Tropical Medicine & International Health, Accepted Article.

Abstract

Background

Despite the low to moderate intensity of malaria transmission present in Ethiopia, malaria is still a leading public health problem. Current vector control interventions, principally long-lasting insecticidal nets and indoor residual spraying, when deployed alone or in combination, are insufficient to control the dominant vector species due to their exophagic and exophilic tendencies. Zooprophylaxis presents a potential supplementary vector control method for malaria; however, supporting evidence for its efficacy has been mixed.

Methods

To identify risk factors of malaria and to estimate the association between cattle and Anopheles vector abundance as well as malaria risk, a cross-sectional study was conducted in a village near Arba Minch, Ethiopia. Epidemiological surveys (households = 95, individuals = 463), mosquito collections using CDC light traps and a census of cattle and human populations were conducted. To capture environmental conditions, land cover and water bodies were mapped using satellite imagery. Risk factor analyses were performed through logistic, Poisson, negative binomial, and spatial weighted regression models.

Results

The only risk factor associated with self-reported malaria illness at an individual level was being a child aged 5 or under, where they had three times higher odds than adults. At the household level, variables associated with malaria vector abundance, especially those indoors, included socioeconomic status, the proportion of children in a household and cattle population density.

Conclusions

Study results are limited by the low abundance of malaria vectors found and use of self-reported malaria incidence. Environmental factors together with a household’s socioeconomic status and host availability played important roles in the risk of malaria infection in southwest Ethiopia. Cattle abundance in the form of higher cattle to human ratios may act as a protective factor against mosquito infestation and malaria risk. Humans should remain indoors to maximize potential protection against vectors and cattle kept outside of homes.

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Introduction

The COVID-19 pandemic has affected communities of colour the hardest. Non-Hispanic black and Hispanic pregnant women appear to have disproportionate SARS-CoV-2 infection and death rates.

Methods and analysis

We will use the socioecological framework and employ a concurrent triangulation, mixed-methods study design to achieve three specific aims: (1) examine the impacts of the COVID-19 pandemic on racial/ethnic disparities in severe maternal morbidity and mortality (SMMM); (2) explore how social contexts (eg, racial/ethnic residential segregation) have contributed to the widening of racial/ethnic disparities in SMMM during the pandemic and identify distinct mediating pathways through maternity care and mental health; and (3) determine the role of social contextual factors on racial/ethnic disparities in pregnancy-related morbidities using machine learning algorithms. We will leverage an existing South Carolina COVID-19 Cohort by creating a pregnancy cohort that links COVID-19 testing data, electronic health records (EHRs), vital records data, healthcare utilisation data and billing data for all births in South Carolina (SC) between 2018 and 2021 (>200 000 births). We will also conduct similar analyses using EHR data from the National COVID-19 Cohort Collaborative including >270 000 women who had a childbirth between 2018 and 2021 in the USA. We will use a convergent parallel design which includes a quantitative analysis of data from the 2018–2021 SC Pregnancy Risk Assessment and Monitoring System (unweighted n>2000) and in-depth interviews of 40 postpartum women and 10 maternal care providers to identify distinct mediating pathways.

Ethics and dissemination

The study was approved by institutional review boards at the University of SC (Pro00115169) and the SC Department of Health and Environmental Control (DHEC IRB.21-030). Informed consent will be provided by the participants in the in-depth interviews. Study findings will be disseminated with key stakeholders including patients, presented at academic conferences and published in peer-reviewed journals.

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Objective

Across Africa, the impact of COVID-19 continues to be acutely felt. This includes Malawi, where a key component of health service delivery to mitigate against COVID-19 are the primary healthcare facilities, strategically placed throughout districts to offer primary and maternal healthcare. These facilities have limited infrastructure and capacity but are the most accessible and play a crucial role in responding to the COVID-19 pandemic. This study assessed health facility preparedness for COVID-19 and the impact of the pandemic on health service delivery and frontline workers.

Setting

Primary and maternal healthcare in Blantyre District, Malawi.

Participants

We conducted regular visits to 31 healthcare facilities and a series of telephone-based qualitative interviews with frontline workers (n=81 with 38 participants) between August 2020 and May 2021.

Results

Despite significant financial and infrastructural constraints, health centres continued to remain open. The majority of frontline health workers received training and access to preventative COVID-19 materials. Nevertheless, we found disruptions to key services and a reduction in clients attending facilities. Key barriers to implementing COVID-19 prevention measures included periodic shortages of resources (soap, hand sanitiser, water, masks and staff). Frontline workers reported challenges in managing physical distancing and in handling suspected COVID-19 cases. We found discrepancies between reported behaviour and practice, particularly with consistent use of masks, despite being provided. Frontline workers felt COVID-19 had negatively impacted their lives. They experienced fatigue and stress due to heavy workloads, stigma in the community and worries about becoming infected with and transmitting COVID-19.

Conclusion

Resource (human and material) inadequacy shaped the health facility capacity for support and response to COVID-19, and frontline workers may require psychosocial support to manage the impacts of the COVID-19 pandemic.

