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2.
Arch Public Health ; 81(1): 72, 2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37106423

ABSTRACT

BACKGROUND: Melghat in India is a hilly, forested, difficult to access, impoverished rural area in northeast part of Maharashtra (Central India) with difficult healthcare access. Melghat has very high Mortality rates, because of grossly inadequate medical facilities. (1) Home deaths contribute to 67% of deaths,(2) which are difficult to track and where cause of death is mostly unknown. METHODS: A feasibility study was carried out in 93 rural villages and 5 hospitals to assess feasibility of tracking real-time community mortality and to ascertain cause of death in 0-60 months and 16-60 years age group using Minimal Invasive Tissue Sampling (MITS) in purpose-modified ambulance. We used the network of village health workers (VHW)s, to establish real-time community mortality tracking. Upon receipt of reports of home death, we performed MITS within 4 h of death in the vicinity of the village. RESULTS: We conducted 16 MITS. Nine, in MITS ambulance in community and seven at MAHAN hospital. The acceptance rate of MITS was 59.26%. Standard operating procedure (SOP) of conducting community MITS in an ambulance, is established. Major challenges were, Covid19 lockdown, reluctance of tribal parents for consent for MITS due to illiteracy, superstitions and fear of organ removal. Ambulance was an easy to reach transport means in remote area, provided a well-designed and discrete facility to perform MITS in community, winning the confidence of bereaved family. This has reduced time interval between time of death and performing MITS. CONCLUSIONS: MITS in purpose-modified Ambulance can be used worldwide for community MITS especially in areas which are remote and lack healthcare access. This solution needs to be assessed in different cultural settings to document culture specific issues.

3.
Vaccine ; 38(41): 6478-6483, 2020 09 22.
Article in English | MEDLINE | ID: mdl-32868130

ABSTRACT

BACKGROUND: A key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination. METHODS: We pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests. We used marginal linear models and generalized estimating equations to examine the impact of time between maternal vaccination and delivery on transplacental antibody transfer, infant titers, and infant seroprotection. RESULTS: For all vaccine components (A/H1N1, A/H3N2, and Type B), >80% of vaccinated women had seroprotective titers, >60% of them seroconverted, and >50% of their infants were born with seroprotective titers. These immunogenicity outcomes occurred more often in vaccine recipients and their infants than in controls. No difference in efficiency of transplacental antibody transfer was observed between vaccine recipients and controls. CONCLUSIONS: Our results provide robust support for further expansion of maternal influenza vaccination recommendations. CLINICAL TRIALS REGISTRATION: NCT01430689 and NCT01306669.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Antibodies, Viral , Female , Hemagglutination Inhibition Tests , Humans , Infant , Influenza A Virus, H3N2 Subtype , Influenza, Human/prevention & control , Mali , Pregnancy , Pregnant Women , Randomized Controlled Trials as Topic , South Africa
4.
Influenza Other Respir Viruses ; 14(6): 671-677, 2020 11.
Article in English | MEDLINE | ID: mdl-32730685

ABSTRACT

BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.


Subject(s)
Quality Assurance, Health Care/statistics & numerical data , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus, Human/isolation & purification , Humans , Laboratories/standards , Molecular Diagnostic Techniques/standards , Pilot Projects , RNA, Viral/genetics , Respiratory Syncytial Virus, Human/genetics , World Health Organization
5.
Lancet Respir Med ; 8(6): 597-608, 2020 06.
Article in English | MEDLINE | ID: mdl-32526188

