Antonia Ho

Risk factors for failure of outpatient parenteral antibiotic therapy (OPAT) in infective endocarditis

Objectives To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). Patients and methods We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. ‘OPAT failure’ was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan–Meier survival analysis up to 36 months following OPAT. Results We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84–29.66), P = 0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01–37.47), P = 0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P = 0.016 log-rank test). Conclusions These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated.

British HIV Association Guidelines on the Use of Vaccines in HIV-Positive Adults 2015

These guidelines provide updated, GRADE-based recommendations on the use of vaccines in HIVpositive adults. Several factors have made the updating of HIV-specific vaccination guidelines important: effective antiretroviral therapy (ART) has substantially modified the natural history of HIV infection, vaccination practices are evolving, and a large number of novel vaccines are becoming available in clinical care. The update contains important new guidance regarding the use of new vaccines against human papillomavirus (HPV), shingles (herpes zoster), and pneumococcus. Further key updates are related to the use of hepatitis B, meningococcus, and pertussis vaccines. Compared with HIV-negative individuals, HIV-positive adults often have an increased risk of infection or experience more severe morbidity following exposure to vaccine-preventable diseases, and therefore a lower threshold for extending indications and offering vaccination may be appropriate relative to the general population. Improved health and prognosis mean that HIV-positive adults are also increasingly likely to engage in travel or occupations that carry a risk of exposure to infectious agents, and these otherwise healthy individuals should not be denied protection or engagement with such activities if evidence indicates vaccination is safe and immunogenic. Immune responses to vaccination are often sub-optimal in HIV-positive patients, and while these improve with ART, they often remain lower and decline more rapidly than in HIV-negative individuals. However, many of these vaccines still afford protection and for some vaccines it is possible to improve immunogenicity by offering modified vaccine schedules, with higher or more frequent doses, without compromising safety. Non-replicating vaccines (e.g., whole inactivated, polysaccharide, conjugated, and subunit vaccines, or virus-like particles) can be used safely in HIV-positive persons, whereas replicating (live) vaccines have traditionally been contraindicated. However, ART-induced Immunorestoration reduces the risk of adverse events, in many cases shifting the risk-benefit ratio in favour of vaccination, whereby the risk of disease with natural infection becomes greater than the risk of live vaccine-related adverse events. Important examples of replicating vaccines that can be used in HIV-positive persons with good immunity include those for measles, mumps and rubella (MMR), varicella-zoster virus (VZV), and yellow fever. For vaccinated individuals, the importance of infection avoidance and infection control should continue to be emphasised. It is envisaged that the HIV specialist should provide overall guidance on vaccine use and enlist the help of primary care physicians for vaccine administration. Education of health care providers and good communication are key requirements to ensure successful implementation of this guidance. Despite evidence that HIV-positive persons benefit from vaccination, there are persisting perceptions about disease incidence and burden, and vaccine effectiveness and safety, which affect vaccination practices among health professionals caring for HIV-positive patients. It is hoped that this guidance will help overcoming such barriers.

Penicillium marneffei infection presenting as an immune reconstitution inflammatory syndrome in an HIV patient.

We describe a case of Penicillium marneffei infection acquired in Thailand, manifesting as an immune reconstitution inflammatory syndrome (IRIS) in a Caucasian man with advanced HIV-related immunosuppression (CD4 72 cells/mm3). Initial presentation was consistent with Pneumocystis jirovecii pneumonia, and empirical co-trimoxazole resulted in clinical improvement. One month after initiating antiretroviral therapy (ART), an enlarging scaly lesion on his forehead and erythematous nodules on his face, trunk and limbs developed. P. marneffei was isolated from a skin aspirate. Response to antifungal therapy was complicated by drug interactions but cure was complete after four months of treatment. Few cases of IRIS associated with P. marneffei have been reported.