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Objective

To understand the sexual behaviours and HIV testing uptake of sexually experienced male college students in China.

Design

A cross-sectional study was conducted between September and November of 2020 among male college students.

Setting

Hangzhou, China.

Participants

Male students who had sexual experience in the previous year were investigated.

Outcome measures

Sexual risk behaviour was defined as having multiple sexual partners or having unprotected sex.

Results

More than half of the sexually experienced male students (556, 53.2%) had their first sexual intercourse under the age of 18 years old. Among participants, 32.82% (343/1045) had causal sex in the last 6 months; 4.21% (44/1045) had paid sex; 37.32% (390/1045) had sex with other men and had two or more sexual partners in last half year; and 33.33% (130/390) used psychoactive drugs during same-sex intercourse. Only 33.5% (350/1045) of male students had undertaken an HIV test before.

Conclusion

Male college students especially men who have sex with men were at risk because they tended to be sexually adventurous, have sex at an early age, have sex with multiple sexual partners and practice unprotected sex. Furthermore, they had a low HIV testing uptake. This highlights the importance of carrying out targeted and timely HIV risk education towards college students.

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Introduction

Neoantigens derived from tumour somatic mutations are recognised as ideal vaccine targets. Tumour neoantigens have been studied in a wide range of tumours. Most of research on neoantigens has focused just on a unique tumour and a single mutated gene. Currently, a few studies have reported using a mixture of neoantigen peptides derived from multiple genetic mutation sites in the treatment of genomic unstable advanced solid malignancies. The trial aims to evaluate the safety and efficacy of individualised tumour neoantigen peptide mixtures in the treatment of genomic unstable advanced solid malignant tumours.

Methods and analysis

This is a prospective, non-randomised, open, single-centre, single-arm, phase I trial. Patients with genomic unstable advanced solid malignancies are eligible for study participations. 20 patients will be included in the trial. Through the whole exome and transcriptome sequencing analysis of the fresh blood and tumour tissues of the enrolled patients, the 20 25-33aa antigen peptides with the highest mutation scores of the patients will be screened out, and the corresponding new antigen peptides will be synthesised and prepared. Patients will be treated with their own individualised neoantigen polypeptide combined with a polypeptide adjuvant (human granulocyte-macrophage colony-stimulating factor). The primary endpoint is safety indicators, including general and specific adverse events which will be monitored continuously. Secondary endpoints are progression-free survival, objective response rate, objective duration of remission, 1-year survival rate and overall survival.

Ethics and dissemination

This study has received approval from the Ethics Committee of Chongqing University Cancer Hospital on 21 November 2019 (207/2019). The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

ChiCTR1900025364.

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Objective

Given the role of sociocultural gender in shaping human behaviours, the main objective of this study was to examine whether sex and gender-related factors were associated with the public’s adherence to COVID-19-recommended protective health behaviours.

Design

This was a retrospective analysis of the survey that captured data on people’s awareness, attitudes and behaviours as they relate to the COVID-19 policies.

Setting

Data from the International COVID-19 Awareness and Responses Evaluation survey collected between March 2020 and February 2021 from 175 countries.

Participants

Convenience sample around the world.

Main outcome measures

We examined the role of sex and gender-related factors in relation to non-adherence of protective health behaviours including: (1) hand washing; (2) mask wearing; and (3) physical distancing. Multivariable logistic regression was conducted to determine the factors associated with non-adherence to behaviours.

Results

Among 48 668 respondents (mean age: 43 years; 71% female), 98.3% adopted hand washing, 68.5% mask wearing and 76.9% physical distancing. Compared with males, females were more likely to adopt hand washing (OR=1.97, 95% CI: 1.71 to 2.28) and maintain physical distancing (OR=1.28, 95% CI: 1.22 to 1.34). However, in multivariable sex-stratified models, females in countries with higher Gender Inequality Indexes (GII) were less likely to report hand washing (adjusted OR (aOR)=0.47, 95% CI: 0.21 to 1.05). Females who reported being employed (aOR=0.22, 95% CI: 0.10 to 0.48) and in countries with low/medium GIIs (aOR=0.18, 95% CI 0.06 to 0.51) were less likely to report mask wearing. Females who reported being employed were less likely to report physical distancing (aOR=0.39, 95% CI: 0.32 to 0.49).

Conclusion

While females showed greater adherence to COVID-19 protective health behaviours, gender-related factors, including employment status and high country-wide gender inequality, were independently associated with non-adherence. These findings may inform public health and vaccination policies in current as well as future pandemics.

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Introduction

Inflammatory bowel disease (IBD) involves an abnormal immune response to healthy gut bacteria. When a person develops IBD, their susceptibility to anxiety and/or depression increases. The ACTforIBD programme, specifically designed for people with IBD and comorbid psychological distress, draws on acceptance and commitment therapy (ACT), which promotes acceptance of situations that cannot be solved such as persistent physical symptoms. There are no ACT trials for IBD using an active control group or a telemedicine approach, which is important to improve accessibility, particularly in the context of the ongoing COVID-19 pandemic. The ACTforIBD programme is administered online with a 4-hour therapist involvement per participant only; if successful it can be widely implemented to improve the well-being of many individuals with IBD.

