Guillain-Barré Syndrome Outbreak in Peru 2019 Associated With Campylobacter jejuni Infection.

OBJECTIVE: To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak. METHODS: We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents. Sera from 41 controls were compared with cases for antibodies to Campylobacter jejuni and gangliosides. Genomic analysis was performed on 4 C jejuni isolates. RESULTS: The 49 included patients had a median age of 44 years (interquartile range [IQR] 30-54 years), and 28 (57%) were male. Thirty-two (65%) had symptoms of a preceding infection: 24 (49%) diarrhea and 13 (27%) upper respiratory tract infection. The median time between infectious to neurologic symptoms was 3 days (IQR 2-9 days). Eighty percent had a pure motor form of GBS, 21 (43%) had the axonal electrophysiologic subtype, and 18% the demyelinating subtype. Evidence of recent C jejuni infection was found in 28/43 (65%). No evidence of recent arbovirus infection was found. Twenty-three cases vs 11 controls (OR 3.3, confidence interval [CI] 95% 1.2-9.2, p < 0.01) had IgM and/or IgA antibodies against C jejuni. Anti-GM1:phosphatidylserine and/or anti-GT1a:GM1 heteromeric complex antibodies were strongly positive in cases (92.9% sensitivity and 68.3% specificity). Genomic analysis showed that the C jejuni strains were closely related and had the Asn51 polymorphism at cstII gene. CONCLUSIONS: Our study indicates that the 2019 Peruvian GBS outbreak was associated with C jejuni infection and that the C jejuni strains linked to GBS circulate widely in different parts of the world.

Impact of fractures and orthopedic surgeries in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis.

INTRODUCTION: In patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) gait disturbance is a predominant feature that leads to falls and fractures, which can further aggravate disability. We sought to evaluate the impact of fractures and orthopedic surgeries in patients with HAM/TSP. METHODS: We retrieved the medical records of HAM/TSP patients enrolled in our study center's HTLV-1 clinical cohort between 1989-2018. The selection criteria included: (1) diagnosis of HTLV-1 infection using two enzyme-linked immunosorbent assays and/or a confirmatory test, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) fractures associated with HAM/TSP. RESULTS: We identified 24 cases of fractures, 70% of which were females. The median age at the time of fracture was 60 years (IQR=24). Six cases reported fractures in patients under 45 years old. Ten patients (42%) had hip/coccyx fractures, seven (29%) were in the lower extremities, and four (17%) in the upper extremities. Half of these patients reported the use of wheelchairs. Five patients who had previously used canes required the use of wheelchairs after the reported fracture. Eight patients underwent corrective orthopedic surgery as a result of the fracture. CONCLUSIONS: For HAM/TSP patients, fractures are a complication that can exacerbate their severe impairment.

Early-Onset HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.

BACKGROUND: Vertical transmission of HTLV-1 could lead to the early development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This significantly affects quality of life and increases morbimortality. OBJECTIVE: To describe the epidemiological and clinical characteristics of patients with early-onset HAM/TSP, defined as disease onset before 20 years of age. METHODS: This is a retrospective study from an HTLV-1 clinical cohort between 1989 and 2019. We searched for medical records of patients with (1) diagnosis of HTLV-1 infection using two ELISA and/or one Western blot, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) HAM/TSP symptom-onset before 20 years of age. RESULTS: A total of 38 cases were identified in the cohort; 25 were female (66%). The median age of onset was 14 years old. 31 (82%) cases had HTLV-1 testing done among family members; 22 out of 25 tested mothers (88%) were HTLV-1 positive. Most patients (27/34) were breastfed for more than one year. Disease progression measured through EDSS and IPEC-1 showed an upward trend towards worsening spasticity with 18 patients (47%) eventually requiring mobility aids. CONCLUSIONS: Cases of early-onset HAM/TSP are not of rare occurrence, which translates into many more years of dependency, the use of mobility aids, and increased overall morbidity.

Impact of fractures and orthopedic surgeries in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis

Abstract INTRODUCTION In patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) gait disturbance is a predominant feature that leads to falls and fractures, which can further aggravate disability. We sought to evaluate the impact of fractures and orthopedic surgeries in patients with HAM/TSP. METHODS: We retrieved the medical records of HAM/TSP patients enrolled in our study center's HTLV-1 clinical cohort between 1989-2018. The selection criteria included: (1) diagnosis of HTLV-1 infection using two enzyme-linked immunosorbent assays and/or a confirmatory test, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) fractures associated with HAM/TSP. RESULTS: We identified 24 cases of fractures, 70% of which were females. The median age at the time of fracture was 60 years (IQR=24). Six cases reported fractures in patients under 45 years old. Ten patients (42%) had hip/coccyx fractures, seven (29%) were in the lower extremities, and four (17%) in the upper extremities. Half of these patients reported the use of wheelchairs. Five patients who had previously used canes required the use of wheelchairs after the reported fracture. Eight patients underwent corrective orthopedic surgery as a result of the fracture. CONCLUSIONS: For HAM/TSP patients, fractures are a complication that can exacerbate their severe impairment.

