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

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

Lymphatic Filariasis: A Systematic Review on Morbidity and Its Repercussions in Countries in the Americas

The Global Program to Eliminate Lymphatic Filariasis (GPELF) is a program that aims to eliminate lymphatic filariasis by 2030. The GPELF strategy is based on interrupting transmission using mass drug administration (MDA) and, in parallel, managing morbidity cases. However, it has been seen that there is a shortage of research in the literature and public policies regarding this last pillar. In this study, we reviewed the literature and available information regarding the burden of filarial morbidity. In addition, we identified that in the Americas, the implementation of structured services with regard to morbidity assistance in the Americas was scarce. We formed a review that aimed to assess the pathogenesis, epidemiology, repercussions, and treatment of filarial morbidity in countries in the Americas where lymphatic filariasis is endemic. Structured searches were carried out on PubMed, LILACS, Scopus, and Web of Science databases without time and language restrictions. Three reviewers evaluated the 2150 studies and performed data extraction, and quality assessment by assigning scores to the studies found. The current literature and available information on the burden of filarial morbidity, as well as the implementation of structured services with regard to morbidity assistance in the Americas, were all found to be scarce. Now that this knowledge gap has been identified, both health services and researchers need to seek the implementation and enhancement of the maintenance of GPELF strategies that relate to the morbidity pillar.

Failure of Repeated MDA with Albendazole for Trichuriasis Control in Schoolchildren of the Yangon Region, Myanmar

Soil-transmitted helminth (STH) infections are still a considerable challenge in Myanmar. We undertook a control program for STH infections (especially Trichuris trichiura) among schoolchildren in Myanmar using mass drug administration (MDA) and health education. Around 1,700 schoolchildren from 15 primary schools in 3 suburban districts (Shwe Pyi Thar, Twantay, and Kyauktan) of the Yangon Region were subjected in this study during 2017-2019. All of the schoolchildren in each school were orally administered albendazole (400 mg in a single dose) 2, 3, and 4 times a year in 2017, 2018, and 2019, respectively. The results revealed that the egg positive rate of any intestinal helminths (including STH) was reduced from 37.6% (649/1,724) in 2017 to 22.8% (352/1,542) in 2019. The egg positive rate of Ascaris lumbricoides was decreased remarkably from 23.3% (402/1,724) in 2017 to 3.6% (56/1,542) in 2019. However, that of T. trichiura was only slightly reduced from 26.9% (464/1,724) in 2017 to 20.2% (312/1,542) in 2019. The intensity of infection with A. lumbricoides and T. trichiura was both more or less reduced, and the proportion of light infection cases with A. lumbricoides and T. trichiura increased from 35.6% in 2017 to 64.3% in 2019 and from 70.3% in 2017 to 81.7% in 2019, respectively. The results indicated that repeated MDAs (2-4 times a year for 3 years) using albendazole on schoolchildren in Myanmar failed to control T. trichiura infection. For a successful control of trichuriasis in Myanmar, new MDA strategies, using a modified albendazole regimen (multiple daily doses for 2 or 3 days) or an alternative anthelmintic drug, such as oxantel pamoate, is strongly recommended.

Coverage evaluation surveys following soil-transmitted helminthiasis and schistosomiasis mass drug administration in Wolaita Zone of Ethiopia—The Geshiyaro project

