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J J Farrar

Publications and source records attributed to J J Farrar.

At least 19 recordsLinked to original sources
PubMed2006

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.

Adult↗
PubMed2006

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.

APACHE↗
PubMed2006

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.

Adolescent↗
PubMed2006

Polymorphisms of the gene coding for copper/zinc superoxide dismutase (SOD1) in patients with Japanese encephalitis.

Japanese encephalitis is the commonest form of encephalitis globally. Most cases develop characteristic encephalitis but some also present with flaccid paralysis. The paralysis is secondary to damage at the alpha motor neurone, the site that is also damaged in amyotrophic lateral sclerosis (ALS). The gene coding for superoxide dismutase 1 (SOD1) is thought to be involved in ALS and may also be linked to susceptibility to Japanese encephalitis. To investigate this possibility, polymorphisms in the SOD1 gene were investigated, in 61 cases of Japanese encephalitis, 61 matched controls and 171 population controls, in Vietnam. Novel polymorphisms, found only in three of the cases and one of the population controls, may be involved with susceptibility to Japanese encephalitis and potentially to other flavivirus infections that lead to damage to the cells of the anterior horn. Further research on this possible association is required.

Adolescent↗
PubMed2004

Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials.

OBJECTIVE: To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia. DESIGN: Cross-sectional survey. SETTING: Pharmacies and shops selling antimalarial drugs in Myanmar (Burma), Lao PDR, Vietnam, Cambodia and Thailand. MAIN OUTCOME MEASURES: Proportion of artemisinin derivatives or mefloquine containing drugs of substandard quality. RESULTS: Of the 188 tablet packs purchased which were labelled as 'artesunate' 53% did not contain any artesunate. All counterfeit artesunate tablets were labelled as manufactured by 'Guilin Pharma', and refinements of the fake blisterpacks made them often hard to distinguish from their genuine counterparts. No other artemisinin derivatives were found to be counterfeited. Of the 44 mefloquine samples, 9% contained <10% of the expected amount of active ingredient. CONCLUSIONS: An alarmingly high proportion of antimalarial drugs bought in pharmacies and shops in mainland SE Asia are counterfeit, and the problem has increased significantly compared with our previous survey in 1999-2000. This is a serious threat to public health in the region.

Antimalarials↗
PubMed2004

The role of the polymerase chain reaction in the diagnosis of bacterial meningitis in Vietnam.

Bacterial meningitis remains an important cause of morbidity and mortality in Vietnam. Diagnosis is hampered by the ready availability of antibiotics in the community, leading to late presentation, masked clinical signs, and poor organism detection during the microscopical examination and culture of cerebrospinal fluid (CSF). In order to improve organism detection at the Hospital for Tropical Diseases in Ho Chi Minh City, a diagnostic PCR-based protocol was developed. This protocol was followed in the investigation of CSF samples from 36 patients with clinical signs of bacterial meningitis. Each sample was first tested in a semi-nested PCR using primers for the 16sRNA gene common to all bacteria. The products of this reaction were then amplified using a 16sru8 primer and primers specific for Neisseria meningitidis, Haemophilus influenzae or Streptococcus spp. The samples found positive for Streptococcus were further investigated in a nested PCR using primers specific for the pneumolysin gene of S. pneumoniae. The sensitivity of detection was increased from 36% with culture to 44% with PCR. Although the sample size was small, the results indicate that PCR would be a feasible and useful adjunct in the diagnosis of bacterial meningitis, particularly in areas where community antibiotic use is common.

Antigens, Bacterial↗
PubMed2003

Characterization of rotaviruses causing diarrhoea in Vietnamese children.

Faecal samples from 123 children admitted to the Centre for Tropical Diseases in Ho Chi Minh city, Vietnam, with acute watery diarrhoea were screened by negative-stain electron microscopy for viral enteropathogens. In addition to the 48 children who were found to be infected with rotavirus only, one had both rotavirus and astrovirus, two had adenovirus 40/41, and one had astrovirus only. The rotaviruses were subjected to molecular analysis by electropherotyping, G- and P-genotyping (by reverse-transcriptase PCR), and amplicon sequencing. By use of newly designed PCR primers, all 49 isolates could be G-genotyped and all but one P-genotyped. Novel variants of G1-G1*--were the most commonly detected G-genotype and such variants of P[8]-P[8*]--were the second commonest P-genotype. The P[8*] and G1* amplicons were, respectively, only 92%-93.4% and 88.1%-89% similar to the corresponding sequences from the prototype P[8] G1 rotavirus, Wa. Several unusual P- and G-genotype combinations were detected. Four (8%) of the children investigated were each found to be co-infected with two different rotaviruses. These data add to our knowledge of the continuing evolution and diversity of human rotaviruses, and should help in the rational design of vaccines.

Adenoviridae↗
PubMed2002

Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features.

BACKGROUND: The diagnosis of tuberculous meningitis is difficult. Discrimination of cases from those of bacterial meningitis by clinical features alone is often impossible, and current laboratory methods remain inadequate or inaccessible in developing countries. We aimed to create a simple diagnostic aid for tuberculous meningitis in adults on the basis of clinical and basic laboratory features. METHODS: We compared the clinical and laboratory features on admission of 251 adults at an infectious disease hospital in Vietnam who satisfied diagnostic criteria for tuberculous (n=143) or bacterial (n=108) meningitis. Features independently predictive of tuberculous meningitis were modelled by multivariate logistic regression to create a diagnostic rule, and by a classification-tree method. The performance of both diagnostic aids was assessed by resubstitution and prospective test data methods. FINDINGS: Five features were predictive of a diagnosis of tuberculous meningitis: age, length of history, white-blood-cell count, total cerebrospinal fluid white-cell count, and cerebrospinal fluid neutrophil proportion. A diagnostic rule developed from these features was 97% sensitive and 91% specific by resubstitution, and 86% sensitive and 79% specific when applied prospectively to a further 42 adults with tuberculous meningitis, and 33 with bacterial meningitis. The corresponding values for the classification tree were 99% and 93% by resubstitution, and 88% and 70% with prospective test data. INTERPRETATION: This study suggests that simple clinical and laboratory data can help in the diagnosis of adults with tuberculous meningitis. Although the usefulness of the diagnostic rule will vary depending on the prevalence of tuberculosis and HIV-1 infection, we suggest it be applied to adults with meningitis and a low cerebrospinal fluid glucose, particularly in settings with limited microbiological resources.

Adolescent↗
PubMed2002

Isoniazid resistance, mycobacterial genotype and outcome in Vietnamese adults with tuberculous meningitis.

SETTING: Centre for Tropical Diseases, a 500-bed hospital for infectious diseases in Ho Chi Minh City, Vietnam. OBJECTIVE: The factors that determine outcome in adults with tuberculous meningitis are poorly understood. The objective of the study was to investigate the relationship between admission clinical features, HIV infection, drug resistance, mycobacterial genotype and outcome in adults with tuberculous meningitis. DESIGN: Clinical and laboratory data were recorded prospectively for 56 Vietnamese adults with tuberculous meningitis confirmed by culture of cerebrospinal fluid. Variables associated with in-hospital mortality, IV infection, drug resistance and microbial genotype were assessed by univariate and multivariate analysis. RESULTS: Admission coma score independently predicted death in hospital (OR 0.73, 95%CI 0.61-0.87, P = 0.001). HIV-infected adults with tuberculous meningitis were more likely to be infected with Mycobacterium tuberculosis resistant to isoniazid (P = 0.011) and streptomycin (P = 0.002). Isoniazid resistance, streptomycin resistance, HIV infection and microbial genotype were not associated with increased in-hospital mortality. CONCLUSION: Treatment of tuberculous meningitis before the onset of coma saves lives. Resistance to isoniazid and/or streptomycin does not appear to affect outcome.

Adolescent↗
PubMed2001

Yersinia pestis pFra shows biovar-specific differences and recent common ancestry with a Salmonella enterica serovar Typhi plasmid.

Population genetic studies suggest that Yersinia pestis, the cause of plague, is a clonal pathogen that has recently emerged from Yersinia pseudotuberculosis. Plasmid acquisition is likely to have been a key element in this evolutionary leap from an enteric to a flea-transmitted systemic pathogen. However, the origin of Y. pestis-specific plasmids remains obscure. We demonstrate specific plasmid rearrangements in different Y. pestis strains which distinguish Y. pestis bv. Orientalis strains from other biovars. We also present evidence for plasmid-associated DNA exchange between Y. pestis and the exclusively human pathogen Salmonella enterica serovar Typhi.

Animals↗
PubMed2001

Serology of typhoid fever in an area of endemicity and its relevance to diagnosis.

Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam in which typhoid is endemic, and their usefulness for the diagnosis of typhoid fever was evaluated. The antibody responses to both antigens were highly variable among individuals infected with serotype Typhi, and elevated antibody titers were also detected in a high proportion of serum samples from healthy subjects from the community. In-house enzyme-linked immunosorbent assays (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum antibodies were compared with other serologically based tests for the diagnosis of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM] dipstick, and IDeaL TUBEX). At a specificity of > or =0.93, the sensitivities of the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity, 0.87; specificity, 0.76). The serological assays based on the detection of IgM antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick) had a significantly higher sensitivity than the Widal TO test when used with a single acute-phase serum sample (P < or = 0.007). These tests could be of use for the diagnosis of typhoid fever in patients who have clinical typhoid fever but are culture negative or in regions where bacterial culturing facilities are not available.

Adolescent↗
PubMed2000

Nasal carriage in Vietnamese children of Streptococcus pneumoniae resistant to multiple antimicrobial agents.

Resistance to antimicrobial agents in Streptococcus pneumoniae is increasing rapidly in many Asian countries. There is little recent information concerning resistance levels in Vietnam. A prospective study of pneumococcal carriage in 911 urban and rural Vietnamese children, of whom 44% were nasal carriers, was performed. Carriage was more common in children <5 years old than in those >/=5 years old (192 of 389 [49.4%] versus 212 of 522 [40.6%]; P, 0.01). A total of 136 of 399 isolates (34%) had intermediate susceptibility to penicillin (MIC, 0.1 to 1 mg/liter), and 76 of 399 isolates (19%) showed resistance (MIC, >1.0 mg/liter). A total of 54 of 399 isolates (13%) had intermediate susceptibility to ceftriaxone, and 3 of 399 isolates (1%) were resistant. Penicillin resistance was 21.7 (95% confidence interval, 7.0 to 67.6) times more common in urban than in rural children (35 versus 2%; P, <0.001). More than 40% of isolates from urban children were also resistant to erythromycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Penicillin resistance was independently associated with an urban location when the age of the child was controlled for. Multidrug resistance (resistance to three or more antimicrobial agent groups) was present in 32% of isolates overall but in 39% of isolates with intermediate susceptibility to penicillin and 86% of isolates with penicillin resistance. The predominant serotypes of the S. pneumoniae isolates were 19, 23, 14, 6, and 18. Almost half of the penicillin-resistant isolates serotyped were serotype 23, and these isolates were often multidrug resistant. This study suggests that resistance to penicillin and other antimicrobial agents is common in carriage isolates of S. pneumoniae from children in Vietnam.

Adolescent↗
PubMed2000

A randomized controlled comparison of azithromycin and ofloxacin for treatment of multidrug-resistant or nalidixic acid-resistant enteric fever.

To examine the efficacy and safety of short courses of azithromycin and ofloxacin for treating multidrug-resistant (MDR, i.e., resistant to chloramphenicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxacin (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in an open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolled in the study (86 with Salmonella enterica serovar Typhi and 2 with S. enterica serovar Paratyphi A). Of these, 44 received azithromycin and 44 ofloxacin. A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC(90) (range) of azithromycin was 8 (4 to 16) microgram/ml for the isolates. The MIC(90) (range) of ofloxacin for the nalidixic acid-sensitive isolates was 0.03 (0.015 to 0.06) microgram/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) microgram/ml. There was no significant difference in the overall clinical cure rate with ofloxacin and azithromycin (38 of 44 [86.4%] versus 42 of 44 [95.5%]; P = 0.27) or in the patients infected with nalidixic acid-resistant typhoid (17 of 21 [81.0%] versus 24 of 25 [96.0%]; P = 0.16). However, patients with nalidixic acid-resistant typhoid treated with ofloxacin had a longer fever clearance time compared with those treated with azithromycin (174 [60 to 264] versus 135 [72 to 186] h; P = 0.004) and had positive fecal cultures after the end of treatment (7 of 17 [41%] versus 0 of 19 [0%]; P = 0.002). Both antibiotics were well tolerated. A 5-day course of azithromycin was effective for the treatment of enteric fever due to MDR and nalidixic-acid-resistant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfactory for these strains.

Adolescent↗
PubMed2000

Epidemic typhoid in vietnam: molecular typing of multiple-antibiotic-resistant Salmonella enterica serotype typhi from four outbreaks.

Multidrug-resistant Salmonella enterica serotype Typhi isolates from four outbreaks of typhoid fever in southern Vietnam between 1993 and 1997 were compared. Pulsed-field gel electrophoresis, bacteriophage and plasmid typing, and antibiotic susceptibilities showed that independent outbreaks of multidrug-resistant typhoid fever in southern Vietnam are caused by single bacterial strains. However, different outbreaks do not derive from the clonal expansion of a single multidrug-resistant serotype Typhi strain.

Bacterial Typing Techniques↗
PubMed2000

Tetanus.

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Adolescent↗