Hospitalised adult patients with Suspected 2009 H1N1 Infection at Regional Infectious Diseases Units in Scotland – Most had alternative final diagnoses

The misdiagnosis of serious illness during the current flu pandemic has been highlighted in your journal by Payne et al, and others have raised their concern. We have reviewed 110 cases of ‘‘query H1N1’’ presenting to our Infectious Diseases service and have found a variety of alternative diagnoses, some of which required significantly different management. Human pandemic Influenza A (H1N1) virus has spread globally during 2009. On the 25th April the first 2 cases confirmed in Europe were in our region, the West of Scotland, United Kingdom. Subsequently suspected and confirmed cases surged throughout the UK. Information regarding the clinical spectrum and risk factors for severe illness are still emerging. The clinical case definition, indications for hospital admission and therapeutic intervention are continually being refined as more experience in managing these patients is gained. In order to add to the growing body of clinical experience in managing this novel infection worldwide, this case series describes the clinical presentation and outcome of all adult patients admitted to the Infectious Diseases units in the West of Scotland with suspected H1N1 infection, during the first three months of the global pandemic. In the West of Scotland, the two regional infectious diseases units at Gartnavel General Hospital in Glasgow and at Monklands District General hospital in Airdrie, serve the populations of Lanarkshire, Forth Valley, and Greater Glasgow and Clyde Health Boards (population approx 1.9 million). Between April and July 2009, all adult patients in the West of Scotland requiring hospitalization for confirmed or suspected H1N1 infection were transferred to one of these two Regional Infectious Diseases unit for isolation and treatment, unless their condition merited direct admission to intensive care. The case definition was a pyrexia 38 C or history of fever AND two or more of the following symptoms: cough, sore throat, headache, rhinorrhoea, limb/ joint pain.

Respiratory Virus–Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition

Background We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering. Methods From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection. Results Hospital-attended influenza virus–positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)–infected children aged 5–9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4–3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3–3.0) and rainy season (aRR, 2.4; 95% CI, 1.6–3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs. Conclusions Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.

Household air pollution, chronic respiratory disease and pneumonia in Malawian adults: A case-control study

Background: Four million people die each year from diseases caused by exposure to household air pollution. There is an association between exposure to household air pollution and pneumonia in children (half a million attributable deaths a year); however, whether this is true in adults is unknown. We conducted a case-control study in urban Malawi to examine the association between exposure to household air pollution and pneumonia in adults. Methods: Hospitalized patients with radiologically confirmed pneumonia (cases) and healthy community controls underwent 48 hours of ambulatory and household particulate matter (µg/m 3) and carbon monoxide (ppm) exposure monitoring. Multivariate logistic regression, stratified by HIV status, explored associations between these and other potential risk factors with pneumonia. Results: 145 (117 HIV-positive; 28 HIV-negative) cases and 253 (169 HIV-positive; 84 HIV-negative) controls completed follow up. We found no evidence of association between household air pollution exposure and pneumonia in HIV-positive (e.g. ambulatory particulate matter adjusted odds ratio [aOR] 1.00 [95% CI 1.00–1.01, p=0.141]) or HIV-negative (e.g. ambulatory particulate matter aOR 1.00 [95% CI 0.99–1.01, p=0.872]) participants. Chronic respiratory disease was associated with pneumonia in both HIV-positive (aOR 28.07 [95% CI 9.29–84.83, p<0.001]) and HIV-negative (aOR 104.27 [95% CI 12.86–852.35, p<0.001]) participants. Conclusions: We found no evidence that exposure to household air pollution is associated with pneumonia in Malawian adults. In contrast, chronic respiratory disease was strongly associated with pneumonia.

Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults: A Prospective Cohort and Parallel Case-Control Study

Human immunodeficiency virus (HIV)–related immunosuppression is a major risk factor for influenza illness and severity in Malawian adults. Household crowding, food insecurity, and poor sanitation are additional risk factors. Influenza preventive strategies should target HIV-infected adults in Africa.

Epidemiology of Severe Acute Respiratory Illness and Risk Factors for Influenza Infection and Clinical Severity among Adults in Malawi, 2011–2013

