Serotype distribution and invasive potential of group B streptococcus isolates causing disease in infants and colonizing maternal-newborn dyads

Background

Serotype-specific polysaccharide based group B streptococcus (GBS) vaccines are being developed. An understanding of the serotype epidemiology associated with maternal colonization and invasive disease in infants is necessary to determine the potential coverage of serotype-specific GBS vaccines.

Methods

Colonizing GBS isolates were identified by vaginal swabbing of mothers during active labor and from skin of their newborns post-delivery. Invasive GBS isolates from infants were identified through laboratory-based surveillance. GBS serotyping was done by latex agglutination. Serologically non-typeable isolates were typed by a serotype-specific PCR method. The invasive potential of GBS serotypes associated with sepsis within seven days of birth was evaluated in association to maternal colonizing serotypes.

Results

GBS was identified in 289 (52.4%) newborns born to 551 women with GBS-vaginal colonization and from 113 (5.6%) newborns born to 2,010 mothers in whom GBS was not cultured from vaginal swabs. The serotype distribution among vaginal-colonizing isolates was as follows: III (37.3%), Ia (30.1%), and II (11.3%), V (10.2%), Ib (6.7%) and IV (3.7%). There were no significant differences in serotype distribution between vaginal and newborn colonizing isolates (P = 0.77). Serotype distribution of invasive GBS isolates were significantly different to that of colonizing isolates (P<0.0001). Serotype III was the most common invasive serotype in newborns less than 7 days (57.7%) and in infants 7 to 90 days of age (84.3%; P<0.001). Relative to serotype III, other serotypes showed reduced invasive potential: Ia (0.49; 95%CI 0.31–0.77), II (0.30; 95%CI 0.13–0.67) and V (0.38; 95%CI 0.17–0.83).

Conclusion

In South Africa, an anti-GBS vaccine including serotypes Ia, Ib and III has the potential of preventing 74.1%, 85.4% and 98.2% of GBS associated with maternal vaginal-colonization, invasive disease in neonates less than 7 days and invasive disease in infants between 7–90 days of age, respectively.     

Invasive Group B Streptococcal Disease in South Africa: Importance of Surveillance Methodology

Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7–89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06–1.43] vs. 1.50 [95%CI 1.30–1.71], respectively, rate ratio 0.82 [95%CI 0.67–1.01]; LOD 1.04 [95% CI 0.90–1.23] vs. 1.22 [95%CI 1.05–1.42], rate ratio 0.85 [95% CI 0.68–1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a probe to better quantify the burden of invasive GBS disease in low-middle resourced settings such as ours. From our study passive systems are important to monitor trends over time as long as they are interpreted with caution; active systems give better detailed information and will have greater representivity when expanded to other surveillance sites.     

Burden of Invasive Group B Streptococcus Disease and Early Neurological Sequelae in South African Infants

Introduction

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0–6 days of life, EOD) and late-onset (7–89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women.

Methods

A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age.

Results

We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24–9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94–386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44–49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17–10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44–120.95) greater in cases (13.2%) than controls (0.4%).

Discussion

The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting.     

Prevalence and significance of vaginal group B streptococcus colonization in pregnant women from Osijek, Croatia

The aim of the study was to determine the prevalence of vaginal group B streptococcus (GBS) colonization in pregnant women from Osijek area, the possible effect of GBS colonization on pregnancy outcome and neonatal complications and the role of intrapartum prophylaxis in this context. This retrospective case-control study took place at the Department of Gynecology and Obstetrics, Osijek University Hospital Center from December 2003 to June 2006. A total of 118 pregnant women was enrolled in study and divided into two groups: 59 women in 35th-37th week of gestation, free from risk factors for infection (control group); and 59 women in 25th-41st week of gestation with risk factors for infection. Low vaginal swab for GBS isolation and identification on selective and enriched medium was obtained from each woman. GBS colonization was recorded in 29 (24.6%) women: 12 (20.3%) control and 17 (28.8%) women at risk of infection, yielding a statistically non-significant difference (Chi2 = 1.480489; p < 0.48). Early neonatal infection was observed in six (20.7%) neonates born to 29 mothers with GBS colonization, pointing to a correlation between vaginal GBS colonization and early neonatal infection (r(s) = 0.99). Early perinatal infection was found in 22 (18.6%) neonates, including 17 (28.8%) pregnancies with risk factors, pointing to a significant correlation between vaginal GBS colonization, risk factors and early perinatal infection (Chi2 = 88.68; p < 0.001); however, gestational age and pregnancy outcome were not influenced by GBS colonization. In eight (36.4%) newborns, early neonatal infection developed in spite of intrapartum administration of antibiotics; three of these children were born to GBS positive mothers, and perinatal GBS infection was demonstrated in one (0.84%) child. Study results revealed a relatively high rate of GBS colonization in the population of pregnant women in Croatia, occasionally leading to early neonatal infection. Large studies are needed to develop national strategy for the prevention of GBS infection in Croatia.     

