Childhood BCG Vaccination Research Articles

BCG vaccination: issues of fuzzy logic in assessing its effectiveness

Background. Vaccination, as a method of specific prevention, is more than 100 years old. Over the years, there have been significant changes in living standards, children’s health, and immunology. The issues of the effectiveness of vaccination, the effectiveness of chemotherapy, and the need for revaccination are relevant in modern conditions. Aim. To evaluate long-term BCG vaccination data among the medical university students with assessment of the effectiveness of vaccination, and MBT infection during 20 years of follow-up. Materials and methods. 274 students of the medical university took part in the study, medical records were used (form No. 112/y). Records of BCG vaccination and Mantoux test results by year in mm. Results. In the long-term assessment of the phthisiological status of the students with 100% BCG vaccination in childhood, it was recognized as effective in 63.1%, ineffective in 18.3%. In 18.6%, the results did not meet the accepted standards. When evaluating the Mantoux 2 TE sample, MBT infection did not differ in the number and size of papules in all groups. Some students remained sensitive to tuberculin in the presence of a positive Diaskintest, in the absence of data for tuberculosis. Conclusion. Not all common concepts about the criteria for the effectiveness of vaccination fit into the existing rules, some aspects relate to the concept of fuzzy logic. Long-term observations using new methods of immunodiagnostics will allow to solve the issues at a new evidentiary level.

"Trained Immunity" from Mycobacterium spp. exposure (BCG vaccination and environmental) may have an impact on the incidence of early childhood leukemia.

Preventive variables for childhood leukemia incidence (LI) remain unknown. Past assertions that childhood vaccinations, especially BCG, may be potentially protective have remained disputed for over five decades because of the lack of a unifying framework to explain variable outcomes in different studies. An examination of the early childhood LI for 2020 in European Region countries with supposedly similar underlying confounders but differential childhood vaccination coverage displays negative covariation with prevailing Mycobacterium spp. exposure in BCG-vaccinated children. The childhood LI in 0-4-year-old populations with >90% childhood BCG vaccination coverage is found to be strongly but negatively correlated with prevailing tuberculin immunoreactivity [r(24): -0.7868, p-value: < 0.0001]. No such correlation existed for the LI in 0-4-year-old populations without BCG vaccinations, though weak associations are hinted at by the available data for MCV2, PCV3, and DTP3 vaccinations. We hypothesize that early childhood BCG vaccination "priming" and subsequent "trained immunity" augmentation by "natural" boosting from Mycobacterium spp. exposure play a preventive and protective role in childhood LI. The non-consideration of prevailing "trained immunity" could have been a cause behind the conflicting outcomes in past studies. Exploratory studies, preferably performed in high-burden countries and controlling for the trained-immunity correlate and other potential confounders, would be warranted in order to establish a role for BCG vaccination and early-life immune training (or lack thereof) in childhood LI and help put the current controversy to rest.

THE SPECTRUM OF MACROPHAGE INHIBITORY FACTOR CYTOKINE RESPONSES IN PADIATRIC BCG VACCINEE

At most BCG vaccination in childhood is being finalized with scar formation. Absence of BCG scar formation few days post-vaccination can be a state of anergy. Though, gradual scar fade up may demonstrate a case of waning immunity. The present work was performed onto three groups of healthy children. Scar bearing BCG vaccinee child, non-scar bearing BCG vaccinee child and non-vaccinated child as controls. Age, scar size and macrophage inhibitory factor MIF cytokines were determined. A fraction of scar bearing BCG vaccinee were showing lower MIF concentration than normal controls. A state of waning cytokine responses in spite of the presence of scar. Likewise, a fraction of non-scar bearing BCG vaccinee were showing MIF concentrations lower than that of normal healthy controls ,a state of waning cytokine responses that parallels the waning of gross manifestation of the scar reactions. These findings point out the condition of heterogeneity or divergency of the immune response to BCG vaccines in childhood. MIF cytokine herd response were showing low moderate, and high responders in vaccinated children. The MIF cytokine herd response plots were of Gaussian distribution plots.

