Effect of COVID-19 on antenatal care: experiences of medical professionals in the Netherlands.

BACKGROUND: COVID-19 has greatly affected the delivery of all health care services globally. Antenatal care is one area of care that has been impacted, despite the fact that attending antenatal check-ups is essential for pregnant women and cannot be postponed. Little is known about how exactly ANC provision has changed in the Netherlands, or how the changes have impacted midwives and gynaecologists providing those services. METHODS: This study used a qualitative research design to investigate changes in individual and national practice following the onset of the COVID-19 pandemic. The study involved a document analysis of protocols and guidelines for ANC provision to evaluate how those changed following the onset of the COVID-19 pandemic and semi-structured interviews with ANC care providers (i.e., gynaecologists and midwives). RESULTS: Guidance was issued by multiple organizations, during the pandemic, on how to approach the risk of infection in pregnant women, recommending several changes to ANC to protect both pregnant women and ANC providers. Both midwives and gynaecologists reported changes in their practice. With less face-to-face consultations happening, digital technologies became critical in the care of pregnant women. Shorter and fewer visits were reported, with midwifery practices adjusting their guidelines further than hospitals. Challenges, with high workloads and lack of personal protective equipment were discussed. CONCLUSIONS: The COVID-19 pandemic has had an immense impact on the health care system. This impact has had both negative and positive effects on the provision of ANC in the Netherlands. It is important to learn from the current COVID-19 pandemic and adapt ANC, as well as health care systems as a whole, to be better prepared for future health crises and ensure continuous provision of good quality care.

COVID-19 has affected the delivery of healthcare services globally. Antenatal care is one of the healthcare services that has been impacted on a global scale. Little is known about how antenatal care provision has changed in the Netherlands during the pandemic period. Our project focuses on examining the effects of COVID-19 on existing antenatal care protocols, as well as the impacts on antenatal care providers, such as midwives and gynaecologists. This knowledge can be beneficial in adapting antenatal care provision in times of health emergencies, to be better prepared and more resilient. This research uses a qualitative approach to investigate changes in practice following COVID-19 pandemic. It involves 20 antenatal care providers, working in the Netherlands, which took part in semi-structured interviews, and 9 national protocols and guidelines which were analysed. This study indicates that antenatal care changed at different levels in the Netherlands. Many changes show that antenatal care is an essential service, which should not be cut back, but it should be implemented, to be prepared for a future health emergency.

Exploring solutions to improve antenatal care in resource-limited settings: an expert consultation.

BACKGROUND: Shortage or low-quality antenatal care is a complex and "wicked" problem relying heavily on contextual, socio-cultural, environmental and intersectional aspects. We report the outcome of an expert consultation discussing solutions to improve antenatal care quality, access and delivery in low- and middle-income countries, and providing recommendations for implementation. METHODS: The social ecological model was used as an analytical lens to map and interpret discussion points and proposed solutions. In addition, a conceptual framework for maternal and neonatal health innovation based on the building blocks of the World Health Organization health system and the Tanahashi Health Systems Performance Model provided a logical overview of discussed solutions. RESULTS: Many barriers and norms continue to hinder antenatal care access. From values, beliefs, traditions, customs and norms, to poor resource allocation, there is a need of reshaping health systems in order to provide high quality, respectful maternal and childcare. The burden of poor maternal health, morbidity and mortality is concentrated among populations who are vulnerable due to gender and other types of discrimination, have financial constraints and are affected by humanitarian crises. CONCLUSIONS: In order to address maternal health issues, good quality and evidence-based services should be guaranteed. Investments in strengthening health systems, including data and surveillance systems and skilled health workforce, should be considered an essential step towards improving maternal health services.

Composition of the vaginal microbiota during pregnancy in women living in sub-Saharan Africa: a PRISMA-compliant review.

