Guillain–Barré syndrome (GBS) remains the leading cause of acute flaccid paralysis in children following poliomyelitis eradication, with diagnostic challenges in pediatric populations. This is an observational cohort study that describes the epidemiological, clinical, and electrophysiological characteristics of pediatric GBS over a 27-year period (1995–2022) in Rio Grande do Norte, Brazil. A total of 132 patients under 18 years were included, with a median age of onset of 8 years; 22% were younger than 3 years. Antecedent events were identified in 71.2%, predominantly respiratory infections and diarrhea. Motor–sensory and pure motor forms were most common. Acute inflammatory demyelinating polyradiculoneuropathy was the predominant electrophysiological subtype, followed by axonal variants. Mechanical ventilation was required in 23.2% of cases, and mortality was 5.3%. Pain and meningeal signs were frequent and associated with elevated cerebrospinal fluid protein levels. Despite severe presentations, outcomes were favorable, with 93% regaining independent ambulation at six months. These findings highlight distinctive pediatric features of GBS and reinforce the importance of early diagnosis and treatment to improve prognosis and decrease morbidity.

Leprosy represents a public health concern; its diagnosis remains clinical. Recently, the Brazilian public health system/SUS incorporated the leprosy-specific IgM anti-PGL-I rapid test Fast ML Flow Hanseníase (MLFH/Bioclin, Brazil; originally ML Flow) to aid leprosy contacts surveillance and diagnosis. Anti-PGL-I antibody levels correlate with bacterial load. This multicenter study evaluated MLFH performance in confirmed leprosy cases from four Brazilian reference centers. MLFH results were compared to anti-PGL-I ELISA, bacilloscopy/BI and analyzed in indeterminate/I, pure neuritic/PN and in Ridley Jopling/RJ categories (tuberculoid/TT, borderline-tuberculoid/BT, borderline/BB, borderline-lepromatous/BL, lepromatous/LL). Leprosy patients’ serum samples (N = 158; 95 multibacillary/MB, 63 paucibacillary/PB) were evaluated. Additionally, 20 previously tested leprosy samples were distributed to each center to assess MLFH repeatability, inter-center and inter-operator reproducibility. Higher MLFH seropositivity (84.8

Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a recessive genetic disease. Affected individuals present musculoskeletal abnormalities, insulin resistance, hepatic steatosis, and may develop cardiomyopathy and mental retardation The mechanism linking AGPAT2 (for CGL1) and BSCL2 (for CGL2) mutations to the syndrome has yet to be fully understood. Here, we analyzed blood cell transcriptomes from individuals with CGL1 (n = 3), CGL2 (n = 12), unaffected BSCL2 heterozygotes (HET, n = 8), and healthy individuals (CTRL, n = 3). Study participants were also evaluated by densitometry (GE Lunar DPX), in addition to biochemical panel and pro-inflammatory cytokines measured in serum. The gene expression profile of CGL1 was similar to CTRL, a result likely due to the compensatory activity of other AGPAT isoforms. CGL2 had 283 differentially expressed genes (DEGs), most enriched for neurodegenerative- and mitochondria-related genes. There was a negative correlation between the top1 gene, NUAK2, and fat mass (rho = −0.55, p = 0.01). The HET group had 105 DEGs, with OLR1, an atherogenic gene, as the most significant (Padj = 0.003). Up-regulation of TNF signaling pathway was also detected, a finding confirmed by high TNF and low IL10 levels in serum. Both CGL2 individuals and their unaffected relatives had abnormal gene expression pattern. Further epidemiological studies should seek to assess cardiovascular risk in heterozygote individuals.

