Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Use of a mHealth System to Improve Antenatal Care in Low and Lower-Middle Income Countries: Report on Patients and Healthcare Workers' Acceptability in Tanzania.

Antenatal care (ANC) is considered a cornerstone of reproductive health programmes, but many women face difficulties in accessing these services, particularly in some sub-Saharan African countries, such as Tanzania. This study aimed to test ANC visit acceptability using mHealth system PANDA (Pregnancy And Newborn Diagnostic Assessment) in the Mufindi district (Tanzania). We investigated the ANC visit acceptability of pregnant women and healthcare workers (HCWs) in an intervention area using the PANDA system compared with a control area. An ad hoc questionnaire was administered to pregnant women in an implementation area (n = 52) and in a control area (n = 46). In the implementation area, group interviews with 50 pregnant women were conducted and five HCWs evaluated ANC visits through a questionnaire. The implementation group was significantly more satisfied with the ANC visit compared with the control group. All the 52 women and the HCWs declared that PANDA icons were useful in understanding and remembering the provided information and the PANDA app was able to improve the ANC quality and to positively influence the relationship of HCWs and pregnant women. HCWs reported that the PANDA app was "easy-to-use" and "able to improve the adherence to ANC WHO recommendations". In underserved areas, many pregnant women could benefit from the PANDA system increasing their access to high-quality ANC and overcoming language and/or literacy barriers.

2.5 Million Annual Deaths-Are Neonates in Low- and Middle-Income Countries Too Small to Be Seen? A Bottom-Up Overview on Neonatal Morbi-Mortality.

(1) Background: Every year, 2.5 million neonates die, mostly in low- and middle-income countries (LMIC), in total disregard of their fundamental human rights. Many of these deaths are preventable. For decades, the leading causes of neonatal mortality (prematurity, perinatal hypoxia, and infection) have been known, so why does neonatal mortality fail to diminish effectively? A bottom-up understanding of neonatal morbi-mortality and neonatal rights is essential to achieve adequate progress, and so is increased visibility. (2) Methods: We performed an overview on the leading causes of neonatal morbi-mortality and analyzed the key interventions to reduce it with a bottom-up approach: from the clinician in the field to the policy maker. (3) Results and Conclusions: Overall, more than half of neonatal deaths in LMIC are avoidable through established and well-known cost-effective interventions, good quality antenatal and intrapartum care, neonatal resuscitation, thermal care, nasal CPAP, infection control and prevention, and antibiotic stewardship. Implementing these requires education and training, particularly at the bottom of the healthcare pyramid, and advocacy at the highest levels of government for health policies supporting better newborn care. Moreover, to plan and follow interventions, better-quality data are paramount. For healthcare developments and improvement, neonates must be acknowledged as humans entitled to rights and freedoms, as stipulated by international law. Most importantly, they deserve more respectful care.

[Telemedicine in maternal health in times of COVID-19: Five national and international projects]. / Télémédecine en santé maternelle en temps de Covid-19 : cinq projets internationaux et nationaux.

Telemedicine in maternal health consists on the use of remote communication to reach, diagnose, treat and follow up patients in the context of pre and post-natal care. Covid-19 has accelerated the use of telemedicine. In the Obstetrics Division of HUG we have developed five projects in Geneva and in low-resource zones of the world with the objective of improving access and quality of care. Based on our experience, the application of telemedicine to maternal health problems has shown three major advantages: improved access to care, standardized procedures and accelerated speed of intervention. However, to be effective, telemedicine requires a health staff with a good level of medical and computer skills as well as fluid communication among all participants and constant follow-up of the information flow.

La télémédecine en santé maternelle consiste à l'utilisation des moyens de communication à distance pour rejoindre, diagnostiquer, traiter et suivre les patientes dans le contexte des soins pré-, per- et postnatals. Le Covid-19 a accéléré l'utilisation de la télémédecine. Dans le Service d'obstétrique des HUG, nous avons développé cinq projets à Genève et dans des régions défavorisées du monde, avec l'objectif d'améliorer l'accès et la qualité des soins. Basée sur notre expérience, l'application de la télémédecine aux problèmes de santé maternelle présente trois avantages essentiels: la facilitation de l'accès aux soins, la standardisation des procédures et la vitesse d'intervention. Mais pour être efficace, elle présuppose un bon niveau de compétence médicale et informatique du staff sanitaire, une communication fluide entre les différents intervenants et un contrôle constant du flux d'informations.

