Hfmd Presentation

HFMD (Hand-Foot-Mouth Disease) An emerging disease Wong Ann Cheng MD (UKM) MRCPCH (UK)

Wednesday October 8, 2008 Sarawak on high alert for HFM disease KUCHING: Sarawak is on high alert for hand, foot and mouth disease following the detection of the EV71 virus, which causes a more severe form of the disease. Deputy Chief Minister Tan Sri Dr George Chan said the situation was under control and steps were being taken to prevent an outbreak.“We monitor for hand, foot and mouth disease all the time. “As soon as we detected EV71 in the state, we went on high alert because we know this virus can cause death,” he told a press conference at his office here yesterday. A total of 5,686 cases have been reported in Sarawak as of Saturday, compared with 6,286 in the same period last year. On Sept 30, a four-year-old child in Sibu died from suspected hand, foot and mouth disease.

SPOT DIAGNOSIS ?

HFMD

Myth

Foot and mouth disease

Hand, foot and mouth diseas

Returning Coxsackie Virus Threatens Sarawak The Star, March 30, 2000   Kuala Lumpur (Malaysia) - All hospitals and clinics in Sarawak have been directed to step up surveillance following the death of two children from symptoms similar to the Coxsackie outbreak three years ago. A Coxsackie outbreak in Sarawak in early 1997 killed 29 children, mostly below five years old.  

Media insistence of using “Coxsackie Outbreak” had misled the public. Virus later identified as EV71. Subsequent lots of effort to correct this misconception

The facts 

  

HFMD is typically a benign and common illness of infants and children It caused by human enterovirus. Often in children under 10 years old. It also affect older children and adult but with milder symptoms http://www.cdc.gov/ncidod/dvrd/revb/enterovirus/hfhf.htm

Symptoms (case definition) 







Usually begins with fever, poor appetite and malaise, often with sore throat After 1-2 days after onset of fever, sores/ulcers develop in the mouth, side of cheek, gum and tongue The non-itchy skin rash/ maculopapular or vesicular appears on palms of the hands and soles of the feet. The rashes may also appear on buttocks and on the legs and arms. http://www.cdc.gov/ncidod/dvrd/revb/enterovirus/hfhf.htm

HAND

FOOT

MOUTH

Differentials

Herpangina

Herpetic gingivostomatitis

Aphthous ulcers

Enterovirus 



Human enteroviruses comprise one genus in the family of Picornaviridae Enterovirus genus that infect humans: Poliovirus  Coxsackievirus A  Coxsackievirus B  Echovirus  Enterovirus 68-71 



HFMD are due to coxsackie virus A16, A5, A9, A10, B2, B5 and EV71

Coxsackie virus 

  

Coxsackie A16 is a frequently encountered pathogen in cases of HFMD occurring throughout the year Clinical course usually uneventful, with full recovery Fatal cases of Cox A16 rare Literature search only revealed 3 fatal cases since 1963. All the cases were infant   

Wright et al: 10-month-old with respiratory infection Goldberg et al: 7-month-old with grunting and tongue ulcer Wang et al: 15-month-old with HFMD

Enterovirus 71 (EV71)   



Responsible for sporadic outbreak More severe course Maybe complicated by meningitis, encephalitis and neurogenic pulmonary oedema In Taiwan, based on 1998 epidemic, significant difference between Cox A16 and EV71 are the higher fever >39ºC and >3 days in EV71

Phylogenetic study of EV71 

 



EV71 strains divided into genogroup A, B, C Further subdivided to (4, 8-10) four genetic lineages of EV71 have been prevalent in the Asia-Pacific region since 1997, including two previously undescribed genogroups (B3 and B4). Genogroups of EV71 isolated during each major outbreak are genetically

Molecular Epidemiology

Epidemiological data 

 



Most HFMD patients were very young children (<4 years old) with a peak incidence at 1 year. Male outnumber female 1.7 to 1 Predominance has also been observed in other enteroviral infection Suggest possible susceptibility at host genetic level Emerging Infectious Diseases • Vol. 9, No. 1, January 2003