Alport syndrome is a progressive and hereditary nephropathy characterized by hematuria and proteinuria as well as extra renal manifestations as hearing loss and eye abnormalities. The disease can be expressed as autosomal recessive or autosomal dominant at COL4A3 and COL4A4 loci, respectively, or X-linked at the COL4A5 locus. This study investigated two unrelated families with nephropathy from Brazil with the aim to identify the mutations involved with the disease. Whole Exome Sequencing was performed for 4 people from each pedigree (case, parents and a sibling). DNA sequences were mapped against the human genome (GRCh38/hg38 build) to identify associated mutations. Two novel deleterious variants in COL4A3 and COL4A4 loci on chromosome 2 were identified. The variants were detected in the probands with mutant alleles in the homozygous state, a premature stop codon at position 481 of COL4A3 protein and a frameshift mutation leading to a stop codon at position 786 of COL4A4 protein. For both Alport cases the putative variants were surrounded by broad Runs of Homozygosity as well as genes associated with other hereditary nephropathies. Genotyping for COL4A3 validated the exome findings. Two novel variants were identified in two unrelated families from northeast of Brazil. The two deleterious variants identified are located on ROH´s locus with all variants in a homozygous state.

Phlebotomine sand flies are responsible for transmitting Leishmania (Ross, 1903) species, the etiological agents of leishmaniases, causing impacts on global public health, especially in northeastern Brazil. The state of Rio Grande do Norte has been recording cases of the disease compulsorily since the 1980s, and the last comprehensive and systematic survey of phlebotomine species was completed in 1997. Since then, new infected species have been identified in the country. Our objectives are to update the inventory of phlebotomine species in Rio Grande do Norte , analyze the natural infection by Leishmania, and detect spatial clusters of leishmaniasis incidence in Rio Grande do Norte . Systematic literature reviews and unpublished surveys were used; for spatial analysis, the calculation of the Local Index of Spatial Association and Moran's Local Index were employed; finally, quantitative PCR targeting the kDNA-7 gene with TaqMan system amplification was used to analyze natural infection. We recorded 30 phlebotomine species, 21 from the literature and 9 newly reported. Three species showed infection with Leishmania infantum (Nicolle, 1908), and we observed the formation of 4 high-incidence clusters of leishmaniases in Rio Grande do Norte . Over 20 yr, there was a significant increase in the number of species recorded in Rio Grande do Norte, since the last survey across the 8 geographic zones of Rio Grande do Norte; additionally, we recorded Psychodopygus wellcomei (Fraiha, Shaw & Lainson, 1971) and Evandromyia walkeri (Newstead, 1914) infected, the latter being the first report of infection with L. infantum. Finally, the cluster formation in the western region of Rio Grande do Norte may be related to local social and economic characteristics.

BACKGROUND:Leishmania infantum can be an opportunistic pathogen, with an immunocompromised status increasing the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL). VL has approximately 5% fatality rate; and HIV coinfection (AIDS/VL) increases this risk. We hypothesized that, relative to those with HIV alone, people with co-infection would have altered T cell activation which could impact on the risk of VL. METHODS:A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of L. infantum infection in people living with HIV (PLHIV) residing in Brazil (n = 1,372). Subsequent incident cases of VL were ascertained from a public health database through 2018 and from a cohort of families with VL. Immune status of 69 participants was evaluated and comparisons made between those with and without HIV, with latent or with active Leishmania infection and those without HIV but with active or resolved Leishmania or T cell hypersensitivity to Leishmania antigen and healthy control subjects. RESULTS:A total of 24.2% of PLHIV had positive anti-IgG L. infantum antibodies. The relative risk of developing AIDS/VL was 2.27 (95% CI: 0.920 to 5.59; p = 0.07) to HIV/Leish coinfected subjects with positive leishmania serology compared to HIV subjects without leishmania serology. Poor adherence to antiretroviral therapy (p = 0.0008) or prior opportunistic infections (p = 0.0007) was associated with development of AIDS/VL in asymptomatic HIV/Leish. CD4+ and CD8+ T cells counts or viral load were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8+CD38+HLA-DR+ T cells were higher in asymptomatic HIV/Leish than HIV. Likewise, senescent (CD57+) and PD1+ CD8+ T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups. CONCLUSION:Although asymptomatic HIV/Leish subjects had CD4+ and CD8+ T cells similar to HIV alone, their CD8+T cells had increased activation and senescence which could contribute to risk of developing VL.

