73 results on '"Ataide, R"'
Search Results
2. Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial
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Pasricha, S-R, Mwangi, MN, Moya, E, Ataide, R, Mzembe, G, Harding, R, Zinenani, T, Larson, LM, Demir, AY, Nkhono, W, Chinkhumba, J, Simpson, JA, Clucas, D, Stones, W, Braat, S, Phiri, KS, Pasricha, S-R, Mwangi, MN, Moya, E, Ataide, R, Mzembe, G, Harding, R, Zinenani, T, Larson, LM, Demir, AY, Nkhono, W, Chinkhumba, J, Simpson, JA, Clucas, D, Stones, W, Braat, S, and Phiri, KS
- Abstract
BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was nu
- Published
- 2023
3. An implementation research programme to support an intravenous iron intervention for pregnant women with moderate and severe anaemia in Malawi: study protocol.
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Prang, K-H, Mamani-Mategula, E, Verbunt, E, Chipeta, E, Ataide, R, Mwangi, M, Phiri, K, Pasricha, S-R, Kelaher, M, Manda-Taylor, L, Prang, K-H, Mamani-Mategula, E, Verbunt, E, Chipeta, E, Ataide, R, Mwangi, M, Phiri, K, Pasricha, S-R, Kelaher, M, and Manda-Taylor, L
- Abstract
BACKGROUND: Antenatal iron supplementation is critical to maternal and child health; however, access and adherence to oral iron are inconsistent in many low- and middle-income countries (LMICs). Modern intravenous (IV) iron products have become available in high-income clinical settings and provide an opportunity to deliver high doses of iron in a single-short infusion during pregnancy. However, there is limited knowledge of the drivers and barriers for such an intervention to be effectively delivered and upscaled in LMICs. In this study protocol, we describe the implementation research programme to support an IV iron intervention in Malawi for pregnant women with moderate and severe anaemia. METHODS: The implementation research programme has three phases, each guided by implementation science conceptual frameworks. In Phase 1, we will conduct formative research (context assessment of the health system with key informant interviews) to determine how IV iron can be effectively introduced into routine antenatal care. We will use the findings to co-develop potential strategies with end-users and healthcare providers to improve intervention implementation. In Phase 2, we will disseminate the implementation strategies to support the uptake and delivery of the intervention in the study settings. In Phase 3, the intervention will be implemented, and we will conduct formative evaluation (interviews with end-users, healthcare providers, and analysis of health services data) to investigate the feasibility and acceptability of the intervention and strategies. We will also identify processes and contextual factors that facilitate or impede the delivery and uptake of IV iron. DISCUSSION: In LMICs, modern IV iron products present a novel opportunity to rapidly cure moderate and severe anaemia in pregnancy, thereby improving maternal and child health outcomes. This implementation research programme will provide guidance and recommendations on how best an IV iron intervention for p
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- 2022
4. Contrasting Epidemiology and Population Genetics of COVID-19 Infections Defined by Multilocus Genotypes in SARS-CoV-2 Genomes Sampled Globally
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Chan, FHM, Ataide, R, Richards, JS, Narh, CA, Chan, FHM, Ataide, R, Richards, JS, and Narh, CA
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Since its emergence in 2019, SARS-CoV-2 has spread and evolved globally, with newly emerged variants of concern (VOCs) accounting for more than 500 million COVID-19 cases and 6 million deaths. Continuous surveillance utilizing simple genetic tools is needed to measure the viral epidemiological diversity, risk of infection, and distribution among different demographics in different geographical regions. To help address this need, we developed a proof-of-concept multilocus genotyping tool and demonstrated its utility to monitor viral populations sampled in 2020 and 2021 across six continents. We sampled globally 22,164 SARS-CoV-2 genomes from GISAID (inclusion criteria: available clinical and demographic data). They comprised two study populations, “2020 genomes” (N = 5959) sampled from December 2019 to September 2020 and “2021 genomes” (N = 16,205) sampled from 15 January to 15 March 2021. All genomes were aligned to the SARS-CoV-2 reference genome and amino acid polymorphisms were called with quality filtering. Thereafter, 74 codons (loci) in 14 genes including orf1ab polygene (N = 9), orf3a, orf8, nucleocapsid (N), matrix (M), and spike (S) met the 0.01 minimum allele frequency criteria and were selected to construct multilocus genotypes (MLGs) for the genomes. At these loci, 137 mutant/variant amino acids (alleles) were detected with eight VOC-defining variant alleles, including N KR203&204, orf1ab (I265, F3606, and L4715), orf3a H57, orf8 S84, and S G614, being predominant globally with > 35% prevalence. Their persistence and selection were associated with peaks in the viral transmission and COVID-19 incidence between 2020 and 2021. Epidemiologically, older patients (≥20 years) compared to younger patients (<20 years) had a higher risk of being infected with these variants, but this association was dependent on the continent of origin. In the global population, the discriminant analysis of principal components (DAPC) showed contrasting patterns of genetic cluster
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- 2022
5. Malaria and immunity during pregnancy and postpartum: a tale of two species
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McLEAN, A. R. D., ATAIDE, R., SIMPSON, J. A., BEESON, J. G., and FOWKES, F. J. I.
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- 2015
- Full Text
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6. A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan.
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Harding, R, Ataide, R, Mwangi, MN, Simpson, JA, Mzembe, G, Moya, E, Truwah, Z, Nkhwazi, BC, Mwabinga, M, Nkhono, W, Phiri, KS, Pasricha, S-R, Braat, S, Harding, R, Ataide, R, Mwangi, MN, Simpson, JA, Mzembe, G, Moya, E, Truwah, Z, Nkhwazi, BC, Mwabinga, M, Nkhono, W, Phiri, KS, Pasricha, S-R, and Braat, S
- Abstract
Background: Anaemia affects more than half of Africa's pregnancies. Standard care, with oral iron tablets, often fails to achieve results, with compliance and gastrointestinal side-effects being a significant issue. In recent years, intravenous iron formulations have become safe, effective, and quick to administer, allowing the complete iron requirements of pregnancy to be provided in one 15-minute infusion. The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) will evaluate whether a modern intravenous iron formulation, ferric carboxymaltose (FCM), given once during the second trimester is effective and safe in improving maternal and neonatal outcomes for treatment of moderate to severe anaemia in sub-Saharan Africa. The objective was to publish the detailed statistical analysis plan for the REVAMP trial prior to unblinding the allocated treatments and performing the analysis. Methods: REVAMP is a multicentre, two-arm, open-label, parallel-group randomized control trial (RCT) in 862 pregnant women in their second trimester. The trial statistician developed the statistical analysis plan in consultation with the trial management team based on the protocol, data collection forms, and study outcomes available in the blinded study database. Results: The detailed statistical analysis plan will support the statistical analyses and reporting of the REVAMP trial after unblinding the treatment allocations. Conclusions: A statistical analysis plan allows for transparency as well as reproducibility of reporting and statistical analyses.
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- 2021
7. Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children
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Hayman, T, Hickey, P, Amann-Zalcenstein, D, Bennett, C, Ataide, R, Sthity, RA, Khandaker, AM, Islam, KM, Stracke, K, Yassi, N, Watson, R, Long, J, Westcott, J, Krebs, NF, King, JC, Black, RE, Islam, MM, McDonald, CM, Pasricha, S-R, Hayman, T, Hickey, P, Amann-Zalcenstein, D, Bennett, C, Ataide, R, Sthity, RA, Khandaker, AM, Islam, KM, Stracke, K, Yassi, N, Watson, R, Long, J, Westcott, J, Krebs, NF, King, JC, Black, RE, Islam, MM, McDonald, CM, and Pasricha, S-R
- Abstract
Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9-11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.
