A story-telling cloth approach to motivating cervical cancer screening in Mali.

Ninety percent of deaths from Cervical cancer (CC) caused by Human Papilloma Virus (HPV) occur in low- and middle-income countries. CC is the 2nd most common cause of cancer in women in West Africa, where 12,000 women develop cervical cancer and more than 6,000 die from the disease, annually. While HPV vaccination and CC screening have dramatically reduced the incidence of CC and mortality from CC in developed countries, prevention of CC in West Africa is often limited to visual inspection of the cervix and surgical intervention. In previous studies of CC in Mali, we demonstrated that knowledge about the link between HPV and CC is limited, and that screening for CC is often delayed until women are symptomatic. For this intervention, a story-telling cloth (West African-style printed pagne) was designed for use as a starting point for educational sessions run by community health workers. Community outreach using the cloth during 6 months of 2015 resulted in a 5-fold higher uptake of cervical cancer screening and increased awareness of the potential to vaccinate adolescents against CC. 3,271 women were motivated to visit one of five participating clinics for CC screening, where a mere 600 women had been screened during the previous year. This study shows that a comprehensive, visual, community-centered education campaign coupled with coordinated support for local clinics improves uptake of CC screening.

[Risk factors and management of uterine rupture in a 1st reference structure in Mali: case of the Bougouni health district]. / Facteurs de risque et prise en charge de la rupture uterine dans une structure de 1ere reference du Mali : cas du district sanitaire de Bougouni.

The objective was to assess the risk factors for and to suggest therapeutic aspects. MATERIALS AND METHODS: We carried out a case-control study at the Bougouni Reference health center in 2019. RESULTS: From January to December 31, 2019; out of 1161 deliveries, 43 uterine rupture were recorded, 3.7% corresponding to one uterine rupture for 27 deliveries. Patients 35 years and older were more affected by uterine rupture (44.2%) with ORaIC95% = 6.3 [1.5 - 26.3]. Obstetric evacuations had an ORaIC95% = 25.6 [7.8-83.7]. All of the patients were housewives (97.7%) versus (82.3%) controls with ORaIC95% = 8.9 (1.1-69). Pauciparous and multiparous had an ORaIC95% = 6.2 [1.8 - 20.3] and 4.1 [1.3 - 12.9], respectively. The uterine scar (20.9%) of cases versus 8.1% of controls had a 95% ORaIC95% = 2.9 [1.1 - 8.7]. Indeed the absence of ANC was a risk factor, ORaIC95% = 3.0 [1.3 - 6.9]. The time to uterine rupture was < 6 hours in 95%. In fact 34 complete uterine rupture (79.1%) and 9 incomplete uterine rupture (20.9) were noted. Only 2.3% of cases gave birth vaginally. Treatment of uterine rupture was based on surgery (100%) supplemented by shock (51.2%) of cases and infection (100%) of cases. CONCLUSION: Uterine rupture is common in our countries under medical care. Its effective prevention involves strategies aimed at acting on risk factors.

L'objectif était d'évaluer les facteurs de risque de la RU et de proposer les aspects thérapeutiques. MATÉRIELS ET MÉTHODES: Nous avons réalisé une étude cas-témoins au centre de santé de Référence de Bougouni en 2019. RÉSULTATS: De janvier au 31 décembre 2019 ; sur 1161 accouchements 43 RU ont été enregistrées soit 3,7% correspondant à une RU pour 27 accouchements. Les patientes de 35 ans et plus ont été plus touchée par la RU (44,2%) avec ORaIC95%= 6,3 [1,5 - 26,3]. Les évacuations obstétricales avaient un ORaIC95%=25,6 [7,8- 83,7]. La totalité des patientes étaient des femmes au foyer (97,7%) des cas versus (82,3%) des témoins avec ORaIC95%=8,9 (1,1-69). Les Paucipares et multipares avaient respectivement un ORaIC95%= 6,2 [1,8 - 20,3] et 4,1[1,3 - 12,9]. La cicatrice utérine (20,9%) des cas contre 8,1 % les témoins avait un ORaIC95%= 2,9 [1,1 - 8,7]. En effet l'absence de CPN étaient un facteur de risque, ORaIC95%= 3,0 [1,3 ­ 6,9]. Le délai de la RU était < 6 heures chez 95%. En effet 34 RU complètes (79,1%) et 9 RU incomplètes (20,9%) ont été notées. Seulement 2,3 % des cas avaient accouché par voie basse. Le traitement de la RU reposait sur la chirurgie (100%) complétée par celui du choc (51,2%) des cas et de l'infection (100%) des cas. CONCLUSION: La RU est fréquente dans nos pays sous médicalisés. Sa prévention efficace passe par des stratégies visant à agir sur les facteurs de risque.

