Análisis de serie de tiempo de patrones estacionales en defunciones por neumonía en el Perú, periodo 2003-2017

Introducción. Es un concepto generalizado que las infecciones respiratorias son estacionales, pero pocas veces se precisan localmente estos períodos de alta frecuencia en un país con diversidad de climas. Anticipar la temporada de neumonía a nivel local puede proveer de un mejor uso de recursos críticos. Objetivo. Examinar la variabilidad estacional en defunciones mensuales por neumonía en el Perú. Métodos. Estudio observacional retrospectivo de análisis de serie de tiempo para identificar períodos de alta mortalidad por neumonía en siete ciudades del Perú. Se revisaron registros administrativos del Ministerio de Salud sobre defunciones por neumonía durante los años 2003-2017. Se calcularon estadísticas descriptivas y se analizó mediante una serie de tiempo a escala mensual la frecuencia de defunciones por neumonía, precipitación acumulada, y la temperatura ambiental máxima y mínima. Resultados. El 94,4% de las defunciones por neumonía (N = 166 844) reportaron como causa "organismo no especificado", y el 75,6% eran adultos mayores de 65 años. En Tarma, Arequipa y Cusco la temperatura mínima tiene una correlación negativa con las defunciones por neumonía en todas las edades y al menos uno de los grupos de riesgo. En Iquitos la temperatura mínima tiene una correlación positiva con las defunciones en menores de 5 años. Pucallpa y Cajamarca no tuvieron correlaciones significativas. El clima de Lima es un caso particular. La distribución durante el año de las muertes por neumonía sugiere una secuencia norte-sur, mientras que el análisis espaciotemporal del clima sugiere un patrón que va de sur-norte. Conclusión. Existen diferentes patrones estacionales en diferentes ciudades y grupos de riesgo.

Introduction. It is generally accepted that respiratory infections are seasonal, but high-frequency periods are rarely identified at the local level in a country with diverse climates. Anticipating the pneumonia season locally can provide a better use of critical resources. Objective. The aim of the study was to examine seasonal variability in monthly deaths due to pneumonia in Peru. Methods. Observational retrospective study using time series analysis to identify periods of high pneumonia mortality in seven cities in Peru. We reviewed administrative reports from the Ministry of Health for pneumonia deaths during 2003-2017. Descriptive statistics were calculated and a time series analysis at a monthly scale was performed on the frequency of deaths due to pneumonia, cumulative rainfall, and maximum and minimum environmental temperatures. Results. 94.4% of pneumonia deaths (N = 166,844) were reported as pneumonia due to "unspecified organism", and 75.6% were adults older than 65 years. In the cities of Tarma, Arequipa and Cusco, minimum ambient temperature is negatively correlated to pneumonia deaths in all age groups and at least one risk group. In Iquitos, minimum temperature is positively correlated with deaths among children under 5 years of age. The cities of Pucallpa and Cajamarca reported no statistically significant correlation. The climate in Lima is a peculiar case. The distribution of pneumonia deaths throughout the year suggests a north-south sequence, while the climate space-time analysis suggests a south-north pattern. Conclusion. Results show different seasonal patterns for pneumonia deaths in different cities and risk groups.

Whole-Genome Analysis of Bartonella ancashensis, a Novel Pathogen Causing Verruga Peruana, Rural Ancash Region, Peru.

The genus Bartonella contains >40 species, and an increasing number of these Bartonella species are being implicated in human disease. One such pathogen is Bartonella ancashensis, which was isolated in blood samples from 2 patients living in Caraz, Peru, during a clinical trial of treatment for bartonellosis. Three B. ancashensis strains were analyzed by using whole-genome restriction mapping and high-throughput pyrosequencing. Genome-wide comparative analysis of Bartonella species showed that B. ancashensis has features seen in modern and ancient lineages of Bartonella species and is more related to B. bacilliformis. The divergence between B. ancashensis and B. bacilliformis is much greater than what is seen between known Bartonella genetic lineages. In addition, B. ancashensis contains type IV secretion system proteins, which are not present in B. bacilliformis. Whole-genome analysis indicates that B. ancashensis might represent a distinct Bartonella lineage phylogenetically related to B. bacilliformis.

