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  1. Dhana A, Hamada Y, Kengne AP, Kerkhoff AD, Rangaka MX, Kredo T, et al.
    Lancet Infect Dis, 2022 Apr;22(4):507-518.
    PMID: 34800394 DOI: 10.1016/S1473-3099(21)00387-X
    BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population.

    METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895.

    FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively.

    INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications.

    FUNDING: World Health Organization.

  2. Schaefer GO, Atuire CA, Kaur S, Parker M, Persad G, Smith MJ, et al.
    Lancet Infect Dis, 2023 Nov;23(11):e489-e496.
    PMID: 37421968 DOI: 10.1016/S1473-3099(23)00364-X
    The COVID-19 pandemic revealed numerous weaknesses in pandemic preparedness and response, including underfunding, inadequate surveillance, and inequitable distribution of countermeasures. To overcome these weaknesses for future pandemics, WHO released a zero draft of a pandemic treaty in February, 2023, and subsequently a revised bureau's text in May, 2023. COVID-19 made clear that pandemic prevention, preparedness, and response reflect choices and value judgements. These decisions are therefore not a purely scientific or technical exercise, but are fundamentally grounded in ethics. The latest treaty draft reflects these ethical considerations by including a section entitled Guiding Principles and Approaches. Most of these principles are ethical-they establish core values that undergird the treaty. Unfortunately, the treaty draft's set of principles are numerous, overlapping, and show inadequate coherence and consistency. We propose two improvements to this section of the draft pandemic treaty. First, key guiding ethical principles should be clearer and more precise than they currently are. Second, the link between ethical principles and policy implementation should be clearly established and define boundaries on acceptable interpretation, ensuring that signatories abide by these principles.
  3. Commons RJ, Simpson JA, Thriemer K, Humphreys GS, Abreha T, Alemu SG, et al.
    Lancet Infect Dis, 2018 Sep;18(9):1025-1034.
    PMID: 30033231 DOI: 10.1016/S1473-3099(18)30348-7
    BACKGROUND: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings.

    METHODS: A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310.

    FINDINGS: Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34·8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32·4% (95% CI 29·8-35·1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0·82, 95% CI 0·69-0·97; p=0·021) and in children younger than 5 years (0·59, 0·41-0·86; p=0·0058). Adding primaquine reduced the risk of recurrence to 4·9% (95% CI 3·1-7·7) by day 42, which is lower than with chloroquine alone (AHR 0·10, 0·05-0·17; p<0·0001).

    INTERPRETATION: Chloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax.

    FUNDING: Wellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.

  4. Fornace KM, Zorello Laporta G, Vythilingham I, Chua TH, Ahmed K, Jeyaprakasam NK, et al.
    Lancet Infect Dis, 2023 Dec;23(12):e520-e532.
    PMID: 37454671 DOI: 10.1016/S1473-3099(23)00298-0
    Simian malaria from wild non-human primate populations is increasingly recognised as a public health threat and is now the main cause of human malaria in Malaysia and some regions of Brazil. In 2022, Malaysia became the first country not to achieve malaria elimination due to zoonotic simian malaria. We review the global distribution and drivers of simian malaria and identify priorities for diagnosis, treatment, surveillance, and control. Environmental change is driving closer interactions between humans and wildlife, with malaria parasites from non-human primates spilling over into human populations and human malaria parasites spilling back into wild non-human primate populations. These complex transmission cycles require new molecular and epidemiological approaches to track parasite spread. Current methods of malaria control are ineffective, with wildlife reservoirs and primarily outdoor-biting mosquito vectors urgently requiring the development of novel control strategies. Without these, simian malaria has the potential to undermine malaria elimination globally.
  5. Rajasekhar M, Simpson JA, Ley B, Edler P, Chu CS, Abreha T, et al.
    Lancet Infect Dis, 2024 Feb;24(2):184-195.
    PMID: 37748497 DOI: 10.1016/S1473-3099(23)00431-0
    BACKGROUND: Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure.

    METHODS: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2-3 and between day 0 and days 5-7 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680.

    FINDINGS: Of 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0·1%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0·375 mg/kg per day), five (0·3%) of 1464 patients treated with an intermediate daily dose (0·375 mg/kg per day to <0·75 mg/kg per day), and six (0·5%) of 1269 patients treated with a high daily dose (≥0·75 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2-3 were -0·6 g/dL (95% CI -0·7 to -0·5), -0·7 g/dL (-0·8 to -0·5), -0·6 g/dL (-0·7 to -0·4), and -0·5 g/dL (-0·7 to -0·4), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2-3 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias.

    INTERPRETATION: Treatment of patients with G6PD activity of 30% or higher with 0·25-0·5 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0·25-1 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses.

    FUNDING: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.

  6. Beran J, Reynales H, Poder A, Yu CY, Pitisuttithum P, Yuan LL, et al.
    Lancet Infect Dis, 2021 07;21(7):1027-1037.
    PMID: 33577767 DOI: 10.1016/S1473-3099(20)30694-0
    BACKGROUND: The absolute degree of protection from influenza vaccines in older adults has not been studied since 2001. This study aimed to show the clinical efficacy of an MF59-adjuvanted quadrivalent influenza vaccine (aQIV) in adults 65 years or older compared with adults not vaccinated to prevent influenza.

    METHODS: We did a randomised, stratified, observer-blind, controlled, multicentre, phase 3 study at 89 sites in 12 countries in 2016-17 northern hemisphere and 2017 southern hemisphere influenza seasons. We enrolled community-dwelling male and female adults aged 65 years and older who were healthy or had comorbidities that increased their risk of influenza complications. We stratified eligible participants by age (cohorts 65-74 years and ≥75 years) and risk of influenza complications (high and low) and randomly assigned them (1:1) via an interactive response technology to receive either aQIV or a non-influenza comparator vaccine. We masked participants and outcome assessors to the administered vaccine. Personnel administering the vaccines did not participate in endpoint assessment. The primary outcome was absolute vaccine efficacy assessed by RT-PCR-confirmed influenza due to any influenza strain in the overall study population (full analysis set) from day 21 to 180 or the end of the influenza season. Vaccine efficacy was calculated on the basis of a Cox proportional hazard regression model for time to first occurrence of RT-PCR-confirmed influenza due to any strain of influenza. Safety outcomes were assessed in the overall study population. This trial was registered with ClinicalTrials.gov, NCT02587221.

    FINDINGS: Northern hemisphere enrolment occurred between Sept 30, 2016, and Feb 28, 2017, and southern hemisphere enrolment between May 26, 2017, and 30 June 30, 2017. aQIV was administered to 3381 participants, who subsequently had 122 (3·6%) RT-PCR-confirmed influenza cases, and the comparator was administered to 3380 participants, who subsequently had 151 (4·5%) influenza cases. The majority, 214 (78·4%) of 273, were caused by influenza A H3N2. Most antigenically characterised isolates were mismatched to the vaccine strain (118 [85%] of 139). Vaccine efficacy was 19·8% (multiplicity-adjusted 95% CI -5·3 to 38·9) against all influenza and 49·9% (-24·0 to 79·8) against antigenically matched strains, when the protocol definition of influenza-like illness was used. The most common local solicited adverse event was injection site pain, reported by 102 (16·3%) of 624 participants in the aQIV group and 71 (11·2%) of 632 of participants in the comparator group. Deaths were evenly distributed; none were considered related to study vaccines. The safety profile for aQIV was similar to previously reported trials.

    INTERPRETATION: The prespecified criterion for showing the efficacy of aQIV in older adults was not met during the influenza seasons with high amounts of vaccine strain mismatch. Vaccine efficacy was higher against influenza cases associated with higher fever, which represent more clinically significant disease.

