- Email: [email protected]
Improving helminth treatment access: costs and opportunities
Comment
communication). Is a combination of an active azole with liposomal amphotericin B or an echinocandin a more potent treatment than the current treatment with either liposomal amphotericin B or an active azole? Some in-vitro indications suggest that it might be.12 Clinical studies of such rare diseases are very difficult or even impossible to do. Alternatively, large well designed and functioning global registries such as FungiScope or Zygomyconet might be helpful for providing data on management of these rare diseases. Bringing active and safe treatments for rare fungal diseases, such as mucormycosis, to clinical practice is difficult, but the present report definitely opened a new path to achievement of this goal.
2
*Emmanuel Roilides, Charalampos Antachopoulos
9
Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, 54642 Thessaloniki, Greece [email protected] ER reports grants, personal fees, and non-financial support from Astellas, Pfizer, Gilead, and Merck, outside the submitted work. CA reports non-financial support from Pfizer; and personal fees and non-financial support from Gilead, outside the submitted work. 1
Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis 2016; published online March 8. http://dx.doi. org/10.1016/S1473-3099(16)00071-2.
3
4
5
6
7
8
10
11
12
Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012; 54 (suppl 1): S23–34. Cornely OA, Arikan-Akdagli S, Dannaoui E, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect 2014; 20 (suppl 3): 5–26. Rybak JM, Marx KR, Nishimoto AT, Rogers PD. Isavuconazole: pharmacology, pharmacodynamics, and current clinical experience with a new triazole antifungal agent. Pharmacother 2015; 35: 1037–51. Luo G, Gebremariam T, Lee H, Edwards JE Jr, Kovanda L, Ibrahim AS. Isavuconazole therapy protects immunosuppressed mice from mucormycosis. Antimicrob Agents Chemother 2014; 58: 2450–53. Maertens JA, Raad, II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 2015; 387: 760–769. Spellberg B, Ibrahim AS, Chin-Hong PV, et al. The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J Antimicrob Chemother 2012; 67: 715–22. Lanternier F, Lortholary O. AMBIZYGO: phase II study of high dose liposomal amphotericin B (AmBisome) [10 mg/kg/j] efficacy against zygomycosis. Med Mal Infect 2008; 38 (suppl 2): S90–91 (in French). Chitasombat MN, Kontoyiannis DP. The ‘cephalosporin era’ of triazole therapy: isavuconazole, a welcomed newcomer for the treatment of invasive fungal infections. Exp Opin Pharmacother 2015; 16: 1543–58. Skiada A, Pagano L, Groll A, et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect 2011; 17: 1859–67. Bitar D, Van Cauteren D, Lanternier F, et al. Increasing incidence of zygomycosis (mucormycosis), France, 1997–2006. Emerg Infect Dis 2009; 15: 1395–401. Katragkou A, McCarthy M, Meletiadis J, et al. In vitro combination of isavuconazole with micafungin or amphotericin B deoxycholate against medically important molds. Antimicrob Agents Chemother 2014; 58: 6934–37.