An Outbreak of Bartonella bacilliformis in an Endemic Andean Community.

BACKGROUND: Bartonellosis affects small Andean communities in Peru, Colombia and Ecuador. Research in this area has been limited. METHODS: Retrospective review of 191 cases of bartonellosis managed in Caraz District Hospital, Peru, during the last outbreak (2003). RESULTS: The majority of cases (65%) were 14 years old and younger. There was a peak in acute cases after the rainy season; chronic cases presented more constantly throughout the year. The sensitivity of blood smear against blood culture in acute disease was 25%. The most commonly used treatment for chronic disease was rifampicin; chloramphenicol was used to treat most acute cases. Complications arose in 6.8% and there were no deaths. CONCLUSIONS: Diagnostic and treatment algorithms for acute and chronic bartonellosis have been developed without a strong evidence base. Preparation of ready-to-go operational research protocols for future outbreaks would strengthen the evidence base for diagnostic and treatment strategies and enhance opportunities for control.

El virus Zika: una revisión de literatura / The Zika virus: a literature review

Presentamos una breve revisión del nuevo virus emergente en América: el virus ZIKA, por ello tocamos los principales aspectos de la historia, epidemiología, clínica, diagnóstico y control de esta dolencia. Esta enfermedad procedente de África, llega a América el 2014 y desde el 2015 se ha expandido de manera rápida y sostenida a casi todo el continente, si bien la enfermedad es de curso benigno y autolimitado, ha creado una seria preocupación, debido a que un grupo importantes de pacientes en Brasil han presentado en forma importante el síndrome de Guillain-Barré y muchas gestantes al ser expuestas al virus han presentado microcefalia con una probable asociación, por ello se ha declarado emergencia sanitaria, siendo el control de esta nueva enfermedad ligado al control del principal vector, el Aedes aegypti. Finalmente un aspecto importante en la lucha contra el virus Zika es el acceso a información práctica, por ello se presentan algunas herramientas informáticas que permita orientar al médico y al paciente en la toma de decisiones...

We present a brief review of the new emerging virus in the Americas: the ZIKA virus. For this reason we deal with the main aspects of its history, epidemiology, clinical features, diagnosis, and control. This disease originated in Africa, reached the Americas in 2014, and from 2015 it expanded quickly and steadily affecting almost the whole continent. Although most cases are benign and self-limited, its spread has created a serious concern, since an important group of patients in Brazil have developed the Guillain-Barré syndrome, and many babies from women exposed to the virus were born with microcephaly, being this occurrence described as probably associated to the Zika virus infection. For these reasons, a sanitary emergency has been declared, and the main strategy for fighting the disease is vector control, limiting the spread of Aedes aegypti. Finally, another important aspect in the fight against the Zika virus is the access to practical information, since there are some computer tools which may orient physicians and patients for decision-making...

Complete Genome Sequence of Bartonella ancashensis Strain 20.00, Isolated from the Blood of a Patient with Verruga Peruana.

Here we present the complete genome sequence of Bartonella ancashensis strain 20.00, isolated from the blood of a Peruvian patient with verruga peruana, known as Carrion's disease. Bartonella ancashensis is a Gram-negative bacillus, phylogenetically most similar to Bartonella bacilliformis, the causative agent of Oroya fever and verruga peruana.

Proteins of Bartonella bacilliformis: Candidates for Vaccine Development.

Bartonella bacilliformis is the etiologic agent of Carrión's disease or Oroya fever. B. bacilliformis infection represents an interesting model of human host specificity. The notable differences in clinical presentations of Carrión's disease suggest complex adaptations by the bacterium to the human host, with the overall objectives of persistence, maintenance of a reservoir state for vectorial transmission, and immune evasion. These events include a multitude of biochemical and genetic mechanisms involving both bacterial and host proteins. This review focuses on proteins involved in interactions between B. bacilliformis and the human host. Some of them (e.g., flagellin, Brps, IalB, FtsZ, Hbp/Pap31, and other outer membrane proteins) are potential protein antigen candidates for a synthetic vaccine.

