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Abstract Background Observational studies have shown that dressings containing chlorhexidine gluconate (CHX) lower the incidence external ventricular drain (EVD)-associated infections (EVDAIs). This prospective, randomized controlled trial (RCT) studies the efficacy of CHX-containing dressings in reducing bacterial colonization. Methods In this RCT, patients aged ≥18 years undergoing emergency EVD placement were randomly given either a CHX-containing or an otherwise identical control dressing at the skin exit wound. The primary end-point was bacterial regrowth in cultured skin swab samples of the EVD exit wound. The secondary end-points were catheters processed by sonication, clinically diagnosed EVDAI and surgical treatment of hydrocephalus. Results From October 2013 to January 2016, a total of 57 patients were randomized to receive either a CHX or a control dressing (29 and 28 patients, respectively). Cutaneous bacterial regrowth at the EVD exit wound was significantly reduced over time (geometric mean ratio, 0.18; 95% confidence interval, .08-.42; P < .001). The incidence of colonized catheters was lower in the CHX group (5 of 28; 18%) than in the control group (10 of 27; 33%), with less microbial colonization on the subcutaneous portion. The infection rate was 4 of 28 (14%) in the CHX group, compared with 7 of 27 (26%) in the control group, with a substantially lower hydrocephalus treatment rate (7 of 28 [25%] vs 14 of 27 [52%], respectively). Conclusion Our data support the use of CHX dressings to reduce EVD exit site contamination, potentially reducing EVDAIs and permanent cerebrospinal fluid diversion procedures for hydrocephalus. Clinical Trials Registration NCT02078830. This prospective, randomized controlled trial studies the effectiveness of chlorhexidine-coated dressings in reducing bacterial colonization of external ventricular drains and supports their use to reduce exit site contamination and potentially reduce infections and permanent cerebrospinal fluid diversion procedures for hydrocephalus.

Background Antimicrobial resistance (AMR) in Sub-Saharan Africa is a significant health threat, with limited data guide treatment. This study investigates multi-drug resistant Escherichia coli in urinary tract infections (UTIs) in rural Tanzania to guide empirical treatment strategies. Methods A cross-sectional prospective study of adults with UTIs was conducted at St. Francis Regional Referral Hospital in Ifakara, Tanzania, from September 2021 to August 2023. Urine culture isolates underwent routine diagnostics in Tanzania and E. coli isolates underwent whole-genome sequencing in Switzerland. Results Of 1055 patients, 248 (23.5%) had positive urine cultures, with E. coli as predominant pathogen ( n  = 87; 55.7%). Extended-spectrum beta-lactamase-producing E. coli (ESBL-E) was identified in 20 (23.0%) isolates, primarily sequence type ST167 carrying CTX-M-27. All ESBL-E cases (20/20, 100.0%) and half of non-ESBL-E cases (29/58, 50.0%) received empiric antibiotics to which the isolates were documented as resistant. ESBL-E showed higher resistance to cotrimoxazole (100.0%) and ciprofloxacin (90.0%) latter recommended for complicated UTIs in Tanzania’s Standard Treatment Guidelines (STG) compared to non-ESBL-E. All ESBL-E isolates were susceptible to nitrofurantoin, as recommended by STG for uncomplicated UTIs, and fosfomycin showed potential alternative for complicated cases. Conclusion Nearly one-quarter of E. coli isolates causing UTIs were ESBL-E, predominantly ST167 harboring bla CTX−M−27 . Notably, nitrofurantoin remained effective for uncomplicated UTIs, similarly, fosfomycin emerged as a viable alternative. However, ciprofloxacin, despite being recommended in local guidelines for complicated UTIs, showed no efficacy. The genetic similarity between human and environmental isolates underscores the critical need for a One Health approach to tackle antimicrobial resistance (AMR) in the region.

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. Retrospective cohort study. 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. 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, = .014 and OR 2.26, 95% CI 1.08-4.73, = .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. 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.

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.

