Jazmin Duque

2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis

BACKGROUND WHO recommends routine use of rotavirus vaccines in all countries, particularly in those with high mortality attributable to diarrhoeal diseases. To establish the burden of life-threatening rotavirus disease before the introduction of a rotavirus vaccine, we aimed to update the estimated number of deaths worldwide in children younger than 5 years due to diarrhoea attributable to rotavirus infection. METHODS We used PubMed to identify studies of at least 100 children younger than 5 years who had been admitted to hospital with diarrhoea. Additionally, we required the studies to have a data collection midpoint of the year 2000 or later, to be done in full-year increments, and to assesses diarrhoea attributable to rotavirus with EIAs or polyacrylamide gel electrophoresis. We also included data from countries that participated in the WHO-coordinated Global Rotavirus Surveillance Network (consisting of participating member states during 2009) and that met study criteria. For countries that have introduced a rotavirus vaccine into their national immunisation programmes, we excluded data subsequent to the introduction. We classified studies into one of five groups on the basis of region and the level of child mortality in the country in which the study was done. For each group, to obtain estimates of rotavirus-associated mortality, we multiplied the random-effect mean rotavirus detection rate by the 2008 diarrhoea-related mortality figures for countries in that group. We derived the worldwide mortality estimate by summing our regional estimates. FINDINGS Worldwide in 2008, diarrhoea attributable to rotavirus infection resulted in 453,000 deaths (95% CI 420,000-494,000) in children younger than 5 years-37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than 5 years. Five countries accounted for more than half of all deaths attributable to rotavirus infection: Democratic Republic of the Congo, Ethiopia, India, Nigeria, and Pakistan; India alone accounted for 22% of deaths (98,621 deaths). INTERPRETATION Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced.

Influenza Surveillance in 15 Countries in Africa, 2006-2010

BACKGROUND In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

Influenza vaccines and influenza antiviral drugs in Africa: are they available and do guidelines for their use exist?

BackgroundInfluenza viruses cause significant morbidity and mortality in Africa, particularly among high-risk groups, but influenza vaccines and antiviral drugs may not be commonly available and used. The main aim of this study was to determine the availability and use of influenza vaccines and antiviral drugs as well as to describe existing related guidelines and policies in Africa.MethodsA self-administered survey was distributed among key influenza experts in 40 African countries.ResultsOf the 40 countries surveyed, 31 (78%) responded; 14/31 (45%) reported availability of seasonal influenza vaccine, and 19/31 (65%) reported availability of antiviral drugs for the treatment of influenza. Vaccine coverage data were only available for 4/14 (29%) countries that reported availability of seasonal influenza vaccine and ranged from <0.5% to 2% of the population.ConclusionsInfluenza vaccines and antiviral drugs are available in many countries in Africa but coverage estimates are low and remain largely unknown. Describing the local burden of disease and identifying funding are essential to encourage countries to use influenza vaccine more widely.

Severe Acute Respiratory Illness Deaths in Sub-Saharan Africa and the Role of Influenza: A Case Series From 8 Countries

Abstract Background. Data on causes of death due to respiratory illness in Africa are limited. Methods. From January to April 2013, 28 African countries were invited to participate in a review of severe acute respiratory illness (SARI)–associated deaths identified from influenza surveillance during 2009–2012. Results. Twenty-three countries (82%) responded, 11 (48%) collect mortality data, and 8 provided data. Data were collected from 37 714 SARI cases, and 3091 (8.2%; range by country, 5.1%–25.9%) tested positive for influenza virus. There were 1073 deaths (2.8%; range by country, 0.1%–5.3%) reported, among which influenza virus was detected in 57 (5.3%). Case-fatality proportion (CFP) was higher among countries with systematic death reporting than among those with sporadic reporting. The influenza-associated CFP was 1.8% (57 of 3091), compared with 2.9% (1016 of 34 623) for influenza virus–negative cases (P < .001). Among 834 deaths (77.7%) tested for other respiratory pathogens, rhinovirus (107 [12.8%]), adenovirus (64 [6.0%]), respiratory syncytial virus (60 [5.6%]), and Streptococcus pneumoniae (57 [5.3%]) were most commonly identified. Among 1073 deaths, 402 (37.5%) involved people aged 0–4 years, 462 (43.1%) involved people aged 5–49 years, and 209 (19.5%) involved people aged ≥50 years. Conclusions. Few African countries systematically collect data on outcomes of people hospitalized with respiratory illness. Stronger surveillance for deaths due to respiratory illness may identify risk groups for targeted vaccine use and other prevention strategies.

