A blood RNA transcriptome signature for COVID-19.

BACKGROUND: COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has not been fully characterised. Analysis of whole-blood RNA expression may provide valuable information on disease pathogenesis. METHODS: We studied 45 patients with confirmed COVID-19 infection within 10 days from onset of illness and a control group of 19 asymptomatic healthy volunteers with no known exposure to COVID-19 in the previous 14 days. Relevant demographic and clinical information was collected and a blood sample was drawn from all participants for whole-blood RNA sequencing. We evaluated differentially-expressed genes in COVID-19 patients (log2 fold change ≥ 1 versus healthy controls; false-discovery rate < 0.05) and associated protein pathways and compared these to published whole-blood signatures for respiratory syncytial virus (RSV) and influenza. We developed a disease score reflecting the overall magnitude of expression of internally-validated genes and assessed the relationship between the disease score and clinical disease parameters. RESULTS: We found 135 differentially-expressed genes in the patients with COVID-19 (median age 35 years; 82% male; 36% Chinese, 53% South Asian ethnicity). Of the 117 induced genes, 14 were found in datasets from RSV and 40 from influenza; 95 genes were unique to COVID-19. Protein pathways were mostly generic responses to viral infections, including apoptosis by P53-associated pathway, but also included some unique pathways such as viral carcinogenesis. There were no major qualitative differences in pathways between ethnic groups. The composite gene-expression score was correlated with the time from onset of symptoms and nasal swab qPCR CT values (both p < 0.01) but was not related to participant age, gender, ethnicity or the presence or absence of chest X-ray abnormalities (all p > 0.05). CONCLUSIONS: The whole-blood transcriptome of COVID-19 has overall similarity with other respiratory infections but there are some unique pathways that merit further exploration to determine clinical relevance. The approach to a disease score may be of value, but needs further validation in a population with a greater range of disease severity.

Asymptomatic COVID-19: disease tolerance with efficient anti-viral immunity against SARS-CoV-2.

The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS-CoV-2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS-CoV-2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro-inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro-inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus-specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS-CoV-2 was observed in asymptomatic patients. In addition, asymptomatic COVID-19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro-inflammatory and more protective immune responses against SARS-CoV-2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID-19.

Effect of Haemophilus influenzae Type b Vaccination on Nasopharyngeal Carriage Rate in Children, Tehran, 2019.

BACKGROUND: Haemophilus influenzae (H. influenzae) strains, which commonly reside as commensals within the human pharynx and can remain as an asymptomatic carrier, but become invasive leading to pneumonia, septic arthritis, or meningitis. The Pentavac (pentavalent vaccine, manufactured by India, SII (DTwP-HepB-Hib)) was introduced to the Iranian National Immunization Plan in November 2014. The aim of this study is to investigate H. influenzae type b (Hib) carrier rate among children under 6 years old in Tehran. METHODS: This cross-sectional study was performed on 902 children including vaccinated/unvaccinated in the age of 6 months to 6 years, in Tehran. Sampling was performed from July 2019 to September 2019. Nasopharyngeal samples were taken from children by sterile swab. The PCR method was used to extract DNA. Then, all H. influenzae isolates were initially confirmed by molecular tests. BexA was used to distinguish typeable H. influenzae strains from nontypeable Haemophilus influenzae (NTHi). RESULTS: A total of 902 children were enrolled in the study: 452 were female (51%). H. influenzae carriage rate was 267 (29%), of that 150 samples (16.6%) were typeable. The nasopharyngeal Hib carrier rate in the children was 2.6% (24/902). 262 cases did not receive Hib vaccine. Analysis in nonnursery's children aged 4 to 6 (unvaccinated) years showed that the lower educational level of father, mother, and family number correlated with increased odds of colonization of children with Hib. CONCLUSION: Our findings showed a significant decrease (60%) in the overall Hib nasopharyngeal carriage in healthy children under six years after 5 years after the start of Hib vaccination.

Chest CT Evaluation of 11 Persistent Asymptomatic Patients with SARS-CoV-2 Infection.

In total, 11 asymptomatic carriers who underwent nasal or oropharyngeal swab tests for SARS-CoV-2 after being in close contact with patients who developed symptomatic 2019 coronavirus disease (COVID-19) were enrolled in this study. The chest multidetector computed tomography (CT) images of the enrolled patients were qualitatively and quantitatively analyzed. The findings of the first chest CT were normal in 3 (27.3%) patients, 2 of whom were aged below 15 years. The lesions of 2 (18.2%) patients involved 1 lobe with unifocal presence. Subpleural lesions were observed in 7 (63.6%) patients. Ground glass opacity (GGO) was the most common sign observed in 7 (63.6%) patients. Crazy-paving pattern and consolidation were detected in 2 (18.2%) and 4 (36.4%) patients, respectively. Based on deep learning and quantitative analysis, the mean volume of intrapulmonary lesions in the first CT image was 85.73 ± 84.46 cm3. In patients with positive findings on CT images, the average interval between positive real-time reverse transcriptase polymerase chain reaction assay and peak volume on CT images was 5.1 ± 3.1 days. In conclusion, typical CT findings can be detected in over 70% of asymptomatic SARS-CoV-2 carriers. The initial presentation is typically GGO along the subpleural regions and bronchi, which absorbs in approximately 5 days.

Natural History of Untreated HBeAg-Positive Chronic HBV Infection With Persistently Elevated HBV DNA but Normal Alanine Aminotransferase.

OBJECTIVES: Nucleos(t)ide analogues (NUCs) are not routinely recommended for patients with hepatitis B e antigen-positive chronic hepatitis B virus (HBV) infection who have persistently elevated serum HBV DNA level (>20,000 IU/mL) but normal alanine aminotransferase (<40 IU/L) level. Here, we evaluated the cumulative risks of hepatocellular carcinoma (HCC) in such patients (the untreated persistently elevated serum HBV DNA [pEDNA] group) compared with inactive carriers (the IC group). METHODS: Patients with untreated pEDNA (n = 126) and IC (n = 621) were enrolled between 2006 and 2012. Patients with cirrhosis or HCC at enrollment or a history of NUC treatment were excluded. RESULTS: The cumulative HCC risks at 5 and 9 years in the untreated pEDNA group were 1.1% and 1.9%, which were comparable with those of the IC group (P = 0.549). Inverse probability of treatment weighting and propensity score matching also showed similar HCC risks. In the untreated pEDNA group, there were no cases of HCC in the subgroup with serum HBV DNA level >1,000,000 IU/mL (immune-tolerant phase), which was significantly (P = 0.002) different compared with those with an intermediate serum HBV DNA level (20,000-1,000,000 IU/mL). DISCUSSION: The cumulative HCC risk in the untreated pEDNA group was minimal and comparable with that of the IC group. Further studies are required to determine whether early NUC treatment, indeed, reduces the HCC risk in patients with an intermediate serum HBV DNA level.

Trans-acting non-synonymous variant of FOXA1 predisposes to hepatocellular carcinoma through modulating FOXA1-ERα transcriptional program and may have undergone natural selection.

Interplay of pioneer transcription factor forkhead box A1 (FOXA1) and estrogen receptor has been implicated in sexual dimorphism in hepatocellular carcinoma (HCC), but etiological relevance of its polymorphism was unknown. In the case control study (1152 patients versus1242 controls), we observed significant increase in HCC susceptibility in hepatitis B virus carriers associated with a non-synonymous Thr83Ala variant of FOXA1 (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.11-1.48, for Ala83-containing genotype, after validation in an independent population with 933 patients versus 1030 controls), a tightly linked (CGC)5/6or7 repeat polymorphism at its promoter (OR 1.32; 95% CI 1.10-1.60, for (CGC)6or7-repeat-containing genotype), and their combined haplotype (OR 1.50; 95% CI 1.24-1.81, for (CGC)6or7-Ala83 haplotype). The susceptible FOXA1-Ala83 impairs its interaction with ERα, attenuates transactivation toward some of their dual target genes, such as type 1 iodothyronine deiodinase, UDP glucuronosyltransferase 2 family, polypeptide B17 and sodium/taurocholate cotransporting polypeptide, but correlates with strengthened cellular expression of α-fetoprotein (AFP) and elevated AFP serum concentration in HCC patients (n = 1096). The susceptible FOXA1 cis-variant with (CGC)6or7 repeat strengthens the binding to transcription factor early growth response 1 and enhances promoter activity and gene expression. Evolutionary population genetics analyses with public datasets reveal significant population differentiation and unique haplotype structure of the derived protective FOXA1-Thr83 and suggest that it may have undergone positive natural selection in Chinese population. These findings epidemiologically highlight the functional significance of FOXA1-ERα transcriptional program and regulatory network in liver cancer development.

Persistent Infection and Transmission of Senecavirus A from Carrier Sows to Contact Piglets.

Senecavirus A (SVA) is a picornavirus that causes acute vesicular disease (VD), that is clinically indistinguishable from foot-and-mouth disease (FMD), in pigs. Notably, SVA RNA has been detected in lymphoid tissues of infected animals several weeks following resolution of the clinical disease, suggesting that the virus may persist in select host tissues. Here, we investigated the occurrence of persistent SVA infection and the contribution of stressors (transportation, immunosuppression, or parturition) to acute disease and recrudescence from persistent SVA infection. Our results show that transportation stress leads to a slight increase in disease severity following infection. During persistence, transportation, immunosuppression, and parturition stressors did not lead to overt/recrudescent clinical disease, but intermittent viremia and virus shedding were detected up to day 60 postinfection (p.i.) in all treatment groups following stress stimulation. Notably, real-time PCR and in situ hybridization (ISH) assays confirmed that the tonsil harbors SVA RNA during the persistent phase of infection. Immunofluorescence assays (IFA) specific for double-stranded RNA (dsRNA) demonstrated the presence of double-stranded viral RNA in tonsillar cells. Most importantly, infectious SVA was isolated from the tonsil of two animals on day 60 p.i., confirming the occurrence of carrier animals following SVA infection. These findings were supported by the fact that contact piglets (11/44) born to persistently infected sows were infected by SVA, demonstrating successful transmission of the virus from carrier sows to contact piglets. Results here confirm the establishment of persistent infection by SVA and demonstrate successful transmission of the virus from persistently infected animals.IMPORTANCE Persistent viral infections have significant implications for disease control strategies. Previous studies demonstrated the persistence of SVA RNA in the tonsil of experimentally or naturally infected animals long after resolution of the clinical disease. Here, we showed that SVA establishes persistent infection in SVA-infected animals, with the tonsil serving as one of the sites of virus persistence. Importantly, persistently infected carrier animals shedding SVA in oral and nasal secretions or feces can serve as sources of infection to other susceptible animals, as evidenced by successful transmission of SVA from persistently infected sows to contact piglets. These findings unveil an important aspect of SVA infection biology, suggesting that persistently infected pigs may function as reservoirs for SVA.

HIV co-infection in HTLV-1 carriers in Spain.

BACKGROUND: Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain. METHODS: A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection. RESULTS: Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia). HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non-Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection. CONCLUSION: HIV coinfection is infrequent (<5%) among HTLV-1 carriers in Spain. More than half of co-infected patients come from Latin America. Sexual contact is the most frequent risk behavior, being MSM one third of cases. Late diagnosis explains the high rate (9/12) of clinical manifestations in our HIV-HTLV co-infected population.

The X factor.

A 45-year-old white woman presented with chronic bilateral, painless, progressive, peripheral vision loss. She was found to have bilateral optic atrophy and nonenhancing multifocal white matter lesions on magnetic resonance imaging of the brain. Cerebrospinal fluid analysis showed an elevated level of myelin basic protein. She was diagnosed as having the carrier state of X-linked adrenoleukodystrophy. X-linked adrenoleukodystrophy can mimic the clinical and radiographic features of multiple sclerosis in a female carrier. To our knowledge, this is the first case report of bilateral optic atrophy in a female X-linked adrenoleukodystrophy carrier in the English ophthalmic literature.

