A New Orthonairovirus Associated with Human Febrile Illness.

BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

Phase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia.

BACKGROUND: Children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency require treatment with glucocorticoids, usually at supraphysiologic doses, to address cortisol insufficiency and reduce excess adrenal androgens. However, such treatment confers a predisposition to glucocorticoid-related complications. In 2-week phase 2 trials, patients with CAH who received crinecerfont, a new oral corticotropin-releasing factor type 1 receptor antagonist, had decreases in androstenedione levels. METHODS: In this phase 3, multinational, randomized trial, we assigned pediatric participants with CAH, in a 2:1 ratio, to receive crinecerfont or placebo for 28 weeks. A stable glucocorticoid dose was maintained for 4 weeks, and the dose was then adjusted to a target of 8.0 to 10.0 mg per square meter of body-surface area per day (hydrocortisone dose equivalents), provided that the androstenedione level was controlled (≤120% of the baseline level or within the reference range). The primary efficacy end point was the change in the androstenedione level from baseline to week 4. A key secondary end point was the percent change in the glucocorticoid dose from baseline to week 28 while androstenedione control was maintained. RESULTS: A total of 103 participants underwent randomization, of whom 69 were assigned to crinecerfont and 34 to placebo; 100 (97%) remained in the trial at 28 weeks. At baseline, the mean glucocorticoid dose was 16.4 mg per square meter per day, and the mean androstenedione level was 431 ng per deciliter (15.0 nmol/liter). At week 4, androstenedione was substantially reduced in the crinecerfont group (-197 ng per deciliter [-6.9 nmol/liter]) but increased in the placebo group (71 ng per deciliter [2.5 nmol/liter]) (least-squares mean difference [LSMD], -268 ng per deciliter [-9.3 nmol/liter]; P<0.001); the observed mean androstenedione value, obtained before the morning glucocorticoid dose, was 208 ng per deciliter (7.3 nmol/liter) in the crinecerfont group, as compared with 545 ng per deciliter (19.0 nmol/liter) in the placebo group. At week 28, the mean glucocorticoid dose had decreased (while androstenedione control was maintained) by 18.0% with crinecerfont but increased by 5.6% with placebo (LSMD, -23.5 percentage points; P<0.001). Headache, pyrexia, and vomiting were the most common adverse events. CONCLUSIONS: In this phase 3 trial, crinecerfont was superior to placebo in reducing elevated androstenedione levels in pediatric participants with CAH and was also associated with a decrease in the glucocorticoid dose from supraphysiologic to physiologic levels while androstenedione control was maintained. (Funded by Neurocrine Biosciences; CAHtalyst Pediatric ClinicalTrials.gov number, NCT04806451.).

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system.

SignificanceMetagenomic pathogen sequencing offers an unbiased approach to characterizing febrile illness. In resource-scarce settings with high biodiversity, it is critical to identify disease-causing pathogens in order to understand burden and to prioritize efforts for control. Here, metagenomic next-generation sequencing (mNGS) characterization of the pathogen landscape in Cambodia revealed diverse vector-borne and zoonotic pathogens irrespective of age and gender as risk factors. Identification of key pathogens led to changes in national program surveillance. This study is a "real world" example of the use of mNGS surveillance of febrile individuals, executed in-country, to identify outbreaks of vector-borne, zoonotic, and other emerging pathogens in a resource-scarce setting.

Molecular Epidemiology of Mayaro Virus among Febrile Patients, Roraima State, Brazil, 2018-2021.

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

Prevalence and impact of viral myocarditis in patients with severe fever with thrombocytopenia syndrome.

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease.

Respiratory pathogen dynamics in community fever cases: Jiangsu Province, China (2023-2024).

