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  • Two fundamental objections to the conclusion that

    2019-05-15

    Two fundamental objections to the conclusion that mass deworming for helminths has no benefits and could therefore be abandoned have been repeatedly raised. First, the underlying studies might have been insufficient to detect benefits, because the follow-up for most studies was too short to detect helminthiasis-associated morbidity (eg, cancer, portal hypertension, and infertility) that takes a long time to accrue. Simultaneously, many short-term symptoms, including diarrhoea and abdominal pain, contribute to global disability burden estimates but are not measured. Second, the conclusion that mass deworming is not beneficial at the population level is logically inconsistent with findings of individual-level benefits for infected individuals. Effects, if present for infected individuals, are diluted when measured across a population that receives little (lightly infected individuals) or no (uninfected) direct benefits from deworming; however, a diluted effect is still a positive effect, and failure to detect this is a problem of measurement or statistical power. The debate is not new, having repeated itself with little variation for almost two decades, and further meta-analyses are unlikely to resolve these fundamental concerns about what is being measured. However, decisions must be made, often amid conflicting evidence or opinions. Low-income and middle-income countries, where helminthiases are rife, need to determine whether mass deworming should be prioritised over other interventions when allocating scarce health resources. Disease control experts will note that both meta-analyses found benefits of screening and targeted treatment for helminthiases, but mass deworming remains a more logistically feasible and inexpensive approach to reach those who would benefit. As Duflo and colleagues noted, “the only reasons to prefer a screening approach is if deworming drugs had negative effects on uninfected children (they do not), or if the costs of treating uninfected children in a mass campaign were greater than the costs of individually testing children to determine whether they required treatment (in fact it is much cheaper to mass treat than to diagnose and treat).”
    Bacterial glycoconjugate vaccines contain capsule-derived bacterial tropisetron chemically conjugated to carrier proteins and are highly immunogenic in the infant population for whom they were originally designed. This class of vaccine has shown a profound impact on the incidence of both invasive disease, such as septicaemia and meningitis, as well as mucosal infections including pneumonia and otitis media, in individuals who receive the vaccine. Unlike purified polysaccharide vaccines, glycoconjugates have also shown a profound indirect impact, reducing the incidence of disease in the unvaccinated population of all ages. This indirect or herd effect is the result of the reduced spread of bacteria from those vaccinated, a consequence of vaccine-induced prevention of bacterial colonisation of the upper respiratory tract. The glycoconjugate vaccines that have shown the most profound indirect effect and which have been best studied are the pneumococcal conjugate vaccines (PCV) first licensed in 2000. The indirect effect of PCV is particularly relevant because the pneumococcus is an important cause of disease in older people and in adults with comorbidities. Most data for the indirect effect of PCV are from developed countries with mature surveillance systems where PCV was introduced into the infant immunisation programme relatively soon after licensure. Surveillance in these countries has revealed not only the reduction of invasive pneumococcal disease in older people but also a reduction in disease rates in adults with underlying comorbidities in whom direct protection might be suboptimal. In , Tinevimbo Shiri and colleagues present a meta-analysis of the indirect effect of PCV, using data from 34 different countries and assessing the reduction in invasive pneumococcal disease and the mean time to maximal impact. Analysis of the impact of the first licensed PCV, which was seven-valent (PCV7), confirmed the near-elimination of invasive pneumococcal disease due to serotypes in the vaccine in the unvaccinated in settings with a mature childhood PCV7 programme. A second-generation vaccine containing 13 serotypes (PCV13) was licensed and introduced in 2010. Shiri and colleagues\' meta-analysis predicts that the residual invasive pneumococcal disease due to the additional six serotypes contained in PCV13 will be halved after an average period of 3·3 years (95% credible interval [CrI] 2·1–6·8) and nearly eradicated after about 9 years following the introduction of PCV13 (5·7–19·7).