- Email: [email protected]
Updating prevaccination rotavirus-associated mortality
Comment
The final answer will be dependent on the proportion of susceptible children immunised with IPV and the extent of effective mucosal immunity induced by IPV. After eradication, use of all live vaccines will cease to prevent otherwise inevitable outbreaks of virulent vaccine-derived polioviruses.12 Inactivated vaccine will be needed for continuing protection against re-emergence of polio from immunodeficient, long-term excretors, laboratory mishap, or purposeful reintroduction.13 Clinical trials14–17 in Guatemala, India, Kenya, Oman, and other developing countries have shown encouraging results when IPV is given as the primary series to infants younger than 6 months. Optimum immunogenicity results when the first dose is given at 8–10 weeks of age and doses are separated by 8 weeks, rather than 4 weeks. Although a three-dose primary series is generally needed to achieve 100% seroconversion, two doses induce seroconversion rates of 86–99%, albeit at the cost of lower geometric mean titres.14-16,18 A two-dose schedule could be acceptable in resource-poor countries where the cost of IPV exceeds that of all other routinely given vaccines. Other methods to spare antigen include use of new delivery devices, intradermal fractional doses, and adjuvants. Findings from the study by Mohammed and colleagues16 in Oman showed satisfactory seroconversion rates to a fifth the standard IPV dose given subcutaneously to infants at 2, 4, and 6 months of age. Other strategies, such as combination of IPV with diphtheria, tetanus, and pertusiss vaccines and production of vaccine in low-cost facilities that meet high regulatory standards, will make access to IPV affordable for all nations. The study by Estívariz and colleagues is a small, but important contribution that advances the global poliomyelitis eradication effort by better defining the use of IPV in resource-poor settings.
John F Modlin Department of Pediatrics, Dartmouth Medical School, Lebanon, NH 03756, USA [email protected] I declare that I have no conflicts of interest 1 2 3 4 5
6 7 8
9
10
11 12
13 14 15
16 17
18
WHO. Global eradication of poliomyelitis by the year 2000. Week Epidemiol Rec 1988; 63: 161–62. Patriarca PA, Wright PF, John TJ. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries. Rev Infect Dis 1991; 13: 926–39. Myaux JA, Unicomb L, Besser RE, et al. Effect of diarrhea on the humoral response to oral polio vaccination. Pediatr Infect Dis J 1996; 15: 204–09. Grassly NC, Fraser C, Wenger J, et al. New strategies for the elimination of polio from India. Science 2006; 314: 1150–53. Caceres VM, Sutter RW. Sabin monovalent oral polio vaccines: review of past experiences and their potential use after polio eradication. Clin Infect Dis 2001; 33: 531–41. Grassly NC, Wenger J, Durrani S, et al. Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study. Lancet 2007; 369: 1356–62. Wright PF, Modlin JF. The demise and rebirth of polio—a modern phoenix? J Infect Dis 2008; 197: 335–36. Estívariz CF, Jafari H, Sutter RW, et al. Immunogenicity of supplemental doses of poliovirus vaccine for children aged 6–9 months in Moradabad, India: a community-based, randomised controlled trial. Lancet Infect Dis 2011; published online Nov 8. DOI:10.1016/S1473-3099(11)70190-6. Krugman RD, Hardy GE Jr, Sellers C. Antibody persistence after primary immunization with trivalent oral poliovirus vaccine. Pediatrics 1977; 60: 80–82. Gelfand HM, LeBlanc DR, Potash L, Fox JP. Studies on the development of natural immunity to poliomyelitis in Louisiana. IV. Natural infections with polioviruses following immunization with a formalin-inactivated vaccine. Am J Hyg 1959; 70: 312–27. Bijkerk H. Poliomyeltis epidemic in the Netherlands. Dev Biol Stand 1979; 43: 195–206. WHO. Global Eradication Initiative Strategic Plan, 2004–2008. 2003. http://www.polioeradication.org/content/publications/2004stratplan.pdf (accessed Dec 31, 2004). WHO. Introduction of inactivated poliovirus vaccine into oral poliovirus vaccine-using countries. Wkly Epidemiol Rec 2003; 78: 241–50. Asturias EJ, Dueger EL, Omer SB, et al. Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants. J Infect Dis 2007; 196: 692–98. Kok PW, Leeuwenburg J, Tukei P, et al. Serological and virological assessment of oral and inactivated poliovirus vaccines in a rural population. Bull World Health Organ 1992; 70: 93–103. Mohammed AJ, AlAwaidy S, Bawikar S, et al. Fractional doses of inactivated poliovirus vaccine in Oman. N Engl J Med 2008; 362: 2351–59. Simoes EA, John TJ. The antibody response of seronegative infants to inactivated poliovirus vaccine of enhanced potency. J Biol Stand 1986; 14: 127–31. The Cuba IPV Study Collaborative Group. Randomized, placebo-controlled trial of inactivated poliovirus vaccine in Cuba. N Engl J Med 2007; 356: 1536–44.
