- Email: [email protected]
Malaria: 2 years in the fast lane
Comment
imaging technology).4 There is also concern that CT is replacing physical examination, and a previous study5 with even more liberal criteria than in today’s report was heavily criticised for unnecessary radiation exposure.6 The radiation dose from whole-body CT is 10–20 mSv, which results in an estimated lifetime cancer mortality for 45-year-old people of about one in 1250 or 0·08%.7 Although the reduction in injury mortality in today’s study would outweigh that risk, the issue is not trivial. Thus indiscriminate use of CT for patients with minor injuries is not justified. The cohort reported by Huber-Wagner did not seem to be minimally injured. Trying to capture true health-care costs in the USA is elusive at best, and perhaps estimates from Europe are more reliable. We often consider hospital charges a poor surrogate for costs in this type of clinical research, largely because of the combination of fixed and variable costs. In Huber-Wagner and colleagues’ study, fixed costs were purchase of the CT hardware and software and technicians’ salaries. Variable costs were those associated with each examination, including depreciation on the hardware. The fixed costs greatly outweigh variable costs. Hospitals cannot provide appropriate care without
fixed CT costs, but I do not believe that health-care cost is a substantial concern with whole-body CT. Overall, today’s study should stimulate the pursuit of further investigations on the usefulness of whole-body CT for trauma assessment. Timothy C Fabian Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA [email protected] I declare that I have no conflict of interest. 1 2
3
4 5
6 7
Shafton GW. Abdominal trauma management in America. Bull Am Coll Surg 1989; 74: 21–35. Fabian TC, Mangiante EC, White TJ, Patterson CR, Boldreghini S, Britt LG. A prospective study of 91 patients undergoing both computed tomography and peritoneal lavage following blunt abdominal trauma. J Trauma 1986; 26: 602–08. Huber-Wagner S, Lefering R, Qvick L-M, et al, on behalf of the Working Group on Polytrauma of the German Trauma Society. Effect of whole-body CT during trauma resuscitation on survival: a retrospective, multicentre study. Lancet 2009; published online March 24. DOI:10.1016/S01406736(09)60232-4. Hayward R. VOMIT (victims of modern imaging technology)—an acronym for our times. BMJ 2003; 326: 1273. Salim A, Sangthong B, Martin M, Brown C, Plurad D, Demetriades D. Whole body imaging in blunt multisystem trauma patients without obvious signs of injury: results of a prospective study. Arch Surg 2006; 141: 468–75. Snyder GE. Whole-body imaging in blunt multisystem trauma patients who were never examined. Ann Emerg Med 2008; 52: 101–03. Brenner DJ, Elliston CD. Estimated radiation risks potentially associated with full-body CT screening. Radiology 2004; 232: 735–38.
Malaria: 2 years in the fast lane World Malaria Day (April 25) is upon us once again. Over the past 2 years, the world has made remarkable advances in malaria. 2 years ago, nobody was mentioning elimination and eradication. Then, on Oct 17, 2007, Bill and Melinda Gates made their famous speech in Seattle, USA, calling for global eradication.1 1 year ago, there was no consensus on how we would achieve a malaria-free world. Currently, a Global Malaria Action Plan2 has been developed under the leadership of Roll Back Malaria, which set out a three-part strategy. First, aggressive control in the malaria heartland to achieve low transmission and mortality in those 61 tropical countries with the highest burden of disease. Second, progressive elimination from the endemic margins inward to shrink the malaria map. Third, research to find a vaccine and better drugs, diagnostics, insecticides, and other tools. For the first part of the strategy, we have witnessed a massive scale-up in antimalaria programmes in the malaria heartland. Global Fund round 7 approved a total www.thelancet.com Vol 373 April 25, 2009
of US$1031 million for malaria and round 8 a further staggering $2911 million.3 The US President’s Malaria Initiative4 and the World Bank’s Booster Programme5 have continued to scale up operations in the malaria heartland. These investments are producing substantial reductions in malaria in countries such as Brazil, India, and Zambia.6 Furthermore, the private sector is increasing its investment to control malaria in countries such as Angola,7 Ghana, and Nigeria. 2 years ago, countries pursuing the second part of the strategy received little support. Elimination is now an active field, from policy to implementation. At present, 39 countries (over a third of all malariaendemic countries) have set ambitious, yet attainable, goals for freeing their country from malaria in the foreseeable future. Among these countries, various regional malaria-elimination collaborations have been established, including the E8 (Elimination 8) in southern Africa and the Asia Pacific Malaria Elimination Network.8