Global Estimates of Prevalent and Incident Herpes Simplex Virus Type 2 Infections in 2012

Background

Herpes simplex virus type 2 (HSV-2) infection causes significant disease globally. Adolescent and adult infection may present as painful genital ulcers. Neonatal infection has high morbidity and mortality. Additionally, HSV-2 likely contributes substantially to the spread of HIV infection. The global burden of HSV-2 infection was last estimated for 2003. Here we present new global estimates for 2012 of the burden of prevalent (existing) and incident (new) HSV-2 infection among females and males aged 15–49 years, using updated methodology to adjust for test performance and estimate by World Health Organization (WHO) region.

Methods and Findings

We conducted a literature review of HSV-2 prevalence studies world-wide since 2000. We then fitted a model with constant HSV-2 incidence by age to pooled HSV-2 prevalence values by age and sex. Prevalence values were adjusted for test sensitivity and specificity. The model estimated prevalence and incidence by sex for each WHO region to obtain global burden estimates. Uncertainty bounds were computed by refitting the model to reflect the variation in the underlying prevalence data. In 2012, we estimate that there were 417 million people aged 15–49 years (range: 274–678 million) living with HSV-2 infection world-wide (11.3% global prevalence), of whom 267 million were women. We also estimate that in 2012, 19.2 million (range: 13.0–28.6 million) individuals aged 15–49 years were newly-infected (0.5% of all individuals globally). The highest burden was in Africa. However, despite lower prevalence, South-East Asia and Western Pacific regions also contributed large numbers to the global totals because of large population sizes.

Conclusions

The global burden of HSV-2 infection is large, leaving over 400 million people at increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV-2 to partners or neonates. These estimates highlight the critical need for development of vaccines, microbicides, and other new HSV prevention strategies.     

Burden of Severe Pneumonia,Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates

The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results highlight the need to improve access to care and increase coverage and equity of pneumonia preventing vaccines in states with high pneumonia burden.     

Studies on the possible application of molecular methods in diagnosing carriers and in similarity analysis of group B streptococci (Streptococcus agalactiae)

The most popular method of GBS identification in Poland currently is by culturing on enriched agar and verifying the Lancefield Group using special latex agglutination kits. However, the classical methods are time-consuming and their sensitivity is insufficient therefore it is becoming more common to try and apply molecular methods which are characterized by high sensitivity and rapid results. Moreover, molecular methods give us the possibility to carry out epidemiological investigations and gene detection, for instance for antibiotic resistance. It was confirmed that PCR and FISH procedures may be effective in rapid detection of GBS. Thanks to RAPD methods we showed that newborns born to colonized mothers were colonized by GBS strains which originated from the mother, irrespective of the way and the course of labour. Additionally, we detected GBS colonization in children who were born to mothers who were not colonized by GBS. These children were probably colonized with strains coming from hospital environment. More studies are needed to elucidate the route of transmission and the role of colonization of the medical staff. Using multiplex PCR we showed the presence of ermA, ermB and ermC genes in phenotypically confirmed MLS, GBS strains.     

Toxocariasis in North America: A Systematic Review

Toxocariasis is an important neglected tropical disease that can manifest as visceral or ocular larva migrans, or covert toxocariasis. All three forms pose a public health problem and cause significant morbidity in areas of high prevalence. To determine the burden of toxocariasis in North America, we conducted a systematic review of the literature following PRISMA guidelines. We found 18 articles with original prevalence, incidence, or case data for toxocariasis. Prevalence estimates ranged from 0.6% in a Canadian Inuit community to 30.8% in Mexican children with asthma. Commonly cited risk factors included: African-American race, poverty, male sex, and pet ownership or environmental contamination by animal feces. Increased prevalence of Toxocara spp. infection was linked in a group of case control studies conducted in Mexico to several high risk groups including waste pickers, asthmatic children, and inpatient psychiatry patients. Further research is needed to determine the true current burden of toxocariasis in North America; however the prevalence estimates gathered in this review suggest that the burden of disease is significant.     

