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Suresh J Antony,
Michelle A Davis,
Monique G Davis,
Nouf K Almaghlouth,
Fernando Del Rey,
Muhammad U Arian,
Bharat V Prakash
Journal of Medical Virology, Accepted Article.
Sayed Mahdid Marashi,
Steven Robert Brenner
Muhammad Junaid Tahir,
Ahsun Rizwan Siddiqi,
Jordi A Matías‐Guiu,
Giovanni Maria Guarrera,
The efficacy of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria in south-western Ethiopia is poorly documented. Regular monitoring of drug efficacy is an important tool for supporting national treatment policies and practice. This study investigated the therapeutic efficacy of AL for the treatment of P. falciparum malaria in Ethiopia.
The study was a one-arm, prospective, evaluation of the clinical and parasitological, responses to directly observed treatment with AL among participants 6 months and older with uncomplicated P. falciparum malaria. Real-time polymerase chain reaction (PCR) and nested PCR reaction methods were used to quantify and genotype P. falciparum. A modified protocol based on the World Health Organization 2009 recommendations for the surveillance of anti-malarial drug efficacy was used for the study with primary outcomes, clinical and parasitological cure rates at day-28. Secondary outcomes assessed included patterns of fever and parasite clearance. Cure rate on day-28 was assessed by intention to treat (ITT) and per protocol (PP) analysis. Parasite genotyping was also performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infection.
Of the 80 study participants enrolled, 75 completed the follow-up at day-28 with ACPR. For per protocol (PP) analysis, PCR-uncorrected and-corrected cure rate of AL among the study participants was 94.7% (95% CI 87.1–98.5) and 96% (95% CI 88.8–99.2), respectively. For intention to treat (ITT) analysis, the cure rate was 90% (95% CI 88.8–99.2). Based on Kaplan–Meier survival estimate, the cumulative incidence of failure rate of AL was 3.8% (95% CI 1.3–11.4). Only three participants 3.8% (95% CI 0.8–10.6) of the 80 enrolled participants were found to be positive on day-3. The day three-positive participants were followed up to day 28 and did not correspond to treatment failures observed during follow-up. Only 7.5% (6/80) of the participants were gametocyte-positive on enrollment and gametocytaemia was absent on day-2 following treatment with AL.
The therapeutic efficacy of AL is considerably high (above 90%). AL remained highly efficacious in the treatment of uncomplicated malaria in the study area resulted in rapid fever and parasite clearance as well as low gametocyte carriage rates despite the use of this combination for more than 15 years.
Hepatitis B virus (HBV) infection is one of the greatest public health burdens, particularly for people living with several barriers to access to health care services, such as the hill tribe adult population in Thailand. People aged 25 years and over who are out of the target population for HBV immunization under the national Expanded Program on Immunization (EPI) are at risk of HBV infection. The study aimed to estimate the prevalence and determine the factors associated with HBV infection among hill tribe adults aged 25 years and over living in Chiang Rai Province, Thailand.
A cross-sectional study design was used to collect information on hill tribe adults aged 25 years and over living in 36 selected hill tribe villages in Chiang Rai Province. All people living in the selected villages who met the criteria were invited to participate in the study. A validated questionnaire and a 5-mL blood specimen were used as research instruments. Hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface (anti-HBs), and antibody to hepatitis B core (anti-HBc) were detected by using the Wondfo Test Kit@, which has high sensitivity and specificity. Logistic regression was used to detect the associations between variables at the significance level of α = 0.05.
A total of 1491 individuals were recruited into the analysis; 60.8% were females, 81.3% were aged between 30 and 60 years, and 86.0% were married. The majority were illiterate (54.9%), were Buddhist (55.7%), worked in agricultural sectors (87.3%), and had an annual income of less than 50,000 baht per year (72.9%). The overall prevalence of hepatitis B infection was 26.6%; 7.6% were positive for HBsAg, 19.2% were positive for anti-HBs, and 18.9% were positive for anti-HBc. In the multivariate analysis, three variables were found to be associated with hepatitis B infection: those who were in the Yao and Lisu tribes had a 1.64-fold (95% CI = 1.08–2.49) and a 1.93-fold (95% CI = 1.10–3.31) greater chance, respectively, of HBV infection than did those in the Karen tribe; those who were Christian had a 1.41-fold (95% CI = 1.06–1.87) greater chance of HBV infection than did those who were Buddhist; and those who did not use alcohol had a 1.29-fold (95% CI = 1.01–1.65) greater chance of HBV infection than did those who used alcohol.
