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Malaria Vaccines: Recent Advances and New Horizons

CiteULike malaria tags - 19 July 2018 - 10:47am
Cell Host & Microbe, Vol. 24, No. 1. (July 2018), pp. 43-56, doi:10.1016/j.chom.2018.06.008
Simon Draper, Brandon Sack, Richter King, Carolyn Nielsen, Julian Rayner, Matthew Higgins, Carole Long, Robert Seder
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A cross-sectional analysis of ITN and IRS coverage in Namibia in 2013

CiteULike malaria tags - 19 July 2018 - 10:23am
Malaria Journal, Vol. 17, No. 1. (16 July 2018), doi:10.1186/s12936-018-2417-z
Sophie Allcock, Elizabeth Young, Manjinder Sandhu
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Integrated pathogen load and dual transcriptome analysis of systemic host-pathogen interactions in severe malaria

CiteULike malaria tags - 5 July 2018 - 11:40am
Science Translational Medicine, Vol. 10, No. 447. (27 June 2018), eaar3619, doi:10.1126/scitranslmed.aar3619
Hyun Lee, Athina Georgiadou, Michael Walther, Davis Nwakanma, Lindsay Stewart, Michael Levin, Thomas Otto, David Conway, Lachlan Coin, Aubrey Cunnington
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Cryo-EM structure of an essential Plasmodium vivax invasion complex

CiteULike malaria tags - 5 July 2018 - 11:36am
Nature, Vol. 559, No. 7712. (27 June 2018), pp. 135-139, doi:10.1038/s41586-018-0249-1
Jakub Gruszczyk, Rick Huang, Li-Jin Chan, Sébastien Menant, Chuan Hong, James Murphy, Yee-Foong Mok, Michael Griffin, Richard Pearson, Wilson Wong, Alan Cowman, Zhiheng Yu, Wai-Hong Tham
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RecQ helicases in the malaria parasite Plasmodium falciparum affect genome stability, gene expression patterns and DNA replication dynamics

CiteULike malaria tags - 5 July 2018 - 10:10am
PLOS Genetics, Vol. 14, No. 7. (2 July 2018), e1007490, doi:10.1371/journal.pgen.1007490

The malaria parasite Plasmodium falciparum has evolved an unusual genome structure. The majority of the genome is relatively stable, with mutation rates similar to most eukaryotic species. However, some regions are very unstable with high recombination rates, driving the generation of new immune evasion-associated var genes. The molecular factors controlling the inconsistent stability of this genome are not known. Here we studied the roles of the two putative RecQ helicases in P. falciparum, PfBLM and PfWRN. When PfWRN was knocked down, recombination rates increased four-fold, generating chromosomal abnormalities, a high rate of chimeric var genes and many microindels, particularly in known ‘fragile sites’. This is the first identification of a gene involved in suppressing recombination and maintaining genome stability in Plasmodium. By contrast, no change in mutation rate appeared when the second RecQ helicase, PfBLM, was mutated. At the transcriptional level, however, both helicases evidently modulate the transcription of large cohorts of genes, with several hundred genes—including a large proportion of vars—showing deregulated expression in each RecQ mutant. Aberrant processing of stalled replication forks is a possible mechanism underlying elevated mutation rates and this was assessed by measuring DNA replication dynamics in the RecQ mutant lines. Replication forks moved slowly and stalled at elevated rates in both mutants, confirming that RecQ helicases are required for efficient DNA replication. Overall, this work identifies the Plasmodium RecQ helicases as major players in DNA replication, antigenic diversification and genome stability in the most lethal human malaria parasite, with important implications for genome evolution in this pathogen. Human malaria is caused by Plasmodium parasites, with most of the mortality (almost half a million deaths each year) being caused by one species, Plasmodium falciparum. This parasite has an unusual genome: it is exceptionally biased towards A and T nucleotides rather than G and C, and it contains specific areas rich in hypervariable virulence-associated genes which evolve very rapidly to produce new variants. This evolution is probably vital for the parasite to evade the human immune system and maintain chronic infections, but how it is controlled at a molecular level remains unknown. We have identified a helicase in the parasite with a huge influence on genome stability and the rate of genome evolution. It appears to function by unwinding various unusual DNA structures, and if this fails then the genome becomes unstable. In addition, the transcription of many genes whose DNA tends to form secondary structures is affected, and DNA replication is impeded. If this helicase was expressed variably in different parasite strains infecting humans, it could influence the parasites’ ability to grow and replicate efficiently, and also, crucially, its ability to evolve and thus evade the human immune system.
Antoine Claessens, Lynne Harris, Slavica Stanojcic, Lia Chappell, Adam Stanton, Nada Kuk, Pamela Veneziano-Broccia, Yvon Sterkers, Julian Rayner, Catherine Merrick
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Genomic analysis of a pre-elimination Malaysian Plasmodium vivax population reveals selective pressures and changing transmission dynamics

CiteULike malaria tags - 5 July 2018 - 9:54am
Nature Communications, Vol. 9, No. 1. (3 July 2018), doi:10.1038/s41467-018-04965-4
Sarah Auburn, Ernest Benavente, Olivo Miotto, Richard Pearson, Roberto Amato, Matthew Grigg, Bridget Barber, Timothy William, Irene Handayuni, Jutta Marfurt, Hidayat Trimarsanto, Rintis Noviyanti, Kanlaya Sriprawat, Francois Nosten, Susana Campino, Taane Clark, Nicholas Anstey, Dominic Kwiatkowski, Ric Price
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Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia

CiteULike malaria tags - 28 June 2018 - 10:10am
Scientific Reports, Vol. 8, No. 1. (26 June 2018), doi:10.1038/s41598-018-28017-5
Alfred Amambua-Ngwa, David Jeffries, Roberto Amato, Archibald Worwui, Mane Karim, Sukai Ceesay, Haddy Nyang, Davis Nwakanma, Joseph Okebe, Dominic Kwiatkowski, David Conway, Umberto D’Alessandro
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CiteULike malaria tags - 22 June 2018 - 4:00am
Lancet (London, England), Vol. 391, No. 10130. (21 April 2018), pp. 1608-1621

Following unsuccessful eradication attempts there was a resurgence of malaria towards the end of the 20th century. Renewed control efforts using a range of improved tools, such as long-lasting insecticide-treated bednets and artemisinin-based combination therapies, have more than halved the global burden of disease, but it remains high with 445 000 deaths and more than 200 million cases in 2016. Pitfalls in individual patient management are delayed diagnosis and overzealous fluid resuscitation in severe malaria. Even in the absence of drug resistance, parasite recurrence can occur, owing to high parasite densities, low host immunity, or suboptimal drug concentrations. Malaria elimination is firmly back as a mainstream policy but resistance to the artemisinin derivatives, their partner drugs, and insecticides present major challenges. Vaccine development continues on several fronts but none of the candidates developed to date have been shown to provide long-lasting benefits at a population level. Increased resources and unprecedented levels of regional cooperation and societal commitment will be needed if further substantial inroads into the malaria burden are to be made. Copyright © 2018 Elsevier Ltd. All rights reserved.
Elizabeth Ashley, Aung Pyae Phyo, Charles Woodrow
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A Surveillance Infrastructure for Malaria Analytics: Provisioning Data Access and Preservation of Interoperability

CiteULike malaria tags - 16 June 2018 - 8:18am
JMIR Public Health Surveill, Vol. 4, No. 2. (15 Jun 2018), doi:10.2196/10218

