Training, experience, and perceptions of chest tube insertion by higher speciality trainees: implications for training, patient safety, and service delivery.

BACKGROUND: Seldinger Chest Tube Insertion (CTI) is a high acuity low occurrence procedure and remains a core capability for UK physician higher speciality trainee's (HST). A multitude of factors have emerged which may affect the opportunity of generalists to perform CTI. In view of which, this paper sought to establish the current experiences, attitudes, training, and knowledge of medical HST performing Seldinger CTI in acute care hospitals in the Peninsula deanery. METHODS: A Scoping review was performed to establish the UK medical HST experience of adult seldinger CTI. Synonymous terms for CTI training were searched across Cochrane, ERIC, Pubmed and British education index databases. Following which, a regional survey was constructed and completed by HST and pleural consultants from five hospitals within the Peninsula deanery between April-July 2022. Data collected included participants demographics, attitudes, training, experience, and clinical knowledge. Outcomes were collated and comparisons made across groups using SPSS. A p-value of < 0.05 was defined as significant. RESULTS: The scoping review returned six papers. Salient findings included low self-reported procedural confidence levels, poor interventional selection for patient cases, inadequate site selection for CTI and 1 paper reported only 25% of respondents able to achieve 5-10 CTI annually. However, all papers were limited by including grades other than HST in their responses. The regional survey was completed by 87 HST (12 respiratory, 63 non-respiratory medical HST and 12 intensivists/anaesthetists HST). An additional seven questionnaires were completed by pleural consultants. Respiratory HSTs performed significantly more Seldinger CTI than general and ICM/anaesthetic registrars (p < 0.05). The percentage of HST able to achieve a self-imposed annual CTI number were 81.8, 12.9 and 41.7% respectively. Self-reported transthoracic ultrasound competence was 100, 8 and 58% respectively (p < 0.001). The approach to clinical management significantly differed with national guidance with pleural consultants showing an agreement of 89%, respiratory HST 75%, general HST 52% and ICM/anaesthetic HST 54% (p = 0.002). CONCLUSION: Compared to respiratory trainees, non-respiratory trainees perform lower numbers of Seldinger CTI, with lower confidence levels, limited knowledge, and a reduced perceived relevance of the skill set. This represents a significant training and service challenge, with notable patient safety implications.

A randomised controlled trial of intrapleural balloon intercostal chest drains to prevent drain displacement.

BACKGROUND: Chest drain displacement is a common clinical problem that occurs in 9-42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement. METHODS: A prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement. RESULTS: 267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13-1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08-0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, p<0.0001). CONCLUSION: Balloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.

Focused Neck Ultrasound and Lymph Node Sampling by Respiratory Physicians in Suspected Lung Cancer.

BACKGROUND: Malignant cervical lymphadenopathy in the setting of lung cancer represents N3 disease, and neck ultrasound (NUS) with sampling is described in the Royal College of Radiologists ultrasound training curriculum for the non-radiologists. This study reviews the incorporation of NUS +/- biopsy in the routine practice of a lung cancer fast-track clinic in the UK. METHODS: We retrospectively assessed 29 months of activity of a lung cancer fast-track clinic. Systematic focused NUS was conducted in suspected thoracic malignancy, sampling nodes with a ≥5-mm short axis, under real-time US using a linear probe (5-12 Mhz). Fine-needle aspirations (FNAs) with or without 18 Ga core biopsies were taken. RESULTS: Between August 2017 and December 2019, of 152 peripheral lymph nodes (LNs)/deposits sampled, 98 (64.5%) were supraclavicular fossa LNs with median [IQR] size 12 [8-18] mm. Core biopsies were performed in 54/98 (55%) patients, while all patients had FNAs. No complications occurred. The representative yield was 90/95 (94.7%) in cases with suspected cancer. No difference was seen between FNA versus core biopsy (p = 0.44). Of the 5 non-diagnostic samples, one was FNA only. The commonest diagnosis was lung cancer in 66/98 (67.3%). PDL-1 was sufficient in 35/36 tested (97.2%). ALK-FISH was successful in 24/25 (96%) cases. EGFR mutation analysis was successful in 28/31 (90.3%) cases. Median time from clinic to initial diagnosis was 7 [5-10] days. Computed tomography (CT) scans reported no significant lymphadenopathy in 18/96 (18.7%) cases, yet 10/18 (55.5%) cases were positive for malignancy. CONCLUSION: Neck nodal sampling by respiratory physicians was safe, timely, with a high diagnostic yield and suitability for molecular testing. Neck US can provide a timely diagnosis in cases that may be missed by CT alone.

To drain or not to drain? Abscess or empyema?

We present a case posing the clinical dilemma of differentiating a large peripheral lung abscess from an empyema, discussing the imaging and management and the clinical issues posed.

Efficient Surveillance of Plasmodium knowlesi Genetic Subpopulations, Malaysian Borneo, 2000-2018.

Population genetic analysis revealed that Plasmodium knowlesi infections in Malaysian Borneo are caused by 2 divergent parasites associated with long-tailed (cluster 1) and pig-tailed (cluster 2) macaques. Because the transmission ecology is likely to differ for each macaque species, we developed a simple genotyping PCR to efficiently distinguish between and survey the 2 parasite subpopulations. This assay confirmed differences in the relative proportions in areas of Kapit division of Sarawak state, consistent with multilocus microsatellite analyses. Analyses of 1,204 human infections at Kapit Hospital showed that cluster 1 caused approximately two thirds of cases with no significant temporal changes from 2000 to 2018. We observed an apparent increase in overall numbers in the most recent 2 years studied, driven mainly by increased cluster 1 parasite infections. Continued monitoring of the frequency of different parasite subpopulations and correlation with environmental alterations are necessary to determine whether the epidemiology will change substantially.

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection. METHODS: Prospective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months. RESULTS: Mortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0-2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3-4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5-7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71-0.83) and 0.77 (95% CI 0.72-0.82), respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.

Clinical features and management of Plasmodium knowlesi infections in humans.

Plasmodium knowlesi is a simian malaria of primarily the macaque species of South East Asia. While it was known that human infections could be induced during the years of malariotherapy, naturally occurring P. knowlesi human infections were thought to be rare. However, in 2004, knowlesi infections became recognized as an important infection amongst human populations in Sarawak, Malaysian Borneo. Since then, it has become recognized as a disease affecting people living and visiting endemic areas across South East Asia. Over the last 12 years, clinical studies have improved our understanding of this potentially fatal disease. In this review article the current literature is reviewed to give a comprehensive description of the disease and treatment.

PET and Neck Ultrasound for the Detection of Cervical Lymphadenopathy in Patients with Lung Cancer and Mediastinal Lymphadenopathy.

BACKGROUND: Cervical lymph nodes are frequently involved in patients with lung cancer and indicate inoperability. Some guidelines recommend neck ultrasound (NUS) in patients with bulky mediastinal lymphadenopathy. Positron emission tomography (PET) is indicated for patients with potentially curable disease. OBJECTIVES: We aimed to assess the diagnostic yield of NUS and the diagnostic accuracy of PET for cervical lymphadenopathy in this group with a high pre-test probability of N3 disease. METHODS: Records of all patients with lung cancer who underwent an NUS over a consecutive 5-year period were reviewed. Only patients with mediastinal lymphadenopathy on computerised tomography (CT) were included. The diagnostic accuracy of PET was assessed with NUS-guided fine needle aspiration cytology used as the reference test. RESULTS: During the study period, 123 patients met the inclusion criteria. Malignant cervical lymphadenopathy was confirmed in 49/123 (39.8% [95% CI 31.1-49.1]). PET-CT had a specificity of 81.1%, sensitivity of 87.5%, negative predictive value of 96.8% and positive predictive value of 50% for the detection of cervical lymphadenopathy, and it contributed no additional staging information in the neck area. Overall, PET led to a change in management in only 2.2% of cases. CONCLUSION: A significant proportion of patients with lung cancer and mediastinal lymphadenopathy have cervical lymphadenopathy detected by NUS. In this group of patients, PET offers minimal additional value in staging and management.

Human infections and detection of Plasmodium knowlesi.

Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection.

The role of a nurse specialist in a modern lung-cancer service.

The delivery of a modern cancer service is dependent on the nurse specialist occupying a central role in the overall pathway. However, there are significant variations in the access to a lung cancer clinical nurse specialist (CNS) across the UK and the USA. In the UK, the lung cancer CNS plays a pivotal role in the delivery of high-quality care and treatment to patients with (presumed) thoracic malignancy. They are in an ideal position to provide holistic care to patients with lung cancer-ensuring that all needs are addressed from the time of initial referral to commencement of definitive treatment or palliative care. In addition the role provides support and advice to people on the increasingly complex treatment options and on survivorship, and plays an essential role in end-of-life care. In the USA, the nurse navigator is a core member of the lung cancer screening programme. In this review the authors provide a transatlantic perspective on the history, current practice and potential future roles for the lung cancer CNS in the UK and nurse navigator in the US.

