Christian Dopfer

Effects of Lumacaftor–Ivacaftor Therapy on Cystic Fibrosis Transmembrane Conductance Regulator Function in Phe508del Homozygous Patients with Cystic Fibrosis

Rationale: The combination of the CFTR (cystic fibrosis transmembrane conductance regulator) corrector lumacaftor with the potentiator ivacaftor has been approved for the treatment of patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. The phase 3 trials examined clinical outcomes but did not evaluate CFTR function in patients. Objectives: To examine the effect of lumacaftor‐ivacaftor on biomarkers of CFTR function in Phe508del homozygous patients with cystic fibrosis aged 12 years and older. Methods: This prospective observational study assessed clinical outcomes including FEV1% predicted and body mass index, and CFTR biomarkers including sweat chloride concentration, nasal potential difference, and intestinal current measurement before and 8‐16 weeks after initiation of lumacaftor‐ivacaftor. Measurements and Main Results: A total of 53 patients were enrolled in the study, and 52 patients had baseline and follow‐up measurements. After initiation of lumacaftor‐ivacaftor sweat chloride concentrations were reduced by 17.8 mmol/L (interquartile range [IQR], −25.9 to −6.1; P < 0.001), nasal potential difference showed partial rescue of CFTR function in nasal epithelia to a level of 10.2% (IQR, 0.0‐26.1; P < 0.011), and intestinal current measurement showed functional improvement in rectal epithelia to a level of 17.7% of normal (IQR, 10.8‐29.0; P < 0.001). All patients improved in at least one CFTR biomarker, but no correlations were found between CFTR biomarker responses and clinical outcomes. Conclusions: Lumacaftor‐ivacaftor results in partial rescue of Phe508del CFTR function to levels comparable to the lower range of CFTR activity found in patients with residual function mutations. Functional improvement was detected even in the absence of short‐term improvement of FEV1% predicted and body mass index. Clinical trial registered with www.clinicaltrials.gov (NCT02807415).

Norovirus outbreaks in german refugee camps in 2015

Purpose Refugees often live in confined housing conditions with shared kitchen and sanitary facilities, rendering susceptible to communicable diseases. We here describe the outbreak, spread and self-limiting nature of a norovirus outbreak in a German refugee camp in the winter of 2015. Methods During a norovirus outbreak, data on clinical symptoms, nationality and living conditions was obtained in a refugee camp in northern Germany in the winter of 2015. Furthermore secondary data on norovirus outbreaks in 2015 was assessed. Results Amongst n = 982 refugees, n = 36 patients (3.7 %) presented with acute norovirus gastroenteritis. The vast majority of cases were children, only the first patient was admitted to the hospital. Intensified hygiene measures were implemented on day 2 of the outbreak, but new cases peaked on day 21 and occurred until one month after the first case. Different cultural backgrounds, eating habits and hygiene standards amongst the refugees made it particularly challenging to implement stringent isolation and hygiene measures. Despite these predisposing factors, only minor norovirus outbreaks were reported in refugee camps in 2015. Conclusion Adults refugees had a low attack rate of symptomatic norovirus infection, while small children are at high risk. Infection spreads despite hygiene measures and camp sites and staff should be prepared for the particular challenges of such situations with a particular focus on cultural-background specific implementation of hygiene measures.

Tuberculosis Specific Interferon-Gamma Production in a Current Refugee Cohort in Western Europe

Background: In 2015, a high number of refugees with largely unknown health statuses immigrated to Western Europe. To improve caretaking strategies, we assessed the prevalence of latent tuberculosis infection (LTBI) in a refugee cohort. Methods: Interferon-Gamma release assays (IGRA, Quantiferon) were performed in n = 232 inhabitants of four German refugee centers in the summer of 2015. Results: Most refugees were young, male adults. Overall, IGRA testing was positive in 17.9% (95% CI = 13.2–23.5%) of subjects. Positivity rates increased with age (0% <18 years versus 46.2% >50 years). Age was the only factor significantly associated with a positive IGRA in multiple regression analysis including gender, C reactive protein, hemoglobin, leukocyte, and thrombocyte count and lymphocyte, monocyte, neutrophil, basophil, and eosinophil fraction. For one year change in age, the odds are expected to be 1.06 times larger, holding all other variables constant (p = 0.015). Conclusion: Observed LTBI frequencies are lower than previously reported in similar refugee cohorts. However, as elderly people are at higher risk for developing active tuberculosis, the observed high rate of LTBI in senior refugees emphasizes the need for new policies on the detection and treatment regimens in this group.

