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Lassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and significant mortality. The lack of approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate in defined regions throughout West Africa with substantial interlineage nucleotide and amino acid diversity. An effective vaccine should be designed to elicit Lassa virus specific humoral and cell mediated immunity across all lineages. Most current vaccine candidates use only lineage IV antigens encoded by Lassa viruses circulating around Sierra Leone, Liberia, and Guinea but not Nigeria where lineages I-III are found. As previous infection is known to protect against disease from subsequent exposure, we sought to determine whether LF survivors from Nigeria and Sierra Leone harbor memory T cells that respond to lineage IV antigens. Our results indicate a high degree of cross-reactivity of CD8+ T cells from Nigerian LF survivors to lineage IV antigens. In addition, we identified regions within the Lassa virus glycoprotein complex and nucleoprotein that contributed to these responses while T cell epitopes were not widely conserved across our study group. These data are important for current efforts to design effective and efficient vaccine candidates that can elicit protective immunity across all Lassa virus lineages.
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Antígenos Virales/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Virus Lassa/inmunología , África Occidental , Reacciones Cruzadas , Femenino , Humanos , Masculino , Especificidad de la EspecieRESUMEN
During 2018, an unusual increase in Lassa fever cases occurred in Nigeria, raising concern among national and international public health agencies. We analyzed 220 Lassa virus genomes from infected patients, including 129 from the 2017-2018 transmission season, to understand the viral populations underpinning the increase. A total of 14 initial genomes from 2018 samples were generated at Redeemer's University in Nigeria, and the findings were shared with the Nigerian Center for Disease Control in real time. We found that the increase in cases was not attributable to a particular Lassa virus strain or sustained by human-to-human transmission. Instead, the data were consistent with ongoing cross-species transmission from local rodent populations. Phylogenetic analysis also revealed extensive viral diversity that was structured according to geography, with major rivers appearing to act as barriers to migration of the rodent reservoir.
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Genoma Viral , Fiebre de Lassa/virología , Virus Lassa/genética , ARN Viral/análisis , Adolescente , Adulto , Animales , Teorema de Bayes , Reservorios de Enfermedades , Femenino , Variación Genética , Humanos , Fiebre de Lassa/epidemiología , Fiebre de Lassa/transmisión , Masculino , Cadenas de Markov , Persona de Mediana Edad , Nigeria/epidemiología , Filogenia , Filogeografía , Roedores , Análisis de Secuencia de ARN , Zoonosis/transmisiónRESUMEN
Early and robust T cell responses have been associated with survival from Lassa fever (LF), but the Lassa virus-specific memory responses have not been well characterized. Regions within the virus surface glycoprotein (GPC) and nucleoprotein (NP) are the main targets of the Lassa virus-specific T cell responses, but, to date, only a few T cell epitopes within these proteins have been identified. We identified GPC and NP regions containing T cell epitopes and HLA haplotypes from LF survivors and used predictive HLA-binding algorithms to identify putative epitopes, which were then experimentally tested using autologous survivor samples. We identified 12 CD8-positive (CD8+) T cell epitopes, including epitopes common to both Nigerian and Sierra Leonean survivors. These data should be useful for the identification of dominant Lassa virus-specific T cell responses in Lassa fever survivors and vaccinated individuals as well as for designing vaccines that elicit cell-mediated immunity.IMPORTANCE The high morbidity and mortality associated with clinical cases of Lassa fever, together with the lack of licensed vaccines and limited and partially effective interventions, make Lassa virus (LASV) an important health concern in its regions of endemicity in West Africa. Previous infection with LASV protects from disease after subsequent exposure, providing a framework for designing vaccines to elicit similar protective immunity. Multiple major lineages of LASV circulate in West Africa, and therefore, ideal vaccine candidates should elicit immunity to all lineages. We therefore sought to identify common T cell epitopes between Lassa fever survivors from Sierra Leone and Nigeria, where distinct lineages circulate. We identified three such epitopes derived from highly conserved regions within LASV proteins. In this process, we also identified nine other T cell epitopes. These data should help in the design of an effective pan-LASV vaccine.
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Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/química , Fiebre de Lassa/inmunología , Virus Lassa/inmunología , Nucleoproteínas/inmunología , Proteínas del Envoltorio Viral/inmunología , Adolescente , Secuencia de Aminoácidos , Animales , Anticuerpos Antivirales/biosíntesis , Antígenos Virales/química , Antígenos Virales/genética , Antígenos Virales/inmunología , Linfocitos T CD8-positivos/virología , Niño , Epítopos de Linfocito T/genética , Epítopos de Linfocito T/inmunología , Femenino , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/inmunología , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/inmunología , Haplotipos , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Sueros Inmunes/análisis , Memoria Inmunológica , Fiebre de Lassa/genética , Fiebre de Lassa/patología , Virus Lassa/patogenicidad , Masculino , Nigeria , Nucleoproteínas/genética , Sierra Leona , Sobrevivientes , Proteínas del Envoltorio Viral/genética , Adulto JovenRESUMEN
We conducted a retrospective review of psychiatric consultations for hospitalized patients with Lassa fever in southern Nigeria. Ten (8.8%) of 113 patients had psychiatric consultations. Delirium was the most common psychiatric manifestation complicating Lassa fever. Findings suggest that psychiatric intervention could improve overall outcomes of Lassa fever.
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Fiebre de Lassa , Humanos , Fiebre de Lassa/diagnóstico , Fiebre de Lassa/epidemiología , Virus Lassa/genética , Nigeria/epidemiología , Derivación y Consulta , Estudios RetrospectivosRESUMEN
Lassa virus is genetically diverse with several lineages circulating in West Africa. This study aimed at describing the sequence variability of Lassa virus across Nigeria and inferring its spatiotemporal evolution. We sequenced and isolated 77 Lassa virus strains from 16 Nigerian states. The final data set, including previous works, comprised metadata and sequences of 219 unique strains sampled between 1969 and 2018 in 22 states. Most of this data originated from Lassa fever patients diagnosed at Irrua Specialist Teaching Hospital, Edo State, Nigeria. The majority of sequences clustered with the main Nigerian lineages II and III, while a few sequences formed a new cluster related to Lassa virus strains from Hylomyscus pamfi Within lineages II and III, seven and five sublineages, respectively, were distinguishable. Phylogeographic analysis suggests an origin of lineage II in the southeastern part of the country around Ebonyi State and a main vector of dispersal toward the west across the Niger River, through Anambra, Kogi, Delta, and Edo into Ondo State. The frontline of virus dispersal appears to be in Ondo. Minor vectors are directed northeast toward Taraba and Adamawa and south toward Imo and Rivers. Lineage III might have spread from northern Plateau State into Kaduna, Nasarawa, Federal Capital Territory, and Bauchi. One sublineage moved south and crossed the Benue River into Benue State. This study provides a geographic mapping of lineages and phylogenetic clusters in Nigeria at a higher resolution. In addition, we estimated the direction and time frame of virus dispersal in the country.IMPORTANCE Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality rate of approximately 30% in Africa. Previous studies disclosed a geographical pattern in the distribution of Lassa virus strains and a westward movement of the virus across West Africa during evolution. Our study provides a deeper understanding of the geography of genetic lineages and sublineages of the virus in Nigeria. In addition, we modeled how the virus spread in the country. This knowledge allows us to predict into which geographical areas the virus might spread in the future and prioritize areas for Lassa fever surveillance. Our study not only aimed to generate Lassa virus sequences from across Nigeria but also to isolate and conserve the respective viruses for future research. Both isolates and sequences are important for the development and evaluation of medical countermeasures to treat and prevent Lassa fever, such as diagnostics, therapeutics, and vaccines.
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Fiebre de Lassa/virología , Virus Lassa/clasificación , Animales , Evolución Molecular , Variación Genética , Humanos , Fiebre de Lassa/epidemiología , Fiebre de Lassa/transmisión , Virus Lassa/genética , Murinae/virología , Nigeria/epidemiología , Filogenia , FilogeografíaAsunto(s)
Fiebre de Lassa/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Adolescente , Adulto , Manejo de la Enfermedad , Femenino , Edad Gestacional , Humanos , Fiebre de Lassa/diagnóstico , Fiebre de Lassa/tratamiento farmacológico , Virus Lassa , Nigeria/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Vigilancia en Salud Pública , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Evaluación de Síntomas , Adulto JovenRESUMEN
Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission.
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Abdomen Agudo/etiología , Abdomen Agudo/patología , Fiebre de Lassa/diagnóstico , Fiebre de Lassa/patología , Abdomen Agudo/cirugía , Adolescente , Adulto , África Occidental , Antivirales/uso terapéutico , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Lactante , Fiebre de Lassa/tratamiento farmacológico , Masculino , Ribavirina/uso terapéutico , Adulto JovenRESUMEN
Effective infectious disease surveillance in high-risk regions is critical for clinical care and pandemic preemption; however, few clinical diagnostics are available for the wide range of potential human pathogens. Here, we conduct unbiased metagenomic sequencing of 593 samples from febrile Nigerian patients collected in three settings: i) population-level surveillance of individuals presenting with symptoms consistent with Lassa Fever (LF); ii) real-time investigations of outbreaks with suspected infectious etiologies; and iii) undiagnosed clinically challenging cases. We identify 13 distinct viruses, including the second and third documented cases of human blood-associated dicistrovirus, and a highly divergent, unclassified dicistrovirus that we name human blood-associated dicistrovirus 2. We show that pegivirus C is a common co-infection in individuals with LF and is associated with lower Lassa viral loads and favorable outcomes. We help uncover the causes of three outbreaks as yellow fever virus, monkeypox virus, and a noninfectious cause, the latter ultimately determined to be pesticide poisoning. We demonstrate that a local, Nigerian-driven metagenomics response to complex public health scenarios generates accurate, real-time differential diagnoses, yielding insights that inform policy.
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Fiebre de Lassa , Virus , Humanos , Nigeria/epidemiología , Metagenómica , Fiebre de Lassa/diagnóstico , Fiebre de Lassa/epidemiología , Virus Lassa/genética , Virus/genéticaRESUMEN
OBJECTIVES: To estimate the burden of Lassa fever in northern and central Edo, a state in south Nigeria where Lassa fever has been reported. METHODS: Blood samples were obtained from 60 patients hospitalised at the Irrua Specialist Teaching Hospital (ISTH), Irrua, with a clinical suspicion of Lassa fever and from 451 febrile outpatients seen at the ISTH and hospitals in Ekpoma, Iruekpen, Uromi, Auchi and Igarra. All samples were tested retrospectively by Lassa virus-specific RT-PCR. Outpatients were additionally screened for Lassa virus-specific antibodies by indirect immunofluorescent antibody assay. RESULTS: Lassa virus was detected in 25 of 60 (42%) patients with a clinical suspicion of Lassa fever. The disease affected persons of all age groups and with various occupations, including healthcare workers. The clinical picture was dominated by gastrointestinal symptoms. The case fatality rate was 29%. Lassa virus was detected in 2 of 451 (0.44%) febrile outpatients, and 8 (1.8%) were positive for Lassa virus-specific IgG. CONCLUSIONS: Lassa fever contributes to hospital mortality in Edo State. The low prevalence of the disease among outpatients and the low seroprevalence may indicate that the population-level incidence is not high. Surveillance for Lassa fever should focus on the hospitalised patient.
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Hospitales de Enseñanza/estadística & datos numéricos , Fiebre de Lassa/epidemiología , Adolescente , Adulto , Anticuerpos Antivirales , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Incidencia , Lactante , Fiebre de Lassa/genética , Fiebre de Lassa/mortalidad , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Prevalencia , ARN Viral/análisis , Estudios Retrospectivos , Factores Socioeconómicos , Adulto JovenRESUMEN
Introduction Sickle cell anemia (SCA) in adults has many clinical manifestations. These manifestations are due to effects of recurrent hemolysis, anemia, and ischemia-reperfusion injury on various organs, including the heart. These factors determine the severity of the disease. Objectives The aim of the study was to assess the severity of SCA using a scoring system consisting of clinical and laboratory parameters. In addition, the study aimed to determine the electrocardiographic abnormalities in the adult SCA population. Study design This was a cross-sectional, observational study conducted in the medical outpatient clinic of Irrua Specialist Teaching Hospital, Irrua, Nigeria. Methodology Sixty SCA patients who were older than 18 years old were recruited for this study between February 2017 and January 2018. Sixty healthy individuals matched for age and sex were recruited to serve as controls. Patients who were pregnant or having an acute crises were excluded from the study. Each participant had an electrocardiogram and a SCA severity score was calculated using their clinical history and complete blood count. Data analysis was carried out using the IBM Statistical Package for Social Sciences Statistics® software, version 21 (IBM SPSS Statistics for Windows, Armonk, NY) and statistical significance assigned to p-values less than 0.05. Results Severity scores for SCA ranged between 7 and 24, with a mean score of 14.5 ± 4.04. Out of the 60 patients, 14 (23.3%), 39 (65%), and seven (11.7%) participants met criteria for mild, moderate, and severe disease, respectively. Tachycardia, prolonged QTc, and the presence of ST-segment and T-wave abnormalities were significantly associated with severe SCA (p = 0.024, p = 0.027, and p = 0.018, respectively). There was positive correlation between SCA severity scores and P-wave duration (r = 0.327, p = 0.011), QRS dispersion (r = 0.298, p = 0.021), QTc interval (r = 0.332, p = 0.010), and QTc dispersion (r = 0.320, p = 0.013). Conclusion This study demonstrated that moderate and severe forms of SCA are common in our region. Tachycardia, left atrial abnormality, prolonged corrected QT interval, and the presence of ST-segment and T-wave changes are electrocardiographic findings associated with more severe forms of the disease. These abnormalities are significant etiologies of cardiac morbidity and mortality in SCA.
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OBJECTIVES: To assess the prevalence of acute kidney injury (AKI), and its impact on outcome in hospitalized pediatric patients with Lassa fever (LF). METHODS: We reviewed the presenting clinical and laboratory features and outcomes of 40 successive hospitalized children with PCR-confirmed LF. The diagnosis and staging of AKI was based on KDIGO criteria. We compared groups of patients using t- or χ2 tests as necessary, and took p-values <0.05 as indicative of the presence of significant differences. RESULTS: Sixteen (40%) children had AKI. Case fatality rate (CFR) was 9/16 (56%) in children with and 1/24 (4%) in those without AKI (OR [95% CI] of CFR associated with AKI = 29.57 [3.17, 275.7]). Presentation with abnormal bleeding (p = 0.008), encephalopathy (p = 0.004), hematuria plus proteinuria (p = 0.013), and elevated serum transaminase levels (p <0.02) were significantly associated with an increased prevalence of AKI. CONCLUSION: AKI prevalence in hospitalized pediatric patients with Lassa fever is high, and correlated with illness severity/CFR. The high prevalence underscores the need for access to hemodialysis, and clinical presentation and/or presence of hematuria plus proteinuria could serve as a ready prompt for referral for such specialized care.
