scispace - formally typeset
Search or ask a question
Author

Robert S Miller

Bio: Robert S Miller is an academic researcher from United States Department of the Army. The author has contributed to research in topics: Plasmodium falciparum & Plasmodium vivax. The author has an hindex of 7, co-authored 9 publications receiving 452 citations.

Papers
More filters
Journal ArticleDOI
TL;DR: PCR appears to be a useful method for detecting Plasmodium parasites during active malaria surveillance in Thailand, and data indicated that the discrepancy between the two methods resulted from poor performance of microscopy at low parasite densities rather thanpoor performance of PCR.
Abstract: The main objective of this study was to compare the performance of nested PCR with expert microscopy as a means of detecting Plasmodium parasites during active malaria surveillance in western Thailand. The study was performed from May 2000 to April 2002 in the village of Kong Mong Tha, located in western Thailand. Plasmodium vivax (PV) and Plasmodium falciparum (PF) are the predominant parasite species in this village, followed by Plasmodium malariae (PM) and Plasmodium ovale (PO). Each month, fingerprick blood samples were taken from each participating individual and used to prepare thick and thin blood films and for PCR analysis. PCR was sensitive (96%) and specific (98%) for malaria at parasite densities ≥ 500/μl; however, only 18% (47/269) of P. falciparum- and 5% (20/390) of P. vivax-positive films had parasite densities this high. Performance of PCR decreased markedly at parasite densities <500/μl, with sensitivity of only 20% for P. falciparum and 24% for P. vivax at densities <100 parasites/μl. Although PCR performance appeared poor when compared to microscopy, data indicated that the discrepancy between the two methods resulted from poor performance of microscopy at low parasite densities rather than poor performance of PCR. These data are not unusual when the diagnostic method being evaluated is more sensitive than the reference method. PCR appears to be a useful method for detecting Plasmodium parasites during active malaria surveillance in Thailand.

177 citations

Journal ArticleDOI
TL;DR: Using this assay as a tool for active case detection is of limited value in western Thailand because of the relatively high cost of these assays, low parasite rates found in the majority of asymptomatic individuals, and low sensitivity of this assay with rates of < 500/microl.
Abstract: Rapid antigen assays provide an effective tool for the detection of malaria in symptomatic patients. However, the efficacy of these devices for detecting asymptomatic malaria, where parasite levels are normally signifi- cantly lower than in symptomatic patients, is less well established. We evaluated the efficacy of a new combined Plasmodium falciparum-Plasmodim vivax immunochromatographic test (ICT Malaria Pf/Pv) in a cross-sectional malaria survey of the village of Ban Kong Mong Tha, Kanchanaburi Provice, Thailand, from August to December 2000. A total of 1,976 bleeds were made from 559 individuals over the course of the study. Blinded microscopy of thick and thin blood films was used as the gold standard; all discordant and 10% of concordant results were cross-checked. Of 1,976 ICT Malaria Pf/Pv dipsticks tested, 98.3% (n 1,943) performed as expected, as evidenced by the appearance of the control line. The ICT Malaria Pf/Pv test was both sensitive (100.0%) and specific (99.7 %) for the diagnosis of falciparum malaria with parasitemias of 500 trophozoites/L; however, only 15.9% (13/82) of infected individuals had parasitemia rates this high. When P. falciparum parasitemia rates were < 500/L, the sensitivity of the diagnosis was only 23.3%, with a positive predictive value (PPV) and a negative predictive value (NPV) of 76.2 and 97.2%, respectively. The ICT Malaria Pf/Pv test was specific, but not sensitive, for the diagnosis of vivax malaria with parasite rates of 500 trophozoites/l, with sensitivity, specificity, PPV, and NPV of 66.7%, 99.9%, 66.7%, and 99.9%, respectively. At parasite rates of < 500/L, corresponding values were 0.0%, 99.9%, 0%, and 95.1%. Because of the relatively high cost of these assays, low parasite rates found in the majority of asymptomatic individuals, and low sensitivity of this assay with rates of < 500/l, use of this assay as a tool for active case detection is of limited value in western Thailand.

76 citations

Journal ArticleDOI
TL;DR: Characteristic increases in the overall HRP2 levels were found during the later ring and the trophozoite stages, and a distinct inhibition of HRP1 production was seen with increasing concentrations of drugs, resulting in sigmoid dose-response curves, similar to those obtained from conventional drug sensitivity assays.

57 citations

Journal ArticleDOI
TL;DR: The sensitivity of the OptiMAL assay for P. falciparum and P. vivax was 25% with > 500 parasites/microl and 10.5% with> 100 parasites/ microl, while the sensitivity at the same parasite rates was 100% and 41.7%, respectively.
Abstract: We evaluated the efficacy of the OptiMAL assay in a cross-sectional malaria survey in western Thailand from April to August 2001. Expert microscopy of Giemsa-stained thick and thin blood films was used as the gold standard. Positive control lines were evident in 99% (1,128 of 1,137) of the assays tested. However, 34% (384 of 1,128) of assays produced an aberrant result (a positive P. falciparum-specific line and a negative panmalarial line). False-positive panmalarial and Plasmodium falciparum-specific lines occurred in 25.9% (270 of 1,042) and 60.3% (628 of 1,042) of microscopy-negative samples, respectively. Due to the preponderance of false-positive test results, it was necessary to develop subjective criteria for test positivity based on line intensity. For determination of assay performance during this study, we therefore considered all test lines that were scored as intermediate or strong as positive and lines that were faint as negative. Using these criteria, we determined that the sensitivity of the OptiMAL assay for P. falciparum was 25% with > 500 parasites/microl and 10.5% with > 100 parasites/microl, while for P. vivax, the sensitivity at the same parasite rates was 100% and 41.7%, respectively. Further studies are required to determine whether the problems we identified are limited to this particular lot of OptiMAL assays.