Updating prevaccination rotavirus-associated mortality Published Online October 25, 2011 DOI:10.1016/S14733099(11)70288-2 See Articles page 136
94
In The Lancet Infectious Diseases, Jacqueline Tate and colleagues1 assess more than 40 reports published between 2008 and 2011 and recent data from WHOcoordinated Global Surveillance Networks, which established the rate of rotavirus-associated acute gastroenteritis in children younger than 5 years who were admitted to hospital in various parts of the world. From these rates and the actual numbers of childhood deaths in
different countries related to all causes of diarrhoea,2 Tate and colleagues obtained estimates of deaths associated with rotavirus disease. By assigning countries to different mortality strata, the investigators confirmed that mortality associated with rotavirus disease is unevenly distributed. Although rotavirus disease only rarely causes death in Europe, North America and Australia, it causes many deaths in countries of southeast Asia (India, www.thelancet.com/infection Vol 12 February 2012
Comment
Pakistan) and sub-Saharan Africa (DR Congo, Ethiopia, Nigeria), adding up to greater than 50% of the worldwide deaths associated with rotavirus disease in these five countries. The 2008 mortality figures update those of 20043 and are based on a much expanded worldwide surveillance programme. Since data collected after the introduction of universal rotavirus vaccination (URVV) programmes were excluded, the 2008 rotavirus mortality estimates are crucially important because they form the basis for assessing the effectiveness of the ongoing URVV programmes in relation to avoided deaths of children. Tate and colleagues are very clear about the assumptions and limitations of their meta-analysis. Their survey did not consider deaths associated with rotavirus disease in the community, and the data they obtained might therefore be underestimates. Their use of numbers of rotavirus-associated acute gastroenteritis in children admitted to hospital as a proxy for the contribution to all-cause diarrhoea-related deaths assumed that the identification of rotavirus in children admitted to hospital was causally related to illness and death. However, rotavirus infections are well known to cause mild disease or no clinical symptoms at all.4 Thus, the data obtained might be overestimates. Also, clinical specimens were only tested for the presence of rotavirus in most studies; thus other potential microbial causes of acute gastroenteritis were excluded. An issue not raised by Tate and colleagues is the difference in balance between the number of clinical samples tested and the overall population of children younger than 5 years who were at risk of acute gastroenteritis in different countries. Thus the statistical weight of the primary data is very different for different geographical locations. However, sampling differences and some bias seem to be unavoidable at present, and the mortality figures obtained are the best available. Compared with the 2004 estimate of deaths associated with rotavirus disease of 527 000 children worldwide,3 the 2008 data of 453 000 represents a decrease of 14%; during the same period the total number of deaths from all-cause diarrhoea in children younger than 5 years has decreased by 33%, from 1·8 million to 1·2 million. Tate and colleagues believe that this discrepancy is probably due to a higher rotavirus detection rate (37% vs 29%) underlying the more recent data. They rightly conclude that “the greater rotavirus detection rate partly offsets the decline in overall diarrhoea-related mortality”. www.thelancet.com/infection Vol 12 February 2012
