SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019-2022.

BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.

Outcomes of treatment with CHOP and EPOCH in patients with HIV associated NHL in a low resource setting.

BACKGROUND: The optimal chemotherapy regimen for treating HIV associated NHL in low resource settings is unknown. We conducted a retrospective study to describe survival rates, treatment response rates and adverse events in patients with HIV associated NHL treated with CHOP and dose adjusted-EPOCH regimens at the Uganda Cancer Institute. METHODS: A retrospective study of patients diagnosed with HIV and lymphoma and treated at the Uganda Cancer Institute from 2016 to 2018 was done. RESULTS: One hundred eight patients treated with CHOP and 12 patients treated with DA-EPOCH were analysed. Patients completing 6 or more cycles of chemotherapy were 51 (47%) in the CHOP group and 8 (67%) in the DA-EPOCH group. One year overall survival (OS) rate in patients treated with CHOP was 54.5% (95% CI, 42.8-64.8) and 80.2% (95% CI, 40.3-94.8) in those treated with DA-EPOCH. Factors associated with favourable survival were BMI 18.5-24.9 kg/m2, (p = 0.03) and completion of 6 or more cycles of chemotherapy, (p < 0.001). The overall response rate was 40% in the CHOP group and 59% in the DA-EPOCH group. Severe adverse events occurred in 19 (18%) patients in the CHOP group and 3 (25%) in the DA-EPOCH group; these were neutropenia (CHOP = 13, 12%; DA-EPOCH = 2, 17%), anaemia (CHOP = 12, 12%; DA-EPOCH = 1, 8%), thrombocytopenia (CHOP = 7, 6%; DA-EPOCH = 0), sepsis (CHOP = 1), treatment related death (DA-EPOCH = 1) and hepatic encephalopathy (CHOP = 1). CONCLUSION: Treatment of HIV associated NHL with curative intent using CHOP and infusional DA-EPOCH is feasible in low resource settings and associated with > 50% 1 year survival.

Malaria parasitemia among blood donors in Uganda.

BACKGROUND: Malaria remains a leading transfusion associated infectious risk in endemic areas. However, the prevalence of malaria parasitemia has not been well characterized in blood donor populations. This study sought to determine the prevalence of Plasmodium in red blood cell (RBC) and whole blood (WB) units after the rainy season in Uganda. METHODS AND MATERIALS: Between May and July 2018, blood was collected from the sample diversion pouch of 1000 WB donors in Kampala and Jinja, Uganda. The RBC pellet from ethylenediamine tetraacetic acid (EDTA) anticoagulated blood was stored at -80°C until testing. DNA was extracted and nested PCR was used to screen samples at the genus level for Plasmodium, with positive samples further tested for species identification. RESULTS: Malaria parasitemia among asymptomatic, eligible blood donors in two regions of Uganda was 15.4%; 87.7% (135/154) of infections were with P. falciparum, while P. malariae and P. ovale were also detected. There were 4.3% of blood donors who had mixed infection with multiple species. Older donors (>30 years vs. 17-19 years; aPR = 0.31 [95% CI = 0.17-0.58]), females (aPR = 0.60 [95% CI = 0.42-0.87]), repeat donors (aPR = 0.44 [95% CI = 0.27-0.72]) and those donating near the capital city of Kampala versus rural Jinja region (aPR = 0.49 [95% CI = 0.34-0.69]) had a lower prevalence of malaria parasitemia. CONCLUSIONS: A high proportion of asymptomatic blood donors residing in a malaria endemic region demonstrate evidence of parasitemia at time of donation. Further research is needed to quantify the risk and associated burden of transfusion-transmitted malaria (TTM) in order to inform strategies to prevent TTM.

Prevalence of lower limb deep venous thrombosis among adult HIV positive patients attending an outpatient clinic at Mulago Hospital.

