Diphtheria resurgence in Sada'a-Yemen, 2017–2020

Background Diphtheria is a contagious vaccine-preventable disease that contributes to the high morbidity and mortality among under 5 children, especially in Yemen. As a consequence of war and collapse of the health system, a fatal epidemic occurred at the end of 2017. This study aims to describe the epidemiology of diphtheria by time, place, and person and vaccination status of affected children. Methods A study was conducted in Sada'a governorate by using accumulative line list of diphtheria from November 2017 to September 2020 at electronic Integrated Disease Early Warning System (eIDEWS). The case definition of WHO was adopted. Data was analyzed by Microsoft Excel and Epi info- version 7.2 and multivariable logistic analysis used for identifying significant associated factors. Results 747 cases were met of WHO case definition. The annual peak of cases started during week 31 and weak 49. Males were slightly more than females (51% vs 49%) and about 35% of cases involved children aged 10 to < 15 years. The overall incidence of diphtheria and case fatality rate (CFR) were 69/ 100,000 and 6.4%, respectively. The highest CFR was among age groups under 5 years 11% (P < 0.001) and among females was 8%. Dysphagia and swollen lymph nodes were the predominant symptoms 98%, 92%, respectively. Based on the Vaccination status, the percentage of unvaccinated and unknown were 53% and 41% respectively, with CFR 11% among cases who received one dose. Furthermore, the most case were from Sahar 40% with case fatality rate 8% and the highest CFR was significantly higher among cases in border and ongoing conflict district (P < 0.05). Conclusions The findings highlight that diphtheria is still an ongoing cause of morbidity and mortality among under 5 children in Sada'a that is rising with the low diphtheria immunization coverage. Therefore, concomitant efforts should now focus on improving and monitoring routine immunization across all age groups and healthcare services, especially in borders and continuing conflict districts.

A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever

Background Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago–the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. Methodology We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. Results A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. Conclusions This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.

Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) Aged 12–20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12–20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC.MethodsWe investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC’s health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC’s Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination.FindingsWe identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12–20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12–20 years had received ≥1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1·0 case per million persons receiving ≥1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated persons.InterpretationIn our case series, we describe a small number of persons with MIS-C who had received ≥1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted.FundingThis work was supported by the Centers for Disease Control and Prevention Clinical Immunization Safety Assessment (CISA] Project contracts 200-2012-50430-0005 to Vanderbilt University Medical Center and 200-2012-53661 to Cincinnati Children’s Hospital Medical Center.Research in context panelEvidence before this studyMultisystem inflammatory syndrome in children (MIS-C), also known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is an uncommon, but serious, complication described after SARS-CoV-2 infection that is characterized by a generalized hyperinflammatory response. A review of the literature using PubMed identified reports of six persons aged 12–20 years who developed MIS-C following COVID-19 vaccination. Search terms used to identify these reports were: “multisystem inflammatory syndrome in children”, “MIS-C”, “MISC”, “multisystem inflammatory syndrome in adults”, “MIS-A”, “MISA”, “paediatric inflammatory multisystem syndrome”, and “PIMS-TS” each with any COVID-19 vaccine type. There were no exclusion criteria (i.e., all ages and languages).Added value of this studyWe conducted integrated surveillance for MIS-C after COVID-19 vaccination using two passive surveillance systems, CDC’s MIS-C national surveillance and the Vaccine Adverse Event Reporting System (VAERS), and clinician or health department outreach to CDC, including through Clinical Immunization Safety Assessment (CISA) Project consultations. We investigated reports of potential MIS-C occurring from December 14, 2020, to August 31, 2021, in persons aged 12–20 years any time after receipt of COVID-19 vaccine to identify those that met the CDC MIS-C case definition. Any positive serology test was accepted as meeting the CDC MIS-C case definition, although anti- nucleocapsid antibody is indicative of SARS-CoV-2 infection, while anti-spike protein antibody may be induced either by SARS-CoV-2 infection or by COVID-19 vaccination. We investigated 47 reports and identified 21 persons with MIS-C after receipt of COVID-19 vaccine. Of the 21 persons with MIS-C, median age was 16 years (range 12–20 years), and 13 (62%) were male. Fifteen (71%) had laboratory evidence of past or recent SARS-CoV-2 infection (positive SARS-CoV-2 nucleic acid amplification test [NAAT], viral antigen, or serology test before or during MIS-C illness evaluation), and 5 (33%) of those 15 had illness onset after their second vaccine dose. Six (29%) of 21 persons had no laboratory evidence of past or recent SARS-CoV-2 infection, and five of those six (83%) had onset of MIS-C after the second vaccine dose.Implications of all the available evidenceDuring the first nine months of the COVID-19 vaccination program in the United States, >21 million persons aged 12 to 20 years received ≥1 dose of COVID-19 vaccine as of August 31, 2021. This case series describes MIS-C in 21 persons following vaccine receipt during this time period; the majority of persons reported also had evidence of SARS-CoV-2 infection. The surveillance has limitations, but our findings suggest that MIS-C as identified in this report following COVID-19 vaccination is rare. In evaluating persons with a clinical presentation consistent with MIS-C after COVID-19 vaccination it is important to consider alternative diagnoses, and anti-nucleocapsid antibody testing may be helpful. Continued surveillance for MIS-C illness after COVID-19 vaccination is warranted, especially as pediatric COVID-19 vaccination expands. Providers are encouraged to report potential MIS-C cases after COVID-19 vaccination to VAERS.

Affinché non MIS-Cappi il caso: la sindrome infiammatoria multisistemica SARS-CoV-2-correlata

Background - Covid-19 is less frequent and milder in children than in adults. However, cases of multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (MIS-C) have been reported in children, whose phenotype resembles atypical Kawasaki disease. Objectives - The paper describes incidence as well as clinical, laboratoristic and radiological findings of MIS-C. Materials and methods - In the Paediatric Infectious Disease Centre of Palermo (Italy), a targeted surveillance for MIS-C from March 2020 to January 2021 was conducted. Case definition included WHO, UK and US criteria. Results - The paper reports the cases of 9 patients with MIS-C out of which 8 (88%) were hospitalized after September 2020. 44% were male and their median age was 6.5 years. Organ-system involvement included gastrointestinal (66%), cardiovascular (66%), mucocutaneous (88%), reticuloendothelial (77%) and respiratory (55%) systems. C-reactive protein (CRP), procalcitonin, D-dimer and pro-B-type natriuretic peptide levels (pro-BNP) were high in all patients. Chest radiography showed bilateral ground glass-opacities (55%) and pleural effusions (44%). Abdominal imaging findings included small-volume ascites (55%) and mesenteric lymphadenopathy (22%). Echocardiogram showed transient valves regurgitation (55%). In all the patients, the left ventricular ejection fraction was normal and coronary-artery aneurysms were not documented. They were treated with immunomodulating therapies. All patients neither received intensive care nor died. Conclusions - MIS-C represents a new systemic inflammatory syndrome with a phenotype resembling Kawasaki disease. MIS-C remains a rare condition, in which gastrointestinal and mucocutaneous involvement is predominant, nevertheless cardiovascular involvement must be investigated. MIS-C could be suspected even if SARS-CoV-2 exposure precedes the onset of the symptoms by more than 6 weeks. In most cases, a good prognosis might be expected.

Characteristics and outcomes of cases of children and adolescents with pediatric inflammatory multisystem syndrome in a tertiary care centre in Mexico City.

Background: pediatric inflammatory multisystem syndrome (PIMS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children that resembles Kawasaki syndrome and poses children at high risk of cardiorespiratory instability and/or cardiac damage. This study aims to describe the clinical presentation and outcomes of patients with PIMS in Mexico City. Methods: this was an observational study (May 1, 2020, to September 30, 2021) of children with PIMS according to Centers of Disease Control and Prevention case definition criteria, hospitalized in a single tertiary care pediatric center in Mexico City. Demographic characteristics, epidemiological data, medical history, laboratory tests, cardiology evaluations, treatment, and clinical outcomes were analyzed. Results: Seventy-five cases fulfilled case-definition criteria for PIMS (median age 10.9 years, IQR: 5.6-15.6). Fifteen (20%) had a severe underlying disease. Forty-eight cases (64%) were admitted to the intensive care unit, 33 (44%) patients required invasive mechanical ventilation, and 39 (52%) received vasopressor support. Two distinct groups of patients were identified: cluster 1 (n=60) who had rash or gastrointestinal symptoms and cluster 2 (n=15) with predominantly respiratory manifestations. Two cases (2.7%) died, both with severe underlying conditions. Five cases (6.7%) developed coronary aneurysms, all of them from cluster 1. Conclusion: clinical manifestations and outcomes are in general comparable what has been previously reported in international series. In our series, there was a high proportion of patients with severe respiratory involvement and positive RT-PCR SARS-CoV-2 and a low frequency of coronary aneurysms which suggests a possible higher proportion of children with severe acute COVID-19 in our included cases.

