Increased hand hygiene compliance in nursing homes after a multimodal intervention: A cluster randomized controlled trial (HANDSOME).

OBJECTIVE: To assess the effect of a multimodal intervention on hand hygiene compliance (HHC) in nursing homes. DESIGN, SETTING, AND PARTICIPANTS: HHC was evaluated using direct, unobtrusive observation in a cluster randomized controlled trial at publicly funded nursing homes in the Netherlands. In total, 103 nursing home organizations were invited to participate; 18 organizations comprising 33 nursing homes (n = 66 nursing home units) participated in the study. Nursing homes were randomized into a control group (no intervention, n = 30) or an intervention group (multimodal intervention, n = 36). The primary outcome measure was HHC of nurses. HHC was appraised at baseline and at 4, 7, and 12 months after baseline. Observers and nurses were blinded. INTERVENTION: Audits regarding hand hygiene (HH) materials and personal hygiene rules, 3 live lessons, an e-learning program, posters, and a photo contest. We used a new method to teach the nurses the WHO-defined 5 moments of HH: Room In, Room Out, Before Clean, and After Dirty. RESULTS: HHC increased in both arms. The increase after 12 months was larger for units in the intervention arm (from 12% to 36%) than for control units (from 13% to 21%) (odds ratio [OR], 2.10; confidence interval [CI], 1.35-3.28). The intervention arm exhibited a statistically significant increase in HHC at 4 of the 5 WHO-defined HH moments. At follow-up, HHC in the intervention arm remained statistically significantly higher (OR, 1.93; 95% CI, 1.59-2.34) for indications after an activity (from 37% to 39%) than for indications before an activity (from 14% to 27%). CONCLUSIONS: The HANDSOME intervention is successful in improving HHC in nursing homes.

Adaptation of the Tool to Estimate Patient Costs Questionnaire into Indonesian Context for Tuberculosis-affected Households.

BACKGROUND: Indonesia is the second-highest country for tuberculosis (TB) incidence worldwide. Hence, it urgently requires improvements and innovations beyond the strategies that are currently being implemented throughout the country. One fundamental step in monitoring its progress is by preparing a validated tool to measure total patient costs and catastrophic total costs. The World Health Organization (WHO) recommends using a version of the generic questionnaire that has been adapted to the local cultural context in order to interpret findings correctly. This study is aimed to adapt the Tool to Estimate Patient Costs questionnaire into the Indonesian context, which measures total costs and catastrophic total costs for tuberculosis-affected households. METHODS: the tool was adapted using best-practice guidelines. On the basis of a pre-test performed in a previous study (referred to as Phase 1 Study), we refined the adaptation process by comparing it with the generic tool introduced by the WHO. We also held an expert committee review and performed pre-testing by interviewing 30 TB patients. After pre-testing, the tool was provided with complete explanation sheets for finalization. RESULTS: seventy-two major changes were made during the adaptation process including changing the answer choices to match the Indonesian context, refining the flow of questions, deleting questions, changing some words and restoring original questions that had been changed in Phase 1 Study. Participants indicated that most questions were clear and easy to understand. To address recall difficulties by the participants, we made some adaptations to obtain data that might be missing, such as tracking data to medical records, developing a proxy of costs and guiding interviewers to ask for a specific value when participants were uncertain about the estimated market value of property they had sold. CONCLUSION: the adapted Tool to Estimate Patient Costs in Bahasa Indonesia is comprehensive and ready for use in future studies on TB-related catastrophic costs and is suitable for monitoring progress to achieve the target of the End TB Strategy.

Socioeconomic benefit to individuals of achieving 2020 targets for four neglected tropical diseases controlled/eliminated by innovative and intensified disease management: Human African trypanosomiasis, leprosy, visceral leishmaniasis, Chagas disease.

