COVID-19 testing in outbreak-free care homes: what are the public health benefits?

BACKGROUND: COVID-19 care home outbreaks represent a significant proportion of COVID-19 morbidity and mortality in the UK. National testing initially focused on symptomatic care home residents, before extending to asymptomatic cohorts. AIM: The aim was to describe the epidemiology and transmission of COVID-19 in outbreak free care homes. METHODS: A two-point prevalence survey of COVID-19, in 34 Liverpool care homes, was performed in April and May 2020. Changes in prevalence were analysed. Associations between care home characteristics, reported infection, prevention and control interventions, and COVID-19 status were described and analysed. FINDINGS: No resident developed COVID-19 symptoms during the study. There was no significant difference between: the number of care homes containing at least one test positive resident between the first (17.6%, 95% confidence interval (CI) 6.8-34.5) and second round (14.7%, 95% CI 5.0-31.1) of testing (p>0.99); and the number of residents testing positive between the first (2.1%, 95% CI 1.2-3.4) and second round (1.0%, 95% CI 0.5-2.1) of testing (P=0.11). Care homes providing nursing care (risk ratio (RR) 7.99, 95% CI 1.1-57.3) and employing agency staff (RR 8.4, 95% CI 1.2-60.8) were more likely to contain test positive residents. Closing residents shared space was not associated with residents testing positive (RR 2.63, 95% CI 0.4-18.5). CONCLUSIONS: Asymptomatic COVID-19 care homes showed no evidence of disease transmission or development of outbreaks; suggesting that current infection prevention and control measures are effective in preventing transmission. Repeat testing at two to three weeks had limited or no public health benefits over regular daily monitoring of staff and residents for symptoms. These results should inform policies calling for regular testing of asymptomatic residents.

Autopsies in HIV: still identifying missed diagnoses.

This study reviews the deaths and autopsies carried out over 23 years, 1983-2005, in a British Infection Unit in HIV patients. Of 115 HIV patients known to have died, we obtained data on 93%. Of this 80% were male, median age 38 (25-68) years; 83% were Caucasian; 12% Black African. Major risk factors were men who have sex with men, 52%; heterosexual in Africa, 17%; and injecting drug use, 8%. The commonest diagnosis pre- and post-autopsy diagnosis was pneumonia. Changes in diagnoses in the 38% who underwent autopsy were high (we requested autopsy in 50%). Primary diagnosis changed in 70%, and 36% of all opportunistic infections were missed. This included six of nine cytomegalovirus, all tuberculosis and 75% of Kaposi's sarcoma. Lymphoma was overdiagnosed. Thus, despite excellent resources, the majority of primary diagnoses were wrong, suggesting inadequacy of current diagnostics. To improve these and improve both epidemiological data and future management autopsy should be considered for all deaths.

Hypoadrenalism is not associated with early mortality during tuberculosis treatment in Malawi.

SETTING: In the developing world, early mortality within 1 month of commencing tuberculosis (TB) treatment is high, particularly with human immunodeficiency virus (HIV) co-infection. In Malawi, 40% of those who die do so in the first month of treatment. Reasons remain unclear and may include delayed diagnosis, opportunistic infections, immune restoration inflammatory syndrome (IRIS) or malnutrition. One possible contributing factor is underlying hypoadrenalism associated with TB-HIV, exacerbated by rifampicin (RMP) induction of P450 and glucocorticoid metabolism. OBJECTIVE: To assess the prevalence of hypoadrenalism in TB patients before and after commencement of TB treatment, and relationship with early mortality. DESIGN: Prospective descriptive study assessing hypoadrenalism before and after anti-tuberculosis treatment, HIV status and outcome up to 3 months post-treatment. RESULTS: Of 51 patients enrolled, 29 (56.9%) were female (median age 32 years, range 18-62). Of 43 patients HIV-tested, 38 (88.3%) were HIV-positive and 15.7% died within the first month. At 3 months, 11 (21.6%) were known to have died. Adequate cortisol levels were found in 49/51 (95.9%) before commencing RMP. Neither of the two with reduced response died. All 34 patients revealed adequate cortisol responses at 2 weeks. CONCLUSION: No evidence of hypoadrenalism was found in this first study to assess adrenal function and outcome of anti-tuberculosis treatment.

Clinical and diagnostic findings of an echovirus meningitis outbreak in the north west of England.