BACKGROUND: Deep venous thrombosis (DVT) and its major complication pulmonary embolism (PE) are collectively known as venous thromboembolism. In Uganda, the prevalence of DVT among HIV patients has not been previously published. The aim of the study was to determine the prevalence and sonographic features of lower limb deep venous thrombosis among HIV positive patients on anti-retroviral treatment (ART). METHODS: This was a cross sectional study in which HIV positive patients on ART were recruited from an out-patient HIV clinic at Mulago National Referral Hospital. Patients were randomly selected and enrolled until a sample size of 384 was reached. Study participants underwent compression and Doppler ultrasound studies of both lower limb deep veins using Medison Sonoacer7 ultrasound machine. RESUTS: We found a prevalence of DVT of 9.1% (35 of 384 participants) among HIV patients on ART. The prevalence of latent (asymptomatic) DVT was 2.3%. Among 35 patients with DVT, 42.8% had chronic DVT; 31.1% had acute DVT and the rest had latent DVT. Among the risk factors, the odds of occurrence of DVT among patients with prolonged immobility were 4.81 times as high as in those with no prolonged immobility (p = 0.023; OR = 4.81; 95% CI 1.25-18.62). Treatment with second line anti-retroviral therapy (ART) including protease inhibitors (PIs) was associated with higher odds of DVT occurrence compared with first line ART (p = 0.020; OR = 2.38; 95% CI 1.14-4.97). The odds of DVT occurrence in patients with a lower CD4 count (< 200 cells/µl) were 5.36 times as high as in patients with CD4 counts above 500 cells/µl (p = 0.008). About 48.6% patients with DVT had a low risk according to Well's score. CONCLUSION: DVT was shown in nearly 10% of HIV patients attending an out-patient clinic in an urban setting in Uganda. Risk factors included protease inhibitors in their ART regimen, prolonged immobility, and low CD4 count (< 200 cells/µl). Clinicians should have a low threshold for performing lower limb Doppler ultrasound scan examination on infected HIV patients on ART who are symptomatic for DVT. Therefore, clinicians should consider anti-coagulant prophylaxis and lower deep venous ultrasound screening of patients who are on second line ART regimen with low CD4 cell counts and/or with prolonged immobility or hormonal contraception.

B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage red blood cells: Results from the TOTAL randomized trial.

BACKGROUND: Prior studies have suggested that transfusion of stored red blood cells (RBCs) with increased levels of cell-free hemoglobin might reduce the bioavailability of recipient nitric oxide (NO) and cause myocardial strain. METHODS: Ugandan children (ages 6-60 months) with severe anemia and lactic acidosis were randomly assigned to receive RBCs stored 1-10 days versus 25-35 days. B-type natriuretic peptide (BNP), vital signs, renal function test results, and plasma hemoglobin were measured. Most children had either malaria or sickle cell disease and were thus at risk for reduced NO bioavailability. RESULTS: Seventy patients received RBCs stored 1-10 days, and 77 received RBCs stored 25-35 days. The median (interquartile range) cell-free hemoglobin was nearly 3 times higher in longer-storage RBCs (26.4 [15.5-43.4] µmol/L) than in shorter-storage RBCs (10.8 [7.8-18.6] µmol/L), P < .0001. Median (interquartile range) BNP 2 hours posttransfusion was 156 (59-650) pg/mL (shorter storage) versus 158 (59-425) pg/mL (longer storage), P = .76. BNP values 22 hours posttransfusion were 110 (46-337) pg/mL (shorter storage) versus 96 (49-310) pg/mL (longer storage), P = .76. Changes in BNP within individuals from pretransfusion to 2 hours (or 22 hours) posttransfusion were not significantly different between the study groups. BNP change following transfusion did not correlate with the concentration of cell-free hemoglobin in the RBC supernatant. Blood pressure, blood urea nitrogen, creatinine, and change in plasma hemoglobin were not significantly different in the 2 groups. CONCLUSION: In a randomized trial among children at risk for reduced NO bioavailability, we found that BNP, blood pressure, creatinine, and plasma hemoglobin were not higher in patients receiving RBCs stored for 25-35 versus 1-10 days.

Possible misdiagnosis of HIV associated lymphoma as tuberculosis among patients attending Uganda Cancer Institute.

BACKGROUND: Early diagnosis of HIV associated lymphoma is challenging because the definitive diagnostic procedure of biopsy, requires skills and equipment that are not readily available. As a consequence, diagnosis may be delayed increasing the risk of mortality. We set out to determine the frequency and risk factors associated with the misdiagnosis of HIV associated lymphoma as tuberculosis (TB) among patients attending the Uganda Cancer Institute (UCI). METHODS: A retrospective cohort study design was used among HIV patients with associated lymphoma patients attending the UCI, Kampala, Uganda between February and March 2015. Eligible patient charts were reviewed for information on TB treatment, socio-demographics, laboratory parameters (Hemoglobin, CD4cells count and lactate dehydrogenase) and clinical presentation using a semi structured data extraction form. RESULTS: A total of 183 charts were reviewed; 106/183 were males (57.9%), the median age was 35 (IQR, 28-45). Fifty six (30.6%) patients had a possible misdiagnosis as TB and their median time on TB treatment was 3.5 (1-5.3) months. In multivariate analysis the presence of chest pain had an odd ratio (OR) of 4.4 (95% CI 1.89-10.58, p < 0.001) and stage III and IV lymphoma disease had an OR of 3.22 (95% CI 1.08-9.63, p < 0.037) for possible misdiagnosis of lymphoma as TB. CONCLUSION: A high proportion of patients with HIV associated lymphoma attending UCI are misdiagnosed and treated as TB. Chest pain and stage III and IV of lymphoma were associated with an increased risk of a possible misdiagnosis of lymphoma as TB.

Platelet transfusion therapy in sub-Saharan Africa: bacterial contamination, recipient characteristics, and acute transfusion reactions.

BACKGROUND: Little data are available on bacterial contamination (BC) of platelet units or acute transfusion reactions to platelet transfusions (PTs) in sub-Saharan Africa (SSA). STUDY DESIGN AND METHODS: This prospective, observational study evaluated the rate of BC in whole blood-derived platelet units (WB-PUs), the utility of performing Gram stains to prevent septic reactions, characteristics of patients receiving PTs, and the rate of acute reactions associated with PTs at the Uganda Cancer Institute in Kampala, Uganda. An aliquot of each WB-PU studied was taken to perform Gram stains and culture using the Bactec 9120 instrument. Study participants were monitored for reactions. RESULTS: In total, 337 WB-PUs were evaluated for BC, of which 323 units were transfused in 151 transfusion episodes to 50 patients. The frequency of BC ranged from 0.3% to 2.1% (according to criteria used to define BC). The Gram stain had high specificity (99.1%) but low sensitivity to detect units with BC. The median platelet count before PT was 10,900 cells/µL (interquartile range, 6000-18,900 cells/µL). Overall, 78% of PTs were given to patients with no bleeding. Acute reactions occurred in 11 transfusion episodes, involving 13 WB-PUs, for a rate of 7.3% (95% confidence interval, 3.7%-12.7%) per transfusion episode. All recipients of units with positive bacterial cultures were receiving antibiotics at the time of transfusion; none experienced a reaction. CONCLUSIONS: The rate of BC observed in this study is lower than previously reported in SSA, but still remains a safety issue. Because Gram staining appears to be an ineffective screening tool, alternate methods should be explored to prevent transfusing bacterially contaminated platelets in sub-Saharan Africa.

Optimisation of the continuum of supportive and palliative care for patients with breast cancer in low-income and middle-income countries: executive summary of the Breast Health Global Initiative, 2014.

Supportive care and palliative care are now recognised as critical components of global cancer control programmes. Many aspects of supportive and palliative care services are already available in some low-income and middle-income countries. Full integration of supportive and palliative care into breast cancer programmes requires a systematic, resource-stratified approach. The Breast Health Global Initiative convened three expert panels to develop resource allocation recommendations for supportive and palliative care programmes in low-income and middle-income countries. Each panel focused on a specific phase of breast cancer care: during treatment, after treatment with curative intent (survivorship), and after diagnosis with metastatic disease. The panel consensus statements were published in October, 2013. This Executive Summary combines the three panels' recommendations into a single comprehensive document covering breast cancer care from diagnosis through curative treatment into survivorship, and metastatic disease and end-of-life care. The recommendations cover physical symptom management, pain management, monitoring and documentation, psychosocial and spiritual aspects of care, health professional education, and patient, family, and caregiver education.

