Comment
induction treatment8 or combined with chemotherapy. However, the balance between effectiveness, safety, and cost of these new approaches needs to be shown in this good-risk population compared to the current standard treatment. Conversely, in the setting of more advanced disease, ABVD exposes patients to a risk of treatment failure of 10–30%,9,10 and combinations incorporating new drugs such as brentuximab vedotin (being tested in NCT01712490) or programmed cell death protein-1 (PD-1) inhibitors11 (NCT01592370) are anticipated.
3
4
5
6
7
Olivier Casasnovas, *Bertrand Coiffier Hématologie Clinique, CHU de Dijon, Dijon, France (OC); and Hématologie Clinique, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite F-69310, France (BC) bertrand.coiffi[email protected] OC and BC have been members of an advisory board for Takeda. 1
2
Behringer K, Goergen H, Hitz F, et al; on behalf of the German Hodgkin Study Group, the Swiss Group for Clinical Cancer Research, and the Österreichische Arbeitsgemeinschaft für Klinische Pharmakologie und Therapie. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet 2014; published online Dec 22. http://dx.doi.org/10.1016/S01406736(14)61469-0. Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 2010; 363: 640–52.
8
9
10
11
Eghbali H, Brice P, Creemers GY, et al. Comparison of three radiation dose levels after EBVP regimen in favorable supradiaphragmatic clinical stages (CS) I–II Hodgkin’s lymphoma (HL): preliminary results of the EORTC-GELA H9-F trial. Blood 2005; 106: 814 (abstr). Radford J, Barrington S, Counsell N. Involved field radiotherapy versus no further treatment in patients with clinical stage IA and IIA Hodgkin lymphoma and a negative PET scan after 3 cycles of ABVD: results of the UK NCRI RAPID trial. Blood 2012; 120: 547 (abstr). Raemaekers JMM, André MPE, Federico M, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/ FIL H10 trial. J Clin Oncol 2014; 32: 1188–94. Meyer RM, Gospodarowicz MK, Connors JM, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med 2012; 366: 399–408. Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 1975; 36: 252–59. Federico M, Pesce EA, Merli M, Luminari S, Chauvie S, Zinzani PL. A pilot phase II study with brentuximab vedotin followed by ABVD in patients with previously untreated Hodgkin lymphoma: a preliminary report. J Clin Oncol 2014; 32 (suppl 5s): 8507 (abstr). Von Tresckow B, Plütschow A, Fuchs M, et al. Dose-intensification in early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol 2012; 30: 907–13. Viviani S, Zinzani PL, Rambaldi A, et al. ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 2011; 365: 203–12. SM Ansell, AM Lesokhin, I Borello, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 2014; published online Dec 6. DOI:10.1056/NEJMoa1411087.
Ebola: the battle plan must include specific treatments The outbreak of Ebola virus disease (EVD) currently devastating west Africa has reached an unprecedented scale. EVD can no longer be viewed as a disease that affects fairly small numbers of people living in remote African villages with few resources. In the 12 months since the first case in Guinea was recognised, WHO reports that 17 942 cases and 6388 deaths had been identified up to Dec 10, 2014, mainly in Sierra Leone, Liberia, and Guinea.1 The true number of infections and deaths is undoubtedly greater. Despite intense national and international mobilisation, there is still no end in sight. At least 350 health-care workers have died from EVD,1 in addition to the countless numbers of informal caregivers who have lost their lives. The epidemic is also causing collateral damage, with disruption of health-care services in affected countries, leaving people with non-EVD-related health disorders without necessary care. Additionally, the fear of EVD has disrupted normal life and is threatening national economies. www.thelancet.com Vol 385 April 11, 2015
For the first time, a small but steady stream of Ebola-virus-infected patients are receiving medical care in high-income countries, predominantly medically evacuated health-care workers. Although focus should not be diverted from helping west African countries to defeat Ebola, a tremendous amount can be learned about both the clinical course of EVD and what interventions might improve survival. In The Lancet, Timo Wolf and colleagues2 describe the clinical course and medical care of a 38-year-old evacuated health-care worker with EVD. The patient’s illness was at the most severe end of the spectrum and caring for him proved to be particularly challenging. Nevertheless, the authors describe the application of specialist interventions, including invasive cardiovascular monitoring, renal replacement therapy, and invasive mechanical ventilation. Maintaining biological safety precautions while delivering intensive care is difficult but essential, and Wolf and colleagues provide helpful details
Published Online December 19, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)62353-9 See Articles page 1428
1373
Bertram Solcher/dpa/Corbis
Comment
about how it can be achieved. For example, they explain how they dealt with infectious waste fluids produced by renal replacement therapy, and how endotracheal intubation was done. The case report also illustrates the challenges of achieving optimum fluid balance in severe EVD. The authors propose that vascular leak syndrome secondary to Ebola virus infection might explain many of the complications reported in this patient. For this reason, the group decided to give an experimental treatment for Ebola-induced vascular leak syndrome, the fibrin-derived peptide, Bβ15-42 (FX06), which was commenced on day 11 of illness and administered intravenously for 3 consecutive days. Although the authors describe virological and clinical improvements, along with anti-Ebola-virus IgG seroconversion after FX06 treatment, whether FX06 directly contributed to the patient’s eventual recovery is impossible to know. Effective treatment of vascular leak syndrome and multiorgan failure through a combination of ventilatory support, antimicrobial therapy, and renal replacement therapy might sustain a patient with severe EVD until virological remission occurs. Up to now, only two patients with EVD are known to have received FX06.3 Experience from west African treatment centres suggests that there might be a natural turning point during the second week of illness, even in those with severe disease.4 The patient described by Wolf and colleagues2 also received other drugs that have been proposed as potential treatments for EVD, including amiodarone, which the patient 1374
self-administered in Sierra Leone. Their attempt to administer a course of favipiravir was abandoned quickly due to problems with dosing, underscoring the difficulties of giving drugs to patients with EVD. A virus-binding haemofiltration cartridge was also tried, but seems to have had little effect on viraemia. The devastating effects of Ebola require an equally strong medical response, not only to prevent new cases, but also to improve survival rates in people who become infected. Public health interventions including isolation of suspected and confirmed patients, hand hygiene, and safe burial practices remain crucially important strategies to control ongoing Ebola transmission; when initiated quickly, they can be effective. Although not impossible to implement, the consistent application of such measures is particularly difficult for an established epidemic of this scale. The accelerated development of Ebola vaccines and experimental therapeutics in clinical trials continues, but many of these agents are not expected to be widely available until well into 2015. For people already infected, mortality might be reduced by providing critical supportive care, especially careful fluid balance and the correction of electrolyte abnormalities.5,6 This task is often difficult in austere environments and requires substantial human resources. It makes sense, therefore, to explore specific treatments that could be given as part of a package of care for EVD. Patients with EVD in Europe and the USA have received experimental treatments under compassionate use authorisation, and some have received several treatments. To date, no single drug has been assessed in clinical trials, but trials of brincidofovir, favipiravir, and convalescent plasma are underway, or are expected to start soon in affected countries; trials of other agents are planned.7,8 It is vital that the most promising agents are selected to enter clinical trials. To this extent, WHO is grading proposed treatments on the basis of several criteria, which include supportive in-vitro and animal data, assessment of any existing human data, scalability, and availability.9 The acceleration of clinical trials of selected agents should be encouraged, as should the collection of standardised data in compassionate use settings. Additionally, many of these trials bring an augmented capacity of clinical care, including www.thelancet.com Vol 385 April 11, 2015
Comment
increased human resources and diagnostic laboratory capabilities that will contribute to improving the standard of care for Ebola-virus-infected patients. Most importantly, we must remember where the greatest burden of disease lies. No matter how effective a treatment might seem in clinical trials, it must be feasible to deliver and be made readily available in all EVD treatment centres in Africa.
1
*Jake Dunning, William Fischer II
5
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK (JD); and Division of Pulmonary and Critical Care Medicine, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA (WF) [email protected] JD is an Investigator for the RAPIDE (Rapid Assessment of Potential Interventions and Drugs for Ebola) Trial, which is funded by the Wellcome Trust and coordinated by the University of Oxford and ISARIC (International Severe Acute Respiratory and emerging Infection Consortium). WF is an investigator with the UNC/Duke consortium funded and coordinated by ClinicalRM.