It is necessary to develop and implement effective public health interventions among hill tribe adult populations who are not part of the EPI-targeted population, particularly Christians, those in the Lisu and Yao tribes, and those who do not use alcohol, to reduce the HBV infection rate, save lives and reduce medical expenses.
In order to effectively combat Tuberculosis, resources to diagnose and treat TB should be allocated effectively to the areas and population that need them. Although a wealth of subnational data on TB is routinely collected to support local planning, it is often underutilized. Therefore, this study uses spatial analytical techniques and profiling to understand and identify factors underlying spatial variation in TB case notification rates (CNR) in Bangladesh, Nepal and Pakistan for better TB program planning.
Spatial analytical techniques and profiling was used to identify subnational patterns of TB CNRs at the district level in Bangladesh (N = 64, 2015), Nepal (N = 75, 2014) and Pakistan (N = 142, 2015). A multivariable linear regression analysis was performed to assess the association between subnational CNR and demographic and health indicators associated with TB burden and indicators of TB programme efforts. To correct for spatial dependencies of the observations, the residuals of the multivariable models were tested for unexplained spatial autocorrelation. Spatial autocorrelation among the residuals was adjusted for by fitting a simultaneous autoregressive model (SAR).
Spatial clustering of TB CNRs was observed in all three countries. In Bangladesh, TB CNR were found significantly associated with testing rate (0.06%, p
Pneumocystis jirovecii pneumonia (PJP) can be challenging to diagnose, often requiring bronchoscopy. Since most patients suspected of PJP undergo imaging, we hypothesized that the findings of these studies could help estimate the probability of disease prior to invasive testing.
We created a cohort of patients who underwent bronchoscopy specifically to diagnose PJP and conducted a nested case-control study to compare the radiographic features between patients with (n = 72) and without (n = 288) pathologically proven PJP. We used multivariable logistic regression to identify radiographic features independently associated with PJP.
Chest x-ray findings poorly predicted the diagnosis of PJP. However, multivariable analysis of CT scan findings found that “increased interstitial markings” (OR 4.3; 95%CI 2.2–8.2), “ground glass opacities” (OR 3.3; 95%CI 1.2–9.1) and the radiologist’s impression of PJP being “possible” (OR 2.0; 95%CI 1.0–4.1) or “likely” (OR 9.3; 95%CI 3.4–25.3) were independently associated with the final diagnosis (c-statistic 0.75).
Where there is clinical suspicion of PJP, the use of CT scan can help determine the probability of PJP. Identifying patients at low risk of PJP may enable better use of non-invasive testing to avoid bronchoscopy while higher probability patients could be prioritized.
Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment.
Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7–10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment.
The South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24–1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product.
Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.
This trial was registered on 17 October 2017 with the South African National Clinical Trial Register (http://www.sanctr.gov.za/; BV-trial1; DOH-27-1117-5579).
Toxoplasma gondii is an obligate intracellular parasite that can infect almost all warm-blooded animals, avian species and humans. Toxoplasmosis is asymptomatic in healthy individuals, whereas it may lead to death in immune suppressed or deficient patients. A vaccine against T. gondii is required to prevent consequences of the infection. The aim of this study is to generate a multivalent recombinant protein vaccine against T. gondii.
49 previously discovered antigenic proteins of T gondii were evaluated by their expression level in E. coli and by comprehensive bioinformatics analyses to determine antigenic epitopes. Based on these analyses, six vaccine candidate proteins were selected to generate a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V. Humoral and cellular immune responses were determined by flow cytometry and ELISA. Vaccinated mice were challenged with T. gondii Ankara strain tachyzoites.
In mice vaccinated with hexavalent vaccine, strong total IgG (P
Frederic Lamoth, Emmanouil Glampedakis, Noémie Boillat-Blanco, Mauro Oddo, Jean-Luc Pagani
The devastating pandemia of the novel Coronavirus Disease 2019 (COVID-19) resulting from the emergence of SARS-CoV-2 is of particular concern because of the development of acute respiratory distress syndrome (ARDS), which is associated with high mortality rates. Besides the impact of viral pneumonia itself, the prognosis can be affected by other infectious complications, such as ventilator-associated bacterial pneumonia or fungal infections. Previous reports of a significant risk of invasive pulmonary aspergillosis (IPA) among patients with severe Influenza raises questions about a similar association with COVID-19 .
N. Robert Bergquist
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), a program focusing on schistosomiasis control in sub-Saharan Africa between 2008 and 2019, investigated ways to improve coverage and efficacy of ongoing chemotherapy programs and concluded that because of continued transmission, mass distribution of praziquantel cannot eliminate the disease without complementary control activities. Schistosomiasis Consortium for Operational Research and Evaluation’s activities comprised large-scale, multicountry field studies comparing various mass drug administration strategies and some specific research avenues, such as assessment of high-sensitivity diagnostics, identification of hotspots, quantification of the role of the snail host, predictive modeling, and changes in schistosome population genetics under drug pressure. The discoveries made and the insights gained regarding cost-effective strategies for delivering preventive chemotherapy should assist policy makers to develop guidelines for the control and ultimate elimination of schistosomiasis.
Daniel G. Colley, Julie A. Jacobson and Sue Binder
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research that would inform practices related to the control and elimination of schistosomiasis. This article traces SCORE’s beginnings and underpinnings. These include an emphasis on openness and contributing to the development of a cohesive schistosomiasis control community, building linkages between researchers and national programs, and focusing on answering questions that will help Neglected Tropical Disease program managers to better control and eliminate schistosomiasis. It describes the development and implementation of SCORE’s multiple projects. SCORE began by drawing on advice from a broad range of experts by holding wide-ranging meetings that informed the priorities and protocols for SCORE research. SCORE’s major efforts included large, multicountry field studies comparing multiple strategies for mass drug administration with praziquantel, assessment of approaches to elimination, evaluation of a point-of-care assay for field mapping Schistosoma mansoni, and increasing the sensitivity of a laboratory-based diagnostic. SCORE also supported studies on morbidity due to schistosomiasis, quantification of vector snails and the detection of schistosome infections in snails, and changes in schistosome population genetics under praziquantel drug pressure. SCORE data and specimens are archived and will remain available for future research. Although much remains to be carried out, our hope is that through the already published articles and SCORE results described in this supplement, we will have provided a body of evidence to assist policy makers in the development of judicious guidelines for the control and elimination of schistosomiasis.
Charles H. King, Nupur Kittur, Sue Binder, Carl H. Campbell Jr., Eliézer K. N’Goran, Aboulaye Meite, Jürg Utzinger, Annette Olsen, Pascal Magnussen, Safari Kinung’hi, Alan Fenwick, Anna E. Phillips, Pedro H. Gazzinelli-Guimaraes, Neerav Dhanani, Josefo Ferro, Diana M. S. Karanja, Pauline N. M. Mwinzi, Susan P. Montgomery, Ryan E. Wiegand, William Evan Secor, Amina A. Hamidou, Amadou Garba and Daniel G. Colley
This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation–funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.
Nupur Kittur, Carl H. Campbell Jr., Sue Binder, Ye Shen, Ryan E. Wiegand, Joseph R. Mwanga, Safari M. Kinung’hi, Rosemary M. Musuva, Maurice R. Odiere, Sultani H. Matendechero, Stefanie Knopp and Daniel G. Colley
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) conducted large field studies on schistosomiasis control and elimination in Africa. All of these studies, carried out in low-, moderate-, and high-prevalence areas, resulted in a reduction in prevalence and intensity of Schistosoma infection after repeated mass drug administration (MDA). However, in all studies, there were locations that experienced minimal or no decline or even increased in prevalence and/or intensity. These areas are termed persistent hotspots (PHS). In SCORE studies in medium- to high-prevalence areas, at least 30% of study villages were PHS. There was no consistent relationship between PHS and the type or frequency of intervention, adequacy of reported MDA coverage, and prevalence or intensity of infection at baseline. In a series of small studies, factors that differed between PHS and villages that responded to repeated MDA as expected included sources of water for personal use, sanitation, and hygiene. SCORE studies comparing PHS with villages that responded to MDA suggest the potential for PHS to be identified after a few years of MDA. However, additional studies in different social-ecological settings are needed to develop generalizable approaches that program managers can use to identify and address PHS. This is essential if goals for schistosomiasis control and elimination are to be achieved.
Charles H. King, Sue Binder, Ye Shen, Christopher C. Whalen, Carl H. Campbell Jr., Ryan E. Wiegand, Annette Olsen, William Evan Secor, Susan P. Montgomery, Rosemary Musuva, Pauline N. M. Mwinzi, Pascal Magnussen, Safari Kinung’hi, Gisele N. Andrade, Amara E. Ezeamama and Daniel G. Colley
The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis—better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE’s larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE’s Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children’s infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity.
Charles H. King, Nupur Kittur, Ryan E. Wiegand, Ye Shen, Yang Ge, Christopher C. Whalen, Carl H. Campbell Jr., Jan Hattendorf and Sue Binder
In 2010, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) began the design of randomized controlled trials to compare different strategies for praziquantel mass drug administration, whether for gaining or sustaining control of schistosomiasis or for approaching local elimination of Schistosoma transmission. The goal of this operational research was to expand the evidence base for policy-making for regional and national control of schistosomiasis in sub-Saharan Africa. Over the 10-year period of its research programs, as SCORE operational research projects were implemented, their scope and scale posed important challenges in terms of research performance and the final interpretation of their results. The SCORE projects yielded valuable data on program-level effectiveness and strengths and weaknesses in performance, but in most of the trials, a greater-than-expected variation in community-level responses to assigned schedules of mass drug administration meant that identification of a dominant control strategy was not possible. This article critically reviews the impact of SCORE’s cluster randomized study design on performance and interpretation of large-scale operational research such as ours.
Daniel G. Colley, Charles H. King, Nupur Kittur, Reda M. R. Ramzy, William Evan Secor, Merlene Fredericks-James, Giuseppina Ortu, Michelle N. Clements, Eugene Ruberanziza, Irenee Umulisa, Udo Wittmann and Carl H. Campbell Jr.
Efforts to control Schistosoma mansoni infection depend on the ability of programs to effectively detect and quantify infection levels and adjust programmatic approaches based on these levels and program goals. One of the three major objectives of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has been to develop and/or evaluate tools that would assist Neglected Tropical Disease program managers in accomplishing this fundamental task. The advent of a widely available point-of-care (POC) assay to detect schistosome circulating cathodic antigen (CCA) in urine with a rapid diagnostic test (the POC-CCA) in 2008 led SCORE and others to conduct multiple evaluations of this assay, comparing it with the Kato–Katz (KK) stool microscopy assay—the standard used for more than 45 years. This article describes multiple SCORE-funded studies comparing the POC-CCA and KK assays, the pros and cons of these assays, the use of the POC-CCA assay for mapping of S. mansoni infections in areas across the spectrum of prevalence levels, and the validation and recognition that the POC-CCA, although not infallible, is a highly useful tool to detect low-intensity infections in low-to-moderate prevalence areas. Such an assay is critical, as control programs succeed in driving down prevalence and intensity and seek to either maintain control or move to elimination of transmission of S. mansoni.
Paul L. A. M. Corstjens, Claudia J. de Dood, Stefanie Knopp, Michelle N. Clements, Giuseppina Ortu, Irenee Umulisa, Eugene Ruberanziza, Udo Wittmann, Thomas Kariuki, Philip LoVerde, William Evan Secor, Lydia Atkins, Safari Kinung’hi, Sue Binder, Carl H. Campbell Jr., Daniel G. Colley and Govert J. van Dam
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato–Katz parasite egg-detection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.
Carl H. Campbell Jr., Sue Binder, Charles H. King, Stefanie Knopp, David Rollinson, Bobbie Person, Bonnie Webster, Fiona Allan, Jürg Utzinger, Shaali M. Ame, Said M. Ali, Fatma Kabole, Eliézer K. N’Goran, Fabrizio Tediosi, Paola Salari, Mamadou Ouattara, Nana R. Diakité, Jan Hattendorf, Tamara S. Andros, Nupur Kittur and Daniel G. Colley
As part of its diverse portfolio, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) included two cluster-randomized trials evaluating interventions that could potentially lead to interruption of schistosomiasis transmission (elimination) in areas of Africa with low prevalence and intensity of infection. These studies, conducted in Zanzibar and Côte d’Ivoire, demonstrated that multiyear mass drug administration (MDA) with praziquantel failed to interrupt the transmission of urogenital schistosomiasis, even when provided biannually and/or supplemented by small-scale implementation of additional interventions. Other SCORE activities related to elimination included a feasibility and acceptability assessment of test–treat–track–test–treat (T5) strategies and mathematical modeling. Future evaluations of interventions to eliminate schistosomiasis should recognize the difficulties inherent in conducting randomized controlled trials on elimination and in measuring small changes where baseline prevalence is low. Highly sensitive and specific diagnostic tests for use in very low–prevalence areas for schistosomiasis are not routinely available, which complicates accurate measurement of infection rates and assessment of changes resulting from interventions in these settings. Although not encountered in these two studies, as prevalence and intensity decrease, political and community commitment to population-wide MDA may decrease. Because of this potential problem, SCORE developed and funded the T5 strategy implemented in Egypt, Kenya, and Tanzania. It is likely that focal MDA campaigns, along with more targeted approaches, including a T5 strategy and snail control, will need to be supplemented with the provision of clean water and sanitation and behavior change communications to achieve interruption of schistosome transmission.
Fiona Allan, Shaali M. Ame, Yves-Nathan T. Tian-Bi, Bruce V. Hofkin, Bonnie L. Webster, Nana R. Diakité, Eliezer K. N’Goran, Fatma Kabole, Iddi S. Khamis, Anouk N. Gouvras, Aidan M. Emery, Tom Pennance, Muriel Rabone, Safari Kinung’hi, Amina Amadou Hamidou, Gerald M. Mkoji, John P. McLaughlin, Armand M. Kuris, Eric S. Loker, Stefanie Knopp and David Rollinson
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created in 2008 to answer questions of importance to program managers working to reduce the burden of schistosomiasis in Africa. In the past, intermediate host snail monitoring and control was an important part of integrated schistosomiasis control. However, in Africa, efforts to control snails have declined dramatically over the last 30 years. A resurgence of interest in the control of snails has been prompted by the realization, backed by a World Health Assembly resolution (WHA65.21), that mass drug administration alone may be insufficient to achieve schistosomiasis elimination. SCORE has supported work on snail identification and mapping and investigated how xenomonitoring techniques can aid in the identification of infected snails and thereby identify potential transmission areas. Focal mollusciciding with niclosamide was undertaken in Zanzibar and Côte d’Ivoire as a part of elimination studies. Two studies involving biological control of snails were conducted: one explored the association of freshwater riverine prawns and snail hosts in Côte d’Ivoire and the other assessed the current distribution of Procambarus clarkii, the invasive Louisiana red swamp crayfish, in Kenya and its association with snail hosts and schistosomiasis transmission. SCORE also supported modeling studies on the importance of snail control in achieving elimination and a meta-analysis of the impact of molluscicide-based snail control programs on human schistosomiasis prevalence and incidence. SCORE’s snail control studies contributed to increased investment in building capacity, and specimens collected during SCORE research deposited in the Schistosomiasis Collections at the Natural History Museum (SCAN) will provide a valuable resource for the years to come.
Joanne P. Webster, Maria Inês Neves, Bonnie L. Webster, Tom Pennance, Muriel Rabone, Anouk N. Gouvras, Fiona Allan, Martin Walker and David Rollinson
Analyses of the population genetic structure of schistosomes under the “Schistosomiasis Consortium for Operational Research and Evaluation” (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent “biological hotspot” sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general.
Charles H. King, David Bertsch, Gisele N. Andrade, Michael Burnim, Amara E. Ezeamama, Sue Binder and Daniel G. Colley
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research to inform global health practices related to the control and elimination of schistosomiasis. The greatest part of the SCORE investment has been in multiyear, long-term efforts, including cluster-randomized trials of gaining and sustaining control of schistosomiasis, trials on elimination of schistosomiasis, and diagnostic test development and evaluation. In the course of planning and conducting SCORE studies, critical questions were raised that could be answered relatively quickly by collecting, collating, and synthesizing existing data. Through its Rapid Answers Project (RAP), the SCORE conducted seven systematic reviews, including four associated meta-analyses, on issues related to screening for schistosomiasis, enhancing mass drug administration, treatment impacts, and the efficacy of snail control for prevention of human schistosomiasis. This article summarizes the findings of the seven RAP reports and provides links to the studies and their supporting information.