Methods and analysis

Our team have codesigned with consumers the ACTforIBD programme, an 8-week intervention of 1-hour sessions, with the first three sessions and the last session delivered one-to-one by a psychologist, and the other sessions self-directed online. This study aims to evaluate the feasibility and preliminary efficacy of ACTforIBD to reduce psychological distress in patients with IBD. Using a randomised controlled trial, 25 participants will be randomised to ACTforIBD, and 25 patients to an active control condition.

Ethics and dissemination

This protocol has been approved by Deakin University Research Ethics Committee in September 2021 (Ref. 2021-263) and the New Zealand Central Health and Disability Ethics Committee in December 2021 (Ref. 2021 EXP 11384). The results of this research will be published in peer-reviewed journals and shared with various stakeholders, including community members, policy-makers and researchers, through local and international conferences.

Trial registration number

ACTRN12621001316897.

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by Yurie Kobashi, Yuzo Shimazu, Takeshi Kawamura, Yoshitaka Nishikawa, Fumiya Omata, Yudai Kaneko, Tatsuhiko Kodama, Masaharu Tsubokura

The purpose of this study was to identify factors associated with the increase in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S1) protein and neutralizing antibody titer following SARS-CoV-2 vaccination. This observational study was conducted among healthcare workers working for a private hospital group in Fukushima Prefecture, Japan. Two blood samples were obtained from each participant. The first sample was obtained before the first dose of BNT162b2 (Pfizer-BioNTech) vaccine, and a second sample was obtained approximately 6 weeks later. Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein, immunoglobulin M (IgM) antibody against SARS-CoV-2 N-protein, and neutralizing activity were measured using the chemiluminescent immunoassay with iFlash 3000. A total of 231 healthcare workers who agreed to participate, and were negative for anti-SARS-CoV-2 IgM antibodies at enrollment, were included in the analysis. All participants had elevated IgG antibodies and neutralizing activity above the cutoff values. A total of 174 (75.3%) and 208 (90.0%) participants experienced adverse reactions after the first and second vaccine doses, respectively. Younger age, female sex, not taking immunosuppressive or antipyretic analgesic medication regularly, a lack of local adverse reactions after the first dose, and the presence of adverse reactions (fever, muscle, and joint pain) after the second dose were associated with higher IgG antibody titers and neutralizing activity. Intake of analgesic antipyretic for adverse reactions to vaccines was not significantly associated with antibody and neutralizing activity titer production. Immune responses after vaccination may differ among individuals, and continued countermeasures to prevent SARS-CoV-2 infection are vital.

by Manjiri Pawaskar, Jaime Fergie, Carolyn Harley, Salome Samant, Phani Veeranki, Oliver Diaz, James H. Conway

Background Our objective was to estimate the impact of universal varicella vaccination (UVV) on the use and costs of antibiotics and antivirals for the management of varicella among children in the United States (US). Methods A decision tree model of varicella vaccination, infections and treatment decisions was developed. Results were extrapolated to the 2017 population of 73.5 million US children. Model parameters were populated from published sources. Treatment decisions were derived from a survey of health care professionals’ recommendations. The base case modelled current vaccination coverage rates in the US with additional scenarios analyses conducted for 0%, 20%, and 80% coverage and did not account for herd immunity benefits. Results Our model estimated that 551,434 varicella cases occurred annually among children ≤ 18 years in 2017. Antivirals or antibiotics were prescribed in 23.9% of cases, with unvaccinated children receiving the majority for base case. The annual cost for varicella antiviral and antibiotic treatment was approximately $14 million ($26 per case), with cases with no complications accounting for $12 million. Compared with the no vaccination scenario, the current vaccination rates resulted in savings of $181 million (94.7%) for antivirals and $78 million (95.0%) for antibiotics annually. Scenario analyses showed that higher vaccination coverage (from 0% to 80%) resulted in reduced annual expenditures for antivirals (from $191 million to $41 million), and antibiotics ($82 million to $17 million). Conclusions UVV was associated with significant reductions in the use of antibiotics and antivirals and their associated costs in the US. Higher vaccination coverage was associated with lower use and costs of antibiotics and antivirals for varicella management.…

by Anna Poma, Patrizia Cesare, Antonella Bonfigli, Anna Rita Volpe, Sabrina Colafarina, Giulia Vecchiotti, Alfonso Forgione, Osvaldo Zarivi

Molecular biology techniques are increasingly being used in sex identification of skeletal remains when traditional anthropometric analyzes are not successful in identifying sex of remains that are incomplete, fragmented and /or of immature individuals. In the present work, we investigated the possibility of determining sex by using the qPCR-duplex method for both ancient and modern DNA samples. This method involves the co-amplification of two genes in a single reaction system and the subsequent analysis of the fusion curves; the gene sequences used for the construction of suitable primers are those of steroid sulfatase (STS) and testis specific protein Y-linked 1 (TSPY) genes which turned out to be two sensitive markers as they have a detection limit of 60 pg and 20 pg respectively on modern DNA. The validity of the method was verified on modern DNA in which gender was identified in all the samples with 100% accuracy; thus, allowing for the same results as the classic method with amelogenin, but in a faster and more immediate way, as it allows for sex determination solely by analyzing the denaturation curves without having to perform an electrophoretic run. The proposed molecular technique proves to be sensitive and precise even on degraded DNA, in fact on 9 archaeological finds dating from the VII-XII century in which sex had been identified through anthropometric analysis, it confirmed the sex of 8 out of 9 finds correctly.

