Showing papers by "World Health Organization published in 2022"

What is the vaccine effect on reducing transmission in the context of the SARS-CoV-2 delta variant?

Abstract: COVID-19 vaccines that have obtained WHO emergency use listing appear to have high efficacy against severe disease and death, but lower efficacy against non-severe infections, and emerging evidence suggests that protection against non-severe disease declines faster following vaccination than that against severe disease and death. What is less clear is whether vaccination not only directly protects individuals but reduces the risk of infection among the contacts of vaccinated people, particularly with respect to the now dominant delta variant. Before the emergence of the delta variant, it was reported that after at least one dose of the mRNA vaccine by Pfizer or the adenoviral vector vaccine by Astra Zeneca, the risk of symptomatic cases in household contacts of vaccinated cases was about 50% lower than that among household contacts of unvaccinated cases.1Harris RJ Hall JA Zaidi A Andrews NJ Dunbar JK Dabrera G Effect of vaccination on household transmission of SARS-CoV-2 in England.N Engl J Med. 2021; 385: 759-760Crossref PubMed Scopus (180) Google Scholar The now globally dominant delta variant is more transmissible2Liu Y Rocklöv J The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus.J Travel Med. 2021; 28taab124Crossref PubMed Scopus (276) Google Scholar and associated with reduced vaccine effectiveness, particularly against mild breakthrough infections, whereas protection against severe disease is not greatly reduced.3Lopez Bernal J Andrews N Gower C et al.Effectiveness of covid-19 vaccines against the B.1.617.2 (delta) variant.N Engl J Med. 2021; 385: 585-594Crossref PubMed Scopus (1539) Google Scholar Data are lacking on whether the effect of vaccination on transmission is lower for the delta variant and new insights on this are provided by a study done in the UK when the delta variant was the predominant strain, reported in The Lancet Infectious Diseases.4Singanayagam A Hakki S Dunning J et al.Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study.Lancet Infect Dis. 2021; (published online Oct 28.)https://doi.org/10.1016/S1473-3099(21)00648-4Summary Full Text Full Text PDF PubMed Scopus (337) Google Scholar Anika Singanayagam and colleagues did a carefully designed cohort study whereby 602 community contacts (household and non-household) identified via the UK contact tracing system and 471 COVID-19 index cases were enrolled through the Assessment of Transmission and Contagiousness of COVID-19 in Contacts (ATACCC) study. These participants contributed 8145 upper respiratory tract samples for up to 20 days, regardless of symptoms. The study had two study arms, with the first group enrolling contacts only, and the second group enrolling both index and contact cases at a time when the delta variant was predominant. What is unique about this study is that both vaccinated and unvaccinated contacts were included, thereby allowing for stratified analyses by vaccination status, both for the index cases and the contacts. To address the primary study outcome to establish the secondary attack rates (SARs) in household contacts, the vaccination statuses for 232 contacts exposed to 162 epidemiologically linked delta-variant-infected index cases were analysed. The SARs in household contacts exposed to the delta variant was 25% in vaccinated and 38% in unvaccinated contacts. These results underpin the key message that vaccinated contacts are better protected than the unvaccinated. All breakthrough infections were mild, and no hospitalisations and deaths were observed. But these results also highlight that breakthrough infections continue to occur in the vaccinated, with an attack rate of 25%. Time since vaccination in fully vaccination contacts was longer for those infected than those uninfected, suggesting that waning of protection might have occurred over time, although teasing out general waning versus reduced vaccine effectiveness due to delta is challenging owing to so many confounding factors. SAR among household contacts exposed to fully vaccinated index cases (25%; 95% CI 15–35) was similar to household contacts exposed to unvaccinated index cases (23%; 15–31). Obviously, infection might also have occurred beyond the household level with unknown exposure in the community. Indeed, genomic and virological analysis confirmed only three index-contact pairs. Owing to the small sample size, the authors were not able to establish the vaccine effectiveness against asymptomatic infections versus symptomatic infections. This limitation together with the unconfirmed source of transmission in many of these index-contact pairs, suggests that the low SAR reported here should be interpreted with caution. Nevertheless, the findings raise concern that the effect of vaccination on reducing transmission might be lower for the delta variant compared with the variants that circulated in the UK before the emergence of delta. Infectiousness of breakthrough infections can be measured by viral densities. Higher SARS-CoV-2 viral density in the upper airways of people infected with the virus are thought to increase transmission to household members.5Marks M Millat-Martinez P Ouchi D et al.Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study.Lancet Infect Dis. 2021; 21: 629-636Summary Full Text Full Text PDF PubMed Scopus (209) Google Scholar, 6Lee LYW Rozmanowski S Pang M et al.SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission.medRxiv. 2021; (published online April 5.) (preprint).https://doi.org/10.1101/2021.03.31.21254687Google Scholar If vaccines reduce viral density in those who do become infected despite vaccination, it would probably lead to lower infectiousness and less onward transmission. Hence, the authors compared the viral kinetics in breakthrough delta variant infections in vaccinated people with delta variant infections in unvaccinated people. They report that peak viral loads showed a faster decline in vaccinated compared with unvaccinated people, although peak viral loads were similar for unvaccinated and vaccinated people. Although preventing severe disease and deaths remains the primary public health goal in the acute phase of the pandemic, and is still being achieved by available COVID-19 vaccines despite the emergence of the delta variant, addressing SARS-CoV-2 transmission is a crucial additional consideration. Reducing transmission is necessary to reduce virus circulation, reach herd immunity and end this tragic pandemic. This study confirms that COVID-19 vaccination reduces the risk of delta variant infection and also accelerates viral clearance in the context of the delta variant. However, this study unfortunately also highlights that the vaccine effect on reducing transmission is minimal in the context of delta variant circulation. These findings have immediate public health implications. Higher vaccination coverage rates need to be achieved because indirect protection from vaccinated to unvaccinated people remains suboptimal. The question of whether booster doses will improve the impact on transmission should be addressed as a top priority.7Gardner BJ Kilpatrick AM Third doses of COVID-19 vaccines reduce infection and transmission of SARS-CoV-2 and could prevent future surges in some populations.medRxiv. 2021; (published online Oct 26.) (preprint).https://doi.org/10.1101/2021.10.25.21265500Google Scholar Research efforts should be directed towards enhancing existing vaccines or developing new vaccines that also protect against asymptomatic infections and onward transmission. Until we have such vaccines, public health and social measures will still need to be tailored towards mitigating community and household transmission in order to keep the pandemic at bay. AWS is a member of The Lancet Commission on COVID-19, and a consultant to WHO. The author alone is responsible for the views expressed here and they do not necessarily represent the decisions, policies, or views of The Lancet Commission or WHO. I declare no competing interests. Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort studyVaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory. Full-Text PDF Open Access

