- Email: [email protected]
Group B streptococcal vaccine for resource-poor countries
Comment
Group B streptococcal vaccine for resource-poor countries
www.thelancet.com Vol 378 July 2, 2011
practical or safe in community settings. Intrapartum vaginal and newborn chlorhexidine washes have not prevented sepsis in independent trials in South Africa and Pakistan,7,8 leaving resource-poor countries with no feasible alternative to vaccination. There are nine recognised serotypes of group B streptococcus: a 4-valent vaccine (types Ia, Ib, III, V) would cover an estimated 85% of cases on the basis of distributions of invasive disease serotypes in industrialised countries and South Africa.2,4 Group B streptococcal conjugate vaccine formulations for group B streptococcus have undergone phase 1 and 2 trials, including one small trial of maternal vaccination in the USA that showed safety and sustained functional antibody responses in mothers and infants 2 months after delivery.9 A phase 2 trial with a serotype III conjugate showed moderate protection against acquisition of serotype III group B streptococcus in the vagina and rectum.10 Casecontrol studies of natural infection have shown immune correlates of protection—crucial surrogates for evaluating vaccine candidates.11 A set of quantitated human-serum pools that are serotype specific are available for further standardisation and refinement of such correlates. There are important gaps in our understanding of the disease burden of group B streptococcus and of the investment case for vaccine development. As pneumococcal and rotavirus vaccine initiatives have shown, rigorous surveillance will be crucial to establishing the global disease burden and the value of vaccine development. To date, studies have
Published Online March 7, 2011 DOI:10.1016/S01406736(10)61932-0
Shehzad Noorani/Still Pictures
Neonatal deaths, which occur mostly in resource-poor countries during the first week of life, constitute 41% of the 8·8 million deaths in children aged less than 5 years worldwide.1 Sepsis and pneumonia cause about a third of neonatal deaths. Maternal immunisation— the prevention cornerstone of neonatal tetanus and influenza programmes—has untapped potential to protect neonates from other infectious diseases. Group B streptococcal vaccines are uniquely suited to maternal immunisation in view of the substantial perinatal morbidity and mortality, particularly in the first 48 h of life. Group B streptococcus emerged in industrialised countries as a leading neonatal pathogen in the 1970s. Transmission is mostly from mother to newborn during the intrapartum period. Sepsis, pneumonia, and meningitis in the first week of life (early-onset) are the most common diseases caused by group B streptococcus. Medical advances have reduced case fatality from 20–50% to 5%;2 however, infants who survive often have long-term neurological sequelae. Although data for neonatal infection from resource-poor countries are sparse, the burden is clear in sub-Saharan Africa, where neonates have the highest risk of dying. Compelling surveillance in southern Africa documents high rates of invasive disease (>2 cases per 1000 livebirths) and death (14–38% of cases).3,4 Data for rural Kenya identify group B streptococcus as a leading neonatal pathogen.5 Maternal and neonatal colonisation rates for more than nine African countries are similar to those in countries with a documented disease burden that is substantial. Intravenous intrapartum antibiotic prophylaxis can prevent early-onset disease from group B streptococcus. Countries that implement this prophylaxis for women colonised with group B streptococcus have experienced substantial declines in early-onset disease.6 However, use of intrapartum antibiotic prophylaxis in 30% of deliveries, as in the USA, is challenging to implement, needs adequate time before delivery for effectiveness, and does not prevent disease after the first week of life. The strategy is also threatened by the emergence of group B streptococcus that is resistant to β-lactam and macrolide antibiotics. For resource-poor countries, prenatal screening and intrapartum antibiotic prophylaxis might not be
11
Comment
systematically underestimated the importance of group B streptococcus because of failure to collect blood cultures on the day of birth (when 80% of earlyonset disease occurs) and surveillance that captures infants only at health facilities. New aetiology studies are likely to fill these gaps, including a multisite study, which launched in January 2011, of serious infections among young infants in the community in southeast Asia. Although we could wait for a more complete evidence base, we believe that now is the time to launch a vaccine development programme for group B streptococcus that targets low-resource countries. The Meningitis Vaccine Project, which spearheaded development of the meningococcal serogroup A conjugate vaccine introduced last year in the African meningitis belt, shows that an orphan vaccine programme can succeed without a strong, industrialised country lobby.12,13 Phase 1 and 2 conjugate group B streptococcal vaccine trials have launched, sponsored by drug companies, including a planned trial for South Africa that includes pregnant women. The European Union is engaged in characterising protective levels of group-B-streptococcus capsular polysaccharide-specific IgG antibody.14 Manufacturers in the developing world are producing low-cost meningococcal conjugate and Haemophilus influenzae type-b vaccines. The successful introductions of hepatitis B and H influenzae type-b vaccines that are supported by the GAVI Alliance, and commitments to pneumococcal and rotavirus vaccines, show that new vaccines can be introduced in an accelerated way in countries that need them most. Accelerated development of vaccines against group B streptococcus, before the global disease burden and cost-effectiveness are firmly established, incurs some risk. However, we believe inaction at this stage incurs even more risk in terms of newborn lives lost.