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Lesión Renal Aguda/epidemiología , Fiebre de Lassa/complicaciones , Fiebre de Lassa/mortalidad , Diálisis Renal , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Preescolar , Femenino , Accesibilidad a los Servicios de Salud , Hematuria/complicaciones , Humanos , Lactante , Recién Nacido , Masculino , Nigeria/epidemiología , Prevalencia , Proteinuria/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Lassa fever is endemic in several west African countries. Case-fatality rates ranging from 21% to 69% have been reported. The pathophysiology of the disease in humans and determinants of mortality remain poorly understood. We aimed to determine host protein biomarkers capable of determining disease outcome. METHODS: In this observational study, we analysed left-over blood samples from patients who tested positive for Lassa fever at Irrua Specialist Teaching Hospital, Nigeria, between January, 2014, and April, 2017. We measured viral load, concentrations of clinical chemistry parameters, and levels of 62 circulating proteins involved in inflammation, immune response, and haemostasis. Patients with a known outcome (survival or death) and at least 200 µL of good-quality diagnostic sample were included in logistic regression modelling to assess the correlation of parameters with Lassa fever outcome. Individuals who gave consent could further be enrolled into a longitudinal analysis to assess the association of parameters with Lassa fever outcome over time. Participants were divided into two datasets for the statistical analysis: a primary dataset (samples taken between Jan 1, 2014, and April 1, 2016), and a secondary dataset (samples taken between April 1, 2016, and April 1, 2017). Biomarkers were ranked by area under the receiver operating characteristic curve (AUC) from highest (most predictive) to lowest (least predictive). FINDINGS: Of 554 patients who tested positive for Lassa fever during the study period, 201 (131 in the primary dataset and 70 in the secondary dataset) were included in the biomarker analysis, of whom 74 (49 in the primary dataset and 25 in the secondary dataset) had died and 127 (82 in the primary dataset and 45 in the secondary dataset) had survived. Cycle threshold values (indicating viral load) and levels of 18 host proteins at the time of admission to hospital were significantly correlated with fatal outcome. The best predictors of outcome in both datasets were plasminogen activator inhibitor-1 (PAI-1; AUC 0·878 in the primary dataset and 0·876 in the secondary dataset), soluble thrombomodulin (TM; 0·839 in the primary dataset and 0·875 in the secondary dataset), and soluble tumour necrosis factor receptor superfamily member 1A (TNF-R1; 0·807 in the primary dataset and 0·851 in the secondary dataset), all of which had higher prediction accuracy than viral load (0·774 in the primary dataset and 0·837 in the secondary dataset). Longitudinal analysis (150 patients, of whom 36 died) showed that of the biomarkers that were predictive at admission, PAI-1 levels consistently decreased to normal levels in survivors but not in those who died. INTERPRETATION: The identification of PAI-1 and soluble TM as markers of fatal Lassa fever at admission, and of PAI-1 as a marker of fatal Lassa fever over time, suggests that dysregulated coagulation and fibrinolysis and endothelial damage have roles in the pathophysiology of Lassa fever, providing a mechanistic explanation for the association of Lassa fever with oedema and bleeding. These novel markers might aid in clinical risk stratification and disease monitoring. FUNDING: German Research Foundation, Leibniz Association, and US National Institutes of Health.
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Biomarcadores/sangre , Fiebre de Lassa/diagnóstico , Fiebre de Lassa/mortalidad , Fiebre de Lassa/fisiopatología , Virus Lassa/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Fiebre de Lassa/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mortalidad , Nigeria/epidemiología , Tasa de Supervivencia , Carga ViralRESUMEN
Lassa virus (LASV) is the causative agent of Lassa fever (LF), an often-fatal hemorrhagic disease. LF is endemic in Nigeria, Sierra Leone and other West African countries. Diagnosis of LASV infection is challenged by the genetic diversity of the virus, which is greatest in Nigeria. The ReLASV Pan-Lassa Antigen Rapid Test (Pan-Lassa RDT) is a point-of-care, in vitro diagnostic test that utilizes a mixture of polyclonal antibodies raised against recombinant nucleoproteins of representative strains from the three most prevalent LASV lineages (II, III and IV). We compared the performance of the Pan-LASV RDT to available quantitative PCR (qPCR) assays during the 2018 LF outbreak in Nigeria. For patients with acute LF (RDT positive, IgG/IgM negative) during initial screening, RDT performance was 83.3% sensitivity and 92.8% specificity when compared to composite results of two qPCR assays. 100% of samples that gave Ct values below 22 on both qPCR assays were positive on the Pan-Lassa RDT. There were significantly elevated case fatality rates and elevated liver transaminase levels in subjects whose samples were RDT positive compared to RDT negative.