    FUNDING: Seqirus UK.

  7. Khan MU, Ahmad A, Balkrishnan R
    Lancet Infect Dis, 2017 02;17(2):136.
    PMID: 28134106 DOI: 10.1016/S1473-3099(17)30012-9
  8. Head MG, Fitchett JR, Newell ML, Scott JAG, Clarke SC, Atun R
    Lancet Infect Dis, 2014 Nov;14(11):1037-1038.
    PMID: 25444398 DOI: 10.1016/S1473-3099(14)70949-1
  9. Kleinschmidt I, Bradley J, Knox TB, Mnzava AP, Kafy HT, Mbogo C, et al.
    Lancet Infect Dis, 2018 Jun;18(6):640-649.
    PMID: 29650424 DOI: 10.1016/S1473-3099(18)30172-5
    BACKGROUND: Scale-up of insecticide-based interventions has averted more than 500 million malaria cases since 2000. Increasing insecticide resistance could herald a rebound in disease and mortality. We aimed to investigate whether insecticide resistance was associated with loss of effectiveness of long-lasting insecticidal nets and increased malaria disease burden.

    METHODS: This WHO-coordinated, prospective, observational cohort study was done at 279 clusters (villages or groups of villages in which phenotypic resistance was measurable) in Benin, Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were the principal form of malaria vector control in all study areas; in Sudan this approach was supplemented by indoor residual spraying. Cohorts of children from randomly selected households in each cluster were recruited and followed up by community health workers to measure incidence of clinical malaria and prevalence of infection. Mosquitoes were assessed for susceptibility to pyrethroids using the standard WHO bioassay test. Country-specific results were combined using meta-analysis.

    FINDINGS: Between June 2, 2012, and Nov 4, 2016, 40 000 children were enrolled and assessed for clinical incidence during 1·4 million follow-up visits. 80 000 mosquitoes were assessed for insecticide resistance. Long-lasting insecticidal net users had lower infection prevalence (adjusted odds ratio [OR] 0·63, 95% CI 0·51-0·78) and disease incidence (adjusted rate ratio [RR] 0·62, 0·41-0·94) than did non-users across a range of resistance levels. We found no evidence of an association between insecticide resistance and infection prevalence (adjusted OR 0·86, 0·70-1·06) or incidence (adjusted RR 0·89, 0·72-1·10). Users of nets, although significantly better protected than non-users, were nevertheless subject to high malaria infection risk (ranging from an average incidence in net users of 0·023, [95% CI 0·016-0·033] per person-year in India, to 0·80 [0·65-0·97] per person year in Kenya; and an average infection prevalence in net users of 0·8% [0·5-1·3] in India to an average infection prevalence of 50·8% [43·4-58·2] in Benin).

    INTERPRETATION: Irrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden.

    FUNDING: Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

  10. Zelenev A, Li J, Mazhnaya A, Basu S, Altice FL
    Lancet Infect Dis, 2018 02;18(2):215-224.
    PMID: 29153265 DOI: 10.1016/S1473-3099(17)30676-X
    BACKGROUND: Chronic infections with hepatitis C virus (HCV) and HIV are highly prevalent in the USA and concentrated in people who inject drugs. Treatment as prevention with highly effective new direct-acting antivirals is a prospective HCV elimination strategy. We used network-based modelling to analyse the effect of this strategy in HCV-infected people who inject drugs in a US city.

    METHODS: Five graph models were fit using data from 1574 people who inject drugs in Hartford, CT, USA. We used a degree-corrected stochastic block model, based on goodness-of-fit, to model networks of injection drug users. We simulated transmission of HCV and HIV through this network with varying levels of HCV treatment coverage (0%, 3%, 6%, 12%, or 24%) and varying baseline HCV prevalence in people who inject drugs (30%, 60%, 75%, or 85%). We compared the effectiveness of seven treatment-as-prevention strategies on reducing HCV prevalence over 10 years and 20 years versus no treatment. The strategies consisted of treatment assigned to either a randomly chosen individual who injects drugs or to an individual with the highest number of injection partners. Additional strategies explored the effects of treating either none, half, or all of the injection partners of the selected individual, as well as a strategy based on respondent-driven recruitment into treatment.

