Transport of Patients With High-Consequence Infectious Diseases: Development of European Capacity in Norway.

Infection of Western aid workers with Ebola virus disease during the 2014-2016 West African outbreak demonstrated the need for medical evacuation to high-level isolation units in Europe and the United States. In Norway, an ad hoc preparedness team was established for aeromedical evacuation in case of need. In October 2014, this team transported an infected aid worker from the military section of Oslo Airport to Oslo University Hospital. To maintain and strengthen the capacity for domestic ambulance transport on the ground and in the air, the Norwegian Medical Emergency Response Team for High Consequence Infectious Diseases (in Norway known as "Nasjonalt medisinsk utrykningsteam for høyrisikosmitte"), or NORTH, was established as a permanent service in 2017. Recognizing the expertise of this domestic team, Norway was subsequently entrusted with the task of enhancing the European aeromedical transport capacity for high-consequence infectious diseases and establishing the Norwegian rescEU Jet Air Ambulance for Transport of Highly Infectious Patients, or NOJAHIP, in 2022. In this case study, we present experiences and lessons learned from these 2 services and discuss how they can be further developed.

SARS-CoV-2 in the Air Surrounding Patients during Nebulizer Therapy.

Nebulizer therapy is commonly used for patients with obstructive pulmonary disease or acute pulmonary infections with signs of obstruction. It is considered a "potential aerosol-generating procedure," and the risk of disease transmission to health care workers is uncertain. The aim of this pilot study was to assess whether nebulizer therapy in hospitalized COVID-19 patients is associated with increased dispersion of SARS-CoV-2. Air samples collected prior to and during nebulizer therapy were analyzed by RT-PCR and cell culture. Total aerosol particle concentrations were also quantified. Of 13 patients, seven had quantifiable virus in oropharynx samples, and only two had RT-PCR positive air samples. For both these patients, air samples collected during nebulizer therapy had higher SARS-CoV-2 RNA concentrations compared to control air samples. Also, for particle sizes 0.3-5 µm, particle concentrations were significantly higher during nebulizer therapy than in controls. We were unable to cultivate virus from any of the RT-PCR positive air samples, and it is therefore unknown if the detected virus were replication-competent; however, the significant increase in smaller particles, which can remain airborne for extended periods of time, and increased viral RNA concentrations during treatment may indicate that nebulizer therapy is associated with increased risk of SARS-CoV-2 transmission.

Dispersion of SARS-CoV-2 in air surrounding COVID-19-infected individuals with mild symptoms.

Since the beginning of the pandemic, the transmission modes of SARS-CoV-2-particularly the role of aerosol transmission-have been much debated. Accumulating evidence suggests that SARS-CoV-2 can be transmitted by aerosols, and not only via larger respiratory droplets. In this study, we quantified SARS-CoV-2 in air surrounding 14 test subjects in a controlled setting. All subjects had SARS-CoV-2 infection confirmed by a recent positive PCR test and had mild symptoms when included in the study. RT-PCR and cell culture analyses were performed on air samples collected at distances of one, two, and four meters from test subjects. Oronasopharyngeal samples were taken from consenting test subjects and analyzed by RT-PCR. Additionally, total aerosol particles were quantified during air sampling trials. Air viral concentrations at one-meter distance were significantly correlated with both viral loads in the upper airways, mild coughing, and fever. One sample collected at four-meter distance was RT-PCR positive. No samples were successfully cultured. The results reported here have potential application for SARS-CoV-2 detection and monitoring schemes, and for increasing our understanding of SARS-CoV-2 transmission dynamics. Practical implications. In this study, quantification of SARS-CoV-2 in air was performed around infected persons with mild symptoms. Such persons may go longer before they are diagnosed and may thus be a disproportionately important epidemiological group. By correlating viral concentrations in air with behavior and symptoms, we identify potential risk factors for viral dissemination in indoor environments. We also show that quantification of total aerosol particles is not a useful strategy for monitoring SARS-CoV-2 in indoor environments.

Best practices of highly infectious decedent management: Consensus recommendations from an international expert workshop.

