scholarly journals Antimicrobial Resistance Following Azithromycin Mass Drug Administration: Potential Surveillance Strategies to Assess Public Health Impact

2019 ◽  
Vol 70 (7) ◽  
pp. 1501-1508 ◽  
Author(s):  
Ines Mack ◽  
Mike Sharland ◽  
James A Berkley ◽  
Nigel Klein ◽  
Surbhi Malhotra-Kumar ◽  
...  
Keyword(s):  
Drug Administration ◽  
Mass Drug Administration ◽  
Controlled Trial ◽  
Population Level ◽  
Health Impact ◽  
Childhood Mortality ◽  
World Health ◽  
Current Evidence ◽  
Multiresistant Pathogens ◽  
Microbiological Techniques

Abstract The reduction in childhood mortality noted in trials investigating azithromycin mass drug administration (MDA) for trachoma control has been confirmed by a recent large randomized controlled trial. Population-level implementation of azithromycin MDA may lead to selection of multiresistant pathogens. Evidence suggests that repeated azithromycin MDA may result in a sustained increase in macrolide and other antibiotic resistance in gut and respiratory bacteria. Current evidence comes from standard microbiological techniques in studies focused on a time-limited intervention, while MDA implemented for mortality benefits would likely repeatedly expose the population over a prolonged period and may require a different surveillance approach. Targeted short-term and long-term surveillance of resistance emergence to key antibiotics, especially those from the World Health Organization Access group, is needed throughout any implementation of azithromycin MDA, focusing on a genotypic approach to overcome the limitations of resistance surveillance in indicator bacteria.

scholarly journals Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome: a randomized, controlled trial

2021 ◽  
Author(s):  
Harry Pickering ◽  
John D. Hart ◽  
Sarah Burr ◽  
Richard Stabler ◽  
Ken Maleta ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Gut Microbiome ◽  
Controlled Trial ◽  
Diarrhoeal Disease ◽  
Childhood Mortality ◽  
Resistant Bacteria ◽  
Clinical Benefits ◽  
The Impact

AbstractBackgroundMass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities.MethodsThis study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.FindingsThe proportion of bacteria carrying macrolide resistance increased after azithromycin treatment; the effect was enhanced in children treated within six months of sampling. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.InterpretationThe impacts of MDA with azithromycin, including increased carriage of macrolide-resistant bacteria, were enhanced in children treated more recently, suggesting effects may be transient. Increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage.FundingBill and Melinda Gates Foundation

scholarly journals Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome in children: a randomized, controlled trial

Gut Pathogens ◽  
2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Harry Pickering ◽  
John D. Hart ◽  
Sarah Burr ◽  
Richard Stabler ◽  
Ken Maleta ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Gut Microbiome ◽  
Controlled Trial ◽  
Diarrhoeal Disease ◽  
Childhood Mortality ◽  
Resistant Bacteria ◽  
Clinical Benefits ◽  
The Impact

Abstract Background Mass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities. This study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo. Results The proportion of bacteria carrying macrolide resistance increased after azithromycin treatment. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment. Conclusions MDA with azithromycin increased carriage of macrolide-resistant bacteria, but had limited impact on clinically relevant bacteria. However, increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage. Trial registration ClinicalTrial.gov, NCT02047981. Registered January 29th 2014, https://clinicaltrials.gov/ct2/show/NCT02047981

scholarly journals Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Benjamin S. Collyer ◽  
Hugo C. Turner ◽  
T. Déirdre Hollingsworth ◽  
Matt J. Keeling
Keyword(s):  
Cost Effectiveness ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Health Benefit ◽  
Population Level ◽  
Cost Effective ◽  
World Health ◽  
Transmission Model ◽  
The Cost

Abstract Background Schistosomiasis is a neglected tropical disease, targeted by the World Health Organization for reduction in morbidity by 2020. It is caused by parasitic flukes that spread through contamination of local water sources. Traditional control focuses on mass drug administration, which kills the majority of adult worms, targeted at school-aged children. However, these drugs do not confer long-term protection and there are concerns over the emergence of drug resistance. The development of a vaccine against schistosomiasis opens the potential for control methods that could generate long-lasting population-level immunity if they are cost-effective. Methods Using an individual-based transmission model, matched to epidemiological data, we compared the cost-effectiveness of a range of vaccination programmes against mass drug administration, across three transmission settings. Health benefit was measured by calculating the heavy-intensity infection years averted by each intervention, while vaccine costs were assessed against robust estimates for the costs of mass drug administration obtained from data. We also calculated a critical vaccination cost, a cost beyond which vaccination might not be economically favorable, by benchmarking the cost-effectiveness of potential vaccines against the cost-effectiveness of mass drug administration, and examined the effect of different vaccine protection durations. Results We found that sufficiently low-priced vaccines can be more cost-effective than traditional drugs in high prevalence settings, and can lead to a greater reduction in morbidity over shorter time-scales. MDA or vaccination programmes that target the whole community generate the most health benefits, but are generally less cost-effective than those targeting children, due to lower prevalence of schistosomiasis in adults. Conclusions The ultimate cost-effectiveness of vaccination will be highly dependent on multiple vaccine characteristics, such as the efficacy, cost, safety and duration of protection, as well as the subset of population targeted for vaccination. However, our results indicate that if a vaccine could be developed with reasonable characteristics and for a sufficiently low cost, then vaccination programmes can be a highly cost-effective method of controlling schistosomiasis in high-transmission areas. The population-level immunity generated by vaccination will also inevitably improve the chances of interrupting transmission of the disease, which is the long-term epidemiological goal.