BACKGROUND: The vaginal microbiota (VMB) are the set of microorganisms residing in the human vagina. During pregnancy, their composition is Lactobacillus-dominant in most Caucasian women. Previous studies suggest that the VMB of women with African ancestry is more likely to be non-Lactobacillus dominant (dysbiotic) compared to other populations, and possibly relate to the high incidence of pregnancy complications, such as preterm birth. This work reviewed the literature on VMB composition in pregnant women from sub-Saharan Africa. METHODS: A search was conducted in PubMed and Embase databases following PRISMA guidelines. Observational and intervention studies analysing VMB communities from sub-Saharan African pregnant women using molecular techniques were included. RESULTS: Ten studies performed in seven sub-Saharan African countries were identified. They independently showed that Lactobacillus-dominant VMB (particularly L. iners or L. crispatus) or VMB containing Lactobacilli are the most prevalent, followed by a more diverse anaerobe-dominant VMB, in the studied populations. The majority of pregnant women with a sexually-transmitted infection had a Lactobacillus-dominant VMB, but with a significantly higher presence of anaerobic species. CONCLUSION: In agreement with studies performed in other populations, Lactobacillus species are the most prevalent VMB species during pregnancy in sub-Saharan African women. The frequency of diverse anaerobe-dominant VMB is high in these populations. In Africa, studies on VMB in pregnancy are scant, heterogeneous in methodology, and knowledge remains limited. More insights on VMB composition and their possible sequalae among these populations is needed.

Risk of eating disorders in a non-western setting: an exploratory study in Khartoum state, Sudan.

PURPOSE: Recent research suggests an emergence of eating disorders [ED] in non-western settings for unknown reasons. This research investigates the presence of ED in Khartoum State [Sudan], and explores relevant factors amongst women at risk of ED and stakeholders involved with mental health care and policy-making. METHODS: Women from four summer schools were approached and screened for risk of ED using a validated and adapted form of the Eating Attitudes Test-26. Focus groups were performed within the schools, selected participants at high risk were interviewed, and interviews with stakeholders were performed. RESULTS: Around a third (32.6%) of participants scored as having high risk of ED. Interviews showed recurring themes determining eating attitudes including: intention, knowledge, environment and habit. Stakeholders' opinions depended on whether they work directly with those affected by ED or in policy-making. The former advocated increased attention on ED, the latter did not. Overall, services for ED were lacking. CONCLUSIONS: A high presence of negative eating attitudes was found amongst screened participants with high risk of ED. Individual intention overrides all other determinants for abnormal eating. Moreover, evidence suggests that westernization may attribute to ED, supporting the view that ED are culturally bound. The differing stakeholders' views, together with other data found in this study, allow a number of recommendations for increasing awareness and identification of ED in Sudan.

A surgical algorithm for partial or total eyebrow flap reconstruction.

The eyebrow is one of the five aesthetic sub-units of the forehead and it plays a key role in communication and facial expression. Reconstruction of this region can be challenging. Several methods have been described, mostly based on the size of the defect and on the part of the eyebrow that they involve. We describe our experience in 48 patients underlining the importance of a surgical algorithm for repairing eyebrow defects.

The association between non-viral sexually transmitted infections and pregnancy outcome in Latin America and the Caribbean: A systematic review.

Introduction: Non-viral sexually transmitted infections are known to be associated with adverse pregnancy outcomes. For these pathogens, standard antenatal screening is not broadly performed in Latin America and the Caribbean. The aim of this study was to comprehensively review the association of non-viral sexually transmitted infections and neonatal outcomes among pregnant women in the region. Methods: Four databases (PubMed, Embase, SciELO and LILACS) were examined to identify eligible studies published up to September 2022. English or Spanish cross-sectional, case-control and cohort studies assessing the association of non-viral sexually transmitted infections and adverse pregnancy outcomes were evaluated. Articles were firstly screened by means of title and abstract. Potential articles were fully read and assessed for inclusion according to the eligibility criteria. Snowballing search was performed by screening of bibliographies of the chosen potentially relevant papers. Risk of bias within studies was assessed using the Joanna Briggs Institute reviewer's manual. Results: A selection of 10 out of 9772 search records from five Latin America and the Caribbean countries were included. Six studies associated Treponema pallidum infection with preterm birth (1/6), history of previous spontaneous abortion (2/6), fetal and infant death (1/6), low birth weight (1/6) and funisitis of the umbilical cord (1/6). Three studies associated Chlamydia trachomatis infection with preterm birth (2/3), ectopic pregnancy (1/3) and respiratory symptoms on the newborn (1/3). One study associated Mycoplasma genitalium infection with preterm birth. Conclusion: This review provides evidence on the association of non-viral sexually transmitted infections with adverse pregnancy outcomes. Further investigation is needed to establish more associations between non-viral sexually transmitted infections and pregnancy outcome, especially for Mycoplasma genitalium, Trichomonas vaginalis and Neisseria gonorrhoeae. Overall, this review calls for more research for public health interventions to promote screening of non-viral sexually transmitted infections during pregnancy, among high-risk population groups of pregnant women living in the region.

Antibiotic Use in Pregnancy: A Global Survey on Antibiotic Prescription Practices in Antenatal Care.

Antibiotic prescription and use practices in the antenatal care setting varies across countries and populations and has the potential to significantly contribute to the global spread of antibiotic resistance. This study aims to explore how healthcare practitioners make decisions about antibiotic prescriptions for pregnant women and what factors play a role in this process. A cross-sectional exploratory survey consisting of 23 questions, including 4 free-text and 19 multiple-choice questions, was distributed online. Quantitative data were collected through multiple-choice questions and was used to identify the most common infections diagnosed and the type of antibiotics prescribed. Qualitative data were gathered through free-text answers to identify gaps, challenges, and suggestions, and the data were analyzed using thematic analysis. A total of 137 complete surveys mostly from gynecologists/obstetricians from 22 different countries were included in the analysis. Overall, national and international clinical guidelines and hospital guidelines/protocols were the most frequently used sources of information. This study highlights the crucial role of laboratory results and guidelines at different levels and emphasizes region-specific challenges and recommendations. These findings underscore the pressing need for tailored interventions to support antibiotic prescribers in their decision-making practice and to address emerging resistance.

The impact of health education interventions on HPV vaccination uptake, awareness, and acceptance among people under 30 years old in India: a literature review with systematic search.

Background: The HPV vaccine is used as one of the main prevention tools for HPV-related cancers globally, yet it is not part of the Indian National Immunization program. In light of the introduction of the indigenous vaccine, we examine the effectiveness of health education about uptake, acceptance, and awareness. Methods: Research was performed in the following databases: PubMed, CINAHL, Scopus, and Embase to identify studies between 2008 and 2022. Studies were included if: they were conducted in India including primary data research and health education intervention, and participants were between 9 and 29 years old. Results: Out of the 10.952 results, 7 studies were included. Four studies focused on adolescent girls, aged from 9 to 20 years old, and 3 on university students aged from 17 to 26 years. Five studies were implemented in urban areas and 2 in rural areas. Health education interventions proved to be effective in increasing uptake, awareness, and acceptance of the HPV vaccine. The barriers included among others: cost, lack of awareness, and cultural barriers. Conclusion: Observations from this study outline immediate action for policymakers to educate and encourage the young population toward HPV vaccination. Future programs should be aimed at different population groups and be adjusted according to their special characteristics and needs. Attention should be given to the male population and marginalized groups. The involvement of various stakeholders proved to be beneficial, and it is highly recommended.

Comparison between the Roche Cobas 4800 Human Papillomavirus (HPV), Abbott RealTime High-Risk HPV, Seegene Anyplex II HPV28, and Novel Seegene Allplex HPV28 Assays for High-Risk HPV Detection and Genotyping in Mocked Self-Samples.