Trachoma

Abstract: Trachoma is a neglected tropical disease caused by infection with conjunctival strains of Chlamydia trachomatis. It can result in blindness. Pathophysiologically, trachoma is a disease complex composed of two linked chronic processes: a recurrent, generally subclinical infectious–inflammatory disease that mostly affects children, and a non-communicable, cicatricial and, owing to trichiasis, eventually blinding disease that supervenes in some individuals later in life. At least 150 infection episodes over an individual’s lifetime are needed to precipitate trichiasis; thus, opportunity exists for a just global health system to intervene to prevent trachomatous blindness. Trachoma is found at highest prevalence in the poorest communities of low-income countries, particularly in sub-Saharan Africa; in June 2021, 1.8 million people worldwide were going blind from the disease. Blindness attributable to trachoma can appear in communities many years after conjunctival C. trachomatis transmission has waned or ceased; therefore, the two linked disease processes require distinct clinical and public health responses. Surgery is offered to individuals with trichiasis and antibiotic mass drug administration and interventions to stimulate facial cleanliness and environmental improvement are designed to reduce infection prevalence and transmission. Together, these interventions comprise the SAFE strategy, which is achieving considerable success. Although much work remains, a continuing public health problem from trachoma in the year 2030 will be difficult for the world to excuse. Trachoma, caused by infection with conjunctival strains of Chlamydia trachomatis, is the most common infectious cause of blindness. This Primer summarizes the epidemiology, pathophysiology and diagnosis of trachoma as well as its management, disease control and elimination, and key areas for future research.

25 years of surveillance of drug-resistant tuberculosis: achievements, challenges, and way forward

