Results of the Cologne Corona Surveillance (CoCoS) project- a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection, and moderate-to-severe course in primarily immunized adults.

BACKGROUND: Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. METHODS: The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants' demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. RESULTS: A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415-0.823) and older age (HR = 0.974, 95%CI 0.966-0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949-0.977). Female sex (HR = 2.570, 95%CI1.435-4.603), smoking (HR = 1.965, 95%CI1.147-3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465-5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. CONCLUSION: The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

"The targets are driving the agenda and that probably needs to change": stakeholder perspectives on HIV partner notification in sub-Saharan Africa.

BACKGROUND: Voluntary assisted partner notification (VAPN) in HIV contact tracing is a globally recommended strategy to identify persons who have been exposed to HIV and link them to HIV testing and follow-up. However, there is little understanding about how VAPN is experienced by stakeholders in sub-Saharan African (SSA) contexts. We conducted a multi-level and multi-national qualitative analysis evaluating stakeholder perspectives surrounding VAPN implementation to inform the development of future VAPN policies. METHOD: We conducted in-depth interviews (IDIs) with VAPN stakeholders at global (n = 5), national (n = 6), and community level (n = 4) across a total of seven SSA countries. Eligible participants were ≥ 18 years old and had experience developing, implementing, or overseeing VAPN policies in SSA. We sought to understand stakeholder's perspectives on policy development, implementation, and perceived outcomes (barriers and facilitators). Interviews were audio recorded, transcribed, and analyzed thematically using a combination of inductive and deductive approaches. RESULTS: Between December 2019 and October 2020 we conducted 15 IDIs. While participants agreed that VAPN resulted in a high yield of people newly diagnosed with HIV; they noted numerous barriers surrounding VAPN implementation across global, national, and community levels, the majority of which were identified at community level. Barriers at global and national level included high target setting, contradictory laws, and limited independent research disenfranchising the experiences of implementing partners. The barriers identified at community level included client-level challenges (e.g., access to healthcare facilities and fear of adverse events); healthcare worker challenges (e.g., high workloads); limited data infrastructure; and cultural/gender norms that hindered women from engaging in HIV testing and VAPN services. In response to these barriers, participants shared implementation facilitators to sustain ethical implementation of VAPN services (e.g., contact tracing methods) and increase its yield (e.g., HIV self-testing integrated with VAPN services). CONCLUSION: Overall, stakeholders perceived VAPN implementation to encounter barriers across all implementation levels (global to community). Future VAPN policies should be designed around the barriers and facilitators identified by SSA stakeholders to maximize the implementation of (ethical) HIV VAPN services and increase its impact in sub-Saharan African settings.

Augmented, Mixed, and Virtual Reality-Based Head-Mounted Devices for Medical Education: Systematic Review.

