Cluster randomised trial of a health system strengthening approach applying person-centred communication for the prevention of female genital mutilation in Guinea, Kenya and Somalia.

INTRODUCTION: There is limited evidence on effective health systems interventions for preventing female genital mutilation (FGM). This study tested a two-level intervention package at primary care applying person-centred communication (PCC) for FGM prevention. METHODS: A cluster randomised trial was conducted in 2020-2021 in 180 antenatal care (ANC) clinics in Guinea, Kenya and Somalia. At baseline, all clinics received guidance and materials on FGM prevention and care; at month 3, ANC providers at intervention sites received PCC training. Data were collected from clinic managers, ANC providers and clients at baseline, month 3 and month 6 on primary outcomes, including delivery of PCC counselling, utilisation of level one materials, health facility preparedness for FGM prevention and care services and secondary outcomes related to clients' and providers' knowledge and attitudes. Data were analysed using multilevel and single-level logistic regression models. RESULTS: Providers in the intervention arm were more likely to deliver PCC for FGM prevention compared with those in the control arm, including inquiring about clients' FGM status (adjusted OR (AOR): 8.9, 95% CI: 6.9 to 11.5; p<0.001) and FGM-related beliefs (AOR: 9.7, 95% CI: 7.5 to 12.5; p<0.001) and discussing why (AOR: 9.2, 95% CI: 7.1 to 11.9; p<0.001) or how (AOR: 7.7, 95% CI: 6.0 to 9.9; p<0.001) FGM should be prevented. They were more confident in their FGM-related knowledge (AOR: 7.0, 95% CI: 1.5 to 32.3; p=0.012) and communication skills (AOR: 1.8; 95% CI: 1.0 to 3.2; p=0.035). Intervention clients were less supportive of FGM (AOR: 5.4, 95% CI: 2.4 to 12.4; p<0.001) and had lower intentions of having their daughters undergo FGM (AOR: 0.3, 95% CI: 0.1 to 0.7; p=0.004) or seeking medicalised FGM (AOR: 0.2, 95% CI: 0.1 to 0.5; p<0.001) compared with those in the control arm. CONCLUSION: This is the first study to provide evidence of an effective FGM prevention intervention that can be delivered in primary care settings in high-prevalence countries. TRIAL REGISTRATION AND DATE: PACTR201906696419769 (3 June 2019).

Prevalence and factors associated with overweight in children under 5 years in West African countries.

Background: Overweight is a risk factor for non-communicable diseases and is affecting an increasing number of children worldwide. The objective of this study was to measure the prevalence and related factors to overweight among children under 5 years in five West African countries. Methods: This study was a secondary analysis of nationally representative cross-sectional data. These data were drawn from Demographic and Health Surveys (DHS) from five countries in the West African region (Benin, Guinea, Mali, Nigeria, and Togo) from 2015 to 2018.Continuous quantitative data were categorized and all analyses were weighted according to the probability that each participant was selected in the sample. Children under 5 years of age were the study population. Multilevel logistic regression was used with Stata 16.0 software. Results: The total sample size for the analysis was 38,657 children. The pooled prevalence of overweight among children under 5 years of age in the five countries was 3%. Guinea had the highest prevalence (6%) compared to the other countries, which had a prevalence of 2%. The likelihood of being overweight was higher among children aged 0-6 months (adjusted odds ratio [AOR] = 3.09; 95% confidence interval [CI] [2.41-3.95]), who had a high birth height (AOR = 1.64; 95% CI [1.29-2.09]), whose mothers were overweight (AOR = 1.35; 95% CI [1.09-1.68]), who lived in households with fewer than five members (AOR = 1.19; 95% CI [1.00-1.46]), or who lived in Guinea (AOR = 2.79; 95% CI [1.62-4.79]). Conclusion: This study showed that overweight concerns few children under 5 years of age in West Africa. However, it does exist, and its prevalence could likely increase if its modifiable factors (maternal overweight, household size, and height at birth) are not taken into account in nutritional interventions.

Disruption of the Expression of the Placental Clock and Melatonin Genes in Preeclampsia.