ABSTRACT

BACKGROUND: Maternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age. METHODS: We did a pooled analysis of three randomised controlled trials done in Nepal (2011-2014), Mali (2011-2014), and South Africa (2011-2013). Pregnant women, gestational age 17-34 weeks in Nepal, 28 weeks or more in Mali, and 20-36 weeks in South Africa, were enrolled. Women were randomly assigned 1:1 to a study group, in which they received trivalent inactivated influenza vaccine (IIV) in all three trials, or a control group, in which they received saline placebo in Nepal and South Africa or quadrivalent meningococcal conjugate vaccine in Mali. Enrolment at all sites was complete by April 24, 2013. Infants and women were assessed for respiratory illness, and samples from those that met the case definition were tested for influenza by PCR testing. Growth measurements, including length and weight, were obtained at birth at all sites, at 24 weeks in South Africa, and at 6 months in Nepal and Mali. The three trials are registered with ClinicalTrials.gov, numbers NCT01430689, NCT01034254, and NCT02465190. FINDINGS: 10 002 women and 9800 liveborn infants were included. Pooled efficacy of maternal vaccination to prevent infant PCR-confirmed influenza up to 6 months of age was 35% (95% CI 19 to 47). The pooled estimate was 56% (28 to 73) within the first 2 months of life, 39% (11 to 58) between 2 and 4 months, and 19% (-9 to 40) between 4 and 6 months. In women, from enrolment during pregnancy to the end of follow-up at 6 months postpartum, the vaccine was 50% (95% CI 32-63) efficacious against PCR-confirmed influenza. Efficacy was 42% (12 to 61) during pregnancy and 60% (36 to 75) postpartum. In women vaccinated before 29 weeks gestational age, the estimated efficacy was 30% (-2 to 52), and in women vaccinated at or after 29 weeks, efficacy was 71% (50 to 83). Efficacy was similar in infants born to mothers vaccinated before or after 29 weeks gestation (34% [95% CI 12 to 51] vs 35% [11 to 52]). There was no overall association between maternal vaccination and low birthweight, stillbirth, preterm birth, and small for gestational age. At 6 months of age, the intervention and control groups were similar in terms of underweight (weight-for-age), stunted (length-for-age), and wasted (weight-for-length). Median centile change from birth to 6 months of age was similar between the intervention and the control groups for both weight and length. INTERPRETATION: The assessment of efficacy for women vaccinated before 29 weeks gestational age might have been underpowered, because the point estimate suggests that there might be efficacy despite wide CIs. Estimates of efficacy against PCR-confirmed influenza and safety in terms of adverse birth outcomes should be incorporated into any further consideration of maternal influenza immunisation recommendations. FUNDING: Bill & Melinda Gates Foundation.


Subject(s)
Child Development/drug effects , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Pregnancy Complications, Infectious/prevention & control , Pregnancy Outcome , Female , Gestational Age , Humans , Infant , Influenza, Human/epidemiology , Mali/epidemiology , Nepal/epidemiology , Pregnancy , South Africa/epidemiology , Time Factors , Treatment Outcome
6.
Pediatr Infect Dis J ; 39(7): 641-644, 2020 07.
Article in English | MEDLINE | ID: mdl-32379201

ABSTRACT

This analysis includes pooled data from 2 placebo-controlled maternal influenza immunization trials, with a separate analysis on a meningococcal conjugate vaccine-controlled maternal influenza immunization trial. Maternal influenza immunization was not associated with infant or maternal all-cause mortality in placebo-controlled trials. In the meningococcal conjugate vaccine-controlled trial, there were fewer deaths during low or any influenza circulation weeks among infants whose mothers received meningococcal conjugate vaccine. ClinicalTrials.gov identifiers: NCT01430689, NCT01034254 and NCT02465190.


Subject(s)
Infant Mortality , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Maternal Mortality , Meningococcal Infections/prevention & control , Meningococcal Vaccines/administration & dosage , Adolescent , Adult , Female , Humans , Incidence , Infant , Meta-Analysis as Topic , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Prospective Studies , Stillbirth , Young Adult
7.
Influenza Other Respir Viruses ; 14(6): 622-629, 2020 11.
Article in English | MEDLINE | ID: mdl-31444997

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV)-associated acute lower respiratory infection is a common cause for hospitalization and hospital deaths in young children globally. There is urgent need to generate evidence to inform immunization policies when RSV vaccines become available. The WHO piloted a RSV surveillance strategy that leverages the existing capacities of the Global Influenza Surveillance and Response System (GISRS) to better understand RSV seasonality, high-risk groups, validate case definitions, and develop laboratory and surveillance standards for RSV. METHODS: The RSV sentinel surveillance strategy was piloted in 14 countries. Patients across all age groups presenting to sentinel hospitals and clinics were screened all year-round using extended severe acute respiratory infection (SARI) and acute respiratory infection (ARI) case definitions for hospital and primary care settings, respectively. Respiratory specimens were tested for RSV at the National Influenza Centre (NIC) using standardized molecular diagnostics that had been validated by an External Quality Assurance program. The WHO FluMart data platform was adapted to receive case-based RSV data and visualize interactive visualization outputs. RESULTS: Laboratory standards for detecting RSV by RT-PCR were developed. A review assessed the feasibility and the low incremental costs for RSV surveillance. Several challenges were addressed related to case definitions, sampling strategies, the need to focus surveillance on young children, and the data required for burden estimation. CONCLUSIONS: There was no evidence of any significant adverse impact on the functioning of GISRS which is primarily intended for virologic and epidemiological surveillance of influenza.


Subject(s)
Influenza, Human/epidemiology , Respiratory Syncytial Virus Infections/epidemiology , Sentinel Surveillance , Algorithms , Global Health , Hospitals , Humans , Influenza, Human/diagnosis , Laboratories , Orthomyxoviridae/genetics , Orthomyxoviridae/isolation & purification , Pilot Projects , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/isolation & purification , World Health Organization
8.
Influenza Other Respir Viruses ; 14(6): 615-621, 2020 11.
Article in English | MEDLINE | ID: mdl-31595655

ABSTRACT

The World Health Organization (WHO) recently completed the first phase of a RSV surveillance pilot study in fourteen countries (two to three in each WHO region) building on the Global Influenza Surveillance and Response System (GISRS). This active surveillance strategy had several objectives including understanding RSV-related health burden in a variety of settings. A range of approaches can be used to estimate disease burden; most approaches could not be applied by participating countries in the WHO surveillance pilot. This article provides the recommendations made by WHO for strengthening and expanding the scope of the RSV surveillance in the next phase to enable burden estimation.


Subject(s)
Cost of Illness , Population Surveillance , Respiratory Syncytial Virus Infections/economics , Data Collection , Humans , Pilot Projects , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus, Human , World Health Organization
9.
Vaccine ; 37(35): 4823-4829, 2019 08 14.
Article in English | MEDLINE | ID: mdl-31362819

ABSTRACT

In response to global interest in the development of a universal influenza vaccine, the Bill & Melinda Gates Foundation, PATH, and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of experts (London, UK, May 2018) to assess the role of a standardized controlled human influenza virus infection model (CHIVIM) towards the development of novel influenza vaccine candidates. This report (in two parts) summarizes those discussions and offers consensus recommendations. This article (Part 1) covers challenge virus selection, regulatory and ethical considerations, and issues concerning standardization, access, and capacity. Part 2 covers specific methodologic considerations. Current methods for influenza vaccine development and licensure require large costly field trials. The CHIVIM requires fewer subjects and the controlled setting allows for better understanding of influenza transmission and host immunogenicity. The CHIVIM can be used to identify immune predictors of disease for at-risk populations and to measure efficacy of potential vaccines for further development. Limitations to the CHIVIM include lack of standardization, limited access to challenge viruses and assays, lack of consensus regarding role of the CHIVIM in vaccine development pathway, and concerns regarding risk to study participants and community. To address these issues, the panel of experts recommended that WHO and other key stakeholders provide guidance on standardization, challenge virus selection, and risk management. A common repository of well-characterized challenge viruses, harmonized protocols, and standardized assays should be made available to researchers. A network of research institutions performing CHIVIM trials should be created, and more study sites are needed to increase capacity. Experts agreed that a research network of institutions working with a standardized CHIVIM could contribute important data to support more rapid development and licensure of novel vaccines capable of providing long-lasting protection against seasonal and pandemic influenza strains.


