Low-level Infection Research Articles

Maternal Obesity Does Not Exacerbate the Effects of LPS Injection on Pregnancy Outcomes in Mice.

Simple SummaryObesity increases the risk of problems during pregnancy, potentially due to inappropriate activation of the immune system. We predicted that, because of this immune activation, obesity in mice would exacerbate the effects of lipopolysaccharide (LPS), a substance that mimics infection, impairs fetal growth and leads to pregnancy loss in animal models. Mice were fed a high- or low-fat diet for thirteen weeks prior to mating, and then received an LPS or control injection during pregnancy. Treatment with LPS induced pregnancy loss in some mice, as expected. However, LPS did not have more severe effects in females fed the high-fat diet, who were heavier. Our results therefore do not support the hypothesis that an otherwise healthy obese pregnancy can be driven to an adverse outcome by a low-level infection. Our study improves the understanding of why obese women are at greater risk of adverse pregnancy outcomes. In doing so, it will contribute to future studies that seek to determine how obese pregnancies at risk of adverse outcomes can be distinguished from healthy obese pregnancies.Obesity increases the risk of a number of pregnancy complications, potentially due to chronic inflammation. We predicted that an obesogenic high-fat diet (HFD) in mice would create an inflammatory environment that would exacerbate the effects of lipopolysaccharide (LPS), an inflammatory insult, administered during pregnancy. Females were placed on a HFD or a low-fat diet (LFD) prior to mating, injected with 2 µg LPS or control on gestational day 7 and collected on day 14. Treatment with LPS increased the odds that a female thought to be pregnant at injection had no conceptuses at day 14 (p = 0.024), suggesting that injection with LPS was more likely to induce complete abortion. However, there was no effect of diet on the odds of having no conceptuses at day 14 and no interaction between diet and LPS injection. Diet and LPS injection had no effect on the number of viable fetuses in females still pregnant at day 14. For fetal weight, there was a significant interaction between diet and treatment (p = 0.017), whereby LPS reduced fetal weight in HFD females but not in LFD females. However, LPS treatment of HFD females reduced fetal weight to that observed in control-injected LFD females. Although LPS increased the odds of abortion, there was little evidence that a HFD exacerbated the effects of LPS.

Mourilyan virus pathogenicity in kuruma shrimp (Penaeus japonicus).

The bunyavirus Mourilyan virus (MoV) occurs commonly in Black tiger (Penaeus monodon) and kuruma shrimp (Penaeusjaponicus) farmed in eastern Australia. There is circumstantial evidence of MoV causing mortalities among P.japonicus moved from farm ponds to tanks for rearing as broodstock. To directly assess its pathogenic potential, independent cohorts of pond- (n=24) or tank-reared juvenile (n=21) P.japonicus were challenged intramuscularly with a cephalothorax tissue homogenate of P.monodon containing high loads of MoV (1.48±0.28×108 MoV RNA copies/µg total RNA). In each trial, mortalities accumulated gradually among the saline-injected controls. Mortality onset occurred 12-14days earlier in the pond-reared shrimp, possibly due to them possessing low-level pre-existing MoV infections. Despite the time to onset of mortality differing, Kaplan-Meier survival analyses confirmed mortality rates to be significantly higher in both the pond- (p=.017) and tank-reared shrimp (p=.031) challenged with MoV. RT-qPCR data on shrimp sampled progressively over each trial showed high loads of MoV to establish following challenge and discounted GAV and other endemic viruses from contributing to mortality. Together, the data show that acute MoV infection can adversely compromise the survival of juvenile P.japonicus.

Economic Essay: The Civil Society – Not the Regulatory State – Should Deal with COVID-19 and the Next Pandemic

Danish politicians have taken credit for the low level of infection in Denmark, but the credit must be largely attributed to civil society, which, in the words of the Prime Minister, has stood together by keeping a distance. The good results call for civil society to play a greater role in the future, while the state's task should be to support civil society to a greater extent. And then the state should to a much lesser extent use prohibitions and injunctions.

Analytical and Clinical Assessment of a Portable, Isothermal Recombinase Polymerase Amplification (RPA) Assay for the Molecular Diagnosis of Urogenital Schistosomiasis.

Accurate diagnosis of urogenital schistosomiasis is crucial for disease surveillance and control. Routine diagnostic methods, however, lack sensitivity when assessing patients with low levels of infection still able to maintain pathogen transmission. Therefore, there is a need for highly sensitive diagnostic tools that can be used at the point-of-care in endemic areas. Recombinase polymerase amplification (RPA) is a rapid and sensitive diagnostic tool that has been used to diagnose several pathogens at the point-of-care. Here, the analytical performance of a previously developed RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic region was assessed using commercially synthesised S. haematobium Dra1 copies and laboratory-prepared samples spiked with S. haematobium eggs. Clinical performance was also assessed by comparing diagnostic outcomes with that of a reference diagnostic standard, urine-egg microscopy. The RT-ShDra1-RPA was able to detect 1 × 101 copies of commercially synthesised Dra1 DNA as well as one S. haematobium egg within laboratory-spiked ddH2O samples. When compared with urine-egg microscopy, the overall sensitivity and specificity of the RT-ShDra1-RPA assay was 93.7% (±88.7–96.9) and 100% (±69.1–100), respectively. Positive and negative predictive values were 100% (±97.5–100) and 50% (±27.2–72.8), respectively. The RT-ShDra1-RPA therefore shows promise as a rapid and highly sensitive diagnostic tool able to diagnose urogenital schistosomiasis at the point-of-care.

Estudo do perfil epidemiológico da tuberculose em Araraquara, SP, no período 2012 - 2017

Introdução: A tuberculose (TB) afeta 1/3 da população mundial e cerca de 10 milhões de pessoas desenvolvem TB a cada ano, resultando em mais de dois milhões de mortes. Objetivos: O principal objetivo deste trabalho é apresentar um estudo do perfil epidemiológico da TB em Araraquara (SP) e comparar o perfil epidemiológico da TB em Araraquara com os padrões da doença no mundo, Américas, Brasil e Estado de São Paulo. Método: As pesquisas e informações foram coletadas do relatório anual da Organização Mundial da Saúde (OMS), do Ministério da Saúde do Brasil, da Secretaria do Estado de São Paulo, da Secretaria Municipal de Saúde e do Serviço Especial de Saúde de Araraquara (SESA). O período de 2012 a 2017 foi analisado considerando-se as projeções das metas da OMS para o fim da TB de 2015 a 2035. Resultados: Todos os dados apresentados, com exceção da cidade de Araraquara, estão acima da projeção requerida pela OMS. Embora ligeiramente abaixo da projeção citada, Araraquara está se encaminhando para reduzir a incidência de TB até o ponto de erradicar a doença. conclusões: Os baixos níveis atuais de infecção por TB em Araraquara podem ser explicados por fatores como, um dos maiores Índices de Desenvolvimento Humano (IDH) do País, a existência de um sanatório especializado no tratamento da doença, políticas públicas e uma eficiente rede de informações sobre TB . Araraquara pode ser um modelo no combate à doença no nível nacional e erradicar a doença até antes do prazo estabelecido pela OMS.

