Estimates of Inactivated Influenza Vaccine Effectiveness Among Children in Senegal: Results From 2 Consecutive Cluster-Randomized Controlled Trials in 2010 and 2011.

BACKGROUND: We report results of years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal. METHODS: We cluster-randomized (1:1) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months-10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness. RESULTS: We vaccinated 74% of 12 408 age-eligible children in year 2 (June 2010-April 11) and 74% of 11 988 age-eligible children in year 3 (April 2011-December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (year 2) and 4.2 (year 3) per 100 mITT child vaccinees of IPV villages. In year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% confidence interval [CI], 32.3-67.0), and the population effectiveness was 36.0% (95% CI, 10.2-54.4) against LCI caused by any influenza strain. The indirect effectiveness against LCI by A/H3N2 was 56.4% (95% CI, 39.0-68.9). In year 3, 74% of influenza detections were vaccine-mismatched to circulating B/Yamagata and 24% were vaccine-matched to circulating A/H3N2. The year 3 total effectiveness against LCI was -14.5% (95% CI, -81.2-27.6). Vaccine effectiveness varied by type/subtype of influenza in both years. CONCLUSIONS: IIV3 was variably effective against influenza illness in Senegalese children, with total and indirect vaccine effectiveness present during the year when all circulating strains matched the IIV3 formulation. CLINICAL TRIALS REGISTRATION: NCT00893906.

Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.

BACKGROUND: There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya. METHODS: We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872). RESULTS: The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit. CONCLUSION: Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.

Building laboratory capacity to detect and characterize pathogens of public and global health security concern in Kenya.

Since 1979, multiple CDC Kenya programs have supported the development of diagnostic expertise and laboratory capacity in Kenya. In 2004, CDC's Global Disease Detection (GDD) program within the Division of Global Health Protection in Kenya (DGHP-Kenya) initiated close collaboration with Kenya Medical Research Institute (KEMRI) and developed a laboratory partnership called the Diagnostic and Laboratory Systems Program (DLSP). DLSP built onto previous efforts by malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) programs and supported the expansion of the diagnostic expertise and capacity in KEMRI and the Ministry of Health. First, DLSP developed laboratory capacity for surveillance of diarrheal, respiratory, zoonotic and febrile illnesses to understand the etiology burden of these common illnesses and support evidenced-based decisions on vaccine introductions and recommendations in Kenya. Second, we have evaluated and implemented new diagnostic technologies such as TaqMan Array Cards (TAC) to detect emerging or reemerging pathogens and have recently added a next generation sequencer (NGS). Third, DLSP provided rapid laboratory diagnostic support for outbreak investigation to Kenya and regional countries. Fourth, DLSP has been assisting the Kenya National Public Health laboratory-National Influenza Center and microbiology reference laboratory to obtain World Health Organization (WHO) certification and ISO15189 accreditation respectively. Fifth, we have supported biosafety and biosecurity curriculum development to help Kenyan laboratories safely and appropriately manage infectious pathogens. These achievements, highlight how in collaboration with existing CDC programs working on HIV, tuberculosis and malaria, the Global Health Security Agenda can have significantly improve public health in Kenya and the region. Moreover, Kenya provides an example as to how laboratory science can help countries detect and control of infectious disease outbreaks and other public health threats more rapidly, thus enhancing global health security.

Respiratory viruses in returning Hajj & Umrah pilgrims with acute respiratory illness in 2014-2015.

BACKGROUND & OBJECTIVES: Respiratory tract infections are common among Hajj and Umrah pilgrims which pose a public health risk of spread of respiratory infections. Influenza has been reported from Indian Hajj and Umrah returning pilgrims, but data on other respiratory pathogens are sparse in India. Here we report the presence of common respiratory viral pathogens in returning Hajj and Umrah pilgrims suffering from acute respiratory illness (ARI) in 2014-2015. METHODS: Respiratory specimens (nasopharyngeal and throat swabs) were collected from 300 consenting pilgrims with ARI in the past one week and tested for influenza and Middle East Respiratory Syndrome coronavirus (MERS-CoV) and other respiratory viruses using in-house standardized quantitative real-time reverse-transcription polymerase chain reaction. Clinical features among the pathogen positive and negative patients were compared. The patients received symptomatic treatment and antivirals where appropriate and were followed telephonically to collect data on illness outcome. RESULTS: Ninety seven (32.3%) of the 300 participants were tested positive for any virus, most common being influenza viruses (n=33, 11%). Other respiratory viruses that were detected included human coronaviruses [n=26, 8.7%; OC43 (n=19, 6.3%) and C229E (n=7, 2.3%)], rhinovirus (n=20, 6%), adenoviruses (n=8, 2.6%), parainfluenza viruses (n=7, 2.3%), respiratory syncytial virus (n=3, 1%) and bocaviruses (n=2, 0.6%). Clinical features observed in pathogen positive and pathogen negative patients did not differ significantly. Eighteen influenza positive patients were treated with oseltamivir. INTERPRETATION & CONCLUSIONS: Pilgrims returning from mass gatherings are often afflicted with respiratory pathogens with a potential to facilitate transmission of respiratory pathogens across international borders. The study reinforces the need for better infection prevention and control measures such as vaccination, health education on cough etiquette and hand hygiene.

