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IDCM Issue 7: Rapid Article Review: Staying Up to Date with ID
Natasha Chida, MD, MSPH
One of the most exciting attributes of the field of infectious diseases is its dynamism. New data are available and new discoveries are made every day. In this issue, Dr. Chida reviews a few findings published recently that are of particular interest for ID providers and relevant for the wider medical community.
More Support for “Treatment as Prevention:” The PARTNER Study
In this prospective observational cohort study of 75 clinics in 14 different European countries, 1166 couples were evaluated to assess the risk of HIV acquisition with condomless sex between non-HIV infected persons and HIV-infected persons on antiretroviral therapy and with an undetectable viral load.1 The mean age in the cohort was 42 years; 61.7% of the couples were heterosexual. Upon enrollment, the median time of prior condomless sex was 2 years.
The mean time to follow up in the study was 1.3 years, which allowed for 1238 couple-years of follow-up. During this time, MSM couples reported a total of 22,000 condomless sex acts, while heterosexual couples reported a total of 36,000 sex acts. At the end of follow-up, the rate of within-couple HIV transmission was zero. The authors note that longer-term follow-up is needed to more precisely estimate risk.
Risk of Infection in Persons Receiving Corticosteroids
In this population-based cohort study, researchers examined the relative risk of infection in persons prescribed any oral glucocorticoid (GC) for the first time by general practitioners in the United Kingdom (UK) between 2000 and 2012.2 The authors accomplished this by abstracting information from the Health Improvement Network primary care database in the UK, which analyzes the EMRs of UK general practices and is considered to represent the general population. The risk of infection in persons who received GCs was compared to the risk of infection in persons who did not receive GCs. In addition, the risk of infection in patients who received GCs for seven specific diseases (asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, inflammatory bowel disease, polymyalgia rheumatica/giant cell arteritis, and connective tissue disease) was compared to the risk of infection in persons with the same diseases who didn’t receive GCs. To be included in the study, the duration of GCs had to be at least 12 days; persons who had previously received GCs were excluded. The median daily dose of GCs was 15 mg (range of 10-30 mg), and the median duration of exposure was 33 days (range 21-70 days).
275,072 adults received GCs during the study time period. The median age of persons in the cohort was 63; 57.8% were women. The authors found those who received GCs had a higher risk of the following: scabies (hazard ratio 1.64); dermatophytosis (1.22); local candidiasis (4.93); varicella (3.44); herpes zoster (2.37); cutaneous cellulitis (2.21); lower respiratory tract infection (5.42); and septicemia (3.96); p<.001 for all. When comparing GC use in persons who had the previously stated 7 diseases, those who received GCs had a higher risk of the following: cellulitis (hazard ratio of 2.01); lower respiratory tract infections (5.84); herpes zoster (2.09); septicemia (2.20); and local candidiasis (5.75); p<.001 for all. Risk was stable over durations of exposure, except for local candidiasis and lower respiratory tract infections, both of which had a higher risk during the first few weeks of exposure. The authors also found the risk of infection increased with age, diabetes, higher GC doses, and low albumin.
The authors note that, as this study utilized a database, misclassification of infectious outcomes and reporting biases were possible. A prospective study with more complete patient information would be helpful.
Evaluation of Malaria Resistance to Artemisinin
Artemisinin is the most effective drug for severe malaria and is the backbone of treatment for Plasmodium falciparum malaria.3 The drug has also been important for malaria control because it kills gametocytes (the form of the organism that is transmissible). Unfortunately, resistance is emerging to artemisinin. It has previously been determined that mutations in the gene encoding the kelch protein (“K13”) are associated with clinical resistance. In this study, the authors analyzed blood samples for evidence of K13 mutations from 13,157 patients with malaria who lived in an endemic region or had traveled to an endemic region. 59 counties were represented from the following regions: Asia, Africa, South America, and Oceania. The authors found resistance-associated mutations only in Southeast Asia and China. No clinically significant mutations were found elsewhere.
Readers should note that artemisinin-resistant malaria has a lower cure rate when therapy is given for the standard 3 days; increasing the duration to 6 days is associated with increase in cure rate up to 97.7%.4Artemisinin in these isolates also has a decreased gametocide activity. The WHO therefore recommends that when treating resistant malaria a single dose of primaquin be added to artemisinin combination therapy to reduce gametocyte reservoirs and decrease transmission.
Safety of reduced antibiotic prescribing for respiratory tract infections (RTIs)
60% of the antibiotics prescribed in primary care are for RTIs (including colds, sore throat, cough, bronchitis, otitis media, and sinusitis.5 In this retrospective population-based cohort study, authors in the UK evaluated the UK Clinical Practice Research Datalink database. The database has electronic medical records for approximately 7% (610) of all UK general practices. Antibiotic prescribing practices and the incidence of pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre’s syndrome were evaluated.