Infectivity of Human Olfactory Neurons to SARS-CoV-2: A Link to Anosmia

Background: Most reports regarding SARS-CoV-2 infection have been dominated by the presence of severe respiratory symptoms: cough, breathlessness, and fever. Initial anecdotal reports suggested anosmia may also be a manifestation. Indeed, recent data suggests that up to 85% of infected individuals may experience an interference in gustation and olfaction, resulting in loss of smell and taste. In many individuals, inability to smell may be the only symptom of infection. We sought to investigate if the loss of smell is primarily due to direct infection of olfactory neurons. Methods: We utilized two olfactory neuronal cell lines, one male and the other female in origin. In addition, we used four undifferentiated and two partially differentiated, human developing neuronal cell lines derived from neuroblastoma of male and female origin to determine the permissiveness of these neurons to SARS-CoV-2. All infections were confirmed by quantitative-reverse transcriptase PCR (RT-qPCR), immunofluorescence assay (IFA) probing with anti-SARS-CoV-2 antibody, and evaluation of cytopathic effects and neurite formation. Since, both olfactory cell lines are terminally differentiated we induced partial differentiation of all cell lines with retinoic acid (RA) to determine if differentiation is a factor in viral permissiveness. To determine the mechanism of viral entry we evaluated the expression of serine protease and transmembrane serine protease 2 (TMPRSS2) by RT-qPCR and IFA. Results: Infection of two olfactory cell lines, JFEN and TC-268, with SARS-CoV-2 was determined by IFA and confirmed by RT-qPCR and morphological observations where dysregulation in neurite formation was documented. Four-to-five days after exposure to the virus both olfactory cell lines exhibited morphological evidence of infection while IFA analyses indicated that ~30% of the neurons were positive. Two weeks following infection between 70-80% of the neurons exhibited positive expression of SARS-CoV-2 antigens. Two partially differentiated: CRL-2266 and CRL-2267 and four undifferentiated cell lines: CRL 2142 CRL 2149, CRL-127 and CDL-2271 were essentially non-permissive when compared against the two olfactory cell lines and only rare neurons (<1:1,000) exhibited positive cells by IFA but no apparent morphological changes could be discerned. The RT-qPCR results showed low levels of infection. After RA treatment only one cell line, CRL-127, exhibited slight permissiveness which was confirmed by RT-qPCR. The TMPRSS2 receptor showed high expression in olfactory neurons but low expression in CRL-127 after RA treatment. Conclusion: Our findings strengthen the reported association of SARS-CoV-2 infection with loss of smell in individuals infected with the virus. Our results suggest that olfactory neurons, originating from both genders, were highly permissive to SARS-CoV-2 infection. Moreover, there were no differences in permissiveness to infection between male and female neurons. The infrequent susceptibility of other undifferentiated or partially differentiated neurons suggest it would be unlikely that SARS-CoV-2 infects other mature human brain neurons since, after birth, they have mostly completed neurogenesis. Our studies confirm the neurotropism of the SARS-CoV-2 to olfactory neurons. Preliminary observations indicate that viral entry is mediated by the TMPRSS2 receptor. Funding Statement: None to declare Declaration of Interests: All authors declare no conflict of interest.

Macroparasite Burden of Obligate and Facultative Symbionts in Symbiotic Communities of Scleractinian Corals

A variety of symbionts inhabit colonies of scleractinian corals, the main component of coral reef ecosystems. Obligate symbionts spend almost their whole lives (except the pelagic larvae stage) on or in the host, while facultative symbionts are less tightly associated with the host and easily leave them when food becomes scarce and competition and predation increase. The influence of parasites on the life traits of obligate and facultative symbionts has not yet been studied. The first step in this direction is the study of basic parameters of parasite infracommunities associated with coral symbionts. It was suggested that obligate symbionts that are tightly associated with their hosts and their symbiotic communities are more often infected. An alternative hypothesis suggests that facultative symbionts are more frequently infected because they easily change habitats and consume a broad food spectrum. For several years, we studied parasites of obligate and facultative symbionts (fish, decapods crustaceans, mollusks) associated with the corals Acropora and Pocillopora in the Nha Trang Bay (South China Sea). The highest abundance and diversity of macroparasites (Monogenea, Cestoda, Trematoda, Nematoda, Copepoda) were found in facultative symbionts of corals, fish-parabionts. Obligate fish-inbionts were infected much less often (Cestoda, Trematoda, Nematoda). Obligate symbionts predominated in the invertebrate symbionts, which were also weakly infected. The low abundance and diversity of parasites in obligate symbionts suggest that there should be significant investments in antiparasitic defense, which, together with efficient antipredation defense, minimize the mortality of obligate symbionts. Their fecundity and population number are usually low. Facultative symbionts presumably suffer higher mortality than obligate symbionts, but a more intensive use of resources and higher population numbers may compensate for this. A significant increase in the infection rate with an increase in host body size is typical of facultative symbionts, which are less protected than obligate symbionts. The latter showed low infection levels in all size groups. The results suggest that the role of parasites in shaping the life strategies of symbionts is no less important than the role of predators.