Epidemiological data    



Large outbreak maybe due to changes in the viral factors Different strain of EV71 were obtained from the each outbreak Genetic determinant of virulence still unclear Co-infection with second virus had been suggested as possible pathogenic factor, supported by concomitant isolation of subgenus B adenovirus from 3 fatal cases in Sarawak. Consideration of unusual medications, treatment or dietary exposure contributed to fatality found no conclusive evidence. Emerging Infectious Diseases • Vol. 9, No. 1, January 2003

Global Epidemiology 





Enterovirus 71 (EV71) infection was first reported in 1969 in California, United States; subsequent outbreaks were reported in worldwide distribution Mainly during summer and early autumn months in temperate countries while prevalent year round in tropical climates

Recorded outbreak of EV71 2008

China

27 500 HFMD, 34 died

2006

Malaysia

14 253 HFMD, 13 died

2005

Thailand

4646 HFMD

2003

Malaysia

Most self limited, few neurological death

2000 1998

Singapore Malaysia, Taiwan Taiwan

3526 cases 83% EV71 4 died of pneumonia, encephalitis Also >300outbreak 000 HFMD, 386 ICU due to

1997

Malaysia

encephalitis, 2140 patients78 31died died

1987

US

1987

Philadelphia

45 patients high rate of meningitis and paralysis 5 polio-like disease, 1 brain stem

1986

Australia

1986

Hong Kong

encephalitis 140 cases, 61 HFMD, 34 meningitis and encephalitis 5 HFMD with flaccid monoplegia

1979

France

5 cases with CNS signs

1978

Hungary

1978

Japan

1550 HFMD, 826 meningitis, 724 encephalitis, 45 death encephalitis 692 HFMD, meningitis,

1977

New York

1975

Bulgaria

29 HFMD, meningitis, encephalitis, monoparesis 705 cases, 149 paralysis, 44 died

Large Outbreaks of HFMD in Asia China 2008 27,500/34

Japan 1978 36,301/ ?

Thailand 2005 4,646/ 0

Taiwan 1998 129,106/ 78

Malaysia 1997 5,999/ 31

Singapore 2000 > 4,000/ 7

Malaysia 2006 14,253/ 13

An emerging infectious disease Malaria

Typhoid Dengue

Leptospirosis

Chikungunya

Melioidosis

HIV Tuberculosis

JE

HFMD

Hepatitis

Malaysia top five notifiable diseases in 2006 1. 2. 3. 4. 5.

Tuberculosis Food poisoning Dengue fever Hand, foot and mouth disease Malaria

HFMD in Sarawak  





HFMD is endemic in Sarawak. Prior to 1997, no baseline data on the epidemiology of HFMD in Sarawak as it is not a notifiable disease.    Between 15 April and 30 June 1997, 31 previously healthy infants and young children in Sarawak died after a short febrile illness against a background of an outbreak of HFMD in the State. Sibu was badly affected during this outbreak as 11 of the death cases were http://www.sarawak.health.gov.my/hfmd.htm reported from Sibu followed by Sarikei with

HFMD in Sarawak 





Surveillance of HFMD was initiated by Sarawak Health Department from 6 June 1997 till December 1997. However, in 1998, following a report of increased cases of HFMD seen in private paediatrician clinics, sentinel surveillance of HFMD in collaboration with UNIMAS was re-started in the State involving urban public and private clinics in Kuching, Sibu and Miri and 3 government hospitals in Sarawak. When the enterovirus outbreak was reported in Taiwan in May 1998, the surveillance of outpatient and inpatient http://www.sarawak.health.gov.my/hfmd.htm

List of HFMD Sentinel Surveillance Clinics in Sarawak ( 2008 ) No.

