Serological diagnosis of strongyloidiasis: An evaluation of three commercial assays.

BACKGROUND: Strongyloidiasis is caused by a neglected nematode, manifesting as chronic intestinal infection with potentially severe manifestations. The disease is an emerging problem in non-endemic countries affecting travelers and migrants. Diagnosis of strongyloidiasis is hampered by the lack of standardization and absence of a gold standard. Since adequate direct methods to detect the motile larvae in stool samples are not widely available, other techniques such as serology have been developed. METHODS: We evaluated three commercial ELISA kits (DRG Instruments, IVD Research, and Bordier Affinity Products) to detect IgG antibodies against Strongyloides stercoralis assays utilizing serum samples from travelers with microscopically confirmed strongyloidiasis (n = 50) and other imported helminthic infections (n = 159) as well as healthy controls (n = 50). RESULTS: The DRG, IVD, and Bordier assays showed sensitivities of 58.0%, 64.0%, and 56.0%, respectively. Specificity values were 96.0%, 96.0%, and 92.0% in healthy controls, and 67.3%, 62.9%, and 76.7% in cases with other helminth infections, respectively. Cross-reactions were mostly observed in cases with other nematodes (37.5%, 42.5%, and 20.0%, respectively), but also in trematode (33.3%, 38.1%, and 19.0%, respectively) and in cestode infections (25.0%, 30.0%, and 32.5%, respectively). CONCLUSION: The study demonstrates the diagnostic limitations of serological assays to detect or exclude cases of strongyloidiasis in returning travelers, who frequently present with recent or acute infections.

Health-related quality of life and impact of socioeconomic status among primary and secondary school students after the third COVID-19 wave in Berlin, Germany.

In the earlier phases of the COVID-19 pandemic, studies in Germany and elsewhere found an overall reduction in health-related quality of life (HRQoL) among students. However, there is little evidence on later pandemic stages as well as socioeconomic influencing factors. We aimed to (1) describe HRQoL in a Berlin student cohort at two time points in mid-2021, and to (2) analyze the effects of household income and education. We assessed HRQoL of students from 24 randomly selected primary and secondary schools in Berlin, Germany, with the KIDSCREEN-10 index in June and September 2021. To adjust for non-response bias, inverse probability weighting was applied. The potential effects of both household income and education (lower vs. higher) were estimated in generalized linear mixed models, based on prior assumptions presented in directed acyclic graphs. Our cohort comprised 660 students aged 7-19 years. In June 2021, 11.3% [95% CI = 9.0% - 14.0%] reported low HRQoL, whereas in September 2021, this increased to 13.7% [95% CI = 11.1% - 16.5%], with adolescent girls more frequently reporting low HRQoL at both time points (20% [95% CI = 17.1% - 23.3%] and 29% [95% CI = 25.5% - 32.5%]) compared to boys and younger children. While there was no statistically significant total effect of lower household income on HRQoL, a negative effect of lower household education was statistically significant (ß = -2.15, SE 0.95, 95% CI = -4.01 to -0.29, p = 0.024). In summary, students' HRQoL in mid-2021 was better than that documented in other studies conducted at pandemic onset using KIDSCREEN-10. Female adolescents reported low HRQoL more often, and lower household education significantly reduced children's HRQoL. Support strategies for psychosocial wellbeing should consider socioeconomically disadvantaged children as important target groups.

SARS-CoV-2 Seroprevalence in a Berlin Kindergarten Environment: A Cross-Sectional Study, September 2021.

SARS-CoV-2 serology may be helpful to retrospectively understand infection dynamics in specific settings including kindergartens. We assessed SARS-CoV-2 seroprevalence in individuals connected to kindergartens in Berlin, Germany in September 2021. Children, staff, and household members from 12 randomly selected kindergartens were interviewed on COVID-19 history and sociodemographic parameters. Blood samples were collected on filter paper. SARS-CoV-2 anti-S and anti-N antibodies were assessed using Roche Elecsys. We assessed seroprevalence and the proportion of so far unrecognized SARS-CoV-2 infections. We included 277 participants, comprising 48 (17.3%) kindergarten children, 37 (13.4%) staff, and 192 (69.3%) household members. SARS-CoV-2 antibodies were present in 65.0%, and 52.7% of all participants were vaccinated. Evidence of previous infection was observed in 16.7% of kindergarten children, 16.2% of staff, and 10.4% of household members. Undiagnosed infections were observed in 12.5%, 5.4%, and 3.6%, respectively. Preceding infections were associated with facemask neglect. In conclusion, two-thirds of our cohort were SARS-CoV-2 seroreactive in September 2021, largely as a result of vaccination in adults. Kindergarten children showed the highest proportion of non-vaccine-induced seropositivity and an increased proportion of previously unrecognized SARS-CoV-2 infection. Silent infections in pre-school children need to be considered when interpreting SARS-CoV-2 infections in the kindergarten context.

