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.

Targeting remaining pockets of malaria transmission in Kenya to hasten progress towards national elimination goals: an assessment of prevalence and risk factors in children from the Lake endemic region.

BACKGROUND: With an overall decline of malaria incidence, elimination of malaria is gradually becoming the next target for many of countries affected by the disease. In Kenya the national malaria control strategy is aiming to reach pre-elimination for most parts of the country. However, considerable heterogeneity in prevalence of the disease within the country and especially the remaining high prevalent region of the Lake endemic region is likely to slow progress towards this target. To achieve a sustained control and an eventual elimination, a clear understanding of drivers of ongoing malaria transmission in remaining hotspots is needed. METHODS: Data from the 2015 Malaria Indicator Survey (MIS) were analysed for prevalence of malaria parasitaemia in children (6 months to 14 years) of different countries within the highly endemic Lake region. Univariate and multivariate logistic regression analysis were preformed to explore associations between selected risk factors and being parasitaemic. A predictive model was built for the association between malaria and the risk factors with the aim of identifying heterogeneities of the disease at the lower administrative levels. RESULTS: Overall, 604/2253 (27%, 95% CI 21.8-32.2) children were parasitaemic. The highest prevalence was observed in Busia County (37%) and lowest in Bungoma County (18%). Multivariate logistic regression analysis showed that the 10-14 years age group (OR = 3.0, 95% CI 2.3-4.1), households in the poorest socio-economic class (OR = 2.1, 95% CI 1.3-3.3), farming (OR = 1.4, 95% CI 1.2-2.5) and residence in Busia (OR = 4.6, 95% CI 2.1-8.2), Kakamega (OR = 2.6, 95% CI 1.3-5.4), and Migori counties (OR = 4.6 95% CI 2.1-10.3) were associated with higher risk of parasitaemia. Having slept under a long-lasting insecticide-treated bed net (LLIN) was associated with a lower risk (OR = 0.7, 95% CI 0.6-0.9). No association were found between malaria infection and the gender of the child, the household head, and the education status of the household head. DISCUSSION AND CONCLUSION: Detailed analysis of malaria prevalence data in a hotspot area can identify new threats and avail opportunities for directing intervention. In the Lake endemic region of Kenya, interventions should be focused more on counties with the highest prevalence, and should target older children as well as children from the lower socio-economic strata. Precisely targeting interventions in remaining hotspots and high-risk populations will likely make impact and accelerate progress towards pre-elimination targets.

Assessment of herd effects among women and heterosexual men after girls-only HPV16/18 vaccination in the Netherlands: A repeated cross-sectional study.

Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls-only HPV16/18 vaccination program in the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross-sectional study, the HPV prevalence among 16- to 24-year-old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio [aPR] 0.62, ptrend < 0.01). Among heterosexual men, the HPV16/18 prevalence decreased from 17% prevaccination to 11% in 2015 (aPR 0.52, ptrend < 0.01). Of the heterosexual men with a steady partner, HPV16/18 prevalence was lower among those whose steady partner had been vaccine-eligible in the national immunization program (aPR 0.13). Among unvaccinated women, the HPV16/18 prevalence in 2015 was not different from prevaccination. The decreasing HPV16/18 prevalence among heterosexual men and the reduced HPV16/18 prevalence among heterosexual men with a vaccine-eligible steady partner strongly suggests herd protection from girls-only vaccination. Absence of notable herd effects among unvaccinated women 6 years postvaccination may be due to the moderate vaccine uptake among girls in the Netherlands.

Methodology for computing the burden of disease of adverse events following immunization.

PURPOSE: Composite disease burden measures such as disability-adjusted life-years (DALY) have been widely used to quantify the population-level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden. METHODS: We developed a practical methodological framework, explicitly describing all steps involved: acquisition of relative or absolute risks and background event incidence rates, selection of disability weights and durations, and computation of the years lived with disability (YLD) measure, with appropriate estimation of uncertainty. We present a worked example, in which YLD is computed for 3 recognized adverse reactions following 3 childhood vaccination types, based on background incidence rates and relative/absolute risks retrieved from the literature. RESULTS: YLD provided extra insight into the health impact of an adverse event over presentation of incidence rates only, as severity and duration are additionally incorporated. As well as providing guidance for the deployment of DALY methodology in the context of adverse events associated with vaccination, we also identified where data limitations potentially occur. CONCLUSIONS: Burden of disease methodology can be applied to estimate the health burden of adverse events following vaccination in a systematic way. As with all burden of disease studies, interpretation of the estimates must consider the quality and accuracy of the data sources contributing to the DALY computation.

Cost-Effectiveness of Dual Antimicrobial Therapy for Gonococcal Infections Among Men Who Have Sex With Men in the Netherlands.

BACKGROUND: In response to the rising threat of resistance to first-line antibiotics for gonorrhea, international guidelines recommend dual antimicrobial therapy. However, some countries continue to recommend monotherapy. We assess the cost-effectiveness of dual therapy with ceftriaxone and azithromycin compared with monotherapy with ceftriaxone, for control of gonorrhea among men who have sex with men in the Netherlands. METHODS: We developed a transmission model and calculated the numbers of new gonorrhea infections, consultations at health care specialists, tests, and antibiotic doses. With these numbers, we calculated costs and quality-adjusted life-years (QALY) with each treatment; and the incremental cost-effectiveness ratio (ICER) of dual therapy compared to monotherapy. The impact of gonorrhea on human immunodeficiency virus transmission was not included in the model. RESULTS: In the absence of initial resistance, dual therapy can delay the spread of ceftriaxone resistance by at least 15 years, compared to monotherapy. In the beginning, when there is no resistance, dual therapy results in high additional costs, without any QALY gains. When resistance spreads over time, the additional costs of dual therapy decline, the gained QALYs increase, the ICER drops off and, after 50 years, falls below &OV0556;20,000 per QALY gained. If azithromycin resistance is initially prevalent, resistance to the first-line treatment rises almost equally fast with both treatment strategies and the ICER remains extremely high. CONCLUSIONS: Compared with ceftriaxone monotherapy, dual therapy with ceftriaxone and azithromycin can considerably delay the spread of ceftriaxone resistance, but may only be cost-effective in the long run and in the absence of initial resistance.

To notify or not to notify: decision aid for policy makers on whether to make an infectious disease mandatorily notifiable.

Mandatory notification can be a useful tool to support infectious disease prevention and control. Guidelines are needed to help policymakers decide whether mandatory notification of an infectious disease is appropriate. We developed a decision aid, based on a range of criteria previously used in the Netherlands or in other regions to help decide whether to make a disease notifiable. Criteria were categorised as being effective, feasible and necessary with regard to the relevance of mandatory notification. Expert panels piloted the decision aid. Here we illustrate its use for three diseases (Vibrio vulnificus infection, chronic Q fever and dengue fever) for which mandatory notification was requested. For dengue fever, the expert panel advised mandatory notification; for V. vulnificus infection and chronic Q fever, the expert panel concluded that mandatory notification was not (yet) justified. Use of the decision aid led to a structured, transparent decision making process and a thorough assessment of the advantages and disadvantages of mandatory notification of these diseases. It also helped identify knowledge gaps that required further research before a decision could be made. We therefore recommend use of this aid for public health policy making.

A Web-Based Respondent Driven Sampling Pilot Targeting Young People at Risk for Chlamydia Trachomatis in Social and Sexual Networks with Testing: A Use Evaluation.

BACKGROUND: With the aim of targeting high-risk hidden heterosexual young people for Chlamydia trachomatis (CT) testing, an innovative web-based screening strategy using Respondent Driven Sampling (RDS) and home-based CT testing, was developed, piloted and evaluated. METHODS: Two STI clinic nurses encouraged 37 CT positive heterosexual young people (aged 16-25 years), called index clients, to recruit peers from their social and sexual networks using the web-based screening strategy. Eligible peers (young, living in the study area) could request a home-based CT test and recruit other peers. RESULTS: Twelve (40%) index clients recruited 35 peers. Two of these peers recruited other peers (n = 7). In total, 35 recruited peers were eligible for participation; ten of them (29%) requested a test and eight tested. Seven tested for the first time and one (13%) was positive. Most peers were female friends (80%). Nurses were positive about using the strategy. CONCLUSIONS: The screening strategy is feasible for targeting the hidden social network. However, uptake among men and recruitment of sex-partners is low and RDS stopped early. Future studies are needed to explore the sustainability, cost-effectiveness, and impact of strategies that target people at risk who are not effectively reached by regular health care.

Chlamydia screening is not cost-effective at low participation rates: evidence from a repeated register-based implementation study in The Netherlands.

