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Abstract Introduction Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries. Methods This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment. Discussion The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention. Trial registration Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020–09-29.

Abstract Background The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania. Methods In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%). Results Median age of the 110 participants was 28.5 years (range 17–45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15–46). After a median follow-up of 8.98 months (IQR 5.72–29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6–77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10–2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19–0.82, p = 0.012). Conclusion Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Abstract Background Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes. Methods We accessed 451 historic (1965–1987) MRSA isolates stored in the Culture Collection of Switzerland, mostly collected from the Zurich region. We determined phenotypic antimicrobial resistance (AMR) and performed whole genome sequencing (WGS) using Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international assemblies from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmec cassette types, AMR, and virulence genes. Results Among the 451 historic Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-III. Early MRSA were predominantly from clonal complex (CC)8. From 1980 to the end of the twentieth century, we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally. Conclusions The combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time.

Abstract Background Reliable species identification of cultured isolates is essential in clinical bacteriology. We established a new study algorithm named NOVA – Novel Organism Verification and Analysis to systematically analyze bacterial isolates that cannot be characterized by conventional identification procedures MALDI-TOF MS and partial 16 S rRNA gene sequencing using Whole Genome Sequencing (WGS). Results We identified a total of 35 bacterial strains that represent potentially novel species. Corynebacterium sp. (n = 6) and Schaalia sp. (n = 5) were the predominant genera. Two strains each were identified within the genera Anaerococcus, Clostridium, Desulfovibrio, and Peptoniphilus, and one new species was detected within Citrobacter, Dermabacter, Helcococcus, Lancefieldella, Neisseria, Ochrobactrum (Brucella), Paenibacillus, Pantoea, Porphyromonas, Pseudoclavibacter, Pseudomonas, Psychrobacter, Pusillimonas, Rothia, Sneathia, and Tessaracoccus. Twenty-seven of 35 strains were isolated from deep tissue specimens or blood cultures. Seven out of 35 isolated strains identified were clinically relevant. In addition, 26 bacterial strains that could only be identified at the species level using WGS analysis, were mainly organisms that have been identified/classified very recently. Conclusion Our new algorithm proved to be a powerful tool for detection and identification of novel bacterial organisms. Publicly available clinical and genomic data may help to better understand their clinical and ecological role. Our identification of 35 novel strains, 7 of which appear to be clinically relevant, shows the wide range of undescribed pathogens yet to define.

Abstract Introduction Prevalence of elevated blood pressure (BP) and diabetes mellitus (DM) is increasing in sub-Saharan Africa. Data on target organ damage such as retinopathy, left ventricular hypertrophy (LVH), renal impairment and peripheral neuropathy (PN) among persons with elevated BP and/or DM in sub-Saharan Africa remain scarce. Aim To determine at community-level the prevalence of retinopathy, LVH, renal impairment, and PN among adults with elevated BP and/or DM, and assess the association of elevated BP and/or DM with target organ damage in Lesotho. Methods During a household-based survey, a sub-sample of adults with elevated BP (≥ 140/90 mmHg) and/or DM (glycosylated hemoglobin ≥ 6.5%), as well as comparators (BP

Abstract Background The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) – a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. Methods In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. Results Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0–31.2) hours with BF-FA-BCIP compared to 45.7 (37.7–51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. Conclusions Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. Trial registration Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

Abstract Background: A reported history of penicillin allergy frequently leads to the prescription of carbapenems as a substitute for penicillin to avoid allergic reactions. Such self-reported allergies need to be accurately characterized to identify targeted antibiotic stewardship interventions that potentially minimize unnecessary carbapenem use. Design: Retrospective cohort study. Method: The proportion of hospitalized patients with penicillin allergy history receiving carbapenem prescriptions was evaluated between January 1st, 2017 and December 31st, 2018 at the University Hospital Basel, Switzerland. The appropriateness of carbapenem prescription of each patient was evaluated using institutional guidelines based on previously published recommendations. Results: Our analysis revealed that among 212 patients with recorded penicillin allergy, of the 247 carbapenem treatment episodes, 79 (32%) were unjustified. Abdominal and lower respiratory tract infections were most frequently associated with inappropriate carbapenem use (OR 2.64, 95% CI 1.22–5.71, P = .014 and OR 2.26, 95% CI 1.08–4.73, P = .031). The recorded allergy type was not documented or unclear in 153 patients (72%) and penicillin allergy was only confirmed in 2 patients (0.9%). Inconsistencies in allergic symptom documentation and allergy types were found between the institution’s two software programs. Conclusion: While a multimodal approach to identify and accurately label penicillin allergies remains essential to reduce inappropriate carbapenem use, our findings highlight the need for comprehensive and easily accessible guidelines for carbapenem utilization and structured history-based allergy assessment as an initial screening tool, embedded in a tailored digital allergy record template.

Abstract Background Solid-organ transplantation due to end-stage organ disease is increasingly performed in people living with HIV. Despite improved transplant outcomes, management of these patients remains challenging due to higher risk for allograft rejection, infection and drug–drug interactions (DDIs). Complex regimens for multi-drug resistant HIV-viruses may cause DDIs particularly if the regimen contains drugs such as ritonavir or cobicistat. Case presentation Here we report on a case of an HIV-infected renal transplant recipient on long-term immunosuppressive therapy with mycophenolate mofetil and tacrolimus dosed at 0.5 mg every 11 days due to the co-administration of a darunavir/ritonavir containing antiretroviral regimen. In the presented case the pharmacokinetic booster was switched from ritonavir to cobicistat for treatment simplification. A close monitoring of tacrolimus drug levels was performed in order to prevent possible sub- or supratherapeutic tacrolimus trough levels. A progressive decrease in tacrolimus concentrations was observed after switch requiring shortening of tacrolimus dosing interval. This observation was unexpected considering that cobicistat is devoid of inducing properties. Conclusions This case highlights the fact that the pharmacokinetic boosters ritonavir and cobicistat are not fully interchangeable. Therapeutic drug monitoring of tacrolimus is warranted to maintain levels within the therapeutic range.