Role of interventional pulmonology in the management of complicated parapneumonic pleural effusions and empyema.

Pleural infection is a major problem that affects 80,000 cases per year in the UK and USA. It is increasing in incidence, and in an ageing population, it presents a complex challenge that requires a combination of medical therapies and may lead to the need for surgery. This article focuses on the role of the interventional pulmonologist in the diagnosis and management of pleural infection. In particular, we examine the role of pleural ultrasound in diagnostics, thoracocentesis and real-time guided procedures, and the current management strategies, including the controversial role of medical thoracoscopy.

Thoracic ultrasound in guiding management of respiratory disease.

INTRODUCTION: The use of ultrasound in respiratory disease has evolved substantially over the past two decades. From a test done to confirm the safe site of pleural fluid drainage, thoracic ultrasound has become a point-of-care test that guides the management of patients on respiratory wards, in clinics and endoscopy. AREAS COVERED: This review overviews the process of ultrasound examination in the chest. It then delves into specific disease areas (pleural disease, lung disease, diaphragm disease, and invasive procedures) to highlight how thoracic ultrasound is being used to refine management. The review concludes with discussion on the training curricula and assessment tools for competency in thoracic ultrasound. Being a scoping review, literature searches were conducted on PubMed using relevant search terms. EXPERT OPINION: In addition to its current uses, there are many avenues where thoracic ultrasound will soon be beneficial. Recent studies show promising roles in areas such as patient-tailored guidance of pleurodesis and non-invasively predicting lung re-expansion after pleural fluid drainage. In addition, auxiliary tools such as contrast-enhanced ultrasound and elastography are proving useful in identifying the etiology and directing the successful sampling of pleural and lung lesions. Studies are also exploring the utility of sonographic biomarkers such as echogenicity and septations to predict outcomes in pleural disease.

The Short versus Long Antibiotic Course for Pleural Infection Management (SLIM) randomised controlled open-label trial.

Introduction: Based on expert opinion, the length of antibiotic treatment for pleural infection in adults is typically recommended to be a minimum of 4 weeks. This clinical trial aimed to assess whether shorter antibiotic courses lead to more treatment failures than standard longer courses. Methods: In an open-label randomised controlled trial, adult patients with pleural infection who were medically treated and stabilised within 14 days of admission were randomised to either a short antibiotic course (total course 14-21 days) or a long antibiotic course (total course 28-42 days). Patients were excluded if their baseline RAPID score was >4 (high-risk category). The primary outcome was the incidence of treatment failure by 6 weeks post-admission. Secondary outcomes were total length of antibiotic treatment, proportion of patients who resumed normal activity levels within 6 weeks post-admission, time from discharge to resuming normal activity levels and incidence of antibiotic-related adverse reactions. Results: Between September 2020 and October 2021, 50 patients (mean±sd age 46±13.7 years; 35 (70%) males) were recruited to the trial and randomly assigned to the short course group (n=25) or the long course group (n=25), with outcome data available for 24 patients in each study group. Treatment failure occurred in four (16.7%) patients in the short course group and three (12.5%) patients in the long course group. In the intention-to-treat analysis the OR for treatment failure in the long course group was 0.714 (95% CI 0.142-3.600; p=0.683). The median (interquartile range) duration of antibiotic treatment in the short course group was 20.5 (18-22.5) days compared with 34.5 (32-38) days in the long course group (p<0.001). There were no statistically significant differences in the other outcomes. Conclusions: In medically treated adult patients with pleural infection a long course of antimicrobial therapy did not lead to fewer treatment failures compared with a shorter course. These findings need to be confirmed in a larger multicentre trial.

Endobronchial Ultrasound-guided Sampling of Centrally Located Intrapulmonary Tumors Provides Suitable Material for Diagnostic and Molecular Testing.

BACKGROUND: Curvilinear endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a key diagnostic and staging procedure for patients with suspected lung cancer. However, sampling centrally located intrapulmonary tumors is feasible but less well established. METHODS: We retrospectively evaluated the diagnostic utility of EBUS-TBNA in patients who underwent sampling of centrally located intrapulmonary tumors. Diagnostic accuracy, sample suitability for molecular testing, and complications were assessed. RESULTS: Between January 2015 and April 2021, 102 EBUS-TBNA procedures sampled centrally located intrapulmonary tumors in 99 patients. The median age was 70 [interquartile range, 63 to 75] years and 51% (51/99) were male. The commonest site was the right upper lobe (n=42/99; 42%). The median tumor size was 29 [interquartile range, 21 to 35] mm. The diagnostic yield was 88/102 (86%) with a false negative rate of 14% (14/102). In addition to intrapulmonary tumor sampling, lymph nodes were sampled in 65/102 procedures and 30/65(46%) were positive for lung cancer. Cancer was diagnosed in 87/99 (88%) cases. When requested, molecular testing was adequate in ≥94% of samples. Complications included minor bleeding in 6/102 (6%) with 2 requiring cold saline instillation, desaturation in 1/102 (1%), and tachycardia in 1/102(1%). One procedure was abandoned due to patient tachycardia. Delayed complications occurred in 1 patient who was hospitalized ≤7 days with pneumonia. CONCLUSION: EBUS-TBNA sampling of centrally located intrapulmonary tumors provides similar diagnostic accuracy to lymph node sampling, provides suitable material for molecular testing, and has a low complication rate.

Time between endobronchial ultrasound needle passes as a metric to monitor progress of trainees.

BACKGROUND: Methods to assess and track progress of new endobronchial ultrasound (EBUS) operators and trainees is desirable to ensure training goals and procedural competence are achieved. Relying on the diagnostic yield or on question-based assessments alone is not sufficient. This study examined the longitudinal change in times taken between needle passes (needle pass time; NPT) during EBUS lymph node sampling as a metric to monitor progress. RESEARCH DESIGN AND METHODS: :The EBUS database of a tertiary hospital was accessed to extract data on the first 50 EBUS procedures for three trainees. The NPT was derived using PACS images that are stored to document every needle pass during an EBUS procedure and an average NPT was calculated. RESULTS: Between the three trainees, 157 procedures were carried out within the study period with 302 nodal stations sampled. The mean NPT (n = 204 stations) was 2:49 ± 0:49 mins. The mean node short axis diameter was 15.5 ± 8.7 mm. There was a negative correlation between node size and time per pass (r - 0.146, p = 0.045).The average NPT showed a negative correlation with procedure order through the first 50 procedures. Less variation between procedures was noted for the three trainees from the 30th procedure onward. On multivariate regression, NPT was significantly associated with procedure order regardless of station sampled or lymph node diameter. CONCLUSION: NPT is novel, easy, and robust metric that can potentially help ensure EBUS trainees are advancing in a given training program.

Plasmodium knowlesi - Clinical Isolate Genome Sequencing to Inform Translational Same-Species Model System for Severe Malaria.

Malaria is responsible for unacceptably high morbidity and mortality, especially in Sub-Saharan African Nations. Malaria is caused by member species' of the genus Plasmodium and despite concerted and at times valiant efforts, the underlying pathophysiological processes leading to severe disease are poorly understood. Here we describe zoonotic malaria caused by Plasmodium knowlesi and the utility of this parasite as a model system for severe malaria. We present a method to generate long-read third-generation Plasmodium genome sequence data from archived clinical samples using the MinION platform. The method and technology are accessible, affordable and data is generated in real-time. We propose that by widely adopting this methodology important information on clinically relevant parasite diversity, including multiple gene family members, from geographically distinct study sites will emerge. Our goal, over time, is to exploit the duality of P. knowlesi as a well-used laboratory model and human pathogen to develop a representative translational model system for severe malaria that is informed by clinically relevant parasite diversity.

Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory. METHODS: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure. RESULTS: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume. CONCLUSIONS: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.

A comparison of the clinical, laboratory and epidemiological features of two divergent subpopulations of Plasmodium knowlesi.

Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia. There are two genetically distinct subpopulations of Plasmodium knowlesi in Malaysian Borneo, one associated with long-tailed macaques (termed cluster 1) and the other with pig-tailed macaques (cluster 2). A prospective study was conducted to determine whether there were any between-subpopulation differences in clinical and laboratory features, as well as in epidemiological characteristics. Over 2 years, 420 adults admitted to Kapit Hospital, Malaysian Borneo with knowlesi malaria were studied. Infections with each subpopulation resulted in mostly uncomplicated malaria. Severe disease was observed in 35/298 (11.7%) of single cluster 1 and 8/115 (7.0%) of single cluster 2 infections (p = 0.208). There was no clinically significant difference in outcome between the two subpopulations. Cluster 1 infections were more likely to be associated with peri-domestic activities while cluster 2 were associated with interior forest activities consistent with the preferred habitats of the respective macaque hosts. Infections with both P. knowlesi subpopulations cause a wide spectrum of disease including potentially life-threatening complications, with no implications for differential patient management.

Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections.

BACKGROUND: Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs. METHODS: A prospective observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group. RESULTS: Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR. CONCLUSIONS: Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi.