Jennifer Keiser

Swiss Tropical and Public Health Institute | Swiss TPH · Department of Epidemiology and Public Health

Albendazole/ivermectin combination therapy is a promising alternative to benzimidazole monotherapy alone for Trichuris trichiura control. We used fecal DNA metabarcoding to genetically characterize Trichuris spp. populations in patient samples from Côte d'Ivoire showing lower (egg reduction rate <70%) albendazole/ivermectin sensitivity than those f...

This study explores the synthesis and evaluation of novel 1,2,3‐triazole‐methyl‐1,4‐naphthoquinone hybrids, focusing on their electrochemical properties and antiparasitic efficacies against two human blood‐dwelling parasites Plasmodium falciparum and Schistosoma mansoni. Using copper‐catalyzed azide‐alkyne cycloaddition (CuAAC), a well‐established...

Trichuris trichiura, a soil-transmitted helminth (STH), often persists after a single dose of anthelminthic treatment. To overcome limited efficacy against T. trichiura of benzimidazoles (albendazole or mebendazole), the primary drugs used in mass drug administration (MDA) campaigns, the World Health Organization endorses the use of a combination o...

Due to their broad-spectrum activities, ivermectin and moxidectin are widely used anthelminthics in veterinary and human medicine. However, ivermectin has recently been shown to perturbate bacterial growth. Given the macrolide-like structure of both ivermectin and moxidectin, there is a need to characterize the antibiotic spectrum of these anthelmi...

Background Schistosomes are highly efficient evaders of human immunity, as evident by their ability to survive in human blood for years. How they protect themselves against the constant attack by a key element of innate immunity, the complement system, has remained unclear. In this study, new light is shed on the interaction between distinct life-c...

Ψ-1,4-naphthoquinones (Ψ-NQ) are non-quinoid compounds in which aromaticity—found in 1,4-naphthoquinones—is broken by the introduction of an angular methyl at C-4a or -8a. This series was designed to act as prodrugs of 1,4-naphthoquinones in an oxidative environment. Furthermore, from a medicinal chemistry point of view, the loss of planarity of th...

The efficacy of the combination therapy of albendazole and ivermectin against Trichuris trichiura infection is higher in Tanzania than in Côte d'Ivoire. This study therefore aimed to investigate the difference between the population pharmacokinetics (PK) at these study sites and to determine if an exposure-response analysis could explain the low ef...

Aryl hydantoins were identified in the early 1980s as a promising antischistosomal chemotype. However, as exemplified by Ro 13-3978, this compound series produced antiandrogenic side effects on the host, a not unexpected outcome given their structural similarity to the antiandrogenic drug nilutamide. The two key advances in our optimization of Ro 1...

Trichuris trichiura is one of four soil-transmitted helminth species that, collectively, are responsible for a considerable public health burden. The World Health Organization recommends preventive chemotherapy as the main intervention to eliminate soil-transmitted helminthiasis as a public health problem. Clinical trials estimated the efficacy of...

Due to recent improvements, Nanopore sequencing has become a promising method for experiments relying on amplicon sequencing. We describe a flexible workflow to generate and annotate high-quality, full-length 16S rDNA amplicons. We evaluated it for two applications, namely, (i) identification of bacterial isolates and (ii) species-level profiling o...

Soil-transmitted helminthiases (STH), including trichuriasis, pose a significant global burden, affecting numerous mammalian hosts. Traditional diagnostic methods have struggled to differentiate species within the Trichuris genus, prompting the use of molecular techniques to understand the diversity and zoonotic transmission of Trichuris spp. among...

Trichuriasis caused by the human whipworm Trichuris trichiura poses a significant public health concern. Albendazole-ivermectin co-medication is currently the most effective treatment. Studies conducted in Tanzania and Côte d’Ivoire unveiled differences in efficacy for albendazole-ivermectin combination therapy in both countries. A pharmacometrics...

Albendazole-ivermectin combination therapy is a promising alternative to benzimidazole monotherapy for Trichuris trichiura control. We used fecal DNA metabarcoding to genetically characterize Trichuris populations in patients from a clinical trial showing lower albendazole-ivermectin efficacy in C&ocircte d'Ivoire (ERR below 70%) than in Lao PDR an...

Trichuriasis is a neglected tropical disease that affects as many as 500 million individuals and can cause significant morbidity, even death. For decades, it is thought to be caused by one species of whipworm, Trichuris trichiura . Discrepancies in response rates to benzimidazole treatment for trichuriasis exist across clinical trial reports, and t...

Background We aimed to gain insights into the role of known single nucleotide polymorphisms (SNPs) in codons 167, 198 and 200 of the ß-tubulin gene as markers for possible benzimidazole resistance in human soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura , Necator americanus and Ancylostsoma duodenale ). Methods Firstly,...

To investigate the physicochemical properties of anti-schistosomal compounds reported between 2008 and 2023, a simple but extensive literature scrutiny was conducted. Keywords were searched in Chemical Abstracts Service (CAS) SciFinder and primary medicinal chemistry and pharmacology literature to locate publications with compounds displaying ex vi...

Introduction: Due to recent improvements, Nanopore sequencing has become a promising method for experiments relying on amplicon sequencing. We describe a flexible workflow to generate and annotate high-quality, full-length 16S rDNA amplicons. We evaluated it for two applications, namely, i) identification of bacterial isolates and ii) species-level...

Background Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The c...

Background. Schistosomiasis is caused by parasitic flatworms and the disease is endemic to most countries in sub-Saharan Africa including Ghana. The current therapeutic agent for managing this disease solely relies on praziquantel. The continual dependence on this single available drug could lead to possible drug resistance. This study seeks to eva...

Background Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infe...

Within the context of our anthelmintic discovery program, we recently identified and evaluated a quinoline derivative, called ABX464 or obefazimod, as a nematocidal candidate; synthesised a series of analogues which were assessed for activity against the free-living nematode Caenorhabditis elegans; and predicted compound-target relationships by the...

Due to their broad-spectrum activities, ivermectin and moxidectin are widely used anthelminthics in veterinary and human medicine. However, ivermectin has recently been shown to perturbate gut-microbial growth. Given the macrolide-like structure of both ivermectin and moxidectin, there is a need to characterize the antibiotic spectrum of these anth...

Spirorchiidosis, caused by blood flukes of the genus Spirorchis, is a disease of great concern for the critically endangered European pond turtle (EPT; Emys orbicularis) in Switzerland. The endogenous life cycle of the parasite often leads to systemic inflammatory reactions, thrombosis, and death. Praziquantel (PZQ) is the treatment of choice again...

Clonorchis sinensis , Opisthorchis viverrini , and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cu...

Trichuriasis is a neglected tropical disease widely distributed among tropical and sub-tropical areas and associated with poverty and lack of access to safe drinking water, sanitation and hygiene. Existing drugs have limited efficacy and face a constant risk of developing resistance, necessitating the search for alternative treatments. However, dru...

In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely praziquantel (PZQ) and niclosamide (NCM) in a 1:3 molar ratio, and it can be obtained through a sustainable one-step mechanochemical process in the presence of micromolar amounts of me...

Malaria and schistosomiasis are two of the neglected tropical diseases that persistently wreak havoc worldwide. Although many antimalarial drugs such as chloroquine are readily available, the emergence of drug resistance necessitates the development of new therapies to combat this disease. Conversely, Praziquantel (PZQ) remains the sole effective d...

Background: The currently recommended benzimidazole monotherapy is insufficiently effective to control infection with the soil-transmitted helminth Trichuris trichiura. Ivermectin-albendazole combination has shown promising, but setting-dependent efficacy, with therapeutic underperformance in Côte d'Ivoire. We evaluated whether moxidectin-albendaz...

Praziquantel (PZQ) is an essential anthelmintic drug recently established to be an activator of a Transient Receptor Potential Melastatin (TRPMPZQ) ion channel in trematode worms. Bioinformatic, mutagenesis and drug metabolism work indicate that the cyclohexyl ring of PZQ is a key pharmacophore for activation of trematode TRPMPZQ, as well as servin...

Ethnopharmacological relevance: Schistosomiasis (bilharzia) is an important, prevalent and neglected tropical disease for which new treatments are urgently required. In the DR Congo and other sub- and tropical countries, traditional medicines are widely used for the control of schistosomiasis. Aim of study: To evaluate 43 Congolese plant species...

Background: Current treatments for soil-transmitted helminth infections in humans have low efficacy against Trichuris trichiura. Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection. Methods: We conducted two phase 2a...

Background Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in sto...

Background Few anthelminthics are currently available, manifesting the urgent need for new treatment options. In vitro profiling of current anthelminthics against larval and adult stage helminths displayed varying effects on closely related worm species and between life stages of the same species. Conversely, limited research has been performed on...

Malnutrition and parasitic infections are often interconnected in a vicious cycle. Malnutrition can lead to changes in immune response, which may affect cytokine concentrations and potentially increase susceptibility to infections. In turn, parasitic infections can exacerbate malnutrition by impairing nutrient absorption. This cross-sectional study...

Praziquantel (PZQ) is a chiral class-II drug, and it is used as a racemate for the treatment of schistosomiasis. The knowledge of several cocrystals with dicarboxylic acids has prompted the realization of solid solutions of PZQ with both enantiomers of malic acid and tartaric acid. Here, the solid form landscape of such a six-component system has b...

Praziquantel, the only drug in clinical use for the treatment and control of schistosomiasis, is inactive against developing infections. Ozonides are synthetic peroxide derivatives inspired by the naturally occurring artemisinin and show particularly promising activity against juvenile schistosomes. We conducted an in-depth characterization of the...

The Front Cover shows how Neglected Tropical Diseases including schistosomiasis don′t have effective strategies to fight the parasite infection. Only a few drugs for treating such diseases display selectivity against parasites over humans, and only some of them exhibit activity against all the parasite stages of life. In schistosomiasis, for exampl...

Ivermectin and moxidectin, two macrocyclic lactones, are potent antiparasitic drugs currently registered and mainly used against filarial diseases; however, their potential value for improved soil-transmitted helminth (STH) control has been acknowledged. This review provides insights on recent studies evaluating the efficacy of ivermectin and moxid...

Background: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in st...

[This corrects the article DOI: 10.1371/journal.pntd.0009144.].

Schistosomiasis infections continue to impact African settings disproportionately, and there is an urgent need for novel tools to evaluate infection control and elimination strategies at the community level. Mobile phone microscopes are portable and semiautomated devices with multiple applications for screening neglected tropical diseases. In a com...

Schistosoma mansoni HDAC8 is a reliable target to fight schistosomiasis, and several inhibitors have been reported in the literature up to now. Nevertheless, only a few displayed selectivity over the human deacetylases and some exhibited very low or no activity against parasite larvae and/or adult worms. We report here the in vitro enzyme and biolo...

Schistosomiasis and soil-transmitted helminths are some of the priority neglected tropical diseases (NTDs) targeted for elimination by the World Health Organization (WHO). They are prevalent in Botswana and although Botswana has begun mass drug administration with the hope of eliminating soil-transmitted helminths as a public health problem, the pr...

Parasitic roundworms (nematodes) cause destructive diseases, and immense suffering in humans and other animals around the world. The control of these parasites relies heavily on anthelmintic therapy, but treatment failures and resistance to these drugs are widespread. As efforts to develop vaccines against parasitic nematodes have been largely unsu...

