High risk of lung cancer in surfactant-related gene variant carriers.

BACKGROUND: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers. METHODS: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers. RESULTS: We identified 99 SRG adult variant carriers (SFTPA1 (n=18), SFTPA2 (n=31), SFTPC (n=24), ABCA3 (n=14) and NKX2-1 (n=12)), including 20 (20.2%) with lung cancer (SFTPA1 (n=7), SFTPA2 (n=8), SFTPC (n=3), NKX2-1 (n=2) and ABCA3 (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01-1.08), smoking (OR 20.7, 95% CI 6.60-76.2) and SFTPA1/SFTPA2 variants (OR 3.97, 95% CI 1.39-13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 (95% CI 7.1-44.7). CONCLUSIONS: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated.

Characterization of novel mutations in the TEL-patch domain of the telomeric factor TPP1 associated with telomere biology disorders.

Telomeres are nucleoprotein structures that protect the chromosome ends from degradation and fusion. Telomerase is a ribonucleoprotein complex essential to maintain the length of telomeres. Germline defects that lead to short and/or dysfunctional telomeres cause telomere biology disorders (TBDs), a group of rare and heterogeneous Mendelian diseases including pulmonary fibrosis, dyskeratosis congenita, and Høyeraal-Hreidarsson syndrome. TPP1, a telomeric factor encoded by the gene ACD, recruits telomerase at telomere and stimulates its activity via its TEL-patch domain that directly interacts with TERT, the catalytic subunit of telomerase. TBDs due to TPP1 deficiency have been reported only in 11 individuals. We here report four unrelated individuals with a wide spectrum of TBD manifestations carrying either heterozygous or homozygous ACD variants consisting in the recurrent and previously described in-frame deletion of K170 (K170∆) and three novel missense mutations G179D, L184R, and E215V. Structural and functional analyses demonstrated that the four variants affect the TEL-patch domain of TPP1 and impair telomerase activity. In addition, we identified in the ACD gene several motifs associated with small deletion hotspots that could explain the recurrence of the K170∆ mutation. Finally, we detected in a subset of blood cells from one patient, a somatic TERT promoter-activating mutation that likely provides a selective advantage over non-modified cells, a phenomenon known as indirect somatic genetic rescue. Together, our results broaden the genetic and clinical spectrum of TPP1 deficiency and specify new residues in the TEL-patch domain that are crucial for length maintenance and stability of human telomeres in vivo.

Differential diagnosis of small hepatocellular nodules in cirrhosis: surrogate histological criteria of TERT promoter mutations.

AIMS: The differential diagnosis of small hepatocellular nodules in cirrhosis between dysplastic nodules and hepatocellular carcinoma (HCC) remains challenging on biopsy. As TERT promoter (pTERT) mutations may indicate the nodules already engaged in the malignant process, the aim of this study was to identify histological criteria associated with pTERT mutations by detecting these mutations by ddPCR in small formalin-fixed paraffin-embedded (FFPE) hepatocellular nodules arising in cirrhosis. METHODS AND RESULTS: We built a bicentric cohort data set of 339 hepatocellular nodules < 2 cm from cirrhotic samples, divided into a test cohort of 299 resected samples and a validation cohort of 40 biopsies. Pathological review, based on the evaluation of 14 histological criteria, classified all nodules. pTERT mutations were identified by ddPCR in FFPE samples. Among the 339 nodules, ddPCR revealed pTERT mutations in 105 cases (31%), including 90 and 15 cases in the test and validation cohorts, respectively. On multivariate analysis, three histological criteria were associated with pTERT mutations in the test cohort: increased cell density (P = 0.003), stromal invasion (P = 0.036) and plate-thickening anomalies (P < 0.001). With the combination of at least two of these major criteria, the AUC for predicting pTERT mutations was 0.84 in the test cohort (sensitivity: 86%, specificity: 83%) and 0.81 in the validation cohort (sensitivity: 87%, specificity: 76%). CONCLUSIONS: We identified three histological criteria as surrogate markers of pTERT mutations that may be used in routine biopsy to more clearly classify small hepatocellular nodules arising in cirrhosis.

