ITEM METADATA RECORD
Title: Malaria diagnose bij kinderen: accuraatheid en kwaliteit van sneltesten
Other Titles: Malaria diagnosis in children: accuracy and quality of rapid diagnostic tests
Authors: Maltha, Jessica
Issue Date: 29-Nov-2013
Abstract: <span style="font-size:11.0pt;line-height:115%;font-family:&quot;Calibri&quot;,&quot;sans-serif&quot;;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:&quot;Times New Roman&quot;;mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-US">Malaria is an infectious disease caused by the Plasmodium parasite which replicates in red blood cells. Almost half of the world population is at risk of acquiring malaria and 660,000 persons died frommalaria in 2010, most of whom were children under the age of five. The World Health Organization (WHO) recommends to confirm the diagnosis of malaria before start of treatment. This confirmation can be done by microscopy, which is often unavailable or of low quality in endemic settings, or by malaria rapiddiagnostic tests (RDTs). RDTs are hand-held cassettes that detect malaria by an antigen-antibody reaction. They are easy to use and provide results within 15-20 minutes. Different formats detecting different antigens exist: Plasmodium falciparum Histidine-rich protein-2 (PfHRP2), parasite lactate dehydrogenase (pLDH) which can be specific for P. falciparum (Pf-pLDH), Plasmodium vivax (Pv-pLDH) or common toall Plasmodium species (pan-pLDH) and aldolase (all Plasmodium species).<span style="font-size:11.0pt;line-height:115%;font-family:&quot;Calibri&quot;,&quot;sans-serif&quot;;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:&quot;Times New Roman&quot;;mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-US">In 2010, 88 million RDTs were used worldwide and more than 200 different products from 60 manufacturers were available. Although worldwide used, we hypothesized several limitations and shortcomings regarding i) diagnostic accuracy, ii) appropriateness for end-users and iii) place in diagnostic algorithms. <span style="font-size:11.0pt;line-height:115%;font-family:&quot;Calibri&quot;,&quot;sans-serif&quot;;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:&quot;Times New Roman&quot;;mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-US"><span style="font-size:11.0pt;line-height:115%;font-family:&quot;Calibri&quot;,&quot;sans-serif&quot;;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:&quot;Times New Roman&quot;;mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-US"><span style="font-size:11.0pt;line-height:115%;font-family:&quot;Calibri&quot;,&quot;sans-serif&quot;;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:&quot;Times New Roman&quot;;mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-US">In Chapter 2 we showed that in 6/9 RDT products evaluated, Plasmodium falciparum samples at high parasite density generated false positive Pv-pLDH lines in 9 – 28% of samples tested, thereby leading to incorrect species diagnosis. In Chapters 3 and 6 we observed as well false positive P. falciparum resultsin case of P. vivax or P. ovale samples respectively.<w:latentstyles deflockedstate="false" defunhidewhenused="true"  <w:lsdexception="" locked="false" priority="0" semihidden="false"  <p="" class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align:justify">In Peru RDTs could be highly beneficial, especially in remote areas of the Peruvian Amazon where it may take several days before a health center can be reached; however no RDT has been incorporated in the national malaria control program yet. In Chapter 3 we evaluated a panel of RDTs in the Peruvian amazon and found that PfHRP2-detecting RDTs had low diagnostic sensitivity due to pfhrp2 gene deletion, which encodes the protein PfHRP2. We showed that Pf-pLDH-detecting RDTs are accurate and hence promising for this region; the Ministry of Health is actually in the decision process upon which RDT product to use.<p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align:justify">Clear and complete instructions are crucial to correct performance and interpretation of RDTs by end-users. We assessed a large panel of RDT products for the quality and completeness of their instructions, packaging and labeling (Chapter 4). Shortcomings were observed in all RDT products, including some with CE label. Some of the major shortcomings included ambiguous labeling of the reading window, incomplete information about test interpretation and critical differences between depicteddevice in the instructions and the device present in the RDT kit. Most of these shortcomings can be corrected at low cost and investment and will help to improve end-user’s performance. <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align:justify">Nowadays RDTs for self-use by travelers are available through the internet. There is increasing interest in the self-use of RDTs, but quality of these products is unknown. We found that only half of the RDT products advertised for self-testing and purchased through internet could reliably diagnose <span style="mso-bidi-font-style:normal">P. falciparum <span style="mso-bidi-font-style:normal">and<span style="mso-bidi-font-style:normal"> P. vivax.<span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"> <span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal">Two products showed positive test lines in nearly all samples, including the Plasmodium negative ones, thereby prohibiting their use. (Chapter 5). All products had major shortcomings in the instructions for use with regard to description of test procedure and interpretation, poor readability and lay-out and user-unfriendly typography. Importantly, strategic issues (‘what to do ifyour test is positive or negative’) were incomplete or not mentioned at all. Before RDTs can be recommended for self-use by travelers, major improvements need to be done and we only recommend RDTs for travelers when comprehensive instructions and a training program are guaranteed.<span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"> <span style="mso-bidi-font-style:normal"><p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align:justify"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal">Malaria is often over-diagnosed in endemic settings. Severe malaria may present with similar symptoms as invasive bacterial infections, such as bacteremia or meningitis. Co-infections of malaria and bacterial infections may occur as well. In order to improve treatment guidelines in children presenting with severe febrile illness in malaria endemic areas, it is important to know to which extent malaria and invasivebacterial infections occur and what the antibiotic resistance rates are. In a group of severely ill children in a seasonal hyperendemic malaria transmission area in Burkina Faso, we observed severe malaria in 50% of the admissions and invasive bacterial infections in 9%. However, case-fatality rates of invasive bacterialinfections were four-fold higher compared to severe malaria. Furthermore, many of the bacteria isolated were resistant against first line antibiotics commonly used in Burkina Faso (Chapter 6). <span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"></><p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align:justify"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal">As malaria rapid diagnostic tests are used in children presenting with severe febrile illness<span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal">, and as they are the only diagnostic tool available in health centers, we assessed the diagnostic accuracy and predictive value of PfHRP2 versus Pf-pLDH detection in the children studied in Chapter 6. We observed similar (high)sensitivities, but the specificity of PfHRP2-detection was significantly lower compared to Pf-pLDH detection, which was reflected by a lower positive predictive value of PfHRP2 detection for all ages and seasons (<span style="mso-bidi-font-weight:normal">Chapter 7). Positive PfHRP2 results do not distinguish between recent (<1 week) or ongoing P.falciparum infections versus past en cured <span style="mso-bidi-font-style:normal">P. falciparum infections more than one week ago. Pf-pLDH probably will be better suited for this purpose as it is rapidly cleared from the bloodstream and should be further studied. <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align:justify"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-weight:normal"><span style="mso-bidi-font-style:normal">In conclusion, we provided information with regard to diagnostic accuracy, end-user performance anddiagnostic practice of malaria RDTs, which when addressed by the respective manufacturers, health regulatory authorities and health care professionals can improve malaria diagnosis in children.<i style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-weight:normal"><span style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-weight:normal"><span style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><span style="mso-bidi-font-style:normal"><span style="mso-bidi-font-weight:normal"><span style="mso-bidi-font-style:normal"><i style="mso-bidi-font-style:normal"><span style="mso-bidi-font-weight:normal"><b style="mso-bidi-font-weight:normal"><i style="mso-bidi-font-style:normal"><w:latentstyles deflockedstate="false" defunhidewhenused="true"  <w:lsdexception="" locked="false" priority="0" semihidden="false"  
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Molecular and Vascular Biology

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