[Tetanus in Ho Chi Minh City, Vietnam: epidemiological, clinical and outcome features of 389 cases at the Hospital for Tropical Diseases]. / Le tétanos à Hô-Chi-Minh-Ville, Vietnam : épidémiologie, clinique et pronostic, à propos de 389 cas à l'Hôpital des maladies tropicales.

The objective of this study is to describe the different aspects of tetanus during the past recent years in southern Vietnam: epidemiology, clinical picture, management, and death risk factors. It is a retrospective study concerning 389 cases admitted in 2007 and 2008 at the reference Hospital for Tropical Diseases in Ho Chi Minh City. 93% of all cases were generalized tetanus, and 50% were severe cases. A majority of patients were adult males (medium age 43, M/ F sex-ratio 2.9). Half of them underwent tracheotomy and 39% assisted ventilation. Case fatality rate was 6.4%, the lowest reported rate worldwide in the last ten years. Fatalities resulted mainly from neuro-vegetative disorders, essentially cardiogenic shock (28% of all deaths) [OR = 16.95; p < 0.001], sepsis (24%) [OR = 3.25; (p < 0,114], and acute renal failure (16%) [OR = 7,22; p < 0.004]. Age over 60-year [OR = 4.53; p < 0.0001] and a leukocyte count>12.000/mm(3) [OR = 2.32; p < 0.020] were significantly associated with fatal outcome, contrarily to incubation and extension phase durations, or delayed serum administration. Systematic extension of vaccination to all adult males, and improved access to post exposure sero-immunization at all levels of health centres throughout the country may further reduce tetanus burden in Vietnam.

Effect of magnesium sulphate on urinary catecholamine excretion in severe tetanus.

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.

Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial.

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.

Urinary catecholamine excretion in tetanus.

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.

Predicting the clinical outcome of tetanus: the tetanus severity score.

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.

Role of quinine in the high mortality of intramuscular injection tetanus.

There has been considerable uncertainty about the risks and severity of tetanus after intramuscular quinine, a widely used treatment of severe malaria in the rural tropics. We have compared the clinical features and outcome of tetanus in which injection was the only apparent site of infection with tetanus acquired by other routes in patients admitted to the Centre for Tropical Diseases, Ho Chi Minh City, Vietnam. In 1081 consecutive patients with tetanus treated between Jan 26, 1989, and May 27, 1991, 27 followed intramuscular quinine and 15 followed injections of other drugs. Overall mortality was 26% (285/1081). Mortality in patients who had not had preceding injections was 24% (250/1039) compared with 96% (26/27) in the quinine group (relative risk 4.0, 95% CI 3.5-4.6) (p < 0.0001), and 60% (9/15) in the other injections group (2.5, 1.6-3.8) (p < 0.005). 21 patients (78%) in the quinine group died within 72 h of admission compared with 5 (33%) in the other intramuscular injections group (p < 0.01) and 4 (7%) of 54 matched controls (p < 0.0001). Tetanus that follows intramuscular injections has a poor prognosis, but when it follows intramuscular quinine it is usually rapidly fatal.