Abstract Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a syndrome characterized by regular, high-fever episodes with healthy periods in between. In a classic phenotype of the syndrome, the fevers begin in childhood before the age of five, and fever flares are accompanied by aphthous stomatitis, pharyngitis, and/or cervical adenitis. The etiology of the syndrome is unknown, but tonsillectomy (TE) has been shown to be an effective treatment for the disease. The purposes of this study were as follows: (1) to assess the long-term outcome of PFAPA patients treated by TE with either the classic or incomplete phenotype (later onset of the disease and/or missing oropharyngeal symptoms), (2) to compare the health and growth of PFAPA patients with healthy controls, and (3) to compare the histological and microbiological findings of the tonsils of PFAPA patients with controls via conventional and modern sequencing technologies. In this approximately 9-year follow up, 97% (n = 56) of patients with the classic phenotype and all patients (n = 50) with the incomplete phenotype achieved a prompt and constant response after TE. There were no differences in either the length of fever episodes or flares between patients with both the classic and incomplete phenotypes. The health and growth of 119 PFAPA patients was compared to that of sex- and age-matched controls (n = 230), and no differences in prevalence of chronic diseases or growth were found between the groups. Infections, oral thrush, and pollen allergy were more common in the history of the PFAPA patients than in the controls. Microbiological and histological findings of the tonsils of PFAPA patients (n = 31) were compared with the findings of the controls (n = 24) who had undergone TE for other reasons. Biofilm formation and Candida albicans were more frequently found among PFAPA patients than the controls, but Staphylococcus aureus, varicella zoster, and herpes simplex viruses were more common in the controls. While comparing the bacterial microbiota between the groups, we found significant differences in the presence and relative abundance of many bacteria. For example, Cyanobacteria were more common and abundant in the case samples than in the controls. Because the long-term outcome after TE was excellent, both in classic and incomplete PFAPA patients; a new diagnostic criteria for the syndrome is proposed. The microbes of the tonsils in PFAPA patients differ from that of the controls, which may play an important role in triggering the inflammatory processes that lead to symptoms of PFAPA. / Tiivistelmä Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrooma, on oireyhtymä, jossa potilaat kärsivät hyvin säännöllisesti ilmaantuvista, toistuvista kuumejaksoista, joiden välillä potilaat ovat terveitä. Klassisessa tautimuodossa kuumeilut alkavat lapsuudessa ennen viiden vuoden ikää ja kuumevaiheeseen liittyy liitännäisoireita: suun limakalvojen rakkuloita, nielutulehdusta ja/tai kaulan imusolmukkeiden suurentumista. Oireyhtymän syytä ei tiedetä, mutta nielurisaleikkaus (TE) on osoittautunut tehokkaaksi hoidoksi. Tutkimuksen tarkoituksena oli (1) arvioida PFAPA potilaiden vointia pitkäaikaisseurannassa TE:n jälkeen ja vertailla taudinkuvaa niiden PFAPA potilaiden välillä, joilla oli klassinen PFAPA tai epätyypillinen PFAPA. (2) Lisäksi tutkimme myös TE:lla hoidettujen PFAPA potilaiden sairastuvuutta, yleistä terveydentilaa ja kasvua vertaamalla näitä sukupuoli- ja ikävakioituihin kontrolleihin ja (3) selvitimme mikrobiologisia ja histologisia löydöksiä PFAPA potilaiden nielurisoissa verrattuna muista syistä TE:ssa käyneiden lasten nielurisoihin. Tässä noin yhdeksän vuoden seurannassa TE:n jälkeen oli täysin parantunut 97% (n = 56) potilaista, joilla oli klassinen PFAPA, ja kaikki (n = 50) potilaat, joilla oli epätyypillinen PFAPA (tauti oli alkanut viiden ikävuoden jälkeen ja/tai klassiset liitännäisoireet puuttuivat). Kuumeprofiilit eivät muilta osin eronneet ennen nielurisaleikkausta näissä ryhmissä. PFAPA potilaiden (n = 119) kasvu ja yleinen terveydentila eivät eronneet väestökontrolleista (n = 230). Krooniset ja autoimmuunisairaudet olivat yhtä harvinaisia