Browsing by Subject "Transmission"

Now showing 1 - 6 of 6
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    Decreasing household contribution to TB transmission with age: a retrospective geographic analysis of young people in a South African township
    (BioMed Central Ltd, 2014) Middelkoop, Keren; Bekker, Linda-Gail; Morrow, Carl; Lee, Namee; Wood, Robin
    BACKGROUND: Tuberculosis (TB) transmission rates are exceptionally high in endemic TB settings. Adolescence represents a period of increasing TB infection and disease but little is known as to where adolescents acquire TB infection. We explored the relationship between residential exposure to adult TB cases and infection in children and adolescents in a South African community with high burdens of TB and HIV. METHODS: TB infection data were obtained from community, school-based tuberculin skin test (TST) surveys performed in 2006, 2007 and 2009. A subset of 2007 participants received a repeat TST in 2009, among which incident TB infections were identified. Using residential address, all adult TB cases notified by the community clinic between 1996 and 2009 were cross-referenced with childhood and adolescent TST results. Demographic and clinic data including HIV status were abstracted for TB cases. Multivariate logistic regression models examined the association of adult TB exposure with childhood and adolescent prevalent and incident TB infection. RESULTS: Of 1,100 children and adolescents included in the prevalent TB infection analysis, 480 (44%) were TST positive and 651 (59%) were exposed to an adult TB case on their residential plot. Prevalent TB infection in children aged 5-9 and 10-14 years was positively associated with residential exposure to an adult TB case (odds ratio [OR]:2.0; 95% confidence interval [CI]: 1.1-3.6 and OR:1.5; 95% CI: 1.0-2.3 respectively), but no association was found in adolescents [greater than or equal to]15years (OR:1.4; 95% CI: 0.9-2.0). HIV status of adult TB cases was not associated with TB infection (p=0.62). Of 67 previously TST negative children, 16 (24%) converted to a positive TST in 2009. These incident infections were not associated with residential exposure to an adult TB case (OR: 1.9; 95% CI: 0.5-7.3). CONCLUSIONS: TB infection among young children was strongly associated with residential exposure to an adult TB case, but prevalent and incident TB infection in adolescents was not associated with residential exposure. The HIV-status of adult TB cases was not a risk factor for transmission. The high rates of TB infection and disease among adolescents underscore the importance of identifying where infection occurs in this age group.
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    HIV-1 subtype C transmitted founders modulate dendritic cell inflammatory responses
    (2020-07-02) Lumngwena, Evelyn N; Metenou, Simon; Masson, Lindi; Cicala, Claudia; Arthos, James; Woodman, Zenda
    Background Heterosexual transmission remains the main route of HIV-1 transmission and female genital tract (FGT) inflammation increases the risk of infection. However, the mechanism(s) by which inflammation facilitates infection is not fully understood. In rhesus macaques challenged with simian immunodeficiency virus, dendritic cell (DC) mediated recruitment of CD4+ T cells to the FGT was critical for infection. The aim of this study was to delineate the mechanisms underlying DC-mediated HIV infection by comparing chemokine and pro-inflammatory cytokine production in response to transmitted founder (TF) and chronic infection (CI) Envelope (Env) pseudotyped viruses (PSV). Results Monocyte-derived DCs (MDDCs) were stimulated with PSV and recombinant gp140 representing matched TF and CI pairs of four individuals and cytokine secretion measured by multiplex immuno-assay. We found that 4/9 Env induced robust MDDC inflammatory responses and of those, three were cloned from TFs. Overall, TF Env induced MDDCs from healthy donors to secrete higher concentrations of inflammatory cytokines and chemokines than those from CI, suggesting TF Env were better inducers of inflammation. Assessing the signalling pathway associated with inflammatory cytokines, we found that PSV of matched TF and CI variants and a gp140 clone activated ERK and JNK to similar levels. Recombinant soluble DC-SIGN inhibited cytokine release and activation of ERK by PSV, suggesting that Env-DC-SIGN binding was partly involved in MDDC stimulation. Therefore, Env clones might differentially stimulate MDDC immune responses via alternative, yet unidentified signalling pathways. Conclusion Overall, this could suggest that the genetics of the virus itself influences inflammatory responses during HIV infection. In the absence of pre-existing infections, induction of greater inflammatory response by TFs might favour virus survival within the healthy FGT by driving an influx of target cells to sites of infection while suppressing immune responses via IL-10.
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    The HIV‑1 transmission bottleneck
    (Biomed Central, 2017-03-25) Kariuki, Samuel Mundia; Selhorst, Philippe; Ariën, Kevin K; Dorfman, Jeffrey Robert
    It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient’s genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor’s general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient’s genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient.
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    Modes of transmission and attack rates of group A Streptococcal infection: a protocol for a systematic review and meta-analysis
    (2021-03-31) Barth, Dylan D; Daw, Jessica; Xu, Ruomei; Enkel, Stephanie; Pickering, Janessa; McRae, Tracy; Engel, Mark E; Carapetis, Jonathan; Wyber, Rosemary; Bowen, Asha C
    Background Group A Streptococcus (Strep A) is an important cause of mortality and morbidity globally. This bacterium is responsible for a range of different infections and post-infectious sequelae. Summarising the current knowledge of Strep A transmission to humans will address gaps in the evidence and inform prevention and control strategies. The objective of this study is to evaluate the modes of transmission and attack rates of group A streptococcal infection in human populations. Methods This systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-analysis Protocols (PRISMA-P) 2015 Statement. Using a comprehensive search strategy to identify any transmission studies that have been published in English since 1980, full-text articles will be identified and considered for inclusion against predefined criteria. We will include all studies reporting on Strep A transmission, who have identified a mode of transmission, and who reported attack rates. Risk of bias will be appraised using an appropriate tool. Our results will be described narratively and where feasible and appropriate, a meta-analysis utilizing the random-effects model will be used to aggregate the incidence proportions (attack rates) for each mode of transmission. In addition, we will also evaluate the emm genotype variants of the M protein causing Strep A infection and the association with transmission routes and attack rates, if any, by setting, socioeconomic background and geographical regions. Discussion We anticipate that this review will contribute to elucidating Strep A modes of transmission which in turn, will serve to inform evidence-based strategies including environmental health activities to reduce the transmission of Strep A in populations at risk of severe disease. Trial registration Systematic review registration: PROSPERO ( CRD42019138472 ).
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    The HIV-1 transmission bottleneck
    (2017) Dorfman, Jeffrey R
    It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient's genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor's general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient's genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient.
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    Open Access
    The HIV-1 transmission bottleneck
    (BioMed Central, 2017-03-23) Kariuki, Samuel M; Selhorst, Philippe; Ariën, Kevin K; Dorfman, Jeffrey R
    It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient’s genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor’s general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient’s genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient.