Last data update: Aug 15, 2025. (Total: 49733 publications since 2009)
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| Query Trace: Sousa L [original query] |
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| Efforts to link HIV-positive and high-risk blood donors to HIV testing, and treatment services, Mozambique, 2019-2020
Kanagasabai U , Sousa L , Chevalier MS , Gutreuter S , Ibraimo D , Salimo S , Naueia E , Daniel L , Khan S , Ujamma D , Behel S , Malimane I , Drammeh B . Sci Rep 2025 15 (1) 20730 Mozambique's National Blood Transfusion Services (NBTS) is tasked with providing safe and available blood but also conducting systematic screening of at-risk potential donors, notifying seropositive blood donors, and linking them to HIV care and treatment services. Potential blood donors who were deferred from donating following a behavioral risk screening and all blood donors who screened seropositive for HIV were notified and offered linkage to HIV testing, care, and treatment services by community-based organizations. A prospective study among HIV-positive blood donors and deferred donors was conducted from May 2019 to July 2020 at Maputo Central Hospital Blood Bank and the National Reference Blood Center. The associations between testing, initiating care and treatment services among HIV-positive blood donors and prospective deferred donors were estimated using fully Bayesian multivariable logistic models and odds ratios. Among 885 prospective blood donors enrolled, 173 (20%) were deferred due to self-reported high-risk behaviors identified through a screening questionnaire, and 712 (80%) passed the behavioral-risk screening tool, donated, and the blood donation tested positive for HIV. There were more than 2.5 times as many male donors as female donors with a positive HIV test, and among the deferred donors, more than 84% were males. 36% (256/712) of seropositive donors and 35% (61/173) of deferred donors were referred to HIV testing services. 62% (158/256) of seropositive donors and 4.9% (3/61) of deferred donors who were successfully referred were linked to care and treatment services, and 96% (152/158) of these seropositive donors and 100% (3/3) of deferred as high-risk donors initiated antiretroviral therapy (ART). Of the three service organizations used, one outperformed the other two in linking seropositive donors to ART treatment. The NBTS can serve as a critical entry point for identifying HIV-positive persons. Improved implementation of risk behavior screening tools is needed and could contribute to early identification and initiation of ART for potential donors. Innovative strategies and solutions by community-based organizations can be used to improve blood donor notification and linkage to HIV testing and treatment services. |
| Establishment of epidemiological cutoff values for Fonsecaea pedrosoi, the primary etiologic agent of chromoblastomycosis, and eight antifungal medications
Smith DJ , Melhem MSC , Dirven J , de Azevedo CMPeS , Marques SG , Jacomel Favoreto de Souza Lima B , Vicente VA , Teixeira Sousa Md G , Venturini J , Wiederhold NP , Seyedmousavi A , Dufresne PJ , de Hoog S , Lockhart SR , Hagen F , Santos DWdCL . J Clin Microbiol 2025 63 (5) e0190324
Chromoblastomycosis, a fungal neglected tropical disease, is acquired through traumatic inoculation and is clinically characterized by a chronic granulomatous infection of the skin and subcutaneous tissue. Fonsecaea pedrosoi is the most commonly reported etiologic agent globally. Itraconazole is considered first-line therapy, but successful treatment with terbinafine, voriconazole, and posaconazole has been reported. F. pedrosoi minimum inhibitory concentration (MIC) data are limited, and epidemiological cutoffs (ECVs) are lacking; such data are important to help monitor antifungal resistance trends and guide initial antifungal selection. Thus, we performed antifungal susceptibility testing (AFST) on F. pedrosoi isolates and determined the MIC distributions and ECVs. AFST on Fonsecaea pedrosoi isolates was conducted at six laboratories from October 2023 to June 2024. Species identification was previously confirmed by DNA sequence analysis. AFST was performed by CLSI M38 standard broth microdilution method for itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, terbinafine, flucytosine, and amphotericin B. The ECVs were established using the iterative statistical method with ECOFFinder (version 2.1) following CLSI M57 guidelines. We analyzed MIC results from 148 Fonsecaea pedrosoi isolates. The calculated ECVs were itraconazole, 0.5 µg/mL; voriconazole, 0.5 µg/mL; posaconazole, 0.5 µg/mL; isavuconazole, 1 µg/mL; ketoconazole, bimodal, no ECV determined; terbinafine, 0.25 µg/mL; flucytosine, rejected; and amphotericin, 8 µg/mL. These Fonsecaea pedrosoi ECVs, obtained through a multicenter international effort, provide a baseline to better understand the in vitro antifungal susceptibility profile of this species and monitor resistance. Clinicians and researchers can use these values to detect non-wild-type isolates with reduced susceptibility, reevaluate therapeutic options, and investigate potential clinical resistance if treatment failure occurs.IMPORTANCEChromoblastomycosis is a neglected tropical disease caused by an environmental, dematiaceous fungus. This fungal disease is acquired after a break in the skin that allows the fungus to enter, leading to a chronic infection in the skin and subcutaneous tissue. It is difficult to treat and often requires years of antifungal treatment. Fonsecaea pedrosoi is the most reported causative agent globally. Limited antifungal susceptibility data exist for F. pedrosoi making interpreting minimum inhibitory concentration (MIC) results difficult. We performed antifungal susceptibility testing on 148 F. pedrosoi isolates to establish MIC distributions and epidemiologic cutoff values (ECVs) for eight antifungals, including those commonly used to treat chromoblastomycosis. The calculated ECVs for the commonly used antifungals itraconazole and terbinafine were 0.5 and 0.25 µg/mL, respectively. ECVs can be helpful in choosing potential treatment options for F. pedrosoi and monitoring antifungal resistance epidemiology. |
| Work-related asthma and its impact on quality of life and work productivity
