BackgroundAccurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region.MethodsThe pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs.ResultsSequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified.ConclusionsThe results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

OBJECTIVEGiven the role of gut microbiota in regulating metabolism, probiotics administered during pregnancy might prevent gestational diabetes mellitus (GDM). This question has not previously been studied in high-risk overweight and obese pregnant women. We aimed to determine whether probiotics (Lactobacillus rhamnosus and Bifidobacterium animalis subspecies lactis) administered from the second trimester in overweight and obese women prevent GDM as assessed by an oral glucose tolerance test (OGTT) at 28 weeks' gestation. Secondary outcomes included maternal and neonatal complications, maternal blood pressure and BMI, and infant body composition. RESEARCH DESIGN AND METHODSThis was a double-blind randomized controlled trial of probiotic versus placebo in overweight and obese pregnant women in Brisbane, Australia. RESULTSThe study was completed in 411 women. GDM occurred in 12.3% (25 of 204) in the placebo arm and 18.4% (38 of 207) in the probiotics arm (P = 0.10). At OGTT, mean fasting glucose was higher in women randomized to probiotics (79.3 mg/dL) compared with placebo (77.5 mg/dL) (P = 0.049). One-and two-hour glucose measures were similar. Preeclampsia occurred in 9.2% of women randomized to probiotics compared with 4.9% in the placebo arm (P = 0.09). Excessive weight gain occurred in 32.5% of women in the probiotics arm (55 of 169) compared with 46% in the placebo arm (81 of 176) (P = 0.01). Rates of small for gestational age (<10th percentile) were 2.4% in the probiotics arm (5 of 205) and 6.5% in the placebo arm (13 of 199) (P = 0.042). There were no differences in other secondary outcomes. CONCLUSIONSThe probiotics used in this study did not prevent GDM in overweight and obese pregnant women.Clinical trial reg. no. ACTRN12611001208998, www.anzctr.org.au This article is part of a special article collection available at http://care.diabetesjournals.org/ gdm-new-evidence.

f Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs. Malaria rapid diagnostic tests (RDTs) are lateral flow immunochromatographic tests that detect parasitic antigens circulating in the blood of malaria-infected patients. Currently, the tests most widely used for diagnosis of Plasmodium falciparum infection target the parasite antigen histidine-rich protein 2 (HRP2).HRP2 is produced in abundance during the asexual cycle and in early gametocyte stages of P. falciparum parasites (5, 6, 9, 10, 12). It has an unusual structure in that it contains multiple contiguous repeats that are rich in alanine, histidine, and aspartic acid, which comprise 37%, 34%, and 10% of the protein, respectively (9, 12). These features make HRP2 an ideal biomarker for immunodetection. A number of monoclonal antibodies (MAbs) against HRP2 have been developed for use in HRP2-detecting RDTs. A major determinant of the performance of these HRP2-detecting malaria RDTs is the binding characteristics of the MAbs. It is plausible that the number of potential target epitopes in the HRP protein of a parasite isolate could be an important determinant of the binding affinity of a MAb, where a higher epitope frequency may result in greater test sensitivity. The frequency or distribution of the target epitopes present in a particular parasite population may have an impact on the efficiency of detection of parasitemia in this population and, hence, the sensitivity of RDTs that use this antibody. An ideal epitope to be targeted by the signal and capture antibodies in an RDT would be one that is present in all isolates (high prevalence) and has a high copy ...

This large prospective intraindividual comparison of [ 18 F]PSMA-1007 PET/CT vs [ 68 Ga]Ga-PSMA-11 PET/CT has demonstrated overall high concordance (92%) for TNM stage in the context of prostate cancer primary staging, biochemical recurrence and evaluation of patients with metastatic disease. Reduced [ 18 F]PSMA-1007 urinary radiotracer excretion improves characterisation of disease adjacent the bladder (prostate or prostate bed following de nitive treatment, including local invasion) and ureters (peri-ureteric nodes) compared to [ 68 Ga]Ga-PSMA-11. [ 18 F]PSMA-1007 demonstrates signi cantly higher uptake within involved nodes and bone metastases, and physiologic tissues including liver, spleen, neural ganglia, bone marrow and benign nodes. Inexperienced reporters of [ 18 F]PSMA-1007 PET should understand that hepatic uptake may obscure metastases within the liver or adjacent adrenal gland, and that [ 18 F]PSMA-1007 is associated with more equivocal bone lesions. Both tracers are acceptable for imaging of prostate cancer, with factors in uencing choice including availability (local generator production of [ 68 Ga]Ga-PSMA-11 vs external cyclotron supply [ 18 F]PSMA-1007), preference for improved characterisation of disease in the prostate and pelvic nodes (favouring [ 18 F]PSMA-1007) versus likelihood of visceral metastasis (favouring [ 68 Ga]Ga-PSMA-11) and the experience of reporting specialists to exclude benign patterns of uptake, particularly neural ganglia and equivocal bone lesions.