Detection of Artemisinin Resistance Marker Kelch-13 469Y in Plasmodium falciparum, South Kivu, Democratic Republic of the Congo, 2022.

Partial artemisinin resistance has emerged in East Africa, posing a threat to malaria control across the continent. The Democratic Republic of the Congo carries one of the heaviest malaria burdens globally, and the South Kivu province directly borders current artemisinin resistance hot spots, but indications of such resistance have not been observed so far. We assessed molecular markers of antimalarial drug resistance in 256 Plasmodium falciparum isolates collected in 2022 in South Kivu, Democratic Republic of the Congo. One isolate carried the P. falciparum Kelch-13 469Y variant, a marker associated with partial artemisinin resistance and decreased lumefantrine susceptibility in Uganda. In addition, the multidrug resistance-1 mutation pattern suggested increased lumefantrine tolerance.

Escalating Plasmodium falciparum K13 marker prevalence indicative of artemisinin resistance in southern Rwanda.

In 2023, we updated data collected since 2010 on Plasmodium falciparum K13 and MDR1 drug resistance markers in Huye district, southern Rwanda. Artemisinin resistance-associated PfK13 markers occurred in 17.5% of 212 malaria patients (561H, 9.0%; 675V, 5.7%; and 469F, 2.8%), nearly double the frequency from 2019. PfMDR1 N86, linked with lumefantrine tolerance, was close to fixation at 98%. In southern Rwanda, markers signaling resistance to artemisinin and lumefantrine are increasing, albeit at a relatively slow rate.

Clinical evaluation of a web-based personalized recommendation system with electronic health record interface to optimize healthcare resources during SARS-CoV-2 surges.

During the SARS-CoV-2 pandemic, the German healthcare system faced challenges of efficiently allocating testing resources. To address this, we developed an open-source personalized recommendation system (PRS) called "CovApp". The PRS utilized a questionnaire to estimate the risk of infection, provided personalized recommendations such as testing, self-isolation, or quarantine, and featured QR code data transmission to electronic health records. The PRS served up to 2.5 million monthly users and received 67,000 backlinks from 1800 domains. We clinically evaluated the PRS at the SARS-CoV-2 testing facility at Charité and observed a 21.7% increase in patient throughput per hour and a 22.5% increase in patients per day. Patients using the PRS were twice as likely to belong to the High Risk group eligible for testing (18.6% vs. 8.9%, p < 0.0001), indicating successful compliance with CovApp's recommendations. CovApp served as a digital bridge between the population and medical staff and significantly improved testing efficiency. As an open-source platform, CovApp can be readily customized to address emerging public health crises. Further, given the EHR interface, the app is of great utility for other applications in clinical settings.

Macrovascular and renal microvascular complications in West Africans with intermediate hyperglycemia living in West Africa and Europe: The RODAM study.

