Francis Ndowa

Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae

Globally, antimicrobial resistance (AMR) in Neisseria gonorrhoeae is increasing in prevalence, both within and across antibiotic classes, including extended-spectrum cephalosporins, raising concerns that gonorrhea may become untreatable in certain circumstances. The AMR surveillance that is essential to optimize standard treatments is often lacking or of poor quality in countries with high disease rates. Recent initiatives by the WHO to enhance global AMR surveillance that focus on multidrug- and extensively drug-resistant N. gonorrhoeae through revision of surveillance standards and use of a new panel of N. gonorrhoeae control strains are described. Keys to meeting these new challenges posed by gonococcal AMR remain the reduction in global burden of gonorrhea combined with implementation of wider strategies for general AMR control, and better understanding of mechanisms of emergence and spread of AMR.

Control of sexually transmitted infections and prevention of HIV transmission: mending a fractured paradigm

Control of sexually transmitted infections (STIs) is feasible, leads to improved sexual and reproductive health and contributes to preventing HIV transmission. The most advanced HIV epidemics have developed under conditions of poor STI control, particularly where ulcerative STIs were prevalent. Several countries that have successfully controlled STIs have documented stabilization or reversal of their HIV epidemics. STI control is a public health outcome measured by reduced incidence and prevalence. The means to achieve this include: (i) targeting and outreach to populations at greatest risk; (ii) promoting and providing condoms and other means of prevention; (iii) effective clinical interventions; (iv) an enabling environment; and (v) reliable data. Clinical services include STI case management, screening and management of STIs in sex partners. Syndromic case management is effective for most symptomatic curable STIs and screening strategies exist to detect some asymptomatic infections. Presumptive epidemiologic treatment of sex partners and sex workers complement efforts to interrupt transmission and reduce prevalence. Clinical services alone are insufficient for control since many people with STIs do not attend clinics. Outreach and peer education have been effectively used to reach such populations. STI control requires effective interventions with core populations whose rates of partner change are high enough to sustain transmission. Effective, appropriate targeting is thus necessary and often sufficient to reduce prevalence in the general population. Such efforts are most effective when combined with structural interventions to ensure an enabling environment for prevention. Reliable surveillance and related data are critical for designing and evaluating interventions and for assessing control efforts.

Constraints faced by sex workers in use of female and male condoms for safer sex in urban Zimbabwe

We investigated whether female condoms are acceptable to sex workers in Harare and whether improved access to male and female condoms increases the proportion of protected sex episodes with clients and boyfriends. Sex workers were randomly placed in groups to receive either male and female condoms (group A, n=99) or male condoms only (group B, n=50) and were followed prospectively for about 3 months each. We found a considerable burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) in our cohort at enrollment (86% tested HIV positive and 34% had at least one STI). Consistent male condom use with clients increased from 0% to 52% in group A and from 0% to 82% in group B between enrollment and first follow-up 2 weeks later and remained high throughout the study. Few women in group A reported using female condoms with clients consistently (3%–9%), and use of either condom was less common with boyfriends than with clients throughout the study (8%–39%) for different study groups, visits, and types of condom). Unprotected sex still took place, as evidenced by an STI incidence of 16 episodes per 100 woman-months of follow-up. Our questionnaire data indicated high self-reported acceptability of female condoms, but focus group discussions revealed that a main obstacle to female condom use was client distrust of unfamiliar methods. This study shows that a simple intervention of improving access to condoms can lead to more protected sex episodes between sex workers and clients. However, more work is needed to help sex workers achieve safer sex in noncommercial relationships.

Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action

In a Policy Forum, Teodora Wi and colleagues discuss the challenges of antimicrobial resistance in gonococci.

The serious threat of multidrug-resistant and untreatable gonorrhoea: the pressing need for global action to control the spread of antimicrobial resistance, and mitigate the impact on sexual and reproductive health

STIs remain a major cause of morbidity and mortality worldwide. The WHO estimated that >498 million new cases of syphilis, gonorrhoea, chlamydial infection and trichomoniasis occurred globally in 2008 in adults (15–49 years of age). More than 106 million were gonococcal infections.1 Accordingly, gonorrhoea remains a major global public health problem with serious health, social and economic consequences. Inadequate control and treatment can result in severe complications, such as pelvic inflammatory disease, leading to infertility or ectopic pregnancy, and neonatal eye infections which can cause blindness. Up to 10% of women who remain untreated (or inadequately treated) for chlamydial and gonococcal infections may become infertile. Urogenital gonorrhoea is also asymptomatic in at least 50% of women, which leaves the infections undetected and untreated with the risk of severe complications. On a global scale, up to 4000 newborn babies, annually, may become blind because of gonococcal and chlamydial ophthalmia neonatorum.2 In men, gonococcal infections cause symptomatic urethritis which, if untreated, can result in epididymitis in 10%–30% of cases,w1 that may lead to infertility. Gonorrhoea also significantly enhances the transmission of HIV. The burden of gonococcal infections is highest in countries that are least able to manage them because of several factors, including stigma, inadequate resources and lack of appropriate diagnostics, surveillance and antimicrobial treatment. The problem is further compounded by the ability of Neisseria gonorrhoeae to develop antimicrobial resistance (AMR) within a relatively short time span.3 w2 w3 Historically, since the advent of the antibiotic era, …

WHO global strategy for the prevention and control of sexually transmitted infections: time for action

STI health professionals should use every opportunity to influence those able to initiate change to improve global STI control and prevention activities

