A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.

Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index.

BACKGROUND: Every year, 1·1 million babies die from prematurity, and many survivors are disabled. Worldwide, 15 million babies are born preterm (<37 weeks' gestation), with two decades of increasing rates in almost all countries with reliable data. The understanding of drivers and potential benefit of preventive interventions for preterm births is poor. We examined trends and estimate the potential reduction in preterm births for countries with very high human development index (VHHDI) if present evidence-based interventions were widely implemented. This analysis is to inform a rate reduction target for Born Too Soon. METHODS: Countries were assessed for inclusion based on availability and quality of preterm prevalence data (2000-10), and trend analyses with projections undertaken. We analysed drivers of rate increases in the USA, 1989-2004. For 39 countries with VHHDI with more than 10,000 births, we did country-by-country analyses based on target population, incremental coverage increase, and intervention efficacy. We estimated cost savings on the basis of reported costs for preterm care in the USA adjusted using World Bank purchasing power parity. FINDINGS: From 2010, even if all countries with VHHDI achieved annual preterm birth rate reductions of the best performers for 1990-2010 (Estonia and Croatia), 2000-10 (Sweden and Netherlands), or 2005-10 (Lithuania, Estonia), rates would experience a relative reduction of less than 5% by 2015 on average across the 39 countries. Our analysis of preterm birth rise 1989-2004 in USA suggests half the change is unexplained, but important drivers include non-medically indicated labour induction and caesarean delivery and assisted reproductive technologies. For all 39 countries with VHHDI, five interventions modelling at high coverage predicted a 5% relative reduction of preterm birth rate from 9·59% to 9·07% of livebirths: smoking cessation (0·01 rate reduction), decreasing multiple embryo transfers during assisted reproductive technologies (0·06), cervical cerclage (0·15), progesterone supplementation (0·01), and reduction of non-medically indicated labour induction or caesarean delivery (0·29). These findings translate to roughly 58,000 preterm births averted and total annual economic cost savings of about US$3 billion. INTERPRETATION: We recommend a conservative target of a relative reduction in preterm birth rates of 5% by 2015. Our findings highlight the urgent need for research into underlying mechanisms of preterm births, and development of innovative interventions. Furthermore, the highest preterm birth rates occur in low-income settings where the causes of prematurity might differ and have simpler solutions such as birth spacing and treatment of infections in pregnancy than in high-income countries. Urgent focus on these settings is also crucial to reduce preterm births worldwide. FUNDING: March of Dimes, USA, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institutes of Health, USA.

Epidemiology of late and moderate preterm birth.

Preterm birth affects 12.5% of all births in the USA. Infants of Black mothers are disproportionately affected, with 1.5 times the risk of preterm birth and 3.4 times the risk of preterm-related mortality. The preterm birth rate has increased by 33% in the last 25 years, almost entirely due to the rise in late preterm births (34-36 weeks' gestation). Recently attention has been given to uncovering the often subtle morbidity and mortality risks associated with moderate (32-33 weeks' gestation) and late preterm delivery, including respiratory, infectious, and neurocognitive complications and infant mortality. This section summarizes the epidemiology of moderate and late preterm birth, case definitions, risk factors, recent trends, and the emerging body of knowledge of morbidity and mortality associated with moderate and late preterm birth.

Attitudes and practices regarding use of progesterone to prevent preterm births.

We sought to describe current attitudes and practices of obstetrician-gynecologists regarding use of progesterone and prevention of preterm birth. A self-administered survey was mailed to American College of Obstetricians and Gynecologists Fellows and Junior Fellows in Practice in March to May 2007. The survey consisted of 36 questions, including respondents' demographic characteristics, preterm birth risk factor knowledge and screening practices, and use of progesterone for the prevention of preterm birth. The response rate was 52% ( N = 345); most respondents were general obstetrician-gynecologists (89%). Many (74%) reported recommending or offering progesterone for prevention of preterm birth. Almost all (93%) reported use for the indication of previous spontaneous preterm birth. However, many also reported use for other indications such as dilated/effaced cervix (37%), short cervix on ultrasound (34%), and cerclage (26%). These results suggest that most obstetricians recommend or offer progesterone to prevent preterm birth for women with a previous spontaneous preterm birth and many also offer it for women with other high-risk obstetric conditions.

The contribution of preterm birth to infant mortality rates in the United States.

