Browsing by Subject "Vaccination and immunization"

Now showing 1 - 13 of 13
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    Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants
    (Public Library of Science, 2011) Randhawa, April Kaur; Shey, Muki S; Keyser, Alana; Peixoto, Blas; Wells, Richard D; de Kock, Marwou; Lerumo, Lesedi; Hughes, Jane; Hussey, Gregory; Hawkridge, Anthony; Kaplan, Gilla; Hanekom, Willem A; Hawn, Thomas R
    The development of effective immunoprophylaxis against tuberculosis (TB) remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG) vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR) variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S) was associated with increased BCG-induced IFN-γ in both discovery (n = 240) and validation (n = 240) cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S) and TLR6_G1083C (synonymous) were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2). After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the development of adaptive immune responses after in vivo vaccination against a bacterial pathogen in humans. These findings could potentially guide novel adjuvant vaccine strategies as well as have implications for IFN-γ-based diagnostic testing for TB.
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    The candidate TB vaccine, MVA85A, induces highly durable Th1 responses
    (Public Library of Science, 2014) Tameris, Michele; Geldenhuys, Hennie; Luabeya, Angelique KanyKany; Smit, Erica; Hughes, Jane E; Vermaak, Samantha; Hanekom, Willem A; Hatherill, Mark; Mahomed, Hassan; McShane, Helen; Scriba,Thomas J
    BACKGROUND: Vaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis ( M.tb ). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone. METHODS: We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011. RESULTS: Of 252 potential participants, 183 (72.6%) consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA−CCR7+ central memory or CD45RA−CCR7− effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination. CONCLUSION: MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants.
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    Continued follow-up of Phambili Phase 2b randomized HIV-1 vaccine trial participants supports increased HIV-1 acquisition among vaccinated men
    (Public Library of Science, 2015) Moodie, Zoe; Metch, Barbara; Bekker, Linda-Gail; Churchyard, Gavin; Nchabeleng, Maphoshane; Mlisana, Koleka; Laher, Fatima; Roux, Surita; Mngadi, Kathryn; Innes, Craig
    BACKGROUND: The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag / pol / nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. METHODS: HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. RESULTS: Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08-2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62). CONCLUSION: The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women. Trial Registration clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539
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    HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice
    (Public Library of Science, 2016) Jongwe, Tsungai Ivai; Chapman, Ros; Douglass, Nicola; Chetty, Shivan; Chege, Gerald; Williamson, Anna-Lise
    Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG Δ panCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (Gag M ) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-Gag M vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-Gag M and boosting with MVA-Gag M elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-Gag M only and MVA-Gag M only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4 + and CD8 + T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (10 4 pfu) can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C).
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    Incidence and risk factors for neonatal tetanus in admissions to County Hospital, Kenya
    (Public Library of Science, 2015) Ibinda, Fredrick; Bauni, Evasius; Kariuki, Symon M; Fegan, Greg; Lewa, Joy; Mwikamba, Monica; Boga, Mwanamvua; Odhiambo, Rachael; Mwagandi, Kiponda; Seale, Anna C
    BACKGROUND: Neonatal Tetanus (NT) is a preventable cause of mortality and neurological sequelae that occurs at higher incidence in resource-poor countries, presumably because of low maternal immunisation rates and unhygienic cord care practices. We aimed to determine changes in the incidence of NT, characterize and investigate the associated risk factors and mortality in a prospective cohort study including all admissions over a 15-year period at a County hospital on the Kenyan coast, a region with relatively high historical NT rates within Kenya. METHODS: We assessed all neonatal admissions to Kilifi County Hospital in Kenya (1999-2013) and identified cases of NT (standard clinical case definition) admitted during this time. Poisson regression was used to examine change in incidence of NT using accurate denominator data from an area of active demographic surveillance. Logistic regression was used to investigate the risk factors for NT and factors associated with mortality in NT amongst neonatal admissions. A subset of sera from mothers (n = 61) and neonates (n = 47) were tested for anti-tetanus antibodies. RESULTS: There were 191 NT admissions, of whom 187 (98%) were home deliveries. Incidence of NT declined significantly (Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81-0.89), P<0.001) but the case fatality (62%) did not change over the study period (P = 0.536). Younger infant age at admission (P = 0.001) was the only independent predictor of mortality. Compared to neonatal hospital admittee controls, the proportion of home births was higher among the cases. Sera tested for antitetanus antibodies showed most mothers (50/61, 82%) had undetectable levels of antitetanus antibodies, and most (8/9, 89%) mothers with detectable antibodies had a neonate without protective levels. CONCLUSIONS: Incidence of NT in Kilifi County has significantly reduced, with reductions following immunisation campaigns. Our results suggest immunisation efforts are effective if sustained and efforts should continue to expand coverage.
