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      PERSISTENCE OF PLASMODIUM FALCIPARUM HRP2 ANTIGEN AFTER EFFECTIVE ANTIMALARIAL THERAPY

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          Abstract

          Introduction:

          Histidine Rich Protein 2 based (HRP2-based) malaria rapid diagnostic tests (mRDTs) have been shown to perform as well as routine light microscopy, however, they are limited by some factors including persistence of HRP2 antigenemia. In this paper we report the evaluation of an HRP2-based mRDT in a prospective study that enrolled children and followed them up for 28 days.

          Methods:

          Children aged below five years, with acute episode of fever/pyrexia, were enrolled. The enrolled participants had expert malaria microscopy and RDT done at enrolment (Day 0), and on days 1, 2, 3, 7, 14, 21, and 28. The malaria RDT test was considered positive when the antigen and control lines were visible in their respective windows, negative when only the control band was visible and invalid when the control band was not visible. Faint test lines were considered positive. The RDT results were compared to those of expert microscopy.

          Results:

          Two hundred and twenty-six children aged 29.2 ± 15.5 months were enrolled. The proportion of children positive by expert malaria microscopy and RDT was 100% and 95.6% respectively. During the 28 day follow up of the children the proportions positive by microscopy and RDT on days 3, 7, 14, and 28 were 1% and 94.6%, 0% and 93.5%, 0% and 91%, and 16.5% and 80.6% respectively. Gender and age dependent analysis of proportion of positive children were similar. Proportion of children with persistence of HRP2 antigen appeared to be lower in those with parasite density below 200/µL, however, this observation requires further evaluation in larger studies.

          Conclusion:

          the study revealed a high proportion of persistence of HRP2 antigen in the children 28 days after effective antimalarial therapy. Histidine rich protein 2 based malaria rapid diagnostic tests are not recommended for monitoring of antimalarial therapies.

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          Most cited references26

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          A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT).

          The absolute necessity for rational therapy in the face of rampant drug resistance places increasing importance on the accuracy of malaria diagnosis. Giemsa microscopy and rapid diagnostic tests (RDTs) represent the two diagnostics most likely to have the largest impact on malaria control today. These two methods, each with characteristic strengths and limitations, together represent the best hope for accurate diagnosis as a key component of successful malaria control. This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials. Reduction of malaria morbidity and drug resistance intensity plus the associated economic loss of these two factors require urgent scaling up of the quality of parasite-based diagnostic methods. An investment in anti-malarial drug development or malaria vaccine development should be accompanied by a parallel commitment to improve diagnostic tools and their availability to people living in malarious areas.
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            Improving community health worker use of malaria rapid diagnostic tests in Zambia: package instructions, job aid and job aid-plus-training

            Background Introduction of artemisinin combination therapy (ACT) has boosted interest in parasite-based malaria diagnosis, leading to increased use of rapid diagnostic tests (RDTs), particularly in rural settings where microscopy is limited. With donor support, national malaria control programmes are now procuring large quantities of RDTs. The scarcity of health facilities and trained personnel in many sub-Saharan African countries means that limiting RDT use to such facilities would exclude a significant proportion of febrile cases. RDT use by volunteer community health workers (CHWs) is one alternative, but most sub-Saharan African countries prohibit CHWs from handling blood, and little is known about CHW ability to use RDTs safely and effectively. This Zambia-based study was designed to determine: (i) whether Zambian CHWs could prepare and interpret RDTs accurately and safely using manufacturer's instructions alone; (ii) whether simple, mostly pictorial instructions (a "job aid") could raise performance to adequate levels; and (iii) whether a brief training programme would produce further improvement. Methods The job aid and training programme were based on formative research with 32 CHWs in Luangwa District. The study team then recruited three groups of CHWs in Chongwe and Chibombo districts. All had experience treating malaria based on clinical diagnosis, but only six had prior RDT experience. Trained observers used structured observation checklists to score each participant's preparation of three RDTs. Each also read 10 photographs showing different test results. The first group (n = 32) was guided only by manufacturer's instructions. The second (n = 21) used only the job aid. The last (n = 26) used the job aid after receiving a three-hour training. Results Mean scores, adjusted for education, age, gender and experience, were 57% of 16 RDT steps correctly completed for group 1, 80% for group 2, and 92% for group 3. Mean percentage of test results interpreted correctly were 54% (group 1), 80% (group 2), and 93% (group 3). All differences were statistically significant (p < 0.05). Conclusion Manufacturer's instructions like those provided with the RDTs used in this study are insufficient to ensure safe and accurate use by CHWs. However, well-designed instructions plus training can ensure high performance. More study is underway to determine how well this performance holds up over time.
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              Artemisinin‐induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure.

              Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an approximately 10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.
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                Author and article information

                Journal
                Ann Ib Postgrad Med
                Ann Ib Postgrad Med
                AIPM
                Annals of Ibadan Postgraduate Medicine
                Association of Resident Doctors (ARD), University College Hospital, Ibadan
                1597-1627
                June 2021
                : 19
                : 1
                : 15-21
                Affiliations
                [1. ]Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Nigeria.
                [2. ]Institute of Child Health, College of Medicine, University of Ibadan, Nigeria.
                Author notes
                Correspondence: Dr. O.S. Michael Dept. of Pharm. and Therapeutics, College of Medicine, University of Ibadan, Email: micobaro@ 123456gmail.com
                Article
                AIPM-19-15
                8935674
                35330886
                5ac472f4-eefb-49bf-bd3d-d73881dd239f
                © Association of Resident Doctors, UCH, Ibadan

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

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                Original Article

                malaria,rdt,persistence,hrp2,nigeria
                malaria, rdt, persistence, hrp2, nigeria

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