Facteurs de risque et prise en charge de la rupture utérine dans une structure de 1ere référence du Mali: cas du district sanitaire de Bougouni / Risk factors and management of uterine rupture in a 1st reference structure in Mali: case of the Bougouni health district

L'objectif était d'évaluer les facteurs de risque de la RU et de proposer les aspects thérapeutiques. Matériels et méthodes : Nous avons réalisé une étude cas-témoins au centre de santé de Référence de Bougouni en 2019. Résultats : De janvier au 31 décembre 2019; sur 1161 accouchements 43 RU ont été enregistrées soit 3,7% correspondant à une RU pour 27 accouchements. Les patientes de 35 ans et plus ont été plus touchée par la RU (44,2%) avec ORaIC95%= 6,3 [1,5 - 26,3]. Les évacuations obstétricales avaient un ORaIC95%=25,6 [7,8- 83,7]. La totalité des patientes étaient des femmes au foyer (97,7%) des cas versus (82,3%) des témoins avec ORaIC95%= 8,9 (1,1-69). Les Paucipares et multipares avaient respectivement un ORaIC95%= 6,2 [1,8 - 20,3] et 4,1[1,3 - 12,9]. La cicatrice utérine (20,9%) des cas contre 8,1 % les témoins avait un ORaIC95%= 2,9 [1,1 - 8,7]. En effet l'absence de CPN étaient un facteur de risque, ORaIC95%= 3,0 [1,3 ­ 6,9]. Le délai de la RU était ˂ 6 heures chez 95%. En effet 34 RU complètes (79,1%) et 9 RU incomplètes (20,9%) ont été notées. Seulement 2,3 % des cas avaient accouché par voie basse. Le traitement de la RU reposait sur la chirurgie (100%) complétée par celui du choc (51,2%) des cas et de l'infection (100%) des cas. Conclusion: La RU est fréquente dans nos pays sous médicalisés. Sa prévention efficace passe par des stratégies visant à agir sur les facteurs de risque

The objective was to assess the risk factors for and to suggest therapeutic aspects. Materials and methods: We carried out a case-control study at the Bougouni Reference health center in 2019. Results: From January to December 31, 2019; out of 1161 deliveries, 43 uterine rupture were recorded, 3.7% corresponding to one uterine rupture for 27 deliveries. Patients 35 years and older were more affected by uterine rupture (44.2%) with ORaIC95% = 6.3 [1.5 - 26.3]. Obstetric evacuations had an ORaIC95% = 25.6 [7.8-83.7]. All of the patients were housewives (97.7%) versus (82.3%) controls with ORaIC95% = 8.9 (1.1-69). Pauciparous and multiparous had an ORaIC95% = 6.2 [1.8 - 20.3] and 4.1 [1.3 - 12.9], respectively. The uterine scar (20.9%) of cases versus 8.1% of controls had a 95% ORaIC95% = 2.9 [1.1 - 8.7]. Indeed the absence of ANC was a risk factor, ORaIC95% = 3.0 [1.3 - 6.9]. The time to uterine rupture was ˂ 6 hours in 95%. In fact 34 complete uterine rupture (79.1%) and 9 incomplete uterine rupture (20.9) were noted. Only 2.3% of cases gave birth vaginally. Treatment of uterine rupture was based on surgery (100%) supplemented by shock (51.2%) of cases and infection (100%) of cases. Conclusion: Uterine rupture is common in our countries under medical care. Its effective prevention involves strategies aimed at acting on risk factors.

Prevalence of cervical HPV infection, sexually transmitted infections and associated antimicrobial resistance in women attending cervical cancer screening in Mali.

