Mycobacterium tuberculosis is estimated to infect 80 to 100 million people annually, the majority of whom do not develop clinical tuberculosis (TB) but instead maintain the infection in a latent state. These individuals generally become positive in response to a tuberculin skin test and may develop clinical TB at a later date, particularly if their immune systems are compromised. Latently infected individuals are interesting for two reasons. First, they are an important reservoir of M. tuberculosis, which needs to be considered for TB control. Second, if detected prior to recrudescence of the disease, they represent a human population that is making a protective immune response to M. tuberculosis, which is very important for defining correlates of protective immunity. In this study, we show that while responsiveness to early secretory antigenic target 6 is a good marker for M. tuberculosis infection, a strong response to the 16-kDa Rv2031c antigen (HspX or ␣-crystallin) is largely restricted to latently infected individuals, offering the possibility of differential immunodiagnosis of, or therapeutic vaccination against, TB. Tuberculosis (TB) is easily transmitted by inhalation of infectiousMycobacterium tuberculosis bacilli from the air and is one of the leading causes of death in adults between the ages of 15 and 45 years (43). The global incidence rate of TB is increasing by approximately 0.4% per year (43), driven by factors such as the human immunodeficiency virus (HIV)/ AIDS epidemic, poverty, and increasing population density. Despite the existence of effective treatment regimens, control of TB is complicated by the chronic nature of the disease. Only 5 to 10% of recently exposed individuals develop clinically active TB in the first 2 years after exposure, and this, together with the often transient nature of exposure, makes accurate tracing of recently exposed and potentially infected individuals extremely difficult.A higher percentage of exposed individuals become infected but are able to limit the growth of the mycobacteria and become latently infected. The exact incidence of latent infection remains unclear, but it is estimated that up to 2 billion people globally may harbor latent TB infections (17,22,43). Latency can only be understood as a dynamic process-an active host immune response is essential to keep the disease in the latent stage, as demonstrated by the high rate of TB recrudescence in individuals with HIV infection (8) or the reactivation of the latent infection in individuals given anti-tumor necrosis factor alpha therapy (29). The decline of the immune system due to old age or malnutrition also increases the risk of latent disease becoming clinically significant.Thus, latently infected individuals provide a highly relevant population to study what human protective immune responses against M. tuberculosis look like. However, identifying these people has been problematic in the past. The classical definition of latent infection (conversion to positivity in the purified protein derivative-ba...

BackgroundHepatitis, a highly contagious viral infection, is one of the leading killer diseases globally caused by hepatitis virus. Among the existing viral causes for hepatic failure, hepatitis B virus (HBV) plays a significant role with devastating implications, especially when combined with other viral infections such as human immunodeficiency virus (HIV). Co-infection with hepatitis B virus and HIV leads to increased morbidity and mortality as compared to independent HIV and HBV infections. In this study, we aimed to assess the seroprevalence of HBV and HIV coinfection and associated risk factors among pregnant women in a selected hospital facility around Addis Ababa, Ethiopia.MethodsA total of 215 pregnant women were recruited between July and October 2014 from Tirunesh Beijing General Hospital. A pretested and structured questionnaire was used to collect socio-demographic characteristics and possible risk factors. In addition, 5 ml venous blood was collected and centrifuged to estimate the seroprevalence of HBV and HIV. Descriptive statistics and logistic regression analysis were done and a P value less than 0.05 was considered statistically significant.ResultsThe overall prevalence of hepatitis B virus infection was 13 (6 %). This positivity was different across different age categories: 1 (11.1 %), 3 (4.5 %), 6 (6 %), 1 (3.2 %), and 2 (25 %) among those between 15–19, 20–24, 25–29, 30–34, and 35–39 years, respectively. However, a statistically significant association was not established between age and HBV. Among the total, 9 (4.2 %) of the positive cases were detected among primary school completed. Multivariate analyses indicated that history of abortion (p = 0.003), history of surgery (p = 0.0.022), and tattooing (p = 0.033) were significantly associated with HBV infection. A total of 9 (4.2 %) women were found to be HIV seropositive, of whom 2 (22.2 %) were co-infected with HBV.ConclusionsWe observed a relatively higher seroprevalence of HBV infection among pregnant women in the study area, in which majority of the cases had underlying risk factors for acquiring the infection. Since none of the mothers were vaccinated for HBV, the possibility of perinatal transmission is inevitable. Hence, routine screening and immunization against HBV during pregnancy and health education are highly warranted to alleviate the situation.

