Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria

Background: Placental malaria (PM) is an important cause of maternal and foetal mortality in tropical areas, and severe sequelae and mortality are related to inflammation in the placenta. Diagnosis is difficult because PM is often asymptomatic, peripheral blood smear examination detects parasitemia as few as half of PM cases, and no peripheral markers have been validated for placental inflammation. Methods: In a cohort of Tanzanian parturients, PM was determined by placental blood smears and placental inflammation was assessed by histology and TNF mRNA levels. Maternal peripheral blood levels of several immune mediators previously implicated in PM pathogenesis, as well as ferritin and leptin were measured. The relationship between the levels of these soluble factors to PM and placental inflammation was examined. Results: Peripheral levels of TNF, TNF-RI, TNF-RII, IL-1, IL-10, and ferritin were elevated during PM, whereas levels of IFN-[gamma], IL-4, IL-5 and IL-6 were unchanged and levels of leptin were decreased. In receiver operating characteristic curve analysis, IL-10 had the greatest area under the curve, and would provide a sensitivity of 60% with a false positive rate of 10%. At a cut off level of 15 pg/mL, IL-10 would detect PM with a sensitivity of 79.5% and a specificity of 84.3%. IL-10 levels correlated with placental inflammatory cells and placental TNF mRNA levels in first time mothers. Conclusion: These data suggest that IL-10 may have utility as a biomarker for inflammatory PM in research studies, but that additional biomarkers may be required to improve clinical diagnosis and management of malaria during pregnancy.This work was supported by grants from Bill and Melinda Gates Foundation (grant 29202), NIH (R01 AI52059 and TW05509) and Puget Sound Partners for Global Health to P.E.D

Vertebrate Host Susceptibility to Heartland Virus

Heartland virus (HRTV) is a recently described phlebovirus initially isolated in 2009 from 2 humans who had leukopenia and thrombocytopenia. Serologic assessment of domestic and wild animal populations near the residence of 1 of these persons showed high exposure rates to raccoons, white-tailed deer, and horses. To our knowledge, no laboratory-based assessments of viremic potential of animals infected with HRTV have been performed. We experimentally inoculated several vertebrates (raccoons, goats, chickens, rabbits, hamsters, C57BL/6 mice, and interferon-α/β/γ receptor–deficient [Ag129]) mice with this virus. All animals showed immune responses against HRTV after primary or secondary exposure. However, neutralizing antibody responses were limited. Only Ag129 mice showed detectable viremia and associated illness and death, which were dose dependent. Ag129 mice also showed development of mean peak viral antibody titers \u3e8 log10 PFU/mL, hemorrhagic hepatic lesions, splenomegaly, and large amounts of HRTV antigen in mononuclear cells and hematopoietic cells in the spleen

Chloroquine resistant vivax malaria in a pregnant woman on the western border of Thailand

Chloroquine (CQ) resistant vivax malaria is spreading. In this case, Plasmodium vivax infections during pregnancy and in the postpartum period were not satisfactorily cleared by CQ, despite adequate drug concentrations. A growth restricted infant was delivered. Poor susceptibility to CQ was confirmed in-vitro and molecular genotyping was strongly suggestive of true recrudescence of P. vivax. This is the first clinically and laboratory confirmed case of two high-grade CQ resistant vivax parasite strains from Thailand

Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial.

BACKGROUND: Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy, and alternative regimens need to be identified. With the return of chloroquine efficacy in southern Africa, we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes. METHODS: We did an open-label, single-centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in southern Malawi. We enrolled pregnant women (first or second pregnancy) at 20-28 weeks' gestation who were HIV negative. Participants were randomly assigned in a 1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine-pyrimethamine (two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2, and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg every week). The primary endpoint was placental malaria in the modified intent-to-treat population, which consisted of participants who contributed placental histopathology data at birth. Secondary outcomes included clinical malaria, maternal anaemia, low birthweight, and safety. This trial is registered with ClinicalTrials.gov, number NCT01443130. FINDINGS: Between February, 2012, and May, 2014, we enrolled and randomly allocated 900 women, of whom 765 contributed histopathological data and were included in the primary analysis. 108 (14%) women had placental malaria, which was lower than the anticipated prevalence of placental malaria infection. Protection from placental malaria was not improved by chloroquine as either prophylaxis (30 [12%] of 259 had positive histopathology; relative risk [RR] 0·75, 95% CI 0·48-1·17) or intermittent therapy (39 [15%] of 253; RR 1·00, 0·67-1·50) compared with intermittent sulfadoxine-pyrimethamine (39 [15%] of 253). In protocol-specified analyses adjusted for maternal age, gestational age at enrolment, bednet use the night before enrolment, anaemia at enrolment, and malaria infection at enrolment, women taking chloroquine as prophylaxis had 34% lower placental infections than did those allocated intermittent sulfadoxine-pyrimethamine (RR 0·66, 95% CI 0·46-0·95). Clinical malaria was reported in nine women assigned intermittent sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0·26), and two allocated chloroquine prophylaxis (p=0·063). Maternal anaemia was noted in five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated intermittent chloroquine (p=0·038), and six assigned chloroquine prophylaxis (p>0·99). Low birthweight was recorded for 31 babies born to women allocated intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine (p=0·78), and 41 allocated chloroquine prophylaxis (p=0·28). Four women assigned intermittent sulfadoxine-pyrimethamine had adverse events possibly related to study product compared with 94 women allocated intermittent chloroquine (p<0·0001) and 26 allocated chloroquine prophylaxis (p<0·0001). Three women had severe or life-threatening adverse events related to study product, of whom all were assigned intermittent chloroquine (p=0·25). INTERPRETATION: Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine. Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy, but studies with larger sample sizes are needed to confirm these results. FUNDING: US National Institutes of Health

Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy.

BACKGROUND: Intermittent treatment with sulfadoxine-pyrimethamine is widely recommended for the prevention of malaria in pregnant women in Africa. However, with the spread of resistance to sulfadoxine-pyrimethamine, new interventions are needed. METHODS: We conducted a double-blind, randomized, controlled trial involving 300 human immunodeficiency virus (HIV)-uninfected pregnant adolescents or women in Uganda, where sulfadoxine-pyrimethamine resistance is widespread. We randomly assigned participants to a sulfadoxine-pyrimethamine regimen (106 participants), a three-dose dihydroartemisinin-piperaquine regimen (94 participants), or a monthly dihydroartemisinin-piperaquine regimen (100 participants). The primary outcome was the prevalence of histopathologically confirmed placental malaria. RESULTS: The prevalence of histopathologically confirmed placental malaria was significantly higher in the sulfadoxine-pyrimethamine group (50.0%) than in the three-dose dihydroartemisinin-piperaquine group (34.1%, P=0.03) or the monthly dihydroartemisinin-piperaquine group (27.1%, P=0.001). The prevalence of a composite adverse birth outcome was lower in the monthly dihydroartemisinin-piperaquine group (9.2%) than in the sulfadoxine-pyrimethamine group (18.6%, P=0.05) or the three-dose dihydroartemisinin-piperaquine group (21.3%, P=0.02). During pregnancy, the incidence of symptomatic malaria was significantly higher in the sulfadoxine-pyrimethamine group (41 episodes over 43.0 person-years at risk) than in the three-dose dihydroartemisinin-piperaquine group (12 episodes over 38.2 person-years at risk, P=0.001) or the monthly dihydroartemisinin-piperaquine group (0 episodes over 42.3 person-years at risk, P<0.001), as was the prevalence of parasitemia (40.5% in the sulfadoxine-pyrimethamine group vs. 16.6% in the three-dose dihydroartemisinin-piperaquine group [P<0.001] and 5.2% in the monthly dihydroartemisinin-piperaquine group [P<0.001]). In each treatment group, the risk of vomiting after administration of any dose of the study agents was less than 0.4%, and there were no significant differences among the groups in the risk of adverse events. CONCLUSIONS: The burden of malaria in pregnancy was significantly lower among adolescent girls or women who received intermittent preventive treatment with dihydroartemisinin-piperaquine than among those who received sulfadoxine-pyrimethamine, and monthly treatment with dihydroartemisinin-piperaquine was superior to three-dose dihydroartemisinin-piperaquine with regard to several outcomes. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT02163447.)

Ebola Virus Disease in Pregnancy: Clinical, Histopathologic, and Immunohistochemical Findings.

Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission

Effect of wet curing duration on long-term performance of concrete in tidal zone of marine environment

A proper initial curing is a very simple and inexpensive alternative to improve concrete cover quality and accordingly extend the service life of reinforced concrete structures exposed to aggressive species. A current study investigates the effect of wet curing duration on chloride penetration in plain and blended cement concretes which subjected to tidal exposure condition in south of Iran for 5 years. The results show that wet curing extension preserves concrete against high rate of chloride penetration at early ages and decreases the difference between initial and long-term diffusion coefficients due to improvement of concrete cover quality. But, as the length of exposure period to marine environment increased the effects of initial wet curing became less pronounced. Furthermore, a relationship is developed between wet curing time and diffusion coefficient at early ages and the effect of curing length on time-to-corrosion initiation of concrete is addressed.Peer reviewedCivil and Environmental Engineerin