OBJECTIVES: To assess the prevalence of sexually transmitted infections (STIs), antimicrobial resistance and cervical lesions among women from Sikasso, Mali. METHODS: Women infected with human immunodeficiency virus (HIV) (n=44) and HIV-negative women (n=96) attending cervical cancer screening were included. Screening for human papillomavirus (HPV), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) was performed using polymerase chain reaction assays, and herpes simplex virus (HSV-1/2) serological status was assessed using enzyme-linked immunosorbent assays. Antibiotic resistance tests were performed for MG- and NG-positive cases. RESULTS: A high prevalence of high-risk HPV (hrHPV) infection (63%) was found. This was associated with cervical lesions in 7.5% of cases. An unusual distribution was found, with HPV31, HPV56 and HPV52 being the most prevalent. The hrHPV distribution differed by HIV status, with HIV-positive cases having HPV35/31/51-52-56 and HIV-negative cases having HPV31/56/52. The seroprevalence of HSV-2 was 49%, and the prevalence of other STIs was as follows: CT, 4%; MG, 9%; NG, 1%; and TV, 7%. Five of nine MG-positive specimens and the NG strains obtained were resistant to fluoroquinolone. CONCLUSIONS: These results showed high prevalence of hrHPV and fluoroquinolone resistance in several NG and MG strains. Further studies are required to confirm these data in Mali, and to improve prevention, screening and management of cervical cancer and other STIs in women.

Type-specific incidence, persistence and factors associated with human papillomavirus infection among female sex workers in Benin and Mali, West Africa.

OBJECTIVES: This study in female sex workers (FSWs) aimed to: (1) estimate type-specific incidence and persistence of human papillomavirus (HPV) infection in Cotonou (Benin) and Bamako (Mali); and (2) identify the factors associated with type-specific incidence and persistence of high-risk HPV (HR-HPV) infection. METHODS: A 1-year prospective cohort study on cervical cancer screening, and HPV and human immunodeficiency virus (HIV) infections was conducted among FSWs in Cotonou and Bamako from 2017 to 2019. Poisson regression models assessed factors associated with the incidence of HR-HPV infection, while log-binomial regression was performed to identify factors associated with the persistence of HR-HPV infection. Adjusted relative risks (ARR) and 95% confidence intervals (95% CI) were estimated. RESULTS: The incidence of HR-HPV infection was 46.98 per 1000 women-months (predominant types HPV16, HPV35 and HPV59). Factors associated with the incidence of HR-HPV infection were age <20 years (ARR 15.10; 95% CI 3.29-69.19), age at sexual debut <18 years (ARR 6.92; 95% CI 1.97-24.27) and sex work duration ≤1 year (ARR 7.40; 95% CI 1.84-29.69). The persistence of HR-HPV infection at 12 months was 38.7% (most persistent types HPV59, HPV52 and HPV51). Persistence of HR-HPV infection was higher in women with chlamydia (P = 0.031), HIV infection (P < 0.001) and multiple-type HPV infections (P < 0.001). CONCLUSION: FSWs in West Africa are at high risk of incident and persistent HR-HPV infection, suggesting an urgent need for cervical cancer screening in this population.

A population-based combination strategy to improve the cervical cancer screening coverage rate in Bamako, Mali.

INTRODUCTION: Cervical cancer screening coverage rate is <5% in Sub-Saharan Africa and <2% in French- speaking African countries. In 2016, we implemented strategies to improve cervical cancer screening in Bamako, the "Weekend70 program". The present study objectives are to determine the effect of this program on women's participation in cervical cancer screening in Bamako, and to estimate the cervical cancer screening coverage rate in Bamako. MATERIAL AND METHODS: From 1 January 2016 to 31 July 2020, we conducted an operational research by developing several strategies to improve the cervical cancer screening coverage rate among adolescents and women ≥15 years old in Bamako, Mali. The strategies consisted of awareness-raising activities, strengthening of screening practices in healthcare facilities and cost-free cervical cancer screening during the weekend. Descriptive statistics were presented. The cervical cancer coverage rate was calculated by dividing the number of women screened by the total number of women ≥20 years old, based on Mali demographic data. RESULTS: The total number of women screened was 289 924. Residents from Bamako represented 91.9% (266 436/289 924) vs 8.1% (23 488/289 924) who lived outside Bamako. The mean age was 33.2 (± 11.5) years old. Around 46.1% of participants attending the cervical cancer screening were between 30 and 49 years old (World Health Organization prioritized target age for cervical cancer screening). Women ≥60 years old represented <5%. Cervical cancer screening participation increased significantly, from <800 women screened per week before the implementation of the program to a peak of 4100 women screened per week during the "Weekend70 program". Overall, the cervical cancer screening coverage rates at the end of the study among women ≥20 years old was 47.3%, and 56.9% in the WHO target population. CONCLUSION: In an impoverished context, a multi-component strategy significantly increases cervical cancer screening participation.

