Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines.

The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-Æ´ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA.

Interventions to reduce acute hepatitis C virus in HIV-positive MSM.

PURPOSE OF REVIEW: The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets. RECENT FINDINGS: With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing. SUMMARY: Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.

A systematic interim assessment of the Australian Government's Food and Health Dialogue.

OBJECTIVE: To evaluate whether the Food and Health Dialogue (the Dialogue), established by the Australian Government in 2009, is having an impact on reducing premature death and disability caused by poor diet in Australia. DESIGN AND SETTING: We used information derived from the Dialogue website, media releases, communiqués and e-newsletters to evaluate the Dialogue's achievements from October 2009 to September 2013, using the RE-AIM (reach, efficacy, adoption, implementation and maintenance) framework. Data describing the processed foods marketed in Australia were extracted from an existing food composition database. MAIN OUTCOME MEASURES: Achievements of the Dialogue (goals, targets, actions and health outcomes). RESULTS: The primary goal of the Dialogue was identified as "raising the nutritional profile of foods" to be achieved "through reformulation, consumer education and portion standardisation". Employing a public-private partnership model, the Dialogue has established a framework for collaboration between government, public health groups and industry. In the first 4 years, targets were set for 11 (8.9%) of a total of 124 possible action areas for food reformulation and portion standardisation. None were yet due to have been achieved. There was no evidence that any education programs had been implemented by the Dialogue. There are no indicators of the extent to which population exposure to target nutrients has changed or whether any positive or negative health impacts have ensued. CONCLUSIONS: The Dialogue has highly creditable goals but the mechanism for delivering on them has proved inadequate. Explicit processes and the outcomes to be delivered within defined timelines are required, along with a clear plan for remediation if they are not achieved.

Characterization of Rare Spontaneous Human Immunodeficiency Virus Viral Controllers Attending a National United Kingdom Clinical Service Using a Combination of Serology and Molecular Diagnostic Assays.

Background: We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Methods: Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Results: Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Conclusions: Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.

HPV self-sampling acceptability and preferences among women living with HIV in Botswana.

OBJECTIVE: To assess the acceptability and preferences of HPV screening with self-sampling and mobile phone results delivery among women living with HIV (WLWH) in Botswana, as an alternative to traditional speculum screening. METHODS: WLWH aged 25 years or older attending an infectious disease clinic in Gaborone were enrolled in a cross-sectional study between March and April 2017. Women self-sampled with a flocked swab, had a speculum exam, and completed an interviewer-administered questionnaire about screening acceptability, experiences, and preferences. RESULTS: Of the 104 WLWH recruited, 98 (94%) had a history of traditional screening. Over 90% agreed self-sampling was easy and comfortable. Ninety-five percent were willing to self-sample again; however, only 19% preferred self-sampling over speculum exam for future screening. Preferences differed by education and residence with self-sampling being considered more convenient, easier, less embarrassing, and less painful. Speculum exams were preferred because of trust in providers' skills and women's low self-efficacy to sample correctly. Almost half (47%) preferred to receive results via mobile phone call. Knowledge of cervical cancer did not affect preferences. CONCLUSION: HPV self-sampling is acceptable among WLWH in Botswana; however, preferences vary. Although self-sampling is an important alternative to traditional speculum screening, education and support will be critical to address women's low self-efficacy to self-sample correctly.

Challenges of HIV diagnosis and management in the context of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review.

INTRODUCTION: Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false-negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection. DISCUSSION: Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified. CONCLUSIONS: With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.

Preoperative blood tests in elective general surgery: cost and clinical implications.

A retrospective observational study was performed in our trust in October 2010 that examined compliance, and the financial and clinical implications of performing inappropriate preoperative blood tests on adult patients prior to elective surgery, against the 2003 NICE guidelines. An unacceptable proportion of inappropriate tests (31.3%) were being performed. None were associated with adverse outcome or changes in management. Based on our results, we estimate that an extrapolated cost of pound 11.2 million is being spent on inappropriate blood tests in NHS England and Wales.

Assessment of abnormal personality in childhood: a Delphi survey of questionnaire data.

As an investigation into the feasibility of recording personality status from questionnaire data in younger people we used a three phase Delphi survey to assess items from the Christchurch Health and Development Study, administered at ages 12 to 16 years. Twelve experts took part in Phase I, and 22 in Phases II and III, 16 of whom were experts in adult personality disorder (PD), and 6 were experts who work with children. In total, 189 questions (55% of the total (238) in the questionnaires) were identified as possibly being related to personality abnormality in one or more clusters with high consensus. Experts who work with children were less likely to label features as related to personality than experts in PD (p < 0.001), and the four personality factors (equivalent to Mulder and Joyce's antisocial, asocial, asthenic, and anankastic) chosen for assessment showed variable agreement. Confirmatory factor analysis showed the best fitting model of the data was a 3 factor solution involving asocial/asthenic, antisocial, and anankastic factors. This represents the first attempt to use existing recorded data to code personality status and the results of this Delphi survey give some grounds for optimism that this approach has potential in the early identification of personality features.