scholarly journals The contribution of mass drug administration to global health: past, present and future

2014 ◽  
Vol 369 (1645) ◽  
pp. 20130434 ◽  
Author(s):  
Joanne P. Webster ◽  
David H. Molyneux ◽  
Peter J. Hotez ◽  
Alan Fenwick
Keyword(s):  
Global Health ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Neglected Tropical Diseases ◽  
World Health Organisation ◽  
Essential Medicines ◽  
World Health ◽  
Diagnostic Tools ◽  
Preventive Chemotherapy ◽  
High Coverage

Mass drug administration (MDA) is a means of delivering safe and inexpensive essential medicines based on the principles of preventive chemotherapy, where populations or sub-populations are offered treatment without individual diagnosis. High-coverage MDA in endemic areas aims to prevent and alleviate symptoms and morbidity on the one hand and can reduce transmission on the other, together improving global health. MDA is the recommended strategy of the World Health Organisation to control or eliminate several neglected tropical diseases (NTDs). More than 700 million people now receive these essential NTD medicines annually. The combined cost of integrated NTD MDA has been calculated to be in the order of $0.50 per person per year. Activities have recently been expanded due, in part, to the proposed attempt to eliminate certain NTDs in the coming two decades. More than 1.9 billion people need to receive MDA annually across several years if these targets are to be met. Such extensive coverage will require additional avenues of financial support, expanded monitoring and evaluation focusing on impact and drug efficacy, as well as new diagnostic tools and social science strategies to encourage adherence. MDA is a means to help reduce the burden of disease, and hence poverty, among the poorest sector of populations. It has already made significant improvements to global health and productivity and has the potential for further successes, particularly where incorporated into sanitation and education programmes. However logistical, financial and biological challenges remain.

scholarly journals Coronavirus Disease 2019 and Gastrointestinal Involvement: A Systematic Review

Medicinus ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 62
Author(s):  
Moryella Monica ◽  
Andree Kurniawan
Keyword(s):  
Systematic Review ◽  
Assessment Tool ◽  
Controlled Trial ◽  
Intestinal Flora ◽  
Gastrointestinal Symptoms ◽  
Good Evidence ◽  
World Health ◽  
Current Evidence ◽  
Future Research ◽  
Gastrointestinal Involvement

<p><strong>Introduction: </strong>The World Health Organization (WHO) announced the Coronavirus 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) toward the end of January 2020. There is still limited evidence to explain the gastrointestinal involvement in COVID-19. In this study, we aimed to further investigate current evidence describing the gastrointestinal involvement in COVID-19 patients.</p><p><strong>Methods: </strong>This systematic review has been registered in PROSPERO (CRD42020181584). A systematic search of literature for observational and randomized controlled trial was conducted in PubMed, PubMed central, and Google Scholar through April 16, 2020. Two reviewers independently searched and selected. The risk of bias was evaluated using the Newcastle-Ottawa Quality assessment tool.<strong> </strong></p><p><strong>Results: </strong>A total of 1,480 articles were screened from which 12 articles with 5584 subjects were selected. SARS-CoV-2 can invade human body by binding to angiotensin converting enzyme 2 (ACE-2) receptor which also located to small intestinal epithelial cells, crypt cells and colon. The virus itself may cause disorders of the intestinal flora. The diagnosis should be based on a set of symptoms diarrhoea, nausea, vomiting, abdominal discomfort or pain, combined with positivity of faecal PCR test. Treatment of COVID-19 mainly is supportive care. The probiotic may modulate the gut microbiota to alter the gastrointestinal symptoms and reduced enteritis, ventilator associated pneumonia, and reverse certain side effect of antibiotics<strong>.</strong></p><p><strong>Conclusion: </strong>Our synthesis of literature showed that there was no good evidence yet in overall area of gastrointestinal manifestations in COVID-19. Future research is needed to explore all areas, especially in mechanism and treatments</p>

scholarly journals From Informed Consent to Adherence: Factors Influencing Involvement in Mass Drug Administration With Ivermectin for Malaria Elimination in The Gambia

