Failure of scabies treatment: a systematic review and meta-analysis.

BACKGROUND: Treatment failure is considered to be an important factor in relation to the increase in scabies incidence over the last decade. However, the regional and temporal differences, in addition to the predictors of therapy failure, are unclear. OBJECTIVES: We aimed to conduct a systematic review of the prevalence of treatment failure in patients with scabies and investigation of associated factors. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Global Health and the Cochrane Central Register of Controlled Trials from inception to August 2021 for randomized and quasi-randomized trials, in addition to observational studies that enrolled children or adults diagnosed with confirmed or clinical scabies treated with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur or lindane, and measured treatment failure or factors associated with treatment failure. We performed a random effects meta-analysis for all outcomes reported by at least two studies. RESULTS: A total of 147 studies were eligible for inclusion in the systematic review. The overall prevalence of treatment failure was 15.2% [95% confidence interval (CI) 12.9-17.6; I2 = 95.3%, moderate-certainty evidence] with regional differences between World Health Organization regions (P = 0.003) being highest in the Western Pacific region (26.9%, 95% CI 14.5-41.2). Oral ivermectin (11.8%, 95% CI 8.4-15.4), topical ivermectin (9.3%, 95% CI 5.1-14.3) and permethrin (10.8%, 95% CI 7.5-14.5) had relatively lower failure prevalence compared with the overall prevalence. Failure prevalence was lower in patients treated with two doses of oral ivermectin (7.1%, 95% CI 3.1-12.3) compared with those treated with one dose (15.2%, 95% CI 10.8-20.2; P = 0.021). Overall and permethrin treatment failure prevalence in the included studies (1983-2021) increased by 0.27% and 0.58% per year, respectively. Only three studies conducted a multivariable risk factor analysis; no studies assessed resistance. CONCLUSIONS: A second dose of ivermectin showed lower failure prevalence than single-dose ivermectin, which should be considered in all guidelines. The increase in treatment failure over time hints at decreasing mite susceptibility for several drugs, but reasons for failure are rarely assessed. Ideally, scabicide susceptibility testing should be implemented in future studies.

Prevalence of vaccine-derived hepatitis B surface antibodies in children and adolescents in Germany: results from a population-based survey, 2014-2017.

INTRODUCTION: Childhood vaccination against hepatitis B has been recommended in Germany since 1995. WHO defines a primary vaccination series as successful if the initial hepatitis B surface antibody (anti-HBs) level is ≥ 10 IU/L directly after vaccination. Anti-HBs levels vary depending on the number of doses, type of vaccine, and time interval between the last two doses. In 2021, Germany began to recommend three instead of four doses of polyvalent hepatitis-B-containing vaccines. Our aim was to estimate the proportion of vaccinated children in Germany with anti-HBs levels < 10 IU/L, 10-99 IU/L, and ≥ 100 IU/L by number and type of vaccine, and assess if number of doses and compliance with recommended time interval between the last two doses are associated with an anti-HBs level ≥ 10 IU/L when considering type of vaccine and time since last dose. METHODS: We used data from a national cross-sectional study (2014-2017) of children (3-17 years). We excluded participants with unknown vaccination dates, unreadable or incomplete vaccination cards, and hepatitis B virus (HBV)-positive participants. We defined a recommended schedule as a vaccination series with at least six months between the two last doses and having three doses or more. We calculated weighted anti-HBs sero-prevalence for three anti-HBs levels: < 10 IU/L, 10-99 IU/L and ≥ 100 IU/L. We fitted two logistic regression models to examine the relationship between number of doses and recommended schedule on anti-HBs levels (≥ 10 IU/L and ≥ 100 IU/L) considering time since last dose and type of vaccine (Infanrix, Hexavac, Monovalent). RESULTS: We included 2,489 participants. The weighted proportion of vaccinated children per anti-HBs level was < 10 IU/L: 36.3% [95%CI 34.0-38.7%], 10-99 IU/L: 35.7% [33.2-38.2%] and ≥ 100 IU/L: 28.0% [25.9-30.2%]. We did not find an association between a recommended schedule of three versus four doses and anti-HBs ≥ 10 IU/L or ≥ 100 IU/L. CONCLUSIONS: Anti-HBs levels in later childhood were about equal, whether children received three or four doses. This implies that the change in the recommendations does not affect the anti-HBs level among children in Germany. Future studies are needed on the association of anti-HBs levels and adequate sustained protection against HBV.

