Background and aims: Most respiratory tract infections (RTI) are self-limiting. Despite this, they are associated with high antibiotic prescription rates in general practice in Sweden. The aim of this thesis was to evaluate the management of respiratory tract infections (RTIs) with particular emphasis on acute otitis media (AOM). Methods: Paper I: A prospective, open, randomized study of 179 children presenting with AOM and performed in primary care. Paper II & III: Study of 6 years data from primary care in Kalmar County on visits for RTI, retrieved from electronic patient records. Paper IV: Observational, clinical study of 71 children presenting with AOM complicated by perforation, without initial use of antibiotics. Results: Children with AOM who received PcV had some less pain, used fewer analgesics and consulted less, but the PcV treatment did not affect the recovery time or complication rate (I). Between 1999 and 2005, 240 445 visits for RTI were analyzed (II & III). Antibiotics were prescribed in 45% of visits, mostly PcV (60%) and doxycycline (18%). Visiting rates for AOM and tonsillitis declined by >10%/year, but prescription rates of antibiotics remained unchanged. For sore throat, 65% received antibiotics. Patients tested but without presence of S.pyogenes received antibiotics in 40% of cases. CRP was analyzed in 36% of consultations for RTI. At CRP<50mg/l antibiotics, mostly doxycycline, were prescribed in 54% of visits for bronchitis. Roughly 50% of patients not tested received antibiotics over the years.Twelve of 71 children with AOM and spontaneous perforation completing the trial received antibiotics during the first nine days due to lack of improvement, one child after 16 days due to recurrent AOM and six had new incidents of AOM after 30 days (IV). Antibiotics were used more frequently when the eardrum appeared pulsating and secretion was purulent and abundant. All patients with presence of S.pyogenes received antibiotics. Results: Children with AOM who received PcV had some less pain, used fewer analgesics and consulted less, but the PcV treatment did not affect the recovery time or complication rate (I). Between 1999 and 2005, 240 445 visits for RTI were analyzed (II & III). Antibiotics were prescribed in 45% of visits, mostly PcV (60%) and doxycycline (18%). Visiting rates for AOM and tonsillitis declined by >10%/year, but prescription rates of antibiotics remained unchanged. For sore throat, 65% received antibiotics. Patients tested but without presence of S.pyogenes received antibiotics in 40% of cases. CRP was analyzed in 36% of consultations for RTI. At CRP<50mg/l antibiotics, mostly doxycycline, were prescribed in 54% of visits for bronchitis. Roughly 50% of patients not tested received antibiotics over the years.Twelve of 71 children with AOM and spontaneous perforation completing the trial received antibiotics during the first nine days due to lack of improvement, one child after 16 days due to recurrent AOM and six had new incidents of AOM after 30 days (IV). Antibiotics were used more frequently when the eardrum appeared pulsating and secretion was purulent and abundant. All patients with presence of S.pyogenes received antibiotics.

<p dir="ltr"><a href="" target="_blank">Almost every case of cervical cancer in the United States is medically preventable with vaccination and proper screening, yet many Americans are insufficiently screened. Over 12 thousand American women suffered from cervical cancer in 2018</a>¹ causing 4 thousand deaths, with over a third in women who had never received a routine screening test².</p><p dir="ltr">New, sensitive testing techniques for cervical cancer screening are facilitating HPV testing without evaluating the cells collected in the sample by eye. This opens the door to new, accessible methods of screening such as rapid testing in clinic and at home, self-sampling, and mail-in testing. As cervical cancer morbidity and mortality is largely a result of healthcare inequities, these methods may have a significant impact on cervical cancer outcomes.</p><p dir="ltr">The goal of this project is to create a proof-of-concept, sample-to-answer rapid test to be used for cervical cancer screening in Indiana outpatient clinics. We began the project by conducting interviews and a survey to explore Indiana clinician perspectives on cervical screening methods such as self-sampling, rapid testing, and home-based screening. Clinicians preferred in-clinic testing with same-visit results, in the hopes that face-to-face explanation of results and scheduling follow-up care in person would improve patient retention for these important follow-up tests. To create such a test, we augmented an isothermal nucleic acid amplification method that copies 13 of the 14 high-risk human papillomavirus (hrHPV) types with an endogenous b-globin sample control and a simple colorimetric lateral flow strip (LFS) readout. When tested with HPV 16 the assay achieved a limit of detection of 1000 HPV copies per reaction, which would detect endocervical samples deemed ‘sufficient’ by clinical guidelines. It also performs in endocervical cells using methods and equipment that could be implemented in an outpatient clinic. The final test accepts swabs or brushes of endocervical cells, lyses them in 5 minutes, copies the target DNA and a sample adequacy control, and delivers the readout within 40 minutes on an LFS readout. Future directions for this assay include soliciting feedback from clinicians and other stakeholders about the prototype developed, adapting the assay to interferents of clinical endocervical samples, and adding probes for other HPV types, such as HPV 18 and eventually the other hrHPV types.</p>

Yes / Background: Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results. However, these connected diagnostics and readily available test results are not used to their full capacity, as we have yet to capitalize on fully understanding the relationship between test results and specific rpoB mutations to elucidate its potential application to real-time surveillance. Objective: We aimed to validate and analyze RDT data in detail, and propose the potential use of connected diagnostics and associated test results for real-time evaluation of RR-TB transmission. Methods: We selected 107 RR-TB strains harboring 34 unique rpoB mutations, including 30 within the rifampicin resistance–determining region (RRDR), from the Belgian Coordinated Collections of Microorganisms, Antwerp, Belgium. We subjected these strains to Xpert MTB/RIF, GenoType MTBDRplus v2.0, and Genoscholar NTM + MDRTB II, the results of which were validated against the strains’ available rpoB gene sequences. We determined the reproducibility of the results, analyzed and visualized the probe reactions, and proposed these for potential use in evaluating transmission. Results: The RDT probe reactions detected most RRDR mutations tested, although we found a few critical discrepancies between observed results and manufacturers’ claims. Based on published frequencies of probe reactions and RRDR mutations, we found specific probe reactions with high potential use in transmission studies: Xpert MTB/RIF probes A, Bdelayed, C, and Edelayed; Genotype MTBDRplus v2.0 WT2, WT5, and WT6; and Genoscholar NTM + MDRTB II S1 and S3. Inspection of probe reactions of disputed mutations may potentially resolve discordance between genotypic and phenotypic test results. Conclusions: We propose a novel approach for potential real-time detection of RR-TB transmission through fully using digitally linked TB diagnostics and shared repository of test results. To our knowledge, this is the first pragmatic and scalable work in response to the consensus of world-renowned TB experts in 2016 on the potential of diagnostic connectivity to accelerate efforts to eliminate TB. This is evidenced by the ability of our proposed approach to facilitate comparison of probe reactions between different RDTs used in the same setting. Integrating this proposed approach as a plug-in module to a connectivity platform will increase usefulness of connected TB diagnostics for RR-TB outbreak detection through real-time investigation of suspected RR-TB transmission cases based on epidemiologic linking. / KCN was supported by Erasmus Mundus Joint Doctorate Fellowship grant 2016-1346, and BCdJ, LR, and CJM were supported by European Research Council-INTERRUPTB starting grant 311725.