Publications by authors named "Agustinus Sutanto"

7 Publications

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Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series.

Lancet Glob Health 2017 10;5(10):e984-e991

Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Netherlands; ReSViNET Respiratory Syncytial Virus Network, Utrecht, Netherlands. Electronic address:

Background: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data.

Methods: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms "RSV", "respiratory syncytial virus", or "respiratory syncytial viral" combined with "mortality", "fatality", "death", "died", "deaths", or "CFR" for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables.

Findings: We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3-11·0) in low-income or lower middle-income countries, 4·0 years (2·0-10·0) in upper middle-income countries, and 7·0 years (3·6-16·8) in high-income countries.

Interpretation: This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries.

Funding: Bill & Melinda Gates Foundation.
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October 2017

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

Ting Shi David A McAllister Katherine L O'Brien Eric A F Simoes Shabir A Madhi Bradford D Gessner Fernando P Polack Evelyn Balsells Sozinho Acacio Claudia Aguayo Issifou Alassani Asad Ali Martin Antonio Shally Awasthi Juliet O Awori Eduardo Azziz-Baumgartner Henry C Baggett Vicky L Baillie Angel Balmaseda Alfredo Barahona Sudha Basnet Quique Bassat Wilma Basualdo Godfrey Bigogo Louis Bont Robert F Breiman W Abdullah Brooks Shobha Broor Nigel Bruce Dana Bruden Philippe Buchy Stuart Campbell Phyllis Carosone-Link Mandeep Chadha James Chipeta Monidarin Chou Wilfrido Clara Cheryl Cohen Elizabeth de Cuellar Duc-Anh Dang Budragchaagiin Dash-Yandag Maria Deloria-Knoll Mukesh Dherani Tekchheng Eap Bernard E Ebruke Marcela Echavarria Carla Cecília de Freitas Lázaro Emediato Rodrigo A Fasce Daniel R Feikin Luzhao Feng Angela Gentile Aubree Gordon Doli Goswami Sophie Goyet Michelle Groome Natasha Halasa Siddhivinayak Hirve Nusrat Homaira Stephen R C Howie Jorge Jara Imane Jroundi Cissy B Kartasasmita Najwa Khuri-Bulos Karen L Kotloff Anand Krishnan Romina Libster Olga Lopez Marilla G Lucero Florencia Lucion Socorro P Lupisan Debora N Marcone John P McCracken Mario Mejia Jennifer C Moisi Joel M Montgomery David P Moore Cinta Moraleda Jocelyn Moyes Patrick Munywoki Kuswandewi Mutyara Mark P Nicol D James Nokes Pagbajabyn Nymadawa Maria Tereza da Costa Oliveira Histoshi Oshitani Nitin Pandey Gláucia Paranhos-Baccalà Lia N Phillips Valentina Sanchez Picot Mustafizur Rahman Mala Rakoto-Andrianarivelo Zeba A Rasmussen Barbara A Rath Annick Robinson Candice Romero Graciela Russomando Vahid Salimi Pongpun Sawatwong Nienke Scheltema Brunhilde Schweiger J Anthony G Scott Phil Seidenberg Kunling Shen Rosalyn Singleton Viviana Sotomayor Tor A Strand Agustinus Sutanto Mariam Sylla Milagritos D Tapia Somsak Thamthitiwat Elizabeth D Thomas Rafal Tokarz Claudia Turner Marietjie Venter Sunthareeya Waicharoen Jianwei Wang Wanitda Watthanaworawit Lay-Myint Yoshida Hongjie Yu Heather J Zar Harry Campbell Harish Nair

Lancet 2017 Sep 7;390(10098):946-958. Epub 2017 Jul 7.

Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK; Public Health Foundation of India, New Delhi, India. Electronic address:

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.

Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.

Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population.

Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.

Funding: The Bill & Melinda Gates Foundation.
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September 2017

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis.

Lancet 2010 May;375(9725):1545-55

Centre for Population Health Sciences, Global Health Academy, The University of Edinburgh, Edinburgh, UK.

Background: The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005.

Methods: We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality.

Findings: In 2005, an estimated 33.8 (95% CI 19.3-46.2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3.4 (2.8-4.3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000-199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting.

Interpretation: Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority.

Funding: WHO; Bill & Melinda Gates Foundation.
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May 2010

Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia.

Pediatr Infect Dis J 2008 May;27(5):438-43

Agence de Médecine Préventive, Institut Pasteur, Paris, France.

Background: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia.

Methods: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and $3.75 per dose.

Results: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and $8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and $74, respectively, versus $4438 and $102 for monovalent vaccine.

Conclusions: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks.
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May 2008

Implementing the birth dose of hepatitis B vaccine in rural Indonesia.

