Bedaquiline, classified as a WHO 2019 group A drug, is a core component of BPaLM, revolutionizing the treatment of MDR/RR tuberculosis (TB). Since 2015, however, concerns about acquired and primary bedaquiline resistance have emerged. We report a diagnostically challenging case of a young asylum seeker from Afghanistan, previously treated for pulmonary TB with standard therapy for five months about four years earlier. After arriving in Switzerland, he presented with chronic dry cough, weight loss, and small upper-lobe nodular lesions. Rifampicin mono-resistant pulmonary TB was diagnosed, and BPaLM was initiated. Five weeks later, phenotypic antimicrobial susceptibility testing showed bedaquiline/clofazimine resistance. Next-generation sequencing revealed an IS6110 insertion in mmpR5. The patient had never received bedaquiline. An individualized regimen with pretomanid, linezolid, moxifloxacin, isoniazid, and pyrazinamide led to clinical and radiological improvement. Treatment was stopped after 9 months, with outcome classified as completed (not cured due to absent sputum production). The patient remains well 1.5 years after treatment completion. This case highlights the diagnostic and therapeutic challenges of primary bedaquiline resistance. Faster, reliable phenotypic and genotypic diagnostic methods, along with clear treatment recommendations, are urgently needed to identify bedaquiline-resistant patients promptly, treat them appropriately, and preserve the effectiveness of the BPaLM regimen.

Highlight: Schistosoma species may show extraordinary longevity, despite not replicating in human hosts. We present a case of active Schistosoma mansoni infection in a Swiss patient 41 years after her one and only possible exposure (swimming in Lake Kivu, Rwanda).

Objectives:To analyze weight changes associated with dolutegravir- versus efavirenz-based antiretroviral therapy (ART) in people with HIV (PWH) in rural Tanzania, where undernutrition is prevalent. Design:Longitudinal, observational study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Methods:We included adult, ART-na & iuml;ve, nonpregnant PWH initiating efavirenz-based ART 12/2016-02/2019 or dolutegravir-based ART 03/2019-12/2022. We used multivariable linear mixed-effects models to assess adjusted weight changes during 18 months after ART start and Cox regression models to assess factors associated with incident obesity, weight gain >= 10% and hypertension. Results:Of 1205 PWH at ART start [median age 40 years (interquartile range (IQR) 32-48); 719 (59.7%) females], 166 (13.8%) individuals were underweight and 317 (26.3%) overweight/obese; 621 (51.5%) initiated efavirenz-based and 584 (48.5%) dolutegravir-based ART. After 18 months, estimated weight gain was 5.1 kg [95% confidence interval (CI) 4.7-5.5] in the dolutegravir versus 4.0 kg (95% CI 3.7-4.4) in the efavirenz group. The weight gain difference between treatment groups was high in men (1.7 kg (95% CI 0.8-2.6; P < 0.001)), in those aged 30-49 years (1.5 kg (0.8-2.1); P < 0.001) and those with CD4+ cell count >= 500/ul (2.5 kg (1.4-3.7), P < 0.001)). Cumulative obesity incidence at 18 months was 10.9% (95% CI 8.3-14.0) in the dolutegravir and 5.1% (95% CI 3.6-7.1) in the efavirenz group. Associated factors were dolutegravir and a pre-ART body mass index (BMI) of 25-29 kg/m2. Dolutegravir and age, but not weight gain were associated with incident of hypertension. Conclusions:Dolutegravir-based ART was associated with more weight gain, higher obesity and hypertension - especially in those with a higher pre-ART BMI compared to efavirenz-based regimens.

Global HIV incidence remains high, particularly in sub-Saharan Africa. Pre-Exposure Prophylaxis (PrEP) prevents HIV transmission in serodifferent couples until the partner with HIV achieves viral suppression on antiretroviral treatment (ART). This study assessed awareness, uptake, and feasibility of a short, 4 month PrEP course alongside the roll-out of dolutegravir-based ART in rural Tanzania. We included serodifferent couples (≥ 15 years), of whom the partner with HIV enrolled in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) and initiated ART between September 2020 and September 2021. Partners without HIV with normal kidney function (eGFR > 60 ml/min) and negative HbsAg were offered PrEP. Both partners completed questionnaires on sexual behavior and adherence. Partners without HIV were tested monthly for HIV. Couples were followed until the partner living with HIV achieved viral suppression (< 200 copies/ml). Among 346 people newly diagnosed with HIV, 184 (53%) reported a sexual partner, 97 (53%) partners were tested and 40 (41%) were HIV negative. PrEP awareness was low (9%). Of 37 eligible seronegative partners, 22 (59%) initiated PrEP, and 9 (41%) completed follow-up. No serious adverse events or HIV seroconversions occurred. 21/22 (96%) of PWH were virally suppressed after 3 months. In our study, partner testing, acceptance and PrEP uptake were low. A 4-month course of PrEP was safe and effectively prevented HIV transmission. These findings highlight gaps in the PrEP care cascade in rural sub-Sahara Africa. Lack of awareness and disclosure of HIV status remain significant barriers to PrEP uptake and HIV prevention among serodifferent couples.

An der Jahresversammlung der Schweizerischen Gesellschaft für Infektiologie 2022 gaben junge Infektiologinnen und Infektiologen einen kurzen Überblick über die aus ihrer Sicht wichtigsten Themen 2022 im Bereich der Infektiologie.

Introduction In 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. Methods We 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 (<7.0 g/dl) anaemia at any visit from January 2019 to December 2020. For each participant, ten PBS images, full blood count and clinical details were shared with a haematologist for remote interpretation (enhanced care). Identification of anaemia etiologies and potential impact on treatment was compared between enhanced and standard care. Results Among 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 <18.5 kg/m 2 , 215 (54%) had HIV WHO stage III/IV, 79 (20%) had a CD4 cell count <200 cells/μl and 317 (89%) had HIV viral load <100 copies/ml. Severe anaemia was diagnosed in 84 (21%). Suspected multiple aetiologies were documented more frequently by enhanced care compared to standard care 267 (67%) vs 20 (5%); p<0.001. Suspected iron deficiency was the most frequent aetiology (n = 337; 84%), followed by chronic disease (n = 199; 50%), folate/vitamin B12 deficiency (n = 78; 20%) and haemoglobinopathy (n = 83; 21%). In 272 participants (68%), enhanced care revealed additional clinically relevant findings with impact on the treatment recommendation. Conclusion Remote 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.

À l’occasion de l’assemblée annuelle 2022 de la Société Suisse d’Infectiologie, de jeunes infectiologues ont donné un bref aperçu des thèmes les plus importants à leurs yeux en 2022 dans le domaine de l’infectiologie.

Abstract Background Virological outcome data after programmatic transition from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir (DTG)-based antiretroviral therapy (ART) regimens in sub-Saharan Africa (SSA) outside of clinical trials are scarce. We compared viral suppression and associated factors in treatment-naïve people living with HIV (PLHIV) starting DTG- based versus NNRTI-based ART. Methods We compared virological suppression at 12 months, after treatment initiation in the two cohorts of participants aged ≥15 years, initiating DTG- and NNRTI-based ART. Drug resistance was assessed among participants with viremia ≥50 copies/mL on DTG. Results Viral suppression was achieved for 165/195 (85%) and 154/211 (73%) participants in the DTG- and NNRTI- cohorts, respectively (P = 0.003). DTG-based ART was associated with >2 times the odds of viral suppression versus NNRTI-based ART (adjusted odds ratio, 2.10 [95% confidence interval {CI}, 1.12–3.94]; adjusted risk ratio, 1.11 [95% CI, 1.00–1.24]). HIV-1 genotypic resistance testing (GRT) before ART initiation was done in 14 of 30 viremic participants on DTG, among whom nucleoside reverse transcriptase inhibitor (NRTI), NNRTI, and protease inhibitors resistance was detected in 0 (0%), 2 (14%) and 1 (7%), respectively. No resistance was found in the 2 of 30 participants with available GRT at the time of viremia ≥50 copies/mL. Conclusions Virological suppression at 1 year was higher in participants initiating DTG- versus NNRTI-based ART. In those with viremia ≥50 copies/mL on DTG-based ART, there was no pretreatment or acquired resistance to the DTG co-administered NRTIs, although the number of samples tested was small.

Background: HIV-related stigma is a major barrier to the timely linkage and retention of patients in HIV care in sub-Saharan Africa, where most people living with HIV/AIDS reside. In this implementation study we aim to evaluate the effect of stigma-directed services on linkage to care and other health outcomes in newly diagnosed HIV-positive patients. Methods: In a nested project of the Kilombero and Ulanga Antiretroviral Cohort in rural Tanzania, we conduct a prospective observational pre-post study to assess the impact of a bundle of stigma-directed services for newly diagnosed HIV positive patients. Stigma-directed services, delivered by a lay person living with HIV, are i) post-test counseling, ii) post-test video-assisted teaching, iii) group support therapy and group health education, and iv) mobile health. Patients receiving stigma services (enrolled from 1st February 2020 to 31st August 2021) are compared to a historical control receiving the standard of care (enrolled from 1st July 2017 to 1st February 2019). The primary outcome is ‘linkage to care’. Secondary endpoints are retention in care, viral suppression, death and clinical failure at 6-12 months (up to 31st August 2022). Self-reported stigma and depression are assessed using the Berger Stigma scale and the PHQ-9 questionnaire, respectively. The sample size calculation was based on cohort data from 2018. Assuming a pre-intervention cohort of 511 newly diagnosed adults of whom 346 (68%) were in care and on antiretroviral treatment (ART) at 2 months, a 10% increase in linkage (from 70 to 80%), a two-sided type I error rate of 5%, and 90% power, 321 adults are required for the post-implementation group. Discussion: We expect that integration of stigma-directed services leads to an increase of proportions of patients in care and on ART. The findings will provide guidance on how to integrate stigma-directed services into routine care in rural sub-Saharan Africa.