2
3
4
6 7 8 9
WHO. Ebola response roadmap situation report. Dec 10, 2014.Geneva: World health Organization, 2014. http://www.who.int/csr/disease/ebola/ situation-reports/en/?m=20141210 (accessed Dec 15, 2014). Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet 2014; published online Dec 19. http://dx.doi.org/10.1016/S01406736(14)62384-9. MCHE. FX-06: a potential new drug for prevention/reduction of vascular instability/ capillary leak in Ebola Virus Disease. October, 2014. http://www. mche.at/fx-06-potential-new-drug-for-ebola-virus-disease/ (accessed Dec 15, 2014). Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. Ebola virus disease in West Africa—clinical manifestations and management. N Engl J Med 2014; 371: 2054–57. Lamontagne F, Clement C, Fletcher T, Jacob ST, Fischer WA 2nd, Fowler RA. Doing today’s work superbly well—treating Ebola with current tools. N Engl J Med 2014; 371: 1565–66. Roberts I, Perner A. Ebola virus disease: clinical care and patient-centred research. Lancet 2014; 384: 2001–02. Check Hayden E. Ebola trials to start in December. Nature 2014; published online Nov 13. DOI:10.1038/nature.2014.16342. Butler D. First trials of Ebola blood-based therapy kick off. Nature 2014; published online Dec 15. DOI:10.1038/nature.2014.16564. WHO. Meeting of the Scientific and Technical Advisory Committee on Ebola experimental interventions—briefing note. Nov 13, 2014. http:// apps.who.int/medicines/ebola-treatment/scientific_tech_meeting/en/ index.html (accessed Dec 15, 2014).
Is malaria control better with both treated nets and spraying? In the past decade, new funding mechanisms such as the Global Fund to Fight AIDS, Tuberculosis and Malaria have led to an increase in international investment in malaria control. WHO estimates that, by 2012, this scaling up of anti-malaria interventions had prevented 3·3 million deaths.1 Most of these epidemiological benefits are attributable to increased coverage with effective vector control; in the past 5 years, over 500 million long-lasting insecticidal nets (LLINs) have been delivered. Attention to the combination of indoor residual spraying with LLINs has been growing in recent years, stimulated by the spread of vector resistance to pyrethroids and variations in the apparent effect of LLINs on malaria transmission. In some places, the effect on malaria has been disappointing, and there is interest in whether a combination of indoor residual spraying and LLINs would give better results. By contrast, elsewhere there has been a dramatic reduction in malaria incidence and prevalence, and local malaria authorities are considering local elimination, and whether this elusive goal could be brought within reach by a combination of indoor residual spraying and LLINs. Against this backdrop, the indoor residual spraying and LLINs trial in The Gambia reported in The Lancet by www.thelancet.com Vol 385 April 11, 2015
Margaret Pinder and colleagues2 is timely, interesting, and important. The trial was a community-randomised efficacy trial, comparing 35 clusters given LLINs and indoor residual spraying (with dichlorodiphenyltrichloroethane [DDT]) with 35 clusters given LLINs alone. Epidemiological outcomes were measured over 2 years by annual cross-sectional surveys and passive case detection. In each cluster, a cohort of between 65 and 213 children aged 6 months to 14 years was followed in 2010 and 2011 for the primary endpoint of clinical malaria. Coverage of indoor residual spraying and LLINs was high throughout the trial. However, no significant differences were observed between the two study groups in any of the outcomes measured: incidence of clinical malaria was 0·047 per child-month at risk in the LLIN group and 0·044 per child-month at risk in the indoor residual spraying and LLIN group in year 1, and 0·032 per child-month at risk in the LLIN group and 0·034 per child-month at risk in the indoor residual spraying and LLIN group in year 2 (incidence rate ratio 1·08, 95% CI 0·80–1·46). Anaemia, parasite, and splenomegaly rates were similar in both study groups in both years. No significant difference was reported in the density of vector mosquitoes caught in light traps in houses over the two transmission seasons.
