In March 2021, Lao People’s Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5-year-old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam, and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security.

Background Physical distancing and facemask use are worldwide recognized as effective non-pharmaceutical interventions (NPIs) against the coronavirus disease 2019 (COVID-19). Since January 2020, Taiwan has introduced both NPIs but their effectiveness on non-COVID-19 respiratory viruses (NCRVs) remain underexplored. Methods This retrospective observational study examined electronic records at a tertiary hospital in northern Taiwan from pre-COVID (January–December 2019) to post-COVID period (January–May 2020). Patients with respiratory syndromes were tested for both enveloped (e.g. influenza virus and seasonal coronavirus) and non-enveloped RVs (e.g. enterovirus and rhinovirus) using multiplex reverse-transcription polymerase chain reaction assays. Monthly positivity rates of NCRVs among adult and pediatric patients were analyzed with comparison between pre- and post-COVID periods. Results A total of 9693 patients underwent 12127 multiplex RT-PCR tests. The average positivity rate of NCRVs reduced by 11.2% (25.6% to 14.4%) after nationwide PHIs. Despite the COVID-19 pandemic, the most commonly identified enveloped and non-enveloped viruses were influenza virus and enterovirus/rhinovirus, respectively. Observed reduction in NCRV incidence was predominantly contributed by enveloped NCRVs including influenza viruses. We did not observe epidemiological impacts of NPIs on non-enveloped viruses but an increasing trend in enterovirus/rhinovirus test positivity rate among pediatric patients. Our data were validated using Taiwan’s national notification database. Conclusions Our frontline investigation suggests that the current NPIs in Taiwan might not effectively control the transmission of non-enveloped respiratory viruses, despite their protective effects against influenza and seasonal coronavirus. Hydrogen peroxide or chloride-based disinfectants should be integrated into national preventative strategies against respiratory viral infections in the post-COVID-19 era.

Evaluation of population-based COVID-19 control measures informs strategies to quell the current pandemic and reduce the impact of those yet to come. Effective COVID-19 control measures may simultaneously reduce the incidence of other acute respiratory infections (ARIs) due to shared transmission modalities. To assess the impact of stay-at-home orders and other physical distancing measures on the prevalence of ARI-related symptoms, we compared symptoms reported by prospective college cohorts enrolled during two consecutive academic years. ARI-related symptoms declined following campus closure and implementation of stay-at-home orders, demonstrating the impact of population-based physical distancing measures on control of a broad range of respiratory infections.

With the rapid increase of reported COVID-19 cases, German policymakers announced a 4-week “shutdown light” starting on Nov 2, 2020. Applying mathematical models, possible scenarios for the evolution of the outbreak in Germany are simulated. The results indicate that independent of the effectiveness of the current restrictive measures they might not be sufficient to mitigate the outbreak. Repeated shutdown periods or permanently applied measures over the winter could be successful alternatives.

Background: Baloxavir marboxil (BXM) is an approved drug that selectively targets cap-dependent endonuclease on PA subunit in the RNA polymerase complex of influenza A and B viruses. Amino acid substitutions at position 38 in the PA subunit were identified as a major pathway for reduced susceptibility to baloxavir acid (BXA), the active form of BXM. Additionally, substitutions found at positions E23, A37, and E199 in the PA subunit impact BXA susceptibility by less than 10-fold. Methods: We comprehensively evaluated the impact of novel amino acid substitutions identified in PA, PB1 and PB2 subunits in BXM clinical trials and influenza sequence databases by means of drug susceptibility and replicative capacity. Results: PA/I38N in A(H1N1) and PA/I38R in A(H3N2) were newly identified as treatment-emergent substitutions in the CAPSTONE-2 study. The I38N substitution conferred reduced susceptibility by 24-fold, whereas replicative capacity of the I38N-substituted virus was impaired compared to the wild-type. The I38R-substituted virus was not viable in cell culture. All other mutations assessed in this extensive study did not significantly affect BXA susceptibility (< 2.4-fold change). Conclusion: These results provide additional information on the impact of amino acid substitutions in the trimeric viral polymerase complex to BXA susceptibility and will further support influenza surveillance.

Adenovirus, a common respiratory pathogen, has witnessed a notable rise in incidence rates across various regions in Pakistan. Utilizing epidemiological data and climate records, this research discerns a potential linkage between the burgeoning adenovirus cases and alterations in regional climate patterns. Through statistical analysis and modeling techniques, the study aims to elucidate the relationship between climatic variables such as temperature, humidity, and precipitation, and the prevalence of adenovirus infections. Understanding these dynamics is crucial for developing effective public health interventions and preparedness strategies to mitigate the impact of adenovirus outbreaks in Pakistan. Furthermore, this research contributes to the broader discourse on the intersection of infectious diseases and climate change, highlighting the need for comprehensive adaptive measures to address emerging health challenges in a changing environment.

