Global burden of drug-resistant tuberculosis in children: a mathematical modelling study

Background: After infection with Mycobacterium tuberculosis, children are at an increased risk of progression to tuberculosis disease; a condition that can be challenging to diagnose. New estimation approaches for children have highlighted the gap between incidence and notifications of M tuberculosis, and suggest there are more cases of isoniazid-resistant and multidrug-resistant (MDR) disease than are identified. No work has yet quantified the burden of drug-resistant infection, or accounted for other types of drug resistance or sampling uncertainty. Methods: We combined a mathematical model of tuberculosis in children with an analysis of drug-resistance patterns to produce country-level, regional, and global estimates of drug-resistant infection and disease. We determined drug resistance using data from the Global Project on Antituberculosis Drug Resistance Surveillance at WHO, from surveys and surveillance reported between 1988 and 2014. We combined 1000 sampled proportions for each country from a Bayesian approach with 10 000 sampled country estimates of tuberculosis disease incidence and M tuberculosis infection prevalence. We estimated the proportions of tuberculosis cases at a country level with isoniazid monoresistance, rifampicin monoresistance, multidrug resistance (MDR), fluoroquinolone-resistant multidrug resistance, second-line injectable-resistant multidrug resistance, and extensive multidrug resistance with resistance to both a fluoroquinolone and a second-line injectable (XDR). Findings: We estimated that 850 000 children developed tuberculosis in 2014; 58 000 with isoniazid-monoresistant tuberculosis, 25 000 with MDR tuberculosis, and 1200 with XDR tuberculosis. We estimate 67 million children are infected with M tuberculosis; 5 million with isoniazid monoresistance, 2 million with MDR, and 100 000 with XDR. Africa and southeast Asia have the highest numbers of children with tuberculosis, but the WHO Eastern Mediterranean region, European region, and Western Pacific region also contribute substantially to the burden of drug-resistant tuberculosis because of their much higher proportions of resistance. Interpretation: Far more drug-resistant tuberculosis occurs in children than is diagnosed, and there is a large pool of drug-resistant infection. This finding has implications for approaches to empirical treatment and preventive therapy in some regions of the world

Influence of hatching order and brood size on growth in jackass penguins

Jackass penguins Spheniscus demersus hatch two different-sized eggs asynchronously: the second-hatched chick, being, on average, 59% of the weight of the first-hatched chick on hatching. We examined the effect of hatching order on growth rates of mass, culmen length and culmen depth by comparing: (i) growth rates of first-and second-hatched chicks, and (ii) chicks from experimentally synchronized broods to chicks from normal asynchronous broods. Only growth rates in mass showed significant variation. Within a brood, B chicks grew more slowly than A chicks. The effect of synchronizing a brood was to lower the growth rate of both chicks to that of a B chick, suggesting that equal-sized siblings feed less efficiently. Chicks hatching from larger A eggs, that had been synchronized for age and size with chiçks from B eggs, did not grow faster, indicating that chicks hatching from A and B eggs do not have intrinsically different growth rates. Single-chick nests result usually from egg infertility. Singletons showed only a non-significant trend towards faster growth in mass than offspring in two-chick broods, even though food availability in one-chick nests should be better than in two-chick nests. Overall, hatching order had more impact on growth rates of mass than did brood size or egg dimensions

The global impact of household contact management for children on multidrug-resistant and rifampicin-resistant tuberculosis cases, deaths, and health-system costs in 2019: a modelling study

Background: Estimates suggest that at least 30 000 children develop multidrug-resistant or rifampicin-resistant tuberculosis each year. Despite household contact management (HCM) being widely recommended, it is rarely done. Methods: We used mathematical modelling to evaluate the potential country-level and global effects and cost-effectiveness of multidrug-resistant or rifampicin-resistant tuberculosis HCM for children younger than 15 years who are living with a person with newly diagnosed multidrug-resistant or rifampicin-resistant tuberculosis. We compared a baseline of no HCM with several HCM strategies and tuberculosis preventive therapy regimens, calculating the effect on multidrug-resistant or rifampicin-resistant tuberculosis cases, deaths, and health-system costs. All HCM strategies involved the screening of children for prevalent tuberculosis disease but with tuberculosis preventive therapy either not given or targeted dependent on age, HIV status, and result of tuberculin skin test. We evaluated the use of fluoroquinolones (ie, levofloxacin and moxifloxacin), delamanid, and bedaquiline as tuberculosis preventive therapy. Findings: Compared with a baseline without HCM, HCM for all adults diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis in 2019 would have entailed screening 227 000 children (95% uncertainty interval [UI]: 205 000–252 000) younger than 15 years globally, and averted 2350 tuberculosis deaths (1940–2790), costing an additional US$63 million (74–95 million). If all the children within the household who had been in contact with the person with multidrug-resistant or rifampicin-resistant tuberculosis received tuberculosis preventive therapy with levofloxacin, 5620 incident tuberculosis cases (95% UI 4540–6890) and an additional 1240 deaths (970–1540) would have been prevented. Incremental cost-effectiveness ratios were lower than half of per-capita gross domestic product for most interventions in most countries. Targeting only children younger than 5 years and those living with HIV reduced the number of incident cases and deaths averted, but improved cost-effectiveness. Tuberculosis preventive therapy with delamanid increased the effect, in terms of reduced incidence and mortality, compared with levofloxacin. Interpretation: HCM for patients with multidrug-resistant or rifampicin-resistant tuberculosis is cost-effective in most settings and could avert a substantial proportion of multidrug-resistant or rifampicin-resistant tuberculosis cases and deaths in children globally. Funding: UK Medical Research Council

