Antiviral use among hepatitis B infected patients in a low resource setting in Africa: a case study of West Nile, Uganda.

Failure to access antiviral medications is a leading cause of hepatitis B (HBV)-associated morbidity and mortality in sub-Saharan Africa (SSA). Despite guideline availability, SSA is not on course to meet its elimination targets. We characterized factors associated with antiviral medication use and challenges to offering chronic care in a large Ugandan institution. We abstracted HBV care data. 2,175/2,209 (98.5%) had HBV-infection. Most participants were men [1,197 (55%)]; median (IQR) age 27 years (19-35); 388/1689 (23.0%) had cirrhosis by sonography and 141/2175 (6.5%) by the aspartate aminotransferase to platelet ratio index (APRI) score ≥2. Of the eligible, 20/141 (14.2%) with APRI score ≥2 and 24/388 (6.2%) with sonographic evidence of liver cirrhosis were not on antiviral medications. Overall, 1,106 (51%) were on medications though 65.8% had not been fully investigated. In multivariate analysis, age ≥35 years [OR (95% CI) = 1.52 (1.01-2.28), p=0.043], APRI ≥2 [OR (95% CI) =1.79 (1.482.16), p<0.001], hepatitis B viral load >2,000IU/mL [OR (95% CI) = 6.22 (5.08-7.62), p<0.001] were associated with antiviral medications use. Over half of participants in care had not been fully evaluated although on treatment and many eligible patients did not access medications. There is need to bridge these gaps for SSA to realise its HBV elimination goals.

Availability of the core components of the World Health Organization infection prevention and control strategies in health facilities in Southwestern Uganda: Implications for control of COVID-19.

BACKGROUND: Infection prevention and control (IPC) practices are required to prevent nosocomial infection by severe acute respiratory syndrome coronavirus 2. In low- and middle-income countries, where resources are often limited, IPC practices are infrequently assessed. AIM: To assess the availability of the core components of World Health Organization (WHO) IPC practices at health facilities in Southwestern Uganda. METHODS: We assessed the availability of WHO IPC core components using a modified WHO IPC Assessment tool. We determined differences between government versus private ownership and by type of health facility. FINDINGS: We assessed 111 of 224 (50%) health facilities in four districts. The most frequently achieved core component of IPC strategies was environmental cleanliness with 75 of 111 (68%) facilities scoring >85%. The most infrequently achieved core component of IPC strategies was personal protective equipment (PPE) with only one of seven (14%) hospitals and no other facilities scoring >85%. Of the 20 hospital or health center IV facilities, five (25%) received an overall score of >85% compared to only one of 91 (1%) health center II or III facilities (odds ratio [OR] 30.0 [95% CI: 3.27-274.99], p=0.003). Of the 73 government facilities, two (3%) received an overall score of >85% compared to five of 38 (13%) private facilities (OR 0.24 [95% CI: 0.04-1.37], p=0.11). CONCLUSION: Few facilities in four districts in Southwestern Uganda achieved >85% availability of WHO IPC core components. Provision of PPE in these facilities should be prioritized.

Dyslipidaemia in a Black African diabetic population: burden, pattern and predictors.

OBJECTIVES: This study sought to assess the burden, pattern and predictors of dyslipidaemia in 425 adult diabetic patients in Uganda. RESULTS: The median (IQR) age of the study participants was 53 (43.5-62) years with a female majority (283, 66.9%). Dyslipidaemia defined as presence of ≥ 1 lipid abnormalities was observed in 374 (88%) study participants. Collectively, the predictors of dyslipidaemia were: female gender, study site (private hospitals), type of diabetes (type 2 diabetes mellitus), statin therapy, increased body mass index and diastolic blood pressure. Proactive screening of dyslipidaemia and its optimal management using lipid lowering therapy should be emphasised among adult diabetic patients in Uganda.

Derivation and validation of a universal vital assessment (UVA) score: a tool for predicting mortality in adult hospitalised patients in sub-Saharan Africa.

