Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections.

Genetic variants that underlie susceptibility to cervical high-risk human papillomavirus (hrHPV) infections are largely unknown. We conducted discovery genome-wide association studies (GWAS), replication, meta-analysis and colocalization, generated polygenic risk scores (PRS) and examined the association of classical HLA alleles and cervical hrHPV infections in a cohort of over 10,000 women. We identified genome-wide significant variants for prevalent hrHPV around LDB2 and for persistent hrHPV near TPTE2, SMAD2, and CDH12, which code for proteins that are significantly expressed in the human endocervix. Genetic variants associated with persistent hrHPV are in genes enriched for the antigen processing and presentation gene set. HLA-DRB1*13:02, HLA-DQB1*05:02 and HLA-DRB1*03:01 were associated with increased risk, and HLA-DRB1*15:03 was associated with decreased risk of persistent hrHPV. The analyses of peptide binding predictions showed that HLA-DRB1 alleles that were positively associated with persistent hrHPV showed weaker binding with peptides derived from hrHPV proteins and vice versa. The PRS for persistent hrHPV with the best model fit, had a P-value threshold (PT) of 0.001 and a p-value of 0.06 (-log10(0.06) = 1.22). The findings of this study expand our understanding of genetic risk factors for hrHPV infection and persistence and highlight the roles of MHC class II molecules in hrHPV infection.

Progression of the first stage of spontaneous labour: A prospective cohort study in two sub-Saharan African countries.

BACKGROUND: Escalation in the global rates of labour interventions, particularly cesarean section and oxytocin augmentation, has renewed interest in a better understanding of natural labour progression. Methodological advancements in statistical and computational techniques addressing the limitations of pioneer studies have led to novel findings and triggered a re-evaluation of current labour practices. As part of the World Health Organization's Better Outcomes in Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring-to-action tool, we examined the patterns of labour progression as depicted by cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave birth vaginally following a spontaneous labour onset. METHODS AND FINDINGS: This was a prospective, multicentre, cohort study of 5,606 women with singleton, vertex, term gestation who presented at ≤ 6 cm of cervical dilatation following a spontaneous labour onset that resulted in a vaginal birth with no adverse birth outcomes in 13 hospitals across Nigeria and Uganda. We independently applied survival analysis and multistate Markov models to estimate the duration of labour centimetre by centimetre until 10 cm and the cumulative duration of labour from the cervical dilatation at admission through 10 cm. Multistate Markov and nonlinear mixed models were separately used to construct average labour curves. All analyses were conducted according to three parity groups: parity = 0 (n = 2,166), parity = 1 (n = 1,488), and parity = 2+ (n = 1,952). We performed sensitivity analyses to assess the impact of oxytocin augmentation on labour progression by re-examining the progression patterns after excluding women with augmented labours. Labour was augmented with oxytocin in 40% of nulliparous and 28% of multiparous women. The median time to advance by 1 cm exceeded 1 hour until 5 cm was reached in both nulliparous and multiparous women. Based on a 95th percentile threshold, nulliparous women may take up to 7 hours to progress from 4 to 5 cm and over 3 hours to progress from 5 to 6 cm. Median cumulative duration of labour indicates that nulliparous women admitted at 4 cm, 5 cm, and 6 cm reached 10 cm within an expected time frame if the dilatation rate was ≥ 1 cm/hour, but their corresponding 95th percentiles show that labour could last up to 14, 11, and 9 hours, respectively. Substantial differences exist between actual plots of labour progression of individual women and the 'average labour curves' derived from study population-level data. Exclusion of women with augmented labours from the study population resulted in slightly faster labour progression patterns. CONCLUSIONS: Cervical dilatation during labour in the slowest-yet-normal women can progress more slowly than the widely accepted benchmark of 1 cm/hour, irrespective of parity. Interventions to expedite labour to conform to a cervical dilatation threshold of 1 cm/hour may be inappropriate, especially when applied before 5 cm in nulliparous and multiparous women. Averaged labour curves may not truly reflect the variability associated with labour progression, and their use for decision-making in labour management should be de-emphasized.

Negotiating quality standards for effective delivery of labor and childbirth care in Nigeria and Uganda.

