Invited Commentary: Thirty-five Years of Leaky Vaccines.

Over the past 35 years, the term "leaky vaccine" has gained widespread use in both mathematical modeling and epidemiologic methods for evaluating vaccines. Here we present a short history as we recall it of how the term was coined in the context of the history of sporozoite malaria vaccines that were thought to be possibly leaky in the 1980s. We draw a contrast with the all-or-none vaccine mechanism and review a few consequences for study design and population level effects. We invite readers to contribute information covering the time period preceding our memories in the 1980s as we may have overlooked something.

Sphingolipids and acylcarnitines are altered in placentas from women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.

Impact of pre-exposure prophylaxis uptake among gay, bisexual, and other men who have sex with men in urban centers in Brazil: a modeling study.

BACKGROUND: Men who have sex with men (MSM) in Brazil remain disproportionately affected by HIV. We estimated the potential incidence reduction by five years with increased uptake of publicly-funded, daily, oral tenofovir/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) among MSM using the Cost Effectiveness of Preventing AIDS Complications microsimulation model. We used national data, local studies, and literature to inform model parameters for three cities: Rio de Janeiro, Salvador, and Manaus. RESULTS: In Rio de Janero, a PrEP intervention achieving 10% uptake within 60 months would decrease incidence by 2.3% whereas achieving 60% uptake within 24 months would decrease incidence by 29.7%; results were similar for Salvador and Manaus. In sensitivity analyses, decreasing mean age at PrEP initiation from 33 to 21 years increased incidence reduction by 34%; a discontinuation rate of 25% per year decreased it by 12%. CONCLUSION: Targeting PrEP to young MSM and minimizing discontinuation could substantially increase PrEP's impact.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants.

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

Slow Spread of SARS-CoV-2 in Southern Brazil Over a 6-Month Period: Report on 8 Sequential Statewide Serological Surveys Including 35 611 Participants.

Objectives. To evaluate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over 6 months in the Brazilian State of Rio Grande do Sul (population 11.3 million), based on 8 serological surveys. Methods. In each survey, 4151 participants in round 1 and 4460 participants in round 2 were randomly sampled from all state regions. We assessed presence of antibodies against SARS-CoV-2 using a validated lateral flow point-of-care test; we adjusted figures for the time-dependent decay of antibodies. Results. The SARS-CoV-2 antibody prevalence increased from 0.03% (95% confidence interval [CI] = 0.00%, 0.34%; 1 in every 3333 individuals) in mid-April to 1.89% (95% CI = 1.36%, 2.54%; 1 in every 53 individuals) in early September. Prevalence was similar across gender and skin color categories. Older adults were less likely to be infected than younger participants. The proportion of the population who reported leaving home daily increased from 21.4% (95% CI = 20.2%, 22.7%) to 33.2% (95% CI = 31.8%, 34.5%). Conclusions. SARS-CoV-2 infection increased slowly during the first 6 months in the state, differently from what was observed in other Brazilian regions. Future survey rounds will continue to document the spread of the pandemic.

Late initiation of antiretroviral therapy: inequalities by educational level despite universal access to care and treatment.

BACKGROUND: Late antiretroviral treatment initiation for HIV disease worsens health outcomes and contributes to ongoing transmission. We investigated whether socioeconomic inequalities exist in access to treatment in a setting with universal access to care and treatment. METHODS: This study investigated the association of educational level, used as a proxy for socioeconomic status, with late treatment initiation and treatment initiation with advanced disease. Study participants included adults (≥25 years) who started treatment from 2005 to 2018 at Instituto Nacional de Infectologia Evandro Chagas of Fundação Oswaldo Cruz (INI/FIOCRUZ), Rio de Janeiro, Brazil. Educational level was categorized following UNESCO's International Standard Classification of Education: incomplete basic education, basic education, secondary level, and tertiary level. We defined late treatment initiation as those initiating treatment with a CD4 < 350 cells/mL or an AIDS-defining event, and treatment initiation with advanced disease as those initiating treatment with a CD4 < 200 cells/mL or an AIDS-defining event. A directed acyclic graph (DAG) was constructed to represent the theoretical-operational model and to understand the involvement of covariates. Logistic regression models were used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Multiple imputation using a chained equations approach was used to treat missing values and non-linear terms for continuous variables were tested. RESULTS: In total, 3226 individuals composed the study population: 876 (27.4%) had incomplete basic education, 540 (16.9%) basic, 1251 (39.2%) secondary level, and 525 (16.4%) tertiary level. Late treatment initiation was observed for 2076 (64.4%) while treatment initiation with advanced disease was observed for 1423 (44.1%). Compared to tertiary level of education, incomplete basic, basic and secondary level increased the odds of late treatment initiation by 89% (aOR:1.89 95%CI:1.47-2.43), 61% (aOR:1.61 95%CI:1.23-2.10), and 35% (aOR:1.35 95%CI:1.09-1.67). Likewise, the odds of treatment initiation with advanced disease was 2.5-fold (aOR:2.53 95%CI:1.97-3.26), 2-fold (aOR:2.07 95%CI:1.59-2.71), 1.5-fold (aOR:1.51 95%CI:1.21-1.88) higher for those with incomplete basic, basic and secondary level education compared to tertiary level. CONCLUSION: Despite universal access to HIV care and antiretroviral treatment, late treatment initiation and social inequalities persist. Lower educational level significantly increased the odds of both outcomes, reinforcing the existence of barriers to "universal" antiretroviral treatment.

Key questions for modelling COVID-19 exit strategies.

Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.

Leptin gene polymorphism (rs7799039; G2548A) is associated with changes in serum lipid concentrations during pregnancy: a prospective cohort study.

PURPOSE: Little is known about the effects of leptin and leptin receptor polymorphisms on lipid changes during pregnancy. The aims of this study were to evaluate the associations between the single nucleotide polymorphisms (SNPs) of leptin and leptin receptor genes and the lipid concentrations during pregnancy; and to test whether dietary intake is a mediator in these associations. METHODS: A prospective cohort of 154 pregnant women was followed up in Rio de Janeiro, Brazil during the following gestational periods: 5-13th, 20-26th and 30-36th weeks. HDL-C, total cholesterol (TC) and triglyceride (TG) were measured by the enzymatic colorimetric method, and LDL-C was calculated. DNA was extracted by the phenol-chloroform method, and leptin (G2548A, rs7799039) and leptin receptor SNPs (Q223R; rs1137101 and K109R; rs1137100) were genotyped using real-time PCR. Statistical analyses included linear mixed-effect models. RESULTS: Women with the AA genotype of G2548A polymorphism reported a higher fat and total energy intake and had a higher increase in TG concentration during pregnancy than women with AG or GG genotype. The association between G2548A SNP and TG concentrations was not attenuated by adjusting for total lipid (g) and energy (kcal) intake. We did not observe significant associations between the Q223R and K109R SNPs and the lipid concentrations. CONCLUSIONS: Women homozygous for the A allele of the leptin SNP (G2548A) had a higher increase in TG concentrations per gestational week compared with women with the AG or GG genotype. This is an exploratory and hypothesis-generating study, and the results need confirmation in studies with larger sample sizes.'

Vector competence, vectorial capacity of Nyssorhynchus darlingi and the basic reproduction number of Plasmodium vivax in agricultural settlements in the Amazonian Region of Brazil.

