A thesis submitted to the Faculty of Health Sciences University of the Witwatersrand. Johannesburg for the degree of Doctor of Philosophy Johannesburg 1997 / a) to develop sensitive tests for the early diagnosis of Crimean-Congo haemorrhagic fever {( '( "II;) infection or humans. based on the detection of viral nucleic add and antibody in serum: [Abbreviated Abstract. Open document to view full version] / MT2017

A febre maculosa, doença de caráter endêmico, já foi diagnosticada em vários estados brasileiros. Em São Paulo a doença é considerada endêmica em algumas regiões e não endêmica ou desconhecida na maior parte do estado. Com o objetivo de estudar a epidemiologia da febre maculosa em regiões consideradas endêmica e não endêmica do estado de São Paulo, foram colhidos carrapatos das pastagens e amostras de sangue de seres humanos, cães e equídeos que viviam em propriedades rurais dos municípios de Pedreiras, (região endêmica); Pirassununga, Sorocaba e Cotia (não endêmica). A colheita de carrapato e de sangue foi efetuada no período de novembro de 2000 a março de 2001, época de predomínio do estágio adulto de ixodideos do gênero Amblyomma na região. Foram colhidos 686 amostras de carrapatos, 50 amostras de sangue de seres humanos, 28 eqüinos, quatro asininos e 16 caninos de região endêmica e 658 amostras de carrapatos, 16 amostras de sangue de seres humanos, 48 eqüinos e cinco caninos de região não endêmica. Os carrapatos foram examinados pelo teste de hemolinfa e pela nested reação em Cadeia da Polimerase (n-PCR). A amplificação de uma região do gene que codifica uma proteína interna de membrana de 17 kDa pela n-PCR, foi utilizada para a detecção do gênero Rickettsia spp nos carrapatos. De um total de 686 amostras de carrapatos de região endêmica, foram encontrados 34 amostras positivas (4,9%) e de 658 amostras de carrapatos de região não endêmica, foram encontrados seis amostras positivas (0,9%). O seqüenciamento de um fragmento de 232 pares de bases do gene 17 kDa efetuados em duas amostras de região endêmica e seis de região não endêmica demonstraram homologia em 100% com a Rickettsia felis. Foi realizada a reação de imunofluorescência indireta (IFI) nos soros sangüíneos utilizando-se antígenos brutos de superfície de Rickettsia rickettsii. Foram considerados positivos soros com títulos superiores a 64. Nenhuma amostra de soro de seres humanos de região endêmica e não endêmica apresentou sorologia positiva. 17 (65,3%) amostras de soros de eqüinos, de região endêmica, apresentaram sorologia positiva, com titulação máxima de 4096. Apenas uma (2,0%) amostra de soro eqüino de região não endêmica apresentou sorologia positiva, com titulação de 128. Cinco (31,2%) amostras de soros de cães de região endêmica apresentaram sorologia positiva, com titulação máxima de 512. Não foi detectada sorologia positiva para cães de região não endêmica. Os títulos elevados da sorologia de cães e eqüinos de região endêmica sugerem indiretamente a circulação de Rickettsia rickettsii nesta localidade. A vigilância epidemiológica em regiões não endêmicas é de grande importância visto que são consideradas vulneráveis a futuros casos de febre maculosa. / Spotted fever, a disease of endemic characteristics, has already been diagnosed in several Brazilian states. The disease is considered to be endemic in some regions of the state of São Paulo and non-endemic or unknown in most of the state. In order to study the epidemiology of spotted fever in endemic and non-endemic regions of the state of São Paulo, ticks were collected from pastures, and blood samples were collected from humans, dogs and horses living in rural properties in the cities of Pedreiras (endemic region); Pirassununga, Sorocaba and Cotia (non-endemic regions). Collection of the ticks was performed from November 2000 to March 2001, a period when adults ticks of the Amblyomma genus predominate in the region. Collection was performed as follows: 686 tick samples, 50 blood samples from humans, 26 blood samples from horses, four blood samples from donkeys and 16 blood samples from dogs in the endemic region. In the non-endemic region, 658 tick samples, 16 blood samples from humans, 48 blood samples from horses and one blood sample from a dog were collected. Ticks were studied using the hemolymph test, and by means of the nested polymerase chain reaction (n-PCR). The amplification, by n-PCR, of a region of the gene that codifies a 17 kDa internal protein in the membrane of the