No Evidence Known Viruses Play a Role in the Pathogenesis of Onchocerciasis-Associated Epilepsy. An Explorative Metagenomic Case-Control Study.

Despite the increasing epidemiological evidence that the Onchocerca volvulus parasite is strongly associated with epilepsy in children, hence the name onchocerciasis-associated epilepsy (OAE), the pathophysiological mechanism of OAE remains to be elucidated. In June 2014, children with unprovoked convulsive epilepsy and healthy controls were enrolled in a case control study in Titule, Bas-Uélé Province in the Democratic Republic of the Congo (DRC) to identify risk factors for epilepsy. Using a subset of samples collected from individuals enrolled in this study (16 persons with OAE and 9 controls) plasma, buffy coat, and cerebrospinal fluid (CSF) were subjected to random-primed next-generation sequencing. The resulting sequences were analyzed using sensitive computational methods to identify viral DNA and RNA sequences. Anneloviridae, Flaviviridae, Hepadnaviridae (Hepatitis B virus), Herpesviridae, Papillomaviridae, Polyomaviridae (Human polyomavirus), and Virgaviridae were identified in cases and in controls. Not unexpectedly, a variety of bacteriophages were also detected in all cases and controls. However, none of the identified viral sequences were found enriched in OAE cases, which was our criteria for agents that might play a role in the etiology or pathogenesis of OAE.

The efficacy of a brief intervention to reduce alcohol use in persons with HIV in South Africa, a randomized clinical trial.

BACKGROUND: Since there is a high prevalence of high risk alcohol use in patients with HIV in Africa, with negative health effects, there is a need for short interventions to reduce alcohol use. METHODS: We studied the efficacy of a short intervention aiming to reduce alcohol use based on the Information-Motivation-Behavioural Skills Model in patients with HIV with high alcohol use (measured by AUDIT). The study was performed in three outpatient clinics in South Africa. The intervention group received in one-session intervention a personalized feedback on AUDIT results trying to make people aware that they are in the medium- or high-risk drinking category. Both the intervention and the control group received a health education leaflet. RESULTS: A total of 560 patients participated in the study with a follow up of 1 year. There was a significant decrease in total AUDIT scores between baseline and follow up points 1 (5 months) and 2 (1 year) in both groups. There was no significant decrease between time points 1 and 2. However, between the intervention and control groups there was no difference in reduction of alcohol use to abstinence or low risk alcohol use over time as there was no difference in absolute decrease in AUDIT-score or percentage of change in AUDIT score. The intervention had no influence on the quality of life outcomes, depression scores, stigma, tobacco use, viral load and therapy adherence at both time points. In all secondary outcomes, there was no significant interaction between intervention and time. CONCLUSION: The brief intervention was not successful at reducing alcohol use both 5 and 12 months after the intervention. However, there was a beneficial effect on reported hazardous or harmful alcohol use at least over a short term follow up period in both study groups. It might be that only an interview and/or the distribution of a health leaflet can be successful in reducing alcohol use but this needs to be investigated with more objective measures of alcohol use. To sustain an effect, most likely repetitive contacts with hazardous or harmful alcohol drinkers will be needed during a long follow up period.

Effect of TB/HIV Integration on TB and HIV Indicators in Rural Ugandan Health Facilities.

BACKGROUND: The World Health Organization recommends integrating services for patients coinfected with tuberculosis (TB) and HIV. We assessed the effect of TB/HIV integration on antiretroviral therapy (ART) initiation and TB treatment outcomes among TB/HIV-coinfected patients using data collected from 14 rural health facilities during 2 previous TB and HIV quality of care studies. METHODS: A facility was considered to have integrated TB/HIV services if patients with TB/HIV had combined treatment for both illnesses by 1 provider or care team at 1 treatment location. We analyzed the effect of integration by conducting a cross-sectional analysis of integrated and nonintegrated facility periods comparing performance on ART initiation and TB treatment outcomes. We conducted logistic regression, with the patient as the unit of analysis, controlling for other intervention effects, adjusting for age and sex, and clustering by health facility. RESULTS: From January 2012 to June 2014, 996 patients with TB were registered, 97% were tested for HIV, and 404 (42%) were HIV-positive. Excluding transfers, 296 patients were eligible for analysis with 117 and 179 from nonintegrated and integrated periods, respectively. Being treated in a facility with TB/HIV integration was associated with lower mortality [adjusted odds ratio (aOR) = 0.38, 95% confidence interval (CI): 0.18 to 0.77], but there was no difference in the proportion initiating ART (aOR = 1.34, 95% CI: 0.40 to 4.47), with TB treatment success (aOR = 1.43, 95% CI: 0.73 to 2.82), lost to follow-up (aOR = 1.64, 95% CI: 0.53 to 5.04), or failure (aOR = 1.21, 95% CI: 0.34 to 4.32). CONCLUSIONS: TB/HIV service integration was associated with lower mortality during TB treatment even in settings with suboptimal proportions of patients completing TB treatment and starting on ART.

Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS.

BACKGROUND: Early initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients who have tuberculosis reduces mortality among patients with low CD4 counts, but it increases the risk of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS). METHODS: We conducted this randomized, double-blind, placebo-controlled trial to assess whether prophylactic prednisone can safely reduce the incidence of paradoxical tuberculosis-associated IRIS in patients at high risk for the syndrome. We enrolled HIV-infected patients who were initiating ART (and had not previously received ART), had started tuberculosis treatment within 30 days before initiating ART, and had a CD4 count of 100 cells or fewer per microliter. Patients received either prednisone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or placebo. The primary end point was the development of tuberculosis-associated IRIS within 12 weeks after initiating ART, as adjudicated by an independent committee. RESULTS: Among the 240 patients who were enrolled, the median age was 36 (interquartile range, 30 to 42), 60% were men, and 73% had microbiologically confirmed tuberculosis; the median CD4 count was 49 cells per microliter (interquartile range, 24 to 86), and the median HIV type 1 RNA viral load was 5.5 log10 copies per milliliter (interquartile range, 5.2 to 5.9). A total of 120 patients were assigned to each group, and 18 patients were lost to follow-up or withdrew. Tuberculosis-associated IRIS was diagnosed in 39 patients (32.5%) in the prednisone group and in 56 (46.7%) in the placebo group (relative risk, 0.70; 95% confidence interval [CI], 0.51 to 0.96; P=0.03). Open-label glucocorticoids were prescribed to treat tuberculosis-associated IRIS in 16 patients (13.3%) in the prednisone group and in 34 (28.3%) in the placebo group (relative risk, 0.47; 95% CI, 0.27 to 0.81). There were five deaths in the prednisone group and four in the placebo group (P=1.00). Severe infections (acquired immunodeficiency syndrome-defining illnesses or invasive bacterial infections) occurred in 11 patients in the prednisone group and in 18 patients in the placebo group (P=0.23). One case of Kaposi's sarcoma occurred in the placebo group. CONCLUSIONS: Prednisone treatment during the first 4 weeks after the initiation of ART for HIV infection resulted in a lower incidence of tuberculosis-associated IRIS than placebo, without evidence of an increased risk of severe infections or cancers. (Funded by the European and Developing Countries Clinical Trials Partnership and others; PredART ClinicalTrials.gov number, NCT01924286 .).

Elevated inflammatory cytokines in aqueous cytokine profile in HIV-1 infected patients with cataracts in Uganda.

BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts. METHODS: A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher's exact test and the Student's t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines. RESULTS: The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p = 0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher among those with a CD4+ T cell count greater than 200cells/mm3 compared to those with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively). CONCLUSION: Cataracts among HIV-positive adults were associated with higher intraocular inflammation relative to the healthy elderly individuals with cataracts. There is need to explore the potential role of intra-ocular anti-inflammatory agents in the management of cataracts among HIV positive patients.

Body Mass Index and Waist Circumference in Patients with HIV in South Africa and Associated Socio-demographic, Health Related and Psychosocial Factors.