Abstract Introduction Monitoring HIV viral load (HVL) in people living with HIV (PLHIV) on antiretroviral therapy (ART) is recommended by the World Health Organization. Implementation of HVL testing programs have been affected by logistic and organizational challenges. Here we describe the HVL monitoring cascade in a rural setting in Tanzania and compare turnaround times (TAT) between an on-site and a referral laboratory. Methods In a nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) we included PLHIV aged ≥ 15 years, on ART for ≥ 6 months after implementation of routine HVL monitoring in 2017. We assessed proportions of PLHIV with a blood sample taken for HVL, whose results came back, and who were virally suppressed (HVL

Abstract Background Cervical cancer (CC) is nearly always caused by persistent human papillomavirus (HPV) infection. It is the most common cancer among women living with HIV (WLWH) and is the leading cause of cancer-related death in women in East Africa, with 10,241 new cases reported in Tanzania in 2020. In 2019, the World Health Organization (WHO) presented a global strategy for the elimination of CC as a public health problem, proposing targets to meet by 2030 for HPV vaccine coverage (90% of all 15-year-old girls), CC screening (70% of all women once at 35 and again at 45 years of age) and treatment delivery, to be scaled at national and subnational levels with a context-sensitive approach. This study aims to evaluate the upscaling of screening and treatment services at a rural referral hospital in Tanzania in order to address the second and third WHO targets. Methods This is an implementation study with a before-and-after design performed at St. Francis Referral Hospital (SFRH) in Ifakara (south-central Tanzania). CC screening and treatment services are integrated within the local HIV Care and Treatment Center (CTC). The standard of care, consisting of visualization of the cervix with acetic acid (VIA) and cryotherapy has been up-scaled with self-sampled HPV testing and also involved the introduction of mobile colposcopy, thermal ablation and loop electrosurgical excision procedure (LEEP). Participants are WLWH aged 18 to 65 years. Outcome measures included the percentage of women screened, HPV prevalence and genotype, and adherence to screening, treatment and follow-up plan. Additionally, we will explore the performance of novel diagnostic tests (QG-MPH®, Prevo-Check® and PT Monitor®), which share the features of being manageable and inexpensive, and thus a potential tool for effective triage in HPV high-prevalence cohorts. Discussion The study will provide relevant information about HPV prevalence and persistence, as well as reproductive and lifestyle indicators in a CC high-risk cohort of WLWH and about upscaling screening and treatment services at the level of a rural referral hospital in Tanzania. Furthermore, it will provide exploratory data on novel assays. Trial registration ClinicalTrials.gov Identifier: NCT05256862, date of registration 25/02/2022. Retrospectively registered.

Objectives This scoping review aims to identify and synthesise existing statistical methods used to assess the progress of HIV treatment programmes in terms of the HIV cascade and continuum of care among people living with HIV (PLHIV).Design Systematic scoping review.Data sources Published articles were retrieved from PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete and Excerpta Medica dataBASE (EMBASE) databases between April and July 2022. We also strategically search using the Google Scholar search engine and reference lists of published articles.Eligibility criteria This scoping review included original English articles that estimated and described the HIV cascade and continuum of care progress in PLHIV. The review considered quantitative articles that evaluated either HIV care cascade progress in terms of the Joint United Nations Programme on HIV and AIDS targets or the dynamics of engagement in HIV care.Data extraction and synthesis The first author and the librarian developed database search queries and screened the retrieved titles and abstracts. Two independent reviewers and the first author extracted data using a standardised data extraction tool. The data analysis was descriptive and the findings are presented in tables and visuals.Results This review included 300 articles. Cross-sectional study design methods were the most commonly used to assess the HIV care cascade (n=279, 93%). In cross-sectional and longitudinal studies, the majority used proportions to describe individuals at each cascade stage (276/279 (99%) and 20/21 (95%), respectively). In longitudinal studies, the time spent in cascade stages, transition probabilities and cumulative incidence functions was estimated. The logistic regression model was common in both cross-sectional (101/279, 36%) and longitudinal studies (7/21, 33%). Of the 21 articles that used a longitudinal design, six articles used multistate models, which included non-parametric, parametric, continuous-time, time-homogeneous and discrete-time multistate Markov models.Conclusions Most literature on the HIV cascade and continuum of care arises from cross-sectional studies. The use of longitudinal study design methods in the HIV cascade is growing because such methods can provide additional information about transition dynamics along the cascade. Therefore, a methodological guide for applying different types of longitudinal design methods to the HIV continuum of care assessments is warranted.

Summary: Background: WHO introduced the STEPwise approach to surveillance (STEPS) to monitor trends in non-communicable diseases. For arterial hypertension, the STEPS protocol takes the average of the last two out of three standard blood pressure measurements (SBPM). This study assesses the diagnostic accuracy of SBPM, same-day and next-day unattended automated measurement (uABP), with 24 h ambulatory measurement (24 h-ABPM) as reference. Methods: This diagnostic accuracy study was done within a population-based household survey on cardiovascular risk factors in two districts in Northern Lesotho. Adults (aged ≥ 18 years) with elevated SBPM (defined as ≥140/90 mmHg), and 2:1 age- and sex-matched participants with normal SBPM during the survey were recruited. Following SBPM, first uABP readings were obtained on survey day. Afterwards, participants received a 24 h-ABPM device. Second uABP readings were taken 24 h later, after retrieval of the 24 h-ABPM. The main outcome was overall diagnostic accuracy of all screening measurements (SBPM, first uABP, and second uABP), determined using area under the receiver operating characteristic curve (AUROC), with 24 h-ABPM as a reference. Findings: Between November 2, 2021 and August 31, 2022, 275 participants (mean age 58 years (SD: 16 years), 163 (59%) female) were enrolled, 183 of whom had elevated and 92 had normal SBPM. Mean difference between systolic daytime 24 h-ABPM and screening measurements was highest for SBPM (mean difference: −13 mmHg; 95% CI: −14 to −11). Mean difference between diastolic daytime 24 h-ABPM and diastolic SBPM was −2 mmHg (95% CI: −4 to −1), whereas no difference was found for mean diastolic first uABP (mean difference: −1 mmHg; 95% CI: −2.0 to 0.3); and mean diastolic second uABP (mean difference: 1.0 mmHg; 95% CI: −0.4 to 2.3). White coat hypertension was highest with SBPM (55 [20%]), followed by first uABP (27 [9.8%]), and second uABP (18 [6.5%]). Using systolic daytime 24 h-ABPM as a reference, the uABPs had higher AUROC (first uABP: 87% [95% CI: 83–91]; second uABP: 88% [95% CI: 84–92]); SBPM: (79% [95% CI: 74–85]). This difference was significant between first uABP and SBPM (P = 0.0024), and between second uABP and SBPM (P = 0.0017). Interpretation: uABP had better diagnostic performance than SBPM. Integration of uABP into STEPS protocol should be considered. Funding: Swiss Agency for Development and Cooperation under the ComBaCaL project, and the World Diabetes Foundation.

Objectives: Despite the availability of international guidelines advocating shorter treatment durations, nonadherence to them is common. We assessed duration of antibiotic treatment for diverticulitis, complicated urinary tract infection (UTI), and endocarditis. Methods: Medical records of patients hospitalized with the previously stated diseases in 2017 and 2018 were randomly selected at a Swiss tertiary care hospital. The appropriateness of antibiotic treatment duration was assessed according to international and local guidelines. Results: A total of 243 patients were included in the study: 100 with diverticulitis, 200 with complicated UTI, and 43 with endocarditis. The dherence to local and international guidelines was 11% and 18% in diverticulitis, 39% and 40% in complicated UTI, and 84% and 86% in endocarditis, respectively. Nonadherence was primarily due to the prolonged treatment in diverticulitis and complicated UTI with a median duration of antibiotic treatment of 11 days (interquartile range 10-13) and 14 days (interquartile range 10-15), respectively. When pooling diverticulitis and complicated UTI cases, the identification of a pathogen in any microbiological sample was associated with an improved adherence to local guidelines in addition to hospitalization in a medical ward and infectious diseases consultation. Conclusion: Prolonged courses of antibiotic treatment were common and the treatment adherence to guidelines were poor in diverticulitis, moderate in complicated UTI, and excellent in endocarditis.

Abstract Background Nearly half of HIV-related deaths occur in East and Southern Africa, yet data on causes of death (COD) are scarce. We determined COD and associated factors among people living with HIV (PLHIV) in rural Tanzania. Methods PLHIV attending the Chronic Diseases Clinic of Ifakara, Morogoro are invited to enrol in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Among adults (≥ 15 years) enrolled in 2005–2018, with follow-up through April 2019, we classified COD in comprehensive classes and as HIV- or non-HIV-related. In the subset of participants enrolled in 2013–2018 (when data were more complete), we assessed cause-specific mortality using cumulative incidences, and associated factors using proportional hazards models. Results Among 9871 adults (65% female, 26% CD4 count

IntroductionThe prevalence of type 2 diabetes mellitus (T2DM) and associated morbidity and mortality are increasing in sub-Saharan Africa (SSA). To facilitate access to quality care and improve treatment outcomes, there is a need for innovative community care models and optimized use of non-physician healthcare workers bringing diagnosis and care closer to patients' homes.AimWe aimed to describe with a scoping review different models of community-based care for non-pregnant adults with T2DM in SSA, and to synthesize the outcomes in terms of engagement in care, blood sugar control, acceptability, and end-organ damage. We further aimed to critically appraise the different models of care and compare community-based to facility-based care if data were available.MethodsWe searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scopus, supplemented with backward and forward citation searches. We included cohort studies, randomized trials and case-control studies that reported on non-pregnant individuals diagnosed with T2DM in SSA, who received a substantial part of care in the community. Only studies which reported at least one of our outcomes of interest were included. A narrative analysis was done, and comparisons made between community-based and facility-based models, where within-study comparison was reported.ResultsWe retrieved 5,335 unique studies, four of which met our inclusion criteria. Most studies were excluded because interventions were facility-based; community care interventions described in the studies were only add-on features of a primarily facility-based care; and studies did not report outcomes of interest. The included studies reported on a total of 383 individuals with T2DM. Three different community care models were identified. 1) A community-initiated model where diagnosis, treatment and monitoring occurred primarily in the community. This model reported a higher linkage and engagement in care at 9 months compared to the corresponding facility model, but only slight reductions of average blood glucose levels at six months compared to baseline. 2) A facility-originated community model where after treatment initiation, a substantial part of follow-up was offered at community level. Two studies reported such a model of care, both had as core component home-delivery of medication. Acceptability of this approach was high. But neither study found improved T2DM control when compared to facility care 3) An eHealth model with high acceptability scores for both patients and care providers, and an absolute 1.76% reduction in average HbA1c levels at two months compared to baseline. There were no reported outcomes on end-organ damage. All four studies were rated as being at high risk for bias.ConclusionEvidence on models of care for persons with T2DM in SSA where a substantial part of care is shifted to the community is scant. Whereas available literature indicates high acceptability of community-based care, we found no conclusive data on their effectiveness in controlling blood sugar and preventing complications. Evidence from larger scale studies, ideally randomized trials with clinically relevant endpoints is needed before roll-out of community-based T2DM care can be recommended in SSA.

IntroductionIn low-resource settings, anaemia is a very common condition. Identification of anaemia aetiologies remains challenging due to the lack of diagnostic tools and expertise. We aimed to improve anaemia diagnostics using peripheral blood smear (PBS) with remote interpretation in people living with HIV (PLHIV) with moderate to severe anaemia.MethodsWe conducted a prospective study nested within the Kilombero and Ulanga Antiretroviral Cohort, including non-pregnant PLHIV aged ≥18 years presenting with moderate (haemoglobin 7.0-9.9 g/dl) or severe (ResultsAmong 400 PLHIV with moderate to severe anaemia, 349 (87%) were female, median age was 40 years (interquartile range (IQR) 35-46)), 65 (17%) had a body mass index ConclusionRemote interpretation of PBS combined with clinical information and blood cell count results can provide insights to the suspected aetiological diagnosis of moderate and severe anaemia in rural low-resource settings and impact specific treatment.

IntroductionIncreased body weight is an important risk factor for cardiovascular disease and is increasingly reported as a health problem in people living with HIV (PLHIV). There is limited data from rural sub-Saharan Africa, where malnutrition usually presents with both over- and undernutrition. We aimed to determine the prevalence and risk factors of underweight and overweight/obesity in PLHIV enrolled in a cohort in rural Tanzania before the introduction of integrase inhibitors.MethodsThis nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort included adults aged ≥19 years initiated on antiretroviral therapy between 01/2013 and 12/2018 with follow-up through 06/2019. Body Mass Index (BMI) was classified as underweight (ResultsAmong 2,129 patients, 22,027 BMI measurements (median 9 measurements: interquartile range 5-15) were analysed. At baseline, 398 (19%) patients were underweight and 356 (17%) were overweight/obese. The majority of patients were female (n = 1249; 59%), and aged 35-44 years (779; 37%). During the first 9 months, for every three additional months on antiretroviral therapy, BMI increased by 2% (95% confidence interval 1-2%, p2 times the hazard of death/LTFU compared to participants with normal BMI.ConclusionWe found a double burden of malnutrition, with underweight being an independent predictor of mortality. Monitoring and measures to address both states of malnutrition among PLHIV should be integrated into routine HIV care.

