Proteomic research on new urinary biomarkers of renal disease in canine leishmaniosis: Survival and monitoring response to treatment.

The objective of our study was to search for survival biomarkers (SB) and treatment response monitoring biomarkers (TRMB) in the urinary proteome of dogs with renal disease secondary to canine leishmaniosis (CanL), using UHPLC-MS/MS. The proteomic data are available via ProteomeXchange with identifier PXD042578. Initially, a group of 12 dogs was evaluated and divided into survivors (SG; n = 6) and nonsurvivors (NSG; n = 6). A total of 972 proteins were obtained from the evaluated samples. Then, bioinformatic analysis reduced them to 6 proteins like potential SB increased in the NSG, specifically, Haemoglobin subunit Alpha 1, Complement Factor I, Complement C5, Fibrinogen beta chain (fragment), Peptidase S1 domain-containing protein, and Fibrinogen gamma chain. Afterwards, SG was used to search for TRMB, studying their urine at 0, 30, and 90 days, and 9 proteins that decreased after treatment were obtained: Apolipoprotein E, Cathepsin B, Cystatin B, Cystatin-C-like, Lysozyme, Monocyte differentiation CD14, Pancreatitis-associated precursor protein, Profilin, and Protein FAM3C. Finally, enrichment analysis provided information about the biological mechanisms in which these proteins are involved. In conclusion, this study provides 15 new candidate urinary biomarkers and an improved understanding of the pathogenesis of kidney disease in CanL.

Evaluation of heart fatty acid-binding protein as a biomarker for canine leishmaniosis.

BACKGROUND: Myocarditis frequently occurs in canine leishmaniosis (CanL). Heart fatty acid-binding protein (HFABP) is a biomarker of myocardial damage. METHODS: This study aimed to compare HFABP concentration (HFABPc) in healthy dogs and dogs at different stages of CanL and evaluate the correlation of this biomarker with several clinicopathological and echocardiographic variables. Thirty-one dogs diagnosed with CanL and 10 healthy dogs were included. RESULTS: HFABPc was not statistically different (p > 0.05) between groups of dogs at different LeishVet stages of CanL or between groups with high versus low to intermediate serology titres. In 70% of CanL dogs, HFABPc was within the 95% confidence interval limits of the mean of healthy dogs. A moderate negative correlation with globulin (r = -0.519; p = 0.03) and haematocrit (HCT) (r = -0.538; p = 0.02) was observed. No other significant correlation (p > 0.05) was observed with any other variable. LIMITATIONS: Many statistical tests were performed, and therefore, type I error cannot be ruled out. CONCLUSION: HFABPc is not consistently elevated in dogs with CanL and is not associated with the severity of the disease, or most echocardiographic or clinicopathological variables studied. The correlation with globulin and HCT was not strong and not considered clinically significant. HFABPc lacks sufficient predictive capacity in dogs with CanL, discouraging further research or clinical use of this biomarker in this disease.

Urinary proteome of dogs with renal disease secondary to leishmaniosis.

Canine leishmaniosis is frequently associated with the development of renal disease. Its pathogenesis is complex and not fully understood. For this reason, this study aimed to describe the urinary proteome, and identify possible new biomarkers in dogs with kidney disease secondary to leishmaniosis. Urine samples were collected from 20 dogs, 5 from healthy dogs, and 15 from stages Leishvet III and IV. Urine samples were analyzed by UHPLC-MS/MS. The data are available via ProteomeXchange with identifier PXD029165. A total of 951 proteins were obtained. After bioinformatic analysis, 93 urinary proteins were altered in the study group. Enrichment analysis performed on these proteins showed an overrepresentation of the complement activation pathway, among others. Finally, 12 discriminant variables were found in dogs with renal disease secondary to leishmaniosis, highlighting C4a anaphylatoxin, apolipoprotein A-I, haptoglobin, leucine-rich alpha-2-glycoprotein 1, and beta-2-microglobulin. This study is the first to describe the urinary proteomics of dogs with renal disease caused by leishmaniosis, and it provides new possible biomarkers for the diagnosis and monitoring of this disease.

Hepatitis B: Anticuerpos contra antígeno de superficie en residentes de pediatría, Hospital Central de Maracay

Introducción: Los profesionales del área de la salud tienen un riesgo incrementado de contraer la infección por el virus de hepatitis B (VHB). Objetivo: Evaluar anticuerpos contra el antígeno de superficie de la hepatitis B, en los residentes de pediatría del Hospital Central de Maracay en el período junio-agosto de 2021. Materiales y métodos: Estudio clínico epidemiológico, no experimental y de corte transversal, en el que se tomó muestra sanguínea a 54 médicos residentes para la determinación de anticuerpos contra el antígeno de superficie del VHB (Anti-HBs). Resultados: El promedio de edad fue 27,48 años con una desviación estándar de 1,6. El 83,33 % pertenecían al sexo femenino, 51,85.% cursaban el 1er año del posgrado, 33,33 % con esquema de vacunación documentado, de estos, 66,67.% completaron el esquema y 77,78 % cumplidos en la adultez. Con respecto al tiempo de la última dosis, el 66,67 % hasta 10 años. Se detectaron niveles de Anti-HBs mayores de 10 mUl/mL en el 94,44 %, con mayor prevalencia de niveles protectores a favor del sexo femenino. Se evidenció una correlación lineal positiva entre los niveles de Anti-HBs y el tiempo desde la última dosis de la vacuna contra la hepatitis B. Conclusiones: Aunque existe una debilidad en los médicos residentes en cuanto a la tenencia y cumplimiento del esquema de inmunización, la mayoría de ellos mostraron niveles protectores de anti-HBs. A mayor tiempo transcurrido desde la última dosis de la vacuna hay un descenso en los niveles de anti-HBs lo que justifica dosis de refuerzo a los 10 años.

Introduction: Health professionals have an increased risk of contracting hepatitis B virus infection (HBV). Objective: To evaluate antibodies against hepatitis B surface antigen in residents of pediatrics of the Central Hospital of Maracay in the period June-August. 2021. Materials and methods: Clinical epidemiological, nonexperimental and cross-sectional study, in which blood samples were taken from fifty-four medical residents for the determination of antibodies against the HBV surface antigen. Results: The average age was 27.48 years with a standard deviation of 1.6. 83.33 % were female, 51.85 % were in the first year of postgraduate studies, 33.33 % had a documented vaccination schedule, of these, 66.67 % completed the schedule and 77.78 % completed it in adulthood. Regarding the time of the last dose, for 66.67 % of the study population, it was up to 10 years ago. Anti-HBs levels greater than 10mUl/ml were detected in 94.44 %, with a higher prevalence of protective levels in favor of the female sex. A positive linear correlation between the levels of Anti-HBs and the time since the last dose of the hepatitis B vaccine was evidenced. Conclusions: Although there is a weakness in the resident doctors in terms of possession and compliance with the immunization schedule, the most of them showed protective levels of anti-HBs. The longer the time elapsed since the last dose of the vaccine, there is a decrease in anti-HBs levels, which justifies a booster dose at 10 years.

Effects of Competitive ELISA-Positive Results of Piroplasmosis on the Performance of Endurance Horses.

Endurance is an increasingly popular equestrian sport. However, in southern Europe, there is a high prevalence of horses that are asymptomatic carriers of equine piroplasmosis (EP), a tick-borne disease that could affect their performance. This study aimed to evaluate the impact and influence of EP on the performance of endurance horses. Blood samples were collected from 40 horses in Extremadura, Spain, before and after a race, in different national elite horse endurance competitions. Hematological and biochemical parameters and EP seroprevalence were analysed by competitive enzyme-linked immunosorbent assay. The global seroprevalence of EP was 70%, with 27 horses testing positive for Theileria equi (67.5%) and three (7.5%) for Babesia caballi, with two of these horses (5%) positive for both. Approximately 82.5% of the horses (33 of 40) completed the competition, with no influence on performance or position achieved in those with subclinical parasitosis. There were also no significant differences in hematological or biochemical values between seropositive and seronegative horses. The data suggest that horses without clinical signs of EP can participate without performance impairment in competitions of up to 80 km. Although it is recommended that longer distance competitions should be further evaluated, this is the first step for decision-making by organizers and participants in this sport.