BACKGROUND: The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). METHODS: A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011-2020 and 2021-2030. The ideal scenario in which the WHO's 2020 targets are met was compared with a counterfactual scenario that assumed the situation of 1990 stayed unaltered. Economic benefit equaled the difference between the two scenarios. Values are reported in 2005 US$, purchasing power parity-adjusted, discounted at 3% per annum from 2010. Probabilistic sensitivity analyses were used to quantify the degree of uncertainty around the base-case impact estimate. RESULTS: The total global productivity gained for the four IDM-NTDs was I$ 23.1 (I$ 15.9 -I$ 34.0) billion in 2011-2020 and I$ 35.9 (I$ 25.0 -I$ 51.9) billion in 2021-2030 (2.5th and 97.5th percentiles in brackets), corresponding to US$ 10.7 billion (US$ 7.4 -US$ 15.7) and US$ 16.6 billion (US$ 11.6 -US$ 24.0). Reduction in OPPs was I$ 14 billion (US$ 6.7 billion) and I$ 18 billion (US$ 10.4 billion) for the same periods. CONCLUSIONS: We faced important limitations to our work, such as finding no OPPs for leprosy. We had to combine limited data from various sources, heterogeneous background, and of variable quality. Nevertheless, based on conservative assumptions and subsequent uncertainty analyses, we estimate that the benefits of achieving the targets are considerable. Under plausible scenarios, the economic benefits far exceed the necessary investments by endemic country governments and their development partners. Given the higher frequency of NTDs among the poorest households, these investments represent good value for money in the effort to improve well-being, distribute the world's prosperity more equitably and reduce inequity.

[Follow-up diagnostics, referral and follow-up of hepatitis B and C patients]. / Vervolgdiagnostiek, follow-up en verwijzing van patiënten met hepatitis B en C.

OBJECTIVE: To study the extent to which follow-up diagnostics, referral to secondary care and follow-up are in accordance with the practice guideline of the Dutch College of General Practitioners 'Viral hepatitis and other liver disorders' after a hepatitis B (HBV) or C (HCV) infection has been diagnosed at the general practice. DESIGN: Retrospective cohort study. METHOD: Patient records were obtained from the Dutch 'Integrated primary care information' (IPCI) database which contains data from patients from general practices. Records of patients with a first-time positive HBsAg or anti-HCV test result in the period between 2008 and 2015 were manually validated and data on follow-up diagnostics, referral and follow-up were found. RESULTS: A total of 117 patients tested positive for HBsAg and 101 patients tested positive for anti-HCV. Most HBV patients were subsequently tested for HBeAg (92%) and ALT (80%). Of the 41 HBV patients who were eligible for referral, 37 (90%) were actually referred to a specialist. 49 HCV patients (49%) were found negative after a confirmation or RNA test. 87% of the remaining 52 HCV patients were referred (n = 45). 21 (43%) of the 49 HBV patients who were not eligible for referral were tested for ALT after an average of 11.5 months. 14 (29%) of these patients subsequently received a second follow-up ALT test and 8 (16%) received a third. CONCLUSION: Almost all HBV and HCV patients who are eligible for referral, are actually referred to a specialist. Most HBV patients received the correct follow-up diagnostics after a positive HbsAg test result. However, in few HBV patients who were not eligible for referral, was the ALT level checked every year for three years. The general practitioner, as well as the patient, should receive a reminder for this.

The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

BACKGROUND: Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)-also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. METHODS: Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. RESULTS: The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. CONCLUSION: Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment required by governments and their development partners within all reasonable scenarios. Given the concentration of the NTDs among the poorest households, these investments represent good value for money in efforts to share the world's prosperity and reduce inequity.

Concerted Efforts to Control or Eliminate Neglected Tropical Diseases: How Much Health Will Be Gained?

BACKGROUND: The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas' disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). METHODS: The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. PRINCIPLE FINDINGS/CONCLUSIONS: Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011-2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts.

Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults.

