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Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study

CiteULike malaria tags - 19 April 2018 - 10:56am
The Lancet Infectious Diseases (April 2018), doi:10.1016/s1473-3099(18)30172-5
Immo Kleinschmidt, John Bradley, Tessa Knox, Abraham Mnzava, Hmooda Kafy, Charles Mbogo, Bashir Ismail, Jude Bigoga, Alioun Adechoubou, Kamaraju Raghavendra, Jackie Cook, Elfatih Malik, Zinga Nkuni, Michael Macdonald, Nabie Bayoh, Eric Ochomo, Etienne Fondjo, Herman Awono-Ambene, Josiane Etang, Martin Akogbeto, Rajendra Bhatt, Mehul Chourasia, Dipak Swain, Teresa Kinyari, Krishanthi Subramaniam, Achille Massougbodji, Mariam Okê-Sopoh, Aurore Ogouyemi-Hounto, Celestin Kouambeng, Mujahid Abdin, Philippa West, Khalid Elmardi, Sylvie Cornelie, Vincent Corbel, Neena Valecha, Evan Mathenge, Luna Kamau, Jonathan Lines, Martin Donnelly
Categories: malaria news feeds

List of keywords of the INRMM meta-information database - part 23

CiteULike malaria tags - 13 April 2018 - 3:59pm
(February 2014)

List of indexed keywords within the transdisciplinary set of domains which relate to the Integrated Natural Resources Modelling and Management (INRMM). In particular, the list of keywords maps the semantic tags in the INRMM Meta-information Database (INRMM-MiD). [\n] The INRMM-MiD records providing this list are accessible by the special tag: inrmm-list-of-tags ( http://mfkp.org/INRMM/tag/inrmm-list-of-tags ).
Categories: malaria news feeds

Alpha-v–containing integrins are host receptors for the Plasmodium falciparum sporozoite surface protein, TRAP

CiteULike malaria tags - 12 April 2018 - 10:24am
Proceedings of the National Academy of Sciences (09 April 2018), 201719660, doi:10.1073/pnas.1719660115
Kirsten Dundas, Melanie Shears, Yi Sun, Christine Hopp, Cecile Crosnier, Tom Metcalf, Gareth Girling, Photini Sinnis, Oliver Billker, Gavin Wright
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Genome-wide transcriptional analyses in Anopheles mosquitoes reveal an unexpected association between salivary gland gene expression and insecticide resistance.

CiteULike malaria tags - 29 March 2018 - 9:05am
BMC genomics, Vol. 19, No. 1. (27 March 2018)

To combat malaria transmission, the Ugandan government has embarked upon an ambitious programme of indoor residual spraying (IRS) with a carbamate class insecticide, bendiocarb. In preparation for this campaign, we characterized bendiocarb resistance and associated transcriptional variation among Anopheles gambiae s.s. mosquitoes from two sites in Uganda. Gene expression in two mosquito populations displaying some resistance to bendiocarb (95% and 79% An. gambiae s.l. WHO tube bioassay mortality in Nagongera and Kihihi, respectively) was investigated using whole-genome microarrays. Significant overexpression of several genes encoding salivary gland proteins, including D7r2 and D7r4, was detected in mosquitoes from Nagongera. In Kihihi, D7r4, two detoxification-associated genes (Cyp6m2 and Gstd3) and an epithelial serine protease were among the genes most highly overexpressed in resistant mosquitoes. Following the first round of IRS in Nagongera, bendiocarb-resistant mosquitoes were collected, and real-time quantitative PCR analyses detected significant overexpression of D7r2 and D7r4 in resistant mosquitoes. A single nucleotide polymorphism located in a non-coding transcript downstream of the D7 genes was found at a significantly higher frequency in resistant individuals. In silico modelling of the interaction between D7r4 and bendiocarb demonstrated similarity between the insecticide and serotonin, a known ligand of D7 proteins. A meta-analysis of published microarray studies revealed a recurring association between D7 expression and insecticide resistance across Anopheles species and locations. A whole-genome microarray approach identified an association between novel insecticide resistance candidates and bendiocarb resistance in Uganda. In addition, a single nucleotide polymorphism associated with this resistance mechanism was discovered. The use of such impartial screening methods allows for discovery of resistance candidates that have no previously-ascribed function in insecticide binding or detoxification. Characterizing these novel candidates will broaden our understanding of resistance mechanisms and yield new strategies for combatting widespread insecticide resistance among malaria vectors.
Alison Isaacs, Henry Mawejje, Sean Tomlinson, Daniel Rigden, Martin Donnelly
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Single-cell RNA-seq reveals hidden transcriptional variation in malaria parasites