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- 2021
8. Protocol for a multicentre, parallel-group, open-label randomised controlled trial comparing ferric carboxymaltose with the standard of care in anaemic Malawian pregnant women: the REVAMP trial
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Mwangi, MN, Mzembe, G, Moya, E, Braat, S, Harding, R, Robberstad, B, Simpson, J, Stones, W, Rogerson, S, Biselele, K, Chinkhumba, J, Larson, L, Ataide, R, Phiri, KS, Pasricha, S-R, Mwangi, MN, Mzembe, G, Moya, E, Braat, S, Harding, R, Robberstad, B, Simpson, J, Stones, W, Rogerson, S, Biselele, K, Chinkhumba, J, Larson, L, Ataide, R, Phiri, KS, and Pasricha, S-R
- Abstract
INTRODUCTION: Anaemia in pregnancy remains a critical global health problem, affecting 46% of pregnant women in Africa and 49% in Asia. Oral iron therapy requires extended adherence to achieve correction of anaemia and replenishment of iron stores. Ferric carboxymaltose (FCM) is a recently established intravenous iron formulation associated with substantial advantages in safety, speed of delivery and total dose deliverable in a single infusion. We aim to determine whether FCM given once during the second trimester of pregnancy compared with standard oral iron distributed through routine antenatal services is effective and safe for treatment of moderate to severe maternal anaemia in sub-Saharan Africa. METHODS AND ANALYSIS: The randomized controlled trial of the effect of intravenous iron on anaemia in Malawian pregnant women (REVAMP) is a two-arm confirmatory individually randomised trial set in Blantyre and Zomba districts in Malawi. The trial will randomise 862 women in the second trimester of pregnancy with a capillary haemoglobin concentration below 100.0 g/L. The study comprises two arms: (a) intravenous FCM (20 mg/kg up to 1000 mg) given once at randomisation, and (b) standard of care oral iron (65 mg elemental iron two times per day) for 90 days (or the duration of pregnancy, whichever is shorter) provided according to local healthcare practices. Both arms receive sulfadoxine-pyrimethamine as intermittent preventive treatment in pregnancy. The primary outcome is the prevalence of anaemia (Hb <110.0 g/L) at 36 weeks' gestation. Secondary outcomes include birth weight, gestation duration and safety outcomes, including clinical malaria, serious perinatal events and postpartum haematologic and health-related outcomes in the mother and child. ETHICS AND DISSEMINATION: Ethical approval was granted by the Research Ethics Committee (COMREC P.02/18/2357) in Malawi and the Human Research Ethics Committee (WEHI: 18/02), Melbourne, Australia. The protocol is registered w
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- 2021
9. Guiding the Immune Response to a Conserved Epitope in MSP2, an Intrinsically Disordered Malaria Vaccine Candidate
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Seow, J, Das, SC, Morales, RAV, Ataide, R, Krishnarjuna, B, Silk, M, Chalmers, DK, Richards, J, Anders, RF, MacRaild, CA, Norton, RS, Seow, J, Das, SC, Morales, RAV, Ataide, R, Krishnarjuna, B, Silk, M, Chalmers, DK, Richards, J, Anders, RF, MacRaild, CA, and Norton, RS
- Abstract
The malaria vaccine candidate merozoite surface protein 2 (MSP2) has shown promise in clinical trials and is in part responsible for a reduction in parasite densities. However, strain-specific reductions in parasitaemia suggested that polymorphic regions of MSP2 are immuno-dominant. One strategy to bypass the hurdle of strain-specificity is to bias the immune response towards the conserved regions. Two mouse monoclonal antibodies, 4D11 and 9H4, recognise the conserved C-terminal region of MSP2. Although they bind overlapping epitopes, 4D11 reacts more strongly with native MSP2, suggesting that its epitope is more accessible on the parasite surface. In this study, a structure-based vaccine design approach was applied to the intrinsically disordered antigen, MSP2, using a crystal structure of 4D11 Fv in complex with its minimal binding epitope. Molecular dynamics simulations and surface plasmon resonance informed the design of a series of constrained peptides that mimicked the 4D11-bound epitope structure. These peptides were conjugated to keyhole limpet hemocyanin and used to immunise mice, with high to moderate antibody titres being generated in all groups. The specificities of antibody responses revealed that a single point mutation can focus the antibody response towards a more favourable epitope. This structure-based approach to peptide vaccine design may be useful not only for MSP2-based malaria vaccines, but also for other intrinsically disordered antigens.
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- 2021
10. Review of Burden, Clinical Definitions, and Management of COVID-19 Cases
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McArthur, L, Sakthivel, D, Ataide, R, Chan, F, Richards, JS, Narh, CA, McArthur, L, Sakthivel, D, Ataide, R, Chan, F, Richards, JS, and Narh, CA
- Abstract
Our understanding of SARS-CoV-2, the virus responsible for coronavirus disease 2019 (COVID-19), its clinical manifestations, and treatment options continues to evolve at an unparalleled pace. This review sought to summarize the key literature regarding transmission, case definitions, clinical management, and the burden of COVID-19. Our review of the literature showed that SARS-CoV-2 was mainly transmitted via inhalation of respiratory droplets containing the virus and had a mean incubation period of 4-6 days. The commonly reported symptoms were fever (75.3% ± 18.7%) and cough (62.6% ± 17.7%) across the spectrum of clinical disease-mild, moderate, severe, and critical, but with the disease phenotype varying with severity. Categorization of these cases for home care or hospital management needs to be defined, with risk stratification accounting for the age of the patient and the presence of underlying comorbidities. The case definitions varied among countries, which could have contributed to the differences in the case fatality rates among affected countries. The severity and risk of death due to COVID-19 was associated with age and underlying comorbidities. Asymptomatic cases, which constitute 40-80% of COVID-19 cases are a considerable threat to control efforts. The presence of fever and cough may be sufficient to warrant COVID-19 testing, but using these symptoms in isolation will miss a proportion of cases. A clear definition of a COVID-19 case is essential for the management, treatment, and tracking of clinical illness, and to inform the quarantine measures and social distancing that can help control the spread of SARS-CoV-2.
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- 2020
11. Improvement on UHMWPE and PMMA Surface Flashover Under Atmospheric Pressure Using PIII Processing
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Rossi, Jose O., primary, Ueda, Mario, additional, Silva, Ataide R., additional, and Neto, Lauro P. Silva, additional
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- 2020
- Full Text
- View/download PDF
12. Contribution of Functional Antimalarial Immunity to Measures of Parasite Clearance in Therapeutic Efficacy Studies of Artemisinin Derivatives
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O'Flaherty, K, Ataide, R, Zaloumis, SG, Ashley, EA, Powell, R, Feng, G, Reiling, L, Dondorp, AM, Day, NP, Dhorda, M, Fairhurst, RM, Lim, P, Amaratunga, C, Pukrittayakamee, S, Tran, TH, Htut, Y, Mayxay, M, Abul Faiz, M, Beeson, JG, Nosten, F, Simpson, JA, White, NJ, Fowkes, FJ, O'Flaherty, K, Ataide, R, Zaloumis, SG, Ashley, EA, Powell, R, Feng, G, Reiling, L, Dondorp, AM, Day, NP, Dhorda, M, Fairhurst, RM, Lim, P, Amaratunga, C, Pukrittayakamee, S, Tran, TH, Htut, Y, Mayxay, M, Abul Faiz, M, Beeson, JG, Nosten, F, Simpson, JA, White, NJ, and Fowkes, FJ
- Abstract
BACKGROUND: Antibodies to the blood stages of malaria parasites enhance parasite clearance and antimalarial efficacy. The antibody subclass and functions that contribute to parasite clearance during antimalarial treatment and their relationship to malaria transmission intensity have not been characterized. METHODS: Levels of immunoglobulin G (IgG) subclasses and C1q fixation in response to Plasmodium falciparum merozoite antigens (erythrocyte-binding antigen [EBA] 175RIII-V, merozoite surface protein 2 [MSP-2], and MSP-142) and opsonic phagocytosis of merozoites were measured in a multinational trial assessing the efficacy of artesunate therapy across 11 Southeast Asian sites. Regression analyses assessed the effects of antibody seropositivity on the parasite clearance half-life (PC½), having a PC½ of ≥5 hours, and having parasitemia 3 days after treatment. RESULTS: IgG3, followed by IgG1, was the predominant IgG subclass detected (seroprevalence range, 5%-35% for IgG1 and 27%-41% for IgG3), varied across study sites, and was lowest in study sites with the lowest transmission intensity and slowest mean PC½. IgG3, C1q fixation, and opsonic-phagocytosis seropositivity were associated with a faster PC½ (range of the mean reduction in PC½, 0.47-1.16 hours; P range, .001-.03) and a reduced odds of having a PC½ of ≥5 hours and having parasitemia 3 days after treatment. CONCLUSIONS: The prevalence of IgG3, complement-fixing antibodies, and merozoite phagocytosis vary according to transmission intensity, are associated with faster parasite clearance, and may be sensitive surrogates of an augmented clearance capacity of infected erythrocytes. Determining the functional immune mechanisms associated with parasite clearance will improve characterization of artemisinin resistance.
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- 2019
13. Effectiveness of repellent delivered through village health volunteers on malaria incidence in villages in South-East Myanmar: a stepped-wedge cluster-randomised controlled trial protocol
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Oo, WH, Cutts, JC, Agius, PA, Aung, KZ, Aung, PP, Aung, T, Zaw, NN, Thu, HK, Htay, WYM, Ataide, R, O'Flaherty, K, Yawn, AP, Soe, AP, Beeson, JG, Crabb, B, Pasricha, N, Fowkes, FJI, Oo, WH, Cutts, JC, Agius, PA, Aung, KZ, Aung, PP, Aung, T, Zaw, NN, Thu, HK, Htay, WYM, Ataide, R, O'Flaherty, K, Yawn, AP, Soe, AP, Beeson, JG, Crabb, B, Pasricha, N, and Fowkes, FJI
- Abstract
BACKGROUND: To combat emerging drug resistance in the Greater Mekong Sub-region (GMS) the World Health Organization and GMS countries have committed to eliminating malaria in the region by 2030. The overall approach includes providing universal access to diagnosis and treatment of malaria, and sustainable preventive measures, including vector control. Topical repellents are an intervention that can be used to target residual malaria transmission not covered by long lasting insecticide nets and indoor residual spraying. Although there is strong evidence that topical repellents protect against mosquito bites, evidence is not well established for the effectiveness of repellents distributed as part of malaria control activities in protecting against episodes of malaria. A common approach to deliver malaria services is to assign Village Health Volunteers (VHVs) to villages, particularly where limited or no services exist. The proposed trial aims to provide evidence for the effectiveness of repellent distributed through VHVs in reducing malaria. METHODS: The study is an open stepped-wedge cluster-randomised controlled trial randomised at the village level. Using this approach, repellent (N,N-diethyl-benzamide - 12% w/w, cream) is distributed by VHVs in villages sequentially throughout the malaria transmission season. Villages will be grouped into blocks, with blocks transitioned monthly from control (no repellent) to intervention states (to receive repellent) across 14 monthly intervals in random order). This follows a 4-week baseline period where all villages do not receive repellent. The primary endpoint is defined as the number of individuals positive for Plasmodium falciparum and Plasmodium vivax infections diagnosed by a rapid diagnostic test. Secondary endpoints include symptomatic malaria, Polymerase Chain Reaction (PCR)-detectable Plasmodium spp. infections, molecular markers of drug resistance and antibodies specific for Plasmodium spp. parasites. DISCUSSION: Thi
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- 2018
14. Implications of population-level immunity for the emergence of artemisinin-resistant malaria: a mathematical model
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Scott, N, Ataide, R, Wilson, DP, Hellard, M, Price, RN, Simpson, JA, Fowkes, FJ, Scott, N, Ataide, R, Wilson, DP, Hellard, M, Price, RN, Simpson, JA, and Fowkes, FJ
- Abstract
BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong Subregion, an area of relatively low transmission, but has yet to be reported in Africa. A population-based mathematical model was used to investigate the relationship between P. falciparum prevalence, exposure-acquired immunity and time-to-emergence of artemisinin resistance. The possible implication for the emergence of resistance across Africa was assessed. METHODS: The model included human and mosquito populations, two strains of malaria ("wild-type", "mutant"), three levels of human exposure-acquired immunity (none, low, high) with two types of immunity for each level (sporozoite/liver stage immunity and blood-stage/gametocyte immunity) and drug pressure based on per-capita treatment numbers. RESULTS: The model predicted that artemisinin-resistant strains may circulate up to 10 years longer in high compared to low P. falciparum prevalence areas before resistance is confirmed. Decreased time-to-resistance in low prevalence areas was explained by low genetic diversity and immunity, which resulted in increased probability of selection and spread of artemisinin-resistant strains. Artemisinin resistance was estimated to be established by 2020 in areas of Africa with low (< 10%) P. falciparum prevalence, but not for 5 or 10 years later in moderate (10-25%) or high (> 25%) prevalence areas, respectively. CONCLUSIONS: Areas of low transmission and low immunity give rise to a more rapid expansion of artemisinin-resistant parasites, corroborating historical observations of anti-malarial resistance emergence. Populations where control strategies are in place that reduce malaria transmission, and hence immunity, may be prone to a rapid emergence and spread of artemisinin-resistant strains and thus should be carefully monitored.
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- 2018
15. Host immunity and the assessment of emerging artemisinin resistance in a multinational cohort
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Ataide, R, Ashley, EA, Powell, R, Chan, J-A, Malloy, M, O'Flaherty, K, Takashima, E, Langer, C, Tsuboi, T, Dondorp, AM, Day, NP, Dhorda, M, Fairhurst, RM, Lim, P, Amaratunga, C, Pukrittayakamee, S, Hien, TT, Htut, Y, Mayxay, M, Faiz, MA, Beeson, JG, Nosten, F, Simpson, JA, White, N, and Fowkes, FJI
- Subjects
parasitic diseases - Abstract
38 Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally-acquired immunity to malaria clears parasites independently of antimalarial drugs. We hypothesise that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 P. falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt½) after artesunate treatment and kelch13 mutations. Linear mixed-effects modelling of pooled individual patient data assessed the association between antibody responses and PCt½. P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt½ were highest (Spearman ρ = -0·90 (95% CI: -0·97, -0·65) and -0·94 (-0·98, -0·77) respectively). P. falciparum antibodies were associated with faster PCt½ (mean difference in PCt½ according to seropositivity -0·16 to -0·65 hours depending on antigen); antibodies have a greater impact on the clearance of kelch13 mutant compared to wild-type parasites (mean difference in PCt½ according to seropositivity -0·22 to -0·61 hours faster in kelch13 mutants compared to wild-type parasites). Naturally-acquired immunity accelerates the clearance of artemisinin-resistant parasites in patients with falciparum malaria, and may confound the current working definition of artemisinin resistance. Immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites.
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- 2017
16. Declining Transmission and Immunity to Malaria and Emerging Artemisinin Resistance in Thailand: A Longitudinal Study
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Ataide, R, Powell, R, Moore, K, McLean, A, Phyo, AP, Nair, S, White, M, Anderson, TJ, Beeson, JG, Simpson, JA, Nosten, F, Fowkes, FJI, Ataide, R, Powell, R, Moore, K, McLean, A, Phyo, AP, Nair, S, White, M, Anderson, TJ, Beeson, JG, Simpson, JA, Nosten, F, and Fowkes, FJI
- Abstract
BACKGROUND: Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time. METHODS: Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period of declining malaria transmission and emerging artemisinin resistance in northwestern Thailand. We investigated the association between antibody levels and both parasite clearance time (PCt½) and artemisinin resistance-associated kelch13 genotypes over time. RESULTS: Immunity to P. falciparum declined prior to 2004, preceding the emergence of artemisinin resistance-associated genotypes and phenotypes (maximum mean change in antibody level per year: anti-MSP142 = -0.17; 95% confidence interval [CI] = -.31 to -.04; P = .01). In this period of declining immunity, and in the absence of kelch13 mutations, PCt½ increased. Between 2007 and 2011, levels of antibodies fluctuated, and higher antibody levels were associated with faster PCt½ (maximum yearly change in PCt½, in hours: EBA140rII = -0.39; 95% CI = -.61 to -.17; P < .001). CONCLUSIONS: Understanding the impact of changing transmission and immunity on the emergence of artemisinin resistance is important particularly as increased malaria control and elimination activities may enhance immunological conditions for the expansion of artemisinin-resistant P. falciparum.
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- 2017
17. Antibody Responses to Plasmodium falciparum and Plasmodium vivax and Prospective Risk of Plasmodium spp. Infection Postpartum
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McLean, ARD, Boel, M, McGready, R, Ataide, R, Drew, D, Tsuboi, T, Beeson, JG, Nosten, F, Simpson, JA, Fowkes, FJI, McLean, ARD, Boel, M, McGready, R, Ataide, R, Drew, D, Tsuboi, T, Beeson, JG, Nosten, F, Simpson, JA, and Fowkes, FJI
- Abstract
Postpartum women may have an altered susceptibility to Plasmodium falciparum and Plasmodium vivax. The relationship between naturally acquired malarial immunity and susceptibility to malaria postpartum is yet to be determined. IgG levels were measured against P. falciparum and P. vivax antigens from delivery in 201 postpartum and 201 nonpregnant controls over 12 weeks. Associations between time-varying antibody levels and time to first microscopically confirmed species-specific infection were determined by Cox regression. Associations between antibody levels and prospective risk of Plasmodium infection were similar in postpartum and control women. A 2-fold increase in P. falciparum antibody levels was associated with increased prospective risk of P. falciparum infection (hazard ratio [HR] range = 1.37-1.94). Antibody levels against most P. vivax antigens displayed no association with prospective risk of P. vivax infection (HR range = 1.02-1.05) with the exception of PvMSP119 antibodies that were weakly associated with prospective risk of P. vivax infection (HR = 1.14 (95% confidence interval = 1.02, 1.28) per 2-fold increase in levels). Associations between antibody levels and prospective risk of infection attenuated when adjusted for documented retrospective exposure. Serology may be a useful tool to predict and monitor women at increased risk of P. falciparum infection postpartum, particularly in the absence of a detailed history of retrospective infections.