Eye Of Science/Science Photo Library
Improving helminth treatment access: costs and opportunities
See Articles page 838
762
Soil-transmitted helminths affect about 1·5 billion people living in the world’s poorest regions.1 The main public health strategy for morbidity control is mass drug administration (MDA; also referred to as preventive chemotherapy), which is the widespread empirical treatment of populations, traditionally school-aged children.2 WHO set a goal of achieving 75% coverage of at-risk populations by 2020, but estimates from 2014 suggest only 47% global coverage of children.3 To reach the WHO 2020 goal, opportunities must be taken to find cost efficiencies, collaborate across health sectors, and improve measurement of the costs and effects of MDA programmes. The substantial gap in target coverage for treatment of soil-transmitted helminths poses a great challenge, but an even greater opportunity to address the global burden from these infections. In The Lancet Infectious Diseases, Hugo Turner and colleagues4 present a much needed and pragmatic analysis
to address knowledge gaps in the cost of school-based MDA against soil-transmitted helminths. In their analysis, they used 3 years of programmatic cost data from six Ugandan districts, and found a relation between higher coverage and lower per-treatment delivery cost (known as economies of scale). Their primary finding that economies of scale apply to MDA, although suspected, had yet to be fully assessed for soil-transmitted helminths. The investigators showed the implications of this finding by using a case study to examine the cost-effectiveness of school-based MDA targeting Ascaris lumbricoides. They found that cost-effectiveness increased with greater treatment coverage when economies of scale were considered, by contrast with projections using a constant cost per treatment, irrespective of coverage, in which cost-effectiveness decreased with scale. For example, when control was scaled up from 10% to 75% coverage of at-risk school-age children, the cost-effectiveness in terms www.thelancet.com/infection Vol 16 July 2016
Comment
of prevention of heavy burden infections was projected to increase when using the cost function, but to decrease when assuming a constant cost per treatment. The investigators suggest that past assumptions of constant costs can therefore be misleading in select cases. The implication of this finding is that past cost-effectiveness estimates were conservative, since no cost advantages were assumed with higher coverage. Indeed, these school-based programmes are likely to be even more costeffective than previously believed when reaching high MDA coverage. As treatment for soil-transmitted helminths is scaled up across countries, substantial opportunities exist to further maximise cost efficiencies through co-delivery of soil-transmitted helminth treatment programmes with other MDAs and general health programming. Such opportunities for an integrated platform that combines soil-transmitted helminth treatment with other health programmes exist across a range of interventions, including other MDAs for neglected tropical diseases (eg, schistosomiasis, lymphatic filariasis, onchocerciasis, and trachoma);5,6 infectious diseases (eg, HIV, tuberculosis, and malaria);7 improvements in water, sanitation, and hygiene programming;8 general public health programmes (eg, vaccination campaigns and vitamin A supplementation campaigns);9 and even household surveys (eg, demographic and health surveys via the DHS Program). Integrated programming is likely to result in cost savings, biological synergies in which several health interventions boost each other’s effect, and a unique opportunity to break down traditional disease silos and collaborate across sectors to improve health care.5–7,9,10 For cost-effectiveness studies, further investigation is needed to improve understanding of disability from helminth infections and formalise a consensus on more conventional outcome measures, including the disabilityadjusted life-year.11 This metric enables economic comparisons across many different health interventions to inform health-care spending,11 and can include all health benefits accrued with individual treatment (eg, albendazole treats many helminths, including A lumbricoides, hookworm, and Trichuris trichiura). Turner and colleagues4 reported effectiveness outcomes of worm-years averted, prevalent infection case-years averted, and heavy infection case-years averted. The challenge with some of these outcome measures is the important non-linear relations between prevalence, worm burden (ie, infection intensity), www.thelancet.com/infection Vol 16 July 2016
and disability, and also limited knowledge about the effect of minor differences in number of worms on an individual’s disability. The investigators presumably chose these outcomes—as opposed to disability-adjusted lifeyears—because of controversy regarding use of a disability weight that adequately captures all disease morbidity. Nevertheless, to accurately make economic comparisons among MDA and other competing health priorities, collaborative development of a consensus regarding disability weights and collection of additional data if there is substantial uncertainty will be important. The investigators also highlight remaining data limitations that can guide future research on programmatic treatment of helminths. Although their analysis focused on school-based programming, evidence and global support is increasing for expansion of treatment from only school-aged children to entire communities to approach disease elimination and avert the substantial morbidity in both children and adults, even if elimination is not reached.6,12 As the investigators discuss, future studies should examine the relation between coverage and cost of community-wide treatment and the increased cost of reaching repeatedly untreated populations (ie, hard-to-reach populations). Furthermore, the study findings of a lower per-person treatment cost associated with higher coverage suggests that populations are likely to be able to receive treatment at a lower prevalence than recommended currently.2 This finding suggests the importance of re-examining current MDA guidelines for helminth infections, and potentially lowering the prevalence thresholds for MDA in these settings.6 Since individual countries determine health priorities, treatment of helminth infections—especially when integrated with other health programming—provides an attractive and cost-effective option. To reach the WHO 2020 goal for 75% coverage, there are great opportunities to integrate soil-transmitted helminth treatment with other health programming, use research to guide programmatic treatment delivery, and improve the measurement of the effect of MDA. If we ignore these opportunities, then we will have to consider the cost of failing to do our best to reach the populations who bear the burden of helminth infections.
