Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Evaluation of the influenza sentinel surveillance system in the Democratic Republic of Congo, 2012-2015.

BACKGROUND: The World Health Organization recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data about the performance of established influenza surveillance systems are limited in Africa, including in the Democratic Republic of Congo (DRC). METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza sentinel surveillance system (ISSS) in DRC during 2012-2015. The performance of the system was evaluated using eight surveillance attributes: (i) data quality and completeness for key variables, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability and (viii) utility. For each attribute, specific indicators were developed and described using quantitative and qualitative methods. Scores for each indicator were as follows: < 60% weak performance; 60-79% moderate performance; ≥80% good performance. RESULTS: During 2012-2015, we enrolled and tested 4339 patients with influenza-like illness (ILI) and 2869 patients with severe acute respiratory illness (SARI) from 11 sentinel sites situated in 5 of 11 provinces. Influenza viruses were detected in 446 (10.3%) samples from patients with ILI and in 151 (5.5%) samples from patients with SARI with higher detection during December-May. Data quality and completeness was > 90% for all evaluated indicators. Other strengths of the system were timeliness, simplicity, stability and utility that scored > 70% each. Representativeness, flexibility and acceptability had moderate performance. It was reported that the ISSS contributed to: (i) a better understanding of the epidemiology, circulating patterns and proportional contribution of influenza virus among patients with ILI or SARI; (ii) acquisition of new key competences related to influenza surveillance and diagnosis; and (iii) continuous education of surveillance staff and clinicians at sentinel sites about influenza. However, due to limited resources no actions were undertaken to mitigate the impact of seasonal influenza epidemics. CONCLUSIONS: The system performed overall satisfactorily and provided reliable and timely data about influenza circulation in DRC. The simplicity of the system contributed to its stability. A better use of the available data could be made to inform and promote prevention interventions especially among the most vulnerable groups.

Sentinel surveillance for influenza-like illness, severe acute respiratory illness, and laboratory-confirmed influenza in Kinshasa, Democratic Republic of Congo, 2009-2011.

Little is known about influenza in central Africa. We conducted sentinel surveillance for influenza-like illness, severe acute respiratory illness, and laboratory-confirmed influenza at 5 sites in Kinshasa, Democratic Republic of Congo, from January 2009 through April 2011. We obtained samples from 4156 patients, of whom 605 (15%) had specimens containing laboratory-confirmed influenza virus. Apart from the period of pandemic influenza due to influenza A virus subtype H1N1, which occurred during August-December 2009, influenza activity peaked at least once each year from January through March, predominantly among children. These data can guide interventions to reduce the burden of influenza in the Democratic Republic of Congo and central Africa.

Community-based COVID-19 active case finding and rapid response in the Democratic Republic of the Congo: Improving case detection and response.

A community-based coronavirus disease (COVID-19) active case-finding strategy using an antigen-detecting rapid diagnostic test (Ag-RDT) was implemented in the Democratic Republic of Congo (DRC) to enhance COVID-19 case detection. With this pilot community-based active case finding and response program that was designed as a clinical, prospective testing performance, and implementation study, we aimed to identify insights to improve community diagnosis and rapid response to COVID-19. This pilot study was modeled on the DRC's National COVID-19 Response Plan and the COVID-19 Ag-RDT screening algorithm defined by the World Health Organization (WHO), with case findings implemented in 259 health areas, 39 health zones, and 9 provinces. In each health area, a 7-member interdisciplinary field team tested the close contacts (ring strategy) and applied preventive and control measures to each confirmed case. The COVID-19 testing capacity increased from 0.3 tests per 10,000 inhabitants per week in the first wave to 0.4, 1.6, and 2.2 in the second, third, and fourth waves, respectively. From January to November 2021, this capacity increase contributed to an average of 10.5% of COVID-19 tests in the DRC, with 7,110 positive Ag-RDT results for 40,226 suspected cases and close contacts who were tested (53.6% female, median age: 37 years [interquartile range: 26.0-50.0)]. Overall, 79.7% (n = 32,071) of the participants were symptomatic and 7.6% (n = 3,073) had comorbidities. The Ag-RDT sensitivity and specificity were 55.5% and 99.0%, respectively, based on reverse transcription polymerase chain reaction analysis, and there was substantial agreement between the tests (k = 0.63). Despite its limited sensitivity, the Ag-RDT has improved COVID-19 testing capacity, enabling earlier detection, isolation, and treatment of COVID-19 cases. Our findings support the community testing of suspected cases and asymptomatic close contacts of confirmed cases to reduce disease spread and virus transmission.

