How should I interpret an interferon gamma release assay result for tuberculosis infection?

Background: Interferon gamma release assays (IGRAs) are the first new diagnostic tests for latent tuberculosis (TB) infection (LTBI) since the century-old tuberculin skin test (TST). They are cell-mediated immune-based blood tests that have revolutionised LTBI diagnosis and are increasingly recommended by national guidelines. / Objectives: With the rapid expansion of the IGRA evidence-base in recent years, the limitations of IGRA and uncertainties in clinical interpretation of IGRA results have increasingly come into focus. In LTBI diagnosis these include: prognostic power of IGRAs relative to TST for quantifying risk of progression to active disease, false-negative rates in immunocompromised patients, the clinical meaning of IGRA reversion and the significance of the size of IGRA response. Furthermore, the role of IGRAs in the diagnostic work-up of active TB is unclear, and there is little evidence supporting use of the tests in anti-TB treatment monitoring. / Methodological approach: On-going large prospective longitudinal clinical endpoint cohort studies of active and latent TB will tackle some of the uncertainties regarding IGRAs. Here we discuss clinical practice and guidance in light of the current uncertainties, based on existing evidence. / Conclusions and impact: Current and planned clinical research will fill the gaps in the evidence-base, narrowing the areas of uncertainty and informing future policy. Translational research into next-generation IGRAs and new T cell-based diagnostic platforms will likely overcome the limitations of current IGRAs in the near future

Progress in interferon-gamma release assay development and applications: an unfolding story of translational research.

The introduction of blood-based tests for M. tuberculosis (Mtb) infection approximately 15 years ago was a turning point for diagnosis of latent tuberculosis (TB). Interferon-gamma release assays (IGRAs), which measure Mtb antigen-specific T cell responses, include the ELISpot-based T-SPOT.TB (Oxford Immunotec, Abingdon, UK) and the ELISA-based QuantiFERON Gold In-Tube (QFT-GIT; Qiagen, Hilden, Germany)

Efficacy and immunogenicity of a single dose of human papillomavirus vaccine compared to no vaccination or standard three and two-dose vaccination regimens: A systematic review of evidence from clinical trials.

OBJECTIVES: This study aimed to systematically review the literature on the efficacy and immunogenicity of single-dose HPV vaccination compared to no vaccination or multi-dose schedules among vaccine trial participants. METHODS: Medline, EMBASE, Global Health Database and Cochrane Central Register of Controlled Trials were searched for publications and conference abstracts (dated January 1999-August 2018) using MeSH and non-MeSH terms for human papillomavirus AND vaccines AND (immunogenicity OR efficacy/effectiveness) AND dosage. Search results were screened against pre-specified eligibility criteria. Data were extracted from included articles, and a narrative synthesis conducted on efficacy against HPV16/18 infection and humoral immunogenicity. RESULTS: Seven of 6,523 unique records identified were included in the review. Six were nested observational studies of participants randomised to receive two or three doses in three large HPV vaccine trials, in which some participants did not complete their allocated schedules. One small pilot study prospectively allocated participants to receive one or no vaccine dose. Frequency of HPV16/18 infection was low (e.g.  0.05 in all cases). Frequency of infection was significantly lower in one-dose recipients compared to unvaccinated controls (p < 0.01 for all infection endpoints in each study). HPV16/18 seropositivity rates were high in all HPV vaccine recipients (100% in three of four studies reporting this endpoint), though antibody levels were lower with one compared to two or three doses. CONCLUSIONS: This review supports the premise that one HPV vaccine dose may be as effective in preventing HPV infection as multi-dose schedules in healthy young women. However, it also highlights the paucity of available evidence from purpose-designed, prospectively-randomised trials. Results from ongoing clinical trials assessing the efficacy and immunogenicity of single-dose HPV vaccination compared to currently-recommended schedules are awaited

Costs of delivering human papillomavirus vaccination using a one- or two-dose strategy in Tanzania.

OBJECTIVE: As part of the Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls (DoRIS; NCT02834637), the current study is one of the first to evaluate the financial and economic costs of the national rollout of an HPV vaccination program in school-aged girls in sub-Saharan Africa and the potential costs associated with a single dose HPV vaccine program, given recent evidence suggesting that a single dose may be as efficacious as a two-dose regimen. METHODS: The World Health Organization's (WHO) Cervical Cancer Prevention and Control Costing (C4P) micro-costing tool was used to estimate the total financial and economic costs of the national vaccination program from the perspective of the Tanzanian government. Cost data were collected in 2019 via surveys, workshops, and interviews with local stakeholders for vaccines and injection supplies, microplanning, training, sensitization, service delivery, supervision, and cold chain. The cost per two-dose and one-dose fully immunized girl (FIG) was calculated. RESULTS: The total financial and economic costs were US$10,117,455 and US$45,683,204, respectively, at a financial cost of $5.17 per two-dose FIG, and an economic cost of$23.34 per FIG. Vaccine and vaccine-related costs comprised the largest proportion of costs, followed by service delivery. In a one-dose scenario, the cost per FIG reduced to $2.51 (financial) and$12.18 (economic), with the largest reductions in vaccine and injection supply costs, and service delivery. CONCLUSIONS: The overall cost of Tanzania's HPV vaccination program was lower per vaccinee than costs estimated from previous demonstration projects in the region, especially in a single-dose scenario. Given the WHO Strategic Advisory Group of Experts on Immunization's recent recommendation to update dosing schedules to either one or two doses of the HPV vaccine, these data provide important baseline data for Tanzania and may serve as a guide for improving coverage going forward. The findings may also aid in the prioritization of funding for countries that have not yet added HPV vaccines to their routine immunizations

An observational study to inform potential drowning intervention strategies among fishing communities in the lake zone of Tanzania (DRIFT)

