WHO | NEGLECTED TROPICAL DISEASES
Ninth meeting of the Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy
Geneva, 12 March 2020
Ninth meeting of the Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy
Geneva, 12 March 2020 Ninth meeting of the Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, Geneva, 12 March 2020 ISBN 978-92-4-001408-4 (electronic version) ISBN 978-92-4-001409-1 (print version)
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1 Background 1
2 Drug efficacy studies 4 2.1 Benzimidazoles 4 2.2 Praziquantel 5 2.3 Discussion 5 2.4 Action and next steps 5
3. Research update on praziquantel efficacy 6 3.1 Discussion 7
4. Updates on drug development 8
5. Manual on assessing anthelminthic drug efficacy 9 5.1 Action and next steps 9
6. Establishing a network of NTD laboratories 10 6.1 Discussion 10
7. Role of the WHO Working Group on Drug Efficacy 11
References 12 Annex 1. List of participants 13 Annex 2. Agenda 15
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1. Background
The World Health Organization (WHO) recommends preventive chemotherapy as a public health strategy to control and prevent morbidity due to four helminth infections (lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiases) and one chlamydial infection (trachoma). In 2018, global coverage of preventive chemotherapy reached 64% in endemic populations, with more than 1.1 billion individuals treated (1). With such a relatively large drug pressure, and one which will be continued over the next few years on the road towards elimination of neglected tropical diseases (NTDs), the potential risk of emerging resistance must be considered.
The Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy has developed a protocol to guide assessments of drug efficacy against both schistosomiasis (with praziquantel) and soil-transmitted helminthiases (with albendazole and mebendazole). It also recommends testing drug combinations and co-administering albendazole and mebendazole with ivermectin to contain the risk of emergence of resistance. Assessments are recommended in particular in areas where preventive chemotherapy programmes have attained a high coverage for more than 5 years. To date, more than 20 drug efficacy trials have been performed in 15 countries Table( 1). While in most countries no signs of resistance to praziquantel have been observed, in others reduced efficacy has been noted. For example, the mean Schistosoma mansoni egg reduction rate in schoolchildren in Uganda who had received 8 or 9 previous rounds of preventive chemotherapy was found to be significantly lower than the mean reduction rate in schoolchildren who had received 5 or a lower number of rounds of preventive chemotherapy (2). Similarly, in some countries, doubtful efficacy results have been reported for mebendazole against hookworm infections.
The objectives of the meeting were:
to evaluate the reports of drug efficacy trials conducted in endemic countries during 2019;
to discuss research updates in the area of anthelminthic resistance;
to propose an update for the WHO manual on assessing anthelminthic drug efficacy; and
to discuss the first draft of a document on establishing a network of laboratories to support periodic evaluation of anthelminthic efficacy in endemic countries.
The two-day meeting was condensed into one day due to the COVID-19 pandemic. Although several participants returned urgently to their home countries before the start of the meeting, many participated online. The list of participants is attached as Annex 1 and the agenda as Annex 2.
1 Table 1. Drug efficacy trials conducted under the supervision of the Working Group on Drug Efficacy, 2010–2019