INTRODUCTION: An outbreak of echovirus meningitis occurred in the north west of England in 2001. This paper reviewed the clinical features and the role of different diagnostic methods. METHODS: This was a prospective study of adults admitted to a regional infectious disease unit with a probable diagnosis of meningitis, March to August 2001. RESULTS: Half the 40 cases were male; median age was 28 (range 16-51) years. Fifteen of 38 (39.5%) were smokers, and 20 of 24 (83.3%) had close contact with children. Median (range) duration of symptoms was 1.1 (0.25-7) days. Symptoms included headache (100%), photophobia (87.5%), and nausea (67.5%), and severity ranged from minimal signs to those consistent with a meningoencephalitis. The diagnosis was confirmed virologically in 29 of 40 (72%); echovirus 30 was isolated from six. Cerebrospinal fluid (CSF) enterovirus polymerase chain reaction (PCR) was positive in 26 of 32 (81%), and CSF virus culture in 3 of 16 (19%). Thirty one per cent of CSF samples had a neutrophil predominance, and 3 of 29 (10%) virologically confirmed cases had normal CSF microscopy and biochemistry. CONCLUSION: CSF microscopy may be normal or suggest bacterial meningitis in a substantial minority of cases of echovirus meningitis. CSF PCR for enterovirus seems to be more sensitive than virus culture of CSF, although PCR does not yield information on circulating virus type. Early and accurate diagnosis could reduce both use of parenteral antibiotics and length of hospital stay with both morbidity and cost implications. Close contact with children may be a risk factor, particularly if good hygiene measures are not practised.

Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.

The clinical utility of HIV outpatient pharmacist prescreening to reduce medication error and assess adherence.

Antiretroviral therapy (ART) is complex and has high propensity for medication error and drug-drug interactions (DDIs). We evaluated the clinical utility of pharmacist prescreening for DDIs, adherence to ART and medicines reconciliation prior to HIV outpatient appointments. A pharmacist took detailed medication histories and ART adherence assessments, then screened medication for DDIs. A template detailing current medication, potential DDIs and adherence was filed in the clinical notes and physicians were asked for structured feedback. Potential DDIs were observed in 58% of 200 patients, with 22 (9%) potential DDIs occurring with medication that was not previously recorded in the patients' notes. Of 103 physician responses, 61.2% reported that the pharmacist consultation told them something they did not know, and pharmacist consultants led to change in management in 13.6% of cases. Pharmacist consultations were more likely to add benefit in patients taking two or more concomitant medications in addition to ART (P = 0.0012).

Lyme disease in a British referral clinic.

BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK. AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed. DESIGN: Descriptive study conducted by retrospective casenotes review. METHODS: Retrospective casenotes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010). RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners. CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

Candida pelliculosa meningitis as an opportunistic infection in HIV: the first reported case.

We describe the first reported case of Candida pelliculosa meningitis in HIV infection. This case highlights the risk of uncommon opportunistic infections in association with the immunocompromised and the importance of autopsy as a diagnostic tool in HIV infection. We discuss the epidemiology, diagnosis and management of C. pelliculosa, a non-albicans species which is rarely associated with disease, and review current literature.

HIV post-exposure prophylaxis programmes in the developed and developing world: can we learn from each other?

In an audit of HIV post-exposure prophylaxis (PEP) programmes in Blantyre, Malawi, and Liverpool, UK, a striking common deficiency was poor attendance of follow-up visits and of HIV testing to determine efficacy of PEP. Causes of poor follow-up after PEP need to be explored in both settings.

Reliability of rapid testing for hepatitis B in a region of high HIV endemicity.

Hepatitis B (HBV) and HIV co-infection is common in resource-poor settings. A recent study from Malawi revealed poor correlation between hepatitis B surface antigen (HBsAg) point-of-care tests and reference tests in patients co-infected with HIV. We studied a cohort of 300 Malawian adults entering a treatment programme for HIV. Sera were tested for HBsAg first using the Determine rapid test and re-tested using a commercial enzyme immunoassay (EIA). All tests were done under optimal conditions in Liverpool, UK. Sera from all 25 patients positive for HBsAg using the rapid test and from 50 who were negative, were re-tested using the EIA, with complete concordance of results. The kappa correlation was 1, specificity 100% (93-100%) and sensitivity 100% (86-100%) compared to the reference test. Patients had advanced immune suppression (mean CD4=175 cells x 10(6)/l). In a non-field setting, the results of point-of-care Determine rapid hepatitis B tests appear reliable in patients with HIV-1 co-infection.

Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection.

BACKGROUND: Few studies have investigated the impact of chronic hepatitis B and C infection on antiretroviral therapy (ART) outcomes in sub-Saharan Africa. Hepatotoxicity may be a particular concern in co-infected patients taking nevirapine-stavudine-lamivudine. METHODS: We conducted a prospective cohort study of 300 Malawian adults starting ART and describe one-year ART outcomes according to viral hepatitis status. RESULTS: At baseline, patients had advanced HIV disease (29.3% were in WHO stage 4; mean CD4 = 157 cells/microL; mean log(10)HIV-1 RNA = 5.24 copies/ml). Co-infection with hepatitis B, C and B + C were present in 6.7%, 5.7% and 1.7% respectively. At 50 weeks, all-cause mortality was 43 (14.3%). Sixteen (5.3%) had transferred to another unit. Eight (2.7%) were lost to follow up. Sixteen (5.3%) had stopped ART. 217 (72.3%) were alive on ART, of whom 82.5% had an HIV-1 RNA <400 copies/ml at week 50. During the first 50 weeks of ART, severe hepatotoxicity (liver enzyme values >5 times upper level of normal) occurred in 9%, but did not result in any ART discontinuations. Clinical hepatitis or jaundice was not observed. There were no significant differences in occurrence of hepatotoxicity, other side effects, mortality, severe morbidity, immune reconstitution or virological failure between hepatitis B and/or C co-infected patients and those who were not. Viral hepatitis co-infection was not associated with severe hepatotoxicity, mortality, severe morbidity or virological failure in multivariate analyses. CONCLUSION: Our data suggest that screening for viral hepatitis B and C and liver enzyme monitoring may not require high priority in ART programmes in sub-Saharan Africa.

Managing alcohol withdrawal syndromes: the place of guidelines.

Alcohol misuse poses a significant problem in terms of morbidity, mortality and cost. Alcohol detoxification and treatment for associated vitamin deficiency syndromes is simple and saves lives. This article discusses the reasons for poor guideline adherence and the current evidence base behind the formulation of these guidelines.

Prevalence of infection with hepatitis B and C virus and coinfection with HIV in medical inpatients in Malawi.

BACKGROUND: Coinfection with hepatitis B (HBV) or hepatitis C (HCV) adversely affects the prognosis of HIV infection and vice versa, and results in complex interactions with antiretroviral therapy. These infections are common in sub-Saharan Africa but there are few data on prevalence of coinfection. All three components of the most common ART regimen used in Africa, stavudine, lamivudine and nevirapine, can cause hepatic problems and lamivudine resistant HBV is known to emerge after HBV monotherapy in coinfected patients. Point of care (POC) tests for HBV and HCV are widely used but have not been validated in field tests in sub-Saharan Africa. METHODS: Prospective observational study of sequential adult inpatients in medical wards of a large urban teaching hospital in Malawi in 2004. Comparison of demographic risk factors with HIV antibody status determined using local double POC test protocols, and with HBsAg and HCV antibody prevalence as estimated in a reference laboratory in Liverpool, UK. Results of locally performed POC tests for HBV using Determine HBsAg (Abbott) and for HCV antibody using HCV-SPOT (Genelabs) were compared with results of reference methods in the UK. RESULTS: Of 226 adults (39% male), median (range) age 35 (14-80) years, 81% had a history of traditional scarification, 12% a history of blood transfusion and 11% a history of jaundice. HIV antibodies were present in 76.1%, HBsAg in 17.5% and HCV in 4.5%, with HIV/HBV coinfection in 20.4% and HIV/HCV coinfection in 5% of those with HIV. There was no correlation between prevalence of any of the three viruses and demographic risk factors or presence of either of the other two viruses. Point of care tests gave misleading results with prevalence estimates of 38% for HBV and 4.5% for HCV. For both of these POC tests the performance indices were unacceptable for individual patient management or epidemiological survey purposes. CONCLUSIONS: The high prevalence of hepatitis/HIV coinfections may impact on treatment with antiretroviral therapy, especially if there are unintended interruptions of therapy, and studies are needed to document the possible clinical impact on ART programmes. The poor performance of POC tests for HBV and HCV may be due to local operational problems or to unexpected technical issues not revealed by early validation tests. These tests are widely used in resource poor settings and should be revalidated in prospective field studies in areas of the tropics with high HIV prevalence rates.