks of FMD differed significantly

between years (χ2=621, P

v

months. Outbreaks of FMD in Peninsular Malaysia were most prevalent in Kedah

(n=95). There was a significant correlation between the number of outbreaks and the

average population size of cattle (r=0.731, P=0.007), buffalo (r=0.625, P=0.03) and

goats (r=0.652, P=0.021). Cattle were involved in most outbreaks (87%). The overall

prevalence of clinical disease was highest in cattle (15.4%), followed by buffalo

(9.9%), goats (6.8%), sheep (6.6%) and pigs (6.5%). Cattle (odds ratio, OR=2.6, 95%

CI 2.5, 2.8) and buffalo (OR=1.6, 95% CI 1.4, 1.8) were significantly more likely to

be reported with clinical signs of disease than pigs. The case-fatality rate in cattle was

0.2% and goats 0.5%. The main sources of outbreaks were hypothesised to be the

introduction of new animals or the illegal movement of animals (66% of outbreaks).

A combination of control measures, including ring vaccination, animal movement

management and quarantine, were implemented during outbreaks.

The animal seroprevalence of FMD by the NSP test in cattle, buffalo, goats and

sheep were 24.2% (95% CI: 23.8, 24.6), 52.7% (95% CI: 50.5, 55), 11.8% (95% CI:

11, 12.6) and 9.5% (95% CI: 6.9, 12.6), respectively. These findings indicate natural

infection and provide evidence that the virus was circulating in the livestock

population. Males were 2.2 (OR 95% CI: 2.04, 2.3) times more likely to be NSP

positive than were females. Cattle belonging to the Murrah breed (OR=1.6, 95% CI:

1.3, 2.0) and dairy breeds (OR=1.3, 95% CI: 1.2, 1.5) were more likely to be

seropositive than were meat breeds. The whole peninsula was infected with FMD

(range of point prevalences 6 to 37% in Kuala Lumpur and Kelantan, respectively).

In cattle, the overall seroprevalence based on the liquid phase blocking ELISA

titre (LPBET) (positive titre >45) for type O (n=3025) was 74% (95% CI: 72, 76) and

52% (95% CI: 50, 53) of animals had protective titres (titre > 90). The findings indicate

that, on average, the protective levels of antibody to type O in cattle were below the

vi

recommended level. In imported cattle (n=3295), more than 90% were positive on the

LPBE percentage inhibition (PI) to type O and 49% were NSP positive indicating that

they had been vaccinated and also exposed to a natural infection. This finding

highlights that infected imported cattle may be an important source of FMD outbreaks,

thus livestock consignments should be closely monitored. Based on the results of the

LPBET adequate protective levels were present to serotype O in buffalo but not in

goats, sheep or pigs.

The results from the simulation study for the risk of introduction of FMD via

importation of live cattle from Thailand showed that there is almost a 100% probability

that there will be at least one infectious animal that is capable of transmitting infection

being accepted for importation into Peninsular Malaysia in any given year. The

estimated total number of outbreaks was 26 per year (range: 10-182; 95% CI: 1, 27)

and the probability of outbreaks following effective contact was 92%. This indicates

that importation of live cattle from Thailand is a strong factor contributing to the

likelihood of outbreaks in Peninsular Malaysia. Furthermore, Malaysia is at

continuous risk as long as the importation of live animals continues from infected

countries. To reduce risk, interventions, including pre-arrival testing, vaccination and

improved farm biosecurity, should be adopted on farms, irrespective if the new

animals are from another country or from within Peninsular Malaysia.

In conclusion, FMD is endemic in Peninsular Malaysia and movement of

animals plays a major role in the spread of FMD. The protective level of immunity

induced by vaccination was below the recommended level. Imported live cattle from

Thailand could be infected with FMD and a potential source for introducing new

strains of virus to Peninsular Malaysia. Therefore, studies should be conducted to trace

the farms of origin of these imported cattle. The findings from this study could be used

vii

to improve the existing control strategy for FMD in Peninsular Malaysia thus

ultimately underpinning the MTM FMD Campaign.

viii

Table of Contents

Abstract iv

Table of Contents viii

Acknowledgments xii

List of tables xiv

List of figures xx

List of abbreviations xxv

Chapter 1 Introduction 1

1.1 Background to the study 1

1.2 Aims and objectives of this study 6

1.3 Structure of the thesis 7

Chapter 2 Literature Review 9

2.1 Foot and mouth disease 9

2.2 Foot and mouth disease virus 10

2.3 Host range and pathogenesis 13

2.4 Clinical signs 14

2.5 Subclinical and persistent infections 17

2.6 Economic losses from outbreaks of foot and

mouth disease (FMD)

18

2.7 Epidemiology of FMD 20

2.7.1 Virus survival 20

2.7.2 Transmission 22

2.7.3 Global distribution of FMD 24

2.7.4 Foot and mouth disease in Malaysia 28

2.7.5 Risk factors for FMD 31

2.7.6 Risk assessment for FMD 33

2.8 Diagnosis of FMD 36

2.8.1 Field diagnosis 36

2.8.2 Laboratory diagnosis 39

2.8.3 Types of samples to collect 45

2.9 Treatment 46

2.10 Prevention and control 47

Chapter 3 Foot and mouth disease in Malaysia from the 1860s to

2005

52

3.1 Introduction 54

3.2 Materials and methods 54

3.2.1 Source of data 54

3.2.2 Data management and analysis 55

3.3 Results 57

3.4 Discussion 66

ix

Chapter 4 Outbreaks of foot and mouth disease in Malaysia from

2001 to 2011

72

4.1 Introduction 72


4.2.1 Study design 75

4.2.2 Target and study population 75

4.2.3 Data analysis 76

4.3 Results 78

4.3.1 Distribution of outbreaks of FMD in

Peninsular Malaysia from 2001 to 2011

78

4.3.2 Distribution of outbreaks by month 80

4.3.3 Distribution of outbreaks of FMD in the

states of Peninsular Malaysia

83

4.3.4 Distribution of outbreaks of FMD in

different species

85

4.3.5 Prevalence of FMD 86

4.3.6 Proportion of animals deaths, culled or

slaughtered because of FMD

90

4.3.7 Spread of FMD 91

4.3.8 Control measures instigated for the

outbreaks

93

4.4 Discussion 94

Chapter 5 A retrospective study of serological surveys of foot and

mouth disease conducted in Malaysia (1995 to 2007)

106

5.1 Introduction 106

5.2 Materials and Methods 106

5.2.1 Population at risk 106

5.2.2 Source of data 107

5.2.3 Disease reporting system and diagnosis 108

5.2.4 National FMD control programme 109

5.2.5 FMD tests used 110

5.2.5.1 Liquid phase blocking ELISA

test (LPBE)

110

5.2.5.2 Non-structural proteins 3ABC

ELISA (NSP ELISA)

111

5.2.6 Data analysis 112

5.3 Results 114

5.3.1 Overall 114

5.3.2 Host factors for FMD 121

5.3.2.1 Species-specific and age 121

5.3.2.2 Gender 127

5.3.2.3 Species 129

5.3.2.3.1 Cattle sera and

specific antibodies

132

5.3.2.3.2 Buffalo sera and

specific antibodies

135

5.3.2.3.3 Goat sera and

specific antibodies

136

x

5.3.2.3.4 Sheep sera and

specific antibodies

137

5.3.2.3.5 Pig sera and specific

antibodies

138

5.3.3 Temporal distribution of foot and mouth

disease

139

5.3.3.1 Seasonal pattern of FMDV

infection based on the results of

the NSP test

139

5.3.4 Geographical distribution of foot and

mouth disease in Malaysia

143

5.3.4.1 Distribution of FMD infection

detected by the non-structural

protein (NSP) test in Malaysia

for the period 1995 to 2007

143

5.3.4.2 Distribution of FMDV

antibodies detected by the

liquid phase blocking ELISA

(LPBE) test in percentage

inhibition (PI) and titre, in

Malaysia, 1995-2007

144

5.3.5 Predictive values of NSP test in the

states of Peninsular Malaysia

148

5.3.6 Simultaneous analysis of the results for

LPBE (PI and titre) and the NSP tests of

Peninsular Malaysia, 1995-2007

148

5.3.7 Relationship between the NSP results

and LPBEPI and LPBET to antibodies

against serotype O, A and Asia1

149

5.3.8 Confidence in FMD-free status of

Wilayah Persekutuan Labuan, Sabah

154

5.3.9 Relationship between the NSP positive

and protective level of antibodies in

Peninsular Malaysia

154

5.3.10 Level of antibody protection in

vaccinated animals

160

5.3.11 Evaluation of the results of samples from

imported cattle

160

5.3.12 Evaluation of samples from active

serological surveillance activity

161

5.4 Discussion 161

Chapter 6 Quantitative risk assessment for the introduction of foot

and mouth disease into Peninsular Malaysia via the

importation of live cattle from Thailand

177

6.1 Introduction 177


6.2.1 General approach 180

6.2.2 Identification of hazard and definition of

the unit of analysis

182

xi

6.2.3 Model formulation 182

6.2.4 Definition of distributions for input

variables

186

6.2.4.1 Prevalence of FMD in Thailand

(Prev. Low-High)

186

6.2.4.2 Number of animals imported

(Nimport)