BACKGROUND: Respiratory infectious diseases have the highest incidence among infectious diseases worldwide. Currently, global monitoring of respiratory pathogens primarily focuses on influenza and coronaviruses. This study included influenza and other common respiratory pathogens to establish a local respiratory pathogen spectrum. We investigated and analyzed the co-infection patterns of these pathogens and explored the impact of lifting non-pharmaceutical interventions (NPIs) on the transmission of influenza and other respiratory pathogens. Additionally, we used a predictive model for infectious diseases, utilizing the commonly used An autoregressive comprehensive moving average model (ARIMA), which can effectively forecast disease incidence. METHODS: From June 2023 to February 2024, we collected influenza-like illness (ILI) cases weekly from the community in Xuanwu District, Nanjing, and obtained 2046 samples. We established a spectrum of respiratory pathogens in Nanjing and analysed the age distribution and clinical symptom distribution of various pathogens. We compared age, gender, symptom counts, and viral loads between individuals with co-infections and those with single infections. An autoregressive comprehensive moving average model (ARIMA) was constructed to predict the incidence of respiratory infectious diseases. RESULTS: Among 2046 samples, the total detection rate of respiratory pathogen nucleic acids was 53.37% (1092/2046), with influenza A virus 479 cases (23.41%), influenza B virus 224 cases (10.95%), and HCoV 95 cases (4.64%) being predominant. Some pathogens were statistically significant in age and number of symptoms. The positive rate of mixed infections was 6.11% (125/2046). There was no significant difference in age or number of symptoms between co-infection and simple infection. After multiple iterative analyses, an ARIMA model (0,1,4), (0,0,0) was established as the optimal model, with an R2 value of 0.930, indicating good predictive performance. CONCLUSIONS: The spectrum of respiratory pathogens in Nanjing, Jiangsu Province, was complex in the past. The primary age groups of different viruses were different, causing various symptoms, and the co-infection of viruses did not correlate with the age and gender of patients. The ARIMA model estimated future incidence, which plateaued in subsequent months.

The relation between low-grade fever during prolonged rupture of membranes (>12 hours) at term and infectious outcomes: a retrospective cohort study.

BACKGROUND: Intrapartum fever (>38°C) is associated with adverse maternal and neonatal outcomes. However, the correlation between low-grade fever (37.5°C-37.9°C) and adverse perinatal outcomes remains controversial. OBJECTIVE: This study aimed to compare maternal and neonatal outcomes of women with prolonged rupture of membranes (≥12 hours) at term between those with low-grade fever and those with normal body temperature. STUDY DESIGN: This retrospective study included women hospitalized in a tertiary university-affiliated hospital between July 2021 and May 2023 with singleton term and rupture of membranes ≥12 hours. Women were classified as having intrapartum low-grade fever (37.5°C-37.9°C) or normal body temperature (<37.5°C). The co-primary outcomes, postpartum endometritis and neonatal intensive care unit admission rates, were compared between these groups. The secondary maternal outcomes were intrapartum leukocytosis (>15,000/mm2), cesarean delivery rate, postpartum hemorrhage, postpartum fever, surgical site infection, and postpartum length of stay. The secondary neonatal outcomes were early-onset sepsis, 5-minute Apgar score of <7, umbilical artery cord pH<7.2 and pH<7.05, neonatal intensive care unit admission length of stay, and respiratory distress. The data were analyzed according to rupture of membranes 12 to 18 hours and rupture of membranes ≥18 hours. In women with rupture of membranes ≥18 hours, intrapartum ampicillin was administered, and chorioamniotic membrane swabs were obtained. The likelihood ratios and 95% confidence intervals were calculated for the co-primary outcomes. A multivariate logistic regression model was used to predict puerperal endometritis controlled for rupture of membranes duration, low-grade fever (compared with normal body temperature), positive group B streptococcus status, mechanical cervical ripening, cervical ripening by prostaglandins, artificial rupture of membranes, meconium staining, epidural analgesia, and cesarean delivery. A multivariate logistic regression model was used to predict neonatal intensive care unit admission controlled for rupture of membranes duration, low-grade fever, positive group B streptococcus status, mechanical cervical ripening, artificial rupture of membranes, meconium staining, cesarean delivery, and neonatal weight of <2500 g. RESULTS: This study included 687 women with rupture of membranes 12 to 18 hours and 1109 with rupture of membranes ≥18 hours. In both latency groups, the rates were higher for cesarean delivery, endometritis, surgical site infections, umbilical cord pH<7.2, neonatal intensive care unit admission, and sepsis workup among those with low-grade fever than among those with normal body temperature. Among women with low-grade fever, the positive likelihood ratios were 12.7 (95% confidence interval, 9.6-16.8) for puerperal endometritis and 3.2 (95% confidence interval, 2.0-5.3) for neonatal intensive care unit admission. Among women with rupture of membranes ≥18 hours, the rates were higher of Enterobacteriaceae isolates in chorioamniotic membrane cultures for those with low-grade fever than for those with normal intrapartum temperature (22.0% vs 11.0%, respectively; P=.006). Low-grade fever (odds ratio, 9.0; 95% confidence interval, 3.7-21.9; P<.001), artificial rupture of membranes (odds ratio, 4.2; 95% confidence interval, 1.5-11.7; P=.007), and cesarean delivery (odds ratio, 5.4; 95% confidence interval, 2.2-13.4; P<.001) were independently associated with puerperal endometritis. Low-grade fever (odds ratio, 3.2; 95% confidence interval, 1.7-6.0; P<.001) and cesarean delivery (odds ratio, 1.9; 95% confidence interval, 1.1-13.1; P=.023) were independently associated with neonatal intensive care unit admission. CONCLUSION: In women with rupture of membranes ≥12 hours at term, higher maternal and neonatal morbidities were reported among those with low-grade fever than among those with normal body temperature. Low-grade fever was associated with a higher risk of Enterobacteriaceae isolates in chorioamniotic membrane cultures. Moreover, low-grade fever may be the initial presentation of peripartum infection.