by Larissa Karoline Dias da Silva Casemiro, Luís Carlos Lopes-Júnior, Fabrine Aguilar Jardim, Mariane Caetano Sulino, Regina Aparecida Garcia de Lima

Introduction Outpatient care for children and adolescents with chronic conditions needs to be continuous and programmed, encompassing comprehensive care, with periodically scheduled consultations, exams, and procedures, to promote quality of life and reduce mortality. In the context of the new coronavirus pandemic, however, outpatient care for children and adolescents with chronic conditions, in person, was hampered in favor of social isolation, a necessary sanitary measure to reduce and prevent the spread of Coronavirus Disease 2019. In response to this need, studies suggest telehealth in pediatrics as a fertile and expanding field especially in times of pandemics. Here, we aimed to map the evidence related to telehealth in outpatient care for children and adolescents with chronic conditions during the COVID-19 pandemic, to identify which strategies were implemented and their impacts on the continuity of care. Methods A scoping review protocol is reported and guided by the Scoping Reviews Manual of the Joanna Briggs Institute. The search for evidence will cover the following databases: MEDLINE/PubMed, Cochrane Libary; Embase; Web of Science; Scopus; Cinahl and PsycINFO, plus additional sources, such as The British Library, Google Scholar, and Preprints [medRXiv]. No date or language restrictions will be employed in this scoping review. Two independent researchers will conduct the search strategy, study selection, data charting, and data synthesis. Results The findings will be presented through tables, charts, narrative summaries, and assessed based on the type of data charted as well as outcomes. Additionally, the meaning of these findings will be considered as they relate to the guiding question, the characterization and measurement of the impact of different telehealth modalities used in outpatient care for children and adolescents with chronic conditions during the COVID-19 pandemic, and the implications for practice and further research. Discussion To the best of our knowledge, this will be the first scoping review to look specifically at the telehealth modalities to be used in outpatient care for children and adolescents with chronic conditions during the COVID-19 pandemic. We expect that our results will be of interest to practitioners as well as researchers concerned with this particular emerging issue in the pandemic context. Also, the plans for the dissemination of this study comprise peer-reviewed publication and conference presentations. trial registration Open Science Framework Registration: osf.io/5pqgu.…

by Mitsuo Uchida, Takenori Yamauchi

Introduction Although influenza surveillance systems have been used to monitor influenza epidemics, these systems generally evaluate diagnostic information obtained from medical institutions and they do not include patients who have not been examined. In contrast, community based epidemiological studies target people with influenza-like illness (ILI) that self-reported influenza-like symptoms whether they have medical examinations or not. Because the criteria for influenza surveillance systems and ILI differ, there is a gap between them. The purpose of this study was to clarify this gap using school-based survey data. Methods Questionnaires about both ILI and the influenza diagnosis history during the 2018/19 season were administered to the guardians of 11,684 elementary schoolchildren in a single city in Japan. Based on their responses, a Bayesian model was constructed to estimate the probability of infection, ILI onset, and diagnosis at medical institutions. Results Responses were obtained from guardians of 10,309 children (88.2%). Of these, 3,380 children (32.8%) had experienced ILI, with 2,380 (23.1%) diagnosed as influenza at a medical institution. Bayesian estimation showed that the probability of influenza cases being diagnosed among ILI symptomatic children was 70% (95% credible interval, 69–71%). Of the infected children, 5% were without ILI symptoms, with 11% of these patients diagnosed with influenza. Conclusions This epidemiological study clarified the proportion gap between ILI and influenza diagnosis among schoolchildren. These results may help to establish epidemic control measures and secure sufficient medical resources.…

by Troy Ganz, Sarah Sanderson, Connor Baush, Melanie Mejia, Manoj Gandhi, Jared Auclair

Clinical evidence for asymptomatic cases of coronavirus disease (COVID-19) has reinforced the significance of effective surveillance testing programs. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assays are considered the ‘gold standard’ for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. However, the labor and resource requirements can be prohibitive with respect to large testing volumes associated with the pandemic. Pooled testing algorithms may serve to increase testing capacity with more efficient resource utilization. Due to the lack of carefully curated cohorts, there is limited evidence for the applicability of RT-PCR pooling in asymptomatic COVID-19 cases. In this study, we compared the analytical sensitivity of the TaqMan™ SARS-CoV-2 Pooling Assay to detect one positive sample in a pool of five anterior nares swabs in symptomatic and asymptomatic cohorts at an institute of higher education. Positive pools were deconvoluted and each individual sample was retested using the TaqPath™ COVID-19 Combo Kit. Both assays target the open reading frame (ORF) 1ab, nucleocapsid (N), and spike (S) gene of the strain that originated in Wuhan, Hubei, China. Qualitative results demonstrated absolute agreement between pooled and deconvoluted samples in both cohorts. Independent t-test performed on Ct shifts supported an insignificant difference between cohorts with p-values of 0.306 (Orf1ab), 0.147 (N), and 0.052 (S). All negative pools were correctly reported as negative. Pooled PCR testing up to five samples is a valid method for surveillance testing of students and staff in a university setting, especially when the prevalence is expected to be low.