Blood utilization at a national referral hospital in sub-Saharan Africa.

BACKGROUND: A safe and adequate supply of blood is critical to improving health care systems in sub-Saharan Africa, where little is known about the current use of blood. The aim of this study was to comprehensively describe the use of blood at a tertiary care hospital to inform future efforts to strengthen blood programs in resource-limited settings. STUDY DESIGN AND METHODS: Data were collected from blood bank documentation for all units issued at Mulago Hospital Complex in Kampala, Uganda, from mid-January to mid-April 2014. RESULTS: A total of 6330 units (69% whole blood, 32% red blood cells, 6% platelets, 2% plasma) were issued over the 3-month study period to 3662 unique patients. Transfusion recipients were 58% female and median age was 27 years (interquartile range [IQR], 14-41). Median pretransfusion hemoglobin was 5.6 g/dL (IQR, 4.0-7.2 g/dL, n = 1090). Strikingly, cancer was the top indication for transfusion (33.5%), followed by pregnancy-related complications (12.4%) and sickle cell disease (6.9%). CONCLUSION: This study provides a comprehensive picture of blood use at a national referral hospital in sub-Saharan Africa. Noncommunicable diseases, particularly oncologic conditions, represent a large proportion of demand for transfusion services.

Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial.

IMPORTANCE: Although millions of transfusions are given annually worldwide, the effect of red blood cell (RBC) unit storage duration on oxygen delivery is uncertain. OBJECTIVE: To determine if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia. DESIGN, SETTING, AND PARTICIPANTS: Randomized noninferiority trial of 290 children (aged 6-60 months), most with malaria or sickle cell disease, presenting February 2013 through May 2015 to a university-affiliated national referral hospital in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher. INTERVENTIONS: Patients were randomly assigned to receive RBC units stored 25 to 35 days (longer-storage group; n = 145) vs 1 to 10 days (shorter-storage group; n = 145). All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours 0 through 2 and, if indicated per protocol, an additional 10 mL/kg during hours 4 through 6. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a lactate level of 3 mmol/L or lower at 8 hours using a margin of noninferiority equal to an absolute difference of 25%. Secondary measures included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health at 30 days after transfusion. Adverse events were monitored up to 24 hours. RESULTS: In the total population of 290 children, the mean (SD) presenting hemoglobin level was 3.7 g/dL (1.3) and mean lactate level was 9.3 mmol/L (3.4). Median (interquartile range) RBC unit storage was 8 days (7-9) for shorter storage vs 32 days (30-34) for longer storage without overlap. The proportion achieving the primary end point was 0.61 (95% CI, 0.52 to 0.69) in the longer-storage group vs 0.58 (95% CI, 0.49 to 0.66) in the shorter-storage group (between-group difference, 0.03 [95% CI, -0.07 to ∞], P < .001), meeting the prespecified margin of noninferiority. Mean lactate levels were not statistically different between the 2 groups at 0, 2, 4, 6, 8, or 24 hours. Kaplan-Meier analysis and global nonlinear regression revealed no statistical difference in lactate reduction between the 2 groups. Clinical assessment, cerebral oxygen saturation, electrolyte abnormalities, adverse events, survival, and 30-day recovery were also not significantly different between the groups. CONCLUSIONS AND RELEVANCE: Among children with lactic acidosis due to severe anemia, transfusion of longer-storage compared with shorter-storage RBC units did not result in inferior reduction of elevated blood lactate levels. These findings have relevance regarding the efficacy of stored RBC transfusion for patients with critical tissue hypoxia and lactic acidosis due to anemia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01586923.

Acute transfusion reactions at a national referral hospital in Uganda: a prospective study.