Vaccine 2007 Aug 14;25(32):5985-93. Epub 2007 Jun 14.

Centre for International Health, The Macfarlane Burnet Institute for Medical Research and Public Health Ltd., Australia.

Reaching mothers and their newborn infants around the time of birth with adequate health services has long been a difficult problem in developing countries. In parallel, similar problems have arisen in attempting to deliver hepatitis B (HepB) vaccine to infants born at home in many countries where mother-to-infant transmission is common. It is logical, and supported by experience in Indonesia, to find a combined solution for both problems. The World Health Organization (WHO) recommends that a timely birth dose of HepB vaccine be given, particularly in areas of high vertical transmission of hepatitis B virus (HBV). This can be achieved relatively easily in situations where almost all births occur in health facilities. But where a significant proportion of births occur at home and without birth attendants able to give injections, this is much more difficult. Barriers to the timely administration of the birth dose of HepB vaccine include weakness in policy development and implementation, difficulties in reliably supplying potent vaccine to community level, limited transport, poor communication, limited cold chain capacity, lack of effective training, and lack of a clear delineation of responsibility between health care professionals. Demonstration projects, such as those in Indonesia, suggest that there are significant opportunities to improve the timely delivery of HepB vaccine birth dose in existing maternal and child health programmes where health workers are trained to provide home delivery care.
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August 2007

Incidences of vaccine-preventable Haemophilus influenzae type b pneumonia and meningitis in Indonesian children: hamlet-randomised vaccine-probe trial.

Lancet 2005 Jan 1-7;365(9453):43-52

Association Pour l'Aide à la Médecine Préventive, Paris, France.

Background: Most studies of Haemophilus influenzae type b (Hib) disease in Asia have found low rates, and few Asian countries use Hib vaccine in routine immunisation programmes. Whether Hib disease truly is rare or whether many cases remain undetected is unclear.

Methods: To estimate incidences of vaccine-preventable Hib pneumonia and meningitis among children younger than 2 years in Lombok, Indonesia, during 1998-2002, we undertook a hamlet-randomised, controlled, double-blind vaccine-probe study (818 hamlets). Children were immunised (WHO schedule) with diphtheria, tetanus, pertussis (DTP) or DTP-PRP-T (Hib conjugate) vaccine. Vaccine-preventable disease incidences were calculated as the difference in rates of clinical outcomes between DTP and DTP-PRP-T groups. Analyses included all children who received at least one vaccine dose.

Findings: We enrolled 55073 children: 28147 were assigned DTP-PRP-T and 26926 DTP. The proportion of pneumonia outcomes prevented by vaccine ranged from less than 0 to 4.8%. Calculated incidences of vaccine-preventable Hib disease (per 10(5) child-years of observation) for outcome categories were: substantial alveolar consolidation or effusion, less than zero (-43 [95% CI -185 to 98]); all severe pneumonia, 264 (95% CI less than zero to 629); all clinical pneumonia, 1561 (270 to 2853); confirmed Hib meningitis, 16 (1.4 to 31); meningitis with cerebrospinal-fluid findings consistent with a bacterial aetiology, 67 (22 to 112); and admission for suspected meningitis or presenting to a clinic with convulsions, 158 (42 to 273).

Interpretation: Hib vaccine did not prevent the great majority of pneumonia cases, including those with alveolar consolidation. These results do not support a major role for Hib vaccine in overall pneumonia-prevention programmes. Nevertheless, the study identified high incidences of Hib meningitis and pneumonia; inclusion of Hib vaccine in routine infant immunisation programmes in Asia deserves consideration.
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February 2005

Acute respiratory illness incidence and death among children under two years of age on Lombok Island, Indonesia.

Am J Trop Med Hyg 2002 Feb;66(2):175-9

Disease Prevention and Health Promotion Division, West Nusa Tenggara Provincial Health Office, Lombok, Indonesia.

No childhood pneumonia incidence data for Indonesia exist, and few data exist for Asia as a whole. From February 1, 1998, to January 31, 1999, we conducted acute respiratory illness (ARI) surveillance among children < 24 months of age in 50 mainly rural villages on Lombok Island, Indonesia. The total number of child-years at risk during the study period was 17,015. The documented incidences of simple, severe, hospitalized, and radiologically confirmed alveolar pneumonia were 21, 8.3, 5.3, and 1.8 per 100 child-years of observation, respectively. For all outcomes, the incidence was higher among younger and rural children. All cause and ARI-specific infant mortality rates were 84 and 33 per 1,000 live births, respectively. More than 65% of deaths due to ARI occurred outside of a hospital setting. The incidence of pneumonia is high in Lombok. Interventions should include introducing vaccines to prevent infections leading to pneumonia and increasing the access of critically ill infants to the health care system.
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February 2002