The importance of early diagnosis of Mycobacterium abscessus complex in patients with cystic fibrosis.

Mycobacterium abscessus complex can cause severe lung infections and has proven to be a serious threat to patients with cystic fibrosis and a challenge for clinicians due to difficulties in timely diagnosis and complex multidrug treatment regimes. Mycobacterial culture is the gold standard for diagnosis, but in most cystic fibrosis centers it is performed less frequently than culture for other pathogens. Consensus today recommends just one annual mycobacterial culture for asymptomatic patients with cystic fibrosis, a strategy likely to lead to diagnostic delays. Postponement of diagnosis might be the deciding factor in whether an early colonization turns into chronic infection. This review highlights the latest developments in knowledge about the pathogenicity and clinical consequences of M. abscessus complex pulmonary disease, addressing the central theme of why pulmonary infection requires early identification and aggressive antibiotic treatment. The window of opportunity, before M. abscessus complex transforms from a mucosal colonizer to a chronic biofilm infection, is where microbial eradication is most likely to be successful, making early diagnosis essential for improved outcomes.

Poliovirus excretion following vaccination with live poliovirus vaccine in patients with primary immunodeficiency disorders: clinicians' perspectives in the endgame plan for polio eradication.

OBJECTIVE: Primary immunodeficiency (PID) patients are prone to developing viral infections and should not be vaccinated with live vaccines. In such patients, prolonged excretion and viral divergence may occur and they may subsequently act as reservoirs in the community introducing mutated virus and jeopardizing polio eradication. One hundred and thirty PID cases were included for poliovirus detection in stool with assessment of divergence of detected polioviruses from oral polio vaccine (OPV) virus. Clinical presentations of PID patients with detectable poliovirus in stool specimens are described. RESULTS: Six PID patients (4.5%) had detectable vaccine-derived poliovirus (VDPV) excretion in stool specimens; of these, five patients had severe combined immunodeficiency (two with acute flaccid paralysis, one with meningoencephalitis and two without neurological manifestations), and one patient had X-linked agammaglobulinemia (paralysis developed shortly after diagnosis of immunodeficiency). All six case-patients received trivalent OPV. Five case-patients had type 2 immunodeficiency-related vaccine-derived polioviruses (iVDPV2) excretion; one had concomitant excretion of Sabin like type 3 virus and one was identified as iVDPV1 excretor. Surveillance for poliovirus excretion among PID patients is critical as these patients represent a potential source to reseed polioviruses into populations.

Hepatitis B virus pre-S/S variants in liver diseases.

Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Because of the spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B virus (HBV) genome evolves during the course of infection under the antiviral pressure of host immunity. The clinical significance of pre-S/S variants has become increasingly recognized in patients with chronic HBV infection. Pre-S/S variants are often identified in hepatitis B carriers with CH, LC, and HCC, which suggests that these naturally occurring pre-S/S variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. This paper reviews the function of the pre-S/S region along with recent findings related to the role of pre-S/S variants in liver diseases. According to the mutation type, five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, which results in liver diseases. Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. Additional investigations are required to explore the molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each stage of liver disease.

Group A Streptococcus infections in children: from virulence to clinical management.

PURPOSE OF REVIEW: Recent findings have open new perspectives on group A Streptococcus (GAS) virulence understanding with special focus on the carrier stage and new hopes for an efficient vaccine against this important pathogen. RECENT FINDINGS: Understanding of carriage state, transmission and role of virulence factors in invasive infections have been recently active research fields questioning the link between carriage and infections and highlighting the potential to prevent invasive diseases. New roles for already well known virulence factors, such as Streptolysin O, M protein or NAD(+)-glycohydrolase have been discovered. Immunological studies have also shown diversity in both clinical and immunological responses toward various GAS antigens raising questions, and hopes, for the development of an efficient global vaccine candidate. SUMMARY: A greater understanding of GAS virulence strategies, and their associated clinical manifestations, may be obtained by shifting our research scope toward virulence determinant interactions and cooperation rather than focusing on individual virulence factor or specific strain characterization only.

