Concordance between two monoclonal antibody-based antigen detection enzyme-linked immunosorbent assays for measuring cysticercal antigen levels in sera from pigs experimentally infected with Taenia solium and Taenia hydatigena.

BACKGROUND: Antigen detection in Taenia solium cysticercosis confirms viable infection in the intermediate host (either pig or human). The reference B158/B60 monoclonal antibody (mAb)-based Ag-enzyme-linked immunosorbent assay (ELISA) has acceptable levels of sensitivity and specificity in human neurocysticercosis with multiple brain cysts, although its sensitivity is lower in cases with single brain cysts, whereas in porcine cysticercosis the assay specificity is affected by its frequent cross-reaction with Taenia hydatigena, another common cestode found in pigs. Our group has produced 21 anti-T. solium mAbs reacting against antigens of the whole cyst, vesicular fluid, and secretory/excretory products, identifying TsW8/TsW5 as the most promising pair of mAbs for an Ag-ELISA. METHODS: We report the use of the TsW8/TsW5 Ag-ELISA to measure cysticercus antigen levels [expressed as optical density (OD) values] in two panels of sera collected from day 0 (baseline) to day 90 postinfection (PI) from pigs experimentally infected with T. solium (n = 26) and T. hydatigena (n = 12). At baseline and on days 28 and 90 PI, we used Bland-Altman (BA) analysis and Lin's concordance correlation coefficients (CCC) to determine the concordance between the TsW8/TsW5 and the B158/B60 Ag-ELISA. RESULTS: The TsW8/TsW5 Ag-ELISA was able to efficiently measure circulating antigen levels in T. solium-infected pigs, similar to that obtained with the B158/B60 Ag-ELISA. Almost all paired log-OD differences between assays were within the limits of agreement (LoA) in the BA analysis at baseline and on days 28 and 90 PI (92.3%, 100%, and 100%, respectively), and a high concordance of log-ODs between assays was also found (Lin's CCC: 0.69, 0.92, and 0.96, respectively, all P < 0.001). In pigs infected with T. hydatigena, almost all paired log-OD differences were within the LoA in the BA analysis, whereas the concordance of log-ODs between assays was low at baseline (Lin's CCC: 0.24) but increased on days 28 and 90 PI (Lins' CCC: 0.88 and 0.98, P < 0.001). CONCLUSIONS/SIGNIFICANCE: The TsW8/TsW5 Ag-ELISA recognizes antigens in pigs with T. solium cysticercosis and is highly concordant with the B158/B60 Ag-ELISA. However, its diagnostic use is hampered by cross-reactions with T. hydatigena, as in other mAb-based Ag-ELISAs.

Whole Genome Assembly of a Hybrid Trypanosoma cruzi Strain Assembled with Nanopore Sequencing Alone.

Trypanosoma cruzi is the causative agent of Chagas disease, which causes 10,000 deaths per year. Despite the high mortality associated with Chagas, relatively few parasite genomes have been assembled to date, with genome assemblies unavailable even for some commonly used laboratory strains. This is at least partially due to T. cruzi's highly complex and highly repetitive genome, which defies investigation using traditional short read sequencing methods. Here, we have generated a high-quality whole genome assembly of the hybrid Tulahuen strain, a commercially available Type VI strain, using long read Nanopore sequencing without short read scaffolding. The assembled genome contains 25% repeat regions, 17% variable multigene family members, and 27% transposable elements and is of comparable quality to T. cruzi genome assemblies that utilized both long and short read data. Notably, we find that regions with transposable elements are significantly enriched for multicopy surface proteins, and that surface proteins are, on average, closer to transposable elements than other coding regions. This finding suggests that mobile genetic elements such as transposons may drive recombination within surface protein gene families. This work demonstrates the feasibility of nanopore sequencing to resolve complex regions of T. cruzi genomes, and with these resolved regions, provides support for a possible mechanism for genomic diversification.

Post-traumatic stress disorder, food insecurity, and social capital after the 2017 coastal El Niño flooding among mothers from Piura, Peru: A mixed method study.