Description of Bartonella ancashensis sp. nov., isolated from the blood of two patients with verruga peruana.

Three novel isolates of the genus Bartonella were recovered from the blood of two patients enrolled in a clinical trial for the treatment of chronic stage Bartonella bacilliformis infection (verruga peruana) in Caraz, Ancash, Peru. The isolates were initially characterized by sequencing a fragment of the gltA gene, and found to be disparate from B. bacilliformis. The isolates were further characterized using phenotypic and genotypic methods, and found to be genetically identical to each other for the genes assessed, but distinct from any known species of the genus Bartonella, including the closest relative B. bacilliformis. Other characteristics of the isolates, including their morphology, microscopic and biochemical properties, and growth patterns, were consistent with members of the genus Bartonella. Based on these results, we conclude that these three isolates are members of a novel species of the genus Bartonella for which we propose the name Bartonella ancashensis sp. nov. (type strain 20.00T = ATCC BAA-2694T = DSM 29364T).

[Carrión's disease complicated with severe acute leptospirosis: a case report]. / Enfermedad de Carrión grave complicada con leptospirosis aguda: reporte de un caso.

The case of an adult, 56 year old male is reported, from Sihuas (Ancash) who presented at Hospital Nacional Dos de Mayo with fever, jaundice and anemia. In three days of hospitalization, he developed severe anemia (Hb: 11.8 to 6.7 g / dL) and generalized myalgias associated with a sudden worsening jaundice correlated with elevated bilirubin (TB 3.2 to 19.6 mg / dL direct dominance) and general deterioration. Microbiological smear and culture were positive for Bartonella bacilliformis. Subsequent serology (microagglutination) was positive for Lesptospira serovar Pomona. The patient was given specific antibiotic therapy (ceftriaxone and ciprofloxacin), transfused two units of packed red blood cells, improved clinically and was discharged.

Enfermedad de Carrión grave complicada con leptospirosis aguda: reporte de un caso / Carrión´s disease complicated with severe acute leptospirosis: a case report

Se reporta el caso de un adulto varón de 56 años, procedente de Sihuas (Ancash) que acude al Hospital Nacional Dos de Mayo con cuadro clínico caracterizado por un síndrome ictérico febril anemizante, en cuya evolución tórpida de solo tres días de hospitalizado presenta anemia severa (Hb: 11,8 a 6,7 g/dL) así como mialgias generalizadas asociadas a un empeoramiento brusco de la ictericia correlacionada con elevación de bilirrubinas (BT: 3,2 a 19,6 mg/dL a predominio directo) y deterioro general del paciente; por ello, se realizó la investigación microbiológica donde se encontró frotis y cultivo positivo para Bartonella bacilliformis, posteriormente, la serología (microaglutinación) resultó positiva para Lesptospira serovar Pomona. El paciente recibe tratamiento antibiótico específico (ceftriaxona y ciprofloxacino), se le transfunde dos paquetes globulares, mejora clínicamente y es dado de alta.

The case of an adult, 56 year old male is reported, from Sihuas (Ancash) who presented at Hospital Nacional Dos de Mayo with fever, jaundice and anemia. In three days of hospitalization, he developed severe anemia (Hb: 11.8 to 6.7 g / dL) and generalized myalgias associated with a sudden worsening jaundice correlated with elevated bilirubin (TB 3.2 to 19.6 mg / dL direct dominance) and general deterioration. Microbiological smear and culture were positive for Bartonella bacilliformis. Subsequent serology (microagglutination) was positive for Lesptospira serovar Pomona. The patient was given specific antibiotic therapy (ceftriaxone and ciprofloxacin), transfused two units of packed red blood cells, improved clinically and was discharged.

Disseminated intra-abdominal hydatidosis.

We present the case of a 26-year-old male Peruvian patient who presented with disseminated intra-abdominal hydatidosis. The patient was treated with surgical removal of the cysts and prolonged medical treatment with albendazole.

