Does smallpox vaccination modify HIV disease progression among ART-naive people living with HIV in Africa?

We examined the association between a history of smallpox vaccination and immune activation (IA) in a population of antiretroviral therapy-naïve people living with HIV (PLHIV). A cross-sectional study was conducted in Senegal from July 2015 to March 2017. Smallpox vaccination was ascertained by the presence of smallpox vaccine scar and IA by the plasma level of ß-2-microglobulin (ß2m). The association was analysed using logistic regression and linear regression models. The study population comprised 101 PLHIV born before 1980 with a median age of 47 years (interquartile range (IQR) = 42-55); 57·4% were women. Smallpox vaccine scar was present in 65·3% and the median ß2m level was 2·59 mg/l (IQR = 2·06-3·86). After adjustment, the presence of smallpox vaccine scar was not associated with a ß2m level ⩾2·59 mg/l (adjusted odds ratio 0·94; 95% confidence interval 0·32-2·77). This result was confirmed by the linear regression model. Our study does not find any association between the presence of smallpox vaccine scar and the ß2m level and does not support any association between a previous smallpox vaccination and HIV disease progression. In this study, IA is not a significant determinant of the reported non-targeted effect of smallpox vaccination in PLHIV.

Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice.

INTRODUCTION: Plasmodium chabaudi AS-infection in pregnant A/J and C57BL/6J mice results in mid-gestational pregnancy loss. Although associated with increased systemic and placental pro-inflammatory responses and coagulopathy, the molecular mechanisms that underlie poor pregnancy outcomes in these mice are not yet fully understood. This study investigates the relationships between inflammation, apoptosis and malaria-induced pregnancy loss. METHODS: Infection with P. chabaudi AS in early murine pregnancy and term human placental tissues from an endemic setting were assessed by histology, immunohistochemistry, TUNEL staining, real-time PCR, flow cytometry, western blot, and ELISA. RESULTS: Quantitative PCR reveals accumulation of lymphocytes and monocytes and upregulation of chemokines that attract these cell types in malaria-exposed mid-gestational A/J conceptuses. Monocyte accumulation is confirmed by flow cytometry and placental immunohistochemistry. Concurrent with initiation of malaria-induced abortion, markers of apoptosis are evident in the junctional zone, but not the labyrinth, of A/J placentae. In contrast, mid-gestation conceptuses in infected C57BL/6J lack evidence for monocyte accumulation, exhibiting low or no in situ placental staining despite trophoblast immunoreactivity for the monokine, CCL2. Additionally, placental apoptosis is not consistently observed, and when evident, appears after malaria-induced abortion typically initiates. Similarly, trophoblast apoptosis in term human placental malaria is not observed. Of those studied, a sole common feature of malaria-induced abortion in A/J and C57BL/6J mice is elevation of plasma tumor necrosis factor. DISCUSSION: Consistent with our previous observations, tumor necrosis factor is likely to be a central driver of malaria-induced pregnancy loss in both strains, but likely operates through mechanisms distinct from placental apoptosis in C57BL/6J mice.

Quantifying the consequences of conifer succession in aspen stands: decline in a biodiversity-supporting community.

Quaking aspen (Populus tremuloides Michaux) stands are important for biodiversity in conifer-dominated forest landscapes. Our goal was to quantify the consequences of conifer succession on understory diversity and litter quality, as well as associated changes in aspen stand condition. We studied aspen stands on national park land in the transition zone between the northern Sierra Nevada and southern Cascade mountain ranges. We field-measured ten metrics of aspen stand condition in 29 aspen stands. Along a gradient of increasing current conifer cover, we observed decreases in herbaceous species diversity and richness and an increase in forest floor O horizon depth. We interpreted aerial photos from 1952 and 1998 to determine whether directional changes in conifer cover had occurred in the stands over the past half century, and used regression modeling to associate succession with the observed range of aspen stand condition. From the period 1952 to 1998, we found that conifer encroachment occurred in half the sampled stands, with an average increase in conifer cover of 1% a year. Aspen were persistent in the remaining stands. Stand cover dynamics and percent total canopy cover interacted to influence species richness, diversity, aspen sprouting, and litter quality. In stands with conifer encroachment, both understory species richness and diversity declined. Although aspen sprouting increased, aspen establishment declined and the relative mass of woody to fine soil litter increased.

Comparative efficacy of uncontrolled and controlled intermittent preventive treatment during pregnancy (IPTp) with combined use of LLTNs in high resistance area to sulfadoxine-pyrimethamine in Côte d'Ivoire.