In order to understand the impacts in the post-disaster scenario of the 2017 El Niño events in the Piura region-Peru, we examined post-traumatic stress disorder (PTSD), food insecurity (FI), and social capital (SC) across three-time points in mothers in highly affected areas. In the Piura, Castilla, and Catacaos districts, we studied mothers combining mixed-method assessments at three (June-July 2017), eight and 12 months after the flooding. Each outcome was measured with the PTSD-Checklist-Civilian (PCL-C), the Household-Food-Insecurity-Access-Scale (HFIAS), the Adapted-Social-Capital-Assessment-Tool (SASCAT) surveys. In-depth interviews at the first evaluation were also conducted. At the first evaluation, 38.1% (n = 21) of 179 mothers reported PTSD; eight months and one year after the flooding, it dropped to 1.9% and virtually zero, respectively. Severe FI also declined over time, from 90.0% three months after the flooding to 31.8% eight months after, to 13.1% one year after. Conversely, high-cognitive SC was increased three months after the flooding (42.1%) and much greater levels at eight and 12 months after (86.7% and 77.7%, respectively). High levels of PTSD and severe FI three months after the flooding consistently decreased to nearly zero one-year post-disaster. High levels of high-cognitive SC may have helped mothers to recover from PTSD and FI in Piura.

Epidemiology of enterotoxigenic Escherichia coli and impact on the growth of children in the first two years of life in Lima, Peru.

Background: Enterotoxigenic E. coli (ETEC) is a leading cause of diarrheal morbidity and mortality in children, although the data on disease burden, epidemiology, and impact on health at the community level are limited. Methods: In a longitudinal birth cohort study of 345 children followed until 24 months of age in Lima, Peru, we measured ETEC burden in diarrheal and non-diarrheal samples using quantitative PCR (LT, STh, and STp toxin genes), studied epidemiology and measured anthropometry in children. Results: About 70% of children suffered from one or more ETEC diarrhea episodes. Overall, the ETEC incidence rate (IR) was 73 per 100 child-years. ETEC infections began early after birth causing 10% (8.9-11.1) ETEC-attributable diarrheal burden at the population level (PAF) in neonates and most of the infections (58%) were attributed to ST-ETEC [PAF 7.9% (1.9-13.5)] and LT + ST-ETEC (29%) of which all the episodes were associated with diarrhea. ETEC infections increased with age, peaking at 17% PAF (4.6-27.7%; p = 0.026) at 21 to 24 months. ST-ETEC was the most prevalent type (IR 32.1) with frequent serial infections in a child. The common colonization factors in ETEC diarrhea cases were CFA/I, CS12, CS21, CS3, and CS6, while in asymptomatic ETEC cases were CS12, CS6 and CS21. Only few (5.7%) children had repeated infections with the same combination of ETEC toxin(s) and CFs, suggested genotype-specific immunity from each infection. For an average ETEC diarrhea episode of 5 days, reductions of 0.060 weight-for-length z-score (0.007 to 0.114; p = 0.027) and 0.061 weight-for-age z-score (0.015 to 0.108; p = 0.009) were noted in the following 30 days. Conclusion: This study showed that ETEC is a significant pathogen in Peruvian children who experience serial infections with multiple age-specific pathotypes, resulting in transitory growth impairment.

60 Years of Michigan Plastic Surgery.

In 1964, the Section of Plastic and Reconstructive Surgery at the University of Michigan opened its doors to future surgeons and leaders in the field. Today, we are celebrating the 60-year history of the program and its significant contributions to the field. Beginning under the leadership of Reed O. Dingman, MD, DDS, the program began with three faculty members and two independent surgical residents. Since that time, it has expanded dramatically to include 24 faculty members and 28 integrated plastic surgery residents. The goals of the program have always been to achieve excellence in all three of our academic missions including clinical care, teaching, and research. Annually, the program sees an average of 35,000 outpatient clinic visits, 4,000 major operations, 200 peer-reviewed publications, $5,000,000 in research spending, and residents who are well trained and highly competitive for fellowships of their choosing every single year. Through scientific collaborations, academic exchanges, and medical missions, the program's influence has spread beyond Michigan, reaching the entire world. In addition to training world-renowned surgeons, Michigan's faculty and graduates have assumed leadership roles in prestigious professional organizations, scientific journals, and research foundations. In this article, we explore the roots of the program and reflect on six decades of impact, innovation, and inspiration.

Telemedicine and Pediatric Care in Rural and Remote Areas of Middle-and-Low-Income Countries: Narrative Review.