Abstract: Tuberculosis is second only to COVID-19 as a cause of death from a single infectious agent. In 2020, almost 10 million people were estimated to have developed tuberculosis and it caused 1·5 million deaths. Around a quarter of deaths caused by antimicrobial resistance are due to rifampicin-resistant tuberculosis. Antimicrobial resistance surveillance systems for many bacterial pathogens are still in the early stages of implementation in many countries, and do not yet allow for the estimation of disease burden at the national level. In this Personal View, we present the achievements, challenges, and way forward for the oldest and largest global antimicrobial resistance surveillance system. Hosted by WHO since 1994, the Global Project on Anti-Tuberculosis Drug Resistance Surveillance has served as a platform for the evaluation of the trends in anti-tuberculosis drug resistance for over 25 years at country, regional, and global levels. With an estimated 465 000 incident cases of multidrug-resistant and rifampicin-resistant tuberculosis in 2019, drug-resistant tuberculosis remains a public health crisis. The COVID-19 pandemic has reversed years of progress in providing essential tuberculosis services and reducing disease burden. The number of people diagnosed with drug-resistant tuberculosis has dropped by 22% since before the pandemic, and the number of patients provided with treatment for drug-resistant tuberculosis has dropped by 15%. Now more than ever, closing gaps in the detection of drug-resistant tuberculosis requires investment in research and development of new diagnostic tools and their rollout, expansion of sample transport systems, and the implementation of data connectivity solutions. Tuberculosis is second only to COVID-19 as a cause of death from a single infectious agent. In 2020, almost 10 million people were estimated to have developed tuberculosis and it caused 1·5 million deaths. Around a quarter of deaths caused by antimicrobial resistance are due to rifampicin-resistant tuberculosis. Antimicrobial resistance surveillance systems for many bacterial pathogens are still in the early stages of implementation in many countries, and do not yet allow for the estimation of disease burden at the national level. In this Personal View, we present the achievements, challenges, and way forward for the oldest and largest global antimicrobial resistance surveillance system. Hosted by WHO since 1994, the Global Project on Anti-Tuberculosis Drug Resistance Surveillance has served as a platform for the evaluation of the trends in anti-tuberculosis drug resistance for over 25 years at country, regional, and global levels. With an estimated 465 000 incident cases of multidrug-resistant and rifampicin-resistant tuberculosis in 2019, drug-resistant tuberculosis remains a public health crisis. The COVID-19 pandemic has reversed years of progress in providing essential tuberculosis services and reducing disease burden. The number of people diagnosed with drug-resistant tuberculosis has dropped by 22% since before the pandemic, and the number of patients provided with treatment for drug-resistant tuberculosis has dropped by 15%. Now more than ever, closing gaps in the detection of drug-resistant tuberculosis requires investment in research and development of new diagnostic tools and their rollout, expansion of sample transport systems, and the implementation of data connectivity solutions. Tuberculosis is a preventable, treatable, and curable disease. However, in 2020, 9·9 million people were estimated to have developed tuberculosis, and 1·5 million people were estimated to have died from it. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of tuberculosis, resulting in an increase in deaths due to tuberculosis, and a reversal in global progress. Tuberculosis is second only to COVID-19 in terms of death from a single infectious agent.1WHOGlobal tuberculosis report 2021.https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2021Date: 2021Date accessed: November 23, 2021Google Scholar Nearly half a million individuals who developed tuberculosis in 2019 had resistance to rifampicin, a crucial first-line drug for the treatment of tuberculosis. Rifampicin resistance could be present either at the onset of disease or it might emerge during the course of the disease due to inadequate treatment.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar Globally, around a quarter of deaths caused by antimicrobial resistance are due to rifampicin-resistant tuberculosis.3O Neill J The review on antimicrobial resistance. Tackling drug-resistant infections globally: final report and recommendations.https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdfDate: 2016Date accessed: November 23, 2021Google Scholar Rifampicin-resistant tuberculosis, which includes multidrug-resistant tuberculosis (defined as combined resistance to rifampicin and isoniazid), accounted for an estimated 180 000 deaths in 2019. Although only 3·3% of patients with new, untreated tuberculosis in 2019 had rifampicin resistance, the costs of providing appropriate diagnosis, treatment, and care for people with drug-resistant tuberculosis are disproportionately high. The epidemic of drug-resistant tuberculosis varies substantially between regions and remains particularly concerning in some countries of eastern Europe and central Asia, including Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, and Ukraine. In these countries, the proportion of new, untreated patients with rifampicin-resistant tuberculosis exceeds 20%. Only 86% of patients diagnosed with rifampicin-resistant tuberculosis in 2019 started treatment. In the cohort of patients enrolled in treatment for rifampicin-resistant tuberculosis in 2017, only 57% had successful treatment outcomes, which was defined as either having completed treatment with no evidence of treatment failure, or showing evidence of cured disease. The absence of decentralised and ambulatory models for the provision of treatment and care for patients with drug-resistant tuberculosis in many countries probably contributes to this low proportion.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar The Global Project on Anti-Tuberculosis Drug Resistance Surveillance is the oldest and largest global surveillance system for antimicrobial resistance in the world.4Zignol M Dean AS Falzon D et al.Twenty years of global surveillance of antituberculosis-drug resistance.N Engl J Med. 2016; 375: 1081-1089Crossref PubMed Scopus (87) Google Scholar Hosted by WHO since 1994, the Global Project has served as a common platform for the evaluation of the magnitude and trends surrounding drug-resistant tuberculosis over 25 years, across country, regional, and global scales. Supported by a WHO global network of supranational reference laboratories for tuberculosis, the data collected are derived from two main sources: (1) routine drug susceptibility testing (DST) using molecular or phenotypic methods for at least rifampicin in the majority (≥80%) of patients with bacteriologically confirmed pulmonary tuberculosis, thus constituting a continuous surveillance system; and (2) periodic epidemiological surveys in settings where routine testing capacity has not yet been established. Implementation of these approaches is detailed in the sixth edition of WHO's global guidance for the surveillance of drug-resistant tuberculosis, published in April, 2021.5WHOGuidance for the surveillance of drug resistance in tuberculosis.6th edition. World Health Organization, Geneva2021Google Scholar By May, 2021, 125 countries had data on rifampicin-resistant tuberculosis from continuous surveillance, and 53 had data from surveys for at least 1 year since 1994. Collectively, these data accounted for more than 99% of the world's population and estimated number of rifampicin-resistant tuberculosis cases. Some of these data could be outdated or only available for individual years, preventing an assessment of trends over time. Nonetheless, there have been continued improvements in surveillance systems over the 5 year period from 2014 to 2019, with the number of WHO member states with data from routine surveillance increasing from 86 to 125 (figure 1).2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar The nationally representative data collected by the Global Project can be used to inform timely public health actions, which can be integrated into national strategic plans for tuberculosis. These include guiding resource allocation, assessing the appropriateness of treatment regimens, planning future drug procurement needs, informing national tuberculosis diagnostic algorithms, and prioritising research and development needs. By contrast, antimicrobial resistance surveillance systems for other bacterial pathogens are still in the early stages of implementation in many countries and do not yet allow an estimation of disease burden at the national level. Infrastructure for clinical microbiological diagnostics, including obtaining appropriate samples from a representative group of patients and performing antimicrobial susceptibility testing, is weak.6WHOGlobal antimicrobial resistance and use surveillance system (GLASS) report 2021.https://www.who.int/publications/i/item/9789240027336Date: 2021Date accessed: November 23, 2021Google Scholar Impressive achievements have been made in the detection of drug-resistant tuberculosis, contributing to the strengthening of surveillance systems. The diagnosis of rifampicin resistance no longer relies solely on culture methods and phenotypic DST, which require months to obtain results. Since 2011, rapid molecular tests have been crucial for improving access to DST by enabling decentralised testing that can be done directly using sputum samples. A variety of different tests with a rapid turnaround time are now available,7WHOWHO consolidated guidelines on tuberculosis, module 3: diagnosis—rapid diagnostics for tuberculosis detection 2021 update.https://www.who.int/publications/i/item/9789240029415Date: 2021Date accessed: November 23, 2021Google Scholar ensuring earlier detection and initiation of appropriate treatment. In 2019, 61% of people with bacteriologically confirmed tuberculosis were tested for rifampicin resistance, a notable increase from 51% in 2017, and only 7% in 2012 (figure 2). In some high-income countries, next-generation sequencing has become routine practice due to scientific innovation and continued reductions in costs. Sequencing is a valuable public health tool that allows the detection and tracing of multi-country outbreaks of drug-resistant tuberculosis, as shown by the pilot of the EUSeqMyTB consortium across the EU and European Economic Area.8Walker TM Merker M Knoblauch AM et al.A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study.Lancet Infect Dis. 2018; 18: 431-440Summary Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 9Tagliani E Anthony R Kohl TA et al.Use of a whole genome sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017–2019: an ECDC pilot study.Eur Respir J. 2021; 572002272Google Scholar The integration of sequencing into national anti-tuberculosis drug resistance surveys in Djibouti, Democratic Republic of the Congo, Eritrea, and Eswatini has shown its value.5WHOGuidance for the surveillance of drug resistance in tuberculosis.6th edition. World Health Organization, Geneva2021Google Scholar, 10Tagliani E Hassan MO Waberi Y et al.Culture and next-generation sequencing-based drug susceptibility testing unveil high levels of drug-resistant-TB in Djibouti: results from the first national survey.Sci Rep. 2017; 717672Crossref PubMed Scopus (19) Google Scholar, 11Kayomo MK Mbula VN Aloni M et al.Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB: results of a national survey in Democratic Republic of the Congo.Sci Rep. 2020; 1010786Crossref PubMed Scopus (4) Google Scholar, 12Mesfin AB Araia ZZ Beyene HN et al.First molecular-based anti-TB drug resistance survey in Eritrea.Int J Tuberc Lung Dis. 2021; 25: 43-51Crossref PubMed Google Scholar The benefits of sequencing include comprehensive results for a greater range of drugs, identification of mutations missed by commercial assays, and epidemiological insights into transmission. In settings where culture methods cannot yet be reliably implemented, targeted sequencing of specific genes can be done directly on sputum samples.11Kayomo MK Mbula VN Aloni M et al.Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB: results of a national survey in Democratic Republic of the Congo.Sci Rep. 2020; 1010786Crossref PubMed Scopus (4) Google Scholar In combination with improved access to diagnostics leading to better case detection, new treatment options could greatly improve the quality of life for people with drug-resistant tuberculosis. These improvements should also facilitate the transition towards case-based surveillance and more accurate monitoring of treatment outcomes. Since 2020, the regimen recommended by WHO for the treatment of rifampicin-resistant tuberculosis no longer relies on injectable agents administered for a period of up to 24 months. Instead, it consists entirely of oral medications administered for 9–11 months, excluding patients with additional resistance to some other drugs or with extensive tuberculosis disease. 90 countries reported using all-oral medication regimens during 2020.1WHOGlobal tuberculosis report 2021.https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2021Date: 2021Date accessed: November 23, 2021Google Scholar For the treatment of rifampicin-resistant tuberculosis with additional fluoroquinolone resistance, WHO has approved the use of an all-oral regimen, BPaL (ie, combined treatment with bedaquiline, pretomanid, and linezolid), administered for 6–9 months under operational research conditions for particular patient groups.13Mirzayev F Viney K Linh NN et al.World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update.Eur Respir J. 2020; 572003300Google Scholar The results of ongoing clinical trials of new combinations of drugs should become available in 2022 for both drug-susceptible tuberculosis and drug-resistant tuberculosis, including universal regimens that can be used for both.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar The COVID-19 pandemic has reversed years of progress in providing essential tuberculosis services and reducing the disease burden. The most obvious impact is an 18% drop in the number of people diagnosed and reported to have tuberculosis globally, falling from 7·1 million in 2019 to 5·8 million in 2020, which is below the 9·9 million people who were estimated to have developed tuberculosis in 2020. Similarly, there was a 22% drop in the number of people diagnosed with drug-resistant tuberculosis, falling from 201 997 in 2019, to 157 903 in 2020. The number of people provided with treatment for drug-resistant tuberculosis dropped by 15% from 177 100 in 2019 to 150 359 in 2020, only reaching around one of three in need.1WHOGlobal tuberculosis report 2021.https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2021Date: 2021Date accessed: November 23, 2021Google Scholar With an estimated 465 000 incident cases of multidrug-resistant tuberculosis and rifampicin-resistant tuberculosis in 2019 before the COVID-19 pandemic, the number of people living with the disease (prevalent cases) is even higher. Despite steady increases in the coverage of rifampicin DST, less than half (44%) of the estimated global incident cases of multidrug-resistant tuberculosis and rifampicin-resistant tuberculosis were detected and notified in 2019, and only slightly more than a third (38%) were enrolled on second-line treatment.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar There are particularly large gaps in the detection, recording, and reporting of rifampicin resistance among children with tuberculosis, due to challenges in obtaining suitable samples for bacteriological confirmation and DST.14McQuaid CF Cohen T Dean AS et al.Ongoing challenges to understanding multidrug- and rifampicin-resistant tuberculosis in children versus adults.Eur Respir J. 2021; 572002504Crossref PubMed Scopus (1) Google Scholar Between 2018 and 2019, 8986 children were enrolled on treatment for rifampicin-resistant tuberculosis, but this number was only 7·8% of the 5 year (2018–22) target of 115 000 that was set in the political declaration of the UN high-level meeting on tuberculosis in 2018.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar Together with rifampicin, isoniazid is an essential component of the first-line treatment regimen for tuberculosis recommended by WHO. It is also the most commonly used preventive drug for tuberculosis. However, the increased DST capacity that has been established for rifampicin is not yet available for isoniazid. In many countries, diagnostic algorithms are driven by initial screening for rifampicin resistance, followed by further DST in patients for whom a rifampicin-resistant treatment regimen is indicated.15Dean AS Zignol M Cabibbe AM et al.Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: a multicountry analysis of cross-sectional data.PLoS Medicine. 2020; 17e1003008Crossref PubMed Google Scholar With an estimated 1 million cases of tuberculosis emerging in 2019 estimated to have resistance to isoniazid without concurrent rifampicin resistance, there is a much higher burden of this form of drug-resistant tuberculosis than with the 465 000 incident cases of rifampicin-resistant tuberculosis.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar A modified, fluoroquinolone-containing regimen is recommended for the treatment of isoniazid-resistant, rifampicin-susceptible tuberculosis, but many eligible patients might not be detected, thus receiving inappropriate treatment and care.16WHOWHO consolidated guidelines on tuberculosis, module 4: treatment. Drug-Resistant tuberculosis treatment.https://www.who.int/publications/i/item/9789240007048Date: 2020Date accessed: November 23, 2021Google Scholar With susceptibility to fluoroquinolones being crucial to the success of the all-oral treatment regimen for rifampicin-resistant tuberculosis, the definitions of extensively drug-resistant (XDR)-tuberculosis and preXDR tuberculosis have been updated. From 2021 onwards, preXDR tuberculosis is defined as rifampicin-resistant tuberculosis with concurrent fluoroquinolone resistance.17WHOMeeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis.https://www.who.int/publications/i/item/meeting-report-of-the-who-expert-consultation-on-the-definition-of-extensively-drug-resistant-tuberculosisDate: 2021Date accessed: November 23, 2021Google Scholar With new and repurposed drugs now core components of the all-oral regimen for rifampicin-resistant tuberculosis, the definition of XDR tuberculosis from 2021 onwards is as follows: preXDR plus resistance to any group A drug recommended for the treatment of rifampicin-resistant tuberculosis (currently, either bedaquiline or linezolid). Of the rifampicin-resistant tuberculosis cases detected in 2019, 71% were tested for resistance to fluoroquinolones. This proportion is greater than the amount tested in 2018 (65%), yet gaps remain. In 2019, only 69 countries provided high-quality data through routine continuous surveillance systems, defined as implementing routine DST for rifampicin for 80% or more of patients with bacteriologically confirmed pulmonary tuberculosis, as well as routine DST for fluoroquinolones for 80% or more of patients with pulmonary rifampicin-resistant tuberculosis. A challenge for the surveillance of XDR tuberculosis is that molecular markers of resistance are not yet well understood, and therefore phenotypic testing done on culture isolates is currently the only reliable way to test for resistance to bedaquiline and linezolid. This knowledge gap is a barrier to the expansion of DST for monitoring the emergence of resistance. In the case of bedaquiline, resistance-conferring mutations are scattered without a defined genetic hotspot region, meaning that the development of a rapid molecular assay might not be feasible.18Kadura S King N Nakhoul M et al.Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.J Antimicrob Chemother. 2020; 75: 2031-2043Crossref PubMed Scopus (40) Google Scholar For laboratory results to be meaningful and actionable, they need to be correctly linked to individual patients and their clinical data in a timely manner. Many diagnostic tests, including molecular assays and liquid culture, can produce results in a digital format, and diagnostic connectivity solutions to allow rapid analysis and communication of results are available.19Global Laboratory InitiativeGLI quick guide to TB diagnostics connectivity solutions.http://www.stoptb.org/wg/gli/assets/documents/gli_connectivity_guide.pdfDate: 2016Date accessed: November 23, 2021Google Scholar However, implementation can be constrained by the absence of unique patient identification codes, multiple samples being tested from the same patient, recurrent episodes of tuberculosis for the same patient, or referral to other health facilities for testing. Drug-resistant tuberculosis remains a public health crisis, and ongoing surveillance of the burden is essential to mounting an effective response. Accurate diagnosis and treatment of tuberculosis, including drug-resistant forms, should be available and accessible to all who need it. All member states of WHO have committed to ending the global tuberculosis epidemic by 2030 through the adoption of WHO's End TB Strategy in 2014, and the UN Sustainable Development Goals in 2015.20WHOResolution WHA67.25: antimicrobial resistance.http://apps.who.int/gb/ebwha/pdf_files/WHA67/A67_R25-en.pdfDate: 2014Date accessed: November 23, 2021Google Scholar, 21UNProgress towards the achievement of global tuberculosis targets and implementation of the political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis.https://undocs.org/en/A/75/236Date: 2020Date accessed: November 23, 2021Google Scholar These commitments were reaffirmed at the UN high-level meeting on tuberculosis in 2018. A crucial component required to fulfil these commitments is improved access to diagnostic testing for tuberculosis, including universal DST. Member states have also called for strengthened efforts to combat antimicrobial resistance, including drug-resistant tuberculosis, in a resolution of the World Health Assembly in 2019.20WHOResolution WHA67.25: antimicrobial resistance.http://apps.who.int/gb/ebwha/pdf_files/WHA67/A67_R25-en.pdfDate: 2014Date accessed: November 23, 2021Google Scholar Now more than ever, closing gaps in the detection of drug-resistant tuberculosis requires investment in laboratory capacity, sample transport systems, and data connectivity solutions. To improve detection requires a multistep process, first requiring improved bacteriological confirmation among presumptive cases of pulmonary tuberculosis. In 2019, globally, only 57% of diagnosed cases of tuberculosis were bacteriologically confirmed, a notable contrast to 84% in high-income countries.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar Improved bacteriological confirmation must be combined with increased DST in cases that are bacteriologically confirmed. New molecular tools are becoming increasingly available for other drugs. In July, 2021, WHO endorsed the use of additional low-complexity and moderate-complexity nucleic acid amplification tests for isoniazid and fluoroquinolone testing, including rapid cartridge-based assays for both drugs.7WHOWHO consolidated guidelines on tuberculosis, module 3: diagnosis—rapid diagnostics for tuberculosis detection 2021 update.https://www.who.int/publications/i/item/9789240029415Date: 2021Date accessed: November 23, 2021Google Scholar Such tools can be decentralised, thereby reducing gaps in the detection of isoniazid-resistant tuberculosis cases and allowing confirmation of the eligibility for the all-oral regimen for rifampicin-resistant tuberculosis. Furthermore, new molecular tools could play an important role in assessing eligibility for, and monitoring emergence of resistance to, new first-line regimens. After reviewing the evidence of the Study 31/A5349 trial, in June, 2021, WHO endorsed the use of a 4 month rifapentine-containing and fluoroquinolone-containing regimen as a possible alternative to the current 6 month first-line regimen for drug-susceptible pulmonary tuberculosis.22WHOTreatment of drug-susceptible tuberculosis: rapid communication.https://www.who.int/publications/i/item/9789240028678Date: 2021Date accessed: November 23, 2021Google Scholar However, access to rifapentine remains problematic due to limited availability and costs, emphasising the crucial need for more manufacturers.23WHOWHO encourages manufacturers to develop quality assured formulations of the game-changing drug rifapentine.https://www.who.int/news/item/15-07-2021-who-encourages-manufacturers-to-develop-quality-assured-formulations-of-the-game-changing-drug-rifapentineDate accessed: November 23, 2021Google Scholar, 24WHONitrosamine concerns for rifapentine and rifampicin: update and FAQs.https://extranet.who.int/pqweb/sites/default/files/documents/FAQ_Nitrosamine_18Dec2020.pdfDate: 2021Date accessed: November 23, 2021Google Scholar Next-generation sequencing has the potential to revolutionise the expansion of comprehensive DST, as it can detect resistance to multiple drugs simultaneously and might also be the only option available when no clear genetic hotspots have been identified for the development of rapid molecular tests. Global uptake has been limited by requirements for advanced bioinformatics and information technology capacity, and by a lack of standardisation for data processing, analysis, and interpretation.25Inzaule SC Tessema SK Kebede Y Ouma AEO Nkengasong JN Genomic-informed pathogen surveillance in Africa: opportunities and challenges.Lancet Infect Dis. 2021; 21: e281-e289Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 26WHOThe use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide.https://www.who.int/publications/i/item/WHO-CDS-TB-2018.19Date: 2018Date accessed: November 23, 2021Google Scholar Portable platforms such as the MinION (developed by Oxford Nanopore Technologies, Oxford, UK), which can be done on raw sputum, and assays done directly on processed sputum, such as Deeplex-MycTB (developed by GenoScreen, Lille, France), could reduce turnaround time and allow live detection of clusters and timely patient management. WHO is collaborating with partners such as the Foundation for Innovative New Diagnostics to address these needs.27GenomeWebSequencing-based tuberculosis drug resistance testing gaining momentum.https://www.360dx.com/clinical-sequencing/sequencing-based-tuberculosis-drug-resistance-testing-gaining-momentum#.YC18qWhKiUkDate: 2020Date accessed: November 23, 2021Google Scholar Different sequencing solutions are being piloted in countries to explore the most appropriate approaches in varied settings, with consideration given to priority patient groups for testing, the type of technology to be used (eg, targeted versus whole-genome sequencing, either directly on sputum or on culture isolates), and the model of delivery within the laboratory network. The first WHO catalogue of mutations was published in June, 2021,28WHOCatalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance.https://www.who.int/publications/i/item/9789240028173Date: 2021Date accessed: November 23, 2021Google Scholar compiling evidence to define the role of different mutations in conferring resistance. This catalogue serves as a global reference for harmonising the analysis and interpretation of sequencing data, and will be reviewed annually. Efforts are needed to minimise the emergence of resistance to the first new drugs to be made available for the treatment of tuberculosis in more than 50 years. These new drugs include bedaquiline, which is critical for the treatment of rifampicin-resistant tuberculosis, pretomanid, for which clinical trial results of combination therapy for drug-resistant tuberculosis are soon anticipated,29Médecins Sans FrontièresTB PRACTECAL.https://msf.org.uk/tb-practecalDate accessed: March 24, 2021Google Scholar and the closely related delamanid. Crucial factors in preventing emergence of resistance to new and repurposed drugs include appropriate patient support to ensure treatment adherence, effective combination therapies incorporating several active drug classes, and early detection of resistance to prevent further spread.30Ndjeka N Ismail NA Bedaquiline and clofazimine: successes and challenges.Lancet Microbe. 2020; 1: e139-e140Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 31Ismail NA Omar SV Joseph L et al.Defining bedaquiline susceptibility, resistance, cross-resistance and associated genetic determinants: a retrospective cohort study.EBioMedicine. 2018; 28: 136-142Summary Full Text Full Text PDF PubMed Scopus (53) Google Scholar Early detection of resistance relies on investment in research and development of new molecular tools. In August, 2021, WHO released updated target product profiles (TPPs) for DST at peripheral centres to inform research and development priorities. The TPPs provide minimal and optimal requirements for new tools to facilitate affordable and equitable access, including the need for point-of-care solutions.32WHOTarget product profile for next-generation tuberculosis drug-susceptibility testing at peripheral centres.https://www.who.int/publications/i/item/9789240032361Date: 2021Date accessed: November 23, 2021Google Scholar For some drugs, portable, targeted next-generation sequencing might be the most promising approach to scaling up testing globally. This upscaling of testing will be reliant on a better understanding of the role of different mutations, which in turn requires paired data from phenotypic DST and whole-genome sequencing. In the interim, in-country capacity for culture and phenotypic testing of these drugs must be strengthened. The expansion of surveillance systems requires more than the strengthening of laboratory capacity and sample transport systems. Countries should strive to transition from paper-based recording and reporting systems to case-based digital surveillance systems, such as those provided by the District Health Information Software 2 (DHIS2). DHIS2 is an open-source, web-based health management information system platform designed in line with WHO standards for service delivery and programme implementation. The DHIS2 case-based module for tuberculosis surveillance provides a relational database with linkage of unique patient identifiers to different laboratory tests and other data. Interactive dashboards allow visualisation of key indicators. DHIS2 can be used for many different diseases, thus consolidating a country's surveillance data into one common platform. It is encouraging that case-based digital surveillance systems covering both drug-susceptible and drug-resistant tuberculosis were available in 136 countries—collectively accounting for 72% of global tuberculosis cases in 2019.2WHOGlobal tuberculosis report 2020.https://www.who.int/publications/i/item/9789240013131Date: 2020Date accessed: November 23, 2021Google Scholar Impressive progress has been made over the past 25 years in improving the diagnosis of, and access to treatment and care for, drug-resistant tuberculosis. The Global Project on Anti-Tuberculosis Drug Resistance Surveillance serves to guide the development and expansion of the surveillance of antimicrobial resistance among other pathogens. Nonetheless, the global epidemic of drug-resistant tuberculosis remains a public health threat, with the COVID-19 pandemic reversing years of progress. Urgent investment is needed from governments, donors, the commercial sector, academic institutions, non-governmental organisations, and other stakeholders.

WHO competency framework for health authorities and institutions to manage infodemics: its development and features

Abstract: In April 2020, the World Health Organization (WHO) Information Network for Epidemics produced an agenda for managing the COVID-19 infodemic. "Infodemic" refers to the overabundance of information-including mis- and disinformation. In this agenda it was pointed out the need to create a competency framework for infodemic management (IM). This framework was released by WHO on 20th September 2021. This paper presents the WHO framework for IM by highlighting the different investigative steps behind its development.The framework was built through three steps. Step 1 included the preparatory work following the guidelines in the Guide to writing Competency Framework for WHO Academy courses. Step 2 was based on a qualitative study with participants (N = 25), identified worldwide on the basis of their academic background in relevant fields of IM or of their professional experience in IM activities at the institutional level. The interviews were conducted online between December 2020 and January 2021, they were video-recorded and analyzed using thematic analysis. In Step 3, two stakeholder panels were conducted to revise the framework.The competency framework contains four primary domains, each of which comprised main activities, related tasks, and knowledge and skills. It identifies competencies to manage and monitor infodemics, to design, conduct and evaluate appropriate interventions, as well as to strengthen health systems. Its main purpose is to assist institutions in reinforcing their IM capacities and implementing effective IM processes and actions according to their individual contexts and resources.The competency framework is not intended to be a regulatory document nor a training curriculum. As a WHO initiative, it serves as a reference tool to be applied according to local priorities and needs within the different countries. This framework can assist institutions in strengthening IM capacity by hiring, staff development, and human resources planning.