A Peruvian family with a high burden of HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T-lymphotropic virus 1 (HTLV-1) is frequent in Peru; an estimated 1-2% of the Peruvian population carry this retrovirus. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic disabling disease that affects about 1% of the carriers of HTLV-1. It is not yet known why some HTLV-1-infected people develop HAM/TSP while others do not. In this case report, we present a family with an unusually high burden of HAM/TSP: 5 (the 2 parents and 3 of their children) of 7 HTLV-1 carriers developed the same disease. We describe the clinical presentation and discuss the clustering of disease against the current knowledge of the pathogenesis of HAM/TSP. Families such as this may hold the key to discovering which factors trigger the development of HAM/TSP.

Frecuencia de las señales de alarma en pacientes con cefalea, atendidos en la emergencia de un hospital de Lima / Frequency of red flags in patients with headaches treated in an emergency unit in Lima

Las cefaleas en emergencia suelen ser un reto diagnóstico para el evaluador cuando se trata de diferenciarlas entreprimaria o secundaria a un trastorno neurológico subyacente.Objetivo: Describir la frecuencia de las señales de alarma en cefaleas secundarias y primarias en pacientes que acuden a emergencia.Materiales y Métodos: Estudio prospectivo de series de casos, que acuden a la Emergencia de Medicina de Adultos del Hospital Nacional CayetanoHeredia por cefalea, en un mes. Se excluyeron a los pacientes con cefalea traumática. Se usó un formato para laobtención de datos. Se clasificó a los pacientes en cefalea primaria o secundaria y se determinó la presencia de señales de alarma. Resultados:Se registraron 32 pacientes. Veintiséis (81%) tuvieron cefalea secundaria. De éstas, 9 se debieron a causas infecciosas y 9 a trastornos vasculares intracraneales. La cantidad de señales de alarma presentes en las cefaleas secundarias vario de 3 a 8, con una moda de 5; y en las primarias de 0 a 2, con una moda de 2. El empeoramiento progresivo y el examen neurológico anormal se presentaron en 96% de los casos de cefalea secundaria. Conclusiones: Las señales de alarma, empeoramiento progresivo y examen neurológico anormal fueronlos más frecuentes. Las cefaleas secundarias fueron más comunes que las cefaleas primarias. Se hace énfasis en la utilidad de usar esta metodología en emergencia

Headaches in the emergency room are usually a diagnostic challenge for the physician when they having to differentiate between a primary and secondary headaches and an underlying neurological disorder. Objectives: Describe the frequency of presentation of “red flags” in primary and secondary headaches, in patients presenting to an emergency department. Methods: A case-series prospective study was conducted in the Emergency room of Hospital Nacional Cayetano Heredia. All patients presenting with headaches within a month were evaluated. Trauma related headaches were excluded. A data collection form was used to determine the presence of red flags as well as other clinical data. The quantity of red flags was assessed in both types of headaches. Results: Thirty two patients were included for study. Twenty-six (81%) had secondary headaches. Nine of them were found to be secondary to infection and other 9 to intracranial vascular disorders. The quantity of red flags present on secondary headaches ranged from 3 to 8 with a mode of 5; on primary headaches they ranged from 0 to 2 with a mode of 2. Progressive worsening of headache and abnormal neurologic exam were present in 25 cases of secondary headache Conclusions: Red flags were progressive worsening of headache and abnormal neurologic exam. Thus the clinical assessment of red flags is useful in the evaluation of patients with secondary headache in the emergency room.

Short communication an interferon-γ ELISPOT assay with two cytotoxic T cell epitopes derived from HTLV-1 tax region 161-233 discriminates HTLV-1-associated myelopathy/tropical spastic paraparesis patients from asymptomatic HTLV-1 carriers in a Peruvian population.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic and progressive disorder caused by the human T-lymphotropic virus type 1 (HTLV-1). In HTLV-1 infection, a strong cytotoxic T cell (CTL) response is mounted against the immunodominant protein Tax. Previous studies carried out by our group reported that increased IFN-γ enzyme-linked immunospot (ELISPOT) responses against the region spanning amino acids 161 to 233 of the Tax protein were associated with HAM/TSP and increased HTLV-1 proviral load (PVL). An exploratory study was conducted on 16 subjects with HAM/TSP, 13 asymptomatic carriers (AC), and 10 HTLV-1-seronegative controls (SC) to map the HAM/TSP-associated CTL epitopes within Tax region 161-233. The PVL of the infected subjects was determined and the specific CTL response was evaluated with a 6-h incubation IFN-γ ELISPOT assay using peripheral blood mononuclear cells (PBMCs) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other proinflammatory and Th1/Th2 cytokines were also quantified in the supernatants by a flow cytometry multiplex assay. In addition, a set of human leukocyte antigen (HLA) class I alleles that bind with high affinity to the CTL epitopes of interest was determined using computational tools. Univariate analyses identified an association between ELISPOT responses to two new CTL epitopes, Tax 173-185 and Tax 181-193, and the presence of HAM/TSP as well as an increased PVL. The HLA-A*6801 allele, which is predicted to bind to the Tax 181-193 peptide, was overpresented in the HAM/TSP patients tested.