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- 2017
18. QUANTIFYING THE IMPORTANCE OF PFEMP1 AND OTHER ANTIGENS EXPRESSED ON THE SURFACE OF PLASMODIUM FALCIPARUM-INFECTED ERYTHROCYTES AS TARGETS OF PROTECTIVE ANTIBODIES AGAINST MALARIA
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Howell, K, Chan, J-A, Reiling, L, Ataide, R, McCallum, F, Bull, PC, Maier, AG, Chesson, J, Warimwe, G, Rogerson, SJ, Cowman, AF, Marsh, K, and Beeson, JG
- Published
- 2016
19. Antibody responses to Plasmodium falciparum and Plasmodium vivax blood-stage and sporozoite antigens in the postpartum period
- Author
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McLean, ARD, Boel, ME, McGready, R, Ataide, R, Drew, D, Tsuboi, T, Beeson, JG, Nosten, F, Simpson, JA, Fowkes, FJI, McLean, ARD, Boel, ME, McGready, R, Ataide, R, Drew, D, Tsuboi, T, Beeson, JG, Nosten, F, Simpson, JA, and Fowkes, FJI
- Abstract
During pregnancy a variety of immunological changes occur to accommodate the fetus. It is unknown whether these changes continue to affect humoral immunity postpartum or how quickly they resolve. IgG levels were measured to P. falciparum and P. vivax antigens in 201 postpartum and 201 controls over 12 weeks. Linear mixed-effects models assessed antibody maintenance over time and the effect of microscopically confirmed Plasmodium spp. infection on antibody levels, and whether this was different in postpartum women compared with control women. Postpartum women had reduced Plasmodium spp. antibody levels compared to controls at baseline. Over 12 weeks, mean antibody levels in postpartum women increased to levels observed in control women. Microscopically confirmed P. falciparum and P. vivax infections during follow-up were associated with an increase in species-specific antibodies with similar magnitudes of boosting observed in postpartum and control women. Antibodies specific for pregnancy-associated, VAR2CSA-expressing parasites did not rapidly decline postpartum and did not boost in response to infection in either postpartum or control women. After pregnancy, levels of malaria-specific antibodies were reduced, but recovered to levels seen in control women. There was no evidence of an impaired ability to mount a boosting response in postpartum women.
- Published
- 2016
20. Malaria in Pregnancy Interacts with and Alters the Angiogenic Profiles of the Placenta
- Author
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Rodrigues, MM, Ataide, R, Murillo, O, Dombrowski, JG, Souza, RM, Lima, FA, Lima, GFMC, Hristov, AD, Valle, SCN, Di Santi, SM, Epiphanio, S, Marinho, CRF, Rodrigues, MM, Ataide, R, Murillo, O, Dombrowski, JG, Souza, RM, Lima, FA, Lima, GFMC, Hristov, AD, Valle, SCN, Di Santi, SM, Epiphanio, S, and Marinho, CRF
- Abstract
Malaria in pregnancy remains a substantial public health problem in malaria-endemic areas with detrimental outcomes for both the mother and the foetus. The placental changes that lead to some of these detrimental outcomes have been studied, but the mechanisms that lead to these changes are still not fully elucidated. There is some indication that imbalances in cytokine cascades, complement activation and angiogenic dysregulation might be involved in the placental changes observed. Nevertheless, the majority of studies on malaria in pregnancy (MiP) have come from areas where malaria transmission is high and usually restricted to Plasmodium falciparum, the most pathogenic of the malaria parasite species. We conducted a cross-sectional study in Cruzeiro do Sul, Acre state, Brazil, an area of low transmission and where both P. vivax and P. falciparum circulate. We collected peripheral and placental blood and placental biopsies, at delivery from 137 primigravid women and measured levels of the angiogenic factors angiopoietin (Ang)-1, Ang-2, their receptor Tie-2, and several cytokines and chemokines. We measured 4 placental parameters (placental weight, syncytial knots, placental barrier thickness and mononuclear cells) and associated these with the levels of angiogenic factors and cytokines. In this study, MiP was not associated with severe outcomes. An increased ratio of peripheral Tie-2:Ang-1 was associated with the occurrence of MiP. Both Ang-1 and Ang-2 had similar magnitudes but inverse associations with placental barrier thickness. Malaria in pregnancy is an effect modifier of the association between Ang-1 and placental barrier thickness.
- Published
- 2015
21. Malaria and immunity during pregnancy and postpartum: a tale of two species
- Author
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Mclean, ARD, Ataide, R, Simpson, JA, Beeson, JG, Fowkes, FJI, Mclean, ARD, Ataide, R, Simpson, JA, Beeson, JG, and Fowkes, FJI
- Abstract
It is well established that pregnant women are at an increased risk of Plasmodium falciparum infection when compared to non-pregnant individuals and limited epidemiological data suggest Plasmodium vivax risk also increases with pregnancy. The risk of P. falciparum declines with successive pregnancies due to the acquisition of immunity to pregnancy-specific P. falciparum variants. However, despite similar declines in P. vivax risk with successive pregnancies, there is a paucity of evidence P. vivax-specific immunity. Cross-species immunity, as well as immunological and physiological changes that occur during pregnancy may influence the susceptibility to both P. vivax and P. falciparum. The period following delivery, the postpartum period, is relatively understudied and available epidemiological data suggests that it may also be a period of increased risk of infection to Plasmodium spp. Here we review the literature and directly compare and contrast the epidemiology, clinical pathogenesis and immunological features of P. vivax and P. falciparum in pregnancy, with a particular focus on studies performed in areas co-endemic for both species. Furthermore, we review the intriguing epidemiology literature of both P. falciparum and P. vivax postpartum and relate observations to the growing literature pertaining to malaria immunology in the postpartum period.
- Published
- 2015
22. P3.07-09 Characterization of the Nutritional Status in Lung Cancer Patients: A Retrospective Study
- Author
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Queiroga, H., Rola, M., Barreira, A., Ataíde, R., Dias, C., and Silva, D.
- Published
- 2018
- Full Text
- View/download PDF
23. Adherence Enhancement of Metallic Film on PZT-Type Ceramic Using Nitrogen Plasma Implantation
- Author
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Silva, Ataide R., primary, Rossi, Jose Osvaldo, additional, Neto, Lauro P. Silva, additional, and Ueda, Mario, additional
- Published
- 2014
- Full Text
- View/download PDF
24. Characterization of Ceramic Dielectrics for Sub-GHz Applications in Nonlinear Transmission Lines
- Author
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Neto, Lauro P. Silva, primary, Rossi, Jose Osvaldo, additional, Barroso, Joaquim J., additional, and Silva, Ataide R., additional
- Published
- 2014
- Full Text
- View/download PDF
25. PIII in batch processing mode using HV Blumlein pulser with pulse extended to the microsecond range
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Silva, Ataide R., primary, Rossi, Jose O., additional, and Ueda, Mario, additional
- Published
- 2014
- Full Text
- View/download PDF
26. Placental Histopathological Changes Associated with Plasmodium vivax Infection during Pregnancy
- Author
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Portillo, HAD, Souza, RM, Ataide, R, Dombrowski, JG, Ippolito, V, Aitken, EH, Valle, SN, Alvarez, JM, Epiphanio, S, Marinho, CRF, Portillo, HAD, Souza, RM, Ataide, R, Dombrowski, JG, Ippolito, V, Aitken, EH, Valle, SN, Alvarez, JM, Epiphanio, S, and Marinho, CRF
- Abstract
Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41), P. vivax exposure (n = 59) or P. falciparum exposure (n = 19). We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045), placental barrier thickness (OR, 25.59, P = 0.021) and mononuclear cells (OR, 4.02, P = 0.046) were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A vivax-score was developed using these thr
- Published
- 2013
27. A tradeoff analysis of Just-In-Time and non Just-In-Time inventory with transportation ramifications
- Author
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Feitler, Jane N., Suchan, James E., NA, Management, Braga, Ataide R., Feitler, Jane N., Suchan, James E., NA, Management, and Braga, Ataide R.