Incidence of febrile post-procedural urinary tract infection following voiding cystourethrography in children without prior urine culture.

PURPOSE: Post-procedural urinary tract infections (ppUTIs) following voiding cystourethrography (VCUG) vary widely, with rates from 0 to 42%, though recent studies suggest rates typically below 5%. Verifying urine sterility before VCUG is traditionally done but questioned. This study assessed the 7-day ppUTI rate post-VCUG without prior urine sterility confirmation and identified associated risk factors. METHODS: A retrospective review of VCUG cases in children under three years at a pediatric hospital over two years was conducted. Exclusions included neuropathic bladder, bladder exstrophy, pre-VCUG urine cultures, and lost-to-follow-up cases. Achieving a ppUTI rate below 5% would support safe VCUG practice without pre-urine culture. RESULTS: Of 318 VCUGs performed on 300 children, 248 (78%) were males (8% circumcised) with a median age of 5 months. Retrograde VCUG was more common than suprapubic cystography (63% vs. 37%). Before the test, 33.6% received antibiotics, mostly prophylactically. Hydronephrosis was present in 66.4%, and 69% had a history of UTI. VCUG results were abnormal in 43% of cases: 85% had vesicoureteral reflux (VUR), 10% had posterior urethral valves (PUV), and 28% had other abnormalities. The 7-day ppUTI rate was 3.8%, with 67% of ppUTI cases having abnormal VCUG results versus 41% without ppUTI (p = 0.06). No significant risk factors for ppUTI were identified. CONCLUSIONS: Omitting systematic urine culture before VCUG was not associated with a high ppUTI rate, even in children with pre-existing urologic conditions or a history of UTI, indicating that VCUG can be safely performed without prior urine sterility confirmation. No risk factors for ppUTI were identified.

Postoperative fever and clinical outcomes after endoscopic surgery for spontaneous intracerebral hemorrhage: a retrospective database study.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) is a severe stroke with high mortality and disability rates. Endoscopic surgery is an increasingly widely used minimally invasive method for the treatment of SICH. However, the impact of fever on patient outcomes remains unclear. METHODS: We retrospectively included patients aged 18 years or older with supratentorial SICH confirmed by CT, who underwent endoscopic hematoma evacuation within 48 h of symptom onset. The primary outcome was the modified Rankin Scale (mRS) score at 3 months. Secondary outcomes included hospital and neurosurgical intensive care unit (NSICU) stays, and perioperative complications. We analyzed the association between postoperative fever (highest temperature within 24 h after surgery) and these outcomes using multivariate analysis, generalized additive models, and segmented regression analysis. RESULTS: Of the 56 patients, 38 had favorable outcomes (mRS ≤ 3) and 18 had unfavorable outcomes (mRS > 3) at 3 months. A threshold effect at 38.2 °C was observed between postoperative body temperature and clinical outcomes. The mean age was 56 years (SD = 9) for the > 38.2 °C group and 58 years (SD = 8) for the ≤ 38.2 °C group, with a similar proportion of male patients (63% vs. 69%, P = 0.635). Patients with postoperative fever had larger hematoma volumes (65 vs. 56 mL; P = 0.008). Other characteristics were similar between the groups. Postoperative fever (> 38.2 °C) was independently associated with a 4.99-fold increased risk of unfavorable outcomes (95% CI = [1.13 to 25.90]; P = 0.040), which remained significant after excluding patients with postoperative complications (adjusted RR = 16.03, 95% CI = [1.69 to 417.24]; P = 0.033). The association was consistent across subgroups with different Glasgow Coma Scale scores, hematoma volumes, and intraventricular extension. Postoperative fever was also associated with longer NSICU stays (3.1 vs. 2.3 days; P = 0.023), longer hospital stays (17.2 vs. 13.6 days; P = 0.010), more residual hematoma, and greater edema volume. Different antipyretic therapies did not affect outcomes. CONCLUSIONS: This study identifies a temperature threshold (38.2 °C) associated with poor outcomes in SICH patients undergoing endoscopic surgery. Further research is needed to mitigate postoperative fever and improve patient outcomes.

Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from China, 1980-2015.

BACKGROUND: Rapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy. METHODS: A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in China (1980-2015). Literature searches were conducted in English and Chinese languages in six databases: Ovid MEDLINE, Global Health, EMBASE, Web of Science™ - Chinese Science Citation Database SM, The China National Knowledge Infrastructure (CNKI), and WanFang Med Online. Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. The number of published articles, reporting a given pathogen were presented, rather than incidence or prevalence of infection. RESULTS: A total of 57,181 records from 13 provinces of China where malaria used to be endemic were screened, of which 392 met selection criteria and were included in this review. The review includes 60 (15.3%) records published from 1980 to 2000, 211 (53.8%) from 2001 to 2010 and 121 (30.9%) from 2011 to 2015;. Of the 392 records, 166 (42.3%) were from the eastern region of China, 120 (30.6%) were from the south-west, 102 (26.0%) from south-central, and four (1.0%) were multi-regional studies. Bacterial infections were reported in 154 (39.3%) records, viral infections in 219 (55.9%), parasitic infections in four (1.0%), fungal infections in one (0.3%), and 14 (3.6%) publications reported more than one pathogen group. Participants of all ages were included in 136 (34.7%) studies, only adults in 75 (19.1%), only children in 17 (4.3%), only neonates in two (0.5%) and the age distribution was not specified in 162 (41.3%) records. The most commonly reported bacterial pathogens included Typhoidal Salmonella (n = 30), Orientia/ Rickettsia tsutsugamushi (n = 31), Coxiella burnetii (n = 17), Leptospira spp. (n = 15) and Brucella spp. (n = 15). The most commonly reported viral pathogens included Hantavirus/Hantaan virus (n = 89), dengue virus (DENV) (n = 76 including those with unknown serovars), Japanese encephalitis virus (n = 21), and measles virus (n = 15). The relative lack of data in the western region of the country, as well as in in neonates and children, represented major gaps in the understanding of the aetiology of fever in China. CONCLUSIONS: This review presents a landscape of non-malaria pathogens causing febrile illness in China over 36 years as the country progressed toward malaria elimination. These findings can inform guidelines for clinical management of fever cases and infection surveillance and prevention, and highlight the need to standardize operational and reporting protocols for better understanding of fever aetiology in the country.

Determinants and prevalence of symptomatic dengue fever among adults in the Central Region of Burkina Faso: a hospital-based cross-sectional study.

