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

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

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

An Interferon-gamma ELISPOT assay with two CTL epitopes derived from HTLV-1 Tax region 161-233 discriminates HAM/TSP 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-gamma enzyme-linked immunospot (ELISPOT) responses against the region spanning aminoacids 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-gamma ELISPOT assay using peripheral blood mononuclear cells (PBMC) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other pro-inflammatory 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, which is predicted to bind to Tax 181-193 peptide, was over-presented in the HAM/TSP patients tested

Building a network for multicenter, prospective research of central nervous system infections in South America: Process and lessons learned

Multicenter collaborative networks are essential for advancing research and improving clinical care for a variety of conditions. Research networks are particularly important for central nervous system infections, which remain difficult to study due to their sporadic occurrence and requirement for collection and testing of cerebrospinal fluid. Establishment of long-term research networks in resource-limited areas also facilitates diagnostic capacity building, surveillance for emerging pathogens, and provision of appropriate treatment where needed. We review our experience developing a research network for encephalitis among twelve hospitals in five Peruvian cities since 2009. We provide practical suggestions to aid other groups interested in advancing research on central nervous system infections in resource-limited areas. Keywords: Central nervous system infections, Encephalitis, Epidemiology, Herpes simplex virus, Virolog

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