Evidence and strategies for malaria prevention and control: a historical analysis.

Public health strategies for malaria in endemic countries aim to prevent transmission of the disease and control the vector. This historical analysis considers the strategies for vector control developed during the first four decades of the twentieth century. In 1925, policies and technological advances were debated internationally for the first time after the outbreak of malaria in Europe which followed World War I. This dialogue had implications for policies in Europe, Russia and the Middle East, and influenced the broader international control agenda. The analysis draws on the advances made before 1930, and includes the effects of mosquito-proofing of houses; the use of larvicides (Paris Green) and larvivorous fish (Gambusia); the role of large-scale engineering works; and the emergence of biological approaches to malaria. The importance of strong government and civil servant support was outlined. Despite best efforts of public health authorities, it became clear that it was notoriously difficult to interrupt transmission in areas of moderately high transmission. The importance of combining a variety of measures to achieve control became clear and proved successful in Palestine between 1923 and 1925, and improved education, economic circumstances and sustained political commitment emerge as key factors in the longer term control of malaria. The analysis shows that the principles for many of the present public health strategies for malaria have nearly all been defined before 1930, apart from large scale usage of pesticides, which came later at the end of the Second World War. No single intervention provided an effective single answer to preventing transmission, but certainly approaches taken that are locally relevant and applied in combination, are relevant to today's efforts at elimination.

Early clinics of the cardiac forms of Chagas' disease: Discovery and study of original medical files (1909-1915).

We have uncovered 80 medical files corresponding to original cases of Chagas' disease used for the classical description of the acute and cardiac forms of the disease. Sixty of them were diagnosed cardiac forms of the disease. The detailed clinical description of these 60 files is in excellent agreement with the nosography of progressive heart disease given by Chagas in his original 1922 paper. The reports we had access to, characterize a novel form of cardiac disease, dominated by progressive AV block, enlargement and displacement of the heart and sudden death, in relatively young adults including juveniles. In contrast to that remarkable clinical description, the assertion made by Chagas that this set of clinical signs was the consequence of an earlier infection by Trypanosoma cruzi rests on weak evidence, due to the difficulty to identify the parasite in most patients. Moreover, the association of thyroid dysfunction with cardiac disease emphasized by Chagas cannot be deduced from the files we have examined. Finally, the main reason why the disease had not been recognized for long as a defined clinical entity, is likely the absence of markedly distinctive clinical signs compared to most other parasitic diseases, poor sanitary conditions and the probable lack of clinical skills of the rare doctors working in the area where the disease was described.

Malaria epidemics in Europe after the First World War: the early stages of an international approach to the control of the disease.

The severity and endemicity of malaria declined gradually in Europe until WWI. During and after the war, the number of malaria cases increased substantially and peaked in 1922-1924. This prompted the Hygiene Commission of the League of Nations to establish a Malaria Commission in 1923 to define the most efficient anti-malaria procedures. Additionally, between 1924 and 1930 there were several international meetings and collaborations concerning malaria, which involved the main institutes of parasitology and the Rockefeller Foundation. The Commission reports, the guidelines for anti-malaria campaigns and the scientific programs which came out of these meetings and collaborations are analyzed in the present paper.

Malaria epidemics in Europe after the First World War: the early stages of an international approach to the control of the disease

The severity and endemicity of malaria declined gradually in Europe until WWI. During and after the war, the number of malaria cases increased substantially and peaked in 1922-1924. This prompted the Hygiene Commission of the League of Nations to establish a Malaria Commission in 1923 to define the most efficient anti-malaria procedures. Additionally, between 1924 and 1930 there were several international meetings and collaborations concerning malaria, which involved the main institutes of parasitology and the Rockefeller Foundation. The Commission reports, the guidelines for anti-malaria campaigns and the scientific programs which came out of these meetings and collaborations are analyzed in the present paper.

The reception by French physicians of Chagas' discovery of Trypanosoma cruzi and American trypanosomiasis (1909-1925).

As soon as they were published early in 1909, Chagas's articles on Trypanosoma cruzi and American trypanosomiasis became the topic of discussions in France. The description of T. cruzi and Chagas disease was added to parasitology textbooks as early as 1912, and elicited active research, particularly on the part of French parasitologist Emile Brumpt. He contributed towards eluciding the lifecycle of T. cruzi and the different ways it could infect humans. Laboratory research on T. cruzi was interrupted by First World War and was not resumed afterwards on the same scale, although interest in the epidemiology of Chagas disease continued.