Background: HIV-related stigma is a major barrier to the timely linkage and retention of patients in HIV care in sub-Saharan Africa, where most people living with HIV/AIDS reside. In this implementation study we aim to evaluate the effect of stigma-directed services on linkage to care and other health outcomes in newly diagnosed HIV-positive patients. Methods: In a nested project of the Kilombero and Ulanga Antiretroviral Cohort in rural Tanzania, we conduct a prospective observational pre-post study to assess the impact of a bundle of stigma-directed services for newly diagnosed HIV positive patients. Stigma-directed services, delivered by a lay person living with HIV, are i) post-test counseling, ii) post-test video-assisted teaching, iii) group support therapy and group health education, and iv) mobile health. Patients receiving stigma services (enrolled from 1st February 2020 to 31st August 2021) are compared to a historical control receiving the standard of care (enrolled from 1st July 2017 to 1st February 2019). The primary outcome is ‘linkage to care’. Secondary endpoints are retention in care, viral suppression, death and clinical failure at 6-12 months (up to 31st August 2022). Self-reported stigma and depression are assessed using the Berger Stigma scale and the PHQ-9 questionnaire, respectively. The sample size calculation was based on cohort data from 2018. Assuming a pre-intervention cohort of 511 newly diagnosed adults of whom 346 (68%) were in care and on antiretroviral treatment (ART) at 2 months, a 10% increase in linkage (from 70 to 80%), a two-sided type I error rate of 5%, and 90% power, 321 adults are required for the post-implementation group. Discussion: We expect that integration of stigma-directed services leads to an increase of proportions of patients in care and on ART. The findings will provide guidance on how to integrate stigma-directed services into routine care in rural sub-Saharan Africa.

Zusammenfassung. In den vergangenen 15 Jahren hat sich die HIV-Epidemie in Subsahara-Afrika durch den verbesserten Zugang zu HIV-Tests und antiretroviralen Medikamenten deutlich verändert. Die Zahl der jährlichen Neuinfektionen ist seit 2005 stark rückläufig, die Lebenserwartung von Menschen mit HIV ist gestiegen und die Anzahl der jährlichen Todesfälle ist gesunken. Allerdings haben Frauen weiterhin ein ungleich hohes Risiko, sich anzustecken, und Stigma und Diskriminierung erschweren das Senken der Infektionsraten. Herausforderungen wie der Mangel an adäquater technischer Ausstattung vor allem zum Bestimmen der Viruslast, Skepsis gegenüber Tests und Gebrauch von mechanischer Verhütung sowie Zunahme der Resistenzen gegen die Erstlinientherapie stehen dem Ende der Epidemie im Weg. Dennoch schaffen neue Teststrategien und Therapien mit höherer Effektivität, die – wenn zuverlässig eingenommen – die Virus-Übertragung verhindern, neue Hoffnung im Kampf gegen das Virus.

HIV in Sub-Saharan Africa: Where Are We Today? In sub-Saharan Africa the HIV epidemic has changed remarkedly due to expanded testing and easier access to antiretroviral medication. The rate of new infections has decreased substantially since 2005, the life expectancy of people living with HIV has increased and the mortality rate has declined. Yet still a lot needs to be achieved to stop the ongoing epidemic. Women are still at a higher risk to get infected and stigma and discrimination are a hindrance to further reduce the incidence. Challenges like the lack of technical capacities, especially to perform viral load and resistance testing, refusal of testing or condom use and increasing drug resistance to first-line therapies jeopardize the goal of 90-90-90: 90 % of people tested, 90 % of positives under care and 90 % of treated persons virologically controlled. New testing strategies and medication with higher efficacies which, when taken regularly, stop the transmission completely, provide hope in the fight against HIV.

Visceral leishmaniasis (VL) is a protozoan disease, which is responsible for 200.000–400.000 yearly infections worldwide. If left untreated, the fatality rate can be as high as 100% within 2 years. 90% of cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. It is thus a disease rarely seen by physicians in Europe or North America. We report on the fatal case of VL in an 80-year-old immunosuppressed patient who presented with a latency of over 15 years after having visited an endemic region. This is the first report showing such extreme latency of VL in a European traveller. This case is furthermore unusual because it suggests primary treatment failure to liposomal amphotericin B.