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AbstractSARS-CoV-2, the causative agent of COVID-19, has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40-100% of the population which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19 symptoms. This effect could contribute to the disparity of disease severity seen in ethnic minorities and those with lower socio-economic status, due to their higher CMV seroprevalence. Our results warrant further clinical investigation as to whether HCMV infection influences the pathogenesis of SARS-CoV-2.

Table of Contents for Volume 28, Number 12-December 2022…

Aerosolized glucocorticoid treatment was independently associated with bacterial isolation in these patients.…

Research Letter - Severe Human Case of Zoonotic Infection with Swine-Origin Influenza A Virus, Denmark, 2021…

Research Letter - Bombali Ebolavirus in Mops condylurus Bats (Molossidae), Mozambique…

Research - Association between Conflict and Cholera in Nigeria and the Democratic Republic of the Congo…

Abstract Background The early diagnosis of sepsis is beneficial to put forward a reasonable clinical treatment plan as soon as possible. This study was to explore the expression of Tripartite Motif 7 (TRIM7) in peripheral blood mononuclear cells (PBMCs) of patients with sepsis and its diagnostic value. Methods This is a cross-sectional study. A total of 69 patients with infectious diseases were enrolled in the emergency room. They were divided into the sepsis group (34 cases) and the non-sepsis infection group (35 cases). There were 25 healthy subjects who were selected as the control group. The expression of TRIM7 in PBMCs was observed by immunofluorescence staining. The correlation between the expression of TRIM7 mRNA and acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor (TNF)-α and interleukin (IL)-6 was discussed. The receiver operating characteristic (ROC) curve was utilized for evaluating the value of TRIM7 expression for the early diagnosis of sepsis. Results The fluorescence intensity representing the expression level of TRIM7 in PBMCs of patients in the sepsis group was the lowest among three groups. The TRIM7 mRNA expression in PBMCs of the sepsis group was greatly decreased in comparison with that of the non-sepsis infection group and control group (P < 0.05). Spearman correlation analysis indicated that TRIM7 mRNA expression was negatively correlated with APACHE II score, SOFA score, WBC, CRP, PCT, TNF-α and IL-6. ROC curve analysis revealed that the area under curve (AUC) of TRIM7 mRNA expression in PBMCs for the diagnosis of sepsis was 0.798, with a 95% confidence interval of 0.691- 0.905, a sensitivity of 73.5%, and a specificity of 77.1%. Conclusion The expression of TRIM7 in PBMCs of patients with sepsis is significantly down-regulated, which has certain clinical value for early diagnosis of sepsis. …

Abstract Background Mycobacterium tuberculosis (Mtb) has been found to persist within cavities in patients who have completed their anti-tuberculosis therapy. The clinical implications of Mtb persistence after therapy include recurrence of disease and destructive changes within the lungs. Data on residual changes in patients who completed anti-tuberculosis therapy are scarce. This case highlights the radiological and pathological changes that persist after anti-tuberculosis therapy completion and the importance of achieving sterilization of cavities in order to prevent these changes. Case presentation This is a case report of a 33 year old female with drug-sensitive pulmonary tuberculosis who despite successfully completing standard 6-month treatment had persistent changes in her lungs on radiological imaging. The patient underwent multiple adjunctive surgeries to resect cavitary lesions, which were culture positive for Mtb. After surgical treatment, the patient’s chest radiographies improved, symptoms subsided, and she was given a definition of cure. Conclusions Medical therapy alone, in the presence of severe cavitary lung lesions may not be able to achieve sterilizing cure in all cases. Cavities can not only cause reactivation but also drive inflammatory changes and subsequent lung damage leading to airflow obstruction, bronchiectasis, and fibrosis. Surgical removal of these foci of bacilli can be an effective adjunctive treatment necessary for a sterilizing cure and improved long term lung health. …

Abstract Background The primary antibody (Ab) response to Plasmodium falciparum is a critical step in developing immunity to malaria. Information on the initial Ab responses of babies in malaria-endemic areas is incomplete, in part, because babies receive maternal IgG via transplacental-transfer and usually become infected before maternal IgG wanes. The study aimed to identify the primary IgM and IgG Ab responses to malarial antigens in Cameroonian babies. Methods Infants (n = 70) living in a high malaria transmission area were followed from birth throughout the first year of life (mean 341 ± 42 days, an average of 8.5 time points per infant). Malaria infection was assessed by microscopy and PCR, and IgM and IgG antibodies (Abs) were measured using a multiplex immunoassay to AMA1, EBA-175, MSP1-42, MSP2, MSP3, RESA, LSA1, and CSP. Results The half-life of maternal IgG varied among the antigens, ranging from 0.7 to 2.5 months. The first infection of 41% of the babies was sub-microscopic and only 11 to 44% of the babies produced IgM to the above antigens; however, when the first infection was detected by microscopy, 59–82% of the infants made IgM Abs to the antigens. Infants were able to produce IgM even when maternal IgG was present, suggesting maternal Abs did not suppress the baby’s initial Ab response. Using longitudinal regression models that incorporated time-varying covariates, infants were found to produce IgG Ab to only AMA-1 when the first infection was sub-microscopic, but they produced IgG Abs to MSP1-42 (3D7, FVO), AMA1 (3D7, FVO) MSP2-FC27, MSP3, RESA, and LSA1, but not MSP 2-3D7, EBA-175, and CSP during their first slide-positive infection. Notably, the primary and secondary IgG responses were short-lived with little evidence of boosting. Conclusions The primary Ab response of babies who had maternal IgG was similar to that reported for primary infections in malaria-naïve adults. …