See Editorial page 1400 See Comment page 1411 See Perspectives page 1419
1409
Comment
Panos Pictures
The printed journal includes an image merely for illustration
The Malaria Elimination Group (MEG) was convened by the Global Health Group at the University of California (San Francisco) to support countries that are pursuing or considering elimination. MEG recently published two documents on elimination.9,10 These documents will assist policy makers, investors, and implementers as they make decisions related to the second part of the strategy. For the third part of the strategy, malaria research— including drugs, vaccines, and diagnostics—has continued to flourish. The Malaria Eradication Research Agenda (MalERA)11 has been recently launched and is developing a comprehensive research agenda to ensure that we have the technologies to free the planet of malaria. Additionally, there has been a remarkable surge of non-governmental organisations and civil-society activity in malaria. Several organisations against malaria have sprung into existence. Malaria No More12 has already raised over $37 million, and aims to create a $100 million malaria fund. Finally, on the political stage, we see the appointment of Ray Chambers as the UN Secretary-General’s special envoy on malaria. Also, the USA has followed the UK in creating a bipartisan and bicameral malaria parliamentary group, known as the Congressional Malaria Caucus.13 Where does all this leave us? The political commitment could hardly be stronger. Big sums of money are now flowing, but whether these sums will survive the recession is debatable. Encouragingly, some wealthy countries have pledged not to let the recession reduce their financial commitments for health and 1410
development.14 The challenge now is the implementation gap between political commitment, ambition, and availability of funds, and the capacity at ground level to do the work that needs to be done. Strong management, effective coordination among all partners in the public and private sectors, a culture of accountability for performance and outcomes, and long-term commitment by financial institutions are all imperative. Overall, we have many reasons to be optimistic. Except for those countries that are politically dysfunctional or suffering major conflicts, the 61 malaria-control countries in the heartland will make great progress in reducing death and sickness from malaria over the next 10 years. Meanwhile, many of the 39 malariaelimination countries will successfully get rid of malaria, and the malaria map will be substantially shrunk. Also, if the pace of malaria research continues, we can expect a first vaccine, important therapeutic advances, and further progress in the development of sensitive and specific point-of-treatment diagnostic tests.15 All this will move us forward towards a malaria-free world in the middle of the 21st century. *Richard G A Feachem, Allison A Phillips Global Health Group, UCSF Global Health Sciences, San Francisco, CA 94105, USA [email protected] RGAF directs the Global Health Group at the University of California partly devoted to malaria elimination and funded by the Bill & Melinda Gates Foundation and ExxonMobil. RGAF serves on the board of Malaria No More and was formerly the executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. AAP manages the Malaria Elimination Initiative at the Global Health Group. We thank Chris Cotter and Cara Smith-Gueye of the Global Health Group for helpful suggestions and research support. 1
2
3
4
5
6
7
Gates B. Keynote address presented at Bill & Melinda Gates Malaria Forum, Seattle, Washington. Oct 17, 2007. http://www.gatesfoundation.org/ speeches-commentary/Pages/bill-gates-malaria-forum.aspx (accessed March 4, 2009). Roll Back Malaria. Global malaria action plan: for a malaria free world. September, 2008. http://www.rollbackmalaria.org/gmap/index.html (accessed March 5, 2009). The Global Fund to Fight AIDS, Tuberculosis and Malaria. Grant portfolio, funding decisions: overview of previous funding rounds. http://www. theglobalfund.org/en/fundingdecisions/?lang=en (accessed March 5, 2009). USAID. The President’s malaria initiative: progress through partnerships: saving lives in Africa. March, 2008. http://www.pmi.gov/resources/ reports/pmi_annual_report08.pdf (accessed March 13, 2009). World Bank Booster Program for Malaria Control in Africa. Scaling-up for impact (SUFI): a two-year progress report. October, 2007. http://web. worldbank.org/WBSITE/EXTERNAL/COUNTRIES/AFRICAEXT/ EXTAFRBOOPRO/0,,contentMDK:21507239~pagePK:64168445~piPK: 64168309~theSitePK:2128617,00.html (accessed March 13, 2009). PATH. MACEPA malaria control partnership. A model for malaria control: raising the bar to halt malaria. http://www.path.org/projects/malaria_ control_partnership.php (accessed March 10, 2009). ExxonMobil. Africa health initiative. http://www.exxonmobil.com/ corporate/community_health_malaria_ahi.aspx (accessed March 10, 2009).