microorganism was used for the detection of the Rickettsia spp genus, in the ticks. From 686 tick samples from the endemic region, 34 were positive (4.9%). From the 658 tick samples collected in the non-endemic region, six were positive (0.9%). Sequencin of a 232 base-pair fragment of the 17 kDa gene, performed in two samples of the endemic region and in six samples of the non-endemic region, showed 100% homology with Rickettsia felis. Indirect immunofluorescence (IFI) was performed in serum samples using crude antigens from Rickettsia rickettsii surface. Serum samples were considered to be positive when presenting titers higher than 64. No human serum sample from the endemic or non-endemic region was positive. Seventeen (65.3%) serum samples from horses in the endemic region were positive, with maximum titer equal to 4096. Only one horse (2,0%) in the non-endemic region presented positive serology, with titer equal to 128. Five (31.2%) dog serum samples from the endemic region were positive, with maximum titer equal to 512. No dog serum sample was positive in the non-endemic region. Epidemiological surveillance in endemic regions is very important, for new spotted fever cases may be expected.

General health screening is needed to decrease the risk of pandemic in high volume areas. Thermal characterization, via infrared imaging, is an effective technique for fever detection, however, strict use requirements in combination with highly controlled environmental conditions compromise the practicality of such a system. Combining advanced processing techniques to thermograms of individuals can remove some of these requirements allowing for more flexible classification algorithms. The purpose of this research was to identify individuals who had febrile status utilizing modern thermal imaging and machine learning techniques in a minimally controlled setting. Two methods were evaluated with data that contained environmental, and acclimation noise due to data gathering technique. The first was a pretrained VGG16 Convolutional Neural Network found to have F1 score of 0.77 (accuracy of 76%) on a balanced dataset. The second was a VGG16 Feature Extractor that gives inputs to a principle components analysis and utilizes a support vector machine for classification. This technique obtained a F1 score of 0.84 (accuracy of 85%) on balanced data sets. These results demonstrate that machine learning is an extremely viable technique to classify febrile status independent of noise affiliated.

Hemorrhagic fever viruses cause severe infections characterized by a hyperactive immune response that often leads to multiorgan failure and death. Current diagnostic tests are based on detecting viral proteins and nucleic acids in the blood. These are late-stage events during infection, which makes it impossible to perform a diagnosis before they are present in the collected sample. In this thesis, I explore an alternative approach using the transcriptional changes of circulating immune cells during the early stages of infection to identify unique markers of viral infection. The main advantage of this method is that it can be used to identify highly pathogenic viruses before standard detection methods become effective. I initially used RNA sequencing data to compare the host patterns of expression of macaques infected with either Lassa virus or Marburg virus, two related hemorrhagic fever viruses. I identified a set of genes that quickly become upregulated after a viral infection and remain highly expressed throughout the entire disease course, irrespective of the specific virus that caused the infection. I was also able to identify a set of biomarker genes that follow unique patterns of expression depending on the type of infection. I used an independent dataset to validate the potential of these genes to be used as biomarkers of infection. Additionally, I compared these results to the patterns of expression of macaques infected with Ebola virus, looking at multiple experimental conditions, tissues and routes of infection. Finally, I validated the host patterns of expression using two independently generated datasets corresponding to infection by different strains of arenaviruses and filoviruses. Studying the host immune response has the potential to improve the diagnosis of viral hemorrhagic fevers and other diseases. It can also accelerate our efforts to understand the underlying molecular mechanisms that lead to pathogenesis and severe disease.