Neutrophils, the first cells to arrive at infection sites, release neutrophil extracellular traps (NETs) comprising nuclear and/or mitochondrial DNA webs decorated with proteins. Similar to other parasites, Leishmania infantum induces NET extrusion. However, our understanding of NET formation and neutrophil fate after NET release in a Leishmania infection context is limited. Our study aimed to determine the DNA origin of the NET scaffolds released by human neutrophils in response to chemical or L. infantum stimulation. Neutrophils were incubated with PMA, PHA, LPS, or L. infantum, followed by DNA and elastase activity quantification; additionally, we evaluated the source of DNA that composes NETs. Neutrophil viability was evaluated by annexin-V/7AAd labeling. Expression of IL6, TNFA, IL10, CXCL1, CXCL8, and FPR1 in response to the L. infantum interaction was assessed. Neutrophils incubated with chemicals or L. infantum released NETs. However, neutrophils stimulated by the chemicals showed lower viability after 1 h in comparison to neutrophils incubated with parasites. NETs from chemically stimulated neutrophils were mainly composed of nuclear DNA. Conversely, the NET induced by the parasites was of mitochondrial DNA origin and had no leishmanicidal activity. After 4 h of parasite stimulation, neutrophils peak the expression of genes such as IL6, TNFA, CXCL1, CXCL8, and FPR1. Our study demonstrates that neutrophils produce NETs after chemical or L. infantum exposure. Although they are not toxic to the parasite, NETs are released as danger signals. These findings support the role of neutrophils in releasing signaling molecules, which influence the inflammatory environment in which the infectious process occurs.

Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil. A case–control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood. GBS typically manifested a week after rash and fever; acute inflammatory demyelinating polyradiculoneuropathy was more frequent. None of the GBS cases had a poor outcome. Serological assays for ZIKV and CHIKV revealed high titers of immunoglobulin G for both viruses in 9 out of 11 subjects. Metatranscriptomic analyses unveiled an increased abundance of reads attributed to Pseudomonas tolaasii and Toxoplasma gondii in the acute phase. Analysis of differentially expressed host genes during the acute phase revealed altered expression of genes associated with axogenesis, synapse assembly, and presynapse organization. Moreover, genes upregulated during acute GBS were primarily related to inflammation and the inflammasome pathways, including AIM2, NLR family genes and LRR-protein genes, and IL-10. These findings suggest that inflammasome activation via AIM2 could play a role in tissue damage during GBS. Further investigation into the general activation of innate inflammatory responses is warranted to elucidate their potential contribution to the pathology of GBS.

The maturation of the glymphatic system initiates fluid dynamics in the central nervous system (CNS). Here, we demonstrate that the initiating glymphatic function results in a steep reduction in the susceptibility of the CNS to Zika virus (ZIKV) infection. In mice, ZIKV injection before glymphatic system maturation leads to widespread infection, vascular deformation, and disruption of Aqp4+ astrocytic networks. After the glymphatic system formation, the same challenge fails to cause disease or persistent infection. Pharmacological inhibition of vasopressin receptor 1a, which reduces perivascular fluid dynamics, reopens the window of susceptibility to ZIKV-related disease. These findings reveal the glymphatic system as an innate protective barrier that limits viral spread in the brain parenchyma and suggest a possible explanation for why late-gestation human fetuses and newborns are less susceptible to ZIKV. Moreover, these data indicate that children with ZIKV-caused malformations can have continuous brain inflammation due to a defective glymphatic system. ### Competing Interest Statement The authors have declared no competing interest. International Centre for Genetic Engineering and Biotechnology, CRP/BRA18-05_EC, CRP/BRA24-02 National Council for Scientific and Technological Development, https://ror.org/03swz6y49, CNPq- 446325/2024-4, INCT-DT- 408294/2024-8, ZIKA- 440893/2016-0

