Scale-up of malaria rapid diagnostic tests and artemisinin-based combination therapy: challenges and perspectives in sub-Saharan Africa.
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ABSTRACT:
SUBMITTER: Bastiaens GJ
PROVIDER: S-EPMC3897367 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
Publications
Scale-up of malaria rapid diagnostic tests and artemisinin-based combination therapy: challenges and perspectives in sub-Saharan Africa.
Bastiaens Guido J H GJ Bousema Teun T Leslie Toby T
PLoS medicine 20140121 1
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Project description:Artemisinin-based combination therapies (ACTs) are currently considered the first-line treatments for uncomplicated Plasmodium falciparum malaria. Among these, artemether-lumefantrine (AL) has been the most widely prescribed ACT in sub-Saharan Africa. Recent clinical trials conducted in sub-Saharan Africa have shown that dihydroartemisinin-piperaquine (DP), a most recent ACT, may have a longer post-treatment prophylactic period and post-treatment infection period (duration of gametocyte carriage) than AL. Using epidemiological and clinical data on the efficacy of AL and DP, we developed and parameterized a mathematical transmission model that we used to compare the population-level impact of AL and DP for reducing P. falciparum malaria transmission in sub-Saharan Africa. Our results showed that DP is likely to more effectively reduce malaria incidence of clinical episodes than AL. However in low P. falciparum transmission areas, DP and AL are likely to be equally effective in reducing malaria prevalence. The predictions of our model were shown to be robust to the empirical uncertainty summarizing the epidemiological parameters. DP should be considered as a replacement for AL as first-line treatment of uncomplicated malaria in highly endemic P. falciparum communities. To optimize the effectiveness of ACTs, it is necessary to tailor treatment policies to the transmission intensity in different settings.
| S-EPMC4350548 | biostudies-literature
Project description:BACKGROUND:There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. METHODS:Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007-2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. RESULTS:Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of < 5-year-olds not prescribed ACT ranged up to 41.8% across sites. The odds of not being prescribed an ACT were 2-32 times higher for patients in settings with lower-transmission intensity (using test positivity as a proxy) compared to areas of higher transmission. mRDT-positive children in low-transmission settings were especially likely not to be prescribed ACT, with proportions untreated up to 70%. Of the 7426 mRDT-positive patients not prescribed an ACT, 4121 (55.5%) were prescribed other, non-recommended non-ACT antimalarial medications, and the remainder (44.5%) were prescribed no antimalarial. CONCLUSIONS:In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children < 5 years and those in low-transmission settings, were most likely to not be prescribed antimalarials, and young children in low-transmission settings were least likely to be treated for malaria. This major public health risk must be addressed in training and practice. TRIAL REGISTRATION:Reported in individual primary studies.
| S-EPMC6990477 | biostudies-literature
Project description:Early parasitological diagnosis and treatment with artemisinin-based combination therapies (ACTs) are key components of worldwide malaria elimination programmes. In general, use of ACTs has been limited to patients with falciparum malaria whereas blood-stage infections with Plasmodium vivax are mostly still treated with chloroquine. We review the evidence for the relative benefits and disadvantages of the existing separate treatment approach versus a unified ACT-based strategy for treating Plasmodium falciparum and P vivax infections in regions where both species are endemic (co-endemic). The separate treatment scenario is justifiable if P vivax remains sensitive to chloroquine and diagnostic tests reliably distinguish P vivax from P falciparum. However, with the high number of misdiagnoses in routine practice and the rise and spread of chloroquine-resistant P vivax, there might be a compelling rationale for a unified ACT-based strategy for vivax and falciparum malaria in all co-endemic regions. Analyses of the cost-effectiveness of ACTs for both Plasmodium species are needed to assess the role of these drugs in the control and elimination of vivax malaria.
