Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in countries.

Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the greatest effect (care around birth, care of small and ill newborn babies), have low and inequitable coverage and are the most sensitive markers of health system function. In eight of the 13 countries with the most neonatal deaths (55% worldwide), we undertook a systematic assessment of bottlenecks to essential maternal and newborn health care, involving more than 600 experts. Of 2465 bottlenecks identified, common constraints were found in all high-burden countries, notably regarding the health workforce, financing, and service delivery. However, bottlenecks for specific interventions might differ across similar health systems. For example, the implementation of kangaroo mother care was noted as challenging in the four Asian country workshops, but was regarded as a feasible aspect of preterm care by respondents in the four African countries. If all high-burden countries achieved the neonatal mortality rates of their region's fastest progressing countries, then the mortality goal of ten or fewer per 1000 livebirths by 2035 recommended in this Series and the Every Newborn Action Plan would be exceeded. We therefore examined fast progressing countries to identify strategies to reduce neonatal mortality. We identified several key factors: (1) workforce planning to increase numbers and upgrade specific skills for care at birth and of small and ill newborn babies, task sharing, incentives for rural health workers; (2) financial protection measures, such as expansion of health insurance, conditional cash transfers, and performance-based financing; and (3) dynamic leadership including innovation and community empowerment. Adapting from the 2005 Lancet Series on neonatal survival and drawing on this Every Newborn Series, we propose a country-led, data-driven process to sharpen national health plans, seize opportunities to address the quality gap for care at birth and care of small and ill newborn babies, and systematically scale up care to reach every mother and newborn baby, particularly the poorest.

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.

Born too soon: accelerating actions for prevention and care of 15 million newborns born too soon.

Preterm birth complication is the leading cause of neonatal death resulting in over one million deaths each year of the 15 million babies born preterm. To accelerate change, we provide an overview of the comprehensive strategy required, the tools available for context-specifi c health system implementation now, and the priorities for research and innovation. There is an urgent need for action on a dual track: (1) through strategic research to advance the prevention of preterm birth and (2) improved implementation and innovation for care of the premature neonate. We highlight evidence-based interventions along the continuum of care, noting gaps in coverage, quality, equity and implications for integration and scale up. Improved metrics are critical for both burden and tracking programmatic change. Linked to the United Nation's Every Women Every Child strategy, a target was set for 50% reduction in preterm deaths by 2025. Three analyses informed this target: historical change in high income countries, recent progress in best performing countries, and modelling of mortality reduction with high coverage of existing interventions. If universal coverage of selected interventions were to be achieved, then 84% or more than 921,000 preterm neonatal deaths could be prevented annually, with antenatal corticosteroids and Kangaroo Mother Care having the highest impact. Everyone has a role to play in reaching this target including government leaders, professionals, private sector, and of course families who are aff ected the most and whose voices have been critical for change in many of the countries with the most progress.

Standardized evaluation of Zika nucleic acid tests used in clinical settings and blood screening.

Early detection of Zika virus (ZIKV) transmission within geographic regions informs implementation of community mitigation measures such as vector reduction strategies, travel advisories, enhanced surveillance among pregnant women, and possible implementation of blood and organ donor screening or deferral. Standardized, comparative assessments of ZIKV assay and testing lab performance are important to develop optimal approaches to ZIKV diagnostic testing and surveillance. We conducted an expanded blinded panel study to characterize and compare the analytical performance of fifteen diagnostic and blood screening ZIKV NAT assays, including detection among single- and multiplex assays detecting ZIKV, dengue virus (DENV) and chikungunya virus (CHIKV). A 300 member blinded panel was constructed, consisting of 11 serial half-log dilutions ranging from ~104 to 10-1 genome equivalents/mL in 25 replicates each of the Tahitian Asian ZIKV isolate in ZIKV-negative human serum. Additionally, clinical samples from individuals with DENV-like syndrome or suspected ZIKV infection in Brazil were evaluated. The majority of assays demonstrated good specificity. Analytical sensitivities varied 1-2 logs, with a substantially higher limit of detection (LOD) in one outlier. Similar analytical sensitivity for ZIKV RNA detection in singleplex and multiplex assays of the Grifols and ThermoFisher tests were observed. Coefficient of Assay Efficiency (CE), calculated to characterize assays' RNA extraction and amplification efficiency, ranged from 0.13 for the Certest VIASURE multiplex and 0.75 for the Grifols multiplex assays. In general, assays using transcription mediated amplification (TMA) technology had greater CE compared to assays using conventional PCR technology. Donor screening NAT assays were significantly more sensitive than diagnostic RT-qPCR assays, primarily attributable to higher sample input volumes. However, ideal assays to maximize sensitivity and throughput may not be a viable option in all contexts, with other factors such as cost, instrumentation, and regulatory approval status influencing assay availability and selection, particularly in resource constrained settings.

