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Background Scant data are available about global patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and global epidemiology of early confirmed cases of COVID-19 outside mainland China. We describe the global spread of SARS-CoV-2 and characteristics of COVID-19 cases and clusters before the characterisation of COVID-19 as a pandemic. Cases of COVID-19 reported between Dec 31, 2019, and March 10, 2020 (ie, the prepandemic period), were identified daily from official websites, press releases, press conference transcripts, and social media feeds of national ministries of health or other government agencies. Case characteristics, travel history, and exposures to other cases were abstracted. Countries with at least one case were classified as affected. Early cases were defined as those among the first 100 cases reported from each country. Later cases were defined as those after the first 100 cases. We analysed reported travel to affected countries among the first case reported from each country outside mainland China, demographic and exposure characteristics among cases with age or sex information, and cluster frequencies and sizes by transmission settings. Among the first case reported from each of 99 affected countries outside of mainland China, 75 (76%) had recent travel to affected countries; 60 (61%) had travelled to China, Italy, or Iran. Among 1200 cases with age or sex information, 874 (73%) were early cases. Among 762 early cases with age information, the median age was 51 years (IQR 35–63); 25 (3%) of 762 early cases occurred in children younger than 18 years. Overall, 21 (2%) of 1200 cases were in health-care workers and none were in pregnant women. 101 clusters were identified, of which the most commonly identified transmission setting was households (76 [75%]; mean 2·6 cases per cluster [range 2–7]), followed by non-health-care occupational settings (14 [14%]; mean 4·3 cases per cluster [2–14]), and community gatherings (11 [11%]; mean 14·2 cases per cluster [4–36]). Cases with travel links to China, Italy, or Iran accounted for almost two-thirds of the first reported COVID-19 cases from affected countries. Among cases with age information available, most were among adults aged 18 years and older. Although there were many clusters of household transmission among early cases, clusters in occupational or community settings tended to be larger, supporting a possible role for physical distancing to slow the progression of SARS-CoV-2 spread. None.

This manuscript presents a report of bullous pemphigoid rash associated with COVID-19 for the first time. The objective of this manuscript is to present a unique dermatological case in the setting of a COVID-19-positive infection to further recognize the virus symptomatology. A 37-year-old female with a past medical history of class III obesity, type II diabetes mellitus, and hypertension presented to the emergency department in September 2020 with inpatient and outpatient follow-up through to November 2020. The patient denied any personal or family history of skin disorders. The patient tested positive for COVID-19 prior to hospitalization and presented to the hospital with severe, persistent, pruritic rash meeting dermatopathological, serologic, and clinical criteria for bullous pemphigoid diagnosis. Histopathology H&E punch biopsy from her left flexor wrist demonstrated epidermal keratinocyte necrosis, subepidermal vesiculation with eosinophils, gossamer stranding of the papillary dermis, and subepidermal edema. Direct immunofluorescence punch biopsy from her left flexor wrist demonstrated strong linear IgG staining at the dermoepidermal junction, with weaker and focal linear C3 staining. Antigen-specific serology was consistent with bullous pemphigoid. There was no previously reported cutaneous association of COVID-19 infection with bullous pemphigoid making this case an important addition to the body of evidence helping to identify bullous pemphigoid in the setting of viral infection.

In February 2021, Peru launched a COVID-19 vaccination campaign among healthcare personnel using an inactivated whole-virus vaccine. The manufacturer recommended 2 vaccine doses 21 days apart. We evaluated vaccine effectiveness among an existing multiyear influenza vaccine cohort at 2 hospitals in Lima. We analyzed data on 290 participants followed during February-May 2021. Participants completed a baseline questionnaire and provided weekly self-collected nasal swab samples; samples were tested by real-time reverse transcription PCR. Median participant follow-up was 2 (range 1-11) weeks. We performed multivariable logistic regression and adjusted for preselected characteristics. During the study, 25 (9%) participants tested SARS-CoV-2-positive. We estimated adjusted vaccine effectiveness at 95% (95% CI 70%-99%) among fully vaccinated participants and 100% (95% CI 88%-100%) among partially vaccinated participants. These data can inform the use and acceptance of inactivated whole-virus vaccine and support vaccination efforts in the region.

Early warning and response surveillance (EWARS) systems were widely used during the early COVID-19 response. Evaluating the effectiveness of EWARS systems is critical to ensuring global health security. We describe the Centers for Disease Control and Prevention (CDC) global COVID-19 EWARS (CDC EWARS) system and the resources CDC used to gather, manage, and analyze publicly available data during the prepandemic period. We evaluated data quality and validity by measuring reporting completeness and compared these with data from Johns Hopkins University, the European Centre for Disease Prevention and Control, and indicator-based data from the World Health Organization. CDC EWARS was integral in guiding CDC's early COVID-19 response but was labor-intensive and became less informative as case-level data decreased and the pandemic evolved. However, CDC EWARS data were similar to those reported by other organizations, confirming the validity of each system and suggesting collaboration could improve EWARS systems during future pandemics.