OBJECTIVES: Caring for children in low- and middle-income countries (LMIC) can be challenging. This review article aims to explore role of telemedicine in supporting pediatric care in LMIC. METHODOLOGY: A narrative review of existing English and Spanish literature was conducted to assess role of telemedicine to support pediatric care in LMIC. RESULTS: Beside medical education and direct pediatric care, telemedicine can provide sub-specialties consultations without extra burden on families. Additionally, telemedicine can help in lowering under-5 mortality by supporting neonatal care, infectious illnesses, and non-communicable diseases (NCDs). Telemedicine can be a gate for universal coverage for all children at a lower cost. For over a decade, it has been implemented successfully and sustained in a few LMIC. However, challenges in implementing telemedicine are enormous. Still, opportunities arise by using simpler technology, low-width band internet, smartphones, instant messaging applications and solar energy. COVID-19 pandemic facilitated acceptance and applicability of telemedicine worldwide including LMIC. Nevertheless, governments must regulate telemedicine by issuing policies and ensuring employment of local experts when possible to meet local resources and cultural competency. CONCLUSION: Telemedicine has proven successful in improving pediatrics care. Many LMIC should take advantage of this innovation to promote equity and access to high quality pediatric care.

Effects of breastfeeding on children's gut colonization with multidrug-resistant Enterobacterales in peri-urban Lima, Peru.

Children living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against children's incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1-16 months during a 2016-19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with children's risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce children's risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against children's incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.

Understanding the pathogenic mechanisms and therapeutic effects in neurocysticercosis.

Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to investigate the impact of anthelmintic treatment on neuropathological features in a rat model of neurocysticercosis. Rats were intracranially infected with Taenia solium oncospheres and treated with albendazole + praziquantel (ABZ), oxfendazole + praziquantel (OXF), or untreated placebo (UT) for 7 days. Following the last dose of treatment, brain tissues were evaluated at 24 h and 2 months. We performed neuropathological assessment for cyst damage, perilesional brain inflammation, presence of axonal spheroids, and spongy changes. Both treatments showed comparable efficacy in cyst damage and inflammation. The presence of spongy change correlated with spheroids counts and were not affected by anthelmintic treatment. Compared to white matter, gray matter showed greater spongy change (91.7% vs. 21.4%, p < 0.0001), higher spheroids count (45.2 vs. 0.2, p = 0.0001), and increased inflammation (72.0% vs. 21.4%, p = 0.003). In this rat model, anthelmintic treatment destroyed brain parasitic cysts at the cost of local inflammation similar to what is described in human neurocysticercosis. Axonal spheroids and spongy changes as markers of damage were topographically correlated, and not affected by anthelmintic treatment.

Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection.

There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens. There is differential recognition of antigens, including TB vaccine candidate antigens, between ATB participants and interferon-gamma release assay (IGRA + /-) individuals. We developed an ATB-specific peptide pool (ATB116) consisting of epitopes exclusively recognized by ATB participants. This pool can distinguish patients with pulmonary ATB from IGRA + /- individuals from various geographical locations, with a sensitivity of over 60% and a specificity exceeding 80%. This proteome-wide screen of T cell reactivity identified infection stage-specific epitopes and antigens for potential use in diagnostics and measuring Mtb-specific immune responses.

Rapid detection of Mycobacterium tuberculosis using recombinase polymerase amplification: A pilot study.

Tuberculosis remains one of the leading causes of death worldwide, especially in low- and middle-income countries. Tuberculosis treatment and control efforts are hindered by the difficulty in making the diagnosis, as currently available diagnostic tests are too slow, too expensive, or not sufficiently sensitive. Recombinase polymerase amplification (RPA) is a novel technique that allows for the amplification of DNA rapidly, at constant temperature, and with minimal expense. We calculated and compared the limit of detection, sensitivity, and specificity of two RPA-based assays for the diagnosis of pulmonary tuberculosis, using two sets of published primers. We also calculated and compared the assays' limits of detection and compared their performance using two different DNA extraction methods prior to amplification (a commercially available DNA extraction kit vs. the chelex method). The RPA-lateral flow assay had a limit of detection of 5 fg/µL of DNA, a sensitivity of 53.2%, and a specificity of 93.3%, while the real time-RPA assay had a limit of detection of 25 fg/µL of DNA, a sensitivity of 85.1%, and a specificity of 93.3%. There was no difference in assay performance when DNA extraction was carried out using the commercial kit vs. the chelex method. The real-time RPA assay has adequate sensitivity and specificity for the diagnosis of pulmonary tuberculosis and could be a viable diagnostic tool in resource-limited settings, but the lateral flow assay did not perform as well, perhaps due to the fact we used stored sputum specimens from a biorepository. More work is needed to optimize the RPA-lateral flow assay, to get a more accurate estimate of its specificity and sensitivity using prospectively collected specimens, and to develop both assays into point-of-care tests that can be easily deployed in the field.

