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Thompson KM. Polio eradication: what kind of world do we want? Lancet Infect Dis 2021; published online Oct 11. https://doi.org/10.1016/S1473-3099(21)00458-8—In this Comment, the final sentence of the third paragraph has been reworded to “Overall they estimate that, within 6 months, the actual outbreak response campaigns in Africa covered only 11% of the predicted at-risk population of children under 5 years”. This correction has been made to the online version as of oct 18, 2021, and will be made to the printed Comment.

Ivermectin is an oral anti-infective medicine that is integral to neglected tropical disease programmes. It is safe and effective for the treatment and control of lymphatic filariasis, scabies, and onchocerciasis, sometimes as part of a mass drug administration, as recognised in the WHO road map for neglected tropical diseases 2021–30.1 The WHO essential medicines list provides recommendations for minimum medicine needs for a basic health-care system, which includes ivermectin as an anthelmintic, antifilarial, and antiectoparasitic treatment.

Although vaccines against pertussis have been in widespread use for several decades, control of this disease has been complicated by several factors. With respect to vaccinology, complications include that the original whole-cell vaccines are effective but associated with undesirable side-effects, that subsequent acellular vaccines have fewer side-effects but offer less protection and durability than whole-cell vaccines, and that the properties of acellular vaccines appear to vary considerably according to formulation and local context.

A shorter-lived protection induced by the new vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in children aged 2–5 years. If similar findings are observed in other countries and clinical trials, these findings should be considered in future pertussis vaccination policies.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Female mosquitoes use chemical and physical cues, including vision, smell, heat, and humidity, to orient toward hosts. Body odors are produced by skin resident bacteria that convert metabolites secreted in sweat into odorants that confer the characteristic body scent. Mosquitoes detect these compounds using olfactory receptors in their antennal olfactory receptor neurons. Such information is further integrated with the senses of temperature and humidity, as well as vision, processed in the brain into a behavioral output, leading to host finding.

by Marian Loveday, Sindisiwe Hlangu, Lee-Megan Larkan, Helen Cox, Johnny Daniels, Erika Mohr-Holland, Jennifer Furin Background There are few data on the on post-treatment experiences of people who have been successfully treated for rifampicin-resistant (RR-)TB. Objective To describe the experiences and impact of RR-TB disease and therapy on post-treatment life of individuals who were successfully treated. Methods In this qualitative study in-depth interviews were conducted among a purposively selected sample from a population of individuals who were successfully treated for RR-TB between January 2008 and December 2018. Interview transcripts and notes were analysed using a thematic network analysis which included grounded theory and a framework for understanding pathophysiological mechanisms for post-TB morbidity and mortality. The analysis was iterative and the coding system developed focused on disease, treatment and post-treatment experiences of individuals. This paper follows the COREQ guidelines. Results For all 12 participants interviewed, the development of RR-TB disease, its diagnosis and the subsequent treatment were a major disruption to their lives as well as a transformative experience. On diagnosis of RR-TB disease, participants entered a liminal period in which their lives were marked with uncertainty and dominated by physical and mental suffering. Irrespective of how long ago they had completed their treatment, they all remembered with clarity the signs and symptoms of the disease and the arduous treatment journey. Post-treatment participants reported physical, social, psychological and economic changes as consequences of their RR-TB disease and treatment. Many participants reported a diminished ability to perform physical activities and, once discharged from the RR-TB hospital, inadequate physical rehabilitation. For some, these physical limitations impacted on their social life, and ultimately on their psychological health as well as on their ability to earn money and support their families. Conclusion The experiences and impact of RR-TB disease and therapy on post-treatment life of individuals successfully treated, highlights gaps in the current health care system that need to be addressed to improve the life of individuals post-treatment. A more holistic and long-term view of post-TB health, including the provision of comprehensive medical and social services for post-treatment care of physical ailments, social re-integration and the mitigation of the perceived fear and risk of getting TB again could be a central part of person-centred TB care.

Objectives: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2 M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). Design: A phase 2b, multicenter, open-label, rollover study. Methods: LATTE participants with plasma HIV-1 RNA less than 50 copies ml−1 who completed at least 300 weeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2 M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA at least 50 copies ml−1 at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements ≥200 copies ml−1), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. Results: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA at least 50 copies ml−1 or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% (n = 77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. Conclusion: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5 years in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12. Correspondence to William R. Spreen, ViiV Healthcare, Research Triangle Park, NC, USA. E-mail: william.r.spreen@viivhealthcare.com Received 14 April, 2021 Revised 17 August, 2021 Accepted 23 August, 2021 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: To test an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), to increase rates of HIV testing and counseling (HTC) in family planning (FP) clinics in Mombasa, Kenya. Design: Cluster randomized trial Methods: Twenty-four FP clinics were randomized 1:1 to implementing SAIA versus usual procedures. Study staff implemented monthly SAIA cycles with FP clinic staff for 12 months. SAIA has five steps. Step 1 uses a “cascade analysis” tool to quantify the number of individuals who complete each step of a process. Step 2 involves sequential process flow mapping to identify modifiable bottlenecks in the system. Step 3 develops and implements workflow modifications to address bottlenecks. Step 4 assesses impact of the modification by recalculating the cascade analysis. Step 5 repeats the cycle. The primary outcome was the proportion of new FP clients tested for HIV during the last quarter of the trial. Results: During the last three months of the trial, 85% (740/868) of new FP clients were counseled for HIV in intervention clinics compared to 67% (1036/1542) in control clinics (prevalence rate ratio [PRR] 1.27, 95% confidence interval [CI] 1.15-1.30). Forty-two percent (364/859) of FP clients were tested for HIV at intervention clinics compared to 32% (485/1521) at control clinics (PRR 1.33, 95%CI 1.16-1.52). Conclusion: SAIA led to a significant increase in HIV testing in FP clinics in Mombasa. Integrating routine HTC into FP clinics is a promising strategy to achieve the UNAIDS goal of 95% of people living with HIV being aware of their status. Correspondence: McKenna C. Eastment, MD, MPH, 325 9th Avenue, Box 359909, Seattle, WA 98104. Tel: +574-210-1120; fax: +206-744-3693; e-mail: mceast@uw.edu Received 12 October, 2020 Revised 28 September, 2021 Accepted 5 October, 2021 Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: To understand the prevalence of HIV-associated wasting (HIVAW) in the US. Design: Medical and pharmacy claims study using IBM® MarketScan® Commercial, Medicare Supplemental and Medicaid Databases. Methods: Study period: 7/2012–9/2018 (first HIV diagnosis claim = HIV index date). People living with HIV (PLWH) were excluded if they were aged …

Objective(s): To estimate the incidence of neonatal mortality among infants born to women living with HIV in the UK and Ireland in 1998–2017, describe causes of neonatal death (NND) and examine risk factors. Design: Population-based surveillance of pregnancies in diagnosed women living with HIV and their infants in the UK and Ireland. Methods: Estimated yearly incidence of NND was reported for 1998–2017 and causes coded using the World Health Organization International Classification of Perinatal Mortality. Risk factor analyses used multivariable logistic regression, including delivery year, maternal origin, maternal age, delivery CD4 count and viral load (VL), antiretroviral therapy (ART) at conception, preterm delivery (PTD), injecting drug use and infant sex. Results: There were 20,012 live-born infants delivered to 12,684 mothers in 19,601 pregnancies. The overall neonatal mortality rate was 4.10 per 1000 livebirths (95%CI, 3.2–5.0), which was higher than that of the general population. Prematurity was the leading cause of death followed by congenital abnormality. Most NND occurred on the first day of life. ART at conception was associated with significantly reduced NND risk. In a restricted 2007–2017 analysis including VL, PTD and detectable maternal VL were associated with significantly increased NND risk. Conclusions: The vertical transmission rate in the UK, at 3 per 1000, is now lower than the neonatal mortality rate among infants born to women with HIV. More research is needed to investigate the complex relationship between ART, preterm delivery and neonatal death in order to improve all perinatal outcomes. Correspondence to Helen Peters, Population, Practice and Policy Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London; e-mail: Helen.peters@ucl.ac.uk Received 19 April, 2021 Revised 29 September, 2021 Accepted 5 October, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Background: Temsavir (TMR), the active agent of the gp120-directed attachment inhibitor fostemsavir (FTR), the CD4-directed attachment inhibitor ibalizumab (IBA) and the CCR5 antagonist maraviroc (MVC) are ARV agents that target steps in HIV-1 viral entry. Although mechanisms of inhibition of the three agents are different, it is important to understand whether there is potential for cross-resistance between these agents since all involve interactions with gp120. Methods: Envelopes derived from plasma samples from participants in the BRIGHTE study who experienced protocol-derived virologic failure (PDVF) and were co-dosed with FTR and either IBA or MVC were analyzed for susceptibility to the agents. Also, CCR5-tropic MVC-resistant envelopes from the MOTIVATE trials were regenerated and studies were performed to understand whether susceptibility to multiple agents were linked. Results: The cloned envelopes exhibited reduced susceptibility to TMR and resistance to the co-dosed agent. At PDVF, emergent or pre-existing amino acid substitutions were present at TMR positions of interest. When amino acid substitutions at these positions were reverted to the consensus sequence, full susceptibility to TMR was restored without effecting resistance to the co-dosed agent. In addition, 5 envelopes from MOTIVATE were regenerated and exhibited R5-tropic-MVC-resistance. Only 1 exhibited reduced susceptibility to TMR and it contained an M426L polymorphism. When reverted to 426 M, full sensitivity for TMR was restored, but it remained MVC resistant. Conclusions: The data confirm that decreased susceptibility to TMR and resistance to IBA or MVC are not linked and that there is no cross-resistance between either of these two agents and FTR. Correspondence to Mark Krystal, ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405. Tel: +203 643 6401; e-mail: mark.r.krystal@viivhealthcare.com Received 11 August, 2021 Revised 21 September, 2021 Accepted 2 October, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: This study was designed to provide information on the genetic diversity of HIV-1 and drug resistance mutations in Nigeria, as there is limited understanding of variants circulating in the country. Methods: We used an advanced next-generation sequencing platform, Primer ID, to: investigate the presence of high and low abundance drug resistance mutations; characterize pre-existing INSTI mutations in ART-experienced but dolutegravir-naive individuals; detect recent HIV-1 infections and characterize subtype diversity from a cohort of people living with HIV-1 (PLWH). Results: HIV-1 subtype analysis revealed the predominance of CRF02_AG and subtype G in our study population. At detection sensitivity of 30% abundance, DRMs were identified in 3% of samples. At a sensitivity level of 10%, DRMs were identified in 27.3% of samples. We did not detect any major INSTI mutation associated with dolutegravir-resistance. Only one recent infection was detected in our study population. Conclusion: Our study suggests that dolutegravir-containing ARV regimens will be effective in Nigeria. Our study also further emphasizes the high genetic diversity of HIV-1 in Nigeria and that CRF02_AG and subtype G are the dominant circulating forms of HIV-1 in Nigeria. These two circulating forms of the virus are largely driving the epidemic in the country. Correspondence to Christian T. Happi, PhD, African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Osun State, Nigeria. e-mail: happic@run.edu.ng Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 Copyright © 2021 Wolters Kluwer Health, Inc.

Objectives and intervention Bloodstream infection, the presence of viable micro-organisms in the blood, is a prevalent clinical event associated with substantial mortality. Patient outcomes may be improved when the causative micro-organism is identified quickly. We assessed the cost-effectiveness of rapid microbial identification by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. Design Economic evaluation alongside a randomised multicentre trial (RAPIDO: RAPId Diagnosis on Outcome) assessing the impact of rapid identification by MALDI-TOF spectrometry. Setting Adult inpatients with bloodstream infections at seven National Health Service hospital trusts in England and Wales. Primary outcome Net monetary benefit, estimated as incremental costs compared with incremental 28-day survival, of rapid identification by MALDI-TOF spectrometry compared with conventional identification. Methods Patients were randomised (1:1) to receive diagnosis by conventional methods of microbial identification (conventional arm) only or by MALDI-TOF spectrometry in addition to conventional identification (RAPIDO arm). Results Data from 5550 patients were included in primary analysis. Mean imputed costs in 2018/2019 prices per patient were lower by £126 in the RAPIDO arm (95% CI –£784 to £532) but the proportion of patients alive at day 28 was lower (81.4% vs 82.3%). The probability of cost-effectiveness of MALDI-TOF was <0.5 at cost-effectiveness thresholds between £20 000 and £50 000. Conclusions Adjunctive MALDI-TOF diagnosis was unlikely to be cost-effective when measured as cost per death avoided at 28 days. However, the differences between arms in cost and effect were modest, associated with uncertainty and may not accurately reflect ‘real-world’ routine use of MALDI-TOF technology in this patient group. Trial registration numbers ISRCTN97107018/UKCRN 11978.

Objectives The global COVID-19 pandemic produced large-scale health and economic complications. Older people and those with comorbidities are particularly vulnerable to this virus, with nursing homes and long term care facilities (LTCF) experiencing significant morbidity and mortality associated with COVID-19 outbreaks. The aim of this rapid systematic review was to investigate measures implemented in LTCF to reduce transmission of COVID-19 and their effect on morbidity and mortality of residents, staff and visitors. Setting Long-term care facilities. Participants Residents, staff and visitors of facilities. Primary and secondary outcome measures Databases (PubMed, EMBASE, CINAHL, Cochrane Databases and repositories and MedRXiv prepublished database) were systematically searched from inception to 27 July 2020 to identify studies reporting assessment of interventions to reduce transmission of COVID-19 in nursing homes among residents, staff or visitors. Outcome measures include facility characteristics, morbidity data, case fatalities and transmission rates. Due to study quality and heterogeneity, no meta-analysis was conducted. Results The search yielded 1414 articles, with 38 studies included. Reported interventions include mass testing, use of personal protective equipment, symptom screening, visitor restrictions, hand hygiene and droplet/contact precautions, and resident cohorting. Prevalence rates ranged from 1.2% to 85.4% in residents and 0.6% to 62.6% in staff. Mortality rates ranged from 5.3% to 55.3% in residents. Conclusions Novel evidence in this review details the impact of facility size, availability of staff and practices of operating between multiple facilities, and for-profit status of facilities as factors contributing to the size and number of COVID-19 outbreaks. No causative relationships can be determined; however, this review provides evidence of interventions that reduce transmission of COVID-19 in LTCF. PROSPERO registration number CRD42020191569.

Introduction Older adults (age ≥65 years) are pursuing increasingly complex, elective surgeries; and, are at higher risk for intraoperative and postoperative complications. Patients and their caregivers frequently struggle with the postoperative recovery process at home, which may contribute to complications. We aim to identify opportunities to intervene during the preoperative period to improve postoperative outcomes by understanding the preparatory behaviours of older adults and their caregivers before a complex, elective surgery. Methods and analysis As a result of the COVID-19 pandemic, we will conduct this study via telephone and videoconferencing. Using a multiphase mixed-methods research design, we will collect data on 10–15 patient–caregiver dyads from a pool of older adults (across a spectrum of cognitive abilities) scheduled for an elective colorectal surgery between 1 July 2020 and 30 May 2021. We will collect quantitative and qualitative data before (T1, T2) and after (T3, T4) surgery. Preoperatively, participants will each complete a cognitive assessment and a semi-structured qualitative interview that focuses on their preparatory behaviours (T1). They will then answer questionnaires about mood, self-efficacy and home environment (T2). Three weeks following hospital discharge, participants will complete another qualitative interview focusing on a comparison of preoperative and postoperative preparedness (T3). Researchers will also collect information about the patient’s medical conditions, the postoperative complications and healthcare utilisation from the patient’s chart 30 days following discharge (T4). We will code and conduct thematic analysis of the qualitative data to identify salient themes. Quantitative data will be analysed using basic descriptive statistics to characterise the participants. We will integrate the qualitative and quantitative findings using results from the quantitative scales to group participants and with use of joint display analysis. Ethics and dissemination Ethics approval was obtained from the University of Michigan IRB. Study findings will be disseminated through peer-reviewed journals and presentations at conferences.

Introduction Accurate and affordable laboratory testing is key to timely diagnosis and appropriate management of patients with COVID-19. New laboratory test protocols are released into the market under emergency use authorisation with limited evidence on diagnostic test accuracy. As such, robust evidence on the diagnostic accuracy and the costs of available tests is urgently needed to inform policy and practice especially in resource-limited settings. We aim to determine the diagnostic test accuracy, cost-effectiveness and utility of laboratory test strategies for COVID-19 in low-income and middle-income countries. Methods and analysis This will be a multistaged, protocol-driven systematic review conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for diagnostic test accuracy studies. We will search for relevant literature in at least six public health databases, including PubMed, Google Scholar, MEDLINE, Scopus, Web of Science and the WHO Global Index Medicus. In addition, we will search Cochrane Library, COVID-END and grey literature databases to identify additional relevant articles before double-screening and abstraction of data. We will conduct a structured narrative and quantitative synthesis of the results guided by the Fryback and Thornbury framework for assessing a diagnostic test. The primary outcome is COVID-19 diagnostic test accuracy. Using the GRADE approach specific to diagnostic accuracy tests, we will appraise the overall quality of evidence and report the results following the original PRISMA statement. The protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO; https://www.crd.york.ac.uk/prospero/). Ethics and dissemination Ethical review was done by the School of Biomedical Sciences Research Ethics Committee and the Uganda National Council for Science and Technology. The published article will be accessible to policy and decision makers. The findings of this review will guide clinical practice and policy decisions and highlight areas for future research. PROSPERO registration number CRD42020209528.

Objective To summarise the literature on frequent attendances to hospital emergency departments (EDs) and describe sociodemographic and clinical characteristics of children who attend EDs frequently. Setting Hospital EDs. Participants Children <21 years, attending hospital EDs frequently. Primary outcome measures Outcomes measures were defined separately in each study, and were predominantly the number of ED attendances per year. Results We included 21 studies representing 6 513 627 children. Between 0.3% and 75% of all paediatric ED users were frequent users. Most studies defined four or more visits per year as a ‘frequent ED’ usage. Children who were frequent ED users were more likely to be less than 5 years old. In the USA, patients with public insurance were more likely to be frequent attenders. Frequent ED users more likely to be frequent users of primary care and have long-term conditions; the most common diagnoses were infections and gastroenteritis. Conclusions The review included a wide range of information across various health systems, however, children who were frequent ED users have some universal characteristics in common. Policies to reduce frequent attendance might usefully focus on preschool children and supporting primary care in responding to primary care oriented conditions.

Objectives In spring 2020, the first COVID-19 national lockdown placed unprecedented restrictions on the behaviour and movements of the UK population. Citizens were ordered to ‘stay at home’, only allowed to leave their houses to buy essential supplies, attend medical appointments or exercise once a day. We explored how lockdown and its subsequent easing changed young children’s everyday activities, eating and sleep habits to gain insight into the impact for health and well-being. Design In-depth qualitative interviews; data analysed using thematic analysis. Setting South West and West Midlands of England. Participants Twenty parents (16 mothers; 4 fathers) of preschool-age children (3–5 years) due to start school in September 2020. Forty per cent of the sample were from Black, Asian or minority ethnic backgrounds and half lived in the most deprived areas. Results Children’s activity, screen time, eating and sleep routines had been disrupted. Parents reported children ate more snacks, but families also spent more time preparing meals and eating together. Most parents reported a reduction in their children’s physical activity and an increase in screen time, which some linked to difficulties in getting their child to sleep. Parents sometimes expressed guilt about changes in activity, screen time and snacking over lockdown. Most felt these changes would be temporary, though others worried about re-establishing healthy routines. Conclusions Parents reported that lockdown negatively impacted on preschool children’s eating, activity and sleep routines. While some positive changes were identified, many participants described lack of routines, habits and boundaries which may have been detrimental for child health and development. Guidance and support for families during COVID-19 restrictions could be valuable to help maintain healthy activity, eating, screen time and sleeping routines to protect child health and ensure unhealthy habits are not adopted.

Objective To study the SARS-CoV-2 infection rate among hospital healthcare workers after the first wave of the COVID-19 pandemic, and provide more knowledge in the understanding of the relationship between infection, symptomatology and source of infection. Design A cross-sectional study in healthcare workers. Setting Northern Limburg, the Netherlands. Participants All employees of VieCuri Medical Center (n=3300) were invited to enrol in current study. In total 2507 healthcare workers participated. Intervention Between 22 June 2020 and 3 July 2020, participants provided venous blood samples voluntarily, which were tested for SARS-CoV-2 antibodies with the Wantai SARS-CoV-2 Ig total ELISA test. Work characteristics, exposure risks and prior symptoms consistent with COVID-19 were gathered through a survey. Main outcome measure Proportion of healthcare workers with positive SARS-CoV-2 serology. Results The overall seroprevalence was 21.1% (n=530/2507). Healthcare workers between 17 and 30 years were more likely to have SARS-CoV-2 antibodies compared with participants >30 years. The probability of having SARS-CoV-2 antibodies was comparable for healthcare workers with and without direct patient (OR 1.42, 95% CI 0.86 to 2.34) and COVID-19 patient contact (OR 1.62, 95% CI 0.80 to 3.33). On the contrary, exposure to COVID-19 positive coworkers (OR 1.83, 95% CI 1.15 to 2.93) and household members (OR 6.09, 95% CI 2.23 to 16.64) was associated with seropositivity. Of those healthcare workers with SARS-CoV-2 antibodies, 16% (n=85/530) had not experienced any prior COVID-19-related symptoms. Only fever and anosmia were associated with seropositivity (OR 1.90, 95% CI 1.42 to 2.55 and OR 10.51, 95% CI 7.86 to 14.07). Conclusions Healthcare workers caring for hospitalised COVID-19 patients were not at an increased risk of infection, most likely as a result of taking standard infection control measures into consideration. These data show that compliance with infection control measures is essential to control secondary transmission and constrain the spread of the virus.

Introduction The effects of climate change and associated extreme weather events (EWEs) present substantial threats to well-being. EWEs hold the potential to harm sexual health through pathways including elevated exposure to HIV and other sexually transmitted infections (STIs), disrupted healthcare access, and increased sexual and gender-based violence (SGBV). The WHO defines four components of sexual health: comprehensive sexuality education; HIV and STI prevention and care; SGBV prevention and care; and psychosexual counselling. Yet, knowledge gaps remain regarding climate change and its associations with these sexual health domains. This scoping review will therefore explore the linkages between climate change and sexual health. Methods and analysis Five electronic databases (MEDLINE, EMBASE, PsycINFO, Web of Science, CINAHL) will be searched using text words and subject headings (eg, Medical Subject Headings (MeSH), Emtree) related to sexual health and climate change from the inception of each database to May 2021. Grey literature and unpublished reports will be searched using a comprehensive search strategy, including from the WHO, World Bank eLibrary, and the Centers for Disease Control and Prevention. The scoping review will consider studies that explore: (a) climate change and EWEs including droughts, heat waves, wildfires, dust storms, hurricanes, flooding rains, coastal flooding and storm surges; alongside (b) sexual health, including: comprehensive sexual health education, sexual health counselling, and HIV/STI acquisition, prevention and/or care, and/or SGBV, including intimate partner violence, sexual assault and rape. Searches will not be limited by language, publication year or geographical location. We will consider quantitative, qualitative, mixed-methods and review articles for inclusion. We will conduct thematic analysis of findings. Data will be presented in narrative and tabular forms. Ethics and dissemination There are no formal ethics requirements as we are not collecting primary data. Results will be published in a peer-reviewed journal and shared at international conferences.

Objectives Fever is a common symptom among children. Parental lack of knowledge about fever could cause anxiety and lead to unnecessary measures to subside fever. There is little evidence about German parents’ knowledge and their fever management. Design A cross-sectional study using a paper-based questionnaire. Setting 16 kindergartens in Saarbrücken and Saarlouis regional association accepted to participate in the study. Parents from these kindergartens were requested during the pickup time to answer the questionnaire. Participants 481 German parents participated in the study, 394 of them were women. Inclusion criteria were good understanding of German and being a parent of at least one child below the age of 7 years. Primary and secondary outcome measures Knowledge and behaviour of parents on paediatric fever management and the factors influencing fever anxiety. Results The older the parents were, the more anxiety they reported. Their definition of fever had a wide range of 30°C–41°C (mean 38.46, SD=0.67) and almost 90% (mean 3.05, SD=2.03) of participants reported fever as useful, whereby they felt more confident the more they found fever useful. 69% of parents felt calm when their child has fever (mean 4.47, SD=2.27). In case of fever, 55% of parents administer paracetamol, 72% ibuprofen and 32% of them would alternate between the two. Paracetamol and ibuprofen are used more by more anxious parents. In explorative factor analysis, reasons to reduce temperature were summarised in three main factors: damage prevention, illness control and well-being protection, whereby the first two were positively related to parental anxiety. Conclusions Both knowledge as well as level of confidence/anxiety vary largely. Taking antipyretics is related to higher level of anxiety, indicating the need for further education. Fever anxiety depends on multiple factors, which have to be further investigated.

Objective To determine the spectrum of cancers in adolescents and young adults (AYAs) living with and without HIV in South Africa. Design Cross-sectional study with cancer records provided by the National Cancer Registry (NCR) and HIV records from the National Health Laboratory Service (NHLS). Setting and participants The NHLS is the largest provider of pathology services in the South African public sector. The NCR is a division of the NHLS. We included AYAs (aged 10–24 years) diagnosed with cancer by public health sector laboratories between 2004 and 2014 (n=8479). HIV status was obtained through record linkages and text mining. Primary and secondary outcomes We determined the spectrum of cancers by HIV status in AYAs. We used multivariable logistic regression to describe the association of cancer in AYAs with HIV, adjusting for age, sex, ethnicity and calendar period. We imputed (post hoc) the HIV status for AYA with unknown HIV status. Results 8479 AYAs were diagnosed with cancer, HIV status was known for 45% (n=3812). Of those whose status was known, about half were HIV positive (n=1853). AYAs living with HIV were more likely to have Kaposi’s sarcoma (adjusted OR (aOR) 218, 95% CI 89.9 to 530), cervical cancer (aOR 2.18, 95% CI 1.23 to 3.89), non-Hodgkin’s lymphoma (aOR 2.12, 95% CI 1.69 to 2.66) and anogenital cancers other than cervix (aOR 2.73, 95% CI 1.27 to 5.86) than AYAs without HIV. About 44% (n=1062) of AYAs with HIV-related cancers had not been tested for HIV. Conclusions Targeted HIV testing for AYAs diagnosed with cancer, followed by immediate start of antiretroviral therapy, screening for cervical precancer and vaccination against human papilloma virus is needed to decrease cancer burden in AYAs living with HIV in South Africa.

Introduction…

Abstract Background COVID-19 cases have been increasing since the epidemic started. One of the major concerns is how clinical symptomatology would behave after coinfection with another virus. Case presentation In this case report, a pediatric native patient from Estado de Mexico (EDOMEX), MEX had severe DENV-2 and acute SARS-CoV-2 at the same time. The clinical features were severe thrombocytopenia, secondary septic shock, cerebral edema, pericardial effusion, fluid overload that exhibited bipalpebral edema in all four extremities, hemophagocytic lymphohistiocytosis (HLH), coronary artery ectasia (CAE), multisystemic inflammatory syndrome in children (MIS-C), and probable COVID-19 pneumonia or acute respiratory distress syndrome (ARDS) that triggered patient intubation. The patient presented unusual symptomatology according to the literature. After 15 days of intubation and 15 more days under surveillance, he was released without respiratory sequelae and without treatment after major clinical improvement. Conclusion The aim of this manuscript is to present clinical challenges that coinfection may cause in pediatric patients, even though COVID-19 in children does not tend to be as severe as in other sectors of the population.

Abstract Background Antigen testing offers rapid and inexpensive testing for SARS-CoV-2 but concerns regarding performance, especially sensitivity, remain. Limited data exists for use of antigen testing in asymptomatic patients; thus, performance and reliability of antigen testing remains unclear. Methods 148 symptomatic and 144 asymptomatic adults were included. A nasal swab was collected for testing by Quidel Sofia SARS IFA (Sofia) as point of care. A nasopharyngeal swab was also collected and transported to the laboratory for testing by Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV RT-PCR (Cepheid). Results Overall, Sofia had good agreement with Cepheid (> 95%) in adults, however was less sensitive. Sofia had a sensitivity of 87.8% and 33.3% for symptomatic and asymptomatic patients, respectively. Among symptomatic patients, testing > 5 days post symptom onset resulted in lower sensitivity (82%) when compared with testing within 5 days of symptom onset (90%). Of the four Sofia false-negative results in the asymptomatic cohort, 50% went on to develop COVID-19 disease within 5 days of testing. Specificity in both symptomatic and asymptomatic cohorts was 100%. Conclusions Sofia has acceptable performance in symptomatic adults when tested < 5 days of symptom onset. Caution should be taken when testing patients with ≥ 5 days of symptoms. The combination of low prevalence and reduced sensitivity results in relatively poor performance of in asymptomatic patients. NAAT-based diagnostic assays should be considered in when antigen testing is unreliable, particularly in symptomatic patients with > 5 days of symptom onset and asymptomatic patients.

Tropical Medicine & International Health, Accepted Article.

Tropical Medicine & International Health, Accepted Article.

Abstract Background Despite the widespread use of histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs), purified native HRP2 antigen is not standardly used in research applications or assessment of RDTs used in the field. Methods This report describes the purification of native HRP2 (nHRP2) from the HB3 Plasmodium falciparum culture strain. As this culture strain lacks pfhrp3 from its genome, it is an excellent source of HRP2 protein only and does not produce the closely-related HRP3. The nHRP2 protein was isolated from culture supernatant, infected red blood cells (iRBCs), and whole parasite lysate using nickel-metal chelate chromatography. Biochemical characterization of nHRP2 from HB3 culture was conducted by SDS-PAGE and western blotting, and nHRP2 was assayed by RDT, ELISA, and bead-based immunoassay. Results Purified nHRP2 was identified by SDS-PAGE and western blot as a − 60 kDa protein that bound anti-HRP-2 monoclonal antibodies. Mouse anti-HRP2 monoclonal antibody was found to produce high optical density readings between dilutions of 1:100 and 1:3,200 by ELISA with assay signal observed up to a 1:200,000 dilution. nHRP2 yield from HB3 culture by bead-based immunoassay revealed that both culture supernatant and iRBC lysate were practical sources of large quantities of this antigen, producing a total yield of 292.4 µg of nHRP2 from two pooled culture preparations. Assessment of nHRP2 recognition by RDTs revealed that Carestart Pf HRP2 and HRP2/pLDH RDTs detected purified nHRP2 when applied at concentrations between 20.6 and 2060 ng/mL, performing within a log-fold dilution of commercially-available recombinant HRP2. The band intensity observed for the nHRP2 dilutions was equivalent to that observed for P. falciparum culture strain dilutions of 3D7 and US06 F Nigeria XII between 12.5 and 1000 parasites/µL. Conclusions Purified nHRP2 could be a valuable reagent for laboratory applications as well as assessment of new and existing RDTs prior to their use in clinical settings. These results establish that it is possible to extract microgram quantities of the native HRP2 antigen from HB3 culture and that this purified protein is well recognized by existing monoclonal antibody lines and RDTs. Graphical Abstract…

Abstract Background Single nucleotide polymorphisms (SNPs) are the most common types of DNA changes in the human genome that leading to phenotypic differences in humans. MicroRNAs (miRNAs) are usually affected by various bacterial infections, and they are involved in controlling the immune responses. MicroRNA-146a (miR-146a) plays an essential role in the development of infectious and inflammatory diseases. The aim of the present study was to investigate the association between risk of brucellosis and genetic variations in miR-146a. Methods This case–control study was conducted on 108 Brucellosis patients and 108 healthy controls. We genotyped two SNPs (rs2910164 and rs57095329) of the miR-146a using tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. Results The rs2910164 SNP was significantly associated with brucellosis in co-dominant [OR = 4.27, 95% CI = (2.35–7.79, P = 0.001] and dominant [OR = 3.52, 95% CI = (1.97–6.30, P = 0.001] models. Co-dominant (P = 0.047) and recessive (P = 0.018) models were significant at position rs57095329 between the two groups of patient and healthy. The A C haplotype (rs2910164 and rs57095329) was associated with brucellosis in the assessed population [OR (95% CI) = 1.98 (1.22–3.20), P = 0.0059]. Conclusions Consequently, our study demonstrated significant differences in genotype and haplotype frequencies of miR-146a variants between brucellosis patients and controls. Further studies on the larger sample sizes are required to verify the observed associations.

