Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019,The Lancet

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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
The Lancet ( IF 168.9 ) Pub Date : 2022-11-21 , DOI: 10.1016/s0140-6736(22)02185-7
Kevin S Ikuta , Lucien R Swetschinski , Gisela Robles Aguilar , Fablina Sharara , Tomislav Mestrovic , Authia P Gray , Nicole Davis Weaver , Eve E Wool , Chieh Han , Anna Gershberg Hayoon , Amirali Aali , Semagn Mekonnen Abate , Mohsen Abbasi-Kangevari , Zeinab Abbasi-Kangevari , Sherief Abd-Elsalam , Getachew Abebe , Aidin Abedi , Amir Parsa Abhari , Hassan Abidi , Richard Gyan Aboagye , Abdorrahim Absalan , Hiwa Abubaker Ali , Juan Manuel Acuna , Tigist Demssew Adane , Isaac Yeboah Addo , Oyelola A Adegboye , Mohammad Adnan , Qorinah Estiningtyas Sakilah Adnani , Muhammad Sohail Afzal , Saira Afzal , Zahra Babaei Aghdam , Bright Opoku Ahinkorah , Aqeel Ahmad , Araz Ramazan Ahmad , Rizwan Ahmad , Sajjad Ahmad , Sohail Ahmad , Sepideh Ahmadi , Ali Ahmed , Haroon Ahmed , Jivan Qasim Ahmed , Tarik Ahmed Rashid , Marjan Ajami , Budi Aji , Mostafa Akbarzadeh-Khiavi , Chisom Joyqueenet Akunna , Hanadi Al Hamad , Fares Alahdab , Ziyad Al-Aly , Mamoon A Aldeyab , Alicia V Aleman , Fadwa Alhalaiqa Naji Alhalaiqa , Robert Kaba Alhassan , Beriwan Abdulqadir Ali , Liaqat Ali , Syed Shujait Ali , Yousef Alimohamadi , Vahid Alipour , Atiyeh Alizadeh , Syed Mohamed Aljunid , Kasim Allel , Sami Almustanyir , Edward Kwabena Ameyaw , Arianna Maever L Amit , Nivedita Anandavelane , Robert Ancuceanu , Catalina Liliana Andrei , Tudorel Andrei , Dewi Anggraini , Adnan Ansar , Anayochukwu Edward Anyasodor , Jalal Arabloo , Aleksandr Y Aravkin , Demelash Areda , Timur Aripov , Anton A Artamonov , Judie Arulappan , Raphael Taiwo Aruleba , Muhammad Asaduzzaman , Tahira Ashraf , Seyyed Shamsadin Athari , Daniel Atlaw , Sameh Attia , Marcel Ausloos , Tewachew Awoke , Beatriz Paulina Ayala Quintanilla , Tegegn Mulatu Ayana , Sina Azadnajafabad , Amirhossein Azari Jafari , Darshan B B , Muhammad Badar , Ashish D Badiye , Nayereh Baghcheghi , Sara Bagherieh , Atif Amin Baig , Indrajit Banerjee , Aleksandra Barac , Mainak Bardhan , Francesco Barone-Adesi , Hiba Jawdat Barqawi , Amadou Barrow , Pritish Baskaran , Saurav Basu , Abdul-Monim Mohammad Batiha , Neeraj Bedi , Melaku Ashagrie Belete , Uzma Iqbal Belgaumi , Rose G Bender , Bharti Bhandari , Dinesh Bhandari , Pankaj Bhardwaj , Sonu Bhaskar , Krittika Bhattacharyya , Suraj Bhattarai , Saeid Bitaraf , Danilo Buonsenso , Zahid A Butt , Florentino Luciano Caetano dos Santos , Jiao Cai , Daniela Calina , Paulo Camargos , Luis Alberto Cámera , Rosario Cárdenas , Muge Cevik , Joshua Chadwick , Jaykaran Charan , Akhilanand Chaurasia , Patrick R Ching , Sonali Gajanan Choudhari , Enayet Karim Chowdhury , Fazle Rabbi Chowdhury , Dinh-Toi Chu , Isaac Sunday Chukwu , Omid Dadras , Fentaw Teshome Dagnaw , Xiaochen Dai , Saswati Das , Anna Dastiridou , Sisay Abebe Debela , Fitsum Wolde Demisse , Solomon Demissie , Diriba Dereje , Msganaw Derese , Hardik Dineshbhai Desai , Fikadu Nugusu Dessalegn , Samuel Abebe A Dessalegni , Belay Desye , Kartik Dhaduk , Meghnath Dhimal , Sameer Dhingra , Nancy Diao , Daniel Diaz , Shirin Djalalinia , Milad Dodangeh , Deepa Dongarwar , Bezabih Terefe Dora , Fariba Dorostkar , Haneil Larson Dsouza , Eleonora Dubljanin , Susanna J Dunachie , Oyewole Christopher Durojaiye , Hisham Atan Edinur , Habtamu Bekele Ejigu , Michael