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    Individual and contextual factors associated with low childhood immunisation coverage in sub-Saharan Africa: a multilevel analysis
    (Public Library of Science, 2012) Wiysonge, Charles S; Uthman, Olalekan A; Ndumbe, Peter M; Hussey, Gregory D
    BACKGROUND: In 2010, more than six million children in sub-Saharan Africa did not receive the full series of three doses of the diphtheria-tetanus-pertussis vaccine by one year of age. An evidence-based approach to addressing this burden of un-immunised children requires accurate knowledge of the underlying factors. We therefore developed and tested a model of childhood immunisation that includes individual, community and country-level characteristics. Method and FINDINGS: We conducted multilevel logistic regression analysis of Demographic and Health Survey data for 27,094 children aged 12-23 months, nested within 8,546 communities from 24 countries in sub-Saharan Africa. According to the intra-country and intra-community correlation coefficient implied by the estimated intercept component variance, 21% and 32% of the variance in unimmunised children were attributable to country- and community-level factors respectively. Children born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to 1.40) with no formal education were more likely to be unimmunised than those born to parents with secondary or higher education. Children from the poorest households were 36% more likely to be unimmunised than counterparts from the richest households. Maternal access to media significantly reduced the odds of children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI 0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23), communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more likely to be unimmunised. CONCLUSION: We found that individual and contextual factors were associated with childhood immunisation, suggesting that public health programmes designed to improve coverage of childhood immunisation should address people, and the communities and societies in which they live.
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    Is obesity a risk factor for vaccine non-responsiveness?
    (Public Library of Science, 2013) Young, Katherine M; Gray, Clive M; Bekker, Linda-Gail
    Understanding the link between vaccine immunogenicity and efficacy is currently a major focus in HIV research. Consequently, recent developments in the HIV-1 vaccine field have led to a closer look at immune responses to known efficacious vaccines. We undertook a study to explore clinical predictors of vaccine efficacy following recombinant hepatitis B (rHBV) vaccination in a cohort of HIV-uninfected, hepatitis B virus naïve women living in a peri-urban setting in Cape Town. Our aim was to define host biological risk factors associated with lack of vaccine uptake. We found a significant association (p=0.009) between body mass index (BMI) and lack of vaccine-specific IgG titre (<10mIU/mL). Obese individuals (BMI ≥ 30kg/m 2 ) were significantly more likely to be non-responders following 2 rHBV vaccine doses (Adjusted Odds Ratio of 8.75; p=0.043). There was no observed association between vaccine responses and age, method of contraception or time from vaccination to antibody measurement. These data suggest that obesity-associated factors interfere with vaccine immunogenicity and possible efficacy.
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    Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women
    (Public Library of Science, 2012) Latka, Mary H; Fielding, Katherine; Gray, Glenda E; Bekker, Linda-Gail; Nchabeleng, Maphoshane; Mlisana, Koleka; Nielson, Tanya; Roux, Surita; Mkhize, Baningi; Mathebula, Matsontso
    BACKGROUND: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. METHODS: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. RESULTS: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)]. CONCLUSIONS: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention. Trial Registration SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT00413725
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    Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells
    (Public Library of Science, 2012) Chapman, Rosamund; Shephard, Enid; Stutz, Helen; Douglass, Nicola; Sambandamurthy, Vasan; Garcia, Irene; Ryffel, Bernhard; Jacobs, William; Williamson, Anna-Lise
    A safe and effective HIV vaccine is required to significantly reduce the number of people becoming infected with HIV each year. In this study wild type Mycobacterium bovis BCG Pasteur and an attenuated pantothenate auxotroph strain (BCGΔ panCD ) that is safe in SCID mice, have been compared as vaccine vectors for HIV-1 subtype C Gag. Genetically stable vaccines BCG[pHS400] (BCG-Gag) and BCGΔ panCD [pHS400] (BCGpan-Gag) were generated using the Pasteur strain of BCG, and a panothenate auxotroph of Pasteur respectively. Stability was achieved by the use of a codon optimised gag gene and deletion of the hsp60-lysA promoter-gene cassette from the episomal vector pCB119. In this vector expression of gag is driven by the mtrA promoter and the Gag protein is fused to the Mycobacterium tuberculosis 19 kDa signal sequence. Both BCG-Gag and BCGpan-Gag primed the immune system of BALB/c mice for a boost with a recombinant modified vaccinia virus Ankara expressing Gag (MVA-Gag). After the boost high frequencies of predominantly Gag-specific CD8 + T cells were detected when BCGpan-Gag was the prime in contrast to induction of predominantly Gag-specific CD4 + T cells when priming with BCG-Gag. The differing Gag-specific T-cell phenotype elicited by the prime-boost regimens may be related to the reduced inflammation observed with the pantothenate auxotroph strain compared to the parent strain. These features make BCGpan-Gag a more desirable HIV vaccine candidate than BCG-Gag. Although no Gag-specific cells could be detected after vaccination of BALB/c mice with either recombinant BCG vaccine alone, BCGpan-Gag protected mice against a surrogate vaccinia virus challenge.
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    A qualitative analysis of factors influencing HPV vaccine uptake in Soweto, South Africa among adolescents and their caregivers
    (Public Library of Science, 2013) Katz, Ingrid T; Nkala, Busisiwe; Dietrich, Janan; Wallace, Melissa; Bekker, Linda-Gail; Pollenz, Kathryn; Bogart, Laura M; Wright, Alexi A; Tsai, Alexander C; Bangsberg, David R
    BACKGROUND: In South Africa, the prevalence of oncogenic Human Papillomavirus (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer-related death among women. The development of efficacious prophylactic vaccines has provided an opportunity for primary prevention. Given the importance of psycho-social forces in vaccine uptake, we sought to elucidate factors influencing HPV vaccination among a sample of low-income South African adolescents receiving the vaccine for the first time in Soweto. METHODS: The HPV vaccine was introduced to adolescents in low-income townships throughout South Africa as part of a nationwide trial to understand adolescent involvement in future vaccine research targeting human immunodeficiency virus (HIV). We performed in-depth semi-structured interviews with purposively-sampled adolescents and their care providers to understand what forces shaped HPV vaccine uptake. Interviews were recorded, transcribed, translated, and examined using thematic analysis. RESULTS: Of 224 adolescents recruited, 201 initiated the vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found that factors driving vaccine uptake reflected a socio-cultural backdrop of high HIV endemnicity, sexual violence, poverty, and an abundance of female-headed households. Adolescents exercised a high level of autonomy and often initiated decision-making. Healthcare providers and peers provided support and guidance that was absent at home. The impact of the HIV epidemic on decision-making was substantial, leading participants to mistakenly conflate HPV and HIV. CONCLUSIONS: In a setting of perceived rampant sexual violence and epidemic levels of HIV, adolescents and caregivers sought to decrease harm by seeking a vaccine targeting a sexually transmitted infection (STI). Despite careful consenting, there was confusion regarding the vaccine's target. Future interventions promoting STI vaccines will need to provide substantial information for participants, particularly adolescents who may exercise a significant level of autonomy in decision-making.
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    Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants
    (Public Library of Science, 2016) Churchyard, Gavin; Mlisana, Koleka; Karuna, Shelly; Williamson, Anna-Lise; Williamson, Carolyn; Morris, Lynn; Tomaras, Georgia D; De Rosa, Stephen C; Gilbert, Peter B; Gu, Niya; Yu, Chenchen; Mkhize, Nonhlanhla N; Hermanus, Tandile; Allen, Mary; Pensiero, Michael; Barnett, Susan W; Gray, Glenda; Bekker, Linda-Gail; Montefiori, David C; Kublin, James; Corey, Lawrence
    BACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 10 9 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS: Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. RESULTS: 184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. CONCLUSIONS: The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. Trial Registration ClinicalTrials.gov NCT01418235
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    Smoking, BCG and employment and the risk of tuberculosis infection in HIV-infected persons in South Africa
    (Public Library of Science, 2012) Oni, Tolu; Gideon, Hannah P; Bangani, Nonzwakazi; Tsekela, Relebohile; Seldon, Ronnett; Wood, Kathryn; Wilkinson, Katalin A; Goliath, Rene T; Ottenhoff, Tom H M; Wilkinson, Robert J
    BACKGROUND: The increased susceptibility to latent tuberculosis infection (LTBI) of HIV-1-infected persons represents a challenge in TB epidemic control. However few studies have evaluated LTBI predictors in a generalized HIV/TB epidemic setting. METHODS: The study recruited 335 HIV-infected participants from Khayelitsha, Cape Town between February 2008 and November 2010. Tuberculin skin tests and interferon-gamma release assays were performed on all participants and active TB excluded using a symptom screen, TB microscopy and culture. RESULTS: LTBI prevalence was 52.7% and 61.2% (TST and IGRA respectively). Being a recent TB contact (OR 2.07; 95% C.I. 1.15-3.69) was associated with TST positivity. Participants with a CD4>200 had a two-fold higher risk of IGRA positivity compared to those with CD4 counts <200 (OR 2.07; 95% C.I. 0.99-4.34). There was also a 19% increase in IGRA positivity risk for every additional year of schooling and a strong association between years of schooling and employment (p = 0.0004). A decreased risk of IGRA positivity was observed in persons with a BCG scar (OR 0.46; 95% C.I. 0.31-0.69) and in smokers (OR 0.47; 95% C.I. 0.23-0.96). CONCLUSION: We report the novel findings of a decreased risk of IGRA positivity in HIV-infected smokers possibly due to decreased interferon production, and in the persons with a BCG scar suggesting a protective role for BCG in this population. We also found an increased risk of TST positivity in employed persons, possibly due to ongoing transmission in public modes of transport.
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    Strengthening the expanded programme on immunization in Africa: looking beyond 2015
    (Public Library of Science, 2013) Machingaidze, Shingai; Wiysonge, Charles S; Hussey, Gregory D
    Shingai Machingaidze and colleagues reflect on the successes and shortfalls of the Expanded Programme on Immunization (EPI) in Africa, and the considerable challenges that must now be addressed to improve immunization systems.