Dataset Information

Insights into the Performance of SD Bioline Malaria Ag P.f/Pan Rapid Diagnostic Test and Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in Madagascar.

ABSTRACT: Plasmodium falciparum histidine-rich protein 2 (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). However, the parasites lacking part or all of the pfhrp2 gene do not express the PfHRP2 protein and are, therefore, not identifiable by PfHRP2-detecting RDTs. We evaluated the performance of the SD Bioline Malaria Ag P.f/Pan RDT together with pfhrp2 variation in Madagascar. Genomic DNA isolated from 260 patient blood samples were polymerase chain reaction (PCR)-amplified for the parasite 18S rRNA and pfhrp2 genes. Post-PCR ligation detection reaction-fluorescent microsphere assay (LDR-FMA) was performed for the identification of parasite species. Plasmodium falciparum histidine-rich protein 2 amplicons were sequenced. Polymerase chain reaction diagnosis of patient samples showed that 29% (75/260) were infected and P. falciparum was present in 95% (71/75) of these PCR-positive samples. Comparing RDT and P. falciparum detection by LDR-FMA, eight samples were RDT negative but P. falciparum positive (false negatives), all of which were pfhrp2 positive. The sensitivity and specificity of the RDT were 87% and 90%, respectively. Seventy-three samples were amplified for pfhrp2, from which nine randomly selected amplicons were sequenced, yielding 13 sequences. Amplification of pfhrp2, combined with RDT analysis and P. falciparum detection by LDR-FMA, showed that there was no indication of pfhrp2 deletion. Sequence analysis of pfhrp2 showed that the correlation between pfhrp2 sequence structure and RDT detection rates was unclear. Although the observed absence of pfhrp2 deletion from the samples screened here is encouraging, continued monitoring of the efficacy of the SD Bioline Malaria Ag P.f/Pan RDT for malaria diagnosis in Madagascar is warranted.

SUBMITTER: Willie N

PROVIDER: S-EPMC6086193 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Insights into the Performance of SD Bioline Malaria Ag P.f/Pan Rapid Diagnostic Test and Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in Madagascar.

Willie Nigani N Mehlotra Rajeev K RK Howes Rosalind E RE Rakotomanga Tovonahary A TA Ramboarina Stephanie S Ratsimbasoa Arsène C AC Zimmerman Peter A PA

The American journal of tropical medicine and hygiene 20180315 6

Plasmodium falciparum histidine-rich protein 2 (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). However, the parasites lacking part or all of the pfhrp2 gene do not express the PfHRP2 protein and are, therefore, not identifiable by PfHRP2-detecting RDTs. We evaluated the performance of the SD Bioline Malaria Ag P.f/Pan RDT together with pfhrp2 variation in Madagascar. Genomic DNA isolated from 260 patient blood samples were polymerase chain rea ...[more]