Clinic

Location

1

T.Y Wee Specialist Clinic For Children

Kuching

2

Bibiana Teo's Specialist Clinic

Kuching

3

KK Jalan Masjid

Kuching

4

KK Kota Sentosa

Kota Sentosa

5

KK Tanah Puteh

Pending, Kuching

6

KK Kota Samarahan

Samarahan

7

Betty Kong's Clinic

Sibu

8

K.T Ting Specialist Clinic For Children

Sibu

9

Sibu Polyclinic

Sibu

10

Sarikei Polyclinic

Sarikei

11

Dr Chen WS Child Specialist

Miri

Sarawak Surveillance programme 



 

EV71 outbreaks has occurred every 3 years in Sarawak – 1997, 2000, 2003, 2006( as predicted) The shape of HFMD epidemiological curves are influence by social factors such as media and people movements during major public holidays (especially Gawai) Only EV71 causes large outbreak The genogroups of EV71 isolated during major outbreak are genetically distinct from each other, but all are first identified in Sarawak and some had spread to Peninsular Malaysia, Singapore and Podin et al; licensee BioMed Central Ltd. Australia

Sarawak Surveilance programme 



The transmission of EV71 in a susceptible cohort is extremely rapid with only 4-6 weeks between first identification of an EV71 case in our sentinel clinics to peaking. These outbreaks can drag on for many months after they peaked, especially if the outbreak has not reached baseline before people start travelling or moving about in the state (eg State elections in 2006, Podin et al; licensee BioMed Central Ltd.

http://www.sarawak.health.gov.my/hfmd.htm

http://www.sarawak.health.gov.my/hfmd.htm

http://www.sarawak.health.gov.my/hfmd.htm

1345 1282 1234 1212 1017

633

567

435

52

49

46

43

40

37

34

31

28

25

22

19

13

10

7

16

431 412 403 397 332 326 322 315 310 274 271 265 253 239 232 198 228 220 174 147 156 112 859795 6340313322372936 26 14 171723

193 98105 53 4 15 4

1400 1300 1200 1100 1000 900 800 700 600 500 400 300 200 100 0

1

Cases

HFMD CASES FOR SARAWAK, 2006

Epid Week

Sarawak centre for disease control (CDC)

HFM D CASES FOR SARAWAK, 2008

500 428 385

400

315

320

300 252 197

183 175 172

200

121 100 58 30

69 75

88

154

139 116 10410810598

78 81 51

61 54

79 74 87

254

245

192

198 189 142

95

48 47 49

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 EPID WEEK

Sarawak centre for disease control (CDC

HFMD CASES FOR KUCHING DIVISION 2008 300 270

275

251

250 225 193

200

181

175 143

150

131 113

125 99 100

83

75

49 51

49 50 25

26 28 6

6

7 11 7

1 2

3

4

3

26

19 18 21 23

13 12

19

11 15 9

7

2

10

16 17

89 76 47

28

0 5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 EP ID WEEK

Sarawak centre for disease control (CDC)

HFMD Cases ( Death ) Year

No.'s Cases

No.'s Death

1997

2628

31

1998

455

0

1999

65

0

2000

3560

3

2001

667

0

2002

621

1

2003

2113

4

2004

56

0

2005

3558

0

2006

14875

13

2007

6571 5716 ( Till 4th October 2008 )

0

2009

?

?

Total

40885

53

2008

1

Sarawak centre for disease control (CDC)

SARS

Deaths of children during an outbreak of HFMD in Sarawak, clinical and pathological characteristics of the disease. 





April -June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, died of rapidly progressive cardiorespiratory failure during an outbreak of HFMD caused primarily by EV71. Hospitalized after a short illness (median duration, 2 days) that usually included fever (in 100% of case children), oral ulcers (66%), and extremity rashes (62%). Illness rapidly progressed to include seizures (28%), flaccid limb weakness (17%), or cardiopulmonary symptoms (of 24 children, 17 had CXR showing pulmonary edema, and 24 had ECHO showing left ventricular et al, CID 2000; 31 (Septembe dysfunction), resulting inChan cardiopulmonary

Chan et al, CID 2000; 31 (September)

