Splenic CD11c+ cells derived from semi-immune mice protect naïve mice against experimental cerebral malaria.

BACKGROUND: Immunity to malaria requires innate, adaptive immune responses and Plasmodium-specific memory cells. Previously, mice semi-immune to malaria was developed. Three cycles of infection and cure ('three-cure') were required to protect mice against Plasmodium berghei (ANKA strain) infection. METHODS: C57BL/6 J mice underwent three cycles of P. berghei infection and drug-cure to become semi-immune. The spleens of infected semi-immune mice were collected for flow cytometry analysis. CD11c(+) cells of semi-immune mice were isolated and transferred into naïve mice which were subsequently challenged and followed up by survival and parasitaemia. RESULTS: The percentages of splenic CD4(+) and CD11c(+) cells were increased in semi-immune mice on day 7 post-infection. The proportion and number of B220(+)CD11c(+)low cells (plasmacytoid dendritic cells, DCs) was higher in semi-immune, three-cure mice than in their naïve littermates on day 7 post-infection (2.6 vs 1.1% and 491,031 vs 149,699, respectively). In adoptive transfer experiment, three months after the third cured P. berghei infection, splenic CD11c(+) DCs of non-infected, semi-immune, three-cure mice slowed Plasmodium proliferation and decreased the death rate due to neurological pathology in recipient mice. In addition, anti-P. berghei IgG1 level was higher in mice transferred with CD11c(+) cells of semi-immune, three-cure mice than mice transferred with CD11c(+) cells of naïve counterparts. CONCLUSION: CD11c(+) cells of semi-immune mice protect against experimental cerebral malaria three months after the third cured malaria, potentially through protective plasmacytoid DCs and enhanced production of malaria-specific antibody.

Identifying SARS-CoV2 transmission cluster category: An analysis of country government database.

BACKGROUND: As a result of the high contagiousness and transmissibility of SARS-CoV-2, studying the location of the case clusters that will follow, will help understand the risk factors related to the disease transmission. In this study, we aim to identify the transmission cluster category and settings that can guide decision-makers which areas to be opened again. METHODS: A thorough review of the literature and the media articles were performed. After data verification, we included cluster data from eight countries as of 16th May 2020. Clusters were further categorized into 10 categories and analysis was performed. The data was organized and presented in an easily accessible online sheet. RESULTS: Among the eight included countries, we have found 3905 clusters and a total number of 1,907,944 patients. Indoor settings (mass accommodation and residential facilities) comprised the highest number of both number of clusters (3315/3905) and infected patients (1,837,019/1,907,944), while the outdoor ones comprised 590 clusters and 70,925 patients. Mass accommodation was associated with the highest number of cases in 5 of the 7 countries with data available. Social events and residential settings were responsible for the highest number of cases in the two remaining countries. In the USA, workplace facilities have reported 165 clusters of infection including 122 food production facilities. CONCLUSIONS: Lockdown could truly be a huge burden on a country's economy. However, with the proper knowledge concerning the transmissibility and the behaviour of the disease, better decisions could be made to guide the appropriate removal of lockdown across the different fields and regions.

Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis.

INTRODUCTION: Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed. METHODS: Electronic searches in PubMed, Scopus, the MEDION database and the Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy. RESULTS: Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square P = 0.1009, I(2) = 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies. CONCLUSIONS: To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers.

Rate of red blood cell destruction varies in different strains of mice infected with Plasmodium berghei-ANKA after chronic exposure.

BACKGROUND: Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC) destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied. METHODOLOGY: To generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated. RESULTS: Upon challenge with Plasmodium berghei ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb) drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%), which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively). Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6), followed by C57BL/6 (8.6), CBA (6.9) and NZW (4.0), p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p < 0.001. CONCLUSION: The results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also influence the outcome of auto-immune mediated destruction of RBC due to the variation in Hb loss per % parasitaemia and differences in antibody titer for each semi-immune mice strain. However, further studies at the molecular level ought to be carried out to confirm this.

Alcohols induce beta-hematin formation via the dissociation of aggregated heme and reduction in interfacial tension of the solution.

The formation of the malarial pigment, a unique hemozoin crystal with unit cells comprised of heme dimers, has been proposed as an ideal target for antimalarial screening. The mechanism of beta-hematin formation (a synthetic crystal structurally identical to hemozoin) has been suggested that a hydrophobic interaction is needed to solubilize heme, but this hypothesis needs further evidence. Direct study of the process of hemozoin formation in the malarial food vacuole has not been performed, due to complicated groups of lipids and proteins. To overcome this difficulty and to explore the environmental conditions for beta-hematin formation, we systematically studied beta-hematin formation induced by a series of small normal alcohols (methanol, ethanol, n-propanol, and n-butanol), which are structurally similar. For the first time, the ability of beta-hematin inducer could be evaluated by its concentration that is required to enhance heme crystallization by 50% (EC(50) values). These values provide a rapid and convenient tool for comparing the ability of initiators in beta-hematin formation. Our results showed that the ability of alcohols to induce beta-hematin formation in the order: n-butanol>n-propanol>ethanol>methanol. The induction of beta-hematin formation by alcohols is related with their degree of hydrophobicity and ability to solubilize heme, suggesting that the dissociation of aggregated heme by alcohols is a major factor in beta-hematin formation. In addition, alcohols can reduce the surface tension of a solution, thus lowering the energy barrier for creating critical nuclei.