Atypical Conjunctival Lesion as the Initial Presentation of Granulomatosis With Polyangiitis in an Adolescent Male.

PURPOSE: The purpose of this study was to report the first case of a conjunctival granulomatous lesion as the presenting sign of granulomatous polyangiitis (GPA) in a pediatric patient. METHODS: This study is a case report. RESULTS: A 14-year-old Hispanic boy presented with a conjunctival lesion on the inferior bulbar conjunctiva of the right eye associated with diffuse conjunctival injection. The mass progressively grew and became painful over the course of 6 weeks. No retinal or orbital abnormalities were noted on examination. The lesion was excised, and histopathological analysis was consistent with granulomatous inflammation. The lesion recurred after 15 months, and a second excisional biopsy was performed. The lesion again slowly recurred, and on presentation to our clinic, an elevated lesion in the inferior limbal/bulbar conjunctiva of the right eye was noted from 4 to 8 o'clock with accompanying forniceal shortening. Five months after the second excision, the patient developed flu-like symptoms with polyarthralgia. A full diagnostic workup revealed multiple pulmonary nodules on chest imaging, proteinuria on urinalysis, and a positive c-antineutrophil cytoplasmic antibody on serological studies. Based on these findings, the patient underwent a kidney biopsy which showed pauci-immune crescentic glomerulonephritis, consistent with a diagnosis of GPA. The patient achieved disease remission with rituximab. Despite treatment, the conjunctival lesion did not regress and remained unchanged in size for 3 years with periodic episodes of inflammation. CONCLUSIONS: This is the first documented case of a conjunctival mass as the initial presenting feature of pediatric GPA. The presence of granulomatous inflammation on histopathology and recurrences after excision should raise suspicion for GPA in children and adults.

Association of myocardial parasitic load with cardiac biomarkers and other selected variables in 10 dogs with advanced Canine Leishmaniasis.

BACKGROUND: The association between myocardial parasitic load (MPL) and cardiac biomarkers in Canine Leishmaniasis (CanL) has not been studied. METHODS: Dogs with advanced CanL were prospectively recruited and were included if they were euthanised. Prior to euthanasia these variables were assessed: hematocrit, globulin, creatinine, N-terminal-pro brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), blood pressure, urine protein/creatinine ratio and echocardiographic parameters. A left ventricular (LV) sample was taken for histopathology and MPL evaluation by quantitative PCR. Correlation of MPL with all variables was analysed. Dogs with lower and higher histopathology scores were compared. RESULTS: Ten dogs were included. NT-proBNP was 6946 pmol/ (interquartile range [IQR] 3751-9268 pmol/L) and cTnI 4.56 ng/mL (IQR 0.46-13.1 ng/mL). In all dogs, echocardiography showed an increase in LV thickening, and histopathology revealed moderate to severe lympho-plasmocytic myocarditis and/or myocardial cell degeneration. MPL was 215.53 parasites/gram (IQR 21.2-1372.63 parasites/gram). A strong correlation (p < 0.001; R = 0.90; R2 0.81) with cTnI was observed but correlation with any of the other variables or differences between the two histopathological scores, were not detected. CONCLUSIONS: MPL in dogs with advanced CanL shows variable but generally high levels. A strong association between MPL and cTnI was observed, which encourages the exploration of cTnI as a marker in CanL.

Comparison of N-terminal proB-type natriuretic peptide levels at different stages of visceral leishmaniosis and in patients with chronic kidney disease.