With the increasing number of highly infectious disease incidents, outbreaks, and pandemics in our society (e.g., Ebola virus disease, Lassa fever, coronavirus diseases), the need for consensus and best practices on highly infectious decedent management is critical. In January 2020, a workshop of subject matter experts from across the world convened to discuss highly infectious live patient transport and highly infectious decedent management best practices. This commentary focuses on the highly infectious decedent management component of the workshop. The absence of guidance or disparate guidance on highly infectious decedent management can increase occupational safety and health risks for death care sector workers. To address this issue, the authorship presents these consensus recommendations on best practices in highly infectious decedent management, including discussion of what is considered a highly infectious decedent; scalability and storage for casualty events; integration of key stakeholders; infection control and facility considerations; transport; care and autopsy; psychological, ethical, and cultural considerations as well as multi-national care perspectives. These consensus recommendations are not intended to be exhaustive but rather to underscore this overlooked area and serve as a starting point for much-needed conversations.

Achievements and Challenges in the Prevention of Mother-to-Child Transmission of HIV-A Retrospective Cohort Study from a Rural Hospital in Northern Tanzania.

Despite the goal of eliminating new human immunodeficiency virus (HIV) infections in children, mother-to-child transmission is still common in resource-poor countries. The aims of this study were to assess the occurrence of mother-to-child transmission of HIV (MTCT) by age 18 months, risk factors for transmission, and the implementation of the national prevention of MTCT (PMTCT) program in a rural hospital in Tanzania. Data were collated from various medical registers and records. We included 172 children and 167 HIV-infected mothers. Among 88 children (51%) with adequate information, 9 (10.2%) were infected. Increased risk of MTCT was associated with late testing of the child (>2 months) [OR = 9.5 (95% CI: 1.8-49.4)], absence of antiretroviral therapy during pregnancy [OR = 9.7 (95% CI: 2.1-46.1)], and maternal CD4 cell count <200 cells/mm3 [OR = 15.3 (95% CI: 2.1-111)]. We were unable to determine the occurrence of MTCT transmission in 84 children (49%). The results from this study highlight that there is an urgent need for enhanced efforts to improve follow-up of HIV-exposed children, to improve documentation in registries and records, and to facilitate ease of linkage between these.

The story of an extraordinary year: Challenges and opportunities in responding to Covid-19.

Little more than a year after the first reports of a new coronavirus in Wuhan, China, the world is in the middle of a pandemic that has brought dramatic changes in societies all over the world. This is our story, as seen from the Department of Immunology and Transfusion at Oslo University Hospital (OUH).

Investigational treatment of COVID-19. / Utprøvende behandling ved covid-19.

What to do in the absence of drugs with proven effect?

The burden of herpes zoster disease in Norway.

BACKGROUND: No national vaccination program against herpes zoster (HZ) is currently in place in Norway. We aimed to quantify the burden of medically attended HZ to assess the need for a vaccination program. METHODS: We linked data from several health registries to identify medically attended HZ cases during 2008-2014 and HZ-associated deaths during1996-2012 in the entire population of Norway. We calculated HZ incidences for primary and hospital care by age, sex, type of health encounter, vaccination status, and co-morbidities among hospital patients. We also estimated HZ-associated mortality and case-fatality. RESULTS: The study included 82,064 HZ patients, of whom none were reported as vaccinated against HZ. The crude annual incidence of HZ was 227.1 cases per 100,000 in primary healthcare and 24.8 cases per 100,000 in hospitals. Incidence rates were higher in adults aged ≥50 years (461 per 100,000 in primary care and 57 per 100,000 in hospitals), and women than in men both in primary healthcare (267 vs 188 per 100,000), and hospitals (28 vs 22 per 100,000). Among hospital patients, 47% had complicated zoster and 25% had comorbidities, according to the Charlson comorbidity index. The duration of hospital stay (median 4 days) increased with the severity of comorbidities. The estimated mortality rate was 0.18 per 100,000; and in-hospital case-fatality rate was 1.04%. CONCLUSIONS: Medically attended HZ poses a substantial burden in the Norwegian healthcare sector. The majority of the zoster cases occurred among adults aged ≥50 years - the group eligible for zoster vaccination - and increased use of zoster vaccination may be warranted, especially among persons with co-morbidities.

Vaccination of healthcare personnel in Europe: Update to current policies.

We investigated and compared current national vaccination policies for health-care personnel (HCP) in Europe with results from our previous survey. Data from 36 European countries were collected using the same methodology as in 2011. National policies for HCP immunization were in place in all countries. There were significant differences in terms of number of vaccinations, target HCP and healthcare settings, and implementation regulations (recommended or mandatory vaccinations). Vaccination policies against hepatitis B and seasonal influenza were present in 35 countries each. Policies for vaccination of HCP against measles, mumps, rubella and varicella existed in 28, 24, 25 and 19 countries, respectively; and against tetanus, diphtheria, pertussis and poliomyelitis in 21, 20, 19, and 18 countries, respectively. Recommendations for hepatitis A immunization existed in 17 countries, and against meningococcus B, meningococcus C, meningococcus A, C, W, Y, and tuberculosis in 10, 8, 17, and 7 countries, respectively. Mandatory vaccination policies were found in 13 countries and were a pre-requisite for employment in ten. Comparing the vaccination programs of the 30 European countries that participated in the 2011 survey, we found that more countries had national vaccination policies against measles, mumps, rubella, hepatitis A, diphtheria, tetanus, poliomyelitis, pertussis, meningococcus C and/or meningococcus A, C, W, Y; and more of these implemented mandatory vaccination policies for HCP. In conclusion, European countries now have more comprehensive national vaccination programs for HCP, however there are still gaps. Given the recent large outbreaks of vaccine-preventable diseases in Europe and the occupational risk for HCP, vaccination policies need to be expanded and strengthened in several European countries. Overall, vaccination policies for HCP in Europe should be periodically re-evaluated in order to provide optimal protection against vaccine-preventable diseases and infection control within healthcare facilities for HCP and patients.

Indirect Effects of Pneumococcal Childhood Vaccination in Individuals Treated With Immunosuppressive Drugs in Ambulatory Care: A Case-cohort Study.

BACKGROUND: The extent to which iatrogenically-immunosuppressed individuals benefit from indirect effects of childhood vaccination with pneumococcal conjugate vaccines (PCVs) is unknown. We determined how the sequential introduction of PCV7 (2006) and PCV13 (2011) in the Norwegian childhood vaccination program has affected the epidemiology of invasive pneumococcal disease (IPD) in individuals treated with immunosuppressants in ambulatory care. METHODS: We conducted a case-cohort study comprising 7926 IPD cases reported to the Norwegian Surveillance System for Communicable Diseases in 2005-2014 and 249998 individuals randomly selected from the National Registry in 2012. We defined immunosuppressive treatment groups based on dispensed prescriptions retrieved from the Norwegian Prescription Database. Incidences and age-adjusted relative risks (RR) were estimated. RESULTS: IPD incidences decreased in all groups. The PCV13 incidence decreased by 5-12% across groups. The non-PCV13 incidence increased by 4-10%, mostly in individuals on chemotherapy (overlapping 95% confidence intervals). In the PCV13 era, the RR for IPD was highest (significant) and the percentage of cases caused by the polysaccharide vaccine PPV23 serotypes lowest (numerical) in individuals on chemotherapy (RR = 20.4, PPV23 = 52%), followed by individuals on corticosteroids (RR = 6.2, PPV23 = 64%), other immunosuppressants (RR = 5.6, PPV23 = 68%), and no immunosuppressants (RR = 1 [reference], PPV23 = 74%). CONCLUSIONS: IPD incidences declined after PCV introduction in both immunocompetent and iatrogenically-immunosuppressed individuals, underscoring the benefit of childhood vaccination for the entire population. Still, individuals treated with immunosuppressants in ambulatory care are at increased risk of IPD caused by a more diverse group of serotypes.

Non-tuberculous mycobacterial pulmonary infections. / Lungeinfeksjoner med ikke-tuberkuløse mykobakterier.

BAKGRUNN: Lungeinfeksjoner med ikke-tuberkuløse mykobakterier påvises jevnlig i klinisk praksis. Diagnostikk og behandling er utfordrende, og internasjonale retningslinjer bygger i stor grad på erfaring og kasuistikker. Temaet er kort og generelt omtalt i Tuberkuloseveilederen, utover det finnes ingen nasjonal behandlingsveileder om temaet. Denne artikkelen sammenfatter den nyeste kunnskapen om emnet, med hovedvekt på diagnostikk og behandling. KUNNSKAPSGRUNNLAG: Vi søkte i PubMed, Embase og Cochrane etter alle oversiktsartikler og systematiske oversiktsartikler i tidsrommet 2007-17 om ikke-tuberkuløse mykobakterier som årsak til lungesykdom. RESULTATER: Ved diagnostikk og behandling av lungeinfeksjoner med ikke-tuberkuløse mykobakterier må både kliniske, radiologiske og mikrobiologiske funn vurderes før man beslutter om det er behandlingsindikasjon. Identifikasjon av art og eventuell underart av påvist mykobakterie og resistensmønster er av stor betydning. Behandlingen består av en kombinasjon av flere medikamenter over lang tid som ofte har mange bivirkninger og interaksjoner. FORTOLKNING: Behandlingsresultatene for lungeinfeksjoner med ikke-tuberkuløse mykobakterier er varierende. Det er viktig å ta stilling til om nytten av behandlingen forventes å oppveie ulempene den kan medføre. For mange pasienter vil optimalisering av øvrig behandling for den underliggende lungesykdommen være viktigst. Pasientene må følges opp regelmessig med ekspektoratprøver og monitorering av bivirkninger.

Stratification by interferon-γ release assay level predicts risk of incident TB.

INTRODUCTION: Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. METHODS: In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. RESULTS: The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). CONCLUSIONS: Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

Human cytomegalovirus (CMV) in Africa: a neglected but important pathogen.

In Africa, human cytomegalovirus (CMV) is an important pathogen in a diverse range of patient groups. Congenital CMV infection is common, and most children undergo primary infection during the first year of life. Preliminary studies suggest that these early primary CMV infections could have population-wide effects on growth and development. In most studies of adults, CMV seroprevalence is close to 100%, but some studies have found that significant minorities of adults are seronegative. CMV is a common cause of pneumonia and meningitis in hospitalised immunosuppressed patient groups, and CMV DNAemia may be an important marker of rapid progression and poor outcomes of HIV infection, despite roll-out of antiretroviral therapy (ART). Diagnosis and treatment of CMV-related disease is broadly neglected in Africa, and no randomised clinical trials of anti-CMV drugs have been conducted to date. Autopsy is rarely performed in Africa, but identifies CMV as a frequent pathogen when it is carried out. Here we review the available literature on CMV in Africa, primarily in adult patients, and discuss this in the context of contemporary understanding of CMV as a human pathogen.

Clinical Management of Ebola Virus Disease in the United States and Europe.

BACKGROUND: Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. METHODS: We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015. RESULTS: A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renal-replacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had respiratory and renal failure, for a mortality of 18.5%. CONCLUSIONS: Among the patients with EVD who were cared for in the United States or Europe, close monitoring and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support, and critical care management for respiratory and renal failure were needed; 81.5% of these patients who received this care survived.

Cytomegalovirus viremia in dried blood spots is associated with an increased risk of death in HIV-infected patients: a cohort study from rural Tanzania.

OBJECTIVES: The objectives of the study were to assess the utility of dried blood spots (DBS) for the detection of cytomegalovirus (CMV) antibody and viremia in a resource-poor setting, to study the prevalence of CMV antibody and viremia in HIV-infected patients with access to antiretroviral therapy (ART) in Tanzania, and to relate CMV viremia to outcome. METHODS: DBS were prepared from 168 ART-naïve patients at baseline. Demographic, clinical, and laboratory data were obtained from patient records. CMV antibody was analyzed by chemiluminescent microparticle immunoassay and viremia by quantitative PCR. RESULTS: All patients were CMV-seropositive. At baseline 38 (22.6%) had detectable CMV viremia and 14 (8.3%) had a CMV viral load ≥ 200 copies/ml. In 135 patients available for follow-up, CMV ≥ 200 copies/ml was an independent risk factor for death with a hazard ratio of 5.0 (95% confidence interval 2.1-11.9) after adjusting for confounders. Symptoms compatible with CMV disease were common with viremia ≥ 200 copies/ml and CD4+ T cell counts <100 cells/mm(3), but confirmatory diagnostic procedures were unavailable. CONCLUSIONS: DBS are suitable for the detection of CMV antibody and viremia in HIV patients in resource-poor areas. CMV viremia was frequent and associated with an increased risk of death. Improved diagnosis and treatment of CMV may improve the prognosis for HIV-infected patients in developing countries and should be addressed in future studies.