Clade I mpox virus genomic diversity in the Democratic Republic of the Congo, 2018-2024: Predominance of zoonotic transmission.

Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC). High-quality genomes were generated for 337 patients from 14/26 provinces to document whether the increase in number of cases is due to zoonotic spillover events or viral evolution, with enrichment of APOBEC3 mutations linked to human adaptation. Our study highlights two patterns of transmission contributing to the source of human cases. All new sequences from the eastern South Kivu province (n = 17; 4.8%) corresponded to the recently described clade Ib, associated with sexual contact and sustained human-to-human transmission. By contrast, all other genomes are clade Ia, which exhibits high genetic diversity with low numbers of APOBEC3 mutations compared with clade Ib, suggesting multiple zoonotic introductions. The presence of multiple clade I variants in urban areas highlights the need for coordinated international response efforts and more studies on the transmission and the reservoir of mpox.

Ebola Virus Transmission Initiated by Relapse of Systemic Ebola Virus Disease.

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).

Implementation of Choosing Wisely® Recommendations for Lymph Node Surgery in Male Breast Cancer.

BACKGROUND: The Choosing Wisely® (CW) campaign recommended de-implementation of surgical management of axillary nodes in specified patients. This study aimed to assess trends in the application of CW guidelines for lymph node (LN) surgery in males with breast cancer. METHODS: The National Cancer Database was queried for males diagnosed with breast cancer from 2017 to 2020. Patients were categorized into two cohorts based on CW criteria. Cohort 1 included all T1-2, clinically node-negative patients who underwent breast-conserving therapy and with ≤ 2 positive nodes, and Cohort 2 included all T1-2, node-negative, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative patients aged ≥ 70 years. In Cohort 1, patients who underwent sentinel LN biopsy (SLNB) alone were compared with axillary LN dissection (ALND) or no LN surgery, while in Cohort 2, patients who underwent LN surgery were compared with those with no LN surgery. RESULTS: Of 617 patients who met the criteria for Cohort 1, 73.1% underwent SLNB alone compared with ALND (11.8%) or no LN surgery (15.1%). Those who received SLNB alone were younger (65 vs. 68 vs. 73 years; p < 0.001). The annual proportion of males who underwent SLNB alone remained stable from 2017 to 2020. Overall, 1565 patients met the criteria for Cohort 2, and 84.9% received LN surgery. LN surgery was omitted in older patients (81 vs. 77; p < 0.001). The proportion of elderly males with early-stage breast cancer who underwent LN surgery increased from 2017 to 2020. CONCLUSION: This study demonstrates that CW recommendations are not being routinely applied to males. These findings reinforce the need for additional studies and subsequent recommendations for optimal application of axillary surgery de-implementation for males diagnosed with breast cancer.

Nationwide Analysis of Locoregional Management for Ductal Carcinoma In Situ in Males: An NCDB Analysis of the Surgical Approach to DCIS in Males.

BACKGROUND: Limited data exist regarding the optimal locoregional approach for males with ductal carcinoma in situ (DCIS). This study examined trends in management and survival for males with DCIS. METHODS: The National Cancer Database (NCDB) was queried for males with a diagnosis of DCIS from 2006 to 2017. Patients were categorized by locoregional management. Continuous variables were evaluated by Kruskal-Wallis and categorical variables by chi-square or Fisher's exact test. Univariable and multivariable logistic regressions were performed to evaluate for predictors of patients receiving partial mastectomy (PM) with radiation. Survival was analyzed by Kaplan-Meier. RESULTS: Between 2006 and 2017, 711 males with DCIS were identified. Most received mastectomy alone (57.1%). No change was observed in management approach from 2006 to 2017. Patients who underwent mastectomy alone were mostly hormone-positive (95.9% were estrogen-positive, 90.9% were progesterone-positive), although this cohort was least likely to receive hormone therapy (17.2%). Among those who underwent PM with radiation, only 61% of those who were hormone-positive received hormone therapy. Univariable analysis demonstrated that those of black race had lower odds of receiving PM with radiation (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.36-0.84), which persisted in the multivariable analysis with control for age and tumor size (OR, 0.32; 95% CI, 0.15-0.67). Overall survival did not differ significantly between the four treatment methods (p = 0.08). CONCLUSIONS: The management approach to male DCIS did not change from 2006 to 2017. Survival did not differ between treatment methods. Demographic and clinicopathologic features, including race, may influence locoregional treatments received, and further studies are needed to further understand this.

Disparities Associated with Decision to Undergo Oncologic Surgery: A Prospective Mixed-Methods Analysis.

BACKGROUND: Underrepresented minority patients with surgical malignancies experience disparities in outcomes. The impact of provider-based factors, including communication, trust, and cultural competency, on outcomes is not well understood. This study examines modifiable provider-based barriers to care experienced by patients with surgical malignancies. METHODS: A parallel, prospective, mixed-methods study enrolled patients with lung or gastrointestinal malignancies undergoing surgical consultation. Surveys assessed patients' social needs and patient-physician relationship. Semi-structured interviews ascertained patient experiences and were iteratively analyzed, identifying key themes. RESULTS: The cohort included 24 patients (age 62 years; 63% White and 38% Black/African American). The most common cancers were lung (n = 18, 75%) and gastroesophageal (n = 3, 13%). Survey results indicated that food insecurity (n = 5, 21%), lack of reliable transportation (n = 4, 17%), and housing instability (n = 2, 8%) were common. Lack of trust in their physician (n = 3, 13%) and their physician's treatment recommendation (n = 3, 13%) were identified. Patients reported a lack of empathy (n = 3, 13%), lack of cultural competence (n = 3, 13%), and inadequate communication (n = 2, 8%) from physicians. Qualitative analysis identified five major themes regarding the decision to undergo surgery: communication, trust, health literacy, patient fears, and decision-making strategies. Five patients (21%) declined the recommended surgery and were more likely Black (100% vs. 21%), lower income (100% vs. 16%), and reported poor patient-physician relationship (40% vs. 5%; all p < 0.05). CONCLUSIONS: Factors associated with declining recommended cancer surgery were underrepresented minority race and poor patient-physician relationships. Interventions are needed to improve these barriers to care and racial disparities.

Examining the Aftermath of Virtual Interviewing on Surgical Residency Matches.

INTRODUCTION: Residency interviews have traditionally been conducted in person; however, COVID-19 forced programs to shift to virtual interviewing. This study delineated the nationwide trends observed after virtual interviewing across multiple application cycles on both surgical residency applicant competitiveness and program workload. METHODS: Publicly available National Residency Matching Program applicant and program data were retrospectively reviewed. Applicant competitiveness was assessed using a validated competitive index (# positions ranked/match rate). Interview types included in-person (2010-2020) or virtual (2021-2023), and programs were classified as general surgery (GS), surgical subspecialty (SS) - orthopedics, otolaryngology and neurosurgery, and integrated specialty (IS) - plastic, thoracic, and vascular surgery. RESULTS: When comparing in-person to virtual cohorts, the competitive index has increased in GS (0.97 ± 0.00 to 1.05 ± 0.01, P < 0.001), SS (0.97 ± 0.02 to 1.06 ± 0.01 P < 0.001), and IS (0.93 ± 0.06 to 1.12 ± 0.03, P = 0.001). United Sates Medical Licensing Examination Step scores and research experiences increased over time in GS and SS (P < 0.05). Program workload, represented by number of applications received per program increased in GS, IS, and SS (P < 0.05), as well as the number of interviews conducted in GS and SS (P < 0.05). Importantly, match rate remained stable in GS and IS, with a decrease in SS (0.69 ± 0.03 to 0.63 ± 0.02, P = 0.04). CONCLUSIONS: The residency application process has been irrevocably changed due to COVID-19. The rise in applicant volume and competitiveness places unique strains on applicants and programs. Additional modifications such as signaling and ACGME guidance are needed to help alleviate strain and ensure that residents and programs alike find their best fit.

Perceptions of the White Coat: Generational, Regional, and Gender Differences Among Surgeons.