Circadian rhythms have been described in numerous tissues of living organisms and are necessary for homeostasis. The understanding of their role in normal and pathological pregnancy is only just emerging. It has been established that clock genes are expressed in the placenta of animals and humans, but the rhythmicity of placenta immune cells is not known. Macrophages from healthy placenta of women at term were isolated and the expression of clock genes BMAL1, CLOCK, PER2, CRY2, and NR1D1 was assessed by qRT-PCR every 4 h over 24 h. Raw data were treated with cosinor analysis to evaluate the significance of the oscillations. Placental macrophages exhibited significant circadian expression of clock genes but one third of placental macrophages lost clock gene rhythmicity; the clock gene oscillations were restored by co-culture with trophoblasts. We wondered if melatonin, a key hormone regulating circadian rhythm, was involved in the oscillations of placental cells. We showed that macrophages and trophoblasts produced melatonin and expressed MT2 receptor. In women who developed preeclampsia during pregnancy, circadian oscillations of placental macrophages were lost and could not be rescued by coculture with trophoblasts from healthy women. Moreover, production and oscillations of melatonin were altered in preeclamptic macrophages. For the first time to our knowledge, this study shows circadian rhythms and melatonin production by placental macrophages. It also shows that preeclampsia is associated with a disruption of the circadian rhythm of placental cells. These results represent a new scientific breakthrough that may contribute to the prevention and treatment of obstetrical pathologies.

Involving the health sector in the prevention and care of female genital mutilation: results from formative research in Guinea.

BACKGROUND: Despite efforts to reduce the burden of female genital mutilation (FGM) in Guinea, the practice remains prevalent, and health care providers are increasingly being implicated in its medicalization. This formative study was conducted to understand the factors that facilitate or impede the health sector in providing FGM prevention and care services to inform the development of health sector-based interventions. METHODS: Between April and May 2018, a mixed methods formative study was carried out using a rapid assessment methodology in three regions of Guinea-Faranah, Labe and Conakry. A structured questionnaire was completed by one hundred and fifty health care providers of different cadres and 37 semi-structured interviews were conducted with health care providers, women seeking services at public health clinics and key stakeholders, including health systems managers, heads of professional associations and schools of nursing, midwifery, and medicine as well as representatives of the Ministry of Health. Eleven focus group discussions were conducted with female and male community members. RESULTS: This study revealed health systems factors, attitudinal factors held by health care providers, and other factors, that may not only promote FGM medicalization but also impede a comprehensive health sector response. Our findings confirm that there is currently no standardized pre-service training on how to assess, document and manage complications of FGM nor are there interventions to promote the prevention of the practice within the health sector. This research also demonstrates the deeply held beliefs of health care providers and community members that perpetuate this practice, and which need to be addressed as part of a health sector approach to FGM prevention. CONCLUSION: As integral members of FGM practicing communities, health care providers understand community beliefs and norms, making them potential change agents. The health sector can support them by incorporating FGM content into their clinical training, ensuring accountability to legal and policy standards, and promoting FGM abandonment as part of a multi-sectoral approach. The findings from this formative research have informed the development of a health sector intervention that is being field tested as part of a multi-country implementation research study in Guinea, Kenya, and Somalia.

Despite the implementation of various interventions to prevent female genital mutilation (FGM), it is still widely practiced in Guinea, and health care providers are increasingly being implicated in the practice. We conducted research in three regions of Guinea, namely, Faranah, Labe and Conakry, to understand factors that might be addressed to strengthen the role of the health sector in prevention and care of women and girls who have undergone FGM. Our findings highlight the need to strengthen the capacity of health care providers to be able to identify cases of FGM and manage complications. The study also highlights the importance of engaging health care providers in efforts to prevent FGM, which will require that any trainings include an opportunity to discuss their own values and beliefs around FGM so that they are better equipped to communicate with their clients and patients in a sensitive and non-judgmental manner, whether during consultation visits or community health outreach activities. The results of this research have informed the development of a health system strengthening intervention package for the prevention and care of FGM, which is being tested in Kenya, Somalia, and Guinea.

RadA, a Key Gene of the Circadian Rhythm of Escherichia coli.

Circadian rhythms are present in almost all living organisms, and their activity relies on molecular clocks. In prokaryotes, a functional molecular clock has been defined only in cyanobacteria. Here, we investigated the presence of circadian rhythms in non-cyanobacterial prokaryotes. The bioinformatic approach was used to identify a homologue of KaiC (circadian gene in cyanobacteria) in Escherichia coli. Then, strains of E. coli (wild type and mutants) were grown on blood agar, and sampling was made every 3 h for 24 h at constant conditions. Gene expression was determined by qRT-PCR, and the rhythmicity was analyzed using the Cosinor model. We identified RadA as a KaiC homologue in E. coli. Expression of radA showed a circadian rhythm persisting at least 3 days, with a peak in the morning. The circadian expression of other E. coli genes was also observed. Gene circadian oscillations were lost in radA mutants of E. coli. This study provides evidence of molecular clock gene expression in E. coli with a circadian rhythm. Such a finding paves the way for new perspectives in antibacterial treatment.

Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3.

Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.

The direct cost of dialysis supported by families for patients with chronic renal failure in Ouagadougou (Burkina Faso).

BACKGROUND: Chronic renal failure can lead to dialysis and/or a kidney transplant in the final stage. The number of patients under dialysis has increased considerably in the world and particularly in sub-Saharan Africa. Dialysis is a very expensive care. This is the reason why this study on the costs of dialysis management was initiated in Burkina Faso. The objective of the study is to determine the direct medical and non-medical costs of managing chronic renal failure among dialysis patients in Ouagadougou in 2020. METHODS: An analytical cross-sectional study was conducted. Data were collected in the hemodialysis department of three public university hospitals in Ouagadougou, Burkina Faso. All dialysis patients with chronic renal failure were included in the study. Linear regression was used to investigate the determinants of the direct medical and non-medical cost of hemodialysis. RESULTS: A total of 290 patients participated in this study, including children, adults, and the elderly with extremes of 12 and 82 years. Almost half of the patients (47.5%) had no income. The average monthly total direct cost across all patients was 75842 CFA or US$134.41.The average direct medical cost was 51315 CFA or US$90.94 and the average direct non-medical cost was 24 527 CFA or US$43.47. Most of the patients (45.2%) funded their hemodialysis by their own source. The multivariate analysis showed that the presence of an accompanying person during treatment, residing in a rural area, ambulatory care, use of personal cars, and treatment at the dialysis center of Yalgado Teaching Hospital were associated with higher direct costs. CONCLUSION: The average cost of dialysis services borne by the patient and his family is very high in Burkina Faso, since it is 2.1 times higher than the country's minimum interprofessional wage (34664 CFA or US$61.4). It appears that the precariousness of the means of subsistence increases strongly with the onset of chronic renal failure requiring dialysis. Thus, to alleviate the expenses borne by dialysis patients, it would be important to extend the government subsidy scheme to the cost of drugs and to promote health insurance to ensure equitable care for these patients.

Stakeholders' perceptions on improving women's health after obstetric fistula repair: results from a qualitative study in Guinea.

The holistic care of obstetric fistula remains a significant public health concern in developing countries. Improving women's outcomes after repair requires perspectives on post-surgical period within which women have to fulfil their social roles and expectations, mainly becoming pregnant, cooking, resuming farming activities or sexual intercourse. Our objective was to explore stakeholders' perceptions of women's health and well-being after fistula repair, and their perspectives on strategies for improving their quality of life in Guinea. A qualitative study involving representatives from the Ministry of Health, regional, district and hospital managers, representatives of NGOs and funding bodies, local leaders, women who underwent fistula surgery and their relatives (husbands, family members), health providers and community health workers at different levels was conducted. Thematic analysis was performed using NVivo software. Overall, 41 in-depth interviews and seven focus group discussions were conducted with 83 various stakeholders. Unanimously, respondents perceived women treated for obstetric fistula are "diminished" and "vulnerable". This "vulnerability" encompasses physical, socio-emotional and economic dimensions. The high risk of maternal and neonatal complications such as fistula recurrence, abortion or stillbirth in these women was mentioned. Stakeholders emphasized the need for a multidisciplinary approach to improve women's health after repair. Social support, economic empowerment and medical follow-up were identified as key components to mitigate women's vulnerability for successful post-repair reintegration. The programmatic level in Guinea should consider women's health after fistula repair a vital component of the holistic fistula care.

Effectiveness of the World Health Organization Safe Childbirth Checklist (WHO-SCC) in preventing poor childbirth outcomes: a study protocol for a matched-pair cluster randomized control trial.