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.

California Very Preterm Birth Study: design and characteristics of the population- and biospecimen bank-based nested case-control study.

Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and racial disparity in the US. The underlying causes of VPTB are multiple and poorly understood. The California Very Preterm Birth Study was conducted to discover maternal and infant genetic and environmental factors associated with VPTB. This paper describes the study design, population, data and specimen collection, laboratory methods and characteristics of the study population. Using a large, population-based cohort created through record linkage of livebirths delivered from 2000 to 2007 in five counties of southern California, and existing data and banked specimens from statewide prenatal and newborn screening, 1100 VPTB cases and 796 control mother-infant pairs were selected for study (385/200 White, 385/253 Hispanic and 330/343 Black cases/controls, respectively). Medical record abstraction of cases was conducted at over 50 hospitals to identify spontaneous VPTB, improve accuracy of gestational age, obtain relevant clinical data and exclude cases that did not meet eligibility criteria. VPTB was defined as birth at <32 weeks in Whites and Hispanics and <34 weeks in Blacks. Approximately 55% of all VPTBs were spontaneous and 45% had medical indications or other exclusions. Of the spontaneous VPTBs, approximately 41% were reported to have chorioamnionitis. While the current focus of the California Very Preterm Birth Study is to assess the role of candidate genetic markers on spontaneous VPTB, its design enables the pursuit of other research opportunities to identify social, clinical and biological determinants of different types of VPTB with the ultimate aim of reducing infant mortality, morbidity and racial disparities in these health outcomes in the US and elsewhere.

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.

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.

External validation of postnatal gestational age estimation using newborn metabolic profiles in Matlab, Bangladesh.

This study sought to evaluate the performance of metabolic gestational age estimation models developed in Ontario, Canada in infants born in Bangladesh. Cord and heel prick blood spots were collected in Bangladesh and analyzed at a newborn screening facility in Ottawa, Canada. Algorithm-derived estimates of gestational age and preterm birth were compared to ultrasound-validated estimates. 1036 cord blood and 487 heel prick samples were collected from 1069 unique newborns. The majority of samples (93.2% of heel prick and 89.9% of cord blood) were collected from term infants. When applied to heel prick data, algorithms correctly estimated gestational age to within an average deviation of 1 week overall (root mean square error = 1.07 weeks). Metabolic gestational age estimation provides accurate population-level estimates of gestational age in this data set. Models were effective on data obtained from both heel prick and cord blood, the latter being a more feasible option in low-resource settings.

Emergence of the Asian lineage of Zika virus in Angola: an outbreak investigation.

BACKGROUND: Zika virus infections and suspected microcephaly cases have been reported in Angola since late 2016, but no data are available about the origins, epidemiology, and diversity of the virus. We aimed to investigate the emergence and circulation of Zika virus in Angola. METHODS: Diagnostic samples collected by the Angolan Ministry of Health as part of routine arboviral surveillance were tested by real-time reverse transcription PCR by the Instituto Nacional de Investigação em Saúde (Ministry of Health, Luanda, Angola). To identify further samples positive for Zika virus and appropriate for genomic sequencing, we also tested samples from a 2017 study of people with HIV in Luanda. Portable sequencing was used to generate Angolan Zika virus genome sequences from three people positive for Zika virus infection by real-time reverse transcription PCR, including one neonate with microcephaly. Genetic and mobility data were analysed to investigate the date of introduction and geographical origin of Zika virus in Angola. Brain CT and MRI, and serological assays were done on a child with microcephaly to confirm microcephaly and assess previous Zika virus infection. FINDINGS: Serum samples from 54 people with suspected acute Zika virus infection, 76 infants with suspected microcephaly, 24 mothers of infants with suspected microcephaly, 336 patients with suspected dengue virus or chikungunya virus infection, and 349 samples from the HIV study were tested by real-time reverse transcription PCR. Four cases identified between December, 2016, and June, 2017, tested positive for Zika virus. Analyses of viral genomic and human mobility data suggest that Zika virus was probably introduced to Angola from Brazil between July, 2015, and June, 2016. This introduction probably initiated local circulation of Zika virus in Angola that continued until at least June, 2017. The infant with microcephaly in whom CT and MRI were done had brain abnormalities consistent with congenital Zika syndrome and serological evidence for Zika virus infection. INTERPRETATION: Our analyses show that autochthonous transmission of the Asian lineage of Zika virus has taken place in Africa. Zika virus surveillance and surveillance of associated cases of microcephaly throughout the continent is crucial. FUNDING: Royal Society, Wellcome Trust, Global Challenges Research Fund (UK Research and Innovation), Africa Oxford, John Fell Fund, Oxford Martin School, European Research Council, Departamento de Ciência e Tecnologia/Ministério da Saúde/National Council for Scientific and Technological Development, and Ministério da Educação/Coordenação de Aperfeicoamento de Pessoal de Nível Superior.