CiteULike malaria tags - 28 March 2018 - 9:37am
eLife, Vol. 7 (27 March 2018), doi:10.7554/elife.33105
Adam Reid, Arthur Talman, Hayley Bennett, Ana Gomes, Mandy Sanders, Christopher Illingworth, Oliver Billker, Matthew Berriman, Mara Lawniczak
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Artemisinin derivatives for treating severe malaria

CiteULike malaria tags - 23 March 2018 - 5:33pm
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

Mefloquine for preventing malaria in non‐immune adult travellers

CiteULike malaria tags - 23 March 2018 - 5:33pm
Cochrane Database of Systematic Reviews, No. 1. (2008), doi:10.1002/14651858.CD000138.pub2

Reason for withdrawal from publication The Editor withdrew this review as of Issue 1, 2008. This review has been updated and replaced following the publication of a new review: Jacquerioz FA, Croft AM Jacquerioz FA, Croft AM. Drugs for preventing malaria in travellers. Cochrane Database of Systematic Reviews 2009 , Issue 4 . Art. No.: CD006491. DOI: 10.1002/14651858.CD006491.pub2 .
AM Croft, P Garner
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Amodiaquine for treating malaria

CiteULike malaria tags - 23 March 2018 - 5:33pm
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
Categories: malaria news feeds

Vaccines for preventing malaria

CiteULike malaria tags - 23 March 2018 - 5:33pm
Cochrane Database of Systematic Reviews, No. 4. (2006), doi:10.1002/14651858.CD000129.pub2

Reason for withdrawal from publication This review has been superseded by three reviews that have been published as: 
 Graves P, Gelband H. Vaccines for preventing malaria (SPf66). Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD005966. DOI: 10.1002/14651858.CD005966. Graves P, Gelband H. Vaccines for preventing malaria (blood‐stage). Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006199. DOI: 10.1002/14651858.CD006199. Graves P, Gelband H. Vaccines for preventing malaria (pre‐erythrocytic). Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006198. DOI: 10.1002/14651858.CD006198. Vaccines for preventing malaria (SPf66) published in Issue 2, 2006; Vaccines for preventing malaria (blood‐stage); and Vaccines for preventing malaria (pre‐erythrocytic) published in Issue 4, 2006.
PM Graves, H Gelband
Categories: malaria news feeds

Chloroquine or amodiaquine combined with sulfadoxine‐pyrimethamine for treating uncomplicated malaria

CiteULike malaria tags - 23 March 2018 - 5:33pm
Cochrane Database of Systematic Reviews, No. 4. (2005), doi:10.1002/14651858.CD000386.pub2