187

6.2.4.3 Number of consignments from

Thailand (Ncons)

187

6.2.4.4 Number of live cattle in each

consignment (N)

188

6.2.4.5 Calculation of the prevalence of

FMD in consignments

188

6.2.4.6 Number of live cattle in the

consignment with clinical signs

(Nclinical)

188

6.2.4.7 Number of “healthy” cattle

detected with clinical signs of FMD

(Nhealthy)

189

6.2.4.8 Number of FMD-infected cattle

not detected by the NSP test (“s”)

189

6.2.4.9 Number of undetected inected

cattle that survived the infection (“s”

new)

189

6.2.4.10 Number of FN cattle that

survived the infection and were

infectious (Ninf)

189

6.2.4.11 Number of animals that were

able to transmit FMD infection to other

cattle on anew farm (Nfinal)

190

6.2.4.12 Number of new infections

(Nnewinf)

190

6.2.5 Relationship between Ninf and Nfinal 191

6.2.6 Comparison of two models with and

without adopting farm-quarantine

191

6.2.7 Model environment and software 191

6.2.8 Sensitivity analysis 192

6.3 Results 192

6.3.1 True prevalence (Ptrue) of FMD in

consignments

192

6.3.2 Summary statistics of the simulations’

results

194

6.3.3 Sensitivity analysis 204

6.4 Discussion 205

Chapter 7 General Discussion 212

References 222

xii

ACKNOWLEDGMENTS

First of all, Alhamdulillah, praise to Allah the Almighty for His blessings in my

life. Secondly, I would like to express my sincere gratitude to my principle supervisor,

Professor Ian Robertson for all that he has taught me about epidemiology, for his

kindness, understanding and support throughout my post-graduate study, and for

always making time, even when he had none, and his kindness to my family; to my

other supervisors: Professor John Edwards for his guidance throughout my study and

appreciate the lively discussion with him on many aspects of FMD particularly in the

context of Southeast Asia (SEA) and as a very important transboundary disease, his

inter-personal relationship with us the international students had made the stay in

Australia more exciting; Associate Professor Dr Latiffah Hassan for her support

throughout the project; and Dr Kamaruddin Md Isa for providing me the data and

networking with the FMD-community in Malaysia. I am also very grateful to Dr Rob

Dobson for his tremendous help with my Chapter 6.

I would like to acknowledge the Civil Service Department then later changed to

the Ministry of Higher Education, and Universiti Putra Malaysia (UPM), for the

financial support throughout the study period. I am also very thankful to the Australian

Biosecurity Cooperative Research Centre (AB-CRC) for the professional scholarship

that had enabled me to attend conferences and workshops.

I am grateful for the help and advice from the former and the current directors

of the national FMD laboratory of Kota Bharu Kelantan of DVS particularly Dr

Mohammed Naheed Mohd Hussein, Dr Azman Shah, and Dr Norlida Othman. The

technical help from En Daud is also acknowledged.

xiii

I would like to thank the Director General of the DVS for the permission to

provide the data for this research, the SEACFMD team in Bangkok: Dr Ronello Abila,

Ms Nicky, and particularly Dr Stephane Forman for the help on the web-based data,

and Dr Banjong Jograkwattana of Thai Department of Livestock Development (DLD)

for his expert opinion. I would also like to thank the members of the Malaysia-

Thailand-Myanmar (MTM) Epidemiological Network (EpiNet) for their commitment

in this network which I believe important in the success of the MTM Campaign.

To my friend Kyaw Naing Oo, I am honoured to know and work with him. The

help and friendship of Pebi, Tum, Jarunee, Acacio, Jim, BicBic, Elaine and Nichole,

are greatly appreciated. Life in Australia was more exciting with the friendship and

moral support from my Malaysian friends: Mawar, Jellie, Aida, Kak Zah, Kak Nyza,

Ain, Ati, Wan Sofiah, and Marina, and also friends at the FPV, UPM.

Lastly, I thank my very dearest family: my mother Marhendon and late father

Ramanoon who had raised me with lots of love and du’a, encouragement, and the

happy moments of childhood despite hardship; to all my brothers and sisters for always

being there for me; to my nephews and nieces who have added more colours to my

life; and finally to my dearest husband Adriandy Lubis for his love, patience, and his

shoulder for me to cry on, and my beloved son Akasha who means so much in our

lives and somehow someway he is one of the reasons for the completion of this thesis.

xiv

List of tables Page

Table 2.1 Summary of sensitivity and specificity of FMD tests 38

Table 2.2 Summary of sensitivity and specificity of FMD tests for

laboratory diagnosis

41

Table 2.3 Summary of sensitivity and specificity of NSP-based

diagnostic tests for FMD

43

Table 3.1 Timing of outbreaks of foot and mouth disease in different

states of Peninsular Malaysia (1909-2005)

60

Table 3.2 Total number of outbreaks (N=34) of foot and mouth disease

in Peninsular Malaysia, and the serotypes involved (1909-

2005)

63

Table 3.3 Distribution of outbreaks of foot and mouth disease in

Peninsular Malaysia by species (1909-2005)

63

Table 3.4 Source of outbreaks recorded from 1860 to 2005 65

Table 3.5 Location of FMD outbreaks in Malaysia recorded from

1860-2005

66

Table 4.1 The population of livestock in the states of Malaysia in 2011 76

Table 4.2 The number of outbreaks of FMD and FMDV serotypes

isolated from outbreaks in Peninsular Malaysia from 2001

to 2011

79

Table 4.3 The association between months and serotypes of FMDV

(2001 to 2011)

82

Table 4.4 Distribution of outbreaks of FMD in Peninsular Malaysia

from 2001 to 2011

83

xv

Table 4.5 The number of outbreaks of FMD in Peninsular Malaysia

with the virus serotypes (2001-2011)

80

Table 4.6 Distribution of the number of outbreaks in different species

of livestock in Peninsular Malaysia (2001-2011)

84

Table 4.7 Distribution of outbreaks in different species and states of

Peninsular Malaysia between 2001 and 2011

85

Table 4.8 The overall prevalence of FMD cases in different species of

livestock in Peninsular Malaysia (2001-2011)

85

Table 4.9 Prevalence and odds ratios of FMD cases between 2001 and

2011 in each susceptible species in Peninsular Malaysia

86

Table 4.10 Average monthly number of cases of FMD in different

species of livestock in Peninsular Malaysia (2001-20011)

88

Table 4.11 Prevalence of FMD in the states of Peninsular Malaysia in

different species (2001-2011)

89

Table 4.12 The percentage of animals dying from FMD, culled because

of disease or being specifically slaughtered due to FMD

(2001-2011)

90

Table 4.13 Epidemiological sources of infection for outbreaks of FMD

in Peninsular Malaysia (2001-2011)

91

Table 4.14 Control measures adopted during outbreaks of FMD in

Malaysia (2001-2007)

92

Table 5.1 Distribution of livestock in Peninsular Malaysia (2006) 107

Table 5.2 Number and percentage of samples from each state tested at

the national laboratory for FMD in Kota Bharu Kelantan

(1995-2007)

115

xvi

Table 5.3 Frequency and percentage distribution of samples by species

and breed that were tested at the FMD laboratory Kota

Bharu Kelantan (1995-2007)

115

Table 5.4 Number of samples processed by the national FMD

laboratory in Kota Bahru Kelantan (1995-June 2007)

117

Table 5.5 Cross-tabulation between age group and NSP test results by

species, with the prevalence (%) and its 95% confidence

intervals (CI)

122

Table 5.6 Descriptive statistics of the results of percentage inhibition

(PI) on the LPBE test for young and adult animals of all

species

124

Table 5.7 Prevalence of FMD virus in adult and young animals based

on LPBEPI (PI>50 as positive)

126

Table 5.8 Relationship between serotypes of FMDV based on LPBE

test results in percentage inhibition (LPBEPI) and antibody

titre (LPBET)

127

Table 5.9 Numbers (95%CI) of male and female animals in Peninsular

Malaysia which were antibody-positive for one or more

serotypes of FMD virus based on LPBEPI

128

Table 5.10 Prevalence and the 95% Confidence Intervals (CI) and the

odds ratios (95% CI) of FMD as determined by the NSP test

in different species and breeds

130

Table 5.11 Frequency and percentage distribution of antibody titres

against serotype O FMDV in cattle (N=3328) according to

the year

133

xvii

Table 5.12 The association between years and seropositivity to FMDV

antibodies type O and the protective level

134

Table 5.13 Reactivity of positive cattle (N=2015) to serotypes O, A, and

Asia 1 (1999-2007)

135

Table 5.14 Distribution of antibody titres against serotype O FMDV in

buffalo (N=123) in 2004 and 2005

136

Table 5.15 Reactivity of positive buffaloes (N=114) to serotypes of

FMDV in 2004 and 2005

136

Table 5.16 Distribution of antibody titres (% prevalence and 95%CI)

against serotype O FMDV in goats (N=120) in 2000, 2004

and 2005 (Missing data for other years)

137

Table 5.17 Reactivity of positive goats (N=54) to serotypes of FMDV

in 2000, 2004 and 2005 (Missing data for other years)

137


sheep (N=42) in 2004 and 2005 (Missing data for other

years)

138

Table 5.19 Reactivity of positive sheep (N=11) to serotypes of FMDV

in 2004 and 2005 (Missing data for other years)

