A Systematic Review of the Statistical Methodology Used in Establishing the Link Between Climate Factors and HFMD Incidence

Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by two main viruses, namely Coxsackievirus A16 and Human Enterovirus 71. It has been a significant public health disease and a substantial burden all over the world since 1969. Prior studies have shown that climate factors are significantly associated with HFMD cases by using various statistical methods. Therefore, this study aims to review the scientific studies related to climate and HFMD and hence, address the analytical techniques used. This study only includes quantitative studies from peer-reviewed and original papers published in international and national journals from the years 1957 to 2020. In total, there were 522 articles identified; however, there were only 29 studies that linked climate change and HFMD. Based on the articles reviewed, the modelling analysis technique, which includes the Generalized Linear Model (GLM), the Generalized Additive Model (GAM), and the Generalized Additive Mixed Model (GAMM), represents the most popular analysis in identifying the association between HFMD and climate factors. The temperature and humidity showed the greatest impact on the occurrence of HFMD, and the suitable incubation period for all climatic factors was not more than three weeks.

First seroepidemiological investigation of human enterovirus 71 in Iran

Background and Objectives: Human Enterovirus 71 (EV-A71) is the causative agent for many dermal to neurological diseases especially polio-like paralysis outbreaks around the world. This study, the first of this kind in Iran, aimed to find neu- tralizing antibodies against EV-A71 in serum of healthy individuals in different age groups based on neutralization test (NT). Materials and Methods: In this cross-sectional study, 547 serum samples were collected from healthy individuals who were referring for routine checkup tests (aged from under 6 months to over 31 years old) to Imam-Khomeini Hospital in Tehran during January-December 2015. Serum samples were examined by NT in cell culture to detect neutralizing antibodies against EV-A71. In the next step, some of the positive samples were subjected to complete titration to determine the exact titer of anti-EV-A71 antibodies. Results: Of 547 samples, 310 (56.7%) were positive for EV-A71 neutralizing antibody. The presence of the antibody in- creased with age (p<0.001), and there was a significant statistical relationship between sex and the presence of antibody (p=0.009). Conclusion: Our results demonstrated an apparent but limited circulation of EV-A71 in our society. After the worldwide eradication of poliovirus, EV-A71 which can cause polio-likes syndrome, might be the new challenge for our health care system as regard more in depth research is however needed.

Global Spatiotemporal Transmission Patterns of Human Enterovirus 71 from 1963 to 2019

ABSTRACT EV71 can cause large outbreaks of HFMD and severe neurological diseases, which is regarded as a major threat to public health especially in Asia-Pacific regions. However, the global spatiotemporal spread of this virus has not been identified. In this study, we used large sequence datasets and a Bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of different EV71 subgroups globally. The study found that subgroups of HFMD presented global spatiotemporal variation, subgroups B0, B1 and B2, have caused early infections in Europe and America, and then subgroups C1, C2, C3, C4 replaced B0-B2 as the predominant genotypes especially in Asia-Pacific countries. The dispersal patterns of genotype B and subgroup C4 showed the complicated routes in Asia and the source might in some Asia countries, while subgroups C1 and C2 displayed more strongly support pathways globally especially in Europe. This study found the predominant subgroup of EV71 and its global spatiotemporal transmission patterns, which may be beneficial to reveal the long term global spatiotemporal transmission patterns of human enterovirus 71 and carry out the HFMD vaccine development.

Correction: Yang et al. Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71. Int. J. Mol. Sci. 2013, 14, 9618

The authors wish to make the following corrections to this paper [...]

Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids

Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.