Country Year Drug Target Egg reduction 95% confidence Drug efficacy Reference rate (%) interval classification SOIL-TRANSMITTED HELMINTHIASES Brazil 2010 ALB A. lumbricoides 100.0 NR Satisfactory (3) Hookworm 97.5 NR Satisfactory (3) Cambodia 2010 ALB Hookworm 97.6 NR Satisfactory (3) Cameroon 2010 ALB A. lumbricoides 99.2 NR Satisfactory (3) T. trichiura 39.2 NR Reduced (3) Hookworm 93.0 NR Satisfactory (3) Ethiopia 2010 ALB A. lumbricoides 100.0 NR Satisfactory (3) T. trichiura 92.4 NR Satisfactory (3) Hookworm 99.7 NR Satisfactory (3) India 2010 ALB Hookworm 87.1 NR Doubtful (3) United Republic of 2010 ALB A. lumbricoides 100.0 NR Satisfactory (3) Tanzania (Zanzibar) T. trichiura 52.0 NR Satisfactory (3) Hookworm 95.3 NR Satisfactory (3) Viet Nam 2010 ALB A. lumbricoides 100.0 NR Satisfactory (3) T. trichiura 92.3 NR Satisfactory (3) Hookworm 100.0 NR Satisfactory (3) Brazil 2013 MEB A. lumbricoides 97.5 95.7–99.3 Satisfactory (4) Hookworm 84.4 80.9–87.9 Satisfactory (4) Cameroon 2013 MEB A. lumbricoides 99.8 99.5–100.0 Satisfactory (4) T. trichiura 56.2 39.4–73.0 Satisfactory (4) Hookworm 71.9 55.6–88.1 Satisfactory (4) Cambodia 2013 MEB Hookworm 79.7 73.7–85.7 Satisfactory (4) Ethiopia 2013 MEB A. lumbricoides 98.6 97.7–99.4 Satisfactory (4) T. trichiura 65.9 57.5–74.4 Satisfactory (4) Hookworm 65.4 55.3–75.6 Doubtful (4) United Republic of 2013 MEB A. lumbricoides 97.1 95.1–99.0 Satisfactory (4) Tanzania (Zanzibar) T. trichiura 51.2 41.3–61.0 Satisfactory (4) Hookworm 74.6 63.8–85.4 Satisfactory (4) Viet Nam 2013 MEB A. lumbricoides 93.9 91.2–96.5 Satisfactory (4) T. trichiura 76.8 67.7–85.8 Satisfactory (4) Hookworm 95.0 91.2–98.9 Satisfactory (4) Ethiopia 2016 ALB A. lumbricoides 99.9 99.8–100 Satisfactory (5) T. trichiura 52.9 39.1–65.7 Satisfactory (5) Hookworm 96.3 92.8–98.5 Satisfactory (5) Lao People’s 2016 ALB A. lumbricoides 99.2 97.7–100 Satisfactory (5) Democratic Republic T. trichiura 36.7 -0.6–57.8 Reduced (5) Hookworm 96.1 93.7–97.7 Satisfactory (5) United Republic of 2016 ALB A. lumbricoides 96.8 92.1–99.5 Satisfactory (5) Tanzania (Pemba) T. trichiura -11.2 -30.4–5.9 Reduced (5) Hookworm 84.2 75.4–90.7 Doubtful (5)
2 Country Year Drug Target Egg reduction 95% confidence Drug efficacy Reference rate (%) interval classification Unpublished Ghana 2019 ALB Hookworm 94.7 92.0–96.9 Satisfactory results, Ugent Unpublished Bangladesh 2019 MEB A. lumbricoides 99.9 99.9–100 Satisfactory results, Ugent Unpublished T. trichiura 90.4 84.0–95.3 Satisfactory results, Ugent Unpublished Cambodia 2019 MEB Hookworm 44.1 18.4–65.0 Reduced results, Ugent Lao People’s Unpublished 2019 MEB A. lumbricoides 99.2 97.2–99.9 Satisfactory Democratic Republic results, Ugent Unpublished T. trichiura 75.8 67.0–83.1 Satisfactory results, Ugent Unpublished Hookworm 67.3 60.3–73.7 Doubtful results, Ugent Unpublished Viet Nam 2019 MEB A. lumbricoides 99.4 98.8–99.8 Satisfactory results, Ugent Unpublished T. trichiura 65.7 58.2–73.3 Satisfactory results, Ugent Unpublished Hookworm 59.3 49.2–68.3 Reduced results, Ugent SCHISTOSOMIASIS Levecke et al. Brazil 2014 PZQ S. mansoni 93.4 88.8–96.8 Satisfactory (submitted) Levecke et al. Cameroon 2014 PZQ S haematobium 98.8 97.7–99.5 Satisfactory (submitted) Levecke et al. PZQ S. mansoni 88.5 79.0–95.1 Doubtful (submitted) Levecke et al. Ethiopia 2014 PZQ S. mansoni 99.9 99.7–100 Satisfactory (submitted) Levecke et al. PZQ S haematobium 99.9 99.6–100 Satisfactory (submitted) Levecke et al. Mali 2014 PZQ S haematobium 92.8 89.2–95.6 Satisfactory (submitted) Levecke et al. PZQ S. mansoni 92.0 84.3–97.1 Satisfactory (submitted) Levecke et al. Philippines 2014 PZQ S. japonicum 90.0 68.4–99.3 Satisfactory (submitted) United Republic of Levecke et al. 2014 PZQ S. haematobium 98.9 98.3–99.4 Satisfactory Tanzania (mainland) (submitted) Levecke et al. PZQ S. mansoni 99.3 98.4–99.8 Satisfactory (submitted) United Republic of Levecke et al. 2016 PZQ S. haematobium 99.7 99.2–100 Satisfactory Tanzania (Zanzibar) (submitted) Tchuem- Cameroon 2016 PZQ S. mansoni 97.2 95.1–98.7 Satisfactory Thuente et al. (in production) Levecke et al. Madagascar 2016 PZQ S. mansoni 90.7 80.8–97.0 Satisfactory (submitted) ALB: albendazole; MEB: mebendazole; NR: not reported; PZQ: praziquantel.
3 2. Drug efficacy studies
2.1. Benzimidazoles
The WHO Collaborating Centre for the monitoring of anthelminthic drug efficacy for soil-transmitted helminthiasis (Ghent University, Belgium) has conducted drug efficacy studies with benzimidazoles in five countries (Bangladesh, Cambodia, Ghana, Lao People’s Democratic Republic and Viet Nam) using the same study design. Dr Vlaminck presented the results of the studies. In all countries except Ghana, the prevalence of soil-transmitted helminthiases and moderate-to-heavy intensity soil-transmitted helminth infections was > 1% for at least one species (Table 2). The efficacy of mebendazole against Ascaris lumbricoides and Trichuris trichiura infections was satisfactory in all study sites, whereas its efficacy against hookworm infection was reduced or doubtful in each of the three study sites. In addition, the efficacy of albendazole against hookworm infections was found to be satisfactory (Fig. 1).
Table 2. Prevalence of soil-transmitted helminthiases and moderate-to-heavy intensity soil-transmitted helminth infections in the five study sites evaluated by the Collaborating Centre, May–October 2019
Country (number of recruited Ascaris lumbricoides Trichuris trichiura Hookworm subjects) Prevalence (% MHI) Prevalence (% MHI) Prevalence (% MHI) Bangladesh (867) 14.1 (3.1) 8.3 (0.1) 0.1 (0) Cambodia (621) 0 (0) 0.8 (0) 29.8 (3.7) Ghana (1166) 0 (0) 0.1 (0) 13.1 (0.1) Lao People’s Democratic 8.4 (3.3) 27.5 (1.3) 59.5 (9.3) Republic (760)
MHI: moderate-to-heavy intensity.
Fig. 1. Drug efficacy of a single benzimidazole dose Egg reduction rates (and 95% confidence intervals) following a single oral dose are presented for A. lumbricoides, T. trichiura and hookworm infections in the five countries where trials were performed. The colour code represents satisfactory (green), doubtful (grey) or reduced (red) drug efficacy levels according to the WHO manual (6). All countries evaluated mebendazole, except for Ghana, where albendazole (*) was used.
A. lumbricoides T. trichiura hookworm
MEB MEB MEB ALB
100 100 100 100 90 90 90 90
ra te 80 80 80 80 70 70 70 70 60 60 60 60 cti on 50 50 50 50 40 40 40 40 30 30 30 30 gg red u 20 20 20 E 20 10 10 10 10 0 0 0 0 Bangladesh Viet Nam Lao People s Bangladesh Viet Nam Lao People s Cambodia Viet Nam Lao People s Ghana (n 98) (n 456) Democratic (n 50) (n 371) Democratic (n 151) (n 166) Democratic (n 143) Republic Republic Republic (n 60) (n 199) (n 418)
ALB: albendazole; MEB: mebendazole.
4 2.2. Praziquantel
Dr Mwinzi (WHO Regional Office for Africa) and Dr Garba-Djirmay (WHO headquarters) presented the results of studies conducted in four countries to evaluate the efficacy and safety of praziquantel donated by Merck in school-aged children against S. haematobium and S. mansoni infections (Table 3).
Table 3. Praziquantel efficacy and safety studies conducted in four African countries, 2016
Before treatment After treatment (3 weeks) Schistosome Cure rate Egg reduction Country Positive Mean egg Number Number Mean egg species children counts of children of children counts (%) rate (%) treated (EPG) examined positive (EPG) Cameroon S. mansoni 369 252.0 369 38 7.0 89.7 97.20 Madagascar S. mansoni 404 632.0 389 39 87.4 90.0 86.20 Nigeria S. haematobium 209 16.2a 209 8 2.0a 96.2 98.80 United Republic of Tanzania S. haematobium 102 233.2 91 8 0.7 91.2 99.70 (Zanzibar)
EPG: eggs per gram. a Geometric mean.
In addition, in Zimbabwe, an impact study on schistosomiasis and soil-transmitted helminthiases was conducted, together with a praziquantel efficacy study, in 868 school- aged children during 2018–2019. The prevalence of S. mansoni and S. haematobium infections was low at pre- (9% and 2%) and post- (2.2% and 0.4%) treatment respectively. The prevalence of soil-transmitted helminth infections was zero for all species.
2.3. Discussion
Participants discussed several methodological issues and the importance of confounding factors on the results of the drug efficacy studies. While performing efficacy studies, it is important to confirm that before-and-after stool specimens originate from the same treated individual. This is not always easy to do, however, as participants often collect stool specimens at home where the source of the specimen cannot be verified. A second important aspect is that some participants might not completely swallow the administered drug tablet(s) or could have vomited post-treatment without reporting it, leading to important under-dosing and a failed treatment. Hence, it is highly recommended to directly observe the swallowing of the tablet(s) to ensure complete intake of the drug. Professor Vercruysse (Ghent University) presented several other confounding factors that can affect drug efficacy, most of which are mentioned in the WHO manual on drug efficacy 6( ), but some additions could be made.
2.4. Action and next steps
Scientific rigour and adherence to the WHO protocol are necessary to reduce bias in the conduct of drug efficacy studies.
The section on confounding factors in the WHO manual requires updating.
With the support of regional focal points, countries will be selected in WHO regions where new drug efficacy studies will be conducted. Criteria for country selection will include total preventive chemotherapy treatment history, number of treatments or coverage, subnational data (if any), treatment coverage evaluation data, political/ economic stability and current prevalence.
5 3. Research update on praziquantel efficacy
Professor Webster (Royal Veterinary College) described recent developments in research on the efficacy of praziquantel. The Infectious Disease Data Observatory has collected data from studies of schistosomiasis drug efficacy conducted between 2000 and 2016. Currently, it contains data on approximately 20 000 individual patients from 104 cohorts. The research agenda includes the optimal dose regimen (efficacy and safety), documentation of suboptimal responses and efficacy of new drug combinations. She also presented the main findings of newly published studies on praziquantel efficacy (Table 4).
Table 4. New (2019) publications on praziquantel efficacy studies
Title Main findings Reference Efficacy of China-made praziquantel for treatment of The efficacy of China-made PZQ [Zanzibar] does not schistosomiasis haematobium in Africa: a randomized differ significantly from PZQ made by Merck KGaA in (7) controlled trial Germany.
PZQ activates a schistosome transient receptor The anthelmintic drug praziquantel activates a potential (TRP) channel, named Sm.TRPMPZQ, (8) schistosome transient receptor potential channel present in parasitic schistosomes and other PZQ- sensitive parasites.
Transcriptomic analysis of reduced sensitivity to No single gene or pathway is associated with reduced (9) praziquantel in Schistosoma mansoni drug sensitivity.
The lack of cure in about one-fifth of the infected Efficacy and safety of praziquantel for treatment of children indicates the need for close PZQ safety Schistosoma mansoni infection among school children (10) monitoring and treatment optimization research to in Tanzania improve efficacy.
PZQ: praziquantel.
Molecular epidemiology is considered to be an increasingly useful diagnostic tool because it allows the investigation of a suspected reduction in drug efficacy. Molecular studies of S. mansoni “persistent hot-spots” by drug pressure in the United Republic of Tanzania revealed that a change in schistosome density-dependent fecundity likely explained the ongoing high infection intensities observed, rather than changes in the efficacy of praziquantel. Conversely, in regions of high drug pressure in Uganda, parasitological, genetic and genomic evidence indicated a reduction in drug efficacy, highlighting the need for future monitoring.
6 For S. haematobium, there has been no evidence of changes in praziquantel efficacy to date. However, recent molecular studies have revealed very high levels of prevalence and intensity in both adults and children involving viable hybridization between the S. haematobium of humans with the S. bovis, S. currasoni or S. mattheii of livestock. While livestock may present refugia mitigating against the evolution of resistance to praziquantel, at the same time, the potential major challenges raised here are the current use (misuse) of praziquantel in animals and the lack of suitable diagnostics for animal schistosomiasis.
Ongoing projects examining the efficacy of praziquantel at parasitological, genetic and genomic levels include randomized control trials in human populations with high morbidity levels near Lake Albert in Uganda and drug access and efficacy for schistosomiasis in livestock within West Africa.
Professor LoVerde (University of Texas Health Science Center) and Professor Gilleard (University of Calgary Department of Comparative Biology and Experimental Medicine) explained the possible application of molecular techniques to investigate suspected reduction of drug efficacy, highlighting the role of molecular markers and the transformative power of recent developments in sequencing technologies to investigate the emergence of anthelminthic drug resistance. The early detection of resistance is critical for mitigation and management, and molecular testing offers a number of specific advantages in this regard. First, it is potentially scalable, enabling a much larger number of populations to be screened than with efficacy testing. Secondly, molecular assays can detect resistance mutations at very low frequencies in parasite popualtions and so they can potentially detect emergence of resistance well before a measurable reduction in drug efficacy occurs.
3.1. Discussion
Comments and discussions concerned the use and the feasability of molecular studies. Many endemic countries do not have the capacity to conduct such studies. One potential approach to overcome this challenge would be for regional centres using molecular diagnostics to undertake both routine widescale surveillance and to investigate suspected cases of reduced drug efficacy identified by Kato–Katz. Another suggestion is to collect samples for molecular analysis while evaluating drug efficacy and, if drug efficacy appears to be doubtful or reduced, to use the samples in molecular confirmation of drug resistance. If drug efficacy is satisfactory, these samples can serve as an important historical references in future studies.
7 4. Updates on drug development
Professor Keiser (Swiss Tropical and Public Health Institute) gave an update on drug development for treatment of schistosomiasis and soil-transmitted helminthiases. For schistosomiasis, there are many drug candidates (e.g. oxamniquine derivatives, Ro 15-5458, Ro 13-3978 analogues, imidazopyridine series) that are still being studied. For paediatric praziquantel, phase III studies are ongoing in Kenya and Côte d’Ivoire; another will start soon in Zimbabwe. For soil-transmitted helminthiases, a new consortium (the Helminth Elimination Platform) will work on drug discovery and development. An ongoing research study on a new molecule, emodepside, is in phase IIA studies against hookworm and T. trichiura infections.
A trial on the safety and efficacy of increasing doses of albendazole in preschool-aged children, school-aged children and adults against T. trichiura and hookworm infections conducted by Patel et al. (under review) has shown that, for Trichuris, there is no increase in cure rate or egg reduction rate despite an increase in the dose of albendazole, whereas for hookworm a dose response was observed in adults. Another study comparing the efficacy, safety, acceptability and age-appropriateness of two tablets (swallowable and chewable) of mebendazole in children aged 3–12 years showed no difference in terms of efficacy; both tablets were well tolerated.
Finally, the preliminary analysis on the efficacy of combined albendazole and ivermectin versus albendazole on T. trichiura showed a statistically significant difference in cure rate between trial sites for albendazole plus ivermectin and a higher egg reduction rate for combined albendazole and ivermectin compared with albendazole alone.
For strongyloidiasis, the preliminary findings of an ongoing trial on moxidectin in the Lao People’s Democratic Republic show that all active treatment arms are highly active against S. stercoralis.
8 5. WHO manual on assessing anthelminthic drug efficacy
The WHO manual Assessing the efficacy of anthelminthic drugs against schistosomiasis and soil-transmitted helminthiases was published in 2013 (6). Professor Vercruysse summarized possible confounding factors in the evaluation of drug efficacy in endemic countries and proposed changes for the next edition of the manual. Dr Levecke presented the proposed changes based on recent field experience.
5.1 Action and next steps
A small team will draft a revision of the manual to be shared with all group members.
9 6. Establishing a network of NTD laboratories
A draft document on a network of NTD laboratories (NTD LABNET) was shared by Dr Montresor. The discussion centred on proposed diagnostic techniques needed at each level and a quality assurance scheme. It was proposed to add coproculture and CCA at national level and DNA extraction at regional level.
6.1 Discussion
Participants commented on and discussed the role and scope of NTD LABNET and whether it would cover all NTDs or only schistosomiasis and soil-transmitted helminthiases. Dr Montresor clarified that the network is for schistosomiasis and soil- transmitted helminthiases only and that its main role is to support countries in evaluating the efficacy of anthelminthic drugs. As many countries will be conducting these evaluations, a laboratory network should be available to support them in case of doubt in the results or a need for further investigation that cannot be performed at country level. Laboratories will be selected as regional or reference laboratories based on clear criteria as defined in the document. Regarding the incentive of regional and reference laboratories to be part of the network, it was noted that the Expanded Special Project for Elimination of Neglected Tropical Diseases has funding for four regional laboratories to support countries in training and quality assurance.
10 7. Role of the WHO Working Group on Drug Efficacy
Dr Dagne and Dr King (WHO headquarters) provided background information on the creation of a new WHO Diagnostic Technical Advisory Group focused on the diagnostic needs for all NTDs. One of the nine focus areas includes schistosomiasis and soil- transmitted helminthiases, the implication being that this current Working Group, which had worked on diagnostics as well as drug efficacy, will now focus on drug efficacy only. Its tasks will be: (i) to identify priority countries in which to conduct drug efficacy trials; (ii) to identify research priorities in the area of drug efficacy; and (iii) to identify drugs or drug combinations of potential value in responding to, or delaying, the emergence of drug resistance.
11 References
1. Schistosomiasis and soil-transmitted helminthiases: numbers of people treated in 2018. Wkly Epidemiol Rec. 2019;94:(50):601–12 (https://www.who.int/wer/2019/ wer9450/en/).
2. Crellen T, Walker M, Lamberton PHL, Kabatereine NB, Tukahebwa EM, Cotton JA, et al. Reduced efficacy of praziquantel againstSchistosoma mansoni is associated with multiple rounds of mass drug administration. Clin Infect Dis. 2016;63(9):1151–9. doi:10.1093/cid/ciw506.
3. Vercruysse J, Albonico M, Behnke JM, Kotze AC, Prichard RK, McCarthy JS, et al. Is anthelmintic resistance a concern for the control of human soil-transmitted helminths? Int J Parasitol Drugs Drug Resist. 2011;1:14–27. doi:10.1016/j. ijpddr.2011.09.002.
4. Levecke B, Montresor A, Albonico M, Ame SM, Behnke JM, Bethony JM, et al. Assessment of anthelmintic efficacy of mebendazole in school children in six countries where soil-transmitted helminths are endemic. PLoS Negl Trop Dis. 8(10):e3204 doi:10.1371/journal.pntd.0003204.
5. Vlaminck J, Cools P, Albonico M, Ame S, Ayana M, Cringoli G, et al. (2019) Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods. PLoS Negl Trop Dis. 13(8):e0007471. doi:10.1371/journal.pntd.0007471.
6. Assessing the efficacy of anthelminthic drugs against schistosomiasis and soil- transmitted helminthiases. Geneva: World Health Organization; 2013 (https://apps. who.int/iris/bitstream/handle/10665/79019/9789241564557_eng.pdf).
7. Wang X-Y, He J, Juma S, Kabole F, Guo J-G, Dai J-R, et al. Efficacy of China-made praziquantel for treatment of schistosomiasis haematobium in Africa: a randomized controlled trial. PLoS Negl Trop Dis. 2019;13(4):e0007238. doi:10.1371/journal. pntd.0007238.
8. Park S. K, Gunaratne GS, Chulkov EG, Moehring F, McCusker P, Dosa PI, et al. The anthelmintic drug praziquantel activates a schistosome transient receptor potential channel. J Biol Chem. 2019;294(49):18873–80. doi:10.1074/jbc.AC119.011093.
9. Sanchez MC, Cupit PM, Bu L, Cunningham C. Transcriptomic analysis of reduced sensitivity to praziquantel in Schistosoma mansoni. Mol Biochem Parasitol. 2019; 228:6–15. doi:10.1016/j.molbiopara.2018.12.005.
10. Mnkugwe RH, Minzi OS, Kinung’hi SM, Kamuhabwa AA, Aklillu E. Efficacy and safety of praziquantel for treatment of Schistosoma mansoni infection among school children in Tanzania. Pathogens. 2019;9(1):28. doi:10.3390/pathogens9010028.
12 Annex 1. List of participants
Members Professor V. Belizario,1 University of the Philippines, Manila, Philippines Professor Z. Bisoffi,1 Sacro Cuore Don Calabria Hospital, Verona, Italy Dr M. Bradley,1 GlaxoSmithKline, Brentford, United Kingdom Dr D. Buonfrate, Centre for Tropical Diseases, Verona, Italy Professor H. El Baz, Theodor Bilharz Research Institute, Embaba, Egypt Professor J. Gilleard, University of Calgary, Calgary, Canada Professor T. Gyorkos, Research Institute of the McGill University Health Centre, Montreal, Canada Dr R. Imtiaz,1 Children Without Worms, Decatur, United States of America Professor J. Keiser,1 Swiss Tropical and Public Health Institute, Basel, Switzerland Dr A. Krolewiecki, National University of Salta, Salta, Argentina Dr B. Levecke,1 Ghent University, Ghent, Belgium Professor P. LoVerde, University of Texas Health Science Center, San Antonio, United States of America Professor P. Olliaro,1 Foundation for Innovative New Diagnostics, Geneva, Switzerland; University of Oxford, Oxford, United Kingdom Professor L. Rinaldi,1 University of Naples Federico II, Naples, Italy Professor D. Rollinson,1 Global Schistosomiasis Alliance, London, United Kingdom Dr P. Steinmann,1 Swiss Tropical and Public Health Institute, Basel, Switzerland Dr L. Stuyver,1 Janssen Diagnostics, Turnhoutseweg, Belgium Professor J. Vercruysse, Ghent University, Ghent, Belgium Dr J. Vlaminck,1 Ghent University, Ghent, Belgium Professor J.P. Webster,1 Royal Veterinary College, Hawkshead, United Kingdom Dr W. Zaadnoordijk,1 Merck, Eysins, Switzerland
Secretariat WHO headquarters Dr D. Dagne, Prevention, Treatment and Care, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland Dr A. Garba-Djirmay, Prevention, Treatment and Care, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland Dr J. King, Prevention, Treatment and Care, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland Dr P. Mbabazi, Strategic Information and Analytics, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland
1 Participated online
13 Dr A. Montresor, Prevention, Treatment and Care, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland Dr D. Mupfasoni, Prevention, Treatment and Care, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland Dr A. Tekle, Strategic Operations, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland
WHO regional offices Dr P. Mwinzi, Communicable and Noncommunicable Diseases, WHO Regional Office for Africa, Brazzaville, Congo Dr V. Pemmaraju, Global Leprosy Programme, WHO Regional Office for South-East Asia, New Delhi, India Dr S. Warusavithana,1 Neglected Tropical Disease Control, WHO Regional Office for the Eastern Mediterranean, Cairo, Egypt
14 Annex 2. Agenda
Time Session Speaker 09:00–09:05 Opening remarks, objectives and introduction of participants Chair
09:05–09:45 Session 1: Drug efficacy studies J. Vlaminck Benzimidazoles a. Bangladesh, Cambodia, Ghana, Lao People’s Democratic A. Lucianez Republic, Viet Nam P. Mwinzi b. Honduras c. Zimbabwe
09:45–09:55 d. Praziquantel: Cameroon, Madagascar, Nigeria, United Republic A. Garba of Tanzania (Zanzibar) J. Vlaminck e. Proposed priority countries for evaluation of drug efficacy
10:00–10:30 Session 2: Research update P. Lo Verde a/b. Praziquantel J. Webster
10:30–11:00 c. Possible application of molecular techniques to investigate J. Gilleard suspected reduction of drug efficacy
11:00–11:20 d. Updates on drug development J. Keiser
Session 3: Manual on evaluation of the efficacy of anthelminthics WHO against schistosomiasis and soil-transmitted helminthiases J. Vercruysse a. The present manual (WHO, 2013) b. Importance of confounding factors
11:40–12:10 c. Proposed changes for the second edition of the document B. Levecke
12:10–12:20 Discussion and next steps Chair
14:00–14:20 Session 4: Establishing a network of NTD laboratories WHO a. Draft document NTD LABNET
14:20–15:00 b. Discussion on proposed diagnostic techniques needed at each WHO level and quality assurance scheme
15:00–15:30 c. Proposed list of regional/reference laboratories WHO
15:30–16:00 d. Reorganization of the working group on drug efficacy WHO Diagnostic work Drug efficacy work
Closure of the meeting
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