This is a useful BCG systematic review concerning childhood protection against TB- worth reading in detail.
Longterm BCG protection into adulthood – vaccine efficacy (VE) 10-19 years post BCG was 58% (95% CI 27 to 76) p=0·002 and there was still a non-significant signal occurring in the 30-39 year group (VE 42%) in this large observational study from Norway.
BCG halves neonatal mortality – also read this important commentary from Dr Frank Shann in 2012. There are also heterologous protective effects of measles vaccination in infants.
A team is running a current RCT of neonatal BCG in Melbourne to examine immune correlates and influence on infection and allergy. Existing evidence of BCG influence on childhood allergy was summarised here by Freyne and Curtis – conflicting relatively weak evidence; hence one of the rationales for the trial . Other related papers of interest include:
- Curtis, N et al. Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia. Vaccine. 2016 Jul 29;34(35):4132-9.
- Curtis, N Et al. BCG-associated heterologous immunity, a historical perspective: experimental models and immunological mechanisms. Trans R Soc Trop Med Hyg. 2015 Jan;109(1):46-51.
As part of your systematic review of a micro-organism species or group of species (e.g. Enterobacteriaceae) , knowledge about the ‘epidemiology‘ is essential, the second element in the ORGANISM knowledge proforma.
“Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems.” [ref1]
In your reading or when asked during a viva examination to “describe the epidemiology” of an organism or disease, concern yourself with a few basic questions- always a lot to say about most bugs! :
- What disease(s) does it cause? What are the reservoirs of the organism? – human, animal, environmental etc
- Who (age, sex) gets colonised ? Who gets infected? Natural history of colonisation and disease.
- Where – geographical determinants,
- When – Are there seasonal differences in disease incidence?
- Why/how- how is it transmitted? Is it an obligate pathogen or an opportunist? Risk factors for disease – immune status, healthcare exposure etc
For an excellent online course see the self learning package from CDC (USA). Knowledge of epidemiology is essential for pathologists, physicians and others.
- Last JM, editor. Dictionary of epidemiology. 4th ed. New York: Oxford University Press; 2001. p. 61.
- DNA extraction – essential first step. Quantity of DNA obtained can be assayed spectrophotometrically.
- Reverse transcriptase step – for detection of RNA viruses
- Nucleic acid amplification – know how PCR works! This PCR animation is easy to understand. Many other methods now that are more complex and are isothermal – do not require cyclers to change the temperature of the reaction.
- Detection of product – most assays rely on closed tube ‘real-time’ detection of product. There are a variety of nucleic acid probe methods described. Have a look here for a short video instruction. Quantification becomes possible and is used widely.
- DNA sequencing – this is a basic technique these days (see below)
Excellent background materials from ICPMR, NSW ( circa 2009):
Molecular-diagnosis-in-microbiology-ferguson-2016: overview presentation.
- pre-analytical and assay factors that affect sensitivity and specificity
- quality control (see above presentation)
- amplification product quantification and its usefulness
N.B. visit your local molecular lab if there is one and examine and understand all of the assays in use – for commercial assays, obtain the product inserts to read.
- Next generation sequencing methods: basically a way of doing massive parallel sequencing of short multiple sequences in the same sample
- GenXpert and similar methods : of great relevance for Nepal, PNG and elsewhere
- Multiplex commercial molecular platforms – e.g. Biofire filmarray
- Whole genome analyses
The online Field Epidemiological Manual is an essential resource. Here are the 10 steps, and 10 pitfalls list we went through.
Suggested format for documenting significant BSI for later analyses. Sub documents with key definitions will be provided soon. Print this sheet onto a single A4 page and maintain a records folder. Include documentation of the clinical liaison process as below. Definitions for significance will be discussed in a future posting. Continue reading
Adenovirus overview -2016-path-north; Prepared for our weekly pathology teaching round by one of our registrars.
Image credit: http://www.daviddarling.info/encyclopedia/A/adenovirus_infection.html