The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.

Determining target populations for leprosy prophylactic interventions: a hotspot analysis in Indonesia.

BACKGROUND: Leprosy incidence remained at around 200,000 new cases globally for the last decade. Current strategies to reduce the number of new patients include early detection and providing post-exposure prophylaxis (PEP) to at-risk populations. Because leprosy is distributed unevenly, it is crucial to identify high-risk clusters of leprosy cases for targeting interventions. Geographic Information Systems (GIS) methodology can be used to optimize leprosy control activities by identifying clustering of leprosy cases and determining optimal target populations for PEP. METHODS: The geolocations of leprosy cases registered from 2014 to 2018 in Pasuruan and Pamekasan (Indonesia) were collected and tested for spatial autocorrelation with the Moran's I statistic. We did a hotspot analysis using the Heatmap tool of QGIS to identify clusters of leprosy cases in both areas. Fifteen cluster settings were compared, varying the heatmap radius (i.e., 500 m, 1000 m, 1500 m, 2000 m, or 2500 m) and the density of clustering (low, moderate, and high). For each cluster setting, we calculated the number of cases in clusters, the size of the cluster (km2), and the total population targeted for PEP under various strategies. RESULTS: The distribution of cases was more focused in Pasuruan (Moran's I = 0.44) than in Pamekasan (0.27). The proportion of total cases within identified clusters increased with heatmap radius and ranged from 3% to almost 100% in both areas. The proportion of the population in clusters targeted for PEP decreased with heatmap radius from > 100% to 5% in high and from 88 to 3% in moderate and low density clusters. We have developed an example of a practical guideline to determine optimal cluster settings based on a given PEP strategy, distribution of cases, resources available, and proportion of population targeted for PEP. CONCLUSION: Policy and operational decisions related to leprosy control programs can be guided by a hotspot analysis which aid in identifying high-risk clusters and estimating the number of people targeted for prophylactic interventions.

Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.

Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.

Chronic hepatitis B and C infections in the Netherlands: estimated prevalence in risk groups and the general population.

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are usually asymptomatic for decades, thus targeted screening can prevent liver disease by timely diagnosis and linkage to care. More robust estimates of chronic HBV and HCV infections in the general population and risk groups are needed. Using a modified workbook method, the total number of ever chronically infected individuals in the Netherlands in 2016 was determined using population size and prevalence estimates from studies in the general and high-risk population. The estimated 2016 chronic HBV infection prevalence is 0.34% (low 0.22%, high 0.47%), corresponding to approximately 49 000 (low 31 000, high 66 000) HBV-infected individuals aged 15 years and older. The estimated ever-chronic HCV infection prevalence is 0.16% (low 0.06%, high 0.27%), corresponding to approximately 23 000 (low 8000, high 38 000) ever-chronic HCV-infected individuals. The prevalence of chronic HBV and HCV infections in the Netherlands is low. First-generation migrants account for most infections with 81% and 60% of chronic HBV and HCV infections, respectively. However, about one-fifth of HCV infections is found in the general population at low risk. This method can serve as an example for countries in need of more accurate prevalence estimates, to help the design and evaluation of prevention and control policies.

Introducing leprosy post-exposure prophylaxis into the health systems of India, Nepal and Indonesia: a case study.

BACKGROUND: Leprosy has a wide range of clinical and socio-economic consequences. India, Indonesia and Nepal contribute significantly to the global leprosy burden. After integration, the health systems are pivotal in leprosy service delivery. The Leprosy Post Exposure Prophylaxis (LPEP) program is ongoing to investigate the feasibility of providing single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) to the contacts of leprosy cases in various health systems. We aim to compare national leprosy control programs, and adapted LPEP strategies in India, Nepal and Indonesia. The purpose is to establish a baseline of the health system's situation and document the subsequent adjustment of LPEP, which will provide the context for interpreting the LPEP results in future. METHODS: The study followed the multiple-case study design with single units of analysis. The data collection methods were direct observation, in-depth interviews and desk review. The study was divided into two phases, i.e. review of national leprosy programs and description of the LPEP program. The comparative analysis was performed using the WHO health system frameworks (2007). RESULTS: In all countries leprosy services including contact tracing is integrated into the health systems. The LPEP program is fully integrated into the established national leprosy programs, with SDR and increased documentation, which need major additions to standard procedures. PEP administration was widely perceived as well manageable, but the additional LPEP data collection was reported to increase workload in the first year. CONCLUSIONS: The findings of our study led to the recommendation that field-based leprosy research programs should keep health systems in focus. The national leprosy programs are diverse in terms of organizational hierarchy, human resource quantity and capacity. We conclude that PEP can be integrated into different health systems without major structural and personal changes, but provisions are necessary for the additional monitoring requirements.

Improving hand hygiene compliance in child daycare centres: a randomized controlled trial.

Gastrointestinal and respiratory infections in children attending daycare centres (DCCs) are common and compliance with hand hygiene (HH) guidelines to prevent infections is generally low. An intervention was developed to increase HH compliance and reduce infections in DCCs. The objective of this paper was to evaluate the effectiveness of this intervention on HH compliance. The intervention was evaluated in a two-arm cluster randomized controlled trial in 71 DCCs in The Netherlands. Thirty-six DCCs received the intervention including: (1) HH products; (2) training about HH guidelines; (3) two team training sessions aimed at goal setting and formulating HH improvement activities; and (4) reminders and cues for action (posters/stickers). Intervention DCCs were compared to 35 control DCCs that continued usual practice. HH compliance of caregivers and children was observed at baseline and at 1, 3 and 6 months follow-up. Using multilevel logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were obtained for the intervention effect. Of 795 caregivers, 5042 HH opportunities for caregivers and 5606 opportunities for supervising children's HH were observed. At 1 month follow-up caregivers' compliance in intervention DCCs was 66% vs. 43% in control DCCs (OR 6·33, 95% CI 3·71-10·80), and at 6 months 59% vs. 44% (OR 4·13, 95% CI 2·33-7·32). No effect of the intervention was found on supervising children's HH (36% vs. 32%; OR 0·64, 95% CI 0·18-2·33). In conclusion, HH compliance of caregivers increased due to the intervention, therefore dissemination of the intervention can be considered.

A hand hygiene intervention to reduce infections in child daycare: a randomized controlled trial.

Infections are common in children attending daycare centres (DCCs). We evaluated the effect of a hand hygiene (HH) intervention for caregivers on the incidence of gastrointestinal and respiratory infections in children. The intervention was evaluated in a two-arm cluster randomized controlled trial. Thirty-six DCCs received the intervention including HH products, training sessions, and posters/stickers. Thirty-five control DCCs continued usual practice. Incidence of episodes of diarrhoea and the common cold in children was monitored by parents during 6 months. Using multilevel Poisson regression, incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were obtained. Diarrhoeal incidence was monitored in 545 children for 91 937 days. During follow-up, the incidence was 3·0 episodes per child-year in intervention DCCs vs. 3·4 in control DCCs (IRR 0·90, 95% CI 0·73-1·11). Incidence of the common cold was monitored in 541 children for 91 373 days. During follow-up, the incidence was 8·2 episodes per child-year in intervention DCCs vs. 7·4 in control DCCs (IRR 1·07, 95% CI 0·97-1·19). In this study, no evidence for an effect of the intervention was demonstrated on the incidence of episodes of diarrhoea and the common cold.

A quality assessment index framework for public health services: a Delphi study.

OBJECTIVES: This study sought consensus-based indices for quality assessment of the public health service (QAPHS) to evaluate the service quality of public health in Shenzhen and other cities in China. STUDY DESIGN: A qualitative study. METHODS: A list of quality assessment indices was formed based on Donabedian theory. These indices were presented to an expert panel in a two-round Delphi study to establish a consensus view. A weight of indices was established to validate the applicability and practicability of the framework. The specialist authority coefficient and Kendall's W were also calculated based on statistical analysis. RESULTS: A total of 30 experts participated in the Delphi study. Consensus was reached on four first-grade indices, nine second-grade indices and 28 third-grade indices. The specialist authority coefficient (Cr) was high (between 0.88 and 0.92), while Kendall's coefficient (W) of all the indices was ＞0.5 with statistical significant differences (P ＜ 0.05). This indicated correlation among panelists and had high reliability. CONCLUSIONS: A unified and hierarchical quality assessment index framework for public health services was established. The framework should be further tested and improved in practice.

Predictors of HPV vaccination uptake: a longitudinal study among parents.

