ORCID Profile
0000-0003-1573-734X
Current Organisations
Timika Research Facility
,
Pediatric Research Office Universitas Gadjah Mada
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Publisher: Springer Science and Business Media LLC
Date: 08-06-2022
DOI: 10.1186/S12916-022-02394-1
Abstract: In Papua (Indonesia), infants with P. falciparum and/or P. vivax malaria are at risk of severe anaemia and death. We hypothesized that in an area of high malaria transmission, intermittent screening and treatment of infants with malaria (ISTi) will reduce morbidity compared to passive case detection (PCDi). We conducted a cluster randomised, open label, superiority trial. A total of 21 clusters of village health posts (VHP) were randomised 1:1 to either IST for infants coinciding with 4 routine immunisation visits or PCDi. Healthy term infants born to consenting mothers enrolled into a maternal malaria cluster randomised trial were included in the study and followed for 12 months. Point of care malaria rapid diagnostic tests were used to detect peripheral parasitaemia at 2, 3, 4 and 9 months old in all infants in ISTi clusters and when symptomatic in PCDi clusters. Infants with detected peripheral parasitaemia were treated with dihydroartemisinin-piperaquine. The co-primary outcomes were the incidence rate of clinical malaria in the first year of life and the prevalence of parasitaemia at age 12 months. The incidence rate ratio and prevalence ratio between ISTi and PCDi were estimated using mixed-effects Poisson and log-binomial regression modelling (accounting for clustering at VHP level). Between May 2014 and February 2017, 757 infants were enrolled into the study, 313 into 10 ISTi clusters, and 444 into 11 PCDi clusters. Overall, 132 episodes of parasitaemia were detected, of whom 17 (12.9%) were in symptomatic infants. Over 12 months, the incidence rate (IR) of clinical malaria was 24 [95% CI, 10–50] per 1000 children-years at risk in the ISTi arm and 19 [95% CI, 8,38] per 1000 children-years in the PCDi arm (adjusted incidence rate ratio [aIRR] 1.77 [95% CI, 0.62–5.01] p = 0.280). The prevalence of parasitaemia at 12 months was 13% (33/254) in the IST clusters and 15% (57/379) in the PCD clusters (adjusted prevalence ratio (aPR) = 0.92 (95% CI, 0.70–1.21), p = 0.55). There was no difference in the risk of anaemia between treatment arms. In high malaria transmission area outside of Africa, our study suggests that compared to PCDi, ISTi offers no significant benefit in reducing the risk of clinical malaria in infants born to women receiving effective protection from malaria during pregnancy. ClinicalTrials.gov NCT 02001428 , registered on 20 Nov 2013.
Publisher: American Society for Clinical Investigation
Date: 15-11-2018
Publisher: Public Library of Science (PLoS)
Date: 31-12-2015
Publisher: Springer Science and Business Media LLC
Date: 24-10-2015
Publisher: American Society for Microbiology
Date: 10-2015
DOI: 10.1128/AAC.00874-15
Abstract: The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum , but susceptibility data for P. vivax are limited. The species- and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum (median [range] 50% inhibitory concentration [IC 50 ]: NQ, 8.0 nM [2.6 to 71.8 nM] and MB, 1.6 nM [0.2 to 7.0 nM]) and P. vivax (NQ, 7.8 nM [1.5 to 34.2 nM] and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC 50 s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P = 0.021) and P. vivax (341.6 versus 6.5 nM, P = 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P = 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.
Publisher: Public Library of Science (PLoS)
Date: 29-08-2017
Publisher: American Society of Tropical Medicine and Hygiene
Date: 07-02-2018
Abstract: Artemisinin combination therapy is recommended for the treatment of multidrug resistant Plasmodium falciparum and Plasmodium vivax . In March 2006, antimalarial policy in Indonesia was changed to a unified treatment with dihydroartemisinin-piperaquine for all species of malaria because of the low efficacy of previous drug treatments. In 2013, a randomized cross-sectional household survey in Papua was used to collect data on demographics, parasite positivity, treatment-seeking behavior, diagnosis and treatment of malaria, and household costs. Results were compared with a similar survey undertaken in 2005. A total of 800 households with 4,010 in iduals were included in the 2013 survey. The prevalence of malaria parasitemia was 12% (348/2,795). Of the in iduals who sought treatment of fever, 67% (66/98) reported attending a public provider at least once compared with 46% (349/764) before policy change ( P 0.001). During the 100 visits to healthcare providers, 95% (95) included a blood test for malaria and 74% (64/86) resulted in the recommended antimalarial for the diagnosed species, the corresponding figures before policy change were 48% (433/894) and 23% (78/336). The proportion of in iduals seeking treatment more than once fell from 14% (107/764) before policy change to 2% (2/98) after policy change ( P = 0.005). The mean indirect cost per fever episode requiring treatment seeking decreased from US$44.2 in 2005 to US$33.8 in 2013 ( P = 0.006). The implementation of a highly effective antimalarial treatment was associated with better adherence of healthcare providers in both the public and private sectors and a reduction in clinical malaria and household costs.
