[The uncomfortable history of Mary Mallon and typhoid fever]. / De ongemakkelijke geschiedenis van Mary Mallon en de buiktyfus.

Mary Mallon (1869-1938) was an Irish immigrant who worked as a cook for rich families in New York. She was responsible for several outbreaks of typhoid fever since she was an asymptomatic carrier of Salmonella typhi. Because of the danger and fear for new outbreaks, she was held in quarantine for years, against her will. What factors contributed to this decision? Was it necessary to keep her isolated? And what was the role of public opinion and media? The history of Mary Mallon is a sad and tragic chapter in medical history, from which we can still draw important lessons.

Neurocognitive Impairment in a Chronically Well-Suppressed HIV-Infected Population: The Dutch TREVI Cohort Study.

We assessed the value of screening for cognitive abnormalities in a chronically infected HIV population (N = 388) and investigated the association with clinical correlates. The mean age was 48 years (±11), the majority of the patients were male (89%), the median duration of infection was 6 years [interquartile range (IQR) = 2-12], the median CD count was 600 (IQR = 450-780), and 326 (84%) had a viral load below 200 copies/mL. Screening for cognitive complaints was applied using the three Simioni questions and the international HIV dementia scale (iHDS). Neuropsychological assessment (NPA) included 13 well-validated tests assessing motor speed, concentration, and memory. A total of 69 patients completed the NPA. CD4 (nadir), viral load, combination antiretroviral therapy (cART) duration, and the presence of comorbidities were evaluated for associations with NPA result. A total of 127 (33%) reported cognitive complaints during screening. The sensitivity and specificity of the Simioni questions were 82% and 24%, respectively. Adding the iHDS resulted in a sensitivity of 50% and a specificity of 73%. A CD4 nadir count <50 cells/m3 was associated with an abnormal NPA (p = 0.01). Comorbidities were more prevalent in patients with an abnormal NPA, although not statistically significant (p = 0.276). Age, current CD4, viral load, and cART duration were not associated with abnormal NPA. The authors conclude that current screening strategies are insufficient in detecting HIV-associated neurocognitive disorder. A low CD4 nadir is associated with poor neurocognitive outcome in HIV.

Bacterial meningitis in adults after splenectomy and hyposplenic states.

OBJECTIVE: To examine the occurrence, disease course, prognosis, and vaccination status of patients with community-acquired bacterial meningitis with a history of splenectomy or functional hyposplenia. PATIENTS AND METHODS: Patients with bacterial meningitis proven by cerebrospinal fluid culture were prospectively included in a nationwide cohort study between March 1, 2006, and September 1, 2011. Splenectomy or diseases associated with functional hyposplenia were scored for all patients. Vaccination status, clinical features, and outcome of patients with a history of splenectomy or functional hyposplenia were analyzed and compared with patients with normal spleen function. RESULTS: Twenty-four of 965 patients (2.5%) had an abnormal splenic function: 16 had a history of splenectomy and 8 had functional hyposplenia. All patients had pneumococcal meningitis. Pre-illness vaccination status could be retrieved for 19 of 21 patients (90%), and only 6 patients (32%) were adequately vaccinated against pneumococci. Pneumococcal serotype was known in 21 patients; 52% of pneumococcal isolates had a serotype included in the 23-valent vaccine. Vaccine failure occurred in 3 patients. Splenectomized patients more often presented with signs of septic shock compared with patients with a normal spleen (63% vs 24%; P=.02). Outcome was unfavorable in 14 patients (58%), and 6 patients died (25%). CONCLUSION: Splenectomy or functional hyposplenia is an uncommon risk factor for bacterial meningitis but results in a high rate of mortality and unfavorable outcome. Most patients were not adequately vaccinated against Streptococcus pneumoniae.

Common polymorphisms in the complement system and susceptiblity to bacterial meningitis.

OBJECTIVE: Risk factors for susceptibility to bacterial meningitis have been identified, but basic causes of inter-individual differences in susceptibility are largely unknown. METHODS: To determine the effect of genetic variation in the complement system on susceptibility to bacterial meningitis we performed a prospective nationwide genetic association study in patients with community-acquired bacterial meningitis. We genotyped 17 common SNPs (minor allele frequencies >5%) in genes coding for complement components and evaluated functional consequences by measuring complement levels in the cerebrospinal fluid. RESULTS: From March 2006 to June 2009 we included 636 adults with community-acquired bacterial meningitis. DNA was available for 439 patients and 302 controls. Rs1047286 (Pro314Leu) in complement component 3 was associated with reduced susceptibility to bacterial meningitis after correction for multiple testing: the protective Leu/Leu genotype was found in 5 of 435 patients (1%) compared to 15 of 302 controls (5%; odds ratio [OR] 4.50, 95% confidence interval [CI] 1.62-12.50, p = 0.0017). Rs1047286 is in strong linkage disequilibrium with Rs2230199 (C3 Arg102Gly), of which the Arg/Arg genotype was associated with higher CSF levels of C3 and lower levels of C5a and terminal complement complex (TCC; soluble C5b-9), indicating decreased consumption of C3 and less activation of the complement system. Rs1047286 was associated with susceptibility albeit not significantly after Bonferroni correction (OR 1.37, 95% CI 1.01-1.87; p = 0.04). CONCLUSIONS: This study shows an association between a common single nucleotide polymorphism in C3 and susceptibility for community-acquired bacterial meningitis.

Genetic variation in the ß2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults.

Recently, the biased ß2-adrenoceptor/ß-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the ß2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the ß2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the ß2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04-1.76; p = 0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12-2.07; p = 0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60-3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88-4.39]; p = 0.09). In conclusion, we identified an association between a genetic variant in the ß2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the ß2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts.

Community-acquired recurrent bacterial meningitis in adults.

BACKGROUND: Community-acquired recurrent bacterial meningitis in adults is a relatively rare disease. All previous data were derived from small retrospective case series. METHODS: We prospectively evaluated episodes of recurrent bacterial meningitis in a nationwide cohort study in The Netherlands. RESULTS: Thirty-four episodes of recurrent bacterial meningitis were identified among 31 patients; 3 patients experienced 2 episodes during the study period. The mean age was 43 years, and 25 (74%) of 34 episodes occurred in men. Predisposing conditions were involved in 26 (77%) of 34 episodes; the most common predisposing conditions were remote head injury (17 [53%] of 32 episodes) and cerebrospinal fluid (CSF) leakage (9 [32%] of 28 episodes). Lumbar puncture revealed an individual CSF indicator of bacterial meningitis for almost all episodes (88%). The outcome was death for 5 (15%) of 34 episodes; 1 additional patient had a suboptimal score on the Glasgow Outcome Scale. CONCLUSION: We conclude that most patients with recurrent meningitis are male and have predisposing conditions, which, in most cases, are remote head injury or CSF leakage.