Suarthana E , Le Moual N , Lemière C , Bousquet J , Pierre S , Sousa-Pinto B , Afadiyanti Parfi A , Van Brussel P , Nassiri Kigloo H , Vandenplas O , Henneberger PK . J Allergy Clin Immunol Pract 2023 BACKGROUND: The impact of work-related asthma (WRA) on quality of life (QoL) and work productivity remains largely neglected/uncertain despite its high prevalence. OBJECTIVE: To investigate the association of WRA with QoL and work productivity as compared with subjects with non-WRA and those without asthma and rhinitis. METHODS: A cross-sectional survey was carried out among workers during their periodic occupational health visit in Belgium. The Mini Asthma Quality of Life Questionnaire, the 8-item Medical Outcome Study Short Form instrument, and the Work Productivity and Activity Impairment-General Health questionnaire were administered. Survey participants were divided into 3 groups: (1) WRA (current asthma with ≥2 respiratory symptoms at work; n = 89); (2) non-WRA (current asthma without work-related respiratory symptoms; n = 119); and (3) the reference group (no asthma and no lower respiratory, nasal, or eye symptoms; n = 815). Associations of QoL and work productivity with WRA were evaluated by multivariable regression analyses. RESULTS: WRA and having poor asthma control were significantly associated with lower global Mini Asthma Quality of Life Questionnaire scores compared with non-WRA. Asthmatic subjects had significantly lower physical and mental health component scores of the 8-item Medical Outcome Study Short Form instrument and overall work productivity compared with the reference group, with greater impairment in workers with WRA than in those without WRA. Moreover, workers with WRA had higher percentages of doctor visits and income reduction because of respiratory symptoms than those with non-WRA. Work-related rhinitis and depression were associated with reduced QoL, independent of the effect of WRA. CONCLUSIONS: WRA should be managed comprehensively to reduce the worsening of QoL and work productivity of those affected. |
| A review of brownfields revitalisation and reuse research in the US over three decades
De Sousa C , Carroll AMM , Whitehead S , Berman L , Coffin S , Heberle L , Hettiarachchi G , Martin S , Sullivan K , Van Der Kloot J . Local Environ 2023 Over the past 30 years, US-based research on contaminated and potentially-contaminated sites, or brownfields, has grown from defining the scope and size of the environmental, health and economic risks posed by abandoned manufacturing sites to exploring and documenting site-specific and area-wide impacts of their cleanup and revitalisation. From early and varied research on environmental and economic policy to equity and public impacts on minority communities, later research considered planning, adding case studies on sustainability and resilience to the scope of research covered. This review paper stems from exchanges of a long-standing network of academic, government agency, and practice professionals working to identify research, policy, and practice gaps. It traces the evolution of US brownfield revitalization research as was informed by, and informed, policy, program and practice. This review summarizes the literature and identifies research gaps and opportunities to further community and agency actions related to investigating, remediating, and redeveloping brownfield sites. It outlines site and area options to build climate resilience, strengthen community action for dismantling structural racism and disinvestment, and reduce the disproportionate risks experienced by communities of colour and areas of low income. The authors propose a new research agenda to address the gaps identified. © 2023 Informa UK Limited, trading as Taylor & Francis Group. |
| Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant (preprint)
Coutinho RM , Marquitti FMD , Ferreira LS , Borges ME , da Silva RLP , Canton O , Portella TP , Poloni S , Franco C , Plucinski MM , Lessa FC , da Silva AAM , Kraenkel RA , de Sousa Mascena Veras MA , Prado PI . medRxiv 2021 2021.03.03.21252706 The variant of concern (VOC) P.1 emerged in the Amazonas state (Brazil) in November-2020. It contains a constellation of mutations, ten of them in the spike protein. Consequences of these specific mutations at the population level have been little studied so far, despite the detection of P.1 variant in 26 countries, with local transmission in at least four other countries in the Americas and Europe. Here, we estimate P.1’s transmissibility and reinfection using a model-based approach, by fitting data from the Brazilian national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December 2020 to February 2021, when the city was devastated by four times more cases than in the previous peak (April 2020). The new variant was found to be about 2.6 times more transmissible (95% Confidence Interval (CI): 2.4–2.8) than previous circulating variant(s). The city already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus (estimated as 78%, CI:73–83%), and the fitted model attributed 28% of the cases during the period to reinfections by the variant P.1. Our estimates rank P.1 as the most transmissible among the current identified SARS-CoV-2 VOCs, posing a serious threat and requiring urgent measures to control its global spread.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialEthics approval was not necessary because this study analysed only publicly available data, not including identifiable information.Funding StatementThis work was supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (Finance Code 001 to FMDM, LSF and TPP), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil (grant number: 315854/2020-0 to MEB, 141698/2018-7 to RLPS, 313055/2020-3 to PIP, 312559/2020-8 to MASMV, 311832/2017-2 to RAK, 305703/2019-6 to AAMS) and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil (grant number: 2019/26310-2 and 2017/26770-8 to CF, 2018/26512-1 to OC, 2018/24037-4 to SPL and contract number: 2016/01343-7 to RAK). Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethics approval was not necessary because this study analysed only publicly available data, not including identifiable information.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data used are publicly available. The data sources are described in the manuscript and in supplementary file. |
| Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant.
