Tomislav Mestrovic

6507240107

Publications - 3

The burden of bacterial antimicrobial resistance in the WHO Eastern Mediterranean Region 1990–2021: a cross-country systematic analysis with forecasts to 2050

Haroon Ahmed Armita Abedi Hmwe Hmwe Kyu Gisela Robles Aguilar Nicole Davis Weaver Eve E. Wool Shahkaar Aziz Tomislav Mestrovic Khalil Azizian Lucien R. Swetschinski Neeraj Bedi Aqeel Ahmad Hiba Jawdat Barqawi James A. Berkley Kenneth Chukwuemeka Iregbu Nabi Jomehzadeh Faisal Ismail Abdollah Jafarzadeh Mahsa Jalili Reza Jalilzadeh Yengejeh Elham Jamshidi Daniel T. Araki Anna Gershberg Hayoon Authia Gray B Chieh Han Jessica Andretta Mendes Jason R. Andrews Amir Mahmoud Ahmadzade Kevin S. Ikuta Rasool Haddadi Mostafa Hadei Sobia Ahsan Halim Emily Rosenblad Abid Ali Zahid Ali Liaqat Ali Syed Shujait Ali Sabah Al-Marwani Omar Almidani Ayesha Fahim Ali Fatehizadeh Muhammed Shaffi Fazaludeen Koya Alireza Feizkhah Saira Afzal Rami H. Al-Rifai Jaffar A. Al-Tawfiq Karem H. Alzoubi Seyyed Shamsadin Athari Maha Moh'd Wahbi Atout Sina Azadnajafabad Natalia V. Bhattacharjee Colin Stewart Brown Ben S. Cooper Sama Ghoba Konstantinos Giannakis Kamal Hezam Mehdi Hosseinzadeh Rebecca L. Hsu Nawfal R. Hussein Mohammad Tarique Imam Omar Makram DE, DF Elaheh Malakan Rad Florian Marks Barney McManigal Yasser Bustanji Christiane Dolecek Abdelaziz Ed-Dra Iman El Sayed Waseem El-Huneidi Christelle Elias Zul Kamal Hengameh Kasraei Faham Khamesipour Nihar Ranjan Dash Muhammed Elhadi Sally Ellis Mohsen Naghavi Ayman Ahmed Ramy Mohamed Ghazy Denise O. Garrett Samer Hamidi Ahmed I. Hasaballah Ibrahim Elsohaby Salahdein Aburuz Babak Eshrati Feriha Fatima Khidri Suwimon Khusuwan Mohammed Kuddus Mansour Adam Mahmoud Sherief Abd-Elsalam Haroon Ahmed Abid Ali Hasan Aalruz Nabi Jomehzadeh Hassan Abolhassani Zarrin Basharat Jalal Arabloo Mosab Arafat Tim Eckmanns Rumina Syeda Hasan Hamidreza Hasani Andrea Haekyung Haselbeck Simon Hay B, C Salahdein Aburuz Mohammad Tarique Imam

Publication Name: Lancet Public Health

Publication Date: 2025-11-01

Volume: 10

Issue: 11

Page Range: e955-e970

Description:

