Albendazole alone or in combination with microfilaricidal drugs for lymphatic filariasis.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis recommends mass treatment of albendazole co-administered with the microfilaricidal (antifilarial) drugs diethylcarbamazine (DEC) or ivermectin; and recommends albendazole alone in areas where loiasis is endemic. OBJECTIVES: To assess the effects of albendazole alone, and the effects of adding albendazole to DEC or ivermectin, in people and communities with lymphatic filariasis. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), Embase (OVID), LILACS (BIREME), and reference lists of included trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify ongoing trials. We performed all searches up to 15 January 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and cluster-RCTs that compared albendazole to placebo or no placebo, or compared albendazole combined with a microfilaricidal drug to a microfilaricidal drug alone, given to people known to have lymphatic filariasis or communities where lymphatic filariasis was known to be endemic. We sought data on measures of transmission potential (microfilariae (mf) prevalence and density); markers of adult worm infection (antigenaemia prevalence and density, and adult worm prevalence detected by ultrasound); and data on clinical disease and adverse events. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials, evaluated the risks of bias, and extracted data. The main analysis examined albendazole overall, whether given alone or added to a microfilaricidal drug. We used data collected from all randomized individuals at time of longest follow-up (up to 12 months) for meta-analysis of outcomes. We evaluated mf density data up to six months and at 12 months follow-up to ensure that we did not miss any subtle temporal effects. We conducted additional analyses for different follow-up periods and whether trials reported on individuals known to be infected or both infected and uninfected. We analysed dichotomous data using the risk ratio (RR) with a 95% confidence interval (CI). We could not meta-analyse data on parasite density outcomes and we summarized them in tables. Where data were missing, we contacted trial authors. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 13 trials (12 individually-randomized and one small cluster-randomized trial) with 8713 participants in total. No trials evaluated population-level effects of albendazole in mass drug administration programmes. Seven trials enrolled people with a variety of inclusion criteria related to filarial infection, and six trials enrolled individuals from endemic areas. Outcomes were reported as end or change values. Mf and antigen density data were reported using the geometric mean, log mean and arithmetic mean, and reductions in density were variously calculated. Two trials discounted any increases in mf density in individuals at follow-up by setting any density increase to zero.For mf prevalence over two weeks to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 0.95, 95% CI 0.85 to 1.07; 5027 participants, 12 trials, high-certainty evidence). For mf density there is no trend, with some trials reporting a greater reduction in mf density with albendazole and others a greater reduction with the control group. For mf density up to six months and at 12 months, we do not know if albendazole has an effect (one to six months: 1216 participants, 10 trials, very low-certainty evidence; at 12 months: 1052 participants, 9 trials, very low-certainty evidence).For antigenaemia prevalence between six to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 1.04, 95% CI 0.97 to 1.12; 3774 participants, 7 trials, high-certainty evidence). For antigen density over six to 12 months, the trend shows little or no effect of albendazole; but we do not know if albendazole has an effect on antigen density (1374 participants, 5 trials, very low-certainty evidence). For adult worm prevalence detected by ultrasound at 12 months, albendazole added to a microfilaricidal drug may make little or no difference (RR 1.16, 95% CI 0.72 to 1.86; 165 participants, 3 trials, low-certainty evidence).For people reporting adverse events, albendazole makes little or no difference (RR 0.97, 95% CI 0.84 to 1.13; 2894 participants, 6 trials, high-certainty evidence).We also provide meta-analyses and GRADE tables by drug, as operationally this may be of interest: for albendazole versus placebo (4 trials, 1870 participants); for albendazole with DEC compared to DEC alone (8 trials, 3405 participants); and albendazole with ivermectin compared to ivermectin alone (4 trials, 3438 participants). AUTHORS' CONCLUSIONS: There is good evidence that albendazole makes little difference to clearing microfilaraemia or adult filarial worms in the 12 months post-treatment. This finding is consistent in trials evaluating albendazole alone, or added to DEC or ivermectin. Trials reporting mf density included small numbers of participants, calculated density data variously, and gave inconsistent results.The review raises questions over whether albendazole has any important contribution to the elimination of lymphatic filariasis. To inform policy for areas with loiasis where only albendazole can be used, it may be worth conducting placebo-controlled trials of albendazole alone.

Report on Proceedings of the Sixteenth Annual European CME Forum, the Hague, Netherlands, November 2023.

There was a renewed vigour among the participants attending the 16th Annual European CME Forum (#16ECF), which took place in the Hague, the Netherlands from 8-10 November 2023. This emanated from the meeting having reverted to an in-person format to promote engagement among attendees. The meeting was subdivided into three main sections to address this year's theme "Voices in CME-CPD": 1) Listening to others; 2) Listening to ourselves; 3) Listening to each other. The Forum unofficially began with the pre-meeting sessions led by two special interest groups and was then formally opened by the programme director. There were panel discussions on designing and implementing CME-CPD programmes, measuring and reporting outcomes, and valuing and defining independence, as well as smaller workshop and breakout sessions led by international presenters. Representatives for the Journal of CME presented on the 2023 Special Collection of articles, with this year's topic "Expanding the voices in CME-CPD" mirroring the meeting theme. Participants interacted with providers, accreditors and grantors, as well as poster authors and a local physician who attended to share a learner's perspective. The meeting concluded with the now familiar "CME unsession" to ensure everyone's voices were heard and no one left the meeting with any unanswered questions.

Report on Proceedings of the 12th Annual European CME Forum, University of Manchester, November 2019.

The 12th Annual European CME Forum (#12ECF) was held 6-8 November 2019 at the Barnes Wallis building in the University of Manchester, Manchester, UK. An international group of attendees participated in highly interactive learning sessions, ranging from workshops to panel discussions to oral presentations by poster authors. Breakout session themes addressed continuing medical education (CME) from the perspective of the learner (micro-practice); collaborations, partnerships and interprofessional approaches (meso-practice); and consideration of compliance and regulatory issues (macro-practice). Topics covered included standards for accreditation, doctor-patient communication, a framework for CME educators' professional development, capacity building and a futurist viewpoint of continuing professional development (CPD) from a global perspective. The high level of engagement by learners set a solid foundation for further collaboration among stakeholders in European CME.

Feasibility of Integrating a Mobile Decision-Support App into a Multicomponent CME Initiative: Developing Clinician Competence at the Point of Care.

Mobile health (mHealth) technologies such as smartphone applications are increasingly being adopted in the healthcare setting to support the delivery of evidence-based care. Given the approaching ubiquity of mHealth tools in medical practice, it is incumbent on the continuing medical education (CME) community to understand how these tools can be leveraged to develop clinician knowledge and competence, and how we can assess these educational outcomes. In this report, we describe our experience developing and incorporating a mobile decision-support tool into multiple activity formats within the European Immuno-Oncology Clinic Companion CME initiative.

The insufficiency of circulating miRNA and DNA as diagnostic tools or as biomarkers of treatment efficacy for Onchocerca volvulus.

Skin snip evaluation for onchocerciasis has insufficient sensitivity when skin microfilarial (mf) densities are low, such as following ivermectin treatment. Mf density is suitable for assessing microfilaricidal efficacy but only serves as an indirect indicator of macrofilaricidal activity. We assessed circulating nucleic acids from Onchocerca volvulus as an alternative to skin snips. We screened a plasma sample set of infected individuals followed up at four, 12 and 21 months after microfilaricidal (ivermectin, n = four), macrofilaricidal (doxycycline, n = nine), or combination treatment (n = five). Two parasite-derived miRNAs, cel-miR-71-5p and bma-lin-4, and O-150 repeat DNA were assessed. Highly abundant DNA repeat families identified in the O. volvulus genome were also evaluated. miRNAs were detected in two of 72 plasma samples (2.8%) and two of 47 samples (4.3%) with microfilaridermia using RT-qPCR. O-150 DNA was detected in eight (44.4%) baseline samples by qPCR and the number of positives declined post-treatment. One doxycycline-treated individual remained O-150 positive. However, only 11 (23.4%) samples with microfilaridermia were qPCR-positive. Analysis by qPCR showed novel DNA repeat families were comparatively less abundant than the O-150 repeat. Circulating parasite-derived nucleic acids are therefore insufficient as diagnostic tools or as biomarkers of treatment efficacy for O. volvulus.

Community drug distributors for mass drug administration in neglected tropical disease programmes: systematic review and analysis of policy documents.

BACKGROUND: Mass drug administration (MDA) programmes for neglected tropical diseases (NTDs) depend on voluntary community drug distributors (CDDs) to deliver drugs, and these volunteer schemes need regular training and supervision. NTD policy now includes integration of multiple disease programmes, but we are unsure if there is clarity in what is currently expected of CDDs and how they are managed. We therefore analysed World Health Organization (WHO) policy, strategy and implementation guidance, and select national NTD programme implementation plans. METHODS: Included are a) WHO global and WHO-Regional Office for Africa guidelines, strategies, operational manuals and meeting reports published between January 2007 to February 2018 that included policy and plans for CDDs; and b) national NTD programme master plans for Cameroon, Ghana, Liberia and Nigeria. For both review components, we examined the CDD responsibilities through a framework developed iteratively against the documents and prepared a narrative synthesis. RESULTS: Twenty WHO policy documents met the inclusion criteria. In the twelve global and eight regional documents, the CDD role was not explicitly or comprehensively defined. Three documents mentioned CDDs will distribute drugs; some mentioned health promotion, data handling and engagement in clinical care. Four WHO documents noted a need for CDD training or management, eight detailed some aspect of this, and one regional document provided a comprehensive overview. In the national plans, additional responsibilities included case management in two countries and transmission control in two countries. Every plan included training and supervision, but this was not always explicit, and details of the purpose and frequency varied. In all national plans, CDD motivation was identified as a challenge but not comprehensively addressed, although one document mentioned provision of bicycles. CONCLUSIONS: WHO and national policies and plans assume CDDs will implement NTD programmes. However, there is almost no clear delineation of responsibilities, nor is there up-to-date practical guidance to guide managers. This ambiguity, in relation to the lack of explicit policies or programmatic guidance, probably impairs the effectiveness of NTD programmes.

Innovative Surveillance Strategies to Support the Elimination of Filariasis in Africa.

Lymphatic filariasis (LF) and onchocerciasis are two neglected tropical diseases (NTDs) of public health significance targeted for global elimination. The World Health Organization (WHO) African Region is a priority region, with the highest collective burden of LF and onchocerciasis globally. Coendemic loiasis further complicates elimination due to the risk of adverse events associated with ivermectin treatment. A public health framework focusing on health-related data, systematic collection of data, and analysis and interpretation of data is used to highlight the range of innovative surveillance strategies required for filariasis elimination. The most recent and significant developments include: rapid point-of-care test (POCT) diagnostics; clinical assessment tools; new WHO guidelines; open-access online data portals; mHealth platforms; large-scale prevalence maps; and the optimisation of mathematical models.