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Introduction: Mayaro Fever (MF) is a tropical disease caused by the Mayaro virus (MAYV), with outbreaks documented in Latin America. Methods: A hospital-based fever surveillance in Leticia, Colombian Amazon, collected sera from 1,460 patients aged 5-89 between December 2020 and April 2023. Results: Dengue and malaria were the main diagnoses (19.4 and 5.8%, respectively), leaving 71.4% of cases unidentified after testing. Metagenomic sequencing and real-time RT-qPCR testing identified MAYV in two patients (25-year-old male and an 80-year-old female) exhibiting typical symptoms, of MF including rash, joint pain, and fever. Phylogenetics analysis of these two viruses revealed a close relationship to Peruvian strains within the MAYV D genotype. Discussion: The study of AFI in Leticia, Colombia, identified dengue as prevalent, with malaria, COVID-19, Influenza, and Zika viruses also detected. Despite extensive testing, most cases remained unexplained until metagenomic sequencing revealed MAYV, previously unseen in Colombia but known in neighboring countries. Conclusion: This study presents the first near full-length genomes of MAYV in Colombia, highlighting the need for further seroprevalence studies and enhanced surveillance to understand and control the spread of the virus in the region.
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Acute febrile illness (AFI) and severe neurological disorders (SNDs) often present diagnostic challenges due to their potential origins from a wide range of infectious agents. Nanopore metagenomics is emerging as a powerful tool for identifying the microorganisms potentially responsible for these undiagnosed clinical cases. In this study, we aim to shed light on the etiological agents underlying AFI and SND cases that conventional diagnostic methods have not been able to fully elucidate. Our approach involved analyzing samples from fourteen hospitalized patients using a comprehensive nanopore metagenomic approach. This process included RNA extraction and enrichment using the SMART-9N protocol, followed by nanopore sequencing. Subsequent steps involved quality control, host DNA/cDNA removal, de novo genome assembly, and taxonomic classification. Our findings in AFI cases revealed a spectrum of disease-associated microbes, including Escherichia coli, Streptococcus sp., Human Immunodeficiency Virus 1 (Subtype B), and Human Pegivirus. Similarly, SND cases revealed the presence of pathogens such as Escherichia coli, Clostridium sp., and Dengue virus type 2 (Genotype-II lineage). This study employed a metagenomic analysis method, demonstrating its efficiency and adaptability in pathogen identification. Our investigation successfully identified pathogens likely associated with AFI and SNDs, underscoring the feasibility of retrieving near-complete genomes from RNA viruses. These findings offer promising prospects for advancing our understanding and control of infectious diseases, by facilitating detailed genomic analysis which is critical for developing targeted interventions and therapeutic strategies.
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Metagenômica , Sequenciamento por Nanoporos , Humanos , Metagenômica/métodos , Sequenciamento por Nanoporos/métodos , Masculino , Feminino , Doenças do Sistema Nervoso/microbiologia , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/virologia , Adulto , Pessoa de Meia-Idade , Nanoporos , Idoso , Metagenoma/genética , Febre/microbiologia , Febre/virologia , Escherichia coli/genéticaRESUMO
BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.
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COVID-19 , Influenza Humana , Humanos , Peru , Influenza Humana/epidemiologia , Estudos de Casos e Controles , SARS-CoV-2 , Febre/epidemiologia , Reação em Cadeia da Polimerase , Instalações de Saúde , Teste para COVID-19RESUMO
Context: Acute febrile disease (AFI) in endemic tropical areas is a frequent reason for consulting the emergency services. Infection by 2 or more etiological agents may modify clinical and laboratory parameters, making diagnosis and treatment a challenge. Case report: We report the case of a patient who came from Africa and consults in Colombia, with AFI with thrombocytopenia that was eventually diagnosed to have concurrent infection with Plasmodium falciparum malaria and dengue. Conclusions: Dengue-malaria coinfection infection reports are scarce; it should be suspected in patients living or returning from areas where both diseases are endemic or during dengue outbreaks. This case serves as a reminder of this important condition that causes high morbidity and mortality if it is not early diagnosed and treated.