Coutinho RM , Marquitti FMD , Ferreira LS , Borges ME , da Silva RLP , Canton O , Portella TP , Poloni S , Franco C , Plucinski MM , Lessa FC , da Silva AAM , Kraenkel RA , de Sousa Mascena Veras MA , Prado PI . Commun Med (Lond) 2021 1 48
BACKGROUND: The SARS-CoV-2 variant of concern (VOC) P.1 (Gamma variant) emerged in the Amazonas State, Brazil, in November 2020. The epidemiological consequences of its mutations have not been widely studied, despite detection of P.1 in 36 countries, with local transmission in at least 5 countries. A range of mutations are seen in P.1, ten of them in the spike protein. It shares mutations with VOCs previously detected in the United Kingdom (B.1.1.7, Alpha variant) and South Africa (B.1.351, Beta variant). METHODS: We estimated the transmissibility and reinfection of P.1 using a model-based approach, fitting data from the national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December-2020 to February-2021. RESULTS: Here we estimate that the new variant is about 2.6 times more transmissible (95% Confidence Interval: 2.4-2.8) than previous circulating variant(s). Manaus already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus and our fitted model attributed 28% of Manaus cases in the period to reinfections by P.1, confirming the importance of reinfection by this variant. This value is in line with estimates from blood donors samples in Manaus city. CONCLUSIONS: Our estimates rank P.1 as one of the most transmissible among the SARS-CoV-2 VOCs currently identified, and potentially as transmissible as the posteriorly detected VOC B.1.617.2 (Delta variant), posing a serious threat and requiring measures to control its global spread. |
| Fatal human alphaherpesvirus 1 infection in free-ranging black-tufted marmosets in anthropized environments, Brazil, 2012-2019
Wilson TM , Ritter JM , Martines RB , Bullock HA , Fair P , Radford KW , Macedo IL , Sousa DER , Goncalves AAB , Romano AP , Passsos PHO , Ramos DG , Costa GRT , Cavalcante KRLJ , de Melo CB , Zaki SR , Castro MB . Emerg Infect Dis 2022 28(4) (4) 802-811 Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals. Copyright © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved. |
| High level of HIV false positives using EIA-based algorithm in survey: Importance of confirmatory testing
Augusto  DR , Iriemenam NC , Kohatsu L , de Sousa L , Maueia C , Hara C , Mula F , Cuamba G , Chelene I , Langa Z , Lohman N , Faife F , Giles D , Sabonete AJ , Samo Gudo E , Jani I , Parekh BS . PLoS One 2020 15 (10) e0239782 The Mozambique Indicators of Immunization, Malaria and HIV/AIDS (IMASIDA) survey was conducted in 2015 and used a two Enzyme Immunoassay (EIA) (Vironostika HIV-1/2 and Murex HIV-1/2) based algorithm to determine the HIV status of the consented participants. The Mozambique Ministry of Health, with support from the US Centers for Disease Control and Prevention (US CDC), added Bio-Rad Geenius™ HIV-1/2 Supplemental Assay to the IMASIDA HIV testing algorithm to confirm all specimens that were found to be reactive on one or both EIAs. In total 11690 specimens were collected to estimate the proportion of HIV positive samples. Results indicate that the proportion of HIV positive samples based on the concordant positive results of two EIA assays was 21.5% (2518/11690). The addition of the Geenius assay to the IMASIDA HIV testing algorithm demonstrated that 792 (31.5%) of 2518 specimens were false-positive and reduced the proportion of HIV positive samples to 14.7% (1722/11690), demonstrating the importance of including a highly specific HIV test to confirm HIV diagnosis. HIV surveys exclusively based on EIA testing algorithm may result in misleading high prevalence results. Our results demonstrate that more specific confirmatory testing should be added to the EIA-based algorithms to ensure accurate HIV diagnosis and correct HIV prevalence estimate in cross-sectional surveys. |
| Citrullination Alters the Antiviral and Immunomodulatory Activities of the Human Cathelicidin LL-37 During Rhinovirus Infection.