Abstract Background Myiasis is caused by dipterous larvae, and rarely affects the mouth. Diagnosis by traditional means is easy to be confused with other similar species. Here, we report a case of oral myiasis, in a 5-month-old infant who was diagnosed by morphological examination and molecular biological methods. Case presentation A 5-month old infant with acute myeloid leukemia was admitted due to recurrent skin masses for more than 4 months. The infant had lip swelling, which prevented him from closing the mouth and membranes were present in his mouth and there were also oral ulcers and erosions. Ten maggots were found in the mouth and one in the ear canal with pus flowing out and were confirmed as the third stage larvae of Sarcophaga ruficornis by morphological examination and a comparison of sequence of cytochrome oxidase subunit 1 (COX1) gene. After removal of the maggots and chemotherapy, the infant ’s condition was gradually improved. Conclusions To the best of our our knowledge, this is the first neonatal oral myiasis case reported in China and its diagnosis requires a high index of suspicion. Microscopy combined with specific DNA sequence analysis is an effective technological tool to provide rapid diagnoses of the larva specimen and cases of rare diseases, as illustrated in the current case.

Abstract Background Melioidosis, the infection caused by Burkholderia pseudomallei, is associated with a high case fatality rate, due in part to difficulties in clinical recognition and diagnostic confirmation of the disease. Although head and neck involvement is common in children, specific disease manifestations differ between geographic regions. The aim of this study was to provide a detailed description of melioidosis of the head and neck among children in Sarawak, Malaysia, and determine if fine-needle aspiration of suspected head or neck lesions could improve melioidosis diagnosis. Methods We conducted a retrospective descriptive study of all children aged < 12 years with culture-confirmed melioidosis presenting with head and neck manifestations and admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2011 until December 2020. Fine-needle aspiration of head and neck lesions suspected to be due to melioidosis with inoculation in blood culture bottles (FNA + BCB) was used from the beginning of 2016. Results Of 34 children with culture-confirmed melioidosis, 20 (59%) had an infection involving one or more sites in the head and neck. Of these, 17 (85%) were diagnosed in or after 2016. Cervical lymph nodes were the most common organ or site affected, involved in 19 (95%) children. Clinical presentations of B. pseudomallei lymph node infections were highly variable. Five (25%) children had salivary gland involvement. Lacrimal gland involvement (dacryocystitis) and skin or soft tissue infection (scalp abscess) were less frequent. B. pseudomallei was isolated from the head or neck using FNA + BCB in 15 (75%) children and by standard culture methods of direct plating of pus on agar following incision and drainage in only 2 (10%) children. B. pseudomallei was isolated from non-head or neck specimens or blood in 3 (15%) children. Conclusions Manifestations of pediatric head and neck melioidosis in Sarawak, Malaysia, differ from those of other regions. Fine-needle aspiration, mainly of affected cervical lymph nodes, facilitates B. pseudomallei detection and enables confirmation of melioidosis infections.

Abstract Background Nowadays, most studies of tuberculous epididymo-orchitis (TBEO) are case reports or small sample cohort series. Our study is aimed to present the largest series of TBEO with our management experiences and long-term follow-up outcomes. Methods Patients diagnosed with TBEO after surgical procedures at Department of Urology, West China Hospital from 2008 to 2019 were included. All clinical features, auxiliary examination results, treatment and histopathological findings were extracted if available. Results Eighty-one patients (mean age 50.77 ± 16.1 years) were included. Scrotal swelling (N = 47, 58.0%) and pain (N = 29, 35.8%) were the most common presenting complaint. Pyuria and microscopic hematuria were observed in twenty-two (27.2%) and eight patients (9.9%), respectively. Urine acid fast bacilli cultures were available in 16 patients and all were negative. The mean duration between the onset of symptoms and the definite diagnosis was 6.42 ± 7.0 months. TBEO was considered in 30 (37.0%), tumors in 28 (34.6%) and nonspecific bacterial epididymo-orchitis in 23 (28.4%) patients. All patients received triple therapy of chemotherapy-surgery-pharmacotherapy and definite diagnosis was confirmed through histopathology of surgical specimens. Fifty-five patients were followed up regularly (mean follow-up 82.35 ± 36.6 months). One patient (1.2%) died from liver cirrhosis and no recurrence was observed. Postoperative complications included erectile dysfunction in 4 patients (4.9%), premature ejaculation in 5 patients (6.2%) and sterility in 7 patients (8.6%). Conclusions We recommend patients with advanced TBEO to receive triple therapy of chemotherapy-surgery-pharmacotherapy. Physicians should pay more attention to patients’ sexual function and fertility during follow up after treatment completed.

Intracellular parasites have evolved intricate strategies to subvert host cell functions for their own survival. These strategies are particularly damaging to the host if the infection involves immune cells, as illustrated by protozoan parasites of the genus Leishmania that thrive inside mononuclear phagocytic cells, causing devastating immunopathologies. While the impact of Leishmania infection on host cell phenotype and functions has been well documented, the regulatory mechanisms underlying host cell subversion were only recently investigated.

Abstract Background Progress in the fight against malaria has stalled in recent years, highlighting the importance of new interventions and tailored approaches. A critical factor that must be considered across contexts and interventions is human behaviour. Main text Factors such as acceptance of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), ability and willingness to consistently use and appropriately care for ITNs and refraining from post-spray wall modifications can all impact the success of core vector control interventions. Understanding factors that can drive or inhibit these behaviours can contribute to improved social and behaviour change strategies and in turn, improved outcomes. Likewise, patterns of nighttime activities can reveal specific gaps in protection that cannot be filled by core interventions and inform development and deployment of complementary tools that meet people’s needs and preferences. There is an opportunity to increase use of approaches such as human-centred design to engage affected communities more actively in identifying and developing sustainable solutions that meet their needs and lifestyles. Integration of social and behavioural research with entomological and epidemiological evaluations will provide a more complete picture of malaria transmission dynamics and inform improved targeting of context-appropriate interventions. Finally, for gains to be maintained, interventions must be rooted within systems that support long-term success. This includes a movement toward more sustainable vector control solutions, increased decision-making and ownership of research, implementation, and strategy development at the country level, and inclusive approaches that ensure all men, women, boys, and girls are engaged as part of the solution. Conclusions No matter how efficacious, a tool will remain ineffective if communities do not engage with it or use it regularly. Entering the next decade in the fight against malaria there is a critical opportunity to elevate the role of social and behaviour change to increase the impact and sustainability of malaria control and elimination efforts. This includes removing social and structural barriers to use of existing tools at all levels, human-centred and inclusive design and implementation of new tools, and movement toward long-term solutions led by affected communities.

Abstract Background In 2018, the National Malaria Control Programme in Vietnam switched from prioritizing malaria control to elimination. However, with the ongoing elimination programme, there are still areas where residual malaria transmission persists, including the central highlands. This entomological survey was conducted to evaluate Anopheles diversity and host-seeking activity of Anopheles vectors in two communes with very low malaria transmission in Gia Lai Province. Methods Anopheles species were collected in Ia DReh commune and Ia KDam commune, Gia Lai Province in the central highlands of Vietnam. Collections were conducted using human-baited double net trap, light trap and manual aspiration collections around cattle sheds, in the dry and rainy season. Mosquito specimens were identified morphologically, and members of species complexes were distinguished molecularly. Mosquito night-feeding patterns were investigated during the dry and rainy seasons. Results Overall, 18,835 specimens including 19 taxa were collected in Ia KDam and Ia DReh communes. These included the primary malaria vectors, Anopheles dirus and Anopheles minimus, and other secondary vector species. Anopheles dirus was observed to be an anthropophilic species, whereas An. minimus and a number of secondary vectors were observed to be zoophilic. Anopheles vagus was the dominant species, followed by Anopheles sinensis and Anopheles peditaeniatus. The majority of specimens were collected in the rainy season due to the relatively large number of An. vagus, while An. peditaeniatus, An. dirus, Anopheles kochi, Anopheles monstrosus and Anopheles tessellatus were collected in greater numbers during the dry season. The peak of host-seeking activity for An. dirus, An. sinensis, and An. vagus was between 18.00 and 19.00 h. Conclusion This study provided information on the diversity, seasonal prevalence and behaviour of Anopheles at the study sites. Identifying the diverse mosquito fauna in the central highlands of Vietnam allows species-specific control measures to be implemented by the National Programme to reduce malaria in areas of very low malaria transmission. The peak Anopheles host-seeking activity observed in this study was between 18.00 and 23.00 h, which highlights the need to better characterize Anopheles behaviour in this region of Vietnam to inform on vector control strategies.

Abstract Background Intermittent preventive treatment of malaria in pregnancy (IPTp) is a comprehensive treatment protocol of anti-malarial drugs administered to pregnant women to prevent malaria, started at the fourth pregnancy month, with at least three doses of sulfadoxine–pyrimethamine (SP), taken as directly observed treatment (DOT) every 30 days at intervals until childbirth, in combination with other preventive measures. This paper introduces feasibility and adoption concepts as implementation research outcomes (IRO), allowing after a defined intervention, to assess the coverage improvement by IPTp for women attending a reference district hospital in Mali. Specifically, the purpose is to evaluate the feasibility of a reminder tool (provider checklist) to enhance pregnant women’s adoption of information about IPTp-SP uptake as immediate and sustained women practices. Methods The implementation strategy used a reminder checklist about malaria knowledge and the recommended preventive tools. Then, the checklist feasibility was assessed during routine practices with the adoption-level about pregnant women’ knowledge. Quantitative data were collected through a questionnaire distributed to a non-probability purposive sampling targeting 200 pregnant women divided into two groups before and after the checklist intervention. In contrast, the qualitative data were based on in-depth face-to-face gynaecologists’ interviews. Results Both the IROs (feasibility and adoption) were satisfactory. The gynaecologists agreed to the use of this checklist during routine practice with a recommendation to generalize it to other health providers. After a gynaecologist visit, a significant increase of the adoption-level about prior knowledge and preventive tools was noticed. A total of 83% of participants were not knowledgeable about malaria disease before checklist use versus 15% after. Similarly, coverage of women’s SP DOT rose from 0 to 59% after introducing the checklist and the IPTp-SP uptake after the visit was highly significant in the second group. The latter reached 95% of pregnant women with 4–8 months’ gestational age, that mostly respected all SP future visits as theoretically scheduled. Conclusions Generalizing such a checklist reminder will improve women’s knowledge about malaria prevention.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

INTRODUCTION…

Cerebral toxoplasmosis is the most common cause of expansive brain lesions in people living with HIV/AIDS (Vidal, 2019), and the incidence may be as high as 40% (Lee SB and Lee TG, 2017). Acquired immune deficiency syndrome-related primary central nervous system lymphoma (AR-PCNSL) is second only to toxoplasmosis as the most common intracranial mass lesion in adult patients (Kasamon and Ambinder, 2005). The initial diagnosis of cerebral toxoplasmosis is usually made empirically if multiple ring-enhancing lesions are present on brain MRI, the blood serology is positive for Toxoplasma gondii, and clinic-radiological improvement after anti-Toxoplasma therapy is observed (Benson et al., 2018).

INTRODUCTION…

Introduction…

Introduction…

Tropical Medicine & International Health, Accepted Article.

New England Journal of Medicine, Ahead of Print.