Abstract - Background Chloroquine (CQ), amodiaquine (AQ), and sulfadoxine‐pyrimethamine (SP) are inexpensive drugs, but treatment failure is a problem. Combination therapy may reduce treatment failure. CQ or AQ plus SP are affordable options of combination treatment, but there is debate about their effectiveness. Objectives To assess the combination of CQ or AQ plus SP compared with SP alone for first‐line treatment of uncomplicated falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL ( The Cochrane Library Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1981 to April 2005), African Index Medicus (1993 to 1998), and reference lists. We also contacted researchers at relevant organizations and a pharmaceutical company. Selection criteria Randomized controlled trials in adults or children with uncomplicated Plasmodium falciparum malaria were eligible for inclusion. The main outcomes of interest were total and clinical failure at day 28 follow up and serious adverse events. Data collection and analysis Two people independently applied the inclusion criteria. One author extracted data and another checked them independently. We used risk ratio (RR) and 95% confidence intervals (CI). Main results Twelve trials (2107 participants) met the inclusion criteria. A meta‐analysis of five AQ trials (461 participants) showed a statistically significant reduction in total failure at day 28 with the combination therapy (RR 0.64, 95% CI 0.46 to 0.91), and meta‐analysis of three trials (384 participants) showed a significant reduction in clinical failure at day 28 (RR 0.23, 95% CI 0.11 to 0.49). The statistical significance in the total failure analysis was sensitive to losses to follow up. Data from two CQ trials showed no advantage for total failure with combination therapy at day 28. There was no evidence from the included trials of serious adverse events. Authors' conclusions The evidence base is not strong enough to support firm conclusions. The available evidence suggests that AQ plus SP can achieve less treatment failure than SP, but this might depend on existing levels of parasite resistance to the individual drugs. Addendum, 2008: The World Health Organization (in 2006) recommended that monotherapy should not be used for treating malaria. Therefore the authors do not intend to update this review. Plain language summary Chloroquine or amodiaquine combined with sulfadoxine‐pyrimethamine for treating uncomplicated malaria Using amodiaquine and sulfadoxine‐pyrimethamine together to treat uncomplicated malaria instead of sulfadoxine‐pyrimethamine alone may reduce treatment failure; adding chloroquine to sulfadoxine‐pyrimethamine may not be beneficial Chloroquine, amodiaquine, and sulfadoxine‐pyrimethamine are relatively inexpensive drugs to treat malaria. Treatment failure is a problem when these drugs are used alone because malaria parasites have become resistant to them. Based on evidence from randomized controlled trials, a combination of amodiaquine plus sulfadoxine‐pyrimethamine may reduce treatment failure in some locations. It appears less likely that chloroquine plus sulfadoxine‐pyrimethamine will have a treatment benefit over sulfadoxine‐pyrimethamine alone.
H McIntosh, KL Jones
Categories: malaria news feeds

Artemisinin derivatives for treating uncomplicated malaria

CiteULike malaria tags - 23 March 2018 - 5:33pm
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

Steroids for treating cerebral malaria

CiteULike malaria tags - 23 March 2018 - 5:33pm
Cochrane Database of Systematic Reviews, No. 3. (1999), doi:10.1002/14651858.CD000972

Abstract - Background Cerebral malaria is associated with swelling of the brain. Corticosteroid drugs could reduce the harmful effects of this swelling, but they could also suppress host immunity to infection. Objectives To assess the effects of corticosteroid drugs in patients with cerebral malaria on death, life‐threatening complications, and residual disability in survivors. Search methods In March 2008, we searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL ( The Cochrane Library 2008, Issue 1), MEDLINE, EMBASE, LILACS, and m RCT. We also checked reference lists. Selection criteria Randomized controlled trials comparing corticosteroids with no corticosteroids in addition to otherwise identical treatments for patients with cerebral malaria. Data collection and analysis Both authors independently assessed trial eligibility and risk of bias (methodological quality), and extracted data. Outcomes sought included death, death with life‐threatening complications, other complications, and disability. Main results Two trials with 143 participants met the inclusion criteria. There were 30 deaths in the two trials, distributed evenly between the corticosteroid and control groups (risk ratio 0.89; 95% confidence interval 0.48 to 1.68; 143 participants). Clinical complications were reported as the number of events in each trial arm and did not exclude complications occurring in fatalities. This made it difficult to interpret the reports of significantly more episodes of gastrointestinal bleeding and seizures in the corticosteroid group. Neither trial examined disability. Authors' conclusions There is currently no evidence of benefit from corticosteroids, but the small number of participants means it is difficult to exclude an effect on death in either direction. Data on clinical complications are difficult to assess. Plain language summary Corticosteroids for treating cerebral malaria Cerebral malaria is a severe form of the disease that can induce convulsions and coma; about 15% to 50% of patients with cerebral malaria will die, and 5% to 10% of survivors are left disabled as a result of brain damage. In the past decades, health professionals often gave corticosteroids such as dexamethasone and hydrocortisone, as well as antimalarial drugs, to patients with cerebral malaria, with the aim of reducing the effects of swelling and inflammation in the brain. This review assesses the effects of corticosteroid drugs given for cerebral malaria, on death, life‐threatening complications, and residual disability in survivors. The authors included two trials with a total of 143 patients (both adults and children). There were no significant differences in the number of deaths between the corticosteroid and control groups, and data on clinical complications were difficult to assess. Neither trial examined disability.
K Prasad, P Garner
Categories: malaria news feeds

Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment

CiteULike malaria tags - 23 March 2018 - 5:33pm
Cochrane Database of Systematic Reviews, No. 10. (2014), doi:10.1002/14651858.CD000169.pub3

Abstract - Background Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide‐treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. Objectives To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of intermittent preventive treatment with sulfadoxine‐pyrimethamine (SP) alone, and preventive regimens for Plasmodium vivax. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. Selection criteria Randomized controlled trials (RCTs) and quasi‐RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria‐endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. Data collection and analysis Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. Main results Seventeen trials enrolling 14,481 pregnant women met our inclusion criteria. These trials were conducted between 1957 and 2008, in Nigeria (three trials), The Gambia (three trials), Kenya (three trials), Mozambique (two trials), Uganda (two trials), Cameroon (one trial), Burkina Faso (one trial), and Thailand (two trials). Six different antimalarials were evaluated against placebo or no intervention; chloroquine (given weekly), pyrimethamine (weekly or monthly), proguanil (daily), pyrimethamine‐dapsone (weekly or fortnightly), and mefloquine (weekly), or intermittent preventive therapy with SP (given twice, three times or monthly). Trials recruited women in their first or second pregnancy (eight trials); only multigravid women (one trial); or all women (eight trials). Only six trials had adequate allocation concealment. For women in their first or second pregnancy, malaria chemoprevention reduces the risk of moderate to severe anaemia by around 40% (RR 0.60, 95% CI 0.47 to 0.75; three trials, 2503 participants, high quality evidence ), and the risk of any anaemia by around 17% (RR 0.83, 95% CI 0.74 to 0.93; five trials,, 3662 participants, high quality evidence ). Malaria chemoprevention reduces the risk of antenatal parasitaemia by around 61% (RR 0.39, 95% CI 0.26 to 0.58; seven trials, 3663 participants, high quality evidence ), and two trials reported a reduction in febrile illness ( low quality evidence ). There were only 16 maternal deaths and these trials were underpowered to detect an effect on maternal mortality ( very low quality evidence ). For infants of women in their first and second pregnancies, malaria chemoprevention probably increases mean birthweight by around 93 g (MD 92.72 g, 95% CI 62.05 to 123.39; nine trials, 3936 participants, moderate quality evidence ), reduces low birthweight by around 27% (RR 0.73, 95% CI 0.61 to 0.87; eight trials, 3619 participants, moderate quality evidence ), and reduces placental parasitaemia by around 46% (RR 0.54, 95% CI 0.43 to 0.69; seven trials, 2830 participants, high quality evidence ). Fewer trials evaluated spontaneous abortions, still births, perinatal deaths, or neonatal deaths, and these analyses were underpowered to detect clinically important differences. In multigravid women, chemoprevention has similar effects on antenatal parasitaemia (RR 0.38, 95% CI 0.28 to 0.50; three trials, 977 participants, high quality evidence )but there are too few trials to evaluate effects on other outcomes. In trials giving chemoprevention to all pregnant women irrespective of parity, the average effects of chemoprevention measured in all women indicated it may prevent severe anaemia (defined by authors, but at least < 8 g/L: RR 0.19, 95% CI 0.05 to 0.75; two trials, 1327 participants, low quality evidence), but consistent benefits have not been shown for other outcomes. In an analysis confined only to intermittent preventive therapy with SP, the estimates of effect and the quality of the evidence were similar. A summary of a single trial in Thailand of prophylaxis against P. vivax showed chloroquine prevented vivax infection (RR 0.01, 95% CI 0.00 to 0.20; one trial, 942 participants). Authors' conclusions Routine chemoprevention to prevent malaria and its consequences has been extensively tested in RCTs, with clinically important benefits on anaemia and parasitaemia in the mother, and on birthweight in infants. Plain language summary The effect of taking antimalarial drugs routinely to prevent malaria in pregnancy Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. For this reason, women are encouraged to try and prevent malaria infection during pregnancy by sleeping under mosquito bed‐nets, and by taking drugs effective against malaria throughout pregnancy as chemoprevention. This Cochrane Review looked at all drug regimens compared to placebo. The review authors sought to summarise and quantify the overall effects of chemoprevention. Seventeen trials were included, all conducted between 1957 and 2008, and all but two in countries of Africa. For women in their first or second pregnancy, malaria chemoprevention prevents moderate to severe anaemia ( high quality evidence ); and prevents malaria parasites being detected in the blood ( high quality evidence ). It may also prevent malaria illness. We don't know if it prevents maternal deaths, as this would require very large studies to detect an effect. In their infants, malaria chemoprevention improves the average birthweight ( moderate quality evidence ), and reduces the number of low birthweight infants ( moderate quality evidence ). We are not sure if chemoprevention reduces mortality of babies in the first week, month and year, as again studies would need to be very large to show these effects.
D Radeva‐Petrova, K Kayentao, FO ter Kuile, D Sinclair, P Garner
Categories: malaria news feeds

