Modelling of hand foot and mouth disease in Hai Phong Vietnam 2012 - 2016

The incidence rate was 106 cases per 100,000 population. The age-specific incidence rate for Hand, foot and mouth disease was highest in the age group of 1 - 3 years old (75.04%). The major aetiologic agents were EV - 71 (52.6%), CV - A6 (21.8%). R0 ranged from 1.0077 - 2.4883. The greatest burden of Hand, foot and mouth disease is in the under five years old age range. Under present conditions, hand, foot and mouth disease will continue to persist in Haiphong. Interventions should target the high risk populations and areas.

JOURNAL OF MEDICAL RESEARCH MODELLING OF HAND FOOT AND MOUTH DISEASE IN HAI PHONG VIETNAM 2012 - 2016 Mbinta Fenibe James1, Pham Quang Thai2, Dao Thi Minh An3, Marc Choisy4, Phan Hong Hai5, Tran Nhu Duong2 District Hospital Roua, Cameroon National Institute of Hygiene and Epidemiology, Hanoi, Vietnam Hanoi Medical University, Vietnam UMR Univ Montpellier, CNRS 5290, IRD 224 Preventive Medicine Center, Hai Phong Hand, foot and mouth disease is an infectious disease caused mainly by Entero virus 71 (EV - 71) and Coxsackie virus A16 (CV - A16) Recent outbreaks of Hand, foot and mouth disease in the West Pacific region have brought the world’s attention to hand, foot and mouth disease due to increasing morbidity and mortality The purpose of this study was to describe the epidemiological distribution of hand, foot and mouth disease cases in Haiphong 2012 - 2016 and develop and test the model of hand, foot and mouth disease in Haiphong The study was done in Haiphong using surveillance data from 2012 - 2016 All statistical analysis were done using R packages (poseid, lubridate, dplyr, magrittr, ggplot2, deSolve, bbmle, fitsir…) SIR model was used to estimate the basic reproductive number (R0) The incidence rate was 106 cases per 100,000 population The age-specific incidence rate for Hand, foot and mouth disease was highest in the age group of - years old (75.04%) The major aetiologic agents were EV - 71 (52.6%), CV - A6 (21.8%) R0 ranged from 1.0077 - 2.4883 The greatest burden of Hand, foot and mouth disease is in the under five years old age range Under present conditions, hand, foot and mouth disease will continue to persist in Haiphong Interventions should target the high risk populations and areas Keyword: HFMD, Epidemiology, Modelling, SIR Model, Basic Reproductive number, Hai Phong I INTRODUCTION Hand, foot and mouth disease (HFMD) is a Aseptic meningitis, encephalomyelitis, acute common infectious disease that occurs most flaccid paralysis, autonomic nervous system often in children (< years) but can occur in dysregulation, cardiorespiratory failure have adolescents and occasionally in adults [1] It is been associated with EV71 [1; 3; 4] There is caused by viruses that belong to the enterovi- currently no specific antiviral treatment and no rus (EV) genus and the major aetiological vaccine to protect against the viruses that agents are the enteroviruses species A cause Hand, foot and mouth disease [1] (EV-A), mainly CA16 and EV71 [1; 2] It is Outbreaks of enterovirus infection were characterized by a brief febrile illness and typi- reported in New York, 1972 and 1977, Austra- cal skin rash, with or without mouth ulcers [1] lia 1972 - 1973 and 1986, Sweden 1973, Japan 1973 and 1978, Bulgaria 1975, Hungary Corresponding author: Mbinta Fenibe James, District Hospital Roua, Cameroon Email: Mbintafenibe@yahoo.com Received: 15/3/2018 Accepted: 19/10/2018 JMR 116 E3 (7) - 2018 1978, France 1979, Hong Kong 1985 and Philadelphia 1987 [1; 5] Recent outbreaks of Hand, foot and mouth disease in the West Pacific region have brought the world’s atten- 75 JOURNAL OF MEDICAL RESEARCH tion to Hand, foot and mouth disease due to disease is mathematical modelling Mathe- increasing morbidity and mortality [1; 5] matical models are used in comparing, plan- Before 1999, ~ 60% of encephalitis (a com- ning, implementing, evaluating and optimizing plication of Hand, foot and mouth disease) in various detection, prevention, therapy and southern Vietnam in children > years of age, control programmes We decided to use were Japanese encephalitis [2] Since 2002, Haiphong for modeling because it is the only less than 27% of encephalitis cases were con- city that has a complete line listing of surveil- firmed as Japanese encephalitis, which indi- lance data from 2012 to 2016 The objectives cated that the epidemiology of viral encephali- of this study were as follows: tis in southern Vietnam maybe changing [2] In Describe the epidemiological distribution 2005, 764 children were diagnosed with Hand, of Hand, foot and mouth disease cases in foot and mouth disease in Ho Chi Minh City Haiphong 2012 - 2016 with most cases (96.2%) being in children < years old [2] In 2006 - 2007, 305 cases were Develop and test the model of Hand, foot and mouth disease in Haiphong diagnosed [1] In northern Viet Nam, there was one case in 2003 [1] From 2005 to 2007, EV71/C5 was identified in children with acute flaccid paralysis and in 2008, 88 cases II METHODS Study location of Hand, foot and mouth disease were re- Haiphong has a population of 2.103.500 ported from 13 provinces [1] Since 2011, the and surface area of 1.507.57 km² The aver- Ministry of Health classified Hand, foot and age annual population growth rate is 4.0% mouth disease as a severe infectious disease Haiphong city is divided into urban districts: with outbreak potential and the disease has Kinh Duong, Do Son, Hai An, Hong Bang, Ngo been reported weekly by the national commu- Quyen, Le Chan and Kien An and suburban nicable disease surveillance system [4] The districts: Thuy Nguyen, An Duong, Tien Lang, first reported case in Haiphong was a year- Vinh Bao, An Lao, Kien Thuy, Cat Hai and th old girl diagnosed on the 17 of Apr 2011 Bach Long Vi [9] From 2011 to 2012, the incidence of Hand, Data: All Hand, foot and mouth disease foot and mouth disease was 524 per 100,000 cases in Hai Phong city were reported to Na- population [6] tional Institute of Hygiene and Epidemiology It is important to understand the dynamics (NIHE), since Feb, 2011 [6] Data from Hai of Hand, foot and mouth disease spread Phong city (2012 - 2016) was extracted from among the susceptible populations in Vietnam the NIHE surveillance data base The data This will enable policy makers to take effective was a line listing of all cases Subjects infor- measures to curb the disease spread and mation collected included but were not limited reduce the adverse impact of the disease [7; to age, residence (district), clinical status, hos- 8] One of the analytical models that can help pital, results of laboratory tests, clinical grade us understand the spread, predict the trans- at hospital admission (mild or severe), date of mission and control of Hand, foot and mouth admission [4; 6] 76 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH Case Definition In Vietnam, Hand, foot and mouth disease is defined as a brief febrile illness in children accompanied by typical skin rash, with or without mouth ulcers The rash is papulo- Districts to show area maps), Person (only age was used to describe the host characteristics), Virus serotype (groups within a single species of microorganisms, which share distinctive surface structures) vesicular, occurring on the palms or soles of Model Development the feet, or both In young children or infants According to the formalism, we categorizes the rash may be maculopapular without vesi- hosts within a population into three state vari- cles and may also involve the buttocks, knees ables or compartments (Susceptible, Infected, or elbows [4] A confirmed Hand, foot and and Recovered) [10] A state variable is a mouth disease case was defined as a patient changing quantity that characterizes the state who had a positive RT–PCR assay for EV71 of the system [8] A parameter is a user de- or other EV [4] In Haiphong city, monthly fined quantity that influences the value of the throat swabs were collected from the Hand, state variables [8] In this model, we defined foot and mouth disease cases in 14/15 dis- two major parameters: effective contact rate tricts of Haiphong city by the Haiphong city (β), recovery rate (γ) [10] Preventive Medicine Center and sent to En- In order to derive a simple model, the fol- terovirus laboratories of NIHE on ice for etio- lowing assumptions were made [10]: The logical assays [6] ‘population is closed’ without demographics; Variables All individuals are equally likely to be infected; The variables used for the epidemiological distribution of Hand, foot and mouth disease in Hai Phong include the following: Time (occurrence of Hand, foot and mouth disease changes over time Cases were analysed in days, weeks, months and years), place (this provided information on the geographic extent of the problem and demonstrated clusters JMR 116 E3 (7) - 2018 There is homogeneous mixing, whereby intricacies affecting the pattern of contacts are discarded; Once infected and recovered, subjects were no