BACKGROUND: Women delivering in health facilities in sub-Saharan Africa and their newborns do not always receive proven interventions needed to prevent and/or adequately manage severe complications. The gaps in quality of care are increasingly pointed out as major contributing factor to the high and slow declining perinatal mortality rates. The World Health Organization Safe Childbirth Checklist (WHO-SCC), as a quality improvement strategy, targets low cost and easy to perform interventions and suits well with the context of limited resource settings. In this matched-pair cluster randomized controlled trial, we assess the effectiveness of the WHO-SCC in improving healthcare providers' adherence to best practices and ultimately improving childbirth outcomes. METHODS: This is a multi-country study. In each country we will carry out a matched-pair cluster randomized controlled trial whereby four pairs of regional hospitals will be randomized on a 1:1 basis to either the intervention or control group. A context specific WHO-SCC will be implemented in the intervention facilities along with trainings of healthcare providers on best childbirth practices and ongoing supportive supervisions. The standard of care will prevail in the control group. The primary outcome is a summary composite metric that combine the following poor childbirth outcomes: stillbirths, maternal deaths, early neonatal deaths, severe postpartum hemorrhage, maternal infections, early neonatal infections, prolonged obstructed labor, severe pre-eclampsia, uterine rupture in the health facility, eclampsia and maternal near miss. The occurrence of these outcomes will be ascertained in a sample of 2530 childbirth events in each country using data extraction. A secondary outcome of interest is the adherence of healthcare providers to evidence best practices. This will be measured through direct observations of a sample of 620 childbirth events in each country. DISCUSSION: Our study has the potential to provide strong evidence on the effectiveness of the WHO-SCC, a low cost and easy to implement intervention that can be easily scaled up if found effective. TRIAL REGISTRATION: The trial was registered in the Pan-African Clinical Trials Registry on 21st January 2020 under the following number: PACTR202001484669907. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9662.

Learning Ordinal Embedding from Sets.

Ordinal embedding is the task of computing a meaningful multidimensional representation of objects, for which only qualitative constraints on their distance functions are known. In particular, we consider comparisons of the form "Which object from the pair (j,k) is more similar to object i?". In this paper, we generalize this framework to the case where the ordinal constraints are not given at the level of individual points, but at the level of sets, and propose a distributional triplet embedding approach in a scalable learning framework. We show that the query complexity of our approach is on par with the single-item approach. Without having access to features of the items to be embedded, we show the applicability of our model on toy datasets for the task of reconstruction and demonstrate the validity of the obtained embeddings in experiments on synthetic and real-world datasets.

Daytime variation in SARS-CoV-2 infection and cytokine production.

S. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of the coronavirus disease (Covid-19). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection of isolated human monocytes, key actor cells in Covid-19 disease, from healthy subjects. The circadian gene expression of BMAL1 and CLOCK genes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6, IL-1ß and IL-10 levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed that BMAL1 and CLOCK transcripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Circadian Time (CT)6 and CT17. After 48 h, the amount of SARS-CoV-2 virus increased in the monocyte infected at CT6 compared to CT17. The high virus amount at CT6 was associated with significant increased release in IL-6, IL-1ß and IL-10 compared to CT17. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.

Monocytes and Macrophages, Targets of Severe Acute Respiratory Syndrome Coronavirus 2: The Clue for Coronavirus Disease 2019 Immunoparalysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) clinical expression is pleiomorphic, severity is related to age and comorbidities such as diabetes and hypertension, and pathophysiology involves aberrant immune activation and lymphopenia. We wondered if the myeloid compartment was affected during COVID-19 and if monocytes and macrophages could be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Monocytes and monocyte-derived macrophages (MDMs) from COVID-19 patients and controls were infected with SARS-CoV-2 and extensively investigated with immunofluorescence, viral RNA extraction and quantification, and total RNA extraction followed by reverse-transcription quantitative polymerase chain reaction using specific primers, supernatant cytokines (interleukins 6, 10, and 1ß; interferon-ß; transforming growth factor-ß1, and tumor necrosis factor-α), and flow cytometry. The effect of M1- vs M2-type or no polarization prior to infection was assessed. RESULTS: SARS-CoV-2 efficiently infected monocytes and MDMs, but their infection is abortive. Infection was associated with immunoregulatory cytokines secretion and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In vitro polarization did not account for permissivity to SARS-CoV-2, since M1- and M2-type MDMs were similarly infected. In COVID-19 patients, monocytes exhibited lower counts affecting all subsets, decreased expression of HLA-DR, and increased expression of CD163, irrespective of severity. CONCLUSIONS: SARS-CoV-2 drives monocytes and macrophages to induce host immunoparalysis for the benefit of COVID-19 progression.SARS-CoV-2 infection of macrophages induces a specific M2 transcriptional program. In Covid-19 patients, monocyte subsets were decreased associated with up-expression of the immunoregulatory molecule CD163 suggesting that SARS-CoV-2 drives immune system for the benefit of Covid-19 disease progression.