O comportamento materno consiste em um conjunto de mudanças comportamentais e fisiológicas, exercidas pelos indivíduos adultos em torno dos indivíduos reprodutivamente imaturos, garantindo sua sobrevivência e a propagação de sua espécie. A interação mãe e filhote é tida tipicamente como simbiótica. Os filhotes quando separados da mãe sinalizam para serem recolhidos através de dicas olfativas, visuais e da vocalização que representa uma forma de comunicação filhote e mãe. O modelo de febre clássico e amplamente empregado envolve a utilização do lipopolissacarídeo (LPS), principal componente da parede celular de bactérias Gram-Negativas. Além da febre, as infecções apresentam uma cadeia de respostas não especificas do hospedeiro que se sabe estarem envolvidos em muitas das funções vitais, incluindo a resposta imune estas incluem a hipozinquemia. Sendo assim, fêmeas virgens, gestantes e lactantes receberam LPS (100 µg/kg, i.p.) e foram tratadas com zinco (2 mg/kg, s.c.) O peso corporal, consumo de água, ração, e a temperatura corporal foram medidas por noventa e seis horas, duas horas após a administração do LPS. No quinto dia de lactação foram observados o comportamento maternal, a atividade geral em campo aberto e a vocalização ultrassônica nos filhotes. No dia do desmame os filhotes dessas fêmeas receberam um desafio com LPS (50 µg/kg, i.p.) e duas horas após a administração, foram observados a atividade geral em campo aberto, e o burst e fagocitose de neutrófilos. Observamos que: 1) Em ratas virgens, gestantes e lactantes, a exposição ao LPS e o tratamento com zinco modificou de forma específica a temperatura e peso corporal, consumo de água e ração e a atividade geral observadas em campo aberto; 2) No período de lactação, houve redução da latência para busca do primeiro filhote. Na prole das fêmeas lactantes verificou-se que: 3) Houve alteração no padrão de vocalização dos filhotes; 4) houve alteração na atividade geral observada em campo aberto e no burst e fagocitose de neutrófilos no vigésimo primeiro dia pós natal, após um desafio com a endotoxina, Assim, os resultados indicam que a administração de LPS e o tratamento com zinco têm seus efeitos modulados conforme o estágio fisiológico em que a fêmea se encontra, e interfere com a interação mãe/filhote, resultando em efeitos de curto e longo prazo sobre o comportamento dos filhotes. A partir deste trabalho, a possibilidade da exposição de mães à endotoxina bacteriana e da modulação de seus efeitos pelo zinco programar as respostas inflamatórias dos filhos torna-se factível / The maternal behavior consists of a set of behavioral and physiological changes, performed by adults around the reproductively immature individuals, ensuring their survival and propagation of their species. The mother and pups’ interaction is typically seen as symbiotic. Puppies give signal to be collected when separated from their mother, through olfactory, visual and vocalization tips that represents a form of communication between mother and pup. The classic disease model is widely used involves the use of lipopolysaccharide (LPS), the major component of the cell wall of Gram-negative bacteria. In addition to fever, infections present a chain of non-specific host responses known to be involved in many vital functions, including the immune response these include hypokinemia. Therefore, virgin, pregnant and lactating female rats received LPS (100 µg/kg, ip) and were treated with zinc (2 mg/kg, sc). Temperature and Body weight, water and food consumptions were measured for ninety-six hours, two hours after LPS administration. On the fifth day of lactation were observed maternal behavior, the overall activity in the open field and ultrasonic vocalization in puppies. On the day of weaning pups of these females received a challenge with LPS (50 µg/kg, ip) two hours after administration were observed general activity in the open field and the burst and phagocytosis of leukocytes. We observed that: In virgin, pregnant and lactating, the exposure to LPS and the treatment with zinc, modified of the form differentially between these females, the temperature and body weight, water and food