longer susceptible to infection i.e lifelong immunity; No vaccines; Transmission is frequency dependent Given the premise that underlying epidemiological probabilities are constant, we get the following SIR equations [10]: 77 JOURNAL OF MEDICAL RESEARCH The parameter γ is called the removal or recovery rate, its reciprocal (1/γ), determines the average infectious period S + I + R = N, S (t) + I (t) + R (t) = the surveillance data and also for sensitivity analysis Data was collected from the routine surveillance system, therefore, there are several limi- At equilibrium, the three equations consti- tations such as reporting biases and quality tuting the system of equations are zeros, i.e and consistency of surveillance data report equations (1) to (3) will be zero as follows: Case definitions may not be applied in the dS dl = 0, dt same way throughout the city We were as- dR = 0, dt = 0, (1) to (3) become: dt sured that the surveillance team took some steps to prevent bias such as the following [6]: Training courses on the Hand, foot and mouth disease case definition and reporting were given to surveillance staff; Complement data gaps by gathering data from multiple sources through telephone, interviews with patients and their families or have meetings with physi- From equation [5], either I = or βS – γ = cians; Comparing sample characteristics to When I = 0, there is disease free equilib- population characteristics were useful for ex- rium, otherwise βS – γ = i.e S = γ/β The amining data for bias initial proportion of susceptible people must Research ethics cross this critical threshold for an epidemic to Ethical clearance was obtained from the occur This is a well-known result referred to National Institute of Hygiene and Epidemiol- as the “threshold phenomenon” [10] S + I + R ogy = N γ/β + I + = N, Let, Therefore β/γ > III RESULTS Epidemiological distribution of cases (R0) of HFMD Statistical analysis The format for raw data was Microsoft Excel 2010 All statistical analysis were done Trend of reported Hand, Foot and Mouth disease cases in Hai Phong using R packages provided by the R commu- A total of 11.684 cases of Hand, foot and nity [11] Some of the packages used include: mouth disease were reported in Hai Phong poseid (ll2incidence), lubridate, dplyr, magrittr, during the year period (2012 - 2016) This ggplot2, deSolve, bbmle, fitsir and EpiEstim was 3.0% (11, 684/404, 338) of all reported Rstudio syntax- cases in Vietnam The highest number of highlighting editor that supports direct code cases were reported in 2012 (35.6%) and execution and a variety of robust tools for plot- lowest in 2015 (10.2%) (Table 1) Cumula- ting, viewing history, debugging and managing tively, the least number of cases were workspace Fitsir was used to fit the model to reported in February (3.5%) and the highest in 78 includes a console, JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH April (11.5%) and September (10.2%) From at least 100 cases were reported per week week 15 - 25 (2012) and week 80 - 92 (2013), (Figure 1) Figure Trend of weekly incidence (2012 – 2016) Figure Weekly and monthly trends comparison (y1 to y5) A comparison of the weekly cases between the years showed that an epidemic of Hand, foot and mouth disease occurred between the 5th and 28th week of 2012, the 10th and 40th week of 2015 and the 35th and 52nd week of 2016 Epidemics occurred at relatively different times of the year (Table 2) The peaks were April - May (2012), June - October (2013), May - August (2014), and August - December (2016) Demographic Characteristics The median and mean ages of reported Hand, foot and mouth disease cases were years and 1.87 years respectively The age-specific incidence rate for Hand, foot and mouth disease was highest in the age group of - years old (75.04%) The highest number of cases in subjects less than year old were reported in 2014 (9.65%) and the lowest in 2015 (4.62%) Between - years, the maximum number was 79.42% (2013) and minimum was 70.37% registered in 2012 (Table 1) JMR 116 E3 (7) - 2018 79 JOURNAL OF MEDICAL RESEARCH Table Characteristics of reported HFMD cases in Hai Phong, 2012 – 2016 2012 (y1) N (%) 2013 (y2) N (%) 2014 (y3) N (%) 2015 (y4) N (%) 2016 (y5) N (%) Cases N = 11684 4165 (35.6) 2853 (24.4) 1471 (12.6) 1190 (10.2) 2005 (17.2) Province Hai Phong 3941 (94.62) 2615 (91.7) 1403 (95.38) 1130 (94.96) 1809 (90.22) Others 224 (5.38) 238 (8.35) 68 (4.62) 60 (5.04) 196 (9.77) Age < 198 (4.75) 149 (5.22) 142 (9.65) 55 (4.62) 109 (5.44) ≤ age < 