Medroxyprogesterone Acetate Alters Mycobacterium Bovis BCG-Induced Cytokine Production in Peripheral Blood Mononuclear Cells of Contraceptive Users

Most individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA) possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs) and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1α, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future

Intermittent preventive treatment for malaria in pregnancy in Africa: What's new, what's needed?

Falciparum malaria is an important cause of maternal, perinatal and neonatal morbidity in high transmission settings in Sub-Saharan Africa. Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT) has proven efficacious in reducing the burden of pregnancy-associated malaria but increasing levels of parasite resistance mean that the benefits of national SP-IPT programmes may soon be seriously undermined in much of the region. Hence, there is an urgent need to develop alternative drug regimens for IPT in pregnancy. This paper reviews published safety and efficacy data on various antimalarials and proposes several candidate combination regimens for assessment in phase II/III clinical trials

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp

Assessment of climate change downscaling and non-stationarity on the spatial pattern of a mangrove ecosystem in an arid coastal region of southern Iran.

Mangrove wetlands exist in the transition zone between terrestrial and marine environments and have remarkable ecological and socio-economic value. This study uses climate change downscaling to address the question of non-stationarity influences on mangrove variations (expansion and contraction) within an arid coastal region. Our two-step approach includes downscaling models and uncertainty assessment, followed by a non-stationary and trend procedure using the Extreme Value Analysis (extRemes code). The Long Ashton Research Station Weather Generator (LARS-WG) model along with two different general circulation model (GCMs) (MIRH and HadCM3) were used to downscale climatic variables during current (1968–2011) and future (2011–2030, 2045–2065, and 2080–2099) periods. Parametric and non-parametric bootstrapping uncertainty tests demonstrated that the LARS-WGS model skillfully downscaled climatic variables at the 95 % significance level. Downscaling results using MIHR model show that minimum and maximum temperatures will increase in the future (2011–2030, 2045–2065, and 2080–2099) during winter and summer in a range of +4.21 and +4.7 °C, and +3.62 and +3.55 °C, respectively. HadCM3 analysis also revealed an increase in minimum (∼+3.03 °C) and maximum (∼+3.3 °C) temperatures during wet and dry seasons. In addition, we examined how much mangrove area has changed during the past decades and, thus, if climate change non-stationarity impacts mangrove ecosystems. Our results using remote sensing techniques and the non-parametric Mann–Whitney two-sample test indicated a sharp decline in mangrove area during 1972,1987, and 1997 periods (p value = 0.002). Non-stationary assessment using the generalized extreme value (GEV) distributions by including mangrove area as a covariate further indicated that the null hypothesis of the stationary climate (no trend) should be rejected due to the very low p values for precipitation (p value = 0.0027), minimum (p value = 0.000000029) and maximum (p value = 0.00016) temperatures. Based on non-stationary analysis and an upward trend in downscaled temperature extremes, climate change may control mangrove development in the future