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.

BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001). CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.

Meeting the reproductive health needs of female sex workers in Côte d'Ivoire: protecting the human right to dignified health.

The sexual and reproductive health needs of female sex workers (FSW) are often understudied and underserved in the context of HIV-related research in countries across Sub-Saharan Africa and West Africa. We assessed the lived experiences of FSW across Côte d'Ivoire to characterize unmet reproductive health needs and opportunities to address them. From February-August, 2020, ENDA Santé, Côte d'Ivoire conducted 75 in-depth interviews and 15 focus group discussions with FSW and community informants in five cities in Côte d'Ivoire. Themes that emerged included the inconsistent use of contraception services, a history of unintended pregnancies, and experiences of stigma at public healthcare facilities. Opportunities to increase the impact of both SRH and HIV services included strengthening existing HIV and family planning service integration for FSW. Taken together, the results highlight the importance of addressing the unmet reproductive health needs of FSW to both optimize the HIV response and increase the delivery of human-rights affirming sexual and reproductive health services for sex workers.

In Côte d'Ivoire, female sex workers (FSW) continue to have an unmet need for sexual and reproductive health (SRH) and HIV prevention services. The disproportionate burden of HIV/STIs is driven by several shared factors including behavioral, social, and structural determinants of HIV, STIs, and pregnancy; as well as biological efficiency of transmission of HIV in the context of STIs. This qualitative study examined the unmet SRH needs of FSW in 5 cities in Côte d'Ivoire to better understand how to offer integrated and high quality SRH and HIV programs and services. Working together with ENDA Santé Côte d'Ivoire, an organization that works closely with FSW, 75 in-depth interviews were held among FSW and community informants, and 15 focus group discussions with FSW. After analyzing the transcripts, several key themes emerged including use of contraceptive methods and unintended pregnancy, the experience of pregnancy and childbirth, HIV care access and quality, FSW-differentiated healthcare services and providers, and opportunities for service integration. The findings from this study underline gaps in the health system for FSW and the benefits of including SRH programming into routine HIV services to strengthen existing efforts.

Simplex Droplet Digital PCR Assays for the Detection of TERT Promoter Mutations in Urine Samples for the Non-invasive Diagnosis of Urothelial Cancer.

Somatic mutations in the telomerase reverse transcriptase (TERT) promoter region are highly frequent in urothelial cancer (UC), and their detection in urine (cell-free DNA from the urine supernatant or DNA from exfoliated cells in the urine pellet) has demonstrated promising evidence as putative non-invasive biomarkers for UC detection and monitoring. However, detecting these tumour-derived mutations in urine requires highly sensitive methods, capable of measuring low-allelic fraction mutations. We developed sensitive droplet digital PCR (ddPCR) assays for detecting urinary TERT promoter mutations (uTERTpm), targeting the two most common mutations (C228T and C250T), as well as the rare A161C, C228A, and CC242-243TT mutations. Here, we described the step-by-step protocol uTERTpm mutation screening using simplex ddPCR assays and give some recommendations for isolation of DNA from urine samples. We also provide limits of detection for the two most frequent mutations and discuss advantages of the method for clinical implementation of the assays for the detection and monitoring of UC.

Associations between punitive policies and legal barriers to consensual same-sex sexual acts and HIV among gay men and other men who have sex with men in sub-Saharan Africa: a multicountry, respondent-driven sampling survey.

BACKGROUND: Few assessments of associations between structural-level factors and HIV among gay men and other men who have sex with men (MSM) have been conducted, especially in sub-Saharan Africa. Our objective was to examine HIV testing history, HIV status, and stigmas among MSM living in ten countries with heterogeneous legal environments. METHODS: This study used pooled data from ten country-specific, cross-sectional studies done in 25 sites in Burkina Faso, Cameroon, Côte d'Ivoire, The Gambia, Guinea-Bissau, Nigeria, Senegal, Eswatini, Rwanda, and Togo. MSM were recruited by respondent-driven sampling and were eligible if they met country-specific requirements for age, area of residence, and self reported being assigned male sex at birth and having anal sex with a man in the past 12 months. Policy related to same-sex sexual behaviour for each country was categorised as not criminalised or criminalised. Countries were also categorised on the basis of recent reports of prosecutions related to same-sex sexual acts. Legal barriers were defined as those that legally prevented registration or operation of sexual orientation related civil society organisations (CSOs). Individual data on HIV testing history, HIV status, and stigma were collected via interviewer-administered sociobehavioural questionnaires and HIV testing. Multilevel logistic regression with random intercepts was used to assess the association between policies, recent prosecutions, legal barriers to CSOs, and HIV-related factors with adjusted odds ratios (aORs) and 95% CIs. FINDINGS: Between Aug 3, 2011, and May 27, 2020, we recruited 8047 MSM with a median age of 23 years (IQR 21-27). 4886 (60·7%) lived in countries that criminalise same-sex sexual acts. HIV prevalence among MSM was higher in criminalised settings than non-criminalised settings (aOR 5·15, 95% CI 1·12-23·57); higher in settings with recent prosecutions than in settings without prosecutions (12·06, 7·19-20·25); and higher in settings with barriers to CSOs than without barriers to CSOs (9·83, 2·00-48·30). HIV testing or status awareness was not associated with punitive policies or practices. Stigma was associated with HIV status but did not consistently vary across legal environments. Disparities in HIV prevalence between MSM and other adult men were highest in punitive settings. INTERPRETATION: Structural risks including discriminatory country-level policies, prosecutions, and legal barriers might contribute to higher HIV prevalence among MSM. Taken together, these data highlight the importance of decriminalisation and decreasing enforcement, alongside stigma reduction, as central to effective control for HIV. FUNDING: National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Genetics in Idiopathic Pulmonary Fibrosis: A Clinical Perspective.

BACKGROUND: Unraveling the genetic background in a significant proportion of patients with both sporadic and familial IPF provided new insights into the pathogenic pathways of pulmonary fibrosis. AIM: The aim of the present study is to overview the clinical significance of genetics in IPF. PERSPECTIVE: It is fascinating to realize the so-far underestimated but dynamically increasing impact that genetics has on aspects related to the pathophysiology, accurate and early diagnosis, and treatment and prevention of this devastating disease. Genetics in IPF have contributed as no other in unchaining the disease from the dogma of a "a sporadic entity of the elderly, limited to the lungs" and allowed all scientists, but mostly clinicians, all over the world to consider its many aspects and "faces" in all age groups, including its co-existence with several extra pulmonary conditions from cutaneous albinism to bone-marrow and liver failure. CONCLUSION: By providing additional evidence for unsuspected characteristics such as immunodeficiency, impaired mucus, and surfactant and telomere maintenance that very often co-exist through the interaction of common and rare genetic variants in the same patient, genetics have created a generous and pluralistic yet unifying platform that could lead to the understanding of the injurious and pro-fibrotic effects of many seemingly unrelated extrinsic and intrinsic offending factors. The same platform constantly instructs us about our limitations as well as about the heritability, the knowledge and the wisdom that is still missing.

TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region.

