2011 SMRU Publication List [total: 31 publication(s)]
List of SMRU papers published in international journals
| Author :A. Annerberg, K. M. Lwin, N. Lindegardh, S. Khrutsawadchai, E. Ashley, N. P. Day, P. Singhasivanon, J. Tarning, N. J. White and F. Nosten |
| Title :A small amount of fat does not affect piperaquine exposure in patients with malaria |
| Journal :Antimicrob Agents Chemother |
| Year :2011 |
| Epub Date :2011-06-29 |
| Page :3971-6 |
| ISSN :1098-6596 (Electronic) 0066-4804 (Linking) |
| Abstract :Dihydroartemisinin-piperaquine is a new, highly effective, and well-tolerated combination treatment for uncomplicated falciparum malaria. The lipophilic characteristic of piperaquine suggests that administration together with fat will increase the oral bioavailability of the drug, and this has been reported for healthy volunteers. This pharmacokinetic study monitored 30 adult patients with uncomplicated falciparum malaria for 4.5 months to evaluate the effects of the concomitant intake of fat on the total piperaquine exposure. The fixed-drug combination of dihydroartemisinin-piperaquine was given with water to fasting patients (n = 15) or was coadministered with 200 ml milk containing 6.4 g fat (n = 15). The drug combination was generally well tolerated, and there were no severe adverse effects reported for either group during the study. Total piperaquine exposure (area under the concentration-time curve from zero to infinity [AUC(0-infinity)]; results are given as medians [ranges]) were not statistically different between fed (29.5 h . mug/ml [20.6 to 58.7 h . mug/ml]) and fasting (23.9 h . mug/ml [11.9 to 72.9 h . mug/ml]) patients, but the interindividual variation was reduced in the fed group. Overall, none of the pharmacokinetic parameters differed statistically between the groups. Total piperaquine exposure correlated well with the day 7 concentrations in the fasted group, but the fed group showed a poor correlation. In conclusion, the coadministration of 6.4 g fat did not have any significant effect on piperaquine pharmacokinetics in the treatment of uncomplicated malaria. |
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| Author Address :Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand. |
| Author :C. Biot, F. Nosten, L. Fraisse, D. Ter-Minassian, J. Khalife and D. Dive |
| Title :The antimalarial ferroquine: from bench to clinic |
| Journal :Parasite |
| Year :2011 |
| Epub Date :2011-09-07 |
| Page :207-14 |
| ISSN :1252-607X (Print) 1252-607X (Linking) |
| Abstract :Ferroquine (FQ, SSR97193) is currently the most advanced organo-metallic drug candidate and about to complete phase II clinical trials as a treatment for uncomplicated malaria. This ferrocene-containing compound is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. This article focuses on the discovery of FQ, its antimalarial activity, the hypothesis of its mode of action, the current absence of resistance in vitro and recent clinical trials. |
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| Author Address :Unite de Catalyse et Chimie du Solide, CNRS UMR 8181, Universite Lille Nord de France. christophe.biot@univ-lille1.fr |
| Author :L. E. Bouillet, M. O. Dias, N. A. Dorigo, A. D. Moura, B. Russell, F. Nosten, L. Renia, E. M. Braga, R. T. Gazzinelli, M. M. Rodrigues, I. S. Soares and O. Bruna-Romero |
| Title :Long-term humoral and cellular immune responses elicited by a heterologous Plasmodium vivax apical membrane antigen 1 protein prime/adenovirus boost immunization protocol |
| Journal :Infect Immun |
| Year :2011 |
| Epub Date :2011-07-07 |
| Page :3642-52 |
| ISSN :1098-5522 (Electronic) 0019-9567 (Linking) |
| Abstract :Apical membrane antigen 1 (AMA-1) is an invasion-related Plasmodium antigen that is expressed during both intracellular and extracellular asexual stages of the parasite's life cycle, making it an ideal target for induction of humoral and cellular immune responses that can protect against malaria. We show here that when it is administered as a recombinant protein (P) in Montanide ISA720 adjuvant, followed by a recombinant human type 5 adenovirus (Ad), intense and long-lasting Plasmodium vivax AMA-1-specific antibody responses (including both IgG1 and IgG2a), as well as proliferative memory T cell responses, can be detected in immunized mice. Memory T cells displayed both central (CD44(hi) CD62L(hi)) and effector (CD44(hi) CD62L(lo)) phenotypes, with the central memory phenotype prevailing (56% of AMA-1-specific proliferating cells). Considering the main traits of the memory immune responses induced against AMA-1, this particular sequence of immunogens (P followed by Ad), but no others (Ad/Ad, Ad/P, or P/P), displayed an optimal synergistic effect. These results give further support to the need for preclinical studies of P. vivax vaccine candidate AMA-1 administered in prime/boost protocols that include recombinant proteins and adenoviral vectors. |
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| Author Address :Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil. |
| Author :S. Campino, S. Auburn, K. Kivinen, I. Zongo, J. B. Ouedraogo, V. Mangano, A. Djimde, O. K. Doumbo, S. M. Kiara, A. Nzila, S. Borrmann, K. Marsh, P. Michon, I. Mueller, P. Siba, H. Jiang, X. Z. Su, C. |
| Title :Population genetic analysis of Plasmodium falciparum parasites using a customized Illumina GoldenGate genotyping assay |
| Journal :PLoS One |
| Year :2011 |
| Epub Date :2011-06-16 |
| Page :e20251 |
| ISSN :1932-6203 (Electronic) 1932-6203 (Linking) |
| Abstract :The diversity in the Plasmodium falciparum genome can be used to explore parasite population dynamics, with practical applications to malaria control. The ability to identify the geographic origin and trace the migratory patterns of parasites with clinically important phenotypes such as drug resistance is particularly relevant. With increasing single-nucleotide polymorphism (SNP) discovery from ongoing Plasmodium genome sequencing projects, a demand for high SNP and sample throughput genotyping platforms for large-scale population genetic studies is required. Low parasitaemias and multiple clone infections present a number of challenges to genotyping P. falciparum. We addressed some of these issues using a custom 384-SNP Illumina GoldenGate assay on P. falciparum DNA from laboratory clones (long-term cultured adapted parasite clones), short-term cultured parasite isolates and clinical (non-cultured isolates) samples from East and West Africa, Southeast Asia and Oceania. Eighty percent of the SNPs (n = 306) produced reliable genotype calls on samples containing as little as 2 ng of total genomic DNA and on whole genome amplified DNA. Analysis of artificial mixtures of laboratory clones demonstrated high genotype calling specificity and moderate sensitivity to call minor frequency alleles. Clear resolution of geographically distinct populations was demonstrated using Principal Components Analysis (PCA), and global patterns of population genetic diversity were consistent with previous reports. These results validate the utility of the platform in performing population genetic studies of P. falciparum. |