Estimates of Incidence and Prevalence of Mongolism and of Congenital Heart Disease in British Columbia

There is a need for accurate ascertainment of incidence and prevalence rates of congenital anomalies. In British Columbia the Registry for Handicapped Children and Adults used in conjunction with vital records has proved a valuable source of information. Birth notifications alone cannot be relied upon for incidence data. It was found that seven times as many cases of congenital heart disease were registered subsequently as were reported at birth. The estimated minimal incidence rates of mongolism and congenital heart disease per 1000 live births were 1.46 and 4.75, respectively. The well-known association of maternal age with mongolism was confirmed. Twice as many babies with congenital heart disease (without mongolism) were born to mothers over 39 years of age as would be expected on the basis of the maternal age distribution for all live births in the population. Prevalence estimates of these two diseases compared favourably with other published estimates.     

Serine-rich repeat proteins and pili promote Streptococcus agalactiae colonization of the vaginal tract

Streptococcus agalactiae (group B streptococcus [GBS]) is a Gram-positive bacterium found in the female rectovaginal tract and is capable of producing severe disease in susceptible hosts, including newborns and pregnant women. The vaginal tract is considered a major reservoir for GBS, and maternal vaginal colonization poses a significant risk to the newborn; however, little is known about the specific bacterial factors that promote GBS colonization and persistence in the female reproductive tract. We have developed in vitro models of GBS interaction with the human female cervicovaginal tract using human vaginal and cervical epithelial cell lines. Analysis of isogenic mutant GBS strains deficient in cell surface organelles such as pili and serine-rich repeat (Srr) proteins shows that these factors contribute to host cell attachment. As Srr proteins are heavily glycosylated, we confirmed that carbohydrate moieties contribute to the effective interaction of Srr-1 with vaginal epithelial cells. Antibody inhibition assays identified keratin 4 as a possible host receptor for Srr-1. Our findings were further substantiated in an in vivo mouse model of GBS vaginal colonization, where mice inoculated with an Srr-1-deficient mutant exhibited decreased GBS vaginal persistence compared to those inoculated with the wild-type (WT) parental strain. Furthermore, competition experiments in mice showed that WT GBS exhibited a significant survival advantage over the ΔpilA or Δsrr-1 mutant in the vaginal tract. Our results suggest that these GBS surface proteins contribute to vaginal colonization and may offer new insights into the mechanisms of vaginal niche establishment.     

The epidemiology of pneumococcal infection in children in the developing world.

Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio-economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing countries. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide-protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.     

B族链球菌感染妊娠妇女产时 抗生素治疗临床效果评价

目的探讨沈阳地区孕晚期妊娠妇女B族链球菌(group B Streptococcus,GBS)的定植率及其耐药性,评估GBS感染妊娠妇女分娩期给予产时抗生素预防(intrapartum antibiotic prophylaxis,IAP)的临床效果。方法选择2017年9月至2017年12月在沈阳市妇婴医院行GBS筛查的691例怀孕35～37周的妊娠妇女为研究对象,将GBS筛查阳性妊娠妇女中采用顺产方式分娩的38例妊娠妇女作为研究组,638例GBS筛查阴性妊娠妇女作为对照组。研究组妊娠妇女给予IAP,对照组妊娠妇女不作处理。分析两组妊娠妇女GBS定植情况、GBS菌株耐药情况及给予IAP后新生儿不良事件发生率。结果 691例妊娠妇女中有53例GBS培养阳性,GBS定植率为7.67%。全部GBS菌株对青霉素、头孢唑林及万古霉素的敏感率均为100.00%;对红霉素、克林霉素耐药率分别为81.48%和73.95%。研究组中新生儿黄疸发生率为7.89%,新生儿窒息发生率为2.63%,脑膜炎、肺炎、败血症的发生率均为0.00%。对照组中新生儿黄疸发生率为3.13%,新生儿窒息发生率为0.63%,肺炎发生率为0.16%,新生儿脑膜炎及败血症发生率均为0.00%。两组新生儿在新生儿黄疸、新生儿窒息、脑膜炎、肺炎和败血症发生率方面比较差异无统计学意义(均P0.05)。结论沈阳地区妊娠妇女GBS带菌率较高,青霉素可作为治疗的首选药物。预防性使用抗生素治疗可以改善新生儿结局。     

A General HIV Incidence Inference Scheme Based on Likelihood of Individual Level Data and a Population Renewal Equation