A high body mass index (BMI) and high waist circumference are important health risk factors predisposing for cardiovascular and metabolic diseases and certain cancers. Historically, underweight was a diagnostic criterion of HIV-infection. In a cross-sectional study the prevalence of BMI-categories and high waist circumference and its associated factors in patients visiting three outpatient HIV clinics in South Africa were measured with anthropometric measurements and structured questionnaires regarding socio-demographic information, quality of life (QoL), AIDS-related stigma, symptoms of depression, alcohol use, HIV related information and level of adherence to ART. The median age of the 2230 included patients was 37 years, 66.5% were women and 88.6% received antiretroviral therapy. The prevalences of overweight, obesity and high waist circumference were 29.2, 21.9 and 44.6% respectively in women and 12.4, 4.0 and 3.9% respectively in men. Underweight was found in 18.2% of men and 6.3% of women. In multinomial regression analysis compared to a normal BMI, both overweight and obesity were associated with female gender, with being married or cohabiting and with a higher QoL score. Underweight was associated with male gender and tobacco use and negatively associated with being married or cohabiting and the physical domain of the QoL measure. A high waist circumference in men was associated with higher age and negatively associated with tobacco use and stigma score. In women it was negatively associated with never being married. A high prevalence of overweight and obesity was observed in HIV-clinics in South Africa, mainly in women. Since overweight and obesity are important health risk factors, effective weight reduction interventions are desirable.

AIDS-Related Endemic Mycoses in Western Cape, South Africa, and Clinical Mimics: A Cross-Sectional Study of Adults With Advanced HIV and Recent-Onset, Widespread Skin Lesions.

BACKGROUND: Skin lesions are common in advanced HIV infection and are sometimes caused by serious diseases like systemic mycoses (SM). AIDS-related SM endemic to Western Cape, South Africa, include emergomycosis (formerly disseminated emmonsiosis), histoplasmosis, and sporotrichosis. We previously reported that 95% of patients with AIDS-related emergomycosis had skin lesions, although these were frequently overlooked or misdiagnosed clinically. Prospective studies are needed to characterize skin lesions of SM in South Africa and to help distinguish these from common HIV-related dermatoses. METHODS: We prospectively enrolled HIV-infected adult patients living in Western Cape, South Africa, with CD4 counts ≤100 cells/µL and widespread skin lesions present ≤6 months that were deemed clinically compatible with SM. We obtained skin biopsies for histopathology and fungal culture and collected epidemiological and clinical data. RESULTS: Of 34 patients enrolled and in whom a diagnosis could be made, 25 had proven SM: 14 had emergomycosis, and 3 each had histoplasmosis and sporotrichosis; for 5 additional patients, the fungal species could not be identified. Antiretroviral therapy (ART) had been initiated in the preceding 4 weeks for 11/25 (44%) patients with SM (vs no patients without SM). Plaques and scale crust occurred more frequently in patients with SM (96% vs 25%, P = .0002; and 67% vs 13%, P = .01, respectively). CONCLUSIONS: Recent ART initiation and presence of plaques or scale crust should make clinicians consider SM in patients with advanced HIV infection in this geographic area. Clinical overlap between SM and other dermatoses makes early skin biopsy critical for timely diagnosis and treatment.

High-risk alcohol use and associated socio-demographic, health and psychosocial factors in patients with HIV infection in three primary health care clinics in South Africa.

Alcohol use may have a negative impact on the course of HIV disease and the effectiveness of its treatment. We studied patients with HIV who use alcohol and associated socio-demographic, health and psychosocial factors. Outcomes from this study may help in selecting patients from clinical practice with high-risk alcohol use and who are likely to benefit most from alcohol reduction interventions. In a cross sectional study in three primary health care clinics in Pretoria, South Africa, from January 2012 to June 2012, patients with HIV infection were interviewed and patients' medical files were reviewed to obtain data on levels of alcohol use (Alcohol Use Disorder Identification Test), patients' socio-demographic characteristics, HIV-related information, health related quality of life (WHOQoL-HIVBref), internalized AIDS stigma, symptoms of depression and adherence to antiretroviral therapy. Analyses consisted of descriptive statistics, bi- and multivariate logistic regression models. A total of 2230 patients (1483 [66.5%] female) were included. The median age was 37 years (interquartile range 31-43), 99.5% were black Africans, 1975 (88.6%) had started ART and the median time on ART was 22 months (interquartile range 9-40). No alcohol was used by 64% of patients, 8.9% were low risk drinkers, 25.1% of patients were hazardous or harmful drinkers and 2.0% had possible alcohol dependence. In multivariate analysis high-risk drinking was positively associated with male gender, never being married, tobacco use, a higher score for the 'level of independence'-domain measured with the WHOQoL-HIVBref questionnaire, and with more depressive symptoms compared to low-risk drinking. This study shows a high prevalence of hazardous or harmful drinking in patients with HIV infection (especially men) attending primary health care clinics in South Africa. Routine screening for alcohol use should be introduced in these clinics and harm reduction interventions should be evaluated, taking into account associated factors.

