Role of selected criteria and preventive chemotherapy in tumor recurrence after liver transplantation

Background:Long-term survival after liver transplantation(LT)for hepatocellular carcinoma(HCC)patients remains poor because of tumor recurrence.To improve the prognosis of HCC patients after LT,we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center.Methods:In total,data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis.The patients were divided into the following three groups:Group 1,within the Milan and Hangzhou criteria(n=51);Group 2,beyond the Milan but within the Hangzhou criteria(n=36);and Group 3,beyond the Milan and Hangzhou criteria(n=112).Survival probabilities for the three groups were calculated using multivariate Cox regression analysis.The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis.Results:Child-Pugh stage C and hepatitis B virus(HBV)infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria.The overall survival rates of the 199 patients showed statistically significant differences among the three groups(P<0.001).Moreover,no significant difference was noted in the survival rate between Group 1 and Group 2(P>0.05).Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria(OR=0.478;95%CI:0.308–0.741;P=0.001).Conclusions:Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT.The Hangzhou criteria were effective and analogous compared with the Milan criteria.Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.

High infection rates for onchocerciasis and soil-transmitted helminthiasis in children under fve not receiving preventive chemotherapy:a bottleneck to elimination

Background:The current mainstay for control/elimination of onchocerciasis and soil-transmitted helminthiasis(STH)relies on ivermectin-and mebendazole/albendazole-based preventive chemotherapies.However,children under fve years of age have been excluded in both research activities and control programs,because they were believed to have insignifcant infection rates.There is therefore a need for up-to-date knowledge on the prevalence and inten‑sity of STH and onchocerciasis infections in this age group.This study aimed at assessing the rates and intensities of onchocerciasis and STH infections in children under fve years of age who are excluded from ivermectin-or mebenda‑zole/albendazole-based preventive chemotherapies.Methods:A series of cross-sectional surveys was conducted in four Health Districts in the Centre and Littoral Regions of Cameroon between 2018 and 2019.All subjects aged 2 to 4 years,were screened for prevalence(or infection rate)and intensity[number of eggs per gram of stool(epg)or number of microflariae per skin snip(mf/ss)]of STH and onchocerciasis infections respectively using the Kato-Katz and skin snip methodologies.Chi-square and the nonparametric tests(Mann Whitney and Kruskal Wallis)were used to compare infection rates and intensities of infections between Health Districts and genders,respectively.Results:A total of 421 children were enrolled in this study.The overall prevalence of onchocerciasis was 6.6%[95% confdence interval(CI):4.3‒9.9],ranging from 3.6%(in the Ntui Health District)to 12.2%(in the Bafa Health District).The intensity of infection ranged from 0.5 to 46 microflariae per skin snip[median:5;interquartile range(IQR):2.25‒8.5].The overall prevalence of STH was 9.6%(95%CI:6.5‒13.9),with a high infection rate(29.6%)in the Akonolinga Health District.Two STH species(Ascaris lumbricoides and Trichuris trichiura)were found among infected individuals.The median intensities of STH infections were 1,992 epg(IQR:210‒28,704)and 96 epg(IQR:48‒168)for A.lumbricoides and T.trichiura,respectively.Conclusions:This study reveals that children<5 years of age are highly infected with STH and onchocerciasis,and could contribute to the spread of these diseases,perpetuating a vicious circle of transmission and hampering elimi‑nation eforts.These fndings reveal the urgent need to provide(or scale)treatments(likely pediatric formulations)to these preschool-aged children,especially in areas of high transmission,to accelerate eforts to reach WHO 2030 target.

Sustained preventive chemotherapy for soil-transmitted helminthiases leads to Pdaes reduction in prevalence and anthelminthic tablets required

