The Lancet Infectious Diseases
Nov 2015 Volume 15 Number 11 p1243-1360
http://www.thelancet.com/journals/laninf/issue/current

.
Comment
Polio eradication: inching forward, with safety nets
Beth D Kirkpatrick, Josyf C Mychaleckyj
Summary
By mid-2015, WHO-reported cases of paralytic disease caused by polioviruses had reached a new low: only 34 cases were caused by wild polioviruses and nine cases were due to circulating vaccine-derived poliovirus (cVDPV).1 In light of this progress, WHO’s Polio Endgame Strategy is moving into a pivotal new stage, focusing on global withdrawal of a vaccine component from primary immunisation schedules. This plan will minimise the time to reach eradication, while maintaining the protection of children in case of disease re-emergence.

Comment
Near full control of human papillomavirus vaccine types
Joakim Dillner
Published Online: 19 July 2015
The Lancet Infectious Diseases, Eric Chow and colleagues1 report on the near elimination of the major human papillomavirus (HPV) types 6, 11, 16, and 18 after introduction of vaccination against these types in Australia when analysed in high-risk women. The authors use the innovative strategy of establishing HPV prevalence in women who are chlamydia positive. Traditional monitoring strategies would typically enrol from the general population, which is both cumbersome and expensive, and potentially biased because volunteering women would tend to be low risk, therefore possibly missing HPV circulation in high-risk core groups.

.

Ebola: missed opportunities for Europe–Africa research
Giuseppe Ippolito, Simone Lanini, Philippe Brouqui, Antonino Di Caro, Francesco Vairo, Salim Abdulla, Francesco Maria Fusco, Sanjeev Krishna, Maria Rosaria Capobianchi, Henry Kyobe-Bosa, David J M Lewis, Vincenzo Puro, Roman Wolfel, Tatjana Avsic-Zupanc, Osman Dar, Peter Mwaba, Matthew Bates, David Heymann, Alimuddin Zumla
Summary
The current unprecedented Ebola virus disease outbreak in parts of west Africa, which has caused more than 11 200 deaths, has emphasised how the medical and scientific communities lack specific pathways for tackling relevant logistical, design, and ethical issues for assessment of novel diagnostics, treatments, and vaccines through implementation of appropriate clinical trials.1,2 The phenomenal outbreak arose because of several weaknesses in local, regional, and international public health responses, which delayed provision and implementation of effective intervention.

.

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study
Miguel O’Ryan, Ananda S Bandyopadhyay, Rodolfo Villena, Mónica Espinoza, José Novoa, William C Weldon, M Steven Oberste, Steve Self, Bhavesh R Borate, Edwin J Asturias, Ralf Clemens, Walter Orenstein, José Jimeno, Ricardo Rüttimann, Sue Ann Costa Clemens, Chilean IPV/bOPV study group
Summary
Background
Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV–bOPV schedules, we assessed the immunogenicity of two different IPV–bOPV schedules compared with an all-IPV schedule in infants.
Methods
We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV–bOPV–bOPV, IPV–IPV–bOPV, or IPV–IPV–IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants.
Findings
Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV–bOPV–bOPV, 192 to IPV–IPV–bOPV, and 188 to IPV–IPV–IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV–bOPV–bOPV, IPV–IPV–bOPV, and IPV–IPV–IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8–99·7; 178 (100%), 97·9–100·0; and 175 (100%), 97·9–100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8–99·4; 177 (100%), 97·9–100·0, and 172 (98·9%) of 174, 95·9–99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV–bOPV–bOPV, IPV–IPV–bOPV, and IPV–IPV–IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8–99·7; 181 (100%), 97·9–100·0; and 177 (100%), 97·9–100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9–99·4; 180 (100%), 97·9–100·0; and 174 (98·9%) of 176, 96·0–99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay’s upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV–bOPV–bOPV, IPV–IPV–bOPV, and IPV–IPV–IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5–83·0; 169 (96·0%) of 176, 92·0–98·0; and 175 (100%), 97·8–100. IPV–bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception).
Interpretation
Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis.
Funding
Bill & Melinda Gates Foundation.

.

Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial
David Rey, Lionel Piroth, Marie-Josée Wendling, Patrick Miailhes, Marie-Louise Michel, Cécilie Dufour, Georges Haour, Philippe Sogni, Alexandra Rohel, Faiza Ajana, Eric Billaud, Jean-Michel Molina, Odile Launay, Fabrice Carrat, ANRS HB04 B-BOOST study group

.

Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers
Michael Jacobs, Emma Aarons, Sanjay Bhagani, Ruaridh Buchanan, Ian Cropley, Susan Hopkins, Rebecca Lester, Daniel Martin, Neal Marshall, Stephen Mepham, Simon Warren, Alison Rodger
Summary
Background
Although a few international health-care workers who have assisted in the current Ebola outbreak in west Africa have been medically evacuated for treatment of Ebola virus disease, more commonly they were evacuated after potential accidental exposure to Ebola virus. An urgent need exists for a consensus about the risk assessment of Ebola virus transmission after accidental exposure, and to investigate the use of post-exposure prophylaxis (PEP). Experimental vaccines have occasionally been used for Ebola PEP, but newly developed experimental antiviral agents have potential advantages. Here, we describe a new method for risk assessment and management of health-care workers potentially exposed to Ebola virus and report the use of experimental antiviral therapies for Ebola PEP in people.
Methods
We devised a risk assessment and management algorithm for health-care workers potentially exposed to Ebola virus and applied this to eight consecutive individuals who were medically evacuated to the UK from west Africa between January, and March, 2015. PEP with antiviral agents was given to health-care workers assessed to have had substantial risk exposures to Ebola virus. Participants were followed up for 42 days after potential exposure.
Findings
Four of eight health-care workers were classified as having had low risk exposures and managed by watchful waiting in the community. None of these health-care workers developed Ebola virus disease. The other four health-care workers had intermediate or maximum risk exposures and were given PEP with antiviral agents. PEP was well tolerated with no serious adverse effects. None of these four health-care workers, including two with maximum risk exposures from penetrating injuries with freshly used hollow-bore needles, developed Ebola virus disease.
Interpretation
Standardised risk assessment should be adopted and consensus guidelines developed to systematically study the efficacy and safety of PEP with experimental agents. New experimental antiviral treatments are a viable option for PEP against Ebola.
Funding
Royal Free London NHS Foundation Trust.

.

Human papillomavirus in young women with Chlamydia trachomatis infection 7 years after the Australian human papillomavirus vaccination programme: a cross-sectional study
Eric P F Chow, Jennifer A Danielewski, Glenda Fehler, Sepehr N Tabrizi, Matthew G Law, Catriona S Bradshaw, Suzanne M Garland