Abstract Background Current efforts to estimate the spatially diverse malaria burden in malaria-endemic countries largely involve the use of epidemiological modelling methods for describing temporal and spatial heterogeneity using sparse interpolated prevalence data from periodic cross-sectional surveys. However, more malaria-endemic countries are beginning to consider local routine data for this purpose. Nevertheless, routine information from health facilities (HFs) remains widely under-utilized despite improved data quality, including increased access to diagnostic testing and the adoption of the electronic District Health Information System (DHIS2). This paper describes the process undertaken in mainland Tanzania using routine data to develop a high-resolution, micro-stratification risk map to guide future malaria control efforts. Methods Combinations of various routine malariometric indicators collected from 7098 HFs were assembled across 3065 wards of mainland Tanzania for the period 2017–2019. The reported council-level prevalence classification in school children aged 5–16 years (PfPR5–16) was used as a benchmark to define four malaria risk groups. These groups were subsequently used to derive cut-offs for the routine indicators by minimizing misclassifications and maximizing overall agreement. The derived-cutoffs were converted into numbered scores and summed across the three indicators to allocate wards into their overall risk stratum. Results Of 3065 wards, 353 were assigned to the very low strata (10.5% of the total ward population), 717 to the low strata (28.6% of the population), 525 to the moderate strata (16.2% of the population), and 1470 to the high strata (39.8% of the population). The resulting micro-stratification revealed malaria risk heterogeneity within 80 councils and identified wards that would benefit from community-level focal interventions, such as community-case management, indoor residual spraying and larviciding. Conclusion The micro-stratification approach employed is simple and pragmatic, with potential to be easily adopted by the malaria programme in Tanzania. It makes use of available routine data that are rich in spatial resolution and that can be readily accessed allowing for a stratification of malaria risk below the council level. Such a framework is optimal for supporting evidence-based, decentralized malaria control planning, thereby improving the effectiveness and allocation efficiency of malaria control interventions. …

Abstract Background Malaria burden among under-five children living in endemic areas of Yemen is largely unknown due to the lack of community-based studies. Therefore, this study determined the prevalence and risk factors associated with falciparum malaria among under-five children in rural communities of Al-Mahweet governorate, Yemen. Methods This community-based, cross-sectional study recruited 400 under-five children from two rural districts of Al-Mahweet governorate in December 2019. Demographic characteristics (gender, age, education and occupation of the child’s parents, and household size) and risk factors associated with malaria were collected through interviews with children’s caregivers using a structured questionnaire. Finger-prick blood was screened for Plasmodium falciparum and non-falciparum species using rapid diagnostic tests (RDTs), and duplicate Giemsa-stained thick and thin blood films were examined for malaria parasites. The density of asexual P. falciparum stages was also estimated. Data were then analysed, and the agreement between the results of thick-film microscopy and RDTs for diagnosing falciparum malaria was assessed using the kappa index. Statistical significance was set at a P-value of < 0.05. Results Plasmodium falciparum was prevalent among 9.8% (95% CI 7.0–13.1) of under-five children in the rural communities of Al-Mahweet, with a median asexual parasite density of 763 ± 2606 parasites/μl of blood (range: 132–4280) and low-to-moderate parasitaemia levels. Approximately one-third of microscopy-confirmed cases were gametocyte carriers. Multivariable logistic regression analysis confirmed that age of three years or older (AOR = 5.6, 95% CI 1.6–19.8; P = 0.007), not sleeping under a mosquito net the previous night of the survey (AOR = 8.0, 95% CI 2.4–27.4; P = 0.001), sleeping outdoors at night (AOR = 4.4, 95% CI 2.0–10.0; P < 0.001), and absence of indoor residual spraying (IRS) during the last year (AOR = 4.2, 95% CI 1.9–9.4; P < 0.001) were the independent predictors of falciparum malaria among under-five children in the rural communities of Al-Mahweet. The observed percentage agreement between thick-film microscopy and RDTs was 98.5%, with a very good agreement (k-index = 0.9) between the two methods for falciparum malaria diagnosis that was statistically significant. Conclusion Approximately one in ten under-five children in rural communities of Al-Mahweet is infected with P. falciparum based on microscopy and RDTs. Age of three years or older, not sleeping under mosquito nets, sleeping outdoors at night and absence of IRS can independently predict falciparum malaria among them. The very good agreement between thick-film microscopy and RDTs for diagnosing falciparum malaria in children supports the usefulness of using RDTs in such resource-limited rural communities. …

