Striving towards true equity in global health: A checklist for bilateral research partnerships.

Interest in "global health" among schools of medicine, public health, and other health disciplines in high-income countries (HIC) continues to rise. Persistent power imbalances, racism, and maintenance of colonialism/neocolonialism plague global health efforts, including global health scholarship. Scholarly projects conducted in low- and middle-income countries (LMIC) by trainees at these schools in HIC often exacerbate these problems. Drawing on published literature and shared experiences, we review key inequalities within each phase of research, from design through implementation and analysis/dissemination, and make concrete and practical recommendations to improve equity at each stage. Key problems facing global health scholarship include HIC-centric nature of global health organizations, paucity of funding directly available for LMIC investigators and trainees, misplaced emphasis on HIC selected issues rather than local solutions to local problems, the dominance of English language in the scientific literature, and exploitation of LMIC team members. Four key principles lie at the foundation of all our recommendations: 1) seek locally derived and relevant solutions to global health issues, 2) create paired collaborations between HIC and LMIC institutions at all levels of training, 3) provide funding for both HIC and LMIC team members, 4) assign clear roles and responsibilities to value, leverage, and share the strengths of all team members. When funding for global health research is predicated upon more ethical and equitable collaborations, the nature of global health collaborations will evolve to be more ethical and equitable. Therefore, we propose the Douala Equity Checklist as a 20-item tool HIC and LMIC institutions can use throughout the conduct of global health projects to ensure more equitable collaborations.

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.

A 77-Year-Old Woman With Capillary Hypoxia and Perioral Cyanosis.

CASE PRESENTATION: A 77-year-old woman with asthma, hypothyroidism, irritable bowel syndrome, overactive bladder, and multiple rheumatologic conditions was sent from the clinic to the ED for evaluation of hypoxia. In the clinic, she reported dizziness without shortness of breath and was noted to have perioral cyanosis with an oxygen saturation measured by pulse oximetry (Spo2) of 80%. She was given a nonrebreather mask delivering oxygen at 8 L/min, but the Spo2 remained at 77% to 82%. In the ED, the patient reported intermittent shortness of breath, 2 to 3 days of mild left lower extremity swelling, and a brief episode of lightheadedness earlier in the day that had since resolved. She denied fevers/chills, upper respiratory symptoms, and chest pain. She had been referred to the pulmonology clinic 3 years earlier to evaluate mild hypoxia with Spo2 readings in the low 90% range, but pulmonary function testing failed to identify an etiology. There was no history of VTE. Her rheumatologic conditions included osteoarthritis, rheumatoid arthritis, Sjögren's syndrome, and fibromyalgia.

Clinical characteristics of Plasmodium falciparum infection among symptomatic patients presenting to a major urban military hospital in Cameroon.

BACKGROUND: Urban malaria has received insufficient attention in the literature. The prevalence and clinical characteristics of Plasmodium falciparum infection amongst patients presenting with suspected malaria were investigated at a major urban hospital in Douala, Cameroon with a particular focus on anaemia. METHODS: A cross-sectional, 18-week demographic and clinical survey was conducted of patients presenting to the Emergency Department of Douala Military Hospital with suspected malaria, largely defined by the presence or recent history of fever. Venous samples were tested for P. falciparum using rapid diagnostic tests and PCR, and anaemia was defined by haemoglobin level according to WHO definitions. Likelihood ratios (LR), odds ratios (OR), and population attributable risk percent (PARP) were calculated. RESULTS: Participants were ages 8 months to 86 years, 51% were women (257/503), and all districts of Douala were represented. Overall, 38.0% (n = 189/497) were anaemic, including 5.2% (n = 26/497) with severe anaemia. Anaemia prevalence was significantly higher (OR: 2.20, 95% CI 1.41-3.45) among children < 15 years (53.1%, n = 52/98) compared to adults (34%, n = 133/392). Plasmodium falciparum was detected in 37.2% by nested PCR. Among all participants, several factors were associated with clinically significant LR for P. falciparum infection, including age 10-14 years (positive LR: 3.73), living in the island district of Douala VI (positive LR: 3.41), travel to any of three northern regions (positive LR: 5.11), and high fever > 40 °C at presentation (positive LR: 4.83). Among all participants, 8.7% of anaemia was associated with P. falciparum infection, while the PARP was 33.2% among those < 15 years of age and 81.0% among 10-14-year-olds. CONCLUSIONS: The prevalence of P. falciparum infection in the urban hospital was high. Mirroring trends in many rural African settings, older children had the highest positivity rate for P. falciparum infection. Anaemia was also common in all age groups, and for those 10-14 years of age, 80% of the risk for anaemia was associated with P. falciparum infection. Malaria rates in major urban population centres can be high, and more research into the multifactorial causes of anaemia across the age spectrum are needed.

Cardiac tamponade as the initial presentation of autoimmune polyglandular syndrome Type 2: a case report.