Published Online December 9, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)61306-4 See Articles page 1436
1375
induction treatment8 or combined with chemotherapy. However, the balance between effectiveness, safety, and cost of these new approaches needs to be shown in this good-risk population compared to the current standard treatment. Conversely, in the setting of more advanced disease, ABVD exposes patients to a risk of treatment failure of 10–30%,9,10 and combinations incorporating new drugs such as brentuximab vedotin (being tested in NCT01712490) or programmed cell death protein-1 (PD-1) inhibitors11 (NCT01592370) are anticipated.
3
4
5
6
7
Olivier Casasnovas, *Bertrand Coiffier Hématologie Clinique, CHU de Dijon, Dijon, France (OC); and Hématologie Clinique, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite F-69310, France (BC) bertrand.coiffi[email protected] OC and BC have been members of an advisory board for Takeda. 1
2
Behringer K, Goergen H, Hitz F, et al; on behalf of the German Hodgkin Study Group, the Swiss Group for Clinical Cancer Research, and the Österreichische Arbeitsgemeinschaft für Klinische Pharmakologie und Therapie. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet 2014; published online Dec 22. http://dx.doi.org/10.1016/S01406736(14)61469-0. Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 2010; 363: 640–52.
8
9
10
11
Eghbali H, Brice P, Creemers GY, et al. Comparison of three radiation dose levels after EBVP regimen in favorable supradiaphragmatic clinical stages (CS) I–II Hodgkin’s lymphoma (HL): preliminary results of the EORTC-GELA H9-F trial. Blood 2005; 106: 814 (abstr). Radford J, Barrington S, Counsell N. Involved field radiotherapy versus no further treatment in patients with clinical stage IA and IIA Hodgkin lymphoma and a negative PET scan after 3 cycles of ABVD: results of the UK NCRI RAPID trial. Blood 2012; 120: 547 (abstr). Raemaekers JMM, André MPE, Federico M, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/ FIL H10 trial. J Clin Oncol 2014; 32: 1188–94. Meyer RM, Gospodarowicz MK, Connors JM, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med 2012; 366: 399–408. Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 1975; 36: 252–59. Federico M, Pesce EA, Merli M, Luminari S, Chauvie S, Zinzani PL. A pilot phase II study with brentuximab vedotin followed by ABVD in patients with previously untreated Hodgkin lymphoma: a preliminary report. J Clin Oncol 2014; 32 (suppl 5s): 8507 (abstr). Von Tresckow B, Plütschow A, Fuchs M, et al. Dose-intensification in early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol 2012; 30: 907–13. Viviani S, Zinzani PL, Rambaldi A, et al. ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 2011; 365: 203–12. SM Ansell, AM Lesokhin, I Borello, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 2014; published online Dec 6. DOI:10.1056/NEJMoa1411087.
Ebola: the battle plan must include specific treatments The outbreak of Ebola virus disease (EVD) currently devastating west Africa has reached an unprecedented scale. EVD can no longer be viewed as a disease that affects fairly small numbers of people living in remote African villages with few resources. In the 12 months since the first case in Guinea was recognised, WHO reports that 17 942 cases and 6388 deaths had been identified up to Dec 10, 2014, mainly in Sierra Leone, Liberia, and Guinea.1 The true number of infections and deaths is undoubtedly greater. Despite intense national and international mobilisation, there is still no end in sight. At least 350 health-care workers have died from EVD,1 in addition to the countless numbers of informal caregivers who have lost their lives. The epidemic is also causing collateral damage, with disruption of health-care services in affected countries, leaving people with non-EVD-related health disorders without necessary care. Additionally, the fear of EVD has disrupted normal life and is threatening national economies. www.thelancet.com Vol 385 April 11, 2015
For the first time, a small but steady stream of Ebola-virus-infected patients are receiving medical care in high-income countries, predominantly medically evacuated health-care workers. Although focus should not be diverted from helping west African countries to defeat Ebola, a tremendous amount can be learned about both the clinical course of EVD and what interventions might improve survival. In The Lancet, Timo Wolf and colleagues2 describe the clinical course and medical care of a 38-year-old evacuated health-care worker with EVD. The patient’s illness was at the most severe end of the spectrum and caring for him proved to be particularly challenging. Nevertheless, the authors describe the application of specialist interventions, including invasive cardiovascular monitoring, renal replacement therapy, and invasive mechanical ventilation. Maintaining biological safety precautions while delivering intensive care is difficult but essential, and Wolf and colleagues provide helpful details
Published Online December 19, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)62353-9 See Articles page 1428