The Prevalence of Tuberculosis among BCG Vaccinated Individuals at the North West Region of Cameroon

Aims: This study focuses as it main objective to determine the effectiveness of early BCG vaccination in preventing tuberculosis.&#x0D; Study Design: It was a cross sectional descriptive study. The study population being all early BCG vaccinated individuals.&#x0D; Place and Duration of Study: This study was carried out from March to June 2017 at the Saint Elizabeth General Hospital Shisong, situated in Kumbo Town (Bui Division), North West region of Cameroon.&#x0D; Methodology: It was based on the administration of a structured questionnaire to all early BCG vaccinated individuals. Biological data were obtained from sputum collected from participants. Sputum was analyzed using Xpert MTB/RIF assay which simultaneously detects MTB-complex and rifampin resistance strain by amplifying and identifying a MTB-complex specific sequence of the rpoB gene.&#x0D; Results: This finding shows an overall prevalence of 13.08% on early BCG vaccinated individuals seeking medical care at the Saint Elizabeth General Hospital Shisong. The prevalence of TB in HIV positive subjects was 22.05%. The occurrence was high among HIV subjects not living on ART, 6 (33.33%) against 3 (13%) in HIV subject on ART. This study also showed that male patients 11 (15.94%) developed TB compared to female patients 3 (7.89%). The rate of infection, 9 (28.13%) occurring within the age range of &gt; 28 - 38 associated to the development of TB with no correlation. Drinking habit was found to be associated with the development of TB with weak correlation and the occurrence of TB do not seem to be associated drinking duration.&#x0D; Conclusion: These results show the necessity of the application of a suitable measure to prevent TB in adults, especially those at high risk of developing the disease irrespective of early childhood BCG vaccination status.

Disease Spectrum in COVID-19 Cohort with Travel History from Iran

Background: Coronavirus disease 2019 (Covid-19), declared as a pandemic in March 2020, is an acute respiratory tract illness caused by coronavirus 2 (SARS-CoV2) with clinical manifestations ranging from mild upper respiratory tract symptoms to severe pneumonia. Objectives: To determine the disease spectrum of Covid-19 in a cohort with a travel history from Iran. Materials &amp; Methods: This cross-sectional study with a retrospective collection of data was conducted at Agha Khan University, Karachi from 15th March to 19th April 2020. One hundred and fifty-five laboratory-confirmed cases of Covid-19 were recruited from a government quarantine facility. Data were obtained from the Punjab Emergency Services (Rescue 1122) database where a record of SARS-CoV-2 positive cases and quarantined persons is maintained. Study subjects with a travel history to Iran were contacted by telephone to obtain information about demographics, symptoms, and co-morbid conditions. SPSS version 24 was used to analyze the data. Frequencies and percentages were calculated. Results: Among the returning travelers, 213 had laboratory-confirmed Covid-19, out of which 155 were included in this study. 56.1% were males with a mean age of 40 years. Among the study participants, 91.6% remained asymptomatic throughout the stay, while 8.4 % became symptomatic. 77.5% of the participants had received BCG vaccination in childhood. Among symptomatic cases 15.4% had asthma and 7.7% had hypertension. The most common clinical manifestation was cough which was present in 38.5% of the study participants. None died among the study participants. Conclusion: A mild presentation of COVID-19 was seen in our study participants with 91.6% among them being asymptomatic, while 8.4% were symptomatic. There was a high positivity rate in males as compared to females.

BCG VACCINATION STATUS AND EARLY OUTCOME OF COVID 19 : AN OBSERVATIONAL STUDY

BACKGROUND AND OBJECTIVES: Hypothesis regarding the protective effect of BCG vaccine on Covid 19 has been proposed since the start of the SARS CoV2 pandemic. BCG vaccination seems to have non- specic benecial effects against other viral infections like RSV, HSV2, Yellow fever and Inuenza. The aim was to nd out signicant association between childhood BCG vaccination and the outcome of COVID 19 in a sample of adult patients who were admitted during the peak of the infection in India. METHODS: We enrolled 370 adult patients by complete enumeration method, admitted in our hospital in July 2020. We looked for the presence of BCG scar and studied the clinical prole of every patient. All of them were followed up till discharge or death and their outcomes were categorised as favourable or unfavourable. The clinical data and the signicance of the presence of scar on the outcome was analysed. RESULTS: 87% patients had a favourable outcome.25% patients had comorbidities like Hypertension, Diabetes Mellitus, Chronic lung disease and Chronic kidney disease. BCG scar was present in 73% of all patients. 75.78% of the patients who had favourable outcome had evidence of the vaccination as compared to the 24.22% without the scar (p value=0.001). This result was however not seen in patients with hypertension and diabetes mellitus suggesting that they could be confounding variables in the study and independent risk factors of poorer outcome. CONCLUSIONS: Adults vaccinated with BCG in childhood seem to have better progression and outcome of Covid 19. Prospective clinical trials would help conrm these results.

Low COVID-19 Associated Mortality in Developing Countries, Could it be the High Flavonoid and Antioxidant Diet?

Since the start of Coronavirus disease 2019 (COVID-19) infection, a significant scenario has emerged that is the difference in the severity of morbidity and mortality being much less in the developing countries compared to the European Union (EU), United States of America (USA) and the United Kingdom (UK). Several speculations have been made, childhood BCG vaccination acquired the most popular explanation but data does not confirm its role, very few have paid attention to different dietary habits, vegetarian and Mediterranean diet and high legumes diet in India, Arabia, Africa, while predominant meat, potato, bread and burgers diet in UK, USA and EU

Citizen science initiative points at childhood BCG vaccination as a risk factor for COVID-19.

