Healthcare seeking outside healthcare facilities and antibiotic dispensing patterns in rural Burkina Faso: A mixed methods study.

OBJECTIVE: Optimising antibiotic use is important to limit increasing antibiotic resistance. In rural Burkina Faso, over-the-counter dispensing of antibiotics in community pharmacies and non-licensed medicine retail outlets facilitates self-medication. We investigated its extent, reasons and dispensing patterns. METHODS: In an exploratory mixed-method design conducted between October 2020 and December 2021, this study first explored illness perceptions, the range of healthcare providers in communities, antibiotics knowledge and reasons for seeking healthcare outside healthcare facilities. Second, frequencies of illness and healthcare utilisation in the last 3 months were quantitatively measured. RESULTS: Participants distinguished between natural and magico-religious illnesses, according to origins. For illnesses considered to be 'natural', healthcare was mainly sought at healthcare facilities, private pharmacies and informal drug outlets. For illnesses considered as magico-religious, traditional healers were mainly visited. Antibiotics were perceived in the community as medicines similar to painkillers. Healthcare-seeking outside healthcare facilities was reported by 660/1973 (33.5%) participants reporting symptoms, including 315 (47.7%) to informal vendors. Healthcare seeking outside facilities was less common for 0-4-year-olds (58/534, 10.9% vs. 379/850, 44.1% for ≥5-year-olds) and decreased with improving socio-economic status (108/237, 45.6% in the lowest quintile; 96/418, 23.0% in the highest). Reported reasons included financial limitation, and also proximity to informal drug vendors, long waiting times at healthcare facilities, and health professionals' non-empathetic attitudes towards their patients. CONCLUSION: This study highlights the need to facilitate and promote access to healthcare facilities through universal health insurance and patient-centred care including reducing patients' waiting time. Furthermore, community-level antibiotic stewardship programmes should include community pharmacies and informal vendors.

Regional heterogeneity of malaria prevalence and associated risk factors among children under five in Togo: evidence from a national malaria indicators survey.

BACKGROUND: Malaria remains a major cause of morbidity and death among children less than 5 years of age. In Togo, despite intensification of malaria control interventions, malaria remained highly prevalent, with significant heterogeneity from one region to another. The aim of this study is to explore further such regional differences in malaria prevalence and to determine associated risk factors. METHODS: Data from a 2017 cross-sectional nationally representative malaria indicator survey was used. Children aged 6-59 months in selected households were tested for malaria using a rapid diagnostic test (RDT), confirmed by microscopy. Univariate and multivariate logistic regression analysis were performed using Generalized Linear Models. RESULTS: A total of 2131 children aged 6-59 months (1983 in rural areas, 989 in urban areas) were enrolled. Overall 28% of children tested positive for malaria, ranging from 7.0% in the Lomé Commune region to 4% 7.1 in the Plateaux region. In multivariate analysis, statistically significant differences between regions persisted. Independent risk factors identified were higher children aged (aOR = 1.46, 95% CI [1.13-1.88]) for those above 24 months compared to those below; households wealth quintile (aOR = 0.22, 95% CI [0.11-0.41]) for those richest compared to those poorest quintiles; residence in rural areas (aOR = 2.02, 95% CI [1.32-3.13]). CONCLUSION: Interventions that target use of combined prevention measures should prioritise on older children living in poorest households in rural areas, particularly in the regions of high malaria prevalence.

Controversies and evidence on Chlamydia testing and treatment in asymptomatic women and men who have sex with men: a narrative review.