While chicken eggs and meat are a critical protein source in low-income settings, antibiotics are routinely fed to chickens with consequences for selection of antimicrobial resistance. Evaluating how poultry gut bacterial communities, including potential human pathogens and high-risk antimicrobial resistance genes, differ from farm to market could help identify where to target interventions to minimize transmission risks to human populations. In this study in Maputo City, Mozambique, we found compositional differences between commercial and local chicken breeds at production and market sites. We also found that while all potentially pathogenic bacteria and many high-risk antimicrobial resistance genes persisted from production and market through processing, some resistance genes were detected on carcass samples only after processing, suggesting human or environmental contamination is occurring within markets. Overall, our findings indicate that open-air markets may represent a critical juncture for human exposures to pathogens and antimicrobial resistance genes from poultry and poultry products.

Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants ( Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.

A study with a test-negative design analyzed 41,552 admissions to 187 hospitals and 21,522 visits to 221 EDs or urgent care clinics. The mRNA-based vaccines (≥14 days after the second dose) were highly effective against SARS-CoV-2 infection leading to hospitalization (89%), ICU admission (90%), or an urgent care visit (91%).

Knockdown resistance ( kdr ) and CYP9K1 genotypes were detected by a MOLDI-TOF based SNP genotyping assay (Sequenom iPLEX) in samples of Anopheles gambiae collected at 13 sites throughout the Union of the Comoros and Dar es Salaam, Tanzania during February and March 2011. All A . gambiae specimens collected in the Comoros were homozygous for the susceptible kdr alleles (+/+) while 96% of A. gambiae from Dar es Salaam were homozygous for the East African kdr resistant genotype (E/E). In contrast, all specimens from Dar es Salaam and the Comoros were homozygous for the cyp3 allele (c3/c3) at the CYP9K1 locus; the locus has been implicated in metabolic resistance against pyrethroid insecticides in West Africa. All specimens had typical A. gambiae genotypes for SNPs within the divergence Islands on all three chromosomes. Although further spatial and temporal studies are needed, the distribution of kdr genotypes between the Comoros and Tanzania further supports isolation of the Comoros populations from A. gambiae populations on mainland Africa .

The Nurses' Health Study II, a large cohort study that evaluated breast cancer risk across a broad age range, found an elevated risk of breast cancer in long-duration night workers,3 which was also seen in a Swedish cohort study. The largest case-control study,4 including more than 6000 breast cancer cases and corresponding controls from five countries, incorporated an extensive exposure assessment protocol and evaluated detailed exposure metrics on both duration and intensity of exposure (eg, number of night shifts per week). Several studies found positive associations between night shift work and prostate cancer risk, particularly in association with longer duration of exposures, but in others there was no, or a very small, increased risk when examining ever versus never exposure to night shift work.5,6 Several informative studies found some evidence of positive associations between colorectal cancer risk and duration of night shift work. Increased incidences of hepatocellular carcinoma were seen in all three strains in comparison with control mice maintained at a stable 12-h light and 12-h dark schedule.8 In another study, exposure to constant light for a lifetime increased the incidences of lung adenocarcinoma, malignant melanoma, and total tumours in female wild-type CBA mice in comparison with control mice maintained at a 12-h light and 12-h dark schedule.9 The evaluation was further supported by positive results in other studies in rodents exposed to shifts in the light–dark schedule or continuous light using carcinogen-induced or transplantable tumour models.

As the landscape of malaria in sub-Saharan Africa changes due to improved control efforts, there is increasing interest in elucidating the epidemiology of asymptomatic P. falciparum infection and its role in disease transmission, particularly in school age children. We conducted a cross-sectional survey in the summer of 2018 of children attending 4 primary/junior high schools within a 5 km radius of HopeXchange Medical Centre in Kumasi, Ghana, a city of 2.5 million inhabitants with year-round malaria transmission. Informed consent/assent and demographic information was obtained from 634 subjects (ages 5-17 years), after which measurements of height/weight/body temperature were recorded and a blood sample was obtained for evaluation by blood film microscopy, rapid diagnostic test (RDT) and nested polymerase chain reaction (PCR) for P. falciparum. Factors associated with malaria parasitemia were analyzed using a qualitative questionnaire covering socioeconomic factors, malaria prevention behaviors, and healthcare access. The overall prevalence of asymptomatic parasitemia varied by diagnostic test (microscopy: 5.5%; RDT: 11.8%; PCR: 23.4%). Agreement between methods was highest for samples with higher levels of parasitemia as measured by microscopy. Bivariate analysis showed that factors associated with a positive malaria test included school, lack of bed net usage and age. After controlling for relevant factors, school of attendance was the single greatest predictor of a positive malaria test in the study population. Across the 4 schools, use of PCR (n=555) increased the measured prevalence of asymptomatic malaria parasitemia when compared to the prevalence measured using microscopy (1.7 vs 7.6%; 2.8 vs 10.3%; 3.2 vs 28.4%; 12.2 vs 40.1%). These data are in agreement with previously described higher sensitivity of PCR for detection of asymptomatic parasitemia. More importantly, these results capture the significant heterogeneity in asymptomatic malaria risk in Kumasi, underscoring the importance of characterizing the epidemiology of asymptomatic malaria, even across urban communities.