BackgroundBlood cultures (BC) are critical for the diagnosis of bloodstream infections, pathogen identification, and resistance testing. Guidelines recommend a blood volume of 8-10 mL per bottle as lower volumes result in decreased sensitivity. We aimed to evaluate factors for non-adherence to recommended volumes and assess the effects on diagnostic performance.MethodsFrom February to April 2020, we measured collected blood volumes by weighing all BC containers from inpatient samples at the University Hospital Basel. Information on BC volumes was merged with clinical and microbiological data, as well as nursing staff schedules. We analyzed factors associated with (i) BC sampling volume, (ii) reaching recommended volumes (≥8 mL), (iii) BC positivity, and (iv) time to positivity using linear and generalized linear mixed effect models.ResultsWe evaluated a total of 4'118 BC bottles collected from 686 patients. A total of 1'495 (36.3%) of all bottles contained the recommended filling volume of ≥8 mL. Using a central venous and arterial catheter for drawing blood resulted in an increase of filling volume by 0.26 mL (95% CI 0.10, 0.41) and 0.50 mL (95% CI 0.31, 0.69) compared to peripheral venipuncture, respectively. Each additional nursing staff working at the time of blood drawing was associated with 6% higher odds of achieving the recommended filling volume. We found no significant correlation between the filling volume and the positivity rate.ConclusionOur results indicate critical pre-analytical quality markers linked to BC collection procedures to reach recommended collection volumes. No significant impact on the positivity rate was found.

The Bacillus cereus-group (B. cereus sensu lato) includes common, usually avirulent species, often considered contaminants of patient samples in routine microbiological diagnostics, as well as the highly virulent B. anthracis. Here we describe 16 isolates from 15 patients, identified as B. cereus-group using a MALDI-TOF MS standard database. Whole genome sequencing (WGS) analysis identified five of the isolates as B. anthracis species not carrying the typical virulence plasmids pXO1 and pXO2, four isolates as B. paranthracis, three as B. cereus sensu stricto, two as B. thuringiensis, one as B. mobilis, and one isolate represents a previously undefined species of Bacillus (B. basilensis sp. nov.). More detailed analysis using alternative MALDI-TOF MS databases, biochemical phenotyping, and diagnostic PCRs, gave further conflicting species results. These cases highlight the difficulties in identifying avirulent B. anthracis within the B. cereus-group using standard methods. WGS and alternative MALDI-TOF MS databases offer more accurate species identification, but so far are not routinely applied. We discuss the diagnostic resolution and discrepancies of various identification methods.

Abstract Background Capnocytophaga canimorsus is a Gram-negative capnophilic rod and part of dogs/cats’ normal oral flora. It can be transmitted by bites, scratches, or even by contact of saliva with injured skin. Asplenic patients and patients with alcohol abuse are at particular risk for fulminant C. canimorsus sepsis. However, also immunocompetent patients can have a severe or even fatal infection. This is the first case of a severe C. canimorsus infection in an immunocompromised host complicated by acute renal cortical necrosis with a “reverse rim sign” in contrast-enhanced computed tomography on hospital admission. Case presentation We report the case of a 44-year functionally asplenic patient after an allogeneic stem cell transplantation, who presented with septic shock after a minor dog bite injury 4 days prior. Because of abdominal complaints, epigastric pain with local peritonism, and radiological gallbladder wall thickening, an abdominal focus was suspected after the initial work-up. The patient underwent emergent open cholecystectomy, but the clinical suspicion of abdominal infection was not confirmed. Septic shock was further complicated by cardiomyopathy and disseminated intravascular coagulation. As a causative pathogen, C. canimorsus could be isolated. The clinical course was complicated by permanent hemodialysis and extensive acral necrosis requiring amputation of several fingers and both thighs. Conclusion We present a severe case of a C. canimorsus infection in a functionally asplenic patient after a minor dog bite. The clinical course was complicated by septic shock, disseminated intravascular coagulation, and the need for multiple amputations. In addition, the rare form of acute renal failure - bilateral acute renal cortical necrosis – was visible as “reverse rim sign” on computed tomography scan. This case is an example of the potential disastrous consequences when omitting pre-emptive antibiotic therapy in wounds inflicted by cats and dogs, particularly in asplenic patients.

Abstract Objectives SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. Methods We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for

Abstract Background Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa. Methods In this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥ 18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90 mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤ 130/80 mmHg and ≤ 140/90 mmHg among those aged

Abstract Background Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART). Methods GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to

Abstract Background Patients with clinically suspected tuberculosis are often treated empirically, as diagnosis - especially of extrapulmonary tuberculosis - remains challenging. This leads to an overtreatment of tuberculosis and to underdiagnosis of possible differential diagnoses. Methods This open-label, parallel-group, superiority randomized controlled trial is done in a rural and an urban center in Tanzania. HIV-positive and -negative adults (≥18 years) with clinically suspected extrapulmonary tuberculosis are randomized in a 1:1 ratio to an intervention- or control group, stratified by center and HIV status. The intervention consists of a management algorithm including extended focused assessment of sonography for HIV and tuberculosis (eFASH) in combination with chest X-ray and microbiological tests. Treatment with anti-tuberculosis drugs is started, if eFASH is positive, chest X-ray suggests tuberculosis, or a microbiological result is positive for tuberculosis. Patients in the control group are managed according national guidelines. Treatment is started if microbiology is positive or empirically according to the treating physician. The primary outcome is the proportion of correctly managed patients at 6 months (i.e patients who were treated with anti-tuberculosis treatment and had definite or probable tuberculosis, and patients who were not treated with anti-tuberculosis treatment and did not have tuberculosis). Secondary outcomes are the proportion of symptom-free patients at two and 6 months, and time to death. The sample size is 650 patients. Discussion This study will determine, whether ultrasound in combination with other tests can increase the proportion of correctly managed patients with clinically suspected extrapulmonary tuberculosis, thus reducing overtreatment with anti-tuberculosis drugs. Trial registration PACTR, Registration number: PACTR201712002829221 , registered December 1st 2017.

Background Frequencies of ultrasonographic findings and diagnoses in emergency departments in sub-Saharan Africa are unknown. This study aimed to describe the frequencies of different sonographic findings and diagnoses found in patients with abdominal symptoms or trauma presenting to a rural referral hospital in Tanzania. Methods In this prospective observational study, we consecutively enrolled patients with abdominal symptoms or trauma triaged to the emergency room of the Saint Francis Referral Hospital, Ifakara. Patients with abdominal symptoms received an abdominal ultrasound. Patients with an abdominal or thoracic trauma received an Extended Focused Assessment with Ultrasound in Trauma (eFAST). Results From July 1st 2020 to June 30th 2021, a total of 88838 patients attended the emergency department, of which 7590 patients were triaged as ‘very urgent’ and were seen at the emergency room. A total of 1130 patients with abdominal symptoms received an ultrasound. The most frequent findings were abnormalities of the uterus or adnexa in 409/754 females (54.2%) and abdominal free fluid in 368 (32.6%) patients; no abnormality was found in 150 (13.5%) patients. A tumour in the abdomen or pelvis was found in 183 (16.2%) patients, an intrauterine pregnancy in 129/754 (17.1%) females, complete or incomplete abortion in 96 (12.7%), and a ruptured ectopic pregnancy in 32 (4.2%) females. In males, most common diagnosis was intestinal obstruction in 54/376 (14.4%), and splenomegaly in 42 (11.2%). Of 1556 trauma patients, 283 (18.1%) received an eFAST, and 53 (18.7%) had positive findings. A total of 27 (9.4%) trauma patients and 51 (4.5%) non-trauma patients were sent directly to the operating theatre. Conclusion In this study, ultrasound examination revealed abnormal findings for the majority of patients with non-traumatic abdominal symptoms. Building up capacity to provide diagnostic ultrasound is a promising strategy to improve emergency services, especially in a setting where diagnostic modalities are limited.

The rollout of antiretroviral drugs in sub-Saharan Africa to address the huge health impact of the HIV pandemic has been one of the largest projects undertaken in medical history and is an unprecedented medical success story. However, the path has been and still is characterized by many far reaching implementational challenges. Here, we report on the building and maintaining of a role model clinic in Ifakara, rural Southwestern Tanzania, within a collaborative project to support HIV services within the national program, training for staff and integrated research to better understand local needs and improve patients’ outcomes.

OBJECTIVES Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking. METHODS In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation 30/min, C-reactive protein levels >75 mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16. RESULTS Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10–24) with 24 days (IQR 14–32) in ICU patients and 10 days (IQR 7–15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients. CONCLUSIONS In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function. Trial registration ClinicalTrials.gov NCT04351503

BACKGROUND Prompt linkage to human immunodeficiency virus (HIV) care after diagnosis is of utmost importance for individual health and reduction of HIV transmission. Different definitions for “linkage to care” have challenged comparisons as a public health marker. Its meaning in the era of “universal test and treat” has transformed in all settings, but is most relevant in sub-Sahara Africa, where the burden of new HIV infection is still highest. METHODS For this narrative review on “linkage to care” definitions with a focus on sub-Saharan Africa, we searched PubMed/Medline between September and December 2020, restricted to the period 2000–2020 using Boolean operators: “HIV” AND (“linkage to care” OR “engagement in care”) and screened for institutional definitions of “linkage to care”. Additionally, as one example of a rural sub-Saharan African setting, we analysed linkage steps within the Chronic Diseases Clinic Ifakara (CDCI) and its associated Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) in rural Tanzania between 1 January 2017 and 31 March 2019. RESULTS We analysed 81 articles that included “linkage to care” within different study settings and HIV organisations. Major differences in defining “linkage to care” exist, according to setting and location, patient populations and the timing of steps within the linkage process. We identified 16 different numerators and 10 denominators used to define linkage with time periods ranging from “same day as diagnosis” up to 12 months after diagnosis among 34 original articles from sub-Saharan Africa. At the CDCI, 1149/1671 (69%) newly diagnosed individuals were enrolled into care after diagnosis. Three months after enrolment into care, 94%, 86%, 85% and 71% of enrolled patients had a laboratory evaluation, a clinical evaluation, were initiated on treatment and had a first clinical follow-up visit after initiation of treatment, respectively. DUSCUSSION To address the inconsistency in defining “linkage to care” and in order to guarantee the comparability of “linkage to care” in the sub-Saharan Africa region, we support the definition from the European region with some adaptions. We suggest a priority list of care indicators if more than one care indicator is available for successful “linkage to care” in the era of “universal test and treat” for sub-Sahara Africa.

AIMS The aim of this study was to analyse the demographics, risk factors and in-hospital mortality rates of patients admitted with coronavirus disease 2019 (COVID-19) to a tertiary care hospital in Switzerland. METHODS In this single-centre retrospective cohort study at the University Hospital Basel, we included all patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalised from 27 February 2020 to 10 May 2021. Patients’ characteristics were extracted from the electronic medical record system. The primary outcome of this study was temporal trends of COVID-19-related in-hospital mortality. Secondary outcomes were COVID-19-related mortality in patients hospitalised on the intensive care unit (ICU), admission to ICU, renal replacement therapy and length of hospital stay, as well as a descriptive analysis of risk factors for in-hospital mortality. RESULTS During the study period we included 943 hospitalisations of 930 patients. The median age was 65 years (interquartile range [IQR] 53–76) and 63% were men. The numbers of elderly patients, patients with multiple comorbidities and need for renal replacement therapy decreased from the first and second to the third wave. The median length of stay and need for ICU admission were similar in all waves. Throughout the study period 88 patients (9.3%) died during the hospital stay. Crude in-hospital mortality was similar over the course of the first two waves (9.5% and 10.2%, respectively), whereas it decreased in the third wave (5.4%). Overall mortality in patients without comorbidities was low at 1.6%, but it increased in patients with any comorbidity to 12.6%. Predictors of all-cause mortality over the whole period were age (adjusted odds ratio [aOR] per 10-year increase 1.81, 95% confidence interval [CI] 1.45–2.26; p

Abstract Objective HIV-1 rapidly establishes a persistent infection that can be contained under life-long antiretroviral therapy (ART) but not cured. One major viral reservoir is the peripheral lymph node (LN) follicles. Studying the impact of novel HIV-1 treatment and vaccination approaches on cells residing in germinal centers is essential for rapid progress towards HIV-1 prevention and cure. Results We enrolled 9 asymptomatic adult volunteers with a newly diagnosed HIV-1 infection and CD4 T cell counts ≥ 350/ml. The patients underwent venous blood collection and inguinal lymph node excision surgery in parallel. Mononuclear cells were extracted from blood and tissues simultaneously. Participants were followed up regularly for 2 weeks until complete healing of the surgical wounds. All participants completed the lymph node excision surgery without clinical complications. Among the 9 volunteers, one elite controller was identified. The number of mononuclear cells recovered from lymph nodes ranged from 68 to 206 million and correlated positively with lymph node size. This is the first study to show that lymph node biopsy is a safe procedure and can be undertaken with local experts in rural settings. It provides a foundation for detailed immune response investigations during future clinical trials.

ObjectiveRitonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa.MethodsUsing data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate ResultsRenal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) ConclusionsIn PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.

(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study from 28 December 2020 to 25 October 2021. Data of all patients with breakthrough infection was compared to data of all vaccine recipients in the Canton of Basel-City, Switzerland. Further, breakthrough infections by Alpha- and Delta-variants were compared. (3) Results: Only 0.39% (488/126,586) of all vaccine recipients suffered from a breakthrough infection during the observational period, whereof most cases were asymptomatic or mild (97.2%). Breakthrough infections after full vaccination occurred in the median after 78 days (IQR 47-123.5). Factors with lower odds for breakthrough infection were age (OR 0.987) and previous COVID-19 infection prior to vaccination (OR 0.296). Factors with higher odds for breakthrough infection included vaccination with Pfizer/BioNTech instead of Moderna (OR 1.459), chronic disease (OR 2.109), and healthcare workers (OR 1.404). (4) Conclusions: Breakthrough infections are rare and mild but can occur early after vaccination. This implies that booster vaccination might be initiated earlier, especially for risk groups. Due to new variants emerging repeatedly, continuous monitoring of breakthrough infections is crucial.

BACKGROUND:Poor adherence to antiretroviral drugs and viral resistance are the main drivers of treatment failure in HIV-infected patients. In sub-Saharan Africa, avoidance of treatment failure on second-line protease inhibitor therapy is critical as treatment options are limited. METHODS:In the prospective observational study of the Kilombero & Ulanga Antiretroviral Cohort in rural Tanzania, we assessed virologic failure (viral load ≥1,000 copies/mL) and drug resistance mutations in bio-banked plasma samples 6-12 months after initiation of a protease inhibitor-based treatment regimen. Additionally, viral load was measured before start of protease inhibitor, a second time between 1-5 years after start, and at suspected treatment failure in patients with available bio-banked samples. We performed resistance testing if viral load was ≥1000 copies/ml. Risk factors for virologic failure were analyzed using logistic regression. RESULTS:In total, 252 patients were included; of those 56% were female and 21% children. Virologic failure occurred 6-12 months after the start of a protease inhibitor in 26/199 (13.1%) of adults and 7/53 of children (13.2%). The prevalence of virologic failure did not change over time. Nucleoside reverse transcriptase inhibitors drug resistance mutation testing performed at 6-12 months showed a positive signal in only 9/16 adults. No cases of resistance mutations for protease inhibitors were seen at this time. In samples taken between 1-5 years protease inhibitor resistance was demonstrated in 2/7 adults. In adult samples before protease inhibitor start, resistance to nucleoside reverse transcriptase inhibitors was detected in 30/41, and to non-nucleoside reverse-transcriptase inhibitors in 35/41 patients. In 15/16 pediatric samples, resistance to both drug classes but not for protease inhibitors was present. CONCLUSION:Our study confirms high early failure rates in adults and children treated with protease inhibitors, even in the absence of protease inhibitors resistance mutations, suggesting an urgent need for adherence support in this setting.

BACKGROUND:In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania. METHODS:We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death. RESULTS:We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31-46) and a median CD4+ cell count of 229/μl (IQR 94-421) at baseline. During the median follow-up of 1.25 years (IQR 0.46-2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2-22.6) and 5.8/1000 py (95% CI 4.0-8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14-2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15-3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08-0.27); p

Abstract Background Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania. Methods Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ 2, Fisher’s exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations. Results Between August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27–41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P

BACKGROUND Information on diagnoses made in emergency departments situated in rural sub-Saharan Africa is scarce. The aim was: to evaluate the frequency of different diagnoses made in a new emergency department to define relevant healthcare requirements; and to find out if in-hospital mortality rates would decrease after the implementation of the emergency department. METHODS In this observational study, we prospectively collated diagnoses of all patients presenting to the emergency department of the St Francis Referral Hospital in Ifakara, Tanzania during 1 year. In addition, we compared in-hospital mortality rates before and after the implementation of the emergency department. RESULTS From July 2016 through to June 2017, a total of 35,903 patients were included. The median age was 33.6 years (range 1 day to 100 years), 57% were female, 25% were children 50-year-olds. Respiratory tract infections peaked in April during the rainy season, whereas malaria peaked 3 months after the rainy season. In-hospital mortality rates did not decrease during the study period (5.6% in 2015 vs 7.6% in 2017). CONCLUSIONS The majority of diagnosed disorders were of infectious or traumatic origin. The majority of febrile illnesses were poorly defined because of the lack of diagnostic methods. Trauma systems and inexpensive accurate diagnostic methods for febrile illnesses are needed in rural sub-Saharan Africa.

BACKGROUND:It has been hypothesized that schistosomiasis negatively influences immune reconstitution in people living with HIV starting antiretroviral therapy (ART). In this study, we investigated the effect of schistosomiasis on the course of HIV infection in patients starting ART in a rural part of Tanzania. METHODOLOGY:Retrospective study including patients prospectively enrolled in a HIV cohort in Ifakara, south-central Tanzania between January 1, 2013 and April 1, 2015. Schistosomal circulating anodic antigen (CAA) was assessed in pre-ART cryopreserved plasma. Regression models were utilized to estimate the effect of CAA positivity on virological and immunological failure and a composite outcome of death/loss to follow-up (LFU). PRINCIPAL FINDINGS:At ART-initiation 19.1% (88/461) of patients were CAA-positive. A tendency of higher CD4 increases was seen in CAA-positive patients (+182 cells/μl, interquartile range (IQR), 87-285 cells/μl) compared to CAA-negative patients (+147 cells/μl, IQR, 55-234 cells/μl, p = 0.09) after 10 months of follow-up. After adjustment for baseline risk factors, CAA-positivity showed no association with virological or immunological failure. In CAA-positive patients, 22.7% (20/88) died or were LFU, compared to 29.5% (110/373) of CAA-negative patients (hazard ratio (HR): 0.76, 95% confidence interval (CI), 0.47-1.22, p = 0.25). After adjustment for age, sex, body mass index, educational attainment, WHO-stage, tuberculosis status, and year of ART initiation, CAA-positivity showed a trend of a decreased hazard of death/LFU (HR: 0.58, 95% CI: 0.32-1.05, p = 0.07), while CD4 count at baseline (HR: 0.86, 95% CI: 0.76-1.00, p = 0.02) and MXD (sum of eosinophils, basophils, and monocytes counts) >1,100 cells/μl (HR: 0.56, 95% CI: 0.34-0.93, p = 0.03) were identified as independently protective factors. CONCLUSIONS/SIGNIFICANCE:Schistosomiasis is prevalent in this HIV cohort and may be beneficial for immunological reconstitution, while no effect on virological failure was apparent. A positive effect of schistosomiasis-induced immunomodulation on survival and retention in care needs confirmation in future studies.

BackgroundLittle is known about heart diseases and their treatment in rural sub-Saharan Africa. This study aimed to describe the occurrence, characteristics, and etiologies of heart diseases, and the medication taken before and prescribed after echocardiography in a rural referral Hospital in Tanzania.MethodsThis prospective descriptive cohort study included all adults and children referred for echocardiography. Clinical and echocardiographic data were collated for analysis.ResultsFrom December 2015 to October 2017, a total of 1'243 echocardiograms were performed. A total of 815 adults and 59 children ≤15 years had abnormal echocardiographic findings; in adults 537/815 (66%) had hypertension, with 230/537(43%) on antihypertensive drugs, and 506/815 (62%) were not on regular cardiac medication; 346/815 (42%) had severe eccentric or concentric left ventricular hypertrophy, and 182/815 (22%) had severe systolic heart failure. Only 44% demonstrated normal left ventricular systolic function. The most frequent heart diseases were hypertensive heart disease (41%), valvular heart disease (18%), coronary heart disease (18%), peripartum cardiomyopathy (7%), and other non-hypertensive dilated cardiomyopathies (6%) in adults, and congenital heart disease (34%) in children. Following echocardiography, 802/815 (98%) adults and 40/59 (68%) children had an indication for cardiac medication, 70/815 (9%) and 2/59 (3%) for oral anticoagulation, and 35/815 (4%) and 23/59 (39%) for cardiac surgery, respectively.ConclusionHypertension is the leading etiology of heart diseases in rural Tanzania. Most patients present with advanced stages of heart disease, and the majority are not treated before echocardiography. There is an urgent need for increased awareness, expertise and infrastructure to detect and treat hypertension and heart failure in rural Africa.

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P

BACKGROUND The Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) is a single-site, open and ongoing prospective cohort of people living with human immunodeficiency virus (PLWHIV) established in 2005 at the Chronic Diseases Clinic of Ifakara (CDCI), within the Saint Francis Referral Hospital (SFRH) in Ifakara, Tanzania. The objectives of KIULARCO are to (i) provide patient and cohort-level information on the outcomes of HIV treatment; (ii) provide cohort-level information on opportunistic infections and comorbidities; (iii) evaluate aspects of human immunodeficiency virus (HIV) care and treatment that have national or international policy relevance; (iv) provide a platform for studies on improving HIV care and treatment in sub-Saharan Africa; and (v) contribute to generating local capacity to deal with the challenges posed by the HIV/AIDS pandemic in this region. Moreover, KIULARCO may serve as a model for other healthcare settings in rural sub-Saharan Africa. METHODS Since 2005, all patients diagnosed with HIV at the Saint Francis Referral Hospital are invited to participate in the cohort, including non-pregnant adults, pregnant women, adolescents, children and infants. The information collected includes demographics, baseline and follow-up clinical data, laboratory data, medication history, drug toxicities, diagnoses and outcomes. Real-time data are captured during the patient encounter through an electronic medical record system that allowed transition to a paperless clinic in 2013. In addition, KIULARCO is associated with a biobank of cryopreserved plasma samples and cell pellets collected from all participants before and at different time-points during antiretroviral treatment. RESULTS Up to the end of 2016, 12 185 PLWHIV have been seen at the CDCI; 9218 (76%) of whom have been enrolled into KIULARCO and 6965 (76%) of these have received ART from the clinic. Patients on ART attend at least every 3 months, with laboratory monitoring every 6 months. KIULARCO data have been used to generate relevant information regarding ART outcomes, opportunistic infections, non-AIDS comorbidities, prevention of mother-to-child transmission of HIV, paediatric HIV, and mortality and retention in care. Requests for collaborations on analyses can be submitted to the KIULARCO scientific committee. CONCLUSIONS KIULARCO provides a framework for improving the quality of care of people living with HIV in sub-Saharan Africa, to generate relevant information to evaluate ART programmes and to build local capacity to deal with HIV/AIDS. The comprehensiveness of the data collected, together with the biobank spanning over ten years has created a unique research platform in rural sub-Saharan Africa.