Background: Metabolic conditions, including intermediate hyperglycemia (IH), affect migrants to a greater extent than the populations of origin. Evidence suggests that IH increases the risk of vascular complications, but it is unclear whether the differences in IH between the non-migrant and migrant populations translate to differences in vascular complications between the two populations. We compared the prevalence of macrovascular and renal microvascular complications among West Africans with IH living in West Africa and their migrant compatriots in Europe. Methods: Data from the multicenter Research on Obesity and Diabetes among African Migrants(RODAM) study were analyzed. Ghanaians with IH(524 non-migrant and 1439 migrants) were included. Logistic regression analyses were used to determine the associations between migrant status and macrovascular [coronary artery disease(CAD) and peripheral artery disease(PAD)] and renal microvascular[nephropathy] complications with adjustment for age, sex, socioeconomic status, smoking, systolic blood pressure, BMI, total cholesterol, HbA1c, C-reactive protein, and serum uric acid. Findings: The prevalence of microvascular/macrovascular complications was higher in non-migrants than in migrants(nephropathy 15.3vs.9.7%; PAD 3.1%vs.1.3%; and CAD 15.8% vs. 5.0%). The differences persisted in the fully adjusted model: nephropathy [odds ratio, 2.12; 95% CI(1.46-3.08); PAD, 4.44(1.87-10.51); CAD 2.35(1.64-3.37)]. Non-migrant females had higher odds of nephropathy[2.14(1.34-3.43)], PAD[7.47(2.38-23.40)] and CAD [2.10(1.34-3.27)] compared to migrant females. Non-migrant males had higher odds of nephropathy[2.54(1.30-4.97)] and CAD[2.85(1.48-5.50)], but not PAD[1.81(0.32-10.29)],than their migrant peers. Interpretation: Macrovascular and renal microvascular complications were more prevalent in non-migrants than in migrant West Africans with IH. Further studies are needed to identify factors that increase the risk to aid preventive/treatment strategies.

ESBL-producing Enterobacteriaceae in a rural Rwandan community: Carriage among community members, livestock, farm products and environment.

OBJECTIVES: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) are spreading globally. However, respective data from African communities including livestock and environmental specimens are rare. In a rural community of southern Rwanda, we assessed intestinal carriage of ESBL-PE among residents and livestock as well as presence in household specimens and examined associated factors. METHODS: Samples of humans and livestock (both rectal swabs), soil, water, vegetables and animal products were collected within 312 community households in Sovu, Southern Rwanda. Specimens were screened for ESBL-PE on chromogenic agar, and susceptibility to common antibiotics was determined by disc diffusion assays. Socio-demographic information was collected with questionnaires focusing on the socio-economic background, alimentation, living conditions, hygiene measures and medical history of the participants. RESULTS: Data and specimens from 312 randomly selected households including 617 human beings, 620 livestock and of approximately each 300 kitchen vegetables, animal products, soil and drinking water were analysed. Overall, 14.8% of 2508 collected samples were positive for ESBL-PE; figures were highest for humans (37.9%) and livestock (15.6%), lower for vegetables (3.8%) and animal products (3.3%), and lowest for soil (1.6%) and water (0.6%). Most detected ESBL-PE were Escherichia coli (93.5%) in addition to Klebsiella pneumoniae (6.5%). Cross-resistance to ampicillin-sulbactam, ciprofloxacin and co-trimoxazole was common. Logistic regression identified increasing age, another ESBL-PE positive household member, prolonged time for fetching water, current diarrhoea and the ability to pay school fees as independent predictors of intestinal ESBL-PE carriage among community members. CONCLUSIONS: ESBL-PE carriage is common in a rural Rwandan farming community. Carriage in livestock is not associated with human carriage. Associated factors suggest few addressable risk factors. The data indicate that in southern Rwanda, ESBL-PE are no longer primarily hospital-based but circulate in the community.

Plasmodium vivax Malaria in Duffy-Positive Patients in Rwanda.

Plasmodium vivax is the second-most common malaria pathogen globally, but is considered very rare in the predominantly Duffy-negative sub-Saharan African population. In 259 malaria patients from highland southern Rwanda, we assessed Plasmodium species and Duffy blood group status by polymerase chain reaction (PCR). Plasmodium falciparum, P. vivax, Plasmodium malariae, and Plasmodium ovale were seen in 90.7%, 8.1%, 11.6%, and 5.0%, respectively. Plasmodium vivax occurred more frequently as a monoinfection than in combination with P. falciparum. All P. vivax-infected individuals showed heterozygous Duffy positivity, whereas this was the case for only 3.1% of patients with P. falciparum monoinfection and malaria-negative control subjects (P < 0.01). Based on PCR diagnosis, P. vivax is not rare in southern Rwanda. All episodes of P. vivax were observed in heterozygous Duffy-positive patients, whereas elsewhere in Africa, P. vivax is also reported in Duffy-negative individuals. Refined mapping of Plasmodium species is required to establish control and elimination strategies including all malaria species.

