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Fulltext Rationale and opportunities in estimating the economic burden of seasonal influenza across countries using a standardized WHO tool and manual

Chaiyakunapruk N, Kotirum S, Newall AT, Lambach P, Hutubessy RCW

Influenza Other Respir Viruses, 2018 01;12(1):13-21.
PMID: 29143498 DOI: 10.1111/irv.12491

Influenza disease burden is recognized as one of the major public health problems globally. Much less is known about the economic burden of influenza especially in low- and middle-income countries (LMICs). A recent systematic review on the economic burden of influenza in LMICs suggests that information is scarce and/or incomplete and that there is a lack of standardized approaches for cost evaluations in LMICs. WHO commissioned and publicized a Manual for estimating the economic burden of seasonal influenza to support the standardization of estimates of the economic burden of seasonal influenza across countries. This article aims to describe the rationale of this manual development and opportunities that lie in collecting data to help policymakers estimate the economic burden of seasonal influenza. It describes a manual developed by WHO to help such estimation and also links to relevant literature and tools to ensure robustness of applied methods to assess the economic burden associated with seasonal influenza, including direct medical costs, direct non-medical costs and indirect costs.
Fulltext The effects of age on clinical characteristics, hospitalization and mortality of patients with influenza-related illness at a tertiary care centre in Malaysia

Wong PL, Sii HL, P'ng CK, Ee SS, Yong Oong X, Ng KT, et al.

Influenza Other Respir Viruses, 2020 05;14(3):286-293.
PMID: 32022411 DOI: 10.1111/irv.12691

BACKGROUND: Age is an established risk factor for poor outcomes in individuals with influenza-related illness, and data on its influence on clinical presentations and outcomes in the South-East Asian settings are scarce. The aim of this study was to determine the above among adults with influenza-related upper respiratory tract infection at a teaching hospital in Malaysia.
METHODS: A retrospective case-note analysis was conducted on a cohort of 3935 patients attending primary care at the University Malaya Medical Centre, Malaysia from February 2012 till May 2014 with URTI symptoms. Demographics, clinical characteristics, medical and vaccination history were obtained from electronic medical records, and mortality data from the National Registration Department. Comparisons were made between those aged <25, ≥25 to <65 and ≥65 years.
RESULTS: 470 (11.9%) had PCR-confirmed influenza virus infection. Six (1.3%) received prior influenza vaccination. Those aged ≥65 years were more likely to have ≥2 comorbidities (P
Fulltext The seroprevalence of SARS-CoV-2 infection in Malaysia: 7 August to 11 October 2020

Chong ZL, Rodzlan Hasani WS, Noor Asari F, Muhammad EN, Mutalip MHA, Robert Lourdes TG, et al.

Influenza Other Respir Viruses, 2023 Oct;17(10):e13193.
PMID: 37789877 DOI: 10.1111/irv.13193

BACKGROUND: From the beginning of the COVID-19 pandemic until mid-October 2020, Malaysia recorded ~15,000 confirmed cases. But there could be undiagnosed cases due mainly to asymptomatic infections. Seroprevalence studies can better quantify underlying infection from SARS-CoV-2 by identifying humoral antibodies against the virus. This study was the first to determine the prevalence of SARS-CoV-2 infection in Malaysia's general population, as well as the proportion of asymptomatic and undiagnosed infections.
METHODS: This cross-sectional seroprevalence study with a two-stage stratified random cluster sampling design included 5,131 representative community dwellers in Malaysia aged ≥1 year. Data collection lasted from 7 August to 11 October 2020 involving venous blood sampling and interviews for history of COVID-19 symptoms and diagnosis. Previous SARS-CoV-2 infection was defined as screened positive using the Wantai SARS-CoV-2 Total Antibody enzyme-linked immunosorbent assay and confirmed positive using the GenScript SARS-CoV-2 surrogate Virus Neutralization Test. We performed a complex sampling design analysis, calculating sample weights considering probabilities of selection, non-response rate and post-stratification weight.
RESULTS: The overall weighted prevalence of SARS-CoV-2 infection was 0.49% (95%CI 0.28-0.85) (N = 150,857). Among the estimated population with past infection, around 84.1% (95%CI 58.84-95.12) (N = 126 826) were asymptomatic, and 90.1% (95%CI 67.06-97.58) (N = 135 866) were undiagnosed.
CONCLUSIONS: Our study revealed a low pre-variant and pre-vaccination seroprevalence of SARS-CoV-2 infection in Malaysia up to mid-October 2020, with a considerable proportion of asymptomatic and undiagnosed cases. This led to subsequent adoption of SARS-CoV-2 antigen rapid test kits to increase case detection rate and to reduce time to results and infection control measures.
Fulltext Nanoparticles in influenza subunit vaccine development: Immunogenicity enhancement

Khalaj-Hedayati A, Chua CLL, Smooker P, Lee KW

Influenza Other Respir Viruses, 2020 Jan;14(1):92-101.
PMID: 31774251 DOI: 10.1111/irv.12697

The threat of novel influenza infections has sparked research efforts to develop subunit vaccines that can induce a more broadly protective immunity by targeting selected regions of the virus. In general, subunit vaccines are safer but may be less immunogenic than whole cell inactivated or live attenuated vaccines. Hence, novel adjuvants that boost immunogenicity are increasingly needed as we move toward the era of modern vaccines. In addition, targeting, delivery, and display of the selected antigens on the surface of professional antigen-presenting cells are also important in vaccine design and development. The use of nanosized particles can be one of the strategies to enhance immunogenicity as they can be efficiently recognized by antigen-presenting cells. They can act as both immunopotentiators and delivery system for the selected antigens. This review will discuss on the applications, advantages, limitations, and types of nanoparticles (NPs) used in the preparation of influenza subunit vaccine candidates to enhance humoral and cellular immune responses.
Fulltext Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: A phase 2 proof-of-concept trial

Huang LM, Schibler A, Huang YC, Tai A, Chi H, Chieng CH, et al.

Influenza Other Respir Viruses, 2023 Jul;17(7):e13176.
PMID: 37502622 DOI: 10.1111/irv.13176

BACKGROUND: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available.
METHODS: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.
RESULTS: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group.
CONCLUSIONS: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.
CLINICAL TRIALS REGISTRATION: NCT02654171.
Fulltext WHO guide on the economic evaluation of influenza vaccination

Newall AT, Chaiyakunapruk N, Lambach P, Hutubessy RCW

Influenza Other Respir Viruses, 2018 Mar;12(2):211-219.
PMID: 29024434 DOI: 10.1111/irv.12510

Influenza is responsible for substantial morbidity and mortality across the globe, with a large share of the total disease burden occurring in low- and middle-income countries (LMICs). There have been relatively few economic evaluations assessing the value of seasonal influenza vaccination in LMICs. The purpose of this guide is to outline the key theoretical concepts and best practice in methodologies and to provide guidance on the economic evaluation of influenza vaccination in LMICs. It outlines many of the influenza vaccine-specific challenges and should help to provide a framework for future evaluations in the area to build upon.
Fulltext Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines

Lim CML, Komarasamy TV, Adnan NAAB, Radhakrishnan AK, Balasubramaniam VRMT

Influenza Other Respir Viruses, 2024 Mar;18(3):e13276.
PMID: 38513364 DOI: 10.1111/irv.13276

Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, in terms of not only health but also the economy. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies is currently underway. Promising approaches include targeting the highly conserved epitopes of haemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e) and internal proteins of the influenza virus. The identification and characterization of broadly neutralizing antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.