BACKGROUND: Brazilian malaria control programmes successfully reduced the incidence and mortality rates from 2005 to 2016. Since 2017, increased malaria has been reported across the Amazon. Few field studies focus on the primary malaria vector in high to moderate endemic areas, Nyssorhynchus darlingi, as the key entomological component of malaria risk, and on the metrics of Plasmodium vivax propagation in Amazonian rural communities. METHODS: Human landing catch collections were carried out in 36 houses of 26 communities in five municipalities in the Brazilian states of Acre, Amazonas and Rondônia states, with API (> 30). In addition, data on the number of locally acquired symptomatic infections were employed in mathematical modelling analyses carried out to determine Ny. darlingi vector competence and vectorial capacity to P. vivax; and to calculate the basic reproduction number for P. vivax. RESULTS: Entomological indices and malaria metrics ranged among localities: prevalence of P. vivax infection in Ny. darlingi, from 0.243% in Mâncio Lima, Acre to 3.96% in Machadinho D'Oeste, Rondônia; daily human-biting rate per person from 23 ± 1.18 in Cruzeiro do Sul, Acre, to 66 ± 2.41 in Lábrea, Amazonas; vector competence from 0.00456 in São Gabriel da Cachoeira, Amazonas to 0.04764 in Mâncio Lima, Acre; vectorial capacity from 0.0836 in Mâncio Lima, to 1.5 in Machadinho D'Oeste. The estimated R0 for P. vivax (PvR0) was 3.3 in Mâncio Lima, 7.0 in Lábrea, 16.8 in Cruzeiro do Sul, 55.5 in São Gabriel da Cachoeira, and 58.7 in Machadinho D'Oeste. Correlation between P. vivax prevalence in Ny. darlingi and vector competence was non-linear whereas association between prevalence of P. vivax in mosquitoes, vectorial capacity and R0 was linear and positive. CONCLUSIONS: In spite of low vector competence of Ny. darlingi to P. vivax, parasite propagation in the human population is enhanced by the high human-biting rate, and relatively high vectorial capacity. The high PvR0 values suggest hyperendemicity in Machadinho D'Oeste and São Gabriel da Cachoeira at levels similar to those found for P. falciparum in sub-Saharan Africa regions. Mass screening for parasite reservoirs, effective anti-malarial drugs and vector control interventions will be necessary to shrinking transmission in Amazonian rural communities, Brazil.

Associations between obesity candidate gene polymorphisms (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor (LEPR)) and dietary intake in pregnant women.

Genetic variants associated with dietary intake may be important as factors underlying the development of obesity. We investigated the associations between the obesity candidate genes (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor) and total energy intake and percentage of energy from macronutrients and ultra-processed foods before and during pregnancy. A sample of 149 pregnant women was followed up in a prospective cohort in Rio de Janeiro, Brazil. A FFQ was administered at 5-13 and 30-36 weeks of gestation. Genotyping was performed using real-time PCR. Associations between polymorphisms and the outcomes were investigated through multiple linear regression and ANCOVA having pre-pregnancy dietary intake as a covariate. The A-allele of FTO-rs9939609 was associated with a -6·5 % (95 % CI -12·3, -0·4) decrease in the percentage of energy from protein and positively associated with the percentage of energy from carbohydrates before pregnancy (ß=2·6; 95 % CI 0·5, 4·8) and with a 13·3 % (95 % CI 0·7, 27·5) increase in the total energy intake during pregnancy. The C-allele of MC4R-rs17782313 was associated with a -7·6 % (95 % CI -13·8, -1·0) decrease in the percentage of energy from protein, and positively associated with the percentage of energy from ultra-processed foods (ß=5·4; 95 % CI 1·1, 9·8) during pregnancy. ANCOVA results revealed changes in dietary intake from pre-pregnancy to pregnancy for FTO-rs9939609 (percentage of energy from ultra-processed foods, P=0·03), MC4R-rs17782313 (total energy intake, P=0·02) and LEP-rs7799039 (total energy intake, P=0·04; percentage of energy from protein, P=0·04). These findings suggest significant associations between FTO-rs9939609, MC4R-rs17782313 and LEP-rs7799039 genes and the components of dietary intake in pregnant women.

Anopheline salivary protein genes and gene families: an evolutionary overview after the whole genome sequence of sixteen Anopheles species.

