Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned.

BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.

Unexpectedly high HIV prevalence among female sex workers in Bangkok, Thailand in a respondent-driven sampling survey.

The pattern of sex work in Thailand has shifted substantially over the last two decades from direct commercial establishments to indirect venues and non-venue-based settings. This respondent-driven sampling survey was conducted in Bangkok in 2007 among female sex workers (FSW) in non-venue-based settings to pilot a new approach to surveillance among this hidden population. Fifteen initial participants recruited 707 consenting participants who completed a behavioural questionnaire, and provided oral fluid for HIV testing, and urine for sexually transmitted infection (STI) testing. Overall HIV prevalence was 20.2% (95% confidence interval [CI] 16.3-24.7). Three-quarters of women were street-based (75.8%, 95% CI 69.9-81.1) who had an especially high HIV prevalence (22.7%, 95% CI 18.2-28.4); about 10 times higher than that found in routine sentinel surveillance among venue-based FSW (2.5%). STI prevalence (Chlamydia trachomatis and Neisseria gonorrhoeae) was 8.7% (95% CI 6.4-10.8) and 1.0% (95% CI 0.2-1.9), respectively. Lower price per sex act and a current STI infection were independently associated with HIV infection (P < 0.05). High HIV prevalence found among FSW participating in the survey, particularly non-venue-based FSW, identifies need for further prevention efforts. In addition, it identifies a higher-risk segment of FSW not reached through routine sentinel surveillance but accessible through this survey method.

Access to HIV testing for sex workers in Bangkok, Thailand: a high prevalence of HIV among street-based sex workers.

We offered voluntary counseling and testing (VCT) for HIV and syphilis to women attending three public sexually transmitted infection (STI) clinics in Bangkok, Thailand from May 2004 to June 2006. The testing was performed at either one of three STI clinics in Bangkok or at mobile VCT in the same area as the outreach activity. Six-hundred eighty-four women were tested. The HIV prevalences among the street-based sex workers, brothel-based sex workers and other women in these areas not reporting sex work who tested in the clinics were 45.8% (38/83), 4.2% (10/236) and 9.9% (28/284), respectively. The prevalences of syphilis in these groups were 13.3%, 2.1%, and 2.6%, respectively. Street-based sex work and longer duration of sex work were independent risk factors for HIV in-fection (p < 0.001 and p = 0.02, respectively). HIV and syphilis prevalences were 21.0% and 3.7% among 81 street-based sex workers accepting mobile VCT, The street-based sex workers in Bangkok had substantially higher HIV and syphilis prevalences than other sex workers. Street-based sex workers should be sampled during routine surveillance to obtain systematic information on disease preva-lence and risk behaviors in this group.

Indicators for sexual HIV transmission risk among people in Thailand attending HIV care: the importance of positive prevention.

BACKGROUND: Almost half of all new HIV infections in Thailand occur among low-risk partners of people infected with HIV, so it is important to include people infected with HIV in prevention efforts. METHODS: Risk for HIV transmission was assessed among people with HIV attending routine care at the National Infectious Disease Institute in Thailand. Sexual risk behaviour, sexually transmitted infection (STI-syphilis, gonorrhoea, chlamydia, trichomoniasis and genital ulcers) prevalence and HIV disclosure status were assessed. Patients were provided with STI care, risk-reduction and HIV disclosure counselling. RESULTS: Baseline data were assessed among 894 consecutive people with HIV (395 men and 499 women) from July 2005 to September 2006. Unprotected last sex with a partner of unknown or negative HIV status (unsafe sex) was common (33.2%) and more likely with casual, commercial or male-to-male sex partners than with steady heterosexual partners (p = 0.03). People receiving antiretroviral treatment were less likely to report unsafe sex (p<0.001). Overall, 10.7% of men and 7.2% of women had a STI (p = 0.08). More women than men had disclosed HIV status to their steady partners (82.5% vs 65.9%; p = 0.05). CONCLUSION: Indicators for HIV transmission risk were common among people attending HIV care in Bangkok. Efforts need to be strengthened to reduce unsafe casual and commercial sex and to increase HIV disclosure from men to their partners. A strategy for STI screening and treatment for people with HIV in Thailand should be developed.

