Dr Louise Thwaites

Research Area: Global Health
Scientific Themes: Tropical Medicine & Global Health and Immunology & Infectious Disease

Antimicrobial resistance is a major concern throughout the world. Since the introduction of penicillin, antibiotics have been used so widely that bacteria have adapted and are becoming more and more resistant to them.  OUCRU’s research focuses on the following areas:

  • Emergence of antimicrobial resistance, looking at how and why antibiotic resistance is developing.
  • Preventing resistance to antimicrobials: working out how best to prevent resistance developing.
  • Alternative treatment options: to find the best treatment options for antimicrobial resistant infections.
  • The role of agriculture: to identify of the main drivers of antimicrobial use and resistance in animal production.

There are no collaborations listed for this principal investigator.

Trieu HT, Anh NTK, Vuong HNT, Dao TTM, Hoa NTX, Tuong VNC, Dinh PT, Wills B, Qui PT, Van Tan L et al. 2017. Long-term outcome in survivors of neonatal tetanus following specialist intensive care in Vietnam. BMC Infect Dis, 17 (1), pp. 646. | Show Abstract | Read more

BACKGROUND: Neonatal tetanus continues to occur in many resource-limited settings but there are few data regarding long-term neurological outcome from the disease, especially in settings with critical care facilities. METHODS: We assessed long-term outcome following neonatal tetanus in infants treated in a pediatric intensive care unit in southern Vietnam. Neurological and neurodevelopmental testing was performed in 17 survivors of neonatal tetanus and 18 control children from the same communities using tools previously validated in Vietnamese children. RESULTS: The median age of children assessed was 36 months. Eight neonatal tetanus survivors and 9 community control cases aged < 42 months were tested using the Bayley III Scales of Infant and Toddler Development (Bayley III-VN) and 8 neonatal tetanus survivors and 9 community controls aged ≥42 months were tested using the Movement Assessment Battery for Children. No significant reductions in growth indices or neurodevelopmental scores were shown in survivors of neonatal tetanus compared to controls although there was a trend towards lower scores in neonatal tetanus survivors. Neurological examination was normal in all children except for two neonatal tetanus survivors with perceptive deafness and one child with mild gross motor abnormality. Neonatal tetanus survivors who had expienced severe disease (Ablett grade ≥ 3) had lower total Bayley III-VN scores than those with mild disease (15 (IQR 14-18) vs 24 (IQR 19-27), p = 0.05) with a significantly lower cognitive domain score (3 (IQR 2-6) severe disease vs 7 (IQR 7-8) mild disease, p = 0.02). CONCLUSIONS: Neonatal tetanus is associated with long-term sequelae in those with severe disease. In view of these findings, prevention of neonatal tetanus should remain a priority.

Thuy DB, Campbell J, Hoang NVM, Trinh TTT, Duong HTH, Hieu NC, Duy NHA, Hao NV, Baker S, Thwaites GE et al. 2017. A one-year prospective study of colonization with antimicrobial-resistant organisms on admission to a Vietnamese intensive care unit. PLoS One, 12 (9), pp. e0184847. | Show Abstract | Read more

There is a paucity of data regarding initial bacterial colonization on admission to Intensive Care Units (ICUs) in low and middle-income countries (LMICs). Patients admitted to ICUs in LMICs are at high-risk of subsequent infection with antimicrobial-resistant organisms (AROs). We conducted a prospective, observational study at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam from November 2014 to January 2016 to assess the colonization and antimicrobial susceptibility of Staphylococcus aureus, Escherichia coli, Klebsiella spp., Pseudomonas spp. and Acinetobacter spp. among adult patients within 48 hours of ICU admission. We found the admission colonization prevalence (with at least one of the identified organisms) was 93.7% (785/838) and that of AROs was 63.1% (529/838). The colonization frequency with AROs among patients admitted from the community was comparable to those transferred from other hospitals (62.2% vs 63.8%). Staphylococcus aureus was the most commonly isolated bacteria from nasal swabs (13.1%, 110/838) and the methicillin-resistant Staphylococcus aureus nasal colonization prevalence was 8.6% (72/838). We isolated Escherichia coli from rectal swabs from almost all enrolled patients (88.3%, 740/838) and 52.1% (437/838) of patients were colonized by extended spectrum β-lactamase producing Escherichia coli. Notably, Klebsiella pneumoniae was the most frequently isolated bacteria from the tracheal swabs (11.8%, 18/153). Vietnamese ICU patients have a high rate of colonization with AROs and are thus at risk of subsequent infections with these organisms if good infection control practices are not in place.