High speed, high power 2D beam steering for mitigation of optomechanical parametric instability in gravitational wave detectors.

In this paper, we propose what we believe to be a novel strategy to control optomechanical parametric instability (PI) in gravitational wave (GW) detectors based on radiation pressure. The fast deflection of a high-power beam is the key element of our approach. We built a 2D deflection system based on a pair of acousto-optic modulators (AOMs) that combines high rapidity and a large scan range. As a fast frequency switching configurable AOM driver, we used a Universal Software Radio Peripheral (USRP) combined with a high-performance personal computer (PC). In this way, we demonstrate a 2D beam steering system with flat efficiency over the whole scan range and with a transition time of 50 ns between two arbitrary consecutive deflection positions for a beam power of 3.6 W.

Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: results from the COViK study.

PURPOSE: COViK, a prospective hospital-based multicenter case-control study in Germany, aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. METHODS: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. RESULTS: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95%CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. CONCLUSION: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.

Duration of Protection After Vaccination Against Yellow Fever: A Systematic Review and Meta-Analysis.

The duration of protection after a single dose of yellow fever vaccine is a matter of debate. To summarize the current knowledge, we performed a systematic literature review and meta-analysis. Studies on the duration of protection after 1 and ≥2 vaccine doses were reviewed. Data were stratified by time since vaccination. In our meta-analysis, we used random-effects models. We identified 36 studies from 20 countries, comprising more than 17 000 participants aged 6 months to 85 years. Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years. In children vaccinated before age 2 years, the seroprotection rate was 52% within 5 years after primary vaccination. For immunodeficient persons, data indicate relevant waning. The extent of waning of seroprotection after yellow fever vaccination depends on age and immune status at primary vaccination.

Seroprevalence of mucosal and cutaneous human papillomavirus (HPV) types among children and adolescents in the general population in Germany.

BACKGROUND: In Germany, HPV vaccination of adolescent girls was introduced in 2007. Nationally representative data on the distribution of vaccine-relevant HPV types in the pre-vaccination era are, however, only available for the adult population. To obtain data in children and adolescents, we assessed the prevalence and determinants of serological response to 16 different HPV types in a representative sample of 12,257 boys and girls aged 1-17 years living in Germany in 2003-2005. METHODS: Serum samples were tested for antibodies to nine mucosal and seven cutaneous HPV types. The samples had been collected during the nationally representative German Health Interview and Examination Survey for Children and Adolescents in 2003-2006. We calculated age- and gender-specific HPV seroprevalence. We used multivariable regression models to identify associations between demographic and behavioral characteristics and HPV seropositivity. RESULTS: We found low but non-zero seroprevalence for the majority of tested HPV types among children and adolescents in Germany. The overall seroprevalence of HPV-16 was 2.6%, with slightly higher values in adolescents. Seroprevalence of all mucosal types but HPV-6 ranged from 0.6% for HPV-33, to 6.4% for HPV-31 and did not differ by gender. We found high overall seroprevalence for HPV-6 with 24.8%. Cutaneous HPV type seroprevalence ranged from 4.0% for HPV-38 to 31.7% for HPV-1. In the majority of cutaneous types, seroprevalence did not differ between boys and girls, but increased sharply with age, (e.g., HPV-1 from 1.5% in 1-3-years-old to 45.1% in 10-11-years-old). Associations between behavioral factors and type-specific HPV prevalence were determined to be heterogeneous. CONCLUSIONS: We report the first nationally representative data of naturally acquired HPV antibody reactivity in the pre-HPV-vaccination era among children and adolescents living in Germany. These data can be used as baseline estimates for evaluating the impact of the current HPV vaccination strategy targeting 9-14-years-old boys and girls.

