Scale-up of Malaria Rapid Diagnostic Tests and Artemisinin-Based Combination Therapy: Challenges and Perspectives in Sub-Saharan Africa

Clinical infection with malaria, caused by parasites of the genus Plasmodium, is considered a serious medical condition with the potential to become a life-threatening emergency. This is especially relevant to low-income countries in tropical and subtropical regions of the world where high rates of malaria-related morbidity and mortality are recorded. As a means to combat this major global public health threat, rapid and effective diagnosis remains the frontline action to initiate a timely and appropriate medical intervention. From all the approaches to parasite detection, rapid diagnostic tests, so-called RDTs, are the easiest to use and most cost-effective. However, some of the limitations inherent in this methodology could hinder effective patient treatment. A primary drawback is that the vast majority of commercially available RDTs detect only one of the five species of human malaria, P. falciparum. While this is the main cause of infection in many areas, it excludes the possibility of infection with another parasite (P. vivax, P. ovale, P. malariae, and P. knowlesi) or of mixed infections containing different species. Hence, a diagnosis of non-P. falciparum malaria is missed. In turn, in resource-constrained settings where optimal microscopy is not available, a misdiagnosis of bacterial infection based on signs and symptoms alone often results in an inappropriate prescription of antibiotics. Here, we discuss how effective diagnosis of malaria and indiscriminate use of antibiotics in sub-Saharan Africa, a hot spot for P. falciparum transmission, may both be addressed by the development of innovative multiplexing RDTs that detect two or more species of Plasmodium.

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

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.64 ◽

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.

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Appropriate targeting of artemisinin‐based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south‐western Uganda

Tropical Medicine & International Health ◽

10.1111/tmi.12748 ◽

2016 ◽

Vol 21 (9) ◽

pp. 1157-1170 ◽

Cited By ~ 15

Author(s):

Richard Ndyomugyenyi ◽

Pascal Magnussen ◽

Sham Lal ◽

Kristian Hansen ◽

Siân E. Clarke

Keyword(s):

Combination Therapy ◽

Community Health ◽

Malaria Transmission ◽

Diagnostic Tests ◽

Randomized Trials ◽

Health Workers ◽

Rapid Diagnostic Tests ◽

Malaria Rapid Diagnostic Tests ◽

Western Uganda ◽

Low Malaria Transmission

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Rapid diagnostic tests for bacterial meningitis applicable in sub-Saharan Africa

Cochrane Database of Systematic Reviews ◽

10.1002/14651858.cd011634.pub2 ◽

2019 ◽

Author(s):

Thomas D Waite ◽

Lilanganee Telisinghe ◽

Maya Gobin ◽

Olivier Ronveaux ◽

Ana-Katya Fernandez ◽

...

Keyword(s):

Bacterial Meningitis ◽

Diagnostic Tests ◽

Rapid Diagnostic Tests ◽

Sub Saharan Africa ◽

Sub Saharan

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Modelling the cost-effectiveness of introducing subsidised malaria rapid diagnostic tests in the private retail sector in sub-Saharan Africa

BMJ Global Health ◽

10.1136/bmjgh-2019-002138 ◽

2020 ◽

Vol 5 (5) ◽

pp. e002138

Author(s):

David Bath ◽

Catherine Goodman ◽

Shunmay Yeung

Keyword(s):

Cost Effectiveness ◽

Diagnostic Tests ◽

Cost Effective ◽

Rapid Diagnostic Tests ◽

Sub Saharan Africa ◽

Small Scale ◽

Retail Sector ◽

First Line ◽

Sub Saharan ◽

The Cost

BackgroundOver the last 10 years, there has been a huge shift in malaria diagnosis in public health facilities, due to widespread deployment of rapid diagnostic tests (RDTs), which are accurate, quick and easy to use and inexpensive. There are calls for RDTs to be made available at-scale in the private retail sector where many people with suspected malaria seek care. Retail sector RDT use in sub-Saharan Africa (SSA) is limited to small-scale studies, and robust evidence on value-for-money is not yet available. We modelled the cost-effectiveness of introducing subsidised RDTs and supporting interventions in the SSA retail sector, in a context of a subsidy programme for first-line antimalarials.MethodsWe developed a decision tree following febrile patients through presentation, diagnosis, treatment, disease progression and further care, to final health outcomes. We modelled results for three ‘treatment scenarios’, based on parameters from three small-scale studies in Nigeria (TS-N), Tanzania (TS-T) and Uganda (TS-U), under low and medium/high transmission (5% and 50% Plasmodium falciparum (parasite) positivity rates (PfPR), respectively).ResultsCost-effectiveness varied considerably between treatment scenarios. Cost per disability-adjusted life year averted at 5% PfPR was US$482 (TS-N) and US$115 (TS-T) and at 50% PfPR US$44 (TS-N) and US$45 (TS-T), from a health service perspective. TS-U was dominated in both transmission settings.ConclusionThe cost-effectiveness of subsidised RDTs is strongly influenced by treatment practices, for which further evidence is required from larger-scale operational settings. However, subsidised RDTs could promote increased use of first-line antimalarials in patients with malaria. RDTs may, therefore, be more cost-effective in higher transmission settings, where a greater proportion of patients have malaria and benefit from increased antimalarial use. This is contrary to previous public sector models, where RDTs were most cost-effective in lower transmission settings as they reduced unnecessary antimalarial use in patients without malaria.

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Implementing COVID-19 (SARS-CoV-2) Rapid Diagnostic Tests in Sub-Saharan Africa: A Review

Frontiers in Medicine ◽

10.3389/fmed.2020.557797 ◽

2020 ◽

Vol 7 ◽

Author(s):

Jan Jacobs ◽

Vera Kühne ◽

Octavie Lunguya ◽

Dissou Affolabi ◽

Liselotte Hardy ◽

...

Keyword(s):

Diagnostic Tests ◽

Rapid Diagnostic Tests ◽

Sub Saharan Africa ◽

Sub Saharan

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Proof of concept: Malaria rapid diagnostic tests and massively parallel sequencing for surveillance of molecular markers of antimalarial resistance in Bissau, Guinea-Bissau during 2014-2017

10.1101/481390 ◽

2018 ◽

Author(s):

Sidsel Nag ◽

Johan Ursing ◽

Amabelia Rodrigues ◽

Marina Crespo ◽

Camilla Krogsgaard ◽

...

Keyword(s):

Treatment Efficacy ◽

Large Scale ◽

Malaria Diagnosis ◽

Rapid Diagnostic Tests ◽

Sub Saharan Africa ◽

Library Preparation ◽

Molecular Surveillance ◽

Malaria Rapid Diagnostic Tests ◽

Antimalarial Resistance ◽

Sub Saharan

AbstractReal-time and large-scale surveillance of molecular markers of antimalarial drug resistance is a potential method of resistance monitoring, to complement therapeutic efficacy studies in settings where the latter are logistically challenging. This study investigates whether routinely used malaria rapid diagnostic tests (RDTs) can be used for massive parallel amplicon sequencing. RDTs used for malaria diagnosis were routinely collected together with patient age and sex between 2014 and 2017, from two health centres in Bissau, Guinea-Bissau. A subset of positive RDTs (n=2,184) were tested for Plasmodium DNA content. Those containing sufficient Plasmodium DNA (n=1,390) were used for library preparation, consisting of amplification of gene fragments from pfcrt, pfmdr1, pfdhfr, pfdhps and pfK13. A total of 5532 gene fragments were successfully analysed on a single Illumina Miseq flow cell. Pre-screening of samples for Plasmodium DNA content proved necessary and the nested PCR protocol applied for library preparation varied notably in PCR-positivity from 13-87%. We found a high frequency of the pfmdr1 codon 86N at 88%-97%, a significant decrease of the pfcrt wildtype CVMNK haplotype and elevated levels of the pfdhfr/pfdhps quadruple mutant ranging from 33%-51% between 2014-2017. No polymorphisms indicating artemisinin tolerance were discovered. Lastly, the demographic data indicate a large proportion of young adults (66%, interquartile range 11-28 years) presenting with P. falciparum infections. With some caution, our findings suggest that routine collection of RDTs could facilitate large-scale molecular surveillance of antimalarial resistance.Importance (word count: 147)Continuous spread and repeated emergence of Plasmodium falciparum parasites resistant towards one or more antimalarials represents an enormous threat to current treatment efficacy levels, especially in sub-Saharan Africa, where 90% of malaria infections occur. In order to prevent substantial treatment failure, it is therefore recommended to monitor treatment efficacy every 2-3 years. Therapeutic efficacy studies, however, can present insurmountable logistical and financial challenges in some settings in sub-Saharan Africa. Molecular surveillance of antimalarial resistance is therefore an important proxy for treatment efficacy. However, the scale by which such studies can be performed depends on the development of high-throughput protocols and the accessibility of samples. If RDTs can be used in the high-throughput protocols available with Next Generation Sequencing (NGS)-technology, surveillance can be performed efficiently for any setting in which RDTs are already used for malaria diagnosis. The majority of settings in sub-Saharan Africa have access to RDTs.

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