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| Author Address :Wellcome Trust Sanger Institute, Hinxton, United Kingdom. sc11@sanger.ac.uk |
| Author :S. Canavati, E. Plugge, S. Suwanjatuporn, S. Sombatrungjaroen and F. Nosten |
| Title :Barriers to immunization among children of migrant workers from Myanmar living in Tak province, Thailand |
| Journal :Bull World Health Organ |
| Year :2011 |
| Epub Date :2011-07-08 |
| Page :528-31 |
| ISSN :1564-0604 (Electronic) 0042-9686 (Linking) |
| Abstract :PROBLEM: Immunization is a cost-effective means of improving child survival but implementation of programmes in low- and middle-income countries is variable. Children of migrants are less likely to be immunized. APPROACH: The qualitative study aimed to identify barriers to the successful implementation of migrant immunization programmes in Tak province, Thailand. We ran a total of 53 focus groups involving 371 participants in three sites. LOCAL SETTING: Tak province in Thailand borders Myanmar and has an estimated 200,000 migrants from Myanmar. Vaccine-preventable diseases are a documented cause of morbidity in this population but there is no systematic or coordinated immunization programme in the area. RELEVANT CHANGES: As a result of the findings, the subsequent immunization campaign targeted children in school to overcome those barriers of distance to immunization services, fear of arrest, not remembering immunization appointments, and the disruption of parental work. The campaigns also included immunization education for both parents and teachers. LESSONS LEARNT: Migrant parents identified similar barriers to accessing childhood immunization programmes as migrant populations elsewhere in the world, although a unique barrier identified by parents from Myanmar was "fear of arrest". The subsequent school-based strategy to overcome these barriers appears to be effective. |
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| Author Address :Shoklo Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, 68/30 Bantung Road, Mae Sod, 63110, Bangkok, Thailand. s.canavatidelatorre@kellogg.oxon.org |
| Author :V. I. Carrara, C. Hogan, C. De Pree, F. Nosten and R. McGready |
| Title :Improved pregnancy outcome in refugees and migrants despite low literacy on the Thai-Burmese border: results of three cross-sectional surveys |
| Journal :BMC Pregnancy Childbirth |
| Year :2011 |
| Epub Date :2011-06-18 |
| Page :45 |
| ISSN :1471-2393 (Electronic) 1471-2393 (Linking) |
| Abstract :BACKGROUND: Maternal and infant health has been associated with maternal education level, which is highly associated with literacy. We aimed at estimating literacy rates among reproductive age women attending antenatal clinics in camps for refugees and in migrant clinics in Tak province, north-western Thailand, to determine whether illiteracy had an impact on birth outcomes. METHODS: Three reading assessments were conducted using an identical method each time, in 1995-97, 2003 and 2008. Midwives chose at random one of four pre-set sentences. Each woman was asked to read aloud and scoring was based on a "pass/fail" system. Pregnancy outcomes were compared with maternal literacy rate. RESULTS: Overall, 47% (1149/2424) of women were able to read. A significant improvement was observed among migrant (34% in 2003 vs. 46% in 2008, p = 0.01), but not refugee (47% in 1995-97, 49% in 2003, and 51% in 2008) women. Literate women were significantly more likely to be of non-Karen ethnicity, primigravidae, non-smokers, to remain free from malaria during pregnancy and to deliver in a health clinic. Significant improvements in pregnancy outcome (reductions in premature births, low birth weight newborns and neonatal death) between 1995-97 and 2003 were unrelated to literacy. CONCLUSIONS: Significant reductions in poor pregnancy outcome over time have not been driven by changes in literacy rates, which have remained low. Access to early diagnosis and treatment of malaria in this population, and delivery with skilled birth attendants, despite ongoing low literacy, appears to have played a significant role. |
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| Author Address :Shoklo Malaria Research Unit, Tak, Thailand. verena@shoklo-unit.com |
| Author :N. M. Douglas, F. Nosten, E. A. Ashley, L. Phaiphun, M. van Vugt, P. Singhasivanon, N. J. White and R. N. Price |
| Title :Plasmodium vivax recurrence following falciparum and mixed species malaria: risk factors and effect of antimalarial kinetics |
| Journal :Clin Infect Dis |
| Year :2011 |
| Epub Date :2011-02-05 |
| Page :612-20 |
| ISSN :1537-6591 (Electronic) 1058-4838 (Linking) |
| Abstract :BACKGROUND: Plasmodium vivax malaria commonly follows treatment of falciparum malaria in regions of co-endemicity. This is an important cause of preventable morbidity. METHODS: We examined the factors contributing to the risk of recurrence of P. vivax infection after treatment of acute falciparum malaria in a series of clinical trials conducted on the Thai-Myanmar border from 1991 through 2005. RESULTS: Overall, 10,549 patients (4960 children aged <15 years and 5589 adults) were treated for falciparum malaria; of these patients, 9385 (89.0%) had Plasmodium falciparum monoinfection and 1164 (11.0%) had mixed P. falciparum/P. vivax infections according to microscopic examinations performed at screening. The cumulative proportion of patients with P. falciparum infection recurrence by day 63 was 21.5% (95% confidence interval [CI], 20.3%-22.8%), and the cumulative proportion with P. vivax infection recurrence was 31.5% (95% CI, 30.1%-33.0%). Significant risk factors for P. vivax infection recurrence were mixed infection at enrollment, male sex, younger age, lower hematocrit, higher asexual P. falciparum parasite density (P < .001 for all factors), and P. falciparum gametocytemia at enrollment (P = .001). By day 63, the cumulative risk of vivax malaria after P. falciparum monoinfection was 51.1% (95% CI, 46.1%-56.2%) after treatment with rapidly eliminated drugs (t(1/2) <1 day), 35.3% (95% CI, 31.8%-39.0%) after treatment with intermediate half-life drugs (t(1/2) 1-7 days), and 19.6% (95% CI, 18.1%-21.3%) after treatment with slowly eliminated drugs (t(1/2) > 7 days) (P < .001, by test for trend). Artemisinin-based combinations containing mefloquine or piperaquine, compared with the artemether-lumefantrine and artesunate-atovaquone-proguanil combinations, were associated with a 3.6-fold to 4.2-fold lower adjusted hazard ratio for P. vivax infection recurrence within 63 days after pure or mixed P. falciparum infections (P < .001, for comparisons with artesunate-mefloquine |