BACKGROUND: Very little has been published about acute transfusion reactions (ATRs) in developing countries. This study was undertaken to determine the incidence, type, imputability, severity, and possible associated factors of ATRs observed in a university-affiliated hospital in Uganda. STUDY DESIGN AND METHODS: We prospectively followed the transfusion of blood units issued over a 7-week period from the hospital blood bank during regular working hours to nonbleeding patients. For each transfusion, we recorded the patient's status before, during, at the end of, and 4 hours after transfusion. Three physicians independently reviewed all reports of suspected ATRs and related hospital charts. Using predefined criteria, the presence, type, imputability, and severity of ATRs were adjudicated by consensus of two of three physicians. Factors potentially associated with ATRs were analyzed for statistical significance. RESULTS: A total of 507 transfusions were analyzed. Fifty-three acute transfusion events were recorded and 49 of 53 or 9.6% of the 507 transfusions were confirmed to be ATRs by physician consensus: 24 febrile, seven allergic, five hypertensive, three hypotensive, three transfusion-associated circulatory overload, two acute hemolytic, and five others. Imputability of ATRs was definite, probable, or possible in 45 of 49 ATRs (92% of ATRs or 8.9% of transfusions) and judged to be severe in nine of 45. No significant associated factors were identified. CONCLUSIONS: Our findings suggest that ATRs may occur more commonly in resource-limited settings than in high-income countries. Although some reactions are unavoidable, improved surveillance of transfusions and implementation of transfusion guidelines could improve the safety of transfusions in these settings.

Advance Care Planning and palliative care for patients with advanced cancer in Uganda.

The study sought to identify the extent to which Advance Care Planning (ACP) is practised by palliative care health professionals providing care to patients with advanced cancer and their families in Uganda. A mixed methods study design using qualitative and quantitative methods was used for the assessment. In-depth interviews with a group of nine highly experienced health professionals were conducted using a semi-structured interview guide. Quantitative data were retrieved and analysed from a survey administered to 124 health professionals of whom only 57 (45.9%) responded. The qualitative data were analysed using inductive thematic analysis and descriptive analysis was used for the quantitative data. Of the 57 health professionals who participated in the survey, 87% were aware of ACP and 55% reported regular practice. Fifty-five (55%) percent reported regular provision of ACP for their patients and 46% reported engaging in informal ACP practices. However, 58.5% resp. 37.5% reported that they routinely provide ACP to more than 50% resp. 75% of their patients. A group of nine highly experienced palliative care professionals had a pooled ACP prevalence of only 1.2%. There was a generally good attitude towards ACP with 98.2% acknowledging that patients should be able to determine their future care. However, 32% reported being uncomfortable withholding or withdrawing life sustaining treatment. There are a number of socio-cultural beliefs and barriers, for instance that discussing death and dying is a "taboo", as well as witchcraft, family influence in decision-making, religious beliefs that do not agree with palliative care practices and a preference to use aggressive treatment like chemotherapy for terminally ill, etc. Institutional barriers like lack of a legal framework for ACP, limited time for health professionals to engage in ACP and other patient factors such as denial of diagnosis and collusion to withhold information from patients were reported by 78.2% resp. 84% of the respondents. Despite the good awareness and attitude to ACP, there is a range of barriers that are affecting the implementation of ACP in Uganda. There is need for development of a legal framework for ACP, more research to understand the contextual barriers and develop appropriate education and public sensitisation programs.

One-Year Survival and Prognosticators of Adults With Acute Leukemia at the Uganda Cancer Institute.

PURPOSE: Acute leukemias are associated with substantial morbidity and mortality, particularly in the adult population. Despite an increasing burden of acute leukemia in developing countries, there are limited data on clinical outcomes and prognostic factors in this setting. In this study, we aimed to describe the clinical characteristics, survival, and prognostic factors of adults with acute leukemia at the Uganda Cancer Institute (UCI). METHODS: A retrospective cohort study was conducted between January 2009 and December 2018, reviewing data of patients 18 years or older with a cytopathologic diagnosis of acute leukemia at UCI. Data were extracted on clinical and laboratory characteristics, response to treatment, and survival. Cox-proportional hazards regression and survival analysis were performed to determine survival rates and associated factors. P < .05 was considered statistically significant. RESULTS: In total, 233 participants were enrolled. Most (59.2%. n = 138) participants were male, with a median age of 32 years (IQR, 23-48 years), and 136 (58.4%) had AML. Overall, the 1-year survival was 16.5%, with a median survival time of 47 (IQR, 21-219) days. Predictors of mortality were being a female (adjusted hazard ratio [aHR], 2.8; 95% CI, 1.2 to 6.7; P = .022) and overweight (aHR, 4.2; 95% CI, 1.3 to 13.4; P = .015). Among the patients who had AML, the predictors were poor Eastern Cooperative Oncology Group (ECOG; aHR, 3.1; 95% CI, 1.6 to 6.2; P = .001) and HIV (aHR, 6.0; 95% CI, 1.7 to 20.5; P = .004). Among the patients who had ALL, the predictors were poor ECOG (aHR, 2.3; 95% CI, 1.3 to 4.1; P = .006). CONCLUSION: Patients with acute leukemia in Uganda have poor overall survival. Prospective studies are recommended to better understand causes of early mortality.