PMID: 29557337

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Project description:There was an increase in the number of malaria cases in Cameroon in 2018 that could reflect changes in provider practice, despite effective interventions. In this study, we assessed the diagnostic performance of two malaria rapid diagnostic tests (mRDTs) for diagnostic confirmation of suspected cases of malaria in public and private health facilities in two malaria transmission settings in Cameroon. We evaluated the diagnostic performance of CareStart pf and SD Bioline Pf/PAN mRDT and compared these parameters by RDT type and transmission setting. Nested PCR and blood film microscopy were used as references. The chi square test was used for independent sample comparisons, while the McNemar's test was used to test for the dependence of categorical data in paired sample testing. A p < 0.05 was considered significant in all comparisons. The R (v.4.0.2) software was used for analyses. A total of 1126 participants consented for the study in the four sites. The diagnostic accuracy of the CareStart Pf mRDT was 0.93.6% (0.911-0.961) in Yaoundé, 0.930% (0.90-0.960) in Ngounso, 0.84% (0.794-0.891) in St Vincent Catholic Hospital Dschang and 0.407 (0.345-0.468) in Dschang district hospital. For SD Bioline Pf/PAN the accuracy was 0.759 (0.738-0.846) for St Vincent Catholic Hospital Dschang and 0.426 (0.372-0.496) for the Dschang district hospital. The accuracy was slightly lower in each case but not statistically different when PCR was considered as the reference. The likelihood ratios of the positive and negative tests were high in the high transmission settings of Yaoundé (10.99 (6.24-19.35)) and Ngounso (14.40 (7.89-26.28)) compared to the low transmission settings of Dschang (0.71 (0.37-1.37)) and St Vincent Catholic hospital (7.37 (4.32-12.59)). There was a high degree of agreement between the tests in Yaoundé (Cohen's Kappa: 0.85 ± 0.05 (0.7-0.95)) and Ngounso (Cohen's Kappa: 0.86 ± 0.05 (0.74, 0.97)) and moderate agreement in St Vincent hospital Dschang (k: 0.58 ± 0.06 (0.44-0.71)) and poor agreement in the District Hospital Dschang (Cohen's Kappa: -0.11 ± 0.05 (-0.21-0.01)). The diagnostic indicators of the SD Bioline Pf/PAN were slightly better than for CareStart Pf mRDT in St Vincent Catholic hospital Dschang, irrespective of the reference test. Publicly procured malaria rapid diagnostic tests in Cameroon have maintained high accuracy (91-94%) in the clinical diagnosis of malaria in high malaria transmission regions of Cameroon, although they failed to reach WHO standards. We observed an exception in the low transmission region of Dschang, West region, where the accuracy tended to be lower and variable between facilities located in this town. These results underscore the importance of the routine monitoring of the quality and performance of malaria RDTs in diverse settings in malaria endemic areas.

Project description:BACKGROUND:Malaria rapid diagnostic tests (RDTs) are precious tools to diagnose malaria. Most RDTs used currently are based on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) in a patient's blood. However, concern has been raised in recent years that deletion of pfhrp2 in the parasite could affect the accuracy of PfHRP2-based RDTs. In addition, genetic variation in pfhrp2 might influence the accuracy and sensitivity of RDTs. In this study, the genetic variation in pfhrp2 and pfhrp3 in Myanmar P. falciparum isolates was analysed. METHODS:Blood samples were collected from malaria patients who were infected with P. falciparum in Mandalay, Naung Cho, Tha Beik Kyin, and Pyin Oo Lwin, Upper Myanmar between 2013 and 2015. The pfhrp2 and pfhrp3 were amplified by nested polymerase chain reaction (PCR), cloned and sequenced. Genetic variation in Myanmar pfhrp2 and pfhrp3 was analysed using the DNASTAR program. Comparative analysis of Myanmar and global pfhrp2 and pfhrp3 isolates was also performed. RESULTS:One-hundred and two pfhrp2 and 89 pfhrp3 were amplified from 105 blood samples, of which 84 pfhrp2 and 56 pfhrp3 sequences were obtained successfully. Myanmar pfhrp2 and pfhrp3 showed high levels of genetic variation with different arrangements of distinct repeat types, which further classified Myanmar pfhrp2 and pfhrp3 into 76 and 47 haplotypes, respectively. Novel amino acid changes were also found in Myanmar pfhrp2 and pfhrp3, but their frequencies were very low. Similar structural organization was shared by Myanmar and global pfhrp2 and pfhrp3, and differences in frequencies of repeat types and lengths were also observed between and among global isolates. CONCLUSION:Length polymorphisms and amino acid substitutions generated extensive genetic variation in Myanmar pfhrp2 and pfhrp3. Comparative analysis revealed that global pfhrp2 and pfhrp3 share similar structural features, as well as extensive length polymorphisms and distinct organizations of repeat types. These results provide a better understanding of the genetic structure of pfhrp2 and pfhrp3 in global P. falciparum populations and suggest useful information to develop RDTs with improved quality.

Dataset Information

Insights into the Performance of SD Bioline Malaria Ag P.f/Pan Rapid Diagnostic Test and Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in Madagascar.

Publications

Insights into the Performance of SD Bioline Malaria Ag P.f/Pan Rapid Diagnostic Test and <i>Plasmodium falciparum</i> Histidine-Rich Protein 2 Gene Variation in Madagascar.

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