scholarly journals Modelling the epidemiology of malaria and spread of HRP2-negative Plasmodium falciparum following the replacement of HRP2-detecting rapid diagnostic tests

2022 ◽  
Vol 2 (1) ◽  
pp. e0000106
Author(s):  
Alisha Chaudhry ◽  
Jane Cunningham ◽  
Qin Cheng ◽  
Michelle L. Gatton
Keyword(s):  
Plasmodium Falciparum ◽  
Diagnostic Tests ◽  
False Negative ◽  
Parasite Prevalence ◽  
Rapid Diagnostic Tests ◽  
Negative Results ◽  
False Negative Results ◽  
Malaria Rapid Diagnostic Tests ◽  
The Impact

Malaria rapid diagnostic tests (RDTs) are dominated by products which use histidine-rich protein 2 (HRP2) to detect Plasmodium falciparum. The emergence of parasites lacking the pfhrp2 gene can lead to high rates of false-negative results amongst these RDTs. One solution to restore the ability to correctly diagnose falciparum malaria is to switch to an RDT which is not solely reliant on HRP2. This study used an agent-based stochastic simulation model to investigate the impact on prevalence and transmission caused by switching the type of RDT used once false-negative rates reached pre-defined thresholds within the treatment-seeking symptomatic population. The results show that low transmission settings were the first to reach the false-negative switch threshold, and that lower thresholds were typically associated with better long-term outcomes. Changing the diagnostic RDT away from a HRP2-only RDT is predicted to restore the ability to correctly diagnose symptomatic malaria infections, but often did not lead to the extinction of HRP2-negative parasites from the population which continued to circulate in low density infections, or return to the parasite prevalence and transmission levels seen prior to the introduction of the HRP2-negative parasite. In contrast, failure to move away from HRP2-only RDTs leads to near fixation of these parasites in the population, and the inability to correctly diagnose symptomatic cases. Overall, these results suggest pfhrp2-deleted parasites are likely to become a significant component of P. falciparum parasite populations, and that long-term strategies are needed for diagnosis and surveillance which do not rely solely on HRP2.

scholarly journals PO 8271 PFHRP2 GENE DELETIONS IN PLASMODIUM FALCIPARUM AND SCHISTOSOMA MANSONI CO-INFECTIONS: AN EMERGING CHALLENGE FOR MALARIA RAPID DIAGNOSTIC TESTS

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A25.2-A25
Author(s):  
Hilda Echelibe ◽  
Masumbe Netongo Palmer ◽  
Nji Akindeh ◽  
Wilfred Mbacham
Keyword(s):  
Plasmodium Falciparum ◽  
Schistosoma Mansoni ◽  
Diagnostic Tests ◽  
False Negative ◽  
Rapid Diagnostic Tests ◽  
Sub Saharan Africa ◽  
P Value ◽  
Gene Deletions ◽  
Malaria Rdts ◽  
Malaria Rapid Diagnostic Tests

BackgroundMalaria and schistosomiasis are infections that have a great impact in sub-Saharan Africa based on their high morbidity and mortality rates. We suggest the possibility that the microenvironment created from interactions between the parasites involved generates a pressure on the malaria parasite which could in turn favour the parasite’s adaptation or escape through Pfhrp2 gene deletions. Thus, this study aimed at determining the association between the co-infection with both parasites and false-negative PfHRP2-based malaria rapid diagnostic tests which occur because of these deletions.MethodsThis pilot study was conducted in a total of 149 children aged 7–17 years living in Yorro, located in the Mbam-Inoubou division of the Center region of Cameroon. We collected fresh stool samples from each participant to identify Schistosoma mansoni (Sm) eggs by Kato Katz method and blood samples to identify the ring stages of Plasmodium falciparum (Pf) by thick smear. Malaria rapid diagnostic test and Pfhrp2 gene polymerase chain reaction were performed. The association between the co-infection with Sm/Pf and the false-negative malaria RDTs was determined by the Fisher’s exact test. A p value<0.05 was considered statistically significant.ResultsOur results showed that samples were singly infected with Sm, Pf, co-infected (Sm/Pf) and negative for both infections at frequencies of 12%, 43%, 30.2% and 14.8% respectively. False-negative PfHRP2-based RDTs were observed in 4.7% of the participants. A higher frequency (5/7) of the cases with false-negative malaria RDTs were co-infected with Sm/Pf. A p value of 0.027 showed statistical significance in the association of Sm/Pf co-infection and false-negative PfHRP2-based RDTs.ConclusionA significant association of Plasmodium falciparum and Schistosoma mansoni co-infection with false-negative PfHRP2-based RDTs supports the case for a plausible implication of Pfhrp2 gene deletions, with consequences for malaria rapid diagnostic testing.