Periodic presumptive treatment of curable sexually transmitted infections among sex workers: a systematic review

Background:Unprotected sex work remains a major driver of HIV/sexually transmitted infection (STI) epidemics in many countries. STI treatment can lower disease burden, complications and prevalence of HIV cofactors. Periodic presumptive treatment (PPT) has been used with sex workers to reduce their high burden of largely asymptomatic STIs. The objective of this review is to assess benefits and harms of PPT among female sex workers. Methods:We searched MEDLINE for studies related to sex work and STIs during 1990–2010, extracted data from eligible studies in duplicate and conducted meta-analysis by study design using random effects models. Results:Two thousand, three hundred and fifteen articles were screened, 18 studies met inclusion criteria and 14 were included in meta-analyses. One published randomized controlled trial (RCT) reported significant reductions of gonorrhoea (Neisseria gonorrhoeae) [rate ratio (RR) 0.46, 95% confidence interval (CI) 0.31–0.68] and chlamydia (Chlamydia trachomatis) (RR 0.38, 95%CI 0.26–0.57), but no effect on serologic syphilis (RR 1.02, 95%CI 0.54–1.95). Similar results were seen for N. gonorrhoeae and C. trachomatis in pooled analyses, including data from one unpublished RCT and across study designs, and correlated with initial prevalence (R2 = 0.155). One observational study reported genital ulcer disease (GUD) declines in sex workers, and two reported impact among male client populations for N. gonorrhoeae [odds ratio (OR) 0.60, 95% CI 0.38–0.94], C. trachomatis (OR 0.47, 95% CI 0.31–0.71) and GUD (OR 0.21, 95% CI 0.11–0.42). No studies reported evidence of risk compensation or antibiotic resistance. Conclusion:PPT can reduce prevalence of gonorrhoea, chlamydia and ulcerative STIs among sex workers in whom prevalence is high. Sustained STI reductions can be achieved when PPT is implemented together with peer interventions and condom promotion. Additional benefits may include impact on STI and HIV transmission at population level.

Using mathematical modelling to estimate the impact of periodic presumptive treatment on the transmission of sexually transmitted infections and HIV among female sex workers.

Background In settings with poor sexually transmitted infection (STI) control in high-risk groups, periodic presumptive treatment (PPT) can quickly reduce the prevalence of genital ulcers, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). However, few studies have assessed the impact on HIV. Mathematical modelling is used to quantify the likely HIV impact of different PPT interventions. Methods A mathematical model was developed to project the impact of PPT on STI/HIV transmission amongst a homogeneous population of female sex workers (FSWs) and their clients. Using data from Johannesburg, the impact of PPT interventions with different coverages and PPT frequencies was estimated. A sensitivity analysis explored how the projections were affected by different model parameters or if the intervention was undertaken elsewhere. Results Substantial decreases in NG/CT prevalence are achieved among FSWs receiving PPT. Although less impact is achieved among all FSWs, large decreases in NG/CT prevalence (>50%) are possible with >30% coverage and supplying PPT every month. Higher PPT frequencies achieve little additional impact, whereas improving coverage increases impact until NG/CT becomes negligible. The impact on HIV incidence is smaller, longer to achieve, and depends heavily on the assumed NG/CT cofactors, whether they are additive, the assumed STI/HIV transmission probabilities and STI durations. Greater HIV impact can be achieved in settings with lower sexual activity (except at high coverage), less STI treatment or high prevalences of Haemophilus ducreyi. Conclusions Despite the models assumption of homogeneous risk behaviour probably resulting in optimistic projections, and uncertainty in STI cofactors and transmission probabilities, projections suggest PPT interventions with sufficient coverage (≥40%) and follow-up (≥2 years) could noticeably decrease the HIV incidence (>20%) among FSW populations with inadequate STI treatment.

Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines

Emilie Alirol and colleagues discuss the development of new treatments for gonorrhea.

Genital Ulcer Disease Treatment Policies and Access to Acyclovir in Eight Sub-Saharan African Countries

Background: Herpes simplex virus-2, the most common cause of genital ulcer disease (GUD) globally, is a cofactor in human immunodeficiency virus type-1 (HIV-1) acquisition and transmission. Current World Health Organization guidelines for sexually transmitted infections recommend acyclovir as first-line syndromic treatment of GUD in countries with high herpes simplex virus-2 prevalence (≥30%). Objective: To assess the extent of adoption of acyclovir as syndromic treatment for GUD, and describe procurement, distribution, and cost of acyclovir in the public and private sectors of 8 sub-Saharan African countries. Methods: We conducted standardized interviews with Ministry of Health (MoH) officials, pharmacists, and other pharmacy workers based in the public and private sectors. Interviews were conducted in Botswana, Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Price comparisons were conducted using the 2007 median international reference price (IRP) for acyclovir. Results: Of the 8 African countries, 4 surveyed had adopted acyclovir as first-line syndromic GUD treatment in both their essential medical lists and sexually transmitted infection guidelines. Country-specific acquisition prices for acyclovir 200 mg were comparable to the median IRP and ranged from 0.74 to 1.95 times the median IRP. The median retail cost of acyclovir in the private sector ranged from 5.85 to 9.76 times the median IRP. Public health facilities faced cost and regulatory barriers that impeded the requisitioning of acyclovir from the central medical stores. Conclusions: Systems for drug procurement, distribution, and access in sub-Saharan African countries need strengthening for a GUD treatment policy using acyclovir to be effective.