by Vanya Rangelova, Ralitsa Raycheva, Sara Sariyan, Ani Kevorkyan

As a member state of the European Union, where vaccines against COVID-19 are available and affordable, Bulgaria reports the lowest immunization coverage and the most pronounced vaccine distrust. The present study aimed to assess the self-reported adverse reactions following COVID-19 vaccination as a possible tool to increase the trust in vaccines. A cross-sectional survey-based study, covering 761 vaccinated respondents, was conducted in Plovdiv (469 with an mRNA vaccine and 292 with an adenoviral vector vaccine). Descriptive statistics parametric and non-parametric methods were applied. Statistical significance was set at p<0.05. The median age of the respondents was 42 years, females (72.5%). At least one adverse reaction was reported in 89.9% of those immunized with mRNA vaccine and 93.8% in the adenoviral vector vaccine group (p>0.05). They were mild to moderate and resolved within several days. The levels of local reactions were comparable: 91.7% in those who received mRNA and 89.7% in those who received an adenoviral vector vaccine (p = 0.366). The most common types of systemic reactions were fatigue, headache, and muscle pains. An association was found between the systemic reactions and the type of vaccine administered: 59.7% in mRNA recipients and 89.4% in adenoviral vector vaccinees (p<0.001). None of the registered systemic reactions required medical attention. There were 3 reports of generalized urticaria after an mRNA and 2 after an adenoviral vector vaccine. The reported reactions are relatively high but expected and no adverse events have been reported that are not listed in the official Summary of Product Characteristics.

by Nina Hangartner, Stefania Di Gangi, Christoph Elbl, Oliver Senn, Fadri Bisatz, Thomas Fehr

During the first year of the COVID-19 pandemic, healthcare facilities worldwide struggled to adequately care for the increasing number of COVID-19 patients while maintaining quality of care for all other patients. The aim of this study was to investigate the displacement and underuse of non-COVID-19 patient care in a medical department of a tertiary hospital in Switzerland. In this retrospective cross-sectional study, internal medicine admissions from 2017 to 2020, emergency outpatient visits from 2019 to 2020 and COVID-19 admissions in 2020 were analyzed and compared using a regression model. Internal medicine admissions were also stratified by diagnosis. A questionnaire was used to assess the pandemic experience of local general practitioners, referring hospitals, and nursing homes. The total number of admissions decreased during the 1st and 2nd waves of the pandemic but increased between the two waves. Elective admissions decreased in 2020 compared to pre-pandemic years: they represented 25% of total admissions in 2020 versus 30% of the total admissions during 2017–2019, p…

by Luke Bracegirdle, Alexander Jackson, Ryan Beecham, Maria Burova, Elsie Hunter, Laura G. Hamilton, Darshni Pandya, Clare Morden, Michael P. W. Grocott, Andrew Cumpstey, Ahilanandan Dushianthan, the REACT COVID-19 Investigators

Background Acute hypoxic respiratory failure (AHRF) is a hallmark of severe COVID-19 pneumonia and often requires supplementary oxygen therapy. Critically ill COVID-19 patients may require invasive mechanical ventilation, which carries significant morbidity and mortality. Understanding of the relationship between dynamic changes in blood oxygen indices and clinical variables is lacking. We evaluated the changes in blood oxygen indices–PaO2, PaO2/FiO2 ratio, oxygen content (CaO2) and oxygen extraction ratio (O2ER) in COVID-19 patients through the first 30-days of intensive care unit admission and explored relationships with clinical outcomes. Methods and findings We performed a retrospective observational cohort study of all adult COVID-19 patients in a single institution requiring invasive mechanical ventilation between March 2020 and March 2021. We collected baseline characteristics, clinical outcomes and blood oxygen indices. 36,383 blood gas data points were analysed from 184 patients over 30-days. Median participant age was 59.5 (IQR 51.0, 67.0), BMI 30.0 (IQR 25.2, 35.5) and the majority were men (62.5%) of white ethnicity (70.1%). Median duration of mechanical ventilation was 15-days (IQR 8, 25). Hospital survival at 30-days was 72.3%. Non-survivors exhibited significantly lower PaO2 throughout intensive care unit admission: day one to day 30 averaged mean difference -0.52 kPa (95% CI: -0.59 to -0.46, p<0.01). Non-survivors exhibited a significantly lower PaO2/FiO2 ratio with an increased separation over time: day one to day 30 averaged mean difference -5.64 (95% CI: -5.85 to -5.43, p<0.01). While all patients had sub-physiological CaO2, non-survivors exhibited significantly higher values. Non-survivors also exhibited significantly lower oxygen extraction ratio with an averaged mean difference of -0.08 (95% CI: -0.09 to -0.07, p<0.01) across day one to day 30. Conclusions As a novel cause of acute hypoxic respiratory failure, COVID-19 offers a unique opportunity to study a homogenous cohort of patients with hypoxaemia. In mechanically ventilated adult COVID-19 patients, blood oxygen indices are abnormal with substantial divergence in PaO2/FiO2 ratio and oxygen extraction ratio between survivors and non-survivors. Despite having higher CaO2 values, non-survivors appear to extract less oxygen implying impaired oxygen utilisation. Further exploratory studies are warranted to evaluate and improve oxygen extraction which may help to improve outcomes in severe hypoxaemic mechanically ventilated COVID-19 patients.…

Abstract

Purpose

This multicenter observational study was done to evaluate risk factors related to the development of BSI in patients admitted to ICU for COVID-19.

Methods

All patients with COVID-19 admitted in two COVID-19 dedicated ICUs in two different hospital between 02–2020 and 02–2021 were recruited.

Result

537 patients were included of whom 265 (49.3%) experienced at least one BSI. Patients who developed bacteremia had a higher SOFA score [10 (8–12) vs 9 (7–10), p < 0.001], had been intubated more frequently [95.8% vs 75%, p < 0.001] and for a median longer time [16 days (9–25) vs 8 days (5–14), p < 0.001]. Patients with BSI had a median longer ICU stay [18 days (12–31.5) vs 9 days (5–15), p < 0.001] and higher mortality [54% vs 42.3%, p < 0.001] than those who did not develop it. Development of BSI resulted in a higher SOFA score [aHR 1.08 (95% CI 1.03–1.12)] and a higher Charlson score [csAHR 1.15 (95% CI 1.05–1.25)].

Conclusion

A high SOFA score and a high Charlson score resulted associated with BSI’s development. Conversely, immunosuppressive therapy like steroids and tocilizumab, has no role in increasing the risk of bacteremia.

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Journal of Medical Virology, Accepted Article.

Background:

Pre-treatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Methods:

HIV-uninfected, sexually active women, aged 18-35 years and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015-2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database.

Results:

We sequenced 275 samples. The median age was 23 years and majority (98.9%, n=272) were infected with HIV-1 subtype C. The prevalence of surveillance drug-resistance mutations (SDRMs) was 13.5% (n=37). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n=34). Few women had NRTI (1.8%, n=5) and protease inhibitor (1.1%, n=3) mutations. Five women had multiple NRTI and NNRTI SDRMs.

Conclusion:

The high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

No abstract available…

Background:

In Sub-Saharan Africa, HIV prevalence in adolescent girls and young women (AGYW) is two- to three-fold higher than in adolescent boys and young men. Understanding AGYW’s perception of HIV risk is essential for HIV prevention efforts.

Methods:

We analyzed data from a HIV bio-behavioral survey conducted in western Kenya in 2018. Data from AGYW aged 15–24 years who had a documented HIV status were included. We calculated weighted prevalences and evaluated factors associated with outcomes of interest (HIV infection and high risk perception) using generalized linear models to calculate prevalence ratios.

Results:

A total of 3,828 AGYW were included; 63% were aged 15–19 years. HIV prevalence was 4.5% and 14.5% of sexually active AGYW had high risk perception. Over 70% of participants had accessed HIV testing and counseling (HTC) in the past 12 months. Factors associated with both HIV infection and high risk perception included: having an HIV-positive partner or partner with unknown status, and having a sexually transmitted infection (STI) in the past 12 months. Having an older (by > 10 years) partner was associated with HIV infection, but not high risk perception. Less than 30% of sexually active AGYW with three or more HIV risk factors had high perception of HIV risk.

Conclusion:

Gaps in perceived HIV risk persist among AGYW in Kenya. High access to HIV testing and prevention services in this population highlights platforms through which AGYW may be reached with improved risk counseling, and to increase uptake of HIV prevention strategies.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Bacteria are protected against the immune system of their human hosts, as well as against predators such as phages, by expressing diverse surface carbohydrates. Some phages produce specialized depolymerases which can degrade those carbohydrates. Here, we discuss the biological role of depolymerases and how they can be exploited to develop new therapeutic strategies against pathogens.

AbstractBackgroundWe hypothesized that oxidative stress in Ugandan children with severe malaria is associated with mortality.MethodsWe evaluated biomarkers of oxidative stress in children with cerebral malaria (CM, n = 77) or severe malarial anemia (SMA, n = 79), who were enrolled in a randomized clinical trial of immediate vs. delayed iron therapy, compared with community children (CC, n = 83). Associations between admission biomarkers and risk of death during hospitalization or risk of readmission within 6 months were analyzed.ResultsNine children with CM and none with SMA died during hospitalization. Children with CM or SMA had higher levels of heme oxygenase-1 (HO-1, p < 0.001) and lower superoxide dismutase (SOD) activity than CC (p < 0.02). Children with CM had a higher risk of death with increasing HO-1 concentration (odds ratio (OR) [95% confidence interval, (CI)], 6.07 [1.17-31.31], p = 0.03), but a lower risk of death with increasing SOD activity (OR [95% CI], 0.02 [0.001-0.70], p = 0.03). There were no associations between oxidative stress biomarkers on admission and risk of readmission within 6 months of enrolment.ConclusionsChildren with CM or SMA develop oxidative stress in response to severe malaria. Oxidative stress is associated with higher mortality in children with CM but not with SMA. Registered at clinicaltrials.gov as NCT01093989.

AbstractBackgroundCombination antiretroviral therapy (cART) initiation during pregnancy reduces the risk of perinatal HIV transmission; however, studies have suggested that there may be unintended adverse consequences on birth outcomes for selected cART regimens.MethodsWe analyzed adverse birth outcomes among a prospective cohort of 1307 pregnant women living with HIV in Dar es Salaam who initiated cART during the first or second trimester of a singleton pregnancy. Our primary analysis compared birth outcomes by gestational age at cART initiation among these women initiating cART in pregnancy.ResultsAmong women who initiated cART in pregnancy, there was no relationship of gestational age at cART initiation with the risk of fetal death or stillbirth. However, women who initiated cART before 20 weeks of gestation as compared to after 20 weeks had increased risk of preterm birth (RR: 1.30, 95% CI: 1.03–1.67), but decreased risk of small-for-gestational age birth (RR: 0.71, 95% CI: 0.55–0.93).ConclusionsWith increasing use of cART preconception and early in pregnancy, clinicians should be aware of the benefits and potential risks of cART regimens to optimize birth outcomes.

SARS-CoV-2 HIV…

AbstractBackgroundLonger-term humoral responses to two-dose COVID-19 vaccines remain incompletely characterized in people living with HIV (PLWH), as do initial responses to a third dose.MethodsWe measured antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement and viral neutralization against wild-type and Omicron strains up to six months following two-dose vaccination, and one month following the third dose, in 99 PLWH receiving suppressive antiretroviral therapy, and 152 controls.ResultsThough humoral responses naturally decline following two-dose vaccination, we found no evidence of lower antibody concentrations nor faster rates of antibody decline in PLWH compared to controls after accounting for sociodemographic, health and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after two doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though Omicron-specific responses were consistently weaker than against wild-type. Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses.ConclusionPLWH receiving suppressive antiretroviral therapy mount strong antibody responses after two- and three-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

AbstractBackgroundThe true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life.MethodsThis prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods.ResultsOf 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval: 5.88–9.08), 5.50 (4.21–7.07), and 2.87 (2.18–3.70) cases/100 person-years in children aged 0–5, 6–11, and 12–23 months. IRs for RSV-LRTI, severe RSV-LRTI and RSV hospitalisation tended to be higher among 0–5-month-olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0–2-month-olds and for ∼20% of LRTIs in older children. Other viruses were co-detected in 29.2% of RSV-positive nasopharyngeal swabs.ConclusionsA substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most.Clinical trial registration: NCT01995175…

AbstractBackgroundHuman Immunodeficiency Virus (HIV) infection during pregnancy is associated with reduced transplacental transfer of maternal antibodies and increased risk of severe infections in children who are exposed and uninfected with HIV (CHEU). The basis of this reduced transfer of maternal immunity has not yet been defined but could involve modifications in the biophysical features of antibodies.ObjectiveTo assess the impact of maternal HIV infection on the biophysical features of serum IgG and transplacental antibody transfer.MethodsMaternal serum IgG subclass levels, Fc glycosylation, Fc Receptor (FcR) binding, and transplacental transfer of pathogen-specific maternal IgG were measured in pregnant women living with HIV (WWH) and pregnant women testing negative for HIV (WNH) in Cape Town, South Africa.ResultsMaternal antibody profiles were strikingly different between pregnant WWH and WNH. Antibody binding to FcγR2a and FcγR2b, IgG1 and IgG3 antibodies, and agalactosylated antibodies were all elevated in WLHIV, whereas digalactosylated and sialylated antibodies were reduced as compared to pregnant WNH. Antibody features that were elevated in WWH were also correlated with reduced transplacental transfer of vaccine antigen-specific antibodies.ConclusionHIV infection is associated with marked alterations of biophysical features of maternal IgG and reduced placental transfer—potentially impairing antimicrobial immunity.

AbstractBackgroundPrevious SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined (“hybrid immunity”), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the U.S. population that have been infected, vaccinated, or with hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies.MethodsIn this serial cross-sectional study, nationwide blood donor specimens collected during January–December 2021 were tested for spike and nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population, and were compared temporally and by demographic factors.ResultsOverall, 1,123,855 blood samples were assayed. From January to December 2021, the weighted percentage of donations with seropositivity due to: vaccination without previous infection increased from 3.5% (95% CI, 3.4%-3.7%) to 64.0%, (95% CI, 63.5%-64.5%); previous infection without vaccination decreased from 15.6% (95% CI, 15.2%-16.0%) to 11.7% (95% CI, 11.4%-12.0%); hybrid immunity increased from 0.7% (95% CI, 0.6%-0.7%) to 18.9% (95% CI, 18.5%-19.3%); and from infection, vaccination, or both increased from 19.8% (95% CI (19.3-20.2) to 94.5% (95% CI, 93.5%-94.0% 0.1%). Infection- and vaccination-induced antibody responses varied significantly by age, race-ethnicity, and region, but not by gender.ConclusionsOur results indicate substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity during 2021. These findings are important to consider in future COVID-19 studies and long-term pandemic mitigation efforts.

AbstractWe describe 2,116 multisystem inflammatory syndrome in children (MIS-C) cases reported to CDC during Delta and Omicron circulation from July 2021–January 2022. Half of MIS-C patients were aged 5-11 years, 52% received ICU-level care, and 1.1% died. Only 3.0% of eligible patients were fully vaccinated prior to MIS-C onset.

AbstractBackgroundSARS-CoV-2 and influenza viruses continue to co-circulate, representing two major public health threats from respiratory infections with similar clinical presentations. SARS-CoV-2 and influenza vaccines can also now be co-administered. However, data on antibody responses to SARS-CoV-2 and influenza co-infection, and vaccine co-administration remains limited.MethodsWe developed a 41-plex antibody immunity assay that can simultaneously characterize antibody landscapes to SARS-CoV-2/influenza/common human coronaviruses. We analyzed sera from 840 individuals (11-93 years), including sera from reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 positive (n = 218) and negative (n = 120) cases, paired sera from SARS-CoV-2 vaccination (n = 29) and infection (n = 11), and paired sera from influenza vaccination (n = 56) and RT-PCR confirmed influenza infection (n = 158) cases. Lastly, we analyzed sera collected from 377 individual that exhibited acute respiratory illness (ARI) in 2020.ResultsThis 41-plex assay has high sensitivity and specificity in detecting SARS-CoV-2 infections. It differentiated SARS-CoV-2 vaccination (antibody responses only to spike protein) from infection (antibody responses to both spike and nucleoprotein). No cross-reactive antibodies were detected to SARS-CoV-2 from influenza vaccination and infection, and vice versa, suggesting no interaction between SARS-CoV-2 and influenza antibody responses. However, cross-reactive antibodies were detected between spike proteins of SARS-CoV-2 and common human coronaviruses that were removed by serum adsorption. Among 377 individual who exhibited ARI in 2020, 129 were influenza positive, none had serological evidence of SARS-CoV-2/influenza co-infections.ConclusionsMultiplex detection of antibody landscapes can provide in-depth analysis of the antibody protective immunity to SARS-CoV-2 in the context of other respiratory viruses including influenza.

AbstractWe describe a case of relapsing babesiosis in an immunocompromised patient. A point mutation in the Babesia microti 23S rRNA gene predicted resistance to azithromycin and clindamycin whereas an amino acid change in the parasite cytochrome b predicted resistance to atovaquone. Following initiation of tafenoquine, symptoms and parasitemia resolved.

AbstractBackgroundThe purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018.MethodsWe developed a Markov model which simulates the natural history and management of syphilis. The model was parameterized by sex and sexual orientation (women who have sex with men, men who have sex with women[MSW], and men who have sex with men[MSM]), and by age at primary infection. We developed a separate decision tree model to quantify health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018.ResultsWe estimated the average number of discounted lifetime QALYs lost per infection as 0.09 [0.03-0.19 95% uncertainty interval (UI)]. The total expected number of QALYs lost due to syphilis acquired in 2018 was 13,349[5,071-31,360]. While per-case loss was the lowest among MSM(0.06), MSM accounted for 47.7% of the overall burden. For each case of congenital syphilis, we estimated 1.79[1.43-2.16] and 0.06[0.01-0.14] QALYs lost in the child and the mother, respectively. We projected 2,332[1,871-2,825] and 79[17-177] QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018.ConclusionsSyphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases.

AbstractWithin two years, novel SARS-CoV-2 vaccines have been developed, rigorously evaluated in large phase 3 trials, and administered to over 5 billion individuals globally. However, adverse events of special interest (AESIs) have been described post-implementation, including myocarditis after mRNA vaccines and thrombosis with thrombocytopenia syndrome (TTS) after adenoviral vector vaccines. AESIs are rare (<1-10/100,000 vaccinees) and less frequent than COVID-19 complications, though they have associated morbidity and mortality. The diversity of: 1) COVID-19 vaccine platforms (e.g., mRNA, viral vector, protein), and 2) rates of AESIs both between and within platforms (e.g., higher rate of myocarditis after mRNA-1273 versus BNT162b2 vaccines) present an important opportunity to advance vaccine safety science. The International Network of Special Immunization Services (INSIS) has been formed with experts in vaccine safety, systems biology, and other relevant disciplines to study cases of AESIs and matched controls to uncover the pathogenesis of rare AESIs and inform vaccine development.

ABSTRACTBackgroundNon-tuberculous Mycobacterium (NTM) infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification.MethodsMycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.ResultsNo adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in eight patients, potentially contributing to lack of treatment response in four cases but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these.ConclusionsPhage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.