Background Antimicrobial resistance (AMR) is an urgent global crisis and one of the world's most complex challenges. Although there is increasing evidence of its impact on human mortality and morbidity, precise burden estimation has many challenges, and thus far has been elusive for the Eastern Mediterranean Region. Here, we present a comprehensive time-trend analysis of regional and country-level AMR burden estimates in the WHO Eastern Mediterranean Region (EMR), between 1990 and 2021, with forecasts up to 2050. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 11 infectious syndromes, 22 bacterial pathogens, and 84 pathogen–drug combinations for the WHO EMR and each of its countries from 1990 to 2021. Data were obtained from mortality registries, surveillance systems, hospital records, systematic literature reviews, and other sources. We based our modelling approach on five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths and DALYs attributable to AMR (considering an alternative scenario where drug-resistant infections are replaced with susceptible infections), and deaths and DALYs associated with AMR (considering an alternative scenario where infections would not occur at all). Predictive statistical modelling was applied to generate estimates of AMR burden for each country. We also generated AMR burden forecasts up to 2050. We generated 95% uncertainty intervals (UIs) for the final estimates by taking the 2·5th and 97·5th percentiles across 500 draws through the multistage computational pipeline, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 380 000 deaths (95% UI 332 000–426 000) associated with bacterial AMR and 92 800 deaths (78 300–111 000) attributable to bacterial AMR in the EMR in 2021. In the past 31 years, there was considerable variation in AMR mortality trends across countries of the region and different age groups. Between 1990 and 2021, associated deaths among children younger than 5 years decreased by 50·0% (38·2–62·0), while those among adults aged 70 and older rose by over 85·7% (95% UI 57·0–115·7). Six pathogens were identified as the primary generators of burden: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii , and Pseudomonas aeruginosa . A substantial increase in the AMR burden due to S aureus was observed between 1990 (28 200 deaths [21 600–34 000]) and 2021 (49 500 deaths [43 100–56 200]); consequently, in 2021, methicillin-resistant S aureus was a leading pathogen–drug combination for most countries in the region for deaths and DALYs attributable to, and associated with AMR. Somalia had the highest age-standardised mortality rates in the region: for deaths attributable to and associated with AMR per 100 000 population in both 1990 and 2021; conversely, the country with the lowest burden in the EMR was Qatar. By 2050, the number of deaths attributable to AMR in region is forecasted to reach 187 000 (157 000–223 000) and deaths associated with AMR were projected to reach 752 000 (629 000–879 000). Interpretation Our study shows that bacterial AMR has been a serious public health threat in the EMR for more than 30 years, with a substantial fatal and non-fatal burden for priority bacterial pathogens and pathogen–drug combinations. The magnitude of this issue, future projects, and the inadequate response capacity in many countries underscore the need for more stringent regional leadership in this field. The insights gained from this study can direct targeted mitigation strategies for individual countries within the region, aiding in resource allocation and funding decisions, and emphasising the need for collaborative multisectoral endeavours among nations to address this issue. Funding Wellcome Trust, and the UK Department of Health and Social Care using aid funding managed by the Fleming Fund.

Open Access: Yes

DOI: 10.1016/S2468-2667(25)00201-4

Global, regional, and national sepsis incidence and mortality, 1990–2021: a systematic analysis

Usha Adiga Samah W. Al-Jabi Meriem Abdoun Quique Bassat Zulfiqar A. Bhutta Hany Aly Ashish Bhargava Hasan Yaser Alniss Razique Anwer Abdul Monim Batiha Asrat Agalu Abejew Samar Abd Elhafeez Mahwish Arooj Matteo Bauckneht Mohammad R. Alqudimat Alok Atreya Abdelazeem M. Algammal Saeid Anvari Auwal Abdullahi Tahira Ashraf Shereen M. Aleidi Mohammad R. Alosta Senthilkumar Balakrishnan Zarrin Basharat Montaha Al-Iede Nasir Abbas Syed Shujait Ali Williams Agyemang-Duah Sahel Majed Alrousan Lucien R. Swetschinski Sonu Bhaskar Anayochukwu Edward Anyasodor Lisa C. Adams Ahmad Naoras Bitar Madineh Abbasi Habib Benzian Intima Alrimawi Nicole Davis Weaver Mohammed Albashtawy Meshack Achore Domenico Azzolino Eve E. Wool Kamoru Ademola Adedokun Fahad A. Alhumaydhi Ahmad Alrawashdeh Aqeel Ahmad Simachew Animen Bante Nelson Alvis-Guzman Umar Muhammad Bello Rafat Ali Kevin S. Ikuta Qorinah Estiningtyas Sakilah Adnani Rajon Banik Amadou Barrow Mina Borran Wondu Feyisa Balcha Chieh Han Gasha Salih Ahmed Aanuoluwapo Adeyimika Afolabi Alaa Aboelnour Badran Anna Gershberg Hayoon Hamed Borhany Nikha Bhardwaj Ahmad Rajeh Al-Qudimat Najim Z. Alshahrani Fentahun Alemnew Mesfin Abebe Md Akib Al-Zubayer Ema Akter Ridwan Olamilekan Adesola Ali Azargoonjahromi Authia P. Gray Mahsa Ahadi Mohammed Usman Ali Zelalem Asmare Hana J. Abukhadijah Alemwork Abie Amani Alansari Asnake Gashaw Belayneh Yaser Mohammed Al-Worafi Filippos Anagnostakis Daniel T. Araki Hassan Abolhassani Sabah Al-Marwani Gokce Belge Bilgin Mohammad Mahdi Bastan Meqdad Saleh Ahmed Rebecca L. Hsu Abiye Assefa Berihun Erin Chung Hiba Jawdat Barqawi Julie Alaere Atta Nurila Aryntayeva Wakgari Mosisa Abdisa Qorinah Estiningtyas Sakilah Adnani Redeat Libanos Assefa Syed Anees Ahmed Haroon Ahmed Sadat Abdulla Aziz Avinash Aujayeb Tomislav Mestrovic