    FINDINGS: Our model estimates show that at the highest baseline HCV prevalence in people who inject drugs (85%), expansion of treatment coverage does not substantially reduce HCV prevalence for any treatment-as-prevention strategy. However, when baseline HCV prevalence is 60% or lower, treating more than 120 (12%) individuals per 1000 people who inject drugs per year would probably eliminate HCV within 10 years. On average, assigning treatment randomly to individuals who inject drugs is better than targeting individuals with the most injection partners. Treatment-as-prevention strategies that treat additional network members are among the best performing strategies and can enhance less effective strategies that target the degree (ie, the highest number of injection partners) within the network.

    INTERPRETATION: Successful HCV treatment as prevention should incorporate the baseline HCV prevalence and will achieve the greatest benefit when coverage is sufficiently expanded.

    FUNDING: National Institute on Drug Abuse.

  11. GBD 2021 Tuberculosis Collaborators
    Lancet Infect Dis, 2024 Mar 19.
    PMID: 38518787 DOI: 10.1016/S1473-3099(24)00007-0
    BACKGROUND: Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020.

    METHODS: We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990-2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data.

    FINDINGS: We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5-14 years, 6·29% (5·05 to 7·70) in those aged 15-49 years, 5·72% (4·02 to 7·39) in those aged 50-69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5-14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15-49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50-69 years, and a 3·29% (-5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (-713 to 2180) fewer deaths.

    INTERPRETATION: Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups.

    FUNDING: Bill & Melinda Gates Foundation.

  12. Thompson GR, Le T, Chindamporn A, Kauffman CA, Alastruey-Izquierdo A, Ampel NM, et al.
    Lancet Infect Dis, 2021 12;21(12):e364-e374.
    PMID: 34364529 DOI: 10.1016/S1473-3099(21)00191-2
    The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.
  13. Hoenigl M, Salmanton-García J, Walsh TJ, Nucci M, Neoh CF, Jenks JD, et al.
    Lancet Infect Dis, 2021 Aug;21(8):e246-e257.
    PMID: 33606997 DOI: 10.1016/S1473-3099(20)30784-2
    With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
  14. Rasheed MK, Hasan SS, Babar ZU, Ahmed SI
    Lancet Infect Dis, 2019 03;19(3):242-243.
    PMID: 30833059 DOI: 10.1016/S1473-3099(19)30051-9
  15. Wernli D, Jørgensen PS, Parmley EJ, Troell M, Majowicz S, Harbarth S, et al.
    Lancet Infect Dis, 2020 Dec;20(12):e307-e311.
    PMID: 32853549 DOI: 10.1016/S1473-3099(20)30392-3
    Improving evidence for action is crucial to tackle antimicrobial resistance. The number of interventions for antimicrobial resistance is increasing but current research has major limitations in terms of efforts, methods, scope, quality, and reporting. Moving the agenda forwards requires an improved understanding of the diversity of interventions, their feasibility and cost-benefit, the implementation factors that shape and underpin their effectiveness, and the ways in which individual interventions might interact synergistically or antagonistically to influence actions against antimicrobial resistance in different contexts. Within the efforts to strengthen the global governance of antimicrobial resistance, we advocate for the creation of an international One Health platform for online learning. The platform will synthesise the evidence for actions on antimicrobial resistance into a fully accessible database; generate new scientific insights into the design, implementation, evaluation, and reporting of the broad range of interventions relevant to addressing antimicrobial resistance; and ultimately contribute to the goal of building societal resilience to this central challenge of the 21st century.
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