consumption, and the general activity observed in the open field; In the lactation period the latency to search the first pup was reduced. In the offspring, it was found that: There was a change in the pattern of vocalization of the puppies; changes in general activity observed in the open field and in burst and phagocytosis of leukocytes in the twenty-first day of lactation after challenge with endotoxin. Thus, the results indicate that administration of LPS and treatment with zinc have effects modulated according to the physiological stage when the female is, and interferes with the interaction between mother and puppies, resulting in short and long term effects on behavior their offspring. From this work, the possibility of the exposure of mothers to bacterial endotoxin modulates the effects caused by zinc, programing the inflammatory responses in their offspring, becomes feasible

A febre maculosa, doença de caráter endêmico, já foi diagnosticada em vários estados brasileiros. Em São Paulo a doença é considerada endêmica em algumas regiões e não endêmica ou desconhecida na maior parte do estado. Com o objetivo de estudar a epidemiologia da febre maculosa em regiões consideradas endêmica e não endêmica do estado de São Paulo, foram colhidos carrapatos das pastagens e amostras de sangue de seres humanos, cães e equídeos que viviam em propriedades rurais dos municípios de Pedreiras, (região endêmica); Pirassununga, Sorocaba e Cotia (não endêmica). A colheita de carrapato e de sangue foi efetuada no período de novembro de 2000 a março de 2001, época de predomínio do estágio adulto de ixodideos do gênero Amblyomma na região. Foram colhidos 686 amostras de carrapatos, 50 amostras de sangue de seres humanos, 28 eqüinos, quatro asininos e 16 caninos de região endêmica e 658 amostras de carrapatos, 16 amostras de sangue de seres humanos, 48 eqüinos e cinco caninos de região não endêmica. Os carrapatos foram examinados pelo teste de hemolinfa e pela nested reação em Cadeia da Polimerase (n-PCR). A amplificação de uma região do gene que codifica uma proteína interna de membrana de 17 kDa pela n-PCR, foi utilizada para a detecção do gênero Rickettsia spp nos carrapatos. De um total de 686 amostras de carrapatos de região endêmica, foram encontrados 34 amostras positivas (4,9%) e de 658 amostras de carrapatos de região não endêmica, foram encontrados seis amostras positivas (0,9%). O seqüenciamento de um fragmento de 232 pares de bases do gene 17 kDa efetuados em duas amostras de região endêmica e seis de região não endêmica demonstraram homologia em 100% com a Rickettsia felis. Foi realizada a reação de imunofluorescência indireta (IFI) nos soros sangüíneos utilizando-se antígenos brutos de superfície de Rickettsia rickettsii. Foram considerados positivos soros com títulos superiores a 64. Nenhuma amostra de soro de seres humanos de região endêmica e não endêmica apresentou sorologia positiva. 17 (65,3%) amostras de soros de eqüinos, de região endêmica, apresentaram sorologia positiva, com titulação máxima de 4096. Apenas uma (2,0%) amostra de soro eqüino de região não endêmica apresentou sorologia positiva, com titulação de 128. Cinco (31,2%) amostras de soros de cães de região endêmica apresentaram sorologia positiva, com titulação máxima de 512. Não foi detectada sorologia positiva para cães de região não endêmica. Os títulos elevados da sorologia de cães e eqüinos de região endêmica sugerem indiretamente a circulação de Rickettsia rickettsii nesta localidade. A vigilância epidemiológica em regiões não endêmicas é de grande importância visto que são consideradas vulneráveis a futuros casos de febre maculosa. / Spotted fever, a disease of endemic characteristics, has already been diagnosed in several Brazilian states. The disease is considered to be endemic in some regions of the state of São Paulo and non-endemic or unknown in most of the state. In order to study the epidemiology of spotted fever in endemic and non-endemic regions of the state of São Paulo, ticks were collected from pastures, and blood samples were collected from humans, dogs and horses living in rural properties in the cities of Pedreiras (endemic region); Pirassununga, Sorocaba and Cotia (non-endemic regions). Collection of the ticks was performed from November 2000 to March 2001, a period when adults ticks of the Amblyomma genus predominate in the region. Collection was performed as follows: 686 tick samples, 50 blood samples from humans, 26 blood samples from horses, four blood samples from donkeys and 16 blood samples from dogs in the endemic region. In the non-endemic region, 658 tick samples, 16 blood samples from humans, 48 blood samples from horses and one blood sample from a dog were collected. Ticks were studied using the hemolymph test, and by means of the nested polymerase chain reaction (n-PCR). The amplification, by n-PCR, of a region of the gene that codifies a 17 kDa internal protein in the membrane of the microorganism was used for the detection of the Rickettsia spp genus, in the ticks. From 686 tick samples from the endemic region, 34 were positive (4.9%). From the 658 tick samples collected in the non-endemic region, six were positive (0.9%). Sequencin of a 232 base-pair fragment of the 17 kDa gene, performed in two samples of the endemic region and in six samples of the non-endemic region, showed 100% homology with Rickettsia felis. Indirect immunofluorescence (IFI) was performed in serum samples using crude antigens from Rickettsia rickettsii surface. Serum samples were considered to be positive when presenting titers higher than 64. No human serum sample from the endemic or non-endemic region was positive. Seventeen (65.3%) serum samples from horses in the endemic region were positive, with maximum titer equal to 4096. Only one horse (2,0%) in the non-endemic region presented positive serology, with titer equal to 128. Five (31.2%) dog serum samples from the endemic region were positive, with maximum titer equal to 512. No dog serum sample was positive in the non-endemic region. Epidemiological surveillance in endemic regions is very important, for new spotted fever cases may be expected.

O comportamento materno consiste em um conjunto de mudanças comportamentais e fisiológicas, exercidas pelos indivíduos adultos em torno dos indivíduos reprodutivamente imaturos, garantindo sua sobrevivência e a propagação de sua espécie. A interação mãe e filhote é tida tipicamente como simbiótica. Os filhotes quando separados da mãe sinalizam para serem recolhidos através de dicas olfativas, visuais e da vocalização que representa uma forma de comunicação filhote e mãe. O modelo de febre clássico e amplamente empregado envolve a utilização do lipopolissacarídeo (LPS), principal componente da parede celular de bactérias Gram-Negativas. Além da febre, as infecções apresentam uma cadeia de respostas não especificas do hospedeiro que se sabe estarem envolvidos em muitas das funções vitais, incluindo a resposta imune estas incluem a hipozinquemia. Sendo assim, fêmeas virgens, gestantes e lactantes receberam LPS (100 µg/kg, i.p.) e foram tratadas com zinco (2 mg/kg, s.c.) O peso corporal, consumo de água, ração, e a temperatura corporal foram medidas por noventa e seis horas, duas horas após a administração do LPS. No quinto dia de lactação foram observados o comportamento maternal, a atividade geral em campo aberto e a vocalização ultrassônica nos filhotes. No dia do desmame os filhotes dessas fêmeas receberam um desafio com LPS (50 µg/kg, i.p.) e duas horas após a administração, foram observados a atividade geral em campo aberto, e o burst e fagocitose de neutrófilos. Observamos que: 1) Em ratas virgens, gestantes e lactantes, a exposição ao LPS e o tratamento com zinco modificou de forma específica a temperatura e peso corporal, consumo de água e ração e a atividade geral observadas em campo aberto; 2) No período de lactação, houve redução da latência para busca do primeiro filhote. Na prole das fêmeas lactantes verificou-se que: 3) Houve alteração no padrão de vocalização dos filhotes; 4) houve alteração na atividade geral observada em campo aberto e no burst e fagocitose de neutrófilos no vigésimo primeiro dia pós natal, após um desafio com a endotoxina, Assim, os resultados indicam que a administração de LPS e o tratamento com zinco têm seus efeitos modulados