Genetic background for moderate resistance against fusarium head blight among winter wheat developed in the Forrest Steppe of Ukraine

Aim. The aim of the work was to evaluate the genetic background of resistance to Fusarium head blight in common winter wheat cultivars based on the allelic state of the TDF_076_2D gene conferring tolerance against Fusarium graminearum Schwabe and F. culmorum (W.G.Sm.) Sacc. fungi. Methods. We studied 91 winter common wheat cultivars developed in the Institute of Plant Physiology and Genetics of NAS of Ukraine. A silica-based commercial kit was used for DNA extraction. For the allelic state detection, the INDEL1 marker co-segregating with the TDF_076_2D gene was used. Results. The frequency of the resistance allele according to the marker for the gene conferring moderate resistance to the Fusarium fungi made up 0.802. Conclusions. The majority of the common wheat cultivars from the studied sample carry the resistance allele of the gene of interest. The data obtained are consistent with the results of previous research for the wider sample of the winter and spring common wheat cultivars. The cultivars with confirmed resistance allele might show lower infection level in the field and serve as a source of the gene in marker assisted selection.&#x0D; Keywords: common wheat, disease resistance genes, Fusarium head blight, molecular markers.

Fine-scale heterogeneity in Schistosoma mansoni force of infection measured through antibody response

Schistosomiasis is among the most common parasitic diseases in the world, with over 142 million people infected in low- and middle-income countries. Measuring population-level transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected using stool microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to S. mansoni soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. We estimated force of infection among children using the seroconversion rate and examined how it varied geographically and by age. At the community level, serological measures of transmission aligned with stool-based measures of infection (ρ = 0.94), and serological measures provided more resolution for between-community differences at lower levels of infection. Force of infection showed a clear gradient of transmission with distance from Lake Victoria, with 94% of infections and 93% of seropositive children in communities <1.5 km from the lake. Force of infection increased through age 3 y, by which time 65% (95% CI: 53%, 75%) of children were SEA positive in high-transmission communities-2 y before they would be reached by school-based deworming programs. Our results show that serologic surveillance platforms represent an important opportunity to guide and monitor schistosomiasis control programs, and that in high-transmission settings preschool-age children represent a key population missed by school-based deworming programs.

Low prevalence (0.13%) of COVID-19 infection in asymptomatic pre-operative/pre-procedure patients at a large, academic medical center informs approaches to perioperative care

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has resulted in reduced performance of elective surgeries and procedures at medical centers across the United States. Awareness of the prevalence of asymptomatic disease is critical for guiding safe approaches to operative/procedural services. As COVID-19 polymerase chain reaction (PCR) testing has been limited largely to symptomatic patients, health care workers, or to those in communal care centers, data regarding asymptomatic viral disease carriage are limited. MethodsIn this retrospective observational case series evaluating UCLA Health patients enrolled in pre-operative/pre-procedure protocol COVID-19 reverse transcriptase (RT)–PCR testing between April 7, 2020 and May 21, 2020, we determine the prevalence of COVID-19 infection in asymptomatic patients scheduled for surgeries and procedures. ResultsPrimary outcomes include the prevalence of COVID-19 infection in this asymptomatic population. Secondary data analysis includes overall population testing results and population demographics. Eighteen of 4,751 (0.38%) patients scheduled for upcoming surgeries and high-risk procedures had abnormal (positive/inconclusive) COVID-19 RT-PCR testing results. Six of 18 patients were confirmed asymptomatic and had positive test results. Four of 18 were confirmed asymptomtic and had inconclusive results. Eight of 18 had positive results in the setting of recent symptoms or known COVID-19 infection. The prevalence of asymptomatic COVID-19 infection was 0.13%. More than 90% of patients had residential addresses within a 67-mile geographic radius of our medical center, the median age was 58, and there was equal male/female distribution. ConclusionThese data demonstrating low levels (0.13% prevalence) of COVID-19 infection in an asymptomatic population of patients undergoing scheduled surgeries/procedures in a large urban area have helped to inform perioperative protocols during the COVID-19 pandemic. Testing protocols like ours may prove valuable for other health systems in their approaches to safe procedural practices during COVID-19.