The introduction of URVV programmes in various countries since 2006 (Australia, Belgium, Brazil, El Salvador, Finland, Mexico, Panama, USA, and others) has resulted in substantial reductions in admission to hospital for rotavirus-associated acute gastroenteritis5 and also to the flattening (and delay) of seasonal epidemiological curves.6,7 The licensed rotavirus vaccines were shown to be less effective in countries of subSaharan Africa and southeast Asia.8,9 However, since vaccine efficacy estimates correlate inversely with disease incidence and child mortality strata, the Strategic Advisory Group of Experts of WHO have recommended the use of rotavirus vaccination worldwide in national immunisation programmes.10 Whether URVV programmes lead to the emergence of rotavirus vaccine escape populations of co-circulating wildtype rotaviruses is at present undecided, also because of rapid, unpredictable changes in the maximum prevalence of particular wildtype rotavirus genotypes.11 Thus, the increased prevalence of G2P[4] rotaviruses in Brazil during a URVV campaign with the G1P[8] vaccine, at an efficacy of 77% against G2P[4] strains,12 could not be unambiguously attributed to URVV since the same genotype emerged simultaneously in neighbouring countries in the absence of URVV,13 and there are similar inconclusive findings of this kind in other countries. It is probable that URVV programmes will result in a decrease in deaths associated with rotavirus disease, and the collated data are eagerly awaited. Ulrich Desselberger Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK [email protected] I declare that I have no conflicts of interest. 1
2 3
4 5
6
Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2011; published online Oct 25. DOI:10.1016/S1473-3099(11)70253-5. Black RE, Cousens S, Johnson HL, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010; 375: 1969–87. Parashar UD, Burton A, Lanata C, et al. Global mortality associated with rotavirus disease among children in 2004. J Infect Dis 2009; 200 (suppl 1): S9–15. Velázquez FR, Matson DO, Calva JJ, et al. Rotavirus infections in infants as protection against subsequent infections. N Engl J Med 1996; 335: 1022–28. Giaquinto C, Dominiak-Felden G, Van Damme P, et al. Summary of effectiveness and impact of rotavirus vaccination with the oral pentavalent rotavirus vaccine: a systematic review of the experience in industrialized countries. Hum Vaccin 2011; 7: 734–48. Centers for Disease Control and Prevention. Reduction in rotavirus after vaccine introduction—United States, 2000–2009. MMWR Morb Mortal Wkly Rep 2009; 58: 1146–49.
95
Comment
7
8
9 10
Tate JE, Mutuc JD, Panozzo CA, et al. Sustained decline in rotavirus detections in the United States following the introduction of rotavirus vaccine in 2006. Pediatr Infect Dis J 2011; 30 (1 suppl): S30–34. Esposito DH, Tate JE, Kang G, Parashar UD. Projected impact and cost-effectiveness of a rotavirus vaccination program in India, 2008. Clin Infect Dis 2011; 52: 171–77. Madhi SA, Cunliffe NA, Steele D, et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med 2010; 362: 289–98. WHO. Meeting of the immunization Strategic Advisory Group of Experts, April 2009—conclusions and recommendations. Wkly Epidemiol Rec 2009; 84: 220–36.
11
12
13
Iturriza-Gómara M, Dallman T, Bányai K, et al. Rotavirus genotypes co-circulating in Europe between 2006 and 2009 as determined by EuroRotaNet, a pan-European collaborative strain surveillance network. Epidemiol Infect 2011; 139: 895–909. Correia JB, Patel MM, Nakagomi O, et al. Effectiveness of monovalent rotavirus vaccine (Rotarix) against severe diarrhea caused by serotypically unrelated G2P[4] strains in Brazil. J Infect Dis 2010; 201: 363–69. Matthijnssens J, Bilcke J, Ciarlet M, et al. Rotavirus disease and vaccination: impact on genotype diversity. Future Microbiol 2009; 4: 1303–16.