conforme o estágio fisiológico em que a fêmea se encontra, e interfere com a interação mãe/filhote, resultando em efeitos de curto e longo prazo sobre o comportamento dos filhotes. A partir deste trabalho, a possibilidade da exposição de mães à endotoxina bacteriana e da modulação de seus efeitos pelo zinco programar as respostas inflamatórias dos filhos torna-se factível / The maternal behavior consists of a set of behavioral and physiological changes, performed by adults around the reproductively immature individuals, ensuring their survival and propagation of their species. The mother and pups’ interaction is typically seen as symbiotic. Puppies give signal to be collected when separated from their mother, through olfactory, visual and vocalization tips that represents a form of communication between mother and pup. The classic disease model is widely used involves the use of lipopolysaccharide (LPS), the major component of the cell wall of Gram-negative bacteria. In addition to fever, infections present a chain of non-specific host responses known to be involved in many vital functions, including the immune response these include hypokinemia. Therefore, virgin, pregnant and lactating female rats received LPS (100 µg/kg, ip) and were treated with zinc (2 mg/kg, sc). Temperature and Body weight, water and food consumptions were measured for ninety-six hours, two hours after LPS administration. On the fifth day of lactation were observed maternal behavior, the overall activity in the open field and ultrasonic vocalization in puppies. On the day of weaning pups of these females received a challenge with LPS (50 µg/kg, ip) two hours after administration were observed general activity in the open field and the burst and phagocytosis of leukocytes. We observed that: In virgin, pregnant and lactating, the exposure to LPS and the treatment with zinc, modified of the form differentially between these females, the temperature and body weight, water and food consumption, and the general activity observed in the open field; In the lactation period the latency to search the first pup was reduced. In the offspring, it was found that: There was a change in the pattern of vocalization of the puppies; changes in general activity observed in the open field and in burst and phagocytosis of leukocytes in the twenty-first day of lactation after challenge with endotoxin. Thus, the results indicate that administration of LPS and treatment with zinc have effects modulated according to the physiological stage when the female is, and interferes with the interaction between mother and puppies, resulting in short and long term effects on behavior their offspring. From this work, the possibility of the exposure of mothers to bacterial endotoxin modulates the effects caused by zinc, programing the inflammatory responses in their offspring, becomes feasible

Rheumatic heart disease is an inflammatory heart disease that affects millions of people around the world. Especially high rates of the disease can be found in Oceania, including the island nation of Samoa. Genetic studies of immune response genes have provided insight into a possible genetic link to increased susceptibility to rheumatic heart disease, including the genes that code for the toll-like receptor (TLR) protein family. One of the functions of TLR proteins is to recognize the presence of bacteria via identification of bacterial flagella. My evaluation of a Samoan family identified a variant in the TLR-5 gene that would inhibit this ability. However, further study showed this variant to not be statistically significant in relation to rheumatic heart disease susceptibility. My contribution to a regional genome-wide association study of Oceania resulted in the discovery of a variant in the IGHV4-61 gene affecting the ability of antibodies to properly bind to bacterial antigens. This variant was associated with a 1.4-fold increased risk of rheumatic heart disease development. The success of this study warrants further investigation of the IGHV4-61 variant in other populations and illustrates the benefits of utilizing a genome-wide association study to study rheumatic heart disease.