Background: Cardiac tamponade is a rare but serious manifestation of autoimmune polyglandular syndrome Type 2 (APS 2). Patients often present with symptoms of thyroid dysfunction and adrenal insufficiency, but the insidious onset of the disease may lead to delayed diagnosis, which can progress rapidly to haemodynamic instability requiring urgent intervention. Case summary: A 39-year-old previously healthy male was admitted with cardiac tamponade complicated by cardiac arrest requiring emergent pericardiocentesis. An extensive work up revealed primary adrenal insufficiency and Hashimoto's thyroiditis. His positive autoantibodies to thyroid peroxidase and 21-hydroxylase combined with rapid improvement with initiation of corticosteroids and levothyroxine confirmed a diagnosis of APS 2. Discussion: Although this disease is often difficult to diagnose given its vague symptoms, it should be considered in the differential diagnosis for young patients presenting with pericardial effusion or cardiac tamponade of unknown origin. Early diagnosis and management are critical and often result in rapid improvement after appropriate treatment.

Perianeurysmal retroperitoneal fibrosis presenting as acute kidney injury: A case report.

Retroperitoneal fibrosis and chronic periaortitis describe overlapping groups of rare diseases characterized by inflammation and fibrosis involving the aorta. The presentation is often non-specific, and while obstructive nephropathy is a common complication, these entities are an uncommon cause of renal failure necessitating dialysis. A 57-year-old man presented multiple times with acute kidney injury, even requiring hemodialysis, with repeated abrupt resolution. Renal ultrasound repeatedly did not reveal acute hydronephrosis. Renal biopsy on his first admission showed acute tubular injury attributed to hypovolemia. Computed tomography finally revealed a retroperitoneal soft tissue mass encasing the infrarenal abdominal aorta and partially encasing the bilateral ureters. Bilateral nephrostomy tubes were placed, steroids were initiated, and the patient experienced rapid and remarkable improvement in renal function. Chronic periaortitis should be considered in older patients with acute kidney injury, even in the absence of ultrasonographic evidence of obstruction. Additional studies are needed to describe the test characteristics of renal sonography for periaortitis, the long-term sequelae of acute kidney injury secondary to periaortitis, and the optimal management to preserve long-term renal function.

Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.

Mechanisms of Diuretic Resistance Study: design and rationale.

INTRODUCTION: Diuretic resistance is a common complication impairing decongestion during hospitalization for acute decompensated heart failure (ADHF). The current understanding of diuretic resistance mechanisms in ADHF is based upon extrapolations from other disease states and healthy volunteers. However, accumulating evidence suggests that the dominant mechanisms in other populations have limited influence on diuretic response in ADHF. Additionally, the ability to rapidly and reliably diagnose diuretic resistance is inadequate using currently available tools. AIMS: The Mechanisms of Diuretic Resistance (MDR) Study is designed to rigorously investigate the mechanisms of diuretic resistance and develop tools to rapidly predict diuretic response in a prospective cohort hospitalized with ADHF. METHODS: Study assessments occur serially during the ADHF hospitalization and after discharge. Each assessment includes a supervised 6-hour urine collection with baseline blood and timed spot urine collections following loop diuretic administration. Patient characteristics, medications, physical exam findings, and both in-hospital and post-discharge HF outcomes are collected. Patients with diuretic resistance are eligible for a randomized sub-study comparing an increased loop diuretic dose with combination diuretic therapy of loop diuretic plus chlorothiazide. CONCLUSIONS: The Mechanisms of Diuretic Resistance Study will establish a prospective patient cohort and biorepository to investigate the mechanisms of diuretic resistance and urine biomarkers to rapidly predict loop diuretic resistance.

Natriuretic Response Is Highly Variable and Associated With 6-Month Survival: Insights From the ROSE-AHF Trial.

OBJECTIVES: This study sought to describe sodium excretion in acute decompensated heart failure (ADHF) clearly and to evaluate the prognostic ability of urinary sodium and fluid-based metrics. BACKGROUND: Sodium retention drives volume overload, with fluid retention largely a passive, secondary phenomenon. However, parameters (urine output, body weight) used to monitor therapy in ADHF measure fluid rather than sodium balance. Thus, the accuracy of fluid-based metrics hinges on the contested assumption that urinary sodium content is consistent. METHODS: Patients enrolled in the ROSE-AHF (Renal Optimization Strategies Evaluation-Acute Heart Failure) trial with 24-h sodium excretion available were studied (n = 316). Patients received protocol-driven high-dose loop diuretic therapy. RESULTS: Sodium excretion through the first 24 h was highly variable (range 0.12 to 19.8 g; median 3.63 g, interquartile range: 1.85 to 6.02 g) and was not correlated with diuretic agent dose (r = 0.06; p = 0.27). Greater sodium excretion was associated with reduced mortality in a univariate model (hazard ratio: 0.80 per doubling of sodium excretion; 95% confidence interval: 0.66 to 0.95; p = 0.01), whereas gross urine output (p = 0.43), net fluid balance (p = 0.87), and weight change (p = 0.11) were not. Sodium excretion of less than the prescribed dietary sodium intake (2 g), even in the setting of a negative net fluid balance, portended a worse prognosis (hazard ratio: 2.02; 95% confidence interval: 1.17 to 3.46; p = 0.01). CONCLUSIONS: In patients hospitalized with ADHF who were receiving high-dose loop diuretic agents, sodium concentration and excretion were highly variable. Sodium excretion was strongly associated with 6-month mortality, whereas traditional fluid-based metrics were not. Poor sodium excretion, even in the context of fluid loss, portends a worse prognosis.