Withholding Antimalarials in Febrile Children Who Have a Negative Result for a Rapid Diagnostic Test

Background. The availability of a rapid diagnostic test for malaria (RDTm) allows accurate diagnosis at all levels of health facilities. The objective of the present study was to evaluate the safety of withholding antimalarials in febrile children who have a negative test result. Methods. We conducted a prospective 2-arm longitudinal study in areas of Tanzania that are moderately and highly endemic for malaria. Children with a history of fever were managed routinely by resident clinicians of 2 health facilities, except that no antimalarials were prescribed if the RDTm result was negative. Children were followed up at home on day 7. The main outcome was the occurrence of complications in children with negative RDTm results; children with positive RDTm results were followed up for the same outcomes for indirect comparison. Results. One thousand children (median age, 24 months) were recruited. Six hundred three children (60%) had a negative RDTm result. Five hundred seventy-three (97%) of these children were cured on day 7. Forty-nine (8%) of the children with negative RDTm results spontaneously visited the dispensary before day 7, compared with 10 (3%) of the children with positive RDTm results. All children who had negative initial results had negative results again when they were tested either at spontaneous attendance or on day 7 because they were not cured clinically, except for 3 who gave positive results on days 2, 4, and 7 respectively but who did not experience any complication. Four children who had negative initial results were admitted to the hospital subsequently, all with negative results for malaria tests upon admission. Two of them died, of causes other than malaria. Conclusions. Not giving antimalarial drugs in febrile children who had a negative RDTm result was safe, even in an area highly endemic for malaria. Our study provides evidence for treatment recommendations based on parasitological diagnosis in children <5 years ol

Dispensary level pilot implementation of rapid diagnostic tests: an evaluation of RDT acceptance and usage by providers and patients – Tanzania, 2005

BACKGROUND\ud \ud Malaria rapid diagnostic tests (RDTs) may assist in diagnosis, improve prescribing practices and reduce potential drug resistance development. Without understanding operational issues or acceptance and usage by providers and patients, the costs of these tests may not be justified.\ud \ud OBJECTIVES\ud \ud To evaluate the impact of RDTs on prescribing behaviours, assess prescribers' and patients' perceptions, and identify operational issues during implementation.\ud \ud METHODS\ud \ud Baseline data were collected at six Tanzanian public dispensaries. RDTs were implemented for eight weeks and data collected on frequency of RDT use, results, malaria diagnoses and the prescription of antimalarials. Patients referred for RDTs completed a standardised exit interview. Qualitative methods assessed attitudes toward and satisfaction with RDTs, perceptions about the test and operational issues related to implementation.\ud \ud RESULTS\ud \ud Of 595 patients at baseline, 200 (33%) were diagnosed clinically with malaria but had a negative RDT. Among the 2519 RDTs performed during implementation, 289 (11.5%) had a negative result and antimalarials prescribed. The proportion of "over-prescriptions" at baseline was 54.8% (198/365). At weeks four and eight this decreased to 16.1% (27/168) and 16.4% (42/256) respectively.A total of 355 patient or parent/caregiver and 21 prescriber individual interviews and 12 focus group discussions (FGDs) were conducted. Patients, caregivers and providers trusted RDT results, agreed that use of RDTs was feasible at dispensary level, and perceived that RDTs improved clinical diagnosis. Negative concerns included community suspicion and fear that RDTs were HIV tests, the need for additional supervision in interpreting the results, and increased work loads without added compensation.\ud \ud CONCLUSION\ud \ud Overprescriptions decreased over the study period. There was a high degree of patient/caregiver and provider acceptance of and satisfaction with RDTs. Implementation should include community education, sufficient levels of training and supervision and consideration of the need for additional staff

Experience of safety monitoring in the context of a prospective observational study of artemether-lumefantrine in rural Tanzania: lessons learned for pharmacovigilance reporting

<p>Abstract</p> <p>Objectives</p> <p>To identify and implement strategies that help meet safety monitoring requirements in the context of an observational study for artemether-lumefantrine (AL) administered as first-line treatment for uncomplicated malaria in rural Tanzania.</p> <p>Methods</p> <p>Pharmacovigilance procedures were developed through collaboration between the investigating bodies, the relevant regulatory authority and the manufacturer of AL. Training and refresher sessions on the pharmacovigilance system were provided for healthcare workers from local health facilities and field recorders of the Ifakara Health Demographic Surveillance System (IHDSS). Three distinct channels for identification of adverse events (AEs) and serious adverse events (SAEs) were identified and implemented. Passive reporting took place through IHDSS and health care facilities, starting in October 2007. The third channel was through solicited reporting that was included in the context of a survey on AL as part of the ALIVE (<b>A</b>rtemether-<b>L</b>umefantrine <b>I</b>n <b>V</b>ulnerable patients: <b>E</b>xploring health impact) study (conducted only in March-April 2008).</p> <p>Results</p> <p>Training was provided for 40 healthcare providers (with refresher training 18 months later) and for six field recorders. During the period 1^stSeptember 2007 to 31^stMarch 2010, 67 AEs were reported including 52 under AL, five under sulphadoxine-pyrimethamine, one under metakelfin, two after antibiotics; the remaining seven were due to anti-pyretic or anti-parasite medications. Twenty patients experienced SAEs; in 16 cases, a relation to AL was suspected. Six of the 20 cases were reported within 24 hours of occurrence.</p> <p>Discussion</p> <p>Safety monitoring and reporting is possible even in settings with weak health infrastructure. Reporting can be enhanced by regular and appropriate training of healthcare providers. SMS text alerts provide a practical solution to communication challenges.</p> <p>Conclusion</p> <p>Experience gained in this setting could help to improve spontaneous reporting of AEs and SAEs to health authorities or marketing authorization holders.</p

Residual antimalarials in malaria patients from Tanzania--implications on drug efficacy assessment and spread of parasite resistance.

BACKGROUND\ud \ud Repeated antimalarial treatment for febrile episodes and self-treatment are common in malaria-endemic areas. The intake of antimalarials prior to participating in an in vivo study may alter treatment outcome and affect the interpretation of both efficacy and safety outcomes. We report the findings from baseline plasma sampling of malaria patients prior to inclusion into an in vivo study in Tanzania and discuss the implications of residual concentrations of antimalarials in this setting.\ud \ud METHODS AND FINDINGS\ud \ud In an in vivo study conducted in a rural area of Tanzania in 2008, baseline plasma samples from patients reporting no antimalarial intake within the last 28 days were screened for the presence of 14 antimalarials (parent drugs or metabolites) using liquid chromatography-tandem mass spectrometry. Among the 148 patients enrolled, 110 (74.3%) had at least one antimalarial in their plasma: 80 (54.1%) had lumefantrine above the lower limit of calibration (LLC = 4 ng/mL), 7 (4.7%) desbutyl-lumefantrine (4 ng/mL), 77 (52.0%) sulfadoxine (0.5 ng/mL), 15 (10.1%) pyrimethamine (0.5 ng/mL), 16 (10.8%) quinine (2.5 ng/mL) and none chloroquine (2.5 ng/mL).\ud \ud CONCLUSIONS\ud \ud The proportion of patients with detectable antimalarial drug levels prior to enrollment into the study is worrying. Indeed artemether-lumefantrine was supposed to be available only at government health facilities. Although sulfadoxine-pyrimethamine is only recommended for intermittent preventive treatment in pregnancy (IPTp), it was still widely used in public and private health facilities and sold in drug shops. Self-reporting of previous drug intake is unreliable and thus screening for the presence of antimalarial drug levels should be considered in future in vivo studies to allow for accurate assessment of treatment outcome. Furthermore, persisting sub-therapeutic drug levels of antimalarials in a population could promote the spread of drug resistance. The knowledge on drug pressure in a given population is important to monitor standard treatment policy implementation

Laborativ matematik : en möjlighet eller en belastning

The past years there has been a big media circus, that states that the Swedish schoolsystem is broken and with dropping results in PISA as a proof of this statement. Voices have been heard that teachers rely on textbooks in a voluminous way and some suggest that this is the main problem as Swedish students dropping in mathematics results. This study shows how teachers perceive their use of laboratory mathematics and is therefore based on a teacher perspective. What I want with this study is to show how teachers looks at the correlation between benefits and disadvantages in using laboratory mathematics, but also to create an awareness for understanding the difficulties that you may face as teacher if you want to use laboratory mathematics as a tool when teaching. In this study, the main focus is on how teachers use laboratory mathematics as an option when teaching. Nine teachers participated in an online survey and answered questions about how they use laboratory mathematics and what benefits or disadvantages it may comprehend. To add, two teachers also attended to a private interview and another two were observed. The result that was found is that teachers can see big advantages in using laboratory mathematics especially when teaching geometry. The teachers pinpoint how using laboratory mathematics supports students deeper understanding for the mathematic contents. Though, teachers also highlight that there is a urgent need for the teacher to have the knowledge to comprehend meaningful and aimful lessons. Apart from knowledge teachers points to the lack of time to plan and execute as a disadvantage. The lack of time combined with insufficient knowledge in how to use laboratory mathematics is the determiner if laboratory mathematics is seen as a possibility or an affliction

Residual plasma concentrations of antimalarials found prior to treatment in 148 malaria patients [ng/mL].

<p>No artemether, artesunate, dihydroartemisinin, amodiaquine, <i>N</i>-desethyl-amodiaquine, piperaquine, pyronaridine, mefloquine, or chloroquine was found.</p

Review of pharmacokinetic studies of sulfadoxine (continued).

a<p>Derived from clearance and plasma half-life (<i>t_½</i>).</p>b<p>Derived from clearance and elimination rate constant (<i>λ</i>).</p>c<p>Derived from <i>V</i>/<i>CL</i> × ln(2).</p>d<p>Corrected by a factor of (<i>BW</i>/11 kg)^0.72 for other body weight (<i>BW</i>) values.</p>e<p>Corrected by a factor of (<i>BW</i>/11 kg)^0..64 for other body weight (<i>BW</i>) values.</p