Impact of Prompt Influenza Antiviral Treatment on Extended Care Needs After Influenza Hospitalization Among Community-Dwelling Older Adults.

BACKGROUND: Patients hospitalized with influenza may require extended care on discharge. We aimed to explore predictors for extended care needs and the potential mitigating effect of antiviral treatment among community-dwelling adults aged ≥ 65 years hospitalized with influenza. METHODS: We used laboratory-confirmed influenza hospitalizations from 3 influenza seasons. Extended care was defined as new placement in a skilled nursing home/long-term/rehabilitation facility on hospital discharge. We focused on those treated with antiviral agents to explore the effect of early treatment on extended care and hospital length of stay using logistic regression and competing risk survival analysis, accounting for time from illness onset to hospitalization. Treatment was categorized as early (≤ 4 days) or late (>4 days) in reference to date of illness onset. RESULTS: Among 6593 community-dwelling adults aged ≥ 65 years hospitalized for influenza, 18% required extended care at discharge. The need for care increased with age and neurologic disorders, intensive care unit admission, and pneumonia were predictors of care needs. Early treatment reduced the odds of extended care after hospital discharge for those hospitalized ≤ 2 or >2 days from illness onset (adjusted odds ratio, 0.38 [95% confidence interval {CI}, .17-.85] and 0.75 [.56-.97], respectively). Early treatment was also independently associated with reduction in length of stay for those hospitalized ≤ 2 days from illness onset (adjusted hazard ratio, 1.81; 95% CI, 1.43-2.30) or >2 days (1.30; 1.20-1.40). CONCLUSIONS: Prompt antiviral treatment decreases the impact of influenza on older adults through shorten hospitalization and reduced extended care needs.

Influenza seasonality and vaccination timing in tropical and subtropical areas of southern and south-eastern Asia.

OBJECTIVE: To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator. METHODS: Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries. FINDINGS: Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator. CONCLUSION: Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.

Improvements in pandemic preparedness in 8 Central American countries, 2008-2012.

BACKGROUND: In view of ongoing pandemic threats such as the recent human cases of novel avian influenza A(H7N9) in China, it is important that all countries continue their preparedness efforts. Since 2006, Central American countries have received donor funding and technical assistance from the U.S. Centers for Disease Control and Prevention (CDC) to build and improve their capacity for influenza surveillance and pandemic preparedness. Our objective was to measure changes in pandemic preparedness in this region, and explore factors associated with these changes, using evaluations conducted between 2008 and 2012. METHODS: Eight Central American countries scored their pandemic preparedness across 12 capabilities in 2008, 2010 and 2012, using a standardized tool developed by CDC. Scores were calculated by country and capability and compared between evaluation years using the Student's t-test and Wilcoxon Rank Sum test, respectively. Virological data reported to WHO were used to assess changes in testing capacity between evaluation years. Linear regression was used to examine associations between scores, donor funding, technical assistance and WHO reporting. RESULTS: All countries improved their pandemic preparedness between 2008 and 2012 and seven made statistically significant gains (p < 0.05). Increases in median scores were observed for all 12 capabilities over the same period and were statistically significant for eight of these (p < 0.05): country planning, communications, routine influenza surveillance, national respiratory disease surveillance, outbreak response, resources for containment, community interventions and health sector response. We found a positive association between preparedness scores and cumulative funding between 2006 and 2011 (R2 = 0.5, p < 0.01). The number of specimens reported to WHO from participating countries increased significantly from 5,551 (2008) to 18,172 (2012) (p < 0.01). CONCLUSIONS: Central America has made significant improvements in influenza pandemic preparedness between 2008 and 2012. U.S. donor funding and technical assistance provided to the region is likely to have contributed to the improvements we observed, although information on other sources of funding and support was unavailable to study. Gains are also likely the result of countries' response to the 2009 influenza pandemic. Further research is required to determine the degree to which pandemic improvements are sustainable.

COVID-19 vaccine equity: a health systems and policy perspective.