Background: The ‘PenCS Flu Topbar’ app was deployed in Central Queensland (CQ), Australia medical practices through a pilot program in March 2021. Methods: We evaluated the app’s user experience and examined whether the introduction of ‘PenCS Flu Topbar’ in medical practices could improve the coverage of NIP funded influenza vaccinations. We conducted a mixed-method study including a qualitative analysis of in-depth interviews with key end-users, and a quantitative analysis of influenza vaccine administrative data. Results: ‘PenCS Flu Topbar’ app users reported positive experiences identifying patients eligible for NIP-funded season influenza vaccination. A total of 3,606 NIP funded influenza vaccinations were administered in the eight intervention practices, 14% higher than the eight control practices. NIP-funded vaccination coverage within practices was significantly higher in intervention practices (31.2%) than the control practices (27.3%) (absolute difference: 3.9%; 95%CI: 2.9%-5.0%; P<0.0001). The coverage was substantially higher in Aboriginal and Torres Strait Islander people aged more than 6 months, pregnant women and children aged 6 months to less than 5 years for the practices where the app was introduced when compared to control practices; Incidence Rate Ration (IRR) 2.4 (95%CI: 1.8-3.2), IRR 2.7 (95%CI: 1.8-4.2) and IRR 2.3 (1.8-2.9) times higher, respectively. Conclusions: Our evaluation indicated that the ‘PenCS Flu Topbar’ app is uuseful for identifying the patients eligible for NIP-funded influenza vaccination and is likely to increase NIP-funded influenza vaccine coverage in the eligible populations. Future impact evaluation including a greater number of practices and a wider geographical area is essential.

Background: Following a locally transmitted case in Sukhbaatar city, Selenge province, we conducted a study with two objectives. First, we aimed to estimate the basic reproduction number of COVID-19, leveraging the epidemiological and clinical characteristics observed in the first 67 confirmed cases. Second, we aimed to model the outbreak considering different patient profiles - asymptomatic, symptomatic, and pre-symptomatic - with the goal of predicting the ultimate scale of the epidemic in the scenario of uninterrupted transmission. Methods: We conducted a prospective case study following the WHO FFX cases generic protocol. The rapid response teams collected the surveillance data from November 14–29, 2020. We created a stochastic process to draw many transmission chains from this greater distribution to better understand and make inferences regarding the outbreak under investigation. Results: The majority of the cases involved household transmissions (35, 52.2%), work transmissions (20, 29.9%), index (5, 7.5%), same apartment transmissions (2, 3.0%), school transmissions (2, 3.0%), and meetup transmissions (1, 1.5%). The posterior means of the basic reproduction number of both the asymptomatic cases, R_0^Asy and pre-symptomatic cases R_0^Pre (1·35 [95% CrI 0·88−1·86] and 1·29 [95% CrI 0·67−2·10], respectively), were lower than that of the symptomatic cases. Conclusion: Our study highlights the heterogeneity of COVID-19 transmission across different symptom statuses and underscores the importance of early identification and isolation of symptomatic cases in disease control. Detailed contact tracing data with advanced statistical methods, can be applied to other infectious diseases, facilitating a more nuanced understanding of disease transmission dynamics.

Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, not only in terms of health but also economic-wise. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies are currently underway. Promising approaches include targeting the highly conserved epitopes of hemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e), and internal proteins of the influenza virus. The identification and characterisation of broadly neutralising antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used, and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.

The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with most monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited of convalescent plasma. At baseline, 49 (68%) of the participants had a WHO score of 5 and 23 (32%) a WHO score of 6. At day 28 the case fatality was 24%. We observed no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or auto-immune diseases. These promising results require controlled studies.

Cameroon was among the most affected African countries during the first wave of the COVID-19 pandemic; however, the true prevalence of SARS-CoV-2 remains unknown. From October-December 2020 we conducted a cross-sectional, age-stratified SARS-CoV-2 seroepidemiological survey at 30 purposively selected community-based sites across Cameroon’s 10 regional capitals, sampling 10,000 individuals aged 5 years or older. We employed a parallel SARS-CoV-2 antibody testing algorithm (WANTAI ELISA and Abbot Architect) to improve both the positive predictive value and negative predictive value of seroprevalence. The overall weighted and adjusted seroprevalence of SARS-CoV-2 antibodies across the 10 urban capitals of Cameroon was 10.5% (95% CI: 9.1%-12.0%) among participants aged ≥5 years. Of the 9332 participants, 730 males (13.1%, 95% CI: 11.5%-14.9%) had SARS-CoV-2 antibodies compared to 293 females (8.0%, 95% CI: 6.8%—9.3%). Among those who reported a comorbidity at the time of testing, 15.8% (95% CI: 12.8%-19.4%) were seropositive. We estimated that over 2 million SARS-CoV-2 infections occurred in the 10 regional capitals of Cameroon between October and December 2020, compared to 21,160 cases officially reported at that time translating to one laboratory-confirmed case was reported for every 110 SARS-CoV-2 infections across the 10 urban capitals. This study’s findings point to extensive and under-reported circulation of SARS-CoV-2 in Cameroon– an almost 100-fold more cases compared to the number of cases reported to the World Health Organization. This finding highlights the importance of conducting serosurveys, especially in settings where access to testing may be limited and to repeat such surveys as part of pandemic tracking.

