Integrated genomic surveillance enables tracing of person-to-person SARS-CoV-2 transmission chains during community transmission and reveals extensive onward transmission of travel-imported infections, Germany, June to July 2021.

BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.

Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Clusters Based on Integrated Genomic Surveillance, Outbreak Analysis and Contact Tracing in an Urban Setting.

BACKGROUND: Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. METHODS: In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. RESULTS: Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. CONCLUSIONS: Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population.

[Air and maritime transport during the COVID-19 pandemic in Germany: challenges for the public health service]. / Flug- und Schiffsverkehr während der COVID-19-Pandemie in Deutschland: Herausforderungen für den Öffentlichen Gesundheitsdienst.

COVID-19 has been challenging our society since January 2020. Due to global travel, the new coronavirus has rapidly spread worldwide. This article aims to provide an overview of the challenges in implementing measures in the air and maritime transport sector from the perspective of the German Public Health Service (Öffentlicher Gesundheitsdienst, ÖGD). Significant events and measures for air and maritime transport between January and August 2020 were selected. Lessons learned are discussed.During the COVID-19 pandemic, the ÖGD has been operating in a field of tension between the dynamics of scientific knowledge, political decision-making, social acceptance and consent.There are specific challenges at points of entry such as airports and seaports. These include staff shortages and the need to implement measures with a high organisational effort at very short notice such as health authority passenger checks carried out on aircraft, the establishment of test centres at points of entry and control of compliance with quarantine measures. Aggravating the situation, passenger lists, which are necessary for effective contact tracing, are often not available or incomplete. There is also a lack of digital tools for contact tracing but also, for example, the exchange of personal data within the ÖGD. Further difficulties in outbreak management arise from the cramped conditions on board ships and from the potential psychological stress on crew members and passengers, which have not yet been sufficiently considered.In view of all these challenges, it is paramount to strengthen the German Public Health Service in general and at points of entry and to intensify the exchange between the national, federal state and local levels.

[Is the school entrance examination a door opener for health sciences research? : Analyzing study participation of hard-to-reach groups]. / Die Schuleingangsuntersuchung als Türöffner für die gesundheitswissenschaftliche Forschung? : Eine Analyse zur Studienteilnahme "schwer erreichbarer" Bevölkerungsgruppen.

BACKGROUND: Additional scientific surveys within the compulsory school entrance examination (SEE) have become increasingly popular, partly because the SEE potentially reaches all socioeconomic groups. However, it has not been sufficiently explored whether selective participation in voluntary supplementary surveys actually results in no selection bias along socioeconomic characteristics. Therefore, the aim of this study is to analyze the participation of potentially hard-to-reach families in a parent survey at the SEE. MATERIALS AND METHODS: The parent survey on the utilization of community prevention has been linked to the SEE in a community in North Rhine-Westphalia. We compared families with low and higher education (CASMIN classification), families with and without migration background (at least one parent was not born in Germany), as well as single-parent and two-parent families. Using logistic regression we analyzed whether survey participation (n = 3410) and non-participation (n = 346) was different along all three indicators. RESULTS: Families with low education were slightly more often among the group of participants compared to non-participants (11.2 vs. 8.8%; odds ratio (OR) 1.29; 95% confidence interval (CI) 0.85-1.95) and single-parent families slightly less often (14.1 vs. 17.7%; OR 0.75; 95% CI 0.55-1.02). Families with migration background participated significantly more often (52.9 vs. 46.1%; OR 1.27; 95% CI 1.01-1.60). CONCLUSIONS: Hard-to-reach families could be recruited for a voluntary parent survey in the SEE to a satisfying degree. This illustrates the potential of the SEE for population-based basic and evaluation research.

[Current Immunization Status of Düsseldorf's Nursery School Children and Staff Members: A Cross-Sectional Study]. / Impfstatus von Kindern und Erzieher(innen) in Kindertageseinrichtungen der Landeshauptstadt Düsseldorf ­ Querschnittsstudie.