Why doesn’t hand hygiene work better? The field of infection control is devoted to reducing the spread of pathogens. Over the years, this endeavour has developed along two distinct lines. In resource-limited communities, as shown by Curtis and colleagues1 in their recent Review, simple hygienic measures can have a remarkable effect on decreasing transmission, although their implementation may be inconsistent. By contrast, modern high-tech hospitals, which occupy the opposite end of the resource spectrum, are ceaselessly haunted by a different set of transmissible pathogens, those that cause health-care-associated infection (HAI). For most problems in health care, those with and without suitable resources use drastically different countermeasures to remedy a problem. However, for this predicament, the core solution is the same, be it for the fancy tertiary care centre or a slum in Kyrgyzstan: hand washing. This odd coincidence might help to explain an unexpected finding that recently has become evident— hand hygiene is not particularly effective in the modern hospital setting.2 After the introduction of alcoholbased hand rub in the past decade, infection control programmes have tried to improve hand hygiene rates. With a large concerted effort we have achieved exactly what we asked for: improved hand hygiene rates. What we have not achieved is a decrease in infection rates, at least not from hand hygiene alone.3 The work reviewed by Curtis and colleagues1 suggests why the initiative has failed. They show the effect of hand hygiene on, for example, community spread of diarrhoea—a simple measure and one long ago shown to work in urban hospitals.4 Indeed, all discussion of clean hands begins with the travails of Ignaz Semmelweis.4 Semmelweis famously reported that pregnant women delivered by training doctors had a mortality rate three to four times higher than those who were delivered 96
by midwives in the Lying-In Hospital in Vienna. Once Semmelweis convinced the doctors to use chlorina liquida (later changed to the cheaper chlorinated lime) between undertaking cadaver exams and pelvic exams, mortality dropped sharply and permanently. This product replaced the simple soap and water used for many years. Semmelweis’ stirring struggle and monumental triumph, his tragic personal fate, and the arrogant stubbornness of the medical establishment who thwarted him provide a poignant narrative.4 But perhaps doctors love the story a bit too much and so have accepted its teachings wholesale. In doing so we have forgotten the study’s context: Semmelweis worked in an environment much more like that described by Curtis and colleagues1 than the gleaming health palaces of the 21st century. For example, at the Lying-In Hospital of Vienna in the 1840s, electricity wasn’t available, plumbing existed but easy access to hot water did not, and women were crowded into large wards when they gave birth. Clinicians have long assumed that hand hygiene could and would have the same effect now as it had back in the 19th century—if only we could coerce our colleagues to just lather up. But now even though their hands are substantially cleaner, the benefit of the enterprise is uncertain. Granted, recent reports from the USA have shown heartening reductions in nosocomial problems such as meticillin-resistant Staphylococcus aureus (MRSA)5 and central line-associated bloodstream infection (CLABSI) in the intensive care unit,3 even as a relative newcomer to the axis of pathogens, Clostridium difficile-associated diarrhea, has continued its upward march.6 However, the specific contribution of improved hand hygiene in these successes is uncertain at best.7 For both MRSA and CLABSI, multipronged approaches from bundles to screening to worrying more and harder to financial (dis)incentives seem operative, not pristine www.thelancet.com/infection Vol 12 February 2012
The final answer will be dependent on the proportion of susceptible children immunised with IPV and the extent of effective mucosal immunity induced by IPV. After eradication, use of all live vaccines will cease to prevent otherwise inevitable outbreaks of virulent vaccine-derived polioviruses.12 Inactivated vaccine will be needed for continuing protection against re-emergence of polio from immunodeficient, long-term excretors, laboratory mishap, or purposeful reintroduction.13 Clinical trials14–17 in Guatemala, India, Kenya, Oman, and other developing countries have shown encouraging results when IPV is given as the primary series to infants younger than 6 months. Optimum immunogenicity results when the first dose is given at 8–10 weeks of age and doses are separated by 8 weeks, rather than 4 weeks. Although a three-dose primary series is generally needed to achieve 100% seroconversion, two doses induce seroconversion rates of 86–99%, albeit at the cost of lower geometric mean titres.14-16,18 A two-dose schedule could be acceptable in resource-poor countries where the cost of IPV exceeds that of all other routinely given vaccines. Other methods to spare antigen include use of new delivery devices, intradermal fractional doses, and adjuvants. Findings from the study by Mohammed and colleagues16 in Oman showed satisfactory seroconversion rates to a fifth the standard IPV dose given subcutaneously to infants at 2, 4, and 6 months of age. Other strategies, such as combination of IPV with diphtheria, tetanus, and pertusiss vaccines and production of vaccine in low-cost facilities that meet high regulatory standards, will make access to IPV affordable for all nations. The study by Estívariz and colleagues is a small, but important contribution that advances the global poliomyelitis eradication effort by better defining the use of IPV in resource-poor settings.