Infection with high-risk human papillomavirus (hrHPV) is well recognized as the main cause of cervical cancer. The recently developed Seegene Allplex HPV28 assay is a novel quantitative PCR (qPCR) assay designed to separately detect and quantify 28 distinct HPV genotypes in a fully automated and user-friendly manner. This study evaluated and compared the performance of this new assay with the performance of the Roche Cobas 4800, the Abbott RealTime high-risk HPV, and the Seegene Anyplex II HPV28 assays. A total of 114 mocked self-samples, i.e., semicervical samples collected by gynecologists using the Viba-Brush, were analyzed with all four HPV assays. Agreement in terms of detecting and genotyping HPV was assessed by the mean of the Cohen's kappa (κ) coefficient. Results of all four HPV assays agreed in 85.9% of the cases when using the Abbott RealTime manufacturer's recommended quantification cycle (Cq) cutoff for positivity (<32.00) and 91.2% when using an adapted range (32.00 to 36.00). An intercomparison of the included assays demonstrated an overall agreement ranging from 85.9 to 100.0% (κ = 0.42 to 1.00) when using the manufacturer's guidelines and 92.9 to 100.0% (κ = 0.60 to 1.00) with the adapted range. For all assays, highly significant, strongly positive Pearson correlations were shown between the Cq values of positive test results. This study thereby shows high concordance between results of the included HPV assays on mocked self-samples. Based on these findings, we imply that the novel Allplex HPV28 assay demonstrates a comparable performance to those of available qPCR HPV assays, potentially providing opportunities for the simplification and standardization of future large-scale testing. IMPORTANCE This study proves that the novel Allplex HPV28 assay has a good diagnostic performance in comparison with the well-known, validated, and frequently used Roche Cobas 4800, Abbott RealTime, and Anyplex II HPV28 assays. According to our experience, the novel Allplex HPV28 assay had a user-friendly and automated workflow with short hands-on time, had an open platform which facilitates the use of add-on assays, and provided quick and easy-to-interpret results. Together with its ability to detect and quantify 28 HPV genotypes, the Allplex HPV28 assay could therefore potentially provide opportunities for the simplification and standardization of future diagnostic testing programs.

The association between adverse pregnancy outcomes and non-viral genital pathogens among women living in sub-Saharan Africa: a systematic review.

Adverse pregnancy outcomes are the main causes of maternal and neonatal morbidity and mortality, including long-term physical and psychological sequelae. These events are common in low- and middle-income countries, particularly in Sub Saharan Africa, despite national efforts. Maternal infections can cause complications at any stage of pregnancy and contribute to adverse outcomes. Among infections, those of the genital tract are a major public health concern worldwide, due to limited availability of prevention, diagnosis and treatment approaches. This applies even to treatable infections and holds true especially in Sub-Saharan Africa. As late as 2017, the region accounted for 40% of all reported treatable non-viral genital pathogens worldwide, many of which have been independently associated with various adverse pregnancy outcomes, and that include Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum. Two databases (PubMed and Embase) were examined to identify eligible studies published up to October 2022. This study reviewed findings on the association between infections by treatable non-viral genital pathogens during pregnancy and adverse pregnancy outcomes among women living in Sub-Saharan Africa. Articles' title and abstract were screened at first using keywords as "sexually transmitted infections", "non-viral", "adverse pregnancy outcome", "Africa", "sub-Saharan Africa", "pregnant women", "pregnancy", and "pregnancy outcome". Subsequently, according to the eligibility criteria, potential articles were read in full. Results showed that higher risk of preterm birth is associated with Treponema pallidum, Chlamydia trachomatis and Candida albicans infections. Additionally, rates of stillbirth, neonatal death, low birth weight and intrauterine growth restriction are also associated with Treponema pallidum infection. A better insight on the burden of non-viral genital pathogens and their effect on pregnancy is needed to inform antenatal care guidelines and screening programs, to guide the development of innovative diagnostic tools and other strategies to minimize transmission, and to prevent short- and long-term complications for mothers and children.

