The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security—its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing.

The transmission of Mycobacterium tuberculosis that we describe aboard a commercial aircraft involved a highly infectious passenger, a long flight, and close proximity of contacts to the index patient.

Background We explored the association between anti-tuberculosis drug pharmacokinetics and treatment outcomes among pulmonary tuberculosis (TB) patients in Botswana. Methods Consenting TB outpatients had blood collected 1, 2, and 6 hours after simultaneous isoniazid, rifampin, ethambutol, and pyrazinamide ingestion. Maximum serum concentrations (Cmax) and areas under the serum concentration-time curve (AUC0-6 h) were determined. Clinical status was monitored throughout treatment. Results Of 225 participants, 36 (16%) experienced a poor treatment outcome (treatment failure or death); 155 (69%) were HIV-infected. Compared with published standards, low isoniazid Cmax occurred in 84 (37%); rifampin in 188 (84%); ethambutol in 87 (39%); and pyrazinamide in 11 (5%) patients. Median rifampin and pyrazinamide levels differed significantly by HIV status and CD4 cell count (HIV-CD4) categories. Only pyrazinamide pharmacokinetics were significantly associated with treatment outcome; low pyrazinamide Cmax was associated with a higher risk of documented poor treatment outcome than normal Cmax (50% vs. 16%; p<0.01). HIV-infected patients with CD4 <200 cells/μL had higher risk of poor treatment outcome (27%) than HIV-uninfected patients (11%) or HIV-infected patients with CD4 ≥ 200 cells/μL (12%); p=0.01. Adjusting for HIV infection and CD4, patients with low pyrazinamide Cmax were thrice more likely to have poor outcomes than patients with normal pyrazinamide Cmax [adjusted risk ratio = 3.38, 95% confidence interval (1.84 – 6.22)]. Conclusions Lower-than-expected anti-tuberculosis drug Cmax occurred frequently and low pyrazinamide Cmax was associated with poor treatment outcome. Exploring the global prevalence and significance of these findings may suggest modifications in treatment regimens that could improve TB cure rates.

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