www.thelancet.com Vol 373 April 25, 2009
Comment
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9
10
11
Barrett C. Malaria to be “wiped out by 2060”. Brisbane Times Feb 10, 2009. http://www.brisbanetimes.com.au/news/queensland/malaria-to-bewiped-out-by-2060/2009/02/09/1234027942213.html (accessed March 5, 2009). Feachem RGA, and the Malaria Elimination Group. Shrinking the malaria map: a guide on malaria elimination for policy makers. 2009. http://www. malariaeliminationgroup.org/publications (accessed March 5, 2009). Feachem RGA, Phillips AA, Targett GAT, eds. Shrinking the malaria map: a prospectus on malaria elimination. 2009. http://www.malaria eliminationgroup.org/publications (accessed March 5, 2009). Roll Back Malaria. Malaria Eradication Research Agenda (MalERA). November, 2008. http://209.85.173.132/search?q=cache:NP2EtRSmX1oJ:www.rbm. who.int/partnership/board/meetings/ppt/15pbm/s2_3.ppt+%22malaria+era dication+research+agenda%22&hl=en&ct=clnk&cd=1&gl=us&client=firefox-a (accessed March 5, 2009).
12 13
14
15
Malaria No More. Malaria no more: timeline. http://www.malarianomore. org/about/timeline.php (accessed March 5, 2009). Congressman Donald M Payne. Congressman Payne, First Lady Laura Bush raise awareness global malaria epidemic. April 24, 2008. http://www.house. gov/list/press/nj10_payne/pr_080424malaria.shtml (accessed March 4, 2009). WHO. The financial crisis and global health. Jan 21, 2009. http://www.who. int/mediacentre/events/meetings/2009_financial_crisis_report_en_.pdf (accessed March 13, 2009). Greenwood BM. Control to elimination: implications for malaria research. Trends Parasitol 2008; 24: 449–54.
