Case study: Prevention of vertical transmission of bacterial neonatal sepsis: The example of Group B streptococcus Instructor(s): Quique Bassat Description As a consequence of the significant injection of funds and drive provided by the establishment of the Millennium Development Goals back in the year 2000, child mortality has substantially decreased in the last decade, dropping by over a third from the 9.6 estimated million deaths in 2000 to circa 6.3 million deaths in 2013[1]. This decreasing tendency has been confirmed in all areas of the world, with the greatest advances in Northern Africa, Eastern and Western Asia and Latin America, although reduction of child mortality has been rather modest in Sub-Saharan Africa. Neonatal deaths (those occurring in the first 28 days of life after having been born alive) have also decreased but at a much slower rate, and thus account for an increasing proportion of child mortality (38.2% in 2000; 44% in 2013) and must be further reduced to achieve Millennium Development Goal (MDG) 4 for child survival[2]. Additionally, stillbirths (delivery or expulsion of a foetus older than 22 weeks of gestation but with no signs of life) also represent a large and disproportionate burden (2.6 million cases annually) but are seldom accounted for in the official child mortality statistics[3]. The geographic distribution of both stillbirths and neonatal deaths shows major inequities, with 99% of those occurring in low and middle-income countries[4]. Undeniably, surviving throughout pregnancy, birth and up until the first 28 days of life in many poor settings has become one of the major challenges occurring in life. Infectious diseases account for at least 23% of the estimated 2.76 million annual deaths occurring in newborns (626,000 deaths annually[1]), and up to half of all stillbirths[3, 4]. The gram-positive bacterium Group B streptococcus (GBS; Streptococcus agalactiae) stands out amongst the major microorganisms responsible for perinatal infections on account of its large burden and associated virulence. Estimates from 2012 describe a global incidence of GBS disease in newborns as high as 0.53 episodes/1000 livebirths (95%CI 0.44-0.62), with an associated case fatality rate (CFR) of 9.6%[5], and a wide heterogeneity of burden from country to country. In spite of the dearth of reliable microbiologically-confirmed studies on the incidence and clinical characterization of GBS disease performed in low-income countries, the scarce available data suggest that the incidence and associated mortality is as of today much higher in Africa than for the rest of the world[5, 6]. Vertical transmission of GBS to the foetus from a colonized mother primarily occurs after the onset of labour or rupture of the membranes[7]. Thus, the prevalence of maternal gastro-intestinal and/or genital-tract carriage during the period closely related to the delivery has been shown to determine the risk of vertical transmission and subsequent early-onset neonatal infection[8], with approximately 50% of the children born of colonized mothers becoming also colonized, and around 1% developing symptomatology[9]. It is generally agreed that 20-30% of all pregnant women are colonized globally[9].

In Western countries, the identification of maternal carriers has allowed the adoption of prophylactic antibiotic schemes that have played a major role in the reduction of the incidence of neonatal invasive infections. The Centers for Disease Control and Prevention (CDC) of the United States have recently reissued updated recommendations for the prevention of perinatal Group B Streptococcal disease[10]. These include the establishment of universal culture-based screening (using vaginal and/or recto-vaginal samples[11]) of all pregnant women at 35-37 weeks' gestation to optimize the identification of colonized women who should receive intrapartum antibiotic prophylaxis. The effectiveness of such prophylactic schemes has been estimated to be around 86-89% in terms of preventing vertical transmission[12]. Nevertheless, neither screening, nor prophylactic antibiotic schemes have been routinely adopted or implemented in the majority of health posts, maternities or hospitals in developing countries, or even in many middle-income ones. This highlights the unpreparedness of middle and low-income countries in terms of identifying GBS as a major public health problem, and the lack of strategies put in place to prevent its vertical transmission to the newborn in such settings. So what can we do to improve the situation in these settings? Learning objectives

1. To discuss the knowledge gaps faced by MoH at the national level in terms of the evaluation of GBS associated burden, morbidity and mortality

2. To discuss the practicalities and challenges of diagnosing and preventing GBS disease in the developing world and the necessary strategies that could be put in place

3. To discuss the need for a vaccine Readings

• Excerpts tables/algorithms from the CDC 2010 reviewed guidelines

Bibliography 1. Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE: Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 2015, 385(9966):430-440. 2. Lawn JE, Kerber K, Enweronu-Laryea C, Massee Bateman O: Newborn survival in low resource settings--are we delivering? BJOG 2009, 116 Suppl 1:49-59. 3. Lawn JE, Blencowe H, Pattinson R, Cousens S, Kumar R, Ibiebele I, Gardosi J, Day LT, Stanton C: Stillbirths: Where? When? Why? How to make the data count? Lancet 2011, 377(9775):1448-1463. 4. Goldenberg RL, McClure EM, Saleem S, Reddy UM: Infection-related stillbirths. Lancet 2010, 375(9724):1482-1490. 5. Edmond KM, Kortsalioudaki C, Scott S, Schrag SJ, Zaidi AK, Cousens S, Heath PT: Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 2012, 379(9815):547-556. 6. Dagnew AF, Cunnington MC, Dube Q, Edwards MS, French N, Heyderman RS, Madhi SA, Slobod K, Clemens SA: Variation in reported neonatal group B streptococcal disease incidence in developing countries. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2012, 55(1):91-102. 7. Subair O, Wagner P, Omojole F, Morgan H: Group B streptococcus disease in neonates: to screen or not to screen? J Obstet Gynaecol 2005, 25(5):462-464. 8. Chan GJ, Lee AC, Baqui AH, Tan J, Black RE: Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis. PLoS Med 2013, 10(8):e1001502. 9. Heath PT: An update on vaccination against group B streptococcus. Expert review of vaccines 2011, 10(5):685-694. 10. Centers for Disease control and Prevention: Prevention of perinatal Group B Streptococcal disease. Revised guidelines from CDC, 2010. In: Morbidity and mortality weekly report. Atlanta; 2010. 11. El Aila NA, Tency I, Claeys G, Saerens B, Cools P, Verstraelen H, Temmerman M, Verhelst R, Vaneechoutte M: Comparison of different sampling techniques and of different culture methods for detection of group B streptococcus carriage in pregnant women. BMC infectious diseases 2010, 10:285. 12. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, Harrison LH, Reingold A, Stefonek K, Smith G et al: A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002, 347(4):233-239.