Charles H. King, Nara Yoon, Xiaoxia Wang, Nathan C. Lo, Ramzi Alsallaq, Martial Ndeffo-Mbah, Emily Li and David Gurarie
An essential mission of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was to help inform global health practices related to the control and elimination of schistosomiasis. To provide more accurate, evidence-based projections of the most likely impact of different control interventions, whether implemented alone or in combination, SCORE supported mathematical modeling teams to provide simulations of community-level Schistosoma infection outcomes in the setting of real or hypothetical programs implementing multiyear mass drug administration (MDA) for parasite control. These models were calibrated using SCORE experience with Schistosoma mansoni and Schistosoma haematobium gaining and sustaining control studies, and with data from comparable programs that used community-based or school-based praziquantel MDA in other parts of sub-Saharan Africa. From 2010 to 2019, models were developed and refined, first to project the likely SCORE control outcomes, and later to more accurately reflect impact of MDA across different transmission settings, including the role of snail ecology and the impact of seasonal rainfall on snail abundance. Starting in 2014, SCORE modeling projections were also compared with the models of colleagues in the Neglected Tropical Diseases Modelling Consortium. To explore further possible improvement to program-based control, later simulations examined the cost-effectiveness of combining MDA with environmental snail control, and the utility of early impact assessment to more quickly identify persistent hot spots of transmission. This article provides a nontechnical summary of the 11 SCORE-related modeling projects and provides links to the original open-access articles describing model development and projections relevant to schistosomiasis control policy.
Sue Binder, Carl H. Campbell Jr., Jennifer D. Castleman, Nupur Kittur, Safari M. Kinung’hi, Annette Olsen, Pascal Magnussen, Diana M. S. Karanja, Pauline N. M. Mwinzi, Susan P. Montgomery, William Evan Secor, Anna E. Phillips, Neerav Dhanani, Pedro H. Gazzinelli-Guimaraes, Michelle N. Clements, Eliézer K. N’Goran, Aboulaye Meite, Jürg Utzinger, Amina A. Hamidou, Amadou Garba, Fiona M. Fleming, Christopher C. Whalen, Charles H. King and Daniel G. Colley
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts.
Sue Binder, Carl H. Campbell Jr., Tamara S. Andros, Jennifer D. Castleman, Nupur Kittur, Charles H. King and Daniel G. Colley
For the past 10 years, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), funded by the Bill & Melinda Gates Foundation, has been supporting operational research to provide a stronger evidence base for controlling and moving toward elimination of schistosomiasis. The SCORE portfolio was developed and implemented with engagement from many stakeholders and sectors. Particular efforts were made to include endemic country neglected tropical disease program managers. Examples of the challenges we encountered include the need to balance rigor (e.g., conducting large cluster-randomized trials) with ensuring relevance to real-world settings, allowing for local contexts while standardizing key study aspects, adjusting to evolving technologies, and incorporating changing technologies into multiyear studies. The Schistosomiasis Consortium for Operational Research and Evaluation’s findings and data and the collected specimens will continue to be useful in the years to come. Our experiences and lessons learned can benefit both program managers and researchers conducting similar work in the future.
Daniel G. Colley, Fiona M. Fleming, Sultani H. Matendechero, Stefanie Knopp, David Rollinson, Jürg Utzinger, Jennifer D. Castleman, Nupur Kittur, Charles H. King, Carl H. Campbell Jr, Fatma M. Kabole, Safari Kinung’hi, Reda M. R. Ramzy and Sue Binder
Herein, we summarize what we consider are major contributions resulting from the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) program, including its key findings and key messages from those findings. Briefly, SCORE’s key findings are as follows: i) biennial mass drug administration (MDA) with praziquantel can control schistosomiasis to moderate levels of prevalence; ii) MDA alone will not achieve elimination; iii) to attain and sustain control throughout endemic areas, persistent hotspots need to be identified following a minimal number of years of annual MDA and controlled through adaptive strategies; iv) annual MDA is more effective than biennial MDA in high-prevalence areas; v) the current World Health Organization thresholds for decision-making based on the prevalence of heavy infections should be redefined; and vi) point-of-care circulating cathodic antigen urine assays are useful for Schistosoma mansoni mapping in low-to-moderate prevalence areas. The data and specimens collected and curated through SCORE efforts will continue to be critical resource for future research. Besides providing useful information for program managers and revision of guidelines for schistosomiasis control and elimination, SCORE research and outcomes have identified additional questions that need to be answered as the schistosomiasis community continues to implement effective, evidence-based programs. An overarching contribution of SCORE has been increased cohesiveness within the schistosomiasis field-oriented community, thereby fostering new and productive collaborations. Based on SCORE’s findings and experiences, we propose new approaches, thresholds, targets, and goals for control and elimination of schistosomiasis, and recommend research and evaluation activities to achieve these targets and goals.