Background Hookworm infections, caused by Ancylostoma duodenale and Necator americanus, are of considerable public health importance. The World Health Organization recommends preventive chemotherapy as the key strategy for morbidity control. Meta-analyses have been conducted to estimate treatment efficacy of available drugs and drug combinations. H...

Background Control efforts against soil-transmitted helminths focus on preventive chemotherapy with albendazole and mebendazole, however these drugs yield unsatisfactory results against Trichuris trichiura infections. We aimed to assess the efficacy and safety of moxidectin and albendazole compared with ivermectin and albendazole against T trichiur...

Background: Despite efforts to control neglected tropical diseases (NTDs) using preventive chemotherapy (PC), soil-transmitted helminthiases and schistosomiasis remain widely prevalent in sub-Saharan Africa. The current PC regimen in endemic settings is defined based on health district-level prevalence. This work aims to highlight the need for hig...

Parasites use different strategies of communication with their hosts. One communication channel that has been studied in recent years is the use of vesicle microRNAs to influence the host immune system by trematodes. sma-microRNA-10, secreted from Schistosoma mansoni, has been shown to influence the fate of host T-cells through manipulation of the...

Opisthorchiasis due to the liver fluke Opisthorchis felineus is highly prevalent in rural regions of Western Siberia, causing severe liver and bile duct maladies. Praziquantel administered as a three-dose regimen is the only drug used to treat O. felineus -infected individuals. A simpler single-dose treatment might serve as an alternative. The aim...

Schistosomiasis is a prevalent yet neglected tropical parasitic disease caused by the Schistosoma genus of blood flukes. Praziquantel is the only currently available treatment, hence drug resistance poses a major threat. Recently, histone deacetylase 8 (HDAC8) selective inhibitors have been proposed as a viable treatment for schistosomiasis. Herein...

“We report a first example of a metal‐free, visible‐light‐induced atom economical and sustainable two‐step domino process, employing an organic dye (fluorescein) as a photosensitizer to obtain tetrahydroisoquinoline‐butenolides with good to high yields (up to 97 %). Furthermore, we show that a simple thiourea additive can significantly improve the...

Background Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control...

The Front Cover illustrates a new efficient metal‐free visible‐light‐driven two‐step (aerobic amine oxidation/vinylogous Mannich) domino reaction. The combination of fluorescein as a cheap organic photosensitizer and thiourea as a simple additive allows a cost‐effective, straightforward, and waste reducing access to a broad scope of bioactive tetra...

Background Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is crucial for maintaining control of these parasitic infections. Methods For this purpose, the aim of the present study was to evaluate the potential anthelmintic activit...

Schistosomiasis is a poverty-associated tropical disease caused by blood dwelling trematodes that threaten approximately 10% of the world population. Praziquantel, the sole drug currently available for treatment, is insufficient to eliminate the disease and the clinical drug development pipeline is empty. Here, we review the characteristics of the...

Neglected tropical diseases (NTDs), including trypanosomiasis, leishmaniasis, and schistosomiasis, result in a significant burden in terms of morbidity and mortality worldwide every year. Current antiparasitic drugs suffer from several limitations such as toxicity, no efficacy toward all of the forms of the parasites’ life cycle, and/or induction o...

Background Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are the three most important human liver fluke species in the Opisthorchiidae family, infecting approximately 25 million people worldwide. Drug treatment is needed to control morbidity and is also useful in lowering transmission. Several drugs used in various regimens...

The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus Schistosoma, except Praziquantel (PZQ), urged to find new alternatives to fight this infection. Carbonic Anhydrase from Schistosoma mansoni (SmCA) is a possible new target against this nematode. Here, we propose new PZQ...

An efficient metal‐free visible‐light‐driven two‐step domino reaction towards new bioactive tetrahydroisoquinoline‐butenolide hybrid compounds was developed for the first time. The combination of fluorescein as photosensitizer and thiourea as an additive was found to be the most effective way to promote an aerobic amine oxidation/vinylogous Mannich...