A vaccine against malaria: a substantial step forward Two recent studies by Philip Bejon1 and Salim Abdulla,2 and their respective colleagues, represent an important step towards the development of a malaria vaccine that shows great promise for being deployable in malaria-control programmes. Bejon and colleagues did a phase II trial in over 800 children aged 5–17 months in Kenya and Tanzania. The researchers aimed to evaluate the efficacy against clinical malaria of the most advanced candidate for a Plasmodium falciparum vaccine, RTS,S/AS01. The control group received rabies vaccine. The efficacy against all clinical episodes of malaria was 56% (95% CI 31–72%), after an average of 8 months’ follow-up after the third vaccine dose. This efficacy is higher than the 27% (6–44%) in an earlier study in Mozambique in children aged 1–4 years with the same vaccine antigen but a different adjuvant (AS02A).3 Although the confidence intervals for these estimates overlap, the AS01 adjuvant is more immunogenic, which is plausibly associated with higher efficacy. Compared with the AS02A adjuvant vaccine, use of AS01 has induced a stronger IgG response to the immunodominant B-cell epitope, together with improved cell-mediated immune responses in adults in non-endemic settings. However, a direct immunological correlate of protection against clinical malaria remains elusive, and Bejon found no association between the levels of circumsporozoite antibodies induced by the vaccine and protection against clinical disease. Abdulla and colleagues’ trial in 340 infants was designed to assess whether the malaria vaccine, given with a different adjuvant AS02, was safe when administered at the same time as vaccines currently in use in the expanded programme on immunisation (EPI), www.thelancet.com Vol 373 April 25, 2009
and whether the co-administration interfered with immune responses to the other vaccines. Infants received RTS,S/AS02 or hepatitis B vaccine co-administered with diphtheria and tetanus toxoid, whole-cell pertussis, and conjugated Haemophilus influenzae type b vaccines. There were no important safety concerns associated with the malaria vaccine and there was no significant reduction in the proportions of infants seroconverting to the EPI vaccines, although there were reductions in the immune responses for all of the co-administered vaccines except hepatitis B. RTS,S/AS01 includes an adjuvant that is not administered with any currently licensed vaccines. Although there have been no safety concerns to date, a key objective of a phase III trial will be to provide further data on vaccine safety. It will be important to follow up the population in Bejon and colleagues’ trial for evidence of lasting protection. Concerns about the possible short duration of protection in the Mozambique trial of RTS,S after 6 months of follow-up,4 as had been observed in an earlier trial of the RTS,S vaccine in adults,5 proved unfounded, and the extended follow-up in the Mozambique trial showed protection at around 30%, which persisted until at least 21 months after vaccination.6 In the Mozambique trial, although it was not a primary endpoint, there was suggestive evidence that the protection against severe malaria was greater than against clinical malaria (49% vs 29%, respectively). The number of cases of severe malaria in Bejon’s trial was small, but it is encouraging that only one of the nine cases was in the vaccinated group. In the planned phase III trial, it would be highly desirable to power the trial to include severe malaria disease as a key endpoint.
See Editorial page 1400 See Comment page 1409 See Perspectives page 1419
1411
imaging technology).4 There is also concern that CT is replacing physical examination, and a previous study5 with even more liberal criteria than in today’s report was heavily criticised for unnecessary radiation exposure.6 The radiation dose from whole-body CT is 10–20 mSv, which results in an estimated lifetime cancer mortality for 45-year-old people of about one in 1250 or 0·08%.7 Although the reduction in injury mortality in today’s study would outweigh that risk, the issue is not trivial. Thus indiscriminate use of CT for patients with minor injuries is not justified. The cohort reported by Huber-Wagner did not seem to be minimally injured. Trying to capture true health-care costs in the USA is elusive at best, and perhaps estimates from Europe are more reliable. We often consider hospital charges a poor surrogate for costs in this type of clinical research, largely because of the combination of fixed and variable costs. In Huber-Wagner and colleagues’ study, fixed costs were purchase of the CT hardware and software and technicians’ salaries. Variable costs were those associated with each examination, including depreciation on the hardware. The fixed costs greatly outweigh variable costs. Hospitals cannot provide appropriate care without
fixed CT costs, but I do not believe that health-care cost is a substantial concern with whole-body CT. Overall, today’s study should stimulate the pursuit of further investigations on the usefulness of whole-body CT for trauma assessment. Timothy C Fabian Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA [email protected] I declare that I have no conflict of interest. 1 2
3
4 5
6 7
Shafton GW. Abdominal trauma management in America. Bull Am Coll Surg 1989; 74: 21–35. Fabian TC, Mangiante EC, White TJ, Patterson CR, Boldreghini S, Britt LG. A prospective study of 91 patients undergoing both computed tomography and peritoneal lavage following blunt abdominal trauma. J Trauma 1986; 26: 602–08. Huber-Wagner S, Lefering R, Qvick L-M, et al, on behalf of the Working Group on Polytrauma of the German Trauma Society. Effect of whole-body CT during trauma resuscitation on survival: a retrospective, multicentre study. Lancet 2009; published online March 24. DOI:10.1016/S01406736(09)60232-4. Hayward R. VOMIT (victims of modern imaging technology)—an acronym for our times. BMJ 2003; 326: 1273. Salim A, Sangthong B, Martin M, Brown C, Plurad D, Demetriades D. Whole body imaging in blunt multisystem trauma patients without obvious signs of injury: results of a prospective study. Arch Surg 2006; 141: 468–75. Snyder GE. Whole-body imaging in blunt multisystem trauma patients who were never examined. Ann Emerg Med 2008; 52: 101–03. Brenner DJ, Elliston CD. Estimated radiation risks potentially associated with full-body CT screening. Radiology 2004; 232: 735–38.