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| Author Address :Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia. |
| Author :m. C. Group |
| Title :A research agenda for malaria eradication: drugs |
| Journal :PLoS Med |
| Year :2011 |
| Epub Date :2011-02-12 |
| Page :e1000402 |
| ISSN :1549-1676 (Electronic) 1549-1277 (Linking) |
| Abstract :Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission. |
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| Author Address :N/A |
| Author :S. Hongsibsong, J. Wipasa, M. Pattarawarapan, S. Chantara, W. Stuetz, F. Nosten and T. Prapamontol |
| Title :Development and Application of an Indirect Competitive Enzyme-Linked Immunosorbent Assay for Detection of p,p'-DDE in Human Milk and Comparison of the Results Against GC-ECD Detection |
| Journal :J Agric Food Chem |
| Year :2011 |
| Epub Date :2011-11-30 |
| Page :N/A |
| ISSN :1520-5118 (Electronic) 0021-8561 (Linking) |
| Abstract :1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) is the major metabolite of insecticide 2,2-bis (p-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT) and one of persistent organic pollutants (POPs) concerning over its bioaccumulation and persistent in the environment and food chain. In the present study, an indirect competitive enzyme-linked immunosorbant assay (ic-ELISA) specific for detection of p,p'-DDE was described. In hapten synthesis, 2,2'-bis(4-chlorophenyl)ethanol and glutaric anhydride were used as precursor and spacer arm, respectively. The hapten was then conjugated to bovine serum albumin (BSA) as immunogen for mice immunization and also conjugated to ovalbumin as coating antigen for ELISA. The developed ic-ELISA was used for detecting p,p'-DDE in human milk samples and validated against the results from conventional gas chromatography-electron capture detection (GC-ECD). Coefficients of variation (%CV) of ELISA were 5.7-10.4% for intra-assay and 10.6-19.6% for inter-assay variations. The Pearson correlation coefficient of p,p'-DDE concentrations between ic-ELISA and GC-ECD was r = 0.766 that was in acceptable range. The results indicated that the developed assay could be an alternative analytical tool for monitoring p,p'-DDE in lipimic matrix like human milk. |
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| Author Address :N/A |
| Author :M. Imwong, M. E. Boel, W. Pagornrat, M. Pimanpanarak, R. McGready, N. P. Day, F. Nosten and N. J. White |
| Title :The First Plasmodium vivax Relapses of Life Are Usually Genetically Homologous |
| Journal :J Infect Dis |
| Year :2011 |
| Epub Date :2011-12-24 |
| Page :N/A |
| ISSN :1537-6613 (Electronic) 0022-1899 (Linking) |
| Abstract :In a prospective infant cohort, 21 infants developed Plasmodium vivax malaria during their first year. Twelve of their mothers also had vivax malaria in the corresponding pregnancies or postpartum period. The genotypes of the maternal and infant infections were all different. Eight of the 12 mothers and 9 of the 21 infants had recurrent infections. Relapse parasite genotypes were different to the initial infection in 13 of 20 (65%) mothers compared with 5 of 24 (21%) infants (P = .02). The first P. vivax relapses of life are usually genetically homologous, whereas relapse in adults may result from activation of heterologous latent hypnozoites acquired from previous inoculations. |
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| Author Address :Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University. |
| Author :M. Imwong, B. Russell, R. Suwanarusk, A. Nzila, M. L. Leimanis, K. Sriprawat, S. Kaewpongsri, A. P. Phyo, G. Snounou, F. Nosten and L. Renia |
| Title :Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax |
| Journal :J Infect Dis |
| Year :2011 |
| Epub Date :2011-02-04 |
| Page :207-10 |
| ISSN :1537-6613 (Electronic) 0022-1899 (Linking) |
| Abstract :Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium vivax isolates ex vivo, 10 of which had multiple dhfr mutations associated with Pyr resistance. Despite high-grade resistance to Pyr (median 50% inhibitory concentration [IC], 13,345 nM), these parasites were all highly susceptible to MTX (median IC, 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation. |
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| Author Address :Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok. |
| Author :R. McGready, S. Lee, J. Wiladphaingern, E. Ashley, M. Rijken, M. Boel, J. Simpson, M. Paw, M. Pimanpanarak, O. Mu, P. Singhasivanon, N. White and F. Nosten |
| Title :Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study |
| Journal :Lancet Infect Dis |
| Year :2011 |
| Epub Date :2011-12-16 |
| Page :N/A |
| ISSN :1474-4457 (Electronic) 1473-3099 (Linking) |
| Abstract :BACKGROUND: The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed first-trimester pregnancies of women from the Thai-Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. METHODS: We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. FINDINGS: Of 48 426 pregnant women, 17 613 (36%) met the inclusion criteria: 16 668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2.70, 95% CI 2.04-3.59) and symptomatic malaria (3.99, 3.10-5.13), and were similar for Plasmodium falciparum and Plasmodium vivax. Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3.63, 95% CI 1.15-11.46) and parasitaemia (1.49, 1.25-1.78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0.86, 95% CI 0.81-0.91). The risk of miscarriage was similar for women treated with chloroquine (92 [26%] of 354), quinine (95 [27%) of 355), or artesunate (20 [31%] of 64; p=0.71). Adverse effects related to antimalarial treatment were not observed. INTERPRETATION: A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage. No additional toxic effects a |
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| Author Address :Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand; Centre for Tropical Medicine, University of Oxford, Oxford, UK. |
| Author :R. McGready, A. P. Phyo, M. Rijken, J. Tarning, N. Lindegardh, W. Hanpithakpon, H. H. Than, N. Hlaing, N. T. Zin, P. Singhasivanon, N. White and F. Nosten |
| Title :Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
| Journal :Br J Clin Pharmacol |
| Year :2011 |
| Epub Date :2011-09-29 |
| Page :N/A |
| ISSN :1365-2125 (Electronic) 0306-5251 (Linking) |
| Abstract :"What this paper adds" statement What is already known about this subject Lowered plasma concentrations of artesunate have been reported in uncomplicated malaria in pregnancy which could risk the life of the mother and fetus. The reason for lowered plasma concentrations in pregnancy is unexplained. Oral artesunate is hydrolysed rapidly in the stomach to the biologically metabolite dihyroartemisinin. What this study adds Following IV artesunate administration for malaria in pregnancy the disposition of artesunate and dihydroartemisinin were similar to controls (the same women studied post-partum without malaria). Whereas higher concentrations of artesunate and dihydroartemisinin were observed after oral administration i.e the disease reduced the pre-systemic metabolism of artesunate. This study did not confirm previous reports and is reassuring regarding current dosing for artesunate in pregnancy. ABSTRACT: Aim: To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution, or increased clearance. Methods: In a randomized cross-over treatment study, pregnant women with uncomplicated falciparum malaria received intravenous artesunate (IV ARS) (4mg/kg) on the first day and oral ARS (4mg/kg) on the second, or, oral on the first and IV on the second, in both groups followed by oral ARS (4mg/kg/day) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid-chromatography-mass-spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (three months post-partum). Results: IV ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n = 20) and in controls (n = 14). Oral administration resulted in higher total drug exposure in pregnancy (AUC (95%CI) in hrxng/mL/(mg/kg)) of 55.1 (30.1-100.0) versus 26.5 (12.2-54.3) for ARS, P = 0.002 and 673 (386-1130) vers |
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| Author Address :Shoklo Malaria Research Unit, PO Box 46 Mae Sot Tak 63110, Thailand Thailand Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, OX3 7LJ, United Kingdom. |
| Author :S. Mok, M. Imwong, M. J. Mackinnon, J. Sim, R. Ramadoss, P. Yi, M. Mayxay, K. Chotivanich, K. Y. Liong, B. Russell, D. Socheat, P. N. Newton, N. P. Day, N. J. White, P. R. Preiser, F. Nosten, A. M. Do |
| Title :Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription |
| Journal :BMC Genomics |
| Year :2011 |
| Epub Date :2011-08-04 |
| Page :391 |
| ISSN :1471-2164 (Electronic) 1471-2164 (Linking) |
| Abstract :BACKGROUND: Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates. RESULTS: In the ring and trophozoite stages, we observed reduced expression of many basic metabolic and cellular pathways which suggests a slower growth and maturation of these parasites during the first half of the asexual intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an increased expression of essentially all functionalities associated with protein metabolism which indicates the prolonged and thus increased capacity of protein synthesis during the second half of the resistant parasite IDC. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of regulatory proteins such as transcription factors or chromatin remodeling associated proteins. In addition, there is a unique and uniform copy number variation pattern in the Cambodian parasites which may represent an underlying genetic background that contributes to the resistance phenotype. CONCLUSIONS: The decreased metabolic activities in the ring stages are consistent with previous suggestions of higher resilience of the early developmental stages to artemisinin. Moreover, the increased capacity of protein synthesis and protein turnover in the schizont stage may contribute to artemisinin resistance by counteracting the protein damage caused by the oxidative stress and/or protein alkylation effect of this drug. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides insight to the complexities of the molecular basis of pathogens with drug re |
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| Author Address :School of Biological Sciences, Nanyang Technological University, Singapore. |
| Author :A. P. Phyo, K. M. Lwin, R. N. Price, E. A. Ashley, B. Russell, K. Sriprawat, N. Lindegardh, P. Singhasivanon, N. J. White and F. Nosten |
| Title :Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand: A Randomized Controlled Trial |
| Journal :Clin Infect Dis |
| Year :2011 |
| Epub Date :2011-10-18 |
| Page :977-84 |
| ISSN :1537-6591 (Electronic) 1058-4838 (Linking) |
| Abstract :Background. Chloroquine (CQ) remains the treatment of choice for Plasmodium vivax malaria. Initially confined to parts of Indonesia and Papua, resistance of P. vivax to CQ seems to be spreading, and alternative treatments are required. Methods. We conducted a randomized controlled study to compare the efficacy and the tolerability of CQ and dihydroartemisinin-piperaquine (DP) in 500 adults and children with acute vivax malaria on the Northwestern border of Thailand. Results. Both drugs were well tolerated. Fever and parasite clearance times were slower in the CQ than in the DP group (P < .001). By day 28, recurrent infections had emerged in 18 of 207 CQ recipients compared with 5 of 230 treated with DP (relative risk, 4.0; 95% confidence interval [CI], 1.51-10.58; P = .0046). The cumulative risk of recurrence with P. vivax at 9 weeks was 79.1% (95% CI, 73.5%-84.8%) in patients treated with CQ compared with 54.9% (95% CI, 48.2%-61.6%) in those receiving DP (hazard ratio [HR], 2.27; 95% CI, 1.8-2.9; P < .001). Children <5 years old were at greater risk of recurrent P. vivax infection (74.4%; 95% CI, 63.2%-85.6%) than older patients (55.3% [95% CI, 50.2%-60.4%]; HR, 1.58 [95% CI, 1.1-2.2]; P = .005). In vitro susceptibility testing showed that 13% of the tested isolates had a CQ median inhibitory concentration >100 nmol/L, suggesting reduced susceptibility. Conclusions. The efficacy of CQ in the treatment of P. vivax infections is declining on the Thai-Myanmar border. DP is an effective alternative treatment. Clinical Trials Registration. ISRCTN87827353. |
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| Author Address :Shoklo Malaria Research Unit, Mae Sod. |
| Author :S. K. Prajapati, H. Joshi, S. Shalini, M. A. Patarroyo, R. Suwanarusk, A. Kumar, S. K. Sharma, A. Eapen, V. Dev, R. M. Bhatt, N. Valecha, F. Nosten, M. A. Rizvi and A. P. Dash |
| Title :Plasmodium vivax lineages: geographical distribution, tandem repeat polymorphism, and phylogenetic relationship |
| Journal :Malar J |
| Year :2011 |
| Epub Date :2011-12-21 |
| Page :374 |
| ISSN :1475-2875 (Electronic) 1475-2875 (Linking) |
| Abstract :BACKGROUND: Multi-drug resistance and severe/complicated cases are the emerging phenotypes of vivax malaria, which may deteriorate current anti-malarial control measures. The emergence of these phenotypes could be associated with either of the two Plasmodium vivax lineages. The two lineages had been categorized as Old World and New World, based on geographical sub-division and genetic and phenotypical markers. This study revisited the lineage hypothesis of P. vivax by typing the distribution of lineages among global isolates and evaluated their genetic relatedness using a panel of new mini-satellite markers. METHODS: 18S SSU rRNA S-type gene was amplified from 420 Plasmodium vivax field isolates collected from different geographical regions of India, Thailand and Colombia as well as four strains each of P. vivax originating from Nicaragua, Panama, Thailand (Pak Chang), and Vietnam (ONG). A mini-satellite marker panel was then developed to understand the population genetic parameters and tested on a sample subset of both lineages. RESULTS: 18S SSU rRNA S-type gene typing revealed the distribution of both lineages (Old World and New World) in all geographical regions. However, distribution of Plasmodium vivax lineages was highly variable in every geographical region. The lack of geographical sub-division between lineages suggests that both lineages are globally distributed. Ten mini-satellites were scanned from the P. vivax genome sequence; these tandem repeats were located in eight of the chromosomes. Mini-satellites revealed substantial allelic diversity (7-21, AE = 14.6 +/- 2.0) and heterozygosity (He = 0.697-0.924, AE = 0.857 +/- 0.033) per locus. Mini-satellite comparison between the two lineages revealed high but similar pattern of genetic diversity, allele frequency, and high degree of allele sharing. A Neighbour-Joining phylogenetic tree derived from genetic distance data obtained from ten mini-satellites also placed both lineages together in every c |
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| Author Address :N/A |
| Author :S. Proux, R. Suwanarusk, M. Barends, J. Zwang, R. N. Price, M. Leimanis, L. Kiricharoen, N. Laochan, B. Russell, F. Nosten and G. Snounou |
| Title :Considerations on the use of nucleic acid-based amplification for malaria parasite detection |
| Journal :Malar J |
| Year :2011 |
| Epub Date :2011-11-01 |
| Page :323 |
| ISSN :1475-2875 (Electronic) 1475-2875 (Linking) |
| Abstract :BACKGROUND: Nucleic acid amplification provides the most sensitive and accurate method to detect and identify pathogens. This is primarily useful for epidemiological investigations of malaria because the infections, often with two or more Plasmodium species present simultaneously, are frequently associated with microscopically sub-patent parasite levels and cryptic mixed infections. Numerous distinct equally adequate amplification-based protocols have been described, but it is unclear which to select for epidemiological surveys. Few comparative studies are available, and none that addresses the issue of inter-laboratory variability. METHODS: Blood samples were collected from patients attending malaria clinics on the Thai-Myanmar border. Frozen aliquots from 413 samples were tested independently in two laboratories by nested PCR assay. Dried blood spots on filter papers from the same patients were also tested by the nested PCR assay in one laboratory and by a multiplex PCR assay in another. The aim was to determine which protocol best detected parasites below the sensitivity level of microscopic examination. RESULTS: As expected PCR-based assays detected a substantial number of infected samples, or mixed infections, missed by microscopy (27 and 42 for the most sensitive assay, respectively). The protocol that was most effective at detecting these, in particular mixed infections, was a nested PCR assay with individual secondary reactions for each of the species initiated with a template directly purified from the blood sample. However, a lesser sensitivity in detection was observed when the same protocol was conducted in another laboratory, and this significantly altered the data obtained on the parasite species distribution. CONCLUSIONS: The sensitivity of a given PCR assay varies between laboratories. Although, the variations are relatively minor, they primarily diminish the ability to detect low-level and mixed infections and are sufficient to obviate the main rati |
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| Author Address :Museum National d'Histoire Naturelle, Paris, France. georges.snounou@upmc.fr. |
| Author :M. J. Rijken, M. E. Boel, B. Russell, M. Imwong, M. L. Leimanis, A. P. Phyo, A. Muehlenbachs, N. Lindegardh, R. McGready, L. Renia, G. Snounou, P. Singhasivanon and F. Nosten |
| Title :Chloroquine resistant vivax malaria in a pregnant woman on the western border of Thailand |
| Journal :Malar J |
| Year :2011 |
| Epub Date :2011-05-07 |
| Page :113 |
| ISSN :1475-2875 (Electronic) 1475-2875 (Linking) |
| Abstract :Chloroquine (CQ) resistant vivax malaria is spreading. In this case, Plasmodium vivax infections during pregnancy and in the postpartum period were not satisfactorily cleared by CQ, despite adequate drug concentrations. A growth restricted infant was delivered. Poor susceptibility to CQ was confirmed in-vitro and molecular genotyping was strongly suggestive of true recrudescence of P. vivax. This is the first clinically and laboratory confirmed case of two high-grade CQ resistant vivax parasite strains from Thailand. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, PO Box 46 Mae Sot, Tak 63110, Thailand. marcus@shoklo-unit.com |
| Author :M. J. Rijken, R. McGready, M. E. Boel, R. Poespoprodjo, N. Singh, D. Syafruddin, S. Rogerson and F. Nosten |
| Title :Malaria in pregnancy in the Asia-Pacific region |
| Journal :Lancet Infect Dis |
| Year :2011 |
| Epub Date :2011-12-24 |
| Page :75-88 |
| ISSN :1474-4457 (Electronic) 1473-3099 (Linking) |
| Abstract :Most pregnant women at risk of for infection with Plasmodium vivax live in the Asia-Pacific region. However, malaria in pregnancy is not recognised as a priority by many governments, policy makers, and donors in this region. Robust data for the true burden of malaria throughout pregnancy are scarce. Nevertheless, when women have little immunity, each infection is potentially fatal to the mother, fetus, or both. WHO recommendations for the control of malaria in pregnancy are largely based on the situation in Africa, but strategies in the Asia-Pacific region are complicated by heterogeneous transmission settings, coexistence of multidrug-resistant Plasmodium falciparum and Plasmodium vivax parasites, and different vectors. Most knowledge of the epidemiology, effect, treatment, and prevention of malaria in pregnancy in the Asia-Pacific region comes from India, Papua New Guinea, and Thailand. Improved estimates of the morbidity and mortality of malaria in pregnancy are urgently needed. When malaria in pregnancy cannot be prevented, accurate diagnosis and prompt treatment are needed to avert dangerous symptomatic disease and to reduce effects on fetuses. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand. |
| Author :M. J. Rijken, R. McGready, V. Jullien, J. Tarning, N. Lindegardh, A. P. Phyo, A. K. Win, P. Hsi, M. Cammas, P. Singhasivanon, N. J. White and F. Nosten |
| Title :Pharmacokinetics of amodiaquine and desethylamodiaquine in pregnant and postpartum women with Plasmodium vivax malaria |
| Journal :Antimicrob Agents Chemother |
| Year :2011 |
| Epub Date :2011-06-29 |
| Page :4338-42 |
| ISSN :1098-6596 (Electronic) 0066-4804 (Linking) |
| Abstract :In order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy, 24 pregnant women in the second and third trimesters of pregnancy and with Plasmodium vivax malaria were treated with amodiaquine (10 mg/kg of body weight/day) for 3 days. The same women were studied again at 3 months postpartum. Plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-tandem mass spectrometry method. Individual concentration-time data were evaluated using noncompartmental analysis. There were no clinically relevant differences in the pharmacokinetics of amodiaquine and desethylamodiaquine between pregnant (n = 24) and postpartum (n = 18) women. The results suggest that the current amodiaquine dosing regimen is adequate for the treatment of P. vivax infections during pregnancy. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, 68/30 Bantung Road, P.O. Box 46, Mae Sot, Tak 63110, Thailand. |
| Author :M. J. Rijken, R. McGready, A. P. Phyo, N. Lindegardh, J. Tarning, N. Laochan, H. H. Than, O. Mu, A. K. Win, P. Singhasivanon, N. White and F. Nosten |
| Title :Pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated falciparum malaria |
| Journal :Antimicrob Agents Chemother |
| Year :2011 |
| Epub Date :2011-09-29 |
| Page :5500-6 |
| ISSN :1098-6596 (Electronic) 0066-4804 (Linking) |
| Abstract :Dihydroartemisinin-piperaquine is a fixed-dose artemisinin-based combination treatment. Some antimalarials have altered pharmacokinetics in pregnancy. Pregnant women in the 2nd or 3rd trimester and matched nonpregnant women with uncomplicated falciparum malaria were treated with a total of 6.4 mg/kg of body weight dihydroartemisinin and 51.2 mg/kg piperaquine once daily for 3 days. Venous blood samples were drawn at prespecified time points over 9 weeks. Plasma dihydroartemisinin and piperaquine concentrations were analyzed by liquid chromatography-mass spectrometry. Piperaquine and dihydroartemisinin pharmacokinetics were well described. There were no significant differences in total piperaquine exposure (P = 0.80) or drug exposure during the terminal elimination phase (72 h to infinity) (P = 0.64) between the two groups. The apparent volume of distribution of piperaquine was significantly smaller (602 liters/kg versus 877 liters/kg) in pregnant women than in nonpregnant women (P = 0.0057), and the terminal elimination half-life was significantly shorter (17.8 days versus 25.6 days; P = 0.0023). Dihydroartemisinin exposure after the first dose was significantly lower (844 h x ng/ml versus 1,220 h x ng/ml, P = 0.0021) in pregnant women, but there were no significant differences in total dihydroartemisinin exposure or maximum concentrations between the two groups. There were no significant differences in any pharmacokinetic parameters between the second and third trimester. These results obtained through noncompartmental analysis suggest that in the treatment of falciparum malaria, there are no clinically important differences in the pharmacokinetics of dihydroartemisinin or piperaquine between pregnant and nonpregnant women. However, a more detailed analysis using population pharmacokinetic modeling is needed to fully investigate the differences found for some of the pharmacokinetic parameters, such as the terminal half-life. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, PO Box 46 Mae Sot, Tak 63110, Thailand. |
| Author :M. J. Rijken, J. A. Rijken, A. T. Papageorghiou, S. H. Kennedy, G. H. Visser, F. Nosten and R. McGready |
| Title :Malaria in pregnancy: the difficulties in measuring birthweight |
| Journal :BJOG |
| Year :2011 |
| Epub Date :2011-02-22 |
| Page :671-8 |
| ISSN :1471-0528 (Electronic) 1470-0328 (Linking) |
| Abstract :Recommendations for interventions to control malaria in pregnancy are often based on studies using birthweight as the primary endpoint. Differences in birthweight may be attributable partly to methodological difficulties. We performed a structured search of the literature using 'malaria', 'pregnancy' and 'birth weight' as search terms. Of the clinical trials reporting birthweight, only 33% (14/43) gave information about the timing of the measurement and details on the scales used. Seventy seven per cent explained how gestational age was estimated. We propose a standardised method for the measurement and reporting of birthweight in future studies. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand. marcus@shoklo-unit.com |
| Author :B. Russell, R. Suwanarusk, C. Borlon, F. T. Costa, C. S. Chu, M. J. Rijken, K. Sriprawat, L. Warter, E. G. Koh, B. Malleret, Y. Colin, O. Bertrand, J. H. Adams, U. D'Alessandro, G. Snounou, F. Nosten |
| Title :A reliable ex vivo invasion assay of human reticulocytes by Plasmodium vivax |
| Journal :Blood |
| Year :2011 |
| Epub Date :2011-07-20 |
| Page :e74-81 |
| ISSN :1528-0020 (Electronic) 0006-4971 (Linking) |
| Abstract :Currently, there are no reliable RBC invasion assays to guide the discovery of vaccines against Plasmodium vivax, the most prevalent malaria parasite in Asia and South America. Here we describe a protocol for an ex vivo P vivax invasion assay that can be easily deployed in laboratories located in endemic countries. The assay is based on mixing enriched cord blood reticulocytes with matured, trypsin-treated P vivax schizonts concentrated from clinical isolates. The reliability of this assay was demonstrated using a large panel of P vivax isolates freshly collected from patients in Thailand. |
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| Author Address :Singapore Immunology Network, Biopolis, Agency for Science Technology and Research, Singapore. bruce_russell@immunol.a-star.edu.sg |
| Author :W. Stuetz, V. I. Carrara, R. McGready, S. J. Lee, J. G. Erhardt, J. Breuer, H. K. Biesalski and F. H. Nosten |
| Title :Micronutrient status in lactating mothers before and after introduction of fortified flour: cross-sectional surveys in Maela refugee camp |
| Journal :Eur J Nutr |
| Year :2011 |
| Epub Date :2011-07-26 |
| Page :N/A |
| ISSN :1436-6215 (Electronic) 1436-6207 (Linking) |
| Abstract :BACKGROUND: Deficiency of micronutrients is common in refugee populations. OBJECTIVES: Identify deficiencies and whether provided supplements and wheat flour fortified with 10 micronutrients impacts upon status among breast-feeding women from Maela refugee camp. METHODS: Two sequential cross-sectional studies were conducted in different groups of lactating mothers at 12 weeks postpartum. The first survey was before and the second 4-5 months after micronutrient fortified flour (MFF) had been provided to the camp (in addition to the regular food basket). Iron status and micronutrients were measured in serum, whole blood, and in breast milk samples. RESULTS: Iron and zinc deficiency and anemia were highly prevalent while low serum retinol and thiamine deficiency were rarely detected. Iron and zinc deficiency were associated with anemia, and their proportions were significantly lower after the introduction of MFF (21 vs. 35% with soluble transferrin receptor (sTfR) >8.5 mg/L, P = 0.042, and 50 vs. 73% with serum zinc <0.66 mg/L, P = 0.001). Serum sTfR, whole-blood thiamine diphosphate (TDP) and serum beta-carotene were significant predictors (P < 0.001) of milk iron, thiamine and beta-carotene, respectively. Lower prevalence of iron deficiency in the MFF group was associated with significantly higher iron and thiamine in breast milk. CONCLUSIONS: High whole-blood TDP and breast milk thiamine reflected good compliance to provided thiamine; high prevalence of iron deficiency suggested insufficient dietary iron and low acceptance to ferrous sulfate supplements. MFF as an additional food ration in Maela refugee camp seemed to have an effect in reducing both iron and zinc deficiency postpartum. |
| URL : Go online |
| Author Address :Department of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70599, Stuttgart-Hohenheim, Germany, wostuetz@uni-hohenheim.de. |
| Author :C. Turner, N. Aye Mya Thein, P. Turner, F. Nosten and N. J. White |
| Title :Rectal pH in Well and Unwell Infants |
| Journal :J Trop Pediatr |
| Year :2011 |
| Epub Date :2011-10-11 |
| Page : N/A |
| ISSN :1465-3664 (Electronic) 0142-6338 (Linking) |
| Abstract :Prompt antibiotic treatment for infants with sepsis has the potential to save lives. A rectal formulation of an antibiotic could be used at a village level before referral to hospital. The development of such a preparation needs to take into account the rectal pH of infants that will affect drug partitioning and absorption. Rectal pH measurements were taken in 100 well and 45 unwell infants. We also measured rectal pH in 14 infants sequentially over the course of their illness. The mean rectal pH was 6.75 with no significant difference in well or unwell infants. The mean (95% CI) rectal pH of well neonates was significantly lower than that of older infants (>28 days): 6.47 (6.29-6.65) vs. 6.90 (6.68 to 7.12) p = 0.003. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, Mae Sot 63110, Thailand. |
| Author :P. Turner, J. Hinds, C. Turner, A. Jankhot, K. Gould, S. D. Bentley, F. Nosten and D. Goldblatt |
| Title :Improved detection of nasopharyngeal cocolonization by multiple pneumococcal serotypes by use of latex agglutination or molecular serotyping by microarray |
| Journal :J Clin Microbiol |
| Year :2011 |
| Epub Date :2011-03-18 |
| Page :1784-9 |
| ISSN :1098-660X (Electronic) 0095-1137 (Linking) |
| Abstract :Identification of Streptococcus pneumoniae in the nasopharynx is critical for an understanding of transmission, estimates of vaccine efficacy, and possible replacement disease. Conventional nasopharyngeal swab (NPS) culture and serotyping (the WHO protocol) is likely to underestimate multiple-serotype carriage. We compared the WHO protocol with methods aimed at improving cocolonization detection. One hundred twenty-five NPSs from an infant pneumococcal-carriage study, containing >/= 1 serotype by WHO culture, were recultured in duplicate. A sweep of colonies from one plate culture was serotyped by latex agglutination. DNA extracted from the second plate was analyzed by S. pneumoniae molecular-serotyping microarray. Multiple serotypes were detected in 11.2% of the swabs by WHO culture, 43.2% by sweep serotyping, and 48.8% by microarray. Sweep and microarray were more likely to detect multiple serotypes than WHO culture (P < 0.0001). Cocolonization detection rates were similar between microarray and sweep, but the microarray identified the greatest number of serotypes. A common serogroup type was identified in 95.2% of swabs by all methods. WHO methodology significantly underestimates multiple-serotype carriage compared to these alternate methods. Sweep serotyping is cost-effective and field deployable but may fail to detect serotypes at low abundance, whereas microarray serotyping is more costly and technology dependent but may detect these additional minor carried serotypes. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, Mae Sot, Thailand. pault@tropmedres.ac |
| Author :P. Turner, S. Melchiorre, M. Moschioni, M. A. Barocchi, C. Turner, W. Watthanaworawit, N. Kaewcharernnet, F. Nosten and D. Goldblatt |
| Title :Assessment of Streptococcus pneumoniae pilus islet-1 prevalence in carried and transmitted isolates from mother-infant pairs on the Thailand-Burma border |
| Journal :Clin Microbiol Infect |
| Year :2011 |
| Epub Date :2011-11-19 |
| Page :N/A |
| ISSN :1469-0691 (Electronic) 1198-743X (Linking) |
| Abstract :Clin Microbiol Infect ABSTRACT: Streptococcus pneumoniae pilus islet-1 (PI-1)-encoded pilus enhances in vitro adhesion to the respiratory epithelium and may contribute to pneumococcal nasopharyngeal colonization and transmission. The pilus subunits are regarded as potential protein vaccine candidates. In this study, we sought to determine PI-1 prevalence in carried pneumococcal isolates and explore its relationship with transmissibility or carriage duration. We studied 896 pneumococcal isolates collected during a longitudinal carriage study that included monthly nasopharyngeal swabbing of 234 infants and their mothers between the ages of 1 and 24 months. These were cultured according to the WHO pneumococcal carriage detection protocol. PI-1 PCR and genotyping by multilocus sequence typing were performed on isolates chosen according to specific carriage and transmission definitions. Overall, 35.2% of the isolates were PI-1-positive, but PI-1 presence was restricted to ten of the 34 serotypes studied and was most frequently associated with serotypes 19F and 23F; 47.5% of transmitted and 43.3% of non-transmitted isolates were PI-1-positive (OR 1.2; 95% CI 0.8-1.7; p 0.4). The duration of first-ever infant pneumococcal carriage was significantly longer with PI-1-positive organisms, but this difference was not significant at the individual serotype level. In conclusion, PI-1 is commonly found in pneumococcal carriage isolates, but does not appear to be associated with pneumococcal transmissibility or carriage duration. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, Mae Sot Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand Centre for Tropical Medicine, University of Oxford, Oxford, UK Novartis Vaccines and Diagnostics |