INTRODUCTION: In recent years, intermittent preventive treatment for pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) has become policy in much of sub-Saharan Africa. But resistance to SP has been spreading across sub-Saharan Africa and thus the effectiveness of IPTp-SP has been questioned. The present study therefore sought to assess the incidence of placental malaria, low birth weight, and anemia of two IPTp-SP approaches (directly observed treatment scheme versus no directly observed treatment) in Anonkoua-Kouté and Samo, Côte d'Ivoire where the reported prevalence of dfr single mutant 108 was 62% and 52.2%, respectively. METHODS: The study was a longitudinal design involving pregnant women and was conducted in Anonkoua-Kouté, a suburban area, and Samo, a rural area, from January 2008 through March 2009. Women of a pregnancy less than 28 weeks duration were randomized to receive SP (1.5 g/0.075 g SP) in a single intake twice and were followed up monthly until delivery. Doses were administered under supervision in the controlled IPTp group, while SP was given free to women in the uncontrolled IPTp group with a recommendation to take it at home. The primary end point was the proportion of low birth weight infants (body weight < 2500 g) and the secondary end point was the rate of severe anemia and placental malaria detected at delivery. RESULTS: A total of 420 pregnant women were enrolled (212 and 208, respectively, in the controlled and uncontrolled groups). Delivery outcome was available for 378 women. In the modified intention-to-treat analysis, low birth weight infants were born from 15.5% of women of the uncontrolled IPTp group and from 11.9% of women in the controlled IPTp group (P = 0.31). The per-protocol population analysis showed consistent results. The proportion of women with placental malaria infection, moderate anemia (hemoglobin < 11 g/dL), and severe anemia (hemoglobin < 8 g/dL) at delivery were similar between the two groups (P > 0.05). CONCLUSION: The study showed that the two approaches were equivalent, suggesting that unsupervised IPTp-SP free of charge should be used in areas where implementation of the directly observed treatment scheme suffers from many constraints.

Plasmodium chabaudi AS induces pregnancy loss in association with systemic pro-inflammatory immune responses in A/J and C57BL/6 mice.

The molecular mechanisms that underlie poor birth outcomes in malaria during pregnancy remain poorly defined. To assess the role of host immune responses, mice known to respond differentially to Plasmodium chabaudi AS infection were studied. Following infection at day 0 of pregnancy, A/J mice developed significantly higher parasitemia than C57BL/6 (B6) mice and succumbed to infection. Both strains had evidence of parasite accumulation in the placenta at mid-gestation and aborted, with significantly higher embryo loss in infected A/J mice on day 9. While infection-induced systemic tumour necrosis factor (TNF) and interleukin (IL)-1ß in the latter were significantly higher at day 11, day 10 IL-10 levels were higher in B6 mice. No differences in the levels of splenic lymphocyte subsets, neutrophils or monocytes between infected pregnant A/J and B6 mice were observed, with most cell types expanding in response to infection regardless of pregnancy. Antibody ablation of TNF exacerbated infection in A/J mice and did not ameliorate pregnancy outcome. Thus, malaria induces poor pregnancy outcome in both the mouse strains in the context of quantitatively different systemic inflammatory responses. Further evaluation of the roles of soluble and cellular immune components, particularly at the uteroplacental level, will be required to define the most critical pregnancy-compromising mechanisms.

Natural hemozoin stimulates syncytiotrophoblast to secrete chemokines and recruit peripheral blood mononuclear cells.

BACKGROUND: Placental malaria is associated with local accumulation of parasitized erythrocytes, deposition of the parasite hemoglobin metabolite, hemozoin, and accumulation of mononuclear cells in the intervillous space. Fetal syncytiotrophoblast cells in contact with maternal blood are known to respond immunologically to cytoadherent Plasmodium falciparum-infected erythrocytes, but their responsiveness to hemozoin, a potent pro-inflammatory stimulator of monocytes, macrophages and dendritic cells, is not known. METHODS: The biochemical and immunological changes induced in primary syncytiotrophoblast by natural hemozoin was assessed. Changes in syncytiotrophoblast mitogen-activated protein kinase activation was assessed by immunoblotting and secreted cytokine and chemokine proteins were assayed by ELISA. Chemotaxis of peripheral blood mononuclear cells was assessed using a two-chamber assay system and flow cytometry was used to assess the activation of primary monocytes by hemozoin-stimulated syncytiotrophoblast conditioned medium. RESULTS: Hemozoin stimulation induced ERK1/2 phosphorylation. Treated cells secreted CXCL8, CCL3, CCL4, and tumor necrosis factor and released soluble intercellular adhesion molecule-1. Furthermore, the dependence of the hemozoin responses on ERK1/2 stimulation was confirmed by inhibition of chemokine release in syncytiotrophoblast treated with an ERK pathway inhibitor. Hemozoin-stimulated cells elicited the specific migration of PBMCs, and conditioned medium from the cells induced the upregulation of intercellular adhesion molecule-1 on primary monocytes. CONCLUSIONS: These findings confirm an immunostimulatory role for hemozoin and expand the cell types known to be responsive to hemozoin to include fetal syncytiotrophoblast. The results provide further evidence that syncytiotrophoblast cells can influence the local maternal immune response to placental malaria.

IFPA Meeting 2010 Workshops Report II: Placental pathology; trophoblast invasion; fetal sex; parasites and the placenta; decidua and embryonic or fetal loss; trophoblast differentiation and syncytialisation.

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb.4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications.

Differences in circulating dendritic cell subtypes in peripheral, placental and cord blood in African pregnant women.

Dendritic cells (DC) are important for induction of primary immune responses and immunological tolerance. Changes in the frequency of DC subsets were analyzed in peripheral blood from pregnant women (mPB) and compared to placental blood (PB) and cord blood (CB). DCs were identified by flow cytometry in whole blood as lineage negative and HLA-DR-positive cells. Different DC subtypes were identified with CD123 and CD11c markers. In these data, the percentage of DC was significantly lower in mPB, PB and CB than in control women, but the absolute number of DC was higher in CB, suggesting that numbers of DC in CB do not explain the decrease of the immune response in newborn infants. Myeloid DCs (MDC) decreased in all compartments of pregnant women compared to control women, especially in mPB where MDC became lower than lymphoid DCs. An increase of less differentiated DC was observed in mPB and CB from pregnant women. DCs in pregnant women were mainly immature DC with a proportion of CD83-positive DC, identical as control women. The levels of IFNgamma, TNFalpha, IL-2, IL-4, IL-5 and IL-10 were not different in the three compartments (mPB, PB, CB). In conclusion, the phenotype and subset of DCs were different in pregnant women than in control women, suggesting a role in maintenance of immune tolerance against the fetus. The distribution of DC subsets was different in mPB, PB and CB. Their role in the regulation of immune response remains to be elicited.

[Mango leaves (Manguifera indica, Anacardiacea) used as biomarker of pollution by pp'Dichlorodiphenyltrichloroethane (pp'DDT)]. / Utilisation des feuilles de manguier (Manguifera indica, Anacardiacea) comme bioindicateur de pollution par le pp'Dichlorodiphényltri-Chloroéthane (pp'DDT).

Dichlorodiphenyltrichloroethane (DDT), organochlorine pesticide, byanother way cumulative pesticide is banned in mostdeveloped countries. Whatever, it is still used in many countries in the Third World. This work consist to check whether this chemical compound is still used in Senegal. The biomarker of pollution by this pesticide for this research was mango leaves (mango tree is widespread in Senegal) open to accumulate halogenated hydrocarbons. Leaves sample were taken in many sites in the centerline of Dakar-Thiès (Senegal), then analysed by gas chromatography. The results allowed to note the presence of DDT and its metabolites [(dichlorodiphenyltrichloroethylen (DDE), (dichlorodiphenyltrichloroethane (DDD)] in most of samples. The comparison of DDT content in relation to those of the principal metabolite allowed to make the difference according to sample sites, an old contamination of an utilisation more or less recent of this pesticide. From those results, we can conclude that DDT, typical pesticide by its big persistence is still used in some spherical zones in this country, in particular in farming gardening zones.

Cultural response to mental illness in Senegal: Reflections through patient companions--Part I. Methods and descriptive data.

Patient records from the Thiaroye mental hospital in Senegal were analyzed to see if the patterns of persons accompanying patients to the hospital could help portray the community's response to mental illness. A systematic sample of 935 records of initial our-patient visits were examined. Patterns of patient companionship were found to strongly correlate with specific patient sociodemographic and clinical characteristics. Interpretation of these findings helped to clarify both prevailing attitudes toward the mentally ill and the social response and management of mental illness. This article presents the study setting, methods, patient sociodemographic and clinical characteristics, and characteristics of patient companions. The second article in this series examines the statistical associations of companion number, gender and kinship relationship with patient sociodemographic and clinical characteristics.

Cultural response to mental illness in Senegal: reflections through patient companions--Part II. Statistical correlates.

Patient records from the Thiaroye Psychiatric Hospital in Senegal were studied to see if analysis of patterns of persons accompanying patients to the hospital could help to portray the community's response to mental illness. A systematic sample of 935 records of initial out-patients visits were examined. Patterns of patient companionship were found to strongly correlate with specific patient sociodemographic and clinical characteristics. Interpretation of these findings helped to clarify both prevailing attitudes toward the mentally ill and the social response and management of mental illness. The first article in this series presented the study setting, methods, sociodemographic and clinical characteristics of the patients, and characteristics of patient companions. The current article examines the statistical associations of companion number, gender and kinship relationship with patient sociodemographic and clinical characteristics.

[Women among a population at a psychiatric service in Senegal (psychosocial aspects)]. / Les femmes dans une population de consultants en psychiatrie au Sénégal (aspects psycho-sociaux).

From a psychiatric consultation of women, the authors have tried to bring up the psychosocial aspects being very much influenced by the cultural context. They have discovered two profiles of these sort of women, they are either, married women under the stress of uncontrolled child-birth and are very much influenced by local tradition or are women being at a turning points of their life; adolescence, premenopause, and menopause. The authors have a well demonstrated the primordial role they take as natural (helpers) aids when a member of the family gives evidence of mental disorder.