To assess among parents longitudinal predictors of human papillomavirus (HPV) vaccination uptake for their daughters, random samples of parents were identified via municipal services and sent baseline questionnaires in June 2009 and follow-up questionnaires in November 2011 after their uptake decision. Hierarchical logistic regression analysis was used to assess whether demographic characteristics, and affective and social cognitive factors, predicted uptake at follow-up. Response rates of the baseline and follow-up questionnaire were 29.8% (1762/5918) and 74.3% (793/1067), respectively. Uptake was predicted by a later (2011) versus earlier (2010) decision about uptake as HPV vaccination implementation [odds ratio (OR) 2.48; 95% confidence interval (CI) 1.11-5.52], anticipated regret about no uptake (OR 1.43; 95% CI 1.08-1.89) and intention (OR 2.61; 95% CI 1.47-4.61). There was an interaction between ambivalence and attitude (OR 1.68; 95% CI 1.14-2.47); parents with a positive attitude and a high ambivalence toward vaccination were more likely to have their daughter vaccinated than parents with a positive attitude and a low ambivalence. An informed choice about uptake (5/7 correct items) was made by 44%. In conclusion, uptake was predicted by intention, a later (2011) versus earlier (2010) decision and by anticipated regret about no uptake. Decisions regarding new vaccines are difficult to make, we recommend a well-balanced implementation process.

Prevalence and risk factors of syphilis infection among female sex workers in Shenzhen, China: an observational study (2009-2012).

OBJECTIVE: To investigate prevalence and risk factors of syphilis infection among female sex workers (FSWs) in Shenzhen, China. METHODS: Observational study among (2009-2012) 1653 FSWs recruited by venue-based sampling using questionnaire-based interviews for socio-demographics, behaviours and syphilis testing results. Logistic regression was used to assess risk factors of syphilis infection. RESULTS: The overall syphilis prevalence was 4.7%, showing a slightly decreasing trend. Factors significantly associated with syphilis infection were inconsistent condom use (OR = 1.87, P = 0.015), illicit drug use (OR = 5.45, P < 0.001) and older age in years (OR = 1.08, P < 0.001). Venues where FSWs were recruited and duration of commercial sex work were not significantly associated with syphilis infection (P > 0.05). CONCLUSIONS: Syphilis is still common among FSWs in Shenzhen, China. Current comprehensive prevention programmes (e.g. condom promotion and peer education) should be continued to maintain and increase safe sexual practices and to reduce illicit drug use among FSWs. Expanding point-of-care syphilis screening programmes may be an important strategy for early diagnosis. We recommend timely and effective treatment programmes to be linked to such screening programmes.

Social contact patterns and leprosy disease: a case-control study in Bangladesh.

Socioeconomic and culturally defined social contact patterns are expected to be an important determinant in the continuing transmission of Mycobacterium leprae in leprosy-endemic areas. In a case-control study in two districts in Bangladesh, we assessed the association between social contact patterns and the risk of acquiring clinical leprosy. Social contacts of 90 recently diagnosed patients were compared to those of 199 controls. Leprosy was associated with a more intensive social contact pattern in the home [odds ratio (OR) 1·09, 95% confidence interval (CI) 1·00-1·19, P = 0·043] and in the nearby neighbourhood (OR 1·07, 95% CI 1·03-1·11, P = 0·001). Although it is known that M. leprae spreads most easily within households of infected persons, in endemic areas social contacts within the neighbourhood, village or urban ward, also appear to be important for transmission. We advise that disease control measures in leprosy-endemic areas should not be limited to households, but include high-risk groups in the nearby neighbourhood of patients.

Unhealthy behaviour is contagious: an invitation to exploit models for infectious diseases.

We argue that the spread of unhealthy behaviour shows marked similarities with infectious diseases. It is therefore interesting and challenging to use infectious disease methodologies for studying the spread and control of unhealthy behaviour. This would be a great addition to current methods, because it allows taking into account the dynamics of individual interactions and the social environment at large. In particular, the application of individual-based modelling holds great promise to address some major public health questions.

Participation of private providers in the National TB Programme in South India.

SETTING: India has the highest number of new TB cases worldwide. The participation of private providers (PPs) in the National TB Elimination Programme (NTEP) has remained suboptimal. OBJECTIVE: To explore the experiences, barriers and facilitators about their participation in the NTEP as perceived by PPs working in varied settings. DESIGN: Focus group discussions and in-depth interviews were used to engage PPs to obtain their views on participation in the NTEP. Framework and thematic content analysis was used to analyse qualitative data. RESULTS: Non-availability of a comprehensive range of diagnostics and lack of flexibility in the NTEP were barriers to participation in NTEP. PPs were predisposed to think that NTEP was for those who could not afford to purchase medications. Attitudes and previous experiences with NTEP made them sceptical about the NTEP regimen. Although more frequent interactions were sought with NTEP, some bitterness about previous interactions was perceived. CONCLUSION: Challenges identified by PPs for the NTEP include improvement of the quality of TB care, especially at the lower levels of care, availability of a comprehensive range of diagnostics, being friendly to PPs and patients, more frequent interactions with PPs, and more caring conversations with patients at NTEP centres.