BACKGROUND: Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) worldwide. CT is mainly asymptomatic. Test-and-treat strategies are widely implemented to prevent transmission and complications. Strategies are not without controversy in asymptomatic women and men who have sex with men (MSM). Concerns are emerging to test and treat asymptomatic persons for urogenital CT ('Controversy 1') and pharyngeal or rectal CT ('Controversy 2'), whereby testing symptomatic persons is not under debate. Opposed views in CT treatment involve using azithromycin versus doxycycline ('Controversy 3'). The objective of this review is to provide coverage of these public health and clinical controversies by reviewing the current scientific evidence. METHODS: A literature search was performed using PubMed for relevant publications between 2018 and September 2021, and iterative retrieval of additional relevant publications. RESULTS: Controversy 1. In women, the majority of asymptomatic CT are at the urogenital site, and detections mostly include viable CT. CT easily transmits to a partner and potentially also between the vaginal and rectal areas; the clinical impact of urogenital CT is established, although risks for adverse outcomes are uncertain. Wide-scale testing in asymptomatic women has not resulted in reduced prevalence. In MSM, evidence for the clinical impact of asymptomatic urogenital CT is lacking. Controversy 2. Rectal CT is common in women diagnosed with urogenital CT, but the clinical impact of asymptomatic rectal CT is uncertain. In MSM, rectal CT is common, and most CT infections are at the rectal site, yet the risk of longer term complications is unknown. In both sexes, pharyngeal CT is uncommon and has no documented clinical impact. Controversy 3. In the treatment of rectal CT, doxycycline has superior effectiveness to azithromycin. Evidence has also accumulated on the harms of test-and-treat strategies. CONCLUSIONS: Current practices vary widely, from widescale test-and-treat approaches to more individual patient- and partner-level case management. Choosing which asymptomatic people to test at what anatomic site, and whether to test or not, requires an urgent (re-)definition of the goals of testing and treating asymptomatic persons. Treatment guidelines are shifting toward universal doxycycline use, and clinical practice now faces the challenge of implementation.

Care-seeking behaviour among febrile children under five in Togo.

BACKGROUND: Fever is one of the warning signs of poor health in children. Care-seeking in febrile children is importance in reducing child deaths and morbidity. This care-seeking by parents in children with fever is however relatively low in sub-Sahara Africa. The aim of this study is to improve understanding of the behaviour of caregivers in seeking care for children under five with fever and to identify associated modifiable risk factors in Togo. METHODS: Data from a 2013-2014 cross-sectional nationally representative malaria indicator survey was used. Advice or care-seeking is defined as any child under 5 years of age with fever in the two weeks prior to the interview for whom advice or treatment was sought in a public medical area, private medical area, store, market, or from an itinerant medicine seller. Univariate and multivariate logistic regression analysis were performed using Generalized Linear Models. RESULTS: A total of 1359 febrile children out of 6529 children under five were enrolled. Care had been sought in 38.9% of cases. In multivariate analysis, independent risk factors associated with formal care seeking were accessibility to the nearest health center (aOR = 1.52, 95% CI [1.18-1.95], mother's education level secondary and above (aOR = 1.85, 95% [1.32-2.59]), mothers who identified as belonging to animist/traditionalist religions compared to mothers who belonged to a formal religion (catholic (aOR = 2. 28, 95% [1.55-3.37]), Muslim (aOR = 2.41, 95% [1.67-3.47]), and Protestant (aOR = 1.9, 95% [1.37-2.65]), Maritime region (aOR = 0.49, 95% [0.29-0.82]) compared to Lome commune. CONCLUSION: Interventions should specifically target women with limited education, not identifying as part of an official church and at longer distance from health center.

Population Impact of Girls-Only Human Papillomavirus 16/18 Vaccination in The Netherlands: Cross-Protective and Second-Order Herd Effects.

BACKGROUND: Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage. METHODS: We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. RESULTS: A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year [95% confidence interval {CI}, 10.6-14.5]), heterosexual men (13.0% per year [95% CI, 8.3-17.5]), and unvaccinated women (5.4% per year [95% CI, 2.9-7.8]). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women). CONCLUSIONS: Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.

Partial Protective Effect of Bivalent Human Papillomavirus 16/18 Vaccination Against Anogenital Warts in a Large Cohort of Dutch Primary Care Patients.

