Tom H. Boyles

Factors Influencing Retention in Care after Starting Antiretroviral Therapy in a Rural South African Programme

Introduction The prognosis of patients with HIV in Africa has improved with the widespread use of antiretroviral therapy (ART) but these successes are threatened by low rates of long-term retention in care. There are limited data on predictors of retention in care, particularly from rural sites. Methods Prospective cohort analysis of outcome measures in adults from a rural HIV care programme in Madwaleni, Eastern Cape, South Africa. The ART programme operates from Madwaleni hospital and seven primary care feeder clinics with full integration between inpatient and outpatient services. Outreach workers conducted home visits for defaulters. Results 1803 adults initiated ART from June 2005 to May 2009. At the end of the study period 82.4% were in active care or had transferred elsewhere, 11.1% had died and 6.5% were lost to follow-up (LTFU). Independent predictors associated with an increased risk of LTFU were CD4 nadir >200, initiating ART as an inpatient or while pregnant, and younger age, while being in care for >6 months before initiating ART was associated with a reduced risk. Independent factors associated with an increased risk of mortality were baseline CD4 count <50 and initiating ART as an inpatient, while being in care for >6 months before initiating ART and initiating ART while pregnant were associated with a reduced risk. Conclusions Serving a socioeconomically deprived rural population is not a barrier to successful ART delivery. Patients initiating ART while pregnant and inpatients may require additional counselling and support to reduce LTFU. Providing HIV care for patients not yet eligible for ART may be protective against being LTFU and dying after ART initiation.

Clinical features of patients isolated for suspected Ebola virus disease at Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study

BACKGROUND The size of the west African Ebola virus disease outbreak led to the urgent establishment of Ebola holding unit facilities for isolation and diagnostic testing of patients with suspected Ebola virus disease. Following the onset of the outbreak in Sierra Leone, patients presenting to Connaught Hospital in Freetown were screened for suspected Ebola virus disease on arrival and, if necessary, were admitted to the on-site Ebola holding unit. Since demand for beds in this unit greatly exceeded capacity, we aimed to improve the selection of patients with suspected Ebola virus disease for admission by identifying presenting clinical characteristics that were predictive of a confirmed diagnosis. METHODS In this retrospective cohort study, we recorded the presenting clinical characteristics of suspected Ebola virus disease cases admitted to Connaught Hospitals Ebola holding unit. Patients were subsequently classified as confirmed Ebola virus disease cases or non-cases according to the result of Ebola virus reverse-transcriptase PCR (EBOV RT-PCR) testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of every clinical characteristic were calculated, to estimate the diagnostic accuracy and predictive value of each clinical characteristic for confirmed Ebola virus disease. RESULTS Between May 29, 2014, and Dec 8, 2014, 850 patients with suspected Ebola virus disease were admitted to the holding unit, of whom 724 had an EBOV RT-PCR result recorded and were included in the analysis. In 464 (64%) of these patients, a diagnosis of Ebola virus disease was confirmed. Fever or history of fever (n=599, 83%), intense fatigue or weakness (n=495, 68%), vomiting or nausea (n=365, 50%), and diarrhoea (n=294, 41%) were the most common presenting symptoms in suspected cases. Presentation with intense fatigue, confusion, conjunctivitis, hiccups, diarrhea, or vomiting was associated with increased likelihood of confirmed Ebola virus disease. Three or more of these symptoms in combination increased the probability of Ebola virus disease by 3·2-fold (95% CI 2·3-4·4), but the sensitivity of this strategy for Ebola virus disease diagnosis was low. In a subgroup analysis, 15 (9%) of 161 confirmed Ebola virus disease cases reported neither a history of fever nor a risk factor for Ebola virus disease exposure. INTERPRETATION Discrimination of Ebola virus disease cases from patients without the disease is a major challenge in an outbreak and needs rapid diagnostic testing. Suspected Ebola virus disease case definitions that rely on history of fever and risk factors for Ebola virus disease exposure do not have sufficient sensitivity to identify all cases of the disease. FUNDING None.

False-positive Xpert® MTB/RIF assays in previously treated patients: need for caution in interpreting results.

Xpert(®) MTB/RIF is the initial diagnostic test of choice for tuberculosis (TB). It is not known if false-positive results are more common in previously treated patients. We report four patients with successful treatment for TB up to 5 years previously who presented with respiratory tract infection and were Xpert-positive, but had negative TB cultures and clinical improvement without anti-tuberculosis treatment. We hypothesise that the Xpert results were false-positive due to the presence of dead Mycobacterium tuberculosis bacilli in lungs and sputum. Further work is required to determine the specificity of Xpert in previously treated patients.

Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates

Background Antibiotic consumption is a major driver of bacterial resistance. To address the increasing burden of multi-drug resistant bacterial infections, antibiotic stewardship programmes are promoted worldwide to rationalize antibiotic prescribing and conserve remaining antibiotics. Few studies have been reported from developing countries and none from Africa that report on an intervention based approach with outcomes that include morbidity and mortality. Methods An antibiotic prescription chart and weekly antibiotic stewardship ward round was introduced into two medical wards of an academic teaching hospital in South Africa between January-December 2012. Electronic pharmacy records were used to collect the volume and cost of antibiotics used, the patient database was analysed to determine inpatient mortality and 30-day re-admission rates, and laboratory records to determine use of infection-related tests. Outcomes were compared to a control period, January-December 2011. Results During the intervention period, 475.8 defined daily doses were prescribed per 1000 inpatient days compared to 592.0 defined daily doses/1000 inpatient days during the control period. This represents a 19.6% decrease in volume with a cost reduction of 35% of the pharmacy’s antibiotic budget. There was a concomitant increase in laboratory tests driven by requests for procalcitonin. There was no difference in inpatient mortality or 30-day readmission rate during the control and intervention periods. Conclusions Introduction of antibiotic stewardship ward rounds and a dedicated prescription chart in a developing country setting can achieve reduction in antibiotic consumption without harm to patients. Increased laboratory costs should be anticipated when introducing an antibiotic stewardship program.

The prevalence of hepatitis B infection in a rural South African HIV clinic

The prevalence of hepatitis B virus (HBV) infection in 1 765 HIV-positive patients in rural Eastern Cape was 7.1%. This is lower than the previously reported rural prevalence and is similar to urban prevalence. Male sex and baseline alanine aminotransferease (ALT) were significant predictors of HBV status. Most HBV-positive patients had normal baseline ALT, making ALT an insensitive screening test for HBV status.

Failure to eradicate Isospora belli diarrhoea despite immune reconstitution in adults with HIV--a case series

Isospora belli causes diarrhoea in patients with AIDS. Most respond to targeted therapy and recommendations are that secondary prophylaxis can be stopped following immune reconstitution with ART. We report eight cases of chronic isosporiasis that persisted despite standard antimicrobial therapy, secondary prophylaxis, and good immunological and virological response to ART. Median CD4 nadir was 175.5 cells/mm3 and median highest CD4 while symptomatic was 373 cells/mm3. Overall 34% of stool samples and 63% of duodenal biopsy specimens were positive for oocytes. Four patients died, two remain symptomatic and two recovered. Possible explanations for persistence of symptoms include host factors such as antigen specific immune deficiency or generalised reduction in gut immunity. Parasite factors may include accumulating resistance to co-trimoxazole. Research is required to determine the optimum dose and duration of co-trimoxazole therapy and whether dual therapy may be necessary. Mortality was high and pending more data we recommend extended treatment with high-dose co-trimoxazole in similar cases.

HIV counselling and testing in South African schools

1748 www.thelancet.com Vol 377 May 21, 2011 measures? Rather than the research and clinical communities retreating into their own silos of expertise to develop solutions, surely now more than ever we require joined-up thinking in the context of cardiovascular risk. It is no longer feasible to divide up both clinical and research resources to tackle these problems individually, since, as Geoff rey Rose has clearly shown, the real solutions lie in small improvements in all risk factors across large populations. Modifi able cardiovascular risk factors should undoubtedly be vigorously tackled to avoid “catastrophic outcomes” down the line. However, rather than continuing the tradition of disease-specifi c research and clinical guidelines, we are calling for a fresh, integrated approach to cardiovascular risk. This is crucial to equip clinicians to adequately deal with the complex patients with multiple diseases seen as the rule rather than the exception in everyday practice. A step in the right direction is the concept of cardiovascular multimorbidity (coexisting cardiovascular disease, diabetes, and chronic kidney disease), which has already been shown to be an independent predictor of prognosis in patients with established cardiovascular disease. Patients with cardiovascular multimorbidity, therefore, do not simply represent an accumulation of conditions but rather an important collision of risk factors promoting the specifi c outcomes of death and cardiovascular events. Every time a new guideline on obesity arrives on my desk, my heart sinks at this missed opportunity to develop a “guideline for each patient not a guideline for each disease”, as so eloquently argued by Martin Dawes.

Clinical practice - the role of appropriate diagnostic testing in acute respiratory tract infections : an antibiotic stewardship strategy to minimise diagnostic uncertainty in primary care : in practice

Antibiotic resistance has increased worldwide to the extent that it is now regarded as a global public health crisis. Interventions to reduce excessive antibiotic prescribing to patients can reduce resistance and improve microbiological and clinical outcomes. Therefore, although improving outpatient antibiotic use is crucial, few data are provided on the key interventional components and the effectiveness of antibiotic stewardship in the primary care setting, in South Africa. The reasons driving the excessive prescription of antibiotics in the community are multifactorial but, perhaps most importantly, the overlapping clinical features of viral and bacterial infections dramatically reduce the ability of GPs to distinguish which patients would benefit from an antibiotic or not. As a consequence, the need for tools to reduce diagnostic uncertainty is critical. In this regard, besides clinical algorithms, a consensus of collaborators in European and UK consortia recently provided guidance for the use of C-reactive protein point-of-care testing in outpatients presenting with acute respiratory tract infections (ARTIs) and/or acute cough, if it is not clear after proper clinical assessment whether antibiotics should be prescribed or not. A targeted application of stewardship principles, including diagnostic stewardship as described in this review, to the ambulatory setting has the potential to affect the most common indications for systemic antibiotic use, in that the majority (80%) of antibiotic use occurs in the community, with ARTIs the most common indication.

Schistosoma haematobium prevalence in school children in the rural Eastern Cape Province, South Africa

The urine of 209 children was examined for haematuria and the presence of schistosome eggs. Comparing the infection rate of 72.3% with existing data suggests an increase in the prevalence over the last decades. Schistosomiasis lacks the attention it deserves in South Africa.

Priorities in Ebola research—a view from the field

The announcement of fast tracked trials of novel treatments for Ebola in west African is welcome. However, there is a danger in doing such trials when the evidence for simpler interventions is lacking. Although it seems likely from case reports of health-care workers evacuated to high-resource settings that modern intensive care is life-saving, it is not clear how to prioritise constrained resources on the ground in west Africa. Through the King’s Sierra Leone Partnership, my experience with patients in Connaught Hospital (Freetown, Sierra Leone) is that they typically receive about 20 minutes of clinician care per day and it is beyond our resources to routinely measure temperature, pulse, blood pressure or any blood parameters. These conditions are far removed from high-resource intensive care units and it is vital to use those 20 minutes in the most effective way. Simple interventions such as routine hand washing and oral rehydration solutions have the greatest impact on survival. There are at least 3 questions that require urgent attention before trials of anti-virals and blood products begin. First is the use of anti-diarrhoeal agents such as loperamide to prevent dehydration. Their use is generally discouraged in febrile and dysenteric diarrhoea, which is common in patients with Ebola. However, there have been suggestions from observational cohorts that there might be benefi t in terms of reducing fluid and electrolyte losses. In our setting in Sierra Leone, there are substantial challenges to replacing fl uid intravenously and so the need to reduce losses is important and anti-diarrhoeals might improve survival. A second question is the use of broad spectrum antibiotics such as ceftriaxone for all patients with Ebola confi rmed. The rationale is that under field conditions it is not possible to determine which patients have developed Gram negative bacteraemia due to translocation of gut flora and it is therefore better to treat all patients presumptively. However, broad spectrum antibiotics also have potential to cause great harm by disrupting gut fl ora leading to loss of bowel-wall integrity and predisposing to Clostridium diffi cile diarrhoea. A third question is the use of large amounts of oral potassium replacement when it is not possible to measure either serum potassium or creatinine. Such an intervention might be benefi cial if patients have persistently low potassium but harmful in those with renal failure and rising potassium levels. For each question there is equipoise, which demands a randomised placebo controlled trial under fi eld conditions. Only once these questions are answered and background treatment is optimised should we move to trials of novel and potentially far more expensive treatments.