No abstract

Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)-and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (IIV), 7 d after vaccination, and 6 wk postpartum. Expression of CD107a (a marker of cytolysis) and production of IFN-γ and macrophage inflammatory protein (MIP) 1β were assessed by flow cytometry. Pregnant women had a significantly increased percentage of NK cells producing a MIP-1β response to pH1N1 virus compared with nonpregnant women pre-IIV [median, 6.66 vs. 0.90% (P = 0.0149)] and 7 d post-IIV [median, 11.23 vs. 2.81% (P = 0.004)], indicating a heightened chemokine response in pregnant women that was further enhanced by the vaccination. Pregnant women also exhibited significantly increased T-cell production of MIP-1β and polyfunctionality in NK and T cells to pH1N1 virus pre-and post-IIV. NK-and T-cell polyfunctionality was also enhanced in pregnant women in response to the H3N2 viral strain. In contrast, pregnant women had significantly reduced NK-and T-cell responses to phorbol 12-myristate 13-acetate and ionomycin. This type of stimulation led to the conclusion that NK-and T-cell responses during pregnancy are suppressed, but clearly this conclusion is not correct relative to the more biologically relevant assays described here. Robust cellular immune responses to influenza during pregnancy could drive pulmonary inflammation, explaining increased morbidity and mortality.

The persistent DNA methylation perturbations we have identified are a plausible explanation for why successful TB therapy must be continued for months after M. tuberculosis culture conversion. These data suggest that it is critical to evaluate whether modulating DNA methylation could effectively augment host antimycobacterial immunity.

Tuberculosis is a major cause of death and disability among children globally, yet children have been neglected in global tuberculosis control efforts. Historically, tuberculosis in children has been thought of as a family disease, and because of this, household contact tracing of children after identification of an adult tuberculosis case has been emphasised as the principal public health intervention. However, the population-level effect of household contact tracing is predicated on the assumption that most paediatric tuberculosis infections are acquired within the household. In this Personal View, we focus on accumulating scientific evidence indicating that the majority of

The highest estimated prevalence of MDR-TB is in India and China. However, the largest number of patients who have been diagnosed with MDR-TB live in the European Region of the WHO. In Belarus, Kazakhstan, Kyrgyzstan, the Republic of Moldova, the Russian Federation and Ukraine, more than 25% of all new patients who have not received treatment for TB in the past, have MDR-TB. 1 Less than one third of notified TB patients worldwide are evaluated with drug susceptibility testing (DST) for RMP; only half of patients with RMP resistance or MDR-TB undergo DST for FQs and second-line injectable drugs. 1 Only 20% of MDR-TB cases have access to adequate treatment. 3,4 It is predicted that the number of patients with MDR-TB and XDR-TB in highburden countries will continue to rise in the coming decades. 5 Treatment for MDR-TB is challenging for patients, relatives, healthcare providers and health systems. 6 The level of drug resistance of the causative strain of M. tuberculosis can be highly variable. 7 Depending on the DST results, current WHO treatment recommendations range from 9 to 20 months of daily combination antibiotic treatment. 8 The treatment is characterised by a high frequency of adverse drug events, often leading to changes in the regimen. 9 Due to high costs, some of the second-line drugs are not available in countries where they are needed most. 10 Despite all of our efforts, according to the latest WHO report, only 55% of patients with MDR-TB and 34% of patients with XDR-TB achieve a successful treatment outcome. 1 Treatment outcomes in MDR-TB and XDR-TB are highly dependent upon available resources. It was recently shown that relapse-free cure-rates in patients with M/XDR-TB can be similar to patients with drug-susceptible TB (DS-TB) when sufficient resources are provided, 11 and treatment can be personalised. 12 The aim of the present article is to update previous TBNET (Tuberculosis Network European Trials) recommendations on the optimal management of patients with M/XDR-TB. 6