Background:The goal of soil-transmitted helminthiases(STH)control programmes is to eliminate STH-associated morbidity in the target population by reducing the prevalence of moderate-and heavy-intensity infections and the overall STH infection prevalence mainly through preventive chemotherapy(PC)with either albendazole or mebendazole.Endemic countries should measure the success of their control programmes through regular epidemiological assessments.We evaluated changes in STH prevalence in countries that conducted effective PC coverage for STH to guide changes in the frequency of PC rounds and the number of tablets needed.Methods:We selected countries from World Health Organization(WHO)^Preventive Chemotherapy and Transmission control(PCT)databank that conducted≥5 years of PC with effective coverage for school-age children(SAC)and extracted STH baseline and impact assessment data using the WHO Epidemiological Data Reporting Form,Ministry of Health reports and/or peer-reviewed publications.We used pooled and weighted means to plot the prevalence of infection with any STH and with each STH species at baseline and after≥5 years of PC with effective coverage.Finally,using the WHO STH decision tree,we estimated the reduction in the number of tablets needed.Results:Fifteen countries in four WHO regions conducted annual or semi-annual rounds of PC for STH for 5 years or more and collected data before and after interventions.At baseline,the pooled prevalence was 48.9%(33.1-64.7%)for any STH,23.2%(13.7-32.7%)for Ascoris lumbricoides,21.01%(9.7-32.3%)for Trichuris trichiuro and 18.2%(10.9-25.5%)for hookworm infections,while after>5 years of PC for STH,the prevalence was 14.3%(7.3-21.3%)for any STH,6.9%(1.3-12.5%)for A.lumbricoides,5.3%(1.06-9.6%)for T.trichiura and 8.1%(4.0-12.2%)for hookworm infections.Conclusions:Countries endemic for STH have made tremendous progress in reducing STH-associated morbidity,but very few countries have data to demonstrate that progress.In this study,the data show that nine countries should adapt their PC strategies and the frequency of PC rounds to yield a 36%reduction in drug needs.The study also highlights the importance of impact assessment surveys to adapt control strategies according to STH prevalence.

The clinical use of interventional chemotherapy and intravesical instillation for preventing recurrence of superficial bladder cancer

Objective To study the therapeutic efficacy of combined interventional chemotherapy and intravesical instillation of mitomycin on preventing bladder cancers from recurring after local ablation. Methods 28 patients with superficial bladder cancers were randomized into combined interventional chemotherapy and intravesical instillation of mitomycin or intravesical instillation of mitomycin alone for preventing recurrence after local ablation. The result was assessed by x2 test. Results The patients have been followed up for 12-26 months (mean 21 months). 1 case has had tumor recurrence in the combined modality therapy group and 4 in the intravesical instillation alone group, the tumor recurrence rate being 7% (1/14) and 29% (4/14) respectively (P【0.05). Conclusion Combined use of interventional chemotherapy and intravesical instillation of mitomycin is effective in preventing superficial bladder cancer from recurring after local ablation with fewer adverse effects. The ragimen is not only reliable but

Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study

Background Mass drug administration(MDA)program of albendazole to at-risk populations as preventive chemo-therapy is the core public health intervention to control soil-transmitted helminths(STHs).Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing reinfection.We assessed the effcacy of albendazole against STH parasite infection and reinfection status after cure.Methods A total of 984 schoolchildren infected with at least one type of STH parasite(hookworm,Ascaris lumbri-coides,Trichuris trichiura)in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March 2019.Stool exams at week-4 and at week-8 of post-MDA were done using Kato Katz technique.The primary outcome was effcacy assessed by cure rate(CR)and fecal egg reduction rates(ERRs)at four weeks of post-MDA.The secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of post-MDA.Group comparisons in CR and related factors were assessed with chi-square or Fisher's exact tests.Predictors of CR were examined through univariate and multi-variate regression analyses.Results The overall CR and ERR for hookworm infection were 97.2%(95%CI:94.6-99.4)and 97.02%,respectively.The overall CR and ERR for A.lumbricoides were 71.5%(95%CI:68.3-74.6)and 84.5% respectively.The overall CR and ERR and for T.trichiura were 49.5%(95%CI:44.8-54.2)and 68.3%,respectively.The CR among moderate T.trichiura infec-tion intensity was 28.6%.Among children cured of hookworm,A.lumbricoides and T.trichiura at week 4 post-MDA,4.6%,18.3% and 52.4% became reinfected at week-8 post-MDA,respectively.Significantly lower CR(36.6%)and higher reinfection after cure(60.6%)among A.lumbricoides and T.trichiura coinfected children than A.lumbricoides only(CR=69.6%,reinfection rate=15.1%)or T.trichiura only infected children(CR=55.6%,reinfection rate=47.1%)was observed.Pre-treatment coinfection with≥two types of STH parasites was significantly associated with re-infec-tion after cure.Conclusion Albendazole MDA is efficacious against hookworm but has reduced efficacy against A.lumbricoides and is not effective against T.trichiura.The low drug efficacy and high reinfection rate after cure underscore the need for alternative treatment and integration of other preventive measures to achieve the target of eliminating STHs as a public health problem by 2030.