Ekholuenetale , Temitope Cyrus Ekundayo , Hassan El-Abid , Muhammed Elhadi , Mohamed A Elmonem , Amir Emami , Luchuo Engelbert Bain , Daniel Berhanie Enyew , Ryenchindorj Erkhembayar , Babak Eshrati , Farshid Etaee , Adeniyi Francis Fagbamigbe , Shahab Falahi , Aida Fallahzadeh , Emerito Jose A Faraon , Ali Fatehizadeh , Ginenus Fekadu , João C Fernandes , Allegra Ferrari , Getahun Fetensa , Irina Filip , Florian Fischer , Masoud Foroutan , Peter Andras Gaal , Muktar A Gadanya , Abhay Motiramji Gaidhane , Balasankar Ganesan , Mesfin Gebrehiwot , Reza Ghanbari , Mohammad Ghasemi Nour , Ahmad Ghashghaee , Ali Gholamrezanezhad , Abdolmajid Gholizadeh , Mahaveer Golechha , Pouya Goleij , Davide Golinelli , Amador Goodridge , Damitha Asanga Gunawardane , Yuming Guo , Rajat Das Gupta , Sapna Gupta , Veer Bala Gupta , Vivek Kumar Gupta , Alemu Guta , Parham Habibzadeh , Atlas Haddadi Avval , Rabih Halwani , Asif Hanif , Md. 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, Himal Kandel , Neeti Kapoor , Samad Karkhah , Bekalu Getnet Kassa , Nicholas J Kassebaum , Patrick DMC Katoto , Mohammad Keykhaei , Himanshu Khajuria , Abbas Khan , Imteyaz A Khan , Maseer Khan , Md Nuruzzaman Khan , Moien AB Khan , Moawiah Mohammad Khatatbeh , Mona M Khater , Hamid Reza Khayat Kashani , Jagdish Khubchandani , Hanna Kim , Min Seo Kim , Ruth W Kimokoti , Niranjan Kissoon , Sonali Kochhar , Farzad Kompani , Soewarta Kosen , Parvaiz A Koul , Sindhura Lakshmi Koulmane Laxminarayana , Fiorella Krapp Lopez , Kewal Krishan , Vijay Krishnamoorthy , Vishnutheertha Kulkarni , Naveen Kumar , Om P Kurmi , Ambily Kuttikkattu , Hmwe Hmwe Kyu , Dharmesh Kumar Lal , Judit Lám , Iván Landires , Savita Lasrado , Sang-woong Lee , Jacopo Lenzi , Sonia Lewycka , Shanshan Li , Stephen S Lim , Wei Liu , Rakesh Lodha , Michael J Loftus , Ayush Lohiya , László Lorenzovici , Mojgan Lotfi , Ata Mahmoodpoor , Mansour Adam Mahmoud , Razzagh Mahmoudi , Azeem Majeed , Jamal Majidpoor , Alaa Makki , Galana Ayana Mamo , Yosef Manla , Miquel Martorell , Clara N Matei , Barney McManigal , Entezar Mehrabi Nasab , Ravi Mehrotra , Addisu Melese , Oliver Mendoza-Cano , Ritesh G Menezes , Alexios-Fotios A Mentis , Georgia Micha , Irmina Maria Michalek , Ana Carolina Micheletti Gomide Nogueira de Sá , Neda Milevska Kostova , Shabir Ahmad Mir , Mojgan Mirghafourvand , Seyyedmohammadsadeq Mirmoeeni , Erkin M Mirrakhimov , Mohammad Mirza-Aghazadeh-Attari , Abay Sisay Misganaw , Awoke Misganaw , Sanjeev Misra , Esmaeil Mohammadi , Mokhtar Mohammadi , Abdollah Mohammadian-Hafshejani , Shafiu Mohammed , Syam Mohan , Mohammad Mohseni , Ali H Mokdad , Sara Momtazmanesh , Lorenzo Monasta , Catrin E Moore , Maryam Moradi , Mostafa Moradi Sarabi , Shane Douglas Morrison , Majid Motaghinejad , Haleh Mousavi Isfahani , Amin Mousavi Khaneghah , Seyed Ali Mousavi-Aghdas , Sumaira Mubarik , Francesk Mulita , Getaneh Baye B Mulu , Sandra B Munro , Saravanan Muthupandian , Tapas Sadasivan Nair , Atta Abbas Naqvi , Himanshi Narang , Zuhair S Natto , Muhammad Naveed , Biswa Prakash Nayak , Shumaila Naz , Ionut Negoi , Seyed Aria Nejadghaderi , Sandhya Neupane Kandel , Che Henry Ngwa , Robina Khan Niazi , Antonio Tolentino Nogueira de Sá , Nafise Noroozi , Hasti Nouraei , Ali Nowroozi , Virginia Nuñez-Samudio , Jerry John Nutor , Chimezie Igwegbe Nzoputam , Ogochukwu Janet Nzoputam , Bogdan Oancea , Rahman Md Obaidur , Vivek Anand Ojha , Akinkunmi Paul Okekunle , Osaretin Christabel Okonji , Andrew T Olagunju , Bolajoko Olubukunola Olusanya , Ahmed Omar Bali , Emad Omer , Nikita Otstavnov , Bilcha Oumer , Mahesh P A , Jagadish Rao Padubidri , Keyvan Pakshir , Tamás Palicz , Adrian Pana , Shahina Pardhan , Jose L Paredes , Utsav Parekh , Eun-Cheol Park , Seoyeon Park , Ashish Pathak , Rajan Paudel , Uttam Paudel , Shrikant Pawar , Hamidreza Pazoki Toroudi , Minjin Peng , Umberto Pensato , Veincent Christian Filipino Pepito , Marcos Pereira , Mario F P Peres , Norberto Perico , Ionela-Roxana Petcu , Zahra Zahid Piracha , Indrashis Podder , Nayanum Pokhrel , Ramesh Poluru , Maarten J Postma , Naeimeh Pourtaheri , Akila Prashant , Ibrahim Qattea , Mohammad Rabiee , Navid Rabiee , Amir Radfar , Saber Raeghi , Sima Rafiei , Pankaja Raghav Raghav , Leila Rahbarnia , Vafa Rahimi-Movaghar , Mosiur Rahman , Muhammad Aziz Rahman , Amir Masoud Rahmani , Vahid Rahmanian , Pradhum Ram , Muhammad Modassar Ali Nawaz Ranjha , Sowmya J Rao , Mohammad-Mahdi Rashidi , Azad Rasul , Zubair Ahmed Ratan , Salman Rawaf , Reza Rawassizadeh , Mohammad Sadegh Razeghinia , Elrashdy Moustafa Mohamed Redwan , Misganu Teshoma Regasa , Giuseppe Remuzzi , Melese Abate Reta , Nazila Rezaei , Aziz Rezapour , Abanoub Riad , Rezaul Karim Ripon , Kristina E Rudd , Basema Saddik , Saeid Sadeghian , Umar Saeed , Mohsen Safaei , Azam Safary , Sher Zaman Safi , Maryam Sahebazzamani , Amirhossein Sahebkar , Harihar Sahoo , Saina Salahi , Sarvenaz Salahi , Hedayat Salari , Sana Salehi , Hossein Samadi Kafil , Abdallah M Samy , Nima Sanadgol , Senthilkumar Sankararaman , Francesco Sanmarchi , Brijesh Sathian , Monika Sawhney , Ganesh Kumar Saya , Subramanian Senthilkumaran , Allen Seylani , Pritik A Shah , Masood Ali Shaikh , Elaheh Shaker , Murad Ziyaudinovich Shakhmardanov , Mequannent Melaku Sharew , Athena Sharifi-Razavi , Purva Sharma , Rahim Ali Sheikhi , Ali Sheikhy , Pavanchand H Shetty , Mika Shigematsu , Jae Il Shin , Hesamaddin Shirzad-Aski , K M Shivakumar , Parnian Shobeiri , Seyed Afshin Shorofi , Sunil Shrestha , Migbar Mekonnen Sibhat , Negussie Boti Sidemo , Mustafa Kamal Sikder , Luís Manuel Lopes Rodrigues Silva , Jasvinder A Singh , Paramdeep Singh , Surjit Singh , Md Shahjahan Siraj , Samarjeet Singh Siwal , Valentin Yurievich Skryabin , Anna Aleksandrovna Skryabina , Bogdan Socea , Damtew Damtew Solomon , Yimeng Song , Chandrashekhar T Sreeramareddy , Muhammad Suleman , Rizwan Suliankatchi Abdulkader , Saima Sultana , Miklós Szócska , Seyed-Amir Tabatabaeizadeh , Mohammad Tabish , Majid Taheri , Elahe Taki , Ker-Kan Tan , Sarmila Tandukar , Nathan Y Tat , Vivian Y Tat , Belay Negash Tefera , Yibekal Manaye Tefera , Gebremaryam Temesgen , Mohamad-Hani Temsah , Samar Tharwat , Arulmani Thiyagarajan , Imad I Tleyjeh , Christopher E Troeger , Krishna Kishore Umapathi , Era Upadhyay , Sahel Valadan Tahbaz , Pascual R Valdez , Jef Van den Eynde , H. Rogier van Doorn , Siavash Vaziri , Georgios-Ioannis Verras , Harimadhav Viswanathan , Bay Vo , Abdul Waris , Gizachew Tadesse Wassie , Nuwan Darshana Wickramasinghe , Sajad Yaghoubi , Gahin Abdulraheem Tayib Yahya Yahya , Seyed Hossein Yahyazadeh Jabbari , Arzu Yigit , Vahit Yiğit , Dong Keon Yon , Naohiro Yonemoto , Mazyar Zahir , Burhan Abdullah Zaman , Sojib Bin Zaman , Moein Zangiabadian , Iman Zare , Mikhail Sergeevich Zastrozhin , Zhi-Jiang Zhang , Peng Zheng , Chenwen Zhong , Mohammad Zoladl , Alimuddin Zumla , Simon I Hay , Christiane Dolecek , Benn Sartorius , Christopher J L Murray , Mohsen Naghavi