Publisher: Oxford University Press (OUP)
Date: 09-09-2011
Publisher: American Society of Tropical Medicine and Hygiene
Date: 04-2010
Publisher: Oxford University Press (OUP)
Date: 05-2008
DOI: 10.1086/586743
Publisher: Springer Science and Business Media LLC
Date: 20-06-2018
Publisher: Springer Science and Business Media LLC
Date: 15-07-2015
Publisher: Springer Science and Business Media LLC
Date: 24-08-2018
Publisher: American Society for Microbiology
Date: 08-2017
DOI: 10.1128/AAC.00355-17
Abstract: High-grade chloroquine (CQ) resistance has emerged in both Plasmodium falciparum and P. vivax . The aim of the present study was to investigate the phenotypic differences of CQ resistance in both of these species and the ability of known CQ resistance reversal agents (CQRRAs) to alter CQ susceptibility. Between April 2015 and April 2016, the potential of verapamil (VP), mibefradil (MF), L703,606 (L7), and primaquine (PQ) to reverse CQ resistance was assessed in 46 P. falciparum and 34 P. vivax clinical isolates in Papua, Indonesia, where CQ resistance is present in both species, using a modified schizont maturation assay. In P. falciparum , CQ 50% inhibitory concentrations (IC 50 s) were reduced when CQ was combined with VP (1.4-fold), MF (1.2-fold), L7 (4.2-fold), or PQ (1.8-fold). The degree of CQ resistance reversal in P. falciparum was highly correlated with CQ susceptibility for all CQRRAs ( R 2 = 0.951, 0.852, 0.962, and 0.901 for VP, MF, L7, and PQ, respectively), in line with observations in P. falciparum laboratory strains. In contrast, no reduction in the CQ IC 50 s was observed with any of the CQRRAs in P. vivax , even in those isolates with high chloroquine IC 50 s. The differential effect of CQRRAs in P. falciparum and P. vivax suggests significant differences in CQ kinetics and, potentially, the likely mechanism of CQ resistance between these two species.
Publisher: Oxford University Press (OUP)
Date: 12-06-2013
Publisher: Public Library of Science (PLoS)
Date: 04-10-2019
Publisher: Oxford University Press (OUP)
Date: 19-11-2018
Abstract: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined. In Papua, Indonesia, we enrolled adults with symptomatic Plasmodium falciparum (n = 47 uncomplicated, n = 8 severe), Plasmodium vivax (n = 37), or Plasmodium malariae (n = 14) malaria asymptomatic P falciparum (n = 19) or P vivax (n = 21) parasitemia and healthy adults (n = 23) without parasitemia. Neutrophil activation and NETs were quantified by immunoassays and microscopy and correlated with parasite biomass and disease severity. In patients with symptomatic malaria, neutrophil activation and NET counts were increased in all 3 Plasmodium species. In falciparum malaria, neutrophil activation and NET counts positively correlated with parasite biomass (Spearman rho = 0.41, P = .005 and r2 = 0.26, P = .002, respectively) and were significantly increased in severe disease. In contrast, NETs were inversely associated with parasitemia in adults with asymptomatic P falciparum infection (r2 = 0.24, P = .031) but not asymptomatic P vivax infection. Although NETs may inhibit parasite growth in asymptomatic P falciparum infection, neutrophil activation and NET release may contribute to pathogenesis in severe falciparum malaria. Agents with potential to attenuate these processes should be evaluated.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2012
Publisher: Springer Science and Business Media LLC
Date: 30-10-2019
DOI: 10.1186/S12879-019-4497-Y
Abstract: In southern Papua, Indonesia, malaria is highly prevalent in young children and is a significant cause of morbidity and early mortality. The association between malaria and delayed mortality is unknown. Routinely-collected hospital surveillance data from southern Papua, Indonesia, were used to assess the risk of recurrent malaria and mortality within 12 months of an initial presentation with malaria in all children younger than 5 years old attending the local hospital. Analysis was primarily by Kaplan Meier and Cox regression methods. In total 15,716 children presenting with malaria between April 2004 and December 2013 were included in the analysis 6184 (39.3%) with Plasmodium falciparum, 7499 (47.7%) with P. vivax , 203 (1.3%) with P. malariae, 3 with P. ovale and 1827 (11.6%) with mixed infections . Within 1 year, 48.4% (7620/15,716) of children represented a total of 16,957 times with malaria (range 1 to 11 episodes), with the incidence of malaria being greater in patients initially presenting with P. vivax infection (1334 [95%CI 1307–1361] per 1000 patient years) compared