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BackgroundDifferent diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)—familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)—and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA.MethodsStep 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients’ diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of the best candidate classification criteria; step 4: nominal group technique consensus conference with 33 panellists for the discussion and selection of the final classification criteria; step 5: cross-sectional validation of the novel criteria.ResultsThe panellists achieved consensus to classify 281 of 360 (78%) patients (32 CAPS, 36 FMF, 56 MKD, 37 PFAPA, 39 TRAPS, 81 undefined recurrent fever). Consensus was reached for two sets of criteria for each HRF, one including genetic and clinical variables, the other with clinical variables only, plus new criteria for PFAPA. The four HRF criteria demonstrated sensitivity of 0.94–1 and specificity of 0.95–1; for PFAPA, criteria sensitivity and specificity were 0.97 and 0.93, respectively. Validation of these criteria in an independent data set of 1018 patients shows a high accuracy (from 0.81 to 0.98).ConclusionEurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity.

Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda’s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one in 2022. To determine the circulating virus lineages and their ancestral origin, two genome sequences from the 2018 outbreak, and thirty-six, forty-one, and thirty-eight sequences of small (S), medium (M), and large (L) genome segments, respectively, from the 2022 outbreak were generated. All of the samples from the 2022 outbreak were collected from slaughterhouses. Both maximum likelihood and Bayesian-based phylogenetic analyses were performed. The findings showed that RVF viruses belonging to a single lineage, C, were circulating during the two outbreaks, and shared a recent common ancestor with RVF viruses isolated in Uganda between 2016 and 2019, and were also linked to the 2006/2007 largest East Africa RVF outbreak reported in Kenya, Tanzania, and Somalia. Alongside the wild-type viruses, genetic evidence of the RVFV Clone 13 vaccine strain was found in slaughterhouse animals, demonstrating a possible occupational risk of exposure with unknown outcome for people working in meat-related industry. These results provide additional evidence of the ongoing wide spread of RVFV lineage C in Africa and emphasize the need for an effective national and international One Health-based collaborative approach in responding to RVF emergencies.

Dengue is a leading cause of fever and mimics other acute febrile illnesses (AFI). In 2009, the World Health Organization (WHO) revised criteria for clinical diagnosis of dengue. The new WHO 2009 classification of dengue divides suspected cases into three categories: dengue without warning signs, dengue with warning signs and severe dengue. We evaluated the WHO 2009 classification vs physicians' subjective clinical diagnosis (gestalt clinical impression) in a large cohort of patients presenting to a tertiary care center in southern Sri Lanka hospitalized with acute febrile illness. We confirmed acute dengue in 388 patients (305 adults ≥ 18 years and 83 children), including 103 primary and 245 secondary cases, of 976 patients prospectively enrolled with AFI. At presentation, both adults and children with acute dengue were more likely than those with other AFI to have leukopenia and thrombocytopenia. Additionally, adults were more likely than those with other AFI to have joint pain, higher temperatures, and absence of crackles on examination whereas children with dengue were more likely than others to have sore throat, fatigue, oliguria, and elevated hematocrit and transaminases. Similarly, presence of joint pain, thrombocytopenia, and absence of cough were independently associated with secondary vs primary dengue in adults whereas no variables were different in children. The 2009 WHO dengue classification was more sensitive than physicians' clinical diagnosis for identification of acute dengue (71.5% vs 67.1%), but was less specific. However, despite the absence of on-site diagnostic confirmation of dengue, clinical diagnosis was more sensitive on discharge (75.2%). The 2009 WHO criteria classified almost 75% as having warning signs, even though only 9 (2.3%) patients had evidence of plasma leakage and 16 (4.1%) had evidence of bleeding. In a large cohort with AFI, we identified features predictive of dengue vs other AFI and secondary vs primary dengue in adults versus children. The 2009 WHO dengue classification criteria had high sensitivity but low specificity compared to physicians' gestaldt diagnosis. Large cohort studies will be needed to validate the diagnostic yield of clinical impression and specific features for dengue relative to the 2009 WHO classification criteria.