Erbb2 DNA vaccine combined with regulatory T cell deletion enhances antibody response and reveals latent low-avidity T cells: potential and limits of its therapeutic efficacy.

Rat (r)Erbb2 transgenic BALB-neuT mice genetically predestined to develop multiple invasive carcinomas allow an assessment of the potential of a vaccine against the stages of cancer progression. Because of rErbb2 expression in the thymus and its overexpression in the mammary gland, CD8(+) T cell clones reacting at high avidity with dominant rErbb2 epitopes are deleted in these mice. In BALB-neuT mice with diffuse and invasive in situ lesions and almost palpable carcinomas, a temporary regulatory T cells depletion combined with anti-rErbb2 vaccine markedly enhanced the anti-rErbb2 Ab response and allowed the expansion of latent pools of low-avidity CD8(+) T cells bearing TCRs repertoire reacting with the rErbb2 dominant peptide. This combination of a higher Ab response and activation of a low-avidity cytotoxic response persistently blocked tumor progression at stages in which the vaccine alone was ineffective. However, when diffuse and invasive microscopic cancers become almost palpable, this combination was no longer able to secure a significant extension of mice survival.

Frequency of Chlamydia trachomatis and Neisseria gonorrhoeae in Patients with Imminent Preterm Delivery on the Island of Curaçao.

Sexually transmitted infections are one of the important risk factors for preterm delivery, which is among the important contributors to perinatal morbidity and mortality. The aim of this study was to assess the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in women with imminent preterm delivery in Curaçao, an island of the Dutch Caribbean. All women from Curaçao with either preterm premature rupture of the membranes or preterm labor, common indications of imminent preterm delivery, and presenting at the Curaçao Medical Center between 15 November 2019 and 31 December 2020, were included in this single cohort study. Data were retrospectively collected from medical records. The presence of Chlamydia trachomatis and Neisseria gonorrhoeae was assessed by Cepheid GeneXpert ® (Xpert) CT/NG assay (Sunnyvale, CA, USA). In the included cohort, the prevalence of Chlamydia trachomatis infection was 15.5% and of Neisseria gonorrhoeae infection was 2.1%. All patients infected with Neisseria gonorrhoeae were co-infected with Chlamydia trachomatis. The prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients with imminent preterm delivery in Curaçao is high. It is recommended to test all patients with imminent preterm delivery for these sexually transmitted infections and possibly consider testing all women in early pregnancy on the island.

A Public Health Perspective of Post-Traumatic Stress Disorder.

Trauma exposure is one of the most important and prevalent risk factors for mental and physical ill-health. Prolonged or excessive stress exposure increases the risk of a wide variety of mental and physical symptoms, resulting in a condition known as post-traumatic stress disorder (PTSD). The diagnosis might be challenging due to the complex pathophysiology and co-existence with other mental disorders. The prime factor for PTSD development is exposure to a stressor, which variably, along with peritraumatic conditions, affects disease progression and severity. Additionally, many factors are thought to influence the response to the stressor, and hence reshape the natural history and course of the disease. With sufficient knowledge about the disease, preventive and intervenient methods can be implemented to improve the quality of life of the patients and to limit both the medical and economic burden of the disease. This literature review provides a highlight of up-to-date literature on traumatic stress, with a focus on causes or triggers of stress, factors that influence response to stress, disease burden, and the application of the social-ecological public health model of disease prevention. In addition, it addresses therapeutic aspects, ethnic differences in traumatic stress, and future perspectives, including potential biomarkers.

The Vaginal Microbiota Composition and Genital Infections during and after Pregnancy among Women in Pemba Island, Tanzania.

We investigated the vaginal microbiota (VMB) composition, prevalence of genital pathogens and their association among pregnant and post-delivery women in Pemba Island, Tanzania. Vaginal swabs were collected from 90 women, at two time points during pregnancy (<20 weeks of gestational age [GA] and ≥20 weeks GA) and once after delivery, when possible. IS-pro assay was used for VMB characterization. Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) and human papillomavirus (HPV) were detected by qPCRs. VMB were mostly Lactobacillus dominant during pregnancy and non-Lactobacillus dominant post-delivery. A significant decrease in VMB richness was observed during pregnancy among paired and unpaired samples. Shannon diversity was significantly lower during pregnancy than post-delivery among unpaired samples. Klebsiella species and Streptococcus anginosus were the most commonly identified pathobionts at all timepoints. A high abundance of pathobionts was mostly seen in women with non-Lactobacillus dominant VMB. At ≥20 weeks GA timepoint during pregnancy, 63.0% of the women carrying one or more genital pathogen (either HPV, CT, TV, or MG) had L. iners dominant VMB. NG was not detected pre-delivery. This study contributes evidence on VMB composition, its changes during pregnancy and post-delivery, and their association with pathobionts and genital pathogens.

A nonclassical non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance.

The importance of immunoregulatory T cells has become increasingly apparent. Both CD4+CD25+ T cells and CD1d-restricted NKT cells have been reported to down-regulate tumor immunity in mouse tumor models. However, the relative roles of both T cell populations have rarely been clearly distinguished in the same tumor models. In addition, CD1d-restricted NKT cells have been reported to play a critical role not only in the down-regulation of tumor immunity but also in the promotion of the immunity. However, the explanation for these apparently opposite roles in different tumor models remains unclear. We show that in four mouse tumor models in which CD1d-restricted NKT cells play a role in suppression of tumor immunity, depletion of CD4+CD25+ T cells did not induce enhancement of immunosurveillance. Surprisingly, among the two subpopulations of CD1d-restricted NKT cells, Valpha14Jalpha18+ (type I) and Valpha14Jalpha18- (type II) NKT cells, type I NKT cells were not necessary for the immune suppression. These unexpected results may now resolve the paradox in the role of CD1d-restricted NKT cells in the regulation of tumor immunity, in that type II NKT cells may be sufficient for negative regulation, whereas protection has been found to be mediated by alpha-galactosylceramide-responsive type I NKT cells.

The impact of antenatal syphilis point of care testing on pregnancy outcomes: A systematic review.

BACKGROUND: Mother-to-child transmission of syphilis remains a leading cause of neonatal death and stillbirth, disproportionally affecting women in low-resource settings where syphilis prevalence rates are high and testing rates low. Recently developed syphilis point-of-care tests (POCTs) are promising alternatives to conventional laboratory screening in low-resource settings as they do not require a laboratory setting, intensive technical training and yield results in 10-15 minutes thereby enabling both diagnosis and treatment in a single visit. Aim of this review was to provide clarity on the benefits of different POCTs and assess whether the implementation of syphilis POCTs is associated with decreased numbers of syphilis-related adverse pregnancy outcomes. METHODS: Following the PRISMA guidelines, three electronic databases (PubMed, Medline (Ovid), Cochrane) were systematically searched for intervention studies and cost-effectiveness analyses investigating the association between antenatal syphilis POCT and pregnancy outcomes such as congenital syphilis, low birth weight, prematurity, miscarriage, stillbirth as well as perinatal, fetal or infant death. RESULTS: Nine out of 278 initially identified articles were included, consisting of two clinical studies and seven modelling studies. Studies compared the effect on pregnancy outcomes of treponemal POCT, non-treponemal POCT and dual POCT to laboratory screening and no screening program. Based on the clinical studies, significantly higher testing and treatment rates, as well as a significant reduction (93%) in adverse pregnancy outcomes was reported for treponemal POCT compared to laboratory screening. Compared to no screening and laboratory screening, modelling studies assumed higher treatment rates for POCT and predicted the most prevented adverse pregnancy outcomes for treponemal POCT, followed by a dual treponemal and non-treponemal POCT strategy. CONCLUSION: Implementation of treponemal POCT in low-resource settings increases syphilis testing and treatment rates and prevents the most syphilis-related adverse pregnancy outcomes compared to no screening, laboratory screening, non-treponemal POCT and dual POCT. Regarding the benefits of dual POCT, more research is needed. Overall, this review provides evidence on the contribution of treponemal POCT to healthier pregnancies and contributes greater clarity on the impact of diverse diagnostic methods available for the detection of syphilis.