OBJECTIVE: Although two thirds of infant deaths in the United States occur among infants born preterm (<37 weeks of gestation), only 17% of infant deaths are classified as being attributable to preterm birth with the standard classification of leading causes of death. To address this apparent discrepancy, we sought to estimate more accurately the contribution of preterm birth to infant mortality rates in the United States. METHODS: We identified the top 20 leading causes of infant death in 2002 in the US linked birth/infant death file. The role of preterm birth for each cause was assessed by determining the proportion of infants who were born preterm for each cause of death and by considering the biological connection between preterm birth and the specific cause of death. RESULTS: Of 27970 records in the linked birth/infant death file for 2002, the 20 leading causes accounted for 22273 deaths (80% of all infant deaths). Among infant deaths attributable to the 20 leading causes, we classified 9596 infant deaths (34.3% of all infant deaths) as attributable to preterm birth. Ninety-five percent of those deaths occurred among infants who were born at <32 weeks of gestation and weighed <1500 g, and two thirds of those deaths occurred during the first 24 hours of life. CONCLUSIONS: On the basis of this evaluation, preterm birth is the most frequent cause of infant death in the United States, accounting for at least one third of infant deaths in 2002. The extreme prematurity of most of the infants and their short survival indicate that reducing infant mortality rates requires a comprehensive agenda to identify, to test, and to implement effective strategies for the prevention of preterm birth.

Transmission of human herpesvirus 8 by blood transfusion.

BACKGROUND: Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic. METHODS: We enrolled patients in Kampala, Uganda, who had received blood transfusions between December 2000 and October 2001. Pretransfusion and multiple post-transfusion blood specimens from up to nine visits over a 6-month period were tested for HHV-8 antibody. We calculated the excess risk of seroconversion over time among recipients of HHV-8-seropositive blood as compared with recipients of seronegative blood. RESULTS: Of the 1811 transfusion recipients enrolled, 991 were HHV-8-seronegative before transfusion and completed the requisite follow-up, 43% of whom received HHV-8-seropositive blood and 57% of whom received seronegative blood. HHV-8 seroconversion occurred in 41 of the 991 recipients. The risk of seroconversion was significantly higher among recipients of HHV-8-seropositive blood than among recipients of seronegative blood (excess risk, 2.8%; P<0.05), and the increase in risk was seen mainly among patients in whom seroconversion occurred 3 to 10 weeks after transfusion (excess risk, 2.7%; P=0.005), a result consistent with the transmission of the virus by transfusion. Blood units stored for up to 4 days were more often associated with seroconversion than those stored for more than 4 days (excess risk, 4.2%; P<0.05). CONCLUSIONS: This study provides strong evidence that HHV-8 is transmitted by blood transfusion. The risk may be diminished as the period of blood storage increases.

Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States.

OBJECTIVE: A multicenter, randomized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate (17P), initiated between 16 and 20 weeks of gestation, reduced preterm birth by 33%. The current study estimated both preterm birth recurrence and the potential reduction in the national preterm birth rate. METHODS: Using 2002 national birth certificate data, augmented by vital statistics from 2 states, we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm birth and prenatal care onset within the first 4 months of pregnancy. The number and rate of recurrent spontaneous preterm births were estimated. To predict effect, the reported 33% reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates. RESULTS: In 2002, approximately 30,000 recurrent preterm births occurred to women eligible for 17P, having had a recurrent preterm birth rate of 22.5%. If 17P therapy were delivered to these women, nearly 10,000 spontaneous preterm births would have been prevented, thereby reducing the overall United States preterm birth rate by approximately 2%, from 12.1% to 11.8% (P < .001), with higher reductions in targeted groups of eligible pregnant women. CONCLUSION: Use of 17P could reduce preterm birth among eligible women, but would likely have a modest effect on the national preterm birth rate. Additional research is urgently needed to identify other populations who might benefit from 17P, evaluate new methods for early detection of women at risk, and develop additional prevention strategies. LEVEL OF EVIDENCE: III.

Kaposi's sarcoma in Uganda: risk factors for human herpesvirus 8 infection among blood donors.

Human herpesvirus 8 (HHV-8) is etiologically linked to Kaposi's sarcoma, a common cancer in Uganda. The authors assessed HHV-8 seroprevalence, risk factors for infection, and HHV-8 assays in a cross-sectional study of Ugandan blood donors. Of 3,736 specimens, the authors selected 203 reactive for HIV, hepatitis B surface antigen (HBsAg), or syphilis, and, randomly, 203 nonreactive specimens. For HHV-8 testing, the authors used two peptide-based enzyme-linked immunosorbent assays (EIAs), ORFK8.1 and ORF65, and an immunofluorescence assay (IFA). Specimens reactive in at least two assays or on IFA alone were considered HHV-8-seropositive. Prevalence estimates were weighted to account for the sampling scheme. Overall HHV-8 seroprevalence was 40%. HHV-8 seroprevalence was higher among HBsAg-positive donors (53%) than HBsAg-negative donors (39%; p =.02) and higher among HIV-positive donors (63%) than HIV-negative donors (39%; p <.001). HHV-8 seroreactivity showed no trend with age. Kappa values for assay concordances were 0.68 (ORFK8.1 EIA and IFA), 0.37 (ORF65 EIA and K8.1 EIA), and 0.29 (ORF65 EIA and IFA). The association between HHV-8 and HBsAg positivity and the lack of association between HHV-8 and age point to primarily nonsexual HHV-8 transmission during childhood. The association with HIV indicates sexual transmission may also occur. The role of ORF65 EIA in testing specimens from Africa warrants further evaluation.