Risk of Myopericarditis following COVID-19 mRNA vaccination in a Large Integrated Health System: A Comparison of Completeness and Timeliness of Two Methods

Purpose: How completely do hospital discharge diagnoses identify cases of myopericarditis after an mRNA vaccine? Methods: We assembled a cohort 12 to 39 years old patients, insured by Kaiser Permanente Northwest, who received at least one dose of an mRNA vaccine (Pfizer BioNTech or Moderna) between December 2020 and October 2021. We followed them for up to 30 days after their second dose of an mRNA vaccine to identify encounters for myocarditis, pericarditis or myopericarditis. We compared two identification methods: A method that searched all encounter diagnoses using a brief text description (e.g., ICD-10-CM code I40.9 is defined as acute myocarditis, unspecified). We searched the text description of all inpatient or outpatient encounter diagnoses (in any position) for myocarditis or pericarditis. The other method was developed by the Centers for Disease Control and Preventions Vaccine Safety Datalink (VSD), which searched for emergency department visits or hospitalizations with a select set of discharge ICD-10-CM diagnosis codes. For both methods, two physicians independently reviewed the identified patient records and classified them as confirmed, probable or not cases using the CDCs case definition. Results: The encounter methodology identified 14 distinct patients who met the confirmed or probable CDC case definition for acute myocarditis or pericarditis with an onset within 21 days of receipt of COVID-19 vaccination. Three of these 14 patients had an ICD-10 code of I51.4 Myocarditis, Unspecified which was overlooked by the VSD algorithm. The VSD methodology identified 11 patients who met the CDC case definition for acute myocarditis or pericarditis. Seven (64%) of the eleven patients had initial care for myopericarditis outside of a KPNW facility and their diagnosis could not be ascertained by the VSD methodology until claims were submitted (median delay of 33 days; range of 12-195 days). Among those who received a second dose of vaccine (n=146,785), we estimated a risk as 95.4 cases of myopericarditis per million second doses administered (95% CI, 52.1 to 160.0). Conclusion: We identified additional valid cases of myopericarditis following an mRNA vaccination that would be missed by the VSDs search algorithm, which depends on select hospital discharge diagnosis codes. The true incidence of myopericarditis is markedly higher than the incidence reported to US advisory committees. The VSD should validate its search algorithm to improve its sensitivity for myopericarditis.

Identifying possible inaccuracy in reported birth head circumference measurements among infants in the US Zika Pregnancy and Infant Registry

The US Zika Pregnancy and Infant Registry (USZPIR) monitors infants born to mothers with confirmed or possible Zika virus (ZIKV) infection during pregnancy. The surveillance case definition for Zika-associated birth defects includes microcephaly based on head circumference (HC). We assessed birth and follow-up data from infants with birth HC measurements <3rd percentile and birthweight ≥10th percentile to determine possible misclassification of microcephaly.We developed a schema informed by literature review and expert opinion to identify possible HC measurement inaccuracy using HC growth velocity and neuroimaging results. Two or more HC measurements between 2-12 months of age were required for assessment. Inaccuracy in birth HC measurement was suspected if growth velocity was >3 centimeters/month in the first three months or HC was consistently >25th percentile during follow-up. Normal neuroimaging was considered supportive of HC measurement inaccuracy. Of 6,799 infants, 351 (5.2%) had Zika-associated birth defects, of which 111 had birth HC measurements <3rd percentile and birthweight ≥10th percentile. Of 84/111 infants with sufficient follow-up, 38/84 (45%) were classified as having possible inaccuracy of birth HC measurement, 19/84 (23%) had HC ≥3rd percentile on follow-up without meeting criteria for possible inaccuracy, and 27/84 (32%) had continued HC <3rd percentile. After excluding possible inaccuracies, the proportion of infants with Zika-associated birth defects including microcephaly decreased from 5.2% to 4.6%.About one-third of infants with Zika-associated birth defects had only microcephaly, but indications of possible measurement inaccuracy were common. Implementation of this schema in ZIKV infection during pregnancy studies can reduce misclassification of microcephaly.

Standards for comparing validity of different treatment methods: the "five E framework"

Background and Aims. Evidence Based Medicine (EBM) neglects factors extrinsic to science. To bypass such a limitation, a global approach for validation of treatment methods is proposed. In addition to effectiveness, further standards are required, in order to include priority issues like bioethics, environment preservation, global financial crisis, and undeclared conflict of interest. Methods. We suggest to evaluate any healing system within a “five E framework” by applying the following standards: 1) evidence (see EBM), 2) epistemology, 3) ethics, 4) ecology, and 5) economy. 2) Preliminary adaptation of any research to the epistemological background of the treatment to be evaluated is needed, in order to compensate for the poor compliance of EBM methodology to holistic methods. The restrictions imposed by the rules of classical epidemiology to study design (see case definition and standardization of treatment) can completely twist the analysis of results. 3) The ethical standard implies giving attention given to treatment invasiveness, related both to life of animals employed in experimental studies and to side effects on health of human volunteers or patients. 4) The ecological standard, consisting in the implications of pharmaceutical production on environment, should be analyzed in terms of ecological footprint, i.e. for the global effects of industrial waste on ecosystems and species. 5) The economical standard evaluates both the impact of financial crisis and the role played by conflict of interest, comparing allopathy with holistic systems. Conclusions. The “five E framework” seems more adequate, for several reasons, to validate homeopathy or other treatment methods, if compared with the sole EBM approach. Misunderstanding of results and consequent publication bias can be avoided by adhering, in study design, to the philosophical foundations of homeopathy, i.e. by choosing a remedy according to the law of similars and the totality of symptoms – individualization of treatment. On the ethical plane, in the case of homeopathy, apart from the absence of drug toxicity and the possibility of avoiding vivisection for experimental purposes, even in the production of drugs from animal species, induction of death can be prevented or strongly circumscribed. About effects on environment, allopathic drug waste causes pollution, alters the features of a given species, or modifies the balance between different species, while the employment of large quantities of natural active principles in drug industry has an impact on biodiversity. Homeopathic industry has no relevant effects on environment, because slag release is insignificant and the productive process is highly efficient. Finally, homeopathy meets relevant economic issues: a) while management of crisis by states with a health system mainly oriented to allopathy imposes a heavy burden to community by reducing public funding of health care, the high sustainability of all holistic systems limits the risk of worsening health care level; b) homeopathy is less subject than allopathy to undeclared conflict of interest; the enormous margins of profit and the chance of competition issued by big allopathic industry have a limited role in classical homeopathy.

Post- COVID-19 multisystem inflammatory syndrome in children

COVID-19 is a severe acute respiratory infection affecting worldwide population. There are many cases of complications after the COVID exposure occurring nowadays. One among is Post-COVID-19 Multisystem Inflammatory Syndrome in Children (MIS-C). As per CDC report till March 1, 2021, 2617 cases of MIS-C were meeting the definite case criteria and among 33 death cases were reported. Here we report a case of COVID-19 associated Multi-system inflammatory syndrome in a child (MIS-C) interpreted with WHO case definition criteria. The patient was a 7-year-old boy, with initial presentation of moderate fever, non-itchy red blanching rashes, breathlessness, later progressed to cardiogenic shock accompanied by positive SARS-CoV-2 antigen result. The emergency cardiogenic shock treatment protocol was followed with initial stabilization and resuscitation strategy. He was successfully managed by three days of IV Immunoglobulin 2g/kgand Methylprednisolone 2mg/kg/day therapy along with other supportive treatments. The patient was discharged after 20 days of hospital stay with improved health condition. Our case report will strengthen the exposure-outcome relations between the coronavirus infection and MIS-C, moreover the strategies carried out in our case will be a future direction for the effective management of MIS-C.

Assessment of Food and Waterborne Viral Outbreaks by Using Field Epidemiologic, Modern Laboratory and Statistical Methods—Lessons Learnt from Seven Major Norovirus Outbreaks in Finland

Seven major food- and waterborne norovirus outbreaks in Western Finland during 2014–2018 were re-analysed. The aim was to assess the effectiveness of outbreak investigation tools and evaluate the Kaplan criteria. We summarised epidemiological and microbiological findings from seven outbreaks. To evaluate the Kaplan criteria, a one-stage meta-analysis of data from seven cohort studies was performed. The case was defined as a person attending an implicated function with diarrhoea, vomiting or two other symptoms. Altogether, 22% (386/1794) of persons met the case definition. Overall adjusted, 73% of norovirus patients were vomiting, the mean incubation period was 44 h (4 h to 4 days) and the median duration of illness was 46 h. As vomiting was a more common symptom in children (96%, 143/149) and diarrhoea among the elderly (92%, 24/26), symptom and age presentation should drive hypothesis formulation. The Kaplan criteria were useful in initial outbreak assessments prior to faecal results. Rapid food control inspections enabled evidence-based, public-health-driven risk assessments. This led to probability-based vehicle identification and aided in resolving the outbreak event mechanism rather than implementing potentially ineffective, large-scale public health actions such as the withdrawal of extensive food lots. Asymptomatic food handlers should be ideally withdrawn from high-risk work for five days instead of the current two days. Food and environmental samples often remain negative with norovirus, highlighting the importance of research collaborations. Electronic questionnaire and open-source novel statistical programmes provided time and resource savings. The public health approach proved useful within the environmental health area with shoe leather field epidemiology, combined with statistical analysis and mathematical reasoning.