Chan et al, CID 2000; 31 (September)

Pathology 

CNS: 

extensive inflammation of brain stem and spinal cord.

suggesting that a central nervous Lung: system infection was responsible for the  marked pulmonary oedema with focal disease, with the cardiopulmonary haemorrhage dysfunction being neurogenic in origin.  Heart: 





Normal myocardium

Virus: EV 71 isolated from fresh brain tissue (brainstem, C-spinal cord, cerebrum) Hsueh C, et al. Modern Pathology 2000  NOT from heart, lung or other organs 

Postulated pathogenesis of severe EV71 infection

EV71 infection classified into 4 stages Stage 1

Hand, foot and mouth disease

Stage 2

CNS involvement

Stage 3

Cardiopulmonary failure

Stage 4

Convalescence

Malaysian Hand-Foot-Mouth disease guideline

FLOW CHART OF HFMD & HERPANGINA MANAGEMENT Hand,Foot & Mouth Disease and Herpangina Admit if have 1 or more following criteria

Does not fit admission criteria

<12 months Vomiting or feeding poorly or dehydration Fever>38.5C or history for fever >/48 hours Toxic/ill looking Inappropriate Tachycardia Tachypnoea Poor perfusion Reduced level of consciousness Seizures or history of seizures Reduced motor activity Increased startle during sleep or when awake Neurological deficit (limb paralysis, cranial nerve palsy, cerebellar signs, nystagmas) Signs of meningism (neck stiffness, Kernig’s sign) Hyperglycaemia > 8.5 mmol/L or total white cell count > 17 500/mL (Page1-2) Clinical Staging (Page 3) • History taking • Physical examination • Investigations (Page 3)

Stage I Symptomatic treatment Ensure adequate hydration

Discharge with advice (Page 8)

Notification by phone & written form

To use standard clerking sheet for HFMD

Stage 2

Stage 3

Stage 4

Admit acute cubicle/ HDU Frequent vital signs monitoring Ensure normal hydration status Empirical IV antibiotics Aggressive control of seizure Intubation & mechanical ventilation when indicated Measures to ↓ ICP (adequate cerebral perfusion, IV Mannitol, hyperventilation) IVIG when indicated (Page 5)

Admit HDU/ICU Intensive monitoring Ensure normal vascular filling pressure Empirical IV antibiotics Oxygen Intubation & mechanical ventilation when indicated Fluid restriction IV Frusemide Correction of metabolic acidosis Use of inotropes: Dobutamine, Dopamine, Milrinone, Adrenaline Use of vasodilator: Nitroglycerin (Page 6 – 7)

Convalescence

Discharge when criteria fulfilled (Page 8)

Clinical sample types 

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Establishing the actual cause of HFMD cases relies on laboratory identification of the virus Diagnostic techniques include isolating virus in continuous cell lines or detecting viral RNA by PCR. Virus isolation remains gold standard; it is cheaper than PCR and more widely used method particularly in developing countries Ranges of sample for virus isolation include Ooi, et al. J. Clinical Microbiology, throat and rectal swab, serum and CSF June 2007

Ooi, et al. J. Clinical Microbiology, June 2007

Clinical sample types 

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



Throat swabs single most useful specimen (49%) Vesicles swab (48%) in patient with vesicles; yield greater if 2 or more vesicles swab Combination of throat and vesicle swab enable identification of virus (67%) Rectal and ulcerOoi, swab identified et al. J. Clinical Microbiology, June 2007 additional (8%)

HFMD guidelines

Transmission Nose Throat discharg e Saliva Fluid from blisters Stools

Mode of transmission  



HFMD is moderately contagious. Most contagious during the first week of the illness. The virus can be transmitted from person to person via 



direct contact with nose and throat discharges, saliva, fluid from blisters, or the stool of infected persons. The virus may continue to be excreted in the stools of infected persons up till 1 month. HFMD is not transmitted to or from pets or other animals.