The behaviour of linear alkyl benzene sulphonate under direct discharge conditions in Vientiane, Lao PDR.

Direct discharge of untreated sewage to surface waters is a common practice in many parts of the world. However, relatively little is known about the behaviour of synthetic organic pollutants under these conditions. This paper describes a sampling campaign designed to track changes in water quality in a surface water system in Vientiane (Lao PDR) receiving significant quantities of untreated waste water. The study was based on following in-channel transport using a fluorescent tracer injected as a pulse, with a focus on the anionic surfactant linear alkylbenzene sulphonate (LAS) and ammonia. Water samples were collected at a number of stations with sampling times estimated to coincide with solute time-of-travel. The reduction in LAS concentration with flow-time could be approximated by first-order kinetics with a half life of about 7 h. Free ammonia concentrations decreased more slowly than LAS and remained above the level believed to be toxic for sensitive aquatic species along the entire channel. Changes in the ratios of LAS alkyl chain homologues to total LAS concentrations suggest a preferential removal of longer chain lengths. The role of biodegradation in the removal of LAS was confirmed by the presence of LAS metabolites (sulphophenylcarboxylates, SPCs) which increased systematically (as a fraction of LAS remaining) with flow-time.

A new generic approach for estimating the concentrations of down-the-drain chemicals at catchment and national scale.

A new generic approach for estimating chemical concentrations in rivers at catchment and national scales is presented. Domestic chemical loads in waste water are estimated using gridded population data. River flows are estimated by combining predicted runoff with topographically derived flow direction. Regional scale exposure is characterised by two summary statistics: PEC(works), the average concentration immediately downstream of emission points, and, PEC(area), the catchment-average chemical concentration. The method was applied to boron at national (England and Wales) and catchment (Aire-Calder) scales. Predicted concentrations were within 50% of measured mean values in the Aire-Calder catchment and in agreement with results from the GREAT-ER model. The concentration grids generated provide a picture of the spatial distribution of expected chemical concentrations at various scales, and can be used to identify areas of potentially high risk.

Measured variation in boron loads reaching European sewage treatment works.

Per capita boron loads reaching 48 sewage treatment works (STWs) in The Netherlands, Germany, Italy, and the UK have been determined from monitoring data. These have been compared with the per capita input predicted from boron in detergents, as determined from detergent product sales data. The resulting distribution of the ratios of measured boron to boron predicted from consumer usage has a 90th percentile of less than 1.5. Boron has previously been shown to be a good marker for substances contained in detergent products, as it cannot be biodegraded and is not substantially adsorbed in the sewer, and there is little or no removal during sewage treatment processes. The monitoring information on the distribution of boron loads found at the different STWs should thus be indicative of the distribution of other substances released to the environment by detergent products, as specified by the relevant industrial category (IC 5-personal/domestic) in the Technical Guidance Documents. Variation in detergent product consumption figures from 18 European countries is also low, with the country with the highest per capita detergent consumption having only 1.3 times the European average detergent use. Thus the present practice of determining a "reasonable worst case" by multiplying the average per capita consumption by a factor of four to account for geographic differences in distribution, is considered to be inappropriate. This should be replaced by a factor of less than two, which combines within country and between country variations to provide a reasonable worst case approximation of the load reaching the sewage treatment facility.

Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.

BACKGROUND: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients. METHODS: We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months. RESULTS: The first primary outcome--a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary outcome or refractory ischemia--occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent). CONCLUSIONS: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.

Gonorrhea in the HIV era: a reversal in trends among men who have sex with men.

OBJECTIVES: Gonorrhea cases among men who have sex with men (MSM) declined in the early years of the HIV epidemic. We evaluated more recent trends in gonorrhea among MSM through the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project. METHODS: Isolates and case information were collected from 29 US sexually transmitted disease (STD) clinics. Gonococcal urethritis cases among MSM were compared with those among heterosexual men, and cases among MSM in 1995 to 1999 were compared with earlier MSM cases. RESULTS: Of 34,942 cases, the proportion represented by MSM increased from 4.5% in 1992 to 13.2% in 1999 (P < .001). Compared with heterosexuals, MSM were older, more often White, and more often had had gonorrhea previously, although fewer had had gonorrhea in the past year. MSM with gonorrhea in 1995 to 1999 were slightly older than those with gonorrhea in 1992 to 1994, and a higher proportion had had gonorrhea in the past year. CONCLUSIONS: MSM account for an increasing proportion of gonococcal urethritis cases in STD clinics. Given recent evidence that gonorrhea may facilitate HIV transmission, these trends demand increased attention to safe sexual behaviors and reducing STDs among MSM.

Clinical utility of measuring white blood cells on vaginal wet mount and endocervical gram stain for the prediction of chlamydial and gonococcal infections.

BACKGROUND: White blood cells on endocervical Gram stain and vaginal wet mount are frequently used to predict chlamydial and gonococcal infections. Previous studies provide conflicting evidence for the clinical utility of these tests. GOAL: To evaluate the clinical utility of measuring white blood cells on vaginal wet mount and endocervical Gram stain for the prediction of chlamydial infection and gonorrhea. STUDY DESIGN: Women undergoing pelvic examinations at 10 county health department family planning and sexually transmitted disease clinics were tested for chlamydial infection by ligase chain reaction assay (n = 4550) and for gonorrhea by culture (n = 4402). Vaginal wet mount and endocervical Gram stains were performed in county laboratories at the time of examination. RESULTS: The prevalences of chlamydial infection and gonorrhea were 8.8% and 3.2%, respectively. For detection of chlamydial or gonococcal infection, the likelihood ratio was 2.85 (95% CI, 2.10-3.87) for > 30 white blood cells on vaginal wet mount and 2.91 (95% CI, 2.07-4.09) for > 30 white blood cells on endocervical Gram stain. Similar results were seen for individual diagnoses either of chlamydial infection or of gonorrhea. CONCLUSION: Vaginal wet mount and endocervical Gram stain white blood cells are useful for the presumptive diagnosis of chlamydial infection or gonorrhea only in settings with a relatively high prevalence of infection or when other predictors can increase the likelihood of infection.

Longitudinal evaluation of serovar-specific immunity to Neisseria gonorrhoeae.

The serovars of Neisseria gonorrhoeae that are predominant in a community change over time, a phenomenon that may be due to the development of immunity to repeat infection with the same serovar. This study evaluated the epidemiologic evidence for serovar-specific immunity to N. gonorrhoeae. During a 17-month period in 1992-1994, all clients of a sexually transmitted disease clinic in rural North Carolina underwent genital culture for N. gonorrhoeae. Gonococcal isolates were serotyped according to standard methods. Odds ratios for repeat infection with the same serovar versus any different serovar were calculated on the basis of the distribution of serovars in the community at the time of reinfection. Of 2,838 patients, 608 (21.4%; 427 males and 181 females) were found to be infected with N. gonorrhoeae at the initial visit. Ninety patients (14.8% of the 608) had a total of 112 repeat gonococcal infections. Repeat infection with the same serovar occurred slightly more often than would be expected based on the serovars prevalent in the community at the time of reinfection, though the result was marginally nonsignificant (odds ratio = 1.5, 95% confidence interval 1.0-2.4; p = 0.05). Choosing partners within a sexual network may increase the likelihood of repeat exposure to the same serovar of N. gonorrhoeae. Gonococcal infection did not induce evident immunity to reinfection with the same serovar.

Antimicrobial resistance in Neisseria gonorrhoeae.

Despite a declining incidence of gonorrhea in much of the industrialized world, antimicrobial resistance continues to present a challenge to the treatment of gonococcal infections. Although no clinically significant resistance to the broad-spectrum cephalosporins has been identified, fluoroquinolone-resistant gonococcal strains are now prevalent in Australia and much of the Far East. Ongoing surveillance for antimicrobial resistance is crucial to obtain the information needed to choose effective empiric therapies for gonorrhea.