Despite the existence of an effective vaccine for yellow fever, there are still almost 80,000 fatalities from this infection each year. Since 2016, there has been a resurgence of cases in Africa and South America—and this at a time when the vaccine is in short supply. The worry is that yellow fever will spread from the forests to the cities, because its vector, Aedes spp. mosquitoes, are globally ubiquitous. Faria et al. integrate genomic, epidemiological, and case distribution data from Brazil to estimate patterns of geographic spread, the risks of virus exposure, and the contributions of rural versus urban transmission (see the Perspective by Barrett). Currently, the yellow fever epidemic in Brazil seems to be driven by infections acquired while visiting forested areas and indicates spillover from susceptible wild primates. Science , this issue p. 894 ; see also p. 847 MinION genomic and case data on a recent yellow fever epidemic indicate that most infections occurred during visits to forest regions. The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

The Georgia-07-like genotype II African swine fever virus (ASFV) with high virulence has been prevalent in China since 2018. Here, we report that genotype I ASFVs have now also emerged in China. Two non-haemadsorbing genotype I ASFVs, HeN/ZZ-P1/21 and SD/DY-I/21, were isolated from pig farms in Henan and Shandong province, respectively. Phylogenetic analysis of the whole genome sequences suggested that both isolates share high similarity with NH/P68 and OURT88/3, two genotype I ASFVs isolated in Portugal in the last century. Animal challenge testing revealed that SD/DY-I/21 shows low virulence and efficient transmissibility in pigs, and causes mild onset of infection and chronic disease. SD/DY-I/21 was found to cause necrotic skin lesions and joint swelling. The emergence of genotype I ASFVs will present more problems and challenges for the control and prevention of African swine fever in China.

Background. Beyond the acute illness phase, chikungunya constitutes a public health problem given its chronic disease phase, which may include long-term arthralgia, arthritis, fatigue, and depression. Currently, there is no consensus on how to define chikungunya chronicity. Methods. A comprehensive cross-sectional survey was performed in Curaçao in June and July 2015 to evaluate 304 adult laboratory-confirmed chikungunya patients 3–16 months after diagnosis. We developed a novel tool, the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score, to classify chronic chikungunya disease and estimate its burden regarding disease duration, clinical presentation, and impact on quality of life. Results. Disease persistence was estimated to be 79% one month after symptom onset and 64% after 400 days. Chikungunya persistence was characterized by higher proportions of arthralgia, weakness, myalgia, and age 41–60 years. Individuals were classified as \"highly affected,\" \"mildly affected,\" and \"recovered.\" \"Highly affected\" disease status was associated with clinical complaints (arthralgia, weakness, loss of vitality, and being diabetic) and major decreases in quality-of-life scores. Conclusions. In the Caribbean, a high proportion of chikungunya patients remains chronically affected. We propose the CLTCS as a suitable score to easily and rapidly classify the severity of chikungunya chronic disease and to assess the need for symptom-alleviating treatment.

The periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an auto-inflammatory condition characterized by recurrent episodes of fever accompanied by aphthosis, cervical adenitis, and pharyngitis. Diagnosis of PFAPA could be challenging due to clinic overlap with familial Mediterranean fever (FMF). An international consensus has been established recently, to define a new set of classification criteria for PFAPA syndrome. We aimed to evaluate the performance of recently proposed PFAPA criteria, to assess their utility in FMF regions. Patients diagnosed with PFAPA syndrome, FMF, and juvenile idiopathic arthritis (JIA) were included. Two investigators blindly evaluated all of patients for the newly proposed PFAPA criteria. A total of 542 patients (322 with PFAPA syndrome, 118 FMF and 102 JIA) were evaluated. Mean age of patients was 6.6 ± 2.81, 12.75 ± 3.9, and 12.42 ± 4.8 years for PFAPA, FMF, and JIA, respectively. We found quite high sensitivity (89.7%) but insufficient specificity of newly proposed PFAPA criteria (69.5%). When applied to control patients separately, specificity was found to be 61% and 79.4% for FMF and JIA patients, respectively. Positive predictive value was 81%, while negative predictive value was 82%. Recently proposed PFAPA criteria have satisfactory sensitivity, but its specificity is still under expectation. There is a need for a distinctive criterion between PFAPA syndrome and FMF, in FMF endemic regions, e.g., cryptic tonsillitis rapidly responsive to single dose of glucocorticoids. Further studies with higher patients’ number in different regions are needed.

