Basel, Switzerland

The Swiss Tropical and Public Health Institute or Swiss TPH, was founded in 1943 as through the initiative of Professor Rudolf Geigy. He recognised the need to combine sound interdisciplinary research within the context of the social and cultural conditions of an endemic area with training and service provision. He felt that this approach would generate new evidence as well as contribute to health development. Since then, this goal remains the mandate of the Swiss TPH - to contribute to the improvement of the health of populations internationally and nationally through excellence in research, services, and teaching and training with a special focus on developing countries.The Swiss TPH consists of five departments working in various disciplines of International Public Health. In June 2009, the Institute for Social and Preventive Medicine of the University of Basel was integrated into the Swiss Tropical Institute, and in January 2010 the Swiss Tropical Institute changed its name to the Swiss Tropical and Public Health Institute.The Swiss TPH is an Associated Institute of the University of Basel, and as a public organization, is partially supported by the Swiss Federal Council and the Canton of Basel-Stadt. The greater part of its funding comes from competitively acquired project funds and the earnings of its service departments: Medical Services, Medicines Research and the Swiss Centre for International Health. Wikipedia.

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Maheu-Giroux M.,Swiss Tropical and Public Health Institute
AIDS | Year: 2017

OBJECTIVE:: To estimate time from HIV infection to linkage-to-care and its determinants. Linkage-to-care is usually assessed using the date of HIV diagnosis as the starting point for exposure time. However, timing of diagnosis is likely endogenous to linkage, leading to bias in linkage estimation. DESIGN:: We used longitudinal serosurveys from a large population-based HIV cohort in KwaZulu-Natal (2004–2013) to estimate time of HIV infection. We linked this data to patient records from a public-sector HIV treatment and care program to determine time from infection to linkage (defined using the date of the first CD4 count). METHODS:: We used Cox proportional-hazards models to estimate time from infection to linkage and the effects of the following covariates on this time: gender, age, education, food security, socio-economic status, area of residence, distance to clinics, knowledge of HIV status, and whether other household members have initiated ART. RESULTS:: We estimated that it would take an average of 4.9 years for 50% of seroconverters to be linked to care (95% confidence intervals (CI): 4.2–5.7). Among all cohort members that were linked to care, the median CD4 count at linkage was 350?cells/μL (95%CI: 330–380). Men and participants?

University of Dundee, Medivir Ab, Consejo Superior De Investigaciones Cientificas, Swiss Tropical, Public Health Institute and SYNGENE INTERNATIONAL Ltd PLC | Date: 2015-06-09

The invention provides compounds of the formula: wherein L^(1 )and L^(2 )are independently selected from O and S; R^(1 )is C_(3)-C_(6 )straight or branched alkyl, C_(3)-C_(7)cycloalkyl, C_(5)-C_(7)cycloalkenyl, adamantly, phenyl or saturated heterocyclyl, any of which being optionally substituted; R^(2 )is H, methyl or ethyl; R^(5 )is NRxCORy, NRxRy, CH_(2)COCH_(3), CH_(2)CN, or a 5- or 6-membered heteroaryl group which is optionally substituted; X, Y and Z are independently N or CH; Rx is independently H or C_(1)-C_(4)alkyl; Ry is independently H, CrC4alkyl, phenyl or benzyl, either of which is optionally substituted; n is 0-3; salts, hydrates and N-oxides, wherein the optional substituents are further defined in the claims. The compounds have utility in the prophylaxis or treatment of trypanosomal diseases, such as T. cruzi (Chagas disease).

Wenk M.R.,National University of Singapore | Wenk M.R.,Swiss Tropical and Public Health Institute
Cell | Year: 2010

Once viewed simply as a reservoir for carbon storage, lipids are no longer cast as bystanders in the drama of biological systems. The emerging field of lipidomics is driven by technology, most notably mass spectrometry, but also by complementary approaches for the detection and characterization of lipids and their biosynthetic enzymes in living cells. The development of these integrated tools promises to greatly advance our understanding of the diverse biological roles of lipids. © 2010 Elsevier Inc.

