Maternal immunization: An intelligent solution to reduce the hidden burden of group B streptococcus perinatal disease

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 past decade, dropping by >20% from the estimated 9.6 million deaths in 2000 to circa 7.6 million deaths in 2010 [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 SubSaharan 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; 40.3% in 2010) and must be further reduced to achieve Millennium Development Goal 4 for child survival [2]. Additionally, stillbirths (delivery or expulsion of a foetus >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 counted 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 lowand 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 27% of the estimated 3.1 million annual deaths occurring in newborns (826 000 deaths annually [1]), and up to half of all stillbirths [3, 4]. The gram-positive bacterium group B streptococcus (GBS; Streptococcus agalactiae) stands out among 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 live births (95% confidence interval 0.44–0.62), with an associated case fatality rate of 9.6% [5], and a wide heterogeneity of burden from country to country. Despite 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]. GBS disease has traditionally been categorized according to the time of onset of symptoms [7]. Earlyonset GBS disease (EOGBS), which can be extremely aggressive, is a vertically transmitted infection, and usually occurs in the first 6 days of life (typically during the first hours after delivery), presenting as sepsis (80–95%), pneumonia (10–15%) or meningitis (5–10%), or more rarely joint and bone involvement [8, 9]. Late-onset GBS disease (LOGBS) can occur anytime between the end of the first week and 3 months of life, has a more insidious presentation, often includes meningitis and is usually communityacquired, although it can also be transmitted from the mother through breastfeeding [10]. Recent estimates suggest that the incidence and associated case fatality rate of EOGBS would double that of LOGBS [5], but the latter is associated with a high incidence of long-term neurological sequelae [8]. Vertical transmission of GBS to the foetus from a colonized mother primarily occurs after the onset of labour or rupture of the membranes [11]. 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 [12], with 50% of the children born of colonized mothers becoming also colonized, and 1% developing symptomatology [13]. A systematic review assessing different studies in Europe showed that GBS vaginal colonization rates ranged from 6.5 to 36%, with one-third of studies reporting rates of 20% [14], and it is generally agreed that 20–30% of all pregnant women are colonized globally [13]. Colonization rates in developing countries have been much less studied, but some data from Africa have suggested that the prevalence of maternal carriage of GBS there is similar to that reported in the USA or Europe, where GBS remains the leading infectious cause of morbidity and mortality among newborns [15]. In this continent, studies from Malawi [16, 17], Kenya, Zimbabwe, Mozambique and South Africa [15, 18] indisputably confirm that GBS remains a significant—although highly underestimated—cause of neonatal sepsis and meningitis [19]. 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. In the 1980s, the effectiveness of JOURNAL OF TROPICAL PEDIATRICS, VOL. 59, NO. 5, 2013