Mapping the landscape of global programmes to evaluate health interventions in pregnancy: the need for harmonised approaches, standards and tools.

Pregnant women and their babies are among the populations most vulnerable to untoward health outcomes. Yet current standards for evaluating health interventions cannot be met during pregnancy because of lack of adequate evidence. The situation is even more concerning in low-income and middle-income countries, where the need for effective interventions is the greatest. Meeting the Sustainable Development Goals for health will require strengthened attention to maternal and child health. In this paper we examine ongoing initiatives aimed at improving the assessment of maternal interventions. We review current methodologies to monitor outcomes of maternal interventions and identify where harmonisation is needed. Based on this analysis we identify settings where different minimal data sets should be considered taking into consideration the clinical realities. Stronger coordination mechanisms and a roadmap to support harmonised monitoring of maternal interventions across programmes and partners, working on improving pregnancy and early childhood health events, will greatly enhance ability to generate evidence-based policies.

Postnatal gestational age estimation using newborn screening blood spots: a proposed validation protocol.

BACKGROUND: Knowledge of gestational age (GA) is critical for guiding neonatal care and quantifying regional burdens of preterm birth. In settings where access to ultrasound dating is limited, postnatal estimates are frequently used despite the issues of accuracy associated with postnatal approaches. Newborn metabolic profiles are known to vary by severity of preterm birth. Recent work by our group and others has highlighted the accuracy of postnatal GA estimation algorithms derived from routinely collected newborn screening profiles. This protocol outlines the validation of a GA model originally developed in a North American cohort among international newborn cohorts. METHODS: Our primary objective is to use blood spot samples collected from infants born in Zambia and Bangladesh to evaluate our algorithm's capacity to correctly classify GA within 1, 2, 3 and 4 weeks. Secondary objectives are to 1) determine the algorithm's accuracy in small-for-gestational-age and large-for-gestational-age infants, 2) determine its ability to correctly discriminate GA of newborns across dichotomous thresholds of preterm birth (≤34 weeks, <37 weeks GA) and 3) compare the relative performance of algorithms derived from newborn screening panels including all available analytes and those restricted to analyte subsets. The study population will consist of infants born to mothers already enrolled in one of two preterm birth cohorts in Lusaka, Zambia, and Matlab, Bangladesh. Dried blood spot samples will be collected and sent for analysis in Ontario, Canada, for model validation. DISCUSSION: This study will determine the validity of a GA estimation algorithm across ethnically diverse infant populations and assess population specific variations in newborn metabolic profiles.

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.

Virologic and immunologic outcomes and programmatic challenges of an antiretroviral treatment pilot project in Abidjan, Côte d'Ivoire.

BACKGROUND: In Côbte d'Ivoire, a pilot project was developed by UNAIDS and the Ministry of Health to improve access to AIDS care, including antiretroviral therapy, for adults and children infected with HIV. This evaluation of the project is the first to provide results of a large number of HIV-infected patients receiving antiretroviral therapy in West Africa. METHODS: We evaluated records of persons who presented for care from August 1998 to August 2000 at six accredited centers in Abidjan. Patients were treated with two nucleoside reverse transcriptase inhibitors (2NRTI) or highly active antiretroviral therapy (HAART). RESULTS: Of 2878 patients who were screened, 2351 (83%) were HIV-infected and eligible (CD4 T lymphocyte count < 500 x 10(6) cells/l or plasma HIV-RNA level > 10 000 copies/ml) for antiretroviral therapy. Of those who were eligible, 81% were symptomatic, 63% had a CD4 cell count < 200 x 10(6) cells/l, 12% had previously taken antiretroviral drugs, and 56% returned to the clinic for follow-up. Of the patients screened, 768 (27%) were started on antiretroviral therapy, including 450 on HAART, 296 on 2NRTI, and 22 on other regimens. We analyzed data from 480 HIV-1-infected adults, who were naive to therapy, were prescribed HAART or 2NRTI, and had at least one clinic visit after starting therapy. In an intent-to-treat analysis of patients who received HAART, the estimated plasma HIV-1 RNA level was approximately 1.9 log10 copies/ml (80-fold) lower, while estimated CD4 cell count was > 100 x 10(6) cells/l higher than baseline values, after 1 year of therapy. Approximately 25% of adults on 2NRTI and 50% of those on HAART had < 200 copies/ml, after 1 year of therapy. The probability of an adverse event occurring within 6 months after starting therapy was 0.20. The probability of survival for at least 1 year was 0.84 (95% confidence interval, 0.80-0.89). CONCLUSION: After starting antiretroviral therapy, these HIV-1-infected patients in West Africa had similar virologic and immunologic outcomes, probability of an adverse event, and estimated survival, as patients enrolled in clinical trials in the USA and Europe. However, only one-third of eligible patients received therapy, highlighting the importance of providing adequate education and support for initiating and adhering to therapy in this and similar programmes.

Prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients who have rebound in viral load while receiving antiretroviral therapy in the UNAIDS-Drug Access Initiative in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine the prevalence of genotypic and phenotypic antiretroviral (ARV) drug-resistant HIV-1 strains among patients with viral load rebound while receiving ARV therapy in Abidjan, Côte d'Ivoire. METHODS: Between August 1998 and April 2000, we selected all patients (n = 241) who had received ARV drug therapy for at least 6 months in the UNAIDS-Drug Access Initiative (DAI), in Abidjan. We analyzed for genotypic and phenotypic drug resistance among 97 (40%) of the 241 patients who had a rebound in plasma viral load, defined as an initial decrease of > 0.5 log10 copies/ml followed by a subsequent increase of > 0.25 log10 copies/ml. RESULTS: Of the viruses isolated from the 97 patients, 86 (88.7%) had usable sequences and 68 (79%) of the 86 patients had genotypic resistance to at least one reverse transcriptase inhibitor (RTI) or protease inhibitor (PI). Resistant mutations were found for zidovudine in 50 (78%) of 64 patients who had received the drug, 11 (68.7%) of 16 patients on lamivudine, for nevirapine in two (2%), for indinavir in one (1%), and for ritonavir in one (1%). Phenotypic resistance to at least one nucleoside RTI was seen in 45 (56%) of the 80 patients tested, to non-nucleoside RTIs in eight (10%), and to PIs in one (1.3%). Multivariate regression analysis showed factors associated with resistance to be initial treatment with dual therapy (P = 0.04) compared with highly active antiretroviral therapy, and maximal initial viral load response (P = 0.006). CONCLUSION: Our results demonstrate a high prevalence of ARV drug resistance associated with dual ARV therapy. These results indicate the limited role for dual ARV therapy.

Development of phenotypic and genotypic resistance to antiretroviral therapy in the UNAIDS HIV Drug Access Initiative--Uganda.

OBJECTIVE: We describe phenotypic drug resistance, response to therapy, and genotypic mutations among HIV-infected patients in Uganda taking antiretroviral medications for > or = 90 days who had a viral load > or = 1000 copies/ml. METHODS: HIV-1 group and subtype, virologic and immunologic responses to antiretroviral therapy, phenotypic resistance to antiretroviral drugs, and associated genotypic mutations among patients at three treatment centers in Uganda between June 1999 and August 2000 were assessed. Therapy was two nucleoside reverse transcriptase inhibitors (NRTIs) or highly active antiretroviral therapy (HAART). RESULTS: All HIV identified was HIV-1, group M, subtypes A, C, and D. Sixty-one (65%) of 94 patients with a phenotypic resistance result had evidence of phenotypic resistance including resistance to a NRTI for 51 of 92 (55%) taking NRTIs, to a non-nucleoside reverse transcriptase inhibitor (NNRTI) for nine of 16 (56%) taking NNRTIs, and to a protease inhibitor (PI) for eight of 37 (22%) taking PIs. At the time of the first specimen with resistance, the median change from baseline viral load was -0.56 log copies/ml [interquartile range (IQR), -1.47 to +0.29] and CD4+ cell count was +35 x 10(6) cells/l (IQR, -18 to +87). Genotypic resistance mutations, matched with phenotypic resistance assay results and drug history, were generally consistent with those seen for HIV-1, group M, subtype B infections in industrialized countries. CONCLUSION: Initial phenotypic resistance and corresponding genotypic mutations among patients treated in Uganda were similar to those with subtype B infections in North America and Europe. These data support policies that promote the use of HAART regimens against HIV-1, group M, non-B subtypes in a manner consistent with that used for subtype B infections.

Prevention of preterm birth: harnessing science to address the global epidemic.

Preterm birth is a leading cause of infant morbidity and mortality worldwide, but current interventions to prevent prematurity are largely ineffective. Preterm birth is increasingly recognized as an outcome that can result from a variety of pathological processes. Despite current research efforts, the mechanisms underlying these processes remain poorly understood and are influenced by a range of biological and environmental factors. Research with modern techniques is needed to understand the mechanisms responsible for preterm labor and birth and identify targets for diagnostic and therapeutic solutions. This review evaluates the state of reproductive science relevant to understanding the causes of preterm birth, identifies potential targets for prevention, and outlines challenges and opportunities for translating research findings into effective interventions.

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.