scholarly journals Prozone-like phenomenon in travellers with fatal malaria: report of two cases

2015 ◽  
Vol 9 (03) ◽  
pp. 321-324 ◽  
Author(s):  
Lurdes Santos ◽  
Nuno Rocha Pereira ◽  
Paulo Andrade ◽  
Paulo Figueiredo Dias ◽  
Carlos Lima Alves ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
False Negative ◽  
Specific Antigen ◽  
Malaria Diagnosis ◽  
High Sensitivity ◽  
Rapid Diagnostic Tests ◽  
Microscopy Observation ◽  
Negative Results ◽  
False Negative Results ◽  
Potential Benefits

Malaria diagnosis remains a concern in non-endemic countries, with rapid diagnosis being crucial to improve patients’ outcome. Rapid diagnostic tests have high sensitivity but they also have flaws and false-negative results that might jeopardize malaria diagnosis. Some false-negative results might relate to a prozone-like effect. The authors describe two patients with false-negative rapid diagnostic tests in which a prozone-like effect might have been involved. The authors highlight that these tests should not be used without accompanying light microscopy observation of blood films and discuss potential benefits of using rapid diagnostic tests with more than one specific antigen for Plasmodium falciparum.

scholarly journals Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania

2020 ◽  
Author(s):  
Catherine Bakari ◽  
Sophie Jones ◽  
Gireesh Subramaniam ◽  
Celine Isaack Mandara ◽  
Mercy G Chiduo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
False Negative ◽  
Malaria Diagnosis ◽  
Positive Control ◽  
Gene Deletions ◽  
Negative Results ◽  
False Negative Results ◽  
Malaria Rapid Diagnostic Tests ◽  
The Status ◽  
Relationship Of

Background: Despite recent reports of false negative results among histidine-rich protein 2 (HRP2) based-malaria rapid diagnostic tests (mRDTs) caused by pfhrp2/3 gene deletions in different countries, there is paucity of data in Tanzania. Methods: This study assessed the status of pfhrp2/3 deletions in 7,543 blood sample using laboratory multiplex antigen detection (Plasmodium lactate dehydrogenase - pLDH, aldolase, and HRP2). Samples showing mRDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped for pfhrp2/3 genes. Results: Of all samples, 2,417 (32.0%) were positive for any Plasmodium antigens while 5,126 (68.0%) were negative. About 99.8% (n=2,411) of antigen positive samples had HRP2, but 6 (0.2%) had only pLDH and/or pAldolase. Thirteen samples had atypical relationships between pan-Plasmodium antigens and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 mRDTs but positive by microscopy were also chosen; all giving 35 samples genotyped for pfhrp2/3. Of 35 samples, 4 (11.4%) failed to consistently amplify positive control genes (pfmsp1 and pfmsp2), and pfhrp2 and pfhrp3 genes were successfully amplified in 31 (88.6%) samples. Conclusions: Lack of pfhrp2 and/or pfhrp3 genes deletions in Plasmodium falciparum parasites supports continued use of HRP2-based mRDTs for routine malaria diagnosis in Tanzania.

scholarly journals Prevalence of Pfhrp2 and Pfhrp3 Gene Deletions in Plasmodium Falciparum Isolates and their Performance of Hrp2 Based Malaria Rapid Diagnostic Tests in Three Districts of Ghana

2021 ◽  
Vol 8 (3) ◽  
pp. 22-30
Author(s):  
Aquel Rene Lopez
Keyword(s):  
Plasmodium Falciparum ◽  
Diagnostic Test ◽  
Rapid Diagnostic Test ◽  
Diagnostic Tests ◽  
False Negative ◽  
False Negative Rate ◽  
Rapid Diagnostic Tests ◽  
Malaria Rapid Diagnostic Test ◽  
Exon 2 ◽  
Malaria Rapid Diagnostic Tests

Malaria rapid diagnostic tests (MRDTs) are important for malaria disease management. However, the performance of the RDTs is affected when the targeted antigens in the parasite have a variation or are altogether absent. The most common parasite target antigen in RDTs, Plasmodium falciparum histidine-rich protein 2 (HRP2), has been reported to be absent in some P. falciparum parasites. 371 patient samples, from Akuapem North (58.5%), Atiwa East (21.3%), and from New Juaben (20.2%), were used in the study. PCR provided the highest number, 14.8% (55/371), of positive detections for falciparum infections. Microscopy detected parasites in 20/261 (7.7%) samples, and the minimum parasite density by microscopy was 430 parasites/µL. Out of the 371 samples, 27 (7.3%) were positive by RDT. The highest RDT positivity rate, 13.3% (10/75), was observed at New Juaben. False-negative RDT results were obtained in 43/55 (78.2%) of the negative branded RDT kits. Only two microscopies positive sample were RDT positive. Using 18SrDNA PCR, 55 (14.8%) samples were positive for P. falciparum. In Akuapem North, 79.2 % (19/24) of the PCR positive samples had P. falciparum parasites that lacked exon 2 of PFHRP2. An overall RDT positivity rate of 7.3% (27/371) and false-negative rate of 78.2% (43/55) were observed for the study sites. Plasmodium falciparum parasite populations with deletions of the PFHRP2 and PFHRP3 genes are present in Ghana. There is an urgent need to investigate the prevalence and geographic distribution of these parasites. Keywords: Histidine Rich Protien (HRP), Malaria Rapid Diagnostic Test (MRDT), Malaria, Rapid Diagnostic Test (RDT).

scholarly journals The 28 + 28 day design is an effective sampling time for analyzing mutant frequencies in rapidly proliferating tissues of MutaMouse animals

2021 ◽  
Vol 95 (3) ◽  
pp. 1103-1116
Author(s):  
Francesco Marchetti ◽  
Gu Zhou ◽  
Danielle LeBlanc ◽  
Paul A. White ◽  
Andrew Williams ◽  
...  
Keyword(s):  
Germ Cells ◽  
False Negative ◽  
Sampling Time ◽  
Male Germ Cells ◽  
Negative Results ◽  
False Negative Results ◽  
Detection Of Mutations ◽  
The Impact ◽  
Sampling Times

AbstractThe Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory submission. The recommended design in TG 488, 28 consecutive daily exposures with tissue sampling three days later (28 + 3d), is optimized for rapidly proliferating tissues such as bone marrow (BM). A sampling time of 28 days (28 + 28d) is considered more appropriate for slowly proliferating tissues (e.g., liver) and male germ cells. We evaluated the impact of the sampling time on mutant frequencies (MF) in the BM of MutaMouse males exposed for 28 days to benzo[a]pyrene (BaP), procarbazine (PRC), isopropyl methanesulfonate (iPMS), or triethylenemelamine (TEM) in dose–response studies. BM samples were collected + 3d, + 28d, + 42d or + 70d post exposure and MF quantified using the lacZ assay. All chemicals significantly increased MF with maximum fold increases at 28 + 3d of 162.9, 6.6, 4.7 and 2.8 for BaP, PRC, iPMS and TEM, respectively. MF were relatively stable over the time period investigated, although they were significantly increased only at 28 + 3d and 28 + 28d for TEM. Benchmark dose (BMD) modelling generated overlapping BMD confidence intervals among the four sampling times for each chemical. These results demonstrate that the sampling time does not affect the detection of mutations for strong mutagens. However, for mutagens that produce small increases in MF, sampling times greater than 28 days may produce false-negative results. Thus, the 28 + 28d protocol represents a unifying protocol for simultaneously assessing mutations in rapidly and slowly proliferating somatic tissues and male germ cells.

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