BACKGROUND: Dengue fever (DF) is a significant public health concern in Burkina Faso, particularly in the Central Region, previously endemic for malaria. However, limited research has focused on dengue prevalence and associated factors among adult febrile patients in this region. This study aimed to estimate the prevalence of symptomatic dengue fever among adults and identify the sociodemographic and clinical determinants of the disease. METHODS: A seroepidemiological cross-sectional study was conducted in the Central Region of Burkina Faso, through a three-stage sampling. Five health facilities, one from each of the region five districts, were purposively selected. Febrile patients aged 16 and older, suspected of having dengue, were included in the study, after consenting. Bivariate analyses and multivariate binary logistic regression were done at a 5% confidence level. RESULTS: A total of 637 patients between the ages of 16 and 90 years were included. Most of the participants were females (58.71%). Most dengue cases resided in Arrondissement 4 (59.62%), or were present in the Arrondissement 4 at daytime during the previous days (51.92%). 52.90% of the participants knew of dengue. Dengue prevalence was estimated at 8.16% (95% CI: 6.16%-10.57%). The most frequent markers for dengue were immunoglobulins M detected in 4.40% (2.94%-6.29%), followed by Antigen NS1 at 4.24% (95% CI: 2.81%-6.11%). The Antigen NS1 marker was associated with myalgia (p = 0.024), vomiting (p < 0.001), hemorrhagic manifestations (p = 0.001), and anorexia (p < 0.001). Staying at Arrondissement 4 (vs staying at Saaba) during daytime (aOR = 2.36 95% CI: 1.03-5.45; p = 0.044) significantly increased the odds of dengue. Dengue cases were about 3 times more likely to have vomited (aOR = 2.99 95% CI: 1.58-5.64; p = 0.001). Participants knowing of dengue (aOR = 0.53 95% CI: 0.29-0.98; p = 0.042) and those coinfected with malaria (aOR = 0.28 95% CI: 0.14-0.57; p < 0.001) instead had reduced odds of dengue. CONCLUSION: The study revealed a relatively high prevalence of symptomatic dengue fever among adults in the Central Region of Burkina Faso in 2022. These findings emphasize the need for continuous surveillance and targeted control measures. The low coinfection of dengue and malaria warrants further investigation.

Systemic inflammatory response syndrome in patients with severe fever with thrombocytopenia syndrome: prevalence, characteristics, and impact on prognosis.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. METHODS: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. RESULTS: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS. CONCLUSIONS: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality.

Epidemiological investigation of dengue fever outbreak and its socioeconomic determinants in Banadir region, Somalia.

BACKGROUND: Dengue has become an alarming global problem and is endemic in many countries, particularly in tropical and subtropical countries. The aim of this study was to investigate dengue fever outbreak in Banadir Region, Somalia, to understand the risk factors (time, place, personal characteristics). METHODS: A descriptive cross-sectional study was undertaken to determine the levels of circulating anti-dengue virus antibodies and DENV NS1 antigen among Banadir Region residents, while a questionnaire survey was conducted to understand the clinical and demographic characteristics of the patients. RESULTS: A total of 735 febrile patients were studied, with 55.6% men and 44.3% women. The majority of the participants were children aged 14 years and younger. Among them, 10.8% tested positive for IgM antibodies against dengue virus (DENV), while the prevalence of DENV NS1 antigen was 11.8%. Fever and myalgia were the most common symptoms observed in the DENV-positive patients. CONCLUSIONS: A dengue fever outbreak has been confirmed in Banadir region, Somalia. This study provides information on the most affected districts and identifies risk factors contributing to DF outbreaks. The study recommends improving outbreak readiness and response, particularly in surveillance and laboratory diagnostics, by fostering intersectoral collaboration and establishing regulatory frameworks for financial and operational participation.

Analysis of influencing factors on long COVID in COVID-19 patients infected with omicron variant three months after discharge: a cross-sectional study.