Long-term follow-up results and complications in cancer patients with persistent nephrostomy due to malignant ureteral obstruction.

We aimed to evaluate the long-term complications and predisposing factors for these complications in patients with malignant ureteral obstruction (MUO) treated with percutaneous nephrostomy (PN). The records of patients with MUO treated with PN between January 2015 and 2018 were retrospectively reviewed for PN dislodgement, PN obstruction, PN replacement, pyelonephritis, hospitalizations due to PN complications, and other complications due to PN such as macroscopic hematuria, skin infections, or renal/perirenal abscess. Data for a total of 147 patients (229 renal units [RU], 107 males, 40 females) were evaluated. In 174 (76%) RU, PN was replaced due to PN dislodgement. The predisposing factors for PN dislodgement were follow-up time, body mass index (BMI), chemotherapy, diabetes mellitus (DM), low educational level (LEL), pyelonephritis, and catheter-related skin infections (CSRI). The PN was replaced in 40 RU due to obstruction. The predisposing factors for obstruction were follow-up time and BMI. Pyelonephritis developed at least once in 61 (41.5%) patients. Follow-up time, BMI, previous surgery, DM, and LEL were the predisposing factors for pyelonephritis. CSRI developed in 16 RU. Follow-up time, BMI, DM, and LEL were the predisposing factors for CSRI. Macroscopic hematuria developed in 11 patients. Follow-up time, previous surgery, DM, chemotherapy, and LEL were predisposing factors for macroscopic hematuria. The most common complication in patients with MUO treated with PN was PN dislodgement. However, life-threatening complications such as macroscopic hematuria and severe infections can also occur. Patients with DM, LEL, and chemotherapy are at high risk of PN-related complications.

Impact of Protoporphyrin Lysine Derivatives on the Ability of Nosema ceranae Spores to Infect Honeybees.

Simple SummaryHoneybees, which are important for the development and maintenance of natural ecosystems, are infected by microsporidia, Nosema apis and N. ceranae. These parasites induce a disease named nosemosis contributing to the impairment of digestion and nutrient absorption, ultimately leading to total colony collapse. The need for research into the control of N. ceranae has become increasingly important. Promising compounds for the treatment of nosemosis are porphyrins. In the present study, we examined the effects of three different porphyrins on the infectivity of N. ceranae microsporidia. A significantly lower level of infection was observed in the bees infected with the porphyrin-treated spores than in the control bees (infected with untreated spores). We showed that protoporphyrin lysine derivatives in particular prevented the development of Nosema spores and simultaneously extended bee life spans (up to 50%). The results also indicate that these porphyrins may contribute to the reduction in digestive nutrient absorption disorders in bees. The present findings can be used to develop a new class of drugs for combating nosemosis. These compounds may serve as preventive or disinfection agents through direct inactivation of Nosema both in the midgut and outside the host body, i.e., in the hive.The effect of two protoporphyrin IX derivatives conjugated with single (PP[Lys(TFA)-OH)]2) or double (PP[Lys(TFA)-Lys(TFA)-OH]2) lysine moieties on the infectious capacity of Nosema ceranae spores was examined, and their efficacies were compared with those of a cationic porphyrin (H2TTMePP). Honeybees were inoculated with spores preincubated with porphyrins or with untreated spores (control). A significantly lower level of infection was observed in the bees infected with the porphyrin-treated spores than in the infected control. Porphyrins 1 and 2 reduced the infectious capability of microsporidia more efficiently than porphyrin 3, with bee mortality declining to almost 50%. Confocal analysis of the midguts of infected bees revealed distinct differences in the number of spores between the control group and the group infected with PP[Lys(TFA)-Lys(TFA)-OH]2-treated spores. Notably, bees with a reduced level of infection consumed less sucrose syrup than the control bees, indicating a reduction in digestive disorders and an improvement in food absorption.