Virologic Nonsuppression Among Patients With HIV Newly Diagnosed With Cancer at Uganda Cancer Institute: A Cross-Sectional Study.

PURPOSE: AIDS-related mortality declined markedly since the introduction of antiretroviral therapy (ART); however, cancer mortality in Africa was higher than its incidence in 2020. People living with HIV (PLWHIV) are at an increased risk of malignancy and death from malignancy compared with the general population. In Uganda, AIDS-defining malignancies (ADMs), including cervical cancer, Kaposi sarcoma, and non-Hodgkin lymphoma, are among the commonest malignancies. Virologic nonsuppression has been identified as an important predictor of mortality among PLWHIV diagnosed with cancer. This study aimed to determine the prevalence and to identify factors associated with virologic nonsuppression among PLWHIV newly diagnosed with cancer. METHODS: This was a cross-sectional study that was carried out between December 2018 and April 2019 at the Uganda Cancer Institute. PLWHIV who had been on ART for at least 6 months and were newly diagnosed with cancer were enrolled. RESULTS: A total of 167 participants were enrolled. Cervical cancer was the commonest ADM (n = 45; 50.6%) of all ADMs, while esophageal and breast cancers were the commonest non-ADMs, accounting for 17.5% (n = 14) each of all non-ADMs. The prevalence of virologic nonsuppression was 15%. Having Kaposi sarcoma (odds ratio [OR], 8.15; P = .003), being poorly adherent to ART (OR, 4.1; P = .045), and being on second-line ART (OR, 5.68; P = .011) were associated with virologic nonsuppression. CONCLUSION: The prevalence of virologic nonsuppression is high among patients with HIV newly diagnosed with cancer. These findings emphasize the need for strengthening of adherence strategies, optimizing ART regimens, and prioritization of viral load testing among PLWHIV with newly diagnosed malignancy.

Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection.

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies.

Foetal haemoglobin and disease severity in sickle cell anaemia patients in Kampala, Uganda.

BACKGROUND: Sickle cell anaemia (SCA) is a major chronic health problem in Uganda. In patients with SCA, the level of foetal haemoglobin (HbF) has been found to be important in influencing the clinical course of the disease. Thus populations with high levels of HbF like those in Saudi Arabia have been described as having a milder clinical course with fewer complications as compared to populations with lower levels. Disease modifying drugs can increase the Hb F levels and modify the presentation of SCA. METHODS: This was a cross sectional study in which we determined foetal haemoglobin levels and examined the relationship between HbF levels and disease severity in SCA patients in Mulago Hospital, Kampala, Uganda. We consecutively enrolled 216 children aged 1 year to 18 years with SCA attending the Sickle Cell Clinic at Mulago Hospital whose guardians had given consent. The history included age at onset of initial symptoms and diagnosis, number of hospitalisations and blood transfusions and other complications of SCA (cardiovascular accidents, avascular hip necrosis and priapism). A detailed physical examination was performed to assess the current state and help describe the disease severity for each patient. Blood samples were drawn for HbF levels. HbF levels ≥10% was defined as high. RESULTS: Of the 216 children, (80) 37% had HbF levels ≥10%. Significant correlations were observed between HbF level and several clinical parameters independent of age including age at diagnosis (p value 0.013), number of hospitalisations (p value 0.024) and transfusions (p value 0.018) since birth. CONCLUSION: A third of the children with SCA attending the Sickle cell clinic in Mulago Hospital have high HbF levels. Higher HbF level is associated with later onset of symptoms and presentation, and less severe disease characterised by fewer hospitalisations and blood transfusions. We suggest HbF levels should be determined at initial contact for patients with SCA to guide counselling and identify those who may need closer follow up and consideration for disease modifying drugs.

