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  1. Md Khairi LNH, Fahrni ML, Lazzarino AI
    Vaccines (Basel), 2022 Aug 12;10(8).
    PMID: 36016194 DOI: 10.3390/vaccines10081306
    COVID-19 vaccines are possibly the most effective medical countermeasures to mitigate and ultimately bring to a halt the COVID-19 pandemic. As we transition to endemicity, inequitable access to vaccines, and particularly in low- and middle-income countries (LMICs), still poses risks of unprecedented disruptions and the emergence of viral mutations, which potentially lead to notorious vaccine-resistant variants. The missteps learned from the previous responses to the human immunodeficiency virus (HIV) and influenza outbreaks founded the hypothetical plan to ensure that vaccine accessibility to LMICs is not impeded. The SARS-CoV-2 vaccines' social promise was to lessen the underlying racial, ethnic, and geographic inequities that COVID-19 has both made apparent and intensified. Vaccine nationalism was evident throughout the COVID-19 crisis. Many high-income countries directly negotiated large advance orders for the vaccines, leaving resource-limited countries scrambling for access. This occurred despite international initiatives to structure the development and equitable distribution of vaccines, channeled through a vaccine pillar: COVID-19 Vaccines Global Access (COVAX). The serious supply shortages and national procurement methods of some countries that bypassed the vaccine pillar hindered the optimal function of COVAX in delivering timely and adequate doses to participating countries. COVAX strategized its approach by promoting fundraising, coordinating vaccine donations from countries with surplus doses, expediting reviews of vaccine candidates, and facilitating the expansion of the manufacturing capacity. While increasing capacity for production, technology transfer led to lesser siloes, enhanced manufacturing standardization, and less secrecy over production data. Ultracold storage requirements for leading vaccines were a considerable hurdle to the global immunization efforts, and particularly in LMICs with limited equipment and resources to support sophisticated cold-chain systems. Manufacturers strived to ease cold-chain restrictions on the basis of stability data submitted to national regulatory bodies. The development of single-dose vaccines offered promising solutions to simplify the administrative and logistic complexities that existed within the COVID-19 vaccination programs. As such, the requirements for both ultracold storage conditions were eased, and concerns over booster doses were addressed. To expand coverage, the dosing intervals of the Oxford/AstraZeneca vaccines were extended according to data from Phase III clinical trials on effectiveness. In addition, with the recent outbreak of monkeypox, the lessons from past experiences of curbing infectious diseases, including COVID-19, must be learned and acted upon. The review summarizes the global efforts with respect to vaccine development, production, allocation, and deployment to achieve equitable access.
  2. Fahrni ML, Misran NFL, Abidin ZZ, Chidambaram SK, Lazzarino AI
    J Infect Public Health, 2023 Jan;16(1):96-103.
    PMID: 36508946 DOI: 10.1016/j.jiph.2022.12.001
    BACKGROUND: While efavirenz-associated adverse drug events (ADEs) were widely established, the clinical relevance is uncertain.

    OBJECTIVES: We aimed to assess the extent of treatment interruption caused by efavirenz-associated ADEs.

    METHODS: A case-control study of efavirenz recipients who did, versus did not (control) develop adverse drug events (ADE), and who were matched for baseline CD4 + at a ratio of 1:1.3 was conducted. Antiretroviral -naïve patients who were started on efavirenz were followed up retrospectively, and their records scrutinized every month for 2 years. Demographic and clinical predictors of treatment interruption were computed using Cox proportional hazard models. Kaplan- Meier curves were plotted to assess time to treatment interruption for the two groups. Clinical endpoints were: i) efficacy -improved CD4 + counts and/or viral load (VL) suppression, ii) safety -absence of treatment-limiting toxicities, and iii) durability - no interruption until follow-up ended.

    RESULTS: Both groups had comparable CD4 + counts at baseline (p = 0.15). At t = 24-months, VL in both groups were suppressed to undetectable levels (<20 copies/mL) while median CD4 + was 353 cells/µL (IQR: 249-460). The mean time on treatment was 23 months (95% CI, 22.3 -23.4) in the control group without ADE and 20 months (95% CI, 18.9 - 21.6) in the ADE group (p = 0.001). Kaplan-Meier plots demonstrated that 59.5% of patients who experienced ≥ 1 ADE versus 81% of those who did not experience any ADE were estimated to continue treatment for up to 24 months with no interruption (p = 0.001). Most interruptions to EFV treatment occurred in the presence of opportunistic infections and these were detected within the first 5 months of treatment initiation. Independent predictors which negatively impacted the dependent variable i.e., treatment durability, were intravenous drug use (adjusted hazard ratio, aHR 2.17, 95% CI, 1.03-4.61, p = 0.043), presence of ≥ 1 opportunistic infection(s) (aHR 2.2, 95% CI, 1.13-4.21, p = 0.021), and presence of ≥ 1 serious ADE(s) (aHR 4.18, 95% CI, 1.98-8.85, p = 0.00).

    CONCLUSION: Efavirenz' role as the preferred first-line regimen for South-East Asia's resource-limited regions will need to be carefully tailored to suit the regional population. Findings have implications to policy-makers and clinicians, particularly for the treatment of patients who develop ADEs and opportunistic infections, and for intravenous drug user subgroups.

  3. Ahmed SK, Abdulqadir SO, Omar RM, Hussein S, Qurbani K, Mohamed MG, et al.
    Vaccines (Basel), 2023 Nov 21;11(12).
    PMID: 38140139 DOI: 10.3390/vaccines11121734
    Although human monkeypox infections had not been recorded in the Kurdistan region of Iraq as of August 2023, the rapid growth of cases worldwide and the detection of monkeypox in neighboring Middle Eastern nations call for careful planning and timely response measures. Educating and empowering frontline healthcare workers (HCWs) so that they can act to curb the spread of monkeypox infections are core elements of primary prevention and protecting public health. Therefore, this study aimed to assess HCWs' knowledge and attitudes about monkeypox and their willingness to vaccinate against monkeypox. By employing a convenience sampling method, an online survey was disseminated via Google Forms between 1 November 2022 and 15 January 2023. The researchers utilized regression analyses to ascertain the factors associated with the three parameters: knowledge, attitude, and the willingness to vaccinate. A total of 637 HCWs were included in the analysis (ages ranged between 21 and 51 years). The mean overall scores were 8.18 of a max score of 16 (SD 3.37), 3.4 of 5 (SD 1.37), and 2.41 of 5 (SD 1.25) for knowledge, attitude, and willingness to vaccinate, respectively. A multivariate logistic regression analysis demonstrated that HCWs who had heard about monkeypox before 2022 rather than later had a higher level of knowledge (AOR: 4.85; 95% CI: 2.81-8.36; p < 0.001). In addition, those who had newly joined the workforce or had less than 1 year experience in practice had more positive attitudes about curbing monkeypox (AOR: 0.35; 95% CI: 0.20-0.59; p < 0.01) than those who practiced for longer. No significant predictors of willingness to vaccinate against monkeypox were identified. The research revealed that HCWs exhibited a relatively low level of monkeypox knowledge. They also had poor attitudes towards monkeypox vaccination and were therefore reluctant to receive the vaccines. Imparting knowledge about the infectious disease can cultivate better awareness and attitudes among HCWs as to their roles in mitigating the spread of an epidemic in the foreseeable future.
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