OBJECTIVE: In three pilot regions of The Netherlands, all 16-29 year olds were invited to participate in three annual rounds of Chlamydia screening. The aim of the present study is to evaluate the cost-effectiveness of repeated Chlamydia screening, based on empirical data. METHODS: A mathematical model was employed to estimate the influence of repeated screening on prevalence and incidence of Chlamydial infection. A model simulating the natural history of Chlamydia was combined with cost and utility data to estimate the number of major outcomes and quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening scenarios (16-29 years annually; 16-24 years annually; women only; biennial screening; biennial screening women only; screening every five years) were compared with no screening in two sexual networks, representing both lower ('national network') and higher ('urban network') baseline prevalence. Incremental cost-effectiveness ratios (ICERs) for the different screening scenarios were estimated. Uncertainty and sensitivity analyses were performed. RESULTS: In all scenarios and networks, cost per major outcome averted are above €5000. Cost per QALY are at least €50,000. The default scenario as piloted in the Netherlands was least cost-effective, with ICERs of €232,000 in the national and €145,000 in the urban sexual network. Results were robust in sensitivity analyses. CONCLUSIONS: It is unlikely that repeated rounds of Chlamydia screening will be cost-effective. Only at high levels of willingness to pay for a QALY (>€50,000) screening may be more cost-effective than no screening.

Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014.

BACKGROUND: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors. METHODS: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group. RESULTS: Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities. CONCLUSIONS: This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian Peninsula is needed to strengthen and specify the prevention of MERS-CoV infections.

Equity in human papilloma virus vaccination uptake?: sexual behaviour, knowledge and demographics in a cross-sectional study in (un)vaccinated girls in the Netherlands.

BACKGROUND: In the Netherlands, human papillomavirus (HPV) vaccination is part of a national program equally accessible for all girls invited for vaccination. To assess possible inequalities in vaccine uptake, we investigated differences between vaccinated and unvaccinated girls with regard to various characteristics, including education and ethnicity, (both associated with non-attendance to the national cervical screening program), sexual behaviour and knowledge of HPV. METHODS: In 2010, 19,939 nationwide randomly-selected 16-17 year-old girls (2009 vaccination campaign) were invited to fill out an online questionnaire. A knowledge scale score and multivariable analyses identified variables associated with vaccination status. RESULTS: 2989 (15%) of the selected girls participated (65% vaccinated, 35% unvaccinated). The participants were comparable with regard to education, ethnicity, most sexual risk behaviour and had similar knowledge scores on HPV transmission and vaccination. However, unvaccinated girls lived in more urbanised areas and were more likely to have a religious background. Irrespective of vaccination status, 81% of the girls were aware of the causal relationship between HPV and cervical cancer, but the awareness of the necessity of cervical screening despite being vaccinated was limited. CONCLUSIONS: HPV vaccine uptake was not associated with knowledge of HPV and with factors that are known to be associated with non-attendance to the cervical cancer screening program in the Netherlands. Furthermore, most sexual behaviour was not related to vaccination status meaning that teenage unvaccinated girls were not at a disproportionally higher risk of being exposed to HPV. Routine HPV vaccination may reduce the social inequity of prevention of cervical cancer.

[More efficient testing policy at STI clinics]. / Doelmatiger testbeleid van soa-poliklinieken GGD.

OBJECTIVE: To assess the efficiency of the testing policy change in 2012 in sexually transmitted infection (STI) outpatient clinics: persons who attend the clinic and are aged < 25 years without other risk factors are initially tested only for chlamydia, and only in the event of a positive test result will they be tested for other STIs. Other possible changes in the STI testing policy were explored. DESIGN: Explorative study. METHOD: To test the new policy, data from STI outpatient clinics from 2011 were used for the risk group "young people under 25 years of age without other STI risks". Other groups who visited STI outpatient clinic were selected from the data from the STI outpatient clinics from 2012. Test cost savings and missed STIs were calculated if STI outpatient clinic attendees from these risk groups first received only a chlamydia or a combination test (chlamydia and gonorrhoea). Test cost savings were divided by the number of missed STIs as a measure of efficiency. RESULTS: The policy change led to an annual test cost saving of € 1.1 million but missed 31 gonorrhoea infections (€ 36,200 at the cost of one missed gonorrhoea infection). Using a combination test for chlamydia and gonorrhoea in heterosexual individuals visiting the clinic aged < 25 years and not from a STI-endemic country could lead to test costs savings of € 3.8 million. Savings at the cost of one missed STI would be about € 350,000; 4 HIV and 7 syphilis infections would have been missed. CONCLUSION: The national policy change has led to a substantial reduction in test costs. The policy measure would be even more efficient if a combination test for chlamydia and gonorrhoea were applied. Testing using a combination test in all heterosexual individuals who attend the clinic and are aged < 25 years and not from an STI-endemic country would lead to additional savings.

Using intervention mapping for the development of a targeted secure web-based outreach strategy named SafeFriend, for Chlamydia trachomatis testing in young people at risk.

BACKGROUND: Many young people at high risk for Chlamydia trachomatis (Ct) are not reached by current sexual health care systems, such as general practitioners and public sexual health care centres (sexually transmitted infection clinics).Ct is the most frequently diagnosed bacterial sexually transmitted infection (STI) among sexually active people and in particular young heterosexuals. Innovative screening strategies are needed to interrupt the transmission of Ct among young people and connect the hidden cases to care. METHODS: Intervention Mapping (IM), a systematic approach to develop theory- and evidence-based interventions, was used to develop a strategy to target Ct testing towards young people who are currently hidden to care in The Netherlands. Both clinical users (i.e. sexual health care nurses) and public users (i.e., young people at risk for Ct) were closely involved in the IM process. A needs assessment study was carried out using semi-structured interviews among users (N = 21), a literature search and by taking lessons learned from existing screening programmes. Theoretical methods and practical applications to reach high risk young people and influence testing were selected and translated into specific programme components. RESULTS: The IM approach resulted in the development of a secure and web-based outreach Ct screening strategy, named SafeFriend. It is developed to target groups of high-risk young people who are currently hidden to care. Key methods include web-based Respondent Driven Sampling, starting from young Ct positive sexual health care centre clients, to reach and motivate peers (i.e., sex partners and friends) to get tested for Ct. Testing and the motivation of peers were proposed as the desired behavioural outcomes and the Precaution Adoption Process Model was chosen as theoretical framework. End users, i.e., young people and sexual health care nurses were interviewed and included in the development process to increase the success of implementation. CONCLUSIONS: IM proved useful to develop an intervention for targeted Ct testing among young people. We believe this to be the first web-based outreach screening strategy which combines chain referral sampling with the delivery of targeted Ct testing to high risk young people within their sexual and social networks.

Sexually transmitted infections screening at HIV treatment centers for MSM can be cost-effective.

OBJECTIVE: To estimate the cost-effectiveness of anorectal chlamydia screening among men who have sex with men (MSM) in care at HIV treatment centers. DESIGN: Transmission model combined with economic analysis over a 20-year period. SETTING AND PARTICIPANTS: MSM in care at HIV treatment centers. INTERVENTION: Once-yearly or twice-yearly screening for anorectal chlamydia among MSM in care at HIV treatment centers. MAIN OUTCOME MEASURES: Averted HIV and chlamydia infections; discounted quality-adjusted life-years and costs; incremental cost-effectiveness ratio (ICER). RESULTS: Costs will be saved by routine chlamydia screening of MSM in care at HIV treatment centers if these patients seek little or no screening elsewhere. Nonroutine screening is considerably more expensive than routine screening offered within a scheduled visit. Adding once-yearly chlamydia screening for MSM in care at HIV treatment centers is cost saving when 30% or fewer of those men seek once-yearly screening elsewhere (1.5 to 8.1 million euro saved). Twice-yearly routine screening at HIV treatment centers is cost-effective only when routine screening takes place without additional nonroutine screening (1.9 million euro saved). CONCLUSIONS: Adding annual chlamydia screening to the HIV consultation will be cost saving as long as only a limited proportion of men are nonroutinely screened. The ICER was most sensitive to the percentage of MSM that continue to be screened elsewhere.

20 years into the Gambia Hepatitis Intervention Study: assessment of initial hypotheses and prospects for evaluation of protective effectiveness against liver cancer.

Primary hepatocellular carcinoma is the commonest cancer in The Gambia. The Gambia Hepatitis Intervention Study (GHIS) was established in 1986 to evaluate the protective effectiveness of infant hepatitis B immunization in the prevention of chronic liver disease, particularly, hepatocellular carcinoma and cirrhosis later in adult life. This program was designed based on a series of assumptions. Here, we used data from observational and epidemiologic studies developed since 1986 to examine the validity of these assumptions. We found that (a) hepatitis B vaccine coverage was 15% more than originally assumed, (b) protection against hepatitis B virus (HBV) infection was not dependent on the number of vaccine doses received, (c) perinatal infection with HBV was of negligible importance, and (d) the HBV attributable risk of hepatocellular carcinoma at age < 50 was 70% to 80%, lower than initially assumed. Based on these data, the final outcome of the GHIS should be measurable from 2017, sooner than originally assumed. The GHIS strategy takes into account-specific patterns of virus epidemiology and natural history of hepatocellular carcinoma in Africa and provides a model for integrating and evaluating new vaccines into the Expanded Programme of Immunization of sub-Saharan African countries.