BACKGROUND: An investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01B adjuvant system is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II trial evaluating different formulations of this vaccine (containing 25µg, 50µg, or 100µg gE) was conducted in adults ≥60 years of age and showed that all formulations elicited robust cellular and humoral immune responses for up to 3 years after vaccination. In this follow-up study in subjects who received two doses of the 50µg gE/AS01B formulation (HZ/su), we assessed the persistence of the immune responses for up to 6 years after vaccination. METHODS: This phase II, open-label, multicenter, single-group trial conducted in the Czech Republic, Germany, Sweden, and the Netherlands followed 129 subjects who had received two doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune responses (frequencies of gE-specific CD4(+) T cells expressing ≥2 activation markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and 72 months after the first HZ/su dose. RESULTS: Six years after vaccination with HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody concentrations had decreased by 20-25% from month 36, but remained higher than the prevaccination values. At month 72, the gE-specific cell-mediated immune response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4 activated gE-specific CD4(+) T cells per 10(6) cells), and the anti-gE antibody concentration was 7.3 times higher than the prevaccination value (8159.0 vs. 1121.3mIU/mL). No vaccine-related serious adverse events were reported between months 36 and 72. CONCLUSIONS: gE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.

The association between hantavirus infection and selenium deficiency in mainland China.

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.

Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study.

BACKGROUND: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system AS01B. METHODS: In this phase II, single-blind, randomized, controlled study, adults aged ≥60years (N=714) received one dose of 100µggE/AS01B, two doses, two months apart, of 25, 50, or 100µggE/AS01B, or two doses of unadjuvanted 100µggE/saline. Frequencies of CD4(+) T cells expressing ≥2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. RESULTS: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01B formulations than after one dose of 100µggE/AS01B or two doses of 100µggE/saline. Frequencies were comparable after two doses of 25, 50, or 100µggE/AS01B. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100µggE/AS01B and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01B formulations were similar but greater than with gE/saline. CONCLUSIONS: The three formulations of gE/AS01B were immunogenic and well tolerated in adults aged ≥60years. Two vaccinations with gE/AS01B induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).

The combined effect of chemoprophylaxis with single dose rifampicin and immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed leprosy cases: a cluster randomized controlled trial (MALTALEP study).

BACKGROUND: Despite almost 30 years of effective chemotherapy with MDT, the global new case detection rate of leprosy has remained quite constant over the past years. New tools and methodologies are necessary to interrupt the transmission of M. leprae. Single-dose rifampicin (SDR) has been shown to prevent 57% of incident cases of leprosy in the first two years, when given to contacts of newly diagnosed cases. Immunization of contacts with BCG has been less well documented, but appears to have a preventive effect lasting up to 9 years. However, one major disadvantage is the occurrence of excess cases within the first year after immunization. The objective of this study is to examine the effect of chemoprophylaxis with SDR and immunoprophylaxis with BCG on the clinical outcome as well as on host immune responses and gene expression profiles in contacts of newly diagnosed leprosy patients. We hypothesize that the effects of both interventions may be complementary, causing the combined preventive outcome to be significant and long-lasting. METHODS/DESIGN: Through a cluster randomized controlled trial we compare immunization with BCG alone with BCG plus SDR in contacts of new leprosy cases. Contact groups of around 15 persons will be established for each of the 1300 leprosy patients included in the trial, resulting in approximately 20,000 contacts in total. BCG will be administered to the intervention group followed by SDR, 2 months later. The control group will receive BCG only. In total 10,000 contacts will be included in both intervention arms over a 2-year period. Follow-up will take place one year as well as two years after intake. The primary outcome is the occurrence of clinical leprosy within two years. Simultaneously with vaccination and SDR, blood samples for in vitro analyses will be obtained from 300 contacts participating in the trial to determine the effect of these chemo- and immunoprophylactic interventions on immune and genetic host parameters. DISCUSSION: Combined chemoprophylaxis and immunoprophylaxis is potentially a very powerful and innovative tool aimed at contacts of leprosy patients that could reduce the transmission of M. leprae markedly. The trial intends to substantiate this potential preventive effect. Evaluation of immune and genetic biomarker profiles will allow identification of pathogenic versus (BCG-induced) protective host biomarkers and could lead to effective prophylactic interventions for leprosy using optimized tools for identification of individuals who are most at risk of developing disease. TRIAL REGISTRATION: Netherlands Trial Register: NTR3087.

Care-seeking behaviour among individuals with TB symptoms in Jogjakarta Province, Indonesia: a community-based study.

BACKGROUND: Care-seeking behaviour of individuals with TB symptoms is a critical factor in early detection and treatment. Thorough understanding of determinants of the care-seeking process helps TB programme managers to improve TB case finding. The aim of this study was to assess determinants of care-seeking behaviour among patients with suspected TB at the population level. METHODS: A cross-sectional survey was conducted among adults with cough for >2 weeks. Data on sociodemographics, onset of TB symptoms, TB knowledge, health facility visited and duration of each visit were collected. RESULTS: Of the 746 respondents interviewed, approximately 10% had not yet sought care. Of those who sought care, less than one-half presented directly to medical healthcare providers. Being female and having multiple symptoms were associated with care-seeking action. The duration of patient delay (i.e. time between onset of symptoms and visiting a health provider) was relatively short, which may be due to the availability of an extended network of healthcare providers in Jogjakarta Province. Being male, a student or self-employed were associated with longer delay in presentation. CONCLUSIONS: Patient delay was relatively short. Efforts need to be focused on encouraging individuals with suspected TB to seek appropriate services through health education and quality improvement of health providers.

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.

BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n=247), HepB (n=247) or HPV co-administered with HepB (HPV+HepB; n=247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort. RESULTS: The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated. CONCLUSIONS: The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov registration number NCT00652938.

Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study.

Six years have passed since the outbreak of severe acute respiratory syndrome (SARS). Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time in recovered SARS patients. It is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another SARS outbreak. Recovered SARS patients were followed up to 6 y to estimate the longevity of specific Ab. The specific memory B cell and T cell responses to SARS-CoV Ags were measured by means of ELISPOT assay. Factors in relation to humoral and cellular immunity were investigated. Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients. Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls. Patients with more severe clinical manifestations seemed to present a higher level of Ag-specific memory T cell response. SARS-specific IgG Ab may eventually vanish and peripheral memory B cell responses are undetectable in recovered SARS patients. In contrast, specific T cell anamnestic responses can be maintained for at least 6 y. These findings have applications in preparation for the possible reemergence of SARS.

Anaplasma phagocytophilum in livestock and small rodents.

To identify the prevalence of Anaplasma phagocytophilum in both wild rodents and domestic animals and to make clear the genetic characteristics of the agents from different animals in China, a total of 105 livestock and 159 small rodents were analyzed by real-time-PCR and sequence analysis. The prevalence rate was 6.7% (7/105) and 14.5% (23/159), respectively. The nucleotide sequences of 16S rRNA (rrs) from the positive livestock and rodents were identical to each other. The phylogenetic analysis based on partial A. phagocytophilum p44ESup1 gene revealed that A. phagocytophilum identified in this study was placed on a separate clade distinct from those in other continents. These findings indicated A. phagocytophilum in rodents might be able to infect livestock and intensified the threats of anaplasmosis to livestock in the area. Further studies on public health significance of the agent are worth investigation in future.

Anaplasma phagocytophilum from Rodents and Sheep, China.

To characterize the strains of Anaplasma phagocytophilum in wild and domestic animals in China, we isolated the organism from rodents and sheep in northeastern China. We isolated 3 strains (2 from rodents and 1 from sick sheep) through propagation in BALB/c mice and then cell culture in HL60 cells. The 3 isolates were identified by Wright-Giemsa staining, immunofluorescence, and electronic microscopy and were characterized by sequence analyses of the 16S rRNA gene, partial citrate synthase gene, major surface protein 4 gene, and heat shock protein gene. The multiple sequences of the 3 isolates were identical to each other but different from all known strains from other countries. The public health and veterinary relevance of the isolates deserves further investigation.

Tick-borne agents in rodents, China, 2004-2006.

A total of 705 rodents from 6 provinces and autonomous regions of mainland People's Republic of China were tested by PCRs for tick-borne agents (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, spotted fever group rickettsiae, and Francisella tularensis). Infection rates were 5.5%, 6.7%, 9.1% and 5.0%, respectively. Eighteen (2.6%) rodents of 10 species were positive for 2 or 3 agents. Sequence analysis of PCR products confirmed the presence and genotypes of detected agents. These findings demonstrate that these tick-borne agents cocirculate and that a variety of rodent species may be involved in their enzootic maintenance.