A Tangled Threesome: Circadian Rhythm, Body Temperature Variations, and the Immune System.

The circadian rhythm of the body temperature (CRBT) is a marker of the central biological clock that results from multiple complex biological processes. In mammals, including humans, the body temperature displays a strict circadian rhythm and has to be maintained within a narrow range to allow optimal physiological functions. There is nowadays growing evidence on the role of the temperature circadian rhythm on the expression of the molecular clock. The CRBT likely participates in the phase coordination of circadian timekeepers in peripheral tissues, thus guaranteeing the proper functioning of the immune system. The disruption of the CRBT, such as fever, has been repeatedly described in diseases and likely reflects a physiological process to activate the molecular clock and trigger the immune response. On the other hand, temperature circadian disruption has also been described as associated with disease severity and thus may mirror or contribute to immune dysfunction. The present review aims to characterize the potential implication of the temperature circadian rhythm on the immune response, from molecular pathways to diseases. The origin of CRBT and physiological changes in body temperature will be mentioned. We further review the immune biological effects of temperature rhythmicity in hosts, vectors, and pathogens. Finally, we discuss the relationship between circadian disruption of the body temperature and diseases and highlight the emerging evidence that CRBT monitoring would be an easy tool to predict outcomes and guide future studies in chronotherapy.

Immune Modulation as a Therapeutic Option During the SARS-CoV-2 Outbreak: The Case for Antimalarial Aminoquinolines.

The rapid spread, severity, and lack of specific treatment for COVID-19 resulted in hasty drug repurposing. Conceptually, trials of antivirals were well-accepted, but twentieth century antimalarials sparked an impassioned global debate. Notwithstanding, antiviral and immunomodulatory effects of aminoquinolines have been investigated in vitro, in vivo and in clinical trials for more than 30 years. We review the mechanisms of action of (hydroxy)chloroquine on immune cells and networks and discuss promises and pitfalls in the fight against SARS-CoV-2, the agent of the COVID-19 outbreak.

A Granulocytic Signature Identifies COVID-19 and Its Severity.

BACKGROUND: An unbiased approach to SARS-CoV-2-induced immune dysregulation has not been undertaken so far. We aimed to identify previously unreported immune markers able to discriminate COVID-19 patients from healthy controls and to predict mild and severe disease. METHODS: An observational, prospective, multicentric study was conducted in patients with confirmed mild/moderate (n = 7) and severe (n = 19) COVID-19. Immunophenotyping of whole-blood leukocytes was performed in patients upon hospital ward or intensive care unit admission and in healthy controls (n = 25). Clinically relevant associations were identified through unsupervised analysis. RESULTS: Granulocytic (neutrophil, eosinophil, and basophil) markers were enriched during COVID-19 and discriminated between patients with mild and severe disease. Increased counts of CD15+CD16+ neutrophils, decreased granulocytic expression of integrin CD11b, and Th2-related CRTH2 downregulation in eosinophils and basophils established a COVID-19 signature. Severity was associated with emergence of PD-L1 checkpoint expression in basophils and eosinophils. This granulocytic signature was accompanied by monocyte and lymphocyte immunoparalysis. Correlation with validated clinical scores supported pathophysiological relevance. CONCLUSIONS: Phenotypic markers of circulating granulocytes are strong discriminators between infected and uninfected individuals as well as between severity stages. COVID-19 alters the frequency and functional phenotypes of granulocyte subsets with emergence of CRTH2 as a disease biomarker.

For Whom the Clock Ticks: Clinical Chronobiology for Infectious Diseases.

The host defense against pathogens varies among individuals. Among the factors influencing host response, those associated with circadian disruptions are emerging. These latter depend on molecular clocks, which control the two partners of host defense: microbes and immune system. There is some evidence that infections are closely related to circadian rhythms in terms of susceptibility, clinical presentation and severity. In this review, we overview what is known about circadian rhythms in infectious diseases and update the knowledge about circadian rhythms in immune system, pathogens and vectors. This heuristic approach opens a new fascinating field of time-based personalized treatment of infected patients.

