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      Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

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      a , b , c
      The Lancet. Infectious Diseases
      Elsevier Ltd.

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          Abstract

          The end of the emergency phase of the COVID-19 pandemic was announced by WHO on May 5, 2023. Reflecting on the legacy of the pandemic in low-income and middle-income countries (LMICs) where most excess deaths occurred, it will be remembered for the pervasive inequities that plagued every crucial aspect of the global response, from access to vaccines and therapeutics to gaps in health-care infrastructure. 1 Despite the many failures of global solidarity, the pandemic also showcased the resilience and innovative capacity of LMICs, providing some positive aspects and a roadmap for continued improvement in infectious disease and health system strengthening. Three pieces in this Series explicitly amplify the voices of experts in LMICs on how to leverage the potential opportunities for sustainable vaccine capabilities in Africa, 2 combating the increasing threat of antimicrobial resistance (AMR), 3 and establishing more equitable structures to ensure effective and fair collaboration among stakeholders and nations during future pandemics. 4 During the COVID-19 pandemic, vaccine nationalism caused substantial delays in vaccine access, particularly in the region of Africa that had the lowest coverage in the world. As a result, nations without local manufacturing capabilities suffered avoidable deaths from COVID-19. 5 Moreover, the absence of vaccines created a void that allowed misinformation and vaccine hesitancy to spread, which also affected the uptake of other vaccines. 6 The pressing need to establish sustainable vaccine development and manufacturing capacity in the continent with the fastest-growing population is undeniable. Africa has a population of 1·2 billion, yet less than 1% of the vaccines used in Africa are manufactured on the continent. 7 Unless this crucial gap is addressed, Africa will be left behind again and have to wait for trickle-down charity from high-income countries (HICs). Bavesh Kana and colleagues examine the landscape of vaccine capability in Africa and propose a comprehensive continuum for vaccine manufacturing, which spans from fundamental discovery to production and distribution. 2 Building on initiatives that emerged during the pandemic, such as the WHO-sponsored mRNA hub, the authors emphasise strategies that can foster sustained growth in this field while establishing what will serve as key indicators for success: equitable access, quality, and affordability. To ensure the affordability of vaccines in Africa, it will be necessary to establish risk-sharing mechanisms among local vaccine manufacturers, governments, and societies. Additionally, the creation of multi-country platforms for vaccine manufacturing and resource pooling could facilitate trade and enhance the availability of vaccines across the continent. African countries can contribute to affordability by making advanced market commitments to purchase locally manufactured vaccines, even at higher prices, thereby increasing demand. Maintaining high manufacturing standards will necessitate a skilled workforce, incentives for quality improvements, and the implementation of robust regulatory and legal frameworks to ensure safety and efficacy. Embracing a broad portfolio of vaccines is especially relevant and essential to promote innovation and develop vaccines, which might not be prioritised by the pharmaceutical industry or HICs. The success of these initiatives will depend on building demand for locally manufactured vaccines, obtaining political buy-in from African governments to invest in vaccine manufacturing for the long term, ensuring geopolitical stability, and navigating existing trade and intellectual property restrictions that are designed to profit pharmaceutical companies and HICs. These challenges can be proactively addressed by treaties and bold trade and intellectual property regulatory frameworks, instead of a reactionary approach in times of crisis. It is crucial to ensure that the mRNA vaccine platform does not remain a monopoly of big pharma and HICs. This novel and highly adaptable platform should be equally available and accessible to LMICs and repurposed for developing new vaccines against other diseases (eg, HIV, malaria, tuberculosis, and influenza). COVID-19 exacerbated the considerable threat of AMR, which ranks among the top ten public health challenges worldwide. Overuse of antimicrobials spiked during the pandemic, 8 and irrational use of ineffective therapies (eg, hydroxychloroquine and ivermectin) was rampant. 9 In 2019, sub-Saharan Africa and south Asia reported the mortality rates attributed to AMR, totalling 4·95 million lives lost and 1·27 million deaths directly caused by resistance. 10 LMICs face unique challenges in fighting AMR due to factors such as inadequate hygiene practices, fragile health-care infrastructure, a lack of essential diagnostics, weak regulatory systems, and suboptimal implementation of infection control strategies. The urgency with which countries addressed the COVID-19 pandemic should be matched when confronting the AMR crisis. Kamini Walia and colleagues highlight the need for LMIC governments to prioritise AMR as a major public health crisis and allocate sufficient funding to mitigate its effects. 3 Additionally, leveraging technology platforms (eg, molecular diagnostics and gene sequencing), which were scaled up during COVID-19, can be extended to enhance AMR diagnosis, surveillance, and reporting. Because of the pandemic, incredible improvements were made in scaling up molecular diagnostics and self-testing technologies. These investments should now be repurposed for other infectious diseases. 11 Telehealthcare, which saw tremendous expansion during the pandemic, also offers opportunities to extend clinical care, education, and antimicrobial stewardship practices. Effective risk communication is a crucial aspect in crafting an effective response to AMR, which can benefit from adopting a consistent and message-centred approach similar to that used during the COVID-19 pandemic. Many individuals within communities perceive AMR as an abstract concept lacking the immediate threat of a newly emerging virus. By improving risk communication on AMR, behavioural modifications can be achieved among both the general population and health-care practitioners, leading to potential long-term benefits. Countries have shown regulatory flexibility during the COVID-19 pandemic to swiftly provide vaccines to their populations. However, vaccination, which has the potential to reduce the need for frequent antibiotic prescriptions and contain AMR, remains underutilised. Expanding the scope of routine vaccination programs to include influenza, pneumococcus, typhoid, and Haemophilus influenzae type B vaccines is another strategy for reducing AMR. Generating evidence to support the economic effect of vaccination on AMR and its long-term effects on morbidity and mortality will inform decision making in this area. The urgent need for genuine solidarity within the global health system cannot be overstated. Insufficiently acting upon the idea resulted in the failure to deliver equity during the pandemic. Ayoade Alakija draws from the lessons of the COVID-19 pandemic and highlights the importance of tailoring interventions in response to pandemics to the unique circumstances of different regions. 4 For example, it is crucial to implement context-specific and evidence-based non-pharmaceutical interventions, which might have a differential effect on the economy and on the lives of individuals depending on the setting and available resources. Successfully instilling public trust and fostering adherence to these interventions cannot be reduced to a single, universal solution. The notion that what worked in affluent HICs will seamlessly translate to other contexts has proven to be misguided. Addressing these challenges will require deft advocacy, effective risk communication, and meaningful community engagement. As we emerge from the COVID-19 emergency, forging a new global health order mandates transparency, deep-rooted trust, global coordination, and substantial investments that can be sustained over time. Realising this vision will necessitate robust regional collaborations, facilitating platforms for cooperation among LMICs, and leadership of countries with limited resources in decision-making processes. Most importantly, it is time to shift from the charity and saviourism model of global health to a model that is rooted in equity, justice, and allyship. 12 HICs should act on solidarity and support the vision of LMICs for self-determination, self-reliance, and self-sustenance. 1 If all HICs supported the equity provisions in the pandemic accord that is under negotiation, that would demonstrate a concrete act of allyship. A pandemic accord that does not include equity, transparency, and accountability is destined to fail. Even as we reflect upon the failures during the COVID-19 crisis, we should capitalise on opportunities for growth and improvement. Amidst the devastation, some positives abound, particularly for LMICs. Seizing these opportunities in the present moment presents a chance to prevent the repetition of past mistakes and ensure better preparedness and a more equitable health future for all. © 2023 Flickr - GovernmentZA 2023 MP serves as an advisor to non-profits organisations namely WHO, Stop TB Partnership, Bill & Melinda Gates Foundation, and Foundation for Innovative New Diagnostics. None of these organisations were involved in this Comment. We declare no competing interests.