BACKGROUND: Critical illness is a leading cause of morbidity and mortality in sub-Saharan Africa (SSA). Identifying patients with the highest risk of death could help with resource allocation and clinical decision making. Accordingly, we derived and validated a universal vital assessment (UVA) score for use in SSA. METHODS: We pooled data from hospital-based cohort studies conducted in six countries in SSA spanning the years 2009-2015. We derived and internally validated a UVA score using decision trees and linear regression and compared its performance with the modified early warning score (MEWS) and the quick sepsis-related organ failure assessment (qSOFA) score. RESULTS: Of 5573 patients included in the analysis, 2829 (50.8%) were female, the median (IQR) age was 36 (27-49) years, 2122 (38.1%) were HIV-infected and 996 (17.3%) died in-hospital. The UVA score included points for temperature, heart and respiratory rates, systolic blood pressure, oxygen saturation, Glasgow Coma Scale score and HIV serostatus, and had an area under the receiver operating characteristic curve (AUC) of 0.77 (95% CI 0.75 to 0.79), which outperformed MEWS (AUC 0.70 (95% CI 0.67 to 0.71)) and qSOFA (AUC 0.69 (95% CI 0.67 to 0.72)). CONCLUSION: We identified predictors of in-hospital mortality irrespective of the underlying condition(s) in a large population of hospitalised patients in SSA and derived and internally validated a UVA score to assist clinicians in risk-stratifying patients for in-hospital mortality. The UVA score could help improve patient triage in resource-limited environments and serve as a standard for mortality risk in future studies.

Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes.

BACKGROUND: Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes. METHODS: This is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12-20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants. RESULTS: The 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0-1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (≥ 2 episodes of symptomatic malaria or ≥ 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80-111.6) and 4.06 (1.73-9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32-8.12) and aRR = 7.07 (2.84-17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46-21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy. CONCLUSION: Higher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes. Trial Registration Current Controlled Trials Identifier NCT02163447.

Improving inpatient medication adherence using attendant education in a tertiary care hospital in Uganda.

QUALITY PROBLEM: Although widely utilized in resource-rich health care systems, the use of quality improvement (QI) techniques is less common in resource-limited environments. Uganda is a resource-limited country in Sub-Saharan Africa that faces many challenges with health care delivery. These challenges include understaffing, inconsistent drug availability and inefficient systems that limit the provision of clinical care. INITIAL ASSESSMENT: Poor adherence to prescribed inpatient medications was identified as a key shortcoming of clinical care on the internal medicine wards of Mulago National Referral Hospital, Kampala, Uganda. Baseline data collection revealed a pre-intervention median inpatient medication adherence rate of 46.5% on the study ward. Deficiencies were also identified in attendant (lay caretaker) education, and prescriber and pharmacy metrics. CHOICE OF SOLUTION: A QI team led by a resident doctor and consisting of a QI nurse, a pharmacist and a ward nurse supervisor used standard QI techniques to address this issue. IMPLEMENTATION: Plan-Do-Study-Act cycle interventions focused on attendant involvement and education, physician prescription practices and improving pharmacy communication with clinicians and attendants. EVALUATION: Significant improvements were seen with an increase in overall medication adherence from a pre-intervention baseline median of 46.5% to a post-intervention median of 92%. Attendant education proved to be the most effective intervention, though resource and staffing limitations made institutionalization of these changes difficult. LESSONS LEARNED: QI methods may be the way forward for optimizing health care delivery in resource-limited settings like Uganda. Institutionalization of these methods remains a challenge due to shortage of staff and other resource limitations.

A simple prognostic index based on admission vital signs data among patients with sepsis in a resource-limited setting.