BACKGROUND: Mosquito saliva is a complex cocktail whose pharmacological properties play an essential role in blood feeding by counteracting host physiological response to tissue injury. Moreover, vector borne pathogens are transmitted to vertebrates and exposed to their immune system in the context of mosquito saliva which, in virtue of its immunomodulatory properties, can modify the local environment at the feeding site and eventually affect pathogen transmission. In addition, the host antibody response to salivary proteins may be used to assess human exposure to mosquito vectors. Even though the role of quite a few mosquito salivary proteins has been clarified in the last decade, we still completely ignore the physiological role of many of them as well as the extent of their involvement in the complex interactions taking place between the mosquito vectors, the pathogens they transmit and the vertebrate host. The recent release of the genomes of 16 Anopheles species offered the opportunity to get insights into function and evolution of salivary protein families in anopheline mosquitoes. RESULTS: Orthologues of fifty three Anopheles gambiae salivary proteins were retrieved and annotated from 18 additional anopheline species belonging to the three subgenera Cellia, Anopheles, and Nyssorhynchus. Our analysis included 824 full-length salivary proteins from 24 different families and allowed the identification of 79 novel salivary genes and re-annotation of 379 wrong predictions. The comparative, structural and phylogenetic analyses yielded an unprecedented view of the anopheline salivary repertoires and of their evolution over 100 million years of anopheline radiation shedding light on mechanisms and evolutionary forces that contributed shaping the anopheline sialomes. CONCLUSIONS: We provide here a comprehensive description, classification and evolutionary overview of the main anopheline salivary protein families and identify two novel candidate markers of human exposure to malaria vectors worldwide. This anopheline sialome catalogue, which is easily accessible as hyperlinked spreadsheet, is expected to be useful to the vector biology community and to improve the capacity to gain a deeper understanding of mosquito salivary proteins facilitating their possible exploitation for epidemiological and/or pathogen-vector-host interaction studies.

1H Nuclear Magnetic Resonance Metabolomics of Plasma Unveils Liver Dysfunction in Dengue Patients.

UNLABELLED: Dengue, due to its global burden, is the most important arthropod-borne flavivirus disease, and early detection lowers fatality rates to below 1%. Since the metabolic resources crucial for viral replication are provided by host cells, detection of changes in the metabolic profile associated with disease pathogenesis could help with the identification of markers of prognostic and diagnostic importance. We applied (1)H nuclear magnetic resonance exploratory metabolomics to study longitudinal changes in plasma metabolites in a cohort in Recife, Brazil. To gain statistical power, we used innovative paired multivariate analyses to discriminate individuals with primary and secondary infection presenting as dengue fever (DF; mild) and dengue hemorrhagic fever (DHF; severe) and subjects with a nonspecific nondengue (ND) illness (ND subjects). Our results showed that a decrease in plasma low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) discriminated dengue virus (DENV)-infected subjects from ND subjects, and also, subjects with severe infection even presented a decrease in lipoprotein concentrations compared to the concentrations in subjects with mild infection. These results add to the ongoing discussion that the manipulation of lipid metabolism is crucial for DENV replication and infection. In addition, a decrease in plasma glutamine content was characteristic of DENV infection and disease severity, and an increase in plasma acetate levels discriminated subjects with DF and DHF from ND subjects. Several other metabolites shown to be altered in DENV infection and the implications of these alterations are discussed. We hypothesize that these changes in the plasma metabolome are suggestive of liver dysfunction, could provide insights into the underlying molecular mechanisms of dengue virus pathogenesis, and could help to discriminate individuals at risk of the development of severe infection and predict disease outcome. IMPORTANCE: Dengue, due to its global burden, is the most important mosquito-borne viral disease. There is no specific treatment for dengue disease, and early detection lowers fatality rates to below 1%. In this study, we observed the effects of dengue virus infection on the profile of small molecules in the blood of patients with mild and severe infection. Variations in the profiles of these small molecules reflected the replication of dengue virus in different tissues and the extent of tissue damage during infection. The results of this study showed that the molecules that changed the most were VLDL, LDL, and amino acids. We propose that these changes reflect liver dysfunction and also that they can be used to discriminate subjects with mild dengue from those with severe dengue.