Casanova V , Sousa FH , Shakamuri P , Svoboda P , Buch C , D'Acremont M , Christophorou MA , Pohl J , Stevens C , Barlow PG . Front Immunol 2020 11 85
Human rhinoviruses (HRV) are the most common cause of viral respiratory tract infections. While normally mild and self-limiting in healthy adults, HRV infections are associated with bronchiolitis in infants, pneumonia in immunocompromised patients, and exacerbations of asthma and COPD. The human cathelicidin LL-37 is a host defense peptide (HDP) with broad immunomodulatory and antimicrobial activities that has direct antiviral effects against HRV. However, LL-37 is known to be susceptible to the enzymatic activity of peptidyl arginine deiminases (PAD), and exposure of the peptide to these enzymes results in the conversion of positively charged arginines to neutral citrullines (citrullination). Here, we demonstrate that citrullination of LL-37 reduced its direct antiviral activity against HRV. Furthermore, while the anti-rhinovirus activity of LL-37 results in dampened epithelial cell inflammatory responses, citrullination of the peptide, and a loss in antiviral activity, ameliorates this effect. This study also demonstrates that HRV infection upregulates PAD2 protein expression, and increases levels of protein citrullination, including histone H3, in human bronchial epithelial cells. Increased PADI gene expression and HDP citrullination during infection may represent a novel viral evasion mechanism, likely applicable to a wide range of pathogens, and should therefore be considered in the design of therapeutic peptide derivatives. |
| Meningococcal carriage in young adults six years after meningococcal C conjugate (MCC) vaccine catch-up campaign in Salvador, Brazil.
Ferreira VM , Ferreira IE , Chang HY , Nunes Ampb , Topaz N , Pimentel ER , Moura Arss , Ribeiro GS , Feitosa CA , Reis MG , Wang X , Campos LC . Vaccine 2020 38 (14) 2995-3002
Meningococcal carriage studies are important to improve the knowledge of disease epidemiology as well as to support appropriate vaccination strategies. We conducted a cross-sectional study to determine the prevalence and genotypic characteristics of meningococci collected from young adults in Salvador, Brazil six years after a meningococcal C conjugate vaccine catch-up campaign. From August through November 2016, oropharyngeal swabs were collected from 407 students aged 1824 years attending a private college in Salvador, Brazil. Neisseria meningitidis was identified by standard microbiology methods and real time PCR. Genetic characteristics of meningococci were assessed by rt-PCR and/or whole genome sequencing. We also investigated potential factors associated with carriage. N. meningitidis was detectable in 50 students, 39 by both culture and rt-PCR, 7 by culture alone and 4 by rt-PCR alone, resulting in an overall meningococcal carriage prevalence of 12.3% (50/407). Carriage was independently associated with male sex (adjusted PR: 1.97; 95% CI: 1.12-3.46; p = 0.018) and attending bars or parties at least once per month (aPR: 3.31; 95% CI: 1.49-7.38; p = 0.003). Molecular tests identified 92% (46/50) N. meningitidis as non-groupable, of which 63% (29/46) had the capsule null genotype; 14 NG isolates contained disrupted capsule backbones and belonged to the following genogroups: 7 B, 3 Z, 3 E and 1 W. One isolate belonged to genogroup C tested only by PCR; 3 isolates contained a complete B capsule backbones, 2 of which were determined to be NG by slide agglutination serogrouping. While most meningococcal carriage isolates were non-groupable, there was a high degree of genetic diversity present in the collection, as evidenced by 25 unique STs being detected. The carriage prevalence of meningococcal serogroup C was low among young adults. Continuous vaccination is important to maintain reduced meningococcal carriage and transmission, inducing herd protection. |
| Compromise of second-line antiretroviral therapy due to high rates of human immunodeficiency virus drug resistance in Mozambican treatment-experienced children with virologic failure
Vaz P , Buck WC , Bhatt N , Bila D , Auld A , Houston J , Cossa L , Alfredo C , Jobarteh K , Sabatier J , Macassa E , Sousa A , DeVos J , Jani I , Yang C . J Pediatric Infect Dis Soc 2018 9 (1) 6-13 Background: Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART. Methods: Children aged 1 to 14 years on ART for >/=12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent. Chart review and caregiver interviews were conducted. VL testing was performed, and specimens with >/=1000 copies/mL were genotyped. Results: Of the 715 children included, the mean age was 103 months, 85.8% had no immunosuppression, 73.1% were taking stavudine/lamivudine/nevirapine, and 20.1% had a history prevention of mother-to-child transmission exposure. The mean time on ART was 60.0 months. VF was present in 259 patients (36.3%); 248 (95.8%) specimens were genotyped, and DR mutations were found in 238 (96.0%). Severe immunosuppression and nutritional decline were associated with DR. M184V and Y181C were the most common mutations. In the 238 patients with DR, standard second-line ART would have 0, 1, 2, and 3 effective antiretrovirals in 1 (0.4%), 74 (31.1%), 150 (63.0%), and 13 (5.5%) patients, respectively. Conclusion: This cohort had high rates of VF and DR with frequent compromise of second-line ART. There is urgent need to scale-up VL monitoring and heat-stable protease inhibitor formulations or integrase inhibitorsfor a more a durable first-line regimen that can feasibly be implemented in developing settings. |
| Phylogenetic Evidence for the Existence of Multiple Strains of Rickettsia parkeri in the New World.
