Tag Archives: Vaccinations

Infection Sensitisation

A previous News Blog [1] discussed the finding that a previous infection with one strain of Dengue fever can sensitise a person so that infection with a second strain will be more severe than would otherwise have been the case. There is new evidence that such Antibody Dependent Enhancement (ADE) may cross species barriers, such that a person sensitised with one type of flavivirus, say Dengue, is more likely to have a severe illness if inflected with another flavivirus, such as the Zika virus.[2] Such cross species ADE has obvious implications for vaccination programmes. In previous News Blogs [3] we have drawn attention to cross-resistance such that vaccines protect against non-target organisms (e.g. small pox vaccines provide protection against HIV). The above paper shows that the reverse can also occur. This is not the first time that vaccination has been shown to have adverse consequences.[4]

— Richard Lilford, CLAHRC WM Director

References:

  1. Lilford RJ. Three hits hypothesis. NIHR CLAHRC West Midlands News Blog. 7 April 2017.
  2. Cohen J. Dengue may bring out the worst in Zika. Science. 2017; 355(6332): 1362.
  3. Lilford RJ. Two papers try to answer the question – do vaccinations for one communicable disease offer protection against others? NIHR CLAHRC West Midlands News Blog. 27 January 2017.
  4. Guzman MG, Alvarez M, Halstead SB. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol. 2013; 158(7): 1445-59.

Two Papers Try to Answer the Question – Do Vaccinations for One Communicable Disease Offer Protection Against Others?

News Blog readers will have read of the hypothesis that withdrawal of vaccination against small-pox exacerbated the HIV epidemic since the antibodies elicited by the small-pox vaccine cross-react with HIV.[1] Other readers know that BCG vaccine (anti-TB) can prove effective against malignant melanoma and other cancers. Kandsomy and colleagues systematically reviewed 77 papers dealing with unintended (non-specific) beneficial effects of common childhood vaccines.[2] Many examples were found where vaccinations against one disease created a biochemical response that should be effective against another. However, clinical effects were not reported, and even the laboratory based results reported were short-term so we do not know how persistent they were. The very next paper in the BMJ tries to answer the clinical question by examining all-cause mortality in clinical trials, cohort studies and case-control studies of vaccines.[3] They found reductions in all-cause mortality greater than could be plausibly attributed to reductions in the targeted disease for BCG and measles vaccines, but the risk appears increased for the ‘triple’ (diphtheria, pertussis and tetanus) vaccine. The reductions in all-cause mortality following measles and BCG vaccination were confirmed when the analysis was restricted to RCTs, so it seems to be real. The issue of the effect of different sequencing regimes are unknown because few high-quality studies have examined this issue.

— Richard Lilford, CLAHRC WM Director

References:

  1. Weinstein RS, Weinstein MM, Alibek K, Bukrinsky MI, Brichacek B. Significantly reduced CCR5-tropic HIV-1 replication in vitro in cells from subjects previously immunized with Vaccinia Virus. BMC Immunol. 2010; 11: 23.
  2. Kandasamy R, Voysey M, McQuid F, et al. Non-specific immunological effects of selected routine childhood immunisations: systematic review. 20116; 355: i5225.
  3. Higgins JPT, Soares-Weiser K, López-López JA, et al. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016; 355: i5170.

Return on Investment from Vaccines

CLAHRC Africa has previously carried out health economic assessments in Low- and Middle-Income Countries (LMICs) concerned with devices,[1] [2] and is now doing so with respect to milk banking and breastfeeding in collaboration with the African Population and Health Research Centre (APHRC). We were therefore interested to read a Return on Investment analysis on vaccines in LMICs.[3] Ten vaccines were considered, singly and in combination. The costs of the programmes were obtained largely from Gavi, the Vaccine Alliance. The costs saved were calculated on the basis of costs of treating cases at home (including days off work for carers), costs of admission by hospital day, transport costs to care facilities, costs of care for disabilities, and lost production costs based on discounted per capita GDP for people who died or could not work. Herd immunity was not taken into account, neither were effects on demographic structures of countries, thereby under-estimating return. The return on investment ([monetised benefit – programme cost] / programme cost) was a whopping $16 per dollar expended. There are few other such studies in LMICs, but the return was even higher than deployment of Community Health Workers at $9 per dollar expended, but lower than improving road safety at $19 per dollar expended. The ratios were positive for all the ten vaccine studied, but the most favourable ratio was for measles, followed by yellow fever (a surprise to the CLAHRC WM Director) and Meningococcal meningitis.

— Richard Lilford, CLAHRC WM Director

References:

  1. Burn SL, Chilton PJ, Gawande AA, Lilford RJ. Peri-operative pulse oximetry in low-income countries: a cost-effectiveness analysis. Bull World Health Organ. 2014; 92(12): 858-67.
  2. Lilford RJ, Burn SL, Diaconu KD, et al. An approach to prioritization of medical devices in low-income countries: an example based on the Republic of South Sudan. Cost Eff Resour Alloc. 2015; 13(1): 2.
  3. Ozawa S, Clark S, Portnoy A, et al. Return on Investment from Childhood Immunization in Low- and Middle-Income Countries, 2011-20. Health Aff. 2016; 35(2): 199-207.

Vaccinations and Anti-retroviral Therapy

When I was at medical school, we were told that BCG vaccination reduced the risk of serious tuberculosis (TB) by a greater proportion than the reduction in infection of a milder or innocuous nature. However, until recently, it has been difficult to distinguish between infection and the effects of an earlier infection, previous BCG vaccination, or non-TB mycobacterial infection. A recent paper, using newer tests that can distinguish between these events, has confirmed what my teachers said at medical school – BCG protects against infection and protects even more against active disease.[1]

Meanwhile, a cluster RCT from CLAHRC Africa collaborators shows that initiating anti-retroviral therapy at home, rather than in hospital, increases uptake of therapy nearly three-fold. This practice was ‘dominant’, promising greater effectiveness at lower upfront and net costs.[2] A lot of research may be a waste of money, but not this study.

–Richard Lilford, CLAHRC WM Director

References:

  1. Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, Snell L, Mangtani P, Adetifa I, Lalvani A, Abubakar I. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ. 2014; 349: g4643.
  2. MacPherson P, Lalloo DG, Webb EL, Maheswaran H, Choko AT, Makombe SD, Butterworth AE, van Oosterhout JJ, Desmond N, Thindwa D, Squire SB, Hayes RJ, Corbett EL. Effect of Optional Home Initiation of HIV Care Following HIV Self-testing on Antiretroviral Therapy Initiation Among Adults in Malawi. A Randomized Clinical Trial. JAMA. 2014; 312(4): 372-9.