2020 ◽  
Author(s):  
Alexandra E. Fehr ◽  
Claudia Nieto-Sanchez ◽  
Joan Muela ◽  
Fatou Jaiteh ◽  
Omar Ceesay ◽  
...  
Keyword(s):  
Decision Making ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Social Dynamics ◽  
The Gambia ◽  
World Health ◽  
Cross Sectional Survey ◽  
Enabling Factors ◽  
Cross Sectional ◽  
Medication Costs

Abstract Background: The World Health Organization (WHO) recommends consideration of mass drug administration (MDA) for malaria control in low-endemic settings approaching elimination. However, MDA remains a controversial strategy, as multiple individual, social, and operational factors have shown to affect its acceptability at local levels. This is further complicated by inconsistent definitions of key indicators derived from individual and community involvement — coverage, adherence, and compliance— that cast doubts about the actual and potential epidemiological impact of MDA on disease control. This study aimed to identify limitations and enabling factors impacting involvement at different stages of a large cluster-randomized trial assessing the effect of combining dihydroartemisinin-piperaquine (DP) and ivermectin (IVM) in malaria transmission in The Gambia. Methods: This social science study used a mixed-methods approach. Qualitative data were collected in intervention and control villages through ethnographic methods, including in-depth interviews (IDIs), focus group discussions (FGDs), and participant observation conducted with trial participants and decliners, community leaders, and field staff. A cross-sectional survey was conducted in the intervention villages after the first year of MDA. Both strands of the study explored malaria knowledge and opinions, social dynamics influencing decision-making, as well as perceived risks, burdens, and benefits associated with this MDA.Results: 157 IDIs and 11 FGDs were conducted, and 864 respondents were included in the survey. Barriers and enabling factors to involvement were differentially influential at the various stages of the MDA. Issues of social influence, concerns regarding secondary effects of the medication, costs associated with malaria, and acceptability of the implementing organization, among other factors, differently affected the decision-making processes throughout the trial. Rather than a linear trajectory, involvement in this MDA trial was subjected to multiple revaluations from enrolment and consent to medicine intake and adherence to treatment. Conclusions: Our study went beyond the individual factors often associated with coverage and adherence, and found that nuanced social dynamics greatly influence the decision-making process at all phases of the trial. These issues need to be consider for MDA implementation strategies and inform discussions about more accurate ways of reporting on critical effectiveness indicators.

scholarly journals Stopping azithromycin mass drug administration for trachoma: A systematic review

2021 ◽  
Vol 15 (7) ◽  
pp. e0009491
Author(s):  
Hamidah Mahmud ◽  
Emma Landskroner ◽  
Abdou Amza ◽  
Solomon Aragie ◽  
William W. Godwin ◽  
...  
Keyword(s):  
Drug Administration ◽  
Mass Drug Administration ◽  
World Health ◽  
Chlamydia Infection ◽  
Measurement Tool ◽  
Infection Prevalence ◽  
Qualitative Synthesis ◽  
Active Trachoma ◽  
Published Evidence ◽  
Over Time

The World Health Organization (WHO) recommends continuing azithromycin mass drug administration (MDA) for trachoma until endemic regions drop below 5% prevalence of active trachoma in children aged 1–9 years. Azithromycin targets the ocular strains of Chlamydia trachomatis that cause trachoma. Regions with low prevalence of active trachoma may have little if any ocular chlamydia, and, thus, may not benefit from azithromycin treatment. Understanding what happens to active trachoma and ocular chlamydia prevalence after stopping azithromycin MDA may improve future treatment decisions. We systematically reviewed published evidence for community prevalence of both active trachoma and ocular chlamydia after cessation of azithromycin distribution. We searched electronic databases for all peer-reviewed studies published before May 2020 that included at least 2 post-MDA surveillance surveys of ocular chlamydia and/or the active trachoma marker, trachomatous inflammation–follicular (TF) prevalence. We assessed trends in the prevalence of both indicators over time after stopping azithromycin MDA. Of 140 identified studies, 21 met inclusion criteria and were used for qualitative synthesis. Post-MDA, we found a gradual increase in ocular chlamydia infection prevalence over time, while TF prevalence generally gradually declined. Ocular chlamydia infection may be a better measurement tool compared to TF for detecting trachoma recrudescence in communities after stopping azithromycin MDA. These findings may guide future trachoma treatment and surveillance efforts.

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