Nieri-Bastos FA , Marcili A , De Sousa R , Paddock CD , Labruna MB . Appl Environ Microbiol 2018 84 (8)
The bacterium Rickettsia parkeri has been reported infecting ticks of the 'Amblyomma maculatum species complex' in the New World, where it causes spotted fever illness in humans. In South America, three additional rickettsial strains, namely Atlantic rainforest, NOD, and Parvitarsum have been isolated from the ticks Amblyomma ovale, Amblyomma nodosum, and Amblyomma parvitarsum, respectively. These three strains are phylogenetically closely related to R. parkeri, Rickettsia africae, and Rickettsia sibirica. Herein, we performed a robust phylogenetic analysis encompassing 5 genes (gltA, ompA, virB4, dnaA, dnaK) and 3 intergenic spacers (mppE-pur, rrl-rrf-ITS, rpmE-tRNA(fmet) ) from 41 rickettsial isolates, including different isolates of R. parkeri, R. africae, R. sibirica, R. conorii, and strains Atlantic rainforest, NOD, and Parvitarsum. In our phylogenetic analyses, all New World isolates grouped in a major clade distinct from the Old World Rickettsia species (R. conorii, R. sibirica, R. africae). This New World clade was subdivided into the following 4 clades: the R. parkeri sensu stricto clade, comprising the type strain Maculatum 20(T) and all other isolates of R. parkeri from North and South America, associated with ticks of the A. maculatum species complex; the strain NOD clade, comprising two South American isolates from A. nodosum ticks; the Parvitarsum clade, comprising two South American isolates from A. parvitarsum ticks; and, the strain Atlantic rainforest clade, comprising six South American isolates from the A. ovale species complex (A. ovale or A. aureolatum). Under such evidences, we propose that strains Atlantic rainforest, NOD, and Parvitarsum are South American strains of R. parkeri.Importance Since the description of Rickettsia parkeri infecting ticks of the 'Amblyomma maculatum species complex' and humans in the New World, three novel phylogenetic close-related ricketsial isolates were reported in South America. Herein, we provide genetic evidence that these novel isolates, namely strains Atlantic rainforest, NOD, and Parvitarsum, are South American strains of R. parkeri. Interestingly, each of these R. parkeri strains seem to be primarily associated with a tick species group, namely, R. parkeri sensu stricto with the 'A. maculatum species group', R. parkeri strain NOD with A. nodosum, R. parkeri strain Parvitarsum with A. parvitarsum, and R. parkeri strain Atlantic rainforest with 'A. ovale species group'. Such rickettsial strain-tick species specificity suggests coevolution of each tick-strain association. Finally, because R. parkeri sensu stricto and R. parkeri strain Atlantic rainforest are human pathogens, the potential of R. parkeri strains NOD and Parvitarsum to be human pathogen cannot be discarded. |
| Cathelicidins display conserved direct antiviral activity towards rhinovirus
Sousa FH , Casanova V , Findlay F , Stevens C , Svoboda P , Pohl J , Proudfoot L , Barlow PG . Peptides 2017 95 76-83 Human rhinoviruses (HRVs) are the most common cause of viral respiratory tract infections, and are associated with significant morbidity and mortality in immunocompromised individuals and patients with pre-existing pulmonary conditions. The therapeutic options available are extremely limited and therefore novel therapeutics for HRV infections are of significant interest. Cathelicidins have been shown to have potent antiviral activity against a range of pathogens and are known to be key immunomodulatory mediators during infection. We therefore assessed the antiviral potential of cathelicidins from humans and other mammalian species against HRV, together with the potential for the human cathelicidin to modulate apoptotic pathways and alter cell viability during HRV infection. We demonstrate that LL-37, the porcine cathelicidin Protegrin-1, and the ovine cathelicidin SMAP-29 display potent antiviral activity towards HRV and that this activity is visible