IFN-gamma production in response to Tax 161-233, and frequency of CD4+ Foxp3+ and Lin HLA-DRhigh CD123+ cells, discriminate HAM/TSP patients from asymptomatic HTLV-1-carriers in a Peruvian population.

Human T-lymphotropic virus 1 (HTLV-1) can cause HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study was to gain insight into the pathogenesis of HAM/TSP by focusing on the CD8(+) T-cell response. Twenty-three HTLV-1-seronegative controls (SC), 29 asymptomatic HTLV-1 carriers (AC) and 48 patients with HAM/TSP were enrolled in the study. We evaluated the production of interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells stimulated with Tax overlapping peptides, the expression of genes related to the CD8(+) cytotoxic T-cell response, the frequency of CD4(+) Foxp3(+) cells and of dendritic cells, and the HTLV-1 provirus load (PVL). The frequency of cells producing IFN-gamma in response to Tax 161-233, but not to Tax 11-19, discriminated patients with HAM/TSP from AC. The increased pro-inflammatory response observed in patients with HAM/TSP was shared by AC with a high PVL, who also exhibited lower levels of granzyme H mRNA in unstimulated CD8(+) T cells than AC with a low PVL. Patients with HAM/TSP showed higher frequencies of CD4(+) Foxp3(+) cells and lower frequencies of plasmacytoid dendritic cells (pDC) than AC. Our findings are consistent with a model in which HTLV-1, along with the host genetic background, drives quantitative and qualitative changes in pDC and CD4(+) Foxp3(+) cells that lead to a predominance of inflammatory responses over lytic responses in the CD8(+) T-cell response of individuals predisposed to develop HAM/TSP.

Early neurologic abnormalities associated with human T-cell lymphotropic virus type 1 infection in a cohort of Peruvian children.

OBJECTIVE: Because human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) may occur in some children infected with HTLV-1, we sought to determine the prevalence of neurologic abnormalities and any associations of neurologic abnormalities with infective dermatitis in these children. STUDY DESIGN: We enrolled 58 children infected with HTLV-1 and 42 uninfected children (ages 3 to 17) of mothers infected with HTLV-1 in a family study in Lima, Peru. We obtained medical and developmental histories, surveyed current neurologic symptoms, and conducted a standardized neurologic examination without prior knowledge of HTLV-1 status. RESULTS: HTLV-1 infection was associated with reported symptoms of lower extremity weakness/fatigue (odds ratio [OR], 6.1; confidence interval [CI], 0.7 to 281), lumbar pain (OR, 1.7; 95% CI, 0.4 to 8), and paresthesia/dysesthesia (OR, 2.6; CI, 0.6 to 15.8). HTLV-1 infection was associated with lower-extremity hyperreflexia (OR, 3.1; CI, 0.8 to 14.2), ankle clonus (OR, 5.0; CI, 1.0 to 48.3), and extensor plantar reflex (OR undefined; P = .2). Among children infected with HTLV-1, a history of infective dermatitis was associated with weakness (OR, 2.7; CI, 0.3 to 33), lumbar pain (OR, 1.3; CI, 0.2 to 8), paresthesia/dysesthesia (OR, 2.9; CI, 0.5 to 20), and urinary disturbances (OR, 5.7; CI, 0.5 to 290). CONCLUSIONS: Abnormal neurologic findings were common in Peruvian children infected with HTLV-1, and several findings were co-prevalent with infective dermatitis. Pediatricians should monitor children infected with HTLV-1 for neurologic abnormalities.

SYBR Green-based quantitation of human T-lymphotropic virus type 1 proviral load in Peruvian patients with neurological disease and asymptomatic carriers: influence of clinical status, sex, and familial relatedness.

To evaluate the human T-lymphotropic virus type 1 (HTLV-1) proviral DNA load in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-1 carriers, a SYBR Green-based real-time quantitative polymerase chain reaction (qPCR) assay was developed. HTLV-1 proviral DNA in peripheral blood mononuclear cells (PBMCs) was quantified using primers targeting the pX region and the HTLV-1 copy number normalized to the amount of ERV-3 (Endogenous Retrovirus 3) cellular DNA. Thirty-three asymptomatic HTLV-1 carriers (ACs) and 39 patients with HAM/TSP were enrolled. Some participants were relatives of HAM/TSP cases (16 ACs and 7 patients with HAM/TSP). On multiple linear regression analysis, the authors found a significant association between clinical status and HTLV-1 proviral load (P < .01), but only among women. ACs showed a median proviral load of 561 copies per 104 PBMCs (interquartile range: 251-1623). In HAM/TSP patients, the median proviral load was 1783 (1385-2914). ACs related to HAM/TSP patients presented a relatively high proviral load (median 1152); however, the association between relatedness to a HAM/TSP patient and proviral load was not significant (P = .1). In HAM/TSP patients, no association was found between proviral load and disease duration, progression or severity. The fact that the effect of HAM/TSP upon the HTLV-1 proviral load differed between sexes and the finding of a high proviral load among asymptomatic relatives of HAM/TSP patients suggest that not yet identified genetic or environmental factors influence the pathogenesis of HTLV-1 infection.