Clostridium difficile: a healthcare associated infection of unknown significance in adults in sub-Saharan Africa

Background: Clostridium difficile infection (CDI) causes a high burden of disease in high-resource healthcare systems, with significant morbidity, mortality and financial implications. CDI is a healthcare-associated infection for which the primary risk factor is antibiotic usage and it is the leading cause of bacterial diarrhoea in HIV infected patients in USA. Little is known about the disease burden of CDI in sub-Saharan Africa, where HIV and healthcare associated infection have a higher prevalence and antibiotic usage is less restricted. Aim: To review published literature on CDI in sub-Saharan Africa, highlighting areas for future research. Methods: English language publications since 1995 were identified from online databases (PubMed, Medline, Google Scholar, SCOPUS) and personal collections of articles, using combinations of keywords to include C. difficile, Africa and HIV. Results: Ten relevant studies were identified. There is considerable variation in methodology to assess for carriage of toxigenic C. difficile and its associations. Eight studies report carriage of toxigenic C. difficile. Three (of four) studies found an association with antibiotic usage. One (of four) studies showed an association with HIV infection. One study showed no association with degree of immunosuppression in HIV. Two (of three) studies showed an association between carriage of toxigenic C. difficile and diarrhoeal illness. Conclusion: Whilst the carriage of toxigenic C. difficile is well described in sub-Saharan Africa, the impact of CDI in the Region remains poorly l understood and warrants high quality research

Ebola preparedness in Oman: An experience from the Middle East

LETTER TO THE EDITOR

Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes. METHODS AND ANALYSIS: We will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes. ETHICS AND DISSEMINATION: The study has been approved by the North West-Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination

An evaluation of 1 year of advice calls to a tropical and infectious disease referral Centre

OBJECTIVES:Many secondary care departments receive external advice calls. However, systematic advice-call documentation is uncommon and evidence on call nature and burden infrequent. The Liverpool tropical and infectious disease unit (TIDU) provides specialist advice locally, regionally and nationally. We created and evaluated a recording system to document advice calls received by TIDU. METHODS:An electronic advice-call recording system was created for TIDU specialist trainees to document complex, predominantly external calls. Fourteen months of advice calls were summarised, analysed and recommendations for other departments wishing to replicate this system made. RESULTS:Five-hundred and ninety calls regarding 362 patients were documented. Median patient age was 44 years (interquartile range 29-56 years) and 56% were male. Sixty-nine per cent of patients discussed were referred from secondary healthcare, half from emergency or acute medicine departments; 43% of patients were returning travellers; 59% of returning travellers had undifferentiated fever, one-third of whom returned from sub-Saharan Africa; 32% of patients discussed were further reviewed at TIDU. Interim 6-month review showed good user acceptability of the system. CONCLUSIONS:Implementing an advice-call recording system was feasible within TIDU. Call and follow-up burden was high with advice regarding fever in returned travellers predominating. Similar systems could improve clinical governance, patient care and service delivery in other secondary care departments

Factors associated with virological rebound in HIV-infected patients receiving protease inhibitor monotherapy

OBJECTIVE: The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial found that protease inhibitor monotherapy as a simplification strategy is well tolerated in terms of drug resistance but less effective than combination therapy in suppressing HIV viral load. We sought to identify factors associated with the risk of viral load rebound in this trial. METHODS: PIVOT was a randomized controlled trial in HIV-positive adults with suppressed viral load for at least 24 weeks on combination therapy comparing a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy versus ongoing triple therapy. In participants receiving monotherapy, we analysed time to confirmed viral load rebound and its predictors using flexible parametric survival models. RESULTS: Of 290 participants initiating protease inhibitor monotherapy (80% darunavir, 14% lopinavir, and 6% other), 93 developed viral load rebound on monotherapy. The risk of viral load rebound peaked at 9 months after starting monotherapy and then declined to approximately 5 per 100 person-years from 18 months onwards. Independent predictors of viral load rebound were duration of viral load suppression before starting monotherapy (hazard ratio 0.81 per additional year <50 copies/ml; P < 0.001), CD4+ cell count (hazard ratio 0.73 per additional 100 cells/µl for CD4+ nadir; P = 0.008); ethnicity (hazard ratio 1.87 for nonwhite versus white, P = 0.025) but not the protease inhibitor agent used (P = 0.27). Patients whose viral load was analysed with the Roche TaqMan-2 assay had a 1.87-fold risk for viral load rebound compared with Abbott RealTime assay (P = 0.012). CONCLUSION: A number of factors can identify patients at low risk of rebound with protease inhibitor monotherapy, and this may help to better target those who may benefit from this management strategy

Differential diagnosis of illness in travelers arriving from sierra Leone, Liberia, or guinea: A cross-sectional study from the Geosentinel surveillance network

Background: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in West Africa since late 2013, has led to export of cases to Europe and North America. Clinicians encountering ill travelers arriving from countries with widespread Ebola virus transmission must be aware of alternate diagnoses associated with fever and other nonspecific symptoms. Objective: To define the spectrum of illness observed in persons returning from areas of West Africa where EVD transmission has been widespread. Design: Descriptive, using GeoSentinel records. Setting: 57 travel or tropical medicine clinics in 25 countries. Patients: 805 ill returned travelers and new mmigrants from Sierra Leone, Liberia, or Guinea seen between September 2009 and August 2014. Measurements: Frequencies of demographic and travelrelated characteristics and illnesses reported. Results: The most common specific diagnosis among 770 nonimmigrant travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe malaria in 267 (86%) and non–P. falciparum malaria in 43 (14%). Acute diarrhea was the second most common diagnosis among nonimmigrant travelers (n= 95 [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary tract infection, and influenza-like illness occurred in only 26, 9, and 7 returning travelers, respectively. Few instances of typhoid fever (n = 8), acute HIV infection (n = 5), and dengue (n = 2) were encountered. Limitation: Surveillance data collected by specialist clinics may not be representative of all ill returned travelers. Conclusion: Although EVD may currently drive clinical evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea, clinicians must be aware of other more common, potentially fatal diseases. Malaria remains a common diagnosis among travelers seen at GeoSentinel sites. Prompt exclusion of malaria and other life-threatening conditions is critical to limiting morbidity and mortality

Clinical and molecular epidemiology of Crimean-Congo hemorrhagic fever in Oman

BackgroundCrimean-Congo hemorrhagic fever (CCHF) is a serious disease with a high fatality rate reported in many countries. The first case of CCHF in Oman was detected in 1995 and serosurveys have suggested widespread infection of humans and livestock throughout the country.MethodologyCases of CCHF reported to the Ministry of Health (MoH) of Oman between 1995 and 2017 were retrospectively reviewed. Diagnosis was confirmed by serology and/or molecular tests in Oman. Stored RNA from recent cases was studied by sequencing the complete open reading frame (ORF) of the viral S segment at Public Health England, enabling phylogenetic comparisons to be made with other S segments of strains obtained from the region.FindingsOf 88 cases of CCHF, 4 were sporadic in 1995 and 1996, then none were detected until 2011. From 2011-2017, incidence has steadily increased and 19 (23.8%) of 80 cases clustered around Eid Al Adha. The median (range) age was 33 (15-68) years and 79 (90%) were male. The major risk for infection was contact with animals and/or butchering in 73/88 (83%) and only one case was related to tick bites alone. Severe cases were over-represented: 64 (72.7%) had a platelet count ConclusionsCCHF is well-established throughout Oman, with a single strain of virus present for at least 20 years. Most patients are men involved in animal husbandry and butchery. The high mortality suggests that there is substantial under-diagnosis of milder cases. Preventive measures have been introduced to reduce risks of transmission to animal handlers and butchers and to maintain safety in healthcare settings

Clinical predictors of encephalitis in UK adults–A multi-centre prospective observational cohort study

Objectives: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body’s immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment. Methods: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes. Results: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had HSV, 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5–50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45–250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness. Conclusions: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy