Application of logistic differential equation models for early warning of infectious diseases in Jilin Province.

BACKGROUND: There is still a relatively serious disease burden of infectious diseases and the warning time for different infectious diseases before implementation of interventions is important. The logistic differential equation models can be used for predicting early warning of infectious diseases. The aim of this study is to compare the disease fitting effects of the logistic differential equation (LDE) model and the generalized logistic differential equation (GLDE) model for the first time using data on multiple infectious diseases in Jilin Province and to calculate the early warning signals for different types of infectious diseases using these two models in Jilin Province to solve the disease early warning schedule for Jilin Province throughout the year. METHODS: Collecting the incidence of 22 infectious diseases in Jilin Province, China. The LDE and GLDE models were used to calculate the recommended warning week (RWW), the epidemic acceleration week (EAW) and warning removed week (WRW) for acute infectious diseases with seasonality, respectively. RESULTS: Five diseases were selected for analysis based on screening principles: hemorrhagic fever with renal syndrome (HFRS), shigellosis, mumps, Hand, foot and mouth disease (HFMD), and scarlet fever. The GLDE model fitted the above diseases better (0.80 ≤ R2 ≤ 0.94, P <  0. 005) than the LDE model. The estimated warning durations (per year) of the LDE model for the above diseases were: weeks 12-23 and 40-50; weeks 20-36; weeks 15-24 and 43-52; weeks 26-34; and weeks 16-25 and 41-50. While the durations of early warning (per year) estimated by the GLDE model were: weeks 7-24 and 36-51; weeks 13-37; weeks 11-26 and 39-54; weeks 23-35; and weeks 12-26 and 40-50. CONCLUSIONS: Compared to the LDE model, the GLDE model provides a better fit to the actual disease incidence data. The RWW appeared to be earlier when estimated with the GLDE model than the LDE model. In addition, the WRW estimated with the GLDE model were more lagged and had a longer warning time.

Relative transmissibility of hand, foot and mouth disease from male to female individuals.

Hand, foot and mouth disease (HFMD) has spread widely and leads to high disease burden in many countries. However, relative transmissibility from male to female individuals remains unclear. HFMD surveillance database was built in Shenzhen City from 2013 to 2017. An intersex transmission susceptible-infectious-recovered model was developed to calculate the transmission relative rate among male individuals, among female individuals, from male to female and from female to male. Two indicators, ratio of transmission relative rate (Rß) and relative transmissibility index (RTI), were developed to assess the relative transmissibility of male vs. female. During the study period, 270 347 HFMD cases were reported in the city, among which 16 were death cases with a fatality of 0.0059%. Reported incidence of total cases, male cases and female cases was 0.0057 (range: 0.0036-0.0058), 0.0052 (range: 0.0032-0.0053) and 0.0044 (range: 0.0026-0.0047), respectively. The difference was statistically significant between male and female (t = 3.046, P = 0.002). Rß of male vs. female, female vs. female, from female to male vs. female and from male to female vs. female was 7.69, 1.00, 1.74 and 7.13, respectively. RTI of male vs. female, female vs. female, from female to male vs. female and from male to female vs. female was 3.08, 1.00, 1.88 and 1.43, respectively. Transmissibility of HFMD is different between male and female individuals. Male cases seem to be more transmissible than female.

Seasonality of the transmissibility of hand, foot and mouth disease: a modelling study in Xiamen City, China.

This study attempts to figure out the seasonality of the transmissibility of hand, foot and mouth disease (HFMD). A mathematical model was established to calculate the transmissibility based on the reported data for HFMD in Xiamen City, China from 2014 to 2018. The transmissibility was measured by effective reproduction number (Reff) in order to evaluate the seasonal characteristics of HFMD. A total of 43 659 HFMD cases were reported in Xiamen, for the period 2014 to 2018. The median of annual incidence was 221.87 per 100 000 persons (range: 167.98/100,000-283.34/100 000). The reported data had a great fitting effect with the model (R2 = 0.9212, P < 0.0001), it has been shown that there are two epidemic peaks of HFMD in Xiamen every year. Both incidence and effective reproduction number had seasonal characteristics. The peak of incidence, 1-2 months later than the effective reproduction number, occurred in Summer and Autumn, that is, June and October each year. Both the incidence and transmissibility of HFMD have obvious seasonal characteristics, and two annual epidemic peaks as well. The peak of incidence is 1-2 months later than Reff.

Transmissibility of hand, foot, and mouth disease in 97 counties of China.

Hand, foot, and mouth disease (HFMD) is a serious disease burden in the Asia-Pacific region, including China. This study calculated the transmissibility of HFMD at county levels in Jiangsu Province, China, analyzed the differences of transmissibility and explored the possible influencing factors of its transmissibility. We built a mathematical model for seasonal characteristics of HFMD, estimated the effective reproduction number (Reff), and compared the incidence rate and transmissibility in different counties using non-parametric tests, rapid cluster analysis and rank-sum ratio in 97 counties in Jiangsu Province from 2015 to 2020. The average daily incidence rate was between 0 and 4 per 100,000 people in Jiangsu Province from 2015-2020. The Quartile of Reff in Jiangsu Province from 2015 to 2020 was 1.54 (0.49, 2.50). Rugao District and Jianhu District had the highest transmissibility according to the rank-sum ratio. Reff generally decreased in 2017 and increased in 2018 in most counties, and the median level of Reff was the lowest in 2017 (P < 0.05). The transmissibility was different in 97 counties in Jiangsu Province. The reasons for the differences may be related to the climate, demographic characteristics, virus subtypes, vaccination, hygiene and other infectious diseases.

Early warning of hand, foot, and mouth disease transmission: A modeling study in mainland, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. METHODS: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. RESULTS: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. CONCLUSIONS: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.

Meteorological Factors and the Transmissibility of Hand, Foot, and Mouth Disease in Xiamen City, China.

Background: As an emerging infectious disease, the prevention and control of hand, foot, and mouth disease (HFMD) poses a significant challenge to the development of public health in China. In this study, we aimed to explore the mechanism of the seasonal transmission characteristics of HFMD and to reveal the correlation and potential path between key meteorological factors and the transmissibility of HFMD. Methods: Combined with daily meteorological data such as average temperature, average relative humidity, average wind velocity, amount of precipitation, average air pressure, evaporation capacity, and sunshine duration, a database of HFMD incidence and meteorological factors was established. Spearman rank correlation was used to calculate the correlation between the various meteorological factors and the incidence of HFMD. The effective reproduction number (R eff ) of HFMD was used as an intermediate variable to further quantify the dynamic relationship between the average temperature and R eff . Results: A total of 43,659 cases of HFMD were reported in Xiamen from 2014 to 2018. There was a significantly positive correlation between the average temperature and the incidence of HFMD (r = 0.596, p < 0.001), and a significantly negative correlation between the average air pressure and the incidence of HFMD (r = -0.511, p < 0.001). There was no correlation between the average wind velocity (r = 0.045, p > 0.05) or amount of precipitation (r = 0.043, p > 0.05) and incidence. There was a temperature threshold for HFMD's transmissibility. Owing to the seasonal transmission characteristics of HFMD in Xiamen, the temperature threshold of HFMD's transmissibility was 13.4-18.4°C and 14.5-29.3°C in spring and summer and in autumn and winter, respectively. Conclusions: HFMD's transmissibility may be affected by the average temperature; the temperature threshold range of transmissibility in autumn and winter is slightly wider than that in spring and summer. Based on our findings, we suggest that the relevant epidemic prevention departments should pay close attention to temperature changes in Xiamen to formulate timely prevention strategies before the arrival of the high-risk period.

Interaction analysis on transmissibility of main pathogens of hand, foot, and mouth disease: A modeling study (a STROBE-compliant article).