Estimating age-time-dependent malaria force of infection accounting for unobserved heterogeneity

CiteULike malaria tags - 7 March 2018 - 12:29pm
Epidemiology and Infection, Vol. 145, No. 12. (5 July 2017), pp. 2545-2562, doi:10.1017/s0950268817001297
L Mugenyi, S Abrams, N Hens
Categories: malaria news feeds

In silico guided reconstruction and analysis of ICAM-1-binding var genes from Plasmodium falciparum

CiteULike malaria tags - 22 February 2018 - 11:17am
Scientific Reports, Vol. 8, No. 1. (19 February 2018), doi:10.1038/s41598-018-21591-8
Eilidh Carrington, Thomas Otto, Tadge Szestak, Frank Lennartz, Matt Higgins, Chris Newbold, Alister Craig
Categories: malaria news feeds

Candidate-gene based GWAS identifies reproducible DNA markers for metabolic pyrethroid resistance from standing genetic variation in East African Anopheles gambiae

CiteULike malaria tags - 16 February 2018 - 8:57am
Scientific Reports, Vol. 8, No. 1. (13 February 2018), doi:10.1038/s41598-018-21265-5
David Weetman, Craig Wilding, Daniel Neafsey, Pie Müller, Eric Ochomo, Alison Isaacs, Keith Steen, Emily Rippon, John Morgan, Henry Mawejje, Daniel Rigden, Loyce Okedi, Martin Donnelly
Categories: malaria news feeds

Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania

CiteULike malaria tags - 8 February 2018 - 11:45am
PLOS Genetics, Vol. 14, No. 1. (30 January 2018), e1007172, doi:10.1371/journal.pgen.1007172