2931 (70.37) 2266 (79.42) 1075 (73.08) 904 (75.97) 1531 (76.36) ≤ age < 10 1018 (24.44) 430 (15.07) 229 (15.57) 228 (19.16) 360 (17.95) age ≥ 10 18 (0.43) (0.28) 18 (1.22) (0.08) (0.25) (0.43) (0.17) Age group (age in years) NA (no values) Summary age characteristic Min (0.00) 1st Qu (1.00) Median (2.00) Mean (1.87) 3rd Qu (2.00) Max (30.00) NA's (9) Incidence Rate (Cases per 100,000 persons), Av IR = 106 IR Yearly IR 190 130 67 54 91 CV - A6 (50.0%) CV - A16 (22.7%) CV - A6 (63.5%) EV - 17 (27.3%) CV - A6 (31.2%) EV - 71 (28.6%) Virus Serotype Major serotype 2012 - 2016 EV - 71 (90.1%) CV - A6 & A16 (3.3% EV - 71 (38.8%) CV - A6 (26.2%) Incidence rate of HFMD in Hai Phong 80 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH Figure Spatial distribution of HFMD cases in Hai Phong province, 2012 - 2016 Do Son (316), An Duong (317), An Lao (318), Bach Long Vi (319), Cat Hai (320), Hong Bang (321), Hai An (322), Kien An (323), Kien Thuy (324), Le Chan (325), Ngo Quyen (326), Thuy Nguyen (327), Tien Lang (328), Vinh Bao (329), Duong Kinh (??) The average incidence of HFMD was 106 cases per 100,000 population The incidence was highest in 2012 (190 cases per 100.000 population) and lowest in 2015 (54 cases per 100.000 population) (Table 1) The highest district incidence (370 cases per 100.000 populations) was recorded in Do Son district in 2012 (Figure 3) Virus Serotype During the period 2011 - 2016, the main enterovirus serotype in Haiphong were EV 71 (52.65%) and CV - A6 (21.8%) The main serotype in circulation during the 2011 epidemic in Haiphong was EV - A 71 (67.7%) (Figure & Table 1) JMR 116 E3 (7) - 2018 81 JOURNAL OF MEDICAL RESEARCH 10 15 20 25 30 35 % Figure Virus serotype in Hai Phong, 2011 - 2016 Development and testing of model of Weekly distribution in 2014 revealed a single epidemic from 5th week (5cases) to 51st week HFMD Considering the weekly distribution of Hand, foot and mouth disease in 2012, there (2 cases) During this period, the highest number of cases were reported between the 20th were two epidemics The first was from 5th and 30th weeks The model fit and R0 were week (26 cases) to the 28th week (41 cases) 67% and 2.3381 respectively and the second from the 28th week (41 cases) nd Weekly distribution of cases in 2016 re- week (28 cases) The parameters vealed two epidemics with almost the same in table produced an 85.9% model fit on real peak, 85 cases and 98 cases respectively to the 52 th data (5 th week) R0 was 1.0159 The first from week (8 cases) to week 27 (14 nd to 28 Regarding the epidemic of 2012 from the cases) and the second from week 27 (14 28th to the 52nd week, a 73% SIR model fit cases) to week 51 (3 cases) Simulation using resulted from the parameters shown in table the parameters in table produce an SIR R0 was 1.0100 In 2013, there was a single model fit to the first epidemic of 80.6% The epidemic from the 6th week (4 cases) to 47th model fit was quantitatively imperfect By com- week (17 cases) There was a plateau from paring the model predictions with real data the 13th to the 25th week and a peak on the during the second epidemic of 2016, the esti- 35th week The parameters produced a Ro of mated R0 was 1.0111 1.0077 The model fit was 79.3% (Table 2) 82 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH Table Summary of Parameters and basic reproductive number Year β Γ Crude R^2 analogue R0 (β/γ) 12.57648 12.37980 0.8589205 1.0159 10.77855 10.67153 0.7314864 1.0100 2013 21.87106 21.70489 0.7935087 1.0077 2015 0.3055560 0.1306831 0.6717174 2.3381 0.5988016 0.2406442 0.8065258 2.4883 16.15805 15.98074 0.5502918 1.0111 2012 2016 R0 ranged from 1.0077 – 2.4883 IV DISCUSSION revealed similar findings [5] Hand, foot and The Hand, foot and mouth epidemics in Hai mouth is common in infants and children Phong during 2012 - 2016 share many simi- younger than years old because they not larities with previous large outbreaks in the yet have immunity (protection) to the viruses Asia-Pacific area [5] The number of cases that cause Hand, foot and mouth [5] The reduced gradually over the years to a mini- lower rate during the first year of life could be mum in 2015 (10.2%) This decrease probably because of a relatively low frequency of con- corresponded to the introduction of interven- tact with other children or to the presence of tion strategies in Haiphong and diminishing maternal antibodies [5] A study in Singapore number of susceptible people [1] The number revealed that, following the decline of maternal of cases peaked between April and Septem- antibodies, the seroprevalance for EV-71 in- ber accounting for 53.9% of all the cases A creased at an average rate of 12% per year in study by Nguyen et al (2014) showed that children from two to five years of age, and Hand, foot and mouth cases occurred virtually reached a steady state of ~ 50% in children throughout the year, with ~ 60% occurring years and above [1] from May to October [4] Analysis of data from The average incidence of Hand, foot and the 2005 epidemic in Vietnam revealed a dif- mouth was 106 cases per 100.000 population ferent trend [2] This is consistent with the (Table 1) This is lower than the incidence rate general trend that epidemics of Hand, foot and of 524 per 100.000 population reported during mouth not occur uniformly throughout the the 2011 - 2012 outbreak [6] The incidence year across Asia especially in the Western rate decreased gradually over the year pe- Pacific Region (5) riod A study in Hong Kong showed that the The age-specific incidence rate for Hand, depletion of susceptible people was the most foot and mouth was highest in the age group important driving factor of the Hand, foot and of - years old (75.04%) A systematic re- mouth transmission dynamics although mete- view of existing evidence by Koh et al, in 2016 orological factors and school vacations also JMR 116 E3 (7) - 2018 83 JOURNAL OF MEDICAL RESEARCH appeared to have an impact on Hand, foot and incidence During the five year period, there mouth transmission [12] The incidence of were six epidemics of Hand, foot and mouth Hand, foot and mouth varied from one district disease in Hai Phong The worst and most to another, within the same district and from severe occurred in the early half of 2012 one year to another (Figure 3) This indicates (Figure 2) that hotspots of Hand, foot and mouth were Analysis revealed that the same parame- not fixed and changed considerably across the ters in the SIR model changed relatively little whole of Hai Phong from 2012 to 2016 A within the year (table 2) although they was study in 2011 in China by Liu et al, found a similar pattern where there was clear variation in incidence between districts of the city in which they conducted their study They called this phenomenon “spatial-temporal clusters” and attributed it partly to differences in climatic, geographic and social factors [13] variation between the years This implies that some level of prediction could be made about the incidence trends in subsequent years with the help of data from 2012 to 2016 in Hai Phong R0 ranged from 1.0077 (2013) to 2.4883 (2016) This variation in R0 was probably due to variation in β and γ between the Regarding virus serotypes, the serotypes various epidemics Persistence of Hand, foot were EV - 71 (52.65%) and CV-A6 (21.8%) and mouth in this geographical area may be There was variation in virus serotype during due to the changing virus (multiple serotypes) the year period as new serotypes were iden- and host (birth, migration) ecology; global tified Probably these serotypes were in circu- warming affecting the climate factors Failure lation previously but at very low levels or they were introduced into Hai Phong from other of control measures might also account for the persistence of Hand, foot and mouth [1; 5; 13] neighbouring provinces It maybe that virus interaction with ecological, climate and human factors lead to serotype conversion Serotype In 2017, Chunqing Wu developed an SEIR mathematical model to estimate R0 Using conversion has already been documented in data from the 2015 - 2016 outbreak of Hand, some microorganisms [14] During the 2011 - foot and mouth in Singapore, it was estimated 2012 Hand, foot and mouth epidemic in Hai that the yearly R0 was 1.1924 (2015) and Phong, 55% of cases were due to EV-71 [6] 1.21462 (2016) Both of them are greater than In 2005, an enterovirus was isolated from 1, which implies that Hand, foot and mouth 53.8% of the cases: 42.1% isolates were was prevalent in Singapore during these two EV71 and 52.1% were CV - A16 (2) During years [15] Generally, estimates of the basic the course of 2008, 37.5% isolates were en- reproduction number range widely from 1.1 to terovirus-positive, including 27.3% with EV71 5.5 [5] and 69.7% with CA16 [1] Our results likely overestimate the actual Analysis revealed that the cases recorded values because the model used was based on in Haiphong from 2012 to 2016 were not a several theoretical assumptions that not result of a continuous epidemic but due to