John F Modlin Department of Pediatrics, Dartmouth Medical School, Lebanon, NH 03756, USA [email protected] I declare that I have no conflicts of interest 1 2 3 4 5
6 7 8
9
10
11 12
13 14 15
16 17
18
WHO. Global eradication of poliomyelitis by the year 2000. Week Epidemiol Rec 1988; 63: 161–62. Patriarca PA, Wright PF, John TJ. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries. Rev Infect Dis 1991; 13: 926–39. Myaux JA, Unicomb L, Besser RE, et al. Effect of diarrhea on the humoral response to oral polio vaccination. Pediatr Infect Dis J 1996; 15: 204–09. Grassly NC, Fraser C, Wenger J, et al. New strategies for the elimination of polio from India. Science 2006; 314: 1150–53. Caceres VM, Sutter RW. Sabin monovalent oral polio vaccines: review of past experiences and their potential use after polio eradication. Clin Infect Dis 2001; 33: 531–41. Grassly NC, Wenger J, Durrani S, et al. Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study. Lancet 2007; 369: 1356–62. Wright PF, Modlin JF. The demise and rebirth of polio—a modern phoenix? J Infect Dis 2008; 197: 335–36. Estívariz CF, Jafari H, Sutter RW, et al. Immunogenicity of supplemental doses of poliovirus vaccine for children aged 6–9 months in Moradabad, India: a community-based, randomised controlled trial. Lancet Infect Dis 2011; published online Nov 8. DOI:10.1016/S1473-3099(11)70190-6. Krugman RD, Hardy GE Jr, Sellers C. Antibody persistence after primary immunization with trivalent oral poliovirus vaccine. Pediatrics 1977; 60: 80–82. Gelfand HM, LeBlanc DR, Potash L, Fox JP. Studies on the development of natural immunity to poliomyelitis in Louisiana. IV. Natural infections with polioviruses following immunization with a formalin-inactivated vaccine. Am J Hyg 1959; 70: 312–27. Bijkerk H. Poliomyeltis epidemic in the Netherlands. Dev Biol Stand 1979; 43: 195–206. WHO. Global Eradication Initiative Strategic Plan, 2004–2008. 2003. http://www.polioeradication.org/content/publications/2004stratplan.pdf (accessed Dec 31, 2004). WHO. Introduction of inactivated poliovirus vaccine into oral poliovirus vaccine-using countries. Wkly Epidemiol Rec 2003; 78: 241–50. Asturias EJ, Dueger EL, Omer SB, et al. Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants. J Infect Dis 2007; 196: 692–98. Kok PW, Leeuwenburg J, Tukei P, et al. Serological and virological assessment of oral and inactivated poliovirus vaccines in a rural population. Bull World Health Organ 1992; 70: 93–103. Mohammed AJ, AlAwaidy S, Bawikar S, et al. Fractional doses of inactivated poliovirus vaccine in Oman. N Engl J Med 2008; 362: 2351–59. Simoes EA, John TJ. The antibody response of seronegative infants to inactivated poliovirus vaccine of enhanced potency. J Biol Stand 1986; 14: 127–31. The Cuba IPV Study Collaborative Group. Randomized, placebo-controlled trial of inactivated poliovirus vaccine in Cuba. N Engl J Med 2007; 356: 1536–44.
Updating prevaccination rotavirus-associated mortality Published Online October 25, 2011 DOI:10.1016/S14733099(11)70288-2 See Articles page 136
94
In The Lancet Infectious Diseases, Jacqueline Tate and colleagues1 assess more than 40 reports published between 2008 and 2011 and recent data from WHOcoordinated Global Surveillance Networks, which established the rate of rotavirus-associated acute gastroenteritis in children younger than 5 years who were admitted to hospital in various parts of the world. From these rates and the actual numbers of childhood deaths in
different countries related to all causes of diarrhoea,2 Tate and colleagues obtained estimates of deaths associated with rotavirus disease. By assigning countries to different mortality strata, the investigators confirmed that mortality associated with rotavirus disease is unevenly distributed. Although rotavirus disease only rarely causes death in Europe, North America and Australia, it causes many deaths in countries of southeast Asia (India, www.thelancet.com/infection Vol 12 February 2012
Comment
Pakistan) and sub-Saharan Africa (DR Congo, Ethiopia, Nigeria), adding up to greater than 50% of the worldwide deaths associated with rotavirus disease in these five countries. The 2008 mortality figures update those of 20043 and are based on a much expanded worldwide surveillance programme. Since data collected after the introduction of universal rotavirus vaccination (URVV) programmes were excluded, the 2008 rotavirus mortality estimates are crucially important because they form the basis for assessing the effectiveness of the ongoing URVV programmes in relation to avoided deaths of children. Tate and colleagues are very clear about the assumptions and limitations of their meta-analysis. Their survey did not consider deaths associated with rotavirus disease in the community, and the data they obtained might therefore be underestimates. Their use of numbers of rotavirus-associated acute gastroenteritis in children admitted to