Emergence of melioidosis in Brazil: a case series.

BACKGROUND: Melioidosis is a serious disease caused by the bacterium Burkholderia pseudomallei which affects humans and animals. It results in a wide spectrum of clinical manifestations, mainly in the respiratory tract, progressing to septic shock and death. CASE PRESENTATION: Herein, we present a series of seven patients (median age: 41 years) with confirmed melioidosis, treated at a public hospital in Piauí State, Brazil between 2019 and 2021. The most common clinical presentations were fever, cough, pneumonia, and abdominal pain. The mean duration of antibacterial therapy with 1 g of meropenem was 28.6 ± 1.1 days. Six patients recovered and one died. The mean hospitalization time was 51.0 ± 39.2 days. CONCLUSIONS: Melioidosis is an emerging infectious disease in Brazil. Health professionals in endemic areas need to be aware of the clinical presentation and appropriate clinical management of the disease because early diagnosis and early initiation of antibiotic therapy can be life-saving.

Melioidosis in Children, Brazil, 1989-2019.

We studied 20 confirmed or suspected cases of melioidosis in children in Ceará, Brazil, during 1989-2019. We observed a high death rate, severe signs and symptoms, and substantial environmental exposure. These data suggest that childhood melioidosis might be more severe in Brazil than in other regions.

Genomic Diversity of Burkholderia pseudomallei in Ceara, Brazil.

Burkholderia pseudomallei is a Gram-negative bacterium that causes the sapronotic disease melioidosis. An outbreak in 2003 in the state of Ceara, Brazil, resulted in subsequent surveillance and environmental sampling which led to the recognition of B. pseudomallei as an endemic pathogen in that area. From 2003 to 2015, 24 clinical and 12 environmental isolates were collected across Ceara along with one from the state of Alagoas. Using next-generation sequencing, multilocus sequence typing, and single nucleotide polymorphism analysis, we characterized the genomic diversity of this collection to better understand the population structure of B. pseudomallei associated with Ceara. We found that the isolates in this collection form a distinct subclade compared to other examples from the Western Hemisphere. Substantial genetic diversity among the clinical and environmental isolates was observed, with 14 sequence types (STs) identified among the 37 isolates. Of the 31,594 core single-nucleotide polymorphisms (SNPs) identified, a high proportion (59%) were due to recombination. Because recombination events do not follow a molecular clock, the observation of high occurrence underscores the importance of identifying and removing recombination SNPs prior to evolutionary reconstructions and inferences in public health responses to B. pseudomallei outbreaks. Our results suggest long-term B. pseudomallei prevalence in this recently recognized region of melioidosis endemicity.IMPORTANCEB. pseudomallei causes significant morbidity and mortality, but its geographic prevalence and genetic diversity are not well characterized, especially in the Western Hemisphere. A better understanding of the genetic relationships among clinical and environmental isolates will improve knowledge of the population structure of this bacterium as well as the ability to conduct epidemiological investigations of cases of melioidosis.

Melioidosis in South America.

Melioidosis is an emerging disease in the Americas. This paper reviews confirmed cases, the presence of Burkholderia pseudomallei and the organization of national surveillance policies for melioidosis in South America. Confirmed cases in humans have been reported from Ecuador, Venezuela, Colombia, Brazil, and Peru. The bacterium has been isolated from the environment in Brazil and Peru. The state of Ceará, northeastern region of Brazil, is the only place where specific public strategies and policies for melioidosis have been developed. We also discuss the urgent need for health authorities in South America to pay greater attention to this disease, which has the potential to have a high impact on public health, and the importance of developing coordinated strategies amongst countries in this region.

Postmortem Findings for 7 Neonates with Congenital Zika Virus Infection.

Postmortem examination of 7 neonates with congenital Zika virus infection in Brazil revealed microcephaly, ventriculomegaly, dystrophic calcifications, and severe cortical neuronal depletion in all and arthrogryposis in 6. Other findings were leptomeningeal and brain parenchymal inflammation and pulmonary hypoplasia and lymphocytic infiltration in liver and lungs. Findings confirmed virus neurotropism and multiple organ infection.

Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis.

Burkholderia pseudomallei, a highly pathogenic bacterium that causes melioidosis, is commonly found in soil in Southeast Asia and Northern Australia(1,2). Melioidosis can be difficult to diagnose due to its diverse clinical manifestations and the inadequacy of conventional bacterial identification methods(3). The bacterium is intrinsically resistant to a wide range of antimicrobials, and treatment with ineffective antimicrobials may result in case fatality rates (CFRs) exceeding 70%(4,5). The importation of infected animals has, in the past, spread melioidosis to non-endemic areas(6,7). The global distribution of B. pseudomallei and the burden of melioidosis, however, remain poorly understood. Here, we map documented human and animal cases and the presence of environmental B. pseudomallei and combine this in a formal modelling framework(8-10) to estimate the global burden of melioidosis. We estimate there to be 165,000 (95% credible interval 68,000-412,000) human melioidosis cases per year worldwide, from which 89,000 (36,000-227,000) people die. Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is probably endemic in a further 34 countries that have never reported the disease. The large numbers of estimated cases and fatalities emphasize that the disease warrants renewed attention from public health officials and policy makers.

Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis.

Burkholderia pseudomallei, a highly pathogenic bacterium that causes melioidosis, is commonly found in soil in Southeast Asia and Northern Australia1,2. Melioidosis can be difficult to diagnose due to its diverse clinical manifestations and the inadequacy of conventional bacterial identification methods3. The bacterium is intrinsically resistant to a wide range of antimicrobials, and treatment with ineffective antimicrobials may result in case fatality rates (CFRs) exceeding 70%4,5. The importation of infected animals has, in the past, spread melioidosis to non-endemic areas6,7. The global distribution of B. pseudomallei and burden of melioidosis, however, remain poorly understood. Here, we map documented human and animal cases, and the presence of environmental B. pseudomallei, and combine this in a formal modelling framework8-10 to estimate the global burden of melioidosis. We estimate there to be 165,000 (95% credible interval 68,000-412,000) human melioidosis cases per year worldwide, of which 89,000 (36,000-227,000) die. Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is likely endemic in a further 34 countries which have never reported the disease. The large numbers of estimated cases and fatalities emphasise that the disease warrants renewed attention from public health officials and policy makers.

A Review of Melioidosis Cases in the Americas.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, a gram-negative saprophytic bacillus. Cases occur sporadically in the Americas with an increasing number of cases observed among people with no travel history to endemic countries. To better understand the incidence of the disease in the Americas, we reviewed the literature, including unpublished cases reported to the Centers for Disease Control and Prevention. Of 120 identified human cases, occurring between 1947 and June 2015, 95 cases (79%) were likely acquired in the Americas; the mortality rate was 39%. Burkholderia pseudomallei appears to be widespread in South, Central, and North America.

Melioidosis diagnostic workshop, 2013.

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions.

Severe coinfection of melioidosis and dengue fever in Northeastern Brazil: first case report.

This report focuses on a fatality involving severe dengue fever and melioidosis in a 28-year-old truck driver residing in Pacoti in northeastern Brazil. He exhibited long-term respiratory symptoms (48 days) and went through a wide-ranging clinical investigation at three hospitals, after initial clinical diagnoses of pneumonia, visceral leishmaniasis, tuberculosis, and fungal sepsis. After death, Burkholderia pseudomallei was isolated in a culture of ascitic fluid. Dengue virus type 1 was detected by polymerase chain reaction in cerebrospinal fluid (CSF); this infection was the cause of death. This description reinforces the need to consider melioidosis among the reported differential diagnoses of community-acquired infections where both melioidosis and dengue fever are endemic.

Severe coinfection of melioidosis and dengue fever in northeastern Brazil: first case report / Coinfecção grave de melioidose e dengue no nordeste do Brasil: primeiro caso

This report focuses on a fatality involving severe dengue fever and melioidosis in a 28-year-old truck driver residing in Pacoti in northeastern Brazil. He exhibited long-term respiratory symptoms (48 days) and went through a wide-ranging clinical investigation at three hospitals, after initial clinical diagnoses of pneumonia, visceral leishmaniasis, tuberculosis, and fungal sepsis. After death, Burkholderia pseudomallei was isolated in a culture of ascitic fluid. Dengue virus type 1 was detected by polymerase chain reaction in cerebrospinal fluid (CSF); this infection was the cause of death. This description reinforces the need to consider melioidosis among the reported differential diagnoses of community-acquired infections where both melioidosis and dengue fever are endemic.

Estudo de caso fatal de coinfecção de melioidose e dengue grave em um motorista de 28 anos, residente no município de Pacoti, nordeste do Brasil. O paciente apresentou inicialmente sintomas respiratórios com evolução por 48 dias. Foi internado em três diferentes unidades de saúde com suspeitas de pneumonia, leishmaniose visceral, tuberculose e sepse fúngica. Após o óbito, a cultura de líquido ascítico identificou a bactéria Burkholderia pseudomallei. O vírus da dengue tipo 1 foi detectado por PCR no líquor do paciente. Esta descrição reforça a necessidade de considerar a melioidose entre os diagnósticos diferenciais de infecções comunitárias onde as duas doenças são endêmicas.

Burkholderia pseudomallei antibodies in individuals living in endemic regions in Northeastern Brazil.

A seroepidemiological investigation was conducted among the population of two municipalities in Northeastern Brazil. Immunoglobulin M (IgM) and IgG antibodies to Burkholderia pseudomallei were positive in 51.27% (161 in 317 samples) and 58.49% (186), respectively. IgM titers were higher in children than in adults. On the contrary, IgG increased progressively with age. We observed a significant association between agricultural occupation and raised IgM titers (P < 0.005) and IgG titers (P < 0.001), and between construction workers and raised IgG titers (P = 0.005). Antibody IgG avidities did not correlate with age. The highest titers of antibodies (1/800) showed the highest antibody avidity indexes (P < 0.01). Most of the serum samples recognized 45-kDa and 200-kDa bands by IgG1 and IgG2 subclasses. Our study showed a high seropositivity among individuals living in endemic regions of the state of Ceará, and highlights the need for further surveillance close to water courses such as dams and rivers in Northeastern Brazil.

Microepidemia de doença de Chagas aguda por transmissão oral no Ceará. / Microepidemics of acute Chagas' disease by oral transmission in Ceará.

No Brasil, em virtude das ações de controle, a transmissão vetorial da doença de Chagas foi reduzida. Por outro lado, vêm se destacando casos de transmissão por via oral. Esse trabalho relata a investigação de um surto de doença de Chagas aguda ocorrido no interior do Ceará no ano de 2006, cuja transmissão se deu provavelmente por via oral. O estudo foi realizado através de revisão de prontuários; entrevistas com pacientes, familiares e profissionais de saúde; achados laboratoriais e da investigação ambiental e entomológica. A microepidemia acometeu 8 integrantes de uma família que estiveram juntos nas férias do mês de janeiro de 2006. Duas mulheres e seis crianças, com idade variando entre 2 e 35 anos. Todos apresentaram quadro inicial de febre, cefaleia, náuseas, vômitos, mialgia e diarreia. Três semanas após o início dos sintomas apresentaram quadro de edema de membros inferiores e de face. Ao exame físico, além de edema, todos apresentaram hepatoesplenomegalia e linfoadenomegalia. O diagnóstico foi confirmado através da demonstração direta de amastigota em linfonodo, tecido muscular e medula. Anticorpos IgM contra Trypanosoma cruzi foram detectados em soro pelo método de hemaglutinação indireta. Todas as culturas para Trypanosoma cruzi foram positivas. A possível fonte de contaminação foi uma sopa à qual tinham sido adicionados coentro e cebolinha liquidificados, provenientes de uma horta domiciliar.

In Brazil, due to control actions, vectorial transmission of Chagas? disease has been largely reduced. On the other hand, oral transmission cases are showing up. This work reports the investigation of an outbreak of acute Chagas? disease in the inland of Ceará state in the year 2006 in which transmission occurred probably by oral route. This research was done through analysis of medical records, interviews with patients, their relatives and health professionals, laboratory data and environmental and entomological investigation. The microepidemics hit eight members of a family that were together on vacations in January 2006: two women and six children, ages ranging from 2 to 35 years. All of them shown initial clinical manifestations of headache, nausea, vomit, myalgia and diarrhea. Three weeks after these initial symptoms they shown edema of the lower limbs and face. Under clinical examination, besides edema, all of them shown hepatosplenomegaly and lymphadenomegaly. Diagnostic was confirmed by direct visualization of amastigota forms in lymph nodes, muscular tissue and bone marrow. IgM antibodies against Trypanosoma cruzi were detected on the serum by indirect hemagglutination assay. All cultures for Trypanosoma cruzi were positive. The probable contamination source was a stew into which liquid coriander and scallion from an orchard were added.

Burkholderia pseudomallei no estado do Ceará: caracterização de reservárias / Burkholderia pseudomallei in the state of Ceará: characterization of reservárias

A melioidose, uma enfermidade causada pelo bacilo Gram-negativo, Burholderia pseudomallei, é endêmica no sudeste da Ásia e na Austrália e tem distribuição esporádica em outras partes do mundo. A doença é descrita nas Américas, sendo emergente no Brasil desde que casos em humanos são bem documentados no Estado do Ceará. Esta pesquisa pretendeu compreender melhor a ecologia da bactéria por meios da caracterização de suas reservárias. O estudo foi realizado em uma pesquisa ambiental de B. pseudomallei no solo dos Municípios de Tejuçuoca e Banabuiú e ma realização de inquérito soro-epidemiológico para a população rural residente nesses locais. Para o estudo ambiental, foram coletadas amostras mensais de solo da superfície até 40 cm de profundidade durante o período de janeiro a dezembro do ano de 2007. Cinco sítios de coleta em cada município, delimitados na residência de pessoas que tiveram melioidose. Para a realização do estudo sorológico, foram coletadas amostras de soro de 321 residentes nessas áreas e efetivado inquérito, que incluiu informações sobre dados demográficos, história de doenças prévias e atividades com exposição relativas a solo e água. A determinação dos títulos sorológicos de anticorpos foi realizada mediante teste imunoenzimático, utilizando microplacas adsorvidas com antígeno filtrado de B. pseudomallei. A bactéria foi encontrada no solo dos Municípios de Tejuçuoca e Banabuiú em 4,3 % (26/600) das amostras investigadas. As duas regiões apresentaram aspectos geoclimáticos e componentes ambientais, como tipo de solo e vegetação, índice pluviométrico, temperatura similares entre si. A detecção de B. pseudomallei ocorreu em clima tropical semi-árido, com índice pluviométrico anual baixo e vegetação de caatinga arbustiva, demonstrando influência de fatores locais que facilitam a sobrevivência e multiplicação do microorganismo...

Melioidosis in the Americas.

Melioidosis is a potentially severe bacterial infection caused by Burkholderia pseudomallei. There has been growing awareness of the disease in the Americas, particularly since the Vietnam conflict when it was diagnosed in returning service personnel. Accidental laboratory exposure indicates the difficulty making a culture-based diagnosis when melioidosis has not been considered in the differential diagnosis. Melioidosis is most likely underdiagnosed in tropical Central and South America where conditions are more suited to persistence of B. pseudomallei in the environment. Recent melioidosis case clusters in northeastern Brazil highlight the threat posed to rural populations located far from specialist services. Increased clinical awareness of the disease and improvements in laboratory diagnostic methods are likely to bring wider recognition of melioidosis in the Americas.

Clinical guideline for diagnosis and management of melioidosis.

Melioidosis is an emerging infection in Brazil and neighbouring South American countries. The wide range of clinical presentations include severe community-acquired pneumonia, septicaemia, central nervous system infection and less severe soft tissue infection. Diagnosis depends heavily on the clinical microbiology laboratory for culture. Burkholderia pseudomallei, the bacterial cause of melioidosis, is easily cultured from blood, sputum and other clinical samples. However, B. pseudomallei can be difficult to identify reliably, and can be confused with closely related bacteria, some of which may be dismissed as insignificant culture contaminants. Serological tests can help to support a diagnosis of melioidosis, but by themselves do not provide a definitive diagnosis. The use of a laboratory discovery pathway can help reduce the risk of missing atypical B. pseudomallei isolates. Recommended antibiotic treatment for severe infection is either intravenous Ceftazidime or Meropenem for several weeks, followed by up to 20 weeks oral treatment with a combination of trimethoprim-sulphamethoxazole and doxycycline. Consistent use of diagnostic microbiology to confirm the diagnosis, and rigorous treatment of severe infection with the correct antibiotics in two stages; acute and eradication, will contribute to a reduction in mortality from melioidosis.

Clinical guideline for diagnosis and management of melioidosis

Melioidose é uma infecção emergente no Brasil e em países vizinhos da América do Sul. O amplo espectro de apresentação clínica inclui pneumonia adquirida na comunidade, septicemia, infecção do sistema nervoso central e infecção de partes moles de menor severidade. O diagnóstico depende essencialmente da identificação microbiológica. Burkholderia pseudomallei, a causa bacteriana da melioidose, é facilmente cultivada em sangue, escarro e em outras amostras clínicas. Entretanto, B. pseudomallei pode ser difícil de identificar com segurança e também ser confundido com outras bactérias Gram negativas. Os exames sorológicos podem dar suporte a um diagnóstico de melioidose, mas não fornece um diagnóstico definitivo por si só. A realização de investigação laboratorial seqüenciada pode ajudar a reduzir o risco de não reconhecer isolados incomuns de B. pseudomallei. O tratamento antibiótico recomendado para infecção severa é Ceftazidima ou Meropenem endovenosos por várias semanas, seguido por um tratamento oral com uma combinação de Sulfametoxazol-Trimetopim e Doxiciclina por até 20 semanas. O uso consistente do diagnóstico microbiológico e o tratamento rigoroso da infecção severa com antibióticos adequados nas duas etapas, aguda e de erradicação, contribuirão para a redução da mortalidade por melioidose.

Melioidosis, northeastern Brazil.

Melioidosis was first recognized in northeastern Brazil in 2003. Confirmation of additional cases from the 2003 cluster in Ceará, more recent cases in other districts, environmental isolation of Burkholderia pseudomallei, molecular confirmation and typing results, and positive serosurveillance specimens indicate that melioidosis is more widespread in northeastern Brazil than previously thought.

Acidose lática fatal associada com terapia anti-retroviral: Relato de dois casos e revisão da literatura / Fatal lactic acidosis associated with antiretroviral therapy: report of two cases and literature review

A terapia anti-retroviral, começando em 1987 com a droga zidovudina (AZT) e posteriormente com outros nucleosideos inibidores da transcriptase reversa, inibidores não-nucleosídeos e inibidores da protease, reduziram significantemente as taxas de morbidade e mortalidade entre pacientes HIV-positivos. A terapia, entretanto, tem sido acompanhada por um numero de efeitos adversos graves, tais como alterações lipidicas, hiperglicemia, lipodistrofia, rash cutaneo e alteracoes mitocontriais, a maioria delas relacionada ao uso dos nucleosideos inibidores e culminando em acidose latica extremamente grave. Apresentamos, neste artigo, dois casos de acidose latica fatal que ocorreram em nosso serviço de atencao a saude e associados com o uso de nucleosideos analogos. Deve-se chamar atencao, neste contexto, a combinacao frequente de estavudina e didanosina.