Clinical and Metagenomic Characterization of Neurological Infections of People With Human Immunodeficiency Virus in the Peruvian Amazon.

Background: Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose. Methods: One hundred forty people with HIV with acute neurological symptoms from Iquitos, Peru, were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF) and for cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples was evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses. Results: Twenty-seven participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow Coma Scale score (P = .05), unilateral focal motor signs (P = .01), positive Babinski reflex (P = .01), and multiple lesions on head computed tomography (CT) (P = .002) were associated with cerebral toxoplasmosis. Photophobia (P = .03) and absence of lesions on head CT (P = .02) were associated with cryptococcal meningitis. mNGS of 42 samples identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, 5 possible cases of tuberculous meningitis, and incidental detections of hepatitis B virus (n = 1) and pegivirus (n = 1). mNGS had a positive percentage agreement of 71% and a negative percentage agreement of 91% with qPCR for T gondii. mNGS had a sensitivity of 78% and specificity of 100% for Cryptococcus diagnosis. Conclusions: An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for central nervous system infections.

Immunologic changes are detectable in the peripheral blood transcriptome of clinically asymptomatic Chagas cardiomyopathy patients.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected parasitic disease that affects approximately 6 million individuals worldwide. Of those infected, 20-30% will go on to develop chronic Chagas cardiomyopathy (CCC), and ultimately many of these individuals will progress to advanced heart failure. The mechanism by which this progression occurs is poorly understood, as few studies have focused on early CCC. In this study, we sought to understand the physiologic changes associated with T. cruzi infection and the development of CCC. We analyzed gene expression in the peripheral blood of asymptomatic Chagas patients with early structural heart disease, Chagas patients without any signs or symptoms of disease, and Chagas-negative patients with and without early structural heart disease. Our analysis shows that early CCC was associated with a downregulation of various peripheral immune response genes, with gene expression changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes were distinct from those of early cardiomyopathy in Chagas-negative patients, suggesting that the processes mediating CCC may be unique from those mediating progression to other cardiomyopathies. This work highlights the importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease. The changes we have identified may serve as biomarkers of progression and could inform strategies for the treatment of CCC in its early stages, before significant cardiac damage has occurred.

Assembly and phylogeographical analysis of novel Taenia solium mitochondrial genomes suggest stratification within the African-American genotype.

BACKGROUND: Taenia solium is a parasite of public health concern, causing human taeniasis and cysticercosis. Two main genotypes have been identified: Asian and African-American. Although characterizing T. solium genotypes is crucial to understanding the genetic epidemiology of its diseases, not much is known about the differences between T. solium mitochondrial genomes from different genotypes. Also, little is known about whether genotypes are further subdivided. Therefore, this study aimed to identify a set of point mutations distributed throughout the T. solium mitochondrial genome that differentiate the African-American from the Asian genotype. Another objective was to identify whether T. solium main genotypes are further stratified. METHODS: One Mexican and two Peruvian T. solium mitochondrial genomes were assembled using reads available in the NCBI Sequence Read Archive and the reference genome from China as a template. Mutations with respect to the Chinese reference were identified by multiple genome alignment. Jensen-Shannon and Grantham scores were computed for mutations in protein-coding genes to evaluate whether they affected protein function. Phylogenies by Bayesian inference and haplotype networks were constructed using cytochrome c oxidase subunit 1 and cytochrome b from these genomes and other isolates to infer phylogeographical relationships. RESULTS: A set of 31 novel non-synonymous point mutations present in all genomes of the African-American genotype were identified. These mutations were distributed across the mitochondrial genome, differentiating the African-American from the Asian genotype. All occurred in non-conserved protein positions. Furthermore, the analysis suggested a stratification of the African-American genotypes into an East African and a West African sublineage. CONCLUSIONS: A novel set of 31 non-synonymous mutations differentiating the main T. solium genotypes was identified. None of these seem to be causing differences in mitochondrial protein function between parasites of the two genotypes. Furthermore, two sublineages within the African-American genotype are proposed for the first time. The presence of the East African sublineage in the Americas suggests an underestimated connection between East African and Latin American countries that might have arisen in the major slave trade between Portuguese Mozambique and the Americas. The results obtained here help to complete the molecular epidemiology of the parasite.