molemmissa ryhmissä. Potilaat raportoivat sairastaneensa enemmän infektioita ja sammasta lapsuudessa ja heillä oli enemmän siitepölyallergioita. PFAPA potilaiden (n = 31) ja muista syistä TE:ssa käyneiden lasten (n = 24) nielurisojen mikrobiologiaa ja histologiaa tutkittiin ja vertailtiin. Biofilmimuodostusta nielurisan pinnalla ja Candida albicansia löytyi enemmän tapauksilta kuin kontrolleilta, kun taas Staphylococcus aureusta, varicella zoster- ja herpes simplex -viruksia tavattiin enemmän kontrolleilla. Myös mikrobiomi erosi ryhmien välillä, esimerkiksi syanobakteerit olivat yleisempiä PFAPA risoissa kuin kontrolleilla. Klassisten ja epätyypillisten PFAPA potilaiden terveydentila TE:n jälkeen oli pitkäaikaisseurannassamme erinomainen ja siksi ehdotamme, että PFAPA –syndrooman diagnostisia kriteereitä tulisi muuttaa. Nielurisojen mikrobisto on erilainen kontrolleihin verrattuna ja tällä voi olla merkitystä PFAPA syndrooman inflammatorisessa prosessissa.

Orientador: Cristina de Campos / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Geociências / Made available in DSpace on 2018-08-22T20:46:44Z (GMT). No. of bitstreams: 1 HernandezTasco_Aleidys_M.pdf: 2499047 bytes, checksum: 236f6901a7068d237ee969ad03880acc (MD5) Previous issue date: 2013 / Resumo: Em 1927 a luta contra a febre amarela parecia finalizada no continente americano. A Fundação Rockefeller, instituição filantrópica estadunidense que tinha como principal objetivo o combate da febre amarela na primeira metade do século XX, assegurava que a doença estava quase erradicada. No entanto, a ocorrência das epidemias de febre amarela no Rio de Janeiro em 1928 (Brasil) e em Socorro em 1929 (Colômbia), colocou em dúvida as medidas profiláticas recomendadas e aplicadas tanto pelos órgãos nacionais de Saúde Pública como os da Fundação Rockefeller que participou da luta contra essa doença em ambos os países. Ao mesmo tempo em que ocorriam as epidemias, uma controvérsia instalou-se em torno à descoberta de Stokes, Bauer e Hudson na África, em 1927, que demonstrou que a febre amarela era facilmente inoculável no Macacus Rhesus. Tal descoberta acabou por rejeitar a concepção etiológica estabelecida em 1919 por Noguchi. A nova descoberta dos pesquisadores, as epidemias e a rejeição da teoria de Noguchi geraram uma enorme desconfiança na época, dando a sensação de que nada era seguro em assuntos relacionados à febre amarela, despertando uma crise nos estudos da doença. Esta pesquisa assume a responsabilidade de fazer um estudo comparativo a partir da ciência, da política e da técnica que ambos os países usaram no combate à doença, com intuito de conhecer as experiências desenvolvidas com o fenômeno da febre amarela. Assim, a dissertação tem dois objetivos principais. Primeiro, analisar o processo histórico da febre amarela, a fim de entender a crise que predominou nos estudos da doença entre os anos de 1927 e 1930. Para isso iremos analisar os múltiplos atores locais, nacionais e internacionais no domínio teórico e técnico da doença, durante a epidemia de febre amarela no Rio de Janeiro, em 1928-29, e em Socorro, em 1929. O segundo objetivo é analisar as manifestações científicas contra o avanço da febre amarela no Brasil e na Colômbia, a partir das duas últimas grandes epidemias registradas no Rio de Janeiro (1928-1929) e em Socorro (1929), através das tensões entre o ideal de uma ciência médica universal, representada pela Fundação Rockefeller e pelas Conferências Pan-Americanas, e as práticas de saúde pública, representadas por médicos e pesquisadores, elaboradas localmente para minimizar o alcance da febre amarela no período de 1930 a 1948 / Abstract: In 1927 the fight against yellow fever seemed to have concluded in American continent. In the first half of the twentieth century, a philanthropic American organization had as primary goal the fight against that outbreak (The Rockefeller Foundation) and, they ensured that epidemic was almost completely eradicated in that time. Nonetheless, two yellow fever outbreaks recorded in Rio de Janeiro in 1928 (Brazil) and Socorro in 1929 (Colombia) put in doubt the prophylactic measures recommended and