Introduction The Geshiyaro project aims to break transmission of soil-transmitted helminths and schistosomiasis in the Wolaita Zone of Ethiopia through a combination of two interventions: behavior change communication (BCC) for increased water, sanitation and hygiene (WaSH) infrastructure use alongside preventive chemotherapy (PC) using albendazole (ALB) and praziquantel (PZQ), targeted to reach 90% treatment coverage. Coverage evaluation surveys (CES) were conducted post-treatment, and the resultant survey coverage was compared to reported administrative coverage. This provided a secondary confirmation of the Geshiyaro project coverages, and is used to monitor the success of each Mass Drug Administration (MDA) round. Methods A community-based cross-sectional study was conducted in 13 woredas (districts) of the Wolaita Zone. All eligible individuals from the selected households were invited for an interview. The study design, sample size, analysis and report writing were conducted according to the World Health Organization (WHO) CES guidelines for PC. Results The study interviewed a total of 3,568 households and 18,875 individuals across 13 woredas in the Wolaita Zone. Overall, the survey coverage across all studied woredas was 81.5% (95% CI; 80.9–82.0%) for both ALB and PZQ. Reported administrative coverage across all studied woredas was higher than survey coverage, 92.7% and 91.2% for ALB and PZQ, respectively. A significant portion of individuals (17.6%) were not offered PC. The predominant reason for not achieving the target coverage of 90% was beneficiary absenteeism during MDA (6.6% ALB, 6.8% PZQ), followed by drug distributors failing to reach all households (4.7% ALB, 4.8% PZQ), and beneficiaries not informed of the program (1.3% ALB, 1.7% PZQ). Conclusion Programmatic actions will need to be taken during the next MDA campaign to achieve the targeted Geshiyaro project coverage threshold across data collection and program engagement. Adequate training and supervision on recording and reporting administrative coverage should be provided, alongside improved social mobilization of treated communities to increase participation, and strengthened institutional partnerships and communication.

An Assessment of Implementation of Mass Drug Administration for Prevention and Control of Schistosomiasis and Soil-Transmitted Helminths in Selected Southern Malawi Districts

Background Mass drug administration (MDA) is one of the key interventions recommended by WHO for prevention and control of neglected tropical diseases. In Malawi, MDA is widely carried out annually since 2012 for prevention and control of schistosomiasis and soil transmitted helminths (STH). No study has been carried out to assess effectiveness of the approach and to document perceptions of health providers and beneficiaries regarding use of MDA. This study aimed to examine perceived strengths and weaknesses, successes and failures, as well as health providers’ and beneficiaries’ perspectives of implementing the strategy in Malawi. Methods As a cross-sectional implementation research, the study was carried out in three southern Malawi districts of Chiradzulu, Mangochi and Zomba. In each district, four health centres and 16 villages were randomly selected to participate. A mixed-methods approach to data collection focusing on quantitative data for coverage and knowledge, attitudes and practices assessments; and qualitative data for assessing perceptions of health providers and beneficiaries regarding MDA was used. Quantitative data were processed and analyzed using IBM SPSS software version 26 while qualitative data were analysed using NVivo 12 for Windows. Results Knowledge levels about schistosomiasis and STH in the districts varied according to disease aspects asked about. Majority are more knowledgeable about what schistosomiasis is (78%) and whether STH are treatable with drugs (97%); with least knowledgeable about the organism that transmits schistosomiasis (18%), types of schistosomiasis (11%) and what causes STH (20%). In 2018 and 2019 the districts registered high coverage rates for praziquantel and albendazole using community-based MDA (73%-100%) and using school-based MDA (75%-91%). Both the health authorities and community members perceived the MDA approach as good because it brings treatment closer to people. Conclusion With the high MDA coverage obtained in schools and communities, the implementation of MDA in the target districts is satisfactory. There are, however, several challenges including disproportionate knowledge levels, which are hampering progress towards attainment of the 2030 global NTD goals. There is a need for promotion of community participation and partnerships as well as implementation of other recommended interventions for sustainable prevention and control of schistosomiasis and STH.

Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection

Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of Schistosoma mansoni infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment of S. mansoni-infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection.

Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa

ObjectivesUnder the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2) based on World Health Organization guidelines. In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa.MethodsWe examined school-level Ag and Ab status (presence/absence of Ag- and Ab- positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson’s chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3.ResultsSchools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5).ConclusionAnti-filarial Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-MDA surveillance and decision making should be further investigated in other settings.