Bladder cancer (BC) is the 10th most common cancer in the world. While there are FDA-approved urinary assays to detect BC, none have demonstrated sufficient sensitivity and specificity to be integrated into clinical practice. Telomerase Reverse Transcriptase (TERT) gene mutations have been identified as the most common BC mutations that could potentially be used as non-invasive urinary biomarkers to detect BC. This study aims to evaluate the validity of these tests to detect BC in the Kerman province of Iran, where BC is the most common cancer in men. Urine samples of 31 patients with primary (n = 11) or recurrent (n = 20) bladder tumor and 50 controls were prospectively collected. Total urinary DNA was screened for the TERT promoter mutations (uTERTpm) by Droplet Digital PCR (ddPCR) assays. The performance characteristics of uTERTpm and the influence by disease stage and grade were compared to urine cytology results. The uTERTpm was 100% sensitive and 88% specific to detect primary BC, while it was 50% sensitive and 88% specific in detecting recurrent BC. The overall sensitivity and specificity of uTERTpm to detect bladder cancer were 67.7% and 88.0%, respectively, which were consistent across different tumor stages and grades. The most frequent uTERTpm mutations among BC cases were C228T (18/31), C250T (4/31), and C158A (1/31) with mutant allelic frequency (MAF) ranging from 0.2% to 63.3%. Urine cytology demonstrated a similar sensitivity (67.7%), but lower specificity (62.0%) than uTERTpm in detecting BC. Combined uTERTpm and urine cytology increased the sensitivity to 83.8%, but decreased the specificity to 52.0%. Our study demonstrated promising diagnostic accuracy for the uTERTpm as a non-invasive urinary biomarker to detect, in particular, primary BC in this population.

Clinical impact of TERT somatic mutation in telomerase-related gene mutation carriers after lung transplantation.

Almost 25% of patients with pulmonary fibrosis referred for lung transplantation have a germline rare variant of a telomere-related gene. Acquired TERT promoter mutations may counterbalanced the germline defect and reduce the risk of hematological complications in this population. In a series of 34 patients with a germline telomere-related gene mutation who underwent lung transplantation, 12 (35%) patients had at least 1 acquired TERT promoter mutation. Six patients presented myelodysplasia before lung transplantation, with no difference between patients with and without an acquired TERT promoter mutation. After lung transplantation, myelodysplasia developed in only 1 of 8 patients with an acquired TERT promoter mutation versus 7 of 18 patients without a mutation. Survival did not differ between patients with and without an acquired mutation. The presence of an acquired TERT promoter mutation could be associated with reduced hematological complications after transplantation and with better outcome in telomere-related gene mutation carriers but requires further study.

Interstitial lung diseases associated with mutations of poly(A)-specific ribonuclease: A multicentre retrospective study.

BACKGROUND AND OBJECTIVE: Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations. METHODS: We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network. RESULTS: We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation. CONCLUSION: IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.

Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study.

BACKGROUND: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability. PATIENTS AND METHODS: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. RESULTS: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. CONCLUSION: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse," complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized" medical care driven by genotypes in the near future.

Determinants of survival after lung transplantation in telomerase-related gene mutation carriers: A retrospective cohort.

Carriers of germline telomerase-related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n = 38; TERT, n = 23, TERC, n = 9, RTEL1, n = 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range [IQR] 46-59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow-up of 26 months (IQR 15-46), 38 patients received LT. The overall post-LT median survival was 3.75 years (IQR 1.8-NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 [95% CI 1.5-11.5]) or short telomere (HR 2.2 [1.0-5.0]) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT.

Disclosure of same-sex practices and experiences of healthcare stigma among cisgender men who have sex with men in five sub-Saharan African countries.

BACKGROUND: For men who have sex with men (MSM) across sub-Saharan Africa (SSA), disclosure of same-sex practices to family and healthcare workers (HCWs) can facilitate access to HIV prevention services and support, but can also lead to experiences of stigma. METHODS: We performed mixed-effects regressions on pooled data from MSM in Cameroon, Senegal, Côte d'Ivoire, Lesotho, and eSwatini to assess associations between disclosure and sexual behavior stigma in healthcare contexts; we used logistic regressions to analyze country-specific data. RESULTS: Compared to participants who had not disclosed to either family or HCWs, those who had disclosed only to family were more likely to have been gossiped about by HCWs (aOR = 1.70, CI = 1.18, 2.45); the association between having disclosed to family and having felt mistreated in a health center approached, but did not achieve, statistical significance (aOR = 1.56, CI = 0.94, 2.59). Those who had disclosed only to HCWs were more likely to have feared to seek health services (aOR = 1.60, CI = 1.14, 2.25), avoided health services (aOR = 1.74, CI = 1.22, 2.50), and felt mistreated in a health center (aOR = 2.62, CI = 1.43, 4.81). Those who had disclosed to both were more likely to have feared to seek health services (aOR = 1.71, CI = 1.16, 2.52), avoided health services (aOR = 1.59, CI = 1.04, 2.42), been gossiped about by HCWs (aOR = 3.78, CI = 2.38, 5.99), and felt mistreated in a health center (aOR = 3.39, CI = 1.86, 6.20). Country-specific analyses suggested that data from Cameroon drove several of these associations. CONCLUSIONS: Research to determine the factors driving disclosure's differential effect on healthcare stigma across contexts is needed. Ultimately, supportive environments enabling safe disclosure is critical to understanding HIV-acquisition risks and informing differentiated HIV-prevention, treatment, and testing services for MSM across SSA.

[Factors associated with scale-up human papillomavirus (HPV) vaccine in Senegal: a case-control survey of parents]. / Facteurs associés à la vaccination contre le virus du papillome humain dans un contexte de passage à l´échelle au Sénégal: enquête cas-témoins auprès des parents.

INTRODUCTION: after a pilot phase, Senegal is the first country in West Africa to introduce cervical cancer vaccine into its Expanded Program on Immunization. Despite the gratuity and availability of the vaccination, coverage was low. The purpose of this study was to identify factors associated with HPV vaccination coverage in girls . METHODS: we conducted a case-control analytical study from 4th to 20th January 2020 in Dakar. The study population consisted of parents or guardians of girls aged 9 to 10. We performed cluster sampling, direct structured interviews and a literature review. Socio-demographic features, parents/guardians' knowledges and information about vaccination procedure were collected using a standardized questionnaire. Logistic regression was used to estimate the odds ratio. RESULTS: during this study, 510 cases and 510 controls and 1020 parents/guardians were interviewed. Significant factors associated with vaccination of girls were: parents/guardians' education (OR=1,97; [1,81-2,25]), knowledge of the disease (OR=3,05; [2,75-4,53], high household income (OR=1,21; [1,13-1,85]), fear of side effects (OR=0,35;[ 0,27-0,44]), reception of messages via internet/social networks (OR=0,54; [0,41-0,92]) and vaccination schedules for the community (OR= 2,12 [1,59-2,64]). CONCLUSION: vaccination of girls can be improved by strengthening parents' knowledge through appropriate channels and a better organization of health services.

A large epidemic of a necrotic skin infection in the Democratic Republic of São Tomé and Principe: an epidemiological study.

INTRODUCTION: In 2016-18, the Democratic Republic of São Tomé and Príncipe suffered a necrotic skin infection epidemic. METHODS: A surveillance system was established after increased hospitalisations for this infection. Microbiology results were available for samples analysed in December 2016 and March 2017 using whole genome sequencing and metagenomics. Negative binomial regression was used to study the association of weather conditions with monthly case counts in a time-series analysis. RESULTS: From October 2016 to October 2018, the epidemic cumulative attack rate was 1.5%. The first peak lasted 5 months, accounting for one-third of total cases. We could not conclusively identify the aetiological agent(s) due to the country's lack of microbiology capacity. Increased relative humidity was associated with increased monthly cases (incidence rate ratio (IRR) 1.05, 95% CI 1.02-1.09), and higher precipitation in the previous month with a higher number of cases in the following month (months with 0-49 mm rainfall compared with months with 50-149 mm and ≥150 mm: IRR 1.44, 95 % CI 1.13-1.78 and 1.50, 95% CI 1.12-1.99, respectively). DISCUSSION: This epidemic was favoured by increased relative humidity and precipitation, potentially contributing to community-based transmission of ubiquitous bacterial strains superinfecting skin wounds. FUNDING: World Health Organization Regional Office for Africa, Ministry of Health.