Surveillance of Gram-negative bacteria: impact of variation in current European laboratory reporting practice on apparent multidrug resistance prevalence in paediatric bloodstream isolates.

This study evaluates whether estimated multidrug resistance (MDR) levels are dependent on the design of the surveillance system when using routine microbiological data. We used antimicrobial resistance data from the Antibiotic Resistance and Prescribing in European Children (ARPEC) project. The MDR status of bloodstream isolates of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was defined using European Centre for Disease Prevention and Control (ECDC)-endorsed standardised algorithms (non-susceptible to at least one agent in three or more antibiotic classes). Assessment of MDR status was based on specified combinations of antibiotic classes reportable as part of routine surveillance activities. The agreement between MDR status and resistance to specific pathogen-antibiotic class combinations (PACCs) was assessed. Based on all available antibiotic susceptibility testing, the proportion of MDR isolates was 31% for E. coli, 30% for K. pneumoniae and 28% for P. aeruginosa isolates. These proportions fell to 9, 14 and 25%, respectively, when based only on classes collected by current ECDC surveillance methods. Resistance percentages for specific PACCs were lower compared with MDR percentages, except for P. aeruginosa. Accordingly, MDR detection based on these had low sensitivity for E. coli (2-41%) and K. pneumoniae (21-85%). Estimates of MDR percentages for Gram-negative bacteria are strongly influenced by the antibiotic classes reported. When a complete set of results requested by the algorithm is not available, inclusion of classes frequently tested as part of routine clinical care greatly improves the detection of MDR. Resistance to individual PACCs should not be considered reflective of MDR percentages in Enterobacteriaceae.

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations.

Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.

Impact of removing the healthcare mask mandate on hospital-acquired COVID-19 rates.

BACKGROUND: Mandatory mask-wearing policies were one of several measures employed to reduce hospital-acquired SARS-CoV-2 infection throughout the pandemic. Many nations have removed healthcare mask mandates, but there remains a risk of new SARS-CoV-2 variants or epidemics of other respiratory viruses. AIM: To demonstrate the impact of removing the healthcare mask mandate. METHODS: SARS-CoV-2 infections were analysed in a large teaching hospital for 40 weeks in 2022 using a controlled interrupted time-series design. The intervention was the removal of a staff/visitor surgical mask-wearing policy for the most wards at week 26 (intervention group) with a subset of specific wards retaining the mask policy (control group). The hospital-acquired SARS-CoV-2 infection rate was adjusted by the underlying community infection rate. FINDINGS: In the context of a surge in SARS-CoV-2 infection, removal of the mask mandate for staff/visitors was not associated with a statistically significant change in the rate of nosocomial SARS-CoV-2 infection in the intervention group (incidence rate ratio: 1.105; 95% confidence interval: 0.523-2.334; P = 0.79) and there was no post-intervention trend (1.013; 0.932-1.100; P = 0.76) to suggest a delayed effect. The control group also showed no immediate or delayed change in infection rate. CONCLUSION: No evidence was found that removal of a staff/visitor mask-wearing policy had a significant effect on the rate of hospital-acquired SARS-CoV-2 infection. This does not demonstrate that masks were ineffective through the pandemic, but provides some objective evidence to justify the removal of healthcare mask mandates once there was widespread immunity and reduced disease severity.

Tuning methods for multigap drift tube linacs.

Multigap cavities are used extensively in linear accelerators to achieve velocities up to a few percent of the speed of light, driving nuclear physics research around the world. Unlike for single-gap structures, there is no closed-form expression to calculate the output beam parameters from the cavity voltage and phase. To overcome this, we propose to use a method based on the integration of the first and second moments of the beam distribution through the axially symmetric time-dependent fields of the cavity. A beam-based calibration between the model's electric field scaling and the machine's rf amplitudes is presented, yielding a fast online energy change method, returning cavity amplitude and phase necessary for a desired output beam energy and energy spread. The method is validated with 23Na6+ beam energy measurements.

A multisite evaluation of antifungal use in critical care: implications for antifungal stewardship.