BACKGROUND: The local health authority (Gesundheitsamt) in Düsseldorf, Germany aimed to investigate the current immunization status of nursery school children and pedagogues in Düsseldorf, Germany. Furthermore, analysing the association between Düsseldorf's 5 social environment clusters and immunization status was of interest. Especially due to recent changes in the German Infection Protection Act closely monitoring adverse immunization trends becomes increasingly important. METHODS: Weighted cluster random sampling was used in order to draw a sample of 50 nursery schools from the 5 social environment clusters. Questionnaires were sent to the nursery schools and data were subsequently analysed using descriptive statistics. RESULTS: The results indicate that 76.0% of the children were immunized in time against MMR, 68.2% against varicella and 75.4% against meningococcal serogroup C. Data indicated a higher number of immunized children among older age groups. 96.4% of staff members born after 1970 were not vaccinated against varicella, 17.9% were not immunized against MMR and 82.1% were not vaccinated against meningococcal serogroup C. CONCLUSION: Immunization rates of children in nursery schools in Düsseldorf are far lower compared to local, federal and nationwide data of children's school entrance health examination. Especially in nursery schools that care for children younger than 12 months, herd immunity is crucial. Therefore, administering vaccines with a delay is considered to be precarious. Due to low response rates, inferential statistics could not be used and conclusions about the staff members' data are limited.

Plasmodium malariae infection in spite of previous anti-malarial medication.

Plasmodium malariae is regarded as usually being susceptible to all anti-malarials whether applied for prophylaxis or treatment. We report on three cases of P. malariae infection which occurred 12-14 weeks after anti-malarial chemoprophylaxis or treatment with mefloquine or atovaquone/proguanil. The most likely explanation for the failure of mefloquine and atovaquone/proguanil to prevent quartan malaria occurring some months later is the insufficient effect on the particularly long-lasting pre-erythrocytic development stages of P. malariae.

Sonographic detection of subcutaneous fly larvae in human myiasis.

Sonographers increasingly face imported diseases such as subcutaneous myiasis. In myiasis, some fly species such as the American Dermatobia hominis and the African Cordylobia anthropophaga use humans as intermediate hosts for the maturation of their larvae. High-resolution gray-scale and color Doppler sonography enabled us to identify D hominis larvae in 2 travelers to Central America by visualizing their typical shape, segmentations, and the continuous fluid transport inside the larval body cavity and spiracles. The small C anthropophaga larva in an individual returning from Namibia was initially not detected. Only when using color Doppler sonography was the larva discerned by its intralarval fluid transport. Sonography enables clinicians to locate viable subcutaneous larvae in suspected cases of myiasis.

Cerebral malaria in spite of peripheral parasite clearance in a patient treated with atovaquone/proguanil.

Cerebral malaria, the most frequent complication of falciparum malaria, is usually predicted by an increased count of asexual parasites in peripheral blood. We report a case of a female returnee from Ghana who developed cerebral malaria in spite of parasite clearance in peripheral blood after therapy with atovaquone/proguanil.

Arthritis associated with Strongyloides stercoralis infection in HLA B-27-positive African.

A 44-year old West-African living in Germany since 18 years presented because of persistent painful swelling of both ankle joints and diffuse lymphoedema of feet occurring after a trip to Morocco. Laboratory tests revealed inflammation and eosinophilia. HLA-B27 was positive. Antinuclear antibodies and rheuma factors were not found. There was no evidence of an infection with bacteria or viruses known to cause arthritis. Filariasis was excluded. Microscopy of fresh stool revealed larvae of Strongyloides stercoralis. Symptoms resolved after specific antihelminthic therapy with ivermectin 0.2 mg kg(-1) day(-1) for 2 days and non-steroidal anti-inflammatorials. Reactive arthritis is known to be caused by various bacterial agents. In some individuals, arthritis may be due to helminths, such as S. stercoralis. Patients with strongyloidiasis may respond to non-steroidal anti-inflammatorials but must not undergo treatment with corticosteroids before having received antihelminthic therapy because immunosuppression may result in life-threatening strongyloides hyperinfection syndrome.

Predictors of short-term success of antiretroviral therapy in HIV infection.

OBJECTIVES: The success of highly active antiretroviral therapy (HAART) in HIV infection may be influenced by numerous host factors. There is a lack of data presenting a combined assessment of a variety of these parameters for treatment efficacy in clinical routine practice. METHODS: Different indices of therapeutic drug monitoring (TDM) were evaluated prospectively in the context of self-reported adherence, health-related quality of life and social determinants, as measured by a questionnaire. RESULTS: A total of 210 individuals were studied between 2002 and 2004, 77% were males, mean age was 44 years, mean CD4 count was 336 cells/mm3 and 63% had a viral load < 50 copies/mL. In univariate analysis, baseline viral load, unscheduled drug levels, a 4 h pharmacokinetic profile (PK-P) at a scheduled visit and self-reported complete adherence within the previous 2 weeks were significantly associated with virological success of HAART at 12 weeks. At 24 weeks, only baseline viral load, the 4 h PK-P and adherence were significantly associated with HAART efficacy. In multivariate analysis, baseline viral load, adherence, unscheduled drug levels, trough levels at a visit with appointment as well as the 4 h PK-P were significantly associated with virological success at 12 weeks. At 24 weeks, only adherence was significantly linked to outcome. The other parameters were not found to have an impact on treatment efficacy. CONCLUSIONS: TDM and self-reported adherence were independently predictive of short-term HAART success in this prospective study. Unscheduled drug measurements provided similar diagnostic information as a 4 h PK-P. Thus, we propose the use of unscheduled drug level monitoring and self-reported adherence to help identify patients with elevated risk of virological failure.

[Knotty skin tumors of an 80-year-old patient presenting with estimated diagnosis of chronic venous insufficiency]. / Livid-knotige Hauttumoren bei einem 80-jährigen Patienten mit initialer Verdachtsdiagnose einer chronisch-venösen Insuffizienz.

Kaposi's sarcoma in HIV-infected patients is a sign of progressive immunodeficiency. It is therefore classified as an AIDS-defining disease according to the CDC classification of 1993. Before antiretroviral therapy became available, disseminated Kaposi's sarcoma was a common therapeutic problem in HIV-infected patients. Therapeutic interventions were limited and in spite of interferon, irradiation or cytostatic drugs, chances of a definitive healing were minimal.Today, disseminated Kaposi's sarcoma is rare even in specialized clinics for infectious diseases. An exception are patients who are not aware of their HIV serostatus until they are diagnosed HIV-positive and who present already with a progressive immunodeficiency.

Efficacy of amodiaquine in uncomplicated falciparum malaria in Nigeria in an area with high-level resistance to chloroquine and sulphadoxine/pyrimethamine.

Falciparum Malaria is hyperendemic in southern Nigeria and chloroquine resistance is an increasing problem. Therefore, the parasitological and haematological response to treatment with amodiaquine was studied in children under 5 years during a 14-day follow-up. Of 105 children who accomplished the study (out of 114 who were enrolled), 95.3% were parasite-negative on thick blood film on day 7, which decreased to 89.5% on day 14. The haemoglobin levels increased on average by 1.3% on day 14 (+/-1.9) and more pronounced in children with anaemia<10 g/dl on enrollment. The number of patients with adverse events (mainly pruritus and nausea) was few. This study shows that amodiaquine is effective, safe and affordable in an area with high resistance to chloroquine.

Co-reactivity of plasmodial histidine-rich protein 2 and aldolase on a combined immuno-chromographic-malaria dipstick (ICT) as a potential semi-quantitative marker of high Plasmodium falciparum parasitaemia.

The combined immuno-chromographic-malaria dipstick (ICT) for the rapid diagnosis of malaria detects both Plasmodium falciparum (P.f.)-specific, histidine-rich protein 2 (HRP-2) and a plasmodial aldolase expressed by all Plasmodium species pathogenic to humans. ICT was applied in 674 febrile returnees from malaria-endemic regions attending our Tropical Diseases Unit. Microscopy confirmed malaria in 69/674 cases, of whom 67/69 had returned from Africa or Madagascar, and 2/69 from the Caribbean. Monoparasitic P.f. infection occurred in 52/69, mixed infection was due to P.f.+ P. ovale (P.o.) in 3/69, and P.f.+P. malariae (P.m.) in 1/69 cases. Monoparasitic P. vivax (P.v.) infection occurred in 8/69 , P.o. in 3/69, and P.m. in 2/69 cases . Whereas a positive HRP-2 band on the test was a highly sensitive indicator for P.f. infection (52/52 patients; sensitivity 100%), this was not the case for a positive aldolase band (25/52 patients; sensitivity 48.1%). Sensitivity of aldolase band for non-falciparum plasmodia was even lower: aldolase was positive in only 3/8 (37.5%) of patients with vivax malaria, and in 0/5 cases with P.o.- or P.m. infection. Co-reaction of both bands occurred more frequently in patients with P.f. parasitaemia of > or =40,000/microl (20/25, 80.0%) as compared to patients with P.f. parasitaemia <40,000/microl (5/27, 18.5%; P<0.00005), and to patients with mixed infection (P.f.+ P.o., P.f.+ P.m.: 2/4, 50.0%; diff. n.s.). In our series, co-reaction of HRP-2 and aldolase indicated monoparasitic falciparum malaria with high P.f. parasitaemia, rather than mixed infection. Whereas the aldolase band is not a reliable qualitative marker for malaria, co-reaction of HRP-2 and aldolase band may have a potential for indicating high parasitaemia in falciparum malaria.

Case report: Plasmodium ovale infection acquired in Malawi.

Malaria due to Plasmodium ovale is uncommon outside West Africa. A 37-year-old male German who had returned from Malawi four months previously presented in September 2003 because of fever recurring every two days. The patient had never been to West Africa. Microscopy of stained thick and thin blood films revealed P. ovale. This is the first report of a P. ovale infection acquired in Malawi, East Africa. Malaria surveillance centres should monitor the possible emergence of autochtonous transmission of P. ovale in the area.

Performance of an immunochromatographic test for the rapid diagnosis of malaria.

The immunochromatographic test (ICT) for the rapid diagnosis of malaria has been marketed for several years. In a study in which three Centres of Tropical Medicine participated and data were pooled, performance of the test varied considerably when comparing the results between each centre. The sensitivity of ICT in 2,343 patients tested in our services was 100% and the specificity 99.74%. Moreover, two patients with a positive ICT would initially have been missed by expert microscopy, with Plasmodium falciparum malaria being confirmed microscopically some hours later. The principal reasons for the better performance of the test in our series appear to be blood collection in EDTA vials and considerable experience with handling and interpreting the ICT test.

Dengue virus infection in travellers returning to Berlin, Germany: clinical, laboratory, and diagnostic aspects.

BACKGROUND: Dengue is a mosquito-borne viral infection endemic throughout the tropics and subtropics. The global prevalence of dengue has grown dramatically in recent years and it has been recognized as a potential hazard to tourists. OBJECTIVE: In this study, we analyzed the epidemiology, clinical manifestations, laboratory features and serological/virological results in a series of German travellers returning to Berlin with acute dengue virus infection. STUDY DESIGN: Laboratory-confirmed dengue virus infections among German travellers returning to Berlin were studied retrospectively during the period of 1993-2001. Seventy-one patients tested positive for dengue fever and were included in this study. RESULTS: The majority of patients (77.5%) contracted the disease in South Central and South East Asia. The most important clinical characteristics were fever and prostration (100%), headache, predominantly frontal or retroorbital (86%), arthralgia (79%), morbilliform rash (66%) and myalgia (48%). The most meaningful laboratory results were: marked leucopenia (72%), thrombocytopenia (70-89%), hyponatremia (41%) and increased hepatic enzymes ALAT (41%), ASAT (45%) and LDH (62%). Dengue virus infection was diagnosed by means of a matching clinico-epidemiological history and positivity of specific serology and/or virus isolation. Hemorrhagic phenomena appeared in 10 of the 71 patients (14%), out of which one was diagnosed with DHF according to WHO criteria. All patients recovered fully. CONCLUSION: Pretravel advice should be given to all travellers to dengue-endemic areas. DF must be included in the differential diagnosis of patients returning febrile from tropical areas.

Clinical and laboratory features of dengue virus-infected travellers previously vaccinated against yellow fever.

Dengue is a mosquito-borne viral infection endemic throughout the tropics and subtropics. The global prevalence of dengue has grown dramatically in recent years and it has become a major international public health concern. The close taxonomic relationships between yellow fever and dengue viruses gave rise to concerns that previous vaccination against yellow fever could modify the course of dengue infection and contribute to the development of dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). This study reports the clinical and laboratory features of dengue virus-infected travellers previously vaccinated against yellow fever.

Comparison of three antigen detection tests for diagnosis and follow-up of falciparum malaria in travellers returning to Berlin, Germany.

We determined the sensitivity and specificity of three rapid immunochromatographic malarial antigen detection test systems (RDTs) for the detection of Plasmodium falciparumand assessed the quality of follow-up results. ParaSight-F and ICT Malaria detect histidine-rich protein-2 (HRP-2), whereas OptiMal detects plasmodial lactate dehydrogenase (pLDH). ParaSight-F performed with 95.1% sensitivity and 97.1% specificity (554 patients tested of whom 144 had falciparum malaria). ICT Malaria performed with 95.7% sensitivity and 99.2% specificity (718 patients tested of whom 184 had falciparum malaria). OptiMal performed with 76.2% sensitivity and 99.7% specificity (539 patients tested of whom 130 had falciparum malaria). In follow-up investigations, HRP-2 did not appear to be a useful antigen due to its long half-life, whereas pLDH offers a reasonable correlation with the presence of viable parasites in those cases initially detected. We therefore conclude that a combination of both antigens might be the best option for creating a reliable RDT for the diagnosis of falciparum malaria.