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Arbovirus infections are frequent causes of acute febrile illness (AFI) in tropical countries. We conducted health facility-based AFI surveillance at four sites in Colombia (Cucuta, Cali, Villavicencio, Leticia) during 2019-2022. Demographic, clinical and risk factor data were collected from persons with AFI that consented to participate in the study (n = 2,967). Serologic specimens were obtained and tested for multiple pathogens by RT-PCR and rapid test (Antigen/IgM), with 20.7% identified as dengue positive from combined testing. Oropouche virus (OROV) was initially detected in serum by metagenomic next-generation sequencing (mNGS) and virus target capture in a patient from Cúcuta. Three additional infections from Leticia were confirmed by conventional PCR, sequenced, and isolated in tissue culture. Phylogenetic analysis determined there have been at least two independent OROV introductions into Colombia. To assess OROV spread, a RT-qPCR dual-target assay was developed which identified 87/791 (10.9%) viremic cases in AFI specimens from Cali (3/53), Cucuta (3/19), Villavicencio (38/566), and Leticia (43/153). In parallel, an automated anti-nucleocapsid antibody assay detected IgM in 27/503 (5.4%) and IgG in 92/568 (16.2%) patients screened, for which 24/68 (35.3%) of PCR positives had antibodies. Dengue was found primarily in people aged <18 years and linked to several clinical manifestations (weakness, skin rash and petechiae), whereas Oropouche cases were associated with the location, climate phase, and odynophagia symptom. Our results confirm OROV as an emerging pathogen and recommend increased surveillance to determine its burden as a cause of AFI in Colombia.
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Infecções por Bunyaviridae , Humanos , Colômbia/epidemiologia , Filogenia , Infecções por Bunyaviridae/complicações , Infecções por Bunyaviridae/epidemiologiaRESUMO
We conducted enhanced acute febrile illness surveillance in an urban slum community in Salvador, Brazil. We found that rickettsial infection accounted for 3.5% of urgent care visits for acute fever. Our results suggest that rickettsiae might be an underrecognized, treatable cause of acute febrile illness in impoverished urban populations in Brazil.
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Infecções por Rickettsia , Rickettsia , Anticorpos Antibacterianos , Brasil/epidemiologia , Febre/epidemiologia , Humanos , Áreas de Pobreza , Infecções por Rickettsia/diagnóstico , Infecções por Rickettsia/epidemiologiaRESUMO
The Acute Febrile Illness (AFI) Surveillance Network in Belize is a country-wide active surveillance program aimed at diagnosing vector-borne, respiratory, and enteric pathogens among patients presenting to 11 participating hospitals and clinics with new onset fever. This study describes the epidemiology of dengue virus (DENV) infections in Belize diagnosed through AFI surveillance in 2020. Of the 894 patients enrolled and PCR-tested for DENV in this period, 44 DENV-positive cases (5%) were identified. All four DENV serotypes were detected, with two cases testing positive for DENV serotype 4, which is the first report of this serotype in Belize since 2004. The majority of DENV cases (66%) were diagnosed in the Belize District, which contains the largest urban center in the country (Belize City). Positive cases were detected between January 2020 and September 2020, with the majority (89%) diagnosed during the dry season between January and April, unlike years prior when cases were more often diagnosed during the wet season. Clinical signs and symptoms varied slightly between DENV serotypes. Active surveillance of DENV among AFI cases provides insight into the epidemiologic and clinical characteristics of DENV in Belize. This information is important for informing public health interventions to mitigate DENV transmission.
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Vírus da Dengue , Dengue , Viroses , Belize , Dengue/diagnóstico , Dengue/epidemiologia , Vírus da Dengue/genética , Febre/epidemiologia , HumanosRESUMO
OBJECTIVE: To describe a severe case of infection by Leptospira in a woman in the northwest of Mexico. CASE REPORT: A 55-yearold woman from Sonora, México arrived at the Intensive Care Unit due to severe multiple organ failure primarily affecting the respiratory, renal and hepatic systems. Diagnostic tests were performed, and they were positive for anti-Leptospira antibodies, IgM and IgG; and spirochetes were observed on dark field microscopy and confirmed by Polymerase Chain Reaction (PCR). Doxycycline and platelet apheresis transfusion were used as treatment, which led to a very slow recovery. CONCLUSION: The information presented in this study may help in the identification of pathology caused by spirochetes. This case report is the first to present a case of severe leptospirosis in Sonora, México.