Measles virus strain diversity, Nigeria and Democratic Republic of the Congo.

We investigated the genetic diversity of measles virus (MV) in Nigeria (2004-2005) and the Democratic Republic of the Congo (DRC) (2002-2006). Genotype B3 strains circulating in Kinshasa, DRC, in 2002-2003 were fully replaced by genotype B2 in 2004 at the end of the second Congo war. In Nigeria (2004-2005), two genetic clusters of genotype B3, both of which were most closely related to 1 variant from 1998, were identified. Longitudinal analysis of MV strain diversity in Nigeria suggested that only a few of the previously described 1997-1998 variants had continued to circulate, but this finding was concomitant with a rapid restoration of genetic diversity, probably caused by low vaccination coverage and high birth rates. In contrast, the relatively low genetic diversity of MV in DRC and the genotype replacement in Kinshasa reflect a notable improvement in local measles control.

Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo.

Little is known about the clinical features and outcomes of SARS-CoV-2 infection in Africa. We conducted a retrospective cohort study of patients hospitalized for COVID-19 between March 10, 2020 and July 31, 2020 at seven hospitals in Kinshasa, Democratic Republic of the Congo (DRC). Outcomes included clinical improvement within 30 days (primary) and in-hospital mortality (secondary). Of 766 confirmed COVID-19 cases, 500 (65.6%) were male, with a median (interquartile range [IQR]) age of 46 (34-58) years. One hundred ninety-one (25%) patients had severe/critical disease requiring admission in the intensive care unit (ICU). Six hundred twenty patients (80.9%) improved and were discharged within 30 days of admission. Overall in-hospital mortality was 13.2% (95% CI: 10.9-15.8), and almost 50% among those in the ICU. Independent risk factors for death were age < 20 years (adjusted hazard ratio [aHR] = 6.62, 95% CI: 1.85-23.64), 40-59 years (aHR = 4.45, 95% CI: 1.83-10.79), and ≥ 60 years (aHR = 13.63, 95% CI: 5.70-32.60) compared with those aged 20-39 years, with obesity (aHR = 2.30, 95% CI: 1.24-4.27), and with chronic kidney disease (aHR = 5.33, 95% CI: 1.85-15.35). In marginal structural model analysis, there was no statistically significant difference in odds of clinical improvement (adjusted odds ratio [aOR] = 1.53, 95% CI: 0.88-2.67, P = 0.132) nor risk of death (aOR = 0.65, 95% CI: 0.35-1.20) when comparing the use of chloroquine/azithromycin versus other treatments. In this DRC study, the high mortality among patients aged < 20 years and with severe/critical disease is of great concern, and requires further research for confirmation and targeted interventions.

Epidemiology of circulating human influenza viruses from the Democratic Republic of Congo, 2015.

INTRODUCTION: The establishment of the influenza sentinel surveillance system in Kinshasa, Bas Congo, Maniema, Katanga, and Kasai Provinces allowed generation of important data on the molecular epidemiology of human influenza viruses circulating in the Democratic Republic of Congo (DRC). However, some challenges still exist, including the need for extending the influenza surveillance to more provinces. This study describes the pattern of influenza virus circulating in DRC during 2015. METHODOLOGY: Nasopharyngeal swabs were collected from January to December 2015 from outpatients with influenza-like illness (ILI) and in all hospitalized patients with Severe Acute Respiratory Infection (SARI). Molecular analysis was done to determine influenza type and subtype at the National Reference Laboratory (NRL) in Kinshasa using real time reverse transcription-polymerase chain reaction (rRT-PCR). Analysis of antiviral resistance by enzyme inhibition assay and nucleotide sequencing was performed by the Collaborating center in the USA (CDC, Atlanta). RESULTS: Out of 2,376 nasopharyngeal swabs collected from patients, 218 (9.1%) were positive for influenza virus. Among the positive samples, 149 were characterized as influenza virus type A (Flu A), 67 as type B (Flu B) and 2 mixed infections (Flu A and B). Flu A subtypes detected were H3N2 and H1N1. The Yamagata strain of Flu B was detected among patients in the country. Individuals aged between 5 and 14 years accounted for the largest age group affected by influenza virus. All influenza viruses detected were found to be sensitive to antiviral drugs such as oseltamivar, zanamivir, peramivir and laninamivar. CONCLUSION: The present study documented the possible involvement of both circulation of Flu A and B viruses in human respiratory infection in certain DRC provinces during 2015. This study emphasises the need to extend the influenza surveillance to other provinces for a better understanding of the epidemiology of influenza in DRC. It is envisioned that such a system would lead to improved disease control and patient management.