Human papillomavirus genotype distribution and factors associated among female sex workers in West Africa.

OBJECTIVES: This study aimed to: (1) Estimate HPV prevalence and genotype distribution among female sex workers (FSWs) in Mali and Benin as well as the prevalence of multiple HPV type infections in this group, and (2) Identify potential risk factors associated with high-risk (HR) HPV infections. METHODS: We analyzed baseline data of 665 FSWs aged ≥ 18 years recruited during a prospective cohort of cervical cancer screening in Cotonou (Benin) and Bamako (Mali) from 2017 to 2018. The Linear Array HPV genotyping test was used to identify HPV genotypes. Descriptive statistics and multivariate log-binomial regression were used. Adjusted prevalence ratios (APR) with 95% confidence intervals (95%CI) were estimated to identify risk factors associated with HR-HPV infections. RESULTS: HPV data were available for 659 FSWs (Benin: 309; Mali: 350). The mean age was 35.0 years (± 10.7) in Benin and 26.8 years (± 7.6) in Mali. The overall HPV prevalence rates were 95.5% in Benin and 81.4% in Mali. About 87.7% and 63.4% of FSWs harbored ≥ 2 HPV types in Benin and Mali, respectively. The top three prevalent HR-HPV among FSWs in Benin were: HPV58 (37.5%), HPV16 (36.6%) and HPV52 (28.8%). Corresponding patterns in Mali were HPV16 (15.7%), HPV51 (14.3%) and HPV52 (12.9%). In Benin, the main factors associated with HR-HPV were vaginal douching (APR = 1.17; 95%CI:1.02-1.34) and gonococcal infection (APR = 1.16; 95%CI:1.04-1.28), while in Mali they were sex work duration ≤ 1 year (APR = 1.35; 95%CI:1.10-1.65) and HIV infection (APR = 1.26; 95%CI: 1.06-1.51). CONCLUSION: Our study found a very high prevalence of HPV infection as well as high frequency of multiple HPV type infections in FSWs in two countries in West Africa. These findings suggest the necessity to emphasize cervical cancer prevention in this high-risk group.

Prevalence and Factors Associated With HIV and Sexually Transmitted Infections Among Female Sex Workers in Bamako, Mali.

BACKGROUND: We aimed to (1) estimate the prevalence of HIV and other sexually transmitted infections (STIs) among female sex workers (FSWs) in Bamako, Mali, and (2) identify factors associated with STIs including HIV infection in this population. METHODS: We analyzed baseline data from a prospective observational cohort study on cervical cancer screening, human papillomavirus, and HIV infections among FSWs 18 years or older recruited in Bamako. Multivariable log-binomial regression was used to estimate the adjusted prevalence ratios (APRs) with 95% confidence interval (95% CI) for HIV infection and STIs versus associated factors. RESULTS: Among 353 women participating in the study, mean age was 26.8 (±7.6) years. HIV prevalence was 20.4%, whereas 35.1% of the FSWs had at least one STI. Factors significantly associated with HIV were older age (P < 0.0001, test for trend), duration of sex work ≥6 years (APR, 1.92; 95% CI, 1.22-3.02), uneducated status (APR, 2.24; 95% CI, 1.16-4.34), less than 10 clients in the last 7 days (APR, 1.55; 95% CI, 1.02-2.34), and gonococcal (APR, 1.85; 95% CI, 1.21-2.82) and chlamydial (APR, 2.58; 95% CI, 1.44-4.62) infections. Younger age (P = 0.018, test for trend), having ≥10 clients in the last week (APR, 1.47; 95% CI, 1.11-1.94), and HIV infection (APR, 2.00; 95% CI, 1.49-2.69) were significantly associated with STIs. CONCLUSIONS: HIV and curable STI prevalence are high among FSWs in Bamako. There is thus a need to enhance the efficiency of interventions toward FSWs in Mali to reduce the burden of HIV and STIs among them and prevent HIV spread to the general population.

Clinical Evaluations Have Low Sensitivity for Identifying Preterm Infants in a Clinical Trial in a Limited Resource Setting.

Preterm birth is a primary outcome of interest in maternal vaccination trials but determination of gestational age is challenging in limited-resource settings. This study compares the New Ballard Score and fundal height measurements with the current standard of early ultrasound for sensitivity of predicting preterm birth. A trial of maternal influenza vaccination was conducted in Bamako, Mali. The New Ballard Score and fundal height were collected on 4038 infants born in the trial, ultrasound data were available for 1893 of those infants. New Ballard Score and fundal height were compared, consecutively, to all ultrasound results, early ultrasound results from the first trimester, and the date of last menstrual period for estimation of gestational age. Sensitivity of the New Ballard Score for identifying preterm infants was 0.33 compared with early ultrasound and 0.1 compared with the last menstrual period based estimates of gestational age. Sensitivity of low birth weight alone was 0.43 compared with early ultrasound. New Ballard Score estimated gestational age within 1 week of ultrasound more frequently than fundal height (53% compared with 7.6%, respectively) yet New Ballard Score identified few infants as preterm (1.8% vs 5.8% by early ultrasound), and was biased toward categorizing low birth weight infants and infants requiring hospitalization as preterm. New Ballard Score is not an ideal measure for identifying preterm births in low-resource settings. Despite the time and cost of training required for correct measurement of New Ballard Score, measurement of low birth weight alone performed better than New Ballard Score for identifying preterm infants.

Knowledge, attitudes, practices and willingness to vaccinate in preparation for the introduction of HPV vaccines in Bamako, Mali.

Although screening for pre-cancerous cervical lesions and human papilloma virus (HPV) vaccination are accepted and effective means to prevent cervical cancer, women in Mali have limited access to these interventions. In addition, cervical cancer prevention by HPV vaccination has been controversial in some settings. To reduce cervical cancer prevalence and increase HPV vaccine uptake, it is important to understand the level of knowledge about cervical cancer screening and practices related to vaccination in at-risk populations. In this study, the level of knowledge about HPV and cervical cancer and attitudes towards vaccination were assessed among 301 participants (male and female, adults and adolescents) in a house-to-house survey in two urban neighborhoods in Bamako, Mali. The survey was combined with a brief educational session on HPV. Prior to the education session, overall knowledge of HPV infection and cervical cancer was very low: only 8% knew that HPV is a sexually transmitted infection (STI). Less than 20% of women had ever consulted a gynecologist and less than 3% had ever had cervical cancer screening. After hearing a description of HPV vaccine, more than 80% would accept HPV vaccination; fathers and husbands were identified as primary decisions makers and local clinics or the home as preferred sites for vaccination. This study provides information on STI knowledge and vaccine acceptance in Bamako, Mali in 2012, prior to the introduction of HPV vaccination.

Prevalence of HPV 16 and 18 and attitudes toward HPV vaccination trials in patients with cervical cancer in Mali.

BACKGROUND: Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV) strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries. AIM: We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials. METHODS: Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire. RESULTS: HPV 16 and 18 were identified in 137/166 (82.5%) cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%). 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women. CONCLUSION: This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali.

Cost-effectiveness of maternal influenza immunization in Bamako, Mali: A decision analysis.

BACKGROUND: Maternal influenza immunization has gained traction as a strategy to diminish maternal and neonatal mortality. However, efforts to vaccinate pregnant women against influenza in developing countries will require substantial investment. We present cost-effectiveness estimates of maternal influenza immunization based on clinical trial data from Bamako, Mali. METHODS: We parameterized a decision-tree model using prospectively collected trial data on influenza incidence, vaccine efficacy, and direct and indirect influenza-related healthcare expenditures. Since clinical trial participants likely had better access to care than the general Malian population, we also simulated scenarios with poor access to care, including decreased healthcare resource utilization and worse influenza-related outcomes. RESULTS: Under base-case assumptions, a maternal influenza immunization program in Mali would cost $857 (95% UI: $188-$2358) per disability-adjusted life year (DALY) saved. Adjusting for poor access to care yielded a cost-effectiveness ratio of $486 (95% UI: $105-$1425) per DALY saved. Cost-effectiveness ratios were most sensitive to changes in the cost of a maternal vaccination program and to the proportion of laboratory-confirmed influenza among infants warranting hospitalization. Mean cost-effectiveness estimates fell below Mali's GDP per capita when the cost per pregnant woman vaccinated was $1.00 or less with no adjustment for access to care or $1.67 for those with poor access to care. Healthcare expenditures for lab-confirmed influenza were not significantly different than the cost of influenza-like illness. CONCLUSIONS: Maternal influenza immunization in Mali would be cost-effective in most settings if vaccine can be obtained, managed, and administered for ≤$1.00 per pregnant woman.

Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial.

BACKGROUND: Despite the heightened risk of serious influenza during infancy, vaccination is not recommended in infants younger than 6 months. We aimed to assess the safety, immunogenicity, and efficacy of maternal immunisation with trivalent inactivated influenza vaccine for protection of infants against a first episode of laboratory-confirmed influenza. METHODS: We did this prospective, active-controlled, observer-blind, randomised phase 4 trial at six referral centres and community health centres in Bamako, Mali. Third-trimester pregnant women (≥28 weeks' gestation) were randomly assigned (1:1), via a computer-generated, centre-specific list with alternate block sizes of six or 12, to receive either trivalent inactivated influenza vaccine or quadrivalent meningococcal vaccine. Study personnel administering vaccines were not masked to treatment allocation, but allocation was concealed from clinicians, laboratory personnel, and participants. Infants were visited weekly until age 6 months to detect influenza-like illness; laboratory-confirmed influenza diagnosed with RT-PCR. We assessed two coprimary objectives: vaccine efficacy against laboratory-confirmed influenza in infants born to women immunised any time prepartum (intention-to-treat population), and vaccine efficacy in infants born to women immunised at least 14 days prepartum (per-protocol population). The primary outcome was the occurrence of a first case of laboratory-confirmed influenza by age 6 months. This trial is registered with ClinicalTrials.gov, number NCT01430689. FINDINGS: We did this trial from Sept 12, 2011, to Jan 28, 2014. Between Sept 12, 2011, and April 18, 2013, we randomly assigned 4193 women to receive trivalent inactivated influenza vaccine (n=2108) or quadrivalent meningococcal vaccine (n=2085). There were 4105 livebirths; 1797 (87%) of 2064 infants in the trivalent inactivated influenza vaccine group and 1793 (88%) of 2041 infants in the quadrivalent meningococcal vaccine group were followed up until age 6 months. We recorded 5279 influenza-like illness episodes in 2789 (68%) infants, of which 131 (2%) episodes were laboratory-confirmed influenza. 129 (98%) cases of laboratory-confirmed influenza were first episodes (n=77 in the quadrivalent meningococcal vaccine group vs n=52 in the trivalent inactivated influenza vaccine group). In the intention-to-treat population, overall infant vaccine efficacy was 33·1% (95% CI 3·7-53·9); in the per-protocol population, vaccine efficacy was 37·3% (7·6-57·8). Vaccine efficacy remained robust during the first 4 months of follow-up (67·9% [95% CI 35·1-85·3] by intention to treat and 70·2% [35·7-87·6] by per protocol), before diminishing during the fifth month (57·3% [30·6-74·4] and 60·7 [33·8-77·5], respectively). Adverse event rates in women and infants were similar among groups. Pain at the injection site was more common in women given quadrivalent meningococcal vaccine than in those given trivalent inactivated influenza vaccine (n=253 vs n=132; p<0·0001), although 354 [92%] reactions were mild. Obstetrical and non-obstetrical serious adverse events were reported in 60 (3%) women in the quadrivalent meningococcal vaccine group and 61 (3%) women in the trivalent inactivated influenza vaccine group. Presumed neonatal infection was more common in infants in the trivalent inactivated influenza vaccine group than in those in the quadrivalent meningococcal vaccine group (n=60 vs n=37; p=0·02). No serious adverse events were related to vaccination. INTERPRETATION: Vaccination of pregnant women with trivalent inactivated influenza vaccine in Mali-a poorly resourced country with high infant mortality-was technically and logistically feasible and protected infants from laboratory-confirmed influenza for 4 months. With adequate financing to procure the vaccine, implementation will parallel the access to antenatal care and immunisation coverage of pregnant women with tetanus toxoid. FUNDING: Bill & Melinda Gates Foundation.

Background rates of adverse pregnancy outcomes for assessing the safety of maternal vaccine trials in sub-Saharan Africa.

BACKGROUND: Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa. METHODS: We developed a mathematical model that calculates a clinical trial's expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM), low birth weight (LBW), prematurity, and major congenital malformations (MCM) in Sub-Saharan African countries were also performed. FINDINGS: Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6-73.3) per 1,000 total births, and the most common causes were hemorrhage (34%), dystocia (22%), and severe hypertensive disorders of pregnancy (22%). Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9-16.4) or premature (median 15.4%, IQR: 10.6-19.1) were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5-17.6), with the musculoskeletal system comprising 30%. INTERPRETATION: Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that quantify population-based background rates of adverse pregnancy outcomes will improve safety assessment of interventions during pregnancy.

Maternal and neonatal outcomes of grand multiparas over two decades in Mali.

OBJECTIVE: To analyze the association between grand multiparity and maternal and neonatal morbidity and mortality. DESIGN: Retrospective cross-sectional study. SETTING: Point G National Hospital, a tertiary care hospital in Bamako, Mali. POPULATION: All singleton births from 1985 to 2003. METHODS: Cross-sectional study of 13 340 singleton births at a tertiary care hospital in Mali (1985-2003) compared outcomes between 3617 grand multiparas (para ≥5) and 9723 pauciparas (para 1-4). Odds ratios (OR) were adjusted for maternal age, prenatal care utilization, socioeconomic status, and region of origin. MAIN OUTCOME MEASURES: Maternal mortality, perinatal mortality, placental abnormalities (previa and abruption), uterine rupture, postpartum infection, postpartum hemorrhage, eclampsia, cesarean delivery, mean birthweight, low birthweight, high birthweight. RESULTS: Grand multiparas were older, poorer, and less likely to have accessed prenatal care. Grand multiparas had a lower adjusted odds of maternal death (adjusted OR, 0.66; 95%CI, 0.45-0.97), but higher adjusted odds of perinatal death (adjusted OR, 1.33; 95%CI, 1.12-1.59), placental abnormalities (adjusted OR, 1.57; 95%CI, 1.21-2.05), and high birthweight (adjusted OR, 1.42; 95%CI, 1.05-1.92). CONCLUSIONS: The healthy person effect may explain grand multiparas' lower odds of maternal death. Reducing grand multiparity and improving grand multiparas' access to prenatal care may improve population-level perinatal outcomes.

A 19-year retrospective investigation of maternal mortality at Point G National Hospital, Bamako, Mali.

OBJECTIVE: To determine the changes in maternal mortality rates over the 19-year period from 1985 to 2003 at Point G National Hospital, Bamako, Mali. METHODS: Data on all pregnant women admitted from January 1, 1985 to December 31, 2003 were collected from all hospital services. Records were entered into a database, and maternal mortality rates and cause-specific fatality rates were analyzed. RESULTS: Significant declines in the fatality rates due to uterine rupture (odds ratio [OR] 0.086; 95% confidence interval [CI], 0.011-0.70) and postpartum infection (OR 0.22; 95% CI, 0.085-0.55) were noted when the period from 1985-1987 was compared with 2001-2003. Overall, there was a significant reduction in the odds of maternal death in the period between 1985-1987 and 2001-2003 (OR 0.529; 95% CI, 0.341-0.821), when adjustments were made for cesarean delivery, complications, and patient age. CONCLUSIONS: Although the crude maternal mortality rate remained high, shifts in the patient population that led to more patients with complications being admitted masked improvements in the odds of death for obstetric patients.