138


pigs (N=54) according to the year

139

Table 5.21 Reactivity of positive pigs (N=6) to 1, 2 or 3 serotypes of

FMDV in 2000 and 2005

139

Table 5.22 Distribution of FMD infection detected by the liquid-phase

ELISA (LPBE) test in (a) percentage inhibition (PI) and (b)

145

xviii

titre, in Malaysia, 1995-2007 expressed as percentage and

the 95% confidence intervals (CI)

Table 5.23 Odds ratio (95% CI) for the association between states of

Peninsular Malaysia and LPBEPI and LPBET to serotype O,

A or Asia 1 (1995-2007)

147

Table 5.24 Relationship between the NSP test, LPBEPI and LPBET for

serotype O, A and Asia 1 tested in livestock in Peninsular

Malaysia (1995-2007)

151

Table 5.25 Summary statistics for the estimated prevalence by beta

distribution of the LPBEPI test on samples from Wilayah

Persekutuan Labuan Sabah

154

Table 5.26 Comparison between protective levels of antibodies to types

O, A and Asia 1 and the NSP tests in Peninsular Malaysia,

1995-2007

157

Table 5.27 Cross-tabulation of test results of liquid-phase blocking

ELISA (LPBE) based on the titre and the non-structural

protein (NSP) 3ABC for FMDV antibody detection in

vaccinated animals (n=222)

160

Table 6.1 Equations, assumptions, and sources of information used to

formulate and to parameterize a model to assess the risk of

the introduction of FMD virus into Peninsular Malaysia

183

Table 6.2 Summary statistics for the true prevalence of FMD in

consignments resulting from simulations performed using

hypothetical data

192

Table 6.3 Summary statistics from the model 193

xix

Table 6.4 Comparison of the summary statistics between the two

models that considered farm-quarantine versus no farm-

quarantine

202

Table 6.5 Sensitivity analysis of the effect of prevalence of FMD in

Thailand in a year (Prev. Low-High) on Nfinal and Nnewinf

203

xx

List of figures Page

Figure 3.1 Zones defined in accordance with the minimum

Standard Definitions and Rules for control and

eradication of FMD in the MTM Peninsula (DVS Plan:

Control Zone, Proposed Eradication Zone)

53

Figure 3.2 Number of outbreaks of foot and mouth disease in

Malaysia from 1860 to 2005

55

Figure 3.3 The number of outbreaks of foot and mouth disease and

serotype of FMD virus in Peninsular Malaysia, 1909-

2005

56

Figure 3.4 Percentage of outbreaks of FMD in Peninsular

Malaysia (N=34) caused by different virus serotypes

(1909-2005)

60

Figure 3.5 Distribution of outbreaks of foot and mouth disease by

species and year, in Peninsular Malaysia (N=168)

(1860-2005)

62

Figure 4.1 Distribution of FMD outbreaks in Peninsular Malaysia

from 2001 to 2011

77

Figure 4.2 Distribution of outbreaks of FMD in Malaysia, by

month of report (2001-2007)

78

Figure 4.3 Relationship between the monthly total number of

outbreaks, (A) mean temperature (ºC), and (B) mean

monthly rainfall (mm) during the 2001-2011 period

79

Figure 4.4 Distribution of outbreaks of FMD in Peninsular

Malaysia between 2001 and 2011

80

xxi

Figure 4.5 Average monthly prevalence of FMD cases in buffalo,

cattle, goats, pigs and sheep (2001-2011)

85

Figure 5.1 Distribution of FMDV antibodies in all samples based

on LPBE test results in percentage inhibition (PI) for

serotypes O(N=72,326), A(N=71,625) and Asia

1(N=72,245)

117

Figure 5.2 Distribution of antibody titre based on LPBE test for

FMDV serotypes O (N=3477), A(N=3497) and Asia 1

(N=3506)

118

Figure 5.3 Boxplot for the LPBEPI for serotypes O, A, and Asia 1

for all processed samples (*, **, *** indicate

significant difference between serotypes at P

xxii

June=4495, July=5284, Aug=2807, Sept=4179,

Oct=3802, Nov=3802, Dec=7962, Overall=65207)

Figure 5.7 Distribution of NSP positive in percentages by month

and year from 1995 to 2007, and the relationship with

the monsoon seasons (Southwest monsoon, May-Sept;

Northeast monsoon, Nov-Mac; Inter-monsoon season-

March, April and October), cultural (the Chinese New

year) and religious festivals (Eid-Fitri and Eid-Adha)

141

Figure 5.8 Prevalence (%) of FMD based on NSP positive in

Peninsular Malaysia between 1995 and 2007

142

Figure 5.9 Comparison of the results between LPBEPI (N:

O=47,128; A=47,162), LPBET (N: O=3,034, Asia

1=3043) and NSP tests performed on samples

submitted by the states of Peninsular Malaysia to the

national FMD laboratory, Kota Bharu Kelantan, 1995-

2007

148

Figure 6.1 Scenario tree for the risk assessment model of FMD for

Peninsular Malaysia resulting from the importation of

live cattle (Description of the parameters are displayed

in Table 6.1)

181

Figure 6.2 Frequency (A) and cumulative probability (B)

distribution for FMD prevalence in consignments of

live cattle in a year for movement into Peninsular

Malaysia

193

xxiii


distribution for the total number of clinically infected

cattle removed (Nclinical) from the consignments each

year

194


distribution for the total number of apparently healthy

live cattle that were accepted (Nhealthy) in a year into

Peninsular Malaysia

195

Figure 6.5 Frequency distribution of the total number of FMD-

infected cattle (“s”) that entered Peninsular Malaysia

each year

196


distribution of the total number of FMD-infected cattle

were test negative and survived infection (“s” new) that

entered Peninsular Malaysia each year

197


distribution of the total number of undetected FMD-

infected cattle that survived infection and were

infectious (Ninf) that were accepted for entry into

Peninsular Malaysia per year

198


distribution of the total number of undetected FMD-

infected cattle that survived infection and were

infectious and established effective contact (Nfinal) in

the new herd in Peninsular Malaysia

199

xxiv


distribution of the total number of new infections of

FMD in Peninsular Malaysia following effective

contact between infected and infectious imported cattle

and susceptible animals (Nnewinf)

200

Figure 6.10 A scatter plot of the relationship between the number of

imported cattle that are able to establish effective

contact, Nfinal, and the number of infectious cattle,

Ninf

201

Figure 6.11 A scatter plot of the relationship between the number of

imported cattle that were able to establish effective

contact, Nfinal and the number of infectious cattle,

Ninf, when farm quarantine was not applied

203

xxv

List of abbreviations

AB-CRC Australian Biosecurity Cooperative Research Centre

ACI Average cumulative incidence

ANOVA Analysis of variance

AP Apparent prevalence

CI Confidence intervals

DLD Department of Livestock Development

DVS Department of Veterinary Services of Malaysia

ELISA Enzyme-linked immunosorbent assay

EpiNet Epidemiological Network

FMD Foot and mouth disease

FMDV Foot and mouth disease virus

FN False negative

FP False positive

HPAI Highly pathogenic avian influenza

LPBE Liquid phase blocking ELISA

LPBEPI Liquid phase blocking ELISA percentage inhibition

LPBET Liquid phase blocking ELISA titre

Max Maximum

ME-SA Middle East-South Asia

Min Minimum

MOU Memorandum of Understanding

MTM Malaysia-Thailand-Myanmar

NPV Negative predictive value

NSP Non-structural protein

xxvi

OIE Office Internationale des Epizooties

OR Odds ratio

PCR Polymerase-chain reaction

PDR Lao People’s Democratic Republic

PPV Positive predictive value

RCU Regional Coordinating Unit

RNA Ribonucleic acid

SAT South African Territories

Se Sensitivity

SE Standard error

SEA Southeast Asia

SEAFMD Southeast Asia Foot and Mouth Disease

SEACFMD Southeast Asia China Foot and Mouth Disease

SD Standard deviation

Sp Specificity

SPSS Statistical Software for Social Sciences

SVD Swine Vesicular Disease

TCID50 Tissue culture infective dose 50

UK United Kingdom

USD United States Dollar

VNT Virus neutralization test

VP Viral protein

WRL World Reference Laboratory for FMD

χ2 Chi-squared

1

Chapter 1

Introduction

1.1 Background to the study

Despite the advances in the understanding of viral pathogenesis and the

development of vaccine technology, foot and mouth disease (FMD) remains a major

threat to the world economy (Kitching, 2005). The disease is endemic in many areas

of Africa, Asia and South America, and the infection has a remarkable ability to spread

over long distances and to cause epidemics in previously free areas, as was seen in the

2001 epidemic in the United Kingdom (UK), France and the Netherlands and in the

outbreaks in South Korea and Japan in 2000 (Knowles et al., 2001b).

The impact of FMD in affected countries can be significant. In endemic

countries FMD causes loss of productivity in adult animals and high mortality in

young stock, however the major impact of the disease is the constraint on the

international trade of livestock and animal products (Geering et al., 1995). Countries

previously free of the disease suffer trade restrictions and severe economic

consequences when outbreaks occur (Samuel and Knowles, 2001a). Estimates of the

cost of disease outbreaks have ranged from $US30 million to $US29.1 billion (Vosloo

et al., 1992; Thomson, 1995; Yang et al., 1999; Paarlberg et al., 2002; Kao, 2003).