Background: According to the World Health Organization, malaria surveillance is weakest in countries and regions with the highest malaria burden. A core obstacle is that the data required to perform malaria surveillance are fragmented in multiple data silos distributed across geographic regions. Furthermore, consistent integrated malaria data sources are few, and a low degree of interoperability exists between them. As a result, it is difficult to identify disease trends and to plan for effective interventions. Objective: We propose the Semantics, Interoperability, and Evolution for Malaria Analytics (SIEMA) platform for use in malaria surveillance based on semantic data federation. Using this approach, it is possible to access distributed data, extend and preserve interoperability between multiple dynamic distributed malaria sources, and facilitate detection of system changes that can interrupt mission-critical global surveillance activities. Methods: We used Semantic Automated Discovery and Integration (SADI) Semantic Web Services to enable data access and improve interoperability, and the graphical user interface-enabled semantic query engine HYDRA to implement the target queries typical of malaria programs. We implemented a custom algorithm to detect changes to community-developed terminologies, data sources, and services that are core to SIEMA. This algorithm reports to a dashboard. Valet SADI is used to mitigate the impact of changes by rebuilding affected services. Results: We developed a prototype surveillance and change management platform from a combination of third-party tools, community-developed terminologies, and custom algorithms. We illustrated a methodology and core infrastructure to facilitate interoperable access to distributed data sources using SADI Semantic Web services. This degree of access makes it possible to implement complex queries needed by our user community with minimal technical skill. We implemented a dashboard that reports on terminology changes that can render the services inactive, jeopardizing system interoperability. Using this information, end users can control and reactively rebuild services to preserve interoperability and minimize service downtime. Conclusions: We introduce a framework suitable for use in malaria surveillance that supports the creation of flexible surveillance queries across distributed data resources. The platform provides interoperable access to target data sources, is domain agnostic, and with updates to core terminological resources is readily transferable to other surveillance activities. A dashboard enables users to review changes to the infrastructure and invoke system updates. The platform significantly extends the range of functionalities offered by malaria information systems, beyond the state-of-the-art.
Sadnan Al Manir, Haël Brenas, Jo Baker, Arash Shaban-Nejad
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The genomics of insecticide resistance: insights from recent studies in African malaria vectors

CiteULike malaria tags - 14 June 2018 - 9:45am
Current Opinion in Insect Science (June 2018), doi:10.1016/j.cois.2018.05.017
Chris Clarkson, Helen Temple, Alistair Miles
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Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria

CiteULike malaria tags - 14 June 2018 - 9:19am
PLOS ONE, Vol. 13, No. 6. (8 June 2018), e0198371, doi:10.1371/journal.pone.0198371

Plasmodium falciparum PfRH5 protein binds Ripr, CyRPA and Pf113 to form a complex that is essential for merozoite invasion of erythrocytes. The inter-genomic conservation of the PfRH5 complex proteins makes them attractive blood stage vaccine candidates. However, little is known about how antibodies to PfRH5, CyRPA and Pf113 are acquired and maintained in naturally exposed populations, and the role of PfRH5 complex proteins in naturally acquired immunity. To provide such data, we studied 206 Ghanaian children between the ages of 1–12 years, who were symptomatic, asymptomatic or aparasitemic and healthy. Plasma levels of antigen-specific IgG and IgG subclasses were measured by ELISA at several time points during acute disease and convalescence. On the day of admission with acute P. falciparum malaria, the prevalence of antibodies to PfRH5-complex proteins was low compared to other merozoite antigens (EBA175, GLURP-R0 and GLURP-R2). At convalescence, the levels of RH5-complex-specific IgG were reduced, with the decay of PfRH5-specific IgG being slower than the decay of IgG specific for CyRPA and Pf113. No correlation between IgG levels and protection against P. falciparum malaria was observed for any of the PfRH5 complex proteins. From this we conclude that specific IgG was induced against proteins from the PfRH5-complex during acute P. falciparum malaria, but the prevalence was low and the IgG levels decayed rapidly after treatment. These data indicate that the levels of IgG specific for PfRH5-complex proteins in natural infections in Ghanaian children were markers of recent exposure only.
Frederica Partey, Filip Castberg, Edem Sarbah, Sarah Silk, Gordon Awandare, Simon Draper, Nicholas Opoku, Margaret Kweku, Michael Ofori, Lars Hviid, Lea Barfod
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An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes

CiteULike malaria tags - 1 June 2018 - 8:23am
Scientific Reports, Vol. 8, No. 1. (25 May 2018), doi:10.1038/s41598-018-26559-2
Michel Theron, Nadia Cross, Paula Cawkill, Leyla Bustamante, Julian Rayner
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Antibodies to ICAM1-binding PfEMP1-DBLβ are biomarkers of protective immunity to malaria in a cohort of young children from Papua New Guinea

CiteULike malaria tags - 24 May 2018 - 12:16pm
Infection and Immunity (21 May 2018), IAI.00485-17, doi:10.1128/iai.00485-17

Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) mediates parasite sequestration to the cerebral microvasculature via binding of DBLβ domains to Intercellular Adhesion Molecule 1 (ICAM1) and is associated with severe cerebral malaria. In a cohort of 187 young children from Papua New Guinea (PNG), we examined baseline antibody levels to the ICAM1-binding PfEMP1 domain, DBLβ3PF11_0521, in comparison to four control antigens including NTS-DBLα and CIDR1 domains from another group A variant and a group B/C variant. Antibody levels for the group A antigens were strongly associated with age and exposure. Antibody responses to DBLβ3PF11_0521 were associated with a 37% reduced risk of high-density clinical malaria in the follow up period (adjusted incidence risk ratio, aIRR = 0.63 [95% CI: 0.45-0.88; p = 0.007]) and a 25% reduction in risk of low-density clinical malaria (aIRR = 0.75 [95% CI: 0.55-1.01; p = 0.06]), whilst there was no such association for other variants. Children who experienced severe malaria also had significantly lower antibody levels to DBLβ3PF11_0521 and the other group A domains than other children. Furthermore, a subset of PNG DBLβ sequences had ICAM1-binding motifs, formed a distinct phylogenetic cluster and were similar to sequences from other endemic areas. PfEMP1 variants associated with these DBLβ were enriched for DC4 and DC13 head-structures implicated in EPCR-binding and severe malaria, suggesting conservation of dual binding specificity. These results provide further support for the development of specific classes of PfEMP1 as vaccine candidates, and as biomarkers for protective immunity against clinical P. falciparum malaria.
Sofonias Tessema, Digjaya Utama, Olga Chesnokov, Anthony Hodder, Clara Lin, Abby Harrison, Jakob Jespersen, Bent Petersen, Livingstone Tavul, Peter Siba, Dominic Kwiatkowski, Thomas Lavstsen, Diana Hansen, Andrew Oleinikov, Ivo Mueller, Alyssa Barry
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Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria

CiteULike malaria tags - 24 May 2018 - 10:48am
Nature Microbiology, Vol. 3, No. 6. (21 May 2018), pp. 687-697, doi:10.1038/s41564-018-0162-2
Thomas Otto, Aude Gilabert, Thomas Crellen, Ulrike Böhme, Céline Arnathau, Mandy Sanders, Samuel Oyola, Alain Okouga, Larson Boundenga, Eric Willaume, Barthélémy Ngoubangoye, Nancy Moukodoum, Christophe Paupy, Patrick Durand, Virginie Rougeron, Benjamin Ollomo, François Renaud, Chris Newbold, Matthew Berriman, Franck Prugnolle
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Comparative study of artemether and quinine in severe Plasmodium falciparum malaria in adults and older children in Cameroon