I declare that I have no conflicts of interest. The other members of the Global Group B Streptococcal Vaccine Working Group are: Carol J Baker (Baylor College of Medicine, Houston, TX, USA), Bernard W Beall (CDC, Atlanta, GA, USA), John W Boslego (PATH, Washington, DC, USA) George M Carlone (CDC, Atlanta, GA, USA), Keith P Klugman (Emory University, Atlanta, GA, USA), Shabir A Madhi (University of the Witwatersrand, Johannesburg, South Africa), Lesley McGee (CDC, Atlanta, GA, USA), Nancy E Messonnier (CDC, Atlanta, GA, USA), Kathleen M Neuzil (PATH, Washington, DC, USA), Anne Schuchat (CDC, Atlanta, GA, USA), Sandra Romero-Steiner (CDC, Atlanta, GA, USA), Jennifer R Verani (CDC, Atlanta, GA, USA), Cynthia G Whitney (CDC, Atlanta, GA, USA), Anita K Zaidi (Aga Khan University, Karachi, Pakistan). The CDC and Flow Applications have a 2001 patent for opsonophagocytic assays. Our views do not necessarily reflect those of the CDC. 1
2
3
4
5 6
7
8
9
10
11
12 13
14
Stephanie J Schrag, for the Global Group B Streptococcal Vaccine Working Group
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. Phares CR, Lynfield R, Farley MM, et al, for the Active Bacterial Core Surveillance/Emerging Infections Program Network. Epidemiology of invasive group B streptococcal disease in the United States, 1999–2005. JAMA 2008; 299: 2056–65. Gray KJ, Bennett SL, French N, Phiri AJ, Graham SM. Invasive group B streptococcal infection in infants, Malawi. Emerg Infect Dis 2007; 13: 223–29. Madhi SA, Radebe K, Crewe-Brown H, et al. High burden of invasive Streptococcus agalactiae disease in South African infants. Ann Trop Paediatr 2003; 23: 15–23. Berkley JA, Lowe BS, Mwangi I, et al. Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 2005; 352: 39–47. Moore MR, Schrag SJ, Schuchat A. Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. Lancet Infect Dis 2003; 3: 201–13. Cutland CL, Madhi SA, Zell ER, et al. Chlorhexidine maternal-vaginal and neonate body wipes in sepsis and vertical transmission of pathogenic bacteria in South Africa: a randomised, controlled trial. Lancet 2009; 374: 1909–16. Saleem S, Rouse DJ, McClure EM, et al. Chlorhexidine vaginal and infant wipes to reduce perinatal mortality and morbidity: a randomized controlled trial. Obstet Gynecol 2010; 115: 1225–32. Baker CJ, Rench MA, McInnes P. Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine. Vaccine 2003; 21: 3468–72. Hillier S, Ferris D, Fine D, et al. Women receiving group B streptococcus serotype III tetanus toxoid (GBS III-TT) vaccine have reduced vaginal and rectal acquisition of GBS type III. Infectious Diseases Society of America Annual Meeting; Philadelphia, USA; Oct 29–Nov 1, 2009: 186 (abstr). Lin FY, Weisman LE, Azimi PH, et al. Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen. J Infect Dis 2004; 190: 928–34. LaForce FM, Konde K, Viviani S, Préziosi MP. The Meningitis Vaccine Project. Vaccine 2007; 25 (suppl): A97–100. Lee CH, Kuo WC, Beri S, et al. Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa. Vaccine 2009; 27: 726–32. DEVANI. Vaccine against neonatal infections: design of a vaccine to immunize neonates against GBS infections through a durable maternal immune response. Oct 5, 2010. http://www.devaniproject.org (accessed Nov 1, 2010).