Foot and mouth disease is a highly contagious viral disease of cloven-hoofed

domesticated animals, such as buffalo, cattle, goats, sheep and pigs (Alexandersen et

al., 2002a; Kitching et al., 2005), and wild animals such as kudu (Tragelaphus

strepsiceros), impala (Aepyceros melampus), warthog (Phacochoerus africanus),

bush pigs (Potamochoerus larvatus) (Hedger et al., 1972) , eland (Taurotragus spp.),

waterbuck (Kobus ellipsiprymnus), sable (Martes zibellina) (Anderson et al., 1993),

gazelles (Gazella spp.) (Nyamsuren et al., 2006), wild deer (family Cervidae)

2

(Kitching et al., 2005), and feral pigs (family Suidae) (Doran and Laffan, 2005; Ward

et al., 2007).

Foot and mouth disease is caused by a virus belonging to the Apthovirus genus

of the family Picornaviridae (Belsham, 2005; Domingo et al., 2005). Seven serotypes

of FMD virus (FMDV) (A, O, C, Southern African Territories (SAT) 1, SAT 2, SAT

3, and Asia 1) have been classified (Brown, 2003). There is no difference in the clinical

disease induced by each serotype (Alexandersen and Mowat, 2005; Kitching, 2005).

To date, more than 60 subtypes have been reported, with between 3 and 31 subtypes

per serotype (Knowles and Samuel, 2003).

The mode of disease transmission is usually associated with the movement of

infected animals and their contact with susceptible animals (Mahy, 2005). Animals

shed virus in all their secretions and also in exhaled air (Alexandersen and Mowat,

2005). Other methods of disease spread include the aerosol route and mechanically by

veterinarians, motor vehicles and other fomites (Mahy, 2005). Cattle, sheep, goats and

other ruminant species that have recovered from FMD, and those that have been

vaccinated against FMD and subsequently exposed to live virus prior to effective

immunity is developed, may become carriers of the virus (Salt, 2004; Doel, 2005).

The characteristic signs of FMD in different livestock species may include fever

and vesicles with subsequent erosions in the mouth, nares, muzzle, feet and teats

(Mahy, 2005). The stomatitis causes excess salivation, lip smacking and cessation of

eating, and rapid weight loss; whereas foot lesions are accompanied by acute lameness

and reluctance to move (Donaldson, 2004). The average mortality from FMD is about

1%, however the morbidity is close to 100% (Mahy, 2005). The disease is milder in

pigs, sheep and goats although abortions may occur, and these species act as reservoirs

from which the disease may spread to cattle (Mahy, 2005).

3

The most conclusive evidence of infection is isolation of live FMD virus,

however sometimes this is not possible (Kitching, 2005). Epithelial samples, whole

and clotted blood, probang samples, and samples of heart muscle from dead young

animals from suspected FMD cases may be used for virus isolation (Kitching, 2005).

Antigen detection tests, including Enzyme Linked Immunosorbent Assays (ELISA)

(Morioka et al., 2009; Longjam et al., 2011) and polymerase chain reaction (PCR)

(Reid et al., 2002; Longjam et al., 2011), can be used to serotype the virus. By

sequencing the viral genome the origin of the circulating virus may be determined

(Kitching et al., 1989b). The gold standard test for detecting antibodies to viral

antigens is the virus neutralization test (VNT)

(http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.05_FMD.pdf,

Accessed 28 March 2013). The VNT has been replaced for routine serology by the

liquid-phase blocking ELISA (LPBE) and subsequently by the solid phase competition

ELISA (SPCE)

(http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.05_FMD.pdf,

Accessed 28 March 2013). Several diagnostic tests developed to differentiate

antibodies induced by natural infection from those stimulated by vaccination are based

on the absence of non-structural proteins (NSP) (Boyle et al., 2004; Clavijo et al.,

2004). A multiplex bead immunoassay that uses a single sample taken from

experimentally infected and vaccinated cattle for the detection of NSP has also been

developed (Clavijo et al., 2006).

Foot and mouth disease is a major constraint to international trade of livestock

and animal products (Alexandersen and Mowat, 2005). Control of the disease in

countries which are FMD-free without vaccination includes exclusion and slaughter

policies. However, emergency “suppressive” vaccination is now an acceptable

http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.05_FMD.pdfhttp://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.05_FMD.pdf

4

alternative (Bouma et al., 2003; Backer et. al, 2012; Porphyre et al., 2013). A ban on

the movement of all livestock, culling of infected herds, pre-emptive culling of

livestock within an area of one km around an outbreak, zoo-sanitary measures and

screening activities have been used to control outbreaks (Bouma et al., 2003). In

Southeast Asian (SEA) countries, where FMD is endemic, control approaches involve

regulatory and quarantine measures, management of animal movements and

vaccination programs (Gleeson, 2002). The identification of market chain of livestock

and critical points within those market chains in Greater Mekong Sub-Region

countries were indicated for intervention measures to reduce the transmission of FMD

targeting the disease at source such as storage depots, transaction areas, slaughter

houses, areas with high numbers of livestock traders, livestock entry points at border

areas and livestock markets (Cocks, 2009b).

A more advanced approach in FMD control using mathematical and statistical

models has been developed. Disease modelling has been used as a tool to study

diseases such as FMD to better understand potential disease spread and control under

different conditions (Garner and Beckett, 2005). Outputs from such models are a

valuable resource to assist with policy development and disease management (Garner

and Beckett, 2005). Accurate epidemiological models can be useful tools for

determining relevant control policies for different scenarios and, conversely,

inaccurate models may interfere with effective disease control (Kitching et al., 2005).

Few studies have been conducted on FMD in Peninsular Malaysia. Regular

sporadic outbreaks of FMD since 1992 have been reported (Palanisamy et al., 2000)

but they were restricted to the northern states of Peninsular Malaysia near the Thai

border (Idris, 1995). However from 2000 outbreaks have occurred throughout the

peninsula (Rozanah, 2003). The illegal importation of cattle from FMD-infected areas

5

in Thailand into Malaysia for breeding and slaughter was believed to be the source of

these outbreaks (Ghan, 1993). Disease subsequently spread through: direct contact

between infected and susceptible livestock in common grazing areas; holding of cattle

in slaughter areas; and unauthorised inter-district movements (Ghan, 1993). A study

on cross-border movement pathways of large ruminants in SEA recognized that

Peninsular Malaysia as one of the main markets with Central Myanmar as an important

source and Thailand as a transit country (Cocks et al., 2009a) driven by high demand

and price. Thus, this fact indicates that transboundary livestock movement could be a

major risk factor for FMD in Peninsular Malaysia. Sabah and Sarawak, located on

Borneo Island, have never recorded FMD and in May 2004 the OIE recognized Sabah

and Sarawak as FMD-free without vaccination (Edwards, 2004).

Before adequate laboratory diagnostic facilities existed in Malaysia, samples

were submitted to the World Reference Laboratory (WRL), Pirbright, UK to confirm

the clinical diagnosis (Ghan, 1993). Nowadays, the national FMD laboratory in Kota

Bahru, Kelantan is the reference laboratory for the country and is capable of

conducting LPBE to confirm the serotypes involved in outbreaks and NSP-ELISA

tests to differentiate naturally infected from vaccinated animals. Polymerase-chain-

reaction tests are also being used for antigen detection from epithelial tissue samples

(J. Senawi, Personal Communication, 2013). Some samples are still sent to the WRL

for subtyping and genotyping (MHM Naheed, 2012,

www.oie.int/doc/ged/D11971.pdf, Accessed on 28 March 2013).

Control measures adopted in Malaysia include restriction of animal movements,

vaccination and supervised slaughter. Clinically infected animals are destroyed (Ghan,

1993) and mass vaccination targeting ruminants in the high-risk areas has been carried

out (Anum, 2003). Recently, the control measures for FMD adopted have included

http://www.oie.int/doc/ged/D11971.pdf

6

import control, management of animal movements, strategic vaccination, legislation,

disease investigation and outbreak index management, surveillance, public awareness

campaigns and disease reporting (www.oie.int/doc/ged/D11971.pdf, Accessed on 28

March 2013).

In late 1997, SEAFMD 2020 was established by the OIE in Bangkok, Thailand.

This plan provided a roadmap for FMD freedom with vaccination by 2020 in Southeast

Asia (OIE-SEAFMD, 2007). Economic studies to assess the SEAFMD control and

eradication plan in Thailand, Laos and the Philippines indicated a positive financial

effect of eradicating the disease from these countries (Perry et al., 1999; Perry et al.,

2002; Randolph et al., 2002). The Malaysia-Thailand-Myanmar (MTM) Peninsular

Campaign for FMD was established on the 6th November 2003. This program was

designed to progressively establish a free zone on the MTM Peninsular

(http://www.seafmd-

rcu.oie.int/documents/SEAFMD%202020%20WEB%20Version.pdf, accessed on 28

March 2013). Recent report on dynamic cross-border movement of livestock within

the region further emphasised the need for regional programs with strong cooperation

between neighbouring countries (Cocks, 2014).

