What information and the extent of information research participants need in informed consent forms: a multi-country survey

Background: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. Methods: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). Results: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be \u27moderately important\u27 to \u27very important\u27 for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). Conclusions: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF

Two-site immunoradiometric assay for detection of Plasmodium falciparum antigen in blood using monoclonal and polyclonal antibodies

Three systems of immunoradiometric assays (IRMAs), a two-site monoclonal antibody sandwich IRMA (MAb-IRMA), two-site polyclonal antibody-monoclonal antibody sandwich IRMA (PAb-MAb-IRMA), and two-site polyclonal antibody sandwich IRMA (PAb-IRMA), were developed to detect low-grade infections with Plasmodium falciparum. The assays showed good correlation with parasitemia when tested against parasites from in vitro cultures (r = 0.996, 0.994, and 0.998 for MAb-, PAb-MAb-, and PAb-IRMA, respectively), with the ability to detect as few as 0.24, 0.67, and 1.82 parasites per 10(7) erythrocytes, respectively. The assays were specific for P. falciparum, since a serially diluted specimen from a patient with vivax malaria with an initial parasitemia of 0.8% and almost all of the undiluted specimens from five other vivax malaria patients were negative. The assays were performed on patients with falciparum malaria before and after treatment with antimalarial drugs. Before treatment, all 24 patients were positive by all three systems of two-site sandwich IRMAs. Two weeks after treatment, 81.8% (18 of 22) of the patients were positive by microscopic examination, but the IRMA positivity rates were 90.9% (20 of 22), 86.4% (19 of 22), and 81.8% (18 of 22) for MAb-, PAb-MAb-, and PAb-IRMA, respectively. Four weeks after treatment, all 19 patients were negative by microscopic examination, but 52.6% (10 of 19) of the patients were still positive with MAb- and PAb-MAb-IRMA and 31.6% (6 of 19) were positive with PAb-IRMA. Comparison between the three systems of IRMA showed that the MAb-IRMA was superior to the other two systems for three reasons. First, it gave a lower count when tested with blood from healthy individuals. Second, it gave a higher count when tested with blood from patients with falciparum malaria. Third, it gave better correlation with parasitemia when blood from falciparum malaria patients was tested. MAb-IRMA is recommended for use for the detection of low-grade P. falciparum infection.</jats:p

Factors contributing to the development of cerebral malaria. II. Endotoxin.

Limulus amoebocyte lysate test (LALT) was used to detect endotoxin-like substances in the plasma of 15 patients with cerebral malaria, 28 patients with uncomplicated falciparum malaria and 30 healthy controls. On admission, 67% of cerebral malaria patients were positive, whereas only 21.4% of uncomplicated malaria patients and none of controls were positive. Among uncomplicated malaria cases, four of eight patients with parasitaemia over 90,000/mm3 were LALT positive whereas only two of 20 patients with parasitaemia of less than 90,000/mm3 were positive. A follow-up study in cerebral malaria patients showed some variation in LALT positivity rate from day to day (85.7% on day 1, 53.3% on day 3 and all negative on discharge from hospital). LALT positivity bore no relationship to gram negative bacteraemia. Leucocytosis and elevated serum enzymes were more frequently found in LALT-positive patients. Our results suggest that endotoxin (LALT positivity) of the plasma of malaria patients is derived from either the parasites themselves or from the gut. It relates to parasitaemia, leucocytosis and elevated serum enzymes, but not to the clinical syndrome of cerebral malaria

Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies.

Abstract Plasmodium falciparum and P. vivax sporozoites were observed to invade cultured human hepatoma cells in vitro. Monoclonal antibodies to the circumsporozoite (CS) protein of each of these malarial species blocked invasion. Inhibition was species-specific, but was independent of the geographic origin of each strain. Because these monoclonal antibodies have been shown to diminish or abolish sporozoite infectivity to susceptible primate hosts, it is suggested that inhibition of invasion of sporozoites (ISI) into cultured cells may represent in in vitro assay for protective antibodies. This was confirmed by the finding that serum taken from volunteers immune to sporozoite challenge also totally blocked sporozoite invasion. The ISI assay also detected naturally acquired invasive-neutralizing antibodies in areas endemic for malaria. This ISI assay may therefore be useful in determining the incidence of inhibitory anti-sporozoite antibodies in general populations, and allow the monitoring of the effect of an anti-malarial vaccine using sporozoite-derived antigens.</jats:p

Detection of heat-stable enterotoxigenic Escherichia coli by hybridization with an RNA transcript probe

Heat-stable enterotoxigenic Escherichia coli was identified by nucleotide hybridization with RNA transcripts of the gene encoding heat-stable A-2 enterotoxin. Radiolabeled enterotoxin gene RNA transcripts are easier to prepare and avoid the preparation of cloned DNA probes that can be nonspecific if they contain cloning vector DNA.</jats:p

Function of the blood-cerebrospinal fluid barrier in human cerebral malaria: rejection of the permeability hypothesis.

We tested the hypothesis that cerebral malaria is caused by blood-brain barrier inflammation and cerebral edema. In a group of 157 Thai patients with strictly defined cerebral malaria, cerebrospinal fluid (CSF) opening pressures were normal in 79% and were lower in fatal cases than in survivors (means +/- 1 SD, 144 +/- 58 and 167 +/- 51 mm CSF, respectively, P = 0.051). CSF: serum albumin ratios (X 10(3)) in 39 of them were significantly higher than in 61 British controls (medians 8.5 and 5.5, respectively, P = 0.04), but were no higher in 7 fatal cases. In a group of 12 patients this ratio was not significantly higher during coma than after full recovery (means +/- 1 SD, 9.0 +/- 6.2 and 6.7 +/- 4.2, respectively, P greater than 0.1). CSF alpha 2-macroglobulin concentrations were always normal. CSF : serum 77Br- ratios were elevated in 11/19 comatose cases but fell to normal 4 to 9 days later in 11/11 cases. Dexamethasone treatment had no significant effect on bromide partition. The percentage of an intravenously administered dose of 125I-human serum albumin detectable per ml of CSF 6 hr after intravenous injection was 2.4 +/- 1.3 X 10(-5) in 14 comatose patients and 4.4 +/- 4.0 X 10(-5) in 9 of them during convalescence (P greater than 0.1). These results demonstrate that the blood-CSF barrier is essentially intact in patients with cerebral malaria and give no support to the idea that cerebral edema is the cause of coma