Amedeo Modigliani and his "great secret": a brief history of medical and social aspects of tuberculosis in the nineteenth and early twentieth century.

The pathography of the famous painter and sculptor Amedeo Modigliani (1884-1920) shows that he had tuberculosis and died of tubercular meningitis aged 35. The nineteenth century was characterized by numerous milestones in the history of tuberculosis. In 1853, Hermann Brehmer, first used the term tuberculosis referred to at the time as "phthisis". In 1865, Jean Antoine Villemin demonstrated the infectious etiology of the disease. This was confirmed in 1882 by Robert Koch by identifying the tubercle bacillus. Koch also invented the diagnostic tuberculin test. Charles Mantoux and Florence Seibert improved this test. Identification of the infectious etiology of tuberculosis led to experiments of effective treatments for this disease. The most successful treatment for tuberculosis was by sanatorium regime. From the late nineteenth century, more invasive therapeutic approaches such as artificial pneumothorax were introduced. The advent of streptomycin in 1945 changed the social view of tuberculosis. This previously romanticized disease became a social stigma which was associated with poor social and moral standards; patients were kept in isolation. Fearing social ostracism, Modigliani refused treatment for tuberculosis and instead deliberately fostered his reputation as an alcoholic and addict in order to conceal the disease.

A treatment-support intervention evaluated in South African paediatric populations with HIV infection or tuberculous meningitis.

OBJECTIVES: To evaluate a paediatric treatment-support intervention for home-based treatment of HIV infection or tuberculous meningitis (TBM). METHODS: A randomised-controlled study comparing local standard care (controls) with standard care plus intervention (combining adherence education, reinforcement and monitoring) in children aged 0-14 years. We recorded adherence measures (self-report, pill-count, drug-assays for isoniazid and rifampicin in urine and pyrazinamide in saliva), difficulties administering medication and PedsQL™questionnaires for health-related quality-of-life (HRQoL) and family impact. RESULTS: In the HIV group (6-months follow-up, n = 195), more children had above-median HRQoL-scores in the intervention group than in the control group (P = 0.009). Problems reported administering medication declined between baseline and follow-up for controls (P = 0.043). Disclosure of HIV status to the child increased between baseline and follow-up in both groups (intervention P < 0.001; control P = 0.031). In the TBM group (3-months follow-up, n = 43), all adherence measures remained high for both intervention and controls, except for rifampicin which declined between baseline and follow-up in the intervention group (P = 0.031). The intervention group maintained above median HRQoL-scores between baseline and follow-up, when the number of children with above-median HRQoL-scores decreased in the controls (P = 0.063). More children in the intervention group had above-median family impact-scores than controls (P = 0.040). CONCLUSIONS: The low-cost, culturally friendly treatment-support intervention had beneficial effects on health-related quality of life, family impact, caregiver disclosure of HIV status to the child, increased caregiver reporting of medication non-adherence and caregiver reporting of difficulties administering medication. Treatment adherence was not significantly affected in either HIV or TBM group.

[Tuberculous meningoencephalitis revealed by psychiatric disorders: about a case]. / Méningo-encéphalite tuberculeuse révélée par des troubles psychiatriques: à propos d'un cas.

Tuberculous meningoencephalitis is fairly frequent in endemic countries and it is the most severe form of tuberculosis. Therapeutic failure is common because of diagnostic delay. This delay is primarily due to a wide clinical polymorphism and, in particular, to misleading forms. We here report a rare clinical case of tuberculous meningitis in a patient in prodromal phase of psychosis.

Paradoxical improvement of function more than 2 years after onset of tuberculous meningitis.

OBJECTIVE: To document the unexpected improvement made by a 50 year-old patient over 2 years after being diagnosed with tuberculous meningitis (TBM). METHODS: Regular neuropsychological assessments were carried out, initially with a test for patients in reduced states of awareness and later with more demanding tests. RESULTS: The patient was diagnosed with TBM in November 2008 and was mute, stuporous and barely more than minimally conscious for over 2 years. By February 2011, following the cessation of TBM medication, her conscious level had improved and she could be assessed on a range of neuropsychological tests. The patient presented with diffuse cognitive impairments coupled with focal neurological signs, but showed marked improvements in cognitive functioning compared to when admitted. CONCLUSIONS: This study demonstrates that late stage neuropsychological improvement is possible, even after 2 years of showing minimal awareness. Such paradoxical improvement of function is considered in the light of other paradoxical phenomena in TBM, comparisons are offered with similar neurological conditions and possible mechanisms underlying the dramatic improvement that took place are suggested.

Predictors of mortality in tuberculous meningitis: a multivariate analysis of 160 cases.

OBJECTIVE: To evaluate predictors of mortality in 160 patients with tuberculous meningitis (TBM). DESIGN: One hundred and sixty patients with TBM who had been followed for 11 years in a tertiary referral centre hospital were assessed retrospectively. Features considered as predictors of mortality in TBM were studied by multivariate logistic regression to develop a prognostic rule. RESULTS: Of 160 patients, 84% were in Stages II and III; 27 (17%) died. In univariate analysis, age, stage, altered sensorium, underlying comorbidities, pulmonary tuberculosis, leukocytosis and cerebrospinal fluid (CSF)/blood glucose < 0.30 and rise in CSF protein were associated with an increased risk of death. In multivariable analysis, age (OR 4.64, 95%CI 1.03-24.74, P = 0.046), altered sensorium (OR 8.62, 95%CI 1.25-110.0, P = 0.036), underlying comorbidity (OR 9.75, 95%CI 1.58-59.95, P = 0.014) and leukocytosis (OR 9.74, 95%CI 1.67-56.7, P = 0.011) were shown to be the best predictors of mortality in TBM. CONCLUSIONS: We observed that TBM patients who died were more likely to be older and have altered mental status on admission, underlying comorbidities and leukocytosis than TBM patients who survived. These factors were the most important predictors of mortality from TBM.

Perspectives of intellectual disability in South Africa: epidemiology, policy, services for children and adults.

PURPOSE OF REVIEW: This review aims to summarize data published in the scientific literature and available on official websites on the epidemiology, policies and services for children and adults with intellectual disability in South Africa. RECENT FINDINGS: There is a paucity of published literature on intellectual disability in South Africa. The lack of evidence-based publications within the prescribed review period of 12-18 months precludes an accurate description of the prevailing epidemiology and burden of disablement in this country. The few studies yielding epidemiological data were conducted prior to 2002. These suggest that the prevalence rate of intellectual disability is greater than in high-income countries. There is little data describing intellectual disability geographically and across population and age groups, further rendering it difficult to identify inequalities and differences in distribution. There is a high burden of preventable causes of intellectual disability. SUMMARY: Despite the existence of policies and services for the population with intellectual disabilities in South Africa, recognition of and provision for their needs carries low priority. It is imperative that the information gap in epidemiology and the burden of disability be recognized in order to plan for and meet the needs of those with intellectual disability across the lifespan.

Behaviour profiles after tuberculous meningitis.

The purpose of the study was to investigate child behaviour in children who recovered from tuberculous meningitis (TBM) and to compare behaviour profiles of stage II and stage III patients. The mean age of the cohort of 74 children at the time of evaluation was 10 years and 7 months. At follow-up all patients underwent a thorough neurological examination and a psychometric test battery, which included intellectual assessment and evaluation of behaviour by means of the CBCL/6-18. Results indicated elevated mean scores (T > 60) on CBCL/6-18 scales which measure problems with anxiety, depression, attention, social relationships, disruptive and rule-breaking behaviour. Mean CBCL scores of stage III patients were significantly higher than the mean scores of stage II patients on scales which measure social problems, disruptive and rule-breaking behaviour. In addition, problems with conduct, attention, attention-deficit/hyperactivity problems, affective problems as well as the total problem scores were more pronounced in the patients with stage III TBM. We conclude that general behavioural disinhibitions as well as internalized emotional disorder probably are long-term complications in more than 10% of the survivors of TBM.

The benefits and risks of bacille Calmette-Guérin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model.