Background: ICUs are settings of high antifungal consumption. There are few data on prescribing practices in ICUs to guide antifungal stewardship implementation in this setting. Methods: An antifungal therapy (AFT) service evaluation (15 May-19 November 2019) across ICUs at three London hospitals, evaluating consumption, prescribing rationale, post-prescription review, de-escalation and final invasive fungal infection (IFI) diagnostic classification. Results: Overall, 6.4% of ICU admissions (305/4781) received AFT, accounting for 11.41 days of therapy/100 occupied bed days (DOT/100 OBD). The dominant prescribing mode was empirical (41% of consumption), followed by targeted (22%), prophylaxis (18%), pre-emptive (12%) and non-invasive (7%). Echinocandins were the most commonly prescribed drug class (4.59 DOT/100 OBD). In total, 217 patients received AFT for suspected or confirmed IFI; 12%, 10% and 23% were classified as possible, probable or proven IFI, respectively. Hence, in 55%, IFI was unlikely. Proven IFI (n = 50) was mostly invasive candidiasis (92%), of which 48% had been initiated on AFT empirically before yeast identification. Where on-site (1 → 3)-ß-d-glucan (BDG) testing was available (1 day turnaround), in those with suspected but unproven invasive candidiasis, median (IQR) AFT duration was 10 (7-15) days with a positive BDG (≥80 pg/mL) versus 8 (5-9) days with a negative BDG (<80 pg/mL). Post-prescription review occurred in 79% of prescribing episodes (median time to review 1 [0-3] day). Where suspected IFI was not confirmed, 38% episodes were stopped and 4% de-escalated within 5 days. Conclusions: Achieving a better balance between promptly treating IFI patients and avoiding inappropriate antifungal prescribing in the ICU requires timely post-prescription review by specialist multidisciplinary teams and improved, evidence-based-risk prescribing strategies incorporating rapid diagnostics to guide AFT start and stop decisions.

Factors influencing antimicrobial prescription attitudes in bloodstream infections: susceptibility results and beyond. An exploratory survey.

BACKGROUND: Novel rapid antimicrobial susceptibility testing (RAST) methods promise quicker de-escalation of broad-spectrum antibiotics. However, other behavioural and situational factors influencing antimicrobial prescription are not well known. AIM: To explore factors associated with optimal antimicrobial prescription in patients with Gram-negative bloodstream infection and to propose specific scenarios in which a rapid antimicrobial susceptibility result may help to optimize prescribing. METHODS: Exploratory survey (April-August 2018) in the UK and Spain using clinical case-related questions. Seniority, specialty and country of practice were recorded. Cases described patients with Gram-negative bloodstream infections, their empirical treatment and clinical course and the hypothetical RAST result. Respondents chose one of several options regarding antibiotic treatment management. Microbiologically optimal antibiotic choice (MOAC) was agreed by expert consensus beforehand. Responses were categorized as MOAC, request for support or sub-optimal choice. The relationship between the RAST result and the clinical course was defined as concordant (susceptible organism-clinical improvement; resistant organism-clinical deterioration) or as discordant otherwise. FINDINGS: A total of 426 respondents (UK: 332; Spain: 94) and 1494 answers were analysed. Multivariate analysis identified that requests for support were 87% less likely in Spain; that antimicrobial resistance and clinical deterioration were associated with both increased request for support (odds ratio (OR) 7.66 and OR 4.26, respectively) and MOAC (OR 2.08 and OR 2.06, respectively). A discordant clinical course was associated with 82% lower odds for MOAC. Out-of-hours results, seniority and specialty did not have an effect. CONCLUSION: Antimicrobial choice is influenced by each country's type of practice, clinical course and susceptibility results. Antimicrobial resistance was associated with increased optimal treatment, suggesting RAST may be less useful for step-down decisions in settings with low baseline resistance rates.

Detection of meticillin-resistant staphylococcus aureus (MRSA) colonization in newborn infants using real-time polymerase chain reaction (PCR).

OBJECTIVE: Meticillin-resistant staphylococcus aureus (MRSA) colonization on neonatal units is a common and important clinical problem. Effectiveness of polymerase chain reaction (PCR) for detecting MRSA nasal colonization of infants was evaluated and compared to culture-based methods. The effect of skin decolonization in affected infants was studied. METHODS: Paired nasal swabs were collected from infants in our neonatal unit over a 12-month period (September 2007-2008). Colonization with MRSA was determined with a commercially available PCR method and compared to culture. RESULTS: A total of 696 paired nasal swabs were taken. Three infants were colonized at the beginning and were included. There were positive PCRs in 12 infants. Five infants cultured MRSA from a nasal swab at the same time. No infants were culture-positive when PCR was negative (sensitivity 100%, specificity 99% compared to culture). PCR results were available within 24 h. Five infants were PCR+ and isolated meticillin-sensitive Staphylococcus aureus. This organism gave a false-positive PCR result. Two infants transferred in on broad-spectrum antibiotics were PCR+ and negative by culture. Decolonization led to negative nasal PCR and culture in 4/5 infants to discharge. CONCLUSIONS: PCR methods are sensitive and specific for detection of MRSA colonization in newborn infants of all gestations with results 1-2 days before culture.

Implementation of the cobas Liat influenza point-of-care test into an emergency department during a high-incidence season: a retrospective evaluation following real-world implementation.

The cobas Liat influenza A/B and respiratory syncytial virus (RSV) assay (Liat) was used in the adult emergency department of a large London hospital from 21st January 2018 to 14th April 2018. Influenza was detected in 308 of 1027 (30%) samples tested; influenza A in 157 (15.3%), influenza B in 149 (14.5%) and RSV in 28 (2.7%). When compared against Fast Track Diagnostics Respiratory Pathogens 21 multiplex polymerase chain reaction and Cepheid Xpert Xpress Flu/RSV assay, Liat performance for the detection of influenza A or B was: sensitivity 85% [95% confidence interval (CI) 76-92)], specificity 98% (95% CI 97-99), negative predictive value 94% (95% CI 92-96) and positive predictive value 95% (95% CI 91-97).

Implementation of influenza point-of-care testing and patient cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes.

BACKGROUND: During high-incidence influenza seasons, a robust infection prevention and control policy is imperative to reduce nosocomial transmission of influenza. AIM: To assess the impact of influenza point-of-care testing (POCT) in an emergency department (ED) and patient cohorting on an influenza ward on infection prevention and control and clinical outcomes. METHODS: Influenza POCT was operational in the study ED from 21st January 2018 and patient cohorting was operational on an influenza ward from 25th January 2018. A retrospective 'before-after' analysis was performed with pre-intervention defined as 1st November 2017 to 20th January 2018 and post-intervention defined as 21st January 2018 to 30th April 2018. The primary outcome was the rate of hospital-acquired influenza. Secondary outcomes included antiviral prescription and length of stay. The length of time that inpatients remained influenza-positive was estimated by polymerase chain reaction (PCR). FINDINGS: There were 654 inpatients with confirmed influenza during the 2017/18 influenza season: 223 pre- and 431 post-intervention. Post-intervention, there were fewer cases of hospital-acquired influenza per day (0.66 vs 0.95, P < 0.0001), median length of stay was shorter (5.5 vs 7.5 days, P = 0.005) and antiviral prescription was more frequent (80% vs 64.1%, P < 0.0001). Cohorting released 779 single rooms for use elsewhere in the trust. The fixed probability of being PCR-negative by the next day (P) was 0.14 [95% confidence interval (CI) 0.12-0.16] for immunocompetent patients. This implies that half of immunocompetent patients are PCR-negative by five days post-diagnosis (95% CI 5-6). CONCLUSION: Influenza POCT in an ED and patient cohorting on an influenza ward were associated with reduced nosocomial transmission of influenza and improved patient flow. A policy of retesting immunocompetent patients five days post-diagnosis could allow half of these patients to come out of respiratory isolation earlier.

'Test n Treat' (TnT): a cluster randomized feasibility trial of on-site rapid Chlamydia trachomatis tests and treatment in ethnically diverse, sexually active teenagers attending technical colleges.

OBJECTIVES: We conducted a cluster-randomized feasibility trial of 90-minute Chlamydia trachomatis tests and same day on-site treatment ('Test n Treat/TnT') in six technical colleges in London, England, to assess TnT uptake rates; follow-up rates; prevalence of C. trachomatis at baseline and 7 months; time to treatment; acceptability of TnT. METHODS: Participants completed questionnaires and provided genitourinary samples at baseline and 7 months. Participants were informed that baseline samples would not be tested for 7 months and were advised to get screened independently. Colleges were randomly allocated 1:1 to intervention (TnT) or control (no TnT). One month and 4 months post recruitment, participants at intervention colleges were texted invitations for on-site free C. trachomatis tests. A purposive sample of students who did/did not attend for screening were interviewed (n = 26). RESULTS: Five hundred and nine sexually active students were recruited: median age 17.9 years, 47% male, 50% black ethnicity, 55% reporting two or more sexual partners in the previous year. TnT uptake was 13% (33/259; 95% CI 8.9-17.4%) at 1 month and 10% (26/259; 6.7-14.4%) at 4 months with overall C. trachomatis positivity 5.1% (3/59; 1.1-14.2%). Follow-up at 7 months was 62% (317/509) for questionnaires and 52% (264/509) for samples. C. trachomatis prevalence was 6.2% (31/503) at baseline and 6.1% (16/264) at 7 months. Median time from test to treatment was 15 h. Interviews suggested low test uptake was associated with not feeling at risk, perceptions of stigma, and little knowledge of sexually transmitted infections (STIs). CONCLUSIONS: Despite high C. trachomatis rates at baseline and follow-up, uptake of testing was low. Like many countries, England urgently needs better sex education, including making STI testing routine/normal. Trial registration ISRCTN58038795.

Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multicentre cross-sectional preclinical evaluation.

OBJECTIVES: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). METHODS: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert. RESULTS: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female). CONCLUSIONS: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.

Severe malaria: metabolic complications.

Metabolic complications of severe malaria are some of the most important and potentially treatable manifestations of this deadly disease. The commonest metabolic complications (lactic acidosis and hypoglycaemia) arise from increased host anaerobic metabolism probably due to a mismatch between tissue oxygen supply and requirement. Optimising treatments for these complications should be guided by detailed understanding of their underlying pathophysiology, and may help to reduce the intolerably high case fatality rate of severe malaria.

Lactic acidosis in Gabonese children with severe malaria is unrelated to dehydration.

BACKGROUND: Hyperlactatemia is an important and common complication of severe malaria. We investigated changes in fluid compartment volumes in patients with severe malaria and control patients with the use of bioimpedence analysis. METHODS: We estimated extracellular water and total body water volumes in a total of 180 children: 56 with severe malaria, 94 with moderate malaria, 24 with respiratory tract infection, and 6 with severe diarrhea. RESULTS: There was a mean (+/-SD) decrease in total body water volume of 17+/-24 mL/kg (or 3% of total body water volume) in patients with severe malaria. This compares with a mean (+/-SD) decrease in total body water volume of 33+/-28 mL/kg (or 6% of total body water volume) in patients with severe diarrhea. There was no increase in extracellular water volume in patients with severe malaria, suggesting no significant intravascular volume depletion in patients with severe malaria. There was no relationship between lactatemia and any changes in fluid compartment volumes. CONCLUSIONS: The changes in fluid volumes that were observed are unlikely to be of physiological significance in the pathophysiology of severe malaria.

Metabolic complications of severe malaria.

Metabolic complications of malaria are increasingly recognized as contributing to severe and fatal malaria. Disorders of carbohydrate metabolism, including hypoglycaemia and lactic acidosis, are amongst the most important markers of disease severity both in adults and children infected with Plasmodium falciparum. Amino acid and lipid metabolism are also altered by malaria. In adults, hypoglycaemia is associated with increased glucose turnover and quinine-induced hyperinsulinaemia, which causes increased peripheral uptake of glucose. Hypoglycaemia in children results from a combination of decreased production and/or increased peripheral uptake of glucose, due to increased anaerobic glycolysis. Patients with severe malaria should be monitored frequently for hypoglycaemia and treated rapidly with intravenous glucose if hypoglycaemia is detected. The most common aetiology of hyperlactataemia in severe malaria is probably increased anaerobic glucose metabolism, caused by generalized microvascular sequestration of parasitized erythrocytes that reduces blood flow to tissues. Several potential treatments for hyperlactataemia have been investigated, but their effect on mortality from severe malaria has not been determined.

European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection.

In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among Europe. An electronic search for literature concerning the laboratory diagnosis of CDI was performed. Studies evaluating a commercial laboratory test compared to a reference test were also included in a meta-analysis. The commercial tests that were evaluated included enzyme immunoassays (EIAs) detecting glutamate dehydrogenase, EIAs detecting toxins A and B and nucleic acid amplification tests. Recommendations were formulated by an executive committee, and the strength of recommendations and quality of evidence were graded using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. No single commercial test can be used as a stand-alone test for diagnosing CDI as a result of inadequate positive predictive values at low CDI prevalence. Therefore, the use of a two-step algorithm is recommended. Samples without free toxin detected by toxins A and B EIA but with positive glutamate dehydrogenase EIA, nucleic acid amplification test or toxigenic culture results need clinical evaluation to discern CDI from asymptomatic carriage.