Data on the epidemiology of severe acute respiratory illness (SARI) in adults from low-income, high human immunodeficiency virus (HIV) prevalence African settings are scarce. We conducted adult SARI surveillance in Blantyre, Malawi. From January 2011 to December 2013, individuals aged ≥ 15 years with SARI (both inpatients and outpatients) were enrolled at a large teaching hospital in Blantyre, Malawi. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses by polymerase chain reaction. We estimated hospital-attended influenza-positive SARI incidence rates and assessed factors associated with influenza positivity and clinical severity (Modified Early Warning Score > 4). We enrolled 1,126 SARI cases; 163 (14.5%) were positive for influenza. Human immunodeficiency virus prevalence was 50.3%. Annual incidence of hospital-attended influenza-associated SARI was 9.7-16.8 cases per 100,000 population. Human immunodeficiency virus was associated with a 5-fold greater incidence (incidence rate ratio 4.91, 95% confidence interval [CI]: 3.83-6.32). On multivariable analysis, female gender, as well as recruitment in hot, rainy season (December to March; adjusted odds ratios (aOR): 2.82, 95% CI: 1.57-5.06) and cool, dry season (April to August; aOR: 2.47, 95% CI: 1.35-4.15), was associated with influenza positivity, whereas influenza-positive patients were less likely to be HIV-infected (aOR: 0.59, 95% CI: 0.43-0.80) or have viral coinfection (aOR: 0.51, 95% CI: 0.36-0.73). Human immunodeficiency virus infection (aOR: 1.86; 95% CI: 1.35-2.56) and recruitment in hot, rainy season (aOR: 4.98, 95% CI: 3.17-7.81) were independently associated with clinical severity. In this high HIV prevalence population, influenza was associated with nearly 15% of hospital-attended SARI. Human immunodeficiency virus infection is an important risk factor for clinical severity in all-cause and influenza-associated SARI. Expanded access to HIV testing and antiretroviral treatment, as well as targeted influenza vaccination, may reduce the burden of SARI in Malawi and other high HIV prevalence settings.

Impact of HIV on the burden and severity of influenza illness in adults in Malawi: a cohort and case-control study

Abstract Background Although annual vaccination of at-risk groups is the cornerstone of influenza prevention in many developed settings, it is unavailable in most sub-Saharan African countries. Since 70% of the estimated total population of HIV-infected persons reside in these countries, they might be an important group for whom policy makers could target influenza control strategies. This study aimed to determine the impact of HIV on the burden and severity of influenza illness in adults in a setting with high HIV prevalence. Methods At the Queen Elizabeth Central Hospital, Blantyre, Malawi, we conducted a prospective cohort study between April 1, 2013, and March 31, 2015, to compare influenza incidence between HIV-infected and HIV-uninfected adults. We also did a case-control study of adults with mild influenza (influenza-like illness) and severe influenza (admission to hospital with lower respiratory tract infection) to explore risk factors for severe influenza presentation. Poisson and unconditional logistic regression models, respectively, were performed. Findings 608 adults were enrolled in the cohort study, of whom 360 (59%) were HIV-reactive (median CD4 count 390 cells per μL [IQR 244–547]). 24 (11%) of 229 episodes of influenza-like illness in HIV-infected and five (4%) of 119 in HIV-uninfected adults were influenza PCR positive (incidence rates 46 vs 15 per 1000 person-years, incidence rate ratio 2·75 [95% CI 1·02–7·44]). In the case-control study, 56 (11%) of 518 patients admitted with lower respiratory tract infection and 88 (14%) of 642 patients with influenza-like illness were influenza PCR positive. HIV prevalence in the influenza-positive cases and controls were 70% (39/56) and 30% (26/88), respectively. HIV was a significant risk factor for severe influenza presentation (odds ratio 4·98 [95% CI 2·09–11·88], population attributable fraction 57%). There was a tendency towards increased incidence and severity in individuals with CD4 count less than 200 cells per μL. Interpretation In a setting with high HIV prevalence, HIV infection is an important risk factor for acquiring influenza infection and for severe presentation. Individuals with advanced immunosuppression can be particularly vulnerable. These results present a strong case to policy makers to consider targeted vaccination policy in HIV-infected adults in sub-Saharan Africa. However, the optimum mechanism for vaccine introduction and evaluation in overstretched health systems will need to be determined. Funding Wellcome Trust.

Viral pneumonia in adults and older children in sub-Saharan Africa — epidemiology, aetiology, diagnosis and management

Community-acquired pneumonia causes substantial morbidity and mortality in sub-Saharan Africa with an estimated 131 million new cases each year. Viruses — such as influenza virus, respiratory syncytial virus and parainfluenza virus — are now recognised as important causes of respiratory disease in older children and adults in the developed world following the emergence of sensitive molecular diagnostic tests, recent severe viral epidemics, and the discovery of novel viruses. Few studies have comprehensively evaluated the viral aetiology of adult pneumonia in Africa, but it is likely to differ from Western settings due to varying seasonality and the high proportion of patients with immunosuppression and co-morbidities. Emerging data suggest a high prevalence of viral pathogens, as well as multiple viral and viral/bacterial infections in African adults with pneumonia. However, the interpretation of positive results from highly sensitive polymerase chain reaction tests can be challenging. Therapeutic and preventative options against viral respiratory infections are currently limited in the African setting. This review summarises the current state of the epidemiology, aetiology, diagnosis and management of viral pneumonia in sub-Saharan Africa.