in- reflect reality (e.g the population is closed, the termittent increase above the baseline rate of time scale of disease transmission, the inflow 84 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH of new susceptible people into the population Mouth Disease, Southern Vietnam, 2005 is negligible) which may not capture the real Emerging Infectious Diseases, 13(11), 1733 - life dynamics of virus and host ecology 1741 Solomon T., Lewthwaite P., Perera D., V CONCLUSION Cardosa MJ et al (2010) Virology, epidemiol- This study established that Hand, foot and mouth virus circulates endemically in ogy, pathogenesis, and control of enterovirus 71 Lancet Infect Dis, 10(11), 778 - 790 Haiphong causing many cases of Hand, foot Nguyen NTB., Pham HV., Hoang CQ., and mouth and thus represents a substantial Nguyen TM., Nguyen LT., Phan HC et al ongoing threat to the health of children (2014) Epidemiological and clinical character- (especially those below years) in Hai Phong istics of children who died from hand, foot and province The major aetiologic agents were EV mouth disease in Vietnam, 2011 BMC Infec- - A71 (52.6%), CV - A6 (21.8%), CV - A16 tious Diseases 14(1), 341 (5.7%) and CV - A10 (6%) There was differ- Koh WM., Bogich T., Siegel K., Jin J ential spatial distribution of Hand, foot and et al (2016) The Epidemiology of Hand, Foot mouth cases and Mouth Disease in Asia: A Systematic Re- The estimated R0 ranged from 1.0077 2.4883, meaning in each year, it was greater than These findings suggest that under current conditions, Hand, foot and mouth will continue to persist in Haiphong view and Analysis Pediatr Infect Dis J, 35(10), 285 - 300 National Institute of Hygiene and Epidemiology (NIHE) Epidemiology and etiological characteristics of HFMD epidemic in Hai Phong city, Vietnam, 2011 - 2012 2017 Improve and strengthen surveillance and Hethcote HW (2000) The Mathematics build a model that captures the realities of vi- of Infectious Diseases SIAM Review, 42(4), rus and host ecology (accuracy, transparency 599 - 653 flexibility) Choisy M., Guégan J-F., Rohani P ACKNOWLEDGEMENTS (2007) Mathematical modeling of infectious diseases dynamics Encyclopedia of infectious This work was supported by IRD project JEAI provided the technical support REFERENCES diseases: modern methodologies, 379 - 404 Invest in Vietnam Red River Delta/ Phong Hanoi: Vietnam Invest Network Corp; [cited 2017 02 - 04] Available from: http:// World Health Organization (2011) West Pacific Region A Guide to clinical man- investinvietnam.vn/report/parent-region/90/112/ Hai-Phong.aspx agement and public health response for hand, 10 Keeling MJ., Rohani P (2008) Mod- foot and mouth disease (HFMD) WHO Library eling Infectious Diseases in Humans and Ani- Cataloguing in Publication Data mals, Princeton, New Jersey 08540: Prince- Van Tu P., Thao NTT., Perera D., Truong KH et al (2007) Epidemiologic and Virologic Investigation of Hand, Foot and JMR 116 E3 (7) - 2018 ton University Press 11 R Development Core Team R (2011): A Language and Environment for Sta85 JOURNAL OF MEDICAL RESEARCH tistical Computing Vienna, Austria Vienna, 14 Stroeher UH., Karageorgos LE., Mo- Austria: the R Foundation for Statistical Computing; 2011 Available from: http://www.R- rona R., Manning PA (1992) Serotype con- project.org/ the National Academy of Sciences of the 12 Yang B., Lau EHY., Wu P., Cowling version in Vibrio cholerae O1 Proceedings of United States of America, 89(7), 2566 - 2570 BJ Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in -Mouth Disease Model with Standard Inci- Hong Kong, 6, 27500 dence Rate and Estimation for Basic Repro- 13 Liu Y., Wang X., Liu Y., Sun D et al (2013) Detecting Spatial-Temporal Clusters of 15 Wu C (2017) Analysis of a Hand-Foot duction Number Mathematical and Computational Applications, 22(2), 29 HFMD from 2007 to 2011 in Shandong Province, China PLoS ONE, 8(5), e63447 86 JMR 116 E3 (7) - 2018 ... disease in Ho Chi Minh City Haiphong 2012 - 2016 with most cases (96.2%) being in children < years old [2] In 2006 - 2007, 305 cases were Develop and test the model of Hand, foot and mouth disease in. .. date of mission and control of Hand, foot and mouth admission [4; 6] 76 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH Case Definition In Vietnam, Hand, foot and mouth disease is defined as... 1.0111 2012 2016 R0 ranged from 1.0077 – 2.4883 IV DISCUSSION revealed similar findings [5] Hand, foot and The Hand, foot and mouth epidemics in Hai mouth is common in infants and children Phong