Isolation of Candidatus Rickettsia vini from Belgian Ixodes arboricola ticks and propagation in tick cell lines

Candidatus Rickettsia vini was originally detected in Ixodes arboricola ticks from Spain, and subsequently reported from several other Western Palearctic countries including Belgium. Recently, the bacterium was isolated in mammalian (Vero) cell culture from macerated male I. arboricola from Czech Republic, but there have been no reports of propagation in tick cells. Here we report isolation in a tick cell line of three strains of Ca. R. vini from I. arboricola collected from nests of great tits (Parus major) in Belgium. Internal organs of one male and two engorged female ticks were dissected aseptically, added to cultures of the Rhipicephalus microplus cell line BME/CTVM23 and incubated at 28 °C. Rickettsia-like bacteria were first seen in Giemsa-stained cytocentrifuge smears between 2 and 15 weeks later. Two of the isolates grew rapidly, destroying the tick cells within 2–4 weeks of onward passage in BME/CTVM23 cells, while the third isolate grew much more slowly, only requiring subculture at 4−5-month intervals. PCR amplification of bacterial 16S rRNA and Rickettsia gltA, sca4, ompB, ompA and 17-kDa genes revealed that all three isolates were Ca. R. vini, with 100 % identity to each other and to published Ca. R. vini sequences from other geographical locations. Transmission electron microscopy revealed typical single Rickettsia bacteria in the cytoplasm of BME/CTVM23 cells. The Ca. R. vini strain isolated from the male I. arboricola tick, designated Boshoek1, was tested for ability to grow in a panel of Ixodes ricinus, Ixodes scapularis and R. microplus cell lines and in Vero cells. The Boshoek1 strain grew rapidly, causing severe cytopathic effect, in the R. microplus line BME26, the I. ricinus line IRE11 and Vero cells, more slowly in the I. ricinus line IRE/CTVM19, possibly established a low-level infection in the I. ricinus line IRE/CTVM20, and failed to infect cells of any of four I. scapularis lines over a 12-week observation period. This study confirmed the applicability of the simple tick organ-cell line co-cultivation technique for isolation of tick-borne Rickettsia spp. using BME/CTVM23 cells.

Evaluation of the susceptibility of Prunus rootstock genotypes to Armillaria and Desarmillaria species

Variation in susceptibility of 28 Prunus rootstock genotypes to the causal agents of Armillaria root rot, Armillaria mellea, A. solidipes, and Desarmillaria tabescens, were studied by conducting in vitro root screening assays. Root segments with wounded and intact periderm were placed next to and on the top of the fungal cultures. At day 21, the percent success of fungal penetration and the circumferential and longitudinal lengths of fungal growth were measured. A parallel investigation using the inoculated root segments was carried out to characterize the active host defense mechanisms involved, including anatomical responses in bark and wood. Overall, the success of penetration and the longitudinal and circumferential spread of Armillaria spp. and D. tabescens were significantly different among various Prunus rootstock genotypes. None of the tested rootstock genotypes were completely resistant to infection. However, plum and plum derived rootstocks, and some of the cherry genotypes were less susceptible to infection compared to the peach genotypes. The host’s ability to limit infection by Armillaria spp. and D. tabescens was not limited to a single mechanism but appeared to be regulated by several collective nonspecific host responses acting together. Differential levels of a series of non-specific coordinated events were triggered in Prunus genotypes such as the formation of new callus tissue on the root surface, a colored reaction zone, necrophylactic periderm, new cells, and new vascular cambium to compartmentalize the pathogen. The host responses were elevated in the genotypes with low level of infection as compared to highly infected genotypes.