Study the current scenario of hand foot mouth disease an Indian prospective

Background: The hand-foot-mouth disease (HFMD) is an acute communicable disease, mostly affecting children under 5 years of age and caused by human enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16). The usual incubation period is 3 to 7 days. Early symptoms are likely to be fever often followed by a sore throat followed by loss of appetite and general malaise. Aim and objectives was to study the trend of hand foot and mouth disease in a private hospital in Uttarakhand over 5 successive years.Methods: This cross-sectional study was carried among 297 cases of HFMD newborn screened at pediatrics department of Sahota Super-specialty hospital, Kashipur, Uttarakhand during year 2015 to 2019 after ethical clearance of institutional ethical committee. Diagnosis is coded with ICD-10. SPSS version 20 was used to calculate frequencies and percentiles.Results: Almost 29 cases of HMFD were picked in 2015, 32 cases in 2016, 43 cases in 2017, 81 cases in 2018, 112 in 2019. Fever observed in 86% cases. Neurological complications were observed in 9 (3%) cases, pneumonitis in 14 (4.7%) cases, cardiomyopathy observed in 3 (<1%) case. One death was reported.Conclusions: It is vital to screen patients with HFMD for these abnormal clinical presentations, allowing timely initiation of appropriate interventions to reduce the mortality. Increased awareness about vaccination in a developing nation like India and vaccination program at the grass root levels have eradicated certain lethal diseases.

Onychomadesis associated with hand, foot, and mouth disease: a prospective observational study from North Chennai

<p class="abstract"><strong>Background:</strong> Hand, foot, and mouth disease (HFMD) is a common febrile illness caused by coxsackievirus A16 and human enterovirus 71 characterized by vesicular eruptions on hands and feet and enanthem on oral mucosa. Resolves usually without complications but onychomadesis can occur as a late sequlae sometimes.</p><p class="abstract"><strong>Methods:</strong> Children with clinical diagnosis of HFMD between April to June 2018 were included in the study. Age, sex, duration of illness, cutaneous features and nail changes were noted at initial visit and during every week for next 6 weeks.<strong></strong></p><p class="abstract"><strong>Results:</strong> 58 children were recruited in the study with boys to girl’s ratio 1.2:1. The average age was 5.3 years. The vesicular lesions predominantly involved palms and soles (88.3%). 65.5% had history of fever and pruritis was the commonest cutaneous symptom. 27 children (48.21%) developed onychomadesis during follow up with average time interval of 3.2 weeks between the clinical diagnosis and nail shedding. Reassurance about spontaneous resolution of the condition given to the parents.</p><p class="abstract"><strong>Conclusions:</strong> Our study strengthened the association between the HFMD and occurrence of onychomadesis. Physician’s awareness about this benign condition is needed to avoid parental anxiety, unnecessary investigations and treatment for the children. </p>

Gambaran Klinis dan Karakteristik Genetik Human Enterovirus 71 Penyebab Hand Foot and Mouth Disease di Banjarmasin – Kalimantan Selatan Tahun 2016

Latar belakang. Hand foot and mouth desease (HFMD) adalah infeksi virus akut yang biasanya menyerang anak dibawah 10 tahun, sangat menular dan dapat menimbulkan komplikasi fatal. Tujuan. Untuk mengetahui gejala klinis, komplikasi, dan serotipe penyebab HFMD di Banjarmasin. Metode. Penelitian deskriptif, sampel diambil di poliklinik RSUD Ulin dan RS. Islam Banjarmasin periode November 2015 sampai dengan Febuari 2016 yang terdiagnosis HFMD oleh dokter spesialis anak, terdapat 23 sampel.Hasil. Dari 23 pasien secara klinis HFMD terdapat 18 (78%) positif entero virus, 71, 2 (9%) positif campak, dan 3 (13%) negatif. Umur rata rata ±20,77 bulan, laki laki 12 (52%) dan perempuan 11 (48%). Gejala klinis demam 17 (74%), rash/ lesi kulit 23 (100%), susah makan 14(61%), batuk 8(35%), pilek 9(39%), diare 5(22%), konjungtivitis 2(9%), muntah 4(17%), nyeri menelan 14(61%), dan kenjang 2(9%).Kesimpulan. Penyebab HFMD terbanyak adalah EV71, umur tesering kurang dari 3 tahun, gejala klinis terbanyak lesi kulit, demam dan tidak didapatkan komplikasi serius (intakranial).