The Natural Course of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium in Pregnant and Post-Delivery Women in Pemba Island, Tanzania.

This study aimed to determine the persistence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) infections during pregnancy and after delivery in vaginal swabs of women from Pemba Island, Tanzania. In the context of an earlier biobanking effort, vaginal swabs were collected at two timepoints during pregnancy and once post-delivery. Detection of CT, NG, TV, and MG was performed by PCR using validated detection kits in samples from 441 pregnant women aged 16-48 years old. Among those, 202 samples were matched during pregnancy and 38 at the second timepoint of the pregnancy and post-delivery CT infection persistence during pregnancy was 100% (n = 11) after an average of eight weeks, that of TV infection 82% (n = 11) after ten weeks, and that of MG infection 75% (n = 4) after ten weeks. Post-delivery (after approximately 22 weeks) infection persistence was 100% for CT (n = 1) and 20% for TV (n = 5). NG was only detected at the last collection timepoint, its persistence rate could not be determined. These results show persistence and clearance of curable infections during and after pregnancy. Analysis of biobanked samples is a valuable approach in the investigation of the natural history of curable pathogens.

Blockade of TGF-beta enhances tumor vaccine efficacy mediated by CD8(+) T cells.

Though TGF-beta inhibition enhances antitumor immunity mediated by CD8(+) T cells in several tumor models, it is not always sufficient for rejection of tumors. In this study, to maximize the antitumor effect of TGF-beta blockade, we tested the effect of anti-TGF-beta combined with an irradiated tumor vaccine in a subcutaneous CT26 colon carcinoma tumor model. The irradiated tumor cell vaccine alone in prophylactic setting significantly delayed tumor growth, whereas anti-TGF-beta antibodies alone did not show any antitumor effect. However, tumor growth was inhibited significantly more in vaccinated mice treated with anti-TGF-beta antibodies compared to vaccinated mice without anti-TGF-beta, suggesting that anti-TGF-beta synergistically enhanced irradiated tumor vaccine efficacy. CD8(+) T-cell depletion completely abrogated the vaccine efficacy, and so protection required CD8(+) T cells. Depletion of CD25(+) T regulatory cells led to the almost complete rejection of tumors without the vaccine, whereas anti-TGF-beta did not change the number of CD25(+) T regulatory cells in unvaccinated and vaccinated mice. Though the abrogation of CD1d-restricted NKT cells, which have been reported to induce TGF-beta production by MDSC through an IL-13-IL-4R-STAT6 pathway, partially enhanced antitumor immunity regardless of vaccination, abrogation of the NKT cell-IL-13-IL-4R-STAT-6 immunoregulatory pathway did not enhance vaccine efficacy. Taken together, these data indicated that anti-TGF-beta enhances efficacy of a prophylactic vaccine in normal individuals despite their not having the elevated TGF-beta levels found in patients with cancer and that the effect is not dependent on TGF-beta solely from CD4(+)CD25(+) T regulatory cells or the NKT cell-IL-13-IL-4R-STAT-6 immunoregulatory pathway.

A multiplex assay for the simultaneous detection of antibodies against 15 Plasmodium falciparum and Anopheles gambiae saliva antigens.