Risk of Guillain-Barré syndrome after vaccination against human papillomavirus: a systematic review and meta-analysis, 1 January 2000 to 4 April 2020.

BackgroundGuillain-Barré syndrome (GBS) is a rare autoimmune disease that can follow viral infections and has in a few cases been linked to vaccinations. Pre-licensure clinical trials did not observe an association between human papillomavirus (HPV) vaccination and GBS, a post-marketing study from 2017 reported an increased relative risk.AimWe assessed the risk of GBS after HPV vaccination through a systematic literature review and meta-analysis.MethodsWe searched Embase, MEDLINE and Cochrane for studies reporting on the risk of GBS after HPV vaccination in individuals aged ≥ 9 years, published between 1 January 2000 and 4 April 2020, excluding studies without a comparator group. Seven studies reporting relative effect sizes were pooled using random-effects meta-analysis. We assessed quality of evidence using the GRADE approach. Study protocol was registered (PROSPERO No. #CRD42019123533).ResultsOf 602 identified records, we included 25 studies. Based on over 10 million reports, cases of GBS were rare. In 22 studies no increased risk was observed, while in three studies a signal of increased risk of GBS after HPV vaccination was identified. Meta-analysis yielded a pooled random-effects ratio of 1.21 (95% CI: 0.60-2.43); I2 = 72% (95% CI: 36-88). This translates to a number needed to harm of one million to be vaccinated to generate one GBS case. Quality of evidence was very low.ConclusionsThe absolute and relative risk of GBS after HPV vaccination is very low and lacks statistical significance. This is reassuring for the already implemented vaccination programmes and should be used in respective communication activities.

[Evaluation of the COVID-19 vaccination after broad implementation-an interim conclusion for Germany in July 2022]. / Evaluation der COVID-19-Impfung nach breiter Anwendung ­ ein Zwischenfazit für Deutschland im Juli 2022.

Vaccines against COVID-19 have been available in Germany since December 2020. At the Robert Koch Institute (RKI), the Immunization Unit is responsible for monitoring vaccination coverage and assessment of vaccine effectiveness. This article provides an overview of the respective reporting structures, vaccination databases, and epidemiological studies established by the Immunization Unit during the COVID-19 pandemic. We describe the COVID-19 Digital Vaccination Coverage Monitoring (DIM), which provides daily updates on vaccination coverage by age group. We next describe how, based on the DIM data and COVID-19 case data, the assessment of vaccine effectiveness against different clinical endpoints (hospitalization, intensive care, death) is performed. While this method is used for a preliminary estimate of vaccine efficacy, population-based nonrandomized studies are able to provide more precise and detailed estimates under "real-world" conditions. In this context, we describe the hospital-based case-control study COViK, which is being conducted in collaboration with the Paul Ehrlich Institute (PEI). We discuss strengths and limitations of the abovementioned structures and tools. Finally, we provide an outlook on future challenges that may arise during the ongoing pandemic and during the transition phase into an endemic situation.

Pre-existing health conditions and severe COVID-19 outcomes: an umbrella review approach and meta-analysis of global evidence.

BACKGROUND: This study applies an umbrella review approach to summarise the global evidence on the risk of severe COVID-19 outcomes in patients with pre-existing health conditions. METHODS: Systematic reviews (SRs) were identified in PubMed, Embase/Medline and seven pre-print servers until December 11, 2020. Due to the absence of age-adjusted risk effects stratified by geographical regions, a re-analysis of the evidence was conducted. Primary studies were extracted from SRs and evaluated for inclusion in the re-analysis. Studies were included if they reported risk estimates (odds ratio (OR), hazard ratio (HR), relative risk (RR)) for hospitalisation, intensive care unit admission, intubation or death. Estimated associations were extracted from the primary studies for reported pre-existing conditions. Meta-analyses were performed stratified for each outcome by regions of the World Health Organization. The evidence certainty was assessed using GRADE. Registration number CRD42020215846. RESULTS: In total, 160 primary studies from 120 SRs contributed 464 estimates for 42 pre-existing conditions. Most studies were conducted in North America, European, and Western Pacific regions. Evidence from Africa, South/Latin America, and the Eastern Mediterranean region was scarce. No evidence was available from the South-East Asia region. Diabetes (HR range 1.2-2.0 (CI range 1.1-2.8)), obesity (OR range 1.5-1.75 (CI range 1.1-2.3)), heart failure (HR range 1.3-3.3 (CI range 0.9-8.2)), COPD (HR range 1.12-2.2 (CI range 1.1-3.2)) and dementia (HR range 1.4-7.7 (CI range 1.2-39.6)) were associated with fatal COVID-19 in different regions, although the estimates varied. Evidence from Europe and North America showed that liver cirrhosis (OR range 3.2-5.9 (CI range 0.9-27.7)) and active cancer (OR range 1.6-4.7 (CI range 0.5-14.9)) were also associated with increased risk of death. Association between HIV and undesirable COVID-19 outcomes showed regional heterogeneity, with an increased risk of death in Africa (HR 1.7 (CI 1.3-2.2)). GRADE certainty was moderate to high for most associations. CONCLUSION: Risk of undesirable COVID-19 health outcomes is consistently increased in certain patient subgroups across geographical regions, showing high variability in others. The results can be used to inform COVID-19 vaccine prioritisation or other intervention strategies.

Hepatitis B vaccination coverage in Germany: systematic review.

BACKGROUND: Despite being considered as a low prevalence country for hepatitis B (HBV), some populations in Germany are at higher risk of infection. In the context of the World Health Organization's (WHO) viral hepatitis elimination goals, a valid epidemiological data base is needed to plan and monitor the national response. Prevention strategies include general and targeted HBV vaccination programmes. OBJECTIVE: The aim of this work was to estimate the HBV vaccination coverage (VC) in the general population (GP) and different population groups in Germany from available evidence and to identify current evidence gaps for future research. METHODS: We conducted a systematic review on HBV VC in the general population and populations at high risk of HBV exposure or severe infection in Germany. We included eligible publications (01/01/2017 to 06/06/2020) from databases Embase, Pubmed and Livivo, from a previous scoping review (including data published 01/01/2005-17/03/2017), from the national surveillance system and screened the reference lists of all publications at full text level. Risk of bias was assessed using the Hoy et al. tool. RESULTS: We included 68 publications of 67 studies and assigned them to one or more suitable population groups. Twenty-one studies contained data among children/adolescents and three among adults from the GP (VC 65.8-90.5% and 22.9-52.1%, respectively), one among travelers (VC 89.0%), 13 among immunocompromised populations (VC 7.8-89.0%), 16 among populations with occupational risk and 16 with non-occupational risk of HBV exposure (VC 63.6-96.5% and 4.4-84.5%, respectively). CONCLUSION: Comprehensive evidence at low risk of bias was identified for children/adolescents. However, 25 years after including HBV in the national immunisation schedule, VC in Germany is still below the 95%-goal defined by WHO. For people at occupational risk of HBV exposure, VC was mostly reported to be over the WHO goal of 80%, but quality of evidence was heterogenous and should be improved. For people at non-occupational risk of HBV exposure, evidence was sparse and of low quality. The low VC highlights the need for future research to plan vaccination programmes targeting these populations.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021.