Gonorrhea in the United States, 1981-1996. Demographic and geographic trends.

OBJECTIVE: To describe demographic and geographic trends in gonorrhea incidence in the United States from 1981 through 1996. STUDY DESIGN: We analyzed aggregate gonorrhea cases reported to the Centers for Disease Control and Prevention by the 50 states, District of Columbia, and 63 large cities. Annual incidence rates (cases/100,000 persons) were calculated. RESULTS: Between 1981 and 1996, the incidence of reported gonorrhea decreased 71.3%, from 431.5 to 124.0 cases/100,000. However, rates among blacks were 35 times higher than rates among whites in 1996 (684.6 versus 19.4) compared with 11 times higher in 1981 (1,894.3 versus 164.3). Among women of all races, 15 to 19 year olds had the highest rates (716.6 in 1996), whereas among men, 20 to 24 year olds had the highest rates (512.9 in 1996). Southern states had higher rates than other regions. CONCLUSIONS: Large segments of the population, including adolescents, young adults, and blacks, continue to have high rates of gonococcal infection; prevention programs and health care providers should address the needs of these groups.

Antimicrobial resistance in Neisseria gonorrhoeae in the United States, 1988-1994: the emergence of decreased susceptibility to the fluoroquinolones.

Antimicrobial susceptibilities of Neisseria gonorrhoeae have been prospectively determined in the Gonococcal Isolate Surveillance Project of the Centers for Disease Control and Prevention. From 1988 through 1994, susceptibilities were determined for 35,263 isolates from 27 clinics. Patients were demographically similar to those in nationally reported gonorrhea cases. In 1994, 30.5% of isolates had chromosomally or plasmid-mediated resistance to penicillin or tetracycline. Penicillin resistance increased from 1988 (8.4%) to 1991 (19.5%) and then decreased in 1994 (15.6%). Tetracycline resistance decreased from 1988 (23.4%) to 1989 (17.3%) and then increased in 1994 (21.7%). Most isolates (99.9%) were highly susceptible to broad-spectrum cephalosporins. Isolates with decreased susceptibility to ciprofloxacin increased from 1991 (0.4%) to 1994 (1.3%); 4 isolates were ciprofloxacin-resistant. Ciprofloxacin-resistant strains may not respond to therapy with recommended doses of fluoroquinolones, and the clinical importance of strains with decreased susceptibility is unknown. The emergence of fluoroquinolone resistance in N. gonorrhoeae in the United States threatens the future utility of this class of antimicrobials for gonorrhea therapy.

Fluoroquinolone resistance in Neisseria gonorrhoeae.

Fluoroquinolones and broad-spectrum cephalosporins are the most effective antimicrobial agents for the treatment of gonorrhea. However, clinically significant resistance to fluoroquinolones has emerged in Neisseria gonorrhoeae. Fluoroquinolone-resistant strains account for approximately 10% of all gonococcal strains in Hong Kong and the Republic of the Philippines. As many as 50% of strains from some Far Eastern countries exhibit decreased susceptibility (intermediate resistance) to fluoroquinolones. Strains with intermediate resistance and clinically significant resistance are being isolated sporadically in North America, where resistant strains have been associated with an outbreak and with failure of infections to respond to treatment with doses of ciprofloxacin and ofloxacin recommended by the Centers for Disease Control and Prevention; strains exhibiting decreased susceptibility to these agents are endemic in at least one metropolitan area. Monitoring for fluoroquinolone resistance is now critical for ensuring adequate treatment of infections with resistant strains and for maximizing the time during which fluoroquinolones may be used to treat gonorrhea.

Vaginal discharge. How to pinpoint the cause.

Vaginal discharge is a common symptom of genital infection in women. Identifying its source can be challenging, because a large number of pathogens cause vaginal and cervical infection, and several infections may coexist. Patient history and physical examination findings may suggest a diagnosis. Useful tests for etiologic diagnosis include pH analysis of vaginal fluid, the "whiff" test, wet mount examination, culture, and Gram's stain. Once the source of infection has been identified, the patient can be treated, usually with oral antibiotics, oral antifungals, or topical vaginal preparations.