Whole Genome Assembly of a Hybrid Trypanosoma cruzi Strain Assembled with Nanopore Sequencing Alone.

Trypanosoma cruzi is the causative agent of Chagas disease, which causes 10,000 deaths per year. Despite the high mortality caused by the pathogen, relatively few parasite genomes have been assembled to date; even some commonly used laboratory strains do not have publicly available genome assemblies. This is at least partially due to T. cruzi's highly complex and highly repetitive genome: while describing the variation in genome content and structure is critical to better understanding T. cruzi biology and the mechanisms that underlie Chagas disease, the complexity of the genome defies investigation using traditional short read sequencing methods. Here, we have generated a high-quality whole genome assembly of the hybrid Tulahuen strain, a commercially available Type VI strain, using long read Nanopore sequencing without short read scaffolding. Using automated tools and manual curation for annotation, we report a genome with 25% repeat regions, 17% variable multigene family members, and 27% transposable elements. Notably, we find that regions with transposable elements are significantly enriched for surface proteins, and that on average surface proteins are closer to transposable elements compared to other coding regions. This finding supports a possible mechanism for diversification of surface proteins in which mobile genetic elements such as transposons facilitate recombination within the gene family. This work demonstrates the feasibility of nanopore sequencing to resolve complex regions of T. cruzi genomes, and with these resolved regions, provides support for a possible mechanism for genomic diversification.

Seroprevalence of Chagas Disease among People of Latin American Descent Living in Suffolk County, Long Island, New York.

This cross-sectional study estimated a one-time point seroprevalence rate of Chagas disease among people of Latin American descent in Suffolk County, Long Island, New York. Subjects who met the inclusion criteria were screened using the Chagas Detect Plus Rapid Test (InBios, Seattle, WA) with confirmation via Trypanosoma cruzi enzyme immunoassay and T. cruzi immunoblot assay. Administration of a questionnaire regarding demographics and risk factors followed. A seroprevalence rate of 10.74% was found. Identified risk factors included prior residence in a palm leaf house (odds ratio [OR], 10.42; P = 0.003; 95% CI, 2.18-49.76), residence in a house with triatomines (OR, 9.03; P = 0.006; 95% CI, 1.90-42.88), and history of triatomine bite (OR, 9.52; P = 0.009; 95% CI, 1.75-51.77). Our findings emphasize the importance of this frequently underdiagnosed disease and help highlight the importance of early screening among high-risk populations.

An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses.

Mycobacterium tuberculosis (M.tb) infection causes marked tissue inflammation leading to lung destruction and morbidity. The inflammatory extracellular microenvironment is acidic, however the effect of this acidosis on the immune response to M.tb is unknown. Using RNA-seq we show that acidosis produces system level transcriptional change in M.tb infected human macrophages regulating almost 4000 genes. Acidosis specifically upregulated extracellular matrix (ECM) degradation pathways with increased expression of Matrix metalloproteinases (MMPs) which mediate lung destruction in Tuberculosis. Macrophage MMP-1 and -3 secretion was increased by acidosis in a cellular model. Acidosis markedly suppresses several cytokines central to control of M.tb infection including TNF-α and IFN-γ. Murine studies demonstrated expression of known acidosis signaling G-protein coupled receptors OGR-1 and TDAG-8 in Tuberculosis which are shown to mediate the immune effects of decreased pH. Receptors were then demonstrated to be expressed in patients with TB lymphadenitis. Collectively, our findings show that an acidic microenvironment modulates immune function to reduce protective inflammatory responses and increase extracellular matrix degradation in Tuberculosis. Acidosis receptors are therefore potential targets for host directed therapy in patients.

Development and Laboratory Evaluation of a Simple, Field-Applicable Coproantigen Enzyme-Linked Immunosorbent Assay for Diagnosis of Taeniasis in Northern Peru.

Coproantigen detection by enzyme-linked immunosorbent assay (coAg ELISA) is a vital tool for detecting and treating cases of Taenia solium taeniasis. However, the assay's procedures require costly materials and sophisticated equipment, which are typically inaccessible in rural settings where the disease is endemic. To overcome these barriers, we developed and evaluated a field-applicable coAg ELISA. The field coAg ELISA was developed and evaluated across four phases using known positive and negative stool samples collected from northern Peru. Phase I focused on field assay development, phase II on a small-scale performance evaluation, phase III on a large-scale evaluation, and phase IV on the use and reliability of a colorimetric scale card. All samples were processed using the field and standard assay procedures and compared using signal-to-noise ratios, correlation tests, performance characteristics, and agreement statistics where appropriate. The field coAg ELISA using reagents stored at -20°C and commercially available water and milk powder, and relying on spontaneous separation of the supernatant, had performance comparable to the standard assay. The field coAg ELISA was strongly correlated with the standard in both the small- and large-scale laboratory evaluation (r = 0.99 and r = 0.98, respectively). Finally, the field assay had an almost perfect agreement between independent readers (kappa = 0.975) and between each reader and the spectrophotometer. The field coAg ELISA demonstrated performance comparable to the standard, providing a low-cost alternative to the standard assay for identifying cases of intestinal taeniasis in a low-resource setting.

No impact of helminth coinfection in patients with smear positive tuberculosis on immunoglobulin levels using a novel method measuring Mycobacterium tuberculosis-specific antibodies.

Helminth/tuberculosis (TB)-coinfection can reduce cell-mediated immunity against Mycobacterium tuberculosis (Mtb) and increase disease severity, although the effects are highly helminth species dependent. Mtb have long been ranked as the number one single infectious agent claiming the most lives. The only licensed vaccine for TB (BCG) offers highly variable protection against TB, and almost no protection against transmission of Mtb. In recent few years the identification of naturally occurring antibodies in humans that are protective during Mtb infection has reignited the interest in adaptive humoral immunity against TB and its possible implementation in novel TB vaccine design. The effects of helminth/TB coinfection on the humoral response against Mtb during active pulmonary TB are however still unclear, and specifically the effect by globally prevalent helminth species such as Ascaris lumbricoides, Strongyloides stercoralis, Ancylostoma duodenale, Trichuris trichiura. Plasma samples from smear positive TB patients were used to measure both total and Mtb-specific antibody responses in a Peruvian endemic setting where these helminths are dominating. Mtb-specific antibodies were detected by a novel approach coating ELISA-plates with a Mtb cell-membrane fraction (CDC1551) that contains a broad range of Mtb surface proteins. Compared to controls without helminths or TB, helminth/TB coinfected patients had high levels of Mtb-specific IgG (including an IgG1 and IgG2 subclass response) and IgM, which were similarly increased in TB patients without helminth infection. These data, indicate that helminth/TB coinfected have a sustained humoral response against Mtb at the level of active TB only. More studies on the species-specific impact of helminths on the adaptive humoral response against Mtb using a larger sample size, and in relation to TB disease severity, are needed.

Impaired spatial working memory and reduced hippocampal neuronal density in a rat model of neurocysticercosis.

Neurocysticercosis (NCC) is the most common parasitic disease affecting the nervous system and is a leading cause of acquired epilepsy worldwide, as well as cognitive impairment, especially affecting memory. The aim of this study was to evaluate the effect of NCC on spatial working memory and its correlation with hippocampal neuronal density, in a rat model of NCC. This experimental study was conducted on female (n = 60) and male (n = 73) Holtzman rats. NCC was induced by intracranial inoculation of T. solium oncospheres in 14 day-old-rats. Spatial working memory was assessed using the T-maze test at 3, 6, 9, and 12 months post-inoculation, and sensorimotor evaluation was performed at 12 months post-inoculation. Hippocampal neuronal density was evaluated by immunostaining of NeuN-positive cells of the CA1 region. Of the rats inoculated with T. solium oncospheres, 87.2% (82/94) developed NCC. The study showed a significant decline in spatial working memory over a 1-year follow-up period in rats experimentally infected with NCC. Males showed an early decline that started at 3 months, while females demonstrated it at 9 months. Additionally, a decrease in neuronal density was observed in the hippocampus of NCC-infected rats, with a more significant reduction in rats with cysts in the hippocampus than in rats with cysts in other brain areas and control rats. This rat model of NCC provides valuable support for the relationship between neurocysticercosis and spatial working memory deficits. Further investigations are required to determine the mechanisms involved in cognitive impairment and establish the basis for future treatments.