Significant selection pressure has been exerted on the genomes of human populations exposed to Plasmodium falciparum infection, resulting in the acquisition of mechanisms of resistance against severe malarial disease. Many host genetic factors, including sickle cell trait, have been associated with reduced risk of developing severe malaria, but do not account for all of the observed phenotypic variation. Identification of novel inherited risk factors relies upon high-resolution genome-wide association studies (GWAS). We present findings of a GWAS of severe malaria performed in a Tanzanian population (n = 914, 15.2 million SNPs). Beyond the expected association with the sickle cell HbS variant, we identify protective associations within two interleukin receptors (IL-23R and IL-12RBR2) and the kelch-like protein KLHL3 (all P<10−6), as well as near significant effects for Major Histocompatibility Complex (MHC) haplotypes. Complementary analyses, based on detecting extended haplotype homozygosity, identified SYNJ2BP, GCLC and MHC as potential loci under recent positive selection. Through whole genome sequencing of an independent Tanzanian cohort (parent-child trios n = 247), we confirm the allele frequencies of common polymorphisms underlying associations and selection, as well as the presence of multiple structural variants that could be in linkage with these SNPs. Imputation of structural variants in a region encompassing the glycophorin genes on chromosome 4, led to the characterisation of more than 50 rare variants, and individually no strong evidence of associations with severe malaria in our primary dataset (P>0.3). Our approach demonstrates the potential of a joint genotyping-sequencing strategy to identify as-yet unknown susceptibility loci in an African population with well-characterised malaria phenotypes. The regions encompassing these loci are potential targets for the design of much needed interventions for preventing or treating malarial disease. Malaria, caused by Plasmodium falciparum parasites, is a major cause of mortality and morbidity in endemic countries of sub-Saharan Africa, including Tanzania. Some gene mutations in the human genome, including sickle cell trait, have been associated with reduced risk of developing severe malaria, and have increased in frequency through natural selection over generations. However, new genetic mutations remain to be discovered, and recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine-scale molecular genotyping tools, are facilitating their identification. Here, we present findings of a GWAS of severe malaria performed in a well characterised Tanzanian population (n = 914). We confirm the expected association with the sickle cell trait, but also identify new gene targets in immunological pathways, some under natural selection. Our approach demonstrates the potential of using GWAS to identify as-yet unknown susceptibility genes in endemic populations with well-characterised malaria phenotypes. The genetic mutations are likely to form potential targets for the design of much needed interventions for preventing or treating malarial disease.
Matt Ravenhall, Susana Campino, Nuno Sepúlveda, Alphaxard Manjurano, Behzad Nadjm, George Mtove, Hannah Wangai, Caroline Maxwell, Raimos Olomi, Hugh Reyburn, Christopher Drakeley, Eleanor Riley, Taane Clark, N in collaboration with MalariaGE
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Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study

CiteULike malaria tags - 2 February 2018 - 9:09am
The Lancet Infectious Diseases (February 2018), doi:10.1016/s1473-3099(18)30068-9
Roberto Amato, Richard Pearson, Jacob Almagro-Garcia, Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Eleanor Drury, Jim Stalker, Olivo Miotto, Rick Fairhurst, Dominic Kwiatkowski
Categories: malaria news feeds

Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance

CiteULike malaria tags - 1 February 2018 - 11:36am
Blood (01 January 2018), blood-2017-11-814665, doi:10.1182/blood-2017-11-814665
Souvik Bhattacharjee, Isabelle Coppens, Alassane Mbengue, Niraja Suresh, Mehdi Ghorbal, Zdenek Slouka, Innocent Safeukui, Hsin-Yao Tang, David Speicher, Robert Stahelin, Narla Mohandas, Kasturi Haldar
Categories: malaria news feeds

Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome

CiteULike malaria tags - 19 January 2018 - 11:00am
Wellcome Open Research, Vol. 2 (22 November 2017), 50, doi:10.12688/wellcomeopenres.11910.2
Abdirahman Abdi, Lu Yu, David Goulding, Martin Rono, Philip Bejon, Jyoti Choudhary, Julian Rayner
Categories: malaria news feeds

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