Current results do not provide conclusive evidence on the effect of BCG vaccination on COVID‐19 alone or in combination with other factors. To address this limitation, in this study we used a citizen science initiative on the COVID‐19 pandemic to collect data worldwide during 2 October 2020–30 October 2020 (1,233 individuals) in a structured way for analysing factors and characteristics of affected individuals in relation to BCG vaccination. For the first time, the results of our study suggested that vaccination with BCG may increase the risk for COVID‐19 at certain age, particularly in individuals vaccinated at childhood. Childhood BCG vaccination increased the likelihood of being diagnosed with COVID‐19 fivefold in COVID‐19 low‐incidence countries and threefold in high‐incidence countries. A reasonable explanation for this effect is the activation of certain innate immunity mechanisms associated with inflammatory reactions. These factors should be considered when analysing the risks associated with this global pandemic.

Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India

Background: Seroprevalence studies for COVID-19 evaluate the extent of undetected transmission in a defined community, with special significance among health care workers (HCW) owing to their greater exposure and potential to transmit.Methods: A total of 1122 HCW (approximately 25% of the employees) of a large tertiary care hospital in India were recruited for this cross-sectional study. COVID PCR-positive HCW were excluded. Based on their risk-assessment, participants were grouped into three categories. A questionnaire was administered and they were tested for SARS-CoV-2-IgG antibodies using the chemiluminescence.Findings: The overall seroprevalence among workers was 11.94%, which included 19.85% in COVID units, 11.09% in non-COVID units, and 8% in administrative workers. Antibody prevalence was highest in the department of gastroenterology (11.94%), followed by oncology (10.53%), pathology (10.26%), emergency medicine (7.84%) and critical care medicine (7%). Housekeeping staff, food and beverage staff, lab assistants and technicians had higher seroprevalence rate than doctors and nurses (p Interpretation: BCG vaccination, HCQ prophylaxis, and the job profile influence the seroprevalence rate in HCW. Seroprevalence rate and follow-up evaluation of its durability may help hospitals to triage their staff at risk, rationalize their placement, prioritize the use of PPE, thereby potentially reducing the risk.Financial Support: No external funding was involved in this study.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study was approved by the internal ethical committee of the institute.

Association of BCG Vaccination in Childhood With Subsequent Cancer Diagnoses

The BCG vaccine is currently the only approved tuberculosis vaccine and is widely administered worldwide, usually during infancy. Previous studies found increased rates of lymphoma and leukemia in BCG-vaccinated populations. To determine whether BCG vaccination was associated with cancer rates in a secondary analysis of a BCG vaccine trial. Retrospective review (60-year follow-up) of a clinical trial in which participants were assigned to the vaccine group by systematic stratification by school district, age, and sex, then randomized by alternation. The original study was conducted at 9 sites in 5 US states between December 1935 and December 1998. Participants were 2963 American Indian and Alaska Native schoolchildren younger than 20 years with no evidence of previous tuberculosis infection. Statistical analysis was conducted between August 2018 and July 2019. Single intradermal injection of either BCG vaccine or saline placebo. The primary outcome was diagnosis of cancer after BCG vaccination. Data on participant interval health and risk factors, including smoking, tuberculosis infection, isoniazid use, and other basic demographic information, were also collected. A total of 2963 participants, including 1540 in the BCG vaccine group and 1423 in the placebo group, remained after exclusions. Vaccination occurred at a median (interquartile range) age of 8 (5-11) years; 805 participants (52%) in the BCG group and 710 (50%) in the placebo group were female. At the time of follow-up, 97 participants (7%) in the placebo group and 106 participants (7%) in the BCG vaccine group could not be located; total mortality was 633 participants (44%) in the placebo group and 632 participants (41%) in the BCG group. The overall rate of cancer diagnosis was not significantly different in BCG vaccine vs placebo recipients (hazard ratio, 0.82; 95% CI, 0.66-1.02), including for lymphoma and leukemia. The rate of lung cancer was significantly lower in BCG vs placebo recipients (18.2 vs 45.4 cases per 100 000 person-years; hazard ratio, 0.38; 95% CI, 0.20-0.74; P = .005), controlling for sex, region, alcohol overuse, smoking, and tuberculosis. Childhood BCG vaccination was associated with a lower risk of lung cancer development in American Indian and Alaska Native populations. This finding has potentially important health implications given the high mortality rate associated with lung cancer and the availability of low-cost BCG vaccines.