when either the virus is exposed to the peptides prior to cell infection or after cells have been infected. We further demonstrate that, in contrast to established findings with bacterial infection models, LL-37 does not induce apoptosis or necrosis in HRV-infected lung epithelial cells at physiological or superphysiological concentrations, but does reduce the metabolic activity of infected cells compared to uninfected cells treated with similar peptide concentrations. Collectively, the findings from this study demonstrate that the mechanism of action of cathelicidins against rhinovirus is by directly affecting the virus and we propose that the delivery of exogenous cathelicidins, or novel synthetic analogues, represent an exciting and novel therapeutic strategy for rhinovirus infection. |
| Performance characteristics of finger-stick dried blood spots (DBS) on the determination of human immunodeficiency virus (HIV) treatment failure in a pediatric population in Mozambique
Chang J , de Sousa A , Sabatier J , Assane M , Zhang G , Bila D , Vaz P , Alfredo C , Cossa L , Bhatt N , Koumans EH , Yang C , Rivadeneira E , Jani I , Houston JC . PLoS One 2017 12 (7) e0181054 Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott's VL test with a paired plasma sample using Roche's VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing. |
| GHSI emergency radionuclide bioassay laboratory network - summary of the second exercise
Li C , Bartizel C , Battisti P , Bottger A , Bouvier C , Capote-Cuellar A , Carr Z , Hammond D , Hartmann M , Heikkinen T , Jones RL , Kim E , Ko R , Koga R , Kukhta B , Mitchell L , Morhard R , Paquet F , Quayle D , Rulik P , Sadi B , Sergei A , Sierra I , de Oliveira Sousa W , Szabomicron G . Radiat Prot Dosimetry 2016 174 (4) 449-456 The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency as a means of enhancing response capability, health outcomes and community resilience. GHSI partners conducted an exercise in collaboration with the WHO Radiation Emergency Medical Preparedness and Assistance Network and the IAEA Response and Assistance Network, to test the participating laboratories (18) for their capabilities in in vitro assay of biological samples, using a urine sample spiked with multiple high-risk radionuclides (90Sr, 106Ru, 137Cs, and 239Pu). Laboratories were required to submit their reports within 72 h following receipt of the sample, using a pre-formatted template, on the procedures, methods and techniques used to identify and quantify the radionuclides in the sample, as well as the bioassay results with a 95% confidence interval. All of the participating laboratories identified and measured all or some of the radionuclides in the sample. However, gaps were identified in both the procedures used to assay multiple radionuclides in one sample, as well as in the methods or techniques used to assay specific radionuclides in urine. Two-third of the participating laboratories had difficulties in determining all the radionuclides in the sample. Results from this exercise indicate that challenges remain with respect to ensuring that results are delivered in a timely, consistent and reliable manner to support medical interventions. Laboratories within the networks are encouraged to work together to develop and maintain collective capabilities and capacity for emergency bioassay, which is an important component of radiation emergency response. |
| Identification of Serologic Markers for School-Aged Children With Congenital Rubella Syndrome
Hyde TB , Sato HK , Hao L , Flannery B , Zheng Q , Wannemuehler K , Ciccone FH , de Sousa Marques H , Weckx LY , Sáfadi MA , de Oliveira Moraes E , Pinhata MM , Olbrich Neto J , Bevilacqua MC , Tabith Junior A , Monteiro TA , Figueiredo CA , Andrus JK , Reef SE , Toscano CM , Castillo-Solorzano C , Icenogle JP . J Infect Dis 2015 212 (1) 57-66 BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. |
| Limited genomic divergence between intraspecific forms of Culex pipiens under different ecological pressures.
