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 ◽  
...  

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

2021 ◽  
Author(s):  
Harry Pickering ◽  
John D. Hart ◽  
Sarah Burr ◽  
Richard Stabler ◽  
Ken Maleta ◽  
...  

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


2019 ◽  
Vol 70 (7) ◽  
pp. 1501-1508 ◽  
Author(s):  
Ines Mack ◽  
Mike Sharland ◽  
James A Berkley ◽  
Nigel Klein ◽  
Surbhi Malhotra-Kumar ◽  
...  

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.


Author(s):  
David J Blok ◽  
Joseph Kamgno ◽  
Sebastien D Pion ◽  
Hugues C Nana-Djeunga ◽  
Yannick Niamsi-Emalio ◽  
...  

Abstract Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.


2021 ◽  
Vol 15 (5) ◽  
pp. e0009011
Author(s):  
Anneke S. de Vos ◽  
Wilma A. Stolk ◽  
Luc E. Coffeng ◽  
Sake J. de Vlas

Background The existence of locations with low but stable onchocerciasis prevalence is not well understood. An often suggested yet poorly investigated explanation is that the infection spills over from neighbouring locations with higher infection densities. Methodology We adapted the stochastic individual based model ONCHOSIM to enable the simulation of multiple villages, with separate blackfly (intermediate host) and human populations, which are connected through the regular movement of the villagers and/or the flies. With this model we explore the impact of the type, direction and degree of connectedness, and of the impact of localized or full-area mass drug administration (MDA) over a range of connected village settings. Principal findings In settings with annual fly biting rates (ABR) below the threshold needed for stable local transmission, persistence of onchocerciasis prevalence can well be explained by regular human traffic and/or fly movement from locations with higher ABR. Elimination of onchocerciasis will then theoretically be reached by only implementing MDA in the higher prevalence area, although lingering infection in the low prevalence location can trigger resurgence of transmission in the total region when MDA is stopped too soon. Expanding MDA implementation to the lower ABR location can therefore shorten the duration of MDA needed. For example, when prevalence spill-over is due to human traffic, and both locations have about equal populations, then the MDA duration can be shortened by up to three years. If the lower ABR location has twice as many inhabitants, the reduction can even be up to six years, but if spill-over is due to fly movement, the expected reduction is less than a year. Conclusions/Significance Although MDA implementation might not always be necessary in locations with stable low onchocerciasis prevalence, in many circumstances it is recommended to accelerate achieving elimination in the wider area.


2020 ◽  
Author(s):  
Paul BIZIMANA ◽  
Katja POLMAN ◽  
Giuseppina ORTU ◽  
Meryam KRIT ◽  
Frédéric NSABIYUMVA ◽  
...  

Abstract Background : Intestinal schistosomiasis is still a public health problem in Burundi. Since 2008, annual mass drug administration with praziquantel have been rolled out in 11 endemic districts. The national programme relies on school-based surveys with Kato-Katz to monitor the impact of mass drug administration. We explored whether routine data on intestinal schistosomiasis as determined by direct fecal smears at health centre level could be used. Methods : From the Burundian National Health Information System, we collected routine incidence data on intestinal schistosomiasis as determined by direct smear examination in all 45 sanitary districts between 2011 and 2015. A temporal trends analysis was performed using a mixed negative binomial regression. Sanitary districts with mass drug administration campaigns with praziquantel (n=11) were compared with those without (n=34). In addition, prevalence data on intestinal schistosomiasis based on Kato-Katz results from a school-based national mapping in 2014 were compared with the incidence data in health centres based on direct smear results, in the same 45 sanitary districts. Findings : In the 11 sanitary districts applying mass drug administration with praziquantel, the incidence rate decreased significantly for the years 2014 (β 2014 =-0.826, p=0.010) and 2015 (β 2015 =-1.294, p<0.001) and for the five-year period (β=-0.286, p<0.001), whereas in the 34 districts where mass drug administration was not delivered, there was no significant decrease over time (β=-0.087, p=0.219). In most of the 45 sanitary districts, the low prevalences based on Kato-Katz in schoolchildren were confirmed by low incidence rates based on direct smear in the health centres. Conclusions : National Health Information System surveillance data, based on routinely collected direct smear results at health centre level, may be able to monitor the impact of mass drug administration with praziquantel on intestinal schistosomiasis in Burundi. Control and elimination of intestinal schistosomiasis call for integration of adequate diagnosis and treatment into routine activities of primary health care facilities, as recommended by the World Health Organization since more than 20 years. When moving towards elimination, more sensitive tests, such as the Point-of-care Circulating Cathodic Antigen assay are desirable. Keywords : Direct smear, Health centre, Mass drug administration, Monitoring, Praziquantel, Routine data, Schistosomiasis, Burundi


2020 ◽  
Author(s):  
Rebecca A. Gladstone ◽  
Ebrima Bojang ◽  
John Hart ◽  
Emma M Harding-Esch ◽  
David Mabey ◽  
...  

ABSTRACTBackgroundMass drug administration (MDA) with azithromycin for trachoma elimination reduces nasopharyngeal carriage of Streptococcus pneumoniae in the short term. We evaluated S. pneumoniae carried in the nasopharynx before and after a round of azithromycin MDA to determine whether MDA was associated with changes in pneumococcal population structure.MethodsWe analysed 514 pneumococcal isolates cultured from nasopharyngeal samples collected in Gambian villages that received MDA for trachoma elimination. The samples were collected during three cross-sectional surveys conducted before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. Whole genome sequencing was conducted on randomly selected isolates. Bayesian Analysis of Population Structure (BAPS) was used to cluster related isolates by capturing variation in the core genome. Serotype and multi-locus sequence type were inferred from the genotype. The Antimicrobial Resistance Identification by Assembly (ARIBA) tool was used to identify macrolide resistance genes.ResultsTwenty-seven BAPS clusters were assigned. These consisted of 81 sequence types (STs), 15 of which were novel additions to pubMLST. Two BAPS clusters, BAPS20 (p-value<=0.016) and BAPS22 (p-value<=0.032) showed an increase in frequency at CSS-3 not associated with antimicrobial resistance. Macrolide resistance within BASP17 increased after treatment (p<0.05) and was carried on a mobile transposable element that also conferred resistance to tetracycline.ConclusionsLimited changes in pneumococcal population structure were observed after the third round of MDA suggesting treatment had little effect on the circulating lineages. An increase in macrolide resistance within one BAPS highlights the need for antimicrobial resistance surveillance in treated villages.


2021 ◽  
Vol 4 (4) ◽  
pp. 513-519
Author(s):  
D. E. Akafyi ◽  
I. S. Ndams ◽  
S. A. Luka ◽  
F. S. Ojeleye ◽  
S. O. Elkanah ◽  
...  

This study was undertaken to evaluate the effects of Mass Drug Administration (MDA) on Wuchereria bancrofti (microfilariae) after two rounds of combined Ivermectin and Albendazole distribution. A total of 221 participants were recruited in three communities in Lau Local Government Area of Taraba State by convenience sampling method. Questionnaires and physical examinations were used to assess clinical manifestations associated with the infection. Blood samples were collected by finger prick method and stained with Giemsa stain for examination to establish the presence of W. bancrofti while immunochromatographic card test was performed to determine the presence of filarial antigen in serum. Previous data were used to determine the pre-drug prevalence of the parasite. The results showed that the drug did not significantly reduce the clinical manifestations reported among the patients. The microfilariae prevalence and microfilaria mean density after two rounds of drug administration was 19.5% and 1.49%, while the pre- MDA prevalence and microfilaria mean density was 27.8% and 2.44% respectively. There was a statistically significant decrease of microfilaria prevalence (P<0.05) after two rounds of MDA. There was no significant effect of MDA by age, sex and occupation-related microfilariae prevalence in the study area.  In conclusion, the study reveals that microfilaria prevalence and load decreased after two rounds of MDA of combined Ivermectin and Albendazole distribution amongst the studied populations. Routine evaluation of the MDA is required to assess the impact of the drug for the eventual elimination of the infection.


2019 ◽  
Vol 4 (6) ◽  
pp. e001776 ◽  
Author(s):  
Hannah R Meredith ◽  
Luis Furuya-Kanamori ◽  
Laith Yakob

BackgroundLong-lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that overdependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability.MethodsHere, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through mathematical model simulation.ResultsThe review identified drugs from four classes commonly used in livestock and companion animals: avermectins, milbemycins, isoxazolines and spinosyns. Simulations predicted that isoxazolines and spinosyns are promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations.ConclusionsThese findings will provide a guide for investigating and applying different systemic insecticides to achieve more effective and sustainable control of malaria transmission.


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