We derive a new method to estimate the age specific incidence of an infection with a differential mortality, using individual level infection status data from successive surveys. The method consists of a) an SI-type model to express the incidence rate in terms of the prevalence and its derivatives as well as the difference in mortality rate, and b) a maximum likelihood approach to estimate the prevalence and its derivatives. Estimates can in principle be obtained for any chosen age and time, and no particular assumptions are made about the epidemiological or demographic context. This is in contrast with earlier methods for estimating incidence from prevalence data, which work with aggregated data, and the aggregated effect of demographic and epidemiological rates over the time interval between prevalence surveys. Numerical simulation of HIV epidemics, under the presumption of known excess mortality due to infection, shows improved control of bias and variance, compared to previous methods. Our analysis motivates for a) effort to be applied to obtain accurate estimates of excess mortality rates as a function of age and time among HIV infected individuals and b) use of individual level rather than aggregated data in order to estimate HIV incidence rates at times between two prevalence surveys.     

High Dengue Case Capture Rate in Four Years of a Cohort Study in Nicaragua Compared to National Surveillance Data

Dengue is a major public health problem in tropical and subtropical regions; however, under-reporting of cases to national surveillance systems hinders accurate knowledge of disease burden and costs. Laboratory-confirmed dengue cases identified through the Nicaraguan Pediatric Dengue Cohort Study (PDCS) were compared to those reported from other health facilities in Managua to the National Epidemiologic Surveillance (NES) program of the Nicaraguan Ministry of Health. Compared to reporting among similar pediatric populations in Managua, the PDCS identified 14 to 28 (average 21.3) times more dengue cases each year per 100,000 persons than were reported to the NES. Applying these annual expansion factors to national-level data, we estimate that the incidence of confirmed pediatric dengue throughout Nicaragua ranged from 300 to 1000 cases per 100,000 persons. We have estimated a much higher incidence of dengue than reported by the Ministry of Health. A country-specific expansion factor for dengue that allows for a more accurate estimate of incidence may aid governments and other institutions calculating disease burden, costs, resource needs for prevention and treatment, and the economic benefits of drug and vaccine development.     

The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths

Background

Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.

Methods and Findings

The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.

Conclusions

Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.     

Joint use of epidemiological and hospital medico-administrative data to estimate prevalence. Application to French data on breast cancer

Background Estimate complete, limited-duration, and hospital prevalence of breast cancer in a French Département covered by a population-based cancer registry and in whole France using complementary information sources. Methods: Incidence data from a cancer registry, national incidence estimations for France, mortality data, and hospital medico-administrative data were used to estimate the three prevalence indices. The methods included a modelling of epidemiological data and a specific process of data extraction from medico-administrative databases. Results: Limited-duration prevalence at 33 years was a proxy for complete prevalence only in patients aged less than 70 years. In 2007 and in women older than 15 years, the limited-duration prevalence at 33 years rate per 100,000 women was estimated at 2372 for Département Isère and 2354 for whole France. The latter rate corresponded to 613,000 women. The highest rate corresponded to women aged 65–74 years (6161 per 100,000 in whole France). About one third of the 33-year limited-duration prevalence cases were diagnosed five years before and about one fourth were hospitalized for breast-cancer-related care (i.e., hospital prevalence). In 2007, the rate of hospitalized women was 557 per 100,000 in whole France. Among the 120,310 women hospitalized for breast-cancer-related care in 2007, about 13% were diagnosed before 2004. Conclusion: Limited-duration prevalence (long- and short-term), and hospital prevalence are complementary indices of cancer prevalence. Their efficient direct or indirect estimations are essential to reflect the burden of the disease and forecast median- and long-term medical, economic, and social patient needs, especially after the initial treatment.     

Systematic Evaluation of Serotypes Causing Invasive Pneumococcal Disease among Children Under Five: The Pneumococcal Global Serotype Project

Background

Approximately 800,000 children die each year due to pneumococcal disease and >90% of these deaths occur in developing countries where few children have access to life-saving serotype-based vaccines. Understanding the serotype epidemiology of invasive pneumococcal disease (IPD) among children is necessary for vaccine development and introduction policies. The aim of this study was to systematically estimate the global and regional distributions of serotypes causing IPD in children <5 years of age.