INTRODUCTION: Recent studies have evaluated patient perception of physician attire; however, few studies have considered physician perceptions of workplace attire. This study aimed to assess current trends regarding attire preferences among surgeons. METHODS: A national, population-based survey was distributed via email and "X" (Twitter). Participants were asked to complete an online questionnaire regarding their perception of the white coat, preferred attire in clinical settings, and reasons for choice of attire. RESULTS: Of 481 participants, 172 (36%) were attendings, 164 (34%) were residents, 125 (26%) were medical students, and 20 (4%) were fellows. Those who practiced in the Midwest region were more likely to wear a white coat daily (35.1% versus 28.5% South, 23.5% Northeast, 20.0% West, P < 0.05). Late career surgeons (practicing >20 y) were more likely to wear a white coat in the hospital and wear it daily (56% versus 36% of middle-career surgeons, 34% early-career surgeons, and 26% in training, P < 0.05). Women surgeons more frequently wore a white coat in clinic (64% versus 54% men, P < 0.05), reported that wearing a white coat was influenced by their program's culture (61% versus 46% of men surgeons, P < 0.05), that they would stop wearing a white coat if other members of their department stopped (50% versus 35% of men, P < 0.05), and that they believe the white coat helps distinguish female doctors from nurses (61% versus 50% of men surgeons, P < 0.05). CONCLUSIONS: This study demonstrates generational, regional, and gender differences among surgeons in their perception of the white coat at a national level.

Primary Team Versus Local Recovery in Liver Transplantation in the Modern Era: A National Analysis of the United Network for Organ Sharing Database.

BACKGROUND: The implementation of acuity circles (AC) in 2020 and the COVID-19 pandemic increased the use of local surgeons to recover livers for transplant; however, the impact on liver transplant (LT) outcomes is unknown. METHODS: Deceased donor adult LT recipients from the UNOS database were identified.  Recipients were grouped by donor surgeon: local versus primary recovery.  Patient and graft survival as well as trends in local recovery in the 2 years pre-AC and post-AC were assessed. RESULTS: The utilization of local recovery in LT increased from 22.3% to 37.9% post-AC (p < 0.01).  LTs with local recovery had longer cold ischemia times (6.5 h [5.4-7.8] vs. 5.3 h [4.4-6.5], p < 0.01) and traveled further (210 miles [89-373] vs. 73 miles [11-196], p < 0.01) than those using primary recovery. Multivariate analyses revealed no differences in patient or graft survival between local and primary recovery, and between OPO and local surgeon. There was no difference in survival when comparing simultaneous liver-kidney, donation after circulatory death, MELD ≥ 30, or redo-LT by recovery team.  Recovery and utilization rates were also noted to be higher post-AC (51.4% vs. 48.6% pre-AC, p < 0.01) as well as when OPO surgeons recovered the allografts (72.5% vs. 66.0%, p < 0.01). CONCLUSION: Nearly 40% of LTs are performed using local recovery, and utilization rates and trends continue to change with changing organ-sharing paradigms such as AC.  This practice appears safe with outcomes similar to recovery by the primary team in appropriately selected recipients and may lead to increased access and the ability to transplant more livers.

Expanding MELD exceptions for colorectal liver metastasis: data and policy.

PURPOSE OF REVIEW: While liver transplant for unresectable colorectal cancer liver metastases (CRLM) has been demonstrated to be a promising treatment in selected patients, the typically low MELD score of these patients and lack of exception points may lead to challenges in receiving a deceased donor liver for transplant. RECENT FINDINGS: Several studies have shown improved outcomes in select patients with CRLM who undergo liver transplant, and several trials are ongoing and will conclude in the next several years. MELD exception points have recently been proposed in qualifying patients with CRLM to help this group obtain more timely quality allografts. Under the current proposal, patients with CRLM would receive a score of the median MELD at transplant (MMaT) for their center minus 20 with a minimum score of 15 in cases where MMaT minus 20 would be less than 15. This would allow them to receive transplants faster without competing unnecessarily with those with greater medical need. SUMMARY: Giving MELD exception points to patients with colorectal cancer liver metastases in need of transplant may decrease time on the waitlist and improve outcomes for these patients.

Safety and use of late-turndown liver allografts to increase rate of transplantation.

BACKGROUND: The demand for liver transplants (LT) in the United States far surpasses the availability of allografts. New allocation schemes have resulted in occasional difficulties with allograft placement and increased intraoperative turndowns. We aimed to evaluate the outcomes related to use of late-turndown liver allografts. METHODS: A review of prospectively collected data of LTs at a single center from July 2019 to July 2023 was performed. Late-turndown placement was defined as an open offer 6 h prior to donation, intraoperative turndown by primary center, or post-cross-clamp turndown. RESULTS: Of 565 LTs, 25.1% (n = 142) received a late-turndown liver allograft. There were no significant differences in recipient age, gender, BMI, or race (all p > 0.05), but MELD was lower for the late-turndown LT recipient group (median 15 vs 21, p < 0.001). No difference in 30-day, 6-month, or 1-year survival was noted on logistic regression, and no difference in patient or graft survival was noted on Cox proportional hazard regression. Late-turndown utilization increased during the study from 17.2% to 25.8%, and median waitlist time decreased from 77 days in 2019 to 18 days in 2023 (p < 0.001). CONCLUSION: Use of late-turndown livers has increased and can increase transplant rates without compromising post-transplant outcomes with appropriate selection.