INTRODUCTION: In sub-Saharan Africa, vital signs are a feasible option for monitoring critically ill patients. We assessed how admission vital signs data predict in-hospital mortality among patients with sepsis. In particular, we assessed whether vital signs data can be incorporated into a prognostic index with reduced segmentation in the values of included variables. METHODS: Subjects were patients with sepsis hospitalized in Uganda, who participated in two cohort studies. Using restricted cubic splines of admission vital signs data, we predicted probability of in-hospital death in the development cohort and used this information to construct a simple prognostic index. We assessed the performance of the index in a validation cohort and compared its performance to that of the Modified Early Warning Score (MEWS). RESULTS: We included 317 patients (167 in the development cohort and 150 in the validation cohort). Based on how vital signs predicted mortality, we created a prognostic index giving a score of 1 for: respiratory rates ≥30 cycles/minute; pulse rates ≥100 beats/minute; mean arterial pressures ≥110/<70 mmHg; temperatures ≥38.6/<35.6°C; and presence of altered mental state defined as Glasgow coma score ≤14; 0 for all other values. The proposed index (maximum score = 5) predicted mortality comparably to MEWS. Patients scoring ≥3 on the index were 3.4-fold (95% confidence interval (CI) 1.6 to 7.3, P = 0.001) and 2.3-fold (95% CI 1.1 to 4.7, P = 0.031) as likely to die in hospital as those scoring 0 to 2 in the development and validation cohorts respectively; those scoring ≥5 on MEWS were 2.5-fold (95% CI 1.2 to 5.3, P = 0.017) and 1.8-fold (95% CI 0.74 to 4.2, P = 0.204) as likely to die as those scoring 0 to 4 in the development and validation cohorts respectively. CONCLUSION: Among patients with sepsis, a prognostic index incorporating admission vital signs data with reduced segmentation in the values of included variables adequately predicted mortality. Such an index may be more easily implemented when triaging acutely-ill patients. Future studies using a similar approach may develop indexes that can be used to monitor treatment among acutely-ill patients, especially in resource-limited settings.

Primary prophylaxis for cryptococcal meningitis and impact on mortality in HIV: a systematic review and meta-analysis.

AIM: To determine the role of primary antifungal prophylaxis in the prevention of cryptococcal meningitis and all-cause mortality in advanced HIV infection. MATERIALS & METHODS: This was a systematic review and meta-analysis of randomized trials and observational studies. Google Scholar™, PubMed and Embase databases were searched for relevant studies. Quality was assessed using different criteria, depending on study type. Publication bias was assessed and subgroup and sensitivity analyses were performed. When the results of the meta-analysis were homogeneous, the fixed-effects model was used; when the results of the meta-analysis were heterogenous, the random effects model was used. RESULTS: Primary prophylaxis prevented cryptococcal meningitis but did not confer protection against overall mortality, although there was evidence of a reduction in cryptococcal-specific mortality in resource-limited settings. CONCLUSION: Primary antifungal prophylaxis should be recommended in patients with advanced HIV infection in resource-limited settings with a high incidence of cryptococcal meningitis.

Endocrine and metabolic abnormalities among HIV-infected patients: a current review.

Multiple endocrine and metabolic abnormalities have been reported among human immunodeficiency virus (HIV) patients since the pre-antiretroviral therapy era. These abnormalities present with either subclinical or overt clinical features. Endocrine and metabolic abnormalities primarily occur due to the direct destructive effects of HIV, malignancies and opportunistic infections on the varied endocrine glands and antiretroviral therapy-associated toxicities. This article offers a broad review on the commonly encountered endocrine and metabolic abnormalities among HIV-infected patients. Timely endocrine or metabolic evaluations should be performed among patients suspected with endocrine or metabolic dysfunction and appropriate treatment instituted since the majority of these conditions pose an increased risk of mortality if undiagnosed or untreated.

Vitamin D deficiency among adult patients with tuberculosis: a cross sectional study from a national referral hospital in Uganda.