Transposable elements in the Anopheles funestus transcriptome.

Transposable elements (TEs) are present in most of the eukaryotic genomes and their impact on genome evolution is increasingly recognized. Although there is extensive information on the TEs present in several eukaryotic genomes, less is known about the expression of these elements at the transcriptome level. Here we present a detailed analysis regarding the expression of TEs in Anopheles funestus, the second most important vector of human malaria in Africa. Several transcriptionally active TE families belonging both to Class I and II were identified and characterized. Interestingly, we have identified a full-length putative active element (including the presence of full length TIRs in the genomic sequence) belonging to the hAT superfamily, which presents active members in other insect genomes. This work contributes to a comprehensive understanding of the landscape of transposable elements in A. funestus transcriptome. Our results reveal that TEs are abundant and diverse in the mosquito and that most of the TE families found in the genome are represented in the mosquito transcriptome, a fact that could indicate activity of these elements.The vast diversity of TEs expressed in A. funestus suggests that there is ongoing amplification of several families in this organism.

Single nucleotide polymorphism coverage and inference of N-acetyltransferase-2 acetylator phenotypes in wordwide population groups.

OBJECTIVE: Several algorithms have been proposed to reduce the genotyping effort and cost, while retaining the accuracy of N-acetyltransferase-2 (NAT2) phenotype prediction. Data from the 1000 Genomes (1KG) project and an admixed cohort of Black Brazilians were used to assess the accuracy of NAT2 phenotype prediction using algorithms based on paired single nucleotide polymorphisms (SNPs) (rs1041983 and rs1801280) or a tag SNP (rs1495741). METHODS: NAT2 haplotypes comprising SNPs rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931 were assigned according to the arylamine N-acetyltransferases database. Contingency tables were used to visualize the agreement between the NAT2 acetylator phenotypes on the basis of these haplotypes versus phenotypes inferred by the prediction algorithms. RESULTS: The paired and tag SNP algorithms provided more than 96% agreement with the 7-SNP derived phenotypes in Europeans, East Asians, South Asians and Admixed Americans, but discordance of phenotype prediction occurred in 30.2 and 24.8% 1KG Africans and in 14.4 and 18.6% Black Brazilians, respectively. Paired SNP panel misclassification occurs in carriers of NATs haplotypes *13A (282T alone), *12B (282T and 803G), *6B (590A alone) and *14A (191A alone), whereas haplotype *14, defined by the 191A allele, is the major culprit of misclassification by the tag allele. CONCLUSION: Both the paired SNP and the tag SNP algorithms may be used, with economy of scale, to infer NAT2 acetylator phenotypes, including the ultra-slow phenotype, in European, East Asian, South Asian and American populations represented in the 1KG cohort. Both algorithms, however, perform poorly in populations of predominant African descent, including admixed African-Americans, African Caribbeans and Black Brazilians.

SARS-CoV-2 transmission in a highly vulnerable population of Brazil: a household cohort study.

Background: Household transmission studies seek to understand the transmission dynamics of a pathogen by estimating the risk of infection from household contacts and community exposures. We estimated within/extra-household SARS-CoV-2 infection risk and associated factors in a household cohort study in one of the most vulnerable neighbourhoods in Rio de Janeiro city. Methods: Individuals ≥1 years-old with suspected or confirmed COVID-19 in the past 30 days (index cases) and household members aged ≥1 year were enrolled and followed at 14 and 28 days (study period November/2020-December/2021). RT-PCR testing, COVID-19 symptoms, and SARS-CoV-2 serologies were ascertained in all visits. Chain binomial household transmission models were fitted using data from 2024 individuals (593 households). Findings: Extra-household infection risk was 74.2% (95% credible interval [CrI] 70.3-77.8), while within-household infection risk was 11.4% (95% CrI 5.7-17.2). Participants reporting having received two doses of a COVID-19 vaccine had lower extra-household (68.9%, 95% CrI 57.3-77.6) and within-household (4.1%, 95% CrI 0.4-16.6) infection risk. Within-household infection risk was higher among participants aged 10-19 years, from overcrowded households, and with low family income. Contrastingly, extra-household infection risk was higher among participants aged 20-29 years, unemployed, and public transportation users. Interpretation: Our study provides important insights into COVID-19 household/community transmission in a vulnerable population that resided in overcrowded households and who struggled to adhere to lockdown policies and social distancing measures. The high extra-household infection risk highlights the extreme social vulnerability of this population. Prioritising vaccination of the most socially vulnerable could protect these individuals and reduce widespread community transmission. Funding: Fundação Oswaldo Cruz, CNPq, FAPERJ, Royal Society, Instituto Serrapilheira, FAPESP.

Genome sequences of the human body louse and its primary endosymbiont provide insights into the permanent parasitic lifestyle.

As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens.

In vitro-reduced susceptibility to artemether in P. falciparum and its association with polymorphisms on transporter genes.

Plasmodium falciparum with reduced sensitivity to artemisinin derivatives has been observed in endemic areas, but the molecular mechanisms for this reduced sensitivity remain unclear. We evaluated the association between in vitro susceptibility of P. falciparum isolates obtained from southwest Nigeria and polymorphisms in selected putative transporter genes (PFE0775C, PF13_0271, pfmrp1, pfcrt, and pfmdr1). Modified schizont inhibition assay was used to determine the in vitro parasite susceptibility to artemether (ATH). Polymorphisms in selected genes were detected by polymerase chain reaction followed by direct DNA sequencing. The half-maximal inhibitory concentration (IC(50)) geometric mean (GM) for all P. falciparum isolates was 1.78 nM (range, 0.03-10.43 nM). Polymorphisms at codons 241, 86, and 76 of PFE0775C, pfmdr1, and pfcrt genes, respectively, were associated with reduced susceptibility to ATH. A new S263P single-nucleotide polymorphism on the PFE0775C gene was also detected in 27% of the isolates. Patient isolates harboring V241L or S263P polymorphisms on the PFE0775C gene showed increased IC(50) (GM: 3.08 nM and 1.79 nM, respectively). Plasmodium falciparum isolates harboring mutant Y86 pfmdr1 and P263 PFE0775C alleles showed a 2.5-5.5-fold increase in ATH IC(50.) This study shows that polymorphisms on the PFE0775C and pfmdr1 genes are associated with reduced sensitivity to ATH in fresh isolates of P. falciparum from Nigeria.

Big data technology in infectious diseases modeling, simulation, and prediction after the COVID-19 outbreak.

After the outbreak of COVID-19, the interaction of infectious disease systems and social systems has challenged traditional infectious disease modeling methods. Starting from the research purpose and data, researchers improved the structure and data of the compartment model or used agents and artificial intelligence based models to solve epidemiological problems. In terms of modeling methods, the researchers use compartment subdivision, dynamic parameters, agent-based model methods, and artificial intelligence related methods. In terms of factors studied, the researchers studied 6 categories: human mobility, nonpharmaceutical interventions (NPIs), ages, medical resources, human response, and vaccine. The researchers completed the study of factors through modeling methods to quantitatively analyze the impact of social systems and put forward their suggestions for the future transmission status of infectious diseases and prevention and control strategies. This review started with a research structure of research purpose, factor, data, model, and conclusion. Focusing on the post-COVID-19 infectious disease prediction simulation research, this study summarized various improvement methods and analyzes matching improvements for various specific research purposes.

Time-dependent vaccine efficacy estimation quantified by a mathematical model.

In this paper we calculate the variation of the estimated vaccine efficacy (VE) due to the time-dependent force of infection resulting from the difference between the moment the Clinical Trial (CT) begins and the peak in the outbreak intensity. Using a simple mathematical model we tested the hypothesis that the time difference between the moment the CT begins and the peak in the outbreak intensity determines substantially different values for VE. We exemplify the method with the case of the VE efficacy estimation for one of the vaccines against the new coronavirus SARS-CoV-2.