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          Most cited references12

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          Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

          (2022)
          Summary Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
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            The WHO estimates of excess mortality associated with the COVID-19 pandemic

            The World Health Organization has a mandate to compile and disseminate statistics on mortality, and we have been tracking the progression of the COVID-19 pandemic since the beginning of 2020 1 . Reported statistics on COVID-19 mortality are problematic for many countries owing to variations in testing access, differential diagnostic capacity and inconsistent certification of COVID-19 as cause of death. Beyond what is directly attributable to it, the pandemic has caused extensive collateral damage that has led to losses of lives and livelihoods. Here we report a comprehensive and consistent measurement of the impact of the COVID-19 pandemic by estimating excess deaths, by month, for 2020 and 2021. We predict the pandemic period all-cause deaths in locations lacking complete reported data using an overdispersed Poisson count framework that applies Bayesian inference techniques to quantify uncertainty. We estimate 14.83 million excess deaths globally, 2.74 times more deaths than the 5.42 million reported as due to COVID-19 for the period. There are wide variations in the excess death estimates across the six World Health Organization regions. We describe the data and methods used to generate these estimates and highlight the need for better reporting where gaps persist. We discuss various summary measures, and the hazards of ranking countries’ epidemic responses. Msemburi et al. describe how the World Health Organization has estimated the excess mortality associated with the COVID-19 pandemic, by month and for 2020 and 2021, and analyse their estimates across the WHO member states, with 14.83 million global excess deaths estimated.
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              Sales of antibiotics and hydroxychloroquine in India during the COVID-19 epidemic: An interrupted time series analysis