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Leptospira , Leptospirose , Insuficiência de Múltiplos Órgãos/microbiologia , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/sangue , Doxiciclina/uso terapêutico , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Unidades de Terapia Intensiva , Leptospira/genética , Leptospira/crescimento & desenvolvimento , Leptospirose/complicações , Leptospirose/diagnóstico , Leptospirose/microbiologia , Leptospirose/terapia , México , Microscopia/métodos , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/terapia , Transfusão de Plaquetas , Reação em Cadeia da Polimerase , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Acute febrile illness (AFI) represent a significant health challenge in the Peruvian Amazon basin population due to their diverse etiologies and the unavailability of specific on-site diagnostic methods, resulting in underreporting of cases. In Peru, one of the most endemic regions to dengue and leptospirosis is Madre de Dios, a region also endemic to emergent bacterial etiologic agents of AFI, such as bartonellosis and rickettsiosis, whose prevalence is usually underreported. We aimed to molecularly identify the presence of Leptospira spp., Bartonella bacilliformis, and Rickettsia spp. by Polymerase Chain Reaction in serum samples from patients with AFI from Puerto Maldonado-Madre de Dios in Peru. METHODS: Serum samples from patients with acute febrile illness were analyzed by real-time PCR for detecting the presence of Bartonella bacilliformis, Leptospira spp. and Rickettsia spp. RESULTS: Bartonella bacilliformis was the most prevalent bacteria identified in 21.6% (30/139) of the samples, followed by Leptospira spp. in 11.5% (16/139) and Rickettsia spp. in 6.5% (9/139) of the samples. No co-infections were observed between these bacteria. The most frequent symptoms associated with fever among all groups, were headaches, myalgias, and arthralgias. We found no statistically significant differences in the clinical presentation between patients infected with each bacterium. CONCLUSIONS: In a previous study, we shown the presence of dengue, chikungunya, Zika and oropouche virus. We were able to identify these pathogens in 29.5% of all the samples, with chikungunya and OROV as the most frequently found in 9.4 and 8.6% of all the samples, respectively. In this study we show that B. bacilliformis (21.6%), Leptospira spp. (11.5%) and Rickettsia spp. (6.5%) accounted for the main etiologies of AFI in samples from Puerto Maldonado-Madre de Dios, Perú. Our analysis of their clinical presentation, further shows the importance of implementing more sensitive and specific on-site diagnostic tools in the national surveillance programs.This study confirms that the un-specificity of signs and symptoms is not only associated with arboviral infections, but also with the clinical presentation of endemic bacterial infections.
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Infecções por Bartonella , Bartonella bacilliformis/genética , Leptospira/genética , Leptospirose , Infecções por Rickettsia , Rickettsia/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Bartonella/diagnóstico , Infecções por Bartonella/epidemiologia , Infecções por Bartonella/genética , Infecções por Bartonella/microbiologia , Bartonella bacilliformis/isolamento & purificação , Criança , Pré-Escolar , Coinfecção , Estudos Transversais , Feminino , Febre/diagnóstico , Febre/epidemiologia , Febre/microbiologia , Humanos , Lactente , Recém-Nascido , Leptospira/isolamento & purificação , Leptospirose/diagnóstico , Leptospirose/epidemiologia , Leptospirose/microbiologia , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Peru/epidemiologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Rickettsia/isolamento & purificação , Infecções por Rickettsia/diagnóstico , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/microbiologia , Rios , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: The causes of acute febrile illness (AFI) in Latin America are diverse and their complexity increases as the proportion of fever due to malaria decreases, as malaria control measures and new pathogens emerge in the region. In this context, it is important to shed light on the gaps in the epidemiological characteristics and the geographic range for many AFI aetiologies. OBJECTIVES: To review studies on community-acquired fever aetiology other than malaria in Latin America, and to highlight knowledge gaps and challenges needing further investigation. SOURCES: PubMed from 2012 to April 2018. CONTENT: We found 17 eligible studies describing 13 539 patients. The median number of pathogens tested per individual was 3.5 (range 2-17). A causative pathogen could be determined for 6661 (49.2%) individuals. The most frequently reported pathogen during the study periods was dengue virus (DENV) (14 studies), followed by chikungunya virus (nine studies) and Zika virus (seven studies). Among the studies reporting concurrent infections, 296 individuals (2.2%) were found to have co-infections. In-hospital mortality was reported in eight (47%) studies, ranging between 0% and 18%. IMPLICATIONS: DENV fever is the febrile illness most frequently reported, reflecting its importance, while chikungunya and zika viruses present increasing trends since their emergence in the region. Studies with systematic and harmonized approaches for detection of multiple pathogens are needed and would probably reveal a higher burden of neglected pathogens such as Rickettsia spp. and arenaviruses. The lack of point-of-care tests and harmonized approach limits the care provided by health professionals and the efficacy of surveillance for AFI in the region.
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Febre/epidemiologia , Febre/etiologia , Doença Aguda , Coinfecção/epidemiologia , Coinfecção/etiologia , Febre/diagnóstico , Febre/terapia , Geografia Médica , Mortalidade Hospitalar , Humanos , América Latina/epidemiologia , Vigilância da População , PrevalênciaRESUMO
BACKGROUND: With their increasing availability in resource-limited settings, mobile phones may provide an important tool for participatory syndromic surveillance, in which users provide symptom data directly into a centralized database. OBJECTIVE: We studied the performance of a mobile phone app-based participatory syndromic surveillance system for collecting syndromic data (acute febrile illness and acute gastroenteritis) to detect dengue virus and norovirus on a cohort of children living in a low-resource and rural area of Guatemala. METHODS: Randomized households were provided with a mobile phone and asked to submit weekly reports using a symptom diary app (Vigilant-e). Participants reporting acute febrile illness or acute gastroenteritis answered additional questions using a decision-tree algorithm and were subsequently visited at home by a study nurse who performed a second interview and collected samples for dengue virus if confirmed acute febrile illness and norovirus if acute gastroenteritis. We analyzed risk factors associated with decreased self-reporting of syndromic data using the Vigilant-e app and evaluated strategies to improve self-reporting. We also assessed agreement between self-report and nurse-collected data obtained during home visits. RESULTS: From April 2015 to June 2016, 469 children in 207 households provided 471 person-years of observation. Mean weekly symptom reporting rate was 78% (range 58%-89%). Households with a poor (<70%) weekly reporting rate using the Vigilant-e app during the first 25 weeks of observation (n=57) had a greater number of children (mean 2.8, SD 1.5 vs mean 2.5, SD 1.3; risk ratio [RR] 1.2, 95% CI 1.1-1.4), were less likely to have used mobile phones for text messaging at study enrollment (61%, 35/57 vs 76.7%, 115/150; RR 0.6, 95% CI 0.4-0.9), and were less likely to access care at the local public clinic (35%, 20/57 vs 67.3%, 101/150; RR 0.4, 95% CI 0.2-0.6). Parents of female enrolled participants were more likely to have low response rate (57.1%, 84/147 vs 43.8%, 141/322; RR 1.4, 95% CI 1.1-1.9). Several external factors (cellular tower collapse, contentious elections) were associated with periods of decreased reporting. Poor response rate (<70%) was associated with lower case reporting of acute gastroenteritis, norovirus-associated acute gastroenteritis, acute febrile illness, and dengue virus-associated acute febrile illness (P<.001). Parent-reported syndromic data on the Vigilant-e app demonstrated agreement with nurse-collected data for fever (kappa=.57, P<.001), vomiting (kappa=.63, P<.001), and diarrhea (kappa=.61, P<.001), with decreased agreement as the time interval between parental report and nurse home visit increased (<1 day: kappa=.65-.70; ≥2 days: kappa=.08-.29). CONCLUSIONS: In a resource-limited area of rural Guatemala, a mobile phone app-based participatory syndromic surveillance system demonstrated a high reporting rate and good agreement between parental reported data and nurse-reported data during home visits. Several household-level and external factors were associated with decreased syndromic reporting. Poor reporting rate was associated with decreased syndromic and pathogen-specific case ascertainment.
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Telefone Celular/estatística & dados numéricos , Febre/terapia , Gastroenterite/terapia , Aplicativos Móveis/estatística & dados numéricos , Vigilância de Evento Sentinela , Doença Aguda , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Guatemala , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco , População RuralRESUMO
BACKGROUND: Malaria is endemic in countries located in tropical and sub-tropical regions. The increasing flow of domestic and international travellers has made malaria a relevant health problem even in non-endemic regions. Malaria has been described as the main diagnosis among travellers presenting febrile diseases after returning from tropical countries. In Brazil, malaria transmission occurs mainly in the Amazon region. Outside this area, malaria transmission is of low magnitude. METHODS: This cross-sectional study aimed to describe the experience in the diagnosis of malaria in a reference centre located outside the Brazilian Amazon Region, emphasizing the differences in clinical and laboratory markers between cases of malaria and those of other febrile diseases (OFD). Medical charts from adult patients (≥18 years) who underwent a thick smear test (TST) for malaria, between January 2001 and December 2014, were retrospectively reviewed. RESULTS: A total of 458 cases referred to perform the TST were included. Malaria was diagnosed in 193 (42 %) episodes. The remaining 265 episodes (58 %) were grouped as OFD. The majority of malaria episodes were acquired in the Brazilian Amazon Region. The median time between the onset of symptoms and the TST was 7 days. Only 53 (11.5 %) episodes were tested within the first 48 h after symptom onset. Comparing malaria with OFD, jaundice, nausea, vomiting, and reports of fever were more prevalent in the malaria group. Low platelet count and elevated bilirubin levels were also related to the diagnosis of malaria. CONCLUSIONS: The results indicate that outside the endemic area travellers presenting febrile disease suspected of being malaria underwent diagnostic test after considerable delay. The reporting of fever combined with a recent visit to an endemic area should promptly evoke the hypothesis of malaria. In these cases, specific diagnostic tests for malaria should be a priority. For cases that jump this step, the presence of elevated bilirubin or thrombocytopaenia should also indicate a diagnosis of malaria.