to those with P. falciparum infection (920 [896–944]). In total 266 (1.7%) children died within 1 year of their initial presentation, 129 (48.5%) within 30 days and 137 (51.5%) between 31 and 365 days. There was no significant difference in the mortality risk in patients infected with P. vivax versus P. falciparum either before 30 days (Hazard Ratio (HR) 1.02 [0.69,1.49]) or between 31 and 365 days (HR = 1.30 [0.90,1.88]). Children who died had a greater incidence of malaria, 2280 [95%CI 1946–2671] per 1000 patient years preceding their death, compared to 1141 [95%CI 1124–1158] per 1000 patient years in those surviving. Children under-5 years old with P. vivax malaria, are at significant risk of multiple representations with malaria and of dying within 1 year of their initial presentation. Preventing recurrent malaria must be a public health priority in this vulnerable population.
Publisher: Public Library of Science (PLoS)
Date: 17-12-2013
Publisher: Public Library of Science (PLoS)
Date: 26-05-2021
DOI: 10.1371/JOURNAL.PMED.1003632
Abstract: A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human in iduals infected with Plasmodium vivax . The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P . vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival. We examined spleen tissue in 22 mostly untreated in iduals naturally exposed to P . vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from in iduals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or s le size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P . vivax , 13 P . falciparum , and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P . vivax -infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P . vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P . vivax - than in P . falciparum -infected spleens. Histological analyses revealed 96% of P . vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted. Immature CD71 + reticulocytes and splenic P . vivax- infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P . vivax infection. Findings provide insight into P . vivax -specific adaptions that have evolved to maximise survival and replication in the spleen.
Publisher: Springer Science and Business Media LLC
Date: 12-2019
DOI: 10.1186/S12936-019-3085-3
Abstract: Intravenous artesunate and its follow on full course dihydroartemisinin–piperaquine are the standard treatment for severe malaria in Indonesia. The current policy suggests that intravenous and oral quinine could be used when standard therapy is not available. Its pragmatic use of both treatment combinations in a field hospital is evaluated. A retrospective study among hospitalized malaria patients receiving intravenous anti-malarial treatments at Mitra Masyarakat Hospital, Timika from April 2004 to December 2013 was conducted. The length of hospital stay (LoS) and the risk of malaria recurrence within 28 days after hospital admission were compared between patients receiving intravenous artesunate and oral dihydroartemisinin–piperaquine (Iv Art + DHP) and those receiving intravenous and oral quinine (Iv + Oral Qu). Of 10,514 patients requiring intravenous therapy, 2759 received Iv + Oral Qu and 7755 received Iv Art + DHP. Plasmodium falciparum infection accounted for 65.8% (6915), while Plasmodium vivax , Mixed infections, Plasmodium malariae and Plasmodium ovale were accounted for 17.0% (1789), 16.4% (1729), 0.8% (79) and 0.01% (2) of the infections, respectively. The majority of severe malaria hospital admissions were highland Papuans (78.0%, 8201/10,501). In total 49% (5158) of patients were older than 15 years and 3463 (32.9%) were children under 5 years old. The median LoS was shorter in patients receiving intravenous artesunate compared to those treated with intravenous quinine (median = 2 [IQR 1–3] versus 3 days [IQR 2–4], p 0.0001). Patients treated with intravenous quinine had higher risk of being hospitalized longer than 2 days (aOR of 1.70 [95% CI 1.54–1.88], p 0.0001). The risk of recurrences within 28 days after hospital admission was 1.94 times higher (95% CI aHR 1.57–2.39, p 0.0001) in patients receiving intravenous quinine with follow on oral quinine treatment than in patients treated with DHP after intravenous artesunate therapy. Intravenous artesunate reduced the LoS of malaria patients and in combination with DHP reduced the risk of malaria recurrence within 28 days after hospital admission compared to those with Iv + Oral Qu treatment. Thus, ensuring continuous supply of intravenous artesunate and artemisinin-based combination therapy (ACT) should be a priority.