Dynamic changes impact the plum pox virus population structure during leaf and bud development

Plum pox virus (PPV) is a worldwide threat to stone fruit production. Its woody perennial hosts provide a dynamic environment for virus evolution over multiple growing seasons. To investigate the impact seasonal host development plays in PPV population structure, next generation sequencing of ribosome associated viral genomes, termed translatome, was used to assess PPV variants derived from phloem or whole leaf tissues over a range of plum leaf and bud developmental stages. Results show that translatome PPV variants occur at proportionately higher levels in bud and newly developing leaf tissues that have low infection levels while more mature tissues with high infection levels display proportionately lower numbers of viral variants. Additional variant analysis identified distinct groups based on population frequency as well as sets of phloem and whole tissue specific variants. Combined, these results indicate PPV population dynamics are impacted by the tissue type and developmental stage of their host.

Immunity to Soil-Transmitted Helminths: Evidence From the Field and Laboratory Models.

Infection with soil-transmitted helminths (STH) remains a major burden on global health and agriculture. Our understanding of the immunological mechanisms that govern whether an individual is resistant or susceptible to infection is derived primarily from model infections in rodents. Typically, experimental infections employ an artificially high, single bolus of parasites that leads to rapid expulsion of the primary infection and robust immunity to subsequent challenges. However, immunity in natura is generated slowly, and is only partially effective, with individuals in endemic areas retaining low-level infections throughout their lives. Therefore, there is a gap between traditional model STH systems and observations in the field. Here, we review the immune response to traditional model STH infections in the laboratory. We compare these data to studies of natural infection in humans and rodents in endemic areas, highlighting crucial differences between experimental and natural infection. We then detail the literature to date on the use of “trickle” infections to experimentally model the kinetics of natural infection.

Loop-mediated isothermal amplification (LAMP) test for diagnosis of uncomplicated malaria in endemic areas: a meta-analysis of diagnostic test accuracy

BackgroundThe global malaria decline has stalled and only a few countries are pushing towards pre-elimination. The aim of the malaria elimination phase is interruption of local transmission of a specified malaria parasite in a defined geographical area. New and improved screening tools and strategies are required for detection and management of very low-density parasitaemia in the field. The objective of this study was to synthesize evidence on the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) test for the detection of malaria parasites among people living in endemic areas.MethodsThis study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guideline. Relevant studies in the health-related electronic databases were searched. According to the criteria set for this study, eligible studies were identified. The quality of included studies was evaluated with the use of a quality assessment checklist. A summary performance estimates such as pooled sensitivity and specificity were stratified by type of LAMP. Bivariate model for data analyses was applied. Summary receiver operating characteristics plots were created to display the results of individual studies in a receiver operating characteristics space. Meta-regression analysis was performed to investigate the sources of heterogeneity among individual studies.ResultsTwenty-seven studies across 17 endemic countries were identified. The vast majority of studies were with unclear risk of bias in the selection of index test. Overall, the pooled test performances were high for Pan LAMP (sensitivity: 0.95, 95% CI 0.91 to 0.97; specificity: 0.98, 95% CI 0.95 to 0.99), Plasmodium falciparum (Pf) LAMP (sensitivity: 0.96, 95% CI 0.94 to 0.98; specificity: 0.99, 95% CI 0.96 to 1.00) or for Plasmodium vivax (Pv) LAMP from 6 studies (sensitivity: 0.98, 95% CI 0.92 to 0.99; specificity: 0.99, 95% CI 0.72 to 1.00). The area under the curve for Pan LAMP (0.99, 95% CI 0.98–1.00), Pf LAMP (0.99, 95% CI 0.97–0.99) and Pv LAMP was (1.00, 95% CI 0.98–1.00) indicated that the diagnostic performance of these tests were within the excellent accuracy range. Meta-regression analysis showed that sample size had the greatest impact on test performance, among other factors.ConclusionsThe current findings suggest that LAMP-based assays are appropriate for detecting low-level malaria parasite infections in the field and would become valuable tools for malaria control and elimination programmes. Future well-designed larger sample studies on LAMP assessment in passive and active malaria surveillances that use PCR as the reference standard and provide sufficient data to construct 2 × 2 diagnostic table are needed.

