To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with ...their importance for national surveillance and epidemiological research.
We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups.
127 pathogens were scored. Eighty-six experts participated in the weighting; "Case fatality rate" was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus.
While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings.
Summary
Objective To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence‐based classification that would better ...reflect clinical severity.
Methods We followed suspected dengue cases daily in seven countries across South‐east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre‐defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not.
Results A total of 2259 patients were recruited during 2006–2007 and 230 (13%) of the 1734 laboratory‐confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three‐tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression.
Conclusions Based on these results, a revised classification system comprised of two entities, ‘Dengue’ and ‘Severe Dengue’, was proposed and has now been incorporated into the new WHO guidelines.
Objectif: Evaluer la classification actuelle de l’OMS pour la dengue dans tous les groupes d’âge et sur une vaste étendue géographique et élaborer une classification révisée, fondée sur des preuves permettant de mieux tenir compte de la sévérité clinique.
Méthodes: Nous avons suivi quotidiennement des cas suspects de dengue dans 7 pays d’Asie du sud‐est et d’Amérique latine, puis les avons classé en trois groupes d’intervention décrivant la sévérité de la maladie en fonction du niveau général du soutien médical et infirmier nécessaire. En utilisant un plan d’analyse prédéfini, nous avons exploré les profils cliniques et de laboratoire, caractéristiques de ces catégories d’intervention et avons soumis pour avis, les options les plus prometteuses pour un système révisé de classification, à un groupe d’experts indépendants de l’OMS pour la dengue. Les signes avant‐coureurs potentiels ont également étéévalués en comparant les données contemporaines de patients qui ont évolué vers une maladie sévère avec les données de ceux qui n’ont pas évolué de cette façon.
Résultats: 2259 patients ont été recrutés en 2006–2007 et 230 (13%) des 1734 patients avec une confirmation de laboratoire ont nécessité une intervention majeure. En appliquant le système actuel de l’OMS, 47/210 (22%) patients atteints de choc ne remplissaient pas tous les critères de dengue hémorragique. Toutefois, aucune révision tertiaire non plus n’a pu décrire adéquatement les différents groupes de sévérité. L’inclusion de complications facilement reconnaissables (choc/pertes vasculaires sévères et/ou saignements sévères et/ou dysfonctionnement sévère d’un organe) a été nécessaire pour concevoir un système permettant d’identifier les patients nécessitant une intervention majeure, avec une sensibilité et une spécificité suffisantes pour être utiles dans la pratique. Seul un petit nombre de sujets (5%) a progressé vers une maladie sévère alors qu’ils étaient sous observation; plusieurs signes d’alerte ont été identifiés, mais beaucoup plus d’études sont nécessaires pour caractériser complètement les caractéristiques associées à la progression de la maladie.
Conclusions: Sur base de ces résultats, un système de classification révisé, composé de deux entités, “Dengue” et “ dengue sévère “, a été proposé et a été intégré dans les nouvelles directives de l’OMS.
The disease transmitting mosquito Aedes Aegypti is an increasing global threat. It breeds in small artificial containers such as rainwater tanks and can be characterized by a short flight range. The ...resulting high spatial variability of abundance is challenging to model. Therefore, we tested an approach to map water tank density as a spatial proxy for urban Aedes Aegypti habitat suitability. Water tank density mapping was performed by a semi-supervised self-training approach based on open accessible satellite imagery for the city of Rio de Janeiro. We ran a negative binomial generalized linear regression model to evaluate the statistical significance of water tank density for modeling inner-urban Aedes Aegypti distribution measured by an entomological surveillance system between January 2019 and December 2021. Our proposed semi-supervised model outperformed a supervised model for water tank detection with respect to the F1-score by 22%. Water tank density was a significant predictor for the mean eggs per trap rate of Aedes Aegypti. This shows the potential of the proposed indicator to enrich urban entomological surveillance systems to plan more targeted vector control interventions, presumably leading to less infectious rates of dengue, Zika, and chikungunya in the future.
•Urban water tank density maps to support Aedes Aegypti control on flight range scale.•Large-scale object detection with low manual labeling effort on open accessible data.•Model improvement by 22% (F1-score) through semi-supervised self-training.•Significance of water tank density for modeling entomological surveillance data.
IntroductionCausal methods have been adopted and adapted across health disciplines, particularly for the analysis of single studies. However, the sample sizes necessary to best inform decision-making ...are often not attainable with single studies, making pooled individual-level data analysis invaluable for public health efforts. Researchers commonly implement causal methods prevailing in their home disciplines, and how these are selected, evaluated, implemented and reported may vary widely. To our knowledge, no article has yet evaluated trends in the implementation and reporting of causal methods in studies leveraging individual-level data pooled from several studies. We undertake this review to uncover patterns in the implementation and reporting of causal methods used across disciplines in research focused on health outcomes. We will investigate variations in methods to infer causality used across disciplines, time and geography and identify gaps in reporting of methods to inform the development of reporting standards and the conversation required to effect change.Methods and analysisWe will search four databases (EBSCO, Embase, PubMed, Web of Science) using a search strategy developed with librarians from three universities (Heidelberg University, Harvard University, and University of California, San Francisco). The search strategy includes terms such as ‘pool*’, ‘harmoniz*’, ‘cohort*’, ‘observational’, variations on ‘individual-level data’. Four reviewers will independently screen articles using Covidence and extract data from included articles. The extracted data will be analysed descriptively in tables and graphically to reveal the pattern in methods implementation and reporting. This protocol has been registered with PROSPERO (CRD42020143148).Ethics and disseminationNo ethical approval was required as only publicly available data were used. The results will be submitted as a manuscript to a peer-reviewed journal, disseminated in conferences if relevant, and published as part of doctoral dissertations in Global Health at the Heidelberg University Hospital.
The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international ...chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers.
Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries.
In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years.
The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It is proposed to use a threshold incidence of > 1 case per 100,000 visits to consider targeted malaria prophylaxis recommendations to minimize use of chemoprophylaxis for low risk exposure during visits to S-E Asia. Policy needs to be adjusted regularly to reflect the changing risk.
Objective
Sulphadoxine–pyrimethamine (SP) is widely used as intermittent preventive treatment (IPT) for malaria in pregnant women in Sub‐Saharan Africa. There are reports of wide‐spread SP resistance ...in countries where SP had once been used as a first‐line treatment. It is unclear whether the development of SP resistance also affects countries where SP is mainly used in the context of IPT, as is the case in Burkina Faso. To assess the efficacy of SP‐based IPT, we monitored the prevalence of SP conferring genetic mutations in the genes dhfr and dhps in Plasmodium falciparum populations in a rural area of Burkina Faso over a period of 13 years.
Methods
Molecular epidemiological study consisted of six consecutive cross‐sectional surveys of rainy and dry seasons (2009–2012). Data from the rainy season in 2000 served as a baseline. Mutations in dhfr and dhps associated with SP resistance were analysed by pyrosequencing in 861 parasite‐positive samples.
Results
The prevalence of the SP resistance conferring triple dhfr mutation 51I, 59R, 108N increased from 1.3% in the rainy season of 2000 to 35.3% in 2009, and 54.3% in 2011 (P ≤ 0.001). Comparing rainy and dry seasons, we observed an increasing step‐like pattern with higher prevalence of the dhfr triple mutant in the respective dry season compared with the preceding rainy season. The proportion of the dhps 437Gly mutation in the rainy season of 2000 was 53.2% and subsequently increased to 77.6% in 2009 (P ≤ 0.001).
Conclusion
The increase in molecular markers linked with SP resistance jeopardises the efficacy of IPTp and the planned IPTi interventions in Burkina Faso, calling for careful monitoring of genotypic resistance markers and in vivo validation of IPT efficacy.
Objectif
Le sulfadoxine‐pyriméthamine (SP) est largement utilisé comme traitement préventif intermittent (TPI) du paludisme chez les femmes enceintes en Afrique subsaharienne. Il y a des rapports sur la résistance répandue au SP dans les pays où il avait autrefois été utilisé comme traitement de première ligne. Il est difficile de savoir si le développement de la résistance au SP affecte aussi les pays où il est principalement utilisé dans le contexte du TPI, comme par exemple au Burkina‐Faso. Pour évaluer l'efficacité du TPI basé sur le SP, nous avons surveillé la prévalence des mutations génétiques associées au SP dans les gènes dhfr et dhps dans des populations de Plasmodium falciparum dans une zone rurale du Burkina‐Faso sur plus de 13 ans.
Méthodes
Etude d’épidémiologie moléculaire composée de six enquêtes transversales consécutives en saisons sèches et pluvieuses (de 2009 à 2012). Les données de la saison des pluies de 2000 ont servi de base. Les mutations dans dhfr et dhps associées à la résistance au SP ont été analysées par pyroséquençage dans 861 échantillons positifs pour le parasite.
Résultats
La prévalence de la résistance au SP associée à une triple mutation dhfr (51I, 59R, 108N) a augmenté de 1,3% au cours de la saison des pluies de l'année 2000 à 35,3% en 2009 et à 54,3% en 2011 (p < = 0,001). En comparant la saison des pluies et la saison sèche, nous avons observé un profil d'augmentation par étape avec une prévalence plus élevée des triples mutants dhfr en saison sèche par rapport aux saisons des pluies respectives. La proportion des mutations 437Gly dans dhps dans la saison des pluies de 2000 était de 53,2% et a par la suite augmenté à 77,6% en 2009 (p < = 0,001).
Conclusion
L'augmentation des marqueurs moléculaires liés à la résistance au SP met en péril l'efficacité du programme TPI et des interventions TPI prévues au Burkina‐Faso, appelant à une surveillance attentive des marqueurs génotypiques de résistance et à la validation in vivo de l'efficacité du TPI.
Objetivo
La sulfadoxina‐pirimetamina (SP) se utiliza de forma amplia como tratamiento preventivo intermitente (IPT) para la malaria en mujeres embarazadas en África subsahariana. Hay informes sobre la amplia diseminación de la resistencia a SP en países en donde se había utilizado alguna vez como primera línea de tratamiento. No está claro si el desarrollo de la resistencia a SP también afecta a países en donde la SP se utiliza principalmente dentro del contexto del IPT, como es el caso de Burkina Faso. Para evaluar la eficacia del IPT basado en SP, hemos monitorizado la prevalencia de mutaciones genéticas inducidas por SP en los genes dhfr y dhps en poblaciones de Plasmodium falciparum en un área rural de Burkina Faso en los últimos 13 años.
Métodos
Estudio de epidemiología molecular que consistió en seis estudios croseccionales consecutivos, durante épocas de lluvia y secas (2009‐2012). Los datos de la época de lluvias en el 2000 sirvieron de base. Las mutaciones en dhfr y dhps asociadas con resistencia a SP se analizaron mediante pirosecuenciación en 861 muestras positivas para parásitos.
Resultados
La prevalencia de resistencia a SP por una triple mutación en dhfr 51I, 59R, 108N aumentó del 1.3% en la época de lluvias del 2000 al 35.3% en 2009, y 54.3% en el 2011 (p<= 0.001). Comparando la época de lluvias y la época seca hemos observado un patrón incremental escalonado con una mayor prevalencia del triple mutante dhfr en la época seca respectiva, comparado con la época lluviosa precedente. La proporción de la mutación dhps 437Gly durante la época lluviosa del 2000 era del 53.2% y aumentó después al 77.6% en el 2009 (p< =0.001).
Conclusión
El aumento en marcadores moleculares relacionado con la resistencia al SP pone en peligro la eficacia del IPTp y las intervenciones de IPTi planeadas en Burkina Faso, requiriendo una monitorización cuidadosa de los marcadores genotípicos de resistencia y la validación in vivo de la eficacia del IPT.
Due to their rising incidence and progressive geographical spread, infections with mosquito-borne viruses, such as dengue (DENV), chikungunya and zika virus, have developed into major public health ...challenges. Since all of these viruses may cause similar symptoms and can occur in concurrent epidemics, tools for their differential diagnosis and epidemiological monitoring are of urgent need.
Here we report the application of a novel strategy to rapidly generate monoclonal antibodies (mAbs) against native viral antigens, exemplified for the DENV nonstructural glycoprotein 1 (NS1). The described system is based on the immunization of mice with transfected mammalian cells expressing the target antigens in multiple displays on their cell surface and thereby presenting them efficiently to the host immune system in their native conformation. By applying this cell-based approach to the DENV NS1 protein of serotypes 1 (D1NS1) and 4 (D4NS1), we were able to rapidly generate panels of DENV NS1 serotype cross-reactive, as well as D1NS1- and D4NS1 serotype-specific mAbs. Our data show that the generated mAbs were capable of recognizing the endogenous NS1 protein in DENV-containing biological samples.
The use of this novel immunization strategy, allows for a fast and efficient generation of hybridoma cell lines, producing mAbs against native viral antigens. Envisaged applications of the mAbs include the development of test platforms enabling a differentiation of the DENV serotypes and high resolution immunotyping for epidemiological studies.
Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel ...Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level,
was identified in 570 (39%) and
in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.
Malaria transmission was reported to have declined in some East African countries. However, a comparable trend has not been confirmed for West Africa. This study aims to assess the dynamics of ...parasite prevalence and malaria species distribution over time in an area of highly seasonal transmission in Burkina Faso. The aim was also to compare frequency of asymptomatic parasitaemia between wet and dry season by parasite density status and age group.
During the years 2009-2012, six cross-sectional studies were performed in the rural village Bourasso in the Nouna Health District in north-west Burkina Faso. In subsequent rainy and dry seasons blood samples were collected to assess the parasite prevalence, species, density and clinical parameters. In total, 1,767 children and adults were examined and compared to a baseline collected in 2000.
The microscopical parasite prevalence (mainly P. falciparum) measured over the rainy seasons decreased significantly from 78.9% (2000) to 58.4%, 55.9% and 49.3%, respectively (2009-2011; p <0.001). The frequency of Plasmodium malariae infections (mono- and co-infections) decreased parallel to the overall parasite prevalence from 13.4% in 2000 to 2.1%, 4.1% and 4.7% in 2009-2011 (p <0.001). Comparing parasite-positive subjects from the rainy season versus dry season, the risk of fever was significantly reduced in the dry season adjusting for parasite density (grouped) and age group.
The results of this study suggest a decline of malaria transmission over the rainy seasons between 2000 and 2009-2011 in the region of Nouna, Burkina Faso. The decreased transmission intensity was associated with lower prevalence of P. malariae infections (both mono-infections and co-infections). Asymptomatic parasitaemia was more frequent in the dry season even adjusting for parasite density and age group in a multivariate regression. Possible reasons for this observation include the existence of less pathogenic Plasmodium falciparum genotypes prevailing in the dry season, or the effect of a reduced incidence density during the dry season.
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