BACKGROUND: The purpose of this study is to analyze the influencing factors associated with Long-COVID in patients infected with Omicron variant of COVID-19 in Changchun City, Jilin Province, China three months after discharge in March 2022. METHODS: In this study, we conducted a telephone follow-up based on the real-world data collected from the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun Tongyuan Shelter Hospital and Changchun Infectious Disease Hospital during the COVID-19 epidemic in Changchun in March 2022. We used the Global COVID-19 Clinical Platform Case Report Form for Post COVID condition as a follow-up questionnaire to collect the general information, past medical history, clinical symptoms, COVID-19 vaccine inoculation doses, and other relevant information to analyze the symptom characteristics of COVID-19 patients three months after discharge from the hospital and related factors affecting Long COVID. RESULTS: A total of 1,806 patients with COVID-19 were included in this study, 977 males and 829 females, with a mean age of 38.5 [30.0, 49.4] years, and the number of female patients suffering from Long COVID (50.87%) was greater than male patients (p = 0.023). The binary logistic regression analysis of factors influencing Long COVID showed that smoking history (OR (95%CI) = 0.551(0.425-0.714), p < 0.001, taking never smoking as a reference), allergy history (OR (95%CI) = 1.618 (1.086-2.413), p-value 0.018, taking no allergy as a reference), first symptoms (OR (95%CI) = 0.636 (0.501-0.807), p < 0.001, with no first symptoms as reference) and COVID-19 vaccine inoculation doses (OR (95%CI) = 1.517 (1.190-1.933), p-value 0.001, with ≤ 2 doses of COVID-19 vaccine inoculation doses as reference) constituted its influencing factors. The first symptoms of patients on admission mainly included fever (512 cases, 71.81%), cough (279 cases, 39.13%) and dry or itchy throat (211 cases, 29.59%). The most common symptoms of Long COVID were persistent fatigue (68 cases), amnesia (61 cases), insomnia (50 cases) and excessive sweating (50 cases). CONCLUSION: The first symptoms on admission were predominantly fever, cough and dry or itchy throat. The most common symptoms of Long COVID were persistent fatigue, amnesia, insomnia and excessive sweating, and female patients were at a higher risk of Long COVID.

Assessment of fever screening at airports in detecting domestic passengers infected with SARS-CoV-2, 2020-2022, Okinawa prefecture, Japan.

BACKGROUND: While airport screening measures for COVID-19 infected passengers at international airports worldwide have been greatly relaxed, observational studies evaluating fever screening alone at airports remain scarce. The purpose of this study is to retrospectively assess the effectiveness of fever screening at airports in preventing the influx of COVID-19 infected persons. METHODS: We conducted a retrospective epidemiological analysis of fever screening implemented at 9 airports in Okinawa Prefecture from May 2020 to March 2022. The number of passengers covered during the same period was 9,003,616 arriving at 9 airports in Okinawa Prefecture and 5,712,983 departing passengers at Naha Airport. The capture rate was defined as the proportion of reported COVID-19 cases who would have passed through airport screening to the number of suspected cases through fever screening at the airport, and this calculation used passengers arriving at Naha Airport and surveillance data collected by Okinawa Prefecture between May 2020 and March 2021. RESULTS: From May 2020 to March 2021, 4.09 million people were reported to pass through airports in Okinawa. During the same period, at least 122 people with COVID-19 infection arrived at the airports in Okinawa, but only a 10 suspected cases were detected; therefore, the capture rate is estimated to be up to 8.2% (95% CI: 4.00-14.56%). Our result of a fever screening rate is 0.0002% (95%CI: 0.0003-0.0006%) (10 suspected cases /2,971,198 arriving passengers). The refusal rate of passengers detected by thermography who did not respond to temperature measurements was 0.70% (95% CI: 0.19-1.78%) (4 passengers/572 passengers). CONCLUSIONS: This study revealed that airport screening based on thermography alone missed over 90% of COVID-19 infected cases, indicating that thermography screening may be ineffective as a border control measure. The fact that only 10 febrile cases were detected after screening approximately 3 million passengers suggests the need to introduce measures targeting asymptomatic infections, especially with long incubation periods. Therefore, other countermeasures, e.g. preboarding RT-PCR testing, are highly recommended during an epidemic satisfying World Health Organization (WHO) Public Health Emergency of International Concern (PHEIC) criteria with pathogen characteristics similar or exceeding SARS-CoV-2, especially when traveling to rural cities with limited medical resources.

Cycle threshold (Ct)values of SARS-CoV2 vary with the type of symptoms and comorbidities of the patients.