CONTEXTE: L'Inde est le pays qui compte le plus grand nombre de nouveaux cas de TB dans le monde. La participation des prestataires privés (PP) au programme national d'élimination de la TB (NTEP) est restée sous-optimale. OBJECTIF: Explorer les expériences, les obstacles et les facilitateurs de leur participation au NTEP, tels qu'ils sont perçus par les prestataires privés travaillant dans des contextes variés. MÉTHODE: Des discussions de groupe et des entretiens approfondis ont été organisés afin d'obtenir le point de vue des professionnels de la santé sur leur participation au NTEP. L'analyse de cadre et de contenu thématique a été utilisée pour analyser les données qualitatives. RÉSULTATS: La non-disponibilité d'une gamme complète de diagnostics et le manque de flexibilité du NTEP ont constitué des obstacles à la participation au NTEP. Les PP étaient prédisposés à penser que le NTEP était destiné à ceux qui n'avaient pas les moyens d'acheter des médicaments. Les attitudes et les expériences antérieures avec le NTEP les ont rendus sceptiques quant au régime du NTEP. Bien qu'ils aient souhaité des interactions plus fréquentes avec le NTEP, ils ont ressenti une certaine amertume à l'égard des interactions antérieures. CONCLUSION: Les défis identifiés par les PP pour le NTEP comprennent l'amélioration de la qualité des soins antituberculeux, en particulier aux niveaux inférieurs de soins, la disponibilité d'une gamme complète de diagnostics, l'amabilité envers les PP et les patients, des interactions plus fréquentes avec les PP et des conversations plus attentionnées avec les patients dans les centres du NTEP.

The effect of a hand hygiene intervention on infections in residents of nursing homes: a cluster randomized controlled trial.

BACKGROUND: The primary goal of hand hygiene is to reduce infectious disease rates. We examined if a nursing home's participation in a hand hygiene intervention resulted in residents having fewer healthcare associated infections (HAIs) when compared to nursing homes without the hand hygiene intervention. METHODS: This study is a part of a cluster randomized controlled trial (RCT) in 33 nursing homes to improve hand hygiene (HANDSOME). The incidence of five illnesses was followed over 13 months: gastroenteritis, influenza-like illness, pneumonia, urinary tract infections and infections from methicillin-resistant Staphylococcus aureus (MRSA). Incidence rates per study arm were reported for baseline (October-December 2016) and two follow-up periods (January-April 2017, May-October 2017). HAI rates were compared in a Poisson multilevel analysis, correcting for baseline differences (the baseline infection incidence and the size of the nursing home), clustering of observations within nursing homes, and period in the study. RESULTS: There was statistically significantly more gastroenteritis (p < 0.001) and statistically significantly less influenza-like illness (p < 0.01) in the intervention arm when compared to the control arm. There were no statistically significant differences or pneumonia, urinary tract infections, and MRSA infections in the intervention arm when compared to the control arm. In a sensitivity analysis, gastroenteritis was no longer statistically significantly higher in the intervention arm (p = 0.92). CONCLUSIONS: As in comparable studies, we could not conclusively demonstrate the effectiveness of an HH intervention in reducing HAIs among residents of nursing homes, despite the use of clearly defined outcome measures, a standardized reporting instrument, and directly observed HH in a multicenter cluster RCT. Trial registration Netherlands Trial Register, trial NL6049 (NTR6188). Registered October 25, 2016, https://www.trialregister.nl/trial/6049 .

Association of environmental surface contamination with hand hygiene and infections in nursing homes: a prospective cohort study.