BACKGROUND: Vitamin D deficiency has been reported among patients with tuberculosis in Africa despite abundant sunshine. Vitamin D plays a fundamental role in improving anti tuberculosis immunity, reducing progression and severity of TB in humans. METHODS: In this descriptive cross sectional study, 260 hospitalized adults with a confirmed diagnosis of TB were enrolled into the study from the pulmonology wards of Mulago national referral and teaching hospital, Uganda. The serum concentrations of 25-hydroxyvitamin D or 25 (OH) D were determined by an electrochemilumniscence immunoassay. Vitamin D deficiency, vitamin D insufficiency, severe and very severe vitamin D deficiency were defined as serum 25(OH) D concentrations of ≤ 20 ng/ml, 21-29 ng/ml, < 10 ng/ml and <5 ng/ml respectively. RESULTS: Majority of the study participants were males (146, 56.2%) and < 35 years (154, 59.2%). The mean age ± SD was 34.7 ± 9.5 years. Two hundred eight (80%) patients were HIV co-infected with a median CD4 count of 68 cells/mm3 (IQR: 17-165). The prevalence of vitamin D deficiency, vitamin D insufficiency, severe and very severe vitamin D deficiency among the hospitalized adult tuberculosis patients was 44.2%, 23.5%, 13.5% and 4.2% respectively. The median (IQR) vitamin D concentration in ng/ml was 22.55 (14.59-33.31). CONCLUSION: Vitamin D deficiency is very common among hospitalized adult tuberculosis patients in Uganda especially in patients with hypoalbuminemia, anemia, HIV co-infected patients with CD4 count <200cells/mm3 and hypocalcemia corrected for serum albumin levels.

Overt diabetes mellitus among newly diagnosed Ugandan tuberculosis patients: a cross sectional study.

BACKGROUND: There is a documented increase of diabetes mellitus in Sub Saharan Africa, a region where tuberculosis is highly endemic. Currently, diabetes mellitus is one of the recognised risk factors of tuberculosis. No study has reported the magnitude of diabetes mellitus among tuberculosis patients in Uganda, one of the countries with a high burden of tuberculosis. METHODS: This was a cross-sectional study conducted among 260 consenting adult patients with a confirmed diagnosis of tuberculosis admitted on the pulmonology wards of Mulago national referral and teaching hospital in Kampala, Uganda to determine the prevalence of diabetes mellitus and associated clinical factors. Laboratory findings as well as the socio-demographic and clinical data collected using a validated questionnaire was obtained. Point of care random blood sugar (RBS) testing was performed on all the patients prior to initiation of anti tuberculosis treatment. Diabetes mellitus was diagnosed if the RBS level was ≥ 200mg/dl in the presence of the classical symptoms of diabetes mellitus. RESULTS: The prevalence of diabetes mellitus among the admitted patients with tuberculosis was 8.5%. Only 5 (1.9%) patients with TB had a known diagnosis of diabetes mellitus at enrolment. Majority of the study participants with TB-DM co-infection had type 2 diabetes mellitus (n=20, 90.9%).At bivariate analysis, raised mean ALT concentrations of ≥80 U/L were associated with DM (OR-6.1, 95% CI 1.4-26.36, p=0.032) and paradoxically, HIV co-infection was protective of DM (OR-0.32, 95% CI 0.13-0.79, P=0.016). The relationship between DM and HIV as well as that with ALT remained statistically significant at multivariate analysis (HIV: OR- 0.17 95%CI 0.06-0.51, p=0.002 and ALT: OR-11.42 95%CI 2.15-60.59, p=0.004). CONCLUSION: This study demonstrates that diabetes mellitus is common among hospitalized tuberculosis patients in Uganda. The significant clinical predictors associated with diabetes mellitus among tuberculosis patients were HIV co-infection and raised mean serum alanine transaminase concentrations.

Spectrum of lithium induced thyroid abnormalities: a current perspective.

BACKGROUND: Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. Thyroid abnormalities associated with treatment with lithium have been widely reported in medical literature to date. These include goitre, hypothyroidism, hyperthyroidism and autoimmune thyroiditis. This current review explores the varied thyroid abnormalities frequently encountered among patients on lithium therapy and their management, since lithium is still a fundamental and widely drug used in psychiatry and Internal Medicine. METHODS: PubMed database and Google scholar were used to search for relevant English language articles relating to lithium therapy and thyroid abnormalities up to December 2012. The search terms used were lithium treatment, thyroid abnormalities, thyroid dysfunction, goitre, hypothyroidism, hyperthyroidism, thyrotoxicosis, autoimmune thyroiditis, lithium toxicity, treatment of affective disorders and depression and side effects of antipsychotic drugs. Reference lists of the identified articles were further used to identify other studies. RESULTS: Lithium affects normal thyroid functioning through multiple mechanisms. At the cellular level, it decreases thyroid hormone synthesis and release. It also decreases peripheral deiodination of tetraiodothyronine (T4) or thyroxine by decreasing the activity of type I 5' de-iodinase enzyme. Hypothyroidism and goitre (clinically and/ultrasonographically detected) are the most prevalent thyroid abnormalities among patients on long term lithium therapy. Lithium induced hyperthyroidism is very infrequent. Lithium increases the propensity to thyroid autoimmunity in susceptible individuals due to its effect of augmenting the activity of B lymphocytes and reducing the ratio of circulating suppressor to cytotoxic T cells. CONCLUSIONS: Thyroid function tests (serum thyroid stimulating hormone, free thyroid hormones-T4 and triiodothyronine [T3] concentrations and thyroid auto-antibodies) and assessment of thyroid size clinically and by thyroid ultrasonography ought to be performed among patients initiating lithium therapy at baseline and later annually. More frequent assessment of thyroid function status and size during the course of therapy is recommended among middle aged females (≥50 years), patients with a family history of thyroid disease and those positive for thyroid auto-antibodies (anti-thyroid peroxidase and TSH receptor antibodies).

Aggregate evaluable organ dysfunction predicts in-hospital mortality from sepsis in Uganda.

We evaluated the association between severity of sepsis and in-hospital mortality in 150 patients with non-surgical sepsis at a regional referral hospital in Uganda. In-hospital mortality occurred in 5 of 52 (9.6%) patients with sepsis, 24 of 71 (33.8%) patients with severe sepsis, and 16 of 27 (59.3%) patients with septic shock. In the multivariate analysis, the identification of severe sepsis (adjusted hazard ratio [AHR] = 2.9, 95% confidence interval [CI] = 1.0-8.2, P = 0.04), septic shock (AHR = 5.7, 95% CI = 1.6-20.3, P = 0.007), and dysfunction of three or more organs (AHR = 2.9, 95% CI = 1.1-7.3, P = 0.03) increased the risk of in-hospital mortality. Adding aggregate organ dysfunction to the multivariate equation that included the sepsis category statistically significantly improved the model, but the opposite did not. Predictors of mortality were easily measurable and could be used to risk stratify critically ill patients in resource-constrained settings.

Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis.

OBJECTIVE: Dysglycemia during sepsis is associated with poor outcomes in resource-rich settings. In resource-limited settings, hypoglycemia is often diagnosed clinically without the benefit of laboratory support. We studied the utility of point-of-care glucose monitoring to predict mortality in severely septic patients in Uganda. DESIGN: Prospective observational study. SETTING: One national and two regional referral hospitals in Uganda. PATIENTS: We enrolled 532 patients with sepsis at three hospitals in Uganda. The analysis included 418 patients from the three sites with inhospital mortality data, a documented admission blood glucose concentration, and evidence of organ dysfunction at admission (systolic blood pressure≤100 mm Hg, lactate>4 mmol/L, platelet number<100,000/µL, or altered mental status). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the association between admission point-of-care blood glucose concentration and inhospital mortality. We also assessed the accuracy of altered mental status as a predictor of hypoglycemia. Euglycemia occurred in 33.5% (140 of 418) of patients, whereas 16.3% (68 of 418) of patients were hypoglycemic and 50.2% (210 of 418) were hyperglycemic. Univariate Cox regression analyses comparing in-hospital mortality among hypoglycemic (35.3% [24 of 68], hazard ratio 2.0, 95% confidence interval 1.2-3.6, p=.013) and hyperglycemic (29.5% [62 of 210], hazard ratio 1.5, 95% confidence interval 0.96-2.4, p=.08) patients to euglycemic (19.3% [27 of 140]) patients showed statistically significantly higher rates of inhospital mortality for patients with hypoglycemia. Hypoglycemia (adjusted hazard ratio 1.9, 95% confidence interval 1.1-3.3, p=.03) remained significantly and independently associated with inhospital mortality in the multivariate model. The sensitivity and specificity of altered mental status for hypoglycemia were 25% and 86%, respectively. CONCLUSION: Hypoglycemia is an independent risk factor for inhospital mortality in patients with severe sepsis and cannot be adequately assessed by clinical examination. Correction of hypoglycemia may improve outcomes of critically ill patients in resource-limited settings.