In conclusion, the successful control and eradication of FMD remains a

challenge for infected countries. In Malaysia, Peninsular Malaysia is infected,

although little research has been conducted on the epidemiology of FMD in this region

of the country. The research reported in this thesis was undertaken to address this

knowledge deficiency.

1.2 Aims and objectives of this study

It is vital for Malaysia to have an effective programme to be able to control and

eradicate FMD efficiently and successfully. The current control strategies are thought

http://www.oie.int/doc/ged/D11971.pdfhttp://www.seafmd-rcu.oie.int/documents/SEAFMD%202020%20WEB%20Version.pdfhttp://www.seafmd-rcu.oie.int/documents/SEAFMD%202020%20WEB%20Version.pdf

7

to be inadequate. Furthermore, there is little published information on the

epidemiology of FMD in Malaysia. Therefore, the present study was carried out with

the aims to provide a comprehensive report on the epidemiology of FMD in Malaysia,

particularly Peninsular Malaysia, and to evaluate the risk of FMD entering and

spreading in the country through a number of pathways. In-depth knowledge and

understanding of the epidemiology and the risk of FMD in Peninsular Malaysia is

needed to establish more effective disease control and prevention programs.

The specific objectives of the study reported in this thesis were to:

1. Describe the occurrence of FMD outbreaks based on historical reports of

outbreaks between 1986 and 2005.

2. Describe the outbreaks of FMD in Peninsular Malaysia between 2000 and 2011.

3. Identify the serotypes of FMDV involved in outbreaks.

4. Determine the seroprevalence of antibodies against FMDV.

5. Describe the distribution of FMD with regards to host, time and location.

6. Evaluate the risk of the introduction and spread of FMD through the importation

of live cattle from Thailand.

Ultimately, the findings from this research may be used to generate

recommendations for the MTM Tri-state Commission and Zoning Working Groups

for the FMD Eradication Campaign.

1.3 Structure of the thesis

There are seven chapters in this thesis. Chapter 1 introduces the research

problems, and outlines the aims and scope of the study and its limitations. In Chapter

2 the literature is reviewed and general and specific topics relevant to the virus, the

disease, its distribution, economic losses, epidemiology, diagnosis, control and

prevention, and finally, risk assessment are discussed. In Chapter 3 historical reports

8

of FMD in Malaysia are analysed and discussed. In Chapter 4 the findings from a

retrospective study of FMD in Peninsular Malaysia are discussed. This involved

analysing data from field outbreaks from 2000 to 2011. These data were obtained from

the Disease Control Unit, Department of Veterinary Services (DVS, 2008)

Headquarters at Putrajaya, Malaysia, and from the website of the OIE Regional

Coordinating Unit (RCU) Bangkok for SEAFMD Control (http://www.seafmd-

rcu.org). In Chapter 5 existing data from the national FMD laboratory Kota Bharu,

Kelantan, Malaysia are analysed and discussed. This is followed by Chapter 6 which

reports on a quantitative risk assessment for the introduction and spread of FMD in

Peninsular Malaysia through the importation of live cattle from Thailand. To assess

the risk, scenario trees were developed to determine risk pathways. Expert opinions

were obtained and literature searched to estimate the probabilities used in the models.

Stochastic models were developed and simulations were run using the software

program PopTools. In Chapter 7 the whole study, together with the research

constraints, recommendations, suggestions on future studies on FMD and finally the

conclusions, are discussed.

In the following chapter the literature relevant to the research topic and

objectives of the present study are reviewed.

http://www.seafmd-rcu.org/http://www.seafmd-rcu.org/

9

Chapter 2

Literature Review

2.1 Foot-and-mouth disease

Foot and mouth disease is an acute vesicular disease of cloven-hoofed animals

such as cattle, pigs, sheep, goats, buffalo (Alexandersen et al., 2002a; Kitching et al.,

2005), camels (Wernery and Kaaden, 2004; Shiilegdamba et al., 2008) and various

wildlife species such as African buffalo (Syncerus caffer) (Bastos et al., 2001; Vosloo

et al., 2006; Vosloo et al., 2007), antelope (Hargreaves et al., 2004), kudu, bush pigs,

warthog (Hedger, 1972), impala (Aepyceros melampus) (Bastos et al., 2001; Vosloo

et al., 2002; Hargreaves et al., 2004; Vosloo et al., 2006), eland (Taurotragus oryx)

(Paling et al., 1979; Ferris et al., 1989; Anderson et al., 1993), waterbuck (Anderson

et al., 1993), sable (Ferris et al., 1989; Anderson et al., 1993), gazelles (Shimshony et

al., 1986; Shimshony, 1988; Nyamsuren et al., 2006), wild deer (Kitching et al., 2005;

Ward et al., 2007), and feral pigs (Doran and Laffan, 2005; Ward et al., 2007). It is

highly contagious and there is rapid onset of disease. The incubation period can be as

short as 24 hours or up to 14 days, depending on the strain and dose of virus, route of

infection, species involved and the husbandry conditions (Gailiunas and Cottral, 1966;

Alexandersen et al., 2003c). The characteristics of FMD include an acute febrile

reaction and vesicles formation in and around the mouth and on the feet (Alexandersen

et al., 2003c). Animals may show lameness, arched back, reluctance to walk or stand,

and inappetance (Alexandersen et al., 2003c). The acute phase lasts for approximately

7 to 10 days (Grubman and Baxt, 2004). An antibody mediated immune response

results in clearance of the infection from most infected animals (Radostits et al., 2007).

10

2.2 Foot-and-mouth disease virus

The first written description of FMD probably occurred in 1514, when

Fracastorius described a similar disease of cattle in Italy. Almost 400 years later, in

1897, Loeffler and Frosch demonstrated that a filterable agent caused FMD.

The aetiological agent of FMD is a virus belonging to Picornaviridae family,

genus Apthovirus. This virus consists of a single-stranded, plus-sense ribonucleic acid

(RNA) genome of approximately 8,500 bases surrounded by four structural proteins

to form an icosahedral capsid (Rueckert, 1996) with no envelope, and is approximately

22-30 nm in diameter (Domingo et al., 2002). The virus is acid-labile and is unstable

below pH 6.8. The genomic RNA contains a variable length of 100-400 nucleotides.

The virus invades host cells and reprograms the cell to produce more virus. The

FMDV RNA molecule codes for 12 viral proteins: L, 1A, 1B, 1C, 1D, 2A, 2B, 2C,

3A, 3B, 3C and 3D. Proteins 1A (VP4), 1B (VP2), 1C (VP3) and 1D (VP1) make up

the protein shell (capsular or structural proteins) (Knowles and Samuel, 2003). Other

viral proteins are involved in replicatory functions and influencing host cell

functionality and are termed non-structural proteins (NSPs). Purification of structural

components of the virus should separate NSPs from the structural proteins. It is

common for traces of NSPs to be retained, particularly the protein 3D (Knowles and

Samuel, 2003). This is important for diagnostic purposes because it differentiates

between vaccinated and naturally infected animals. In naturally infected animals, the

NSP ELISA tests will detect the antibodies to the non-structural components from the

virus, thus giving positive results. In vaccinated animals, because of no viral

replication, they develop antibodies to the structural proteins of the virus present in

the viral capsid and there is no expression of the NSPs and the animal will not develop

11

antibodies to these proteins (Kitching, 2002b). Therefore, the NSP test will give

negative results in vaccinated animals.

There are seven immunologically distinct serotypes of FMDV namely A, O, C,

Asia 1, Southern African Territories (SAT)1, SAT2, and SAT3 (Samuel and Knowles,

2001a). Serotype O was named for Oise in France and type A for Allemagne

(Germany), type C as an additional type in Germany; whereas SAT1, SAT2, and SAT3

were isolated from South African outbreaks (Bachrach, 1968; Mahy, 2005). There is

considerable antigenic variability within the seven serotypes. Over 60 subtypes have

been described and new subtypes arise continuously as a result of a high mutation rate

and possibly RNA recombination (Domingo et al., 2002; Knowles and Samuel, 2003).

Non-structural proteins are more highly conserved since these proteins are essential

for replication and changes are more likely to be lethal. An animal that is immune to

one serotype is still susceptible to infection with another serotype and animals immune

to one strain (subtype) may still be susceptible to infection with another strain

(Knowles and Samuel, 2003). The antigenic diversity and lack of cross-protection

means that a number of vaccine strains are required even within one serotype. It is

necessary to monitor the appearance of new strains consistently to ensure available

vaccines are protective. Antigenic variation within a serotype can be such that vaccines

must be carefully matched to outbreak strains to ensure efficacy (Samuel and Knowles,

2001a). These characteristics have made laboratory diagnosis and control of FMD

more challenging than many other viral diseases.

Foot and mouth disease viruses are further divided into genotypes based on

comparison of VP1 sequence data. By genotyping, it has been possible to group many

FMDVs based on their geographic origin and these are referred to as “topotypes”.

Based on nucleotide sequence analysis, the seven serotypes of FMDV have been

12

shown to be clustered into distinct genetic lineages with approximately 30-50%

differences in the VP1 genes (Knowles and Samuel, 2003). Using these techniques,

they have also been able to unequivocally show the pandemic spread of a FMDV type

O pandemic strain (also called PanAsia strain) through the whole of Asia, Middle East,

Africa and Europe (Knowles et al., 2005). The virus that caused the UK outbreak was

first detected in 1990 in India and rapidly spread both eastward and westward. In

another comprehensive study of FMD type O strains it was demonstrated that strains

could be grouped into eight topotypes based on nucleotide differences of up to 15%.