BACKGROUND: Literature depicts no association of cycle threshold values for SARS-CoV-2 with the patient's demographics or clinical history. However, the severity of the COVID-19 symptoms showed some associations with Ct values in previous studies. We aimed to study the relationship of Ct values with type of the symptoms and comorbidities of the patients. METHODS AND RESULTS: We examined the individuals (n = 8660) that consulted a private diagnostic center for COVID-19 testing. Nasopharyngeal samples were collected from the patients and SARS-CoV-2 was detected by RT-PCR assays using Sansure Biotech kit. Clinical and demographic information was collected by the attending healthcare professional. The differences between groups were analyzed by t-test (unpaired). P-values < 0.05 were considered statistically significant. We found that the mean age of asymptomatic patients (41.47 ± 17.01 years) and symptomatic patients (47.75 ± 17.51) varies significantly (p value < 0.0001). Among the most prevalent symptoms were fever (77.74%) and cough (66.46%). The Ct values of COVID-19 patients with symptoms (25.70 for Orf1ab, 24.25 for N gene) were significantly lower than the Ct values of the patients without symptoms (28.99 for Orf1ab, 28.17 for N gene) (p value < 0.0001). Patients having co-occurrence of cough with fever (24.67 for Orf1ab, 22.86 for N gene) and solely fever (25.12 for Orf1ab, 24.01 for N gene) showed significantly lower Ct values than the patients without symptoms (28.99 for Orf1ab, 28.17 for N gene, p value < 0.0001). However, this difference was independent of patients sex and dependent upon patient's age and SARS-CoV-2 detected gene. The most prevalent comorbidities among COVID-19 patients were blood pressure (64.7%) and diabetes (50.5%). The patients having blood pressure and diabetes together showed significantly lower Ct values (23.37 for Orf1ab, 23.33 for N gene) than patients without comorbidities (27.65 for Orf1ab, 26.75 for N gene, p value < 0.001). CONCLUSION: We conclude that the Ct values of the SARS-CoV-2 detected gene (either Orf1ab or N) is associated with the types of symptoms and comorbidities of the COVID-19 patients. Furthermore, the relationship between Ct values and symptomology or comorbidity of the patients is independent of patient's sex but dependent upon patient's age and SARS-CoV-2 detected gene.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Contributing Factors Affecting the Length of Hospital Stay among Febrile Patients with Omicron Reported in Suzhou.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had global attention with regard to the urgent challenging threat to global public health. Currently, the novel Omicron variant is showing rapid transmission across the world, which appears to be more contagious than the previous variants of COVID-19. Early recognition of disease is critical for patients' prognosis. Fever is the most common symptom. We evaluated the clinical characteristics of febrile patients with COVID-19 reported in Suzhou and explored the predictors for a longer duration of hospitalization in febrile patients. METHODS: This retrospective study was carried out in 146 Omicron variant infected patients confirmed by nucleic acid tests in the Affiliated Infectious Hospital of Soochow University between February 13, 2022 and March 2, 2022. Data of febrile and afebrile laboratory-confirmed patients on hospital admission in Suzhou were collected and compared. According to the median length of stay (LOS), febrile cases were divided into short and long LOS groups. Then the predictive factors for a prolonged duration of hospitalization were analyzed using logistic regression methods. Receiver Operating Characteristic (ROC) Curve analysis was used to analyze the effectiveness of the risk factors for prolonged duration of hospitalization in febrile COVID-19 patients. RESULTS: Of the 146 discharged patients in our study, 112 patients (76.7%) caught a fever. Compared to afebrile Omicron patients, febrile patients showed a significantly longer duration of hospitalization (15.00 (5.80) vs. 13.00 (6.00), p = 0.002). Taking the median LOS (15 days) as the dividing point, 64 febrile cases were assigned to the short LOS group and the rest to the long LOS group. The long LOS group had a longer virus shedding duration than the short LOS group (18.42 ± 2.86 vs. 11.94 ± 2.50 days, p < 0.001). Compared to short LOS febrile patients, long LOS patients were older (44.88 ± 21.36 vs. 30.89 ± 17.95 years, p < 0.001) and showed a higher proportion of greater than 60 years old (33.3% vs. 9.4%, p = 0.002; Supplemental Table S2). Febrile patients with long LOS also showed a higher proportion of hypertension (25% vs. 6.3%, p = 0.005) and higher levels of cTnI (5.00 (3.00) vs. 4.00 (2.00) µg/L, p = 0.025). The multivariate analysis indicated that virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was the independent risk factor associated with long-term hospital stay in febrile patients with Omicron. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for virus shedding duration to diagnose prolonged duration of hospitalization in febrile COVID-19 patients was 0.951 (95% CI 0.913 - 0.989). The cutoff point was set at 14.5 days. CONCLUSIONS: More than half of the non-severe patients exposed to the new Omicron variant had symptoms of fever. In total, 42.86% of the febrile patients were discharged within 15 days since hospital admission. Febrile Omicron cases took a longer duration of hospitalization compared to afebrile patients, and virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was probably a predictive factor for long-term hospital stays.