Transmission 





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Infants in diapers appears to be the most efficient transmitter. The virus may be excreted in stools for many weeks The virus can survive for days on formites at room temperature Resistant to many disinfectants – use chlorinated or iodinized disinfectant

Transmission rate       

To household contacts 52% Siblings 84% Cousins 83% Parents 41% Grandparents 28% Uncle and aunts 26% Intrafamilial and kindergarden transmission major mode of transmission (both in Taiwan and Singapore) JAMA 2004; 291: 222-7

Pediatr 2002; 109: e88

Risks factors       

Children more susceptible due to lack of immunity Parents sending sick children to centre Cases not detected and isolated Close contact among classmates Asymptomatic cases Poor personal hygiene Contamination of toys, furniture and premises

Immunity 



Infection results in immunity to specific virus Second episode may occur following infection with other enterovirus

Treatment 

 

No specific antiviral treatment available for HFMD Mainly supportive. ?immunoglobulin

Health screening for HFMD  



Early detection and prompt isolation Children should be monitored daily, noting any unusual symptoms or behaviour A child should not be allowed to continue class if he/she appears unwell

Hygiene and sanitation   

Hand washing not emphasized enough One of the most important route of transmission of infection Single most effective practice to prevent spread of germs Practice it  Teach it  Monitor and enforcement of good handwashing practices 

Outbreak control measures  



 

Continue health screening Ensure high level of personal and environmental hygiene Eliminate communal activities where all children congregate Public educational effort Closure of kindergarden and school for 10 days to break the chain of transmission

Poster

Pamphlets

Booklets

Message  





From Sarawak, since 1997, EV71 outbreak had occurred every three years Shape of epidemiological curve influence by social factors such as media and people’s movement during public holidays Genogroups of EV71 isolated during each major outbreak are genetically distinct from each other Transmission of EV71 in susceptible cohort extremely rapid with only 4-6 weeks between first identification in sentinel clinics to peaking

Message 





From Singapore, transmission occur mainly in places where preschool children congregate, and public health measures to focus on these places From Taiwan 1998 outbreak showed that HFMD spreads easily through contact leading to mostly symptomatic cases in children and mostly asymptomatic cases in adult Proper surveillance system works showing trends and the current circulating viruses and predicting coming outbreak

Challenges 



Identify reservoir of EV71 in the inter-epidemic periods Develop simple rapid diagnostic tests that can be used to differentiate EV71 from CA16

References   

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http://www.sarawak.health.gov.my/hfmd.htm http://en.wikipedia.org/wiki/HFMD Chan, L. G., U. D. Parashar, M. S. Lye, et al. 2000. Deaths of children during an outbreak of hand, foot and mouth disease in Sarawak, Malaysia: clinical and pathological characteristics of the disease. Clin. Infect. Dis. 31:678-683[Medline]

Cardosa, M. J., S. Krishnan, P. H. Tio, et al. 1999. Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot and mouth disease in Sibu, Sarawak. Lancet 354:987-991 [Medline].

Chong CY, Chan KP, Shah VA, Ng WY, Lau G, Teo TE, et al. Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases. Acta Paediatr. Oct 2003;92(10):1163-9. [Medline]. Ooi MH, Wong SC, Clear D, Perera D, Krishnan S, Preston T, et al. Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot-andmouth disease in Sarawak, Malaysia. Clin Infect Dis. Mar 1 2003;36(5):550-9.  [Medline]. Shekhar K, Lye MS, Norlijah O, Ong F, Looi LM, Khuzaiah R, et al. Deaths in children during an outbreak of hand, foot and mouth disease in Peninsular Malaysia--clinical and pathological characteristics. Med J Malaysia. Aug 2005;60(3):297-304. [Medline]. Tseng FC, Huang HC, Chi CY, Lin TL, Liu CC, Jian JW, et al. Epidemiological survey of enterovirus infections occurring in Taiwan between 2000 and 2005: Analysis of sentinel physician surveillance data. J Med Virol. Dec 2007;79(12):1850-60.  [Medline].

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