Division of Bacterial Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA [email protected]
12
www.thelancet.com Vol 378 July 2, 2011
Group B streptococcal vaccine for resource-poor countries
www.thelancet.com Vol 378 July 2, 2011
practical or safe in community settings. Intrapartum vaginal and newborn chlorhexidine washes have not prevented sepsis in independent trials in South Africa and Pakistan,7,8 leaving resource-poor countries with no feasible alternative to vaccination. There are nine recognised serotypes of group B streptococcus: a 4-valent vaccine (types Ia, Ib, III, V) would cover an estimated 85% of cases on the basis of distributions of invasive disease serotypes in industrialised countries and South Africa.2,4 Group B streptococcal conjugate vaccine formulations for group B streptococcus have undergone phase 1 and 2 trials, including one small trial of maternal vaccination in the USA that showed safety and sustained functional antibody responses in mothers and infants 2 months after delivery.9 A phase 2 trial with a serotype III conjugate showed moderate protection against acquisition of serotype III group B streptococcus in the vagina and rectum.10 Casecontrol studies of natural infection have shown immune correlates of protection—crucial surrogates for evaluating vaccine candidates.11 A set of quantitated human-serum pools that are serotype specific are available for further standardisation and refinement of such correlates. There are important gaps in our understanding of the disease burden of group B streptococcus and of the investment case for vaccine development. As pneumococcal and rotavirus vaccine initiatives have shown, rigorous surveillance will be crucial to establishing the global disease burden and the value of vaccine development. To date, studies have
Published Online March 7, 2011 DOI:10.1016/S01406736(10)61932-0
Shehzad Noorani/Still Pictures
Neonatal deaths, which occur mostly in resource-poor countries during the first week of life, constitute 41% of the 8·8 million deaths in children aged less than 5 years worldwide.1 Sepsis and pneumonia cause about a third of neonatal deaths. Maternal immunisation— the prevention cornerstone of neonatal tetanus and influenza programmes—has untapped potential to protect neonates from other infectious diseases. Group B streptococcal vaccines are uniquely suited to maternal immunisation in view of the substantial perinatal morbidity and mortality, particularly in the first 48 h of life. Group B streptococcus emerged in industrialised countries as a leading neonatal pathogen in the 1970s. Transmission is mostly from mother to newborn during the intrapartum period. Sepsis, pneumonia, and meningitis in the first week of life (early-onset) are the most common diseases caused by group B streptococcus. Medical advances have reduced case fatality from 20–50% to 5%;2 however, infants who survive often have long-term neurological sequelae. Although data for neonatal infection from resource-poor countries are sparse, the burden is clear in sub-Saharan Africa, where neonates have the highest risk of dying. Compelling surveillance in southern Africa documents high rates of invasive disease (>2 cases per 1000 livebirths) and death (14–38% of cases).3,4 Data for rural Kenya identify group B streptococcus as a leading neonatal pathogen.5 Maternal and neonatal colonisation rates for more than nine African countries are similar to those in countries with a documented disease burden that is substantial. Intravenous intrapartum antibiotic prophylaxis can prevent early-onset disease from group B streptococcus. Countries that implement this prophylaxis for women colonised with group B streptococcus have experienced substantial declines in early-onset disease.6 However, use of intrapartum antibiotic prophylaxis in 30% of deliveries, as in the USA, is challenging to implement, needs adequate time before delivery for effectiveness, and does not prevent disease after the first week of life. The strategy is also threatened by the emergence of group B streptococcus that is resistant to β-lactam and macrolide antibiotics. For resource-poor countries, prenatal screening and intrapartum antibiotic prophylaxis might not be
11
Comment
systematically underestimated the importance of group B streptococcus because of failure to collect blood cultures on the day of birth (when 80% of earlyonset disease occurs) and surveillance that captures infants only at health facilities. New aetiology studies are likely to fill these gaps, including a multisite study, which launched in January 2011, of serious infections among young infants in the community in southeast Asia. Although we could wait for a more complete evidence base, we believe that now is the time to launch a vaccine development programme for group B streptococcus that targets low-resource countries. The Meningitis Vaccine Project, which spearheaded development of the meningococcal serogroup A conjugate vaccine introduced last year in the African meningitis belt, shows that an orphan vaccine programme can succeed without a strong, industrialised country lobby.12,13 Phase 1 and 2 conjugate group B streptococcal vaccine trials have launched, sponsored by drug companies, including a planned trial for South Africa that includes pregnant women. The European Union is engaged in characterising protective levels of group-B-streptococcus capsular polysaccharide-specific IgG antibody.14 Manufacturers in the developing world are producing low-cost meningococcal conjugate and Haemophilus influenzae type-b vaccines. The successful introductions of hepatitis B and H influenzae type-b vaccines that are supported by the GAVI Alliance, and commitments to pneumococcal and rotavirus vaccines, show that new vaccines can be introduced in an accelerated way in countries that need them most. Accelerated development of vaccines against group B streptococcus, before the global disease burden and cost-effectiveness are firmly established, incurs some risk. However, we believe inaction at this stage incurs even more risk in terms of newborn lives lost.
