TB and TB-HIV care for adolescents and young adults.

SETTING: Nine high-burden public tuberculosis (TB) clinics in Gaborone, Botswana.OBJECTIVE: To evaluate the challenges encountered, healthcare worker (HCW) approaches, and supported interventions in TB and TB-HIV (human immunodeficiency virus) care for adolescents and young adults (AYA, aged 10-24 years).DESIGN: Semi-structured interviews with HCW in TB clinics, analyzed using thematic analysis.RESULTS: Sixteen HCWs were interviewed. AYA developmental needs included reliance on family support for care, increasing autonomy, attending school or work, building trust in HCWs, and intensive TB education and adherence support. Stigma strongly influenced care engagement, including clinic attendance and HIV testing. Health system barriers to optimal AYA TB care included limited staffing and resources to follow-up or support. HCWs utilized intensive education and counseling, and transitioned AYA to community-based directly observed therapy whenever feasible. HCWs supported implementation of youth-friendly services, such as AYA-friendly spaces or clinic days, training in AYA care, use of mobile applications, and peer support interventions, in addition to health system strengthening.CONCLUSION: HCWs utilize dedicated approaches for AYA with TB, but have limited time and resources for optimal care. They identified several strategies likely to improve care and better retain AYAs in TB treatment. Further work is needed to study interventions to improve AYA TB care and outcomes.

Registrar wellness in Botswana: Measuring burnout and identifying ways to improve wellness

Background. Burnout during registrar training is high, especially in resource-limited settings where stressors are intensified. Burnout leads to decreased quality of life for doctors, poor job and patient satisfaction, and difficulty retaining doctors.Objectives. Primary: to measure burnout among registrars working at Princess Marina Hospital in Gaborone, Botswana. Secondary: to determine factors contributing to burnout and identify potential wellness interventions.Methods. The validated Maslach Burnout Inventory was used to measure the degree of emotional exhaustion, depersonalisation and personal accomplishment. Work-related difficulties and potential wellness interventions were explored through multiple-choice and open-ended questions.Results. Of 40 eligible registrars, 20 (50%) completed the survey. High levels of burnout were reported for emotional exhaustion in 65% (13/20), depersonalisation in 45% (9/20), and personal accomplishment in 35% (7/20) of registrars. A high degree of burnout was reported by 75% (15/20) of registrars in one or more domains. In the previous 7 days, registrars worked an average of 77 hours, took 1.5 overnight calls, slept 5.7 hours per night, and 53% (10/19) had ≥1 of their patients die. Five (25%) registrars considered leaving Botswana to work in another country, which correlated with those with the highest degree of burnout. The most common frustrations included insufficient salary and limited medical resources. Suggested interventions included improved mentorship and wellness lectures.Conclusions. There is a high degree of burnout, especially emotional exhaustion, among registrars. Encouragingly, most registrars have a desire to work in Botswana after training. Future research on improving registrar wellness in low-resource settings is urgently needed

Loss to follow-up among adolescents with tuberculosis in Gaborone, Botswana.

SETTING: Nine high-burden public tuberculosis (TB) clinics in Gaborone, Botswana. OBJECTIVE: To describe clinical characteristics and outcomes among adolescents with TB and compare loss to follow-up (LTFU) rates with that among youth and adult cases. DESIGN: Retrospective cohort study of TB cases registered from 2012 to 2014. Clinical characteristics and treatment outcomes were compared among adolescents (age 10-19 years), youth (20-24 years) and a systematic sample of adults (⩾25 years). RESULTS: We analyzed 120 adolescent, 210 youth, and 548 adult cases. Adolescents had twice the risk of LTFU over adults (RR 2.0, 95%CI 1.1-3.7, P = 0.03), and higher LTFU than youth; this was not significant (RR 1.4, 95%CI 0.7-2.9, P = 0.32). Of those with human immunodeficiency virus (HIV) infection, 8/35 (22.9%) adolescents were LTFU, compared with 3/51 (5.9%) youth, and 25/407 (6.1%) adults (P = 0.001). In a multivariable model, adolescence (OR 3.0, 95%CI 1.3-6.5, P < 0.01), HIV positivity (OR 2.2, 95%CI 1.1-4.5, P = 0.02), and extra-pulmonary TB (OR 2.2, 95%CI 1.2-4.0, P = 0.01) were each associated with LTFU. CONCLUSION: Adolescents treated for TB had greater LTFU than youth and adults, particularly in the setting of TB-HIV coinfection. Further work should clarify the generalizability of these findings and investigate poor outcomes among adolescents with TB.

Treatment initiation factors and cognitive outcome in youth with perinatally acquired HIV infection.

OBJECTIVES: Although cognitive outcomes among perinatally infected youth have improved with highly active antiretroviral therapy (HAART), the impact of the age of initiation of treatment and the central nervous system (CNS) penetration effectiveness (CPE) of the regimen on cognitive outcomes is unknown. We aimed to describe the association between initiation age/regimen CPE score and cognitive outcomes in perinatally HIV-infected youth. METHODS: Linear regression was used to retrospectively assess the association between full-scale IQ score (FSIQ) and age of initiation of HAART, regimen CPE, and the presence/absence of an AIDS diagnosis before initiation of HAART in an urban US cohort. RESULTS: A total of 88 of 181 subjects (48.6%) had an AIDS diagnosis. In 69, AIDS preceded the start of HAART. Mean FSIQ (mean age 155.4 months) was 86.3 [standard deviation (SD) 15.6]. Neither age of initiation of HAART (P = 0.45) nor regimen CPE score (P = 0.33) was associated with FSIQ. Mean FSIQ for patients with an AIDS diagnosis before HAART initiation [82 (SD 17.0)] was significantly lower than for patients initiating HAART before an AIDS diagnosis [90 (SD 13)] (P = 0.001). Of the 129 subjects without AIDS by age 5 years, 41 (31.8%) initiated HAART before age 5 years; four of 41 later developed AIDS, compared with 32 of 88 of those who did not initiate HAART before age 5 years. The relative risk of AIDS if HAART was initiated before age 5 years was 0.19 (95% confidence interval 0.05-0.60). CONCLUSIONS: Earlier age at HAART initiation and higher CPE score of a regimen did not improve cognitive outcomes. However, initiating HAART prior to AIDS protected against AIDS and was associated with a significantly higher FSIQ.

Impact of the human immunodeficiency virus on early multidrug-resistant tuberculosis treatment outcomes in Botswana.

SETTING: The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear. OBJECTIVE: To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana. DESIGN: Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs). RESULTS: A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4). CONCLUSION: We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.

Homocysteine elevation in sickle cell disease.

OBJECTIVE: Ischemic complications are common in patients with sickle cell disease. Hyperhomocysteinemia is a risk factor for arteriosclerosis and venous thrombosis, and given the propensity of patients with sickle cell disease to develop ischemic complications, we hypothesized that they might have elevated plasma homocysteine concentrations. METHODS: Plasma concentrations of homocysteine, vitamin B12 and folate were measured in 49 adults with sickle cell disease and 16 normotensive Black controls. All subjects with sickle cell disease had been prescribed folic acid 1 mg by mouth daily. RESULTS: The median plasma concentration of homocysteine of subjects with sickle cell disease was approximately 1.5-fold higher than that of controls (p=0.0008). This difference persisted, even when subjects with renal insufficiency were excluded. Plasma folate levels were 1.5-fold higher in subjects with sickle cell disease than in controls (p=0.0498). There was no significant difference in plasma vitamin B12 concentrations between the two groups. There was no difference in plasma homocysteine concentrations between transfused and non-transfused sickle cell subjects. CONCLUSIONS: Patients with sickle cell disease have elevated plasma concentrations of homocysteine in spite of elevated plasma folate levels and vitamin B12 concentrations similar to those observed in controls. Based on these data, we hypothesize that the concentration of folate required to normalize plasma homocysteine levels in patients with sickle cell disease may be higher than that of normal controls and that patients with sickle cell disease have a higher nutritional requirement for folic acid than the general population.

Retinopathy secondary to anemia from myeloid metaplasia in polycythemia vera.

BACKGROUND: Polycythemia vera is a chronic clonal disorder associated with excessive proliferation of erythrocytes, leukocytes, and thrombocytes, as well as an accompanying splenomegaly. Ocular manifestations of polycythemia vera include occipital cortex transient ischemic attacks, transient monocular blindness, vaso-occlusive disease, and retinal hemorrhages. CASE REPORT: A 56-year old man with longstanding polycythemia vera sought treatment for a chief symptom of blurred vision in the left eye and a red tinge to things first noticed on awakening that morning. He had preretinal and intraretinal hemorrhages and was subsequently found to be severely anemic as a result of postpolycythemic myeloid metaplasia after years of phlebotomy. Splenectomy controlled his anemia and thrombocytopenia, allowing transient improvement of the retinal hemorrhages. Acute leukemia subsequently developed and the patient died 7 weeks after initial examination. CONCLUSION: In this case, preretinal and intraretinal hemorrhages were found in a patient with longstanding polycythemia vera. The exact origin of these hemorrhages is uncertain. They are probably secondary to anemia, but the possibility that they are sites of extramedullary hematopoiesis must be considered. The appearance of retinal hemorrhages warrants careful investigation to rule out diabetes, hypertension, and anemia, as well as the various other blood dyscrasias.

Sickle cell acute chest syndrome associated with parvovirus B19 infection: case series and review.

Acute Chest Syndrome (ACS) continues to be a major source of morbidity and mortality among patients with sickle cell disease. It is characterized by the presence of pleuritic chest pain, fever, raises on lung auscultation, and pulmonary infiltrates on chest x-ray [Castro et all: Blood 84:643-649]. The pathophysiology of this disorder remains poorly understood leading to the descriptive term "Acute Chest Syndrome" designated by Charache et al. [Arch Intern Med 139:67-69, 1979]. Typical bacterial pathogens are seldom isolated in adults, although they play a significant role in the pathogenesis of this entity in children. Until recently, the technology to accurately study viral infection as a precipitating cause of ACS has been unavailable. Parvovirus B19 is being increasingly recognized as an important human pathogen, and has been established as the cause of transient "aplastic crisis" in patients with sickle cell diseases [Saarien et al: Blood 67:-11411-11417, 1986; Young: Sem Hematol 25:159-172, 1988]. We present three patients with hemoglobin SC variant of sickle cell disease who developed ACS in association with acute parvovirus B19 infection, one of which died of respiratory failure. Parvovirus B19 infection was established by polymerase chain reaction for parvovirus B19 DNA, and the presence of parvovirus B19 specific IgM antibodies. These cases suggest that parvovirus B19 may be associated with more than self-limited illness in patients with sickle cell disease, and that this ubiquitous virus may merit further study as a precipitating cause of ACS.