Schultz MJ, Dunser MW, Dondorp AM, Adhikari NKJ, Iyer S, Kwizera A, Lubell Y, Papali A, Pisani L, Riviello BD et al. 2017. Current challenges in the management of sepsis in ICUs in resource-poor settings and suggestions for the future. Intensive Care Med, 43 (5), pp. 612-624. | Show Abstract | Read more

BACKGROUND: Sepsis is a major reason for intensive care unit (ICU) admission, also in resource-poor settings. ICUs in low- and middle-income countries (LMICs) face many challenges that could affect patient outcome. AIM: To describe differences between resource-poor and resource-rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU. FINDINGS: Although many bacterial pathogens causing sepsis in LMICs are similar to those in high-income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources. CONCLUSIONS: Addressing both disease-specific and setting-specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost-effective in LMIC setting, more detailed evaluation at both at a macro- and micro-economy level is necessary. Sepsis management in resource-limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.

Thwaites CL. 2017. Botulism and tetanus Medicine, 45 (12), pp. 739-742. | Show Abstract | Read more

© 2017 Botulism and tetanus are diseases caused by neurotoxins produced by Clostridium botulinum and Clostridium tetani, respectively. The bacteria and the toxins they produce are closely related. Both diseases are rare in the UK and the developed world, but tetanus, in particular, is a major cause of death in the developing world, causing between 100,000 and 200,000 deaths each year. In botulism a descending flaccid paralysis occurs, whereas in tetanus generalized muscle spasms develop. Autonomic nervous system dysfunction can occur in either disease, and in tetanus cardiovascular parameters can fluctuate widely. Early involvement of respiratory muscles means that rapid recognition and prompt institution of supportive measures are important in improving survival.

Thuy DB, Campbell JI, Thanh TT, Thuy CT, Loan HT, Hao NV, Minh YL, Tan LV, Boni MF, Thwaites CL. 2017. Tetanus in Southern Vietnam: Current Situation. Am J Trop Med Hyg, 96 (1), pp. 93-96. | Show Abstract | Read more

In Vietnam, there are no accurate data on tetanus incidence to allow assessment of disease burden or vaccination program efficacy. We analyzed age structure of 786 tetanus cases admitted to a tertiary referral center in Vietnam for three separate years during an 18-year period to examine the impact of tetanus prevention programs, namely the Expanded Program on Immunization (EPI) and the Maternal and Neonatal Tetanus (MNT) initiative. Most cases were born before the initiation of EPI. Median age increased from 33 (interquartile range: 20-52) in 1994, to 46 (32-63) in 2012 (P < 0.001). Birth-year distribution was unchanged, indicating the same birth cohorts presented with tetanus in 1994, 2003, and 2012. Enzyme-linked immunosorbent assay measurements in 90 men and 90 women covered by MNT but not EPI showed 73.3% (95% confidence interval [CI]: 62.9-82.1%) of women had anti-tetanus antibody compared with 24.4% (95% CI: 15.9-34.7%) of men, indicating continued tetanus vulnerability in older men in Vietnam.