There is an increasing body of evidence which suggests that IL-4 plays a role in the pathogenesis of TB, but a general consensus on its role remains elusive. We have previously published data from a cohort of Ethiopian TB patients, their contacts, and community controls suggesting that enhanced IL-4 production is associated with infection with M. tuberculosis, rather than overt disease and that long-term protection in infected community controls is associated with co-production of the IL-4 antagonist IL-4d2, alongside elevated IL-4. Here, for the first time, we compare data on expression of IFN-γ, IL-4 and IL-4δ2 over time in TB patients and their household contacts. During the follow-up period, the TB patients completed therapy and ceased to display TB-like symptoms. This correlated with a decrease in the relative amount of IL-4 expressed. Over the same period, the clinical status of some of their contacts also changed, with a number developing TB-like symptoms or clinically apparent TB. IL-4 expression was disproportionately increased in this group. The findings support the hypothesis that elevated IL-4 production is generally associated with infection, but that TB disease is associated with a relatively increased expression of IL-4 compared to IFN-γ and IL-4δ2. However, the data also suggest that there are no clear-cut differences between groups: the immune response over time appears to include changes in the expression of IFN-γ, IL-4 and IL-4δ2, and it is the relative, not absolute levels of cytokine expression that are characteristic of clinical status.

It is well known that the majority of healthy individuals exposed to Mycobacterium tuberculosis do not become clinically ill. We have previously shown that in recently exposed healthy contacts of tuberculosis (TB) patients, a strong immune response to the M. tuberculosis 6-kDa early secreted antigenic target (ESAT-6) virulence factor correlated with a higher risk of subsequent disease, although the mechanism was unclear at that time. Inspired by recent reports that elevated expression of interleukin-4 (IL-4) in health care workers exposed to M. tuberculosis also correlated with a higher risk of their subsequently developing disease, we examined expression of IL-4, its competitive antagonist IL-4␦2, and gamma interferon (IFN-␥) in healthy household contacts of TB patients from Ethiopia. We then compared cytokine expression to their recognition of ESAT-6 (which is largely restricted to members of the tuberculosis complex and which serves as a reliable marker of infection) or to Ag85A (an antigen that is conserved among the mycobacteria and serves as a nonspecific control). Our study shows that in these recently exposed individuals, there is a correlation between a strong response to ESAT-6 and elevated expression of IL-4. Further, elevated expression of IL-4 is associated with lower expression of its antagonistic splice variant IL-4␦2 and with the Th1 cytokine IFN-␥, suggesting that in these at-risk individuals, immunity is skewed away from a protective Th1 response, even before the development of clinical symptoms.

Scaling up of diagnostic capacity is needed to mitigate the global pandemic of SARS-CoV2. However, there are challenges including shortage of sample collection swabs and transport medium. Saliva has been recommended as a simple, low-cost, non-invasive option. However, data from different populations and settings are limited. Here, we showed that saliva could be a good alternative sample to diagnose COVID-19 patients. Pair of NPS-saliva samples was collected from 152 symptomatic; confirmed COVID-19 patients, and compared their positivity rate, viral load, and duration of viral shedding. From 152 patients, 80 (52.63%) tested positive and 72 (47.37%) were negative for SARSA-CoV2 in NPS sample. In saliva, 129 (92.14%) were tested positive and 11 (7.86%) were negative on the day of admission to hospital. The overall percent agreement of RT-PCR result of Saliva to NPS was 70% (196/280). A comparison of viral load from 72 NPS-saliva pair samples on day of admission shows saliva contains significantly higher viral load (P < 0.001). In conclusion, saliva has higher yield in detecting SARS-CoV2, and COVID-19 patients show higher viral load and prolonged period of viral shedding in saliva. Therefore, we recommend saliva as a better alternative sample to NPS to diagnose COVID-19 patients.