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Anticuerpos Antivirales/metabolismo , Pruebas Diagnósticas de Rutina/métodos , Fiebre de Lassa/diagnóstico , Virus Lassa/aislamiento & purificación , ARN Viral/genética , Adulto , Antígenos Virales/inmunología , Brotes de Enfermedades , Femenino , Humanos , Virus Lassa/genética , Virus Lassa/inmunología , Masculino , Persona de Mediana Edad , Nigeria , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Análisis de Secuencia de ARN , Adulto JovenRESUMEN
Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI's (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II-IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.
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Reacciones Cruzadas/inmunología , Fiebre de Lassa/inmunología , Virus Lassa/inmunología , Anticuerpos/inmunología , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Variación Genética , Humanos , Inmunidad Humoral , Inmunización , Virus Lassa/patogenicidad , Nigeria/epidemiología , Nucleoproteínas , Proteínas Recombinantes , Sierra Leona/epidemiología , SobrevivientesRESUMEN
Few reports on the prevalence of acute abdomen (AAbd) in pediatric patients with Lassa fever (LF) are available, and no firm policy on its management exists. Here, we report on its prevalence in and the response to treatment among a cohort of children with confirmed LF. Six (10.3%) of 58 children with LF had AAbd, whereas 6 (2.8%) of 215 children with AAbd had LF. Nonoperative treatment was successful in 5 of the 6 children with both AAbd and LF. We conclude that AAbd is not uncommon in pediatric patients with LF, and it could be responsive to nonoperative treatment. Testing for LF in all children with febrile AAbd might be justified in areas in which LF is endemic.
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Abdomen Agudo/complicaciones , Abdomen Agudo/epidemiología , Fiebre de Lassa/complicaciones , Fiebre de Lassa/epidemiología , Abdomen Agudo/diagnóstico por imagen , Abdomen Agudo/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Nigeria , Prevalencia , Resultado del TratamientoRESUMEN
BACKGROUND: Although stroke is a leading cause of morbidity and mortality in Nigeria, there is no information on awareness of its warning signs. This study was designed to assess awareness of stroke warning signs in Nigerians at increased risk. METHODS: A hospital-based cross-sectional study conducted at Irrua Specialist Teaching Hospital, in southern Nigeria. Patients with a diagnosis of hypertension, diabetes or both were interviewed for the warning signs of stroke in the outpatient clinic by trained interviewers. The main outcome measure was ability to identify at least one stroke warning sign. RESULTS: There were 225 respondents with a mean age of 58.0 +/- 11.7 years. Only 39.6% could identify at least one stroke warning sign while the commonest sign identified was sudden unilateral limb weakness (24.4%). On multivariate logistic regression analysis, male sex (beta = 0.26, 95% CI = 0.14-0.39, p < 0.001) and 11 or more years of education (beta = 0.16, 95% CI = 0.03-0.29, p = 0.02) emerged the independent predictors of ability to identify at least one warning sign. CONCLUSION: Awareness of stroke warning signs is poor among Nigerians at increased risk for the disease. Efforts should be made to improve on the level of awareness through aggressive health education.
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Conocimientos, Actitudes y Práctica en Salud , Accidente Cerebrovascular/prevención & control , Causalidad , Comorbilidad , Estudios Transversales , Diabetes Mellitus/epidemiología , Escolaridad , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Debilidad Muscular/epidemiología , Nigeria/epidemiología , Riesgo , Distribución por Sexo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Población Suburbana/estadística & datos numéricosRESUMEN
It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of Lassa fever infection without associated bleeding, and to find Lassa virus (LAV) in the cerebrospinal fluid (CSF) but not in the serum. We report the case of a 38-year-old Nigerian woman with mainly CNS manifestation of Lassa fever. She was admitted twice within 11 days because of persistent fever. A clinical diagnosis of acute LAV encephalitis was made because of a high index of suspicion and CNS involvement confirmed by positive reverse transcriptase polymerase chain reaction (RT-PCR) for LAV in the CSF, while her blood was repeatedly negative for LAV by RT-PCR test. She recovered fully following supportive care coupled with treatment with an 18-day course of ribavirin, and suffered no long-term neurological complication or relapse. Post-treatment CSF examination by RT-PCR did not detect LAV.
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BACKGROUND: Lassa fever is a viral haemorrhagic disease endemic to west Africa. No large-scale studies exist from Nigeria, where the Lassa virus (LASV) is most diverse. LASV diversity, coupled with host genetic and environmental factors, might cause differences in disease pathophysiology. Small-scale studies in Nigeria suggest that acute kidney injury is an important clinical feature and might be a determinant of survival. We aimed to establish the demographic, clinical, and laboratory factors associated with mortality in Nigerian patients with Lassa fever, and hypothesised that LASV was the direct cause of intrinsic renal damage for a subset of the patients with Lassa fever. METHODS: We did a retrospective, observational cohort study of consecutive patients in Nigeria with Lassa fever, who tested positive for LASV with RT-PCR, and were treated in Irrua Specialist Teaching Hospital. We did univariate and multivariate statistical analyses, including logistic regression, of all demographic, clinical, and laboratory variables available at presentation to identify the factors associated with patient mortality. FINDINGS: Of 291 patients treated in Irrua Specialist Teaching Hospital between Jan 3, 2011, and Dec 11, 2015, 284 (98%) had known outcomes (died or survived) and seven (2%) were discharged against medical advice. Overall case-fatality rate was 24% (68 of 284 patients), with a 1·4 times increase in mortality risk for each 10 years of age (p=0·00017), reaching 39% (22 of 57) for patients older than 50 years. Of 284 patients, 81 (28%) had acute kidney injury and 104 (37%) had CNS manifestations and thus both were considered important complications of acute Lassa fever in Nigeria. Acute kidney injury was strongly associated with poor outcome (case-fatality rate of 60% [49 of 81 patients]; odds ratio [OR] 15, p<0·00001). Compared with patients without acute kidney injury, those with acute kidney injury had higher incidence of proteinuria (32 [82%] of 39 patients) and haematuria (29 [76%] of 38) and higher mean serum potassium (4·63 [SD 1·04] mmol/L) and lower blood urea nitrogen to creatinine ratio (8·6 for patients without clinical history of fluid loss), suggesting intrinsic renal damage. Normalisation of creatinine concentration was associated with recovery. Elevated serum creatinine (OR 1·3; p=0·046), aspartate aminotransferase (OR 1·5; p=0·075), and potassium (OR 3·6; p=0·0024) were independent predictors of death. INTERPRETATION: Our study presents detailed clinical and laboratory data for Nigerian patients with Lassa fever and provides strong evidence for intrinsic renal dysfunction in acute Lassa fever. Early recognition and treatment of acute kidney injury might significantly reduce mortality. FUNDING: German Research Foundation, German Center for Infection Research, Howard Hughes Medical Institute, US National Institutes of Health, and World Bank.
Asunto(s)
Fiebre de Lassa/patología , Fiebre de Lassa/terapia , Adulto , Estudios de Cohortes , Femenino , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Nigeria/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Therefore, we aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using recombinant Lassa virus nucleoprotein (NP) as antigen. METHODOLOGY/PRINCIPAL FINDINGS: The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and the IgG ELISA is based on capturing IgG antibody-antigen complexes using rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic (Ghana and Germany) areas. Using the IFA as reference method, we observed 91.5-94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to hospital in an endemic area revealed a clinical sensitivity for the stand-alone IgM ELISA of 31% (95% CI 25-37) and for combined IgM/IgG detection of 26% (95% CI 21-32) compared to RT-PCR. The specificity of IgM and IgG ELISA was estimated at 96% (95% CI 93-98) and 100% (95% CI 99-100), respectively, in non-Lassa fever patients from non-endemic areas. In patients who seroconverted during follow-up, Lassa virus-specific IgM and IgG developed simultaneously rather than sequentially. Consistent with this finding, isolated IgM reactivity, i.e. IgM in the absence of IgG, had no diagnostic value. CONCLUSIONS/SIGNIFICANCE: The ELISAs are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they are of value in diagnosing patients at later stage. The IgG ELISA may be useful for epidemiological studies and clinical trials due its high specificity, and the higher throughput rate and easier operation compared to IFA.