Pulmonary melioidosis in CAMBODIA: a prospective study

<p>Abstract</p> <p>Background</p> <p>Melioidosis is a disease caused by <it>Burkholderia pseudomallei </it>and considered endemic in South-East Asia but remains poorly documented in Cambodia. We report the first series of hospitalized pulmonary melioidosis cases identified in Cambodia describing clinical characteristics and outcomes.</p> <p>Methods</p> <p>We characterized cases of acute lower respiratory infections (ALRI) that were identified through surveillance in two provincial hospitals. Severity was defined by systolic blood pressure, cardiac frequency, respiratory rate, oxygen saturation and body temperature. <it>B. pseudomallei </it>was detected in sputum or blood cultures and confirmed by API20NE gallery. We followed up these cases between 6 months and 2 years after hospital discharge to assess the cost-of-illness and long-term outcome.</p> <p>Results</p> <p>During April 2007 - January 2010, 39 ALRI cases had melioidosis, of which three aged ≤2 years; the median age was 46 years and 56.4% were males. A close contact with soil and water was identified in 30 patients (76.9%). Pneumonia was the main radiological feature (82.3%). Eleven patients were severe cases. Twenty-four (61.5%) patients died including 13 who died within 61 days after discharge. Of the deceased, 23 did not receive any antibiotics effective against <it>B. pseudomallei</it>. Effective drugs that were available did not include ceftazidime. Mean total illness-related costs was of US$65 (range$25-$5000). Almost two-thirds (61.5%) incurred debt and 28.2% sold land or other belongings to pay illness-related costs.</p> <p>Conclusions</p> <p>The observed high fatality rate is likely explained by the lack or limited access to efficient antibiotics and under-recognition of the disease among clinicians, which led to inappropriate therapy.</p

Klebsiella pneumoniae related community-acquired acute lower respiratory infections in CAMBODIA: clinical characteristics and treatment

<p>Abstract</p> <p>Background</p> <p>In many Asian countries, <it>Klebsiella pneumoniae </it>(KP) is the second pathogen responsible for community-acquired pneumonia. Yet, very little is known about <it>KP </it>etiology in ALRI in Cambodia, a country that has one of the weakest medical infrastructures in the region. We present here the first clinico-radiological description of <it>KP </it>community-acquired ALRI in hospitalized Cambodian patients.</p> <p>Methods</p> <p>Through ALRI surveillance in two provincial hospitals, <it>KP </it>was isolated from sputum and blood cultures, and identified by API20E gallery from patients ≥ 5 years-old with fever and respiratory symptoms onset ≤14 days. Antibiotics susceptibility testing was provided systematically to clinicians when bacteria were isolated. We collected patients' clinical, radiological and microbiological data and their outcome 3 months after discharge. We also compared <it>KP</it>-related with other bacteria-related ALRI to determine risk factors for <it>KP </it>infection.</p> <p>Results</p> <p>From April 2007 to December 2009, 2315 ALRI patients ≥ 5 years-old were enrolled including 587 whose bacterial etiology could be assigned. Of these, 47 (8.0%) had <it>KP </it>infection; their median age was 55 years and 68.1% were females. Reported prior medication was high (42.5%). Patients' chest radiographs showed pneumonia (61.3% including 39% that were necrotizing), preexisting parenchyma lesions (29.5%) and pleural effusions alone (4.5%) and normal parenchyma (4.5%). Five patients had severe conditions on admission and one patient died during hospitalization. Of the 39 patients that were hospital discharged, 14 died including 12 within 1 month after discharge. Only 13 patients (28%) received an appropriate antibiotherapy. Extended-spectrum beta-lactamases (ESBL) - producing strains were found in 8 (17.0%) patients. Female gender (Odds ratio (OR) 2.1; <it>p </it>= 0.04) and diabetes mellitus (OR 3.1; <it>p </it>= 0.03) were independent risk factors for <it>KP</it>-related ALRI.</p> <p>Conclusions</p> <p><it>KP </it>ALRI in Cambodia has high fatality rate, are more frequently found in women, and should be considered in diabetic patients. The extremely high frequency of ESBL-producing strains in the study is alarming in the context of uncontrolled antibiotic consumption and in absence of microbiology capacity in most public-sector hospitals.</p

Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. Methods: In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. Findings: We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI −0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus −0·2 months [−0·6 to 0·1]; respiratory syncytial virus 0·1 months [−0·2 to 0·4]). Interpretation: This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Funding: European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU)

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

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

Modélisation du processus d'application des connaissances entre Recherche et Santé publique

Health research generates a growing body of scientific literature. However this scientific production is not systematically integrated into public health. Researchers and policy makers have operations and constraints that do not naturally facilitate exchanges and knowledge translation (KT) from research into health policy. This thesis focuses on the gap between research and health policy and analyzes the determinants of success or failure of KT between research and health policies in Cambodia.The first chapter defines the KT process and reviews the scarce KT interventions reported in the literature. This review shows that KT is not a new concept, even though it remains somewhat under applied. In this chapter, we also look at the tools used to model processes and health research. We conclude that the UML (unified modeling language) appears to be the best modeling tool available to analyze the KT process.The second chapter describes a KT intervention we implemented and subsequently analyzes its impact and the determinants of its partial success, using UML tools. Most of identified barriers were related to either a lack of synchronization between the production of knowledge and the health policy making, or to some lack of mutual understanding between researchers and policymakers. Among the contributing factors, we identified the key roles of an actor who was both policymaker and researcher, and of organizations which acted as communication vectors between researchers and policymakers.The third chapter first includes the quantitative and qualitative analysis of the health research scientific production in Cambodia. It shows that even though more than 85% of articles published were accessible free of charge they do not cover all public health priorities of Cambodia. The following study identifies the main sources of information for policy makers who contributed to the preparation of the first national health policy against antibiotic resistance. We show that, as elsewhere, the scientific literature is not an appropriate medium to communicate with the Cambodian health authorities.Finally in the last chapter we integrate the various findings from previous chapters into the analysis of the determinants of KT. From this analysis we draw a generic UML model (class diagram), that we test on four research projects also conducted in Cambodia. This model may be used in Cambodia or in other countries with limited resources.We conclude that if the principles of the CA can be summarized in a few simple rules, they face many barriers when they are operationally implemented. KT is a dynamic, complex , iterative, and highly context –dependent process. A number of barriers to KT identified in Cambodia are identical to those found in the West. Among the facilitating factors for KT, we show that the connection between research institutions and national or provincial health is a major asset.La recherche en santé génère des publications scientifiques de plus en plus nombreuses. Or cette production scientifique n'est pas systématiquement intégrée dans la santé publique. Chercheurs et décideurs politiques ont des fonctionnements et des contraintes qui ne facilitent pas naturellement les échanges et l'application des connaissances (AC) issues de la recherche dans les politiques de santé. Cette thèse porte sur cet écart entre recherche et politiques de santé et analyse les facteurs déterminants du succès ou de l'échec du transfert des connaissances entre recherche et politiques de santé au Cambodge. Le premier chapitre définit le processus d'application des connaissances (AC) et passe en revue les rares interventions d'AC rapportées dans la littérature. Cette revue montre que l'AC n'est pas un concept nouveau, même s'il demeure peu maîtrisé et peu développé. Dans ce chapitre, nous passons également en revue les outils utilisés pour modéliser des processus et des recherches en santé. Nous concluons que l'UML (langage unifié de modélisation) apparait comme le meilleur outil de modélisation disponible pour analyser le processus d'AC. Le deuxième chapitre décrit une intervention d'AC que nous avons mise en place, puis analyse son impact et les déterminants de son succès partiel, utilisant pour cela les outils UML. La plupart des barrières étaient liées soit à une désynchronisation entre la production de connaissances, soit à la prise de décisions politiques et au manque de connaissance mutuelle entre chercheurs et décideurs. Parmi les facteurs favorisants, on a relevé le rôle déterminant d'un acteur qui était à la fois ‘décideur' et chercheur, ainsi que les bénéfices liés à l'intervention vecteurs de communication entre chercheurs et décideurs. Le troisième chapitre analyse tout d'abord quantitativement et qualitativement la production scientifique de la recherche en santé au Cambodge et montre que cette production scientifique ne couvre qu'en partie les priorités de santé publique du Cambodge même si plus de 85% des articles publiés sur la santé au Cambodge étaient accessibles gratuitement. L'étude suivante permet d'identifier les principales sources d'information des décideurs politiques ayant contribué à la préparation de la première loi nationale de lutte contre l'antibio-résistance. Nous montrons que la littérature scientifique n'est pas, au Cambodge comme ailleurs, un média approprié pour communiquer avec des autorités sanitaires. Finalement, en dernier chapitre, nous intégrons les diverses conclusions des précédents chapitres dans l'analyse des déterminants de l'AC, en tirons un modèle générique UML (diagramme de classes), que nous vérifions ensuite sur quatre projets de recherche conduits également au Cambodge dont trois ont réussi leur transfert de connaissances. Ce modèle qui pourrait être utilisable au Cambodge ou dans d'autres pays à ressources limitées. Nous concluons que si les principes de l'AC peuvent se résumer en quelques règles, ils se heurtent à de nombreuses barrières lorsqu'ils sont déclinés opérationnellement. L'AC est un processus complexe, itératif, dynamique et très contexte-dépendant. Un certain nombre de barrières à l'AC identifiées au Cambodge sont strictement identiques à celles rencontrées en Occident. Parmi les facteurs favorisants de l'AC, nous montrons que le rapprochement entre chercheurs et institutions nationales ou provinciales de santé est un atout majeur