The national and provincial burden of medically attended influenza-associated influenza-like illness and severe acute respiratory illness in the Democratic Republic of Congo, 2013-2015.

BACKGROUND: Estimates of influenza-associated outpatient consultations and hospitalizations are severely limited in low- and middle-income countries, especially in Africa. METHODS: We conducted active prospective surveillance for influenza-like illness (ILI) and severe acute respiratory illness (SARI) at 5 healthcare facilities situated in Kinshasa Province during 2013-2015. We tested upper respiratory tract samples for influenza viruses using a reverse transcription-polymerase chain reaction assay. We estimated age-specific numbers and rates of influenza-associated ILI outpatient consultations and SARI hospitalizations for Kinshasa Province using a combination of administrative and influenza surveillance data. These estimates were extrapolated to each of the remaining 10 provinces accounting for provincial differences in prevalence of risk factors for pneumonia and healthcare-seeking behavior. Rates were reported per 100 000 population. RESULTS: During 2013-2015, the mean annual national number of influenza-associated ILI outpatient consultations was 1 003 212 (95% Confidence Incidence [CI]: 719 335-1 338 050 - Rate: 1205.3; 95% CI: 864.2-1607.5); 199 839 (95% CI: 153 563-254 759 - Rate: 1464.0; 95% CI: 1125.0-1866.3) among children aged <5 years and 803 374 (95% CI: 567 772-1 083 291 - Rate: 1154.5; 95% CI: 813.1-1556.8) among individuals aged ≥5 years. The mean annual national number of influenza-associated SARI hospitalizations was 40 361 (95% CI: 24 014-60 514 - Rate: 48.5; 95% CI: 28.9-72.7); 25 452 (95% CI: 19 146-32 944 - Rate: 186.5; 95% CI: 140.3-241.3) among children aged <5 years and 14 909 (95% CI: 4868-27 570 - Rate: 21.4; 95% CI: 28.9-72.7) among individuals aged ≥5 years. CONCLUSIONS: The burden of influenza-associated ILI outpatient consultations and SARI hospitalizations was substantial and was highest among hospitalized children aged <5 years.

Molecular Analysis of Influenza A(H3N2) and A(H1N1)pdm09 Viruses circulating in the Democratic Republic of Congo, 2014.

BACKGROUND: Very little is known about influenza viruses circulating in the Democratic Republic of Congo (DRC). We aim to characterize genetically and antigenically Influenza A(H3N2) and A(H1N1)pdm09 viruses circulating in the country. METHODS: From August to December 2014, specimens were collected from patients with influenza like-illness (ILI) or severe acute respiratory infection (SARI) in various surveillance sites. Specimens were tested using real time reverse transcription polymerase chain reaction (RT-PCR) method for the detection of influenza viruses. Positive influenza samples with a cycle threshold (Ct) <30 were genetically and antigenically characterized. RESULTS: 32 samples tested were found positive to influenza A with Ct <30. At CDC Atlanta, 28 out of 32 samples (88%) were tested positive for influenza A virus, including 26 seasonal influenza A viruses subtype H3N2 and 2 pandemic influenza A viruses subtype H1N1pdm 2009. The majority of influenza A(H3N2) viruses were antigenically related to the A/Switzerland/9715293/2013 vaccine virus, while two influenza A(H1N1)pdm09 isolates were antigenically characterized as A/California/07/2009-like. All A(H3N2) and A(H1N1)pdm09 virus isolates characterized were sensitive to oseltamivir and zanamivir. CONCLUSION: Two genetically distinct influenza subtypes were co-circulating in the DRCongo. Effective measures against influenza have been suggested.