Ingela Berggren

Primary Tuberculosis Infection in 35 Children at a Swedish Day Care Center

Background and Method: The decline of tuberculosis (TB) in the Swedish population since the middle of the 20th century resulted in decreased awareness of the disease. Increased migration from TB-endemic countries has resulted in new cases and risk of transmission. A day care provider was diagnosed with cavitary TB after being symptomatic for 5 months. We describe the contact tracing at the day care center, the clinical and radiographic findings, and treatment of the infected children. Results: We stratified the children by contact with the source case and examined the most exposed first. Thirty-two of 53 attending and 3 of 84 visiting preschool children were infected. All of them had spent at least 3 days at the center. Symptoms were usually mild and nonspecific. Seventeen children had pulmonary radiographic changes compatible with primary TB, and one had miliary TB. The radiographic resolution was slow, with normalization in 50% after 12 months. Eighteen months after termination of treatment, there have been no relapses. The children with latent infection were treated with rifampin for 4 months and none has developed TB. Conclusions: The manifestations of primary TB in children today are similar to those described 50–70 years ago. The tuberculin skin test is an effective tool for contact tracing in an unvaccinated, previously nonexposed childhood population. Rapid detection of contagious patients and thorough contact investigation remain our most important means to reduce transmission.

Molecular epidemiology of drug-resistant tuberculosis in Sweden

Drug-resistant tuberculosis (TB), including the more severe forms of multidrug- and extensively drug-resistant forms, is an increasing public health concern globally. In Sweden the majority of patients with TB are immigrants from countries with a high incidence of TB including the drug-resistant forms. In this study, the spread of resistant TB in Sweden was investigated by molecular fingerprinting. Isolates resistant to at least one of the drugs, isoniazid, rifampicin, ethambutol or streptomycin, from 400 patients collected between 1994 and 2005, were studied by restriction fragment length polymorphism (RFLP) and by spoligotyping. Thirty-five clusters of patients infected with strains with identical RFLP and spoligotyping patterns (2-96 patients per cluster), comprising a total of 203 patients, were found. One large outbreak of isoniazid resistant tuberculosis was identified, involving 96 patients, mainly from the Horn of Africa. To identify chains of transmission, molecular epidemiological characterization of TB isolates should, if possible, be performed on isolates from all new TB patients.

It is more than the issue of taking tablets: the interplay between migration policies and TB control in Sweden.

OBJECTIVES Tuberculosis is re-emerging as a critical public health concern in Sweden among the immigrants. The aim of this study was to explore the experiences of the Somali community of TB care in the Stockholm area. METHODS Focus group discussions were conducted with 34 adult women and men by a Somali speaking moderator. Each group consisted of 6-9 participants-men and women separately. The audio taped discussions were transcribed, translated and read many times and in the process patterns and codes were identified and migration emerged as important theme in the context of TB control. RESULTS Fear of being deported emerged as barrier to sharing of complete health information with the doctor. The routine contact tracing and follow-up of infected cases in TB control was expressed as a source of concern since it was feared the health care providers could share the information with the immigration authorities. Interpreter use was expressed as barrier particularly if of same female gender. CONCLUSION It is important to be aware of how a countrys immigration policies impact on TB control activities among immigrants The existing TB control measures, such as contact tracing, assume new meanings for immigrants. Further research is therefore needed to understand this emerging complexity in order to make TB control more effective.

Comparison between RFLP and MIRU-VNTR Genotyping of Mycobacterium tuberculosis Strains Isolated in Stockholm 2009 to 2011

Our aim was to analyze the difference between methods for genotyping of Mycobacterium tuberculosis complex isolates. We collected genotyping results from Restriction Fragment Length Polymorphism (RFLP) and Mycobacterial Interspersed Repetitive Units - Variable Numbers of Tandem Repeat (MIRU-VNTR) in a geographically limited area (Stockholm) during a period of three years. The number and proportion of isolates belonging to clusters was reduced by 45 and 35% respectively when combining the two methods compared with using RFLP or MIRU-VNTR only. The mean size of the clusters was smaller when combining methods and smaller with RFLP compared to MIRU-VNTR. In clusters with confirmed epidemiological links RFLP coincided slightly better than MIRU-VNTR but where there was a difference, the variation in MIRU-VNTR pattern was only in a single locus. In isolates with few IS6110 bands in RFLP, MIRU-VNTR differentiated the isolates more, dividing the RFLP clusters. Since MIRU-VNTR is faster and less labour-intensive it is the method of choice for routine genotyping. In most cases it will be sufficient for epidemiological purposes but true clustering might still be considered if there are epidemiological links and the MIRU-VNTR results differ in only one of its 24 loci.

Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy

Abstract The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery.

Tuberculosis among HIV-infected patients in Stockholm, Sweden, 1987–2010: Treatment outcomes and adverse reactions

Abstract Background: The treatment of patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB) is challenging. The aim of this study was to compare socio-demographic and clinical characteristics among HIV-infected patients before and after the introduction of combined antiretroviral therapy (cART) in a Swedish cohort, and to identify factors associated with anti-TB treatment success as well as adverse reactions. Methods: This was a retrospective observational study of HIV/TB co-infected patients in Stockholm County from 1987 to 2010. The study population was stratified into an early and a late cohort (before and after the introduction of cART in 1996). Data were analyzed using descriptive statistics and multiple logistic regression analysis. Results: The study population comprised 127 patients; the majority were foreign-born (87%). The proportion of female patients more than doubled from the early to the late cohort, and anti-TB treatment success increased from 65% to 91%. The median duration of successful treatment was 8 months in both cohorts. Predictors of treatment success in the late cohort were cART (odds ratio (OR) 13.3, 95% confidence interval (CI) 1.5–114.8) and a CD4 cell count at TB diagnosis > 200 cells/μl (OR 17.2, 95% CI 1.2–236.6). Severe adverse reactions in the late cohort occurred in 23% and were associated with the initiation of cART after TB diagnosis (OR 13.3, 95% CI 1.6–112.4). Conclusion: The introduction of cART was favourable for the treatment outcome of HIV-infected patients with concomitant TB. However, adverse reactions increased in patients who initiated cART during anti-TB treatment and these patients require careful attention.

Complexity in estimating recent tuberculosis transmission among predominantly immigrant school children in Stockholm, Sweden 2006.

In January 2006, an after-school carer in Stockholm was diagnosed with open pulmonary tuberculosis (TB) after having been symptomatic for 3 months. The aim of this paper is to illustrate the difficulties encountered in estimating recent transmission of TB among children in an immigrant school population. A tuberculin skin test was performed on 261 pupils aged 6–15 y and an additional interferon-gamma release assay was performed on 20 children. In total, 76% of the children were born in Sweden; however, 95% of the parents originated from countries with TB incidence >25/100,000. Three active TB cases were identified, 1 of whom was culture-positive with the same strain as the index case. Latent tuberculous infection (LTBI) was diagnosed in 35 children. However, the increased risk of earlier infection in this population makes it difficult to evaluate when transmission occurred. The magnitude of recent transmission from the index case will thus be uncertain and indications to treat less clear.

Incidence of tuberculosis and the need of prophylactic treatment in persons living with HIV in Stockholm during the era of anti-retroviral therapy 1996–2013

Abstract Background: The aim of this observational cohort study was to determine the incidence and risk factors of active tuberculosis (TB) in persons living with HIV in a low endemic setting over a 17-year time period when combination antiretroviral therapy (ART) has been available. We thereby aimed to understand the usefulness of TB chemoprophylaxis among HIV patients with latent TB. Methods: All 2127 adult patients diagnosed with HIV January 1996–December 2013 at the Karolinska University Hospital in Stockholm County were eligible. After exclusion of 259 patients transferred to other clinics, 1868 were followed until TB diagnosis, death or end of study period (December 2013). The median follow-up time was 7.9 years (interquartile range, 3.9–11.5). Results: Active TB was diagnosed in 92 patients, corresponding to an incidence rate of 6.2 cases (95% CI 5.1–7.6) per 1000 person-years with a significant decline over time. The majority (52%) of TB cases were diagnosed within 1 month from HIV diagnosis. Being a migrant from a TB-endemic region, was the only patient characteristic associated with significantly higher risk of active TB (Hazard Ration, HR: 8.54, 95% confidence interval, CI: 3.09–23.61 in a multivariate regression analysis controlling for route of HIV transmission, year of HIV diagnosis and CD4-cell count and viral load at HIV diagnosis. The number needed to treat to prevent one case of TB among patients in this high-risk group was 22 (95% CI 26–47). Conclusion: The incidence of active TB in persons living with HIV in Stockholm County declined significantly after the introduction of ART but was still 80 times higher than in the general population at the end of the study period. The therapeutic gain of chemoprophylaxis in low endemic settings should be weighed against costs and side effects.

Dynamics of Two Separate but Linked HIV-1 CRF01_AE Outbreaks among Injection Drug Users in Stockholm, Sweden, and Helsinki, Finland

ABSTRACT Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.

The dynamics of two separate but linked CRF01_AE outbreaks among IDUs in Stockholm and Helsinki

ABSTRACT Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.