Molecular typing of "Candidatus Bartonella ancashi," a new human pathogen causing verruga peruana.

A recently described clinical isolate, "Candidatus Bartonella ancashi," was obtained from a blood sample of a patient presenting with verruga peruana in the Ancash region of Peru. This sample and a second isolate obtained 60 days later from the same patient were molecularly typed using multilocus sequence typing (MLST) and multispacer sequence typing (MST). The isolates were 100% indistinguishable from each other but phylogenetically distant from Bartonella bacilliformis and considerably divergent from other known Bartonella species, confirming their novelty.

Novel Bartonella agent as cause of verruga peruana.

While studying chronic verruga peruana infections in Peru from 2003, we isolated a novel Bartonella agent, which we propose be named Candidatus Bartonella ancashi. This case reveals the inherent weakness of relying solely on clinical syndromes for diagnosis and underscores the need for a new diagnostic paradigm in developing settings.

Bartonella bacilliformis: a systematic review of the literature to guide the research agenda for elimination.

BACKGROUND: Carrion's disease affects small Andean communities in Peru, Colombia and Ecuador and is characterized by two distinct disease manifestations: an abrupt acute bacteraemic illness (Oroya fever) and an indolent cutaneous eruptive condition (verruga Peruana). Case fatality rates of untreated acute disease can exceed 80% during outbreaks. Despite being an ancient disease that has affected populations since pre-Inca times, research in this area has been limited and diagnostic and treatment guidelines are based on very low evidence reports. The apparently limited geographical distribution and ecology of Bartonella bacilliformis may present an opportunity for disease elimination if a clear understanding of the epidemiology and optimal case and outbreak management can be gained. METHODS: All available databases were searched for English and Spanish language articles on Carrion's disease. In addition, experts in the field were consulted for recent un-published work and conference papers. The highest level evidence studies in the fields of diagnostics, treatment, vector control and epidemiology were critically reviewed and allocated a level of evidence, using the Oxford Centre for Evidence-Based Medicine (CEBM) guidelines. RESULTS: A total of 44 studies were considered to be of sufficient quality to be included in the analysis. The majority of these were level 4 or 5 (low quality) evidence and based on small sample sizes. Few studies had been carried out in endemic areas. CONCLUSIONS: Current approaches to the diagnosis and management of Carrion's disease are based on small retrospective or observational studies and expert opinion. Few studies take a public health perspective or examine vector control and prevention. High quality studies performed in endemic areas are required to define optimal diagnostic and treatment strategies.

Respuesta inmune en pacientes con bartonelosis humana en un área endémica de Perú / Immune response in patients with human Bartonella infection in an endemic area of Peru

Se llevó a cabo un estudio piloto en una zona de bartonelosis endémica humana en el Perú, con la captación de pacientes en fase aguda y crónica para el mejor conocimiento de su respuesta inmunitaria.

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study.

Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4(+) and CD8(+) T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study / Citoquinas y recuento de Linfocitos T en pacientes en fase aguda y crónica de infección por Bartonella bacilliformis, en una área endémica del Perú: estudio piloto

Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4+ and CD8+ T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

La Bartonelosis Humana, tiene una fase aguda caracterizada por fiebre y anemia hemolítica, así como una fase crónica con lesiones semejantes a angiomatosis bacilar. En un estudio transversal piloto los patrones inmunológicos en pacientes con Bartonelosis Humana fueron estudiados mediante muestras pre y post tratamiento. Pacientes entre 5 y 60 años en fase aguda y crónica fueron incluidos en área endémica del Perú. En aquellos pacientes con fase aguda, una fase de tolerancia inmunológica periférica es necesaria para la persistencia de la infección. Los hallazgos de significativa elevación de citoquina anti-inflamatoria (IL-10) y anormalidades numéricas en el recuentos de Linfocitos T CD4+ y CD8+ correlacionan con un estado inmune que favorece la infección. Durante la fase crónica, elevados niveles de INF-γ y IL-4 observados en la serie de pacientes correlacionan con previos hallazgos en modelos animales que favorecen la invasión del endotelio por B. henselae.