Estimation of the infectious reservoir of Plasmodium falciparum in natural vector populations based on oocyst size

A method for determining the infectious reservoir of malaria (K) and vector survival rate (P) by measuring oocyst size and discriminating between the most recent and other infections is described. In the laboratory the mean diameter of 3 d oocysts in Anopheles gambiae, kept at 26 °C, was 11·5 μm and the mean diameter at day 5 was 24·5 μm. Oocyst sizes in wild caught mosquitoes from southern Tanzania, that had fed on the occupants of bed nets with holes in the sides, were more variable. 2060 A. gambiae s.l. and 1982 A. Funestus were examined for oocysts 3 d after feeding; 796 and 654 oocysts from the 153 and 170 infected females, respectively, were measured. Because of misclassification errors, the use of a simple cut-off model, in which all oocysts less than 17.5 μm in diameter were considered to have arisen from the most recent feed, was thought to overestimate K and underestimate P. A statistical model which allows for overlap in the oocyst size distributions is described. Estimates of the infectious reservoir derived from this model were 2.8% for A. gambiae s.l. and 4.2% for A. funestus, and the estimated survival rates per gonotrophic cycle were 65.5% and 52.9%, respectively. The utility of measuring oocyst size in naturally infected mosquitoes is discusse

Lipolytic sensitivity to catecholamines in patients with human immunodeficiency virus infection

Lipolysis is higher in patients with acquired immunodeficiency syndrome (AIDS) than in healthy control subjects. To evaluate whether this increase in lipolysis is related to increased beta-adrenergic sensitivity, we compared the lipolytic response to epinephrine (approximately 15 ng x kg(-1) x min(-1)) of six AIDS patients with that of six matched control subjects. Lipolysis was measured by infusion of [2H2]glycerol and [2H2]palmitate. The baseline rates of appearance of palmitate (2.06 +/- 0.21 compared with 1.45 +/- 0.07 micromol x kg(-1) x min(-1)) and glycerol (2.35 +/- 0.16 compared with 1.35 +/- 0.06 micromol x kg(-1) x min(-1)) were higher in AIDS patients (P <0.05). The absolute increase in lipolysis, an indicator of the responsiveness to epinephrine, was not different between groups for the rate of appearance of palmitate (86 +/- 14 compared with 75 +/- 7 micromol x L(-1) x min(-1)) or glycerol (79 +/- 13 compared with 59 +/- 6 micromol x L(-1) x min(-1)). Plasma concentrations of epinephrine were not different between groups. Lipolysis was higher whereas the lipolytic response to epinephrine was normal in AIDS patients. Increased lipolytic sensitivity to catecholamines is not the cause of increased lipolysis in AID

Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites

A highly effective vaccine that confers sterile protection to malaria is urgently needed. Immunization under chemoprophylaxis with sporozoites (CPS) consistently confers high levels of protection in the Controlled Human Malaria infection (CHMI) model. To provide a broad, unbiased assessment of the composition and kinetics of direct ex vivo human immune responses to CPS, we profiled whole-blood transcriptomes by RNA-seq before and during CPS immunization and following CHMI challenge. Differential expression of genes enriched in modules related to T cells, NK cells, protein synthesis, and mitochondrial processes were detected in fully protected individuals four weeks after the first immunization. Non-protected individuals demonstrated transcriptomic changes after the third immunization and the day of treatment, with upregulation of interferon and innate inflammatory genes and downregulation of B-cell signatures. Protected individuals demonstrated more significant interactions between blood transcription modules compared to non-protected individuals several weeks after the second and third immunizations. These data provide insight into the molecular and cellular basis of CPS-induced immune protection from P. falciparum infection

Applied Remote Sensing Program (ARSP)

There are no author-identified significant results in this report

Recombinant human interleukin 6 in metastatic renal cell cancer: a phase II trial.

A phase II trial investigating the anti-tumour effects of recombinant human interleukin 6 (rhIL-6) in patients with metastatic renal cell cancer was carried out. RhIL-6 (150 microgram) was administered as a daily subcutaneous injection for 42 consecutive days on an outpatient basis. Forty-nine patients were studied, 12 with and 37 without previous immunotherapy. Forty patients were evaluable for response. A partial remission was noted in two patients, stable disease in 17 and progressive disease in 21. Toxicity was moderate and reversible and consisted mainly of fever, flu-like symptoms, nausea, weight loss and hepatotoxicity. Anaemia, leucocytosis and thrombocytosis and induction of acute phase protein synthesis were noted in most patients. In 15% of the patients anti-IL-6 antibodies developed, and were neutralising in only one patient. Baseline plasma IL-6 concentrations did not correlate with tumour behaviour before or after rhIL-6 treatment. In conclusion, rhIL-6 can be safely administered on an outpatient basis for prolonged period of time and has moderate, reversible toxicity. Its administration induces IL-6-antibody production in only a minority of patients. Antitmour effects of rhIL-6 in metastatic renal cancer are limited

Optimal nutrition during the period of mechanical ventilation decreases mortality in critically ill, long-term acute female patients: a prospective observational cohort study

ABSTRACT: INTRODUCTION: Optimal nutrition for intensive care patients has been proposed to be the provision of energy as determined by indirect calorimetry, and protein provision of at least 1.2 grams/kg pre-admission weight per day. The evidence supporting these nutritional goals is based on surrogate outcomes and is not yet substantiated by patient oriented, clinically meaningful endpoints. In the present study we evaluated the effects of achieving optimal nutrition in intensive care unit (ICU) patients during their period of mechanical ventilation on mortality. METHODS: Prospective observational cohort study in a mixed medical-surgical, 28-bed intensive care unit in an academic hospital. 243 sequential mixed medical-surgical patients were enrolled on day 3 to 5 after admission if they had an expected stay of at least another 5 to 7 days. They underwent indirect calorimetry as part of routine care. Nutrition was guided by the result of indirect calorimetry and we aimed to provide at least 1.2 grams of protein/kg/day. Cumulative balances were calculated for the period of mechanical ventilation. Outcome parameters were ICU, 28-day and hospital mortality. RESULTS: In women, when corrected for weight, height, Apache II score, diagnosis category, and hyperglycaemic index, patients who reached their nutritional goals compared to those who did not, showed a hazard ratio (HR) of 0.199 for ICU mortality (confidence interval [CI] 0.048 - 0.831; P = 0.027), a HR of 0.079 for 28 day mortality (CI 0.013 - 0.467; P = 0.005) and a HR of 0.328 for hospital mortality (CI 0.113 - 0.952; P = 0.04). Achievement of energy goals whilst not reaching protein goals, did not affect ICU mortality; the HR for 28-day mortality was 0.120 (CI 0.027 - 0.528; P = 0.005) and 0.318 for hospital mortality (CI 0.107 - 0.945; P=0.039). No difference in outcome related to optimal feeding was found for men. CONCLUSIONS: Optimal nutritional therapy improves ICU, 28-day and hospital survival in female ICU patients. Female patients reaching both energy and protein goals have better outcomes than those reaching only the energy goal. In the present study men did not benefit from optimal nutritio

Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seronegative patients with Pneumocystis carinii pneumonia

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