Controlled human malaria infection with graded numbers of Plasmodium falciparum NF135.C10- or NF166.C8-infected mosquitoes

Controlled human malaria infections (CHMIs) with Plasmodium falciparum (Pf) parasites are well established. Exposure to five Pf (NF54)-infected Anopheles mosquitoes results in 100% infection rates in malaria-näive volunteers. Recently Pf clones NF135.C10 and NF166.C8 were generated for application in CHMIs. Here, we tested the clinical infection rates of these clones, using graded numbers of Pf-infected mosquitoes. In a double-blind randomized trial, we exposed 24 malaria-näive volunteers to bites from one, two, or five mosquitoes infected with NF135.C10 or NF166.C8. The primary endpoint was parasitemia by quantitative polymerase chain reaction. For both strains, bites by five infected mosquitoes resulted in parasitemiain4/4 volunteers; 3/4 volunteers developed parasitemia after exposure to one or two infected mosquitoes infected with either clone. The prepatent period was 7.25 ± 4.0 days (median ± range). There were no serious adverse events and comparable clinical symptoms between all groups. These data confirm the eligibility of NF135.C10 and NF166.C8 for use in CHMI studies

Vitamin B-6 deficiency is common and associated with poor long-term outcome in renal transplant recipients

Background: Previous studies have reported low circulating concentrations of pyridoxal-5-phospate (PLP) in renal transplant recipients (RTRs). It is unknown whether this is because of low intake or altered handling, and it is also unknown whether variation in circulating concentrations of PLP influences long-term outcome. Objective: We compared Vitamin B-6 intake and circulating PLP concentrations of RTRs with those of healthy controls and investigated long-term clinical implications of Vitamin B-6 deficiency in stable outpatient RTRs. Design: In a longitudinal cohort of 687 stable RTRs (57% male; mean ± SD age: 53 ± 13 y) with a median (IQR) follow-up of 5.3 y (4.8-6.1 y) and 357 healthy controls (47% male; age 54 ± 11 y), baseline Vitamin B-6 was measured as plasma PLP by highperformance liquid chromatography (HPLC). Vitamin B-6 deficiency was defined as PLP<20 nmol/L, and insufficiency as PLP 20-30 nmol/L. Dietary intake was assessed by validated foodfrequency questionnaires. Results: At inclusion [5.3 y (1.8-12.1 y) after transplantation], the mean Vitamin B-6 intakes in RTRs and healthy controls were 1.77 ± 0.49 and 1.85 ± 0.56 mg/d, respectively (P = 0.23). In these groups, the median plasma PLP concentrations were 29 nmol/L (17-50 nmol/L) and 41 nmol/L (29-60 nmol/L), respectively (P<0.001). Accordingly, deficiency was present in 30% of RTRs compared with 11% of healthy controls. PLP concentrations were inversely associated with glucose homeostasis variables and inflammation variables (all P<0.01). During follow-up, 149 (21%) RTRs died and 82 (12%) developed graft failure. In RTRs, Vitamin B-6 deficiency was associated with considerably higher mortality risk (HR 2.14; 95% CI: 1.48, 3.08) than a sufficient Vitamin B-6 status, independent of potential confounders. No associations were observed for graft failure (P = 0.18). Conclusions: Vitamin B-6 deficiency is common in RTRs and does not seem to be a consequence of inadequate intake. In addition, this deficient state is clinically relevant and independently associated with an increased risk of mortality in RTRs. The cohort on which the study was based [TransplantLines Food and Nutrition Biobank and Cohort Study (TxL-FN)] was registered at clinicaltrials.gov as NCT02811835. Am J Clin Nutr 2017;105:1344-50.</p