Nyt fra tidsskrifterne

Abstract

Background

There is no consensus on the optimal secondary antifungal prophylaxis (SAP) regimen in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the efficacy and safety of posaconazole oral suspension as secondary prophylaxis of invasive fungal disease (IFD) for allo-HSCT patients.

Methods

We retrospectively reviewed clinical data from prior IFD patients who received posaconazole oral suspension as systemic antifungal prophylaxis between June 2016 and January 2021 and have a follow-up period of 1 year after HSCT. The clinical outcomes of patients with a prior history of IFD (n = 30) and those without (n = 93) were compared.

Results

The 1-year cumulative incidence of prophylaxis failure was 58.3% in the group with prior history of IFD and 41.6% in the group without a prior history of IFD (p = 0.459). The cumulative incidence of proven, probable or possible IFD within 1 year after allo-HSCT was 23.1% in the group with prior history of IFD and 14.1% in the group without prior history of IFD (p = 0.230). There was no significant difference between the cumulative incidence of proven or probable IFD within 1-year after allo-HSCT in the group with a prior history of IFD and the group without (p = 0.807). Multivariate logistic regression revealed cytomegalovirus disease as risk factor for post-transplantation IFD occurrence in posaconazole oral suspension prophylaxis. There was not a significant difference in overall survival between the patients with IFD history and those without (P = 0.559).

Conclusions

Our study support that allo-HSCT recipients with a prior history of IFD and normal GI absorption can choose posaconazole oral suspension as a safe and effective SAP option.

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Abstract

Background

The COVID-19 pandemic and its collateral damage severely impact health systems globally and risk to worsen the malaria situation in endemic countries. Malaria is a leading cause of morbidity and mortality in Ghana. This study aims to describe the potential effects of the COVID-19 pandemic on malaria cases observed in health facilities in the Northern Region of Ghana.

Methods

Monthly routine data from the District Health Information Management System II (DHIMS2) of the Northern Region of Ghana were analysed. Overall outpatient department visits (OPD) and malaria case rates from the years 2015–2019 were compared to the corresponding data of the year 2020.

Results

Compared to the corresponding periods of the years 2015–2019, overall visits and malaria cases in paediatric and adult OPDs in northern Ghana decreased in March and April 2020, when major movement and social restrictions were implemented in response to the pandemic. Cases slightly rebounded afterwards in 2020, but stayed below the average of the previous years. Malaria data from inpatient departments showed a similar but more pronounced trend when compared to OPDs. In pregnant women, however, malaria cases in OPDs increased after the first COVID-19 wave.

Conclusions

The findings from this study show that the COVID-19 pandemic affects the malaria burden in health facilities of northern Ghana, with declines in inpatient and outpatient rates except for pregnant women. They may have experienced reduced access to insecticide-treated nets and intermittent preventive malaria treatment in pregnancy, resulting in subsequent higher malaria morbidity. Further data, particularly from community-based studies and ideally complemented by qualitative research, are needed to fully determine the impact of the pandemic on the malaria situation in Africa.

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Abstract

Background

Species of Plasmodium (Haemosporida, Plasmodiidae) are remarkably diverse haemoparasites. Information on genetic diversity of avian malaria pathogens has been accumulating rapidly, however exo-erythrocytic development of these organisms remains insufficiently addressed. This is unfortunate because, contrary to Plasmodium species parasitizing mammals, the avian malaria parasites undergo several cycles of exo-erythrocytic development, often resulting in damage of various organs. Insufficient knowledge on the exo-erythrocytic development in most described Plasmodium species precludes the understanding of mechanisms of virulence during avian malaria. This study extends information on the exo-erythrocytic development of bird malaria parasites.

Methods

A roadkill fieldfare (Turdus pilaris) was sampled in Switzerland and examined using pathologic, cytologic, histologic, molecular and microbiologic methods. Avian malaria was diagnosed, and erythrocytic and exo-erythrocytic stages of the parasite were identified using morphologic characteristics and barcode DNA sequences of the cytochrome b gene. The species-specific characteristics were described, illustrated, and pathologic changes were reported.