Abstract Plasmodium cynomolgi (Pcy), a simian malaria parasite, is a recent perfect example of emerging zoonotic transfer in human. This review summarizes the current knowledge on the epidemiology of natural Pcy infections in humans, mosquitoes and monkeys, along with its biological, clinical and drug sensitivity patterns. Knowledge gaps and further studies on Pcy in humans are also discussed. This parasite currently seems to be geographically limited in South-East Asia (SEA) with a global prevalence in human ranging from 0 to 1.4%. The Pcy infections were reported in local SEA populations and European travelers, and range from asymptomatic carriage to mild/moderate attacks with no evidence of pathognomonic clinical and laboratory patterns but with Pcy strain-shaped clinical differences. Geographical distribution and competence of suitable mosquito vectors and non-primate hosts, globalization, climate change, and increased intrusion of humans into the habitat of monkeys are key determinants to emergence of Pcy parasites in humans, along with its expansion outside SEA. Sensitization/information campaigns coupled with training and assessment sessions of microscopists and clinicians on Pcy are greatly needed to improve data on the epidemiology and management of human Pcy infection. There is a need for development of sensitive and specific molecular tools for individual diagnosis and epidemiological studies. The development of safe and efficient anti-hypnozoite drugs is the main therapeutic challenge for controlling human relapsing malaria parasites. Experience gained from P. knowlesi malaria, development of integrated measures and strategies—ideally with components related to human, monkeys, mosquito vectors, and environment—could be very helpful to prevent emergence of Pcy malaria in humans through disruption of transmission chain from monkeys to humans and ultimately contain its expansion in SEA and potential outbreaks in a context of malaria elimination.…

Abstract Purpose The aim was to describe the prevalence, molecular epidemiology and clinical manifestations of human bocavirus (HBoV) in patients attended at a tertiary hospital in Barcelona, Spain. Methods From October 2014 to May 2017, respiratory specimens from paediatric patients were collected for respiratory viruses’ laboratory-confirmation. Phylogenetic analyses from partial VP1 sequences were performed from all HBoV laboratory-confirmed specimens. Clinical features were retrospectively studied. Results 178/10271 cases were HBoV laboratory-confirmed. The median age was 1.53 (IQR 1.0–2.3). Co-detection was highly reported (136; 76%). All viruses belonged into HBoV1 genotype but one into HBoV2. Non-reported mutations were observed and two sites were suggestive to be under negative selection. 61% (109/178) cases had lower RTI (LRTI), of whom 84 had co-detections (77%) and 76 had comorbidities (70%). LRTI was the cause of hospitalization in 85 out of 109 cases (78%), and no differences were found regarding severity factors during hospitalization between co- and single-detections, except for median length of respiratory support, which was longer in cases with co-detections. Conclusions Close monitoring of predominant HBoV1 showed a high similarity between viruses. The presence of comorbidities might explain the high prevalence of LRTI. Symptomatology in HBoV single-detected cases suggest that HBoV is a true pathogen. …

AbstractBackgroundThe COVIH-study is a prospective SARS-CoV-2 vaccination study in 1154 people with HIV (PWH), of whom 14% showed a reduced or absent antibody response after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders.MethodsConsenting hyporesponders received an additional 100µg mRNA-1273 vaccination. The primary endpoint was the increase in antibodies 28 days thereafter. Secondary endpoints were the correlation between participant characteristics and antibody response, levels of neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity.ResultsOf the 66 participants, 40 previously received two doses ChAdOx1-S, 22 two doses BNT162b2, and four a single dose Ad26.COV2.S. The median age was 63[IQR:60-66], 86% were male, pre-vaccination CD4+ T-cell count was median 650/μL[IQR:423-941] and 96% had HIV-RNA < 50 copies/mL. The mean S1-specific antibody level increased from 35 BAU/mL (95%CI:24–46) to 4317 BAU/mL (95%CI:3275–5360) post-vaccination (p < 0.0001). Of all participants, 97% showed an adequate response (>300 BAU/mL) and the 45 antibody negative participants all seroconverted (>33.8 BAU/mL). A significant increase in the proportion of PWH with detectable ancestral S-specific CD4+ T-cells (p = 0.04) and S-specific B-cells (p = 0.02) was observed.ConclusionAn additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination.