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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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.

Malaria and helminth infections are thought to negatively affect children's nutritional status and to impair their physical and cognitive development. Yet, the current evidence-base is weak. The purpose of this study was to determine the effect of deworming against soil-transmitted helminthiasis and schistosomiasis on children's physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic setting of Côte d'Ivoire. We designed an intervention study with a 5-month follow-up among schoolchildren aged 5-14 years from Niablé, eastern Côte d'Ivoire. In late 2012, a baseline cross-sectional survey was conducted. Finger-prick blood, stool and urine samples were subjected to standardised, quality-controlled techniques for the diagnosis of Plasmodium spp., Schistosoma spp., soil-transmitted helminths and intestinal protozoa infections. Haemoglobin level was determined and anthropometric measurements were taken for appraisal of anaemia and nutritional status. Children underwent memory (digit span) and attention (code transmission) cognitive testing, and their physical fitness and strength were determined (20 m shuttle run, standing broad jump and grip strength test). All children were treated with albendazole (against soil-transmitted helminthiasis) and praziquantel (against schistosomiasis) after the baseline cross-sectional survey and again 2 months later. Five months after the initial deworming, the same battery of clinical, cognitive and physical fitness tests was performed on the same children. Lower scores in strength tests were significantly associated with children with harbouring nutritional deficiencies. Surprisingly, boys infected with Schistosoma mansoni achieved longer jumping distances than their non-infected counterparts. Light-intensity infection with S. mansoni was associated with slightly better aerobic capacity. Deworming showed no effect on haemoglobin levels and anaemia, but children with moderate- to heavy-intensity Schistosoma infection at baseline gained weight more pronouncedly than non-infected children. Interestingly, children with soil-transmitted helminth or Schistosoma infection at baseline performed significantly better in the sustained attention test than their non-infected counterparts at the 5-month follow-up. This study revealed conflicting results regarding clinical parameters and cognitive behaviour of children after two rounds of deworming. We speculate that potential beneficial effects of deworming are likely to be undermined in areas where malaria is co-endemic and nutritional deficiencies are widespread.

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.

Yap P.,Swiss Tropical and Public Health Institute
Journal of visualized experiments : JoVE | Year: 2012

Soil-transmitted helminth (STH) infections are common. Indeed, more than 1 billion people are affected, mainly in the developing world where poverty prevails and hygiene behavior, water supply, and sanitation are often deficient. Ascaris lumbricoides, Trichuris trichiura, and the two hookworm species, Ancylostoma duodenale and Necator americanus, are the most prevalent STHs. The estimated global burden due to hookworm disease, ascariasis, and trichuriasis is 22.1, 10.5, and 6.4 million disability-adjusted life years (DALYs), respectively. Furthermore, an estimated 30-100 million people are infected with Strongyloides stercoralis, the most neglected STH species of global significance which arguably also causes a considerable public health impact. Multiple-species infections (i.e., different STHs harbored in a single individual) are common, and infections have been linked to lowered productivity and thus economic outlook of developing countries. For the diagnosis of common STHs, the World Health Organization (WHO) recommends the Kato-Katz technique, which is a relatively straightforward method for determining the prevalence and intensity of such infections. It facilitates the detection of parasite eggs that infected subjects pass in their feces. With regard to the diagnosis of S. stercoralis, there is currently no simple and accurate tool available. The Baermann technique is the most widely employed method for its diagnosis. The principle behind the Baermann technique is that active S. stercoralis larvae migrate out of an illuminated fresh fecal sample as the larvae are phototactic. It requires less sophisticated laboratory materials and is less time consuming than culture and immunological methods. Morbidities associated with STH infections range from acute but common symptoms, such as abdominal pain, diarrhea, and pruritus, to chronic symptoms, such as anemia, under- and malnutrition, and cognitive impairment. Since the symptoms are generally unspecific and subtle, they often go unnoticed, are considered a normal condition by affected individuals, or are treated as symptoms of other diseases that might be more common in a given setting. Hence, it is conceivable that the true burden of STH infections is underestimated by assessment tools relying on self-declared signs and symptoms as is usually the case in population-based surveys. In the late 1980s and early 1990s, Stephenson and colleagues highlighted the possibility of STH infections lowering the physical fitness of boys aged 6-12 years. This line of scientific inquiry gained new momentum recently. The 20-meter (m) shuttle run test was developed and validated by Léger et al. and is used worldwide to measure the aerobic fitness of children. The test is easy to standardize and can be performed wherever a 20-m long and flat running course and an audio source are available, making its use attractive in resource-constrained settings. To facilitate and standardize attempts at assessing whether STH infections have an effect on the physical fitness of school-aged children, we present methodologies that diagnose STH infections or measure physical fitness that are simple to execute and yet, provide accurate and reproducible outcomes. This will help to generate new evidence regarding the health impact of STH infections.

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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