Publication Name: Lancet Global Health

Publication Date: 2025-12-01

Volume: 13

Issue: 12

Page Range: e2013-e2026

Description:

Background: The global burden of sepsis, a life-threatening dysregulated host response to infection leading to organ dysfunction, remains challenging to quantify. We aimed to comprehensively estimate the global, regional, and national burden of sepsis, including the impact of the COVID-19 pandemic and underlying causes of sepsis-related deaths with co-occurring infectious syndromes. Methods: We used multiple cause-of-death, hospital, minimally invasive tissue sampling, and linked death certificate and hospital record data representing 149 million deaths, covering 4290 location-years with mortality estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to capture explicit and implicit sepsis cases and deaths. We estimated age-location-sex-specific fractions of sepsis-related deaths from 195 underlying causes of death and 22 infectious syndromes from 1990 to 2021 using binomial logistic regression models, and estimated sepsis-related deaths using GBD cause-specific mortality estimates. Using 250 million hospital admissions and 7·82 million deaths from hospital data, representing 1310 location-years, we modelled case fatality rates by use of binomial logistic regression, applied to sepsis death estimates to estimate sepsis incidence by age, location, and year. Findings: In 2021, we estimated 166 million (95% uncertainty interval 135–201) sepsis cases and 21·4 million (20·3–22·5) all-cause sepsis-related deaths globally, representing 31·5% of total global deaths. Sepsis-related deaths decreased between 1990 and 2019, followed by a surge in 2020 and 2021. As of 2021, individuals aged 15 years and older experienced increases across incidence (230%) and mortality (26·3%) since 1990. Those aged 70 years and older had the highest sepsis-related mortality in 2021 (9·28 million [8·74–9·86] deaths). Sepsis-related deaths from infectious underlying causes decreased from 11·8 million (11·1–12·5) in 1990 to 8·34 million (7·72–9·01) in 2019, then increased by 86·4% to 15·5 million (14·7–16·4) in 2021. Sepsis-related mortality due to non-infectious underlying causes of death increased from 4·69 million (4·35–5·05) in 1990 to 5·81 million (5·40–6·25) in 2021; the leading non-infectious underlying causes of death with sepsis were stroke, chronic obstructive pulmonary disease, and cirrhosis. In 2021, bloodstream infections inclusive of HIV and malaria (3·08 million [2·83–3·35]) and lower respiratory infections inclusive of COVID-19 (11·33 million [1·20–1·47]) were the most prominent infectious syndromes complicating sepsis-related deaths from non-infectious underlying causes, representing a consistent trend since 1990. Interpretation: The global burden of sepsis increased in 2020 and 2021, reversing progress from 1990. Sepsis incidence and mortality increased in people aged 15 years and older, especially those aged 70 years and older, and as a complication of non-infectious underlying causes of death such as stroke, primarily through bloodstream infections and lower respiratory infections. The global burden of sepsis is substantial, and sepsis is increasingly a complication of non-infectious causes of death. Funding: Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Open Access: Yes

DOI: 10.1016/S2214-109X(25)00356-0

Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030: a systematic analysis for the Global Burden of Disease Study 2023