Gomes B , Wilding CS , Weetman D , Sousa CA , Novo MT , Savage HM , Almeida AP , Pinto J , Donnelly MJ . BMC Evol Biol 2015 15 (1) 197
BACKGROUND: Divergent selection can be a major driver of ecological speciation. In insects of medical importance, understanding the speciation process is both of academic interest and public health importance. In the West Nile virus vector Culex pipiens, intraspecific pipiens and molestus forms vary in ecological and physiological traits. Populations of each form appear to share recent common ancestry but patterns of genetic differentiation across the genome remain unknown. Here, we undertook an AFLP genome scan on samples collected from both sympatric and allopatric populations from Europe and the USA to quantify the extent of genomic differentiation between the two forms. RESULTS: The forms were clearly differentiated but each exhibited major population sub-structuring between continents. Divergence between pipiens and molestus forms from USA was higher than in both inter- and intra-continental comparisons with European samples. The proportion of outlier loci between pipiens and molestus ( approximately 3 %) was low but consistent in both continents, and similar to those observed between sibling species of other mosquito species which exhibit contemporary gene flow. Only two of the outlier loci were shared between inter-form comparisons made within Europe and USA. CONCLUSION: This study supports the molestus and pipiens status as distinct evolutionary entities with low genomic divergence. The low number of shared divergent loci between continents suggests a relatively limited number of genomic regions determining key typological traits likely to be driving incipient speciation and/or adaptation of molestus to anthropogenic habitats. |
| Working toward a sustainable laboratory quality improvement programme through country ownership: Mozambique's SLMTA story
Masamha J , Skaggs B , Pinto I , Mandlaze AP , Simbine C , Chongo P , de Sousa L , Kidane S , Yao K , Luman ET , Samogudo E . Afr J Lab Med 2014 3 (2) 253 BACKGROUND: Launched in 2009, the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme has emerged as an innovative approach for the improvement of laboratory quality. In order to ensure sustainability, Mozambique embedded the SLMTA programme within the existing Ministry of Health (MOH) laboratory structure. OBJECTIVE: This article outlines the steps followed to establish a national framework for quality improvement and embedding the SLMTA programme within existing MOH laboratory systems. METHODS: The MOH adopted SLMTA as the national laboratory quality improvement strategy, hired a dedicated coordinator and established a national laboratory quality technical working group comprising mostly personnel from key MOH departments. The working group developed an implementation framework for advocacy, training, mentorship, supervision and audits. Emphasis was placed on building local capacity for programme activities. After receiving training, a team of 25 implementers (18 from the MOH and seven from partner organisations) conducted baseline audits (using the Stepwise Laboratory Quality Improvement Process Towards Accreditation [SLIPTA] checklist), workshops and site visits in six reference and two central hospital laboratories. Exit audits were conducted in six of the eight laboratories and their results are presented. RESULTS: The six laboratories demonstrated substantial improvement in audit scores; median scores increased from 35% at baseline to 57% at exit. It has been recommended that the National Tuberculosis Reference Laboratory apply for international accreditation. CONCLUSION: Successful implementation of SLMTA requires partnership between programme implementers, whilst effectiveness and long-term viability depend on country leadership, ownership and commitment. Integration of SLMTA into the existing MOH laboratory system will ensure durability beyond initial investments. The Mozambican model holds great promise that country leadership, ownership and institutionalisation can set the stage for programme success and sustainability. |
| HIV risk perception and behavior among sex workers in three major urban centers of Mozambique
Langa J , Sousa C , Sidat M , Kroeger K , McLellan-Lemal E , Belani H , Patel S , Shodell D , Shodell M , Benech I , Needle R . PLoS One 2014 9 (4) e94838 HIV risk perceptions and behaviors of 236 commercial sex workers from three major Mozambican urban centers were studied using the International Rapid Assessment, Response and Evaluation (I-RARE) methodology. All were offered HIV testing and, in Maputo, syphilis testing was offered as well. Sixty-three of the 236 opted for HIV testing, with 30 (48%) testing positive for HIV. In Maputo, all 30 receiving HIV tests also had syphilis testing, with 6 (20%) found to be positive. Results include interview excerpts and qualitative results using I-RARE methodology and AnSWR-assisted analyses of the interviews and focus group sessions. |
| Evaluation of a high-throughput diagnostic system for detection of HIV-1 in dried blood spot samples from infants in Mozambique.