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccine is given to Canadian Aboriginal neonates in selected communities. Severe reactions and deaths associated with BCG have been reported among infants born with immunodeficiency syndromes. The main objective of this study was to estimate threshold values for severe combined immunodeficiency (SCID) incidence, above which BCG is associated with greater risk than benefit. METHODS: A Markov model was developed to simulate the natural histories of tuberculosis (TB) and SCID in children from birth to 14 years. The annual risk of tuberculous infection (ARI) and SCID incidence were varied in analyses. The model compared a scenario of no vaccination to intervention with BCG. Appropriate variability and uncertainty analyses were conducted. Outcomes included TB incidence and quality-adjusted life years (QALYs). RESULTS: In sensitivity analyses, QALYs were lower among vaccinated infants if the ARI was 0.1% and the rate of SCID was higher than 4.2 per 100,000. Assuming an ARI of 1%, this threshold increased to 41 per 100,000. In uncertainty analyses (Monte Carlo simulations) which assumed an ARI of 0.1%, QALYs were not significantly increased by BCG unless SCID incidence is 0. With this ARI, QALYs were significantly decreased among vaccinated children if SCID incidence exceeds 23 per 100,000. BCG is associated with a significant increase in QALYs if the ARI is 1%, and SCID incidence is below 5 per 100,000. CONCLUSION: The possibility that Canadian Aboriginal children are at increased risk for SCID has serious implications for continued BCG use in this population. In this context, enhanced TB Control--including early detection and treatment of infection--may be a safer, more effective alternative.

[Human immunodeficiency virus-associated tuberculous meningoencephalitis causing abnormal behaviour in a prisoner]. / HIV-assoziierte tuberkulöse Meningoenzephalitis als Ursache abnormen Verhaltens in Haft.

Little is known about the type and frequency of psycho-organic syndromes among prisoners. We report the case of a 20-year-old African HIV-I-positive male asylum seeker who developed increasingly bizarre behaviour in prison. The observation of complex behavioural disturbances with a hallucinatory-delusional state led to the diagnosis of delirium caused by AIDS-defining tuberculous meningoencephalitis. The patient improved with specific, symptomatic treatment. This case illustrates the difficulties in diagnosis when communication is impeded. Scrupulous differential diagnosis is necessary for all prisoners manifesting behavioural disturbances. We discuss the pathogenesis and diagnostic procedures of tuberculous meningoencephalitis.

The effect of tuberculous meningitis on the cognitive and motor development of children.

OBJECTIVE: To evaluate and compare the different degrees of cognitive and motor impairment of children surviving tuberculous meningitis (TBM), with a view to establishing areas amenable to remedial intervention. DESIGN: Neurodevelopmental testing of a previously reported cohort, performed 1-7 years after completion of 9-12 months of treatment of TBM. SETTING: Bloemfontein and environs. PARTICIPANTS: A total of 19 subjects out of a possible 25 (76%) in a geographically accessible area. MAIN OUTCOME MEASURES: Cognitive and fine and gross motor development. RESULTS: Cognitive and motor development were scored and expressed as percentages of those expected for normal children of similar age and background. The median cognitive development was 66.9% (95% confidence intervals (CIs) 59.1-73.2). The degree of impairment was similar for all 10 cognitive areas tested, ranging from 61.8% to 70.4%. The median fine motor development score was 68.6% (95% CIs 54.7-81.5). The median gross motor function score was 51.2% (95% CIs 36.4-77.1). Comparison of impairment between stage 2 and stage 3 disease showed median differences of 28.7% (95% CI 2.7-55.1) (P = 0.02) for cognitive function, 21.6% (95% CI -9.9-54.1) (P = 0.15) for fine motor function, and 35.2% (95% CI 14.2-59.6) (P = 0.01) for gross motor function. No TBM relapses had occurred. CONCLUSIONS: Our findings show the occurrence of marked generalised impairment of cognitive and motor development following TBM, with no specific areas amenable to early remedial intervention. Shortened treatment regimens of 9-12 months were effective, but prevention of TBM remains the priority.

Defaults, defaulter action and retrieval of patients during studies on tuberculous meningitis in children.

Chemotherapy studies were undertaken on 180 children, aged between 1 and 12 years, with tuberculous meningitis. They received therapy for 12 months. As approximately one-half of the patients came from outside Madras city, retrieval action was not possible in all cases of default. Despite this, a high rate of compliance and punctuality was achieved as a result of initial and periodic motivation. This report highlights the role and importance of motivation in the prevention of default and the retrieval of defaulters during the treatment of children with tuberculous meningitis.

Chronic hypothermia following tuberculous meningitis.

A patient who developed chronic hypothermia following tuberculous meningitis is described. A central defect of thermoregulation was discovered, probably due to a discrete vascular lesion in the anterior hypothalmus.