Subgroups of adult-onset diabetes: a data-driven cluster analysis in a Ghanaian population.

Adult-onset diabetes mellitus (here: aDM) is not a uniform disease entity. In European populations, five diabetes subgroups have been identified by cluster analysis using simple clinical variables; these may elucidate diabetes aetiology and disease prognosis. We aimed at reproducing these subgroups among Ghanaians with aDM, and establishing their importance for diabetic complications in different health system contexts. We used data of 541 Ghanaians with aDM (age: 25-70 years; male sex: 44%) from the multi-center, cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) Study. Adult-onset DM was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L, documented use of glucose-lowering medication or self-reported diabetes, and age of onset ≥ 18 years. We derived subgroups by cluster analysis using (i) a previously published set of variables: age at diabetes onset, HbA1c, body mass index, HOMA-beta, HOMA-IR, positivity of glutamic acid decarboxylase autoantibodies (GAD65Ab), and (ii) Ghana-specific variables: age at onset, waist circumference, FPG, and fasting insulin. For each subgroup, we calculated the clinical, treatment-related and morphometric characteristics, and the proportions of objectively measured and self-reported diabetic complications. We reproduced the five subgroups: cluster 1 (obesity-related, 73%) and cluster 5 (insulin-resistant, 5%) with no dominant diabetic complication patterns; cluster 2 (age-related, 10%) characterized by the highest proportions of coronary artery disease (CAD, 18%) and stroke (13%); cluster 3 (autoimmune-related, 5%) showing the highest proportions of kidney dysfunction (40%) and peripheral artery disease (PAD, 14%); and cluster 4 (insulin-deficient, 7%) characterized by the highest proportion of retinopathy (14%). The second approach yielded four subgroups: obesity- and age-related (68%) characterized by the highest proportion of CAD (9%); body fat-related and insulin-resistant (18%) showing the highest proportions of PAD (6%) and stroke (5%); malnutrition-related (8%) exhibiting the lowest mean waist circumference and the highest proportion of retinopathy (20%); and ketosis-prone (6%) with the highest proportion of kidney dysfunction (30%) and urinary ketones (6%). With the same set of clinical variables, the previously published aDM subgroups can largely be reproduced by cluster analysis in this Ghanaian population. This method may generate in-depth understanding of the aetiology and prognosis of aDM, particularly when choosing variables that are clinically relevant for the target population.

A COVID-19 isolation facility for people experiencing homelessness in Berlin, Germany: a retrospective patient record study.

Introduction: People experiencing homelessness (PEH) are disproportionately affected by the COVID-19 pandemic. For many PEH it is impossible to isolate due to the lack of permanent housing. Therefore, an isolation facility for SARS-CoV-2 positive PEH was opened in Berlin, Germany, in May 2020, offering medical care, opioid and alcohol substitution therapy and social services. This study aimed to assess the needs of the admitted patients and requirements of the facility. Materials and methods: This was a retrospective patient record study carried out in the isolation facility for PEH in Berlin, from December 2020 to June 2021. We extracted demographic and clinical data including observed psychological distress from records of all PEH tested positive for SARS-CoV-2 by RT-PCR. Data on duration and completion of isolation and the use of the facilities' services were analyzed. The association of patients' characteristics with the completion of isolation was assessed by Student's t-test or Fisher's exact test. Results: A total of 139 patients were included in the study (89% male, mean age 45 years, 41% with comorbidities, 41% non-German speakers). 81% of patients were symptomatic (median duration 5 days, range 1-26). The median length of stay at the facility was 14 days (range 2-41). Among the patients, 80% had non-COVID-19 related medical conditions, 46% required alcohol substitution and 17% opioid substitution therapy. Three patients were hospitalized due to low oxygen saturation. No deaths occurred. Psychological distress was observed in 20%, and social support services were used by 65% of PEH. The majority (82%) completed the required isolation period according to the health authority's order. We did not observe a statistically significant association between completion of the isolation period and sociodemographic characteristics. Conclusion: The specialized facility allowed PEH a high compliance with completion of the isolation period. Medical care, opioid and alcohol substitution, psychological care, language mediation and social support are essential components to address the specific needs of PEH. Besides contributing to infection prevention and control, isolation facilities may allow better access to medical care for SARS-CoV-2 infected PEH with possibly positive effects on the disease course.

Generalized anxiety disorder in Berlin school children after the third COVID-19 wave in Germany: a cohort study between June and September 2021.

BACKGROUND: During the COVID-19 pandemic, children and adolescents worldwide have disproportionally been affected in their psychological health and wellbeing. We conducted a cohort study among German school children, aiming at assessing levels of general anxiety disorder (GAD) and identifying associated factors in the second pandemic year. METHODS: A cohort of 660 students from 24 Berlin schools was recruited to fill in questionnaires including the GAD-7 tool on anxiety symptoms at three time points between June and September 2021. To adjust for non-random attrition, we applied inverse probability weighting. We describe reported GAD levels stratified by time point, sex, and school type and report odds ratios from univariate logistic regression. RESULTS: In total, 551 participants (83%) filled in at least one questionnaire at any time point. At the first time point in June 2021, 25% of the children and adolescents reported anxiety symptoms with a GAD-7 score ≥ 5, decreasing to 16% in August 2021 directly after the summer holidays and rising again to 26% in September 2021. The majority of reported anxiety levels belonged to the least severe category. Being female, attending secondary school, coming from a household with lower education or with lower income level, and being vaccinated against COVID-19 were significantly linked with reporting anxiety symptoms. Preceding COVID-19 infection and anxiety were negatively associated. CONCLUSION: Overall, anxiety in school children was lower in mid-2021 than in the first pandemic year, but still double compared to pre-pandemic data. Reporting of anxiety symptoms during the second pandemic year was especially high in females and in secondary school students. Policy makers should pay additional attention to the mental health status of school children, even as the pandemic situation might stabilize.

Associations of psychosocial stress with type 2 diabetes and glycaemic control among Ghanaians: The RODAM study.

BACKGROUND: The extent to which psychosocial stress relates to type 2 diabetes among sub-Saharan Africans is not well understood. We assessed associations of psychosocial stresses with type 2 diabetes status and glycaemic control among Ghanaians. METHODS: We used data from Research on Obesity and Diabetes among African Migrants (RODAM) study. We performed logistic and linear regression models to assess association of psychosocial stresses with type 2 diabetes and HbA1c respectively with adjustments for age, sex, education and other stresses. We also assessed moderation effects of migration status (migrant Ghanaians vs. non-migrant Ghanaians), age, sex and education by adding interaction terms in models. RESULTS: Four thousand eight hundred and forty one Ghanaians were included with 44% resident in Ghana, 62% women, mean age of 46 years and 10% having type 2 diabetes. Psychosocial stress at home and at work were not associated with type 2 diabetes or HbA1c levels. Negative life events in past 12 months were negatively associated with type 2 diabetes (adjusted odds ratio = 0.93, 95% CI 0.87-0.99). Perceived discrimination was positively associated with type 2 diabetes (aOR = 1.01, 95% CI 1.004-1.03). Both associations were more pronounced in men. Perceived discrimination was also positively associated with HbA1c levels, especially among those with type 2 diabetes (adjusted ß = 0.01, 95% CI 0.007-0.02). CONCLUSIONS: Perceived discrimination and negative life events are associated with type 2 diabetes and glycaemic control among Ghanaians, especially in men. Further studies are needed to identify context-specific mechanisms underlying these associations.

A Multicenter Clinical Diagnostic Accuracy Study of SureStatus, an Affordable, WHO Emergency Use-Listed, Rapid, Point-Of-Care Antigen-Detecting Diagnostic Test for SARS-CoV-2.

Access to reverse transcription-PCR (RT-PCR) testing, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection, is limited throughout the world, due to restricted resources, available infrastructure, and high costs. Antigen-detecting rapid diagnostic tests (Ag-RDTs) overcome some of these barriers, but independent clinical validations in settings of intended use are scarce. To inform the World Health Organization's (WHO) emergency use listing (EUL) procedure and ensure affordable, high-quality Ag-RDTs, we assessed the performance and ease of use of the SureStatus for SARS-CoV-2. For this prospective, multicenter diagnostic accuracy study, we recruited unvaccinated participants with presumed SARS-CoV-2 infection in India and Germany from December 2020 to March 2021, when the Alpha (B.1.1.7) variant was predominantly circulating. Paired swabs were performed for (i) routine clinical RT-PCR testing (sampling was either nasopharyngeal [NP] or combined NP and oropharyngeal [NP/OP]) and (ii) Ag-RDT (sampling was NP). Performance of the Ag-RDT was compared to RT-PCR overall and by predefined subgroups, e.g., cycle threshold (CT) value, symptoms, and days from symptom onset. To understand the usability, a system usability scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. A total of 1,119 participants were included in the analysis, of whom 205 (18.3%) were RT-PCR positive. SureStatus detected 169 out of 205 RT-PCR-positive participants, reporting a sensitivity of 82.4% (95% confidence interval [CI]: 76.6% to 87.1%) and a specificity of 98.5% (95% CI: 97.4% to 99.1%). In the first 7 days post-symptom onset, the sensitivity was 90.7% (95% CI: 83.5% to 94.9%), when CT values were low and viral loads were high. The test was characterized as easy to use (SUS, 85/100) and considered suitable for point-of-care settings, although quality concerns were raised due to visibly contaminated packaging of swabs included in the test kits. The SureStatus diagnostic test can be considered a reliable test during the first week of SARS-CoV-2 infection, with high sensitivity in combination with excellent usability. IMPORTANCE Our manufacturer-independent, prospective diagnostic accuracy study assessed clinical performance in participants presumed to have a SARS-CoV-2 infection at three study sites in two countries. We assessed the accuracy overall and in predefined subgroups (CT values and symptom duration). SureStatus performed with high sensitivity. Its sensitivity was particularly high in the first 3 days after symptom onset and when CT values were low (i.e., the viral load was high). The system usability and ease-of-use assessment complements the accuracy assessment of the test and highlights critical factors to facilitate the widespread use of SureStatus in point-of-care settings. The high sensitivity demonstrated by the evaluated Ag-RDT within the first days of symptoms, when most transmission occurs, supports the role of Ag-RDTs for public health-relevant screening. Evidence from this study was used to inform the World Health Organization Emergency Use Listing procedure.

Psychosocial Wellbeing of Schoolchildren during the COVID-19 Pandemic in Berlin, Germany, June 2020 to March 2021.

The COVID-19 pandemic and related restrictions have affected the wellbeing of schoolchildren worldwide, but the extent and duration of specific problems are still not completely understood. We aimed to describe students' psychosocial and behavioral parameters and associated factors during the COVID-19 pandemic in Berlin, Germany. Our longitudinal study included 384 students from 24 randomly selected Berlin primary and secondary schools, assessing psychosocial wellbeing at four time points between June 2020 and March 2021. We analyzed temporal changes in the proportions of anxiety, fear of infection, reduced health-related quality of life (HRQoL), physical activity and social contacts, as well as sociodemographic and economic factors associated with anxiety, fear of infection and HRQoL. During the observation period, the presence of anxiety symptoms increased from 26.2% (96/367) to 34.6% (62/179), and fear of infection from 28.6% (108/377) to 40.6% (73/180). The proportion of children with limited social contacts (<1/week) increased from 16.4% (61/373) to 23.5% (42/179). Low physical activity (<3 times sports/week) was consistent over time. Low HRQoL was observed among 44% (77/174) of children. Factors associated with anxiety were female sex, increasing age, secondary school attendance, lower household income, and the presence of adults with anxiety symptoms in the student´s household. Fear of infection and low HRQoL were associated with anxiety. A substantial proportion of schoolchildren experienced unfavorable psychosocial conditions during the COVID-19 pandemic in 2020/2021. Students from households with limited social and financial resilience require special attention.

In Vitro Confirmation of Artemisinin Resistance in Plasmodium falciparum from Patient Isolates, Southern Rwanda, 2019.

Artemisinin resistance in Plasmodium falciparum is conferred by mutations in the kelch 13 (K13) gene. In Rwanda, K13 mutations have increased over the past decade, including mutations associated with delayed parasite clearance. We document artemisinin resistance in P. falciparum patient isolates from Rwanda carrying K13 R561H, A675V, and C469F mutations.