Effectiveness of ivermectin mass drug administration in the control of soil-transmitted helminth infections in endemic populations: a systematic review and meta-analysis

Background Current soil-transmitted helminth(STH)control guidelines endorse the use of albendazole or meben-dazole for school-based targeted preventive chemotherapy(PC),yet their reduced efficacy against Strongyloides sterc-oralis and Trichuris trichiura presents significant limitations.Emerging evidence indicates that community-wide PC[or mass drug administration(MDA)]using ivermectin,commonly used in other neglected tropical disease(NTD)control programs,may play an important role in controlling these parasites.We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations.Methods We searched Pubmed,EMBASE,and Web of Science on February 14,2023,for studies that investigated the effectiveness of ivermectin PC,either alone or in combination with other anthelmintic drugs,on STH infec-tions,and provided a measure of STH prevalence before and after PC.We calculated pooled prevalence reductions for each STH using random-effects meta-analyses.Our protocol is available on PROSPERO(registration number CRD42023401219).Results A total of 21 were eligible for the systematic review,of which 15 were eligible for meta-analysis.All studies delivered ivermectin through MDA.The pooled prevalence reduction of S.stercoralis following MDA with ivermec-tin alone was 84.49%(95%CI:54.96-94.66)across five studies and 81.37%(95% CI:61.62-90.96)across seven studies with or without albendazole.The prevalence reduction of T.trichiura was 49.93%(95%CI:18.23-69.34)across five studies with ivermectin alone,and 89.40%(95%CI:73.66-95.73)across three studies with the addition of albendazole.There was high heterogeneity for all syntheses(I^(2)>65%).Conclusions This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S.stercoralis and T.trichiura.Based on these findings,revising inter-national STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination ofSTHsandotherNTDs.

Moving from control to elimination of schistosomiasis in sub-Saharan Africa:time to change and adapt strategies

Schistosomiasis is a water borne parasitic disease of global importance and with ongoing control the disease endemic landscape is changing.In sub-Saharan Africa,for example,the landscape is becoming ever more heterogeneous as there are several species of Schistosoma that respond in different ways to ongoing preventive chemotherapy and the inter-sectoral interventions currently applied.The major focus of preventive chemotherapy is delivery of praziquantel by mass drug administration to those shown to be,or presumed to be,at-risk of infection and disease.In some countries,regional progress may be uneven but in certain locations there are very real prospects to transition from control into interruption of transmission,and ultimately elimination.To manage this transition requires reconsideration of some of the currently deployed diagnostic tools used in surveillance and downward realignment of existing prevalence thresholds to trigger mass treatment.A key challenge will be maintaining and if possible,expanding the current donation of praziquantel to currently overlooked groups,then judging when appropriate to move from mass drug administration to selective treatment.In so doing,this will ensure the health system is adapted,primed and shown to be cost-effective to respond to these changing disease dynamics as we move forward to 2020 targets and beyond.

The fight against lymphatic filariasis:perceptions of community drug distributors during mass drug administration in coastal Kenya

Background:Lymphatic filariasis(LF)#a neglected tropical disease(NTD)and leading cause of global disability,is endemic in 32 countries in Africa with almost 350 million people requiring regular drug administration,and only 16 countries achieving target coverage.Community Drug Distributors(CDDs)are critical for the success of NTD programs,and the distribution of medicines during mass drug administration(MDA)in Africa;however they could also be a weak link.The primary aim of this study is to explore and describe perceptions of CDDs during MDA for LF in Mvita sub-county in Mombasa county and Kaloleni sub-county in Kilifi county,Kenya;and provide recommendations for the effective engagement of communities and CDDs in low-resource settings.Methods:In September 2018,we conducted six focus group discussions with community members in each sub-county,three with men aged 18-30,31-50,and 51 years and above and three with women stratified into the same age groups.In each sub-county,we also conducted semi-struaured interviews with nine community health extension workers(CHEWs),the national LF focal point,the county NTD focal points,and seven community leaders.Content analysis of the data was conducted,involving a process of reading,coding,and displaying data in order to develop a codebook.Results:We found that several barriers and facilitators impact the engagement between CDDs and community members during MDA.These barriers include poor communication and trust between CDDs and communities;community distrust of the federal government;low community knowledge and perceived risk of LF,poor timing of MDA,fragmented supervision of CDDs during MDA;and CDD bias when distributing medicines.We also found that CDD motivation was a critical factor in their ability to successfully meet MDA targets.It was acknowledged that directly observed treatment and adequate health education were often not executed by CDDs.The involvement of community leaders as informal supervisors of CDDs and community members improves MDA.Conclusions:In order to achieve global targets around the elimination of LF,CDDs and communities must be effectively engaged by improving planning and implementation of MDA.

Control programs for strongyloidiasis in areas of high endemicity: an economic analysis of different approaches

Background:Implementation of control programmes for Strongyloides stercoralis infection is among the targets of the World Health Organization Roadmap to 2030.Aim ofthis work was to evaluate the possible impact in terms of economic resources and health status of two different strategies of preventive chemotherapy(PC)compared to the current situation(strategy A,no PC):administration of ivermectin to school-age children(SAC)and adults(strategy B)versus ivermectin to SAC only(strategy C).Methods:The study was conducted at the IRCCS Sacro Cuore Don Calabria hospital,Negrar di Valpolicella,Verona,Italy,at the University of Florence,Italy,and at the WHO,Geneva,Switzerland,from May 2020 to April 2021.Data for the model were extracted from literature.A mathematical model was developed in Microsoft Excel to assess the impact of strategies B and C in a standard population of 1 million subjects living in a strongyloidiasis endemic area.In a case base seenario,15%prevalence of strongyloidiasis was considered;the 3 strategies were then evaluated at different thresholds of prevalenee,ranging from 5 to 20%.The results were reported as number of infected subjects,deaths,costs,and Incremental-Effectiveness Ratio(ICER).A 1-year and a 10-year horizons were considered.Results:In the case base seenario,cases of infections would reduce dramatically in the first year of implementation of PC with both strategy B and C:from 172500 cases to 77040 following strategy B and 146700 following strategy C.The additional cost per recovered person was United States Dollar(USD)2.83 and USD 1.13 in strategy B and C,respectively,compared to no treatment in the first year.For both strategies,there was a downtrend in costs per recovered person with increasing prevalenee.The number of adverted deaths was larger for strategy B than C,but cost to advert one death was lower for strategy C than B.Conclusions:This analysis permits to estimate the impact of two PC strategies for the control of strongyloidiasis in terms of costs and adverted infections/deaths.This could represent a basis on which each endemic country can evaluate which strategy can be implemented,based on available funds and national health priorities.

Estimated need for anthelminthic medicines to control soil-transmitted helminthiases in school-aged children,2020–2030

Background:Soil-transmitted helminthiases(STH)are part of the group of neglected tropical diseases traditionally treated with preventive chemotherapy interventions.In recent years,drug donations have been essential to expanding preventive chemotherapy and achieving progressive control of morbidity from STH.This study aims to evaluate the need for anthelminthic medicines during 2020–2030.Methods:To estimate the need for anthelminthic medicines,we considered three different scenarios:(1)the control programmes continues to expand coverage and maintains the frequency of drug administration established at baseline;(2)the programmes continues to expand coverage but adapts the frequency of drug administration when the STH prevalence is reduced and(3)the STH programme becomes self-sustainable in some endemic countries.Results:We estimate that the number of anthelmintic medicines needed to treat school-aged children will increase by 40%by 2025 and by 52%by 2030 if countries do not change the frequency of preventive chemotherapy(scenario 1);that the number of tablets needed will reduce by 32.4%by 2025 and by 49.1%in 2030 if endemic countries reduce the frequency of preventive chemotherapy(scenario 2);and drug donations could be reduced by 54.4%by 2025 and 74.4%by 2030 if some endemic countries could become independent in drug procurement(scenario 3).Conclusions:The number of anthelmintic medicines needed to achieve elimination of morbidity due to STH in school-aged children will decline during 2020–2030.The decline will be substantial if a number of“upper-middle income”countries in which STH are endemic procure,as expected,anthelminthic medicines independently.