Hand, foot, and mouth disease (HFMD) has spread widely and led to high disease burden in many countries. In this study, we aimed to analyze the interaction of the main pathogens of HFMD using a mathematical model.A dataset on reported HFMD cases was collected from April, 2009 to December, 2017 in Changsha City. A long-term etiological surveillance was conducted focusing on the pathogens of the disease including enterovirus A71 (EV71), coxsachievirus A16 (CA16), and other enteroviruses. A susceptible-infectious-recovered model was adopted to calculate the reproduction number during the ascending period of reported cases (defined as Rasc) and the descending period (defined as Rdes).About 214,178 HFMD cases (including clinically diagnosed cases and confirmed cases) were reported in Changsha City, among which 31 were death cases with a fatality of 0.01%. The number of reported HFMD cases increased yearly with a Linear model of "f(t) = 18542.68 + 1628.91t" where f(t) and t referred to number of reported cases and sequence of year, respectively. The fatality of the disease decreased yearly with a linear model of "f(t) = - 0.012 + 0.083/t". About 5319 stool or anal swab specimens were collected from the reported cases. Among them, 1201 were tested EV71 positive, 836 were CA16 positive, and 1680 were other enteroviruses positive. Rasc and Rdes of HFMD was 1.34 (95% confidence interval [CI]: 1.28-1.40) and 0.73 (95% CI: 0.69-0.76), respectively. EV71 and CA16 interacted with each other, and the interaction between EV71 and other enteroviruses and the interaction between CA16 and other enteroviruses were both directional. However, during the reported cases decreasing period, interactions only occurred between EV71 and other enteroviruses and between CA16 and other enteroviruses. These interactions all decreased Rasc but increased Rdes of affected pathogens.The interactions of the pathogens exist in Changsha City. The effective reproduction number of the affected pathogen is adjusted and verges to 1 by the interaction.

[Clinical and genetic analysis for a Joubert syndrome family with CC2D2A gene mutations].

OBJECTIVE: To confirm the genetic diagnosis for providing services for genetic counseling and prenatal diagnosis, we analyzed the clinical and genetic data of a pedigree which is clinically diagnosed as Joubert syndrome. METHOD: A Joubert syndrome pedigree was enrolled as subject of this study from our hospital's outpatients in 2013. Following the medical history collection of the proband and the suffering fetus, target sequence capture and the next-generation sequencing technology were used for the proband and the suffering fetus to find the causative genes and sanger sequencing for the members of the pedigree to check and verify if the inherited mutations are in accordance with the Mendelian inheritance. Combining the clinical symptoms and signs with the total testing results, we analyzed the Joubert syndrome pedigree clinically and genetically. RESULT: The proband showed abnormal respiratory patterns (neonatal tachypnea) and hypertonia without abnormal eye movements, and reflected the molar tooth sign on the magnetic resonance imaging. And afterwards the patient developed hypotonia, ataxia, growth and intellectual disability accompanied by congenital blepharoptosis. There were no any symptoms and signs of liver, kidney and eyesight abnormalities so far. The affected fetus showed hydrocephalus by the auxiliary examination during the second trimesters of pregnancy without any appearance deformities. Both the proband and the affected fetus carried a missense mutation of CC2D2A gene c.2999A > T (p.Glu1000Val) from their father and carried the deletion of exon 20-21 on the same gene. Both variations were confirmed to be the Mendelian genetic compound heterozygous pattern. Whereas, the missense mutations c.2999A > T (p.Glu1000Val) on the CC2D2A gene have been proved to be inherited from the proband's father and the proband as well as the affected fetus. However, the proband's mother was normal at this locus of CC2D2A gene. The missense mutations c.2999A >T (p.Glu1000Val) have been confirmed to accord with Mendelian inheritance. CONCLUSION: The Joubert syndrome patient may show hypertonia in the early postnatal days as a result of hydrocephalus during the second and third trimesters of pregnancy besides manifesting hypotonia, ataxia, growth and intellectual disability markedly with age accompanied by the congenital blepharoptosis and revealing the molar tooth sign on the magnetic resonance imaging, considering the medical history and the whole testing results, the compound heterozygous mutations of c.2999A > T (p.Glu1000Val) and deletion of exon 20-21 of CC2D2A gene in the pedigree may be the causal gene mutations.