1373
Bertram Solcher/dpa/Corbis
Comment
about how it can be achieved. For example, they explain how they dealt with infectious waste fluids produced by renal replacement therapy, and how endotracheal intubation was done. The case report also illustrates the challenges of achieving optimum fluid balance in severe EVD. The authors propose that vascular leak syndrome secondary to Ebola virus infection might explain many of the complications reported in this patient. For this reason, the group decided to give an experimental treatment for Ebola-induced vascular leak syndrome, the fibrin-derived peptide, Bβ15-42 (FX06), which was commenced on day 11 of illness and administered intravenously for 3 consecutive days. Although the authors describe virological and clinical improvements, along with anti-Ebola-virus IgG seroconversion after FX06 treatment, whether FX06 directly contributed to the patient’s eventual recovery is impossible to know. Effective treatment of vascular leak syndrome and multiorgan failure through a combination of ventilatory support, antimicrobial therapy, and renal replacement therapy might sustain a patient with severe EVD until virological remission occurs. Up to now, only two patients with EVD are known to have received FX06.3 Experience from west African treatment centres suggests that there might be a natural turning point during the second week of illness, even in those with severe disease.4 The patient described by Wolf and colleagues2 also received other drugs that have been proposed as potential treatments for EVD, including amiodarone, which the patient 1374
self-administered in Sierra Leone. Their attempt to administer a course of favipiravir was abandoned quickly due to problems with dosing, underscoring the difficulties of giving drugs to patients with EVD. A virus-binding haemofiltration cartridge was also tried, but seems to have had little effect on viraemia. The devastating effects of Ebola require an equally strong medical response, not only to prevent new cases, but also to improve survival rates in people who become infected. Public health interventions including isolation of suspected and confirmed patients, hand hygiene, and safe burial practices remain crucially important strategies to control ongoing Ebola transmission; when initiated quickly, they can be effective. Although not impossible to implement, the consistent application of such measures is particularly difficult for an established epidemic of this scale. The accelerated development of Ebola vaccines and experimental therapeutics in clinical trials continues, but many of these agents are not expected to be widely available until well into 2015. For people already infected, mortality might be reduced by providing critical supportive care, especially careful fluid balance and the correction of electrolyte abnormalities.5,6 This task is often difficult in austere environments and requires substantial human resources. It makes sense, therefore, to explore specific treatments that could be given as part of a package of care for EVD. Patients with EVD in Europe and the USA have received experimental treatments under compassionate use authorisation, and some have received several treatments. To date, no single drug has been assessed in clinical trials, but trials of brincidofovir, favipiravir, and convalescent plasma are underway, or are expected to start soon in affected countries; trials of other agents are planned.7,8 It is vital that the most promising agents are selected to enter clinical trials. To this extent, WHO is grading proposed treatments on the basis of several criteria, which include supportive in-vitro and animal data, assessment of any existing human data, scalability, and availability.9 The acceleration of clinical trials of selected agents should be encouraged, as should the collection of standardised data in compassionate use settings. Additionally, many of these trials bring an augmented capacity of clinical care, including www.thelancet.com Vol 385 April 11, 2015
Comment
increased human resources and diagnostic laboratory capabilities that will contribute to improving the standard of care for Ebola-virus-infected patients. Most importantly, we must remember where the greatest burden of disease lies. No matter how effective a treatment might seem in clinical trials, it must be feasible to deliver and be made readily available in all EVD treatment centres in Africa.
1
*Jake Dunning, William Fischer II
5
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK (JD); and Division of Pulmonary and Critical Care Medicine, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA (WF) [email protected] JD is an Investigator for the RAPIDE (Rapid Assessment of Potential Interventions and Drugs for Ebola) Trial, which is funded by the Wellcome Trust and coordinated by the University of Oxford and ISARIC (International Severe Acute Respiratory and emerging Infection Consortium). WF is an investigator with the UNC/Duke consortium funded and coordinated by ClinicalRM.
2
3
4
6 7 8 9
WHO. Ebola response roadmap situation report. Dec 10, 2014.Geneva: World health Organization, 2014. http://www.who.int/csr/disease/ebola/ situation-reports/en/?m=20141210 (accessed Dec 15, 2014). Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet 2014; published online Dec 19. http://dx.doi.org/10.1016/S01406736(14)62384-9. MCHE. FX-06: a potential new drug for prevention/reduction of vascular instability/ capillary leak in Ebola Virus Disease. October, 2014. http://www. mche.at/fx-06-potential-new-drug-for-ebola-virus-disease/ (accessed Dec 15, 2014). Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. Ebola virus disease in West Africa—clinical manifestations and management. N Engl J Med 2014; 371: 2054–57. Lamontagne F, Clement C, Fletcher T, Jacob ST, Fischer WA 2nd, Fowler RA. Doing today’s work superbly well—treating Ebola with current tools. N Engl J Med 2014; 371: 1565–66. Roberts I, Perner A. Ebola virus disease: clinical care and patient-centred research. Lancet 2014; 384: 2001–02. Check Hayden E. Ebola trials to start in December. Nature 2014; published online Nov 13. DOI:10.1038/nature.2014.16342. Butler D. First trials of Ebola blood-based therapy kick off. Nature 2014; published online Dec 15. DOI:10.1038/nature.2014.16564. WHO. Meeting of the Scientific and Technical Advisory Committee on Ebola experimental interventions—briefing note. Nov 13, 2014. http:// apps.who.int/medicines/ebola-treatment/scientific_tech_meeting/en/ index.html (accessed Dec 15, 2014).
Is malaria control better with both treated nets and spraying? In the past decade, new funding mechanisms such as the Global Fund to Fight AIDS, Tuberculosis and Malaria have led to an increase in international investment in malaria control. WHO estimates that, by 2012, this scaling up of anti-malaria interventions had prevented 3·3 million deaths.1 Most of these epidemiological benefits are attributable to increased coverage with effective vector control; in the past 5 years, over 500 million long-lasting insecticidal nets (LLINs) have been delivered. Attention to the combination of indoor residual spraying with LLINs has been growing in recent years, stimulated by the spread of vector resistance to pyrethroids and variations in the apparent effect of LLINs on malaria transmission. In some places, the effect on malaria has been disappointing, and there is interest in whether a combination of indoor residual spraying and LLINs would give better results. By contrast, elsewhere there has been a dramatic reduction in malaria incidence and prevalence, and local malaria authorities are considering local elimination, and whether this elusive goal could be brought within reach by a combination of indoor residual spraying and LLINs. Against this backdrop, the indoor residual spraying and LLINs trial in The Gambia reported in The Lancet by www.thelancet.com Vol 385 April 11, 2015
Margaret Pinder and colleagues2 is timely, interesting, and important. The trial was a community-randomised efficacy trial, comparing 35 clusters given LLINs and indoor residual spraying (with dichlorodiphenyltrichloroethane [DDT]) with 35 clusters given LLINs alone. Epidemiological outcomes were measured over 2 years by annual cross-sectional surveys and passive case detection. In each cluster, a cohort of between 65 and 213 children aged 6 months to 14 years was followed in 2010 and 2011 for the primary endpoint of clinical malaria. Coverage of indoor residual spraying and LLINs was high throughout the trial. However, no significant differences were observed between the two study groups in any of the outcomes measured: incidence of clinical malaria was 0·047 per child-month at risk in the LLIN group and 0·044 per child-month at risk in the indoor residual spraying and LLIN group in year 1, and 0·032 per child-month at risk in the LLIN group and 0·034 per child-month at risk in the indoor residual spraying and LLIN group in year 2 (incidence rate ratio 1·08, 95% CI 0·80–1·46). Anaemia, parasite, and splenomegaly rates were similar in both study groups in both years. No significant difference was reported in the density of vector mosquitoes caught in light traps in houses over the two transmission seasons.
Published Online December 9, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)61306-4 See Articles page 1436
1375