Comparison of methods for the rapid laboratory assessment of children with malaria.

Rapid diagnosis and accurate quantification of Plasmodium falciparum parasitemia are important for the management of malaria. The assessment of disease severity also depends on evaluation of metabolic indexes such as blood glucose and lactate concentrations. Here we describe an accurate and rapid alternative to conventional thick film examination (Lambaréné method). We also assess near-patient methods for measuring blood glucose (OneTouch) and lactate (Accusport). The accuracy of the Lambaréné method is similar to that of thin films. Results from the OneTouch glucose meter also are in good agreement with a YSI 2300 reference meter. Overall, the Accusport lactate meter agrees poorly with the YSI 2300 reference meter. However, the sensitivity and specificity to detect hyperlactatemia (blood lactate > or = 5 mmol/L) are 0.94 and 0.98, respectively.

Nitric oxides in plasma, urine, and cerebrospinal fluid in patients with severe falciparum malaria.

It has been suggested that nitric oxide (NO) plays an important role in the pathogenesis of severe falciparum malaria. Since NO has a very short half-life, nitrate and nitrite (NOx) levels, stable metabolites of NO, are used as measures of NO production. We measured plasma NOx levels in 24 adults with severe falciparum malaria on the Thai-Burmese border. After correction for renal function, there was no correlation between plasma NOx levels, or the total amount of NOx excreted in the urine, and disease severity. Plasma NOx levels decreased after the first 48 hr in all patients (P = 0.007), suggesting decreased NO production. The NOx levels in cerebrospinal fluid (CSF) correlated well with plasma NOx levels, but these did not show a correlation with coma depth, and were not significantly different from those in a healthy control group. These findings do not support the hypothesis that excessive NO production contributes to the pathogenesis of severe falciparum malaria. However, local changes in NO production, e.g., in the central nervous system, might not be reflected in the total NOx production or NOx levels in the CSF.

Plasma glutamine and glutamate concentrations in Gabonese children with Plasmodium falciparum infection.

BACKGROUND: Low plasma glutamine levels in critical illness, neonates and burns patients are associated with poor outcome and increased risk of intercurrent infection. AIM: To investigate the relationship between plasma glutamine/glutamate levels and severity/outcome of malaria. DESIGN: Two-hospital prospective study, with both febrile and healthy controls. METHODS: We measured plasma glutamine and glutamate concentrations in 239 Gabonese patients: 145 children with malaria (86 with severe, 36 with moderate and 23 with uncomplicated disease), 42 healthy children, 44 febrile controls and eight healthy adults, and related findings to conventional markers of disease severity such as plasma lactate. RESULTS: Median (IQR) plasma glutamine was lower in uncomplicated falciparum malaria and in moderate malaria than in healthy controls: 353 (287-474) and 379 (293-448) vs. 485 (428-531) micromol/l, respectively; p<0.01 for both malaria groups vs. controls. In contrast, plasma glutamine was within the normal range in those with severe malaria and in febrile control children: 431 (342-525) and 472 (338-547) micromol/l, respectively. Furthermore, plasma glutamine was significantly higher in the children who died with malaria than in survivors: 514 (374-813) (n=12) vs. 399 (316-475) micromol/l (n=133), respectively; p=0.001. There were no significant differences in plasma glutamate concentrations between any of the study groups. DISCUSSION: In severe malaria, there was a positive correlation between plasma glutamine and lactate levels (p=0.009, r=0.281). This correlation may reflect impaired gluconeogenesis. Glutamine supplementation is probably not justified in severe P. falciparum infection.

Plasma glutamine levels and falciparum malaria.

Glutamine deficiency is associated with increased rates of sepsis and mortality, which can be prevented by glutamine supplementation. Changes in glutamine concentration were examined in Ghanaian children with acute falciparum malaria and control cases. The mean (SD) plasma glutamine concentration was lower in patients with acute malaria (401 (82) mumol/L, n = 50) than in control patients (623 (67) mumol/L, n = 7; P < 0.001). Plasma glutamine concentrations all rose in convalescence. The mean (SD) increase in plasma glutamine was 202 (123) mumol/L (n = 18; P < 0.001) compared with acute infection. We conclude that acute falciparum malaria is associated with large decreases in plasma glutamine and these falls may increase susceptibility to sepsis and dyserythropoeisis.