Pregnancy Related Health Care Needs in Refugees—A Current Three Center Experience in Europe

Background: Immigration into Europe has reached an all-time high. Provision of coordinated healthcare, especially to refugee women that are at increased risk for adverse pregnancy outcomes, is a challenge for receiving health care systems. Methods: We assessed pregnancy rates and associated primary healthcare needs in three refugee cohorts in Northern Germany during the current crisis. Results: Out of n = 2911 refugees, 18.0% were women of reproductive age, and 9.1% of these were pregnant. Pregnancy was associated with a significant, 3.7-fold increase in primary health care utilization. Language barrier and cultural customs impeded healthcare to some refugee pregnant women. The most common complaints were demand for pregnancy checkup without specific symptoms (48.6%), followed by abdominal pain or urinary tract infections (in 11.4% of cases each). In 4.2% of pregnancies, severe complications such as syphilis or suicide attempts occurred. Discussion: We present data on pregnancy rates and pregnancy associated medical need in three current refugee cohorts upon arrival in Germany. Healthcare providers should be particularly aware of the requirements of pregnant migrants and should adapt primary caretaking strategies accordingly.

Healthcare Utilization in a Large Cohort of Asylum Seekers Entering Western Europe in 2015

During the current period of immigration to Western Europe, national healthcare systems are confronted with high numbers of asylum seekers with largely unknown health status. To improve care taking strategies, we assessed healthcare utilization in a large, representative cohort of newly arriving migrants consisting of n = 1533 residents of a reception center in Northern Germany in 2015. Most asylum seekers were young, male adults, and the majority came from the Eastern Mediterranean region. Overall, we observed a frequency of 0.03 visits to the onsite primary healthcare ward per asylum seeker and day of camp residence (IQR 0.0–0.07, median duration of residence 38.0 days, IQR 30.0–54.25). Female asylum seekers showed higher healthcare utilization rates than their male counterparts, and healthcare utilization was particularly low in asylum seekers in their second decade of life. Furthermore, a significant correlation between time after camp entrance and healthcare utilization behavior occurred: During the first week of camp residence, 37.1 visits/100 asylum seekers were observed, opposed to only 9.5 visits/100 asylum seekers during the sixth week of camp residence. This first data on healthcare utilization in a large, representative asylum seeker cohort entering Western Europe during the current crisis shows that primary care is most needed in the first period directly after arrival. Our dataset may help to raise awareness for refugee and migrant healthcare needs and to adapt care taking strategies accordingly.

Immunodiagnosis of tuberculosis infection in children under the age of five - Which testing is feasible?

Immunodiagnosis of tuberculosis infection (TB) in children under the age of five is challenging. Current German guidelines recommend tuberculin skin testing (TST), but not interferon gamma release assays (IGRAs) as first line diagnosis. In 71 TB exposed, non BCG vaccinated and asymptomatic children under the age of five TST (cut off < 5mm) and IGRA (QuantiFERON TB Gold in tube) were performed simultanously. In four children (6%) the IGRA was inconclusive. In seven (10%) of the remaining 67 children both TST and IGRA were positive. One of those children had pulmonary TB. In one child only the TST and in five children (7%) only the IGRA was positive. One of these children developed active TB during the follow up. Conflicting results were detected in six children (9%) in total. All children with negative tests were treated with isoniazide (INH) for three months, all children with at least one positive test result were treated with INH/rifampicine for three months. This study shows that there is a number of inconclusive IGRAs in children under the age of five. Therefore, IGRAs should not replace the TST in TB diagnosis in this age group. Nevertheless, they could add sensitivity to the results of the TST testing.