abstract: Valley Fever (VF), is a potentially lethal fungal pneumonia caused by Coccidioides spp., which is estimated to cause ~15-30% of all community-acquired pneumonias in the highly endemic Greater Phoenix and Tucson areas of Arizona. However, an accurate antigen-based diagnostic is still lacking. In order to identify protein and glycan antigen biomarkers of infection, I used a combination of genomics, proteomics and glycomics analyses to provide evidence of genus-specific proteins and glycosylations. The next goal was to determine if Coccidioides-specific glycans were present in biological samples from VF patients. Urine collected from 77 humans and 63 dogs were enriched for glycans and evaluated by mass spectrometry for Coccidioides-specific glycans and evaluated against a panel of normal donor urines, urines from patients infected with other fungi, and fungal cultures from closely related pneumonia-causing fungi. A combination of 6 glycan biomarkers was 100% sensitive and 100% specific in the diagnosis of human VF subjects, while only 3 glycan biomarkers were needed for 100% sensitivity and 100 specificity in the diagnosis of dog VF subject. Additionally, a blinded trial of 23 human urine samples was correctly able to classify urine samples with 93.3% sensitivity and 100% specificity. The results of this research provides evidence that Coccidioides genus-specific glycosylations have potential as antigens in diagnostic assays. / Dissertation/Thesis / Doctoral Dissertation Microbiology 2019

Les infections rickettsiales et la fièvre aiguë indifférenciée (FAI) sont des problèmes de santé publique importants sous les tropiques. Ce projet a été réalisé dans le but d'explorer les agents de rickettsies et autres étiologies de la FAI au Vietnam.Dans la première cohorte de 67 participants se concentrant sur les patients cliniquement suspectés de typhus des broussailles, le diagnostic de typhus des broussailles a été confirmé pour 32 patients (47,8%) par qPCR ou IFA. Parmi les 20 patients pour lesquels des escarres et du sang total ont été obtenus, 17 (85%) des échantillons d'escarre et 5 (25%) des échantillons de sang total étaient positifs pour O. tsutsugamushi par qPCR. L'analyse génétique des séquences du gène TSA 56-kDa a démontré que les 14 séquences étaient apparentées à 4 génotypes: Karp, Kawasaki, Gilliam (JG-v et TG-v) et TA716. Ensuite, une analyse prospective des étiologies de la FAI au Vietnam a été réalisée avec 378 patients adultes fébriles (FAIs) et 384 patients adultes fébriles (Contrôles). L'étiologie la plus courante était le virus de la grippe (20,9% dans les FAIs versus 0% dans les Contrôles), suivi des rickettsies (11,11% vs 0,26%), virus de la dengue (7,67% vs 0,52%), Leptospira (4,76% vs 0,78%), adénovirus (4,76% vs 1,04%) et entérovirus (2,12% vs 0%) (p<0,05).Par conséquent, de telles données sur les rickettsies et autres étiologies obtenues au Vietnam pourraient être très utiles pour l’établissement d’une méthode d’approche pour les patients atteints de FAI dans les aspects de diagnostic, de gestion et de prévention au Vietnam et dans les régions tropicales dans l'avenir. / Rickettsial infections and acute undifferentiated fever (AUF) are the important public health issues in the tropics. This project was performed with the aim to explore the rickettsial agents and other etiologies of AUF in Vietnam. In the first 67-participant cohort of patients who were clinically suspected of having scrub typhus, 32 (47.8%) patients were confirmed as scrub typhus by either qPCR or IFA. Among the 20 patients for whom both eschar and whole blood were obtained, 17 (85%) of the eschar specimens and 5 (25%) of the whole blood specimens tested positive for O. tsutsugamushi by qPCR. Genetic analysis of the 56-kDa TSA gene sequences demonstrated that the 14 sequences were related to 4 groups: Karp, Kawasaki, Gilliam (JG-v and TG-v) and TA716.Subsequently, a prospective case-control analysis of the etiologies of AUF in Vietnam was performed. A total of 378 febrile adult patients (AUFs) and 384 afebrile adult patients (Controls) were enrolled. The most common etiology was influenza virus (20.9% in AUFs versus 0% in Controls), followed by rickettsial agents (11.11% in AUFs versus 0.26% in Controls), dengue virus (7.67% vs 0.52%), Leptospira (4.76% vs 0.78%), adenovirus (4.76% vs 1.04%), and enterovirus (2.12% vs 0%) (p<0.05). Consequently, such data of rickettsial agents and other etiologies in Vietnam obtained from this project are extremely useful in guiding the diagnosis, management and preventive-health methods for patients with AUF in the future in Vietnam as well as in the tropics worldwide.