- Abstract
The purpose of this research is to investigate when a Just-In-Time (JIT) inventory management technique is a worthwhile approach to managing inventories. Some experts in the field maintain that the additional transportation costs derived from using JIT and its costs due to frequent shipping is more than offset by the reduction in inventory levels. In this study a simulation is developed using the cost structure of Naval Air Station Lemoore for managing a selected group of items. Lemoore is considered the Inventory Control Point and the Stock Point for those items. Research results indicate that despite all the advantages of using JIT, JIT is not always the lowest cost approach. Recommendations are that inventory managers delineate the associated costs using each technique and perform a thorough analysis that compares the two alternatives, and that JIT is not a general solution leading to the lowest cost for management of all inventory items., http://archive.org/details/atradeoffnalysis1094532710, NA, Brazilian Navy author., Approved for public release; distribution is unlimited.
- Published
- 2013
28. PIII in batch processing mode using HV Blumlein pulser with pulse extended to the microsecond range.
- Author
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Silva, Ataide R., Rossi, Jose O., and Ueda, Mario
- Published
- 2015
- Full Text
- View/download PDF
29. Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity
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Chan, J-A, Howell, KB, Reiling, L, Ataide, R, Mackintosh, CL, Fowkes, FJI, Petter, M, Chesson, JM, Langer, C, Warimwe, GM, Duffy, MF, Rogerson, SJ, Bull, PC, Cowman, AF, Marsh, K, Beeson, JG, Chan, J-A, Howell, KB, Reiling, L, Ataide, R, Mackintosh, CL, Fowkes, FJI, Petter, M, Chesson, JM, Langer, C, Warimwe, GM, Duffy, MF, Rogerson, SJ, Bull, PC, Cowman, AF, Marsh, K, and Beeson, JG
- Abstract
Plasmodium falciparum is the major cause of malaria globally and is transmitted by mosquitoes. During parasitic development, P. falciparum-infected erythrocytes (P. falciparum-IEs) express multiple polymorphic proteins known as variant surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein 1 (PfEMP1). VSA-specific antibodies are associated with protection from symptomatic and severe malaria. However, the importance of the different VSA targets of immunity to malaria remains unclear, which has impeded an understanding of malaria immunity and vaccine development. In this study, we developed assays using transgenic P. falciparum with modified PfEMP1 expression to quantify serum antibodies to VSAs among individuals exposed to malaria. We found that the majority of the human antibody response to the IE targets PfEMP1. Furthermore, our longitudinal studies showed that individuals with PfEMP1-specific antibodies had a significantly reduced risk of developing symptomatic malaria, whereas antibodies to other surface antigens were not associated with protective immunity. Using assays that measure antibody-mediated phagocytosis of IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the major target of these functional antibodies. Taken together, these data demonstrate that PfEMP1 is a key target of humoral immunity. These findings advance our understanding of the targets and mediators of human immunity to malaria and have major implications for malaria vaccine development.
- Published
- 2012
30. Antibodies That Induce Phagocytosis of Malaria Infected Erythrocytes: Effect of HIV Infection and Correlation with Clinical Outcomes
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Braga, EM, Ataide, R, Mwapasa, V, Molyneux, ME, Meshnick, SR, Rogerson, SJ, Braga, EM, Ataide, R, Mwapasa, V, Molyneux, ME, Meshnick, SR, and Rogerson, SJ
- Abstract
HIV infection increases the burden of disease of malaria in pregnancy, in part by impairing the development of immunity. We measured total IgG and phagocytic antibodies against variant surface antigens of placental-type CS2 parasites in 187 secundigravidae (65% HIV infected). In women with placental malaria infection, phagocytic antibodies to CS2(VSA) were decreased in the presence of HIV (p = 0.011) and correlated positively with infant birth weight (coef = 3.57, p = 0.025), whereas total IgG to CS2(VSA) did not. Phagocytic antibodies to CS2(VSA) are valuable tools to study acquired immunity to malaria in the context of HIV co-infection. Secundigravidae may be an informative group for identification of correlates of immunity.
- Published
- 2011
31. Using an Improved Phagocytosis Assay to Evaluate the Effect of HIV on Specific Antibodies to Pregnancy-Associated Malaria
- Author
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Snounou, G, Ataide, R, Hasang, W, Wilson, DW, Beeson, JG, Mwapasa, V, Molyneux, ME, Meshnick, SR, Rogerson, SJ, Snounou, G, Ataide, R, Hasang, W, Wilson, DW, Beeson, JG, Mwapasa, V, Molyneux, ME, Meshnick, SR, and Rogerson, SJ
- Abstract
BACKGROUND: Pregnant women residing in malaria endemic areas are highly susceptible to Plasmodium falciparum malaria, particularly during their first pregnancy, resulting in low birth weight babies and maternal anaemia. This susceptibility is associated with placental sequestration of parasitised red blood cells expressing pregnancy-specific variant surface antigens. Acquisition of antibodies against these variant surface antigens may protect women and their offspring. Functions of such antibodies may include prevention of placental sequestration or opsonisation of parasitised cells for phagocytic clearance. METHODOLOGY/FINDINGS: Here we report the development and optimisation of a new high-throughput flow cytometry-based phagocytosis assay using undifferentiated Thp-1 cells to quantitate the amount of opsonizing antibody in patient sera, and apply this assay to measure the impact of HIV on the levels of antibodies to a pregnancy malaria-associated parasite line in a cohort of Malawian primigravid women. The assay showed high reproducibility, with inter-experimental correlation of r(2) = 0.99. In primigravid women, concurrent malaria infection was associated with significantly increased antibodies, whereas HIV decreased the ability to acquire opsonising antibodies (Mann-Whitney ranksum: p = 0.013). This decrease was correlated with HIV-induced immunosuppression, with women with less than 350 x 10(6) CD4+ T- cells/L having less opsonising antibodies (coef: -11.95,P = 0.002). Levels of antibodies were not associated with protection from low birth weight or anaemia. CONCLUSIONS/SIGNIFICANCE: This flow cytometry-based phagocytosis assay proved to be efficient and accurate for the measurement of Fc-receptor mediated phagocytosis-inducing antibodies in large cohorts. HIV was found to affect mainly the acquisition of antibodies to pregnancy-specific malaria in primigravidae. Further studies of the relationship between opsonising antibodies to malaria in pregnancy and HIV a
- Published
- 2010
32. VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
- Author
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Stevenson, MM, Epiphanio, S, Campos, MG, Pamplona, A, Carapau, D, Pena, AC, Ataide, R, Monteiro, CAA, Felix, N, Costa-Silva, A, Marinho, CRF, Dias, S, Mota, MM, Stevenson, MM, Epiphanio, S, Campos, MG, Pamplona, A, Carapau, D, Pena, AC, Ataide, R, Monteiro, CAA, Felix, N, Costa-Silva, A, Marinho, CRF, Dias, S, and Mota, MM
- Abstract
The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.
- Published
- 2010
33. A tradeoff analysis of Just-In-Time and non Just-In-Time inventory with transportation ramifications
- Author
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Braga, Ataide R., Feitler, Jane N., Suchan, James E., and Management
- Subjects
ComputerApplications_COMPUTERSINOTHERSYSTEMS ,NA - Abstract
The purpose of this research is to investigate when a Just-In-Time (JIT) inventory management technique is a worthwhile approach to managing inventories. Some experts in the field maintain that the additional transportation costs derived from using JIT and its costs due to frequent shipping is more than offset by the reduction in inventory levels. In this study a simulation is developed using the cost structure of Naval Air Station Lemoore for managing a selected group of items. Lemoore is considered the Inventory Control Point and the Stock Point for those items. Research results indicate that despite all the advantages of using JIT, JIT is not always the lowest cost approach. Recommendations are that inventory managers delineate the associated costs using each technique and perform a thorough analysis that compares the two alternatives, and that JIT is not a general solution leading to the lowest cost for management of all inventory items. http://archive.org/details/atradeoffnalysis1094532710 NA Brazilian Navy author. Approved for public release; distribution is unlimited.
- Published
- 1998
34. Genetically attenuated P36p-deficient Plasmodium berghei sporozoites confer long-lasting and partial cross-species protection.
- Author
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Douradinha, B.G., Dijk, M.R. van, Ataide, R., Gemert, G.J.A. van, Thompson, J., Franetich, J.F., Mazier, D., Luty, A.J.F., Sauerwein, R.W., Janse, C.J., Waters, A.P., Mota, M.M., Douradinha, B.G., Dijk, M.R. van, Ataide, R., Gemert, G.J.A. van, Thompson, J., Franetich, J.F., Mazier, D., Luty, A.J.F., Sauerwein, R.W., Janse, C.J., Waters, A.P., and Mota, M.M.
