Susan van den Hof

A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999.

In 1999, an outbreak of Legionnaires’ disease affected many visitors to a flower show in the Netherlands. To identify the source of the outbreak, we performed an environmental investigation, as well as a case-control study among visitors and a serologic cohort study among exhibitors to measure exposure to possible sources. Of 77,061 visitors, 188 became ill (133 confirmed and 55 probable cases), for an attack rate of 0.23% for visitors and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the exhibition and a sprinkler in hall 8 were culture positive for Legionella pneumophila. One of three genotypes found in both whirlpool spas was identical to the isolates from 28 of 29 culture-positive patients. Persons who paused at the whirlpool spa in hall 3 were at increased risk for becoming ill. This study illustrates that whirlpool spas may be an important health hazard if disinfection fails.

Ring Vaccination and Smallpox Control

We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number R0, for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.

Measles epidemic in the Netherlands, 1999-2000.

In 1999–2000, a measles epidemic occurred in The Netherlands, with 3292 reported cases; 94% of the affected patients had not been vaccinated. Only 1 patient had received 2 doses of vaccine. Three patients died, and 16% had complications. For the unvaccinated population, the incidence per 1000 inhabitants 15 months to 14 years old increased from 83 (95% confidence interval [CI], 53–113), in municipalities with vaccine coverage rates 90%, to 200 (95% CI, 153–247), in municipalities with coverage rates 195%; for the vaccinated population, the incidence increased from 0.2 (95% CI, 0.1–0.4) to 1.4 (95% CI, 0.9–1.9). Unvaccinated individuals were 224 times (95% CI, 148–460 times) more likely to acquire measles than were vaccinated individuals; the relative risk increased with decreasing vaccine coverage. Herd immunity outside unvaccinated clusters was high enough to prevent further transmission. More case patients came from the vaccine-accepting population living among unvaccinated clusters than from individuals who declined vaccination and who lived among the vaccine-accepting population. Although measles, mumps, and rubella (MMR) national vaccine coverage is high in The Netherlands (94%–96% for both doses), coverage is not homogeneously distributed within the country [1]. In 1999, 36 (7%) of 539 municipalities had a coverage rate of !90%; 12 of those municipalities had coverage rates of !80%. These municipalities are situated in a geographic belt from the southwest to the middle of the northern part of the country (figure 1A), where a relatively high number of members of orthodox-reformed churches reside. Most individuals from these sociogeographically clustered religious communities, estimated to comprise 2% of the total population, decline vaccination. Individuals who decline vaccination for their children for other reasons may be greater in numbers but live more or less scattered throughout the country.

Evaluation of Serological and Virological Tests in the Diagnosis of Clinical and Subclinical Measles Virus Infections during an Outbreak of Measles in The Netherlands

We evaluated different approaches for diagnosing measles virus (MV) infection in unvaccinated children and in healthy contact persons (n=194) during a measles epidemic in The Netherlands. MV RNA was detected by reverse-transcriptase polymerase chain reaction in throat-swab specimens from 93% of the patients with clinical symptoms. MV RNA was detected from 5 days before until 12 days after the onset of symptoms. Most patients (88%) also secreted MV RNA in their urine until 5 weeks after the onset of symptoms. Oral fluid proved to be the most practical specimen for the simultaneous detection of MV-specific IgM antibody and viral RNA, which, together, confirmed 93% of measles cases. Viral RNA was also detected in oropharyngeal specimens from 3 healthy contact persons with serological proof of MV infection. The results of this study emphasize the feasibility of combined detection of viral RNA and MV-specific IgM antibodies in oropharyngeal specimens for the diagnosis of clinical and subclinical MV infection.

Prevalence of tuberculosis drug resistance in 10 provinces of China

BackgroundThe emergence of drug-resistant tuberculosis (TB) hampers TB control. Ten provinces in China performed drug resistance surveys among tuberculosis (TB) patients in 1996–2004 to assess levels of drug resistance.MethodsProvincial drug resistance surveys included all isolates from newly diagnosed, smear-positive TB patients. Drug susceptibility testing (DST) against isoniazid, rifampicin, streptomycin and ethambutol was carried out in the provincial laboratories. For purposes of quality assurance, a random sample (11.6%) was re-tested by the national reference laboratory (NRL).ResultsOf 14,059 patients tested 11,052 (79%) were new TB cases. The weighted mean prevalence of multi-drug resistant tuberculosis (MDR-TB) among all cases was 9.3% (range 2.2%–10.4%); 5.4% (range 2.1% – 10.4%) among new cases and 25.6% (range 11.7%–36.9%) among previously treated cases. Adjusting the drug resistance proportions using the re-testing results did not change the estimated national mean prevalence significantly. However, in some individual provinces the estimated resistance proportions were greatly influenced, especially among re-treatment patients.ConclusionMDR-TB levels varied greatly between provinces in China, but on average were high compared to the global estimated average of 4.8%. This study shows the importance of quality-assured laboratory performance. Programmatic management of drug-resistant TB, including high quality DST for patients at high risk of resistance and treatment with second-line drugs, should become the standard, especially in high MDR-TB settings.

Which New Diagnostics for Tuberculosis, and When?

Recently, new diagnostic tools for tuberculosis detection and resistance testing have become available. The World Health Organization endorses new tuberculosis diagnostics by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. This endorsement process takes place when limited evidence beyond test accuracy is available. There is a need to provide guidance to tuberculosis programs about which new diagnostics to scale up and how best to position them in diagnostic algorithms. To speed adoption of new diagnostics for tuberculosis, the policy recommendation process should be revised to consist of 2 steps: technical recommendation and programmatic recommendation. Technical recommendation would follow the GRADE process and be based on accuracy with limited cost and feasibility data, while programmatic recommendation would include patient-important outcomes, cost-effectiveness when implemented under routine conditions, and factors critical to successful scale-up. The evidence for both steps should be systematically collected, but each requires different study designs.