CiteULike malaria tags - 21 May 2018 - 11:14am
Vol. 59, No. 2. (1999), 151‐156

From June 1993 to June 1994, a study was carried out to compare artemether and quinine for management of severe falciparum malaria in adults and adolescents in Cameroon. Artemether was administered intramuscularly at a dose of 3.6 mg/kg on the first day and 1.6 mg/kg for the following 4 days. Quinine was administered intravenously at a dose of 1.6 mg/kg for the first 4 hours and 8 mg every 8 hours for the next 3 days. The files of 84 of the 95 patients recruited were validated for inclusion in the final study. There were 40 patients in the artemether group and 44 in the quinine group. The two groups were comparable with regard to all factors at the time of inclusion. Findings showed that artemether was more effective than quinine with regard to total clearance of parasitemia, 90 p. 100 clearance, and fever control and that it was as effective with regard to 50 p. 100 clearance and recovery of consciousness. In view of its good performance and of the simplicity of its administration by intramuscular injection, artemether would appear to be an excellent alternative for treatment of severe malaria and cerebral malaria in areas with poor medical facilities.
JJ Fargier, FJ Louis, S Duparc, C Hounsinou, P Ringwald, M Danis
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Comparative clinical trial of four regimens of dihydroartemisinin-mefloquine in multidrug-resistant falciparum malaria

CiteULike malaria tags - 21 May 2018 - 11:13am
Vol. 4, No. 9. (1999), 602‐610

We conducted a randomized, comparative trial at the Bangkok Hospital for Tropical Diseases during 1996‐98 to evaluate the clinical efficacy and tolerability of four combination regimens of dihydroartemisinin‐mefloquine. 207 male patients aged 18‐25 years, weighing 49.3‐55.1 kg were randomized to receive a single oral dose of 300 mg dihydroartemisinin plus one or two doses of mefloquine as follows: regimen I (n = 26): 750 mg mefloquine concurrently, or regimen II (n = 22): 750 mg mefloquine 24 h later, or regimen III (n = 78): 750 and 500 mg mefloquine at 24 and 30 h, or regimen IV (n = 81): 750 and 500 mg mefloquine (at 0 and 24 h). All patients improved clinically within 24 h of initiation of treatment. The initial therapeutic response was rapid and identical in all treatment groups (median PCT vs. FCT: 36 vs. 24, 36 vs. 28, 36 vs. 26, and 34 vs. 26 h, for regimen I, II, III and IV, respectively). All combination regimens generally showed acceptable tolerability profiles. Compliance with follow‐up (42 days) was achieved by 86.5% (179 cases). Recrudescent parasitaemia was significantly higher in patients treated with low‐dose mefloquine combinations (regimens I, II:8/23, 9/16) than in those who received high‐dose mefloquine (regimens III, IV: 2/70, 3/70). No RII or RIII type of response was observed. There were no significant differences in susceptibility to mefloquine between primary and recrudescent isolates. Dose‐adjusted whole blood mefloquine concentrations were significantly higher in high‐dose mefloquine regimens (III and IV). Patients who vomited within the first hour of mefloquine administration had markedly lower whole blood mefloquine concentrations than those who did not vomit.
K Na-Bangchang, P Tippanangkosol, R Ubalee, S Chaovanakawee, S Saenglertsilapachai, J Karbwang
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Artemisinin derivatives for treating uncomplicated malaria

CiteULike malaria tags - 21 May 2018 - 10:51am
Cochrane Database of Systematic Reviews, No. 2. (1999), doi:10.1002/14651858.CD000256

Abstract - Background Artemisinin derivatives are a relatively new group of drugs with antimalarial properties. As resistance to other antimalarial drugs continues to increase, artemisinin drugs may be useful alternatives. Objectives The objective of this review was to assess the effects of artemisinin drugs for treating uncomplicated falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Science Citation Index, LILACS, African Index Medicus, conference abstracts, and reference lists of relevant articles. We contacted organisations, researchers in the field, and drug companies. Selection criteria Randomised and quasi‐randomised trials of artemisinin derivatives, alone or in combination with other antimalarials, compared with standard antimalarial treatments, in adults or children with uncomplicated falciparum malaria. Only trials where treatment was given by mouth or suppository were included. Comparisons between different artemisinin derivatives and treatment regimens were also included. Data collection and analysis Eligibility and trial quality were assessed and data were extracted independently by the two reviewers. Main results Forty‐one trials involving over 5000 patients were included. Variation in study design and quality made synthesis of the data problematic. Allocation concealment was adequate in only two trials. Most data were from areas of multidrug resistant falciparum malaria in South‐East Asia. Compared with standard antimalarial treatments, artemisinin drugs showed fast parasite clearance and high cure rates at follow‐up, provided the duration of treatment with artemisinin drugs was adequate. Combination with mefloquine improved sustained parasite clearance and was effective in multidrug resistant areas. When doses were adequate, the combination shortened the duration of treatment. We found no evidence that artemisinin drugs are more harmful than standard treatment drugs over a typical trial period of 28 days. Authors' conclusions The evidence suggests that artemisinin drugs are effective and safe for treating uncomplicated malaria. There is no evidence from randomised trials that one artemisinin derivative is better than the others. In areas where there is mefloquine resistance, combination therapy with an artemisinin derivative appears to improve sustained parasite clearance compared with either drug alone. This review summarizes trials up to 1999. For the reasons in the 'What's new' section, this review will no longer be updated. Plain language summary Artemisinin drugs for treating uncomplicated malaria are better used in combination therapy Artemisinin drugs come originally from a plant that has been used since ancient times in China as a traditional medicine for fever and malaria. These drugs act quickly and few side effects have been reported. Malaria parasites have so far not developed resistance to artemisinin drugs. The review shows that artemisinin drugs clear malaria parasites from the blood more effectively than standard treatment drugs. In areas where malaria parasites are more resistant to existing drugs, such as South‐East Asia, artemisinin drugs are not better at sustained parasite clearance than standard treatment with quinine or mefloquine. Combination treatment using an artemisinin drug together with the longer‐acting antimalarial drug mefloquine improves sustained clearance of parasites, but mefloquine is associated with adverse effects. There are few studies on combination treatment with longer‐acting antimalarial drugs that are safer than mefloquine. There is no evidence from trials that any of the several artemisinin derivatives is better than the others.
H McIntosh, P Olliaro
Categories: malaria news feeds

Amodiaquine for treating malaria

CiteULike malaria tags - 21 May 2018 - 10:51am
Cochrane Database of Systematic Reviews, No. 2. (2003), doi:10.1002/14651858.CD000016

Abstract - Background Using a pilot system we have categorised this review as: Historical question ‐ no update intended. Please see "Published notes" section of the review for more details. Since 2001, the World Health Organization has recommended that antimalarial drug combinations be used for uncomplicated falciparum malaria and that monotherapy should no longer be used. For the most up‐to‐date information on malaria combination treatment, please refer to Sinclair D, Zani B, Donegan S, Olliaro P, Garner P. Artemisinin‐based combination therapy for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007483. DOI: 10.1002/14651858.CD007483.pub2. Amodiaquine has been widely used to treat malaria. Fatal adverse reactions have been reported in adults taking it for prophylaxis. This has led some authorities to suggest it is withdrawn as a first line treatment for malaria. Objectives To compare amodiaquine with chloroquine or sulfadoxine‐pyrimethamine for treating uncomplicated Plasmodium falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group specialized trials register (February 2003), The Cochrane Central Register of Controlled Trials ( The Cochrane Library Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1980 to December 2002), LILACS (February 2003). We contacted researchers in the field and pharmaceutical companies. Selection criteria Randomised and quasi‐randomised trials. Data collection and analysis Two reviewers independently extracted data and assessed trial quality. Main results 56 studies included, mostly from Africa. Treatment allocation was adequately concealed in three trials, and unclear or inadequate in the remainder. Amodiaquine was more effective than chloroquine for parasite clearance (day 7, Peto odds ratio 4.42 (95% confidence interval 3.65 to 5.35); day 14, Peto odds ratio 6.44 (95% confidence interval (CI) 5.09 to 8.15). Comparisons with sulfadoxine/pyrimethamine were more mixed, with sulfadoxine/pyrimethamine more effective on day 28 (Peto odds ratio 0.41; 95% CI 0.28 to 0.61). No significant difference for adverse events was observed between amodiaquine and chloroquine and sulfadoxine/pyrimethamine. Reported adverse effects were minor or moderate. No life threatening events were detected. Authors' conclusions There is evidence to support the continued use of amodiaquine to treat uncomplicated malaria, although local drug resistance patterns need to be considered. Monitoring for adverse events should continue. This review summarizes trials up to 2003. For the reasons in the 'What's new' section, this review will no longer be updated. Plain language summary Amodiaquine for treating malaria Using a pilot system we have categorised this review as: Historical question ‐ no update intended. Please see "Published notes" section of the review for more details. Since 2001, the World Health Organization has recommended that antimalarial drug combinations be used for uncomplicated falciparum malaria and that monotherapy should no longer be used.
PL Olliaro, P Mussano
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Artemisinin derivatives for treating severe malaria

