Goldblatt, D

Madhi, SA

UCL Discovery

Commentwww.thelancet.com/infection   Vol 19   May 2019 453In The Lancet Infectious Diseases, Beth Temple and colleagues1 report on a head-to-head comparison of the immunogenicity, in a low-income to middle-income setting (Vietnam), of the currently licenced ten-valent (PCV10) and 13-valent (PCV13) pneumococcal conjugate vaccines. The two vaccines were administered in a two-dose primary series (2 months and 4 months of age), with a booster dose at 9 months of age (a 2 + 1 schedule), with the primary comparison of immunogenicity between the vaccines being the proportion of recipients with serotype-specific antibody concentrations above the recommended composite putative threshold of protection developed for invasive pneumococcal disease (serotype-specific IgG concentration ≥0·35 µg/mL).2 By this measure, PCV10 and PCV13 did not differ in immunogenicity. This finding was supplemented by assessment of the prevalence of functional antibody (opsonophagocytic index ≥8) post-vaccination, which was also similar between groups. The similarity of PCV10 compared with PCV13 in the 2 + 1 dosing schedule was evident after both the primary series and the booster dose.The perceived benefit of PCV13 over that of PCV10 has been the superior coverage of PCV13 for three additional disease-causing serotypes (serotypes 3, 6A, and 19A). Evidence suggests that PCV13 has no effect on serotype 3 invasive pneumococcal disease,3 whereas evidence of a direct effect on serotypes 6A and 19A invasive pneumococcal disease in countries using PCV10 suggests some cross-protection.4 Similarly to past studies, the data in this paper show cross-reactive IgG and functional antibodies to serotype 6A and 19A in 61–67% of PCV10 recipients after a booster dose; however, these percentages were lower than the percentage (>99%) of PCV13 recipients in whom functional antibodies to these serotypes were induced. Furthermore, the geometric mean opsonophagocytic indices were 15–77 times higher for serotypes 6A and 19A after the primary series, and 23–32 times higher after the booster dose in PCV13 recipients versus PCV10 recipients. The effect of these higher titres on direct protection is unclear. The lower cross-reactive responses to 19A might explain the reported failure of PCV10 to reduce 19A colonisation in children and provide indirect protection against 19A in unvaccinated individuals.5Another important observation by Temple and colleagues1 was that the immunogenicity of a two-dose primary series of PCV13 was similar to a three-dose primary series of PCV10 (3 + 0). These data indicate the potential for using three doses of PCV13 in a 2 + 1 schedule rather than a 3 + 0 schedule. This schedule could potentially address the waning of protection against serotype 1, as reported in African efficacy trials of a nine-valent PCV (including serotype 1), which only immunised with a three-dose primary series.6The interpretation of results from this and other similar immunogenicity studies, however, have limitations in extrapolating to overall direct vaccine effectiveness. These limitations include the likelihood of serotype-specific differences in thresholds of antibody associated with protection against invasive pneumococcal disease;7 the possibility that concentrations required for protection against invasive pneumococcal dis-ease are not the same as those required for non-invasive pneumococcal disease syndromes, such as non-bacteraemic pneumococcal pneumonia, which constitutes the largest burden of severe pneumococcal disease;8 and that concentrations of IgG required to protect against colonisation might be significantly higher than those required to protect against invasive pneumococcal disease.9 PCVs protect against the acquisition of nasopharyngeal colonisation,10 and this protection is key to reducing the transmission of pneumococci and, thus, to the indirect protection from pneumococcal disease in unvaccinated individuals. A pooled analysis, which used seroincidence as a proxy of serotype-specific colonisation, suggested that sero-type-specific antibody concentrations associated with reduced odds of nasopharyngeal colonisation range from 0·50 μg/mL (62% lower odds of imputed serotype 6B colonisation) to 2·54 μg/mL (87% reduced odds of imputed serotype 19F colonization).11 These estimates are approximately 3·1 times higher than the respective serotype-specific threshold estimated to confer 90% reduced risk of invasive pneumococcal disease for The duopoly of ten-valent and 13-valent pneumococcal conjugate vaccines: do they differ?Published Online April 3, 2019 http://dx.doi.org/10.1016/S1473-3099(18)30785-0See Articles page 497Flickr/Electric ShutterComment454 www.thelancet.com/infection   Vol 19   May 2019sero types 6B (0·16 µg/mL), and 2·2 times higher than that for serotype 19F (1·17 µg/mL).7,11In summary, Temple and colleagues’ study showing non-inferiority of PCV10 versus PCV13 in terms of immunogenicity against invasive pneumococcal disease provides important endorsement of existing WHO advice on the use of PCVs for infant immunisation.12 Furthermore, these data indicate that an individual country’s decision on which vaccine to use in a 2 + 1 schedule to directly protect against vaccine-serotype invasive pneumococcal disease might well be influenced primarily by the cost of vaccine procurement. The effects of the differences between the vaccines in terms of absolute antibody concentrations are unclear, but might have implications for the effect of vaccines on non-invasive disease, carriage, and indirect protection for at least some serotypes. However, these questions require further study.*Shabir A Madhi, David GoldblattMedical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Faculty of Health Science, Johannesburg, 2013, South Africa (SAM); Department of Science/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa (SAM); and Immunobiology Unit, UCL Great Ormond Street Institute of Child Health, London, UK (DG) madhis@rmpru.co.zaSAM reports grants and personal fees from the Bill & Melinda Gates Foundation, and grants from GlaxoSmithKline, Pfizer, and Sanofi Pasteur outside of the submitted work. DG reports grants from GlaxoSmithKline outside of the submitted work.Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.1 Temple B, Toan NT, Dai VTT, et al. Immunogenicity and reactogenicity of PCV10 versus PCV13 among infants in Ho Chi Minh City, Vietnam: a randomised controlled trial. Lancet Infect Dis 2019; published online April 8. http://dx.doi.org/10.1016/S1473-3099(18)30734-5.2 Jodar L, Butler J, Carlone G, et al. Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants. Vaccine 2003; 21: 3265–72.3 Ladhani SN, Collins S, Djennad A, et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study. Lancet Infect Dis 2018; 18: 441–51.4 Mrkvan T, Pelton SI, Ruiz-Guinazu J, Palmu AA, Borys D. Effectiveness and impact of the 10-valent pneumococcal conjugate vaccine, PHiD-CV: review of clinical trials and post-marketing experience. Expert Rev Vaccines 2018; 17: 797–818.5 Isturiz R, Sings HL, Hilton B, Arguedas A, Reinert RR, Jodar L. Streptococcus pneumoniae serotype 19A: worldwide epidemiology. Expert Rev Vaccines 2017; 16: 1007–27.6 Klugman KP, Madhi SA, Adegbola RA, Cutts F, Greenwood B, Hausdorff WP. Timing of serotype 1 pneumococcal disease suggests the need for evaluation of a booster dose. Vaccine 2011; 29: 3372–73.7 Andrews NJ, Waight PA, Burbidge P, et al. Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study. Lancet Infect Dis 2014; 14: 839–46.8 Wahl B, O’Brien KL, Greenbaum A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15. Lancet Glob Health 2018; 6: e744–57.9 Shiri T, Datta S, Madan J, et al. Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis. Lancet Glob Health 2017; 5: e51–59.10 Klugman KP. Efficacy of pneumococcal conjugate vaccines and their effect on carriage and antimicrobial resistance. Lancet Infect Dis 2001; 1: 85–91.11 Voysey M, Fanshawe TR, Kelly DF, et al. Serotype-specific correlates of protection for pneumococcal carriage: an analysis of immunity in 19 countries. Clin Infect Dis 2018; 66: 913–20.12 WHO. Pneumococcal vaccines WHO position paper—2012. Wkly Epidemiol Rec 2012; 87: 129–44.Control of scabies and secondary impetigo: optimising treatment effectiveness in endemic settingsScabies is more than a common parasitic skin disease1 and health authorities in low-income and middle-income countries now recognise it as a public health issue. In 2017, WHO added scabies to the list of neglected tropical diseases for the following reasons: it is very common (point prevalence of up to 200 million),2 has a substantial global burden in disability-adjusted life-years,3,4 has notable psychosocial and economic effects caused by stigma and work disruption, and the major sleep disturbances and damage to the skin barrier caused by scratching. Sarcoptes scabiei also inhibits complement pathways, leading to streptococcal and staphyloccocal super-infection of the skin.5Controlling secondary bacterial pyodermas caused by scabies is crucial. Patients in tropical areas with Staphylococcus aureus bacteraemia and scabies have a higher mortality than those without scabies;6 but other life threatening infections such as cellulitis or necrotising soft tissue infection might occur, and impetigo might lead to haematuria or post-streptococcal glomerulonephritis and acute rheumatic fever or rheumatic heart disease.7,8In The Lancet Infectious Diseases, Lucia Romani and colleagues9 report on the efficacy of the Flickr/UN Women/Marni GilbertPublished Online April 4, 2019 http://dx.doi.org/10.1016/S1473-3099(19)30068-4See Articles page 510For WHO list of neglected tropical diseases see http://www.who.int/neglected_diseases/diseases/en/

The duopoly of ten-valent and 13-valent pneumococcal conjugate vaccines: do they differ?

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The duopoly of ten-valent and 13-valent pneumococcal conjugate vaccines: do they differ?

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