Use of Sentinel Surveillance Platforms for Monitoring SARS-CoV-2 Activity: Evidence From Analysis of Kenya Influenza Sentinel Surveillance Data.

BACKGROUND: Little is known about the cocirculation of influenza and SARS-CoV-2 viruses during the COVID-19 pandemic and the use of respiratory disease sentinel surveillance platforms for monitoring SARS-CoV-2 activity in sub-Saharan Africa. OBJECTIVE: We aimed to describe influenza and SARS-CoV-2 cocirculation in Kenya and how the SARS-CoV-2 data from influenza sentinel surveillance correlated with that of universal national surveillance. METHODS: From April 2020 to March 2022, we enrolled 7349 patients with severe acute respiratory illness or influenza-like illness at 8 sentinel influenza surveillance sites in Kenya and collected demographic, clinical, underlying medical condition, vaccination, and exposure information, as well as respiratory specimens, from them. Respiratory specimens were tested for influenza and SARS-CoV-2 by real-time reverse transcription polymerase chain reaction. The universal national-level SARS-CoV-2 data were also obtained from the Kenya Ministry of Health. The universal national-level SARS-CoV-2 data were collected from all health facilities nationally, border entry points, and contact tracing in Kenya. Epidemic curves and Pearson r were used to describe the correlation between SARS-CoV-2 positivity in data from the 8 influenza sentinel sites in Kenya and that of the universal national SARS-CoV-2 surveillance data. A logistic regression model was used to assess the association between influenza and SARS-CoV-2 coinfection with severe clinical illness. We defined severe clinical illness as any of oxygen saturation <90%, in-hospital death, admission to intensive care unit or high dependence unit, mechanical ventilation, or a report of any danger sign (ie, inability to drink or eat, severe vomiting, grunting, stridor, or unconsciousness in children younger than 5 years) among patients with severe acute respiratory illness. RESULTS: Of the 7349 patients from the influenza sentinel surveillance sites, 76.3% (n=5606) were younger than 5 years. We detected any influenza (A or B) in 8.7% (629/7224), SARS-CoV-2 in 10.7% (768/7199), and coinfection in 0.9% (63/7165) of samples tested. Although the number of samples tested for SARS-CoV-2 from the sentinel surveillance was only 0.2% (60 per week vs 36,000 per week) of the number tested in the universal national surveillance, SARS-CoV-2 positivity in the sentinel surveillance data significantly correlated with that of the universal national surveillance (Pearson r=0.58; P<.001). The adjusted odds ratios (aOR) of clinical severe illness among participants with coinfection were similar to those of patients with influenza only (aOR 0.91, 95% CI 0.47-1.79) and SARS-CoV-2 only (aOR 0.92, 95% CI 0.47-1.82). CONCLUSIONS: Influenza substantially cocirculated with SARS-CoV-2 in Kenya. We found a significant correlation of SARS-CoV-2 positivity in the data from 8 influenza sentinel surveillance sites with that of the universal national SARS-CoV-2 surveillance data. Our findings indicate that the influenza sentinel surveillance system can be used as a sustainable platform for monitoring respiratory pathogens of pandemic potential or public health importance.

The 2020 immunization programme landscape: Piloting an assessment metric to evaluate the maturity of national immunization programmes across the life course.

BACKGROUND: The World Health Organization (WHO) encourages countries to provide appropriate vaccinations for children, adolescents, and relevant adult populations. Childhood programme have been the focus of global investments, but recent pandemics have increasingly demonstrated the value of life course vaccination. Our objective is to compare national life course immunization programmatic maturity prior to mass COVID-19 vaccine introduction, the largest adult vaccination programme, globally. As coverage estimates (typically used to assess childhood programmes) are not available for adult vaccinations, this analysis pilots a standardized quantitative metric of programmatic maturity. METHODS: Through consultation with vaccination experts, we developed a standardized approach to assess national immunization programme maturity across the life course. In accordance with expert input, five vaccines were selected to represent delivery across the life course: diphtheria tetanus toxoid and pertussis (DTP); measles (MCV) second dose; human papillomavirus (HPV) final dose; pneumococcal conjugate (PCV) final dose; and seasonal influenza annual dose. Experts recommended inclusion of the following indicators for each vaccine: a legal mandate (national policy), experience delivering the vaccine (programme duration), and vaccine use (uptake for relevant populations). We developed a metric accordingly that provides up to 5 points per vaccine ("vaccine specific maturity score") which when summed forms the "life course maturity score", with a maximum score of 25. We analysed the prevalence of national policies, experience, and use by region and World Bank income group. RESULTS: More than 55% of the 194 WHO Member States had childhood vaccine policies for all three of the vaccines considered (DTP, MCV, and PCV) compared to 60% for HPV (proxy for adolescent vaccination programme) and 52% for seasonal influenza (proxy for adult vaccination programme). Childhood vaccination programmes (e.g., MCV and DTP) had the highest vaccine specific maturity scores, while seasonal influenza and HPV vaccination programmes had much lower scores. The national life course maturity scores ranged from 1 to 23, with a global median of 12 (IQR: 8; 16). DISCUSSION: The piloted metric provides an overview of the maturity of life course immunization programmes. The metric is structured to be a flexible, rapid resource that can be used to assess other combinations of vaccines across the life course. The findings from this paper provide a baseline of immunization programme maturity for childhood, adolescent, and adult vaccination programmes immediately prior to the COVID-19 vaccine introduction. This maturity score, or adaptations of this approach, could be used to monitor the trajectory of national immunization programme maturity across the life course in the years ahead.

Assessing the relationship between existing childhood, adolescent and adult immunization programmes and national COVID-19 vaccination capacities in 2021.

BACKGROUND: During the COVID-19 pandemic, nearly all countries introduced COVID-19 vaccination programmes. Yet, countries had a wide range of programmatic experiences. This analysis aims to identify national characteristics associated with COVID-19 vaccination programmatic success. METHODS: We used the following outcome measures: the presence of national COVID-19 vaccination capacities and COVID-19 coverage as of December 2021, June 2022, and December 2022. We developed a standardized metric for assessing national COVID-19 vaccination capacities as a proxy for speed of introduction. We developed this metric through adaptation of the WHO Guide for Conducting an Expanded Programme on Immunization Review and consultations with technical experts specializing in vaccine introduction and emergency deployment; monitoring and data; childhood, adolescent and adult programmes; and COVID-19 vaccination roll-out. Through multivariable linear regressions, we evaluated whether having a mature immunization programme for children, adolescents and adults; recent use of emergency vaccination; World Bank income classification; past early adoption of new vaccines; density of the health workforce; and/or trust in science and government were associated with higher COVID-19 vaccination capacities and coverage. RESULTS: The COVID-19 vaccination capacities scores ranged from 0 to 5 points with a global median score of 2 and an interquartile range of 1;4. After adjusting for World Bank income classifications, the presence of a mature influenza vaccination programme was independently correlated with statistically significant higher scores of national COVID-19 vaccination capacities and higher COVID-19 vaccination coverage in December 2021, June 2022, and December 2022. Trust in government was also associated with higher coverage for all three time stamps. CONCLUSIONS: As countries consider how to prepare for and respond to future pandemics, having an adult seasonal influenza vaccination programme, building trust in government, and ensuring equitable access to vaccines supply emerged as key aspects that can benefit from additional national and global focus.

Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation.

PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk. METHODS: Patients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR). RESULTS: Of 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD-, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32). CONCLUSION: Assessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS (ClinicalTrials.gov identifier: NCT02872662).

Timing of seasonal influenza epidemics for 25 countries in Africa during 2010-19: a retrospective analysis.

BACKGROUND: Using country-specific surveillance data to describe influenza epidemic activity could inform decisions on the timing of influenza vaccination. We analysed surveillance data from African countries to characterise the timing of seasonal influenza epidemics to inform national vaccination strategies. METHODS: We used publicly available sentinel data from African countries reporting to the WHO Global Influenza Surveillance and Response FluNet platform that had 3-10 years of data collected during 2010-19. We calculated a 3-week moving proportion of samples positive for influenza virus and assessed epidemic timing using an aggregate average method. The start and end of each epidemic were defined as the first week when the proportion of positive samples exceeded or went below the annual mean, respectively, for at least 3 consecutive weeks. We categorised countries into five epidemic patterns: northern hemisphere-dominant, with epidemics occurring in October-March; southern hemisphere-dominant, with epidemics occurring in April-September; primarily northern hemisphere with some epidemic activity in southern hemisphere months; primarily southern hemisphere with some epidemic activity in northern hemisphere months; and year-round influenza transmission without a discernible northern hemisphere or southern hemisphere predominance (no clear pattern). FINDINGS: Of the 34 countries reporting data to FluNet, 25 had at least 3 years of data, representing 46% of the countries in Africa and 89% of Africa's population. Study countries reported RT-PCR respiratory virus results for a total of 503 609 specimens (median 12 971 [IQR 9607-20 960] per country-year), of which 74 001 (15%; median 2078 [IQR 1087-3008] per country-year) were positive for influenza viruses. 248 epidemics occurred across 236 country-years of data (median 10 [range 7-10] per country). Six (24%) countries had a northern hemisphere pattern (Algeria, Burkina Faso, Egypt, Morocco, Niger, and Tunisia). Eight (32%) had a primarily northern hemisphere pattern with some southern hemisphere epidemics (Cameroon, Ethiopia, Mali, Mozambique, Nigeria, Senegal, Tanzania, and Togo). Three (12%) had a primarily southern hemisphere pattern with some northern hemisphere epidemics (Ghana, Kenya, and Uganda). Three (12%) had a southern hemisphere pattern (Central African Republic, South Africa, and Zambia). Five (20%) had no clear pattern (Côte d'Ivoire, DR Congo, Madagascar, Mauritius, and Rwanda). INTERPRETATION: Most countries had identifiable influenza epidemic periods that could be used to inform authorities of non-seasonal and seasonal influenza activity, guide vaccine timing, and promote timely interventions. FUNDING: None. TRANSLATIONS: For the Berber, Luganda, Xhosa, Chewa, Yoruba, Igbo, Hausa and Afan Oromo translations of the abstract see Supplementary Materials section.

Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020.

Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019-2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019-2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019-2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets.