Encephalitis secondary to nitrous oxide and vitamin B12 deficiency.

A 27-year-old woman presented with confusion, agitation and fever. Having initially been treated as an infective encephalitis case her initial and subsequent lumbar punctures revealed cerebrospinal fluid with a worsening pleocytosis and elevated protein. It was initially felt she had been suffering from tuberculous meningitis and started on treatment it later became apparent that she had a severe vitamin B12 deficiency related to recreational nitrous oxide use. She also was noted to have a peripheral neuropathy. After replacing her vitamin B12 and later stopping her tuberculous medication once cultures were negative her cognition and peripheral neuropathy continued to improve.

Mycobacterium shimoidei: an uncommon non-tuberculous infection in a UK patient.

We present the case of a 69-year-old man with significant respiratory comorbidities who presented with slow growing pulmonary nodules which cavitated. Subsequent sputum sampling grew Mycobacterium shimoidei, a non-tuberculous mycobacterium species and an uncommon cause of infection in the UK. We describe the diagnostic process and subsequent treatment regimen.

Tuberculosis microepidemics among dispersed migrants, Birmingham, UK, 2004-2013.

To determine if local transmission was responsible for rising tuberculosis incidence in a recently dispersed migrant community in Birmingham, UK, during 2004-2013, we conducted enhanced epidemiologic investigation of molecular clusters. This technique identified exact locations of social mixing and chains of apparent recent transmission, which can be helpful for directing resources.

Percutaneous breast implant herniation: a rare complication of miliary TB.

We describe the case of a 46-year-old female patient treated for disseminated tuberculosis (TB) infection involving the lungs, urinary tract and skin. Following initiation of antituberculous therapy, the patient's right breast implant eroded through the overlying skin and was seen to be herniating through the resulting defect. The breast implant was removed under local anaesthetic and histological analysis of the resected tissue demonstrated granuloma formation consistent with periprosthetic TB. Wound healing following implant removal was poor and future breast augmentation surgery was only considered following completion of 12 months anti-TB treatment. This case constitutes the first report in the literature of percutaneous breast implant herniation resulting from periprosthetic infection with TB. A high index of suspicion is required to ensure early detection and timely management of TB and, in cases where periprosthetic pus aspirate is sterile, mycobacterial infection must be actively excluded.

Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study.

BACKGROUND: Tuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks. METHODS: In a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data. FINDINGS: We sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis. The estimated rate of change in DNA sequences was 0.5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0.3-0.7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p<0.0001). Genetic trees and clinical and epidemiological data suggest that super-spreaders were present in two community clusters. INTERPRETATION: Whole-genome sequencing can delineate outbreaks of tuberculosis and allows inference about direction of transmission between cases. The technique could identify super-spreaders and predict the existence of undiagnosed cases, potentially leading to early treatment of infectious patients and their contacts. FUNDING: Medical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.

Multidrug-resistant tuberculosis (MDR-TB) treatment in the UK: a study of injectable use and toxicity in practice.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an increasing challenge to health services globally. Although new drugs are in development, current guidelines still recommend prolonged use of injectable antimicrobials (usually amikacin, kanamycin or capreomycin). The evidence base to inform treatment and monitoring strategies is very limited. METHODS: We conducted a retrospective study of patients initiating injectable antimicrobials for MDR-TB treatment in five UK centres between January 2004 and December 2009. (i) Current treatment and monitoring strategies were reviewed. (ii) The incidence of ototoxicity (defined both clinically and on audiological testing) and factors associated with ototoxicity were investigated using logistic regression. RESULTS: (i) The choice of injectable antimicrobial varied. Of 50 MDR-TB patients, 29/50 (58%) received amikacin, 11/50 (22%) received capreomycin and 10/50 (20%) received streptomycin or a combination; reflecting a difference in policy between centres. Only 21/50 (42%) patients received baseline screening by audiogram within 2 weeks of starting treatment and 16/50 (32%) then had monthly audiograms, with the majority screened more infrequently and 12/50 (24%) receiving no screening. (ii) Of the 50 patients, 14 (28%) experienced ototoxicity, with 9/50 (18%) left with long-term hearing loss. Increased age (P = 0.02), use of amikacin (P = 0.02) and decreased renal function (P = 0.01) were significantly associated with ototoxicity. CONCLUSIONS: There is local variation in both the choice of injectable agent and in ototoxicity screening practices. Long-term morbidity from injectable treatment is significant even in this well-resourced setting, and the data suggest capreomycin might be associated with less ototoxicity when compared with amikacin. There is a need for more high-quality clinical data to inform future guidelines for treatment and monitoring.

Treatment of cryptococcal meningitis in resource limited settings.

PURPOSE OF REVIEW: Cryptococcal meningitis most commonly occurs in advanced HIV. Although diminishing in the developed world with antiretroviral therapy (ART), it remains a major problem in resource-limited settings. ART rollout will improve long-term HIV survival if opportunistic infections are effectively treated. Considering cryptococcal meningitis in that context, this review addresses excess morbidity and mortality in developing countries, treatment in areas of limited drug availability and challenges posed by combined anticryptococcal and HIV therapy. RECENT FINDINGS: From Early Fungicidal Activity (EFA) studies, amphotericin B-flucytosine is best induction therapy but often unavailable; high dose amphotericin B monotherapy may be feasible in some settings. Where fluconazole is the only option, higher doses are more fungicidal. Serum cryptococcal antigen testing may identify patients at highest disease risk and primary prophylaxis is effective; the clinical role of such interventions needs to be established. Timing of ART introduction remains controversial; early initiation risks Immune Reconstitution Disease (IRD) delays may increase mortality. SUMMARY: Amphotericin B based treatment is appropriate where possible. More studies are needed to optimize fluconazole monotherapy doses. Other research priorities include management of raised intracranial pressure, appropriate ART initiation and IRD treatment. Studies should focus on developing countries where problems are greatest.

Healthcare-seeking behaviour and use of traditional healers after snakebite in Hlabisa sub-district, KwaZulu Natal.

OBJECTIVE: To quantify snakebite incidence in Hlabisa sub-district and examine healthcare seeking behaviour, focussing on the use of traditional healers and medications. METHODS: Snakebite incidence was calculated by retrospective register review at Hlabisa Hospital for the period 2000-2005 and at associated primary health care clinics for 2005. Fifty consecutive in-patient snakebite victims were interviewed. Treatment-seeking pathways, bite-to-admission times and factors associated with delay or use of traditional therapy were analysed. RESULTS: The annual hospital snakebite incidence was 53 bites per 100,000 population. In 2005, combined hospital and community incidence was 58 per 100,000. Eighty per cent of admitted snakebite victims used traditional medicine and 62.5% of these consulted a traditional health practitioner (THP). The median time until admission was 7 h 15 min (interquartile range: 4-14.25 h). The median time until THP consultation was 15 min (interquartile range 5-50 min). THP consultation was associated with bite-to-hospital admission delays of more than 6 h [relative risk: 1.82, 95% confidence interval (CI): 1.09-3.03, P = 0.0016). Non-statistically significant trends towards THP use were observed if hospital access was poor or if patients were younger than 9 years.