Human mesenchymal stem cell based intracellular dormancy model of Mycobacterium tuberculosis

Understanding the biology of the tuberculosis pathogen during dormant asymptomatic infection, called latent tuberculosis is crucial to decipher a resilient therapeutic strategy for the disease. Recent discoveries exhibiting presence of pathogen’s DNA and bacilli in mesenchymal stem cells (MSCs) of human and mouse despite completion of antitubercular therapy, indicates that these specific cells could be one of the niches for dormant Mycobacterium tuberculosis in humans. To determine if in vitro infection of human MSCs could recapitulate the in vivo characteristics of dormant M. tuberculosis, we examined survival, phenotype, and drug susceptibility of the pathogen in MSCs. When a very low multiplicity of infection (1:1) was used, M. tuberculosis could survive in human bone marrow derived MSCs for more than 22 days without any growth. At this low level of infection, the pathogen did not cause any noticeable host cell death. During the later phase of infection, MSC-residing M. tuberculosis exhibited increased expression of HspX (a 16-kDa alpha-crystallin homolog) with a concurrent increase in tolerance to the frontline antitubercular drugs Rifampin and isoniazid. These results present a human MSC-based intracelllular model of M. tuberculosis infection to dissect the mechanisms through which the pathogen acquires and maintains dormancy in the host.

Immune response related to Pelibuey sheep naturally infected with gastrointestinal nematodes in a tropical region of Mexico

We analysed the immune response involved in sheep naturally infected with gastrointestinal (GI) nematodes. Fifteen Pelibuey lambs were grazed in paddocks contaminated with GI nematodes for 13weeks. To assess the infection, the number of eggs per gram (epg) and the percentage of packed cell volume (pcv) were evaluated. Blood and abomasal tissue samples were collected at week 8 post-infection to analyse the expression levels of IL-4, IL-5, IL-6, IL-8, IL-13, TGF-β and FCεR1A genes. The nematode Haemonchus contortus was the main species identified. In addition, two groups of lambs were classified based on the x±SE of epg and pcv values: G-1, with 151 ± 28 and 29±0.33%, respectively, and G-2, with 475±59.5 and 26±0.38%, respectively. For G-1, upregulation of IL-4, IL-8, IL-13, TGF-β and FCεR1A genes from 2.42- to 14.99-fold was observed in blood and abomasal tissue samples (p>.05), and IL-5, IL-8 and TGF-β genes had significant gene expression levels in blood (p<.05). For G-2, moderate gene expression levels, ranging from 1.22- to 3.45-fold, were observed in abomasal tissue (p>.05), and the IL-5 gene presented significant gene expression in blood (p<.05). Strong positively correlated values (r) between pcv and IL-4, IL-8 and TGF-β genes were observed in G-1. In contrast, significant negative correlations between epg and IL-4, IL-5 and FCεR1A genes indicate acute infection for G-2. Our results suggest that IL-4, IL-5, IL-13, TGF-β and FCεR1A genes are important modulators of GI nematode infections of Pelibuey lambs.

Early detection of disease infection in chilli crops using sensors

Control of diseases is a key aspect of profitable chilli (Capsicum annuum L.) crop production, and early detection of disease incidence is therefore an important aspect of crop management. Visual crop assessment is the most commonly used approach, but it is expensive where labour costs are high and tends to be unreliable, especially at low levels of infection. Alternative cost-effective approaches for detection of diseases and pests at an early stage are therefore desirable. This trial focused on the potential of sensor technologies to detect diseases in a chilli crop earlier than is currently possible with visual assessment. Experiments were conducted to determine whether multispectral data could be used to detect disease infection at the individual leaf and whole plant level. A multispectral camera mounted on an unmanned aerial vehicle (UAV) and a hand-held NDVI sensor were used to collect weekly data on plants in a fungicide field trial. Bacterial spot incidence in all treatments was low (<20%) but was detectable using the sensors. The hand-held NDVI sensor was able to detect diseased plants between 5 and 20 days before significant disease symptoms were visually recorded. The hand-held sensor was found to be much more sensitive in detecting diseased plants than the UAV mounted sensor.