The Delta variant has become the dominant strain of SARS-CoV-2. We summarised the evidence on COVID-19 vaccine effectiveness (VE) identified in 17 studies that investigated VE against different endpoints. Pooled VE was 63.1% (95% confidence interval (CI): 40.9-76.9) against asymptomatic infection, 75.7% (95% CI: 69.3-80.8) against symptomatic infection and 90.9% (95% CI: 84.5-94.7) against hospitalisation. Compared with the Alpha variant, VE against mild outcomes was reduced by 10-20%, but fully maintained against severe COVID-19.

Efficacy and effectiveness of COVID-19 vaccines against SARS-CoV-2 infection: interim results of a living systematic review, 1 January to 14 May 2021.

Evidence on COVID-19 vaccine efficacy/effectiveness (VE) in preventing asymptomatic SARS-CoV-2 infections is needed to guide public health recommendations for vaccinated people. We report interim results of a living systematic review. We identified a total of 30 studies that investigated VE against symptomatic and/or asymptomatic infection. In fully vaccinated individuals, VE against symptomatic and asymptomatic infections was 80-90% in nearly all studies. Fully vaccinated persons are less likely to become infected and contribute to transmission.

[COVID-19 patients in Germany: exposure risks and associated factors for hospitalization and severe disease]. / COVID-19-Patientinnen und -Patienten in Deutschland: Expositionsrisiken und assoziierte Faktoren für Hospitalisierungen und schwere Krankheitsverläufe.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) spread worldwide in 2020. By the end of June 2021, over 3.7 million people had been infected in Germany. The spread of the infection, however, is not evenly distributed across all parts of the population. Some groups are at a higher risk for SARS-CoV­2 infections or severe coronavirus disease 2019 (COVID-19) trajectories than others.This narrative review provides an overview of the parts of the population in Germany that are most affected by COVID-19. In addition, risk factors associated with hospitalization or severe courses of COVID-19 are identified.SARS-CoV­2 transmission may occur in various locations and settings. Professional settings, e.g., in the meat-processing industry, but also leisure activities and large public events are particularly affected. In the course of the pandemic, certain comorbidities associated with an increased risk for hospitalization or severe courses of COVID-19 have been identified. These include preexisting pulmonary, cardiovascular, and metabolic diseases. Patients with organ transplants and people with Down syndrome (trisomy 21) have the highest risk for hospitalization after SARS-CoV­2 infection.The identified settings that contribute to the spread of SARS-CoV­2 and the knowledge about vulnerable groups with a higher risk for hospitalization or severe disease trajectories form an important evidence base for the planning of prevention strategies and the fight against the pandemic.

Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review.

BACKGROUND: Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy. METHODS: We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach. RESULTS: We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome. CONCLUSION: Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented. TRIAL REGISTRATION: PROSPERO CRD42018087814, CRD42018090357.

Systematic Review and Meta-analysis of Chickenpox Vaccination and Risk of Herpes Zoster: A Quantitative View on the "Exogenous Boosting Hypothesis".

BACKGROUND: The "exogenous boosting hypothesis" postulates that reexposure to circulating varicella zoster virus (VZV) over the life span inhibits reactivation of VZV. Consequently, if circulation of VZV is suppressed by introduction of chickenpox vaccination, incidences of herpes zoster may rise. METHODS: We performed a systematic review and metaanalysis on impact of chickenpox vaccination on herpes zoster incidence and time trend, focusing on population-level effects by analyzing interrupted time-series (ITS) studies. We searched Medline and Embase for ITS reporting incidences of chickenpox and herpes zoster before and after implementation of chickenpox vaccination. Autoregressive integrated moving average models were calculated. Change in trend and incidence from studies were pooled. RESULTS: Twelve studies were included, of which 6 were eligible for metaanalysis. Metaanalysis revealed a significant increase in chickenpox cases prior to implementation of chickenpox vaccination and a reversed trend thereafter, particularly in individuals aged 1-4 years. The increase in age-adjusted herpes zoster incidence before implementation of chickenpox vaccination did not change thereafter. However, separate analysis of age groups revealed a net increase of hospitalized herpes zoster cases in individuals aged 10-49 years after implementation of chickenpox vaccination. This very small effect (fewer than 2 additional cases per 100 000 persons) did not occur in other age groups. CONCLUSIONS: To date, no conclusive evidence exists that chickenpox vaccination has a substantial population-level impact on herpes zoster in nonvaccinated age groups. While exogenous boosting may exist, the effect size generated by chickenpox vaccination might be rather small on the population level.

A probable case of tick-borne encephalitis (TBE) acquired in England, July 2019.

The United Kingdom (UK) has thus far been considered to be free from tick-borne encephalitis (TBE), yet in July 2019, a German infant developed serologically diagnosed TBE following a tick bite in southern England. This first report of a probable human case together with recent findings of TBE virus in ticks in foci in England suggest that TBE may be acquired in parts of England and should be considered in patients with aetiologically-unexplained neurological manifestations.

[The new standard operating procedure of the German standing committee on vaccination (STIKO): history, structure, and implementation]. / Die neue Standardvorgehensweise der Ständigen Impfkommission (STIKO): Entstehung, Struktur und Umsetzung.

In Germany, the Standing Committee on Vaccination (STIKO) develops recommendations on vaccinations and other measures of specific prophylaxis against communicable diseases. Myths, wrong assumptions, and conspiracy theories are able to disturb the implementation of vaccination recommendations. Evidence and transparency of recommendations are needed to rationalize the discussion.In November 2011, STIKO adopted a new standard operating procedure (SOP) for the development of evidence-based vaccination recommendations. Following guidance provided by the SOP, a number of new vaccination recommendations have been developed since 2011. Furthermore, existing recommendations were revised or extended accordingly. This article provides an overview on the methodology of the SOP, describes experiences made so far, and characterizes future challenges.

Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review.

BACKGROUND: Human papillomavirus (HPV) vaccination is safe and effective in preventing cervical cancer in females. As HPV infections can also induce cancers of the anus, penis and oral cavity, male vaccination is also advocated, but systematic reviews on efficacy and safety in males are lacking. METHODS: We performed a systematic review on the efficacy, effectiveness and safety of HPV vaccination in males of any age. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to April 2017. RESULTS: We identified 5196 articles and seven studies (four randomized controlled trials (RCTs), three non-randomized studies) were included, comprising a total of 5294 participants. Vaccine efficacy against at least 6-month persisting anogenital HPV 16 infections was 46.9% (95% confidence interval (CI) 28.6-60.8%), whereas efficacy against persisting oral infections was 88% (2-98%). A vaccine efficacy of 61.9% (21.4-82.8%) and 46.8% (- 20 to -77.9%) was observed against anal intraepithelial neoplasia grade 2 and grade 3 lesions, respectively. No meaningful estimates were available on vaccine efficacy or effectiveness against penile intraepithelial neoplasia grade 2 or 3, and no data were identified for anal, penile or head and neck squamous cell cancer. In participants who were HPV-seronegative and PCR-negative at enrolment, efficacy against all outcomes was higher as compared to seropositive and/or PCR-positive individuals. Risk of bias was low in three RCTs and high in one, while the three non-randomized studies were at serious to critical risk of bias. Grading of Recommendations Assessment, Development and Evaluation evidence quality was moderate to low for most outcomes. CONCLUSIONS: HPV vaccination in males is moderately effective against persistent anogenital HPV infection and high-grade anal intraepithelial lesions in studies where the population consists mainly of HPV-infected males. Vaccine effectiveness was high in study groups comprising HPV-naïve males. This supports a recommendation for vaccination of boys before the onset of sexual activity with the goal of establishing optimal vaccine-induced protection. Mathematical modelling studies will still be needed to assess the effects of adding males to existing HPV vaccination programs in females. TRIAL REGISTRATION: Prospective Register for Systematic Reviews (PROSPERO) registration CRD42016038965 .