Adaptation and implementation of the WHO Safe Childbirth Checklist around the world.

BACKGROUND: The World Health Organization (WHO) published the WHO Safe Childbirth Checklist in 2015, which included the key evidence-based practices to prevent the major causes of maternal and neonatal morbidity and mortality during childbirth. We assessed the current use of the WHO Safe Childbirth Checklist (SCC) and adaptations regarding the SCC tool and implementation strategies in different contexts from Africa, Southeast Asia, Europe, and North America. METHODS: This explanatory, sequential mixed methods study-including surveys followed by interviews-of global SCC implementers focused on adaptation and implementation strategies, data collection, and desired improvements to support ongoing SCC use. We analyzed the survey results using descriptive statistics. In a subset of respondents, follow-up virtual semi-structured interviews explored how they adapted, implemented, and evaluated the SCC in their context. We used rapid inductive and deductive thematic analysis for the interviews. RESULTS: Of the 483 total potential participants, 65 (13.5%) responded to the survey; 55 completed the survey (11.4%). We analyzed completed responses from those who identified as having SCC implementation experience (n = 29, 52.7%). Twelve interviews were conducted and analyzed. Ninety percent of respondents indicated that they adapted the SCC tool, including adding clinical and operational items. Adaptations to structure included translation into local language, incorporation into a mobile app, and integration into medical records. Respondents reported variation in implementation strategies and data collection. The most common implementation strategies were meeting with stakeholders to secure buy-in, incorporating technical training, and providing supportive supervision or coaching around SCC use. Desired improvements included clarifying the purpose of the SCC, adding guidance on relevant clinical topics, refining items addressing behaviors with low adherence, and integrating contextual factors into decision-making. To improve implementation, participants desired political support to embed SCC into existing policies and ongoing clinical training and coaching. CONCLUSION: Additional adaptation and implementation guidance for the SCC would be helpful for stakeholders to sustain effective implementation.

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Description of Maternal Morbidities Amongst 1000 Women During Pregnancy in Ambanja, Madagascar - Opportunities and Challenges of Using an mHealth System.

BACKGROUND: The estimated burden of maternal morbidities in lower-income countries, such as Madagascar, is high. However, there is still a lack of data on maternal morbidities, in part due to an absence of standardized assessment tools. This cross-sectional study aims to report maternal morbidities among 1015 women in the district of Ambanja, Madagascar, and to describe the advantages and limitations of a mHealth system. METHODS: Data were collected using the PANDA (pregnancy and newborn diagnosis assessment) system, an mHealth device that incorporates the WHO recommendations for antenatal care (ANC). Data, including personal and medical information, but also clinical data such as hypertension, anemia or HIV were collected from more than 1000 women attending ANC. RESULTS: A total of 1015 pregnant women were recruited from January 2015 to August 2018. The average age was 24.6 years old, and most women were married (82.3%). The majority lived in urban areas and were unemployed. Prevalence of hypertension and gestational diabetes was relatively low (4% vs 2.2%). Malaria infection was diagnosed in 2.2% and HIV was diagnosed in 1.2% of pregnant women. The most common morbidity was anemia (68.4%) and the only significant factor associated was being single compared to being married (OR 1.68, 95% CI 1.05-2.70, p-value 0.032). DISCUSSION: The prevalence of anemia in our study population was much higher than previously reported in Sub-Saharan Africa. This finding highlights the need for regular iron supplementation during pregnancy, especially in vulnerable (eg, single) women. The PANDA mHealth system provides unique opportunities due to its standardization of ANC and creation of a digital database accessible from a distance. However, one of the main challenges was that even a mHealth system such as the PANDA remains dependent on the local procurement chain. Therefore, future studies need to access opportunities of mHealth systems to support health service delivery. TRIAL REGISTRATION: Registered on ISRCTN on 14th October 2015, number ISRCTN18270380. Retrospectively registered.