BACKGROUND: There is ongoing debate about the possible protective effect of the bivalent human papillomavirus (2vHPV) vaccine, targeting oncogenic types HPV-16/18, against anogenital warts (AGWs), commonly attributed to HPV-6/11. We performed a retrospective registry-based open cohort study to assess the effect of 2vHPV vaccination on AGWs. METHODS: We linked general practice (ie, primary care) data from women born between 1993 and 2002, who had been eligible for HPV vaccination in the Netherlands, to the Dutch national immunization registry on an individual level. Women were followed until their first AGW diagnosis or end of follow-up. Adjusted incidence rate ratios (aIRRs) were estimated using Poisson regression with vaccination status as a time-dependent exposure. RESULTS: We linked data of 96 468 women with a total of 328 019 years observation time and 613 AGW diagnoses (incidence: 1.87/1000 person-years). At the end of follow-up, 61% were 2vHPV vaccinated (≥ 1 dose) of whom 91% were fully vaccinated. The AGW incidence was lower among those with ≥ 1 dose vs 0 doses (aIRR, 0.75 [95% confidence interval {CI}, .64-.88]). The effect of vaccination was stronger after full vaccination (aIRR, 0.72 [95% CI, .61-.86]) and for women who were offered vaccination at 12-13 years of age (aIRR, 0.69 [95% CI, .51-.93]) vs those at 13-16 years of age (aIRR, 0.77 [95% CI, .64-.93]). CONCLUSIONS: This is the largest population-based study so far to examine the effect of 2vHPV vaccination on AGWs, with reliable individual information on AGW diagnoses and vaccination status. The results indicate that 2vHPV vaccination partially protects against AGWs, especially when administered in early adolescence.

Early childhood infections and body mass index in adolescence.

BACKGROUND: The incidence of childhood overweight and obesity is rising. It is hypothesized that infections in early childhood are associated with being overweight. This study investigated the association between the number of symptomatic infections or antibiotic prescriptions in the first 3 years of life and body mass index (BMI) in adolescence. SUBJECTS: The current study is part of the Prevention and Incidence of Asthma and Mite Allergy population-based birth cohort study. Weight and height were measured by trained research staff at ages 12 and 16 years. The 3015 active participants at age 18 years were asked for informed consent for general practitioner (GP) data collection and 1519 gave written informed consent. Studied exposures include (1) GP-diagnosed infections, (2) antibiotic prescriptions, and (3) parent-reported infections in the first 3 years of life. Generalized estimating equation analysis was used to determine the association between each of these exposures and BMI z-score. RESULTS: Exposure data and BMI measurement in adolescence were available for 622 participants. The frequencies of GP-diagnosed infections and antibiotic prescriptions were not associated with BMI z-score in adolescence with estimates being 0.14 (95% CI -0.09-0.37) and 0.10 (95% CI -0.14-0.34) for the highest exposure categories, respectively. Having ≥6 parent-reported infections up to age 3 years was associated with a 0.23 (95% CI 0.01-0.44) higher BMI z-score compared to <2 parent-reported infections. CONCLUSIONS: For all infectious disease measures an increase in BMI z-score for the highest childhood exposure to infectious disease was observed, although only statistically significant for parent-reported infections. These results do not show an evident link with infection severity, but suggest a possible cumulative effect of repeated symptomatic infections on overweight development.

Where to go to in chlamydia control? From infection control towards infectious disease control.