N-terminal proB-type natriuretic peptide (NT-proBNP) may be a useful marker in canine leishmaniosis (CanL). The aim was to compare NT-proBNP in dogs at different LeishVet stages of CanL and with idiopathic chronic kidney disease (CKD). Dogs diagnosed with CanL or CKD and a group of healthy dogs were included (group A, five normal dogs; group B, six dogs LeishVet 1-2; group C, 13 dogs LeishVet 3-4; group D, six dogs with CKD). NT-proBNP was higher (P<0.001) in group C (7.616 pmol/l, interquartile range (IQR) 3537-10,000 pmol/l) than in group A (293 pmol/l, IQR 257-373), group B (388.5 pmol/l, IQR 324-793) and group D (740 pmol/l, IQR 557-962 pmol/l). International Renal Interest Society (IRIS) kidney stage was not different between groups C and D or between groups A and B, but was different within all the rest of the group comparisons (P<0.001). In group C all dogs had echocardiographic increase in left ventricular mass index. NT-proBNP had negative correlation with haematocrit (P<0.001, r=0.749) and positive correlation with systemic blood pressure (P<0.001, r=0.728). NT-proBNP is consistently elevated in dogs with advanced CanL and is strongly correlated with the degree of systemic hypertension and anaemia. Moreover, dogs with advanced CanL exhibit increase in left ventricular mass. NT-proBNP may however be a less desirable cardiac marker as unlike cardiac troponin I it is often not elevated at earlier stages of CanL.

Loss of postnatal quiescence of neural stem cells through mTOR activation upon genetic removal of cysteine string protein-α.

Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.

Hospitalization and death among patients with influenza, Guatemala, 2008-2012.

BACKGROUND: Influenza is a major cause of respiratory illness resulting in 3-5 million severe cases and 291,243-645,832 deaths annually. Substantial health and financial burden may be averted by annual influenza vaccine application, especially for high risk groups. METHODS: We used an active facility-based surveillance platform for acute respiratory diseases in three hospitals in Guatemala, Central America, to estimate the incidence of laboratory-confirmed hospitalized influenza cases and identify risk factors associated with severe disease (defined as admission to the intensive care unit (ICU) or death). We enrolled patients presenting with signs and symptoms of acute respiratory infection (ARI) and obtained naso- and oropharyngeal samples for real-time reverse transcriptase polymerase chain reaction (RT-PCR). We used multivariable logistic regression to identify risk factors for ICU admission or death, adjusted for age and sex. RESULTS: From May 2008 to July 2012, among 6326 hospitalized ARI cases, 446 (7%) were positive for influenza: of those, 362 (81%) had influenza A and 84 (18%) had influenza B. Fifty nine percent of patients were aged ≤ 5 years, and 10% were aged ≥ 65 years. The median length of hospitalization was 5 days (interquartile range: 5). Eighty of 446 (18%) were admitted to the ICU and 28 (6%) died. Among the 28 deaths, 7% were aged ≤ 6 months, 39% 7-60 months, 21% 5-50 years, and 32% ≥ 50 years. Children aged ≤ 6 months comprised 19% of cases and 22% of ICU admissions. Women of child-bearing age comprised 6% of cases (2 admitted to ICU; 1 death). In multivariable analyses, Santa Rosa site (adjusted odds ratio [aOR] = 10, 95% confidence interval [CI] = 2-50), indigenous ethnicity (aOR = 4, 95% CI = 2-13, and radiologically-confirmed pneumonia (aOR = 5, 95% CI = 3-11) were independently associated with severe disease. Adjusted for hospital utilization rate, annual incidence of hospitalized laboratory-confirmed influenza was 24/100,000 overall, 93/100,000 for children aged < 5 years and 50/100,000 for those ≥ 65 years. CONCLUSIONS: Influenza is a major contributor of hospitalization and death due to respiratory diseases in Guatemala. Further application of proven influenza prevention and treatment strategies is warranted.

Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing.