Methods and Findings

We systematically reviewed studies with IPD serotype data among children <5 years of age from the published literature and unpublished data provided by researchers. Studies conducted prior to pneumococcal conjugate vaccine (PCV) introduction, from 1980 to 2007, with ≥12 months of surveillance, and reporting ≥20 serotyped isolates were included. Serotype-specific proportions were pooled in a random effects meta-analysis and combined with PD incidence and mortality estimates to infer global and regional serotype-specific PD burden. Of 1,292, studies reviewed, 169 were included comprising 60,090 isolates from 70 countries. Globally and regionally, six to 11 serotypes accounted for ≥70% of IPD. Seven serotypes (1, 5, 6A, 6B, 14, 19F, 23F) were the most common globally; and based on year 2000 incidence and mortality estimates these seven serotypes accounted for >300,000 deaths in Africa and 200,000 deaths in Asia. Serotypes included in both the 10- and 13-valent PCVs accounted for 10 million cases and 600,000 deaths worldwide.

Conclusions

A limited number of serotypes cause most IPD worldwide. The serotypes included in existing PCV formulations account for 49%–88% of deaths in Africa and Asia where PD morbidity and mortality are the highest, but few children have access to these life-saving vaccines. Please see later in the article for the Editors'' Summary     

Identification of the High-Virulence Clone of Group B Streptococci in Mexican Isolates by Growth Characteristics at 40°C

Group B streptococci (GBS) colonizing the vagina and rectum of pregnant women cause invasive disease of the offspring in a small number of cases. The immune status of the host and differences in virulence among strains appear to be the main determinants for neonatal infection. A high-virulence clone (HVC) was proposed to cause much of the morbidity and mortality when a collection of GBS isolates was examined by multilocus enzyme electrophoresis. HVC isolates could be further distinguished by their inability to grow at 40°C. This characteristic was used in the present study to examine a collection of 57 GBS isolates from Mexico City for the HVC. Three serotype III invasive strains were classified in the HVC. The other eleven invasive strains and all carrier isolates had growth curves unaffected at 40°C. These results demonstrate the presence of the HVC in Mexico. Such a low prevalence could explain in part the low rate of GBS invasive neonatal disease in Mexico. Received: 21 May 1998 / Accepted: 14 September 1998     

Serotype-specific invasiveness and colonization prevalence in Streptococcus pneumoniae correlate with the lag phase during in vitro growth

Serotypes of Streptococcus pneumoniae differ in colonization prevalence and the likelihood of causing disease. In vitro growth in brain heart infusion broth with or without 5% fetal calf serum (FCS) was compared for 47 clinical isolates representing 15 pneumococcal serotypes. Serotype-specific colonization prevalence and odds ratios for the invasive potential were obtained from an international and a local epidemiological study. The duration of the lag phase increased with the invasiveness and was inversely associated with the colonization prevalence of a serotype. Supplementation with FCS shortened the lag phase preferentially in serotypes associated with invasive disease (P=0.007). Reduction of oxidative stress by addition of manganese (Mn(2+)), Tiron, mannitol or catalase did not influence the duration of the lag phase significantly. Serotype specific invasiveness and colonization prevalence of S. pneumoniae are associated with the length of the lag phase during in vitro growth. This may correlate with serotype specific selection in vivo.     

Global burden of oropharyngeal cancer attributable to human papillomavirus by anatomical subsite and geographic region

BackgroundOropharynx is the anatomical site with the highest human papillomavirus (HPV) infection in head and neck. Many studies on HPV prevalence and p16^INK4a positivity in oropharyngeal cancer have been published in recent years. We aimed to update the global burden estimates of oropharyngeal cancer attributable to HPV with the latest data and estimate global burden of tonsillar cancer and base of tongue cancer attributable to HPV by region and country.MethodsWe calculated the number of new cancer cases using the Cancer Incidence in Five Continents Volume XI (CI5XI) and country-specific population in 2012 issued by the United Nations. Estimates of HPV prevalence and p16^INK4a positivity were obtained from literature search and pooled analyses where necessary.ResultsGlobally the number of oropharyngeal cancer and tonsillar cancer attributable to HPV were 42,000 and 20,000 in 2012, corresponding to AFs of 42.7% and 52.7%. The number of cancer cases attributable to HPV among males was about 4-fold greater than that among females. For both oropharyngeal cancer and tonsillar cancer, AFs were higher in more developed countries. Among HPV positive oropharyngeal cancer cases, 86.7%, 87.8%, and 92.5% could have been prevented by bivalent (2v), quadrivalent (4v), and nonavalent (9v) HPV vaccines.ConclusionsIt is worth considering the inclusion of HPV immunization in males, especially in the regions where oropharyngeal cancer is highly prevalent.