BACKGROUND: Little is known about the presence of infections in nursing home residents, the causative micro-organisms, how hand hygiene (HH) influences the presence of infections in residents, and the extent to which environmental contamination is associated with the incidence of infection among residents. AIMS: To establish if environmental contamination can be used as an indicator for HH compliance, and if environmental contamination is associated with the incidence of infection. METHODS: Environmental surface samples (ESS) were collected in an exploratory study as part of a HH intervention in 60 nursing homes. ESS results from three distinct surfaces (nurses' station, communal toilet and residents' shared living area) were compared with nurses' HH compliance and the incidence of infection among residents. Real-time polymerase chain reaction assays were used to detect norovirus genogroup I and II, rhinovirus and Escherichia coli. HH compliance was measured by direct observation. The incidence of infection was registered weekly. FINDINGS: Rhinovirus (nurses' station: 41%; toilet: 14%; living area: 29%), norovirus (nurses' station: 18%; toilet: 12%; living area: 16%) and E. coli (nurses' station: 14%; toilet: 58%; living area: 54%) were detected. No significant (P<0.05) associations were found between HH compliance and the presence of micro-organisms. An association was found between E. coli contamination and the incidence of disease in general (P=0.04). No other associations were found between micro-organisms and the incidence of disease. CONCLUSION: Rhinovirus, norovirus and E. coli were detected on surfaces in nursing homes. No convincing associations were found between environmental contamination and HH compliance or the incidence of disease. This study provides reference data about surface contamination.

Transmission of methicillin-resistant Staphylococcus aureus to household contacts.

The frequency of and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) transmission from a MRSA index person to household contacts were assessed in this prospective study. Between January 2005 and December 2007, 62 newly diagnosed MRSA index persons (46 patients and 16 health care workers) and their 160 household contacts were included in the study analysis. Transmission of MRSA from an index person to household contacts occurred in nearly half of the cases (47%; n = 29). These 29 index persons together had 84 household contacts, of which two-thirds (67%; n = 56) became MRSA positive. Prolonged exposure time to MRSA at home was a significant risk factor for MRSA transmission to household contacts. In addition, MRSA colonization at least in the throat, younger age, and eczema in index persons were significantly associated with MRSA transmission; the presence of wounds was negatively associated with MRSA transmission. Furthermore, an increased number of household contacts and being the partner of a MRSA index person were household-related risk factors for MRSA acquisition from the index person. No predominant pulsed-field gel electrophoresis (PFGE) type was observed to be transmitted more frequently than other PFGE types. To date, screening household contacts and providing MRSA eradication therapy to those found positive simultaneously with the index person is not included in the "search-and-destroy" policy. We suggest including both in MRSA prevention guidelines, as this may reduce further spread of MRSA.

[Prevention and control of infectious diseases with pandemic potential: the EU-project SARSControl]. / Prävention und Kontrolle von pandemischen Infektionskrankheiten: Das EU-Projekt SARSControl.

INTRODUCTION: The influenza pandemics of the 20th century, the SARS epidemic in 2002/03 and the growing number of human cases infected with the H5N1 avian influenza virus clearly demonstrate that the threat of new pandemics is very real. These events have intensified pandemic prevention and control activities worldwide. "SARSControl" is a three-year project funded by the European Commission with the objective to aid European member states in the public health management of new emerging infections. This article summarises the main research results and recommendations arising from this project. METHOD: The reports and papers published in the SARSControl project form the basis of this article. In addition, a literature search for SARS and pandemic influenza was conducted and information on pandemic planning and management guidelines obtained from the WHO and EU websites. The project results are discussed in this context. RESULTS: A lack of knowledge and delayed international communication resulted in the rapid spread of SARS, highlighting the importance of a global system for rapid and transparent information transfer. Epidemiological and economic modelling studies have shown that, in comparison to travel restrictions, applying intervention measures to interrupt local transmission within a country and investing into vaccine research and anti-viral stockpiling, is a more cost-effective and efficient use of resources for the containment of pandemics. A study investigating the perceived threat associated with pandemics showed that the subjective risk perception of people varies among countries. This influences human behaviour and should hence be considered during risk communication and implementation of pandemic control measures. DISCUSSION: The basic prerequisites of an efficient pandemic management are operationalisable pandemic plans, subjected to regular exercises, backed by adequate resources and a sound health-care infrastructure. At international level cross-border co-operation and information exchange on infection control is the key to pandemic mitigation and containment. Strengthening surveillance systems at the international level, to allow the timely monitoring of infectious agents and outbreaks is essential. Transferring such outbreak information in real time into mathematical models and the resulting essential epidemiological information to policy makers would facilitate a more efficient use of scarce resources. Involvement of the public in decisions regarding the implementation of restrictive control measures which often curtail individual liberty is necessary for the acceptance and ultimate success of pandemic control.