Background Among people living with HIV, there has been a shift of focus from HIV-related health issues to cardiovascular diseases and cancer. For both, tobacco smoking is a major but insufficiently addressed etiological factor. Evidence from randomized trials suggests that nicotine substitute products such as e-cigarettes and nicotine patches can reduce tobacco smoking and its associated health burden. However, most previous smoking cessation trials primarily included people who are motivated to quit smoking and focused on testing a single nicotine substitute product. The effectiveness of offering a menu of nicotine substitute products to tobacco smokers regardless of their willingness to quit smoking (“opt-out” approach) is unknown. Methods Reduce tobacco use in people living with HIV in Switzerland (RETUNE, NCT06789692) is a pragmatic, 1:1 randomized, multicenter, superiority clinical trial using the Trials within Cohorts (TwiCs) design within the Swiss HIV Cohort Study. RETUNE assesses the effectiveness of offering a menu of different nicotine substitute products, namely electronic cigarettes, nicotine pouches, and nicotine patches, versus usual care. Cohort participants are eligible if they smoke more than one tobacco cigarette per day, do not use any of the substitute products, and have signed the randomization consent following the TwiCs design. Participants randomized to the intervention may choose any of the offered substitutes to be used free of charge for 6 months or decline the offer. Overall, we plan to recruit 972 participants. The primary outcome is tobacco abstinence at 6 months measured as participant-reported past 7-day prevalence abstinence. The primary outcome will be assessed in the intention-to-treat set using a logistic regression model adjusted for region, men having sex with men, current drug users, and number of cigarettes per day at baseline. Secondary outcomes are long-term smoking cessation rates and tobacco-associated health outcomes. Discussion RETUNE started recruitment in February 2025 and is currently ongoing. RETUNE using the TwiCs design will clarify the effectiveness of a preference-based opt-out smoking cessation intervention among people living with HIV. Trial registration Clinicaltrials.gov NCT06789692. Registered on January 17th, 2025. The manuscript is aligned with the registry. https://clinicaltrials.gov/study/NCT06789692?cond=NCT06789692&rank=1

Little 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. This prospective descriptive cohort study included all adults and children referred for echocardiography. Clinical and echocardiographic data were collated for analysis. From 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. Hypertension 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.

Data on rural sub-Saharan African high-dependency units (HDU) are lacking. We describe patient's characteristics, diagnoses, and outcomes of patients admitted to a Tanzanian HDU, and identified factors associated with in-hospital mortality. This prospective single-center cohort study was conducted in the HDU of a Tanzanian rural referral hospital. All patients admitted to the HDU were eligible. Descriptive analyses, and univariate and multivariate modeling to identify predictors of in-hospital mortality were done. Kaplan-Meier survival curves were employed to estimate mortality rates over time. The area under the receiver operating characteristic curve was used to assess the predictive accuracy of early warning scores. From April 4th 2023 to March 29th 2024, 491 patients were included and followed-up until hospital discharge. Median age was 46 years (IQR 29-65); 259 (53%) were females. Most common diagnoses were sepsis (N = 96, 20%), arterial hypertension (N = 91, 19%), diabetes mellitus (N = 84, 17%), acute kidney injury (N = 66, 13%), decompensated heart failure (N = 64, 13%), aspiration pneumonia (N = 60, 12%), and stroke (N = 59, 12%). Mortality during HDU- and hospital stay was 30%(N = 146) and 37%(N = 182), respectively. 54% of patients with sepsis, 51% with stroke, 65% with aspiration pneumonia and 27% with heart failure died in the HDU. Predictors of in-hospital mortality were age ≥ 45 years versus 18-44 (adjusted Hazard Ratio (aHR) 1.56, 95% CI 1.07-2.28, p = 0.03), blood pressure <90mmHg (aHR 2.33, 95%CI 1.48-3.81, p < 0.001), Glasgow Coma Scale score ≤8 versus 14-15 (aHR 2.13, 95%CI 1.24-3.64, p = 0.02) and oxygen saturation at room air < 90% (aHR 1.62, 95%CI 1.04-2.51, p = 0.03). The area under the curve predicting in-hospital mortality was 0.69 (95%CI 0.65-0.73) for the NEWS- and UVA scores, 0.66 (95%CI 0.62-0.70) for the MEWS-, and 0.65 (95%CI 0.61-0.69) for the qSOFA score. Sepsis and non-communicable diseases were the most common diagnoses. Scores predicted in-hospital mortality with a moderate accuracy.

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. 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). 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. 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.

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. 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. 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 <0.001]. Extrapulmonary tuberculosis was a frequent manifestation in this cohort of PLHIV. The diagnosis of EPTB in the absence of histopathology and mycobacterial culture remains challenging even with availability of Xpert® MTB/RIF. Patients with EPTB had increased rates of mortality and LTFU despite early recognition of the disease after enrollment.

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.