- Abstract
Contains fulltext : 51720.pdf (publisher's version ) (Closed access), Immunisation with live, radiation-attenuated sporozoites (RAS) or genetically attenuated sporozoites (GAS) of rodent plasmodial parasites protects against subsequent challenge infections. We recently showed that immunisation with Plasmodium berghei GAS that lack the microneme protein P36p protects mice for a period of up to 4 months. Here, we show that the period of full protection induced by p36p(-)-sporozoites lasts 12 and 18 months in C57Bl6 and BALB/c mice, respectively. Full protection is also achieved with three doses of only 1000 p36p(-) (but not RAS) sporozoites. Subcutaneous, intradermal or intramuscular routes of administration also lead to partial protection. In addition, immunisation with either P. berghei RAS- or, to a lesser extent, p36p(-)-sporozoites inhibits parasite intrahepatic development in mice challenged with Plasmodium yoelii sporozoites. Since naturally acquired malaria infections or subunit-based vaccines only induce short-term immune responses, the protection conferred by immunisation with p36p(-)-sporozoites described here further emphasises the potential of GAS as a vaccination strategy for malaria.
- Published
- 2007
35. A Tradeoff Analysis of Just-In-Time and Non Just-In-Time Inventory with Transportation Ramifications.
- Author
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NAVAL POSTGRADUATE SCHOOL MONTEREY CA, Braga, Ataide R., NAVAL POSTGRADUATE SCHOOL MONTEREY CA, and Braga, Ataide R.
- Abstract
The purpose of this research is to investigate when a Just-In-Time (JIT) inventory management technique is a worthwhile approach to managing inventories. Some experts in the field maintain that the additional transportation costs derived from using JIT and its costs due to frequent shipping is more than offset by the reduction in inventory levels. In this study a simulation is developed using the cost structure of Naval Air Station Lemoore for managing a selected group of items. Lemoore is considered the Inventory Control Point and the Stock Point for those items. Research results indicate that despite all the advantages of using JIT, JIT is not always the lowest cost approach. Recommendations are that inventory managers delineate the associated costs using each technique and perform a thorough analysis that compares the two alternatives, and that JIT is not a general solution leading to the lowest cost for management of all inventory items.
- Published
- 1998
36. A tradeoff analysis of Just-In-Time and non Just-In-Time inventory with transportation ramifications
- Author
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Feitler, Jane N., Suchan, James E., NA, Management, Braga, Ataide R., Feitler, Jane N., Suchan, James E., NA, Management, and Braga, Ataide R.
- Abstract
The purpose of this research is to investigate when a Just-In-Time (JIT) inventory management technique is a worthwhile approach to managing inventories. Some experts in the field maintain that the additional transportation costs derived from using JIT and its costs due to frequent shipping is more than offset by the reduction in inventory levels. In this study a simulation is developed using the cost structure of Naval Air Station Lemoore for managing a selected group of items. Lemoore is considered the Inventory Control Point and the Stock Point for those items. Research results indicate that despite all the advantages of using JIT, JIT is not always the lowest cost approach. Recommendations are that inventory managers delineate the associated costs using each technique and perform a thorough analysis that compares the two alternatives, and that JIT is not a general solution leading to the lowest cost for management of all inventory items.
- Published
- 1998
37. Community use of oral antibiotics transiently reprofiles the intestinal microbiome in young Bangladeshi children.
- Author
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Baldi A, Braat S, Imrul Hasan M, Bennett C, Barrios M, Jones N, Moir-Meyer G, Abdul Azeez I, Wilcox S, Saiful Alam Bhuiyan M, Ataide R, Clucas D, Harrison LC, Arifeen SE, Bowden R, Biggs BA, Jex A, and Pasricha SR
- Subjects
- Humans, Bangladesh epidemiology, Infant, Male, Female, Administration, Oral, Drug Resistance, Bacterial genetics, Feces microbiology, Metagenomics methods, Bacteria genetics, Bacteria drug effects, Bacteria classification, Bacteria isolation & purification, Cephalosporins administration & dosage, Cephalosporins pharmacology, Cephalosporins therapeutic use, Enterococcus drug effects, Enterococcus genetics, Enterococcus isolation & purification, Antimicrobial Stewardship, Gastrointestinal Microbiome drug effects, Gastrointestinal Microbiome genetics, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents pharmacology, RNA, Ribosomal, 16S genetics
- Abstract
Antibiotics may alter the gut microbiome, and this is one of the mechanisms by which antimicrobial resistance may be promoted. Suboptimal antimicrobial stewardship in Asia has been linked to antimicrobial resistance. We aim to examine the relationship between oral antibiotic use and composition and antimicrobial resistance in the gut microbiome in 1093 Bangladeshi infants. We leverage a trial of 8-month-old infants in rural Bangladesh: 61% of children were cumulatively exposed to antibiotics (most commonly cephalosporins and macrolides) over the 12-month study period, including 47% in the first 3 months of the study, usually for fever or respiratory infection. 16S rRNA amplicon sequencing in 11-month-old infants reveals that alpha diversity of the intestinal microbiome is reduced in children who received antibiotics within the previous 7 days; these samples also exhibit enrichment for Enterococcus and Escherichia/Shigella genera. No effect is seen in children who received antibiotics earlier. Using shotgun metagenomics, overall abundance of antimicrobial resistance genes declines over time. Enrichment for an Enterococcus-related antimicrobial resistance gene is observed in children receiving antibiotics within the previous 7 days, but not earlier. Presence of antimicrobial resistance genes is correlated to microbiome composition. In Bangladeshi children, community use of antibiotics transiently reprofiles the gut microbiome., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
38. The REVAMP trial: key questions remain - Authors' reply.
- Author
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Pasricha SR, Moya E, Ataide R, Mzembe G, Harding R, and Phiri K
- Published
- 2024
- Full Text
- View/download PDF
39. Iron deficiency, pregnancy, and neonatal development.
- Author
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Ataide R, Fielding K, Pasricha SR, and Bennett C
- Subjects
- Infant, Newborn, Infant, Female, Pregnancy, Humans, Placenta, Iron physiology, Anemia, Iron-Deficiency epidemiology, Iron Deficiencies, Anemia
- Abstract
Anemia affects 36% of pregnant women worldwide. Of those affected, around 40% is due to iron deficiency (ID). Iron is an essential micronutrient involved in vital processes such as erythropoiesis, immune responses, and importantly-during pregnancy-placental and fetal development. Although menstrual bleeding can impact the incidence of ID even before the onset of pregnancy, this narrative review is pregnancy focused and will explore the impact of ID on placental development and iron uptake, fetal development and immunity, and maternal and infant susceptibility to infection. Although there have been advances in this area of research, much is needed to understand the regulation of iron and the effects of ID during pregnancy. Notably, more human studies are essential to generate the best evidence to advance strategies to reduce the incidence of ID during pregnancy to improve maternal, neonatal, and infant health., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)
- Published
- 2023
- Full Text
- View/download PDF
40. Iron homeostasis governs erythroid phenotype in polycythemia vera.
- Author
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Bennett C, Jackson VE, Pettikiriarachchi A, Hayman T, Schaeper U, Moir-Meyer G, Fielding K, Ataide R, Clucas D, Baldi A, Garnham AL, Li-Wai-Suen CSN, Loughran SJ, Baxter EJ, Green AR, Alexander WS, Bahlo M, Burbury K, Ng AP, and Pasricha SR
- Subjects
- Animals, Mice, Hepcidins genetics, Genome-Wide Association Study, Iron metabolism, Phenotype, Homeostasis, Polycythemia Vera genetics, Polycythemia Vera complications
- Abstract
Polycythemia vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients' hematocrit and hemoglobin concentrations, placing them at risk of life-threatening thrombotic events. Our genome-wide association study of 440 PV cases and 403 351 controls using UK Biobank data showed that single nucleotide polymorphisms in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed overrepresentation of homozygous HFE variants in patients with PV. HFE influences the expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of mouse models of PV, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Furthermore, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signaling via GP130-coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
41. Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.
- Author
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Pasricha SR, Mwangi MN, Moya E, Ataide R, Mzembe G, Harding R, Zinenani T, Larson LM, Demir AY, Nkhono W, Chinkhumba J, Simpson JA, Clucas D, Stones W, Braat S, and Phiri KS
- Subjects
- Infant, Newborn, Female, Humans, Pregnancy, Iron therapeutic use, Pregnant Women, Pregnancy Trimester, Second, Birth Weight, Malawi epidemiology, Anemia, Iron-Deficiency drug therapy, Malaria drug therapy, Malaria prevention & control, Anemia drug therapy
- Abstract
Background: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women., Methods: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up., Findings: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34)., Interpretation: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight., Funding: Bill & Melinda Gates Foundation (INV-010612)., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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42. Contrasting Epidemiology and Population Genetics of COVID-19 Infections Defined by Multilocus Genotypes in SARS-CoV-2 Genomes Sampled Globally.