African swine fever (ASF) entered China in August 2018 and rapidly spread across the entire country, severely threatening the Chinese domestic pig population, which accounts for more than 50% of the pig population worldwide. In this study, an ASFV isolate, Pig/Heilongjiang/2018 (Pig/HLJ/18), was isolated in primary porcine alveolar macrophages (PAMs) from a pig sample from an ASF outbreak farm. The isolate was characterized by using the haemadsorption (HAD) test, Western blotting and immunofluorescence, and electronic microscopy. Phylogenetic analysis of the viral p72 gene revealed that Pig/HLJ/18 belongs to Genotype II. Infectious titres of virus propagated in primary PAMs and pig marrow macrophages were as high as 10 7.2 HAD 50 /ml. Specific-pathogen-free pigs intramuscularly inoculated with different virus dosages at 10 3.5 -10 6.5 HAD 50 showed acute disease with fever and haemorrhagic signs. The incubation periods were 3-5 days for virus-inoculated pigs and 9 days for contact pigs. All virus-inoculated pigs died between 6-9 days post-inoculation (p.i.), and the contact pigs died between 13-14 days post-contact (p.c.). Viremia started on day 2 p.i. in inoculated pigs and on day 9 p.c. in contact pigs. Viral genomic DNA started to be detected from oral and rectal swab samples on 2-5 days p.i. in virus-inoculated pigs, and 6-10 days p.c. in contact pigs. These results indicate that Pig/HLJ/18 is highly virulent and transmissible in domestic pigs. Our study demonstrates the threat of ASFV and emphasizes the need to control and eradicate ASF in China.

Until now, the diagnosis of familial Mediterranean fever (FMF) was based on validated subsets of clinical criteria, but recently new Eurofever/PRINTO classification criteria concerning genetic analyses were proposed. The study aimed to compare the performances of three validated diagnostic criteria (Tel-Hashomer, Livneh, pediatric criteria) and new Eurofever/PRINTO classification criteria. The medical charts of study and control groups were reviewed retrospectively. Patients were evaluated for three diagnostic criteria and new Eurofever/PRINTO classification criteria. Control group consists of patients with other autoinflammatory diseases. A total of 1291 patients were classified into three groups according to their mutations: group 1: 447 patients with homozygous mutations; group 2: 429 patients with compound heterozygous mutations; and group 3: 415 patients with one heterozygous mutation. Similar diagnostic utility was found according to Livneh criteria between groups. But, proportion of patients fulfilling Tel-Hashomer and pediatric criteria was higher in groups 1 and 2. According to Eurofever/PRINTO criteria, 98.2% of patients with homozygous mutations, 94.2% of patients with compound heterozygous mutations and 80.2% of patients with heterozygous mutations were classified as FMF. In control group, 99.2% of them fulfilled the Livneh criteria, 66.9% met the pediatric criteria and 0.8% satisfied the Tel-Hashomer criteria, while none of control patients met the Eurofever/PRINTO classification criteria. Performances of three validated diagnostic criteria and new Eurofever/PRINTO classification criteria for FMF were similar and provide high utility in diagnosing/classifying patients with homozygous and compound heterozygous mutations. However, both Eurofever/PRINTO classification criteria and Tel-Hashomer criteria had significantly lower performance in heterozygous patients.

In 2007, African swine fever virus (ASFV) was introduced into the Transcaucasian countries and Russia. Since then, it has spread alarmingly and reached the European Union. ASFV strains are highly virulent and lead to almost 100 % mortality under experimental conditions. However, the possibility of dose-dependent disease courses has been discussed. For this reason, a study was undertaken to assess the risk of chronic disease and the establishment of carriers upon low-dose oronasal infection of domestic pigs and European wild boar. It was demonstrated that very low doses of ASFV are sufficient to infect especially weak or runted animals by the oronasal route. Some of these animals did not show clinical signs indicative of ASF, and they developed almost no fever. However, no changes were observed in individual animal regarding the onset, course and outcome of infection as assessed by diagnostic tests. After amplification of ASFV by these animals, pen- and stablemates became infected and developed acute lethal disease with similar characteristics in all animals. Thus, we found no indication of prolonged or chronic individual courses upon low-dose infection in either species. The scattered onset of clinical signs and pathogen detection within and among groups confirms moderate contagiosity that is strongly linked with blood contact. In conclusion, the prolonged course at the “herd level” together with the exceptionally low dose that proved to be sufficient to infect a runted wild boar could be important for disease dynamics in wild-boar populations and in backyard settings.