I declare that I have no conflicts of interest. The other members of the Global Group B Streptococcal Vaccine Working Group are: Carol J Baker (Baylor College of Medicine, Houston, TX, USA), Bernard W Beall (CDC, Atlanta, GA, USA), John W Boslego (PATH, Washington, DC, USA) George M Carlone (CDC, Atlanta, GA, USA), Keith P Klugman (Emory University, Atlanta, GA, USA), Shabir A Madhi (University of the Witwatersrand, Johannesburg, South Africa), Lesley McGee (CDC, Atlanta, GA, USA), Nancy E Messonnier (CDC, Atlanta, GA, USA), Kathleen M Neuzil (PATH, Washington, DC, USA), Anne Schuchat (CDC, Atlanta, GA, USA), Sandra Romero-Steiner (CDC, Atlanta, GA, USA), Jennifer R Verani (CDC, Atlanta, GA, USA), Cynthia G Whitney (CDC, Atlanta, GA, USA), Anita K Zaidi (Aga Khan University, Karachi, Pakistan). The CDC and Flow Applications have a 2001 patent for opsonophagocytic assays. Our views do not necessarily reflect those of the CDC. 1
2
3
4
5 6
7
8
9
10
11
12 13
14
Stephanie J Schrag, for the Global Group B Streptococcal Vaccine Working Group
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. Phares CR, Lynfield R, Farley MM, et al, for the Active Bacterial Core Surveillance/Emerging Infections Program Network. Epidemiology of invasive group B streptococcal disease in the United States, 1999–2005. JAMA 2008; 299: 2056–65. Gray KJ, Bennett SL, French N, Phiri AJ, Graham SM. Invasive group B streptococcal infection in infants, Malawi. Emerg Infect Dis 2007; 13: 223–29. Madhi SA, Radebe K, Crewe-Brown H, et al. High burden of invasive Streptococcus agalactiae disease in South African infants. Ann Trop Paediatr 2003; 23: 15–23. Berkley JA, Lowe BS, Mwangi I, et al. Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 2005; 352: 39–47. Moore MR, Schrag SJ, Schuchat A. Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. Lancet Infect Dis 2003; 3: 201–13. Cutland CL, Madhi SA, Zell ER, et al. Chlorhexidine maternal-vaginal and neonate body wipes in sepsis and vertical transmission of pathogenic bacteria in South Africa: a randomised, controlled trial. Lancet 2009; 374: 1909–16. Saleem S, Rouse DJ, McClure EM, et al. Chlorhexidine vaginal and infant wipes to reduce perinatal mortality and morbidity: a randomized controlled trial. Obstet Gynecol 2010; 115: 1225–32. Baker CJ, Rench MA, McInnes P. Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine. Vaccine 2003; 21: 3468–72. Hillier S, Ferris D, Fine D, et al. Women receiving group B streptococcus serotype III tetanus toxoid (GBS III-TT) vaccine have reduced vaginal and rectal acquisition of GBS type III. Infectious Diseases Society of America Annual Meeting; Philadelphia, USA; Oct 29–Nov 1, 2009: 186 (abstr). Lin FY, Weisman LE, Azimi PH, et al. Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen. J Infect Dis 2004; 190: 928–34. LaForce FM, Konde K, Viviani S, Préziosi MP. The Meningitis Vaccine Project. Vaccine 2007; 25 (suppl): A97–100. Lee CH, Kuo WC, Beri S, et al. Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa. Vaccine 2009; 27: 726–32. DEVANI. Vaccine against neonatal infections: design of a vaccine to immunize neonates against GBS infections through a durable maternal immune response. Oct 5, 2010. http://www.devaniproject.org (accessed Nov 1, 2010).
Division of Bacterial Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA [email protected]
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www.thelancet.com Vol 378 July 2, 2011