Improving the Quality of Antenatal Care Using Mobile Health in Madagascar: Five-Year Cross-Sectional Study.

BACKGROUND: Despite many efforts, maternal mortality remains a major burden in most developing countries. Mobile health (mHealth) has the potential to improve access to obstetric care through apps that help patients and providers. OBJECTIVE: This study aimed to use mHealth to provide antenatal care (ANC) to 1446 pregnant women in a rural area in Madagascar and evaluate the quality of ANC provided by an mHealth system designed to change the behaviors of providers and patients. METHODS: We included 1446 women who attended ANC visits in rural Madagascar from 2015 to 2019 using an mHealth system called Pregnancy and Newborn Diagnostic Assessment (PANDA). This cross-sectional study used data from different participants, with information collected over several years, to analyze the outputs related to the quality of ANC over time. Specifically, we examined the timing of the first ANC visit, the relationship between the visit duration and the risk factors among pregnant women, and the number of ANC visits per woman. RESULTS: Following the implementation of the mHealth system in 2015, we observed that women started to come earlier for their first ANC visit; more women attended their first ANC visit in the second trimester of pregnancy in 2019 than in the previous years (P<.001). In 2019, fewer women attended their first ANC visit in the third trimester (57/277, 20.6%) than in 2015 (147/343, 42.9%). There were statistically significant associations between the ANC visit durations and the risk factors, including age (>35 years; 25.0 min, 95% CI 24.0-25.9), educational level (longer visit for women with lower than primary education and for women who attended university and shorter for women with primary school-level education; 40.7 min, 95% CI 30.2-51.3 and 25.3 min, 95% CI 24.4-26.3 vs 23.3 min, 95% CI 22.9-23.8; P=.001), experience of domestic violence during pregnancy, gravidity, parity, infectious diseases (HIV, malaria, and syphilis), and level of anemia. Statistically significant associations were observed for all quality indicator variables. We observed a statistically significant increase in the number of ANC visits per woman over time from 2015 to 2017; the number of ANC visits per woman then became stable after the third year of implementing the PANDA mHealth system. CONCLUSIONS: This study shows the potential of an mHealth system to improve the quality of ANC, change provider behavior by standardizing ANC visits, and change patient behavior by increasing the willingness to return for subsequent visits and encouraging ANC attendance early in pregnancy. As this is an exploratory study, further studies are necessary to better understand how mHealth can change behavior and identify the conditions required for behavioral changes to persist over time.

Prognostic factors and long-term outcomes of obstetric fistula care using the Tanguiéta model.

OBJECTIVES: To identify factors influencing the long-term prognosis after surgical repair of obstetric fistula, establish a prognosis-based classification system, and examine changes in quality of life after surgery. METHODS: A retrospective study of 308 women who underwent obstetric fistula repair at Saint Jean de Dieu Hospital, Tanguiéta, Benin, between 2008 and 2016, and were supported by a multidisciplinary management model. All participants were from rural areas of Burkina Faso. The women completed interviews before, immediately after, and 2, 4-6, and 12 months after surgery to assess their clinical state and socioeconomic and psychologic status. RESULTS: Overall, the fistulae of 230/274 (83.9%) women were considered to be repaired after 12 months. Factors associated with poor repair outcome included the presence of sclerotic tissue (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.11-0.53) and intraoperative complications (OR, 0.16; 95% CI, 0.07-0.39). Women with successful surgery had a better quality of life as compared with women with an unrepaired fistula (Ditrovie score, 1.1 vs 3.9; P<0.001). CONCLUSION: The multidisciplinary Tanguiéta model for management of obstetric fistula allowed successful fistula closure, thereby facilitating the women's long-term social reintegration, and improved quality of life.

HPV self-testing for primary cervical cancer screening in Madagascar: VIA/VILI triage compliance in HPV-positive women.