Inherited pulmonary cylindromas: extending the phenotype of CYLD mutation carriers.

BACKGROUND: Germline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas. OBJECTIVES: To search for clinical and radiological features of multiple pulmonary cylindromas in a cohort of 16 patients with CYLD mutations. METHODS: A retrospective case-note review was carried out in a tertiary dermatogenetics clinic where CYLD mutation carriers are reviewed on an annual basis. In-depth investigation was carried out for patients with pulmonary tumours. RESULTS: Four patients had radiological imaging of their lungs, of which two had multiple pulmonary cylindromas that were confirmed histologically. Serial computed tomography monitoring allowed for pre-emptive endobronchial laser ablation, preventing major airway obstruction and pulmonary collapse. CONCLUSIONS: Pulmonary cylindromas are an unrecognized, but infrequently symptomatic, aspect of the phenotype in these patients that can have implications for patient care. They should be considered in patients with a high tumour burden that present with respiratory symptoms, and where appropriate, monitored with serial imaging.

Identifying characteristic features of the retinal and choroidal vasculature in choroideremia using optical coherence tomography angiography.

PurposeUsing optical coherence tomography angiography (OCTA) to investigate the area with flow in the superficial retinal vessel network (SVRN) and choriocapillaris (CC) layer among male subjects with choroideremia (CHM), female carriers, and normal controls to identify vascular changes.Patients and methodsImages of SRVN and CC layer were acquired in 9 affected males, 5 female carriers, and 14 age- and gender-matched controls using the Angiovue software of the RTVue XR Avanti.ResultsThe mean age was 33 years for affected male CHM patients (median 30 years), 46 years for female carriers (median 53 years), and 39 years for controls (median 38.5). Mean SRVN area±SD in subjects with CHM was 12.93±2.06 mm2, in carrier subjects 15.36±0.60 mm2, and in controls 15.30±1.35 mm2 (P<0.01). The mean CC area±SD with flow was 6.97±5.26 mm2 in CHM subjects, 21.65±0.17 mm2 in carriers and 21.36±0.76 mm2 in controls (P<0.01). SRVN and CC area with flow showed a negative correlation in CHM subjects with the age (r=-0.86; P<0.003 and r=-0.77; P<0.01, respectively). CC area with flow had a positive correlation with SRVN (r=0.83, P<0.001). Overall, visual acuity had a negative correlation with SRVN and CC area with flow (r=-0.67, P<0.001 and r=-0.57, P<0.002, respectively). CONCLUSIONS: This is the first study to highlight changes in the SRVN in CHM subjects. OCTA detected a reduced area with flow in both retinal and choroidal circulations, and may be a useful tool for monitoring natural history and disease progression in forthcoming clinical trials.

Synergistic impact of mutations in Hepatitis B Virus genome contribute to its occult phenotype in chronic Hepatitis C Virus carriers.

We characterized occult HBV (OHBV) from hepatitis B surface antigen (HBsAg)-negative chronic HCV carriers of Eastern India to explore the impact of genomic variability of HBV in causing undetectability of HBsAg and low viremia that define the occult phenomenon. Screening of sera samples revealed the presence of OHBV in 17.8% of HCV-infected patients. Determination of full-length OHBV sequences and comparison with that from HBsAg-positive carriers led to the detection of distinct substitutions/mutations in PreS2, S, P and X ORFs and in X-promoter and Enhancer-II of OHBV. These mutations were introduced in wild-type HBV and their effects were evaluated by transfection in Huh7 cells. In vitro assays demonstrated that S-substitutions resulted in antigenically modified HBsAg that escaped detection by immunoassays whereas those in ORF-P caused significant decline in viral replication. Impairment in Enhancer-II and X-promoter activities were noted due to occult-associated mutations that generated reduced pregenomic RNA and intracellular HBV-DNA. Additionally, Enhancer-II mutations altered the small to large surface protein ratio and diminished extracellular HBV-DNA and HBsAg secretion. Further, mutations in PreS2, X and enhancer-II increased Grp78-promoter activity, suggesting that OHBV could trigger endoplasmic reticulum stress. Thus viral mutations contribute synergistically towards the genesis of occult phenotype and disease progression.