Thwaites CL, Lundeg G, Dondorp AM, sepsis in resource-limited settings–expert consensus recommendations group* of the European Society of Intensive Care Medicine (ESICM) and the Mahidol-Oxford Research Unit (MORU) in Bangkok, Thailand. 2016. Infection management in patients with sepsis and septic shock in resource-limited settings. Intensive Care Med, 42 (12), pp. 2117-2118. | Read more

Thwaites CL, Lundeg G, Dondorp AM, sepsis in resource-limited settings–expert consensus recommendations group of the European Society of Intensive Care Medicine (ESICM) and the Mahidol-Oxford Research Unit (MORU) in Bangkok, Thailand. 2016. Recommendations for infection management in patients with sepsis and septic shock in resource-limited settings. Intensive Care Med, 42 (12), pp. 2040-2042. | Read more

Hoang VMT, Nguyen TA, Tran TT, Ha MT, Do V, Ho V, Nguyen TH, Huu KT, Le N, Vinh CNV et al. 2016. Clinical features and virology of hand foot mouth disease in Southern Vietnam, July 2013 March 2015 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 45 pp. 20-20. | Read more

Thwaites CL, Loan HT. 2015. Eradication of tetanus. Br Med Bull, 116 (1), pp. 69-77. | Show Abstract | Read more

INTRODUCTION: The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. SOURCES OF DATA: Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. AREAS OF AGREEMENT: The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. AREAS OF CONTROVERSY: Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. AREAS TIMELY FOR DEVELOPING RESEARCH: It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses.

Trieu HT, Lubis IN, Qui PT, Yen LM, Wills B, Thwaites CL, Sabanathan S. 2016. Neonatal Tetanus in Vietnam: Comprehensive Intensive Care Support Improves Mortality. J Pediatric Infect Dis Soc, 5 (2), pp. 227-230. | Show Abstract | Read more

We report a 66% reduction in neonatal tetanus mortality after introducing a new management bundle integrating antibiotic therapy, muscle relaxation and invasive monitoring. The latter allowed rapid detection of autonomic instability which was treated with magnesium sulphate. This is the first report of its use in neonatal tetanus.

Le Minh V, Thi Khanh Nhu N, Vinh Phat V, Thompson C, Huong Lan NP, Thieu Nga TV, Thanh Tam PT, Tuyen HT, Hoang Nhu TD, Van Hao N et al. 2015. In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam. J Med Microbiol, 64 (10), pp. 1162-1169. | Show Abstract | Read more

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

Cited:

25

Scopus

Thwaites CL, Beeching NJ, Newton CR. 2015. Maternal and neonatal tetanus The Lancet, 385 (9965), pp. 362-370. | Read more

Lam PK, Trieu HT, Lubis IND, Loan HT, Thuy TTD, Wills B, Parry CM, Day NPJ, Qui PT, Yen LM, Thwaites CL. 2015. Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants. Int J Infect Dis, 33 pp. 7-11. | Show Abstract | Read more

OBJECTIVES: Most data regarding the prognosis in neonatal tetanus originate from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low- and middle-income countries have affected indicators of a poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcomes in a Vietnamese hospital with neonatal intensive care facilities. METHODS: Data were collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of 'death or prolonged hospital stay'. RESULTS: Multivariable analysis showed that only younger age (odds ratio (OR) for mortality 0.69, 95% confidence interval (CI) 0.48-0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01-0.54) were significantly associated with both the combined endpoint and death. A shorter period of onset (OR 0.94, 95% CI 0.88-0.99), raised white cell count (OR 1.17, 95% CI 1.02-1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14-12.51) were also indicators of mortality. CONCLUSIONS: Risk factors for a poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission, and leukocytosis.

Thwaites CL, Beeching NJ, Newton CR. 2015. Maternal and neonatal tetanus. Lancet, 385 (9965), pp. 362-370. | Show Abstract | Read more

Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58,000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure.

Nhu NTK, Lan NPH, Campbell JI, Parry CM, Thompson C, Tuyen HT, Hoang NVM, Tam PTT, Le VM, Nga TVT et al. 2014. Emergence of carbapenem-resistant Acinetobacter baumannii as the major cause of ventilator-associated pneumonia in intensive care unit patients at an infectious disease hospital in southern Vietnam. J Med Microbiol, 63 (Pt 10), pp. 1386-1394. | Show Abstract | Read more

Ventilator-associated pneumonia (VAP) is a serious healthcare-associated infection that affects up to 30 % of intubated and mechanically ventilated patients in intensive care units (ICUs) worldwide. The bacterial aetiology and corresponding antimicrobial susceptibility of VAP is highly variable, and can differ between countries, national provinces and even between different wards in the same hospital. We aimed to understand and document changes in the causative agents of VAP and their antimicrobial susceptibility profiles retrospectively over an 11 year period in a major infectious disease hospital in southern Vietnam. Our analysis outlined a significant shift from Pseudomonas aeruginosa to Acinetobacter spp. as the most prevalent bacteria isolated from quantitative tracheal aspirates in patients with VAP in this setting. Antimicrobial resistance was common across all bacterial species and we found a marked proportional annual increase in carbapenem-resistant Acinetobacter spp. over a 3 year period from 2008 (annual trend; odds ratio 1.656, P = 0.010). We further investigated the possible emergence of a carbapenem-resistant Acinetobacter baumannii clone by multiple-locus variable number tandem repeat analysis, finding a blaOXA-23-positive strain that was associated with an upsurge in the isolation of this pathogen. We additionally identified a single blaNDM-1-positive A. baumannii isolate. This work highlights the emergence of a carbapenem-resistant clone of A. baumannii and a worrying trend of antimicrobial resistance in the ICU of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

Sabanathan S, Tan LV, Thwaites L, Wills B, Qui PT, Rogier van Doorn H. 2014. Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges. J Epidemiol Community Health, 68 (6), pp. 500-502. | Read more

Cited:

23

Scopus

Sabanathan S, Van Tan L, Thwaites L, Wills B, Qui PT, Van Doorn HR. 2014. Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: Current situation and ongoing challenges Journal of Epidemiology and Community Health, 68 (6), pp. 500-502. | Read more

Thwaites GE, Thwaites CL. 2012. Tetanus pp. 508-510. | Read more

Loan HT, Parry J, Nga NTN, Yen LM, Binh NT, Thuy TTD, Duong NM, Campbell JI, Thwaites L, Farrar JJ, Parry CM. 2012. Semi-recumbent body position fails to prevent healthcare-associated pneumonia in Vietnamese patients with severe tetanus Transactions of the Royal Society of Tropical Medicine and Hygiene, 106 (2), pp. 90-97. | Show Abstract | Read more

Healthcare-associated pneumonia (HCAP) is a common complication in patients with severe tetanus. Nursing tetanus patients in a semi-recumbent body position could reduce the incidence of HCAP. In a randomised controlled trial we compared the occurrence of HCAP in patients with severe tetanus nursed in a semi-recumbent (30°) or supine position. A total of 229 adults and children (aged ≥1 year) with severe tetanus admitted to hospital in Vietnam, were randomly assigned to a supine (n = 112) or semi-recumbent (n = 117) position. For patients maintaining their assigned positions and in hospital for > 48. h there was no significant difference between the two groups in the frequency of clinically suspected pneumonia [22/106 (20.8%) vs 26/104 (25.0%); p = 0.464], pneumonia rate/1000 intensive care unit days (13.9 vs 14.6; p = 0.48) and pneumonia rate/1000 ventilated days (39.2 vs 38.1; p = 0.72). Mortality in the supine patients was 11/112 (9.8%) compared with 17/117 (14.5%) in the semi-recumbent patients (p = 0.277). The overall complication rate [57/112 (50.9%) vs 76/117 (65.0%); p = 0.03] and need for tracheostomy [51/112 (45.5%) vs 69/117 (58.9%); p = 0.04) was greater in semi-recumbent patients. Semi-recumbent body positioning did not prevent the occurrence of HCAP in severe tetanus patients. [Clinical Trials.gov Identifier: NCT01331252]. © 2011 Royal Society of Tropical Medicine and Hygiene.

Loan HT, Parry J, Nga NTN, Yen LM, Binh NT, Thuy TTD, Duong NM, Campbell JI, Thwaites L, Farrar JJ, Parry CM. 2012. Semi-recumbent body position fails to prevent healthcare-associated pneumonia in Vietnamese patients with severe tetanus. Trans R Soc Trop Med Hyg, 106 (2), pp. 90-97. | Show Abstract | Read more

Healthcare-associated pneumonia (HCAP) is a common complication in patients with severe tetanus. Nursing tetanus patients in a semi-recumbent body position could reduce the incidence of HCAP. In a randomised controlled trial we compared the occurrence of HCAP in patients with severe tetanus nursed in a semi-recumbent (30°) or supine position. A total of 229 adults and children (aged ≥1 year) with severe tetanus admitted to hospital in Vietnam, were randomly assigned to a supine (n=112) or semi-recumbent (n=117) position. For patients maintaining their assigned positions and in hospital for>48h there was no significant difference between the two groups in the frequency of clinically suspected pneumonia [22/106 (20.8%) vs 26/104 (25.0%); p=0.464], pneumonia rate/1000 intensive care unit days (13.9 vs 14.6; p=0.48) and pneumonia rate/1000 ventilated days (39.2 vs 38.1; p=0.72). Mortality in the supine patients was 11/112 (9.8%) compared with 17/117 (14.5%) in the semi-recumbent patients (p=0.277). The overall complication rate [57/112 (50.9%) vs 76/117 (65.0%); p=0.03] and need for tracheostomy [51/112 (45.5%) vs 69/117 (58.9%); p=0.04) was greater in semi-recumbent patients. Semi-recumbent body positioning did not prevent the occurrence of HCAP in severe tetanus patients.

Thwaites CL, Yen LM, Cordon SM, Thwaites GE, Loan HT, Thuy TTD, White NJ, Soni N, Macdonald IA, Farrar JJ. 2008. Effect of magnesium sulphate on urinary catecholamine excretion in severe tetanus. Anaesthesia, 63 (7), pp. 719-725. | Show Abstract | Read more

Severe tetanus is characterised by muscle spasms and autonomic dysfunction. We recently reported the results of a randomised placebo controlled trial of magnesium sulphate infusions for the treatment of severe tetanus which showed magnesium was associated with improved muscle spasm and cardiovascular control. We hypothesised that magnesium controlled autonomic dysfunction by reducing catecholamine release and thus urinary excretion. Urinary adrenaline and noradrenaline concentrations were measured during the first 24 h of therapy in 180 adults with severe tetanus randomised to treatment with magnesium (n = 92) or placebo (n = 88). Magnesium therapy was associated with lower urinary adrenaline excretion and higher urinary noradrenaline excretion. High urinary adrenaline concentrations were associated with documented autonomic dysfunction. Patients given magnesium had significantly less autonomic dysfunction, required less cardiovascular stabilising drugs, and had lower urinary concentrations of adrenaline. These findings suggest adrenaline is important in the pathophysiology of severe tetanus and magnesium controls autonomic dysfunction by reducing adrenaline release.

Thwaites CL, Yen LM, Loan HT, Thuy TTD, Thwaites GE, Stepniewska K, Soni N, White NJ, Farrar JJ. 2006. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet, 368 (9545), pp. 1436-1443. | Show Abstract | Read more

BACKGROUND: The most common cause of death in individuals with severe tetanus in the absence of mechanical ventilation is spasm-related respiratory failure, whereas in ventilated patients it is tetanus-associated autonomic dysfunction. Our aim was to determine whether continuous magnesium sulphate infusion reduces the need for mechanical ventilation and improves control of muscle spasms and autonomic instability. METHODS: We did a randomised, double blind, placebo controlled trial in 256 Vietnamese patients over age 15 years with severe tetanus admitted to the Hospital for Tropical Medicine, Ho Chi Minh City, Vietnam. Participants were randomly assigned magnesium sulphate (n=97) or placebo solution (n=98) intravenously for 7 days. The primary outcomes were requirement of assisted ventilation and of drugs to control muscle spasms and cardiovascular instability within the 7-day study period. Analyses were done by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN74651862. FINDINGS: No patients were lost to follow-up. There was no difference in requirement for mechanical ventilation between individuals treated with magnesium and those receiving placebo (odds ratio 0.71, 95% CI 0.36-1.40; p=0.324); survival was also much the same in the two groups. However, compared with the placebo group, patients receiving magnesium required significantly less midazolam (7.1 mg/kg per day [0.1-47.9] vs 1.4 mg/kg per day [0.0-17.3]; p=0.026) and pipecuronium (2.3 mg/kg per day [0.0-33.0] vs 0.0 mg/kg per day [0.0-14.8]; p=0.005) to control muscle spasms and associated tachycardia. Individuals receiving magnesium were 4.7 (1.4-15.9) times less likely to require verapamil to treat cardiovascular instability than those in the placebo group. The incidence of adverse events was not different between the groups. INTERPRETATION: Magnesium infusion does not reduce the need for mechanical ventilation in adults with severe tetanus but does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability.

Thwaites CL, Yen LM, Cordon SM, Binh NT, T N, Nga N, White NJ, Soni N, MacDonald IA, Farrar JJ. 2006. Urinary catecholamine excretion in tetanus. Anaesthesia, 61 (4), pp. 355-359. | Show Abstract | Read more

Imperfect understanding of the pathophysiology of tetanus has limited therapeutic advances. Autonomic disturbance is a major cause of mortality and is believed to be associated with catecholamine release, predominantly norepinephrine. We measured epinephrine and norepinephrine concentrations in 24-h urine collections from tetanus and critically ill patients suffering from other severe diseases. In patients with severe tetanus, mean (SD) epinephrine was 164.18 (129.37) nmol x day(-1) compared with 45.18 (37.74) nmol x day(-1) in mild-moderate disease (p = 0.008). In the severe group, mean (SD) norepinephrine was 411.64 (208.5), and 121.00 (81.81) nmol x day(-1) in moderately ill patients (p < 0.001). Compared with critically ill control patients, median epinephrine was 331.77 in tetanus patients and 89.70 nmol x day(-1) in controls (p < 0.001). Median norepinephrine concentration was 788.02 nmol x day(-1) in tetanus and 300.05 nmol x day(-1) in control patients, p = 0.006. The study finds a novel result of increased epinephrine excretion in tetanus and confirms that catecholamine excretion in tetanus exceeds that in other critically ill patients. These results should be considered in designing more effective therapeutic strategies.

Thwaites CL, Yen LM, Glover C, Tuan PQ, Nga NTN, Parry J, Loan HT, Bethell D, Day NPJ, White NJ et al. 2006. Predicting the clinical outcome of tetanus: the tetanus severity score. Trop Med Int Health, 11 (3), pp. 279-287. | Show Abstract | Read more