OBJECTIVE: To assess triage compliance and the effect of the time from screening to triage on follow-up among HPV-positive women. METHODS: We recruited 1232 women in a screening campaign in Madagascar from February to October 2015. In the first period (February-May), HPV tests were performed remotely using the cobas test. In the second period (May-October), testing was performed on-site using the Xpert HPV assay. HPV-positive women were invited for triage with visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). Systematic biopsy and endocervical brushing were performed on all HPV-positive women for quality control. Three groups were defined according to time from HPV testing to triage invitation for HPV-positive women-Group I: delayed (> 3 months), Group II: prompt (24-48 hours), and Group III: immediate (< 24 hours). RESULTS: A total 1232 self-sampled HPV tests were performed in the study period (496 in Group I, 512 in Group II, and 224 in Group III). Participants' mean age was 43.2 ± 9.3 years. Mean time from screening to VIA/VILI testing was 103.5 ± 43.6 days. Overall HPV prevalence was 28.0%. HPV prevalence was 27.2% in Group I (cobas test), 29.2% in Group 2 (Xpert test), and 26,7% in Group III (Xpert test). The VIA/VILI compliance rate was 77.8% for Group I, 82.7% for Group II, and 95.0% for Group III. Of women undergoing VIA/VILI, 56.3% in Group I and 43.5% in Groups II/III had positive results. Prevalence of cervical intraepithelial neoplasia grade 2 or worse among HPV-positive women was 9.8% for Group I and 6.8% for Groups II/III. Non-adherence was higher among rural women, uneducated women, and women in Group I. CONCLUSION: HPV-positive women with immediate VIA/VILI triage invitation had the best triage compliance. A single-day test and triage strategy is preferred for low-resource settings.

A comparison of cotton and flocked swabs for vaginal self-sample collection.

OBJECTIVE: Vaginal self-sampling for human papillomavirus (HPV) testing has recently been proposed to optimize cervical cancer screening coverage. The objective of this study was to compare the performance of self-taken samples using flocked and cotton swabs for HPV detection and cellular retrieval. METHODS: We recruited women aged 21-65 years, referred to colposcopy at the Division of Gynecology of the Geneva University Hospitals between May and September 2016. Each participant collected 2 vaginal samples: 1 with a cotton swab and 1 with a flocked swab. A 1:1 randomization determined the order in which the 2 samples were taken. The swabs were introduced into a 20 mL PreservCyt® vial. Real-time polymerase chain reaction analysis using the Anyplex™ II HPV HR assay, cytofluorometric analysis and cytological cell counting were performed on each sample. RESULTS: A total of 119 participants were recruited in the study. Their mean ± standard deviation age was 35.1±8.9 years. The HPV prevalence was 29.7% and 38.1% according to the cotton and flocked swab, respectively (p=0.006). The mean number of cells collected per milliliter according to cytofluorometry was 96,726.6 with the cotton swab and 425,544.3 with the flocked swab (p<0.001). The mean number of cells detected at cytological cell count was 13,130.42 using the cotton swab and 17,503.6 using the flocked swab (p<0.001). CONCLUSION: The flocked swab achieved a greater cellular retrieval and showed an improved performance in HPV detection. Further studies are needed to assess the usability and cost-effectiveness of the 2 self-sampling devices.

Cross-sectional survey of knowledge of obstetric danger signs among women in rural Madagascar.

BACKGROUND: Antenatal care (ANC) has the potential to identify and manage obstetric complications, educate women about risks during pregnancy and promote skilled birth attendance during childbirth. The aim of this study was to assess women's knowledge of obstetric danger signs and factors associated with this knowledge in Ambanja, Madagascar. It also sought to evaluate whether the participation in a mobile health (mHealth) project that aimed to provide comprehensive ANC to pregnant women in remote areas influenced women's knowledge of obstetric danger signs. METHODS: From April to October 2015, a non-random, convenience sample of 372 women in their first year postpartum were recruited, including 161 who had participated in the mHealth project. Data were analyzed using bivariate and multivariate logistic regression. RESULTS: Knowledge of at least one danger sign varied from 80.9% of women knowing danger sign(s) in pregnancy, to 51.9%, 50.8% and 53.2% at delivery, postpartum and in the newborn, respectively. Participation in the mHealth intervention, higher household income, and receipt of information about danger signs during pregnancy were associated with knowledge of danger signs during delivery, in bivariate analysis; only higher household income and mHealth project participation were independently associated. Higher educational attainment and receipt of information about danger signs in antenatal care were associated with significantly higher odds of knowing danger sign(s) for the newborn in both bivariate and multivariate analysis. CONCLUSIONS: Knowledge of obstetric danger signs is low. Information provision during pregnancy and with mHealth is promising. TRIAL REGISTRATION: This trial was retrospectively registered at the International Standard Randomized Controlled Trial Register (identifier ISRCTN15798183 ; August 22, 2015).

An Innovative Mobile Health System to Improve and Standardize Antenatal Care Among Underserved Communities: A Feasibility Study in an Italian Hosting Center for Asylum Seekers.

Innovative migrant-friendly tools are needed to assist health personnel manage the high number of pregnancies within reception centers. This study tests functionality and acceptability of a new mHealth system in providing antenatal care amongst migrants. The study, carried out between 2014 and 2016, involved 150 pregnant women residing in the largest European migrant reception center in Sicily. A ticket tracking system assessed the system's functionality and a questionnaire assessed women's acceptability. The system facilitated the collection of clinical data, enabling the creation of electronic patient records and identifying 10% of pregnancies as high-risk. The application's digital format increased health providers' adherence to antenatal-care recommendations, while the graphic interface facilitated women's engagement and retention of the health education modules. The study recorded a 91.9% patient satisfaction rate. The system was efficient in providing comprehensive and high-quality antenatal care amongst migrants, facilitating the continuity of care for a population undergoing frequent relocations.

Efficacy of thermoablation in treating cervical precancerous lesions in a low-resource setting.

INTRODUCTION: Treating cervical intraepithelial neoplasia (CIN) grades 2 and 3 is the recommended strategy for preventing invasive carcinoma in low- and middle-income countries (LMICs). Our objective was to assess the efficacy of thermoablation in the treatment of CIN2 and CIN3 in a screen-and-treat approach. METHODS: Women aged 30-49 years in Dschang, Cameroon, were invited to undergo vaginal sampling for human papillomavirus (HPV), samples being assessed by an Xpert HPV Assay. HPV-positive women underwent visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), cervical biopsy, and endocervical curettage. Women positive for HPV-16/18/45 or other HPV types with abnormal VIA/VILI were treated by thermoablation on the same day. The primary outcome was persistence of high-grade disease on cytologic examination at 12 months. RESULTS: Of a total of 1,012 recruited women, 188 were HPV-positive, 121 patients required thermoablation, and 99 had a CIN of grade <2, making the overtreatment rate 9.9%. The cure rate for CIN2 and CIN3 at 12 months was 70.6%. Failure (higher risk of persistent disease) was associated with the presence of occult endocervical lesions at baseline diagnosis (adjusted odds ratio [aOR] =128.97 [95% confidence interval [CI], 8.80-1,890.95]; p<0.0001). First sexual intercourse before the age of 15 was also a risk factor (aOR =0.003 [95% CI, 0.001-0.61]; p=0.023). CONCLUSION: In LMICs, use of thermoablation in a screen-and-treat approach is a valuable treatment option for CIN2 and CIN3. Studies comparing thermoablation with cryotherapy are needed to determine the most appropriate treatment for cervical precancer in such countries.

Cervical cancer screening in low-resource settings: a smartphone image application as an alternative to colposcopy.