Jani IV , Sabatier J , Vubil A , Subbarao S , Bila D , de Sousa A , Mabunda N , Garcia A , Skaggs B , Ellenberger D , Ramos A . J Clin Microbiol 2012 50 (4) 1458-60
We performed a comparative analysis between Roche Amplicor HIV-1 DNA test and CAPTAQ assay for the detection of HIV in 830 dried blood spot (DBS) pediatric samples collected in Mozambique. Our results demonstrated no statistical difference between these assays. The CAPTAQ assay approached nearly 100% repeatability/accuracy. The increased throughput of testing with minimal operator interference in performing the CAPTAQ assay clearly demonstrated that this method is an improvement over the Roche Amplicor HIV-1 DNA test, version 1.5. |
| Phylogeographical footprint of colonial history in the global dispersal of human immunodeficiency virus type 2 group A
Faria NR , Hodges-Mameletzis I , Silva JC , Rodes B , Erasmus S , Paolucci S , Ruelle J , Pieniazek D , Taveira N , Trevino A , Goncalves MF , Jallow S , Xu L , Camacho RJ , Soriano V , Goubau P , de Sousa JD , Vandamme AM , Suchard MA , Lemey P . J Gen Virol 2012 93 889-99
Human immunodeficiency virus type 2 (HIV-2) emerged in West Africa and has spread further to countries that share socio-historical ties with this region. However, viral origins and dispersal patterns at a global scale remain poorly understood. Here, we adopt a Bayesian phylogeographic approach to investigate the spatial dynamics of HIV-2 group A (HIV-2A) using a collection of 320 partial pol and 248 partial env sequences sampled throughout 19 countries worldwide. We extend phylogenetic diffusion models that simultaneously draw information from multiple loci to estimate location states throughout distinct phylogenies and explicitly attempt to incorporate human migratory fluxes. Our study highlights that Guinea-Bissau, together with Cote d'Ivoire and Senegal, have acted as the main viral sources in the early stages of the epidemic. We show that convenience sampling can obfuscate the estimation of the spatial root of HIV-2A. We explicitly attempt to circumvent this by incorporating rate priors that reflect the ratio of human flow from and to West Africa. We recover four main routes of HIV-2A dispersal that are laid out along colonial ties: Guinea-Bissau and Cape Verde to Portugal, Cote d'Ivoire and Senegal to France. Within Europe, we find strong support for epidemiological linkage from Portugal to Luxembourg and to the UK. We demonstrate that probabilistic models can uncover global patterns of HIV-2A dispersal providing sampling bias is taken into account and we provide a scenario for the international spread of this virus. |
| The national study to prevent blood exposure in paramedics: rates of exposure to blood
Boal WL , Leiss JK , Ratcliffe JM , Sousa S , Lyden JT , Li J , Jagger J . Int Arch Occup Environ Health 2010 83 (2) 191-9 OBJECTIVE: The purpose of this analysis is to present incidence rates of exposure to blood among paramedics in the United States by selected variables and to compare all percutaneous exposure rates among different types of healthcare workers. METHODS: A survey on blood exposure was mailed in 2002-2003 to a national sample of paramedics. Results for California paramedics were analyzed with the national sample and also separately. RESULTS: The incidence rate for needlestick/lancet injuries was 100/1,000 employee-years [95% confidence interval (CI), 40-159] among the national sample and 26/1,000 employee-years (95% CI, 15-38) for the California sample. The highest exposure rate was for non-intact skin, 230/1,000 employee-years (95% CI, 130-329). The rate for all exposures was 465/1,000 employee-years (95% CI, 293-637). California needlestick/lancet rates, but not national, were substantially lower than rates in earlier studies of paramedics. Rates for all percutaneous injuries among paramedics were similar to the mid to high range of rates reported for most hospital-based healthcare workers. CONCLUSIONS: Paramedics in the United States are experiencing percutaneous injury rates at least as high as, and possibly substantially higher than, most hospital-based healthcare workers, as well as substantially higher rates of exposure to blood on non-intact skin. |
| Molecular epidemiology and risk factors for nasal carriage of Staphylococcus aureus and methicillin-resistant S. aureus in infants attending day-care centers in Brazil
Lamaro-Cardoso J , de Lencastre H , Kipnis A , Pimenta FC , Oliveira LS , Oliveira RM , Nouer S , Aires-de-Sousa M , Milheirico C , Andrade AL . J Clin Microbiol 2009 47 (12) 3991-7
Investigations regarding Staphylococcus aureus carriage among Brazilian children are scarce. We evaluated the determinants of S. aureus and methicillin-resistant S. aureus (MRSA) nasal carriage in infants attending day-care centers (DCCs) and the molecular features of the MRSA strains. A total of 1,192 children aged 2 months to 5 years attending 62 DCCs were screened for S. aureus and MRSA nasal carriage. MRSA isolates were characterized by pulsed-field gel electrophoresis, multilocus sequence typing, spa typing, staphylococcal cassette chromosome (SCC) mec typing and the presence of the Panton-Valentine leukocidin gene. Logistic regression was performed to determine risk factors associated with S. aureus and MRSA colonization. S. aureus and MRSA carriage were detected in 371 (31.1%) and 14 (1.2%) children, respectively. Variables found to be independently associated with an increased risk for S. aureus carriage included being older than 24 months (OR=1.8; 95%CI 1.3-2.6) and previous DCC attendance (OR=1.5; 95%CI 1.0-2.2). Having a mother with a high degree of education was a protective factor for nasal colonization (OR=0.4; 95%CI 0.2-0.8). Moreover, we observed that more children carrying MRSA had younger siblings compared to children not colonized by MRSA. Among the 14 MRSA strains, three SCCmec types (IIIA, IV and V) were detected, together with a multidrug resistant dominant MRSA lineage sharing 82.7% genetic similarity with the Brazilian clone (ST239-MRSA-IIIA). Although SCCmec type V was recovered from one healthy child who had been exposed to known risk factors for hospital associated MRSA, its genetic background was compatible with community-related MRSA. Our data suggest that DCC attendees could be contributing to MRSA cross-transmission between healthcare and community settings. |
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