Results

An infection with Plasmodium matutinum lineage pLINN1 was detected. Parasitaemia was relatively low (0.3%), with all erythrocytic stages (trophozoites, meronts and gametocytes) present in blood films. Most growing erythrocytic meronts were markedly vacuolated, which is a species-specific feature of this parasite’s development. Phanerozoites at different stages of maturation were seen in leukocytes, macrophages, and capillary endothelial cells in most organs examined; they were particularly numerous in the brain. Like the erythrocytic meronts, growing phanerozoites were markedly vacuolated. Conspicuous exo-erythrocytic development and maturation in leucocytes suggests that this fieldfare was not adapted to the infection and the parasite was capable to escape from cellular immunity.

Conclusions

This is the first report of exo-erythrocytic development of the malaria parasite lineage pLINN1 during single infection and the first report of this lineage in the fieldfare. The findings of multiple phanerozoites in brain, skeletal muscle, and eye tissue in combination with signs of vascular blockage and thrombus formation strongly suggest an impaired vision and neuromuscular responsiveness as cause of the unexpected collision with a slowly moving car. Further studies on exo-erythrocytic stages of haemosporidian parasites are pivotal to understand the true level of populational damage of avian malaria in wild birds.

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Abstract

Background

Targeting the asymptomatic liver stage of Plasmodium infection through chemoprevention could become a key intervention to reduce malaria-associated incidence and mortality.

Methods

M5717, a Plasmodium elongation factor 2 inhibitor, was assessed in vitro and in vivo with readily accessible Plasmodium berghei parasites. In an animal refinement, reduction, replacement approach, the in vitro IC99 value was used to feed a Population Pharmacokinetics modelling and simulation approach to determine meaningful effective doses for a subsequent Plasmodium sporozoite-induced volunteer infection study.

Results

Doses of 100 and 200 mg would provide exposures exceeding IC99 in 96 and 100% of the simulated population, respectively.

Conclusions

This approach has the potential to accelerate the search for new anti-malarials, to reduce the number of healthy volunteers needed in a clinical study and decrease and refine the animal use in the preclinical phase.

Graphical Abstract

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Abstract

Background

Malaria is a potentially fatal disease spread by the bites of Plasmodium-infected Anopheles mosquitoes. Despite long-term efforts to control malaria in Rwanda, malaria incidence increased from 48 to 403 cases/1000 individuals between 2012 and 2016. The diagnosis and treatment of malaria occurs at multiple levels, but the costs of these activities are not well understood. This research was conducted to estimate the direct medical costs incurred by the Ministry of Health in diagnosing and treating malaria in three districts of Rwanda in 2018.

Methods

A cross-sectional and retrospective costing analysis was conducted in three districts that represented low (5–200 cases per 1000 individuals), moderate (> 200–400 cases per 1000 individuals), and high (> 400 cases per 1000 individuals) endemicity regions. Data on malaria cases managed at three healthcare levels (community, health centre, district hospital) was obtained from national databases. The direct medical costs of cases per malaria severity (‘simple malaria’, ‘simple malaria with minor digestive symptoms’, and ‘severe malaria’) were calculated based on the minimum package of health services provided. Total costs for each of the three districts were also calculated.

Results

A total of 298,381 malaria cases were recorded in Burera, Kirehe, and Southern Kayonza districts in 2018. The average unit cost per case ranged from USD 1.36 (for simple malaria at the community level) to USD 92.80 (for severe malaria with cerebral complications at district hospitals). Simple malaria cases managed at health centres and district hospitals were more than two-fold (USD 2.99–USD 3.00) and more than eight-fold (USD 12.10–USD 12.12) higher, respectively, than those managed in the community (USD 1.36). Overall, the Ministry of Health incurred USD 645,647.68 in direct medical costs related to malaria management across the three districts in 2018. Changes in disease rates from different endemicity regions and costs of anti-malarial oral medications significantly impacted the study results.

Conclusion

In Rwanda, severe malaria results in much higher expenses compared to other malaria types. Prompt diagnosis and appropriate treatment are crucial to prevent the progression of simple malaria to severe malaria, to reduce Ministry of Health malaria expenditures, and to reduce community transmission.

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: Due to the spread of the Omicron variant, many countries have experienced COVID-19 case numbers unseen since the start of the pandemic. We aimed to compare the epidemiological characteristics of Omicron with prior variants and different strains of influenza, to provide context for public health responses.

Introduction:…

The female schistosome's dependence on the male to reach sexual maturity has puzzled scientists for decades. Using various molecular techniques, Chen et al. dissect the synthesis pathway of the β-alanyl-tryptamine dipeptide (BATT), emitted by the male into its environment, which induces sexual maturation and egg-laying in the female.

Abstract

Background

Since the beginning of the pandemic, hospitals have been constantly overcrowded, with several observed waves of infected cases and hospitalisations. To avoid as much as possible this situation, efficient tools to facilitate the diagnosis of COVID-19 are needed.

Objective

To evaluate and compare prediction models to diagnose COVID-19 identified in a systematic review published recently using performance indicators such as discrimination and calibration measures.

Methods

A total of 1618 adult patients present at two Emergency Department triage centers and for whom qRT-PCR tests had been performed were included in this study. Six previously published models were reconstructed and assessed using diagnostic tests as sensitivity (Se) and negative predictive value (NPV), discrimination (Area Under the Roc Curve (AUROC)) and calibration measures. Agreement was also measured between them using Kappa’s coefficient and IntraClass Correlation Coefficient (ICC). A sensitivity analysis has been conducted by waves of patients.

Results

Among the 6 selected models, those based only on symptoms and/or risk exposure were found to be less efficient than those based on biological parameters and/or radiological examination with smallest AUROC values (< 0.80). However, all models showed good calibration and values above > 0.75 for Se and NPV but poor agreement (Kappa and ICC < 0.5) between them. The results of the first wave were similar to those of the second wave.

Conclusion

Although quite acceptable and similar results were found between all models, the importance of radiological examination was also emphasized, making it difficult to find an appropriate triage system to classify patients at risk for COVID-19.

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Abstract

Background

Acute respiratory infections (ARIs) and severe acute respiratory illness (SARI) are public health burdens globally. The percentage of non-SARS CoV-2 respiratory viruses among patients having ARI and SARI who visit Car Nicobar's hospital settings is undocumented. Changes in the epidemiology of other respiratory viruses during COVID19 pandemic is being reported worldwide.

Methods

Inpatient and outpatient settings at BJR hospital, Car Nicobar Island, India, were used to conduct prospective monitoring for ARI and SARI among Nicobarese tribal members. The patients with ARI and SARI were enlisted in BJR hospital from June 2019 to May 2021. At the ICMR-NIV in Pune, duplex RT-PCR assays were used to test the presence of respiratory viruses. The prevalence of non- SARS CoV-2 respiratory viruses was measured by comparing here between pandemic and pre-pandemic periods.

Results

During the COVID19 pandemic, Influenza A (H3N2) and rhinovirus were predominantly reported non-SARS CoV-2 respiratory viruses while Human metapneumovirusand influenza A (H1N1)pdm09were most commonly reported in the prepandemic period. This result indicates the altered circulation of non-SARS CoV-2 during pandemic.

Conclusions

A considerable proportion of respiratory infection was correlated with respiratory viruses. Prevalence of non-SARS CoV-2 respiratory viruses was high at the time of infection when compared with pre-pandemic period, at Car Nicobar Island. This study enlightened the change in circulation of other respiratory viruses among the indigenous Nicobarese tribes. Clinicians and allied medical staff should be more prudent of these respiratory infections.

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Objectives

To understand whether and how effective integration of health and social care might occur in the context of major system disruption (the COVID-19 pandemic), with a focus on how the initiative may overcome past barriers to integration.

Design

Rapid, descriptive case study approach with deviant case sampling to gather and analyse key informant interviews and relevant archival documents.

Setting

The innovation (‘COVID-19 Protect’) took place in Norfolk and Waveney, UK, and aimed to foster integration across highly diverse organisations, capitalising on existing digital technology to proactively identify and support individuals most at risk of severe illness from COVID-19.

Participants

Twenty-six key informants directly involved with project conceptualisation and early implementation. Participants included clinicians, executives, digital/information technology leads, and others. Final sample size was determined by theoretical saturation.

Results

Four primary recurrent themes characterised the experiences of diverse team members in the project: (1) ways of working that supported rapid collaboration, (2) leveraging diversity and clinician input for systems change, (3) allowing for both central control and local adaptation and (4) balancing risk taking and accountability.

Conclusions

This rapid case study underscores the role of leadership in large systems change efforts, particularly in times of major disruption. Project leadership overcame barriers to integration highlighted by prior studies, including engaging with aversion to clinical/safety risk, fostering distributed leadership and developing shared organisational practices for data sharing and service delivery. These insights offer considerations for future efforts to support strategic integration of health and social care.

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Introduction

Human immunodeficiency virus (HIV) prevention interventions focused at reducing risky sexual behaviours are an important strategy for preventing HIV infection among youth (15–24 years) who continue to be vulnerable to the disease. This systematic review aims to synthesise current global evidence on the effectiveness of HIV prevention interventions for reducing risky sexual behaviour among youth in the last decade.

Methods and analysis

MEDLINE/PubMed, EMBASE, PsychINFO, ProQuest Central, CINAHL and Web of Science databases, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform and reference lists of included studies and systematic reviews on effectiveness of HIV prevention interventions for reducing risky sexual behaviour among youth will be searched for articles published from August 2011 to August 2021. Eligible studies will be longitudinal studies including randomised controlled trials and quasi-experimental studies that examined the effectiveness of HIV prevention interventions among youth populations (15–24 years) with risky sexual behaviour as a primary or secondary outcome. Study selection and quality assessment will be undertaken independently by three reviewers and disagreements will be resolved through consensus. Data analysis will be undertaken using RevMan software V.5.3.3. A random effects meta-analysis will be conducted to report heterogeneous data where statistical pooling is achievable. We will use I2 statistics to test for heterogeneity. Where appropriate, a funnel plot will be generated to assess publication bias. Where statistical pooling is unachievable, the findings will be reported in a narrative form, together with tables and figures to assist in data presentation if required. Reporting of the systematic review will be informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Ethics and dissemination

Ethical approval is not required. Findings of the systematic review will be published in a peer-reviewed journal. The findings will be of interest to researchers, healthcare practitioners and policymakers.

PROSPERO registration number

CRD42021271774.

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Objectives

This pilot study aimed to evaluate the acceptability of a codesigned, culturally tailored, faith-based online intervention to increase uptake of breast, colorectal and cervical screening in Scottish Muslim women. The intervention was codesigned with Scottish Muslim women (n=10) and underpinned by the reframe, reprioritise and reform model and the behaviour change wheel.

Setting

The study was conducted online, using Zoom, due to the COVID-19 pandemic.

Participants

Participants (n=18) taking part in the intervention and subsequently in its evaluation, were Muslim women residing in Scotland, recruited through purposive and snowball sampling from a mosque and community organisations. Participants were aged between 25 years and 54 years and of Asian and Arab ethnicity.

Design

The study’s codesigned intervention included (1) a peer-led discussion of barriers to screening, (2) a health education session led by a healthcare provider, (3) videos of Muslim women’s experiences of cancer or screening, and (4) a religious perspective on cancer screening delivered by a female religious scholar (alimah). The intervention was delivered twice online in March 2021, followed 1 week later by two focus groups, consisting of the same participants, respectively, to discuss participants’ experiences of the intervention. Focus group transcripts were analysed thematically.

Results

Participants accepted the content and delivery of the intervention and were positive about their experience of the intervention. Participants reported their knowledge of screening had increased and shared positive views towards cancer screening. They valued the multidimensional delivery of the intervention, appreciated the faith-based perspective, and in particular liked the personal stories and input from a healthcare provider.

Conclusion

Participatory and community-centred approaches can play an important role in tackling health inequalities in cancer and its screening. Despite limitations, the intervention showed potential and was positively received by participants. Feasibility testing is needed to investigate effectiveness on a larger scale in a full trial.

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Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

D. Saikia et al.

J. Virtanen et al.

Ż. Zajączkowska et al.

C. Botto-Mahan et al.

AbstractBackgroundCerebral malaria (CM) is a rare, but severe and frequently fatal outcome of infections with Plasmodium falciparum. Pathogenetic mechanisms include endothelial activation and sequestration of parasitized erythrocytes in the cerebral microvessels. Increased concentrations of glycosaminoglycans in urine and plasma of malaria patients have been described, suggesting involvement of endothelial glycocalyx.MethodsWe used lectin histochemistry on postmortem samples to compare the distribution of multiple sugar epitopes on cerebral capillaries in children who died from CM and from non-malarial comas.ResultsN-acetyl glucosamine residues detected by tomato lectin are generally reduced in children with CM compared to controls. We used the vascular expression of intercellular adhesion molecule-1 and mannose residues on brain capillaries of CM as evidence of local vascular inflammation, and both were expressed more highly in CM patients than controls. Sialic acid residues were found to be significantly reduced in patients with CM. By contrast, the levels of other sugar epitopes regularly detected on the cerebral vasculature were unchanged, and this suggests specific remodeling of cerebral microvessels in CM patients.ConclusionsOur findings support and expand upon earlier reports of disruptions of the endothelial glycocalyx in children with severe malaria.

AbstractBackgroundWaning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity has raised the need for booster vaccinations. However, which combination of COVID-19 vaccines offers the strongest immune response against Omicron variant is unknown.MethodsThis randomized, subject-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. 100 BNT162b2-vaccinated individuals were enrolled and randomized 1: 1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; ‘BBB’) or heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ‘BBM’). Primary endpoint was the level of neutralizing antibodies against SARS-CoV-2 wild-type and VOCs at Day 28.Results51 participants were allocated to BBB and 49 to BBM; 50 and 48 respectively were analyzed for safety and immunogenicity outcomes. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22,382  IU/mL 95% CI, 18,210 to 27,517) vs BBM (29,751  IU/mL 95% CI, 25,281 to 35,011, p = 0.034) as was the median level of neutralizing antibodies: BBB 99.0% (IQR 97.9 to 99.3%) vs BBM 99.3% (IQR 98.8 to 99.5%, p = 0.021). On sub-group analysis, significant differences in mean spike antibody titer and live Omicron neutralization titer was only observed in older adults. Median surrogate neutralizing antibody level against all VOCs was also significantly higher with BBM in older adults, and against Omicron was BBB 72.8% (IQR 54.0 to 84.7%) vs BBM 84.3% (IQR 78.1 to 88.7%, p = 0.0073). Both vaccines were well tolerated.ConclusionsHeterologous mRNA-1273 booster vaccination induced a stronger neutralizing response against the Omicron variant in older individuals compared with homologous BNT123b2.

AbstractA positive follow-up blood culture for methicillin-resistant Staphylococcus aureus (MRSA) while on seemingly appropriate therapy is a common and ominous development. However, the definition and management of persistent MRSA bacteremia is unstandardized. In this Opinion Paper we identify the presence of bacteremia for > 1 calendar day as a ‘worry point’ that should trigger an intensive diagnostic evaluation to identify metastatic infection sites. Next, we define the duration of MRSA bacteremia that likely constitutes ‘antibiotic failure’, and outline a proposed management algorithm for such patients. Finally, we propose pragmatic clinical trial designs to test treatment strategies for persistent MRSA bacteremia.

AbstractStaphylococcus aureus bacteremia (SAB) causes considerable morbidity and mortality and requires comprehensive assessment for metastatic infection. The roles of routine imaging beyond echocardiography in SAB, including 18F-FDG-PET/CT, remain contentious. We performed a literature review of studies reporting impact of 18F-FDG-PET/CT on the clinical management or outcomes of SAB published through 3/1/2022. We identified seven observational studies, in which 18F-FDG-PET/CT frequently identified metastatic foci of infection, revealed foci undetected by prior investigations, led to additional source control procedures, and was associated with fewer infection relapses and lower mortality. Calculated numbers needed to treat (NNTs) for receipt of 18F-FDG-PET/CT were 7-9 to change antimicrobial therapy, 10-27 to lead to an additional source control procedure, and 4-8 to prevent death. These data are comparable to the evidence for clinical impact of other diagnostic modalities accepted as standard of care in SAB, and form a compelling basis for advocacy to expand access to 18F-FDG-PET/CT.

AbstractGlobal access to COVID vaccines has been extraordinarily unequal and remains an ongoing source of global health insecurities due to the evolution of viral variants in the bodies of the unvaccinated. There have nevertheless been at least three significant alternatives developed to this disastrous bioethical failure. These alternatives are reviewed in this article in the terms of ‘vaccine diplomacy’, ‘vaccine charity’, and ‘vaccine liberty’. Vaccine diplomacy includes the diverse bilateral deliveries of vaccines organized by the geopolitical considerations of countries strategically seeking various kinds of global and regional advantages in international relations. Vaccine charity centrally involves the humanitarian work of the global health agencies and donor governments that have organized the COVAX program as an antidote to unequal access. Despite their many promises, however, both vaccine diplomacy and vaccine charity have failed to deliver the doses needed to overcome the global vaccination gap. Instead, they have unfortunately served to immunize the global vaccine supply system from more radical demands for a ‘People’s Vaccine’, technological transfer and compulsory licensing of vaccine intellectual property (IP). These more radical demands represent the third alternative to vaccine access inequalities. As a mix of NGO-led and politician-led social justice demands, they are diverse and multifaceted, but together they have been articulated as calls for vaccine liberty. After first describing the realities of vaccine access inequalities, this article compares and contrasts the effectiveness thus far of the three alternatives. In doing so, it also provides a critical bioethical framework for reflecting on how the alternatives have come to compete with one another in the context of the vaccine property norms and market structures entrenched in global IP law. The uneven and limited successes of vaccine diplomacy and vaccine charity in delivering vaccines in underserved countries can be re-considered in this way as compromised successes that not only compete with one another, but which have also worked together to undermine the promise of universal access through vaccine liberty.

AbstractOn February 2022, samples collected in Northwest France showed discordant molecular results. After virological and epidemiological investigations, 17 cases of Deltacron XD recombinant SARS-CoV-2 were confirmed by sequencing or suspected due to epidemiological links, showing evidence of an extended transmission event and circulation of this form, with low clinical severity.

AbstractBackgroundSARS-CoV-2 infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus.MethodsWe measured Spike-specific immunoglobulin G (anti-S IgG) and A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in two academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity.ResultsThe study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P) and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation (VAX-L). VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (p < .0001), while INF mothers had higher BM: serum anti-S IgA ratios compared to VAX mothers (p = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (p < 0.0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, p = 0.013), but not infection.ConclusionsBNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S Ig, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM Ig production. Next generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.