46 citations

Journal ArticleDOI
TL;DR: The safety of injectable AS, even at the highest dose of 8 mg/kg increases the probability of therapeutic success of the drug even in patients with large variability of parasitaemia.
Abstract: Severe malaria results in over a million deaths every year, most of them in children aged less than five years and living in sub-Saharan Africa. Injectable artesunate (AS) was recommended as initial treatment for severe malaria by WHO in 2006. The Walter Reed Army Institute of Research (WRAIR) has been developing a novel good manufacturing practice (GMP) injection of AS, which was approved by the US FDA for investigational drug use and distribution by the CDC. Tolerability and pharmacokinetics of current GMP intravenous AS, as an anti-malarial agent, were evaluated after ascending multiple doses of 2, 4, and 8 mg/kg daily for three days with 2-minute infusion in 24 healthy subjects (divided into three groups) in the Phase 1 clinical trial study. Results showed that there were no dose-dependent increases in any adverse events. Drug concentrations showed no accumulation and no decline of the drug during the three days of treatment. After intravenous injection, parent drug rapidly declined and was converted to dihydroartemisinin (DHA) with overall mean elimination half-lives ranging 0.15-0.23 hr for AS and 1.23-1.63 hr for DHA, but the peak concentration (Cmax) of AS was much higher than that of DHA with a range of 3.08-3.78-folds. In addition, the AUC and Cmax values of AS and DHA were increased proportionally to the AS climbing multiple doses. The safety of injectable AS, even at the highest dose of 8 mg/kg increases the probability of therapeutic success of the drug even in patients with large variability of parasitaemia.

39 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: RDTs are highlighted, including challenges in assessing their performance, internationally available RDTs, their effectiveness in various health care settings, and the selection of R DTs for different health care systems.
Abstract: To help mitigate the expanding global impact of malaria, with its associated increasing drug resistance, implementation of prompt and accurate diagnosis is needed. Malaria is diagnosed predominantly by using clinical criteria, with microscopy as the current gold standard for detecting parasitemia, even though it is clearly inadequate in many health care settings. Rapid diagnostic tests (RDTs) have been recognized as an ideal method for diagnosing infectious diseases, including malaria, in recent years. There have been a number of RDTs developed and evaluated widely for malaria diagnosis, but a number of issues related to these products have arisen. This review highlights RDTs, including challenges in assessing their performance, internationally available RDTs, their effectiveness in various health care settings, and the selection of RDTs for different health care systems.

489 citations

Journal ArticleDOI
TL;DR: A systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique found that microscopy can miss a substantial proportion of P. Falconerum infections in surveys of endemic populations, especially in areas with low transmission of infection.
Abstract: Introduction. Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. Methods. We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy: PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. Results. Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was >75% versus 12.0% when the prevalence determined by PCR was <10%). Discussion. Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.

487 citations

Journal ArticleDOI
TL;DR: In achieving this goal, the shift from symptom-based diagnosis to parasite-based management of malaria can bring significant improvements to tropical fever management, rather than represent a further burden on poor, malaria-endemic populations and their overstretched health services.
Abstract: The replacement of conventional antimalarial drugs with high-cost, artemisinin-based alternatives has created a gap in the successful management of malaria. This gap reflects an increased need for accurate disease diagnosis that cannot be met by traditional microscopy techniques. The recent introduction of rapid diagnostic tests (RDTs) has the potential to meet this need, but successful RDT implementation has been curtailed by poor product performance, inadequate methods to determine the quality of products and a lack of emphasis and capacity to deal with these issues. Economics and a desire for improved case management will result in the rapid growth of RDT use in the coming years. However, for their potential to be realized, it is crucial that high-quality RDT products that perform reliably and accurately under field conditions are made available. In achieving this goal, the shift from symptom-based diagnosis to parasite-based management of malaria can bring significant improvements to tropical fever management, rather than represent a further burden on poor, malaria-endemic populations and their overstretched health services.

354 citations

Journal ArticleDOI
TL;DR: In this paper, the authors focus on identification and elimination of foci of infections through both passive and active methods of case detection, which need appropriate treatment of both clinical cases and asymptomatic infections combined with targeted vector control.

341 citations

Journal ArticleDOI
TL;DR: Without strategies accounting for P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded.
Abstract: Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. These traits affect both its geographic distribution and transmission patterns. Asymptomatic infections, high-risk groups, and resulting case burdens are described in this review. Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign. Plasmodium vivax can be associated with severe and even fatal illness. Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year. Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded.

300 citations