Unveiling the burden of scrub typhus in acute febrile illness cases across India: A systematic review & meta-analysis.

Background & objectives Scrub typhus is an emerging mite-borne zoonotic infection that has been overlooked, despite being one of the most widespread severe vector-borne diseases. With an estimated one billion people at risk worldwide and one million annual cases, it poses a significant public health concern. While various studies have investigated the prevalence of scrub typhus in different regions of India, a comprehensive regional systematic review and meta-analysis on the seropositivity of scrub typhus among acute febrile cases has been lacking. To address this gap, we conducted a systematic review and meta-analysis to compile information on the current seroprevalence of scrub typhus in acute febrile illness cases in India. Methods A literature search of multiple databases on prevalence of scrub typhus in acute febrile illness in India, 60 eligible studies out of 573 studies. The prevalence of individual studies was double arcsine transformed, and the pooled prevalence was calculated using inverse variance method. Results In total, these studies encompassed 34,492 febrile cases. The overall seroprevalence of scrub typhus among acute febrile illness cases in India was found to be 26.41 per cent [95% confidence interval (CI): 22.03-31.03]. Additionally, the pooled case fatality rate (based on data from six studies) among scrub typhus-positive cases yielded a case fatality rate of 7.69 per cent (95% CI: 4.37-11.72). Interpretation & conclusions This meta-analysis shows that scrub typhus is a significant health threat in India. Preventive measures to control scrub typhus need to be given priority.

Serious bacterial infection risk in recently immunized febrile infants in the emergency department.

STUDY OBJECTIVES: Fever following immunizations is a common presenting chiefcomplaint among infants. The 2021 American Academy of Pediatrics (AAP) febrile infant clinical practice guidelines exclude recently immunized (RI) infants. This is a challenge for clinicians in the management of the febrile RI young infant. The objective of this study was to assess the prevalence of SBI in RI febrile young infants between 6 and 12 weeks of age. METHODS: This was a retrospective chart review of infants 6-12 weeks who presented with a fever ≥38 °C to two U.S. military academic Emergency Departments over a four-year period. Infants were considered recently immunized (RI) if they had received immunizations in the preceding 72 h prior to evaluation and not recently immunized (NRI) if they had not received immunizations during this time period. The primary outcome was prevalence of serious bacterial infection (SBI) further delineated into invasive-bacterial infection (IBI) and non-invasive bacterial infection (non-IBI) based on culture and/or radiograph reports. RESULTS: Of the 508 febrile infants identified, 114 had received recent immunizations in the preceding 72 h. The overall prevalence of SBI was 11.4% (95% CI = 8.9-14.6) in our study population. The prevalence of SBI in NRI infants was 13.7% (95% CI = 10.6-17.6) compared to 3.5% (95% CI = 1.1-9.3) in RI infants. The relative risk of SBI in the setting of recent immunizations was 0.3 (95% CI = 0.1-0.7). There were no cases of invasive-bacterial infections (IBI) in the RI group with all but one of the SBI being urinary tract infections (UTI). The single non-UTI was a case of pneumonia in an infant who presented with respiratory symptoms within 24 h of immunizations. CONCLUSION: The risk of IBI (meningitis or bacteremia) in RI infants aged 6 to 12 weeks is low. Non-IBI within the first 24 h following immunization was significantly lower than in febrile NRI infants. UTIs remain a risk in the RI population and investigation with urinalysis and urine culture should be encouraged. Shared decision making with families guide a less invasive approach to the care of these children. Future research utilizing a large prospective multi-center data registry would aid in further defining the risk of both IBI and non-IBI among RI infants.