OBJECTIVE: "Negotiated standards" describe a level of quality of care that is acceptable and achievable within a specific health system, based on consensus between key stakeholders. This paper presents the development of negotiated standards for effective labor and childbirth care in selected hospitals and communities in Nigeria and Uganda. METHODS: A four-step development process involving different methodologies. The process included: (1) review and synthesis of internationally recognized intrapartum clinical principles and practices; (2) primary qualitative research to assess values and preferences of women and healthcare providers, and practices that align with these preferences; (3) draft contextualization of effective and ineffective behaviors to reflect values and preferences; and (4) WHO-mediated negotiations between relevant stakeholders, including community members, providers, and administrators. RESULTS: The primary outcomes of this process were a comprehensive set of effective behaviors and clinical practices covering the main domains of quality of care, which are practical and easy to communicate, implement, and audit across all levels of healthcare delivery. CONCLUSION: The process demonstrates that health facilities and providers can be motivated to adopt standards of care that uphold the values and preferences of both service users and providers, while adhering to international best practices.

Attitude to Human Papillomavirus Deoxyribonucleic Acid-Based Cervical Cancer Screening in Antenatal Care in Nigeria: A Qualitative Study.

OBJECTIVES: Human papillomavirus (HPV) deoxyribonucleic acid (DNA)-based testing is increasingly used for cervical cancer screening in developed countries, but the best approach to utilizing it in low- and middle-income countries (LMIC) is unclear. Incorporation of HPV DNA-based testing into routine antenatal care (ANC) is a potential yet poorly explored strategy for cervical cancer screening in LMIC. We explored the attitude of health care workers and pregnant women to the incorporation of HPV DNA-based tests into routine ANC in Nigeria. METHODS: We conducted nine focus group discussions with 82 pregnant women and 13 in-depth interviews with obstetricians and midwives at four health care facilities in Abuja, Nigeria. We used qualitative content analysis to analyze the data and the theory of planned behavior as a theoretical framework to examine the responses. RESULTS: Pregnant women expressed a favorable attitude toward HPV DNA testing for cervical cancer screening as part of routine ANC. Acceptability of this approach was motivated by the expected benefits from early detection and treatment of cervical cancer. The factors most commonly cited as likely to influence acceptability and uptake of HPV DNA-based tests are recommendations by their care providers and mandating testing as part of ANC services. Discussants mentioned lack of awareness and affordability as factors that may inhibit uptake of HPV DNA-based cervical cancer screening. Midwives expressed concerns about the safety of sampling procedure in pregnancy, while obstetricians fully support the integration of HPV DNA-based testing into routine ANC. CONCLUSION: Our results show that incorporating HPV DN-based cervical cancer screening into routine ANC is acceptable to pregnant women and health care providers. Making the test affordable and educating health care workers on its efficacy and safety if performed during ANC will enhance their willingness to recommend it and increase its uptake.

Rearing the maize weevil, Sitophilus zeamais, on an artificial maize-cassava diet.

Dry artificial diet pellets prepared with maize, cassava chips, and amino acid supplements (lysine and methionine) were evaluated for mass culture of Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), a highly polyphagous pest of many stored grains. Evaluation was done in the laboratory at temperature 26 ± 2 °C, 60-70% RH, 12:12 L:D photoperiod. The artificial diet was compounded from different proportions of maize (M) variety TZPB-SW-R, cassava (C) variety TMS-2110, and amino acid supplements, and was pelletized into 6 mm diameter pellets on which five pairs of one-day-old S. zeamais were bioassayed. The diet M(9)C(1) (90% M and 10% C) was the most suitable diet with comparatively shorter developmental period (34.8 days) and the highest F(1) emergence of progeny (145.4) compared to the control, M(10)C(0) (100% M and 0% C).

Determinants of perinatal mortality in Nigeria.

OBJECTIVE: To determine risk factors for perinatal mortality among hospital-based deliveries in Nigeria. METHODS: The WHO Global Maternal and Perinatal Health Survey was implemented in Nigeria as a first step in establishing a global system for monitoring maternal and perinatal health. Twenty-one health facilities with more than 1000 deliveries annually were selected by a stratified multistage cluster sampling strategy. Information was recorded on all women who delivered and their neonates within a 3-month period. RESULTS: Overall, there were 9208 deliveries, comprising 8526 live births, 369 fresh stillbirths, 282 macerated stillbirths, 70 early neonatal deaths, and 721 perinatal deaths. The stillbirth and perinatal mortality rates were, respectively, 71 and 78 per 1000 deliveries; the early neonatal death rate was 8 per 1000 live births. Approximately 10% of all newborns weighed less than 2500 g, and 12.3% were born at less than 37 weeks of gestation. Predictors of perinatal mortality were mother's age, lack of prenatal care, unbooked status, prematurity, and birth asphyxia. CONCLUSION: The perinatal mortality rate remains unacceptably high in Nigeria. Fresh stillbirth accounted for most perinatal deaths. Interventions to improve the utilization and quality of prenatal care, in addition to the quality of intrapartum care, would considerably reduce perinatal death.