Catherine Bisignano Ashley A. Harris Amanda E. Smith Paulina A. Lindstedt Simeon Okechukwu Ajakwe Olivia D. Nesbit Taylor Noyes Noga Shalev Latera Tesfaye Olana Catherine M. Antony Nancy Fullman Sharareh Eskandarieh Mushood Ahmed Naveed Ahmed Rana Kamal Abu Farha Kamoru Ademola Adedokun Nurudeen A. Adegoke Aanuoluwapo Adeyimika Afolabi Giuseppina Affinito Dolapo Emmanuel Ajala Eman Abu-Gharbieh Reed J.D. Sorensen Chun Wei Yuan Stein Emil Vollset Stephen S. Lim Jonathan F. Mosser Andy Stergachis Farbod Khosravi Sonali Kochhar Armita Abedi Usha Adiga Mitra Abbasifard Mohammad Amin Aalipour Faezeh Abbaspour Tomislav Mestrovic Dariush Abtahi Ripon Kumar Adhikary Mohd Adnan Aqeel Ahmad Simon I. Hay Abdollah Jafarzadeh Williams Agyemang-Duah Hana J. Abukhadijah Danish Ahmad Amin Sharifan Rotimi Felix Afolabi Saira Afzal Emad M. Abdallah Samar Abd Elhafeez Meqdad Saleh Ahmed Muktar Beshir Ahmed Syed Anees Ahmed Suneth Buddhika Agampodi Khurshid Ahmad Tauseef Ahmad Sepehr Aghajanian Ayman Ahmed Ramy Mohamed Ghazy Meriem Abdoun Salahdein Aburuz Lucas Guimarães Abreu Alireza Shakeri Qorinah Estiningtyas Sakilah Adnani Emily Haeuser Sam Byrne Jason Nguyen Catalina Raggi Susan A. McLaughlin Hedayat Abbastabar Rana Kamal Abu Farha Sherief Abd-Elsalam Dmitry Abramov Adam Abdullahi Faezeh Abbaspour Reda Abdel-Hameed Samar Abd ElHafeez Atef Abdelkader Deldar Morad Abdulah Haroon Ahmed Lisa C. Adams Toufik Abdul-Rahman Constanza Elizabeth Aguilera Arriagada Mahsa Ahadi Rabbiya Ahmad Shoaib Ahmad Asrat Agalu Abejew Abdu A. Adamu Juliana Bunmi Adetunji Kulmira Abdykerimova Rahim Abo Kasem Nagah M. Abourashed Mohamed Abouzid Roberto Ariel Abeldaño Zuñiga Juan Manuel Acuna Anirudh Balakrishna Acharya Meshack Achore Ousman Adal Habeeb Abiodun Afolabi Hasan Aalruz Arman Abdous Auwal Abdullahi Bilyaminu Abubakar David Adedia Syed Hani Abidi Olumide Abiodun Hassan Abolhassani Richard Gyan Aboagye Ulric Sena Abonie Abdullahi Tunde Aborode Wakgari Mosisa Abdisa Oyelola A. Adegboye Mohammad Mahdi Bastan Dhiraj Motilal Agarwal Tajudeen Adesanmi Adebisi Oluwatobi E. Adegbile Olumide Thomas Adeleke Mache Tsadik Adhana Molalegne Bitew Feven Sahle Gebre Leticia Akua Adzigbli Alireza Mirkheshti Sohrab Salimi Seyed Mohammad Seyed Alshohadaei Hafsa Zia Gizachew Taddesse Akalu Jiawei He Prince Owusu Adoma Dorsa Salabat Mohamed Jalloh Vafa Rahimi-Movaghar Sina Shool Melika Jameie Jafar Karami Farzad Kompani Mohammad Ali Mansournia Abdolreza Mohammadi Amin Mohsenzadeh Aleksandr Y. Aravkin Omid Dadras Iman M. Talaat Ali H. Mokdad Xiaochen Dai Lalit Dandona Rakhi Dandona Sara Bagheri Fereshteh Baghizadeh Mahdis Bayat Minoo Heidari Almasi Ali Asghar Kolahi Ali Nikoobar Mohammad Mahdi Rashidi Firoozeh Madadi Mehdi Safari Mastooreh Sagharichi Maryam Shayan Georgia Smith Samuel James Herold Annie Haakenstad Christopher J.L. Murray Zahra Siavashpour Mohsen Rezaeian Shakiba Ghasemi Assl Atakan Orscelik Yigit Can Senol Michael Zastrozhin Hannah Elizabeth Robinson-Oden Amin Azizan Nazila Rezaei Pegah Salimi Pormehr Amin Sedigh Farshad Shahkarami Kazem Ghaffari Ghazal Arjmand Mahsa Asadi Anar Rasoul Ebrahimi Seyed Ataollah Madinezad Behnaz Niroomand Seyed Kiarash Sadat Rafiei Antonio Olivas-Martinez

Publication Name: Lancet

Publication Date: 2025-07-19

Volume: 406

Issue: 10500

Page Range: 235-260

Description:

Background: Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years. Methods: Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030. Findings: Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1–77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6–20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6–17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities. Interpretation: Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO's Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals. Funding: The Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Open Access: Yes

DOI: 10.1016/S0140-6736(25)01037-2