| Author :P. Turner, L. Po, C. Turner, D. Goldblatt and F. Nosten |
| Title :Detection of respiratory viruses by PCR assay of nasopharyngeal swabs stored in skim milk-tryptone-glucose-glycerol transport medium |
| Journal :J Clin Microbiol |
| Year :2011 |
| Epub Date :2011-04-01 |
| Page :2311-3 |
| ISSN :1098-660X (Electronic) 0095-1137 (Linking) |
| Abstract :We analyzed 129 paired nasopharyngeal aspirates (stored in viral transport medium [VTM]) and nasopharyngeal swabs (stored in skim milk-tryptone-glucose-glycerol [STGG] bacterial transport and storage medium) using PCRs to detect adenoviruses, influenza virus A or B, and respiratory syncytial virus (RSV). Overall, swabs stored in STGG medium without antimicrobials were found to be an acceptable alternative to aspirates stored in antimicrobial-containing VTM, with PCR agreement of 90.2% (kappa of 0.8). |
| URL : Go online |
| Author Address :Shoko Malaria Research Unit, Mae Sot, Thailand. pault@tropmedres.ac |
| Author :P. Turner, C. Turner, N. Kaewcharernnet, N. Y. Mon, D. Goldblatt and F. Nosten |
| Title :A prospective study of urinary pneumococcal antigen detection in healthy Karen mothers with high rates of pneumococcal nasopharyngeal carriage |
| Journal :BMC Infect Dis |
| Year :2011 |
| Epub Date :2011-04-28 |
| Page :108 |
| ISSN :1471-2334 (Electronic) 1471-2334 (Linking) |
| Abstract :BACKGROUND: Detection of Streptococcus pneumoniae C-polysaccharide in urine is a useful rapid diagnostic test for pneumococcal infections in adults. In young children, high rates of false positive results have been documented due to detection of concurrent nasopharyngeal pneumococcal carriage. The relationship between pneumococcal carriage and urinary antigen detection in adults from developing countries with high pneumococcal carriage prevalence has not been well established. METHODS: We nested an evaluation of the BinaxNOW S. pneumoniae test within a longitudinal mother-infant pneumococcal carriage study in Karen refugees on the Thailand-Myanmar border. Paired urine and nasopharyngeal swab specimens were collected from 98 asymptomatic women at a routine study follow-up visit. The urine specimens were analyzed with the BinaxNOW test and the nasopharyngeal swabs were semi-quantitatively cultured to identify pneumococcal colonization. RESULTS: 24/98 (25%) women were colonized by S. pneumoniae but only three (3%) had a positive BinaxNOW urine test. The sensitivity of the BinaxNOW test for detection of pneumococcal colonization was 4.2% (95% CI: 0.1-21.1%) with a specificity of 97.3% (95% CI: 90.6-99.7%). Pneumococcal colonization was not associated with having a positive BinaxNOW test (odds ratio 1.6; 95% CI: 0.0-12.7; p=0.7). CONCLUSIONS: Significant numbers of false positive results are unlikely to be encountered when using the BinaxNOW test to diagnose pneumococcal infection in adults from countries with moderate to high rates of pneumococcal colonization. |
| URL : Go online |
| Author Address :Shoklo Malaria Research Unit, Mae Sot, Thailand. pault@tropmedres.ac |
| Author :M. I. Veiga, P. E. Ferreira, L. Jornhagen, M. Malmberg, A. Kone, B. A. Schmidt, M. Petzold, A. Bjorkman, F. Nosten and J. P. Gil |
| Title :Novel polymorphisms in Plasmodium falciparum ABC transporter genes are associated with major ACT antimalarial drug resistance |
| Journal :PLoS One |
| Year :2011 |
| Epub Date :2011-06-03 |
| Page :e20212 |
| ISSN :1932-6203 (Electronic) 1932-6203 (Linking) |
| Abstract :Chemotherapy is a critical component of malaria control. However, the most deadly malaria pathogen, Plasmodium falciparum, has repeatedly mounted resistance against a series of antimalarial drugs used in the last decades. Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial combination therapies. Alterations in the parasitic membrane proteins Pgh-1, PfCRT and PfMRP1 are believed to be major contributors to resistance through decreasing intracellular drug accumulation. The pfcrt, pfmdr1 and pfmrp1 genes were sequenced from a set of P.falciparum field isolates from the Thai-Myanmar border. In vitro drug susceptibility to artemisinin, dihydroartemisinin, mefloquine and lumefantrine were assessed. Positive correlations were seen between the in vitro susceptibility responses to artemisinin and dihydroartemisinin and the responses to the arylamino-alcohol quinolines lumefantrine and mefloquine. The previously unstudied pfmdr1 F1226Y and pfmrp1 F1390I SNPs were associated significantly with artemisinin, mefloquine and lumefantrine in vitro susceptibility. A variation in pfmdr1 gene copy number was also associated with parasite drug susceptibility of artemisinin, mefloquine and lumefantrine. Our work unveils new candidate markers of P. falciparum multidrug resistance in vitro, while contributing to the understanding of subjacent genetic complexity, essential for future evidence-based drug policy decisions. |
| URL : Go online |
| Author Address :Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Isabel.veiga@ki.se |
| Author :L. J. White, S. J. Lee, K. Stepniewska, J. A. Simpson, S. L. Dwell, R. Arunjerdja, P. Singhasivanon, N. J. White, F. Nosten and R. McGready |
| Title :Estimation of gestational age from fundal height: a solution for resource-poor settings |
| Journal :J R Soc Interface |
| Year :2011 |
| Epub Date :2011-08-19 |
| Page :N/A |
| ISSN :1742-5662 (Electronic) 1742-5662 (Linking) |
| Abstract :Many women in resource-poor settings lack access to reliable gestational age assessment because they do not know their last menstrual period; there is no ultrasound (US) and methods of newborn gestational age dating are not practised by birth attendants. A bespoke multiple-measures model was developed to predict the expected date of delivery determined by US. The results are compared with both a linear and a nonlinear model. Prospectively collected early US and serial symphysis-pubis fundal height (SFH) data were used in the models. The data were collected from Karen and Burmese women attending antenatal care on the Thai-Burmese border. The multiple-measures model performed best, resulting in a range of accuracy depending on the number of SFH measures recorded per mother (for example six SFH measurements resulted in a prediction accuracy of +/-2 weeks). SFH remains the proxy for gestational age in much of the resource-poor world. While more accurate measures should be encouraged, we demonstrate that a formula that incorporates at least three SFH measures from an individual mother and the slopes between them provide a significant increase in the accuracy of prediction compared with the linear and nonlinear formulae also using multiple SFH measures. |
| URL : Go online |
| Author Address :Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, , Oxford OX3 7LJ, UK. |
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