Preventing Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in High-Risk Patients: Protocol of a Randomized Placebo-Controlled Trial of Prednisone (PredART Trial).

BACKGROUND: Early antiretroviral therapy (ART) initiation in patients diagnosed with HIV-associated tuberculosis (TB) reduces mortality among those with the lowest CD4 counts. At the same time, both early ART and a low CD4 count heighten the risk of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). TB is common in patients starting ART in sub-Saharan Africa. Safe interventions that reduce the incidence or severity of TB-IRIS are needed. Prednisone has been shown to reduce symptoms and markers of inflammation when used to treat TB-IRIS. OBJECTIVE: To determine whether prophylactic prednisone in patients at high risk for paradoxical TB-IRIS initiating ART reduces the incidence of TB-IRIS. METHODS: We are conducting a randomized, double-blind, placebo-controlled trial of prophylactic prednisone (40 mg/day for 2 weeks, followed by 20 mg/day for 2 weeks) initiated at the same time as ART in patients at high risk for TB-IRIS (starting ART within 30 days of TB treatment and CD4 count ≤100/µL). The primary endpoint is development of TB-IRIS, defined using an international consensus case definition. Secondary endpoints include time to TB-IRIS event, severity of TB-IRIS, quality of life, mortality, hospitalization, other infections and malignancies, and adverse events including corticosteroid adverse effects. RESULTS: Enrollment for the trial began in August 2013. All 240 participants have been enrolled, and safety follow-up will be completed in March 2017. CONCLUSION: No preventive strategies for TB-IRIS currently exist. If results of this trial demonstrate the efficacy and safety of prednisone, this will provide clinicians with an evidence-based preventive strategy in patients at high risk for paradoxical TB-IRIS when initiating ART.

Hepatitis B virus genotypes A and D in Uganda.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection in Uganda is 10%. Hepatitis B virus genotypes impact on treatment response, rate of spontaneous recovery and progression of chronic HBV infection and hepatocellular carcinoma. There is little information on the HBV genotypic distribution in Uganda. OBJECTIVES: To determine HBV genotypes in Uganda. METHODS: The MBN clinical laboratory performs HBV viral load and genotype testing in Uganda. It receives hepatitis B surface antigen (HBsAg)-positive samples from all over the country for additional HBV testing. Samples are stored for 6 months before being discarded. Our study used delinked stored samples. PCR-positive samples had DNA extracted and used as template for HBV genome amplification by nested PCR. Reverse hybridisation was performed and genotypes were determined by the line probe assay method (INNO-LiPA). RESULTS: One hundred stored HBsAg-positive plasma samples with detectable viral loads were analysed. Of these, 93 samples showed PCR amplification products and gave genotype-specific probe lines on the INNO-LiPA assay. Of the patients, where gender was recorded, 60.9% were female, and the overall median age (IQR) was 25 (2-60) years. There was a predominance of HBV genotype D (47 patients; 50.5%), followed by genotype A, (16 patients; 17.2%). One patient (1.1%) had genotype E. In 28% of the samples mixed infections were detected with genotypes A/E (9.7%) and A/D (6.5%) being most common. Genotypes B, C, E and H only occurred as part of mixed infections. CONCLUSION: Hepatitis B genotypes D and A were predominant in our study population.

Reasons for Missing Antiretroviral Therapy: Results from a Multi-Country Study in Tanzania, Uganda, and Zambia.

OBJECTIVES: To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence. METHODS: Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥ 18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients' medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months. RESULTS: Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2-7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1-1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms. CONCLUSIONS: Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes.

Temporal trends in death causes in adults attending an urban HIV clinic in Uganda: a retrospective chart review.

OBJECTIVE: To study temporal trends of mortality in HIV-infected adults who attended an HIV clinic in Kampala, Uganda, between 2002 and 2012. DESIGN: Descriptive retrospective study. METHODS: Two doctors independently reviewed the clinic database that contained information derived from the clinic files and assigned one or more causes of death to each patient >18 years of age with a known date of death. Four cause-of-death categories were defined: 'communicable conditions and AIDS-defining malignancies', 'chronic non-communicable conditions', 'other non-communicable conditions' and 'unknown'. Trends in cause-of-death categories over time were evaluated using multinomial logistic regression with year of death as an independent continuous variable. RESULTS: 1028 deaths were included; 38% of these individuals were on antiretroviral therapy (ART). The estimated mortality rate dropped from 21.86 deaths/100 person years of follow-up (PYFU) in 2002 to 1.75/100 PYFU in 2012. There was a significant change in causes of death over time (p<0.01). Between 2002 and 2012, the proportion of deaths due to 'communicable conditions and AIDS-defining malignancies' decreased from 84% (95% CI 74% to 90%) to 64% (95% CI 53% to 74%) and the proportion of deaths due to 'chronic non-communicable conditions', 'other non-communicable conditions' and a combination of 'communicable and non-communicable conditions' increased. Tuberculosis (TB) was the main cause of death (34%). Death from TB decreased over time, from 43% (95% CI 32% to 53%) in 2002 to a steady proportion of approximately 25% from 2006 onwards (p<0.01). CONCLUSIONS: Mortality rate decreased over time. The proportion of deaths from communicable conditions and AIDS-defining malignancies decreased and from non-communicable diseases, both chronic and non-chronic, increased. Nevertheless, communicable conditions and AIDS-defining malignancies continued to cause the majority of deaths, with TB as the main cause. Ongoing monitoring of cause of death is warranted and strategies to decrease mortality from TB and other common opportunistic infections are essential.

Weight status and associated factors among HIV infected people on antiretroviral therapy in rural Dikgale, Limpopo, South Africa.

BACKGROUND: Underweight in human immunodeficiency virus (HIV)-infected people on antiretroviral therapy (ART) complicates the management of HIV infection and contributes to mortality, whereas overweight increases the risk of cardiovascular disease (CVD). AIM: The study determined weight status and associated factors in people with HIV infection receiving ART. SETTING: Rural primary health care clinics in Dikgale, Limpopo province, South Africa. METHODS: A cross-sectional study in which data were collected using the World Health Organization (WHO) stepwise approach to surveillance (STEPS) questionnaire and calculated using WHO analysis programmes guide. Weight and height were measured using standard WHO procedures, and body mass index was calculated as weight (kg)/height (m2). Data on ART duration were extracted from patients' files. CD4 lymphocyte counts and viral load were determined using standard laboratory techniques. RESULTS: Of the 214 participants, 8.9%, 54.7% and 36.4% were underweight, normal weight and overweight, respectively. Physical activity (OR: 0.99, p = 0.001) and male gender (OR: 0.29, p = 0.04) were negatively associated with overweight. Men who used tobacco were more likely to be underweight than non-tobacco users (OR: 10.87, p = 0.02). Neither ART duration nor viral load or CD4 count was independently associated with underweight or overweight in multivariate analysis. CONCLUSION: A high proportion of people on ART were overweight and a smaller proportion underweight. There is a need to simultaneously address the two extreme weight problems in this vulnerable population through educating them on benefits of avoiding tobacco, engaging in physical activity and raising awareness of CVD risk.

Challenges from Tuberculosis Diagnosis to Care in Community-Based Active Case Finding among the Urban Poor in Cambodia: A Mixed-Methods Study.

BACKGROUND: While community-based active case finding (ACF) for tuberculosis (TB) holds promise for increasing early case detection among hard-to-reach populations, limited data exist on the acceptability of active screening. We aimed to identify barriers and explore facilitators on the pathway from diagnosis to care among TB patients and health providers. METHODS: Mixed-methods study. We administered a survey questionnaire to, and performed in-depth interviews with, TB patients identified through ACF from poor urban settlements in Phnom Penh, Cambodia. Additionally, we conducted focus group discussions and in-depth interviews with community and public health providers involved in ACF, respectively. RESULTS: Acceptance of home TB screening was strong among key stakeholders due to perceived reductions in access barriers and in direct and indirect patient costs. Privacy and stigma were not an issue. To build trust and facilitate communication, the participation of community representatives alongside health workers was preferred. Most health providers saw ACF as complementary to existing TB services; however, additional workload as a result of ACF was perceived as straining operating capacity at public sector sites. Proximity to a health facility and disease severity were the strongest determinants of prompt care-seeking. The main reasons reported for delays in treatment-seeking were non-acceptance of diagnosis, high indirect costs related to lost income/productivity and transportation expenses, and anticipated side-effects from TB drugs. CONCLUSIONS: TB patients and health providers considered home-based ACF complementary to facility-based TB screening. Strong engagement with community representatives was believed critical in gaining access to high risk communities. The main barriers to prompt treatment uptake in ACF were refusal of diagnosis, high indirect costs, and anticipated treatment side-effects. A patient-centred approach and community involvement were essential in mitigating barriers to care in marginalised communities.

Clinical Characteristics, Diagnosis, Management, and Outcomes of Disseminated Emmonsiosis: A Retrospective Case Series.

BACKGROUND: We describe the geographic distribution, clinical characteristics, and management of patients with disease caused by Emmonsia sp., a novel dimorphic fungal pathogen recently described in South Africa. METHODS: We performed a multicenter, retrospective chart review of laboratory-confirmed cases of emmonsiosis diagnosed across South Africa from January 2008 through February 2015. RESULTS: Fifty-four patients were diagnosed in 5/9 provinces. Fifty-one patients (94%) were human immunodeficiency virus coinfected (median CD4 count 16 cells/µL [interquartile range, 6-40]). In 12 (24%) of these, antiretroviral therapy had been initiated in the preceding 2 months. All patients had disseminated disease, most commonly involving skin (n = 50/52, 96%) and lung (n = 42/48, 88%). Yeasts were visualized on histopathologic examination of skin (n = 34/37), respiratory tissue (n = 2/4), brain (n = 1/1), liver (n = 1/2), and bone marrow (n = 1/15). Emmonsia sp. was cultured from skin biopsy (n = 20/28), mycobacterial/fungal and aerobic blood culture (n = 15/25 and n = 9/37, respectively), bone marrow (n = 12/14), lung (n = 1/1), lymph node (n = 1/1), and brain (n = 1/1). Twenty-four of 34 patients (71%) treated with amphotericin B deoxycholate, 4/12 (33%) treated with a triazole alone, and none of 8 (0%) who received no antifungals survived. Twenty-six patients (48%) died, half undiagnosed. CONCLUSIONS: Disseminated emmonsiosis is more widespread in South Africa and carries a higher case fatality rate than previously appreciated. Cutaneous involvement is near universal, and skin biopsy can be used to diagnose the majority of patients.

Practice of percutaneous needle autopsy; a descriptive study reporting experiences from Uganda.

BACKGROUND: Percutaneous needle autopsy can overcome a number of barriers that limit the use of complete autopsies. We performed blind-and ultrasound guided needle autopsies in HIV-infected adults in Uganda. In this study we describe in detail the methods we used, the ability of both procedures to obtain sufficient tissue for further examination and the learning curve of the operators over time. METHODS: If written informed consent was granted from the next of kin, we first performed a blind needle autopsy, puncturing brain, heart, lungs, liver, spleen and kidneys using predefined surface marking points. We then performed an ultrasound guided needle autopsy puncturing heart, liver, spleen and kidneys. The number of attempts, expected success and duration of the procedure were noted. A pathologist read the slides and indicated if the target tissue was present and of sufficient quality for pathological review. We report the predicted and true success rates, compare the yield of blind to ultrasound guided needle biopsies and evaluate the failure rate over time. RESULTS: Two operators performed 96 blind needle autopsies and 95 ultrasound guided needle autopsies. For blind needle biopsies true success rates varied from 56-99% and predicted success rates from 89-99%. For ultrasound guided needle biopsies true success rates varied from 72-100% and predicted success rates from 84-98%. Ultrasound guidance led to a significantly higher success rate in heart and left kidney. A learning curve was observed over time with decreasing failure rates with increasing experience and a shorter duration of the needle autopsy. CONCLUSION: Needle autopsy can successfully obtain tissue for further pathological review in the vast majority of cases, with a decrease in failure rate with increasing experience of the operator. The benefit of ultrasound guidance will depend on the population, the disease and organ of interest and the local circumstances. Our results justify further evaluation of needle autopsies as a method to establish a cause of death.