Background

Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes.

Methods

We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest.

Findings

From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths.

Interpretation

The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development.

Funding

Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.

中文翻译：

2019 年与 33 种细菌病原体相关的全球死亡率：2019 年全球疾病负担研究的系统分析

背景

减少感染造成的死亡负担是全球公共卫生的紧迫任务。先前的研究估计了与耐药感染和败血症相关的死亡人数，并发现感染仍然是全球死亡的主要原因。了解常见细菌病原体（对抗菌药物敏感和耐药）的全球负担对于确定对公共卫生的最大威胁至关重要。据我们所知，这是第一项对 11 种主要感染综合症中 33 种细菌病原体相关死亡进行全球综合估计的研究。

方法

除了全球负担中描述的输入数据的子集之外，我们还使用 2019 年全球疾病、伤害和风险因素负担研究 (GBD) 的方法估计了 2019 年与 11 种感染综合症的 33 个细菌属或种相关的死亡人数2019 年抗菌素耐药性研究。这项研究包括 3.43 亿条个人记录或菌株，涵盖 11 361 个研究地点年。我们使用三个建模步骤来估计与每种病原体相关的死亡人数：感染发挥作用的死亡人数、可归因于给定感染综合征的感染死亡比例以及感染综合征导致的死亡比例归因于给定的病原体。2019 年，我们对 204 个国家和地区的所有年龄段、男性和女性进行了估算。

发现

2019 年估计有 13·700 万人 (95% UI 10·9–17·1) 与感染相关的死亡，其中 7·700 万人 (5·7–10·2) 与 33 种细菌病原体（均为细菌性病原体）相关。在本研究估计的 11 种感染综合症中，对抗菌药物耐药和敏感）。我们估计 2019 年与 33 种细菌病原体相关的死亡占全球所有死亡的 13·6% (10·2–18·1) 和所有败血症相关死亡的 56·2% (52·1–60·1) . 五种主要病原体——金黄色葡萄球菌、大肠杆菌、肺炎链球菌、肺炎克雷伯菌和铜绿假单胞菌— 导致所调查细菌中 54·9% (52·9–56·9) 的死亡。最致命的传染病和病原体因地点和年龄而异。与这些细菌病原体相关的年龄标准化死亡率在撒哈拉以南非洲大区域最高，每 10 万人口中有 230 人死亡 (185-285 人)，在高收入大区域最低，为 52 人。每 10 万人中有 2 人死亡 (37·4–71·5)。金黄色葡萄球菌是 135 个国家的主要细菌死亡原因，也是全球 15 岁以上人群死亡人数最多的细菌。在 5 岁以下儿童中，肺炎链球菌是与大多数死亡相关的病原体。2019年，三种细菌感染综合症导致超过600万人死亡，其中下呼吸道感染和血液感染分别导致超过200万人死亡，腹膜和腹腔内感染导致超过100万人死亡。

解释

我们在本研究中调查的 33 种细菌病原体是全球健康损失的重要根源，它们在不同感染综合症和地点之间的分布存在很大差异。与GBD 3级根本死因相比，与这些细菌相关的死亡将成为2019年全球第二大死因；因此，它们应被视为全球卫生界干预的紧迫优先事项。解决细菌感染负担的策略包括预防感染、优化抗生素的使用、提高微生物分析能力、开发疫苗以及改进和更普遍地使用现有疫苗。这些估计可用于帮助确定疫苗需求、需求和开发的优先顺序。