Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis.

Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6-3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care ("default") over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion

Decolonising global health in the time of COVID-19

The persistent influence of coloniality both from external actors and from within threatens the response to COVID-19 in Africa. This essay presents historical context for the colonial inheritance of modern global health and analyses two controversies related to COVID-19 that illustrate facets of coloniality: comments made by French researchers regarding the testing of BCG vaccine in Africa, and the claims by Madagascar’s president Andry Rajoelina that the country had developed an effective traditional remedy named Covid-Organics. Leveraging both historical sources and contemporary documentary sources, I demonstrate how the currents of exploitation, marginalisation, pathologisation and saviourism rooted in coloniality are manifested via these events. I also discuss responses to coloniality, focussing on the misuse and co-optation of pan-Africanist rhetoric. In particular, I argue that the scandal surrounding Covid-Organics is a reflection of endogenised coloniality, whereby local elites entrench and benefit from inequitable power structures at the intersubjective (rather than trans-national) scale. I conclude with a reflection on the need for equity as a guiding principle to dismantle global health colonialism

Selected key input parameters for estimating transmission impact of shorter TB regimens^*.

<p>* Additional model parameters are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096389#pone-0096389-t001" target="_blank">Table 1</a></p>†<p>The transmission rate was initially calibrated to TB incidence. In sensitivity analyses, incidence was varied by varying one of these two parameters (both gave similar results); the two parameters were then also varied over the ranges listed, with the other parameter varied to maintain constant incidence.</p

Model compartments and transition rates.

<p>Boxes represent the proportions of the modeled population that are susceptible to infection, latently infected with <i>M. tuberculosis</i>, in active TB disease, under treatment, or cured. Arrows represent the transitions between various states, including up to four sequential phases of treatment. Rates of transition are described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096389#s2" target="_blank">Methods</a> section and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096389#pone.0096389.s001" target="_blank">Appendix S1</a>.</p

Reduction in TB incidence and mortality achievable from shorter-course regimens over time.

<p>Assuming TB incidence of 125 per 100,000/year, and 7% overall treatment default, the implementation of a four-month regimen vs. a six-month regimen results in a 1.9% reduction in incidence at 10 years (vertical line marks year 10 after introduction of a new regimen). Hypothetical two-month and two-week regimens decrease incidence by 4.3% and 6.7% respectively.</p

Sensitivity analyses.

<p>One-way and two-way sensitivity analyses of the difference in incidence at year 10 after introduction of a four-month regimen versus continuation of a six-month regimen of equal efficacy. A) One-way sensitivity analyses. Input parameters were varied one at a time within ranges consistent with estimates in the literature (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096389#pone-0096389-t002" target="_blank">Table 2</a>). In this figure, we varied incidence by varying the transmission rate, but no major differences were observed when we instead varied the proportion of rapid progression to active disease. The parameters that most significantly influenced the impact of a four-month vs. six-month treatment regimen were the degree of protection afforded by latent infection, incidence of TB disease, and the proportion of treated patients who default at baseline. B) Two-way sensitivity analysis. The two most influential parameters likely to vary widely across epidemiological settings (TB disease incidence and proportion of treated patients defaulting at baseline) were varied simultaneously in a stepwise manner, within a range consistent with estimates in the literature and various epidemiologic settings (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096389#pone-0096389-t002" target="_blank">Table 2</a>). Colors correspond to the range of projected incidence reduction for each combination of baseline incidence and treatment default and selected countries with representative estimates are shown. The highest estimates for both treatment default (25%) and baseline incidence (1,000 per 100,000/year) resulted in no more than 8.3% incidence reduction with a four-month vs. six-month regimen at 10 years.</p

Proportion cured after default, by treatment phase and regimen duration.

<p>The proportion cured after default in a six-month treatment regimen was based on outcomes of early TB treatment clinical trials. For each hypothetical shortened treatment regimen, the proportion cured after default is increased according to the proportion of the total treatment duration completed. Detailed examples of calculations are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096389#pone.0096389.s001" target="_blank">Appendix S1</a>.</p

Model inputs for TB treatment outcomes, by treatment phase.

<p>Model inputs for TB treatment outcomes, by treatment phase.</p

Willingness to Get the COVID-19 Vaccine among Residents of Slum Settlements

Slum residents are more vulnerable to COVID-19 infection. Without a specific treatment, vaccination became the main strategy against COVID-19. In this study, we determined the rate and factors associated with the willingness to get vaccinated against COVID-19 among slum residents and their main reasons associated with the vaccine intention. The study was conducted in Pau da Lima, a slum community in Salvador Brazil. In total, 985 residents were interviewed. Among them 66.0% (650/985) were willing to get vaccinated, 26.1% (257/985) were hesitant to take the vaccine and 7.9% (78/285) were not sure. The main reasons cited for vaccine hesitancy or being unsure were concerns about vaccine efficacy and potential side effects. In contrast, the main reasons cited for wanting the vaccine were the high incidence of COVID-19 cases and participants’ self-perception of their own health history. Multivariate analysis identified that COVID-19 vaccine hesitancy was associated with younger age and low social capital, summarized as low perceived importance of vaccination to protect one’s family, friends and community. Slum residents have been less willing to vaccinate than the general population. Social capital presents a critical opportunity in the design of communication campaigns to increase COVID-19 vaccine acceptance in slum settings