Operational Differences between Product Development Partnership, Pharmaceutical Industry, and Investigator Initiated Clinical Trials.

Medicine development is a lengthy endeavour. Increasing regulatory stringency and trial complexity might lead to reduced efficiency, dwindled output, and elevated costs. However, alternative models are possible.

Real-time OCT feedback-controlled RPE photodisruption in ex vivo porcine eyes using 8 microsecond laser pulses.

Selective retinal pigment epithelium (RPE) photodisruption requires reliable real-time feedback dosimetry (RFD) to prevent unwanted overexposure. In this study, optical coherence tomography (OCT) based RFD was investigated in ex vivo porcine eyes exposed to laser pulses of 8 µs duration (wavelength: 532 nm, exposure area: 90 × 90 µm, radiant exposure: 247 to 1975 mJ/µm). For RFD, fringe washouts in time-resolved OCT M-scans (central wavelength: 870 nm, scan rate: 85 kHz) were compared to an RPE cell viability assay.

Key Contributions by the Swiss Tropical and Public Health Institute Towards New and Better Drugs for Tropical Diseases.

Thanks to its expertise in clinical research, epidemiology, infectious diseases, microbiology, parasitology, public health, translational research and tropical medicine, coupled with deeply rooted partnerships with institutions in low- and middle-income countries (LMICs), the Swiss Tropical and Public Health Institute (Swiss TPH) has been a key contributor in many drug research and development consortia involving academia, pharma and product development partnerships. Our know-how of the maintenance of parasites and their life-cycles in the laboratory, plus our strong ties to research centres and disease control programme managers in LMICs with access to field sites and laboratories, have enabled systems for drug efficacy testing in vitro and in vivo, clinical research, and modelling to support the experimental approaches. Thus, Swiss TPH has made fundamental contributions towards the development of new drugs - and the better use of old drugs - for neglected tropical diseases and infectious diseases of poverty, such as Buruli ulcer, Chagas disease, food-borne trematodiasis (e.

Repurposing Know-how for Drug Development: Case Studies from the Swiss Tropical and Public Health Institute.

In pursuing novel therapeutic solutions, drug discovery and development rely on efficiently utilising existing knowledge and resources. Repurposing know-how, a strategy that capitalises on previously acquired information and expertise, has emerged as a powerful approach to accelerate drug discovery and development processes, often at a fraction of the costs of de novo developments. For 80 years, collaborating within a network of partnerships, the Swiss Tropical and Public Health Institute (Swiss TPH) has been working along a value chain from innovation to validation and application to combat poverty-related diseases.

Assessing caregivers' perceptions of treatment-seeking for suspected severe malaria in the Democratic Republic of the Congo.

Background: Malaria remains a major public health issue in the Democratic Republic of the Congo (DRC), accounting for 44% deaths among outpatient visits in children < 5 years of age, and 22% of facility deaths. Understanding determinants of caregivers' treatment-seeking patterns and decision-making is crucial in reducing the malaria burden.

Methods: In the frame of the Community Access to Rectal Artesunate for Malaria (CARAMAL) project, cross-sectional household surveys that randomly sampled villages and households were carried-out in three rural DRC health zones prior to the rollout of pre-referral Rectal Artesunate (RAS) and then 9 and 19 months after RAS rollout (post-RAS).

Opportunities and challenges for decentralised clinical trials in sub-Saharan Africa: a qualitative study.

Introduction: Digital health has gained traction in research and development, and clinical decision support systems. The COVID-19 pandemic accelerated the adoption of decentralised clinical trials (DCTs) as a mitigation and efficiency improvement strategy. We assessed the opportunities and challenges of a digital transformation in clinical research in sub-Saharan Africa from different stakeholders' perspectives.

Strategies and interventions to strengthen pharmacovigilance systems in low-income and middle-income countries: a scoping review.

Objectives: The slow progress of pharmacovigilance (PV) in low-income and middle-income countries (LMIC) raises questions about core challenges on the growth of PV, and the appropriateness of strategies used so far to develop PV. Therefore, this scoping review aims to describe strategies and interventions to strengthen PV in LMIC and to propose recommendations for future investments in PV capacity building.

Inclusion Criteria: Publications included were primary studies, articles, policy and guideline papers, describing interventions to strengthen PV in LMIC.

Starting at the community: Treatment-seeking pathways of children with suspected severe malaria in Uganda.

Community health workers (CHW) usually refer children with suspected severe malaria to the nearest public health facility or a designated public referral health facility (RHF). Caregivers do not always follow this recommendation. This study aimed at identifying post-referral treatment-seeking pathways that lead to appropriate antimalarial treatment for children less than five years with suspected severe malaria.

Investigation of the Influence of Pulse Duration and Application Mode on Microsecond Laser Microsurgery of the Retinal Pigment Epithelium.

Optical microsurgery confined to the retinal pigment epithelium (RPE) requires locally optimized laser parameters and reliable real-time feedback dosimetry (RFD) to prevent unwanted neuroretinal overexposure. This study aimed to compare pulses of different durations and application modes (single, ramp, burst). Moreover, optical coherence tomography (OCT)-based RFD was investigated in an ex vivo experiment, utilizing nine porcine eyes that were exposed to laser pulses of 8, 12, 16 and 20 µs duration (wavelength: 532 nm, exposure area: 90 × 90 µm, radiant exposure: 247 to 1975 mJ/µm).

High-Precision Optical Coherence Tomography Navigated Laser Retinopexy for Retinal Breaks.

The prevalent cause of retinal detachment is a full-thickness retinal break and the ingress of fluid into the subretinal space. To prevent progression of the detachment, laser photocoagulation (LPC) lesions are placed around the break in clinical practice to seal the tissue. Unlike the usual application under indirect ophthalmoscopy, we developed a semi-automatic treatment planning software based on a sequence of optical coherence tomography (OCT) scans to perform navigated LPC treatment.

Feasibility and Acceptability of a Strategy Deploying Multiple First-Line Artemisinin-Based Combination Therapies for Uncomplicated Malaria in the Health District of Kaya, Burkina Faso.

(1) Background: Effective malaria case management relies on World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs), but partial resistance to artemisinin has emerged and is spreading, threatening malaria control and elimination efforts. The strategy of deploying multiple first-line therapies (MFT) may help mitigate this threat and extend the therapeutic life of current ACTs. (2) Methods: A district-wide pilot quasi-experimental study was conducted, deploying three different ACTs at the public health facility (PHF) level for uncomplicated malaria treatment from December 2019 to December 2020 in the health district (HD) of Kaya, Burkina Faso.

Correction: Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

[This corrects the article DOI: 10.1371/journal.pmed.

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

Background: For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years.

Methods And Findings: This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020.

Health system readiness and the implementation of rectal artesunate for severe malaria in sub-Saharan Africa: an analysis of real-world costs and constraints.

Background: Rectal artesunate, an efficacious pre-referral treatment for severe malaria in children, was deployed at scale in Uganda, Nigeria, and DR Congo. In addition to distributing rectal artesunate, implementation required additional investments in crucial but neglected components in the care for severe malaria. We examined the real-world costs and constraints to rectal artesunate implementation.

Acceptability of pre-referral rectal artesunate for severe malaria in children under 5 years by health workers and caregivers in the Democratic Republic of the Congo, Nigeria and Uganda.

Background: For children below 6 years with suspected severe malaria attending a health care provider unable to provide parenteral malaria treatment, pre-referral rectal artesunate (RAS) is recommended by the World Health Organization to prevent death and disability. A number of African countries are in the process of rolling out quality-assured RAS for pre-referral treatment of severe malaria at community-level. The success of RAS depends, among other factors, on the acceptability of RAS in the communities where it is being rolled-out.

Fexinidazole for Human African Trypanosomiasis, the Fruit of a Successful Public-Private Partnership.

After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenges of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules.

Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study.

Background: To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay.

Key factors predicting suspected severe malaria case management and health outcomes: an operational study in the Democratic Republic of the Congo.

Background: Evidence suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings in Africa. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management.

Methods: This was an observational study conducted in three Health Zones of the Democratic Republic of the Congo to determine the distribution of dangers signs for severe malaria and assess their impact on RAS use, referral completion, injectable treatment and ACT provision, and health outcomes including death.

Examining African contributions to global health: Reflections on knowledge circulation and innovation.

This article unites different disciplinary debates on 'southern innovation', 'theory from the South', and 'decolonisation of knowledge' in order to discuss existing understandings around the role of Africa in the production of health-related knowledge, public health policy, and medical innovation. Arguing that high-income countries have much to learn from the global South when it comes to health-related knowledge and practices, we propose an interdisciplinary research approach to uncovering and examining African contributions to global health, drawing on an ongoing collaborative project funded by the Swiss National Science Foundation. We present four empirical case studies concerning drug development, healthcare systems, and urban planning to critically enquire into both historical and contemporary transcontinental knowledge circulation and learning potentials, as much as cases of forgetting and silencing.

Care Seeking and Treatment of Febrile Children with and without Danger Signs of Severe Disease in Northern Uganda: Results from Three Household Surveys (2018-2020).

Identification, stabilization, and prompt referral of children with signs of severe febrile disease (danger signs) in rural communities are crucial for preventing complications and death from severe malaria, pneumonia, and diarrhea. We set out to determine the treatment-seeking practices and treatment patterns for children < 5 years of age with an acute febrile illness, with or without danger signs of severe disease, in a highly malaria-endemic area of northern Uganda. Three household surveys were conducted from November through December each year in 2018, 2019, and 2020.

Determinants of Patients' Adherence to Malaria Treatment in the Democratic Republic of the Congo.

(1) Background: Malaria heavily affects the Democratic Republic of the Congo (DRC) despite the use of effective drugs. Poor adherence to malaria treatment may contribute to this problem. (2) Methods: In one rural and one urban health area in each of the 11 former provinces of the DRC, all households with a case of malaria in the 15 days preceding the survey were selected and the patients or caregivers were interviewed.