Effectiveness and knowledge, attitudes and practices of seasonal influenza vaccine in primary healthcare settings in South Africa, 2010–2013

Influenza vaccine effectiveness (VE) and coverage data for sub‐Saharan Africa are scarce. Using a test‐negative case–control design, we estimated influenza VE annually among individuals with influenza‐like illness presenting to an outpatient sentinel surveillance programme in South Africa from 2010 to 2013. A knowledge, attitudes and practices (KAP) influenza vaccine survey of programme clinicians was conducted in 2013.

The Unrecognized Burden of Influenza in Young Kenyan Children, 2008-2012

Influenza-associated disease burden among children in tropical sub-Saharan Africa is not well established, particularly outside of the 2009 pandemic period. We estimated the burden of influenza in children aged 0–4 years through population-based surveillance for influenza-like illness (ILI) and acute lower respiratory tract illness (ALRI). Household members meeting ILI or ALRI case definitions were referred to health facilities for evaluation and collection of nasopharyngeal and oropharyngeal swabs for influenza testing by real-time reverse transcription polymerase chain reaction. Estimates were adjusted for health-seeking behavior and those with ILI and ALRI who were not tested. During 2008–2012, there were 9,652 person-years of surveillance among children aged 0–4 years. The average adjusted rate of influenza-associated hospitalization was 4.3 (95% CI 3.0–6.0) per 1,000 person-years in children aged 0–4 years. Hospitalization rates were highest in the 0–5 month and 6–23 month age groups, at 7.6 (95% CI 3.2–18.2) and 8.4 (95% CI 5.4–13.0) per 1,000 person-years, respectively. The average adjusted rate of influenza-associated medically attended (inpatient or outpatient) ALRI in children aged 0–4 years was 17.4 (95% CI 14.2–19.7) per 1,000 person-years. Few children who had severe laboratory-confirmed influenza were clinically diagnosed with influenza by the treating clinician in the inpatient (0/33, 0%) or outpatient (1/109, 0.9%) settings. Influenza-associated hospitalization rates from 2008–2012 were 5–10 times higher than contemporaneous U.S. estimates. Many children with danger signs were not hospitalized; thus, influenza-associated severe disease rates in Kenyan children are likely higher than hospital-based estimates suggest.

Severe Influenza Is Characterized by Prolonged Immune Activation: Results From the SHIVERS Cohort Study

Background The immunologic factors underlying severe influenza are poorly understood. To address this, we compared the immune responses of influenza-confirmed hospitalized individuals with severe acute respiratory illness (SARI) to those of nonhospitalized individuals with influenza-like illness (ILI). Methods Peripheral blood lymphocytes were collected from 27 patients with ILI and 27 with SARI, at time of enrollment and then 2 weeks later. Innate and adaptive cellular immune responses were assessed by flow cytometry, and serum cytokine levels were assessed by a bead-based assay. Results During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza virus-specific CD8+ and CD4+ T cells as compared to ILI. By the convalescent phase, however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza virus-specific, CD8+ T cells as compared to ILI cases. SARI was also associated with reduced amounts of cytokines that regulate T-cell responses (ie, interleukin 4, interleukin 13, interleukin 12, interleukin 10, and tumor necrosis factor β) and hematopoiesis (interleukin 3 and granulocyte-macrophage colony-stimulating factor) but increased amounts of a proinflammatory cytokine (tumor necrosis factor α), chemotactic cytokines (MDC, MCP-1, GRO, and fractalkine), and growth-promoting cytokines (PDGFBB/AA, VEGF, and EGF) as compared to ILI. Conclusions Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation, compared with mild influenza cases.

Knowledge attitudes and practices of South African healthcare workers regarding the prevention and treatment of influenza among HIV-infected individuals.

Background The South African Department of Health (DOH) publishes annual guidelines identifying priority groups, including immunosuppressed individuals and healthcare workers (HCW), for influenza vaccination and treatment. How these guidelines have impacted HCW and their patients, particularly those infected with HIV, remains unknown. Methods We aimed to describe the knowledge, attitudes and practices regarding influenza and the vaccine among South African HCW. Surveys were distributed by two local non-governmental organizations in public health clinics and hospitals in 21 districts/municipalities (5 of 9 provinces). Results There were 1164 respondents; median age 41 years; 978/1126 (87%) female; 801/1122 (71%) nurses. One-third (34%) of HCW reported getting influenza vaccine 2013/2014 and most (94%) recommended influenza vaccine to patients infected with HIV. Ability to get vaccine free of charge (aOR 1.69; 95% CI 1.21–2.37) and having received influenza government training (aOR 1.50; 95% CI 1.04–2.15) were significantly associated with self-reported vaccination in 2013/2014. Self-reported 2013/2014 vaccination (aOR 3.76; 95% CI 1.28–11.03) and availability of influenza vaccine during the healthcare visit (aOR 2.56; 95% CI 1.18–5.57) were significantly associated with recommending influenza vaccine to patients infected with HIV/AIDS. Conclusion Only one-third of participants were vaccinated in 2013–2014 but those who were vaccinated were more likely to recommend vaccination to their patients. Free and close access to influenza vaccine were associated with a higher likelihood of getting vaccinated in 2013/2014. HCW who reported getting the influenza vaccine themselves, had vaccine to offer during the patient consult and were familiar with DOH guidelines/trainings were more likely to recommend vaccine to HIV-infected patients.

Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012–2015

BACKGROUND Little is known about inactivated influenza vaccine effectiveness (IVE) in preventing very severe disease, including influenza-associated intensive care unit (ICU) admissions. METHODS The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project enrolled adults (aged ≥ 18 years) with acute respiratory illness (ARI) in general ward (GW) hospital settings (n = 3034) and ICUs (n = 101) during 2012-2015. IVE was assessed using a test-negative design comparing the odds of influenza vaccination among influenza positives vs. negatives (confirmed by real-time reverse transcription polymerase chain reaction). All models were adjusted for season, weeks from season peak, and a vaccination propensity score. RESULTS Influenza virus infection was confirmed in 28% of GW hospital and 41% of ICU patients; influenza vaccination was documented for 56% and 41%, respectively. Across seasons, IVE was 37% (95% confidence intervals [CI] = 23-48%) among GW patients and 82% (95% CI = 45-94%) among ICU patients. IVE point estimates were > 70% against ICU influenza and consistently higher than IVE against GW influenza when stratified by season, by virus (sub)types, and for adults with or without chronic medical conditions and for both adults aged <65 and ≥65 years old. Among hospitalized influenza positives, influenza vaccination was associated with a 59% reduction in the odds of ICU admission (aOR = 0.41, 95% CI = 0.18-0.96) and with shorter ICU lengths of stay (LOS), but not with radiograph-confirmed pneumonia or GW hospital LOS. CONCLUSION Inactivated influenza vaccines prevented influenza-associated ICU admissions, may have higher effectiveness in ICU than GW hospital settings, and appeared to reduce the risk of severe disease among those who are infected despite vaccination.

Risk Factors and Attack Rates of Seasonal Influenza Infection: Results of the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) Seroepidemiologic Cohort Study

Background Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking. Methods In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI). Results Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%-38%]) of 911 unvaccinated participants, of whom 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza PCR-confirmed ILI, and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged <5 years vs those aged ≥5 years (14% vs 4%; P < .001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; P < .001). Conclusions Measurement of antineuraminidase antibodies in addition to antihemagglutinin antibodies may be important in capturing the true influenza infection rates.