implemented by the National Agencies of Public Health and the Rockefeller Foundation. This later institution took part in the fight against the disease in both countries. A controversy was established, while those epidemics took place in both countries, due to the discovery made by Stokes, Bauer e Hudson in Africa in 1927, which demonstrated Macacus Rhesus could be easily inoculated with the virus of yellow fever. That discovery eventually rejected the etiological agent theory established by Noguchi in 1919. In this fashion, with the new discovery, the epidemics and the rejecting of Noguchi's theory, a huge distrust grew up in those days, giving the impression that nothing was safe in issues related to yellow fever, and generating a crisis in studies of disease. Therefore, a comparative study from science, policy and technical that both Colombia and Brazil used in fighting against disease is carried out in this research in order to know the experiences developed with the yellow fever. In this manner, this dissertation has two mains objectives. First, the historical process of yellow fever will be analyzed by this research to understand the crisis that prevailed in studies of that disease between 1927 and 1930. For this reason, the multiple local actors, national and international in theoretical and technical field of the disease were analyzed during yellow fever outbreak in 1928-29 in Rio de Janeiro and in 1929 in Socorro. Second, several scientific manifestations against the progress of yellow fever in Brazil and Colombia were also studied from the last two major epidemics recorded in Rio de Janeiro (1928-1929) and Socorro (1929). Thus, controversies between an ideal of universal medical science represented by Rockefeller Foundation and Pan-American Conference, and the local public health practices developed to minimize the propagation of yellow fever in the period between 1930 and 1948 / Mestrado / Politica Cientifica e Tecnologica / Mestra em Política Científica e Tecnológica

O risco de transmissão placentária para o feto, associados à susceptibilidade de neuroinvasão pelo vírus 17D levaram à recomendação de que a vacina contra febre amarela (FA) não fosse administrada durante a gravidez. Pretendeu-se avaliar o efeito desta no desempenho gestacional de camundongos prenhes. Os resultados mostraram decréscimo na viabilidade fetal causado pela vacinação. Reatividade ao antígeno da FA foi observada nos tecidos hepáticos maternos e de fetos vivos. Na placenta, o antígeno viral não foi observado na barreira materno-fetal. Nos fetos natimortos e em reabsorção, esta passagem pareceu mais acentuada; reatividade foi observada em diversos órgãos. O antígeno viral foi detectado em todas as regiões placentárias. A detecção de RNA viral nas amostras indica que há atividade viral nos tecidos fetais. Nossos achados indicam que há fases gestacionais mais susceptíveis à infecção viral vacinal e que podem determinar perdas fetais. A presença do antígeno e de atividade viral no fígado fetal sugere que o vírus vacinal é transmitido da mãe para o feto. / The risk of placental transmission to the fetus, associated with susceptibility to neuroinvasion of the 17D virus led to the recommendation that the vaccine against yellow fever (YF) was not administered during pregnancy. Intended to evaluate the effect of the vaccine in gestational performance of pregnant mice. The results showed a decrease in fetal viability caused by vaccination. Antigen reactivity of YF was observed in maternal and live fetuses liver tissue. In the placenta, the viral antigen was not observed in maternal-fetal barrier. In the stillborn fetuses and resorption, this passage seemed more pronounced; reactivity was observed in several organs. The viral antigen was detected in all placental regions. The detection of viral RNA in the samples indicates that there is viral activity in fetal tissues. Our findings indicate that there are stages of pregnancy more susceptible to viral vaccine infection that could determine fetal loss. The presence of the antigen and viral activity in fetal liver suggests that the vaccine virus is transmitted from mother to fetus.

Neste projeto, objetivou-se o diagnóstico de riquétsias, utilizando metodologia molecular, em material de humanos, carrapatos, pulgas, cães e equinos de áreas endêmicas dos estados de São Paulo (SP) e Rio de Janeiro (RJ). Diagnosticou-se Rickettsia rickettsii infectando Amblyomma cajennense e humanos no estado de SP, indicando ser esta a única espécie responsável pela doença. Rickettsia conorii foi diagnosticada em um paciente procedente de Portugal. No estado do RJ, Rickettsia felis foi detectada Ctenocephalides felis e em Am. cajennense enquanto que R. rickettsii em Amblyomma aureolatum, Am. cajennense, Anocentor nitens, Boophilus microplus, Ct. felis e Rhipicephalus sanguineus. As frequências mínimas de vetores infectados do estado do RJ apresentaram valores superiores àqueles registrados em outras regiões do país. Demonstrou-se, de forma inédita, o envolvimento de algumas destas espécies no ciclo da bactéria. R. rickettsii foi diagnosticada em cães e equinos indicando a importância dos animais domésticos na manutenção do ciclo da riquetsiose. / This project aimed to diagnose rickettsial diseases using molecular analysis methods on human, tick, flea, dog and horse samples from endemic areas in the States of São Paulo (SP) and Rio de Janeiro (RJ). A diagnosis of Rickettsia rickettsii infecting Amblyomma cajennense and humans in the State of SP was made, indicating that this is the only species responsible for the disease. Rickettsia conorii was diagnosed in a patient from Portugal. In RJ, Rickettsia felis was detected in Ctenocephalides felis and Am. cajennense, while R. rickettsii was detected in Amblyomma aureolatum, Am. cajennense, Anocentor nitens, Boophilus microplus, Ct. felis and Rhipicephalus sanguineus. In the State of RJ the minimum frequency of infected vectors presented higher values than those recorded in other regions of the country. The involvement of some of these species in the bacterium cycle has been demonstrated for the first time. R. rickettsii was diagnosed in dogs and horses indicating the importance of livestock in the maintenance cycle of rickettsial infection.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease caused by a virus of the family Bunyaviridae, genus Phlebovirus. It is responsible for extensive outbreaks of disease in livestock in Africa with significant mortality and economic impact. Virus neutralization is considered the gold standard for confirming Rift Valley fever virus (RVFV) infection but the procedure is time consuming and expensive. Real-time reverse transcription-polymerase chain reaction (rRT-PCR), histopathology, and immunohistochemistry (IHC) are the diagnostic methods most often used in South Africa to confirm or exclude a diagnosis of RVF in necropsied animals. Validated estimates of diagnostic accuracy of these tests, in naturally infected livestock, however, have not been published. The objective of this study was to estimate the diagnostic sensitivity and specificity of rRT-PCR, histopathology, and IHC using Bayesian latent class methods in the absence of a gold standard. A secondary objective was to estimate stratum-specific values based on species, age, degree of specimen autolysis, and the presence/absence of tissue pigments. The Sensitivity (Se) and Specificity (Sp) of qRT-PCR were 97.4% (95% credibility interval (CI): 95.2% - 98.8%) and 71.7% (95% CI: 65% - 77.9%) respectively. The extraordinary analytical sensitivity of PCR makes this test very susceptible to false positive reactions, and thus reduced specificity. This is more likely during large-scale epidemics due to crosscontamination of specimens at necropsy facilities or testing laboratories. The Se and Sp of histopathology were 94.6% (95% CI: 91% - 97.2%) and 92.3% (95% CI: 87.6% - 95.8%) respectively. Single cases of RVF could be confused with acute poisoning with plants, bacterial septicaemias, and viral diseases such as infectious bovine rhinotracheitis and Wesselsbron disease. Most of these conditions, however, can be excluded using histological examination of the liver, special stains, bacterial culture, and toxicological or serological investigations. The Se and Sp of IHC were 97.6% (95% CI: 93.9% - 99.8%) and 99.4% (95% CI: 96.9% - 100%) respectively. Immunohistochemistry is highly specific because characteristic positive immunolabelling of the cytoplasm of hepatocytes can be correlated with the presence of hepatocellular injury typical for RVFV infection. False negative results are sometimes obtained with IHC because of reader error or loss of the antigenic epitopes due to advanced autolysis. Scant positive immunolabelling might be missed or viral proteins might be absent from sections of liver with advanced hepatocellular damage. The stratified analysis suggested differences in test accuracy in foetuses and severely autolysed specimens. The Sp of histopathology in foetuses (83.0%) was 9.3% lower than the value obtained for the sample population (92.3%). Lesions in some foetuses are more subtle and the typical eosinophilic intranuclear inclusions are often difficult to detect. In severely autolysed specimens, the Se of IHC decreased by 16.1% and the Sp of rRT-PCR by 17.4%. There is no plausible biological explanation for this decrease in the Sp of rRTPCR since the RNA of RVFV is resistant to degradation in autolysed tissues. Conversely, the antibody used to detect RVFV using IHC detects epitopes raised against nucleoproteins of the virus and it is possible that viral proteins become too widely dispersed and/or degraded in autolysed tissues to detect by light microscopy. It is possible that the marked decrease in Se of histopathology and IHC in severely autolysed specimens caused an apparent decrease in Sp of rRT-PCR, due to the latent class method. In conclusion, the high estimated Sp (99.4%) of IHC and the low Sp of rRT-PCR (71.3%) suggests that the definitive diagnosis or exclusion of RVF should not rely on a single PCR test and that IHC would be an effective confirmatory test for rRT-PCR positive field cases necropsied during an epidemic. Immunohistochemistry results from severely autolysed specimens, however, should be interpreted with caution and aborted foetuses in areas endemic for RVF should be screened using a variety of tests. The diagnostic Se and Sp of histopathology was much higher than expected confirming the value of routine post mortem examinations and histopathology of liver specimens. The most feasible RVF testing option in areas that do not have suitably equipped PCR laboratories, and where disease is often not detected in livestock until after human cases have been diagnosed, would be routine histopathology screening with IHC confirmation. Key Words: Rift Valley fever; Rift Valley fever virus; Bayesian; latent-class model; real-time reverse transcription-polymerase chain reaction; immunohistochemistry; histopathology; diagnosis; sensitivity; specificity. / Dissertation (MSc)--University of Pretoria, 2014. / gm2014 / Paraclinical Sciences / unrestricted

Introduction The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARSCoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever. Materials and methods A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed. Results 464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARSCoV-2, both with (12.50%). The presence of polyarthralgias in hands (43.75%, p<0.01) and feet (31.25%, p = 0.05) were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM (11.45%, p<0.01). The rest of the symptoms were similar among all the study groups. Conclusion SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens. Copyright: / Revisión por pares

Introduction/background: Epidemics of infectious diseases (ID) are re-occurring now more often and spreads faster into many different parts of the world due to globalization. The increasing evidence of climate change and man-made events have shown impacts to increase the emergency and re-emerging of animal- borne IDs. Studies claims that background factors of these IDs are biological, environmental and human-lifestyle related changes. The pathogen Lassa fever virus (LASV) is a zoonotic organismthat circulates in rodent reservoirs, and the animal´s hosts are rodent species (rats) of the genus Mastomys natalensis. Mastomys natalensis is primarily the reservoir species of the animal-borne disease of Lassa fever (LF) which is most prevalent in west Africa, particularly in Nigeria. Lassa fever (LF) has limited information with under-documented cases, its health effect on pregnant women especially in Nigeria is within the rural areas of Edo, Ondo, Delta, Ebony, Bauchi, Taraba and Plateau states where maternal mortalities are higher.  