INTRODUCTION: The global COVID-19 vaccine rollout has highlighted inequities in the accessibility of countries to COVID-19 vaccines. Populations in low- and middle-income countries have found it difficult to have access to COVID-19 vaccines. AREAS COVERED: This perspective provides analyses on historical and contemporary policy trends of vaccine development and immunization programs, including the current COVID-19 vaccination drive, and governance challenges. Moreover, we also provide a comparative health system analysis of the COVID-19 vaccine deployment in some countries from different continents. It recommends that the international Access to COVID-19 Tools Accelerator (ACT-A) partnership requires a strong governance mechanism and urgent financial investment. EXPERT OPINION: All WHO member states should agree on technology transfer and voluntary license-sharing via a commonly governed technology access pool and supported by a just Intellectual Property regime. Contextualized, dynamic understandings and country-specific versions of health systems strengthening are needed to improve vaccine equity in a sustainable matter.

Provider perspectives on demand creation for maternal vaccines in Kenya.

Background . Expansion of maternal immunization, which offers some of the most effective protection against morbidity and mortality in pregnant women and neonates, requires broad acceptance by healthcare providers and their patients. We aimed to describe issues surrounding acceptance and demand creation for maternal vaccines in Kenya from a provider perspective. Methods . Nurses and clinical officers were recruited for semi-structured interviews covering resources for vaccine delivery, patient education, knowledge and attitudes surrounding maternal vaccines, and opportunities for demand creation for new vaccines. Interviews were conducted in English and Swahili, transcribed verbatim from audio recordings, and analyzed using codes developed from interview guide questions and emergent themes. Results . Providers expressed favorable attitudes about currently available maternal immunizations and introduction of additional vaccines, viewing themselves as primarily responsible for vaccine promotion and patient education.  The importance of educational resources for both patients and providers to maintain high levels of maternal immunization coverage was a common theme. Most identified barriers to vaccine acceptance and delivery were cultural and systematic in nature. Suggestions for improvement included improved patient and provider education, including material resources, and community engagement through religious and cultural leaders. Conclusions . The distribution of standardized, evidence-based print materials for patient education may reduce provider overwork and facilitate in-clinic efforts to inform women about maternal vaccines. Continuing education for providers should address communication surrounding current vaccines and those under consideration for introduction into routine schedules. Engagement of religious and community leaders, as well as male decision-makers in the household, will enhance future acceptance of maternal vaccines.

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.

Update on rotavirus vaccines.

Rotavirus was discovered in 1973, and 10 years later the first report of a rotavirus vaccine clinical trial appeared. This update reviews the epidemiology of rotavirus infections, assesses past and current vaccines and presents ideas for implementation of vaccination programs in developed and developing countries.

Norovirus and child care: challenges in outbreak control.

An infant with diarrhea attended a community playgroup. In the subsequent 48 hours, 6 of the 7 mothers and children reported gastroenteritis; fecal specimens from 5 persons tested positive for norovirus, with identical sequences. No breach of hygiene or contact with fecal matter was identified. Excluding the child with gastroenteritis from the playgroup could have prevented this outbreak.

Rotavirus disease and its prevention.

PURPOSE OF REVIEW: Rotavirus infection is the foremost cause of severe gastroenteritis of young children worldwide. Efforts to develop safe and effective vaccines resulted in licensure of the first live oral vaccine, tetravalent, rhesus-based rotavirus vaccine (RRV-TV), which was incorporated into the US immunization schedule in 1998. Less than 1 year later, however, the vaccine was withdrawn when reports of cases of intussusception were linked to recent vaccination. This setback created significant hurdles as well as new opportunities for the development of the next generation of rotavirus vaccines. This review focuses on new information related to the clinical presentation and pathogenesis of rotavirus infection, the associated global disease burden, and the ongoing efforts to develop and introduce the next generation of rotavirus vaccines for widespread use. RECENT FINDINGS: Recent studies have confirmed that rotavirus infection is not confined only to the gut but can have extraintestinal manifestations, including viremia. Estimates of the global disease burden of rotavirus diarrhea have been refined and suggest that mortality has not declined, and that among hospitalized cases of diarrhea, the fraction associated with rotavirus has increased in many countries. In the United States, the estimated number of hospitalizations attributed to rotavirus has increased. Debate continues about the magnitude of the attributable risk of the association between RRV-TV and intussusception. Several new rotavirus vaccines are in late stages of development. One vaccine was licensed in Mexico in 2004 and a second has completed clinical trials in the United States and Europe and may be licensed within 2 to 3 years. SUMMARY: The tremendous burden of rotavirus diarrhea among children all over the world continues to drive the remarkable pace of vaccine development and the variety of approaches to creating rotavirus vaccines.