In the 1997 Taiwan outbreaks in pigs, type O Cathay topotype strain was shown to be

very virulent for pigs but lacked virulence in cattle due to an altered 3A protein

(Knowles et al., 2001a). In the case of the SAT serotypes, the level for inclusion within

a topotype was raised to 20% since the VP1-coding sequence of these viruses appears

to be more inherently variable than other serotypes (Samuel and Knowles, 2001a). An

Argentinean study analysed complete or partial VP1 sequences of 31 FMDV

belonging to serotypes A, O and C to determine the genetic relatedness of field strains

of FMDV that had circulated in Argentina between 1961 and 1994. It was found that

FMD type A strains showed the highest genetic heterogeneity and could be divided

into five lineages with a sequence divergence of 0.9–18.5% between strains. Most of

the FMD type O viruses were grouped into two clusters (within cluster sequence

divergence ranging from 0.2 to 6.0%), and FMD type C viruses were grouped into two

clusters with a 13.4% nucleotide sequence divergence between each cluster (Konig et

al., 2001). An increased understanding of how FMDV strains move between

geographical regions will play a pivotal role in the development of future disease

control strategies.

13

2.3 Host range and pathogenesis

All cloven-hoofed animals, including cattle, sheep, goats, buffaloes and wild

ruminants and pigs, can be affected by FMD (Kitching and Hughes, 2002;

Alexandersen and Mowat, 2005). Under field conditions susceptible animals may be

infected by FMDV directly or by indirect contact with infected animals or an infected

environment. When animals are close together the transfer of airborne droplets and

droplet nuclei (aerosols) from the breath of infected animals to the respiratory tract of

recipient animals is probably the most common form of transmission. The virus also

may gain entry into susceptible hosts through damaged integument. Long-range

airborne transmission of virus is uncommon but important under certain conditions.

Sometimes, other factors, together with route of infection, are important factors for

FMD transmission including animal species, the number of the excreting and inhaling

animals and favourable topographical and meteorological conditions. The

pathogenesis of FMD has been studied mainly in cattle and pigs (Thomson et al.,

2003). Infection in pigs is usually through the oral route (Kitching and Alexandersen,

2002). Infection in other susceptible animals usually occurs by inhalation and the

initial site for virus replication is believed to be the lung bronchioles (Brown et al.,

1996) and mainly in the pharynx for cattle (Geering et al., 1995). The virus then

spreads via the bloodstream to epithelial cells. In infected animals FMDV is

disseminated to many epidermal sites, but lesions only develop in areas subject to

mechanical trauma or physical stress (Gailiunas and Cottral, 1966; Thomson et al.,

2003). Vesicles develop at multiple sites (mostly feet and tongue), and are usually

preceded by fever. The incubation period is generally between two to eight days

(sometimes 1 - 14 days), depending on the infectious dose, the strain of virus, route of

infection and mechanism of infection (Donaldson, 2004).

14

2.4 Clinical signs

In Bovidae, the first indication of the disease is fever (often above 40◦C), severe

depression, excessive salivation, lameness, inappetance and decreased milk

production (Kitching, 2002a; Donaldson, 2004; Klein, 2009). This is followed within

a day or so by the development of vesicles, the predilection sites for which are the

tongue, lips, gums, dental pad, interdigital skin of the feet, coronary bands, bulbs of

the heels and teats (Kitching, 2002a). Occasionally, vesicles appear inside the nostrils

or on the muzzle or vulva (Kitching, 2002a). The lesions begin as small hyperaemic

foci at one or more of these sites. These very quickly progress to vesicles, which are

initially 1-2 cm in diameter but rapidly enlarge and coalesce (Kitching, 2002a). They

are filled with a clear straw-coloured fluid and their overlying epithelium is blanched

(Kitching, 2002a). The vesicles rupture within 24 hours to leave raw, painful ulcers

surrounded by ragged tags of necrotic epithelium. In the mouth, vesicles are

particularly prominent on the tongue, dental pad and buccal mucosa (Kitching, 2002a).

In severe cases, most of the mucosa of the dorsal surface of the tongue may slough.

The painful stomatitis associated with intact and freshly ruptured vesicles leads to

excess salivation, lip smacking and animals stopping eating (Kitching, 2002a). There

is rapid loss of body weight (Kitching, 2002a). In uncomplicated cases, mouth lesions

heal quite rapidly within a 10-day period and eating may resume within a few days of

rupture of the vesicles (Kitching, 2002a). Foot lesions are accompanied by acute

lameness and reluctance to move (Kitching, 2002a). Secondary infections may lead to

severe involvement of the deeper structures of the foot (Kitching, 2002a). Teat lesions

may also be complicated by secondary mastitis (Kitching, 2002a). Although there is a

high morbidity rate of up to 100% (Spickler et al., 2010), the mortality rate in adult

animals is generally less than 5% (Geering and Lubroth, 2002; Spickler et al., 2010),

15

although it can be above 90% in young animals (Spickler et al., 2010). Young animals

may die due to myocardial necrosis (Gulbahar et al., 2007). There is often a prolonged

convalescence with significant reduction in milk production and weight loss, and

reduced draught power (Gulbahar et al., 2007). Long-term sequelae may include foot

deformities and permanent damage to the udder. Occasionally, endocrine gland

damage leads to a chronic ‘panting’ syndrome characterised by dyspnoea and ill-thrift

(Ghanem and Abdel-Hamid, 2010). Infection of very young calves may cause sudden

death, without vesicular lesions, as a result of cardiac lesions and this is associated

with high mortality (Kitching and Alexandersen, 2002; Kitching and Hughes, 2002;

Donaldson, 2004). The clinical signs of FMD in native breeds of cattle in endemic

areas are usually milder than those described above (Geering et al., 1995; Kitching,

2002a; Kitching et al., 2005).

In pigs, the early signs include lameness, fever, depression and anorexia

(Donaldson, 2004). The most pronounced vesicles are on the feet. These vesicles cause

acute lameness, pain, recumbency and reluctance to move, particularly if the pigs are

housed on a hard floor (Donaldson, 2004). However, the disease is sometimes difficult

to detect when affected pigs are housed on soft bedding (Donaldson, 2004). Vesicles

may occur on the coronets, interdigital skin, or bulbs of the heel (Donaldson, 2004).

Vesicles that encircle the coronet may lead to separation of the keratinised layers of

the hoof from the corium (Donaldson, 2004). In severe cases there may be sloughing

of the hoof. Otherwise, a line of separation between old and new horn moves steadily

down the hoof at a rate of about 1 mm a week, starting a week after rupture of the

coronary band vesicles (Donaldson, 2004). The age of FMD lesions in pigs can often

be estimated this way (Donaldson, 2004). Vesicles may occur on the snout; relatively

uncommon on tongue in pigs, and when they occur are small and heal rapidly

16

(Donaldson, 2004). Sows often develop vesicles on their teats and abortion

(Donaldson, 2004). There may be high mortality in suckling piglets, with sudden

deaths but no vesicular lesions and in some herds this is the first overt sign of the

disease (Geering et al., 1995; Donaldson, 2004).

In sheep and goats, the first signs are often a severe lameness accompanied with

depression, anorexia and pyrexia or sudden death in lambs or kids (Donaldson, 2004).

The mortality rate may be as high as 90% (Geering et al., 1995; Kitching and Hughes,

2002) due to multifocal necrosis of the myocardium (Donaldson, 2004). Foot lesions

are most evident on the coronary bands and interdigital skin (Donaldson, 2004).

Lameness is often the only overt sign of the disease in a flock. Foot lesions in sheep

are particularly prone to secondary bacterial infections, including footrot (Donaldson,

2004). Mouth lesions are not prominent in these animals (Donaldson, 2004). Vesicles

are more likely to occur on the dental pad and the posterior portion of the dorsal surface

of the tongue, small size and heal rapidly (Donaldson, 2004). Clinical disease is similar

in sheep to other species but up to 25% of infected sheep may fail to develop lesions

and only one lesion may form in an additional 20% of animals (Donaldson, 2004). The

disease in sheep and goats is generally mild and can be difficult to distinguish from

other common conditions (Kitching and Hughes, 2002; Grubman and Baxt, 2004).

In captive African buffalo calves, the index case in an FMD outbreak due to

SAT 1 occurred six months after the calves arrived at the bomas (Vosloo et al., 2007).

The authors described a case of a 30-month-old heifer with foamy mouth but no

drooling of saliva, anorexia, inappetance and soaked her mouth in the water trough.

Severe lesions on the dorsal surface of the tongue and hard palate developed two days

later and later sloughed off. Another five animals were also found to have lesions on

the tongue, buccal mucosa and, in one case, on the hard palate. Some lesions were

17

large (70 mm x 30 mm), foul smelling and the affected epithelium was brittle and

came off in granules. The calves also showed depression, pyrexia and moderate

anorexia. Within a week, ulcers/erosions formed with rounded epithelial edges and a

clear pink floor. After two weeks the tongue lesions were visible as pale, weakly

circumscribed areas with poorly developed papillae. Weight loss and lymphopenia

were also observed. No foot lesions occurred in any of the animals (Vosloo et al.,

2007).

2.5 Subclinical and persistent infections

There are two types of inapparent infections of FMDV (Klein, 2009). Firstly,

those animals that become infected and spread the virus without showing clinical signs

and secondly, those animals in which the virus persists after animals have recovered

from displaying clinical signs of disease (Sutmoller and Casas, 2002).

Persistent infection with FMDV in ruminants, so-called carriers, are defined as

those being virus positive for a minimum of 28 days (Sutmoller et al., 1968), both in

ruminants recovered from the acute infection and in vaccinated ruminants if they are

subsequently exposed to infectious virus (Alexandersen and Mowat, 2005). The site

of viral persistence is probably the pharynx. Virus can be routinely recovered from

cells and secretions collected from the pharynx and anterior oesophagus using

‘probang cups’ (Sutmoller and Gaggero, 1965). Another study reported that virus

persists in the basal layer cells of the pharyngeal epithelium, mainly the dorsal soft

palate (Zhang and Kitching, 2001). Other workers reported specific genetic sequences

of FMDV in multiple sites but not in isolates from the pharyngeal region of cattle up

to 2 years after infection (Bergmann et al., 1996). In cattle, the maximum duration of

the carrier state is 3.5 years; in sheep, 9 months; in goat, 4 months; in African buffalo,

5 years; in water buffalo, it is unknown; and pigs are not considered carriers because

18

persistence has not been demonstrated (Alexandersen et al., 2002b). The prevalence

of carrier ruminants was reported to be 15-20% , over 50% (Kitching, 2002b) and in

African buffalo, 50-70% (Condy et al., 1985). However, a Kenyan study found very

few carrier sheep and goats (Anderson et al., 1976). Field transmission from carriers

has, so far, only been shown from African buffaloes to cattle and impala (Dawe et al.,

1994; Bastos et al., 2000). However, experimental studies have shown saliva, obtained

from carrier animals, that was injected into cattle and pigs induced infection

(Alexandersen et al., 2002b). The number of carrier animals in a population depends

on the species, the individual, the incidence of infection and the herd immune status

(vaccinated or not) (Alexandersen et al., 2002b). Virus challenge and the genetics of

the host could also influence the development and duration of persistent infection

(Salt, 2004).

Subclinically infected animals may be highly contagious (Gibbens et al., 2001).

As occurred in the UK outbreak in 2007 due to a vaccine strain with a reduced

virulence, only a few infected animals showed clinical signs (Klein, 2009). Subclinical

infection can occur within vaccinated herds, with a high challenge of FMDV in

animals with high immunity or a low challenge in animals with low vaccine titre

(Yadin et al., 2007). It is possible that subclinically infected animals may play an

important role in the maintenance of FMD in endemic countries (Kitching, 2005).

2.6 Economic losses from outbreaks of foot-and-mouth disease (FMD)

Foot and mouth disease is present in two-thirds of the 167 OIE member

countries, where it creates severe economic problems and provides a reservoir of virus

with the potential to spread into virus free areas (Clavijo et al., 2004). Economic losses

from this disease can be severe due to loss of export markets, consumer fears

(Paarlberg et al., 2002) and trade restrictions on live animals and livestock products

19

(Gleeson, 2002). It has been estimated that FMD would cost Australia $AUS3.5

billion, mainly from the loss of export markets (Garner et al., 2002). The cost of

disease control and restriction of trade had direct effects on the UK economy in the

2001 outbreak (James and Rushton, 2002). In that outbreak FMD not only affected the

agricultural industry but also impacted the tourism industry. It was reported that £3.1

billion was lost due to losses in agriculture (compensation, disposal and clean-up) and

food chain (abattoir, auction markets, processors). Meanwhile, survey data of the

tourism industry revealed the loss was between £2.7-3.2 billion as a result of reduced

number of visitors to the countryside (Thompson et al., 2002). The financial cost of

the FMD epidemic in Taiwan was estimated at US$378.6 million, including

indemnities, vaccines, carcase disposal plus environmental protection, miscellaneous

expenses and loss of market value. However when losses arising from the ban on

exports of pork to Japan were included the total economic cost to Taiwan's pig industry

was approximately US$1.6 billion (Yang et al., 1999).

The economic effects of FMD have been summarised by James and Rushton,

(2002). Losses were from production losses in dairy and pig kept intensively, high cost

of disease control activities (by stamping-out or vaccination, prevention and

emergency preparedness in FMD-free countries) and barrier to international trade of

which markets with highest prices for livestock and products.

The management of FMD epidemics in France was evaluated through a

simulation model using epidemiological and economic data (Mahul and Durand,

2000). The strategy of stamping out infected herds and dangerous in-contact herds was

found effective in reducing the economic consequences of an FMD epidemic.

Furthermore, the importance of reducing the period of the import bans for livestock

product could also avoid further losses (Mahul and Durand, 2000).

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Foot and mouth disease is considered an obstacle for successful access to

domestic and export markets for livestock and their products. The control of FMD

may be used as a major development opportunity in a global environment. Previous

authors have reported that controlling FMD may contribute to the growth of

developing nations (Perry and Rich, 2007).

2.7 Epidemiology of FMD

2.7.1 Virus survival

Foot and mouth disease virus is most stable at near neutral pH and is sensitive

to mild acidity (Hyslop, 1970). Although temperatures above 50°C destroy most

infectivity, a small proportion of virus particles in most populations are relatively

resistant to heat and pH. Approximately 90% of virus is inactivated at a temperature

of 4 to 61°C within 18 weeks to 30 seconds, and between 1 second to more than five

weeks at a pH of 5 to 10 (Pharo, 2002). Generally the virus survives less than three

months in the environment however in very cold climates survival up to six months is

possible. The virus has been reported to survive on bran and hay for more than three

months under laboratory conditions and can also survive in wool at 4°C for

approximately two months and up to three months on fomites (Bartley et al., 2002).

In aerosols, FMDV survives best when the relative humidity exceeds 70% with

poor survival when it is below 55-60% (Sellers et al., 1971; Alexandersen et al.,

2003c). An example of the danger of infectious aerosols occurred on the Isle of Wight

where infection resulted from aerosol transmission over a distance of over 250 km

from the source in Brittany, France (Mahy, 2005). Sunlight and ultraviolet radiation

significantly affect the survival of FMDV in the environment (Donaldson and Ferris,

1975).

21

Fresh faeces collected off the floor have been found to contain small quantities

of virus and these can survive for up to 10 days in pig faeces (Parker, 1971) and at

least 12 days in cattle (Parker, 1971; Bartley et al., 2002). Survival of virus in frozen

or liquid manure was demonstrated to be longer than six months in winter (Cottral,

1969). Bartley et al., (2002) reported that organic material protected the virus from

drying and enhanced its survival on fomites.

The virus has been shown to survive for up to 12 years in soil attached to a

Wellington boot and at least a year in cell culture medium at 4°C (Mahy, 2005), up to

20 weeks on hay or straw, up to 4 weeks on cow’s hair maintained at 18-20°C, up to

14 days in dry faeces, up to 39 days in urine, and on soil for 3 days in summer and up

to 28 days in autumn (Alexandersen et al., 2003c).

In raw milk, virus is shed up to 33 hours before dairy cows show clinical signs

of disease (Tomasula and Konstance, 2004). This feature is important in the

epidemiology of disease transmission. Blood remains infective for 36 days and bone

marrow for 96 days (Blackwell, 1980). The virus can survive for long periods in

chilled pig lymph nodes (70 days) or in the bone marrow of pigs and cattle (42 and

210 days, respectively) (Cottral, 1969). Virus persistence in meat and other animal

products is enhanced when the pH remains 6.0 or above (Bartley et al., 2002). Studies

on the survival of virus has also been undertaken in meat and offal (Henderson and

Brooksby, 1948) and it has been shown to survive for up to 90 days in smoked meat

(Panina et al., 1989) and up to 313 days in salted meat products (McKercher et al.,

1987).

In the pharyngeal mucosa of ruminants, FMDV may persist for a long time,

however this is not the case with pigs (Moonen and Schrijver, 2000). In humans,

22

FMDV may also be carried in the nasal passages for 28 hours after exposure to infected

animals (Spickler et al., 2010).

2.7.2 Transmission

The most common method of spread of FMDV is by contact between an infected

and a susceptible animal (Kitching et al., 2005). Cattle and sheep are very susceptible

to infection by the aerosol route requiring at least 10 Tissue Culture Infective Dose

(TCID50). In contrast pigs are less susceptible to aerosol infection, requiring as much

as 6000 TCID50 (Alexandersen et al., 2002a; Alexandersen et al., 2002c). Infection

can occur either across damaged epithelium or orally (Kitching et al., 2005). Although

less susceptible than ruminants, pigs can aerosolise up to 3000 times more virus per

day than ruminants during acute stage of infection. Aerosol virus can potentially

spread a considerable distance with appropriate weather conditions (Kitching et al.,

2005) as indicated in the outbreaks in southern England in 1981 that originated from

Brittany France (Donaldson et al., 1982). Gloster et al. (2005b) used epidemiological

and meteorological data to reassess the likelihood of airborne spread of FMD at the

start of the 1967-1968 epidemics. The findings confirmed that airborne virus was the

most likely cause of the rapid early development of the disease up to 60 km from the

source (Gloster et al., 2005b). The same was concluded for the 2001 UK epidemic

after analysis of three epidemiological case studies. The distances for the airborne

spread ranged from less than one km to 16 km. Six of the farms were over six km from

the source and involved the passage of virus over the sea combined with

meteorological conditions which strongly favoured airborne disease transmission

(Gloster et al., 2005a).