Oberle M.,Swiss Tropical and Public Health Institute
PLoS pathogens | Year: 2010

African trypanosomes are digenetic parasites that undergo part of their developmental cycle in mammals and part in tsetse flies. We established a novel technique to monitor the population dynamics of Trypanosoma brucei throughout its life cycle while minimising the confounding factors of strain differences or variation in fitness. Clones derived from a single trypanosome were tagged with short synthetic DNA sequences in a non-transcribed region of the genome. Infections were initiated with mixtures of tagged parasites and a combination of polymerase chain reaction and deep sequencing were used to monitor the composition of populations throughout the life cycle. This revealed that a minimum of several hundred parasites survived transmission from a tsetse fly to a mouse, or vice versa, and contributed to the infection in the new host. In contrast, the parasites experienced a pronounced bottleneck during differentiation and migration from the midgut to the salivary glands of tsetse. In two cases a single tag accounted for > or =99% of the population in the glands, although minor tags could be also detected. Minor tags were transmitted to mice together with the dominant tag(s), persisted during a chronic infection, and survived transmission to a new insect host. An important outcome of the bottleneck within the tsetse is that rare variants can be amplified in individual flies and disseminated by them. This is compatible with the epidemic population structure of T. brucei, in which clonal expansion of a few genotypes in a region occurs against a background of frequent recombination between strains.

Herzog C.,Swiss Tropical and Public Health Institute
Expert Review of Vaccines | Year: 2014

Vaccines have to be administered via an appropriate route, i.e. a route, which is optimal regarding safety, immunogenicity and practicability. In addition, there are factors, such as body site, needle length, injection technique, depth of injection, type of antigen, vaccine formulation, adjuvants, age, sex, race/ethnicity, body mass, and pre-existing immunity, which can have an impact on the reactogenicity and tolerability and/or on the immunogenicity of a given vaccine. For parenteral vaccine administration there are currently three routes licensed: intramuscular, subcutaneous and intradermal, either by using conventional hypodermic needles or by using alternative or needle-free injection devices. The factors potentially impacting on the 'performance' of a given route of administration, as reported in recent literature, are outlined and discussed in view of their importance. These factors need to be accounted and controlled for when designing vaccine studies and should be reported in a transparent and standardised way in publications. © 2014 Informa UK Ltd.

Gagneux S.,Swiss Tropical and Public Health Institute
Current Topics in Microbiology and Immunology | Year: 2013

Recent years have witnessed an increased appreciation of the extent and relevance of strain-to-strain variation in Mycobacterium tuberculosis. This paradigm shift can largely be attributed to an improved understanding of the global population structure of this organism, and to the realisation that the various members of the M. tuberculosis complex (MTBC) harbour more genetic diversity than previously realised. Moreover, many studies using experimental models of infection have demonstrated that MTBC diversity translates into significant differences in immunogenecity and virulence. However, linking these experimental phenotypes to relevant clinical phenotypes has been difficult, and to date, largely unsuccessful. Nevertheless, emerging high-throughput technologies, in particular next-generation sequencing, offer new opportunities, and have already lead to important new insights. Given the complexity of the host-pathogen interaction in tuberculosis, systems approaches will be key to define the role of MTBC diversity in the fight against one of humankind's most important pathogens. © Springer-Verlag Berlin Heidelberg 2013.