Malaria: 2 years in the fast lane World Malaria Day (April 25) is upon us once again. Over the past 2 years, the world has made remarkable advances in malaria. 2 years ago, nobody was mentioning elimination and eradication. Then, on Oct 17, 2007, Bill and Melinda Gates made their famous speech in Seattle, USA, calling for global eradication.1 1 year ago, there was no consensus on how we would achieve a malaria-free world. Currently, a Global Malaria Action Plan2 has been developed under the leadership of Roll Back Malaria, which set out a three-part strategy. First, aggressive control in the malaria heartland to achieve low transmission and mortality in those 61 tropical countries with the highest burden of disease. Second, progressive elimination from the endemic margins inward to shrink the malaria map. Third, research to find a vaccine and better drugs, diagnostics, insecticides, and other tools. For the first part of the strategy, we have witnessed a massive scale-up in antimalaria programmes in the malaria heartland. Global Fund round 7 approved a total www.thelancet.com Vol 373 April 25, 2009
of US$1031 million for malaria and round 8 a further staggering $2911 million.3 The US President’s Malaria Initiative4 and the World Bank’s Booster Programme5 have continued to scale up operations in the malaria heartland. These investments are producing substantial reductions in malaria in countries such as Brazil, India, and Zambia.6 Furthermore, the private sector is increasing its investment to control malaria in countries such as Angola,7 Ghana, and Nigeria. 2 years ago, countries pursuing the second part of the strategy received little support. Elimination is now an active field, from policy to implementation. At present, 39 countries (over a third of all malariaendemic countries) have set ambitious, yet attainable, goals for freeing their country from malaria in the foreseeable future. Among these countries, various regional malaria-elimination collaborations have been established, including the E8 (Elimination 8) in southern Africa and the Asia Pacific Malaria Elimination Network.8
See Editorial page 1400 See Comment page 1411 See Perspectives page 1419
1409
Comment
Panos Pictures
The printed journal includes an image merely for illustration
The Malaria Elimination Group (MEG) was convened by the Global Health Group at the University of California (San Francisco) to support countries that are pursuing or considering elimination. MEG recently published two documents on elimination.9,10 These documents will assist policy makers, investors, and implementers as they make decisions related to the second part of the strategy. For the third part of the strategy, malaria research— including drugs, vaccines, and diagnostics—has continued to flourish. The Malaria Eradication Research Agenda (MalERA)11 has been recently launched and is developing a comprehensive research agenda to ensure that we have the technologies to free the planet of malaria. Additionally, there has been a remarkable surge of non-governmental organisations and civil-society activity in malaria. Several organisations against malaria have sprung into existence. Malaria No More12 has already raised over $37 million, and aims to create a $100 million malaria fund. Finally, on the political stage, we see the appointment of Ray Chambers as the UN Secretary-General’s special envoy on malaria. Also, the USA has followed the UK in creating a bipartisan and bicameral malaria parliamentary group, known as the Congressional Malaria Caucus.13 Where does all this leave us? The political commitment could hardly be stronger. Big sums of money are now flowing, but whether these sums will survive the recession is debatable. Encouragingly, some wealthy countries have pledged not to let the recession reduce their financial commitments for health and 1410