Aim: The overarching aim of this thesis is to analyse and discuss the health effects of Lassa fever occurrence and outcomes on pregnant women in Nigeria, with emphasis on the maternal mortality and fatality during pregnancy. Method: A statistical and systematic review was performed from retrospective studies of case series, case-control, observational and cohort studies of patients in Nigeria (pregnant women with gestation ages of pregnancy from 2 weeks –32 weeks) that tested positive to LASV. Publication status and publication date was applied for the inclusion of respective studies by electronic searches via Web of Science, Google scholar, MEDLINE and PubMed. Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines (PRISMA) was used to illustrate the flow of relevant articles in my study. R-commander and R-Studio software was used to analyze the data and to find the causal significant relationship between LF and maternal mortality using “Linear regression and linear model plot”. Result: The total number of full-text and Peer-view publications on Lassa fever virus cases was 1 609 articles. 94 articles out of the 1 609 articles were eligible for full text revision. Exclusion criteria finally yielded 6 studies that were relatively relevant to my study. However, 3 out of the 6 articles were statistically reviewed to know the influence of Lassa fever and the risk of maternal mortality during pregnancy.  Conclusion: Lassa fever occurrence have significantly shown potential increase in the severity of maternal mortality, and is predominant among pregnant women from 39 - 45 years old in Nigeria especially within the risk endemic areas of Ondo, Edo, Ebony and Bauchi states showing significant long-term diseases on LF affected pregnant women, such as encephalopathy, acute kidney dysfunction and acute kidney failure that leads to further health problems or complications like coma and sensorineural deafness.

Enteric fever remains the most common febrile illness in urban Nepal. Some individuals may have recurrent infection and some may even progress to become long term chronic carriers. The aim of this thesis was to investigate the rate and factors leading to relapse with typhoid fever in patients who were enrolled in clinical treatment trials for acute enteric fever. The results show that relapses in enteric fever is a common complication and is more likely to be associated with the treatment antimicrobial, cefixime. Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining enteric fever transmission as humans are the only known natural host. This thesis, therefore, also aimed to investigate the prevalence, characteristics, immunological responses, and mechanism of carriage of invasive Salmonella in the gallbladder by examining bile and tissue obtained from individuals who underwent cholecystectomy in Kathmandu. Data presented here demonstrate that S. Paratyphi A is almost as prevalent as S. Typhi in the gallbladder and that carriage may not be driven by antimicrobial resistance. Gallbladders that contained Salmonella were more likely to show evidence of acute inflammation with extensive neutrophil infiltrate. Chronic carriers were found to have dramatically elevated levels of IgG to O:2 and Vi antigens with high bactericidal activity yet low pro-inflammatory cytokine levels suggesting that Salmonella are stimulating a constant immunological response, in the form of antibody. S. Typhi may be controlling the inflammatory process through the expression of the Vi capsule in the gallbladder. Genome sequencing of S. Typhi isolated from chronic carriers were different from those S. Typhi causing acute disease. These data question the current dogmas surrounding the carriage of S. Typhi in gallbladder and predict a pivotal role of Vi capsule and gallstones in maintaining carriage. Therefore, prospectively identifying these individuals is paramount for rapid local and regional elimination. Furthermore, combining cytokine profiles and antibody levels may be a method of prospectively detecting carriers in the general population.

Throughout the early twentieth century, dengue fever was considered to be a nonthreatening illness, only infecting visitors of the tropics. However, in the last fifty years, there has been a resurgence of dengue fever; it is now considered to be the most consequential arbovirus, infecting more than 50 million people each year and leaving about half of the world's current population at risk of infection. The purpose of this thesis is to explore the various environmental factors that have contributed to the resurgence of dengue fever that has been seen in the last half century. Most notable of these factors are climate change and the increasing urbanization associated with population growth. Specifically, increasing temperatures and precipitation increases the available habitat for the dengue fever vector, the Aedes mosquito, while concurrently increasing both the longevity of the virus and the mosquito. Furthermore, changing sociodemographic factors associated with urbanization have helped spread the mosquito around the world, as the vector largely relies on human transportation. Finally, substandard housing often associated with insufficient water management systems creates the ideal breeding spots for the dengue vector. The Aedes mosquito is known to be one of the most versatile and one of the toughest mosquitoes in the world, which has allowed it to quickly adapt and succeed in these changing environments. Understanding these factors and their influence on the spread of dengue fever is vital in order to effectively manage current and future outbreaks. This is specifically important in regards to dengue fever and severe dengue as no vaccine or medications currently exists to treat this virus.

Varón de 15 años, con 2 meses de enfermedad caracterizada por sudoración profusa y dolor en miembros inferiores que le dificultaba caminar. El dolor aumento de intensidad asociándose después a taquipnea y disnea al caminar 50 m más náuseas y vómitos, disnea en reposo y edema de miembros inferiores. Ingreso por Emergencia al Hospital Nacional Dos de Mayo (HNDM) el 27/04/2016, presentando a su ingreso palpitaciones y disnea a pequeños esfuerzos. El Servicio de Cardiología del HNDM, diagnostico : Insuficiencia aórtica y mitral severa, insuficiencia tricúspidea leve e hipertensión pulmonar. Pulso arterial: 104 lat/min, FR: 32 resp/min, PA: 110/50 mm Hg, T°: 36,5°C, choque de la punta en 7mo espacio intercostal izquierdo, Soplo diastólico III/IV en foco aórtico, S sistólico III/IV en foco mitral, pulso radial en martillo de agua. Glucosa 74 mg/dl., creatinina 0.47 mg/dl, antiesptreptolisina (ASO) : 355 IU/ml, AAN: negativo, Hb : 11.6 g/dl, Proteínas Totales: 6.09gr/dl, albumina: 3.19gr/dl, globulina : 2.90gr/dl, Ecocardiograma: dilatación severa de aurícula y ventrículo izquierdo, hipertrofia de VI, dilatación de aurícula derecha, dilatación de arteria pulmonar y ramas. Insuficiencia severa aórtica y mitral, insuficiencia tricuspídea leve. Sometido a reemplazo valvular, hubo notable mejoria. / 15 years old, male, with 2 months clinical record characterized by profuse sweating and lower limbs pain that produced trouble on walking. Increased pain intensity was associated to tachypnea nausea,vomiting and dyspnea after walking 50 m.Beside it he had dyspnea at rest and lower limb edema. He entered to Dos de Mayo National Hospital (HNDM) on 04.27.2016, presenting palpitations and dyspnea at small efforts. HNDM, Department of Cardiology, diagnosed : severe mitral and aortic insufficiency, mild tricuspid regurgitation and pulmonary hypertension. Arterial pulse: 104 beats/min, FR: 32 breaths/min, PA: 110/50 mm Hg, T °: 36.5 ° C, tip heart beat at 7th left intercostal space, diastolic murmur III/IV at aortic focus, systolic murmur III/IV at mitral focus, water hammer radial pulse, glucose 74 mg/dl, creatinine 0.47 mg/dL, antiesptreptolisina (ASO) : 355 IU/ml, AAN: negative, Hb: 11.6 g / dl, total proteins: 6.09gr/dl, albumin: 3.19gr/dL globulin : 2.90gr/dl, Echocardiogram : severe dilated atrium and left ventricle hypertrophy, dilated right atrium, pulmonary artery and branches dilatation. Severe aortic and mitral insufficiency, mild tricuspid regurgitation. After valve replacement, the patient showed remarkable improvement.