Modeling the knowledge translation process between Research and Public Health

La recherche en santé génère des publications scientifiques de plus en plus nombreuses. Or cette production scientifique n'est pas systématiquement intégrée dans la santé publique. Chercheurs et décideurs politiques ont des fonctionnements et des contraintes qui ne facilitent pas naturellement les échanges et l'application des connaissances (AC) issues de la recherche dans les politiques de santé. Cette thèse porte sur cet écart entre recherche et politiques de santé et analyse les facteurs déterminants du succès ou de l'échec du transfert des connaissances entre recherche et politiques de santé au Cambodge. Le premier chapitre définit le processus d'application des connaissances (AC) et passe en revue les rares interventions d'AC rapportées dans la littérature. Cette revue montre que l'AC n'est pas un concept nouveau, même s'il demeure peu maîtrisé et peu développé. Dans ce chapitre, nous passons également en revue les outils utilisés pour modéliser des processus et des recherches en santé. Nous concluons que l'UML (langage unifié de modélisation) apparait comme le meilleur outil de modélisation disponible pour analyser le processus d'AC. Le deuxième chapitre décrit une intervention d'AC que nous avons mise en place, puis analyse son impact et les déterminants de son succès partiel, utilisant pour cela les outils UML. La plupart des barrières étaient liées soit à une désynchronisation entre la production de connaissances, soit à la prise de décisions politiques et au manque de connaissance mutuelle entre chercheurs et décideurs. Parmi les facteurs favorisants, on a relevé le rôle déterminant d'un acteur qui était à la fois ‘décideur' et chercheur, ainsi que les bénéfices liés à l'intervention vecteurs de communication entre chercheurs et décideurs. Le troisième chapitre analyse tout d'abord quantitativement et qualitativement la production scientifique de la recherche en santé au Cambodge et montre que cette production scientifique ne couvre qu'en partie les priorités de santé publique du Cambodge même si plus de 85% des articles publiés sur la santé au Cambodge étaient accessibles gratuitement. L'étude suivante permet d'identifier les principales sources d'information des décideurs politiques ayant contribué à la préparation de la première loi nationale de lutte contre l'antibio-résistance. Nous montrons que la littérature scientifique n'est pas, au Cambodge comme ailleurs, un média approprié pour communiquer avec des autorités sanitaires. Finalement, en dernier chapitre, nous intégrons les diverses conclusions des précédents chapitres dans l'analyse des déterminants de l'AC, en tirons un modèle générique UML (diagramme de classes), que nous vérifions ensuite sur quatre projets de recherche conduits également au Cambodge dont trois ont réussi leur transfert de connaissances. Ce modèle qui pourrait être utilisable au Cambodge ou dans d'autres pays à ressources limitées. Nous concluons que si les principes de l'AC peuvent se résumer en quelques règles, ils se heurtent à de nombreuses barrières lorsqu'ils sont déclinés opérationnellement. L'AC est un processus complexe, itératif, dynamique et très contexte-dépendant. Un certain nombre de barrières à l'AC identifiées au Cambodge sont strictement identiques à celles rencontrées en Occident. Parmi les facteurs favorisants de l'AC, nous montrons que le rapprochement entre chercheurs et institutions nationales ou provinciales de santé est un atout majeur.Health research generates a growing body of scientific literature. However this scientific production is not systematically integrated into public health. Researchers and policy makers have operations and constraints that do not naturally facilitate exchanges and knowledge translation (KT) from research into health policy. This thesis focuses on the gap between research and health policy and analyzes the determinants of success or failure of KT between research and health policies in Cambodia.The first chapter defines the KT process and reviews the scarce KT interventions reported in the literature. This review shows that KT is not a new concept, even though it remains somewhat under applied. In this chapter, we also look at the tools used to model processes and health research. We conclude that the UML (unified modeling language) appears to be the best modeling tool available to analyze the KT process.The second chapter describes a KT intervention we implemented and subsequently analyzes its impact and the determinants of its partial success, using UML tools. Most of identified barriers were related to either a lack of synchronization between the production of knowledge and the health policy making, or to some lack of mutual understanding between researchers and policymakers. Among the contributing factors, we identified the key roles of an actor who was both policymaker and researcher, and of organizations which acted as communication vectors between researchers and policymakers.The third chapter first includes the quantitative and qualitative analysis of the health research scientific production in Cambodia. It shows that even though more than 85% of articles published were accessible free of charge they do not cover all public health priorities of Cambodia. The following study identifies the main sources of information for policy makers who contributed to the preparation of the first national health policy against antibiotic resistance. We show that, as elsewhere, the scientific literature is not an appropriate medium to communicate with the Cambodian health authorities.Finally in the last chapter we integrate the various findings from previous chapters into the analysis of the determinants of KT. From this analysis we draw a generic UML model (class diagram), that we test on four research projects also conducted in Cambodia. This model may be used in Cambodia or in other countries with limited resources.We conclude that if the principles of the CA can be summarized in a few simple rules, they face many barriers when they are operationally implemented. KT is a dynamic, complex , iterative, and highly context –dependent process. A number of barriers to KT identified in Cambodia are identical to those found in the West. Among the facilitating factors for KT, we show that the connection between research institutions and national or provincial health is a major asset

Melioidosis Requires Better Data Sharing for Improved Diagnosis and Management in the Mekong Region

International audienc