The reception by French physicians of Chagas' discovery of Trypanosoma cruzi and American trypanosomiasis (1909-1925) / A recepção dos médicos franceses à descoberta do Tripanosoma cruzi e da tripanosomíase americana (1909-1925) por Carlos Chagas

As soon as they were published early in 1909, Chagas's articles on Trypanosoma cruzi and American trypanosomiasis became the topic of discussions in France. The description of T. cruzi and Chagas disease was added to parasitology textbooks as early as 1912, and elicited active research, particularly on the part of French parasitologist Emile Brumpt. He contributed towards eluciding the lifecycle of T. cruzi and the different ways it could infect humans. Laboratory research on T. cruzi was interrupted by First World War and was not resumed afterwards on the same scale, although interest in the epidemiology of Chagas disease continued.

Assim que os artigos de Carlos Chagas sobre o Tripanosoma cruzi e a tripanosomíase americana foram publicados em 1909, passaram a ser tema de discussões na França. A descrição do T. cruzi e da doença de Chagas foram adicionadas a livros de parasitologia ainda em 1912, e ajudaram a elucidar pesquisas, particularmente as que vinham sendo desenvolvidas pelo parasitologista Emile Brumpt. Ele contribuiu para o esclarecimento do ciclo de vida do T. cruzi e as diferentes maneiras que poderiam infectar osseres humanos. Pesquisa de laboratório sobre o T. cruzi foi interrompida durante a Primeira Guerra Mundial e não foi retomada mais tarde na mesma escala, a despeito do fato de os estudos epidemiológicos sobre a doença de Chagas continuarem despertando muito interesse.

The reception by French physicians of Chagas' discovery of Trypanosoma cruzi and American trypanosomiasis (1909-1925)

As soon as they were published early in 1909, Chagas's articles on Trypanosoma cruzi and American trypanosomiasis became the topic of discussions in France. The description of T. cruzi and Chagas disease was added to parasitology textbooks as early as 1912, and elicited active research, particularly on the part of French parasitologist Emile Brumpt. He contributed towards eluciding the lifecycle of T. cruzi and the different ways it could infect humans. Laboratory research on T. cruzi was interrupted by First World War and was not resumed afterwards on the same scale, although interest in the epidemiology of Chagas disease continued.(AU)

The designing of anti-diphtheria serotherapy at the Institut Pasteur (1888-1900): the role of a supranational network of microbiologists.

The development of anti-diphtheria serotherapy at the Institut Pasteur immediately follows the crisis known as the Pasteur-Koch debate. Research on diphtheria in Paris is indicative of the importance granted by Pasteurian scientists to Koch's school criticisms. After 1887, relations between French and German bacteriologists become more relaxed. A scientific and social network develops between them. It later extends to other fields of research at the Institut Pasteur, particularly therapeutic chemistry. The evolution of Franco-German relations at the Institut Pasteur is placed in the general framework of the way French universities considered German science.

Emile Brumpt's contribution to the characterization of parasitic diseases in Brasil, 1909-1914

Mais do que contar a história das missões de Brumpt na América do Sul, objetiva fazer um levantamento da adaptaçäo progressiva de seu método, sua abordagem ou conceito de pesquisa na parasitologia. Faz um esboço de sua contribuiçäo para a nosografia das doenças parasitárias na América do Sul.(AU)

Injection of the immuno-modulatory drug alpha-galactosylceramide results in the recruitment of a large population of antigen-presenting cells into the liver of C57BL/6 mice.

Injection of the immuno-modulatory drug alpha-galactosylceramide into C57BL/6 mice leads to the already known apoptosis of natural killer T (NKT) cells and to thus far undescribed large changes in the leukocyte populations of the liver. These changes are characterized by the recruitment of neutrophils and that of a population of large monocytic cells. The latter cells display the morphological and immunological features of natural suppressor cells. Their recruitment in the liver depends on the presence of NKT cells, most probably through the local release of cytokines and chemokines by activated NKT cells. We discuss the ubiquitous, long-term effects of alpha-galactosylceramide injection on immuno-pathological processes mediated through the NKT-triggered recruitment of a subset of large macrophages/monocytes.

A biased Valpha24+ T-cell repertoire leads to circulating NKT-cell defects in a multiple sclerosis patient at the onset of his disease.