CiteULike malaria tags - 21 May 2018 - 10:51am
Cochrane Database of Systematic Reviews, No. 2. (2000), doi:10.1002/14651858.CD000527

Abstract - Background Artemisinin derivatives may have advantages over quinoline drugs for treating severe malaria since they are fast acting and effective against quinine resistant malaria parasites. Objectives The objective of this review was to assess the effects of artemisinin drugs for severe and complicated falciparum malaria in adults and children. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, Science Citation Index, LILACS, African Index Medicus, conference abstracts, and reference lists of articles. We contacted organisations, researchers in the field and drug companies. Selection criteria Randomised and pseudo‐randomised trials comparing artemisinin drugs (rectal, intramuscular or intravenous) with standard treatment, or comparisons between artemisinin derivatives in adults or children with severe or complicated falciparum malaria. Data collection and analysis Eligibility, trial quality assessment and data extraction were done independently by two reviewers. Study authors were contacted for additional information. Main results Twenty three trials are included, allocation concealment was adequate in nine. Sixteen trials compared artemisinin drugs with quinine in 2653 patients. Artemisinin drugs were associated with better survival (mortality odds ratio 0.61, 95% confidence interval 0.46 to 0.82, random effects model). In trials where concealment of allocation was adequate (2261 patients), this was barely statistically significant (odds ratio 0.72, 95% CI 0.54 to 0.96, random effects model). In 1939 patients with cerebral malaria, mortality was also lower with artemisinin drugs overall (odds ratio 0.63, 95% CI 0.44 to 0.88, random effects model). The difference was not significant however when only trials reporting adequate concealment of allocation were analysed (odds ratio 0.78, 95% CI 0.55 to 1.10, random effects model) based on 1607 patients. No difference in neurological sequelae was shown. Compared with quinine, artemisinin drugs showed faster parasite clearance from the blood and similar adverse effects. Authors' conclusions The evidence suggests that artemisinin drugs are no worse than quinine in preventing death in severe or complicated malaria. No artemisinin derivative appears to be better than the others. This review summarizes trials up to 1999. For the reasons in the 'What's new' section, this review will no longer be updated. Plain language summary Artemisinin derivatives for treating severe malaria Artemisinin drugs improve survival in severe malaria. Artemisinin drugs come originally from a plant that has been used since ancient times in China as a traditional medicine for fever and malaria. They are fast acting and effective against malaria parasites that have developed resistance to quinine. The review shows that treatment with artemisinin drugs may be better than quinine at preventing death in adults and children with severe and complicated malaria. There is no evidence so far against early treatment with suppositories in rural areas whilst patients are transferred to hospital. Few side effects have been reported with these drugs.
H McIntosh, P Olliaro
Categories: malaria news feeds