Common genetic contributions to autism spectrum disorder (ASD) reside in risk gene variants that individually have minimal effect sizes. As environmental factors that perturb neurodevelopment also underlie idiopathic ASD, it is crucial to identify altered regulators that can orchestrate multiple ASD risk genes during neurodevelopment. Cytoplasmic polyadenylation element binding proteins 1-4 (CPEB1-4) regulate the translation of specific mRNAs by modulating their poly(A)-tails and thereby participate in embryonic development and synaptic plasticity. Here we find that CPEB4 binds transcripts of most high-confidence ASD risk genes. The brains of individuals with idiopathic ASD show imbalances in CPEB4 transcript isoforms that result from decreased inclusion of a neuron-specific microexon. In addition, 9% of the transcriptome shows reduced poly(A)-tail length. Notably, this percentage is much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of ASD risk genes. An equivalent imbalance in CPEB4 transcript isoforms in mice mimics the changes in mRNA polyadenylation and protein expression of ASD risk genes and induces ASD-like neuroanatomical, electrophysiological and behavioural phenotypes. Together, these data identify CPEB4 as a regulator of ASD risk genes.

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits.

The striatum integrates motor behavior using a well-defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line-derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast-spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF-independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.

Rilonacept maintains long-term inflammatory remission in patients with deficiency of the IL-1 receptor antagonist.

BACKGROUND: Deficiency of IL-1 receptor antagonist (DIRA) is a rare autoinflammatory disease that presents with life-threatening systemic inflammation, aseptic multifocal osteomyelitis, and pustulosis responsive to IL-1-blocking treatment. This study was performed (a) to investigate rilonacept, a long-acting IL-1 inhibitor, in maintaining anakinra-induced inflammatory remission in DIRA patients, (b) to determine doses needed to maintain remission, and (c) to evaluate the safety and pharmacokinetics of rilonacept in young children (<12 years). METHODS: Six mutation-positive DIRA patients (children, ages 3-6 years), treated with daily anakinra, were enrolled into an open-label pilot study of subcutaneous rilonacept for 24 months. Clinical symptoms and inflammatory blood parameters were measured at all visits. A loading dose (4.4 mg/kg) was administered, followed by once weekly injections (2.2 mg/kg) for 12 months. Dose escalation (4.4 mg/kg) was allowed if inflammatory remission was not maintained. Subjects in remission at 12 months continued rilonacept for an additional 12 months. RESULTS: Five of six patients required dose escalation for findings of micropustules. Following dose escalation, all patients were in remission on weekly rilonacept administration, with stable laboratory parameters for the entire study period of 24 months. All children are growing at normal rates and have normal heights and weights. Quality of life improved while on rilonacept. No serious adverse events were reported. CONCLUSION: Rilonacept was found to maintain inflammatory remission in DIRA patients. The once weekly injection was well tolerated and correlated with increased quality of life, most likely related to the lack of daily injections. TRIAL REGISTRATION: ClinicalTrials.gov NCT01801449. FUNDING: NIH, NIAMS, and NIAID.

Toward the Inner Nanostructure of a Secretory Vesicle.

The release of chemical mediators is an essential element of cell-to-cell communication. Signaling molecules such as neurotransmitters and hormones are stored in membrane-bound organelles called secretory vesicles. Some of these organelles can store molecules at high concentrations, overcoming the osmotic shock that could burst the organelle. These organelles contain a proteinaceous matrix that traps the molecules and avoids high intravesicular osmotic pressure. The functional nanostructure and internal organization of the matrix is not well understood. A report by Lovric et al. in this issue of ACS Nano provides insight into the storage of a small molecule-dopamine-within the intraluminal compartments of a secretory vesicle. Lovric et al. used a powerful combination of high spatial resolution mass spectrometry and transmission electron microscopy in conjunction with amperometric measurements of exocytotic release to delineate the temporal and spatial fate of intravesicular dopamine and its interaction with the matrix.

A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss.

Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, we identified a missense mutation in POGLUT1 (protein O-glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo experiments demonstrated that the mutation reduces O-glucosyltransferase activity on Notch and impairs muscle development. Muscles from patients revealed decreased Notch signaling, dramatic reduction in satellite cell pool and a muscle-specific α-dystroglycan hypoglycosylation not present in patients' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent PAX7+ cells. A robust rescue of the myogenesis was demonstrated by increasing Notch signaling. None of these alterations were found in muscles from secondary dystroglycanopathy patients. These data suggest that a key pathomechanism for this novel form of muscular dystrophy is Notch-dependent loss of satellite cells.

Two for the Price of One: A Neuroprotective Chaperone Kit within NAD Synthase Protein NMNAT2.

One of the most fascinating properties of the brain is the ability to function smoothly across decades of a lifespan. Neurons are nondividing mature cells specialized in fast electrical and chemical communication at synapses. Often, neurons and synapses operate at high levels of activity through sophisticated arborizations of long axons and dendrites that nevertheless stay healthy throughout years. On the other hand, aging and activity-dependent stress strike onto the protein machineries turning proteins unfolded and prone to form pathological aggregates associated with neurodegeneration. How do neurons protect from those insults and remain healthy for their whole life? Ali and colleagues now present a molecular mechanism by which the enzyme nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) acts not only as a NAD synthase involved in axonal maintenance but as a molecular chaperone helping neurons to overcome protein unfolding and protein aggregation.

Estimating the burden of influenza-associated hospitalizations and deaths in Central America.

OBJECTIVES: Our objective was to estimate the incidence of influenza-associated hospitalizations and in-hospital deaths in Central American Region. DESIGN AND SETTING: We used hospital discharge records, influenza surveillance virology data, and population projections collected from Costa Rica, El Salvador, Guatemala, Honduras, and Nicaragua to estimate influenza-associated hospitalizations and in-hospital deaths. We performed a meta-analysis of influenza-associated hospitalizations and in-hospital deaths. MAIN OUTCOME MEASURES: The highest annual incidence was observed among children aged <5 years (136 influenza-associated hospitalizations per 100 000 persons). RESULTS: Annually, 7 625-11 289 influenza-associated hospitalizations and 352-594 deaths occurred in the subregion. CONCLUSIONS: Our results suggest that a substantive number of persons are annually hospitalized because of influenza. Health officials should estimate how many illnesses could be averted through increased influenza vaccination.

Influenza Illness among Case-Patients Hospitalized for Suspected Dengue, El Salvador, 2012.

We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded) patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.

Demographic and clinical characteristics of deaths associated with influenza A(H1N1) pdm09 in Central America and Dominican Republic 2009-2010.

BACKGROUND: The demographic characteristics of pandemic influenza decedents among middle and low-income tropical countries are poorly understood. We explored the demographics of persons who died with influenza A (H1N1)pdm09 infection during 2009-2010, in seven countries in the American tropics. METHODS: We used hospital-based surveillance to identify laboratory-confirmed influenza deaths in Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, Panama and Dominican Republic. An influenza death was defined as a person who died within two weeks of a severe acute respiratory infection (SARI) defined as sudden onset of fever >38 °C, cough or sore-throat, and shortness of breath, or difficulty breathing requiring hospitalization, and who tested positive for influenza A (H1N1)pdm09 virus by real time polymerase chain reaction. We abstracted the demographic and clinical characteristics of the deceased from their medical records. RESULTS: During May 2009-June 2010, we identified 183 influenza deaths. Their median age was 32 years (IQR 18-46 years). One-hundred and one (55 %) were female of which 20 (20 %) were pregnant and 7 (7 %) were in postpartum. One-hundred and twelve decedents (61 %) had pre-existing medical conditions, (15 % had obesity, 13 % diabetes, 11 % asthma, 8 % metabolic disorders, 5 % chronic obstructive pulmonary disease, and 10 % neurological disorders). 65 % received oseltamivir but only 5 % received it within 48 h of symptoms onset. CONCLUSIONS: The pandemic killed young adults, pregnant women and those with pre-existing medical conditions. Most sought care too late to fully benefit from oseltamivir. We recommend countries review antiviral treatment policies for people at high risk of developing complications.