Publisher: Public Library of Science (PLoS)
Date: 19-11-2020
DOI: 10.1371/JOURNAL.PMED.1003393
Abstract: There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an in idual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P . vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P . vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P . falciparum monoinfection and 1,195 (7.8%) mixed infection with P . falciparum and P . vivax . The median age was 17.0 years (interquartile range [IQR] = 9.0–29.0 years range = 0–80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P . falciparum was 31.1% (95% CI 28.9–33.4) after AL, 14.1% (95% CI 10.8–18.3) after AA, 7.4% (95% CI 6.7–8.1) after AM, and 4.5% (95% CI 3.9–5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6–43.3), 42.4% (95% CI 34.7–51.2), 22.8% (95% CI 21.2–24.4), and 12.8% (95% CI 11.4–14.5), respectively. In multivariable analyses, the highest rate of P . vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0–19.5 p = 0.002) patients treated with AL (AHR = 6.2, 95% CI 4.6–8.5 p 0.001), AA (AHR = 2.3, 95% CI 1.4–3.7 p = 0.001), or AM (AHR = 1.4, 95% CI 1.0–1.9 p = 0.028) compared with DP and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4–2.3 p 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. In this meta-analysis, we found a high risk of P . vivax parasitaemia after treatment of P . falciparum malaria that varied significantly between studies. These P . vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent however, the benefits of such a novel strategy will vary considerably between geographical areas.
Publisher: Public Library of Science (PLoS)
Date: 27-10-2016
Publisher: Springer Science and Business Media LLC
Date: 18-11-2014
Publisher: Springer Science and Business Media LLC
Date: 24-08-2018
Publisher: Springer Science and Business Media LLC
Date: 16-06-2016
Publisher: Springer Science and Business Media LLC
Date: 19-03-2019
Publisher: American Society of Hematology
Date: 06-02-2017
DOI: 10.1182/BLOOD-2018-05-849307
Abstract: Platelets directly interact with and kill circulating Plasmodium parasites in patients with malaria to help control parasitemia. In vitro platelet antiplasmodicidal activity against P knowlesi involves platelet–cell binding and intracellular accumulation of PF4.
Publisher: Elsevier
Date: 2012
Publisher: Public Library of Science (PLoS)
Date: 29-05-2019
Publisher: Public Library of Science (PLoS)
Date: 07-05-2020
Publisher: Elsevier BV
Date: 2012
Publisher: Public Library of Science (PLoS)
Date: 14-05-2020
Publisher: Oxford University Press (OUP)
Date: 16-05-2018
DOI: 10.1093/CID/CIY403
Abstract: In Papua, splenectomized in iduals have greater risk of malaria in the 12 months following splenectomy but not of mortality. Malaria risk was higher for Plasmodium vivax than P. falciparum. Early radical cure and prophylaxis are warranted in malaria endemic areas.
Publisher: Springer Science and Business Media LLC
Date: 21-06-2016
Publisher: American Society for Microbiology
Date: 09-2015
DOI: 10.1128/AAC.01048-15
Abstract: Chloroquine (CQ) has been the mainstay of malaria treatment for more than 60 years. However, the emergence and spread of CQ resistance now restrict its use to only a few areas where malaria is endemic. The aim of the present study was to investigate whether a novel combination of a CQ-like moiety and an imipramine-like pharmacophore can reverse CQ resistance ex vivo . Between March to October 2011 and January to September 2013, two “reversed chloroquine” (RCQ) compounds (PL69 and PL106) were tested against multidrug-resistant field isolates of Plasmodium falciparum ( n = 41) and Plasmodium vivax ( n = 45) in Papua, Indonesia, using a modified ex vivo schizont maturation assay. The RCQ compounds showed high efficacy against both CQ-resistant P. falciparum and P. vivax field isolates. For P. falciparum , the median 50% inhibitory concentrations (IC 50 s) were 23.2 nM for PL69 and 26.6 nM for PL106, compared to 79.4 nM for unmodified CQ ( P 0.001 and P = 0.036, respectively). The corresponding values for P. vivax were 19.0, 60.0, and 60.9 nM ( P 0.001 and P = 0.018, respectively). There was a significant correlation between IC 50 s of CQ and PL69 (Spearman's rank correlation coefficient [ r s ] = 0.727, P 0.001) and PL106 ( r s = 0.830, P 0.001) in P. vivax but not in P. falciparum . Both RCQs were equally active against the ring and trophozoite stages of P. falciparum , but in P. vivax , PL69 and PL106 showed less potent activity against trophozoite stages (median IC 50 s, 130.2 and 172.5 nM) compared to ring stages (median IC 50 s, 17.6 and 91.3 nM). RCQ compounds have enhanced ex vivo activity against CQ-resistant clinical isolates of P. falciparum and P. vivax , suggesting the potential use of reversal agents in antimalarial drug development. Interspecies differences in RCQ compound activity may indicate differences in CQ pharmacokinetics between the two Plasmodium species.