hospital as a proxy for the contribution to all-cause diarrhoea-related deaths assumed that the identification of rotavirus in children admitted to hospital was causally related to illness and death. However, rotavirus infections are well known to cause mild disease or no clinical symptoms at all.4 Thus, the data obtained might be overestimates. Also, clinical specimens were only tested for the presence of rotavirus in most studies; thus other potential microbial causes of acute gastroenteritis were excluded. An issue not raised by Tate and colleagues is the difference in balance between the number of clinical samples tested and the overall population of children younger than 5 years who were at risk of acute gastroenteritis in different countries. Thus the statistical weight of the primary data is very different for different geographical locations. However, sampling differences and some bias seem to be unavoidable at present, and the mortality figures obtained are the best available. Compared with the 2004 estimate of deaths associated with rotavirus disease of 527 000 children worldwide,3 the 2008 data of 453 000 represents a decrease of 14%; during the same period the total number of deaths from all-cause diarrhoea in children younger than 5 years has decreased by 33%, from 1·8 million to 1·2 million. Tate and colleagues believe that this discrepancy is probably due to a higher rotavirus detection rate (37% vs 29%) underlying the more recent data. They rightly conclude that “the greater rotavirus detection rate partly offsets the decline in overall diarrhoea-related mortality”. www.thelancet.com/infection Vol 12 February 2012
The introduction of URVV programmes in various countries since 2006 (Australia, Belgium, Brazil, El Salvador, Finland, Mexico, Panama, USA, and others) has resulted in substantial reductions in admission to hospital for rotavirus-associated acute gastroenteritis5 and also to the flattening (and delay) of seasonal epidemiological curves.6,7 The licensed rotavirus vaccines were shown to be less effective in countries of subSaharan Africa and southeast Asia.8,9 However, since vaccine efficacy estimates correlate inversely with disease incidence and child mortality strata, the Strategic Advisory Group of Experts of WHO have recommended the use of rotavirus vaccination worldwide in national immunisation programmes.10 Whether URVV programmes lead to the emergence of rotavirus vaccine escape populations of co-circulating wildtype rotaviruses is at present undecided, also because of rapid, unpredictable changes in the maximum prevalence of particular wildtype rotavirus genotypes.11 Thus, the increased prevalence of G2P[4] rotaviruses in Brazil during a URVV campaign with the G1P[8] vaccine, at an efficacy of 77% against G2P[4] strains,12 could not be unambiguously attributed to URVV since the same genotype emerged simultaneously in neighbouring countries in the absence of URVV,13 and there are similar inconclusive findings of this kind in other countries. It is probable that URVV programmes will result in a decrease in deaths associated with rotavirus disease, and the collated data are eagerly awaited. Ulrich Desselberger Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK [email protected] I declare that I have no conflicts of interest. 1
2 3
4 5
6
Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2011; published online Oct 25. DOI:10.1016/S1473-3099(11)70253-5. Black RE, Cousens S, Johnson HL, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010; 375: 1969–87. Parashar UD, Burton A, Lanata C, et al. Global mortality associated with rotavirus disease among children in 2004. J Infect Dis 2009; 200 (suppl 1): S9–15. Velázquez FR, Matson DO, Calva JJ, et al. Rotavirus infections in infants as protection against subsequent infections. N Engl J Med 1996; 335: 1022–28. Giaquinto C, Dominiak-Felden G, Van Damme P, et al. Summary of effectiveness and impact of rotavirus vaccination with the oral pentavalent rotavirus vaccine: a systematic review of the experience in industrialized countries. Hum Vaccin 2011; 7: 734–48. Centers for Disease Control and Prevention. Reduction in rotavirus after vaccine introduction—United States, 2000–2009. MMWR Morb Mortal Wkly Rep 2009; 58: 1146–49.
95
Comment
7
8
9 10
Tate JE, Mutuc JD, Panozzo CA, et al. Sustained decline in rotavirus detections in the United States following the introduction of rotavirus vaccine in 2006. Pediatr Infect Dis J 2011; 30 (1 suppl): S30–34. Esposito DH, Tate JE, Kang G, Parashar UD. Projected impact and cost-effectiveness of a rotavirus vaccination program in India, 2008. Clin Infect Dis 2011; 52: 171–77. Madhi SA, Cunliffe NA, Steele D, et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med 2010; 362: 289–98. WHO. Meeting of the immunization Strategic Advisory Group of Experts, April 2009—conclusions and recommendations. Wkly Epidemiol Rec 2009; 84: 220–36.
11
12
13
Iturriza-Gómara M, Dallman T, Bányai K, et al. Rotavirus genotypes co-circulating in Europe between 2006 and 2009 as determined by EuroRotaNet, a pan-European collaborative strain surveillance network. Epidemiol Infect 2011; 139: 895–909. Correia JB, Patel MM, Nakagomi O, et al. Effectiveness of monovalent rotavirus vaccine (Rotarix) against severe diarrhea caused by serotypically unrelated G2P[4] strains in Brazil. J Infect Dis 2010; 201: 363–69. Matthijnssens J, Bilcke J, Ciarlet M, et al. Rotavirus disease and vaccination: impact on genotype diversity. Future Microbiol 2009; 4: 1303–16.
Why doesn’t hand hygiene work better? The field of infection control is devoted to reducing the spread of pathogens. Over the years, this endeavour has developed along two distinct lines. In resource-limited communities, as shown by Curtis and colleagues1 in their recent Review, simple hygienic measures can have a remarkable effect on decreasing transmission, although their implementation may be inconsistent. By contrast, modern high-tech hospitals, which occupy the opposite end of the resource spectrum, are ceaselessly haunted by a different set of transmissible pathogens, those that cause health-care-associated infection (HAI). For most problems in health care, those with and without suitable resources use drastically different countermeasures to remedy a problem. However, for this predicament, the core solution is the same, be it for the fancy tertiary care centre or a slum in Kyrgyzstan: hand washing. This odd coincidence might help to explain an unexpected finding that recently has become evident— hand hygiene is not particularly effective in the modern hospital setting.2 After the introduction of alcoholbased hand rub in the past decade, infection control programmes have tried to improve hand hygiene rates. With a large concerted effort we have achieved exactly what we asked for: improved hand hygiene rates. What we have not achieved is a decrease in infection rates, at least not from hand hygiene alone.3 The work reviewed by Curtis and colleagues1 suggests why the initiative has failed. They show the effect of hand hygiene on, for example, community spread of diarrhoea—a simple measure and one long ago shown to work in urban hospitals.4 Indeed, all discussion of clean hands begins with the travails of Ignaz Semmelweis.4 Semmelweis famously reported that pregnant women delivered by training doctors had a mortality rate three to four times higher than those who were delivered 96
by midwives in the Lying-In Hospital in Vienna. Once Semmelweis convinced the doctors to use chlorina liquida (later changed to the cheaper chlorinated lime) between undertaking cadaver exams and pelvic exams, mortality dropped sharply and permanently. This product replaced the simple soap and water used for many years. Semmelweis’ stirring struggle and monumental triumph, his tragic personal fate, and the arrogant stubbornness of the medical establishment who thwarted him provide a poignant narrative.4 But perhaps doctors love the story a bit too much and so have accepted its teachings wholesale. In doing so we have forgotten the study’s context: Semmelweis worked in an environment much more like that described by Curtis and colleagues1 than the gleaming health palaces of the 21st century. For example, at the Lying-In Hospital of Vienna in the 1840s, electricity wasn’t available, plumbing existed but easy access to hot water did not, and women were crowded into large wards when they gave birth. Clinicians have long assumed that hand hygiene could and would have the same effect now as it had back in the 19th century—if only we could coerce our colleagues to just lather up. But now even though their hands are substantially cleaner, the benefit of the enterprise is uncertain. Granted, recent reports from the USA have shown heartening reductions in nosocomial problems such as meticillin-resistant Staphylococcus aureus (MRSA)5 and central line-associated bloodstream infection (CLABSI) in the intensive care unit,3 even as a relative newcomer to the axis of pathogens, Clostridium difficile-associated diarrhea, has continued its upward march.6 However, the specific contribution of improved hand hygiene in these successes is uncertain at best.7 For both MRSA and CLABSI, multipronged approaches from bundles to screening to worrying more and harder to financial (dis)incentives seem operative, not pristine www.thelancet.com/infection Vol 12 February 2012