Relationship between liver injury and serum cytokeratin 18 levels in asymptomatic hepatitis B virus carriers and in patients with chronic hepatitis B infection.

BACKGROUND AND STUDY AIMS: Apoptosis represents a well-known mechanism of cell death involved in most chronic liver injuries. Our aim was to investigate the serum fragment level of cytokeratin 18 (CK18), M30, in asymptomatic hepatitis B virus (HBV) carriers and patients with chronic hepatitis B (CHB) and to evaluate the relationship between serum M30 levels and the severity of hepatic injury. PATIENTS AND METHODS: Asymptomatic HBV carriers (n=169), patients with CHB (n=100), and healthy control subjects (n=43) were enrolled in the study. Serum CK18 (M30) levels were analysed in all subjects. Liver biopsy for histopathological assessment was performed in asymptomatic HBV carriers and in patients with CHB infection. RESULTS: Serum CK18 (M30) levels were significantly higher in asymptomatic HBV carriers (198.77±77.62U/L) than in healthy control subjects (146.92±40.18U/L). Patients with CHB (283.02±147.45U/L) had significantly higher CK18 (M30) levels than asymptomatic HBV carriers (p=0.001). The diagnostic efficacy of CK18 (M30) levels in distinguishing patients with HBeAg-negative CHB from asymptomatic HBV carriers was found to be moderate (c-statistics: 0.695), and the diagnostic cut-off value of CK18 (M30) was 262U/L (specificity: 85%, sensitivity: 48%, positive likelihood ratio: 3.35, and negative likelihood ratio: 0.60). There was a positive correlation between serum CK18 (M30) levels and histological activity index scores in asymptomatic HBV carriers and patients with CHB. CONCLUSIONS: Serum CK18 (M30) levels may be a valuable indicator in distinguishing asymptomatic HBV carriers from patients with HBeAg-negative CHB when considered together with ALT and HBV-DNA levels.

No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their rodent reservoir host in natural conditions.

BACKGROUND: In order to optimize net transmission success, parasites are hypothesized to evolve towards causing minimal damage to their reservoir host while obtaining high shedding rates. For many parasite species however this paradigm has not been tested, and conflicting results have been found regarding the effect of arenaviruses on their rodent host species. The rodent Mastomys natalensis is the natural reservoir host of several arenaviruses, including Lassa virus that is known to cause Lassa haemorrhagic fever in humans. Here, we examined the effect of three arenaviruses (Gairo, Morogoro and Lassa virus) on four parameters of wild-caught Mastomys natalensis: body mass, head-body length, sexual maturity and fertility. After correcting for the effect of age, we compared these parameters between arenavirus-positive (arenavirus RNA or antibody) and negative animals using data from different field studies in Guinea (Lassa virus) and Tanzania (Morogoro and Gairo viruses). RESULTS: Although the sample sizes of our studies (1297, 749 and 259 animals respectively) were large enough to statistically detect small differences in body conditions, we did not observe any adverse effects of these viruses on Mastomys natalensis. We did find that sexual maturity was significantly positively related with Lassa virus antibody presence until a certain age, and with Gairo virus antibody presence in general. Gairo virus antibody-positive animals were also significantly heavier and larger than antibody-free animals. CONCLUSION: Together, these results suggest that the pathogenicity of arenaviruses is not severe in M. natalensis, which is likely to be an adaptation of these viruses to optimize transmission success. They also suggest that sexual behaviour might increase the probability of M. natalensis to become infected with arenaviruses.