Publisher: EMBO
Date: 04-2022
Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 08-11-2016
Publisher: Springer Science and Business Media LLC
Date: 02-04-2019
Publisher: Oxford University Press (OUP)
Date: 28-08-2015
Publisher: Springer Science and Business Media LLC
Date: 27-09-2018
Publisher: Springer Science and Business Media LLC
Date: 02-03-2016
Publisher: American Society for Microbiology
Date: 2016
DOI: 10.1128/AAC.02207-15
Abstract: Chloroquine (CQ)-resistant Plasmodium vivax is present in most countries where P. vivax infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of P. vivax crt-o ( pvcrt-o ) has been correlated with in vivo CQ resistance in an area with low-grade resistance. We assessed pvcrt-o expression in isolates from Papua (Indonesia), where P. vivax is highly CQ resistant. Ex vivo drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of pvcrt-o were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in pvcrt-o expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the P. vivax β-tubulin gene and from 0.01 to 24 relative to that seen with the P. vivax aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5 P 0.001). Twenty-nine isolates fulfilled the criteria for ex vivo drug susceptibility testing and showed high variability in CQ responses (median, 107.9 [range, 6.5 to 345.7] nM). After controlling for the parasite stage, we found that pvcrt-o expression levels did not correlate with the ex vivo response to CQ or with that to any of the other antimalarials tested. Our results highlight the importance of development-stage composition for measuring pvcrt-o expression and suggest that pvcrt-o transcription is not a primary determinant of ex vivo drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and P. vivax drug resistance.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 07-03-2018
Publisher: American Society for Microbiology
Date: 08-2015
DOI: 10.1128/IAI.00226-15
Abstract: Clinical illness with Plasmodium falciparum or Plasmodium vivax compromises the function of dendritic cells (DC) and expands regulatory T (Treg) cells. In iduals with asymptomatic parasitemia have clinical immunity, restricting parasite expansion and preventing clinical disease. The role of DC and Treg cells during asymptomatic Plasmodium infection is unclear. During a cross-sectional household survey in Papua, Indonesia, we examined the number and activation of blood plasmacytoid DC (pDC), CD141 + , and CD1c + myeloid DC (mDC) subsets and Treg cells using flow cytometry in 168 afebrile children (of whom 15 had P. falciparum and 36 had P. vivax infections) and 162 afebrile adults (of whom 20 had P. falciparum and 20 had P. vivax infections), alongside s les from 16 patients hospitalized with uncomplicated malaria. Unlike DC from malaria patients, DC from children and adults with asymptomatic, microscopy-positive P. vivax or P. falciparum infection increased or retained HLA-DR expression. Treg cells in asymptomatic adults and children exhibited reduced activation, suggesting increased immune responsiveness. The pDC and mDC subsets varied according to clinical immunity (asymptomatic or symptomatic Plasmodium infection) and, in asymptomatic infection, according to host age and parasite species. In conclusion, active control of asymptomatic infection was associated with and likely contingent upon functional DC and reduced Treg cell activation.
Publisher: Public Library of Science (PLoS)
Date: 17-01-2014
Publisher: Public Library of Science (PLoS)
Date: 09-08-2016
Publisher: Oxford University Press (OUP)
Date: 15-06-2009
DOI: 10.1086/599041
Location: Indonesia
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jeanne Rini Poespoprodjo.