OBJECTIVES: To create a new tetanus score and compare it with the Phillips and Dakar scores. METHODS: We used prospectively acquired data from consecutive patients admitted to the Hospital for Tropical Diseases, Ho Chi Minh City, to create the Tetanus Severity Score (TSS) with multivariate logistic regression. We compared the new score with Phillips and Dakar scores by means of resubstituted and prospective data, assessing performance in terms of sensitivity, specificity and area under receiver operator characteristic curves. RESULTS: Resubstitution testing yielded a sensitivity of 77% (298/385) and a specificity of 82% (1,183/1,437) for the TSS; 89% (342/385) and 20% (281/1,437) for the Phillips score; and 13% (49/385) and 98% (1,415/1,437) for the Dakar score. The TSS showed greatest discrimination with 0.89 area under the receiver operator characteristic curve (95% CI 0.88-0.90); this was 0.74 for the Dakar score and (95% CI 0.71-0.77) and 0.66 for the Phillips score (95% CI 0.63-0.70; P values <0.001). Prospective testing showed 65% (13/20) sensitivity and 91% (210/230) specificity for the TSS; 80% (16/20) and 51% (118/230) for the Phillips score; and 25% (5/20) and 96% (221/230) for the Dakar score. The TSS achieved the greatest area under TSS of 0.89 (95% CI 0.82-0.96), significantly greater than the Phillips score [0.74 (0.6-0.88), P = 0.049] but not the Dakar score [0.80, (0.71-0.90), P = 0.090]. CONCLUSIONS: The TSS is the first prospectively developed classification scheme for tetanus and should be adopted to aid clinical triage and management and as a basis for clinical research.

Thwaites CL. 2005. Tetanus Current Anaesthesia & Critical Care, 16 (1), pp. 50-57. | Show Abstract | Read more

Despite long-standing availability of a vaccine, tetanus continues to cause high morbidity and mortality throughout the world. In the developed world, the elderly have traditionally been most at risk due to decline in protective antibody levels, however recent cases have occurred in younger people, particularly injecting drug users. Much of the management is supportive, although treatment aimed at preventing toxin release and uptake into the central nervous system should be given. Recent studies have focussed on optimizing antitoxin effect and improving control of muscle spasms and cardiovascular instability. This paper reviews these and other current concepts regarding the pathophysiology and management of tetanus. © 2005 Elsevier Ltd. All rights reserved.

Thwaites CL, Yen LM, Nga NTN, Parry J, Binh NT, Loan HT, Thuy TTD, Bethell D, Parry CM, White NJ et al. 2004. Impact of improved vaccination programme and intensive care facilities on incidence and outcome of tetanus in southern Vietnam, 1993-2002. Trans R Soc Trop Med Hyg, 98 (11), pp. 671-677. | Show Abstract | Read more

Unvaccinated individuals throughout the world are vulnerable to tetanus, but there are few data regarding the impact of focused vaccination programmes and modern intensive care facilities on the disease, particularly in the developing world. The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam admitted 2422 patients with tetanus aged > or =1 year between April 1993 and December 2002, during which time vaccine coverage and treatment facilities improved. The proportion of children < or =10 years old admitted with tetanus fell from 11.1 to 5.6% over the 10 year period (P = 0.002). The proportion of women aged 20-40 years fell from 10.1 to 1.2% (P < 0.001). Mortality rates fell from a maximum of 27.81% in 1994 to 10.04% in 2002 (P < 0.001). Thus, a marked reduction in tetanus incidence has occurred in age groups specifically targeted by the national vaccination programme. However, tetanus continues to be a major cause of morbidity and mortality in individuals outside the target population. Improved intensive care facilities, such as mechanical ventilation and low-cost infection control procedures are associated with a significant reduction in mortality.

Thwaites G, Thwaites L, Hien TT, Farrar J. 2003. Ethics of large clinical trials in rapidly lethal diseases. Lancet, 361 (9365), pp. 1296. | Read more

Thwaites CL, Farrar JJ. 2003. Magnesium sulphate as a first line therapy in the management of tetanus. Anaesthesia, 58 (3), pp. 286. | Read more

Thwaites CL, Farrar JJ. 2003. Preventing and treating tetanus. BMJ, 326 (7381), pp. 117-118. | Read more

Thwaites G, Thwaites L, Hien TT, Farrar J. 2003. Ethics of large clinical trials in rapidly lethal diseases. Lancet, 361 (9365), pp. 1296.

Thwaites CL. 2002. Tetanus Practical Neurology, 2 (3), pp. 130-137. | Read more

2770