"Super-Spreaders" and Person-to-Person Transmission of Andes Virus in Argentina.

BACKGROUND: From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions. METHODS: Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events. RESULTS: After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18-19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission. CONCLUSIONS: Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission. (Funded by the Ministerio de Salud y Desarrollo Social de la Nación Argentina and others.).

Retrospective Genomic Characterization of a 2017 Dengue Virus Outbreak, Burkina Faso.

Knowledge of contemporary genetic composition of dengue virus (DENV) in Africa is lacking. By using next-generation sequencing of samples from the 2017 DENV outbreak in Burkina Faso, we isolated 29 DENV genomes (5 serotype 1, 16 serotype 2 [DENV-2], and 8 serotype 3). Phylogenetic analysis demonstrated the endemic nature of DENV-2 in Burkina Faso. We noted discordant diagnostic results, probably related to genetic divergence between these genomes and the Trioplex PCR. Forward and reverse1 primers had a single mismatch when mapped to the DENV-2 genomes, probably explaining the insensitivity of the molecular test. Although we observed considerable homogeneity between the Dengvaxia and TetraVax-DV-TV003 vaccine strains as well as B cell epitopes compared with these genomes, we noted unique divergence. Continual surveillance of dengue virus in Africa is needed to clarify the ongoing novel evolutionary dynamics of circulating virus populations and support the development of effective diagnostic, therapeutic, and preventive countermeasures.

Plasticity of fimbrial genotype and serotype within populations of Bordetella pertussis: analysis by paired flow cytometry and genome sequencing.

The fimbriae of Bordetella pertussis are required for colonization of the human respiratory tract. Two serologically distinct fimbrial subunits, Fim2 and Fim3, considered important vaccine components for many years, are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and the World Health Organization recommends the inclusion of strains expressing both fimbrial serotypes in whole-cell pertussis vaccines. Each of the fimbrial major subunit genes, fim2, fim3, and fimX, has a promoter poly(C) tract upstream of its -10 box. Such monotonic DNA elements are susceptible to changes in length via slipped-strand mispairing in vitro and in vivo, which potentially causes on/off switching of genes at every cell division. Here, we have described intra-culture variability in poly(C) tract lengths and the resulting fimbrial phenotypes in 22 recent UK B. pertussis isolates. Owing to the highly plastic nature of fimbrial promoters, we used the same cultures for both genome sequencing and flow cytometry. Individual cultures of B. pertussis contained multiple fimbrial serotypes and multiple different fimbrial promoter poly(C) tract lengths, which supports earlier serological evidence that B. pertussis expresses both serotypes during infection.

Breast infections: A review of current literature.

Breast infections are common, affect women of all ages, and are associated with significant morbidity. Despite overall prevalence, treatment varies significantly based on provider or institution and no central treatment guidelines exist to direct the management of breast infections. This article provides a summary of the current trends in management of breast infections. The etiology, epidemiology, risk factors, presentation, diagnosis, and treatment of mastitis and breast abscesses (and their relative subdivisions) are explored based on the current literature. Trends in microbiology are reviewed and an approach to antibiotic coverage is proposed. Overall, there is a lack of randomized-controlled trials focused on the treatment of breast infections. This has resulted in an absence of clinical practice guidelines for the management of breast abscesses and variable practice patterns. The development of best-care protocols or pathways could provide more uniformity in care of breast infections.

Implementation of Choosing Wisely guidelines: Omission of lymph node surgery.

OBJECTIVES: In 2016, the Choosing Wisely campaign published guidelines recommending omission of sentinel lymph node biopsy in clinically node-negative women ≥70 years with early-stage (cT1-2), hormone receptor-positive, and human epidermal growth factor receptor 2-negative breast cancers. This study aimed to evaluate the implementation of this guideline. METHODS: The National Cancer Database was queried from 2017 to 2020. All patients who met criteria for lymph node surgery omission were included and compared with those who underwent lymph node surgery. RESULTS: Of 138,648 patients who met criteria for lymph node surgery omission, 26,070 (21.0%) had lymph node surgery omission and 109,482 (79.0%) underwent lymph node surgery. Those who had lymph node surgery omission were older (median 79 [75-84] vs 75 [72-79] years, P < .01) and had increased comorbidities (28.3% with Charlson/Deyo score ≥3 had lymph node surgery omission vs 20.2% with score 0, P < .01). Academic/research institutions most frequently practiced lymph node surgery omission (25.8% vs 16.5% community cancer programs, 19.3% comprehensive community cancer programs, and 20.6% integrated network cancer programs, P < .01). A greater percentage of lymph node surgery omission was noted with ductal carcinoma (21.4% vs 17.6% lobular and 19.4% mixed, P < .01) and lower-grade tumors (21.7% of grade 1 vs 19.4% of grade 2 and 17.8% of grade 3, P < .01). Throughout the period studied, the overall rate of lymph node surgery omission increased from 17.7% in 2017 to 23.1% in 2020 (P < .01). CONCLUSION: Despite the evidence-based Choosing Wisely guideline recommending lymph node surgery omission in selected patients with breast cancer, more than 75% of patients meeting criteria were still being subjected to lymph node surgery as of 2020. Future work is warranted to determine factors affecting implementation of the Choosing Wisely guideline.

Does using artificial intelligence take the person out of personal statements? We can't tell.

BACKGROUND: Use of artificial intelligence to generate personal statements for residency is currently not permitted but is difficult to monitor. This study sought to evaluate the ability of surgical residency application reviewers to identify artificial intelligence-generated personal statements and to understand perceptions of this practice. METHODS: Three personal statements were generated using ChatGPT, and 3 were written by medical students who previously matched into surgery residency. Blinded participants at a single institution were instructed to read all personal statements and identify which were generated by artificial intelligence; they then completed a survey exploring their opinions regarding artificial intelligence use. RESULTS: Of the 30 participants, 50% were faculty (n = 15) and 50% were residents (n = 15). Overall, experience ranged from 0 to 20 years (median, 2 years; interquartile range, 1-6.25 years). Artificial intelligence-derived personal statements were identified correctly only 59% of the time, with 3 (10%) participants identifying all the artificial intelligence-derived personal statements correctly. Artificial intelligence-generated personal statements were labeled as the best 60% of the time and the worst 43.3% of the time. When asked whether artificial intelligence use should be allowed in personal statements writing, 66.7% (n = 20) said no and 30% (n = 9) said yes. When asked if the use of artificial intelligence would impact their opinion of an applicant, 80% (n = 24) said yes, and 20% (n = 6) said no. When survey questions and ability to identify artificial intelligence-generated personal statements were evaluated by faculty/resident status and experience, no differences were noted (P > .05). CONCLUSION: This study shows that surgical faculty and residents cannot reliably identify artificial intelligence-generated personal statements and that concerns exist regarding the impact of artificial intelligence on the application process.

Fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease in the Democratic Republic of the Congo: a case report study.

BACKGROUND: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence. METHODS: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques. FINDINGS: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2. INTERPRETATION: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence. FUNDING: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, US National Cancer Institute (National Institutes of Health), French National Research Institute for Development, and WHO.

2020 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation.

BACKGROUND: The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak. METHODS: We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak. FINDINGS: Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD. INTERPRETATION: Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks. FUNDING: WHO and US Centers for Disease Control and Prevention.

Sensitive poliovirus detection using nested PCR and nanopore sequencing: a prospective validation study.

Timely detection of outbreaks is needed for poliovirus eradication, but gold standard detection in the Democratic Republic of the Congo takes 30 days (median). Direct molecular detection and nanopore sequencing (DDNS) of poliovirus in stool samples is a promising fast method. Here we report prospective testing of stool samples from suspected polio cases, and their contacts, in the Democratic Republic of the Congo between 10 August 2021 and 4 February 2022. DDNS detected polioviruses in 62/2,339 (2.7%) of samples, while gold standard combination of cell culture, quantitative PCR and Sanger sequencing detected polioviruses in 51/2,339 (2.2%) of the same samples. DDNS provided case confirmation in 7 days (median) in routine surveillance conditions. DDNS enabled confirmation of three serotype 2 circulating vaccine-derived poliovirus outbreaks 23 days (mean) earlier (range 6-30 days) than the gold standard method. The mean sequence similarity between sequences obtained by the two methods was 99.98%. Our data confirm the feasibility of implementing DDNS in a national poliovirus laboratory.