As natural killer T (NKT) cells have been implicated in the regulation of multiple sclerosis (MS), we investigated expression of the Valpha24JalphaQ canonical rearrangement in MS patients during relapses. We observed major changes in the entire blood Valpha24(+) T-cell repertoire. Seven of the eight patients showed a marked decrease in Valpha24(+) transcript number and a decrease in the diversity of the Valpha24(+) T-cell repertoire, with the exception of a few expanded clones. These perturbations, exacerbated in patient MS (A), led to circulating NKT cell defects.

The same TCR (N)Dbeta(N)Jbeta junctional region is associated with several different vbeta13 subtypes in a multiple sclerosis patient at the onset of the disease.

In multiple sclerosis (MS), the T-cell receptors (TCRS) of autoreactive T lymphocytes recognize various myelin components or derivatives including peptides of the myelin basic protein (MBP). Using the exhaustive immunoscope approach we showed that the T-cell repertoires of MS patients differ from those of healthy controls, with expansion of Vbeta13 cell clones in cerebrospinal fluid (CSF) and in peripheral blood lymphocytes (PBLs). Sequencing of the beta13(+) chains of T cells recovered from the CSF revealed high interindividual diversity, and no particular Vbeta13(+) rearrangements were shown to be myelin-autoreactive. Within the overall Vbeta13 repertoire in the CSF of patient MS3 at the onset of the disease, most of the overrepresented (N)Dbeta(N)Jbeta junctional regions were found to be associated with two or three different Vbeta13 segments. These rearrangements were most common in the PBLs of patient MS3. No such associations were detected in the Vbeta5 multigene family that was used as a control. Thus, Vbeta13 T cells infiltrating the CSF from patient MS3 may have been selected on the basis of both the Vbeta13 segments and the (N)Dbeta(N)Jbeta junctional CDR3 sequence.

The intratumoral application of poly-G-oligodeoxynucleotides does not augment the naturally induced antitumoral CD8-T-cell response in P815 mastocytomas.

DNA sequences containing CpG have been described to induce a strong immune reaction by acting on a variety of immune cells including a strong and pronounced antitumoral response. Poly-G-oligodeoxynucleotides (ODNs) on the other hand have been attributed the preferential induction of CD8-T-cell proliferation when used in vitro. This activity led us to the investigation of the possible antitumoral properties of poly-G-ODNs in an established CD8-dependent tumor eradication model. We used the well described poly-G-ODN 1628 in its capacity to enhance antitumoral CD8 response in the cutaneous mastocytoma P815. When injecting 30 microg of the purified phosphothioate-modified oligo into the tumor bearing area of P815 challenged mice for up to 12 consecutive days we did not observe increased tumor rejection as compared to the group of mice injected with a control oligo. The 1628-injected mice did not produce higher numbers of P815-specific CD8 cells as measured by P1A-, and P1E-tetramer staining and Immunoscope analysis. Furthermore, tumor-specific CD8 cells in 1628 did not show enhanced antitumoral cytotoxicity when analyzing lymphocyte-tumor cell co-cultures or transcription of the cytotoxic CD8-cell associated molecules interferon gamma, FAS ligand, perforin, or granzyme B by quantitative real-time RT-PCR. These experiments show that there is no enhanced induction of an antitumoral CD8 response after in situ administration of poly-G-ODNs in the P815 mastocytoma model.

Follow-up of the T-cell clonality in Sezary patients treated by extracorporeal photopheresis using a new assay: the immunoscope technique.

Sezary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma related to the malignant proliferation of clonal CD4+ T-cells. Extracorporeal photochemotherapy (ECP) may induce a transient improvement of the clinical signs but it's efficiency is discussed. In order to investigate the T-cell clonality in the peripheral blood of patients with Sezary syndrome and to monitor its evolution in 8 patients treated by ECP, we used the Immunoscope technique. In one patient, we observed a decrease of the T-cell clonality from 15.6% to 0%, paralleling a complete remission of the clinical disease with a disappearance of the circulating Sezary cells. In the other cases, the evolution of the relative frequency paralleled the clinical status of the patient. In 3 cases, we observed a quick-acting direct cytotoxicity of the association 8MOP + UVA on the T-cell clone present in the cellular product. Immunoscope technique appears to be an efficient assay to appreciate the amount of tumoral cells and monitor the evolution of the clonal component in Sezary syndrome.