Lake Victoria, Africa's largest lake, is surrounded by an abundance of lakeside communities and supports a huge fishing industry. A recent study in Uganda suggested that drowning is a common threat within these communities. Perceived risk of drowning among fisher-folk on Lake Victoria is high, and possibly of greater concern than Human Immunodeficiency Virus (HIV) infection. Yet anecdotal evidence from Tanzanian communities suggests that risky behaviours associated with drowning are common practice. DRIFT was a mixed-methods study. We first obtained estimates of the drowning incidence among the lake-side communities by collecting data on all deaths occurring in each community over the past two years. Second, data on risk factors associated with drowning, risky behaviours in the fishing communities, perceived health risks and threats, and perceptions of potential interventions were collected from fishermen and the wider communities at eight lakeside fishing villages through structured surveys/questionnaires, in-depth interviews, focus group discussions, in-depth death reviews and observational analyses of behaviour. Preliminary data on social and economic impacts of drowning deaths were collected by interviewing family members and colleagues of victims

Drowning among fishing communities on the Tanzanian shore of lake Victoria: a mixed-methods study to examine incidence, risk factors and socioeconomic impact.

OBJECTIVES: To estimate the incidence of unintentional fatal drowning and describe associated risk factors among Lake Victoria fishing communities, and to assess perceived social, financial and other impacts among families and colleagues of persons who drowned. DESIGN: A retrospective, observational mixed-methods study, conducted between September 2017 and February 2018. SETTING: Eight Tanzanian fishing communities on Lake Victoria. PARTICIPANTS: Persons who drowned in the preceding 24 months were identified using an extensive community networking approach. Adult family members, colleagues or community members familiar with the habits and behaviours of people who drowned and/or circumstances of drowning incidents participated in surveys (n=44) and in-depth interviews (n=22). MAIN OUTCOME MEASURES: Pooled drowning incidence, with sensitivity analyses allowing for uncertainties in population estimates. Risk factors were identified through the evaluation of behavioural characteristics of persons who drowned and circumstances of drowning incidents. Perceived socioeconomic impacts were assessed through semi-structured interviews with their family members and colleagues. RESULTS: The estimated drowning incidence was 217/100 000 person-years (95% CI 118 to 425/100 000). Of 86 victims identified, 70 (81%) were fishermen (79% aged 18-40 years; all men) and 9 were children (all ≤10 years). All deaths occurred in the lake. Most adults (65/77; 84%) were fishing from a boat when they drowned; 57/77 (74%) died in the evening (from ~5 pm) or at night. Six children (67%) drowned while swimming/playing at the lakeshore unsupervised. Few victims (2/86; 2%) were wearing a life jacket at the time of death. Reported socioeconomic impacts of these deaths ranged from income loss to family break-up. CONCLUSIONS: Drowning is a significant risk in Tanzanian lakeside fishing communities, with estimated mortality exceeding national incidence rates of fatal malaria, tuberculosis or HIV, but preventative strategies appear uncommon. Socioeconomic impact at the family level may be substantial. Intervention strategies are required to reduce the drowning burden among this neglected at-risk population

Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial

Background An estimated 15% of girls aged 9-14 years worldwide have been vaccinated against human papillomavirus (HPV) with the recommended two-dose or three-dose schedules. A one-dose HPV vaccine schedule would be simpler and cheaper to deliver. We report immunogenicity and safety results of different doses of two different HPV vaccines in Tanzanian girls. Methods In this open-label, randomised, phase 3, non-inferiority trial, we enrolled healthy schoolgirls aged 9-14 years from Government schools in Mwanza, Tanzania. Eligible participants were randomly assigned to receive one, two, or three doses of either the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart) or the 9-valent vaccine (Gardasil-9, Sanofi Pasteur MSD, Lyon). The primary outcome was HPV 16 specific or HPV 18 specific seropositivity following one dose compared with two or three doses of the same HPV vaccine 24 months after vaccination. Safety was assessed as solicited adverse events up to 30 days after each dose and unsolicited adverse events up to 24 months after vaccination or to last study visit. The primary outcome was done in the per-protocol population, and safety was analysed in the total vaccinated population. This study was registered in ClinicalTrials.gov, NCT02834637. Findings Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility. 72 girls were excluded. 930 girls were enrolled and randomly assigned to receive one dose of Cervarix (155 participants), two doses of Cervarix (155 participants), three doses of Cervarix (155 participants), one dose of Gardasil-9 (155 participants), two doses of Gardasil-9 (155 participants), or three doses of Gardasil-9 (155 participants). 922 participants received all scheduled doses within the defined window (three withdrew, one was lost to follow-up, and one died before completion; two received their 6-month doses early, and one received the wrong valent vaccine in error; all 930 participants were included in the total vaccinated cohort). Retention at 24 months was 918 (99%) of 930 participants. In the accordingto-protocol cohort, at 24 months, 99% of participants who received one dose of either HPV vaccine were seropositive for HPV 16 IgG antibodies, compared with 100% of participants who received two doses, and 100% of participants who received three doses. This met the prespecified non-inferiority criteria. Anti-HPV 18 seropositivity at 24 months did not meet non-inferiority criteria for one dose compared to two doses or three doses for either vaccine, although more than 98% of girls in all groups had HPV 18 antibodies. 53 serious adverse events (SAEs) were experienced by 42 (4.5%) of 930 girls, the most common of which was hospital admission for malaria. One girl died of malaria. Number of events was similar between groups and no SAEs were considered related to vaccination. Interpretation A single dose of the 2-valent or 9-valent HPV vaccine in girls aged 9-14 years induced robust immune responses up to 24 months, suggesting that this reduced dose regimen could be suitable for prevention of HPV infection among girls in the target age group for vaccination. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.