BACKGROUND: Augmented reality (AR), mixed reality (MR), and virtual reality (VR), realized as head-mounted devices (HMDs), may open up new ways of teaching medical content for low-resource settings. The advantages are that HMDs enable repeated practice without adverse effects on the patient in various medical disciplines; may introduce new ways to learn complex medical content; and may alleviate financial, ethical, and supervisory constraints on the use of traditional medical learning materials, like cadavers and other skills lab equipment. OBJECTIVE: We examine the effectiveness of AR, MR, and VR HMDs for medical education, whereby we aim to incorporate a global health perspective comprising low- and middle-income countries (LMICs). METHODS: We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) and Cochrane guidelines. Seven medical databases (PubMed, Cochrane Library, Web of Science, Science Direct, PsycINFO, Education Resources Information Centre, and Google Scholar) were searched for peer-reviewed publications from January 1, 2014, to May 31, 2019. An extensive search was carried out to examine relevant literature guided by three concepts of extended reality (XR), which comprises the concepts of AR, MR, and VR, and the concepts of medicine and education. It included health professionals who took part in an HMD intervention that was compared to another teaching or learning method and evaluated with regard to its effectiveness. Quality and risk of bias were assessed with the Medical Education Research Study Quality Instrument, the Newcastle-Ottawa Scale-Education, and A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies of Interventions. We extracted relevant data and aggregated the data according to the main outcomes of this review (knowledge, skills, and XR HMD). RESULTS: A total of 27 studies comprising 956 study participants were included. The participants included all types of health care professionals, especially medical students (n=573, 59.9%) and residents (n=289, 30.2%). AR and VR implemented with HMDs were most often used for training in the fields of surgery (n=13, 48%) and anatomy (n=4, 15%). A range of study designs were used, and quantitative methods were clearly dominant (n=21, 78%). Training with AR- and VR-based HMDs was perceived as salient, motivating, and engaging. In the majority of studies (n=17, 63%), HMD-based interventions were found to be effective. A small number of included studies (n=4, 15%) indicated that HMDs were effective for certain aspects of medical skills and knowledge learning and training, while other studies suggested that HMDs were only viable as an additional teaching tool (n=4, 15%). Only 2 (7%) studies found no effectiveness in the use of HMDs. CONCLUSIONS: The majority of included studies suggested that XR-based HMDs have beneficial effects for medical education, whereby only a minority of studies were from LMICs. Nevertheless, as most studies showed at least noninferior results when compared to conventional teaching and training, the results of this review suggest applicability and potential effectiveness in LMICs. Overall, users demonstrated greater enthusiasm and enjoyment in learning with XR-based HMDs. It has to be noted that many HMD-based interventions were small-scale and conducted as short-term pilots. To generate relevant evidence in the future, it is key to rigorously evaluate XR-based HMDs with AR and VR implementations, particularly in LMICs, to better understand the strengths and shortcomings of HMDs for medical education.

The prevalence of renal impairment in individuals seeking HIV testing in Urban Malawi.

BACKGROUND: Chronic kidney disease (CKD) poses a major health threat to people living in low- and middle-income countries, especially when it is combined with HIV, antiretroviral treatment (ART) or communicable and non-communicable diseases. Data about the prevalence of CKD and its association with other diseases is scarce, particularly in HIV-negative individuals. This study estimated the prevalence of CKD in individuals who were either HIV-positive (and ART-naïve) or HIV-negative in an urban Malawian population. METHODS: This cross-sectional study was conducted at a HIV Testing and Counselling Centre in Lilongwe, Malawi. Consecutive clients who were ≥18 years and consented to participate were enrolled over a 3-month period. Clients were screened for potential renal disease and other conditions. Their blood pressure was measured, urine examined via dipstick and albumin/creatinine ratio and blood drawn for creatinine, cystatin C and sero-markers for schistosomiasis. Estimated glomerular filtration (eGFR) rate was calculated using a cystatin C-based formula and classified according to the matching CKD stages by K/DOQI (The National Kidney Foundation Kidney Disease Outcome Quality Initiative). We performed a descriptive analysis and compared differences between HIV-positive (and ART naïve) and -negative participants. RESULTS: Out of 381 consecutive clients who were approached between January and March 2012, 366 consented and 363 (48% female; 32% HIV-positive) were included in the analysis. Reasons for exclusion were missing samples or previous use of ART. HIV-positive and negative clients did not differ significantly with regard to age, sex or medical history, but they did differ for BMI-21.3 (±3.4) vs. 24 (±5.1), respectively (p < 0.001). Participants also differed with regard to serum cystatin C levels, but not creatinine. Reduced kidney function (according to CKD stages 2-5) was significantly more frequent 15.5 vs. 3.6%, respectively (p < 0.001) among HIV-positive clients compared to the HIV-negative group. Differences in renal function were most pronounced in the eGFR range 60-89 ml/min/1.73 m2 accompanied by proteinuria with results as 11.2% vs. 1.2%, respectively for clients who were HIV-positive vs. HIV-negative (p = 0.001). CONCLUSIONS: Reduced glomerular filtration and/or proteinuria occurred in 15.5% of HIV-positive, and 3.6% of HIV-negative patients in this urban Malawian cohort. Since generalized renal monitoring is not feasible in Malawi or other resource-limited countries, strategies to identify patients at risk for higher stages of CKD and appropriate preventive measures are needed for both HIV-positive and HIV-negative patients.

Comparison of Various Equations for Estimating GFR in Malawi: How to Determine Renal Function in Resource Limited Settings?

BACKGROUND: Chronic kidney disease (CKD) is a probably underrated public health problem in Sub-Saharan-Africa, in particular in combination with HIV-infection. Knowledge about the CKD prevalence is scarce and in the available literature different methods to classify CKD are used impeding comparison and general prevalence estimates. METHODS: This study assessed different serum-creatinine based equations for glomerular filtration rates (eGFR) and compared them to a cystatin C based equation. The study was conducted in Lilongwe, Malawi enrolling a population of 363 adults of which 32% were HIV-positive. RESULTS: Comparison of formulae based on Bland-Altman-plots and accuracy revealed best performance for the CKD-EPI equation without the correction factor for black Americans. Analyzing the differences between HIV-positive and -negative individuals CKD-EPI systematically overestimated eGFR in comparison to cystatin C and therefore lead to underestimation of CKD in HIV-positives. CONCLUSIONS: Our findings underline the importance for standardization of eGFR calculation in a Sub-Saharan African setting, to further investigate the differences with regard to HIV status and to develop potential correction factors as established for age and sex.

Epstein-barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis.

Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that-particularly in individuals infected with human immunodeficiency virus (HIV)-herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV-infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation.

Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting.

OBJECTIVES: Cryptococcal meningitis (CM) and tuberculous meningitis (TBM) are common in HIV-infected adults in Africa and difficult to diagnose. Inaccurate diagnosis results in adverse outcomes. We describe patterns of meningitis in a Malawian hospital, focusing on features which differentiate CM and TBM with the aim to derive an algorithm using only clinical and basic laboratory data available in this resource-poor setting. METHODS: Consecutive patients admitted with meningitis were prospectively recruited, clinical features were recorded and cerebrospinal fluid (CSF) was examined. RESULTS: A total of 573 patients were recruited, and 263 (46%) had CSF consistent with meningitis. One hundred and twelve (43%) had CM and 46 (18%) had TBM. CM was associated with high CSF opening pressure and low CSF leukocyte count. Fever, neck stiffness and reduced conscious level were associated with TBM. A diagnostic index was constructed demonstrating sensitivity 83%and specificity 79% for the differentiation of CM and TBM. An algorithm was derived with 92% sensitivity for the diagnosis of CM, but only 58% specificity. CONCLUSIONS: Although we demonstrate features associated with CM and TBM, a sufficiently sensitive and specific diagnostic algorithm could not be derived, suggesting that the diagnosis of CM and TBM in resource-limited settings still requires better access to laboratory tools.

Lessons learned from a paying antiretroviral therapy service in the public health sector at Kamuzu Central Hospital, Malawi: 1-year experience.

BACKGROUND: In October 2001, a paying antiretroviral therapy service was introduced at a Central Hospital in Malawi using stavudine 40 mg/lamivudine 150 mg/nevirapine 200 mg (triomune). The objective of this study was to determine characteristics of patients seeking antiretroviral therapy, retention in care, clinical outcomes, and outlines for program improvement. METHODS: Retrospectively, all patients seeking anti-retroviral therapy initiation (October 2001 to October 2002; follow-up through April 2003) were evaluated for laboratory results, retention in care, toxicity, and mortality. Hazard ratios for factors associated with dropout were determined. RESULTS: Of 757 patients seeking evaluation, 625 began treatment. Documented mortality rate was 61 of 757. Total dropout rate was 50%. Factors associated with dropout include CD4 count <50 cells/mm(3) and Kaposi's sarcoma. Twenty-seven of 625 patients discontinued therapy for toxicity. CONCLUSIONS: The paying antiretroviral therapy program showed an unacceptable dropout rate associated with advanced baseline disease. Severe toxicity rate was low. Areas for improved program performance include lower cost, wide and earlier access to antiretroviral therapy, and targeted retention strategies.