Few seroprevalence studies were performed on coronavirus disease (COVID-19) in Nepal. Here, we aimed to estimate seroprevalence and assess risk factors for infection in the general population of Nepal by conducting two rounds of sampling. The first round in October 2020 at the peak of the first generalized wave of COVID-19 and the second round in July-August 2021 following the peak of the wave caused by the delta variant of SARS-COV-2. We used cross-sectional probability-to-size (PPS)-based multistage cluster sampling to estimate the seroprevalence in the general population of Nepal at the national and provincial levels. We tested for the presence of anti-SARS-CoV-2 total antibody using the WANTAI SARS-CoV-2 Ab ELISA kit. In Round 1, the overall national seroprevalence was 14.4%, with provincial estimates ranging from 5.3% in Sudurpaschim to 27.3% in Madesh province. In Round 2, the estimated national seroprevalence was 70.7%, with the highest estimated seroprevalence in Madesh Province (84.8%) and the lowest in the Gandaki Province (62.9%). Seroprevalence was comparable between males and females (Round 1, 15.8% vs 12.2% and Round 2, 72.3% vs. 68.7%). The seroprevalence in the ecozones—terai, hills, and mountains—was 76.3%, 65.3%, and 60.5% in Round 2 and 17.7%, 11.7%, and 4.6% in Round 1, respectively. In Nepal, COVID-19 vaccination was introduced in January, 2021. At the peak of the first generalized wave of COVID-19, most of the population of Nepal remained unexposed to SARS-COV-2 and towards the end of the second generalized wave in April 2021, two-thirds of the population was exposed.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been the most significant public health challenge in over a century. SARS-COV-2 has infected over 765 million people worldwide, resulting in over 6.9 million deaths. This study aimed to detect community transmission of SARS-CoV-2 and monitor the co-circulation of SARS-CoV-2 with other acute respiratory pathogens in Rift Valley, Kenya. We conducted a cross-sectional active sentinel surveillance for the SARS-CoV-2 virus among patients with acute respiratory infections at four sites in Rift Valley from January 2022 to December 2022. 1271 patients of all ages presenting with influenza-like illness were recruited into the study. Nasopharyngeal swab specimens were screened using a multiplex RT–qPCR for SARS-CoV-2, Influenza A, Influenza B and RSV. Influenza A and RSV samples were subtyped, and all the SARS-CoV-2 positive samples were further screened for 12 viral and 7 bacterial respiratory pathogens. We had a prevalence of 13.93% SARS-CoV-2, Influenza A 5.7%, Influenza B 1.96% and 0.94%. Influenza A-H1pdm09 and RSV B were the most dominant circulating subtypes of Influenza A and RSV, respectively. The most common co-infecting pathogens were Streptococcus pneumoniae and Haemophilus influenzae, accounting for 16.4% and 10.7% of all the SARS-CoV-2 positive samples. Augmenting syndromic testing in ARI surveillance is crucial to inform evidence-based clinical and public health interventions.

Since 2004, the U.S. Centers for Disease Control and Prevention (CDC) Influenza Division (ID) has supported seven countries in the Eastern Mediterranean region and the World Health Organization Regional Office for the Eastern Mediterranean to establish and strengthen influenza surveillance. There has been substantial growth in influenza surveillance capacities in the region over two decades that demonstrates commitment by national governments to strengthen national programs and contribute to global influenza surveillance. CDC ID remains committed to continuing support to the region and supporting partners to translate surveillance data into policies and programs effectively.

Background We explored whether hospital-based surveillance is useful in detecting severe acute respiratory infection (SARI) clusters and how often these events result in outbreak investigation and community mitigation. Methods During May 2009– December 2020, physicians at 14 sentinel hospitals prospectively identified SARI clusters (i.e., ≥2 SARI cases who developed symptoms ≤10 days of each other and lived <30 minute walk or <3 km from each other). Oropharyngeal and nasopharyngeal swabs were tested for influenza and other respiratory viruses by rRT-PCR. We describe the demographic of persons within clusters, laboratory results, and outbreak investigations. Results Physicians identified 464 clusters comprising 1,427 SARI cases (range 0–13 clusters per month). Sixty percent of clusters had three, 23% had 2, and 17% had ≥4 cases. Their median age was 2 years (interquartile [IQR] 0.4–25) and 63% were male. Laboratory results were available for the 464 clusters a median 9 days (IQR = 6–13 days) after cluster identification. Less than one in five clusters had cases that tested positive for the same virus: RSV in 58 (13%), influenza viruses in 24 (5%), HMPV in 5 (1%), HPIV in 3 (0.6%), adenovirus in 2 (0.4%). While 102/464 (22%) had poultry exposure, none tested positive for influenza A(H5N1) or A(H7N9). None of the 464 clusters led to field deployments for outbreak response. Conclusions For 11 years, none of the hundreds of identified clusters led to emergency response. The value of this event-based surveillance might be improved by seeking larger clusters, with stronger epidemiologic ties or decedents.