OBJECTIVES: The clinical and public health relevance of widespread case finding by testing for asymptomatic chlamydia infections is under debate. We wanted to explore future directions for chlamydia control and generate insights that might guide for evidence-based strategies. In particular, we wanted to know the extent to which we should pursue testing for asymptomatic infections at both genital and extragenital sites. METHODS: We synthesised findings from published literature and from discussions among national and international chlamydia experts during an invitational workshop. We described changing perceptions in chlamydia control to inform the development of recommendations for future avenues for chlamydia control in the Netherlands. RESULTS: Despite implementing a range of interventions to control chlamydia, there is no practice-based evidence that population prevalence can be reduced by screening programmes or widespread opportunistic testing. There is limited evidence about the beneficial effect of testing on pelvic inflammatory disease prevention. The risk of tubal factor infertility resulting from chlamydia infection is low and evidence on the preventable fraction remains uncertain. Overdiagnosis and overtreatment with antibiotics for self-limiting and non-viable infections have contributed to antimicrobial resistance in other pathogens and may affect oral, anal and genital microbiota. These changing insights could affect the outcome of previous cost-effectiveness analysis. CONCLUSION: The balance between benefits and harms of widespread testing to detect asymptomatic chlamydia infections is changing. The opinion of our expert group deviates from the existing paradigm of 'test and treat' and suggests that future strategies should reduce, rather than expand, the role of widespread testing for asymptomatic chlamydia infections.

Comparative assessment of the prevalence, practices and factors associated with self-medication with antibiotics in Africa.

OBJECTIVE: To evaluate and compare the prevalence, reasons, sources and factors associated with self-medication with antibiotics (SMA) within Africa. METHODS: Systematic review and meta-analysis. An electronic search of PubMed and Google Scholar databases was performed for observational studies conducted between January 2005 and February 2020. Two reviewers independently screened abstracts and full texts using the PRISMA flowchart and performed quality assessment of eligible studies. Both qualitative and quantitative syntheses were carried out. RESULTS: Forty studies from 19 countries were eligible for qualitative synthesis. The prevalence of SMA in Africa ranged from 12.1% to 93.9% with a median prevalence of 55.7% (IQR 41-75%). Western Africa was the sub-region with the highest reported prevalence of 70.1% (IQR 48.3-82.1%), followed by Northern Africa with 48.1% (IQR 41.1-64.3%). We identified 27 antibiotics used for self-medication from 13 different antibiotic classes. Most frequently used antibiotics were penicillins (31 studies), tetracyclines (25 studies) and fluoroquinolones (23 studies). 41% of these antibiotics belong to the WHO Watch Group. The most frequent indications for SMA were upper respiratory tract infections (27 studies), gastrointestinal tract symptoms (25 studies) and febrile illnesses (18 studies). Common sources of antibiotics used for self-medication were community pharmacies (31 studies), family/friends (20 studies), leftover antibiotics (19 studies) and patent medicine stores (18 studies). The most frequently reported factor associated with SMA was no education/low educational status (nine studies). CONCLUSIONS: The prevalence of SMA is high in Africa and varies across sub-regions with the highest prevalence reported in Western Africa. Drivers of SMA are complex, comprising of socio-economic factors and insufficient access to health care coupled with poorly implemented policies regulating antibiotic sales.

Bivalent Vaccine Effectiveness Against Anal Human Papillomavirus Positivity Among Female Sexually Transmitted Infection Clinic Visitors in the Netherlands.

Human papillomavirus (HPV) vaccines are indicated for anal cancer prevention, but evidence for vaccine effectiveness (VE) against anal HPV infections among women is limited. We estimated the VE (≥1 dose) against anal HPV positivity of the bivalent vaccine, whose target types HPV-16/18 are associated with approximately 90% of HPV-related anal cancers. Among 548 female STI clinic visitors 16-24 years old who provided an anal swab sample as part of a repeated cross-sectional survey, VE against HPV-16/18 was 89.9% (95% confidence interval, 63.0%-97.2%). Type-specific VE correlated well with VE against cervicovaginal HPV (Spearman ρ = 0.76), suggesting comparable effectiveness of HPV-16/18 vaccination against genital and anal infections.

Hepatitis B prevention: Can we learn from the response to HIV/AIDS?

Mirjam Kretzschmar and Marianne van der Sande discuss the accompanying research study by Anna McNaughton and colleagues on strategies to reduce the burden of hepatitis B in African countries.

Pregnancies and Time to Pregnancy in Women With and Without a Previous Chlamydia trachomatis Infection.

BACKGROUND: A Chlamydia trachomatis infection (chlamydia) can result in tubal factor infertility in women. To assess if this association results in fewer pregnant women, we aimed to assess pregnancy incidences and time to pregnancy among women with a previous chlamydia infection compared with women without one and who were participating in the Netherlands Chlamydia Cohort Study (NECCST). METHODS: The NECCST is a cohort of women of reproductive age tested for chlamydia in a chlamydia screening trial between 2008 and 2011 and reinvited for NECCST in 2015 to 2016. Chlamydia status (positive/negative) was defined using chlamydia screening trial-nucleic acid amplification test results, chlamydia immunoglobulin G presence in serum, or self-reported chlamydia infections. Data on pregnancies were collected via questionnaires in 2015-2016 and 2017-2018. Overall pregnancies (i.e., planned and unplanned) and time to pregnancy (among women with a pregnancy intention) were compared between chlamydia-positive and chlamydia-negative women using Cox regressions. RESULTS: Of 5704 women enrolled, 1717 (30.1%; 95% confidence interval [CI], 28.9-31.3) women was chlamydia positive. Overall pregnancy proportions were similar in chlamydia-positive and chlamydia-negative women (49.0% [95% CI, 46.5-51.4] versus 50.5% [95% CI, 48.9-52.0]). Pregnancies per 1000 person-years were 53.2 (95% CI, 51.5-55.0) for chlamydia negatives and 83.0 (95% CI, 78.5-87.9) for chlamydia positives. Among women with a pregnancy intention, 12% of chlamydia-positive women had a time to pregnancy of >12 months compared with 8% of chlamydia negatives (P < 0.01). CONCLUSIONS: Overall pregnancy rates were not lower in chlamydia-positive women compared with chlamydia-negative women, but among women with a pregnancy intention, time to pregnancy was longer and pregnancy rates were lower in chlamydia-positive women. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR-5597.

Utility of emergency call centre, dispatch and ambulance data for syndromic surveillance of infectious diseases: a scoping review.

BACKGROUND: Syndromic surveillance can supplement conventional health surveillance by analyzing less-specific, near-real-time data for an indication of disease occurrence. Emergency medical call centre dispatch and ambulance data are examples of routinely and efficiently collected syndromic data that might assist in infectious disease surveillance. Scientific literature on the subject is scarce and an overview of results is lacking. METHODS: A scoping review including (i) review of the peer-reviewed literature, (ii) review of grey literature and (iii) interviews with key informants. RESULTS: Forty-four records were selected: 20 peer reviewed and 24 grey publications describing 44 studies and systems. Most publications focused on detecting respiratory illnesses or on outbreak detection at mass gatherings. Most used retrospective data; some described outcomes of temporary systems; only two described continuously active dispatch- and ambulance-based syndromic surveillance. Key informants interviewed valued dispatch- and ambulance-based syndromic surveillance as a potentially useful addition to infectious disease surveillance. Perceived benefits were its potential timeliness, standardization of data and clinical value of the data. CONCLUSIONS: Various dispatch- and ambulance-based syndromic surveillance systems for infectious diseases have been reported, although only roughly half are documented in peer-reviewed literature and most concerned retrospective research instead of continuously active surveillance systems. Dispatch- and ambulance-based syndromic data were mostly assessed in relation to respiratory illnesses; reported use for other infectious disease syndromes is limited. They are perceived by experts in the field of emergency surveillance to achieve time gains in detection of infectious disease outbreaks and to provide a useful addition to traditional surveillance efforts.

Salmonella Typhi From Blood Cultures in the Democratic Republic of the Congo: A 10-Year Surveillance.

BACKGROUND: This study gives an overview of a decade (2007-2017) of hospital-based Salmonella Typhi bloodstream infection (BSI) surveillance in the Democratic Republic of the Congo (DRC), at 4 main sampling sites. METHODS: Blood cultures were sampled in hospital-admitted patients with suspected BSI, according to standardized clinical indications. The results of the surveillance period 2015-2017 were compiled with those of previous surveillance periods (2007-2010 and 2011-2014). Whole genome sequencing of isolates with decreased ciprofloxacin susceptibility (DCS) was performed. RESULTS: Salmonella Typhi was isolated in 1.4% (531/37 388) and 10.3% (531/5177) of suspected and culture-confirmed BSI episodes, respectively. Salmonella Typhi ranked first among the BSI pathogens in adults (n = 220), but was mostly (n = 301 [56.7%]) isolated from children, of which 72.1% (217/301) and 31.6% (95/301) were <10 years and <5 years old, respectively. Multidrug resistance (MDR), DCS, and combined MDR/DCS were found in 38.3% (n = 180), 24.5% (n = 115), and 11.9% (n = 56) of 470 first isolates, respectively. MDR and DCS rates had increased since 2007, but remained stable during 2015-2017 with no geographical clustering at the province level. Most (91/93 [97.8%]) DCS isolates sequenced belonged to Genotyphi genotype 2.5.1, and gyr S83 was the most frequent DCS mutation (76/93 [81.7%]). Infections occurred perennially, but increased during the rainy season. CONCLUSIONS: Salmonella Typhi was a frequent cause of BSI in adults and children in DRC, with high rates of antibiotic resistance. Sustainable surveillance and implementation of vaccination are compelling.

Recurrent Cholera Outbreaks, Democratic Republic of the Congo, 2008-2017.

In 2017, the exacerbation of an ongoing countrywide cholera outbreak in the Democratic Republic of the Congo resulted in >53,000 reported cases and 1,145 deaths. To guide control measures, we analyzed the characteristics of cholera epidemiology in DRC on the basis of surveillance and cholera treatment center data for 2008-2017. The 2017 nationwide outbreak resulted from 3 distinct mechanisms: considerable increases in the number of cases in cholera-endemic areas, so-called hot spots, around the Great Lakes in eastern DRC; recurrent outbreaks progressing downstream along the Congo River; and spread along Congo River branches to areas that had been cholera-free for more than a decade. Case-fatality rates were higher in nonendemic areas and in the early phases of the outbreaks, possibly reflecting low levels of immunity and less appropriate prevention and treatment. Targeted use of oral cholera vaccine, soon after initial cases are diagnosed, could contribute to lower case-fatality rates.

Relation between Chlamydia trachomatis infection and pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility in a Dutch cohort of women previously tested for chlamydia in a chlamydia screening trial.

OBJECTIVES: A better understanding of Chlamydia trachomatis infection (chlamydia)-related sequelae can provide a framework for effective chlamydia control strategies. The objective of this study was to estimate risks and risk factors of pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility (TFI) with a follow-up time of up until 8 years in women previously tested for chlamydia in the Chlamydia Screening Implementation study (CSI) and participating in the Netherlands Chlamydia Cohort Study (NECCST). METHODS: Women who participated in the CSI 2008-2011 (n=13 498) were invited in 2015-2016 for NECCST. Chlamydia positive was defined as a positive CSI-PCR test, positive chlamydia serology and/or self-reported infection (time dependent). Data on PID, ectopic pregnancy and TFI were collected by self-completed questionnaires. Incidence rates and HRs were compared between chlamydia-positive and chlamydia-negative women corrected for confounders. RESULTS: Of 5704 women included, 29.5% (95% CI 28.3 to 30.7) were chlamydia positive. The incidence rate of PID was 1.8 per 1000 person-years (py) (1.6 to 2.2) overall, 4.4 per 1000 py (3.3 to 5.7) among chlamydia positives compared with 1.4 per 1000 py (1.1 to 1.7) for chlamydia negatives. For TFI, this was 0.4 per 1000 py (0.3 to 0.5) overall, 1.3 per 1000 py (0.8 to 2.1) and 0.2 per 1000 py (0.1 to 0.4) among chlamydia positives and negatives, respectively. And for ectopic pregnancy, this was 0.6 per 1000 py (0.5 to 0.8) overall, 0.8 per 1000 py (0.4 to 1.5) and 0.6 per 1000 py (0.4 to 0.8) for chlamydia negatives. Among chlamydia-positive women, the strongest risk factor for PID was symptomatic versus asymptomatic infection (adjusted HR 2.88, 1.4 to 4.5) and for TFI age <20 versus >24 years at first infection (HR 4.35, 1.1 to 16.8). CONCLUSION: We found a considerably higher risk for PID and TFI in chlamydia-positive women, but the incidence for ectopic pregnancy was comparable between chlamydia-positive and chlamydia-negative women. Overall, the incidence rates of sequelae remained low. TRIAL REGISTRATION: NTR-5597.

Bivalent Vaccine Effectiveness Against Type-Specific HPV Positivity: Evidence for Cross-Protection Against Oncogenic Types Among Dutch STI Clinic Visitors.

Background: Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. Results: We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who were offered vaccination 5/6 years ago, we estimated similar VE against HPV-16/18 (92%) and all hrHPV types (35%) compared to women who were offered vaccination <5 years ago (83% and 33%, respectively). Conclusion: We demonstrated high VE of the bivalent vaccine against HPV-16/18 and cross-protection against HPV-45/35/31/52. Protection against HPV-16/18 was sustained up to 6 years postvaccination.

Detection of Incident Anal High-Risk Human Papillomavirus DNA in Men Who Have Sex With Men: Incidence or Reactivation?

Background: We aimed to assess whether sexual exposure may explain all incident anal human papillomavirus (HPV) detections among men who have sex with men (MSM). Methods: A longitudinal study among MSM was conducted between 2010 and 2013 with visits every 6 months and up to 24 months of follow-up. Risk-factor questionnaires, blood samples, and anal and penile self-swabs were collected at each visit. Self-swabs were used for detection and genotyping of HPV by the broad spectrum L1 based SPF10 PCR DNA/enzyme immunoassay LiPA25 system. Serum samples were tested for high-risk HPV (hrHPV) antibodies. Incident anal HPV detection rates among sexually non-, low, and highly exposed MSM were compared. Factors associated with incident anal hrHPV detection were assessed using multivariable Cox regression. Results: Seven hundred fourteen men (median age, 40 years; 39% human immunodeficiency virus [HIV] infected) were included in the analysis. Incident anal detections of all hrHPV types were observed among both sexually nonexposed and exposed MSM. In multivariable analyses, being highly sexually exposed, being HIV infected, and having a penile HPV infection were positively associated with incident anal HPV detection; those reporting more sex partners had a nonsignificantly increased risk of HPV detection. Conclusions: Incident anal hrHPV detection is common among recently nonexposed MSM, suggesting that a reactivated latent HPV infection instead of an incident infection may underlie incident HPV detection.

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 .

Anal HPV 16 and 18 viral load: A comparison between HIV-negative and -positive MSM and association with persistence.

Does anal HPV viral load explain the difference in anal HPV persistence between HIV-negative and -positive men who have sex with men (MSM)? MSM ≥18 years were recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were collected every 6 months and genotyped (SPF10 -PCR-DEIA-LIPA25 -system). HPV16 and HPV18 load was determined with a type specific quantitative (q)PCR, and compared between HIV-negative and -positive men using ranksum test. Persistence was defined as ≥3 positive samples for the same HPV-type. Determinants of persistent HPV16/18 infection and its association with HPV16/18 load were assessed with logistic regression. Of 777 recruited MSM, 54 and 22 HIV negative men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV-positive MSM. The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1-38.0) and of HPV18 8.6 (95%CI 2.7-27.5) DNA copies/human cell. HPV16 and HPV18 load did not differ significantly between HIV-negative and -positive MSM (P = 0.7; P = 0.8, respectively). In multivariable analyses HPV16 load was an independent determinant of HPV16 persistence (OR 1.8, 95%CI 1.3-2.4). No difference in anal HPV viral load was found between HIV-positive and HIV-negative MSM. HPV 16/18 viral load is an independent determinant of type-specific persistence.