For the DHS Program see http://dhsprogram.com/data/
*Nathan C Lo, Jason R Andrews, Isaac I Bogoch Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA (NCL,
763
Comment
JRA); Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada (IIB); and Divisions of Infectious Diseases and General Internal Medicine, Toronto General Hospital, University Health Network, Toronto, ON M5G 2C4, Canada (IIB) [email protected]
6
7
We declare no competing interests. Copyright © Lo et al. Open Access article distributed under the terms of CC BY-NC-ND. 1
2 3 4
5
Karagiannis-Voules DA, Biedermann P, Ekpo UF, et al. Spatial and temporal distribution of soil-transmitted helminth infection in sub-Saharan Africa: a systematic review and geostatistical meta-analysis. Lancet Infect Dis 2015; 15: 74–84. WHO. Helminth control in school-age children: a guide for managers of control programmes. Geneva: World Health Organization, 2011. WHO. Preventive chemotherapy for helminth diseases: progress report, 2014. Wkly Epidemiol Rec 2016; 91: 93–103. Turner HC, Truscott JE, Fleming FM, Hollingsworth TD, Brooker SJ, Anderson RM. Cost-effectiveness of scaling up mass drug administration for the control of soil-transmitted helminths: a comparison of cost function and constant costs analyses. Lancet Infect Dis 2016; published online Feb 17. http://dx.doi.org/10.1016/S1473-3099(15)00268-6. Molyneux DH, Hotez PJ, Fenwick A. “Rapid-impact interventions”: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med 2005; 2: e336.
8
9
10
11
12
Lo NC, Bogoch II, Blackburn BG, et al. Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study. Lancet Glob Health 2015; 3: e629–38. Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med 2006; 3: e102. Freeman MC, Ogden S, Jacobson J, et al. Integration of water, sanitation, and hygiene for the prevention and control of neglected tropical diseases: a rationale for inter-sectoral collaboration. PLoS Negl Trop Dis 2013; 7: e2439. Strunz EC, Suchdev PS, Addiss DG. Soil-transmitted helminthiasis and vitamin A deficiency: two problems, one policy. Trends Parasitol 2016; 32: 10–18. Ezeamama AE, McGarvey ST, Acosta LP, et al. The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children’s anemia burden. PLoS Negl Trop Dis 2008; 2: e245. WHO. WHO guide to cost-effectiveness analysis. 2003. http://www.who. int/choice/publications/p_2003_generalised_cea.pdf (accessed April 18, 2016). Anderson R, Truscott J, Hollingsworth TD. The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths. Philos Trans R Soc Lond B Biol Sci 2014; 369: 20130435.