As much of western Europe begins to ease countrywide lockdowns, globally the pandemic may still be in its infancy, with more than 160 000 new cases reported each day since June 25. Individual countries count cases differently, so direct comparisons are difficult, but the numbers illustrate a worrying pattern. At a subnational level the picture is nuanced, with local hotspots, but at a country level the picture is clear—the world is facing a worsening multipolar pandemic.
Vitiligo is an acquired depigmentation of the skin, which affects approximately 1% of the population worldwide. The condition can profoundly affect the wellbeing and the social, sexual, and professional lives of affected individuals and thus induces a strong therapeutic demand.1 Actual treatments rely on the use of topical steroids or topical calcineurin inhibitors, and are better combined with sun exposure or phototherapy.1,2 The best results are achieved on the face, while some areas such as bony prominences and hands and feet show a very poor repigmentation rate.
Belgium has the sad distinction of leading the world league table of deaths from COVID-19. At 843 deaths per million, Belgium is ahead of the UK (650 per million), Italy (576 per million), Sweden (537 per million), and France (458 per million). COVID-19 was first reported in Belgium on Feb 4, 2020, in a 54-year-old man who had been repatriated from Wuhan, China. Community transmission was confirmed in early March after holiday makers returned from school vacation breaks in northern Italy. The national sense of failure and anger is spurring a serious effort to initiate an international inquiry into the global response to the pandemic.
The court's decision means that Louisiana's three abortion clinics will remain open. Susan Jaffe reports.
An artist can turn bad luck into good fortune. Texas-born author Katherine Anne Porter caught and nearly died from influenza in the 1918–19 pandemic, but the experience gave her the material for Pale Horse, Pale Rider—the title piece of this selection from Penguin Modern Classics—and not only the finest of her very fine short stories, but also the greatest literary account of the “Spanish” influenza. Very few writers besides Porter addressed the disease, effectively making her the laureate of a tragedy that no one much cared to remember until the parallels with COVID-19 recalled it to collective consciousness.
Paediatrician who identified what became known as Kawasaki disease. Born on Feb 7, 1925, in Tokyo, Japan, he died on June 5, 2020, in Tokyo, aged 95 years.
Till J Bugaj, Anna Cranz, Christoph Nikendei
Nick Watts and colleagues' 2019 report of the Lancet Countdown on health and climate change1 leaves no doubt that global warming will heavily affect every child born today. Young people—the generation that will have to live through the consequences of a warming world for the longest—are actively taking part in raising awareness for climate change. Inspired by the Fridays for Future movement, thousands of young people have been doing everything possible to bring about social change towards a sustainable ecological lifestyle.
Matthew Eckelman, Marina Romanello, Jodi Sherman, Nicholas Watts
We thank Till Bugaj and colleagues and Helga Weisz and colleagues for their comments.
Gerald Chi, Jolanta Marszalek
We read with interest the Article by Deepak L Bhatt and colleagues1 on the incremental effect of ticagrelor to aspirin for patients with diabetes and stable coronary artery disease. The THEMIS trial suggested a reduction in ischaemic events but not irreversible harms in the overall population.2 The trial also hypothesised that patients with a history of previous percutaneous coronary intervention (PCI) would show a favourable efficacy–safety tradeoff. The authors found a favourable net clinical benefit in patients with previous PCI but not in those without previous PCI (appendix).
Deepak L Bhatt, Philippe Gabriel Steg
Gerald Chi and Jolanta Marszalek raise questions about subgroup analysis and interaction terms in the THEMIS trial. Interaction terms are generally underpowered. At the same time, when several subgroups are compared, interaction terms might be positive by chance because of multiplicity of testing. These are two opposing forces in the interpretation of interaction terms that have long been appreciated in clinical trials. With respect to our work, the THEMIS trial was a positive trial in which we found significant efficacy benefit of ticagrelor in the overall population of patients with stable coronary artery disease and diabetes who were studied.
Marco Antonio Bessa, Ronaldo Laranjeira, David Martin
Illegal drugs and their effect on public health were discussed in a 2019 Lancet Series.1 However, the Series authors did not report how a global criminal enterprise, the drug–abuse industrial complex,2 is the origin of the problem. This global network of organised crime, corrupt politicians, money laundering, and distribution systems perpetuates this public health crisis. We have reason to believe the drug trade is now expanding under the guise of legal cannabis and cannabidiol, especially in North America, with outreach to other markets in South America, Europe, and Asia.
Sheila M Bird, J Roy Robertson
The Lancet Series on drug use1 began with a paper on global patterns of opioid dependence but insufficiently emphasised that the sequelae of these epidemics persist over decades. The risk of drug-related death increases with age in people who are opioid-dependent, and the advantage that young women users (
Angeliki Vgontzas, William Renthal
Erenumab is a CGRP receptor monoclonal antibody for the preventive treatment of migraine. It has been widely prescribed in the USA after receiving US Food and Drug Administration approval in May, 2018. An estimated 7000 prescriptions are written per week,1 which, along with postmarketing reporting, have resulted in the rapid detection of serious adverse events that were not seen during clinical trials. As a result, the product label was revised on Oct 4, 2019, to include constipation with serious complications, including cases requiring hospitalisation and surgery, with most cases reported after a single dose of erenumab.
David Rosmarin, Amit G Pandya, Mark Lebwohl, Pearl Grimes, Iltefat Hamzavi, Alice B Gottlieb, Kathleen Butler, Fiona Kuo, Kang Sun, Tao Ji, Michael D Howell, John E Harris
Treatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo.
Daniel Pan, Leslie R Bridges, John du Parcq, Ula Mahadeva, Shantanu Roy, Ibne K M Ali, Catherine A Cosgrove, Peter L Chiodini, Liqun Zhang
An 85-year-old Gujarati woman with a 1-day history of confusion, left-sided weakness, and slurred speech attended our hospital. She had a history of headaches, which had been extensively investigated for 2 years from 2013. She also had hypertension. She had no history of recent travel.
Bruce C V Campbell, Pooja Khatri
Stroke is a major cause of death and disability globally. Diagnosis depends on clinical features and brain imaging to differentiate between ischaemic stroke and intracerebral haemorrhage. Non-contrast CT can exclude haemorrhage, but the addition of CT perfusion imaging and angiography allows a positive diagnosis of ischaemic stroke versus mimics and can identify a large vessel occlusion target for endovascular thrombectomy. Management of ischaemic stroke has greatly advanced, with rapid reperfusion by use of intravenous thrombolysis and endovascular thrombectomy shown to reduce disability.
Hoogerwerf M, Koopman J, Janse J, et al.
AbstractBackgroundControlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability and egg output of repeated exposure to hookworm larvae.MethodsTwenty-four healthy volunteers were randomized double blind to one, two or three doses of 50 Necatoramericanus L3 larvae at 2-week intervals. Volunteers were monitored weekly and were treated with albendazole at week 20.ResultsThere was no association between larval dose and number or severity of adverse events. Geomean egg loads stabilized at 697, 1668 and 1914 eggs per gram feces for the 1x50L3, 2x50L3 and 3x50L3 group respectively. Bayesian statistical modelling showed that egg count variability relative to the mean was reduced with a second infectious dose, however the third dose did not increase egg load or decrease variability. We therefore suggest 2x50L3 as an improved challenge dose. Model-based simulations indicates increased frequency of stool sampling optimizes power of hypothetical vaccine trials.DiscussionRepeated infection with hookworm larvae increased egg counts to levels comparable to the field and reduced relative variability in egg output without aggravating adverse events.
International Liver Congress (ILC) 2020
27.08.2020 - 29.08.2020
World Sepsis Day
Det 8. videnskabelige nationale møde om infektiøs endokarditis
International Congress for Tropical Medicine and Malaria (ICTMM) 2020
20.09.2020 - 24.09.2020
Meeting of the European Society for Immunodeficiencies (ESID) 2020
14.10.2020 - 17.10.2020
COVID-19 retningslinje (2020)
National handlingsplan for antibiotika til mennesker (2017)
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Infections in Patients Colonized with Extended-Spectrum Beta-Lactamase-Producing Enterobacterales – a Retrospective Cohort Study
30.07.2020Clinical Infectious Diseases Advance Access
Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2
22.07.2020Emerging Infectious Diseases Journal
Coronavirus Disease among Persons with Sickle Cell Disease, United States, March 20–May 21, 2020
22.07.2020Emerging Infectious Diseases Journal
COVID-19: the worst may be yet to come
First step in a new era for treatment of patients with vitiligo
Hvad tænker Professor Jens Lundgren om"Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV."?
Hvorfor anbefaler Professor Troels Lillebæk artiklen"The global prevalence of latent tuberculosis: a systematic review and meta-analysis."?
Hvad synes Professor Lars Østergaard om"Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial."?
Hvorfor anbefaler Professor Thomas Benfield artiklen"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvad synes Professor Niels Obel om"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
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