BACKGROUND: Visual inspection after application of acetic acid (VIA) and Lugol's iodine (VILI) is a cervical cancer (CC) screening approach that has recently been adopted in low- and middle-income countries (LMIC). Innovative technologies allow the acquisition of consecutive cervical images of VIA and VILI using a smartphone application. The aim of this study was to evaluate the quality of smartphone images in order to assess the feasibility and usability of a mobile application for CC screening in LMIC. METHODS: Between May and November 2015, women aged 30-65 years were recruited in a CC screening campaign in Madagascar. Human papillomavirus-positive women were invited to undergo VIA/VILI assessment. Pictures of their cervix were taken using a Samsung Galaxy S5 with an application called "Exam", which was designed to obtain high-quality images and to classify them in the following sequence: native, VIA, VILI and posttreatment. Experts in colposcopy were asked to evaluate if the quality of the pictures was sufficient to establish the diagnosis and to assess sharpness, focus and zoom. RESULTS: The application use was simple and intuitive, and 208 pictures were automatically classified and recorded in the patient's file. The quality was judged as adequate for diagnosis in 93.3% of cases. The interobserver agreement was κ =0.45 (0.23-0.58), corresponding to a moderate agreement on the common scale of kappa values. CONCLUSION: This smartphone application allows the acquisition of good quality images for VIA/VILI diagnosis. The classification of images in a patient database makes them accessible to on- and off-site experts, and allows continuous clinical education. Smartphone applications may offer an alternative to colposcopy for CC screening in LMIC.

A Smartphone-Based Approach for Triage of Human Papillomavirus-Positive Sub-Saharan African Women: A Prospective Study.

BACKGROUND: Sub-Saharan African countries are marked by a high incidence of cervical cancer. Madagascar ranks 11th among the countries with the highest cervical cancer incidence worldwide. OBJECTIVE: The aim of the study was to evaluate the performances of digital smartphone-based visual inspection with acetic acid (D-VIA) and Lugol's iodine (D-VILI) for diagnosing cervical precancer and cancer. METHODS: Human papillomavirus (HPV)-positive women recruited through a cervical screening campaign had D-VIA and D-VILI examinations with endocervical curettage (ECC) and cervical biopsy. Three images were captured for each woman (native, D-VIA, D-VILI) using a smartphone camera. The images were randomly coded and distributed on 2 online databases (Google Forms). The D-VIA form included native and D-VIA images, and the D-VILI form included native and D-VILI images. Pathological cases were defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Physicians rated the images as non-pathological or pathological. Using the ECC and cervical biopsy results as references, the sensitivity and specificity of D-VIA and D-VILI examinations for each and all physicians were calculated. RESULTS: Altogether, 15 clinicians assessed 240 images. Sensitivity was higher for the D-VIA interpretations (94.1%; 95% CI 81.6-98.3) than for the D-VILI interpretations (78.8%; 95% CI 54.1-92.1; P=.009). In contrast, the specificity was higher for the D-VILI interpretations (56.4%; 95% CI 38.3-72.9) than for the D-VIA interpretations (50.4%; 95% CI 35.9-64.8; P=.005). CONCLUSION: Smartphone-based image for triage of HPV-positive women is more accurate for detecting CIN2+ lesions with D-VIA than D-VILI, although with a small loss of specificity.

Feasibility of thermocoagulation in a screen-and-treat approach for the treatment of cervical precancerous lesions in sub-Saharan Africa.

BACKGROUND: The use of thermocoagulation for the treatment of cervical precancerous lesions has recently generated a great deal of interest. Our aim was to determine the feasibility of this outpatient procedure in the context of a cervical cancer (CC) screen-and-treat campaign in sub-Saharan Africa. METHODS: Between July and December 2015, women living in the area of Dschang (Cameroon) aged between 30 and 49 years, were enrolled in a CC screening study. HPV self-sampling was performed as a primary screening test and women who were either "HPV 16/18/45-positive" or "positive to other HPV types and to VIA" were considered screen-positive, thus requiring further management. The primary outcome was the percentage of screen-positive patients who met the criteria to undergo thermocoagulation. The secondary outcome was the assessment of the procedure's side effects immediately after treatment and at the 1-month follow-up visit. RESULTS: A total of 1012 women were recruited in the study period. Among 121 screen-positive women, 110 of them (90.9%) were eligible to be treated with thermocoagulation. No patients discontinued treatment because of pain or other side effects. The mean ± SD (Standard Deviation) score measured on the 10-point Visual Analogue Scale (VAS) was 3.0 ± 1.6. Women having less than 2 children were more likely to report a higher pain score than those with more than two (4.2 ± 2.0 versus 2.9 ± 1.5, respectively; p value = 0.016). A total of 109/110 (99.1%) patients came to the 1-month follow-up visit. Vaginal discharge was reported in 108/109 (99.1%) patients throughout the month following treatment. Three patients (2.8%) developed vaginal infection requiring local antibiotics. No hospitalizations were required. CONCLUSION: The majority of screen-positive women met the criteria and could be treated by thermocoagulation. The procedure was associated to minor side effects and is overall feasible in the context of a CC screen-and-treat campaign in sub-Saharan Africa. TRIAL REGISTRATION: The trial was retrospectively registered on November 11, 2015 with the identifier: ISRCTN99459678 .

Usability and feasibility of a mobile health system to provide comprehensive antenatal care in low-income countries: PANDA mHealth pilot study in Madagascar.

Background Madagascar's maternal health mortality ratio in 2013 was 478 deaths per 100,000 live births. Most deaths are related to direct complications during pregnancy and childbirth and could be reduced by providing comprehensive antenatal care (ANC). Objective The objective of the study was to assess the usability and feasibility of a mobile health system (mHealth) to provide high-quality ANC, according to World Health Organization (WHO) recommendations. Methods PANDA (Pregnancy And Newborn Diagnostic Assessment) is an easy-to-use mHealth system that uses affordable communications technology to support diagnosis and health care worker decision-making regarding ANC. From January to March 2015, a cross-sectional pilot study was conducted in Ambanja District, Madagascar, in which ANC using PANDA was provided to 100 pregnant women. The collected data were transmitted to a database in the referral hospital to create individual electronic patient records. Accuracy and completeness of the data were closely controlled. The PANDA software was assessed and the number of abnormal results, treatments performed, and participants requiring referral to health care facilities were monitored. Results The PANDA system facilitated creation of individual electronic patient records that included socio-demographic and medical data for 100 participants. Duration of ANC visits averaged 29.6 min. Health care providers were able to collect all variables (100%) describing personal and medical data. No major technical problems were encountered and no data were lost. During 17 ANC visits (17%), an alert function was generated to highlight abnormal clinical results requiring therapy or referral to an affiliated hospital. Participants' acceptability of the system was very high. Conclusion This pilot study proved the usability and feasibility of the PANDA mHealth system to conduct complete and standardised ANC visits according to WHO guidelines, thus providing a promising solution to increase access to high-quality and standardised ANC for pregnant women in remote areas.

Human papillomavirus prevalence and type-specific distribution of high- and low-risk genotypes among Malagasy women living in urban and rural areas.

BACKGROUND: Cervical cancer (CC) is the most common cancer among sub-Saharan African women. Efficient, global reduction of CC will only be achieved by incorporation of human papillomavirus (HPV) vaccination into existing programmes. We aimed to investigate the overall and type-specific prevalences and distributions of oncogenic HPVs. METHODS: A total of 1081 women aged 30-65 years were recruited to three sequential studies in Madagascar. Demographic and historical data were obtained from participants, and specimens were self-collected for HPV testing using real-time polymerase chain reaction. HPV-positive women underwent detailed pelvic examination, visual inspection of the cervix with acetic acid, biopsy, and endocervical curettage. Data were analysed using χ(2) and t-tests, and logistic regression. RESULTS: The prevalence of all 19 high-risk types of HPV was 39.3%. There were no differences in the prevalences of HPV and CC between rural and urban Malagasy women. The most common high-risk HPV types were HPV-53 (6.2%) and HPV-68 (5.8%), followed by HPV-52 (5.2%), HPV-35 (4.5%), HPV-73 (3.4%), HPV-31 (3.4%), HPV-16 (3.1%), and HPV-18 (3.1%). The prevalence of cervical intraepithelial neoplasia≥grade 2 (CIN2+) was 9.4%. CIN1-CIN3 lesions were more common in women in their 30s. The median age of participants with CIN2+ was 44 years (range 37-55). Overall, 25.8% of CIN2+ cases were associated with HPV-16/18. CONCLUSIONS: This study provides evidence to support the introduction of HPV vaccination in eastern African countries such as Madagascar. Further studies are needed to screen younger women and adolescents, to provide a global vision of HPV genotype distributions and to maximize the impact of HPV vaccination.