BackgroundHansen's Disease (HD), caused byMycobacterium leprae, remains aglobal health concern, particularly in Brazil. Mossor & oacute;, a city in Rio Grande do NorteState, presents high HD incidence and has been a focus for disease control efforts.ObjectiveThis study aimed to assess the utility of a qualitative anti-PGL-I antibodyrapid test for screening multibacillary (MB) HD cases among males in high-riskneighbourhoods of Mossor & oacute;.MethodsThe study comprised serological testing using the ML Flow rapid test onmales aged 18 and above living in seven hyperendemic neighbourhoods independentlyof known HD contact. Seropositive individuals underwent medical assessment andreceived home visits for evaluation of their contacts ResultsAmong 623 individuals tested, 87 (14%) were seropositive for anti-PGL-IIgM antibodies and four among 79 who attended a medical assessment (5.1%) wereconfirmedasnewHDcases.Themappingandspatialdensityanalysisofseropositivityamong individuals without HD reflected differences in the geographic distribution ofHDcasesinthemunicipality.Among210contactsexamined,fouradditionalHDcaseswere identified.LimitationsThe study's focus on male population in specific neighbourhoods did notrepresent the whole urban area.ConclusionAlthough the leprosy new case detection rate obtained with this strategywas only 0.6% of all tested individuals, the study suggests that mapping anti-PGL-I seropositivity in the healthy population can aid in identifying HD high-risk areas.Future research with broader population samples is recommended to validate thesefindings and enhance HD control strategies in endemic regions

BACKGROUND AND AIMS:Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil. METHODS:A case-control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood. RESULTS:GBS typically manifested a week after rash and fever; acute inflammatory demyelinating polyradiculoneuropathy was more frequent. None of the GBS cases had a poor outcome. Serological assays for ZIKV and CHIKV revealed high titers of immunoglobulin G for both viruses in 9 out of 11 subjects. Metatranscriptomic analyses unveiled an increased abundance of reads attributed to Pseudomonas tolaasii and Toxoplasma gondii in the acute phase. Analysis of differentially expressed host genes during the acute phase revealed altered expression of genes associated with axogenesis, synapse assembly, and presynapse organization. Moreover, genes upregulated during acute GBS were primarily related to inflammation and the inflammasome pathways, including AIM2, NLR family genes and LRR-protein genes, and IL-10. INTERPRETATION:These findings suggest that inflammasome activation via AIM2 could play a role in tissue damage during GBS. Further investigation into the general activation of innate inflammatory responses is warranted to elucidate their potential contribution to the pathology of GBS.

Background In Brazil, dogs are considered the main reservoir for Leishmania infantum , the main causative agent of visceral leishmaniasis (VL) for dogs and humans. The goal of this study was to evaluate the effectiveness of deltamethrin impregnated collars for controlling of canine L. infantum infection. Methods A prospective case-control intervention study was performed in paired neighborhoods, implementing deltamethrin-impregnated collars in one area and culling VL dogs in both. Four cross-sectional serosurvey of canine, and one of human L. infantum infections were performed. Sand flies were monitored along 19 months. Bayesian model and Moran’s index of canine L. infantum infection rates were used to detect spatial autocorrelation. Results A total of 11,285 dog evaluations were performed over 27 months. At baseline, rates of canine L. infantum infection differed between areas: 10% in the intervention and 19.7% in control area [odds ratio 0.454 (95% CI: 0.364, 0.566)]. Human L. infantum infection also varied, with rates of 4% and 14.3% in the intervention and control areas, respectively. Comparing dogs and humans L. infantum infections within each area, the OR of infection were 2.405 [95% CI: (1.720, 3.363) in the control area and 1.459 [(95% CI: 1.117, 1.906) in the intervention area. The pooled OR across both areas was 1.776 [95% CI: (1.441, 2.189)]. Large scale implementation of insecticide collars was effective at 6 months [ OR 0.448, 95% CI: (0.343, 0.584)], but the effect was not sustained thereafter. Nonetheless, dogs wearing collar had lower of L. infantum seroconversion (p = 0.044), and households with collared dogs had reduction in sand fly abundance. Collar coverage remained below 80%, and approximately 40% of collars were lost before the scheduled replacement at 6-month interval. Reduction in VL dog culling was observed in both areas at 6 and 12 months. Spatial analysis revealed outlier blocks of canine infection, forming clusters that influence infection dynamics in neighboring areas. Conclusions There was reduction in Leishmania seroconversion in dogs that used collars. The use of collars reduced sand fly density in the household. Culling of VL dogs were not systematic because of loss of follow up or non-consent from the owners.