Subject(s)
Congresses as Topic , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Vaccination/ethics , Vaccination/legislation & jurisprudence , Antibodies, Viral/blood , Clinical Trials as Topic , Human Experimentation/ethics , Humans , Influenza A Virus, H1N1 Subtype , Influenza Vaccines/adverse effects , Licensure , London , Pandemics/prevention & control , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , World Health Organization
10.
Vaccine ; 37(35): 4830-4834, 2019 08 14.
Article in English | MEDLINE | ID: mdl-31362820

ABSTRACT

In response to global interest in the development of a universal influenza vaccine, the Bill & Melinda Gates Foundation, PATH, and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of experts (London, UK, May 2018) to assess the role of a standardized controlled human influenza virus infection model (CHIVIM) towards the development of novel influenza vaccine candidates. This report (in two parts) summarizes those discussions and offers consensus recommendations. Part 1 covers challenge virus selection, regulatory and ethical considerations, and issues concerning standardization, access, and capacity. This article (Part 2) summarizes the discussion and recommendations concerning CHIVIM methods. The panelists identified an overall need for increased standardization of CHIVIM trials, in order to produce comparable results that can support universal vaccine licensure. Areas of discussion included study participant selection and screening, route of exposure and dose, devices for administering challenge, rescue therapy, protection of participants and institutions, clinical outcome measures, and other considerations. The panelists agreed upon specific recommendations to improve the standardization and usefulness of the model for vaccine development. Experts agreed that a research network of institutions working with a standardized CHIVIM could contribute important data to support more rapid development and licensure of novel vaccines capable of providing long-lasting protection against seasonal and pandemic influenza strains.


Subject(s)
Congresses as Topic , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Vaccination/methods , Antibodies, Viral/blood , Cross Protection , Human Experimentation , Humans , Influenza Vaccines/adverse effects , Licensure , London , Pandemics/prevention & control , Research Design , Vaccination/adverse effects , World Health Organization
12.
Pediatr Infect Dis J ; 37(5): 436-440, 2018 05.
Article in English | MEDLINE | ID: mdl-29443825

ABSTRACT

BACKGROUND: To evaluate the effect of antenatal influenza vaccination on all-cause severe infant pneumonia, we performed pooled analysis of 3 randomized controlled trials conducted in Nepal, Mali and South Africa. METHODS: The trials were coordinated from the planning phase. The follow-up period was 0-6 months postpartum in Nepal and Mali and 0-24 weeks in South Africa. Pregnant women with gestational age 17-34 weeks in Nepal, ≥28 weeks in Mali and 20-36 weeks in South Africa were enrolled. Trivalent inactivated influenza vaccine (IIV) was compared with either saline placebo (Nepal and South Africa) or quadrivalent meningococcal conjugate vaccine (Mali). In South Africa, cases were hospitalized and were therefore considered to have severe pneumonia. In Nepal and Mali, severe infant pneumonia diagnosis was based on the WHO Integrated Management of Childhood Illness definition. RESULTS: A total of 10,002 mothers and 9801 live-born eligible infants were included in the present analysis. There was a 31% lower incidence rate of severe pneumonia in the IIV group compared with the control group in Nepal [incidence rate ratio (IRR): 0.69; 95% CI: 0.50-0.94; ]. In South Africa, there was a 43% lower incidence rate of severe pneumonia in the IIV group versus the control group (IRR: 0.57; 95% CI: 0.33-1.0). There was no difference in incidence rates between the IIV group and the control group in Mali. Overall, incidence rate of severe pneumonia was 20% lower in the IIV group compared with the control group (IRR: 0.80; 95% CI: 0.66-0.99; P = 0.04). Protection was highest in the high influenza circulation period (IRR: 0.44; 95% CI: 0.23-0.84). CONCLUSIONS: Maternal influenza immunization may reduce severe pneumonia episodes among infants-particularly those too young to be completely vaccinated against Streptococcus pneumoniae and influenza.


Subject(s)
Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Meningococcal Vaccines/therapeutic use , Pneumonia, Bacterial/prevention & control , Pneumonia, Viral/prevention & control , Data Analysis , Female , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Influenza, Human/epidemiology , Mali/epidemiology , Mothers , Nepal/epidemiology , Pneumonia, Bacterial/epidemiology , Pneumonia, Viral/epidemiology , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/virology , Randomized Controlled Trials as Topic , South Africa/epidemiology , Vaccination , Vaccines, Conjugate/therapeutic use
13.
PLoS One ; 13(12): e0210124, 2018.
Article in English | MEDLINE | ID: mdl-30596775

ABSTRACT

BACKGROUND: We previously reported that despite HIV-infected pregnant women had modest humoral immune responses to inactivated influenza vaccine (IIV) measured by hemagglutination-inhibition (HAI) assay, the observed vaccine efficacy against influenza disease was higher than predicted by HAI; suggesting that IIV may confer protection to HIV-infected individuals by additional mechanisms. We evaluated the response to IIV by microneutralization (MN) and HAI assays and correlated both methods in HIV-infected and HIV-uninfected pregnant women. METHODS: MN and HAI antibodies were measured pre-vaccination and approximately one-month post-vaccination in 80 HIV-infected and 75 HIV-uninfected women who received IIV. Geometric mean titers (GMTs), fold-change in titers and seroconversion rates were determined for the three influenza stains in the vaccine. RESULTS: After vaccination there were significant increases in MN and HAI GMTs for the three vaccine strains in both HIV-infected and HIV-uninfected women. HIV-infected women had, however, a lower immune response compared to HIV-uninfected. Fold-increases were 2 to 3-times higher for MN assay compared to HAI assay for the influenza-A strains. Also a higher percentage of women seroconverted by MN than by HAI assay for the influenza-A strains. There was high positive correlation between MN and HAI assays, except for the B/Victoria strain at pre-vaccination. CONCLUSIONS: In general, the MN assay was more sensitive than the HAI assay. Microneutralization antibodies might correlate better with protection against influenza infection.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , HIV Infections/blood , HIV-1 , Influenza Vaccines/administration & dosage , Pregnancy Complications, Infectious/blood , Vaccination , Adult , Female , Hemagglutination/drug effects , Humans , Pregnancy
16.
Vaccine ; 33(32): 3801-12, 2015 Jul 31.
Article in English | MEDLINE | ID: mdl-26095508

ABSTRACT

Influenza infection in pregnancy can have adverse impacts on maternal, fetal, and infant outcomes. Influenza vaccination in pregnancy is an appealing strategy to protect pregnant women and their infants. The Bill & Melinda Gates Foundation is supporting three large, randomized trials in Nepal, Mali, and South Africa evaluating the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants <6 months of age. Results from these individual studies are expected in 2014 and 2015. While the results from the three maternal immunization trials are likely to strengthen the evidence base regarding the impact of influenza immunization in pregnancy, expectations for these results should be realistic. For example, evidence from previous influenza vaccine studies - conducted in general, non-pregnant populations - suggests substantial geographic and year-to-year variability in influenza incidence and vaccine efficacy/effectiveness. Since the evidence generated from the three maternal influenza immunization trials will be complementary, in this paper we present a side-by-side description of the three studies as well as the similarities and differences between these trials in terms of study location, design, outcome evaluation, and laboratory and epidemiological methods. We also describe the likely remaining knowledge gap after the results from these trials become available along with a description of the analyses that will be conducted when the results from these individual data are pooled. Moreover, we highlight that additional research on logistics of seasonal influenza vaccine supply, surveillance and strain matching, and optimal delivery strategies for pregnant women will be important for informing global policy related to maternal influenza immunization.


Subject(s)
Immunization/methods , Influenza Vaccines/administration & dosage , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Pregnancy Complications, Infectious/prevention & control , Female , Humans , Mali , Nepal , Pregnancy , Randomized Controlled Trials as Topic , South Africa
18.
Am J Obstet Gynecol ; 207(3 Suppl): S28-32, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22920055

ABSTRACT

Pregnant women and young infants are at increased risk from influenza. The World Health Organization and public health guidelines from Australia, Canada, and the United States recommend immunizing pregnant women with trivalent inactivated influenza vaccine. However, there are multiple barriers to the uptake of this recommendation. Additionally, current vaccines are not licensed for infants <6 months of age. Immunizing pregnant women would provide protection to both mothers and infants. The Bill & Melinda Gates Foundation (BMGF) and the National Institute of Allergy and Infectious Diseases (NIAID) are trying to address some of the issues associated with maternal immunization, which could be an effective intervention in both high- and low-resource settings to combat the significant maternal and infant morbidity and mortality due to influenza. BMGF and NIAID efforts are complementary to each other, focusing on evaluating the immunogenicity, efficacy, and safety of influenza vaccines during pregnancy; and the potential effect of maternal immunization on outcomes in infants in low-resource populations.


Subject(s)
Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Pregnancy Complications, Infectious/prevention & control , Prenatal Care , Vaccination , Female , Global Health , Health Promotion , Humans , Influenza Vaccines/immunology , Influenza, Human/immunology , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/immunology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology
19.
Influenza Other Respir Viruses ; 6(2): 142-52, e1-5, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21819547

ABSTRACT

• For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. • The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy-making community of the complexity of influenza vaccine virus selection. • The selection process is highly coordinated and involves continual year-round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). • Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non-antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. • Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. • Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. • Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays - for example based upon advanced recombinant DNA and protein technologies - may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development. • Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large-scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. • Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well-characterized banks of age-stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. • Advances in high-throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X-ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. • Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non-mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. • The adoption of alternative vaccine technologies - such as live-attenuated, quadrivalent or non-HA-based vaccines - has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high-growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. • The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.


Subject(s)
Influenza Vaccines/immunology , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Orthomyxoviridae/immunology , Orthomyxoviridae/isolation & purification , Vaccination/methods , Global Health , Humans , Influenza, Human/virology , Switzerland , World Health Organization
20.
J Infect Dis ; 204 Suppl 1: S403-13, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21666192

ABSTRACT

Measles is a childhood disease that causes great morbidity and mortality in India and worldwide. Because measles surveillance in India is in its infancy, there is a paucity of countrywide data on circulating Measles virus genotypes. This study was conducted in 21 of 28 States and 2 of 7 Union Territories of India by MeaslesNetIndia, a national network of 27 centers and sentinel practitioners. MeaslesNetIndia investigated 52 measles outbreaks in geographically representative areas from 2005 through June 2010. All outbreaks were serologically confirmed by detection of antimeasles virus immunoglobulin M (IgM) antibodies in serum or oral fluid samples. Molecular studies, using World Health Organization (WHO)-recommended protocols obtained 203 N-gene, 40 H-gene, and 4 M-gene sequences during this period. Measles genotypes D4, D7, and D8 were found to be circulating in various parts of India during the study period. Further phylogenetic analysis revealed 4 lineages of Indian D8 genotypes: D8a, D8b, D8c, and D8d. This study generated a large, countrywide sequence database that can form the baseline for future molecular studies on measles virus transmission pathways in India. This study has created support and capabilities for countrywide measles molecular surveillance that must be carried forward.


Subject(s)
Measles virus/genetics , Measles/epidemiology , Measles/virology , Adolescent , Adult , Age Distribution , Antibodies, Viral/blood , Child , Child, Preschool , Disease Outbreaks/statistics & numerical data , Genotype , Humans , Immunoglobulin M/blood , India/epidemiology , Infant , Measles virus/classification , Measles virus/immunology , Molecular Epidemiology , Phylogeny , Serologic Tests , Young Adult
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