Antigen-specific interferon-gamma responses and innate cytokine balance in TB-IRIS.

BACKGROUND: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. METHODS: In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex. RESULTS: Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. CONCLUSION: TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS.

Concentration of lymph node aspirate improves the sensitivity of acid fast smear microscopy for the diagnosis of tuberculous lymphadenitis in Jimma, southwest Ethiopia.

BACKGROUND: Tuberculous lymphadenitis (TBLN) is the most common form of extrapulmonary tuberculosis. The cytomorphological features of lymph node smears have reduced specificity for the diagnosis of tuberculosis. The diagnosis of TBLN with direct smear microscopy lacks sensitivity due to the limited number of bacilli in lymph node aspirate. Therefore, we aimed to assess whether the concentration of lymph node aspirate improves the sensitivity of acid fast smear microscopy for the diagnosis of tuberculous lymphadenitis. METHODS: A cross-sectional comparative study was conducted on 200 patients clinically suspected for tuberculous lymphadenitis in Jimma, Ethiopia. Lymph node aspirate was collected. The first two drops were used for cytomorphological study and direct acid fast staining. The remaining aspirate was treated with N-acetyl-L-cysteine (NALC) and concentrated by centrifugation at 3000 g for 15 minutes. The sediment was used for acid fast staining and culture. Differentiation of M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM) was done by para-nitrobenzoic acid susceptibility test. RESULT: Complete data were available for 187 study subjects. 68% (127/187) were positive for M. tuberculosis on culture. Four isolates, 2.1% (4/187), were identified as NTM. The detection rate of direct smear microscopy was 25.1% and that of the concentration method 49.7%. Cytomorphologically, 79.7% of cases were classified as TBLN. The sensitivity of direct smear microscopy was 34.6%, for concentrated smear microscopy 66.1%, and for cytomorphology 89.8%. Two AFB positive cases on concentration method were non-tuberculosis mycobacteria (NTM). The concentration method yielded a positive result from seven cases diagnosed as suppurative abscess by cytology. Both for the direct and concentration methods the highest rate of AFB positivity was observed in smears showing caseous necrosis alone. Smear positivity rate decreased with the appearance of epithelioid cell aggregates. CONCLUSION: The concentration of lymph node aspirates for acid fast smear microscopy had significantly higher sensitivity than direct microscopy.

Needle autopsy to establish the cause of death in HIV-infected hospitalized adults in Uganda: a comparison to complete autopsy.

INTRODUCTION: Minimal invasive but accurate methods to establish the cause of death in HIV-infected patients are needed. We studied the agreement in cause of death between blind and ultrasound-guided needle autopsy and complete autopsy in HIV-infected patients in Uganda. METHODS: We subsequently performed a blind and ultrasound-guided needle autopsy followed by a complete autopsy in HIV-infected adults who died during hospitalization. Two teams of pathologists reviewed the tissue from either the needle autopsies or the complete autopsy and formulated the major diagnoses, that is, diseases directly contributing to death. The primary outcome was concordance in major diagnosis between needle and complete autopsies. RESULTS: We performed 96 blind needle and complete autopsies and 95 ultrasound-guided needle autopsies. Concordance in major diagnosis between blind needle and complete autopsy was 50%. For the main major diagnosis, tuberculosis (TB) concordance was higher (71%; P < 0.01). Blind needle autopsy identified at least 1 major diagnosis in 60% of patients; and in 46%, there was complete concordance for all major diagnoses. The main reason for discordance was sampling error of the lesion. Concordance with the addition of ultrasound guidance was 52% for all major diagnoses and 79% for TB. Major diagnoses were mainly identified in tissue cores from the liver (76%) and the spleen (82%). DISCUSSION: Blind needle autopsy identified half of the major diagnosis. The addition of ultrasound guidance did not significantly improve the performance of needle autopsy. Needle autopsy is a valuable method to confirm causes of death in HIV-infected patients, especially for highly prevalent diseases like TB.