The incidence of human Visceral Leishmaniasis (VL) has decreased in Brazil; however, the number of areas reporting human and canine cases has increased, with Leishmania infantum usually preceding human infection. This study aimed to analyze the profile of infectious diseases that are endemic for both human and canine VL, in dogs housed in a shelter located in the state of Rio Grande do Norte, Northeast Brazil. Data was obtained between November/2021 to April/2022. All dogs residing at the shelter (98 dogs) were examined and blood was collected for testing for L. infantum, Ehrlichia canis, and Babesia sp. Statistical analyses considered the clinical and laboratory findings. Of the 98 animals, approximately 43% were positive for L. infantum antibodies, 19% were positive for L. infantum kDNA, and 18% were L. infantum positive by culture. Greater levels of anti-leishmania antibodies were observed in dogs with symptoms suggestive of VL. The dogs tested positive for E. canis (19/ 98) and B. canis (18/98). Lutzomyia longipalpis was captured inside the shelter, representing 74.25% (n = 225) of whole sandflies in the dog shelter. Concomitant infection by L. infantum and E. canis increased the odds of death. Treatment of VL included the use of allopurinol (n = 48) and miltefosine (n = 8). Treated animals showed more signs of Leishmania infection. Tickborn parasites and Leishmania were prevalent in sheltered dogs in a VLendemic area, which increases the odds of death and poses an additional challenge for caring for abandoned dogs and at the same time setting protocols to manage reservoirs of L. infantum.

Berardinelli-Seip congenital lipodystrophy (CGL), a rare autosomal recessive disorder, is characterized by a lack of adipose tissue. Infections are one of the major causes of CGL individuals' premature death. The mechanisms that predispose to infections are poorly understood. We used Leishmania infantum as an in vitro model of intracellular infection to explore mechanisms underlying the CGL infection processes, and to understand the impact of host mutations on Leishmania survival, since this pathogen enters macrophages through specialized membrane lipid domains. The transcriptomic profiles of both uninfected and infected monocyte-derived macrophages (MDMs) from CGL (types 1 and 2) and controls were studied. MDMs infected with L. infantum showed significantly downregulated expression of genes associated with infection-response pathways (MHC-I, TCR-CD3, and granzymes). There was a transcriptomic signature in CGL cells associated with impaired membrane trafficking and signaling in response to infection, with concomitant changes in the expression of membrane-associated genes in parasites (e.g. δ-amastins). We identified pathways suggesting the lipid storage dysfunction led to changes in phospholipids expression and impaired responses to infection, including immune synapse (antigen presentation, IFN-γ signaling, JAK/STAT); endocytosis; NF-kappaB signaling; and phosphatidylinositol biosynthesis. In summary, lipid metabolism of the host plays an important role in determining antigen presentation pathways.

SARS-CoV-2 genome underwent mutations since it started circulating within the human population. The aim of this study was to understand the fluctuation of the spike clusters concomitant to the population immunity either due to natural infection and/or vaccination in a state of Brazil that had both high rate of natural infection and vaccination coverage. A total of 1725 SARS-CoV-2 sequences from the state of Rio Grande do Norte, Brazil, were retrieved from GISAID and subjected to cluster analysis. Immunoinformatics were used to predict T- and B-cell epitopes, followed by simulation to estimate either pro- or anti-inflammatory responses and to correlate with circulating variants. From March 2020 to June 2022, the state of Rio Grande do Norte reported 579,931 COVID19 cases with a 1.4% fatality rate across the three major waves: May-Sept 2020, Feb-Aug 2021, and Jan-Mar 2022. Cluster 0 variants (wild type strain, Zeta) were prevalent in the first wave and Delta (AY.*), which circulated in Brazil in the latter half of 2021, featuring fewer unique epitopes. Cluster 1 (Gamma (P.1 + P.1.*)) dominated the first half of 2021. Late 2021 had two new clusters, Cluster 2 (Omicron, (B.1.1.529 + BA.*)), and Cluster 3 (BA.*) with the most unique epitopes, in addition to Cluster 4 (Delta sub lineages) which emerged in the second half of 2021 with fewer unique epitopes. Cluster 1 epitopes showed a high pro-inflammatory propensity, while others exhibited a balanced cytokine induction. The clustering method effectively identified Spike groups that may contribute to immune evasion and clinical presentation, and explain in part the clinical outcome.