All meat and organs from infected animals will contain FMDV and the virus

will survive if meat is frozen before rigor mortis. An outbreak of FMD would be likely

23

when the infected products are fed to a susceptible species (e.g. pigs) (Kitching et al.,

2005). Inactivation of FMDV will result from exposure to high temperatures, drying

or where pH is less than 6 or more than 10. Therefore, allowing carcase maturation at

2ºC for 24 h will allow development of lactic acid that will kill any virus in the meat

by reducing the pH to

24

refilling (Kitching et al., 2005). A similar observation was made during the 2001

epidemic in the UK (Gibbens et al., 2001).

Animal movements of all species, particularly as a result of intensive animal

husbandry practices, are especially dangerous for the spread of FMDV (Sutmoller et

al., 2003). Unauthorised activities, such as the importation of infected meat and

feeding to pigs of non-heat treated swill and the unauthorised trans-boundary

movement of animals, have resulted in the introduction of FMD into previously non-

infected countries. Movement of sheep from the UK were responsible for the spread

of virus to animals in Western France (Sutmoller et al., 2003). Sexual transmission in

African buffalo has also been suspected to have occurred during an outbreak in the

Kruger National Park, South Africa (Bastos et al., 1999; Vosloo et al., 2007).

In two experimental studies to determine direct and indirect virus transmission

among individually housed calves, it was found that none of the in-contact animals

seroconverted. This highlighted that virus transmission did not occur among the

individually housed calves (Bouma et al., 2004).

2.7.3 Global distribution of FMD

Some areas of the world, such as Australia, New Zealand, North America and

parts of South America, are free from FMD, whereas it is endemic or occurs

sporadically in many countries in Asia, Africa and Eastern Europe

(http://www.oie.int/?id=246, accessed on 6 Feb 2014).

The distributions of FMD serotypes are not uniform throughout the world

(Rweyemamu et al., 2008). Six of the seven serotypes of FMD (O, A, C, SAT1, SAT2,

and SAT3) have been detected in Africa, while animals in Asia have been infected

with four serotypes (O, A, C, Asia 1), and animals from South America with only three

http://www.oie.int/?id=246

25

(O, A, C). Periodically there have been incursions of SAT1 and SAT2 from Africa

into the Middle East (Rweyemamu et al., 2008).

Serotype O, with different distribution of topotypes, indicates epidemiological

clustering in endemic areas (Rweyemamu et al., 2008). There are South American

topotypes, Africa has five different topotypes of type O (East Africa1 and 2, West

Africa, Middle East-South Asia, Unknown), and Asia also has several sublineages

(Southeast Asia, Cathay, ME-SA, Indonesia1/Indonesia2). Of these, ME-SA is the

dominant topotype, with the Pan-Asia strain originating in South Asia, and the Cathay

and SEA topotypes are still present in the region. The movement of infected animals

has been shown to be the most important factor in the spread of FMD within these

endemic regions (Rweyemamu et al., 2008).

In Europe almost all countries west of the Russian Federation and the Balkan

countries are free of FMD without vaccination (Rweyemamu et al., 2008). However

in some areas in Turkey the disease is endemic. There have been a few reported

outbreaks in the Russian Federation but the true prevalence is difficult to establish

(Rweyemamu et al., 2008).

In Africa, FMD free countries without vaccination include the Indian ocean

Island Countries (Rweyemamu et al., 2008). South African Development Community

(SADC) countries (Swaziland, Lesotho, Republic of South Africa, Botswana and

Namibia) have zonal or country freedom status. In some of these countries, there are

FMD-infected wildlife areas but game ranching or other conservation activities are not

allowed within FMD-free zones. The disease was brought under control in the north

SADC cluster and some parts have remained largely unaffected, but other parts are

under constant threat of infection. In the Angola subregion FMD is possibly endemic,

however the true incidence is not known. The East African countries and eastern part

26

of the Democratic Republic of Congo contain the most complicated FMD situation in

the world. The Horn of Africa/Inter-Governmental Authority on Development (IGAD)

cluster is probably the major FMD endemic foci in Africa. The Soudan/Sahel cluster

is predominantly pastoral. Thus it may be an important disease corridor cluster linking

the IGAD with West Africa, and West Africa with North Africa. The Coastal belt

countries of West and Central Africa are considered secondary endemic clusters that

get infected from the Soudan/Sahel cluster. Some parts of North Africa have had no

reported outbreaks since 1999 (Rweyemamu et al., 2008). However, widespread field

outbreaks of FMD occurred in Egypt in 2012 that were phylogenetically shown to be

from Libya (Ahmed et al., 2012).

The situation of FMD in the Middle East is unclear and it is not known if it is a

primary or secondary endemic cluster (Rweyemamu et al., 2008). It is likely that the

situation will continue to be unstable and there is a high possibility of incursions of

exotic viral strains. Results from molecular characterization indicate a link between

the virus strains of Asia (i.e. Pakistan) and Africa (Rweyemamu et al., 2008).

In South-East Asia, FMD is endemic in seven countries namely Cambodia,

Laos, Malaysia, Myanmar, the Philippines, Thailand and Vietnam, and three are free

of the disease (Brunei, Indonesia and Singapore) (Gleeson, 2002). Part of the

Philippines (Mindanao, Visayas and recently Luzon) and Malaysia (Sabah and

Sarawak) are also recognised internationally as being free zones of FMD without

vaccination (http://www.oie.int/?id=246, accessed on 6 Feb 2014). Seven genetically

distinct lineages (O/SEA/Mya-98, O/SEA/Cam-94, O/ME-SA/PanAsia, O/ME-

SA/PanAsia-2, O/CATHAY, A/ASIA/Sea-97, and serotype Asia 1) co-circulate in

mainland Southeast Asia (Abdul-Hamid et al., 2011a). In East Asia, Japan regained

its free status and the Republic of Korea and Taiwan are on suspension of their FMD-

http://www.oie.int/?id=246

27

free status (http://www.oie.int/fileadmin/Home/js/images/fmd/FMD_Asia_ENG.gif,

accessed on 6 Feb 2014). The Cathay topotype O serotype appears endemic in pigs in

southern China. The Eurasian pandemic of type O Pan-Asia topotype spread to the

UK in 2001 resulting in massive outbreaks. The two topotypes along with Asia 1

entered Vietnam and then spread into Cambodia, Laos and eventually Thailand.

Additionally, FMDV regularly moves from Myanmar and Laos into Yunnan Province,

China. Viruses of types O, A and Asia 1 (http://www.oie.int/eng/A_FMD2012,

accessed on 6 Feb 2014) which originate in South Asia, have spread into SEA through

the movement of livestock from Bangladesh into Myanmar and onwards to Thailand

and Malaysia (Rweyemamu et al., 2008). Afghanistan, Bahrain, Pakistan, Iran and

Turkey had outbreaks of Asia 1 in 2012 (http://www.oie.int/eng/A_FMD2012,

accessed on 6 Feb 2014).

With the South Asia Cluster, India and Pakistan are central to the progressive

control of FMD in South and Central Asia due to their large cattle population which

act as a source of livestock for neighbouring countries (Rweyemamu et al., 2008).

Movement of these animals has facilitated FMDV transmission

(http://www.oie.int/eng/A_FMD2012, accessed on 6 Feb 2014).

The Central Asia cluster is no longer capable to cope with increased cross-border

trade as FMD type O and Asia 1 are now widespread and reporting of outbreaks is not

optimal (Rweyemamu et al., 2008).

The epidemiology of FMD in South America is described based on ecological

zones (Rweyemamu et al., 2008). The knowledge gathered has demonstrated that

livestock production systems play important role in the maintenance and spread of

FMDV in the animal populations. Types O, A and C have all been recorded in South

America (Rweyemamu et al., 2008).

http://www.oie.int/fileadmin/Home/js/images/fmd/FMD_Asia_ENG.gifhttp://www.oie.int/eng/A_FMD2012http://www.oie.int/eng/A_FMD2012http://www.oie.int/eng/A_FMD2012

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2.7.4 Foot and mouth disease in Malaysia

Malaysia has recently shown renewed interest in controlling and eradicating

FMD in livestock. This move was seen to have economic advantages with respect to

the international trade of livestock and livestock products however this requires

establishing freedom from FMD. Responding to this need, a regional coordination unit

(RCU) to promote improved control of FMD was established by the OIE in Bangkok,

Thailand in late 1997 and was called SEAFMD 2020. This plan provides a roadmap

for FMD freedom with vaccination by 2020 in South-east Asia (OIE-SEAFMD,

2007). Economic studies to assess the impact of SEAFMD control and eradication

plans in Thailand, Laos and the P

SITI ZUBAIDAH BINTI RAMANOON DVM (UPM), MSC (GUELPH · 2016. 8. 2. · 2.1 Foot and mouth disease 9 2.2 Foot and mouth disease virus 10 2.3 Host range and pathogenesis 13 2.4 Clinical

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