- Author
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Chan FHM, Ataide R, Richards JS, and Narh CA
- Subjects
- COVID-19 Vaccines, Genetics, Population, Genome, Viral, Genotype, Humans, Mutation, Phylogeny, Spike Glycoprotein, Coronavirus genetics, COVID-19 epidemiology, SARS-CoV-2 genetics
- Abstract
Since its emergence in 2019, SARS-CoV-2 has spread and evolved globally, with newly emerged variants of concern (VOCs) accounting for more than 500 million COVID-19 cases and 6 million deaths. Continuous surveillance utilizing simple genetic tools is needed to measure the viral epidemiological diversity, risk of infection, and distribution among different demographics in different geographical regions. To help address this need, we developed a proof-of-concept multilocus genotyping tool and demonstrated its utility to monitor viral populations sampled in 2020 and 2021 across six continents. We sampled globally 22,164 SARS-CoV-2 genomes from GISAID (inclusion criteria: available clinical and demographic data). They comprised two study populations, “2020 genomes” (N = 5959) sampled from December 2019 to September 2020 and “2021 genomes” (N = 16,205) sampled from 15 January to 15 March 2021. All genomes were aligned to the SARS-CoV-2 reference genome and amino acid polymorphisms were called with quality filtering. Thereafter, 74 codons (loci) in 14 genes including orf1ab polygene (N = 9), orf3a, orf8, nucleocapsid (N), matrix (M), and spike (S) met the 0.01 minimum allele frequency criteria and were selected to construct multilocus genotypes (MLGs) for the genomes. At these loci, 137 mutant/variant amino acids (alleles) were detected with eight VOC-defining variant alleles, including N KR203&204, orf1ab (I265, F3606, and L4715), orf3a H57, orf8 S84, and S G614, being predominant globally with > 35% prevalence. Their persistence and selection were associated with peaks in the viral transmission and COVID-19 incidence between 2020 and 2021. Epidemiologically, older patients (≥20 years) compared to younger patients (<20 years) had a higher risk of being infected with these variants, but this association was dependent on the continent of origin. In the global population, the discriminant analysis of principal components (DAPC) showed contrasting patterns of genetic clustering with three (Africa, Asia, and North America) and two (North and South America) continental clusters being observed for the 2020 and 2021 global populations, respectively. Within each continent, the MLG repertoires (range 40−199) sampled in 2020 and 2021 were genetically differentiated, with ≤4 MLGs per repertoire accounting for the majority of genomes sampled. These data suggested that the majority of SARS-CoV-2 infections in 2020 and 2021 were caused by genetically distinct variants that likely adapted to local populations. Indeed, four GISAID clade-defined VOCs - GRY (Alpha), GH (Beta), GR (Gamma), and G/GK (Delta variant) were differentiated by their MLG signatures, demonstrating the versatility of the MLG tool for variant identification. Results from this proof-of-concept multilocus genotyping demonstrates its utility for SARS-CoV-2 genomic surveillance and for monitoring its spatiotemporal epidemiology and evolution, particularly in response to control interventions including COVID-19 vaccines and chemotherapies.
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- 2022
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43. An implementation research programme to support an intravenous iron intervention for pregnant women with moderate and severe anaemia in Malawi: study protocol.
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Prang KH, Mamani-Mategula E, Verbunt E, Chipeta E, Ataide R, Mwangi M, Phiri K, Pasricha SR, Kelaher M, and Manda-Taylor L
- Abstract
Background: Antenatal iron supplementation is critical to maternal and child health; however, access and adherence to oral iron are inconsistent in many low- and middle-income countries (LMICs). Modern intravenous (IV) iron products have become available in high-income clinical settings and provide an opportunity to deliver high doses of iron in a single-short infusion during pregnancy. However, there is limited knowledge of the drivers and barriers for such an intervention to be effectively delivered and upscaled in LMICs. In this study protocol, we describe the implementation research programme to support an IV iron intervention in Malawi for pregnant women with moderate and severe anaemia., Methods: The implementation research programme has three phases, each guided by implementation science conceptual frameworks. In Phase 1, we will conduct formative research (context assessment of the health system with key informant interviews) to determine how IV iron can be effectively introduced into routine antenatal care. We will use the findings to co-develop potential strategies with end-users and healthcare providers to improve intervention implementation. In Phase 2, we will disseminate the implementation strategies to support the uptake and delivery of the intervention in the study settings. In Phase 3, the intervention will be implemented, and we will conduct formative evaluation (interviews with end-users, healthcare providers, and analysis of health services data) to investigate the feasibility and acceptability of the intervention and strategies. We will also identify processes and contextual factors that facilitate or impede the delivery and uptake of IV iron., Discussion: In LMICs, modern IV iron products present a novel opportunity to rapidly cure moderate and severe anaemia in pregnancy, thereby improving maternal and child health outcomes. This implementation research programme will provide guidance and recommendations on how best an IV iron intervention for pregnant women with anaemia can be implemented in an LMIC setting like Malawi. We will develop locally relevant and culturally appropriate implementation strategies by engaging with key stakeholders (pregnant women, healthcare providers, and policymakers) and identifying factors likely to facilitate successful implementation. The findings of this research can guide the implementation of an IV iron intervention in Malawi and other LMICs., (© 2022. The Author(s).)
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- 2022
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44. A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan.
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Harding R, Ataide R, Mwangi MN, Simpson JA, Mzembe G, Moya E, Truwah Z, Nkhwazi BC, Mwabinga M, Nkhono W, Phiri KS, Pasricha SR, and Braat S
- Abstract
Background: Anaemia affects more than half of Africa's pregnancies. Standard care, with oral iron tablets, often fails to achieve results, with compliance and gastrointestinal side-effects being a significant issue. In recent years, intravenous iron formulations have become safe, effective, and quick to administer, allowing the complete iron requirements of pregnancy to be provided in one 15-minute infusion. The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) will evaluate whether a modern intravenous iron formulation, ferric carboxymaltose (FCM), given once during the second trimester is effective and safe in improving maternal and neonatal outcomes for treatment of moderate to severe anaemia in sub-Saharan Africa. The objective was to publish the detailed statistical analysis plan for the REVAMP trial prior to unblinding the allocated treatments and performing the analysis. Methods: REVAMP is a multicentre, two-arm, open-label, parallel-group randomized control trial (RCT) in 862 pregnant women in their second trimester. The trial statistician developed the statistical analysis plan in consultation with the trial management team based on the protocol, data collection forms, and study outcomes available in the blinded study database. Results: The detailed statistical analysis plan will support the statistical analyses and reporting of the REVAMP trial after unblinding the treatment allocations. Conclusions: A statistical analysis plan allows for transparency as well as reproducibility of reporting and statistical analyses., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Harding R et al.)
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- 2022
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45. A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan.
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Harding R, Ataide R, Mwangi MN, Simpson JA, Mzembe G, Moya E, Truwah Z, Nkhwazi BC, Mwabinga M, Nkhono W, Phiri KS, Pasricha SR, and Braat S
- Abstract
Background: Anaemia affects more than half of Africa's pregnancies. Standard care, with oral iron tablets, often fails to achieve results, with compliance and gastrointestinal side-effects being a significant issue. In recent years, intravenous iron formulations have become safe, effective, and quick to administer, allowing the complete iron requirements of pregnancy to be provided in one 15-minute infusion. The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) will evaluate whether a modern intravenous iron formulation, ferric carboxymaltose (FCM), given once during the second trimester is effective and safe in improving maternal and neonatal outcomes for treatment of moderate to severe anaemia in sub-Saharan Africa. The objective was to publish the detailed statistical analysis plan for the REVAMP trial prior to unblinding the allocated treatments and performing the analysis. Methods: REVAMP is a multicentre, two-arm, open-label, parallel-group randomized control trial (RCT) in 862 pregnant women in their second trimester. The trial statistician developed the statistical analysis plan in consultation with the trial management team based on the protocol, data collection forms, and study outcomes available in the blinded study database. Results: The detailed statistical analysis plan will support the statistical analyses and reporting of the REVAMP trial after unblinding the treatment allocations. Conclusions: A statistical analysis plan allows for transparency as well as reproducibility of reporting and statistical analyses., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Harding R et al.)
- Published
- 2021
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46. Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children.