Global impact of COVID-19 on childhood tuberculosis: an analysis of notification data

Background There is concern that the COVID-19 pandemic has damaged global childhood tuberculosis management. Quantifying changes in childhood tuberculosis notifications could support more targeted interventions to restore childhood tuberculosis services. We aimed to use time-series modelling to evaluate the impact of COVID-19 on child tuberculosis notifications. Methods Annual tuberculosis case notification data reported to WHO by 215 countries were used to calculate annual notification counts for the years 2014–20, stratified by age groups (0–4, 5–14, and ≥15 years) and sex. We used time-series modelling to predict notification counts for 2020, and calculated differences between these predictions and observed notifications in 2020 for each of the six WHO regions and at the country level for 30 countries with high tuberculosis burden. We assessed associations between these differences and the COVID-19 stringency index, a measure of COVID-19 social impact. Findings From 2014 to 2019, annual tuberculosis notification counts increased across all age groups and WHO regions. More males than females in the 0–4 years age group and ≥15 years age group had notifications in all years from 2014 to 2020 and in all WHO regions. In the 5–14 years age group, more females than males were notified globally in all years, although some WHO regions had higher notifications from males than females. In 2020, global notifications were 35·4% lower than predicted (95% prediction interval –30·3 to –39·9; 142 525 observed vs 220 794 predicted notifications [95% prediction interval 204 509 to 237 078]) for children aged 0–4 years, 27·7% lower (–23·4 to –31·5; 256 398 vs 354 578 [334 724 to 374 431]) in children aged 5–14 years, and 18·8% lower (–15·4 to –21·9; 5 391 753 vs 6 639 547 [6 375 086 to 6 904 007]) for people aged 15 years or older. Among those aged 5–14 years, the reduction in observed relative to predicted notifications for 2020 was greater in males (–30·9% [–24·8 to –36·1]) than females (–24·5% [–18·1 to –29·9]). Among 28 countries with high tuberculosis burden, no association was observed between the stringency of COVID-19 restrictions and the relative difference in observed versus predicted notifications. Interpretation Our findings suggest that COVID-19 has substantially affected childhood tuberculosis services, with the youngest children most affected. Although children have mostly had fewer severe health consequences from COVID-19 than have adults, they have been disproportionately affected by the effects of the pandemic on tuberculosis care. Observed sex differences suggest that targeted interventions might be required. As countries rebuild health systems following the COVID-19 pandemic, it is crucial that childhood tuberculosis services are placed centrally within national strategic plans

Counting children with tuberculosis: why numbers matter.

In the last 5 years, childhood tuberculosis (TB) has received increasing attention from international organisations, national TB programmes and academics. For the first time, a number of different groups are developing techniques to estimate the burden of childhood TB. We review the challenges in diagnosing TB in children and the reasons why cases in children can go unreported. We discuss the importance of an accurate understanding of burden for identifying problems in programme delivery, targeting interventions, monitoring trends, setting targets, allocating resources appropriately and providing strong advocacy. We briefly review the estimates produced by new analytical methods, and outline the reasons for recent improvements in our understanding and potential future directions. We conclude that while innovation, collaboration and better data have improved our understanding of the childhood TB burden, it remains substantially incomplete

A novel method for fine-scale biodiversity assessment and prediction across diverse urban landscapes reveals social deprivation-related inequalities in private, not public spaces

The value of urban biodiversity is increasingly emphasised from both social and ecological perspectives, as biodiversity has been linked to providing multiple benefits ranging from supporting city sustainability to enhancing the health and well-being of individual residents. At present many urban studies lack integrated methods of assessing urban biodiversity that would allow the capture of both social and ecological values of green space and enable better management and planning for urban biodiversity. Here we introduce a method of scoring urban habitats at a fine scale, which measures habitat attributes that act as biodiversity indicators common to both social and ecological fields. This provides a single, comparable score that represents the capacity of habitats to support biodiversity and people’s connection to that biodiversity. Our results show a clear ranking of urban spaces from those characterised as being wilder and greener, to those dominated by paved surfaces that are more highly managed. We applied this scoring approach to predict and compare biodiversity across neighbourhoods in three New Zealand cities. We found biodiversity across neighbourhoods was significantly related to socioeconomic class, due mainly to the greater cover of mature gardens of high biodiversity value in regions of higher socio-economic status. As such, while all neighbourhoods provided opportunities for residents to connect to nature through public green space, those people living in more deprived neighbourhoods are less likely to be exposed to nearby biodiverse spaces, and therefore may encounter fewer opportunities to connect to nature and gain the benefits which urban biodiversity can afford

Spin-orbit effects at chiral surfaces

Two-dimensional hexagonal and oblique lattices were investigated theoretically with the aim of observing differences in the spin expectation values between chiral and achiral systems. The spinresolved band structures were derived from the energy eigenvalues and eigenfunctions of a Hamiltonian that includes the lattice potential and the spin-orbit interaction. The spin texture of the achiral hexagonal system was shown to have two non-zero components of the spin polarisation, whereas all three components were calculated to be non-zero for the chiral system. The longitudinal component, found to be zero in the achiral lattice, was observed to invert between the enantiomorphs of the chiral lattice. A heuristic model was introduced to discern the origin of this inverting spin polarisation by considering the dynamics of an electron in chiral and achiral lattices. This model was further used to demonstrate the change in magnitude of the spin polarisation as a function of the lattice parameters and an electric field perpendicular to the lattice.Comment: 8 pages, 6 figure