| S-EPMC3350863 | biostudies-other
Project description:Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at presenting the current scenario of drug resistance molecular markers, either selected or involved in treatment failures (TF) during in vivo ACT efficacy studies from sub-Saharan Africa (sSA) and India. Eight electronic databases were comprehensively used to search relevant articles and finally a total of 28 studies were included in the review, 21 from sSA and seven from India. On analysis, Artemether + lumefantrine (AL) and artesunate + sulfadoxine-pyrimethamine (AS + SP) are the main ACT in African and Indian regions with a 28-day efficacy range of 54.3-100% for AL and 63-100% for AS + SP respectively. It was observed that mutations in the Pfcrt (76T), Pfdhfr (51I, 59R, 108N), Pfdhps (437G) and Pfmdr1 (86Y, 184F, 1246Y) genes were involved in TF, which varied with respect to ACTs. Based on studies that have genotyped the Pfk13 gene, the reported TF cases, were mainly linked with mutations in genes associated with resistance to ACT partner drugs; indicating that the protection of the partner drug efficacy is crucial for maintaining the efficacy of ACT. This review reveals that ACT are largely efficacious in India and sSA despite the fact that some clinical efficacy and epidemiological studies have reported some validated mutations (i.e., 476I, 539T and 561H) in circulation in these two regions. Also, the role of PfATPase6 in ART resistance is controversial still, while P. falciparum plasmepsin 2 (Pfpm2) in piperaquine (PPQ) resistance and dihydroartemisinin (DHA) + PPQ failures is well documented in Southeast Asian countries but studied less in sSA. Hence, there is a need for continuous molecular surveillance of Pfk13 mutations for emergence of artemisinin (ART) resistance in these countries.
| S-EPMC7887327 | biostudies-literature
Project description:Numerous national public initiatives offering first-line combination antiretroviral therapy (cART) for HIV infection have commenced in sub-Saharan Africa since 2002. Presently, 2.1 million of an estimated seven million Africans in need of cART are receiving treatment. Analyses from the region report favorable clinical/treatment outcomes and impressive declines in AIDS-related mortality among HIV-1-infected adults and children receiving cART. While immunologic recovery, virologic suppression and cART adherence rates are on par with resource-rich settings, loss to follow-up and high mortality rates, especially within the first 6 months of treatment, remain a significant problem. Over the next decade, cART coverage rates are expected to improve across the region, with attendant increases in healthcare utilization for HIV- and non-HIV-related complications and the need for expanded laboratory and clinical services. Planned and in-progress trials will evaluate the use of cART to prevent primary HIV-1 infection with so-called 'test and treat' expansions of coverage and treatment. Education and training programs as well as patient-retention strategies will need to be strengthened as national cART programs are expanded and more people require lifelong monitoring and care.
| S-EPMC2774911 | biostudies-literature
Project description:Introduction: For the COVID-19 (SARS-CoV-2) response, COVID-19 antigen (Ag), and antibody (Ab) rapid diagnostic tests (RDTs) are expected to complement central molecular testing particularly in low-resource settings. The present review assesses requirements for implementation of COVID-19 RDTs in sub-Saharan Africa. Methods: Review of PubMed-published articles assessing COVID-19 RDTs complemented with Instructions for Use (IFU) of products. Results: In total 47 articles on two COVID-19 Ag RDTs and 54 COVID-19 Ab RDTs and IFUs of 20 COVID-19 Ab RDTs were retrieved. Only five COVID-19 Ab RDTs (9.3%) were assessed with capillary blood sampling at the point-of-care; none of the studies were conducted in sub-Saharan Africa. Sampling: Challenges for COVID-19 Ag RDTs include nasopharyngeal sampling (technique, biosafety) and sample stability; for COVID-19 Ab RDTs equivalence of whole blood vs. plasma/serum needs further validation (assessed for only eight (14.8%) products). Sensitivity-Specificity: sensitivity of COVID-19 Ag and Ab RDTs depend on viral load (antigen) and timeframe (antibody), respectively; COVID-19 Ab tests have lower sensitivity compared to laboratory test platforms and the kinetics of IgM and IgG are very similar. Reported specificity was high but has not yet been assessed against tropical pathogens. Kit configuration: For COVID-19 Ag RDTs, flocked swabs should be added to the kit; for COVID-19 Ab RDTs, finger prick sampling materials, transfer devices, and controls should be added (currently only supplied in 15, 5, and 1/20 products). Usability and Robustness: some COVID-19 Ab RDTs showed high proportions of faint lines (>40%) or invalid results (>20%). Shortcomings were reported for buffer vials (spills, air bubbles) and their instructions for use. Stability: storage temperature was ≤ 30°C for all but one RDT, in-use and result stability were maximal at 1 h and 30 min, respectively. Integration in the healthcare setting requires a target product profile, landscape overview of technologies, certified manufacturing capacity, a sustainable market, and a stringent but timely regulation. In-country deployment depends on integration in the national laboratory network. Discussion/Conclusion: Despite these limitations, successful implementation models in triage, contact tracing, and surveillance have been proposed, in particular for COVID-19 Ab RDTs. Valuable experience is available from implementation of other disease-specific RDTs in sub-Saharan Africa.
| S-EPMC7662157 | biostudies-literature
Project description:Malaria remains a major cause of morbidity and mortality in Africa, particularly in children under five years of age. Availability of effective anti-malarial drug treatment is a cornerstone for malaria control and eventual malaria elimination. Artemisinin-based combination therapy (ACT) is worldwide the first-line treatment for uncomplicated falciparum malaria, but the ACT drugs are starting to fail in Southeast Asia because of drug resistance. Resistance to artemisinins and their partner drugs could spread from Southeast Asia to Africa or emerge locally, jeopardizing the progress made in malaria control with the increasing deployment of ACT in Africa. The development of triple artemisinin-based combination therapy (TACT) could contribute to mitigating the risks of artemisinin and partner drug resistance on the African continent. However, there are pertinent ethical and practical issues that ought to be taken into consideration. In this paper, the most important ethical tensions, some implementation practicalities and preliminary thoughts on addressing them are discussed. The discussion draws upon data from randomized clinical studies using TACT combined with ethical principles, published literature and lessons learned from the introduction of artemisinin-based combinations in African markets.
| S-EPMC7910789 | biostudies-literature
Project description:A characteristic of Plasmodium falciparum infections is the gradual acquisition of clinical immunity resulting from repeated exposures to the parasite. While the molecular basis of protection against clinical malaria remains unresolved, its effects on epidemiological patterns are well recognized. Accumulating epidemiological data constitute a valuable resource that must be intensively explored and interpreted as to effectively inform control planning.Here we apply a mathematical model to clinical data from eight endemic regions in sub-Saharan Africa. The model provides a quantitative framework within which differences in age distribution of clinical disease are assessed in terms of the parameters underlying transmission. The shorter infectious periods estimated for clinical infections induce a regime of bistability of endemic and malaria-free states in regions of mesoendemic transmission. The two epidemiological states are separated by a threshold that provides a convenient measure for intervention design. Scenarios of eradication and resurgence are simulated.In regions that support mesoendemic transmission, intervention success depends critically on reducing prevalence below a threshold which separates endemic and malaria-free regimes.
| S-EPMC2262141 | biostudies-other
Project description:ObjectiveTo perform critical methodological assessments on designs, outcomes, quality and implementation limitations of studies evaluating the impact of malaria rapid diagnostic tests (mRDTs) on patient-important outcomes in sub-Saharan Africa.DesignA systematic review of study methods.Data sourcesMEDLINE, EMBASE, Cochrane Library, African Index Medicus and clinical trial registries were searched up to May 2022.Eligibility criteriaPrimary quantitative studies that compared mRDTs to alternative diagnostic tests for malaria on patient-important outcomes within sub-Sahara Africa.Data extraction and synthesisStudies were sought by an information specialist and two independent reviewers screened for eligible records and extracted data using a predesigned form using Covidence. Methodological quality was assessed using the National Institutes of Health tools. Descriptive statistics and thematic analysis guided by the Supporting the Use of Research Evidence framework were used for analysis. Findings were presented narratively, graphically and by quality ratings.ResultsOur search yielded 4717 studies, of which we included 24 quantitative studies; (15, 62.5%) experimental, (5, 20.8%) quasi-experimental and (4, 16.7%) observational studies. Most studies (17, 70.8%) were conducted within government-owned facilities. Of the 24 included studies, (21, 87.5%) measured the therapeutic impact of mRDTs. Prescription patterns were the most reported outcome (20, 83.3%). Only (13, 54.2%) of all studies reported statistically significant findings, in which (11, 45.8%) demonstrated mRDTs' potential to reduce over-prescription of antimalarials. Most studies (17, 70.8%) were of good methodological quality; however, reporting sample size justification needs improvement. Implementation limitations reported were mostly about health system constraints, the unacceptability of the test by the patients and low trust among health providers.ConclusionImpact evaluations of mRDTs in sub-Saharan Africa are mostly randomised trials measuring mRDTs' effect on therapeutic outcomes in real-life settings. Though their methodological quality remains good, process evaluations can be incorporated to assess how contextual concerns influence their interpretation and implementation.Prospero registration numberCRD42018083816.
| S-EPMC11409401 | biostudies-literature
Project description:There are already 40 cities in Africa with over 1 million inhabitants and the United Nations Environmental Programme estimates that by 2025 over 800 million people will live in urban areas. Recognizing that malaria control can improve the health of the vulnerable and remove a major obstacle to their economic development, the Malaria Knowledge Programme of the Liverpool School of Tropical Medicine and the Systemwide Initiative on Malaria and Agriculture convened a multi-sectoral technical consultation on urban malaria in Pretoria, South Africa from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies for the assessment and control of urban malaria. This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria.
| S-EPMC552321 | biostudies-literature