Data from 2005 to 2014 were analyzed, leading to 45.5 million person years of follow up. When comparing practices that had the lowest antibiotic prescribing for RTI (38%) to the highest (65%), lower prescribing practices had 4 more patients per 10,000 develop pneumonia over a year, and less than 1 patient per 10,000 develop a tonsillar abscess. No differences between the other conditions was found. The authors estimate that if a general practice with an average of 7000 patients were to reduce antibiotic prescriptions for RTI visits by 10%, they might observe 1.1 more cases of pneumonia annually and 0.9 more cases of peritonsillar abscess every 10 years. The number of cases of mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre’s syndrome would likely not change. The authors do note that as this was a population-based study; individual-level patient data was not evaluated. They also note that future research should include a randomized controlled trial to more fully answer this question and consider comorbidities, prior antibiotic prescriptions, and other factors.
- Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, van Lunzen J, Corbelli GM, Estrada V, Geretti AM, Beloukas A, Asboe D, Viciana P, Gutiérrez F, Clotet B, Pradier C, Gerstoft J, Weber R, Westling K, Wandeler G, Prins JM, Rieger A, Stoeckle M, Kümmerle T, Bini T, Ammassari A, Gilson R, Krznaric I, Ristola M, Zangerle R, Handberg P, Antela A, Allan S, Phillips AN, Lundgren J; PARTNER Study Group. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA. 2016;316(2):171-181. PMID: 27404185.https://www.ncbi.nlm.nih.gov/pubmed/27404185
- >Fardet L, Petersen I, Nazareth I. Common infections in patients prescribed systemic GCs in primary care: A population-based cohort study. PLoS Med 2016; 13:e1002024. PMID: 27218256.https://www.ncbi.nlm.nih.gov/pubmed/27218256
- Ménard D, Khim N, Beghain J, Adegnika AA, Shafiul-Alam M, Amodu O, Rahim-Awab G, Barnadas C, Berry A, Boum Y, Bustos MD, Cao J, Chen JH, Collet L, Cui L, Thakur GD, Dieye A, Djallé D, Dorkenoo MA, Eboumbou-Moukoko CE, Espino FE, Fandeur T, Ferreira-da-Cruz MF, Fola AA, Fuehrer HP, Hassan AM, Herrera S, Hongvanthong B, Houzé S, Ibrahim ML, Jahirul-Karim M,Jiang L, Kano S, Ali-Khan W, Khanthavong M, Kremsner PG, Lacerda M, Leang R, Leelawong M, Li M, Lin K, Mazarati JB,Ménard S, Morlais I, Muhindo-Mavoko H, Musset L, Na-Bangchang K, Nambozi M, Niaré K, Noedl H, Ouédraogo JB, Pillai DR,Pradines B, Quang-Phuc B, Ramharter M, Randrianarivelojosia M, Sattabongkot J, Sheikh-Omar A, Silué KD, Sirima SB,Sutherland C, Syafruddin D, Tahar R, Tang LH, Touré OA, Tshibangu-wa-Tshibangu P, Vigan-Womas I, Warsame M, Wini L, Zakeri S, Kim S, Eam R, Berne L, Khean C, Chy S, Ken M, Loch K, Canier L, Duru V, Legrand E, Barale JC, Stokes B, Straimer J,Witkowski B, Fidock DA, Rogier C, Ringwald P, Ariey F, Mercereau-Puijalon O; KARMA Consortium. A worldwide map ofPlasmodium falciparum. K13-propeller polymorphisms. N Engl J Med. 2016;374(25):2453-64. PMID: 27332904.https://www.ncbi.nlm.nih.gov/pubmed/27332904
- Daily JP. K13-propeller mutations and malaria resistance. N Engl J Med. 2016;374(25):2492-3. PMID: 27332909. https://www.ncbi.nlm.nih.gov/pubmed/27332909
- Gulliford MC, Moore MV, Little P, Hay AD, Fox R, Prevost A, Juszczyk D, Charlton J, Ashworth M. Safety of reduced antibiotic prescribing for self limiting respiratory tract infections in primary care: cohort study using electronic health records. BMJ. 2016;354:i3410. PMID: 27378578. https://www.ncbi.nlm.nih.gov/pubmed/27378578
The Johns Hopkins Center for Clinical Global Health Education is a clinical research, education, and leadership development center in the Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine. We conduct clinical research, and we train, support, and empower healthcare providers and researchers working in resource-limited communities who share our commitment to improve health outcomes.