Exacerbation of circadian rhythms of core body temperature and sepsis in trauma patients.

PURPOSE: This study aimed to describe by mathematical modeling an accurate course of core body temperature (CBT) in severe trauma patients and its relation to sepsis. METHODS: In a cohort of severe trauma, the CBT measurements were collected for 24 h on day 2 after admission and rhythmicity assessed by Fourier transform and Cosinor analysis to describe circadian features (frequency and amplitude). CBT was compared between patients who developed sepsis or not during the early ICU stay. RESULTS: 33 patients were included in this analysis. 24 patients (73%) had a predominant rhythm of 24 h (period). The main period was lower in the 9 remaining patients (6 of 12 h, 1 of 8 h, and 2 of 6 h). Other significant frequencies of oscillation (second and third frequencies) were found, which showed an association of several well-marked rhythms. Patients with sepsis (n = 12) had a significantly higher level of CBT, but also more intense rhythms and higher amplitudes of CBT. CONCLUSION: Trauma patients exhibit complex temperature circadian rhythms. Early exacerbation of the temperature rhythmicity (in frequency and amplitude) is associated with the development of sepsis. This observation accentuates the concept of circadian disruption and sepsis in ICU patients.

Full-Term Human Placental Macrophages Eliminate Coxiella burnetii Through an IFN-γ Autocrine Loop.

The intracellular bacterium Coxiella burnetii is responsible for Q fever, an infectious disease that increases the risk of abortion, preterm labor, and stillbirth in pregnant women. It has been shown that C. burnetii replicates in BeWo trophoblast cell line and inhibits the activation and maturation of decidual dendritic cells. Although tissue macrophages are known to be targeted by C. burnetii, no studies have investigated the interplay between placental macrophages and C. burnetii. Here, CD14+ macrophages from 46 full-term placentas were isolated by positive selection. They consisted of a mixed population of maternal and fetal origin as shown by genotype analysis. We showed that C. burnetii organisms infected placental macrophages after 4 h. When these infected macrophages were incubated for an additional 9-day culture, they completely eliminated organisms as shown by quantitative PCR. The ability of placental macrophages to form multinucleated giant cells was not affected by C. burnetii infection. The transcriptional immune response of placental macrophages to C. burnetii was investigated using quantitative real-time RT-PCR on 8 inflammatory and 10 immunoregulatory genes. C. burnetii clearly induced an inflammatory profile. Interestingly, the production by placental macrophages of interferon-γ, a cytokine known to be involved in efficient immune responses, was dramatically increased in response to C. burnetii. In addition, a clear correlation between interferon-γ production and C. burnetii elimination was found, suggesting that macrophages from full-term placentas eliminate C. burnetii under the control of an autocrine production of interferon-γ.

Molecular profile of breast cancers in Guinean oncological settings.

Breast cancer is a complex disease characterized by the accumulation of multiple molecular alterations giving each tumor phenotype and an own evolutionary potential. This study aimed to describe the distribution of the profile and molecular subtypes of breast cancers followed at Surgical Oncology Unit of Donka National Hospital. This was retrospective and descriptive study on cases of breast cancer in which the hormone receptor status and expression of the Her2 oncogene have been performed from 2007 to 2016. We recorded 58 cases including 56 (96.6%) women and 2 (3.4%) men. The average age was 48.2 ± 10.9. Invasive ductal carcinoma accounted for 50 (86.2%) cases. The SBR grade was II in 31(53.4%) cases, III in 21 (36.2%) cases and I in 6 (10.3%) cases. The tumor was classified as T4 in 36 (62.1%) cases; it was metastatic in 11(19.0%) cases. Estrogen receptors were positive in 29 (50.0%) cases, progesterone receptors positive in 25 (43.1%) cases, the Her2 oncogene was positive in 22 (39.3%) cases. The distribution of molecular sub-types was: 20 (34.5%) luminal A, 15 (25.9%) triple negative, 13 (22.4%) Her2 overexpressed, 8 (13.8%) luminal B and 2 (3.2%) undetermined. This preliminary study showed the poor accessibility of immunohistochemistry for the molecular diagnosis of breast cancer in our country. Luminal A subtypes and triple negatives were more common. The determination of molecular subtypes is a rational basis for hormone therapy and targeted therapy, thus personalizing the treatment of breast cancer.