Strategies to improve the uptake of Prevention of Mother-To-Child Transmission of HIV (PMTCT) are needed. We integrated HIV and maternal, newborn and child health services in a One Stop Clinic to improve the PMTCT cascade in a rural Tanzanian setting.The One Stop Clinic of Ifakara offers integral care to HIV-infected pregnant women and their families at one single place and time. All pregnant women and HIV-exposed infants attended during the first year of Option B+ implementation (04/2014-03/2015) were included. PMTCT was assessed at the antenatal clinic (ANC), HIV care and labour ward, and compared with the pre-B+ period. We also characterised HIV-infected pregnant women and evaluated the MTCT rate.1,579 women attended the ANC. Seven (0.4%) were known to be HIV-infected. Of the remainder, 98.5% (1,548/1,572) were offered an HIV test, 94% (1,456/1,548) accepted and 38 (2.6%) tested HIV-positive. 51 were re-screened for HIV during late pregnancy and one had seroconverted. The HIV prevalence at the ANC was 3.1% (46/1,463). Of the 39 newly diagnosed women, 35 (90%) were linked to care. HIV test was offered to >98% of ANC clients during both the pre- and post-B+ periods. During the post-B+ period, test acceptance (94% versus 90.5%, p

BACKGROUND: Travel activity and travel-related risks of patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT) remain largely unknown. The aim of our study was to examine travel activity after allo-HSCT including travel behaviour and travel patterns. METHODS: We analysed travel characteristics of allo-HSCT recipients by using a retrospective cross-sectional survey. Allo-HSCT patients were asked to complete a questionnaire during their annual health visits from 2010 to 2012. RESULTS: Overall, 118/153 (77%) participating patients reported travel activity for a total of 201 travelling episodes. Travellers versus non-travellers were receiving immunosuppressive treatment in 35.6% versus 65.7% (p = 0.002), and had graft-versus-host-disease (GvHD) in 52.5% versus 62.9% (p = 0.17). In a multivariate analysis, the time between the transplantation and the survey was the only factor associated with travel activity (p

Most hospital-acquired infections arise from colonising bacteria. Intensive care patients and immunocompromised individuals are at highest risk for microbial invasion and subsequent infection due to multiple invasive procedures in addition to frequent application of chemotherapeutics and presence of poor microperfusion leading to mucosal disruption. In this narrative review, we summarise the literature on bacterial colonisation in intensive care patients, in particular the epidemiology, the clinical impact and respective infection control strategies of three pathogens, i.e., Enterococcusspp., extended-spectrum ß-lactamase producing gram-negative bacteria and Clostridium difficile, which have evolved from commensals to a public health concern today.

Infectious pathogens are responsible for high utilisation of healthcare resources globally. Attributable morbidity and mortality remains exceptionally high. Vaccines offer the potential to prime a pathogen-specific immune response and subsequently reduce disease burden. Routine vaccination has fundamentally altered the natural history of many frequently observed and serious infections. Vaccination is also recommended for persons at increased risk of severe vaccine-preventable disease. Many current nonadjuvanted vaccines are poorly effective in the elderly and immunocompromised populations, resulting in nonprotective postvaccine antibody titres, which serve as surrogate markers for protection. The vaccine-induced immune response is influenced by: (i.) vaccine factors i.e., type and composition of the antigen(s), (ii.) host factors i.e., genetic differences in immune-signalling or senescence, and (iii.) external factors such as immunosuppressive drugs or diseases. Adjuvanted vaccines offer the potential to compensate for a lack of stimulation and improve pathogen-specific protection. In this review we use influenza vaccine as a model in a discussion of the different mechanisms of action of the available adjuvants. In addition, we will appraise new approaches using “vaccine-omics” to discover novel types of adjuvants.

Little is known about optimal management of prosthetic vascular graft infections, which are a rare but serious complication associated with graft implants. The goal of this study was to compare and characterize these infections with respect to the location of the graft and to identify factors associated with outcome.This was a retrospective study over more than a decade at a tertiary care university hospital that has an established multidisciplinary approach to treating graft infections. Cases of possible prosthetic vascular graft infection were identified from the hospital's infectious diseases database and evaluated against strict diagnostic criteria. Patients were divided into groups according to the locations of their grafts: thoracic-aortic, abdominal-aortic, or peripheral-arterial. Statistical analyses included evaluation of patient and infection characteristics, time to treatment failure, and factors associated specifically with cure rates in aortic graft infections. The primary endpoint was cure at one year after diagnosis of the infection.Characterization of graft infections according to the graft location did show that these infections differ in terms of their characteristics and that the prognosis for treatment seems to be influenced by the location of the infection. Cure rate and all-cause mortality at one year were 87.5% and 12.5% in 24 patients with thoracic-aortic graft infections, 37.0% and 55.6% in 27 patients with abdominal-aortic graft infections, and 70.0% and 30.0% in 10 patients with peripheral-arterial graft infections. In uni- and multivariate analysis, the type of surgical intervention used in managing infections (graft retention versus graft replacement) did not affect primary outcome, whereas a rifampicin-based antimicrobial regimen was associated with a higher cure rate.We recommend that future prospective studies differentiate prosthetic vascular graft infections according to the location of the grafts and that rifampicin-based antimicrobial regimens be evaluated in clinical trials involving vascular graft infections caused by staphylococci.

We report a case series of 11 patients with severe E. faeciuminfections treated with daptomycin. All strains were resistant to ampicillin (MIC >8 mg/l), but susceptible to vancomycin. Seven out of 11 strains were also highly resistant to gentamicin (MIC >500 mg/l). All patients were treated with multiple broad-spectrum antibiotics prior to isolation of E. faecium and had severe underlying diseases. Our experience suggests that salvage therapy with daptomycin might be a safe and efficacious treatment for E. faecium infections.

Background Recurrence of prior invasive fungal infection (relapse rate of 30–50%) limits the success of stem cell transplantation. Secondary prophylaxis could reduce disease burden and improve survival.Design and Methods A prospective, open-label, multicenter trial was conducted evaluating voriconazole (4 mg/kg/12 h intravenously or 200 mg/12 h orally) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection. Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100–150 days. Patients were followed for 12 months. The primary end-point of the study was the incidence of proven or probable invasive fungal infection.Results Forty-five patients were enrolled, 41 of whom had acute leukemia. Previous invasive fungal infections were proven or probable aspergillosis (n=31), proven candidiasis (n=5) and other proven or probable infections (n=6); prior infection could not be confirmed in three patients. The median duration of voriconazole prophylaxis was 94 days. Eleven patients (24%) died within 12 months of transplantation, but only one due to systemic fungal disease. Three invasive fungal infections occurred post-transplant: two relapses (one candidemia and one fatal scedosporiosis) and one new zygomycosis in a patient with previous aspergillosis. The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6%. Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity).Conclusions Voriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation. The observed incidence of 6.7% (with one attributable death) is considerably lower than the relapse rate reported in historical controls, thus suggesting that voriconazole is a promising prophylactic agent in this population.