Infection control and the burden of tuberculosis infection and disease in health care workers in china: a cross-sectional study

BackgroundHospitals with inadequate infection control are risky environments for the emergence and transmission of tuberculosis (TB). We evaluated TB infection control practices, and the prevalence of latent TB infection (LTBI) and TB disease and risk factors in health care workers (HCW) in TB centers in Henan province in China.MethodsA cross-sectional survey was conducted in 2005. To assess TB infection control practices in TB centers, checklists were used. HCW were tuberculin skin tested (TST) to measure LTBI prevalence, and were asked for sputum smears and chest X-rays to detect TB disease, and questionnaires to assess risk factors. Differences between groups for categorical variables were analyzed by binary logistic regression. The clustered design of the study was taken into account by using a multilevel logistic model.ResultsThe assessment of infection control practices showed that only in a minority of the centers the patient consultation areas and X-ray areas were separated from the waiting areas and administrative areas. Mechanical ventilation was not available in any of the TB centers. N95 respirators were not available for HCW and surgical masks were not available for TB patients and suspects. The LTBI prevalence of HCW with and without BCG scar was 55.6% (432/777) and 49.0% (674/1376), respectively (P = 0.003). Older HCW, HCW with longer duration of employment, and HCW who worked in departments with increased contact with TB patients had a higher prevalence of LTBI. HCW who work in TB centers at the prefecture level, or with an inpatient ward also had a higher prevalence of LTBI. Twenty cases of pulmonary TB were detected among 3746 HCW. The TB prevalence was 6.7/1000 among medical staff and 2.5/1000 among administrative/logistic staff.ConclusionTB infection control in TB centers in Henan, China, appears to be inadequate and the prevalence of LTBI and TB disease among HCW was high. TB infection control practices in TB centers should be strengthened in China, including administrative measures, renovation of buildings, and use of respirators and masks. Regular screening of HCW for TB disease and LTBI needs to be considered, offering preventive therapy to those with TST conversions.

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

Background Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. Methods This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. Results In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Conclusion Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold.

Factors associated with low cure rate of tuberculosis in remote poor areas of Shaanxi Province, China: a case control study

BackgroundThe directly observed therapy-short course (DOTS) strategy was introduced in Shaanxi province, China to improve tuberculosis (TB) control by means of improved case detection (target: > = 70%) and treatment success rates (target: > = 85%) in new smear positive (SS+) TB patients. At a provincial level the targets were both reached in 2005. However in 30 (28%) out of 107 counties of Shaanxi province the cure rate was below 85%. This study aimed to investigate patient and treatment characteristics associated with non-cure after tuberculosis (TB) treatment in these counties.MethodsIn this case-control study, new smear positive TB cases in 30 counties with a cure rate <85% were included. Cured patients were compared to non-cured patients using logistic regression analysis to assess determinants for non-cure.ResultsOf the 659 patients included, 153 (23.2%) did not have cure as treatment outcome. Interruption of treatment was most strongly associated with non-cure (OR = 8.7, 95% CI 3.9-18.4). Other independent risk factors were co-morbidity, low education level, lack of appetite as an initial symptom of TB disease, diagnosis of TB outside of the government TB control institutes, missing sputum re-examinations during treatment, and not having a treatment observer. Twenty-six percent of patients did not have a treatment observer. The non-cure rate was better for those with a doctor (odds ratio (OR) 0.38, 95% confidence interval (CI) 0.17-0.88) as treatment observer than for those with a family member (OR 0.62, 95%CI 0.37-1.03). The main reason for interrupted treatment mentioned by patients was presence of adverse effects during treatment (46.5%).ConclusionsInterruption of treatment was most strongly associated with non-cure. Although treatment observation by medical staff is preferred, in order to diminish the proportion of patients who do not have a treatment observer and thereby reduce the proportion of patients who interrupt treatment, we suggest making it possible for family members, after sufficient training, to be treatment observers in remote areas where it is logistically difficult to have village doctors observe treatment for all patients.

Mycobacterial factors relevant for transmission of tuberculosis

BACKGROUND Tuberculosis (TB) transmission is associated with patient-related risk factors. However, DNA fingerprint analysis has provided anecdotal evidence suggesting a role for bacteriological factors. METHODS To examine the importance of the bacteriological component in TB transmission, we investigated the number of tuberculin skin test-positive (TST induration, ≥ 10 mm) contacts and secondary cases observed in contact investigations around TB cases in relation to the size of the genotype cluster the patient belonged to at the time of diagnosis. We also compared the number of TST-positive contacts and secondary cases of patients with drug-resistant and drug-susceptible TB. RESULTS Larger clusters were independently associated with an increased number of positive contacts. The mean number of positive contacts ranged from 3.8 for clusters of 2 cases, to 4.7 for clusters of 3-10 cases, to 6.0 for cases in clusters of >10 cases (mean increase in number of positive contacts for every extra case in the cluster, 0.21; 95% confidence interval, 0.09-0.26). The mean number of positive contacts was significantly lower among index cases with isoniazid-monoresistant TB (1.6) than among index cases with pan-susceptible TB (4.6; relative number, 0.45; 95% confidence interval, 0.22-0.92). CONCLUSION These results suggest that spread of tuberculosis also depends on bacteriological factors.