Chris Gallagher/Science Photo Library
Next steps for antimicrobial stewardship
Published Online March 2, 2016 http://dx.doi.org/10.1016/ S1473-3099(16)00099-2 See Articles page 847
764
The rising tide of antimicrobial resistance, coupled with a paucity of new drug development, have led to increasingly clamorous calls for improved antimicrobial stewardship to reduce the oft-cited 30–50% rate of inappropriate antimicrobial therapy.1–5 Much attention has been given to what approaches stewardship programmes should include to achieve specific objectives, such as adherence to local guidelines, use of pathogen-directed therapy, discontinuation of therapy when infection is found to be unlikely, timely switching from parenteral to oral treatment, and appropriate duration of therapy. However, a substantial degree of uncertainty remains about which specific strategies will best achieve these objectives (eg, drug restrictions, audit and feedback, computerised decision support systems), how to assure successful implementation, and whether interventions sustainably reduce antimicrobial use and lead to meaningful improvements in outcomes at the patient level (eg, adverse events, mortality) and societal level (costs and bacterial resistance).6,7 In The Lancet Infectious Diseases, Emelie C Schuts and colleagues,8 instead of taking the usual approach of focusing on the strategies aimed at achieving stewardship objectives, focus instead on the effect of meeting these objectives. The authors identified 14 relevant objectives compiled via expert Delphi procedures and from
guidelines, and exhaustively reviewed the literature to find studies that had assessed the effects of meeting each one on patient-level and society-level outcomes (clinical outcomes, adverse events, costs, and bacterial resistance rates). Data were available on nine of the 14 objectives in 145 unique studies. Significant benefits were seen for at least one outcome for the following outcomes: empirical therapy according to guidelines, de-escalation of therapy, switch from intravenous to oral treatment, therapeutic drug monitoring, use of a list of restricted antibiotics, and bedside consultation. For mortality, significant effects were seen with adherence to guidelines (relative risk reduction 35%; relative risk 0·65, 95% CI 0·54–0·80, p<0·0001) and de-escalation of therapy (66%; 0·44, 0·30–0·66, p<0·0001). Schuts and colleagues have assembled a comprehensive and well organised compendium that identifies the gaps in data linking stewardship objectives to practical outcomes. Unfortunately, almost all studies were of poor quality owing to inconsistency, indirectness, and imprecision in data reporting, and overall risk of bias was high. Nevertheless, the effect on mortality achieved with de-escalation of therapy, which was based on culture results derived from 25 studies in diverse clinical settings, is provocative. The decrease in mortality associated with guideline-concordant www.thelancet.com/infection Vol 16 July 2016
communication). Is a combination of an active azole with liposomal amphotericin B or an echinocandin a more potent treatment than the current treatment with either liposomal amphotericin B or an active azole? Some in-vitro indications suggest that it might be.12 Clinical studies of such rare diseases are very difficult or even impossible to do. Alternatively, large well designed and functioning global registries such as FungiScope or Zygomyconet might be helpful for providing data on management of these rare diseases. Bringing active and safe treatments for rare fungal diseases, such as mucormycosis, to clinical practice is difficult, but the present report definitely opened a new path to achievement of this goal.
2
*Emmanuel Roilides, Charalampos Antachopoulos
9
Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, 54642 Thessaloniki, Greece [email protected] ER reports grants, personal fees, and non-financial support from Astellas, Pfizer, Gilead, and Merck, outside the submitted work. CA reports non-financial support from Pfizer; and personal fees and non-financial support from Gilead, outside the submitted work. 1
Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis 2016; published online March 8. http://dx.doi. org/10.1016/S1473-3099(16)00071-2.
3
4
5
6
7
8
10
11
12
Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012; 54 (suppl 1): S23–34. Cornely OA, Arikan-Akdagli S, Dannaoui E, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect 2014; 20 (suppl 3): 5–26. Rybak JM, Marx KR, Nishimoto AT, Rogers PD. Isavuconazole: pharmacology, pharmacodynamics, and current clinical experience with a new triazole antifungal agent. Pharmacother 2015; 35: 1037–51. Luo G, Gebremariam T, Lee H, Edwards JE Jr, Kovanda L, Ibrahim AS. Isavuconazole therapy protects immunosuppressed mice from mucormycosis. Antimicrob Agents Chemother 2014; 58: 2450–53. Maertens JA, Raad, II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 2015; 387: 760–769. Spellberg B, Ibrahim AS, Chin-Hong PV, et al. The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J Antimicrob Chemother 2012; 67: 715–22. Lanternier F, Lortholary O. AMBIZYGO: phase II study of high dose liposomal amphotericin B (AmBisome) [10 mg/kg/j] efficacy against zygomycosis. Med Mal Infect 2008; 38 (suppl 2): S90–91 (in French). Chitasombat MN, Kontoyiannis DP. The ‘cephalosporin era’ of triazole therapy: isavuconazole, a welcomed newcomer for the treatment of invasive fungal infections. Exp Opin Pharmacother 2015; 16: 1543–58. Skiada A, Pagano L, Groll A, et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect 2011; 17: 1859–67. Bitar D, Van Cauteren D, Lanternier F, et al. Increasing incidence of zygomycosis (mucormycosis), France, 1997–2006. Emerg Infect Dis 2009; 15: 1395–401. Katragkou A, McCarthy M, Meletiadis J, et al. In vitro combination of isavuconazole with micafungin or amphotericin B deoxycholate against medically important molds. Antimicrob Agents Chemother 2014; 58: 6934–37.
Eye Of Science/Science Photo Library
Improving helminth treatment access: costs and opportunities
See Articles page 838
762
Soil-transmitted helminths affect about 1·5 billion people living in the world’s poorest regions.1 The main public health strategy for morbidity control is mass drug administration (MDA; also referred to as preventive chemotherapy), which is the widespread empirical treatment of populations, traditionally school-aged children.2 WHO set a goal of achieving 75% coverage of at-risk populations by 2020, but estimates from 2014 suggest only 47% global coverage of children.3 To reach the WHO 2020 goal, opportunities must be taken to find cost efficiencies, collaborate across health sectors, and improve measurement of the costs and effects of MDA programmes. The substantial gap in target coverage for treatment of soil-transmitted helminths poses a great challenge, but an even greater opportunity to address the global burden from these infections. In The Lancet Infectious Diseases, Hugo Turner and colleagues4 present a much needed and pragmatic analysis
to address knowledge gaps in the cost of school-based MDA against soil-transmitted helminths. In their analysis, they used 3 years of programmatic cost data from six Ugandan districts, and found a relation between higher coverage and lower per-treatment delivery cost (known as economies of scale). Their primary finding that economies of scale apply to MDA, although suspected, had yet to be fully assessed for soil-transmitted helminths. The investigators showed the implications of this finding by using a case study to examine the cost-effectiveness of school-based MDA targeting Ascaris lumbricoides. They found that cost-effectiveness increased with greater treatment coverage when economies of scale were considered, by contrast with projections using a constant cost per treatment, irrespective of coverage, in which cost-effectiveness decreased with scale. For example, when control was scaled up from 10% to 75% coverage of at-risk school-age children, the cost-effectiveness in terms www.thelancet.com/infection Vol 16 July 2016
Comment
of prevention of heavy burden infections was projected to increase when using the cost function, but to decrease when assuming a constant cost per treatment. The investigators suggest that past assumptions of constant costs can therefore be misleading in select cases. The implication of this finding is that past cost-effectiveness estimates were conservative, since no cost advantages were assumed with higher coverage. Indeed, these school-based programmes are likely to be even more costeffective than previously believed when reaching high MDA coverage. As treatment for soil-transmitted helminths is scaled up across countries, substantial opportunities exist to further maximise cost efficiencies through co-delivery of soil-transmitted helminth treatment programmes with other MDAs and general health programming. Such opportunities for an integrated platform that combines soil-transmitted helminth treatment with other health programmes exist across a range of interventions, including other MDAs for neglected tropical diseases (eg, schistosomiasis, lymphatic filariasis, onchocerciasis, and trachoma);5,6 infectious diseases (eg, HIV, tuberculosis, and malaria);7 improvements in water, sanitation, and hygiene programming;8 general public health programmes (eg, vaccination campaigns and vitamin A supplementation campaigns);9 and even household surveys (eg, demographic and health surveys via the DHS Program). Integrated programming is likely to result in cost savings, biological synergies in which several health interventions boost each other’s effect, and a unique opportunity to break down traditional disease silos and collaborate across sectors to improve health care.5–7,9,10 For cost-effectiveness studies, further investigation is needed to improve understanding of disability from helminth infections and formalise a consensus on more conventional outcome measures, including the disabilityadjusted life-year.11 This metric enables economic comparisons across many different health interventions to inform health-care spending,11 and can include all health benefits accrued with individual treatment (eg, albendazole treats many helminths, including A lumbricoides, hookworm, and Trichuris trichiura). Turner and colleagues4 reported effectiveness outcomes of worm-years averted, prevalent infection case-years averted, and heavy infection case-years averted. The challenge with some of these outcome measures is the important non-linear relations between prevalence, worm burden (ie, infection intensity), www.thelancet.com/infection Vol 16 July 2016
and disability, and also limited knowledge about the effect of minor differences in number of worms on an individual’s disability. The investigators presumably chose these outcomes—as opposed to disability-adjusted lifeyears—because of controversy regarding use of a disability weight that adequately captures all disease morbidity. Nevertheless, to accurately make economic comparisons among MDA and other competing health priorities, collaborative development of a consensus regarding disability weights and collection of additional data if there is substantial uncertainty will be important. The investigators also highlight remaining data limitations that can guide future research on programmatic treatment of helminths. Although their analysis focused on school-based programming, evidence and global support is increasing for expansion of treatment from only school-aged children to entire communities to approach disease elimination and avert the substantial morbidity in both children and adults, even if elimination is not reached.6,12 As the investigators discuss, future studies should examine the relation between coverage and cost of community-wide treatment and the increased cost of reaching repeatedly untreated populations (ie, hard-to-reach populations). Furthermore, the study findings of a lower per-person treatment cost associated with higher coverage suggests that populations are likely to be able to receive treatment at a lower prevalence than recommended currently.2 This finding suggests the importance of re-examining current MDA guidelines for helminth infections, and potentially lowering the prevalence thresholds for MDA in these settings.6 Since individual countries determine health priorities, treatment of helminth infections—especially when integrated with other health programming—provides an attractive and cost-effective option. To reach the WHO 2020 goal for 75% coverage, there are great opportunities to integrate soil-transmitted helminth treatment with other health programming, use research to guide programmatic treatment delivery, and improve the measurement of the effect of MDA. If we ignore these opportunities, then we will have to consider the cost of failing to do our best to reach the populations who bear the burden of helminth infections.
For the DHS Program see http://dhsprogram.com/data/
*Nathan C Lo, Jason R Andrews, Isaac I Bogoch Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA (NCL,
763
Comment
JRA); Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada (IIB); and Divisions of Infectious Diseases and General Internal Medicine, Toronto General Hospital, University Health Network, Toronto, ON M5G 2C4, Canada (IIB) [email protected]
6
7
We declare no competing interests. Copyright © Lo et al. Open Access article distributed under the terms of CC BY-NC-ND. 1
2 3 4
5
Karagiannis-Voules DA, Biedermann P, Ekpo UF, et al. Spatial and temporal distribution of soil-transmitted helminth infection in sub-Saharan Africa: a systematic review and geostatistical meta-analysis. Lancet Infect Dis 2015; 15: 74–84. WHO. Helminth control in school-age children: a guide for managers of control programmes. Geneva: World Health Organization, 2011. WHO. Preventive chemotherapy for helminth diseases: progress report, 2014. Wkly Epidemiol Rec 2016; 91: 93–103. Turner HC, Truscott JE, Fleming FM, Hollingsworth TD, Brooker SJ, Anderson RM. Cost-effectiveness of scaling up mass drug administration for the control of soil-transmitted helminths: a comparison of cost function and constant costs analyses. Lancet Infect Dis 2016; published online Feb 17. http://dx.doi.org/10.1016/S1473-3099(15)00268-6. Molyneux DH, Hotez PJ, Fenwick A. “Rapid-impact interventions”: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med 2005; 2: e336.
8
9
10
11
12
Lo NC, Bogoch II, Blackburn BG, et al. Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study. Lancet Glob Health 2015; 3: e629–38. Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med 2006; 3: e102. Freeman MC, Ogden S, Jacobson J, et al. Integration of water, sanitation, and hygiene for the prevention and control of neglected tropical diseases: a rationale for inter-sectoral collaboration. PLoS Negl Trop Dis 2013; 7: e2439. Strunz EC, Suchdev PS, Addiss DG. Soil-transmitted helminthiasis and vitamin A deficiency: two problems, one policy. Trends Parasitol 2016; 32: 10–18. Ezeamama AE, McGarvey ST, Acosta LP, et al. The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children’s anemia burden. PLoS Negl Trop Dis 2008; 2: e245. WHO. WHO guide to cost-effectiveness analysis. 2003. http://www.who. int/choice/publications/p_2003_generalised_cea.pdf (accessed April 18, 2016). Anderson R, Truscott J, Hollingsworth TD. The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths. Philos Trans R Soc Lond B Biol Sci 2014; 369: 20130435.
Chris Gallagher/Science Photo Library
Next steps for antimicrobial stewardship
Published Online March 2, 2016 http://dx.doi.org/10.1016/ S1473-3099(16)00099-2 See Articles page 847
764
The rising tide of antimicrobial resistance, coupled with a paucity of new drug development, have led to increasingly clamorous calls for improved antimicrobial stewardship to reduce the oft-cited 30–50% rate of inappropriate antimicrobial therapy.1–5 Much attention has been given to what approaches stewardship programmes should include to achieve specific objectives, such as adherence to local guidelines, use of pathogen-directed therapy, discontinuation of therapy when infection is found to be unlikely, timely switching from parenteral to oral treatment, and appropriate duration of therapy. However, a substantial degree of uncertainty remains about which specific strategies will best achieve these objectives (eg, drug restrictions, audit and feedback, computerised decision support systems), how to assure successful implementation, and whether interventions sustainably reduce antimicrobial use and lead to meaningful improvements in outcomes at the patient level (eg, adverse events, mortality) and societal level (costs and bacterial resistance).6,7 In The Lancet Infectious Diseases, Emelie C Schuts and colleagues,8 instead of taking the usual approach of focusing on the strategies aimed at achieving stewardship objectives, focus instead on the effect of meeting these objectives. The authors identified 14 relevant objectives compiled via expert Delphi procedures and from
guidelines, and exhaustively reviewed the literature to find studies that had assessed the effects of meeting each one on patient-level and society-level outcomes (clinical outcomes, adverse events, costs, and bacterial resistance rates). Data were available on nine of the 14 objectives in 145 unique studies. Significant benefits were seen for at least one outcome for the following outcomes: empirical therapy according to guidelines, de-escalation of therapy, switch from intravenous to oral treatment, therapeutic drug monitoring, use of a list of restricted antibiotics, and bedside consultation. For mortality, significant effects were seen with adherence to guidelines (relative risk reduction 35%; relative risk 0·65, 95% CI 0·54–0·80, p<0·0001) and de-escalation of therapy (66%; 0·44, 0·30–0·66, p<0·0001). Schuts and colleagues have assembled a comprehensive and well organised compendium that identifies the gaps in data linking stewardship objectives to practical outcomes. Unfortunately, almost all studies were of poor quality owing to inconsistency, indirectness, and imprecision in data reporting, and overall risk of bias was high. Nevertheless, the effect on mortality achieved with de-escalation of therapy, which was based on culture results derived from 25 studies in diverse clinical settings, is provocative. The decrease in mortality associated with guideline-concordant www.thelancet.com/infection Vol 16 July 2016