Background First Few “X” (FFX) studies provide evidence to guide public health decision making and resource allocation. The adapted WHO Unity FFX protocol for COVID-19 was implemented to gain an understanding of the clinical, epidemiological, virological, and household transmission dynamics of the first cases of COVID-19 infection detected in Juba, South Sudan. Methods Laboratory-confirmed COVID-19 cases were identified through the national surveillance system, and an initial visit was conducted with eligible cases to identify all close contacts. Consenting cases and close contacts were enrolled between June 2020 and December 2020. Demographic, clinical information and biological samples were taken at enrolment and 14–21 days post-enrolment for all participants. Results Twenty-nine primary cases and 82 contacts were included in analyses. Most primary cases (n=23/29, 79.3%) and contacts (n=61/82, 74.4%) were male. Many primary cases (n=18/29, 62.1%) and contacts (n=51/82, 62.2%) were seropositive for SARS-CoV-2 at baseline. The secondary attack rate among susceptible contacts was 12.9% (4/31; 95% CI: 4.9%–29.7%). All secondary cases and most (72%) primary cases were asymptomatic. Reported symptoms included coughing (n=6/29, 20.7%), fever or history of fever (n=4/29, 13.8%), headache (n=3/29, 10.3%) and shortness of breath (n=3/29, 10.3%). Of 38 cases, two were hospitalised (5.3%) and one died (2.6%). Conclusions These findings were used to develop the South Sudanese Ministry of Health surveillance and contract tracing protocols, informing local COVID-19 case definitions, follow-up protocols and data management systems. This investigation demonstrates that rapid FFX implementation is critical in understanding the emerging disease and informing response priorities.

Background: In Angola, COVID-19 cases have been reported in all provinces, resulting in >105,000 cases and >1,900 deaths. However, no detailed genomic surveillance into the introduction and spread of the SARS-CoV-2 virus has been conducted in Angola. We aimed to investigate the emergence, and epidemic progression during the peak of the COVID-19 pandemic in Angola. Methods: We generated 1,210 whole-genome SARS-CoV-2 sequences, contributing West African data to the global context, that were phylogenetically compared against global strains. Viral movement events were inferred using ancestral state reconstruction. Results: The epidemic in Angola was marked by four distinct waves of infection, dominated by 12 viral lineages, including VOCs, VOIs, and the VUM C.16, which was unique to Southwestern Africa and circulated for an extended period within the region. Viral exchanges occurred between Angola and its neighboring countries, and strong links with Brazil and Portugal reflected the historical and cultural ties shared between these countries. The first case likely originated from southern Africa. Conclusion: A lack of a robust genome surveillance network and strong dependence on out-of-country sequencing limit real-time data generation to achieve timely disease outbreak responses, which remains of the utmost importance to mitigate future disease outbreaks in Angola.

Background: The transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is complex and multifactorial. We aimed to identify the risk factors for infection among the household contacts of index patients and to determine the incubation period, serial interval, and estimates of secondary infection rate. Methods: We conducted a study in three districts of Kerala among the inhabitants of households of reverse transcriptase polymerase chain reaction (RT-PCR)-positive coronavirus disease (COVID-19) patients between January and July 2021. COVID-19-positive patients and corresponding contacts were enrolled and followed up for 28 days to determine RT-PCR positivity and the presence of total antibodies against SARS-CoV-2 on days 1, 7, 14, and 28 from the date of enrolment. Results: The mean incubation period, serial interval, and generation time were 1.6, 3, and 3.9 days, respectively. The secondary infection rate was 43.0%. Individuals who worked outside the home were protected, whereas those who had kissed the COVID-19-positive patients during illness were more than twice at risk of infection than those who had not kissed the COVID-19-positive patients. Similarly, the contacts who had shared a toilet with the COVID-19-positive patients were more at risk than those who had not shared a toilet. However, the contacts who reported using masks were at a higher risk of infection in household settings. Conclusions Assessment of SARS-CoV-2 transmission in household settings is important, considering its high secondary infection rate. Close physical contact and toilet sharing increase the risk of infection. This study demonstrates shorter incubation period and serial interval.