A Mycobacterium tuberculosis cluster demonstrating the use of genotyping in urban tuberculosis control.

BACKGROUND: DNA fingerprinting of Mycobacterium tuberculosis isolates offers better opportunities to study links between tuberculosis (TB) cases and can highlight relevant issues in urban TB control in low-endemic countries. METHODS: A medium-sized molecular cluster of TB cases with identical DNA fingerprints was used for the development of a visual presentation of epidemiologic links between cases. RESULTS: Of 32 cases, 17 (53%) were linked to the index case, and 11 (34%) to a secondary case. The remaining four (13%) could not be linked and were classified as possibly caused by the index patient. Of the 21 cases related to the index case, TB developed within one year of the index diagnosis in 11 patients (52%), within one to two years in four patients (19%), and within two to five years in six patients (29%). CONCLUSION: Cluster analysis underscored several issues for TB control in an urban setting, such as the recognition of the outbreak, the importance of reinfections, the impact of delayed diagnosis, the contribution of pub-related transmissions and its value for decision-making to extend contact investigations. Visualising cases in a cluster diagram was particularly useful in finding transmission locations and the similarities and links between patients.

Effects of a short individually tailored counselling session for HIV prevention in gay and bisexual men receiving Hepatitis B vaccination.

BACKGROUND: There is currently a trend towards unsafe unprotected anal intercourse (UAI) among men who have sex with men. We evaluated a short individual counselling session on reducing UAI among gay and bisexual men. METHODS: A quasi-experimental design was used to evaluate the counselling session. This session was conducted during consulting hours at four municipal health clinics during a Hepatitis B vaccination campaign. These clinics offered free vaccination to high-risk groups, such as gay and bisexual men.All gay and bisexual men attending health clinics in four cities in the Netherlands were asked to participate. Each participant in the intervention group received a fifteen-minute individual counselling based on the Theory of Planned Behaviour and Motivational Interviewing. Changes in UAI were measured over a 5-months period, using self-administered questionnaires. UAI was measured separately for receptive and insertive intercourse in steady and casual partners. These measures were combined in an index-score (range 0-8). RESULTS: While UAI in the counselling group remained stable, it increased in the controls by 66% from 0.41 to 0.68. The results show that the intervention had a protective effect on sexual behaviour with steady partners. Intervention effects were strongest within steady relationships, especially for men whose steady-relationship status changed during the study. The intervention was well accepted among the target group. CONCLUSION: The fifteen-minute individually tailored counselling session was not only well accepted but also had a protective effect on risk behaviour after a follow-up of six months.

Lower cellular immune responses to influenza A (H3N2) in the elderly.

Influenza epidemic is an important cause of severe illness in the elderly. Age-dependent morbidity of influenza in the elderly is associated with weakened immunity. The baseline age-related memory T cell activity in Chinese persons who are exposed to influenza virus through natural infection, are associated with the protective response to the virus after vaccination, thus providing important pre-vaccination information. A cohort from the general population was established at the end of an influenza season in an area where influenza occurs regularly, and followed for 24 weeks. The subjects had no vaccination history for 5 years. Memory T cell responses were evaluated using a set of peptides spanning the influenza A (H3N2) entire proteome in a gamma interferon (IFN-gamma)-enzyme-linked immunospot (ELISPOT) assay, prior to the next influenza season. Changes of hemagglutination inhibition (HI) antibody titers were also evaluated. IFN-gamma(+) T cell responses against influenza peptides were significantly lower in subjects of 60 years and older. Although the age-related decline of cellular immune response was clear, no significant association of antibody titers with age was found. The pre-vaccination baseline of memory IFN-gamma(+) T cell immunity state in elderly Chinese was significantly lower than in people younger than 60 years. Measurement of the ex vivo cellular immune responses to influenza should be incorporated into the evaluation of protective immunity in elderly persons.