A Breath of Fresh Air: BCG Prevents Adult Pulmonary Tuberculosis

ObjectivesThe efficacy of childhood BCG vaccination in the prevention of adult pulmonary tuberculosis is not universally accepted. MethodsWe reviewed the published literature and summarized studies of BCG vaccination reporting long-term protection against pulmonary TB. ResultsWe identified 15 papers reporting prospective studies and their long-term follow up, retrospective studies or systematic reviews. ConclusionsGood quality evidence supports the efficacy of BCG vaccination in the prevention of adult pulmonary tuberculosis.

First assessment of interferon gamma release assay results among healthcare workers at a general hospital in China.

China has a very high tuberculosis (TB) burden. The interferon-gamma release assay (IGRA) is more specific for the diagnosis of latent tuberculosis infection (LTBI) than the tuberculin skin test, especially among populations with a high degree of coverage by the BCG vaccine. To evaluate the first screening of healthcare workers (HCW) for LTBI using the IGRA at a general hospital in Beijing. A pilot screening program for LTBI was triggered by accidental contact between HCW and two patients with active TB in the emergency department (ED). Given the necessity of estimating the overall LTBI prevalence in the institution, a sample of 518 HCW was enrolled in our cross-sectional study. The second IGRA was repeated with 43 of the 121 HCW in the ED after exposure to index TB cases. Data on putative risk factors were collected with a self-administered questionnaire. The prevalence of LTBI in the targeted population was 21.8%. Differences in the prevalence of LTBI were significantly related to age, employment duration, and history of occupational exposure. A lack of childhood BCG vaccination was independently associated with the prevalence of LTBI (adjusted OR: 1.686, 95% CI: 1.045-2.723, P=.0325). No new LTBI was diagnosed 12 weeks postexposure. No HCW adopted the preventive treatment for LTBI. Considering the high morbidity of LTBI among HCW even in general hospitals, it is essential to formulate government policies and institutional operation protocols for the systematic screening, registration, and administration of prophylaxes for the control of LTBI.

The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial

BackgroundNew, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31® adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. MethodsIn this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis-uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150μg H4 formulated in 500nmol IC31®, two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. ResultsThirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ+TNF-α+IL-2+ or TNF-α+IL-2+ cells. These memory responses persisted up to the end of follow up, on study day 182. ConclusionsH4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15μg dose appeared to induce the most optimal immune response.

The present situation of prophylactic vaccination in Japan for travel abroad

The current situation of vaccination in Japan is reviewed from a viewpoint of overseas travelers. Vaccinations before travel to developing countries, where the risk of infection is high, are recommended for two reasons: "individual protection" and "prevention of communicable disease importation". However, there are problems in Japan; some vaccines available commonly in foreign nations are not approved in Japan and the vaccination schedule is not convenient for travelers. Vaccination is sometimes needed also for travel to Europe and North America. This is because certain vaccinations are required for entering school or studying abroad. In Japan, there is no regulation which recommends vaccination as an entrance requirement. Compared with other nations, Japanese children receive fewer vaccines routinely. On the other hand, there are different features from other industrialized nations, such as routine childhood BCG vaccination and immunization against Japanese encephalitis in Japan. Compared with foreign nations, awareness as regards "travel medicine" is lower in Japan. Recognizing this situation will lead to improvement of vaccination of travelers.

The influence of childhood BCG vaccination on tuberculin reactivity in adults with different risk factors

The influence of childhood BCG vaccination on tuberculin reactivity in adults with different risk factors

Leukocyte migration inhibition in bacillus Calmette-Guérin vaccinated healthy adults and in tuberculosis assayed by a rapid photoelectric procedure

A sensitive photoelectric method was used for reading migrations of human peripheral blood leukocytes from agarose microdroplets. Its rapidity enabled the use of a wide range (12 logs) of in vitro concentrations of antigen. Inhibition of migration of leukocytes (LMI) of healthy subjects having had BCG vaccination in childhood was found to occur in two zones of PPD concentrations, one high, from 10 −1 to 1000 μg/ml with a peak at 100 μg/ml, and one low, from 10 −8 to 10 −2 μg/ml. While three-fifths of subjects showed high zone LMI, in one-fifth it was bizonal and in another fifth observed only in the low zone. In patients with active pulmonary tuberculosis LMI, prior to all treatment, was reduced, absent, or replaced by enhanced migration, particularly in the low zone or in both zones. One and a half to four months after treatment LMI was found to be bizonal, enhanced migration having disappeared. These observations suggest the participation of two cell populations with widely different sensitivity to PPD in LMI in tuberculous and BCG vaccinated subjects and the presence of migration stimulatory lymphokine(s) during active tuberculosis.