Measuring the Commercial Determinants of Health and Disease: A Proposed Framework.

Abstract: The commercial determinants of health (CDoH) describe the adverse health effects associated with for-profit actors and their actions. Despite efforts to advance the definition, conceptualization, and empirical analyses of CDoH, the term's practical application to mitigate these effects requires the capacity to measure the influences of specific components of CDoH and the cumulative impacts of CDoH on the health and well-being of specific populations. Building on the Global Burden of Disease Study, we begin by conceptualizing CDoH as risk factor exposures that span agency and structural influences. We identify 6 components of these influences and propose an initial set of indicators and datasets to rank exposures as high, medium, or low. These are combined into a commercial determinants of health index (CDoHi) and illustrated by 3 countries. Although now a proof of concept, comparative analysis of CDoH exposures by population, over time and space, and their associated health outcomes will become possible with further development of indicators and datasets. Expansion of the CDoHi and application to varied populations groups will enable finer targeting of interventions to reduce health harms. The measurement of improvements to health and wellness from such interventions will, in turn, inform overall efforts to address the CDoH.

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study

Abstract: Summary Background Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. Methods We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita. We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) — the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested — the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection. Findings Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable. Interpretation The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. Funding World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust

Characteristics and birth outcomes of pregnant adolescents compared to older women: An analysis of individual level data from 140,000 mothers from 20 RCTs

Abstract: Adolescence is a critical period of maturation when nutrient needs are high, especially among adolescents entering pregnancy. Using individual-level data from 140,000 participants, we examined socioeconomic, nutrition, and pregnancy and birth outcomes for adolescent mothers (10-19 years) compared to older mothers in low and middle-income countries.This study was conducted between March 16, 2018 and May 25, 2021. Data were obtained from 20 randomised controlled trials of micronutrient supplementation in pregnancy. Stratified analyses were conducted by age (10-14 years, 15-17 years, 18-19 years, 20-29 years, 30-39 years, 40+ years) and geographical region (Africa, Asia). Crude and confounder-adjusted means, prevalence and relative risks of pregnancy, nutrition and birth outcomes were estimated using multivariable linear and log-binomial regression models with 95% confidence intervals.Adolescent mothers comprised 31.6% of our data. Preterm birth, small-for-gestational age (SGA), low birthweight (LBW) and newborn mortality followed a U-shaped trend in which prevalence was highest among the youngest mothers (10-14 years) and then reduced gradually, but increased again for older mothers (40+ years). When compared to mothers aged 20-29 years, there was a 23% increased risk of preterm birth, a 60% increased risk of perinatal mortality, a 63% increased risk of neonatal mortality, a 28% increased risk of LBW, and a 22% increased risk of SGA among mothers 10-14 years. Mothers 40+ years experienced a 22% increased risk of preterm birth and a 103% increased risk of stillbirth when compared to the 20-29 year group.The youngest and oldest mothers suffer most from adverse pregnancy and birth outcomes. Policy and programming agendas should consider both biological and socioeconomic/environmental factors when targeting these populations.Bill and Melinda Gates Foundation (Grant No: OP1137750).

HiTOP Assessment of Externalizing Antagonism and Disinhibition.

Abstract: This article outlines the Phase 1 efforts of the HiTOP Measure Development group for externalizing constructs, which include disinhibited externalizing, antagonistic externalizing, attention deficit hyperactivity disorder, substance use, and externalizing/maladaptive behaviors. We provide background on the constructs included and the process and issues involved in developing a measure for this diverse range of psychopathology symptoms, traits, and behaviors.

Population-level salt intake in the WHO European Region in 2022: a systematic review

Abstract: Abstract Objective: The WHO recommends that adults consume less than 5 g of salt per day to reduce the risk of CVD. This study aims to examine the average population daily salt intake in the fifty-three Member States of the WHO European Region. Design: A systematic review was conducted to examine the most up-to-date salt intake data for adults published between 2000 and 2022. Data were obtained from peer-reviewed and grey literature, WHO surveys and studies, as well as from national and global experts. Setting: The fifty-three Member States of the WHO European Region. Participants: People aged 12 years or more. Results: We identified fifty studies published between 2010 and 2021. Most countries in the WHO European Region ( n 52, 98 %) reported salt intake above WHO recommended maximum levels. In almost all countries ( n 52, 98 %), men consume more salt than women, ranging between 5·39 and 18·51 g for men and 4·27 and 16·14 g for women. Generally, Western and Northern European countries have the lowest average salt intake, whilst Eastern European and Central Asian countries have the highest average. Forty-two percentage of the fifty-three countries ( n 22) measured salt intake using 24 h urinary collection, considered the gold standard method. Conclusions: This study found that salt intakes in the WHO European Region are significantly above WHO recommended levels. Most Member States of the Region have conducted some form of population salt intake. However, methodologies to estimate salt intake are highly disparate and underestimations are very likely.

Dengue vaccine development: challenges and prospects

Abstract: Dengue vaccine development is a high public health priority. To date, no dengue vaccine is in widespread use. Here we review the challenges in dengue development and the latest results for the second-generation dengue vaccines.The biggest hurdle is the immunological interaction between the four antigenically distinct dengue serotypes. The advantages of second-generation dengue vaccines are the inclusion of nonstructural proteins of the dengue backbone and a more convenient dosing with reduced numbers of doses needed.Although dengue-primed individuals can already benefit from vaccination with the first licensed dengue vaccine CYD-TDV, the public health need for the dengue-naive population has not yet been met. The urgent need remains to identify correlates of both protection and enhancement; until such correlates have been identified, all second-generation dengue vaccines still need to go through full phase 3 trials. The 5-year efficacy and safety data for both second-generation dengue vaccines are imminent.

Effect of a single dose of 8 mg moxidectin or 150 μg/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection

Abstract: Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150μg/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI).Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, ≥20-<50, ≥50-<80, ≥80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p≤0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p<0.006). Odds ratios for UD1-6, UD1-12 or UD1-18 after moxidectin versus ivermectin treatment exceeded 7.0. Suboptimal response (SmfD 12 months post-treatment >40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively.The benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated.Registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence

Abstract: This review summarises the latest information of the epidemiology of HIV drug resistance (HIVDR) in low- and middle-income countries and the updated WHO global strategy for HIVDR surveillance and monitoring.Finding from recent national-representative surveys show a rise in pretreatment drug resistance (PDR) to reverse transcriptase inhibitors and especially to the class of nonnucleoside reverse transcriptase inhibitors. Levels of PDR are especially high in infants <18 months and adults reporting prior exposure to antiretrovirals. Although viral suppression rates are generally high and increasing among adults on antiretroviral therapy, those with unsuppressed viremia have high levels of acquired drug resistance (ADR). Programmatic data on HIVDR to integrase-transfer-inhibitor resistance is scarce, highlighting the need to increase integrase-inhibitors resistance surveillance. As the landscape of HIV prevention, treatment and monitoring evolves, WHO has also adapted its strategy to effectively support countries in preventing and monitoring the emergence of HIVDR. This includes new survey methods for monitoring resistance emerging from patients diagnosed with HIV while on preexposure prophylaxis, and a laboratory-based ADR survey leveraging on remnant viral load specimens which are expected to strengthen dolutegravir-resistance surveillance.Monitoring HIVDR remains pivotal to ensure countries attain and sustain the global goals for ending HIV as a public health threat by 2030.

Development of the first edition of African treatment guidelines for common bacterial infections and syndromes

Abstract: Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis). The Africa Centres for Disease Control and Prevention convened expert panels to develop first edition antibiotic treatment guidelines for priority infectious diseases and clinical syndromes for pediatric and adult patient populations in Africa. The purpose of the guidelines is to provide healthcare workers with treatment guidance by harmonising existing national STGs, filling gaps where existing STGs are not available, and serving as a model for future guidelines. Two expert panels of 28 total clinicians, pharmacists, and other relevant stakeholders from 14 AU member states representing each continental region convened to develop consensus treatment recommendations for select priority bacterial infections and clinical syndromes. In developing recommendations, the panels considered treatment recommendations from existing STGs, drug availability, clinical experience, and available antimicrobial resistance data. The guidelines underwent an external review process where clinical stakeholders who did not serve on either panel were invited to submit feedback prior to their publication. The guidelines provide empiric antibiotic therapy guidelines - including drug selection, route of administration, formulation, dosage, and therapy duration - and principles of stewardship for 28 bacterial infections or clinical syndromes. The first edition guidelines for the treatment of common infectious diseases and clinical syndromes in Africa aims to improve clinical treatment and antimicrobial stewardship and will serve as a template for future regional guidelines.

Environmental effect on temporal patterns in lentil seed quality development

Abstract: Abstract To maximize seed longevity, seeds should be harvested at optimal maturity, that is, when seeds have acquired maximum physiological quality before deterioration begins. The aim of this study was to map the variation in temporal patterns of lentil ( Lens culinaris Medik.) seed quality development when grown across four regeneration environments, which differ in the level of temperature and humidity control throughout the growing season, at the Australian Grains Genebank. Seeds of two lentil accessions (76080 and 76072) were harvested at different stages throughout development, commencing at 21 d after 50% anthesis until a maximum of 130 d. At each harvest, physiological quality traits, including germinability (fresh and dried seeds) and seed longevity, were determined, as well as seed dry weight and moisture content. Seeds of both accessions, and in all environments, started to accumulate physiological quality early on in development but did not reach their maximum until 3–54 d after mass maturity. The temporal patterns of desiccation tolerance and storage longevity were highly influenced by the environmental conditions during the maturation drying phase, affecting both ‘when’ maximum quality was attained and for how long it was maintained, thereafter. Seeds did not show a typical developmental response, rather variation was observed in seed quality development both between and within accessions grown in the different environments. The poorest storage longevity was seen when seeds of both accessions were grown in the cooler, temperature-controlled glasshouse, and the maximum longevity was observed in the warmer, semi-protected environments of the green and the big igloo for accessions 76080 and 76072, respectively.