Burri C.,Swiss Tropical and Public Health Institute
Parasitology | Year: 2010

For over fifty years, human African trypanosomiasis (HAT, sleeping sickness) has been treated with suramin, pentamidine and the very toxic organo-arsenical melarsoprol that was the only drug available for effective treatment of the second stage of the disease. Recently there have been significant efforts using molecular and biochemical approaches to drug design, including high-throughput screening, but the number of lead compounds with promising activity against T. brucei spp. and an acceptable toxicity index has remained astonishingly small. Clinical research continues to be difficult due to the economic constraints and the complexity of trials on a low prevalence disease in remote and impoverished African regions. Despite those limitations the situation for the patients is improving thanks to the combination of a number of critical factors. By the late 1990s the disease had reached epidemic levels that triggered political support. WHO would sign a donation agreement with the manufacturers for all drugs to treat HAT. A result of this agreement was that eflornithine which is much safer than melarsoprol became available and widely used by non-governmental organizations. The Impamel I and II programmes demonstrated that against all odds the conduct of clinical trials on HAT was feasible. This allowed the initiation of trials on combination therapies which eventually resulted in the nifurtimox-eflornithine combination treatment (NECT). This combination is currently being introduced as first line treatment, and there is even the prospect of having a new compound, fexinidazole, in the development pipeline. This review summarizes the key information about the existing drugs and gives a comprehensive summary about the recent and currently ongoing efforts towards new drugs. © 2010 Cambridge University Press.

Brites D.,Swiss Tropical and Public Health Institute | Gagneux S.,Swiss Tropical and Public Health Institute
Immunological Reviews | Year: 2015

The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future 'genome-to-genome' studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines. Video podcast available Go to to watch an interview with Guest Editor Carl Nathan. © 2015 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.

Gagneux S.,Swiss Tropical and Public Health Institute
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

Tuberculosis (TB) is a disease of antiquity. Yet TB today still causes more adult deaths than any other single infectious disease. Recent studies show that contrary to the common view postulating an animal origin for TB, Mycobacterium tuberculosis complex (MTBC), the causative agent of TB, emerged as a human pathogen in Africa and colonized the world accompanying the Out-of- Africa migrations of modern humans. More recently, evolutionarily 'modern' lineages of MTBC expanded as a consequence of the global human population increase, and spread throughout the world following waves of exploration, trade and conquest. While epidemiological data suggest that the different phylogenetic lineages of MTBC might have adapted to different human populations, overall, the phylogenetically 'modern' MTBC lineages are more successful in terms of their geographical spread compared with the 'ancient' lineages. Interestingly, the global success of 'modern' MTBC correlates with a hypo-inflammatory phenotype in macrophages, possibly reflecting higher virulence, and a shorter latency in humans. Finally, various human genetic variants have been associated with different MTBC lineages, suggesting an interaction between human genetic diversity and MTBC variation. In summary, the biology and the epidemiology of human TB have been shaped by the long-standing association between MTBC and its human host.

Agency: GTR | Branch: MRC | Program: | Phase: Research Grant | Award Amount: 257.96K | Year: 2012

Millions of people are infected with the liver flukes Opisthorchis viverrini in Southeast Asia and Clonorchis sinensis in China. The diseases are associated with abdominal and hepato-biliar symptoms and serious manifestations such as obstructive jaundice and ascending cholangitis. Long-term consequences include the development of a fatal bile-duct cancer. Since there is currently only one drug available for the treatment of O. viverrini and C. sinensis, there is a need to develop novel trematocidal drugs. In a recent proof of concept trial with tribendimidine, a drug used in China for the treatment of roundworm infections, a high efficacy (based on changes in egg output after drug treatment) against infections with O. viverrini was observed. In addition, the drug was well tolerated. There is a need to follow up on these promising results. In the framework of 3 randomized trials the efficacy and safety of tribendimidine will be studied. First, we will study the dose-response of tribendimidine in O. viverrini patients and assess drug disposition. Second, once the ideal dose has been determined a phase 2b clinical trial will be conducted to compare the efficacies and safeties of tribendimidine with praziquantel. Finally, the efficacy and safety of tribendimidine against C. sinensis infections will be studied in a proof-of concept trial. The first two trial will be conducted in Laos, the third trial in China. In case tribendimidine has demonstrated adequate efficacy and safety in these trials we will pursue the registration of tribendimidine.

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