development.14 The challenge now is the implementation gap between political commitment, ambition, and availability of funds, and the capacity at ground level to do the work that needs to be done. Strong management, effective coordination among all partners in the public and private sectors, a culture of accountability for performance and outcomes, and long-term commitment by financial institutions are all imperative. Overall, we have many reasons to be optimistic. Except for those countries that are politically dysfunctional or suffering major conflicts, the 61 malaria-control countries in the heartland will make great progress in reducing death and sickness from malaria over the next 10 years. Meanwhile, many of the 39 malariaelimination countries will successfully get rid of malaria, and the malaria map will be substantially shrunk. Also, if the pace of malaria research continues, we can expect a first vaccine, important therapeutic advances, and further progress in the development of sensitive and specific point-of-treatment diagnostic tests.15 All this will move us forward towards a malaria-free world in the middle of the 21st century. *Richard G A Feachem, Allison A Phillips Global Health Group, UCSF Global Health Sciences, San Francisco, CA 94105, USA [email protected] RGAF directs the Global Health Group at the University of California partly devoted to malaria elimination and funded by the Bill & Melinda Gates Foundation and ExxonMobil. RGAF serves on the board of Malaria No More and was formerly the executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. AAP manages the Malaria Elimination Initiative at the Global Health Group. We thank Chris Cotter and Cara Smith-Gueye of the Global Health Group for helpful suggestions and research support. 1
2
3
4
5
6
7
Gates B. Keynote address presented at Bill & Melinda Gates Malaria Forum, Seattle, Washington. Oct 17, 2007. http://www.gatesfoundation.org/ speeches-commentary/Pages/bill-gates-malaria-forum.aspx (accessed March 4, 2009). Roll Back Malaria. Global malaria action plan: for a malaria free world. September, 2008. http://www.rollbackmalaria.org/gmap/index.html (accessed March 5, 2009). The Global Fund to Fight AIDS, Tuberculosis and Malaria. Grant portfolio, funding decisions: overview of previous funding rounds. http://www. theglobalfund.org/en/fundingdecisions/?lang=en (accessed March 5, 2009). USAID. The President’s malaria initiative: progress through partnerships: saving lives in Africa. March, 2008. http://www.pmi.gov/resources/ reports/pmi_annual_report08.pdf (accessed March 13, 2009). World Bank Booster Program for Malaria Control in Africa. Scaling-up for impact (SUFI): a two-year progress report. October, 2007. http://web. worldbank.org/WBSITE/EXTERNAL/COUNTRIES/AFRICAEXT/ EXTAFRBOOPRO/0,,contentMDK:21507239~pagePK:64168445~piPK: 64168309~theSitePK:2128617,00.html (accessed March 13, 2009). PATH. MACEPA malaria control partnership. A model for malaria control: raising the bar to halt malaria. http://www.path.org/projects/malaria_ control_partnership.php (accessed March 10, 2009). ExxonMobil. Africa health initiative. http://www.exxonmobil.com/ corporate/community_health_malaria_ahi.aspx (accessed March 10, 2009).
www.thelancet.com Vol 373 April 25, 2009
Comment
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11
Barrett C. Malaria to be “wiped out by 2060”. Brisbane Times Feb 10, 2009. http://www.brisbanetimes.com.au/news/queensland/malaria-to-bewiped-out-by-2060/2009/02/09/1234027942213.html (accessed March 5, 2009). Feachem RGA, and the Malaria Elimination Group. Shrinking the malaria map: a guide on malaria elimination for policy makers. 2009. http://www. malariaeliminationgroup.org/publications (accessed March 5, 2009). Feachem RGA, Phillips AA, Targett GAT, eds. Shrinking the malaria map: a prospectus on malaria elimination. 2009. http://www.malaria eliminationgroup.org/publications (accessed March 5, 2009). Roll Back Malaria. Malaria Eradication Research Agenda (MalERA). November, 2008. http://209.85.173.132/search?q=cache:NP2EtRSmX1oJ:www.rbm. who.int/partnership/board/meetings/ppt/15pbm/s2_3.ppt+%22malaria+era dication+research+agenda%22&hl=en&ct=clnk&cd=1&gl=us&client=firefox-a (accessed March 5, 2009).
12 13
14
15
Malaria No More. Malaria no more: timeline. http://www.malarianomore. org/about/timeline.php (accessed March 5, 2009). Congressman Donald M Payne. Congressman Payne, First Lady Laura Bush raise awareness global malaria epidemic. April 24, 2008. http://www.house. gov/list/press/nj10_payne/pr_080424malaria.shtml (accessed March 4, 2009). WHO. The financial crisis and global health. Jan 21, 2009. http://www.who. int/mediacentre/events/meetings/2009_financial_crisis_report_en_.pdf (accessed March 13, 2009). Greenwood BM. Control to elimination: implications for malaria research. Trends Parasitol 2008; 24: 449–54.
A vaccine against malaria: a substantial step forward Two recent studies by Philip Bejon1 and Salim Abdulla,2 and their respective colleagues, represent an important step towards the development of a malaria vaccine that shows great promise for being deployable in malaria-control programmes. Bejon and colleagues did a phase II trial in over 800 children aged 5–17 months in Kenya and Tanzania. The researchers aimed to evaluate the efficacy against clinical malaria of the most advanced candidate for a Plasmodium falciparum vaccine, RTS,S/AS01. The control group received rabies vaccine. The efficacy against all clinical episodes of malaria was 56% (95% CI 31–72%), after an average of 8 months’ follow-up after the third vaccine dose. This efficacy is higher than the 27% (6–44%) in an earlier study in Mozambique in children aged 1–4 years with the same vaccine antigen but a different adjuvant (AS02A).3 Although the confidence intervals for these estimates overlap, the AS01 adjuvant is more immunogenic, which is plausibly associated with higher efficacy. Compared with the AS02A adjuvant vaccine, use of AS01 has induced a stronger IgG response to the immunodominant B-cell epitope, together with improved cell-mediated immune responses in adults in non-endemic settings. However, a direct immunological correlate of protection against clinical malaria remains elusive, and Bejon found no association between the levels of circumsporozoite antibodies induced by the vaccine and protection against clinical disease. Abdulla and colleagues’ trial in 340 infants was designed to assess whether the malaria vaccine, given with a different adjuvant AS02, was safe when administered at the same time as vaccines currently in use in the expanded programme on immunisation (EPI), www.thelancet.com Vol 373 April 25, 2009
and whether the co-administration interfered with immune responses to the other vaccines. Infants received RTS,S/AS02 or hepatitis B vaccine co-administered with diphtheria and tetanus toxoid, whole-cell pertussis, and conjugated Haemophilus influenzae type b vaccines. There were no important safety concerns associated with the malaria vaccine and there was no significant reduction in the proportions of infants seroconverting to the EPI vaccines, although there were reductions in the immune responses for all of the co-administered vaccines except hepatitis B. RTS,S/AS01 includes an adjuvant that is not administered with any currently licensed vaccines. Although there have been no safety concerns to date, a key objective of a phase III trial will be to provide further data on vaccine safety. It will be important to follow up the population in Bejon and colleagues’ trial for evidence of lasting protection. Concerns about the possible short duration of protection in the Mozambique trial of RTS,S after 6 months of follow-up,4 as had been observed in an earlier trial of the RTS,S vaccine in adults,5 proved unfounded, and the extended follow-up in the Mozambique trial showed protection at around 30%, which persisted until at least 21 months after vaccination.6 In the Mozambique trial, although it was not a primary endpoint, there was suggestive evidence that the protection against severe malaria was greater than against clinical malaria (49% vs 29%, respectively). The number of cases of severe malaria in Bejon’s trial was small, but it is encouraging that only one of the nine cases was in the vaccinated group. In the planned phase III trial, it would be highly desirable to power the trial to include severe malaria disease as a key endpoint.
See Editorial page 1400 See Comment page 1409 See Perspectives page 1419
1411