Transmission classification model to determine place and time of infection of tuberculosis cases in an urban area.

We conducted a population-based study in the Rotterdam region of The Netherlands to determine the place and time of infection of tuberculosis (TB) cases using conventional epidemiological and genotyping information. In particular, we focused on the extent of misclassification if genotyping was not combined with epidemiological information. Cases were divided into those with a unique mycobacterial DNA fingerprint, a clustering fingerprint, and an unknown fingerprint. We developed transmission classification trees for each category to determine whether patients were infected in a foreign country or recently (2 years) infected in The Netherlands. Of all TB cases during the 12-year study period, 38% were infected in a foreign country, 36% resulted from recent transmission in The Netherlands, and 18% resulted from remote infection in The Netherlands, while in the remaining cases (9%) either the time or place of infection could not be determined. The conventional epidemiological data suggested that at least 29% of clustered cases were not part of recent chains of transmission. Cases with unknown fingerprints, almost all culture negative, relatively frequently had confirmed epidemiological links with a recent pulmonary TB case in The Netherlands and were more often identified by contact tracing. Our findings highlight the idea that genotyping should be combined with conventional epidemiological investigation to establish the place and time of infection of TB cases as accurately as possible. A standardized way of classifying TB into recently, remotely, and foreign-acquired disease provides indicators for surveillance and TB control program performance that can be used to decide on interventions and allocation of resources.

MUSIDH, multiple use of simulated demographic histories, a novel method to reduce computation time in microsimulation models of infectious diseases.

Microsimulation of infectious diseases requires simulation of many life histories of interacting individuals. In particular, relatively rare infections such as leprosy need to be studied in very large populations. Computation time increases disproportionally with the size of the simulated population. We present a novel method, MUSIDH, an acronym for multiple use of simulated demographic histories, to reduce computation time. Demographic history refers to the processes of birth, death and all other demographic events that should be unrelated to the natural course of an infection, thus non-fatal infections. MUSIDH attaches a fixed number of infection histories to each demographic history, and these infection histories interact as if being the infection history of separate individuals. With two examples, mumps and leprosy, we show that the method can give a factor 50 reduction in computation time at the cost of a small loss in precision. The largest reductions are obtained for rare infections with complex demographic histories.

[Chronic hepatitis B virus (HBV) infection: usefulness of the combination of HBeAg and ALT determination to predict a high HBV-DNA level and therefore the necessity of referral to a specialist for possible antiviral treatment]. / Chronische hepatitis B-virus(HBV)-infectie: bruikbaarheid van de combinatie van HBeAg- en ALAT-bepaling als voorspeller van een hoog HBV-DNA-niveau en voor verwijzing naar de 2e lijn voor eventuele antivirale behandeling.

OBJECTIVE: To assess the usefulness of a simple practical guideline based on hepatitis B e-antigen (HBeAg) status and a single alanine aminotransferase (ALT) determination to predict hepatitis B virus (HBV) load in chronic HBV patients as a criterion for referral to a specialist for possible antiviral therapy. DESIGN: Prospective observational study. METHOD: 420 patients with chronic HBV infection were seen at the Municipal Health Service (MHS) in Rotterdam between 2002 and 2005. The usefulness ofa guideline based on HBeAg positivity and/or elevated ALT levels to predict high HBV DNA levels (defined as more than 10(5) copies/ml) was determined. Patients with HBeAg or an elevated ALT level were referred to a specialist according to the practical guideline. Positive and negative predictive value, sensitivity, and specificity of the referral guideline for a high HBV-DNA level were calculated. RESULTS: Less than half, 43% (181/420) of the patients, were eligible for referral to specialist care. The positive predictive value of the referral guideline was 45% (82/181, 95% CI: 38-53). The negative predictive value, i.e. the proportion of patients with low viral loads who were (rightly) not selected for referral, was 95% (227/239; 95% CI: 71-97). The sensitivity was 87% (95% CI: 80-93): the patients selected included 82 of 94 patients with a high HBV DNA level. Of the 12 patients with high viral loads not referred according to the guideline, 11 had a viral load of between 10(5)-10(6) copies/ml. CONCLUSION: A referral guideline based on HBeAg status and a single ALT determination can successfully predict viral load in chronic HBV patients and can be used in primary care to select patients for referral to specialist care. This guideline may limit the number of unnecessarily referred patients, enhancing the efficiency of the care for patients with chronic HBV infection.