BACKGROUND: Assessment exposure and immunity to malaria is an important step in the fight against the disease. Increased malaria infection in non-immune travellers under anti-malarial chemoprophylaxis, as well as the implementation of malaria elimination programmes in endemic countries, raises new issues that pertain to these processes. Notably, monitoring malaria immunity has become more difficult in individuals showing low antibody (Ab) responses or taking medications against the Plasmodium falciparum blood stages. Commonly available techniques in malaria seroepidemiology have limited sensitivity, both against pre-erythrocytic, as against blood stages of the parasite. Thus, the aim of this study was to develop a sensitive tool to assess the exposure to malaria or to bites from the vector Anopheles gambiae, despite anti-malarial prophylactic treatment. METHODS: Ab responses to 13 pre-erythrocytic P. falciparum-specific peptides derived from the proteins Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, CSP and Pf11.1, and to 2 peptides specific for the Anopheles gambiae saliva protein gSG6 were tested. In this study, 253 individuals from three Senegalese areas with different transmission intensities and 124 European travellers exposed to malaria during a short period of time were included. RESULTS: The multiplex assay was optimized for most but not all of the antigens. It was rapid, reproducible and required a small volume of serum. Proportions of Ab-positive individuals, Ab levels and the mean number of antigens (Ags) recognized by each individual increased significantly with increases in the level of malaria exposure. CONCLUSION: The multiplex assay developed here provides a useful tool to evaluate immune responses to multiple Ags in large populations, even when only small amounts of serum are available, or Ab titres are low, as in case of travellers. Finally, the relationship of Ab responses with malaria endemicity levels provides a way to monitor exposure in differentially exposed autochthonous individuals from various endemicity areas, as well as in travellers who are not immune, thus indirectly assessing the parasite transmission and malaria risk in the new eradication era.

The Association Between Vaginal Microbiota Dysbiosis, Bacterial Vaginosis, and Aerobic Vaginitis, and Adverse Pregnancy Outcomes of Women Living in Sub-Saharan Africa: A Systematic Review.

Background: Previous studies have described the association between dysbiosis of the vaginal microbiota (VMB) and related dysbiotic conditions, such as bacterial vaginosis (BV) and aerobic vaginitis (AV), and various adverse pregnancy outcomes. There is limited overview of this association from countries in sub-Saharan Africa (SSA), which bear a disproportionally high burden of both vaginal dysbiotic conditions and adverse pregnancy outcomes. This systematic review assesses the evidence on the association between VMB dysbiosis, BV, and AV, and late adverse pregnancy outcomes in women living in SSA. Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis Statement (PRISMA) guidelines were followed. Three databases [PubMed, Embase (Ovid), and Cochrane] were used to retrieve observational and intervention studies conducted in SSA that associated VMB dysbiosis, BV, or AV and preterm birth/labor/delivery, preterm rupture of membranes (PROM), low birthweight, small for gestational age, intrauterine growth restriction, intrauterine infection, intrauterine (fetal) death, stillbirth, perinatal death, or perinatal mortality. Results: Twelve studies out of 693 search records from five SSA countries were included. One study identified a positive association between VMB dysbiosis and low birthweight. Despite considerable differences in study design and outcome reporting, studies reported an association between BV and preterm birth (7/9), low birthweight (2/6), PROM (2/4), intrauterine infections (1/1), and small for gestational age (1/1). None of the retrieved studies found an association between BV and pregnancy loss (5/5) or intrauterine growth retardation (1/1). At least two studies support the association between BV and PROM, low birthweight, and preterm birth in Nigerian pregnant women. No reports were identified investigating the association between AV and late adverse pregnancy outcomes in SSA. Conclusion: Two of the included studies from SSA support the association between BV and PROM. The remaining studies show discrepancies in supporting an association between BV and preterm birth or low birthweight. None of the studies found an association between BV and pregnancy loss. As for the role of VMB dysbiosis, BV, and AV during pregnancy among SSA women, additional research is needed. These results provide useful evidence for prevention efforts to decrease vaginal dysbiosis and its contribution to adverse pregnancy outcomes in SSA.