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Hayman T, Hickey P, Amann-Zalcenstein D, Bennett C, Ataide R, Sthity RA, Khandaker AM, Islam KM, Stracke K, Yassi N, Watson R, Long J, Westcott J, Krebs NF, King JC, Black RE, Islam MM, McDonald CM, and Pasricha SR
- Subjects
- Bangladesh, Female, Humans, Infant, Male, Powders, Tablets, Zinc deficiency, Cytokines blood, Dietary Supplements, Gene Expression drug effects, Micronutrients administration & dosage, Zinc administration & dosage
- Abstract
Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9-11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.
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- 2021
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47. Guiding the Immune Response to a Conserved Epitope in MSP2, an Intrinsically Disordered Malaria Vaccine Candidate.
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Seow J, Das SC, Morales RAV, Ataide R, Krishnarjuna B, Silk M, Chalmers DK, Richards J, Anders RF, MacRaild CA, and Norton RS
- Abstract
The malaria vaccine candidate merozoite surface protein 2 (MSP2) has shown promise in clinical trials and is in part responsible for a reduction in parasite densities. However, strain-specific reductions in parasitaemia suggested that polymorphic regions of MSP2 are immuno-dominant. One strategy to bypass the hurdle of strain-specificity is to bias the immune response towards the conserved regions. Two mouse monoclonal antibodies, 4D11 and 9H4, recognise the conserved C-terminal region of MSP2. Although they bind overlapping epitopes, 4D11 reacts more strongly with native MSP2, suggesting that its epitope is more accessible on the parasite surface. In this study, a structure-based vaccine design approach was applied to the intrinsically disordered antigen, MSP2, using a crystal structure of 4D11 Fv in complex with its minimal binding epitope. Molecular dynamics simulations and surface plasmon resonance informed the design of a series of constrained peptides that mimicked the 4D11-bound epitope structure. These peptides were conjugated to keyhole limpet hemocyanin and used to immunise mice, with high to moderate antibody titres being generated in all groups. The specificities of antibody responses revealed that a single point mutation can focus the antibody response towards a more favourable epitope. This structure-based approach to peptide vaccine design may be useful not only for MSP2-based malaria vaccines, but also for other intrinsically disordered antigens.
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- 2021
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48. Review of Burden, Clinical Definitions, and Management of COVID-19 Cases.
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McArthur L, Sakthivel D, Ataide R, Chan F, Richards JS, and Narh CA
- Subjects
- Asymptomatic Infections, Betacoronavirus, COVID-19, Comorbidity, Cough virology, Fever virology, Humans, Pandemics, SARS-CoV-2, Coronavirus Infections diagnosis, Coronavirus Infections mortality, Coronavirus Infections therapy, Cost of Illness, Pneumonia, Viral diagnosis, Pneumonia, Viral mortality, Pneumonia, Viral therapy
- Abstract
Our understanding of SARS-CoV-2, the virus responsible for coronavirus disease 2019 (COVID-19), its clinical manifestations, and treatment options continues to evolve at an unparalleled pace. This review sought to summarize the key literature regarding transmission, case definitions, clinical management, and the burden of COVID-19. Our review of the literature showed that SARS-CoV-2 was mainly transmitted via inhalation of respiratory droplets containing the virus and had a mean incubation period of 4-6 days. The commonly reported symptoms were fever (75.3% ± 18.7%) and cough (62.6% ± 17.7%) across the spectrum of clinical disease-mild, moderate, severe, and critical, but with the disease phenotype varying with severity. Categorization of these cases for home care or hospital management needs to be defined, with risk stratification accounting for the age of the patient and the presence of underlying comorbidities. The case definitions varied among countries, which could have contributed to the differences in the case fatality rates among affected countries. The severity and risk of death due to COVID-19 was associated with age and underlying comorbidities. Asymptomatic cases, which constitute 40-80% of COVID-19 cases are a considerable threat to control efforts. The presence of fever and cough may be sufficient to warrant COVID-19 testing, but using these symptoms in isolation will miss a proportion of cases. A clear definition of a COVID-19 case is essential for the management, treatment, and tracking of clinical illness, and to inform the quarantine measures and social distancing that can help control the spread of SARS-CoV-2.
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- 2020
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49. Effectiveness of repellent delivered through village health volunteers on malaria incidence in villages in South-East Myanmar: a stepped-wedge cluster-randomised controlled trial protocol.
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Win Han Oo, Cutts JC, Agius PA, Kyaw Zayar Aung, Poe Poe Aung, Aung Thi, Nyi Nyi Zaw, Htin Kyaw Thu, Wai Yan Min Htay, Ataide R, O'Flaherty K, Ai Pao Yawn, Aung Paing Soe, Beeson JG, Crabb B, Pasricha N, and Fowkes FJI
- Subjects
- Community Health Workers, Humans, Incidence, Myanmar epidemiology, Insect Repellents administration & dosage, Insect Repellents therapeutic use, Malaria epidemiology, Malaria prevention & control
- Abstract
Background: To combat emerging drug resistance in the Greater Mekong Sub-region (GMS) the World Health Organization and GMS countries have committed to eliminating malaria in the region by 2030. The overall approach includes providing universal access to diagnosis and treatment of malaria, and sustainable preventive measures, including vector control. Topical repellents are an intervention that can be used to target residual malaria transmission not covered by long lasting insecticide nets and indoor residual spraying. Although there is strong evidence that topical repellents protect against mosquito bites, evidence is not well established for the effectiveness of repellents distributed as part of malaria control activities in protecting against episodes of malaria. A common approach to deliver malaria services is to assign Village Health Volunteers (VHVs) to villages, particularly where limited or no services exist. The proposed trial aims to provide evidence for the effectiveness of repellent distributed through VHVs in reducing malaria., Methods: The study is an open stepped-wedge cluster-randomised controlled trial randomised at the village level. Using this approach, repellent (N,N-diethyl-benzamide - 12% w/w, cream) is distributed by VHVs in villages sequentially throughout the malaria transmission season. Villages will be grouped into blocks, with blocks transitioned monthly from control (no repellent) to intervention states (to receive repellent) across 14 monthly intervals in random order). This follows a 4-week baseline period where all villages do not receive repellent. The primary endpoint is defined as the number of individuals positive for Plasmodium falciparum and Plasmodium vivax infections diagnosed by a rapid diagnostic test. Secondary endpoints include symptomatic malaria, Polymerase Chain Reaction (PCR)-detectable Plasmodium spp. infections, molecular markers of drug resistance and antibodies specific for Plasmodium spp. parasites., Discussion: This study has been approved by relevant institutional ethics committees in Myanmar and Australia. Results will be disseminated through workshops, conferences and peer-reviewed publications. Findings will contribute to a better understanding of the optimal distribution mechanisms of repellent, context specific effectiveness and inform policy makers and implementers of malaria elimination programs in the GMS., Trial Registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12616001434482 ). Retrospectively registered 14th October 2016.
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- 2018
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50. Implications of population-level immunity for the emergence of artemisinin-resistant malaria: a mathematical model.
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Scott N, Ataide R, Wilson DP, Hellard M, Price RN, Simpson JA, and Fowkes FJI
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- Africa epidemiology, Humans, Malaria, Falciparum immunology, Malaria, Falciparum parasitology, Models, Biological, Antimalarials therapeutic use, Artemisinins therapeutic use, Drug Resistance, Malaria, Falciparum epidemiology, Plasmodium falciparum drug effects
- Abstract
Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong Subregion, an area of relatively low transmission, but has yet to be reported in Africa. A population-based mathematical model was used to investigate the relationship between P. falciparum prevalence, exposure-acquired immunity and time-to-emergence of artemisinin resistance. The possible implication for the emergence of resistance across Africa was assessed., Methods: The model included human and mosquito populations, two strains of malaria ("wild-type", "mutant"), three levels of human exposure-acquired immunity (none, low, high) with two types of immunity for each level (sporozoite/liver stage immunity and blood-stage/gametocyte immunity) and drug pressure based on per-capita treatment numbers., Results: The model predicted that artemisinin-resistant strains may circulate up to 10 years longer in high compared to low P. falciparum prevalence areas before resistance is confirmed. Decreased time-to-resistance in low prevalence areas was explained by low genetic diversity and immunity, which resulted in increased probability of selection and spread of artemisinin-resistant strains. Artemisinin resistance was estimated to be established by 2020 in areas of Africa with low (< 10%) P. falciparum prevalence, but not for 5 or 10 years later in moderate (10-25%) or high (> 25%) prevalence areas, respectively., Conclusions: Areas of low transmission and low immunity give rise to a more rapid expansion of artemisinin-resistant parasites, corroborating historical observations of anti-malarial resistance emergence. Populations where control strategies are in place that reduce malaria transmission, and hence immunity, may be prone to a rapid emergence and spread of artemisinin-resistant strains and thus should be carefully monitored.
- Published
- 2018
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