Cytoreductive surgery for giant locally advanced intra-abdominal tumors in Uganda.

Cytoreductive surgery is removal of tumor as much as possible when complete resection is impossible because of advanced disease. It is a management option for giant intra-abdominal tumors with pressure symptoms. We present three patients who underwent cytoreductive surgery for giant intra-abdominal tumors between May 2019 and November 2021. Patient 1 had a gastrointestinal stromal tumor (GIST) involving stomach, spleen and transverse colon. En bloc resection of the GIST with the involved viscera was done. Patient 2 had a liposarcoma measuring 25.8 × 19.6 × 15.3 cm infiltrating the stomach, spleen and the left hemidiaphragm. Involved viscera and liposarcoma were resected en bloc. Patient 3 had a liposarcoma measuring 40 × 35 × 12 cm and encasing the left ureter. Mass was excised together with part of the left ureter and left ureter reconstructed. Giant intra-abdominal tumors are rare. Involvement of adjacent structures may necessitate multivisceral resections with or without organ reconstruction.

An update on the global use of risk assessment models and thromboprophylaxis in hospitalized patients with medical illnesses from the World Thrombosis Day steering committee: Systematic review and meta-analysis.

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. The majority of VTE events are hospital-associated. In 2008, the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) multinational cross-sectional study reported that only approximately 40% of medical patients at risk of VTE received adequate thromboprophylaxis. METHODS: In our systematic review and meta-analysis, we aimed at providing updated figures concerning the use of thromboprophylaxis globally. We focused on: (a) the frequency of patients with an indication to thromboprophylaxis according with individual models; (b) the use of adequate thromboprophylaxis; and (c) reported contraindications to thromboprophylaxis. Observational nonrandomized studies or surveys focusing on medically ill patients were considered eligible. RESULTS: After screening, we included 27 studies from 20 countries for a total of 137 288 patients. Overall, 50.5% (95% confidence interval [CI]: 41.9-59.1, I2 99%) of patients had an indication to thromboprophylaxis: of these, 54.5% (95% CI: 46.2-62.6, I2 99%) received adequate thromboprophylaxis. The use of adequate thromboprophylaxis was 66.8% in Europe (95% CI: 50.7-81.1, I2 98%), 44.9% in Africa (95% CI: 31.8-58.4, I2 96%), 37.6% in Asia (95% CI: 25.7-50.3, I2 97%), 58.3% in South America (95% CI: 31.1-83.1, I2 99%), and 68.6% in North America (95% CI: 64.9-72.6, I2 96%). No major differences in adequate thromboprophylaxis use were found across risk assessment models. Bleeding, thrombocytopenia, and renal/hepatic failure were the most frequently reported contraindications to thromboprophylaxis. CONCLUSIONS: The use of anticoagulants for VTE prevention has been proven effective and safe, but thromboprophylaxis prescriptions are still unsatisfactory among hospitalized medically ill patients around the globe with marked geographical differences.

The Mirasol Evaluation of Reduction in Infections Trial (MERIT): study protocol for a randomized controlled clinical trial.

BACKGROUND: Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8). METHODS: MERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated. DISCUSSION: Screening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda. TRIAL REGISTRATION: Mirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669 . Registered on 9 November 2018.

Palliative care: what approaches are suitable in developing countries?

The enormous burden of life-threatening illnesses, including cancer, human immunodeficiency virus infection, and others, such as sickle cell disease, associated with physical and psychosocial suffering explains the illustrious need for palliative care in developing countries. Despite the demonstrated need, current provision of palliative care in Africa is at best limited, and at worst non-existent. Access to essential pain medicines, particularly oral morphine, for control of pain is extremely limited and far below the global mean. There is a general lack of government policies that recognize palliative care as an essential component of health care and there is inadequate training for both health care professionals and the general public about palliative care. A public health strategy, as recommended by the World Health Organization (WHO), offers the best approach for translating knowledge and skills into evidence-based, cost-effective interventions that can reach everyone in need of palliative care in developing countries.