              Background We assessed the impact of the coronavirus disease 2019 (COVID-19) epidemic in India on the consumption of antibiotics and hydroxychloroquine (HCQ) in the private sector in 2020 compared to the expected level of use had the epidemic not occurred. Methods and findings We performed interrupted time series (ITS) analyses of sales volumes reported in standard units (i.e., doses), collected at regular monthly intervals from January 2018 to December 2020 and obtained from IQVIA, India. As children are less prone to develop symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a predominant increase in non-child-appropriate formulation (non-CAF) sales. COVID-19-attributable changes in the level and trend of monthly sales of total antibiotics, azithromycin, and HCQ were estimated, accounting for seasonality and lockdown period where appropriate. A total of 16,290 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. However, the proportion of non-CAF antibiotics increased from 72.5% (95% CI: 71.8% to 73.1%) in 2019 to 76.8% (95% CI: 76.2% to 77.5%) in 2020. Our ITS analyses estimated that COVID-19 likely contributed to 216.4 million (95% CI: 68.0 to 364.8 million; P = 0.008) excess doses of non-CAF antibiotics and 38.0 million (95% CI: 26.4 to 49.2 million; P < 0.001) excess doses of non-CAF azithromycin (equivalent to a minimum of 6.2 million azithromycin treatment courses) between June and September 2020, i.e., until the peak of the first epidemic wave, after which a negative change in trend was identified. In March 2020, we estimated a COVID-19-attributable change in level of +11.1 million doses (95% CI: 9.2 to 13.0 million; P < 0.001) for HCQ sales, whereas a weak negative change in monthly trend was found for this drug. Study limitations include the lack of coverage of the public healthcare sector, the inability to distinguish antibiotic and HCQ sales in inpatient versus outpatient care, and the suboptimal number of pre- and post-epidemic data points, which could have prevented an accurate adjustment for seasonal trends despite the robustness of our statistical approaches. Conclusions A significant increase in non-CAF antibiotic sales, and particularly azithromycin, occurred during the peak phase of the first COVID-19 epidemic wave in India, indicating the need for urgent antibiotic stewardship measures. Giorgia Sulis and co-workers analyze sales of antimicrobials and hydroxchloroquine in India during 2018-20 to assess possible changes across the COVID-19 epidemic. Why was this study done? There are concerns that the widespread and often inappropriate use of antibiotics has been aggravated by the COVID-19 pandemic, but little is known regarding the true impact of the pandemic on antibiotic use, particularly in low- and middle-income countries (LMICs). India is the largest antibiotic user in the world and is among the countries that are most severely affected by the pandemic. About 75% of healthcare in India is private, and this unregulated and fragmented private sector accounts for 90% of antibiotic consumption, raising major concerns about the potential effects of COVID-19 on prescribing and dispensing practices. What did the researchers do and find? Using an interrupted time series (ITS) design, we examined sales volumes of total antibiotics, azithromycin alone, and hydroxychloroquine (HCQ) in India’s private sector from January 2018 to December 2020. Focusing on non-pediatric formulations and adjusting for underlying seasonal and non-seasonal trends and accounting for the effect of lockdown, we estimated the impact of the first epidemic wave on monthly sales. Based on our models, COVID-19 likely contributed to about 216 million excess doses (95% CI: 68.0 to 364.8 million; P = 0.008) of total antibiotics and 38.0 million excess doses (95% CI: 26.4 to 49.2 million; P < 0.001) of azithromycin between June and September 2020 (i.e., after the lockdown and until the epidemic peak). HCQ sales peaked in March 2020, reflecting the widespread use of this drug for both prophylaxis and treatment of COVID-19 (+11.1 million doses [95% CI: 9.2 to 13.0 million]; P < 0.001), followed by a slow decline afterwards. What do these findings mean? Our findings indicate a significant increase in antibiotic sales, particularly of azithromycin, during the peak phase of the first COVID-19 epidemic wave in India. Similar trends are likely to have occurred in other LMICs, where antibiotics are often overused. The medium- and long-term consequences for bacterial resistance patterns are highly concerning, highlighting the need for urgent antibiotic stewardship measures.
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                Author and article information

                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Ltd.
                1473-3099
                1474-4457
                5 June 2023
                5 June 2023
                Affiliations
                [a ]Division of Infectious Disease, Emory University School of Medicine, Emory University, Atlanta, GA, USA
                [b ]School of Population and Global Health, McGill University, Montreal, QC H3A 1G1, Canada
                [c ]Manipal McGill Program in Infectious Diseases, Manipal Center for Infectious Diseases, Manipal Academy of Higher Education, Manipal, India
                Article
                S1473-3099(23)00354-7
                10.1016/S1473-3099(23)00354-7
                10241487
                84c0f2b8-f2bd-4ac5-b165-937504bdfe45
                © 2023 Elsevier Ltd. All rights reserved.

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