Chikungunya, Dengue, and Zika viruses are endemic to Brazil, with a high annual incidence rate. As COVID-19 emerged as a pandemic, the diagnosis of arboviruses was underestimated. Hence, this study aimed to characterize the sociodemographic and clinical aspects of arboviruses in the context of the COVID-19 pandemic in the state of Maranhão, Brazil. Sociodemographic and clinical data were obtained by applying questionnaires to 179 patients treated at health units in São José de Ribamar, Paço do Lumiar, Raposa, Santa Inês, and Vargem Grande municipalities. Serological and polymerase chain reaction analyses were performed do detect Chikungunya, Zika, Dengue, and COVID-19 infections. The Maranhão state registered 706 probable cases of Chikungunya from 2019 to 2020. In 2020, the cases were reduced by 74.8% compared to those reported in 2019. The test results were analyzed separately. Here, 46.3% of the Chikungunya virus test results were negative, and 36.8% were positive. For the Zika virus tests, most (79.9%) were positive, as well as the DENV1, DENV2, DENV3, and DENV4 tests (88.3%, 88.3%, 89.4%, and 65.9%, respectively). For the COVID-19 tests, of the 146 individuals tested, 52.7% were reactive when considering the anti-S test, and 17.8% were positive when considering the anti-N test. Fever and myalgia were the symptoms most frequently reported by patients. Our results emphasize the importance of continuous epidemiological surveillance of arboviruses in northeastern Brazil, and simultaneous testing for Chikungunya, Dengue, and Zika viruses among suspected patients.

Background: The incidence of Guillain-Barré syndrome (GBS) has increased in Brazil since 2015, which initially was speculated to be secondary to the ZIKV and other newly introduced pathogens. The prognosis and overall outcome of Zika virus-associated GBS remain unclear. Objective: To investigate long-term neurological residua after GBS after ZIKV infection in the state of Rio Grande do Norte, Brazil Methods: The study included all GBS subjects diagnosed in 2015. Cases were considered having ZIKV disease if they had a rash with at least two other ZIKV-like symptoms in addition to positive anti ZIKV IgM or IgG. Information on signs or symptoms during the acute phase of the disease was retrieved from medical records. Patients were personally interviewed and re-examined or were contacted by phone 3 to 9 years after disease onset about residual symptoms and changes in daily living. Disability and handicap were assessed using the Hughes scale. Results: 34 patients were diagnosed with GBS during this period, 22 (64.7%) were included and examined at mean 52.81 months (SD 28.84) after disease onset. In the acute phase: mean age, years, was 44.41 mean (SD 15.79); 11 (50%) gender male; AIDP was the most frequent subtype, 18 patients (81.1%). The nadir varied from one day to 3 to 25 days (mean 8.5; SD 5). At that time 15 (68.18%) were severely disabled (grades 4 or 5 of the Hughes’ scale). Four (18.8%) participants required ventilator support. All received IVIG treatment. At follow-up, the facial paralysis found in 3 (13.6%) participant and 3 (13.6) participants experienced paresthesia. 18 (81.8%) participants had completely recovered (Hughes 0); 3 (13.6%) patients able to run with minor signs or symptoms (Hughes 1) and 1 (4.5%) participant were incapable of running (Hughes 2). Conclusion: Over 90 % of GBS patients diagnosed when ZIKV was first introduced in Brazil had a more or less complete functional recovery. These data suggest that long-term outcomes and prognosis of Zika virus-associated GBS do not differ in severity from GBS due to other triggers., but of also importance was the prompt IVIG treatment provided timewise.

ABSTRACT An outbreak of births of microcephalic patients in Brazil motivated multiple studies on this incident. The data left no doubt that infection by Zika virus (ZIKV) was the cause, and that this virus promotes reduction in neuron numbers and neuronal death. Analysis of patients' characteristics revealed additional aspects of the pathology alongside the decrease in neuronal number. Here, we review the data from human, molecular, cell and animal model studies attempting to build the natural history of ZIKV in the embryonic central nervous system (CNS). We discuss how identifying the timing of infection and the pathways through which ZIKV may infect and spread through the CNS can help explain the diversity of phenotypes found in congenital ZIKV syndrome (CZVS). We suggest that intraneuronal viral transport is the primary mechanism of ZIKV spread in the embryonic brain and is responsible for most cases of CZVS. According to this hypothesis, the viral transport through the blood–brain barrier and cerebrospinal fluid is responsible for more severe pathologies in which ZIKV-induced malformations occur along the entire anteroposterior CNS axis.

Visceral leishmaniasis (VL) is a neglected tropical disease that is globally distributed and has the potential to cause very serious illness. Prior literature highlights the emergence and spread of VL is influenced by multiple factors, such as socioeconomic status, sanitation levels or animal and human reservoirs. The study aimed to retrospectively investigate the presence and infectiousness of VL in Rio Grande do Norte (RN), Brazil between 2007 and 2020. We applied a hierarchical Bayesian approach to estimate municipality-specific relative risk of VL across space and time. The results show evidence that lower socioeconomic status is connected to higher municipality-specific VL risk. Overall, estimates reveal spatially heterogeneous VL risks in RN, with a high probability that VL risk for municipalities within the West Potiguar mesoregion are more than double the expected VL risk. Additionally, given the data available, results indicate there is a high probability of increasing VL risk in the municipalities of Natal, Patu and Pau dos Ferros. These findings demonstrate opportunities for municipality-specific public health policy interventions and warrant future research on identifying epidemiological drivers in at-risk regions.

Background: Leishmania infantum is an opportunistic parasitic infection. An immunocompromised state increases the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL), which has a ~5% fatality rate even with treatment. HIV coinfection increases the risk of death from VL. Methods: A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of L. infantum infection in HIV positive subjects residing in the state of Rio Grande do Norte, Brazil (n=1,372) and of these a subgroup of subjects were followed longitudinally. Subsequent incident cases of VL were ascertained from a public health database through 2018. A subgroup (n=69) of the cross-sectional study subjects was chosen to assess immune status (T cell activation, senescence, exhaustion) and outcome. The data were compared between asymptomatic HIV+/L. infantum+ (HIV/Leish), symptomatic visceral leishmaniasis (VL), recovered VL, DTH+ (Delayed-Type Hypersensitivity response – Leishmanin skin test), AIDS/VL, HIV+ only (HIV+), and Non-HIV/Non L. infantum infection (control subjects). Results: The cross-sectional study showed 24.2% of HIV+ subjects had positive anti-IgG Leishmania antibodies. After 3 years, 2.4% (8 of 333) of these HIV/Leish coinfected subjects developed AIDS/VL, whereas 1.05% (11 of 1,039) of HIV subjects with negative leishmania serology developed AIDS/VL. Poor adherence to antiretroviral therapy (p=0.0008) or prior opportunistic infections (p=0.0007) was associated with development of AIDS/VL. CD4+ (p=0.29) and CD8+ (p=0.38) T cells counts or viral load (p=0.34) were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8+CD38+HLA-DR+ T cells were higher in asymptomatic HIV/Leish than HIV group. Likewise, senescent (CD57+) or exhausted (PD1+) CD8+ T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups. Conclusion: Although asymptomatic HIV/Leish subjects had normal and similar CD4+ and CD8+ T cells counts, their CD8+T cells had increased activation, senescence, and exhaustion, which could contribute to risk of developing VL.