Elissa K. Butler

Multisite Validation of Cryptococcal Antigen Lateral Flow Assay and Quantification by Laser Thermal Contrast

This assay is a major advance in the diagnosis of cryptococcal meningitis.

Significantly Improved Analytical Sensitivity of Lateral Flow Immunoassays by Using Thermal Contrast

The ability to rapidly identify diseases enables prompt treatment and improves outcomes. This has increased the development and use of rapid point-of-care diagnostic devices capable of biomolecular detection in both high-income and resource-limited settings.[1] Lateral flow assays (LFAs) are inexpensive, simple, portable, and robust,[2] making LFAs commonplace in medicine, agriculture, and over-the-counter personal use such as for pregnancy testing. Although the analytical performance of some LFAs are comparable to laboratory based methods,[1a] the sensitivity of most LFAs is in the mM to μM range,[2–3] which is many folds less sensitive than other molecular techniques such as enzyme-linked immunoassays (ELISA). As a consequence, LFAs are not particularly useful for detection early in a disease course when there is low level of antigen. Due to the increasing need for highly sensitive molecular diagnostics, researchers have focused on developing microfluidics,[1a, 1b] biobar codes,[1c, 1d] and enzyme-based immunoassay technologies[4] technologies to fulfill the need since these technologies have nM to pM detection sensitivity for protein analysis and can potentially be miniaturized as handheld point-of-care diagnostic devices.[1c] These emerging technologies are still early in development and are not yet field-ready.

Long Term 5-Year Survival of Persons with Cryptococcal Meningitis or Asymptomatic Subclinical Antigenemia in Uganda

Data presented previously as an abstract at the 2011 CUGH Global Health Conference in Montreal, Canada on 15 Nov 2011. The long-term survival of HIV-infected persons with symptomatic cryptococcal meningitis and asymptomatic, subclinical cryptococcal antigenemia (CRAG+) is unknown. We prospectively enrolled 25 asymptomatic, antiretroviral therapy (ART)-naïve CRAG+ Ugandans with CD4<100 cells/mcL who received pre-emptive fluconazole treatment (CRAG+ cohort) and 189 ART-naïve Ugandans with symptomatic cryptococcal meningitis treated with amphotericin (CM cohort). The 10-week survival was 84% (95%CI: 70–98%) in the CRAG+ cohort and 57% (95%CI: 50%–64%) in the CM cohort. The CRAG+ cohort had improved five-year survival of 76% (95%CI: 59%–93%) compared to 42% (95%CI: 35%–50%) in the CM cohort (P = 0.001). The two cohorts had similar immunosuppression pre-ART with median CD4 counts of 15 vs. 21 CD4/mcL in the CRAG+ and CM cohorts, respectively (P = 0.45). Despite substantial early mortality, subsequent 5-year survival of persons surviving 6-months was excellent (>88%), demonstrating that long term survival is possible in resource-limited settings. Pre-ART CRAG screening with preemptive fluconazole treatment and improved CM treatment(s) are needed to reduce AIDS-attributable mortality due to cryptococcosis which remains 20–25% in sub-Saharan Africa.

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

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.

Burden of Surgical Conditions in Uganda: A Cross-sectional Nationwide Household Survey.

Objective: To quantify the burden of surgical conditions in Uganda. Background: Data on the burden of disease have long served as a cornerstone to health policymaking, planning, and resource allocation. Population-based data are the gold standard, but no data on surgical burden at a national scale exist; therefore, we adapted the Surgeons OverSeas Assessment of Surgical Need survey and conducted a nation-wide, cross-sectional survey of Uganda to quantify the burden of surgically treatable conditions. Methods: The 2-stage cluster sample included 105 enumeration areas, representing 74 districts and Kampala Capital City Authority. Enumeration occurred from August 20 to September 12, 2014. In each enumeration area, 24 households were randomly selected; the head of the household provided details regarding any household deaths within the previous 12 months. Two household members were randomly selected for a head-to-toe verbal interview to determine existing untreated and treated surgical conditions. Results: In 2315 households, we surveyed 4248 individuals: 461 (10.6%) reported 1 or more conditions requiring at least surgical consultation [95% confidence interval (CI) 8.9%–12.4%]. The most frequent barrier to surgical care was the lack of financial resources for the direct cost of care. Of the 153 household deaths recalled, 53 deaths (34.2%; 95% CI 22.1%–46.3%) were associated with surgically treatable signs/symptoms. Shortage of time was the most frequently cited reason (25.8%) among the 11.6% household deaths that should have, but did not, receive surgical care (95% CI 6.4%–16.8%). Conclusions: Unmet surgical need is prevalent in Uganda. There is an urgent need to expand the surgical care delivery system starting with the district-level hospitals. Routine surgical data collection at both the health facility and household level should be implemented.

Epidemiology of pediatric surgical needs in low-income countries.

Objective According to recent estimates, at least 11% of the total global burden of disease is attributable to surgically-treatable diseases. In children, the burden is even more striking with up to 85% of children in low-income and middle-income countries (LMIC) having a surgically-treatable condition by age 15. Using population data from four countries, we estimated pediatric surgical needs amongst children residing in LMICs. Methods A cluster randomized cross-sectional countrywide household survey (Surgeons OverSeas Assessment of Surgical Need) was done in four countries (Rwanda, Sierra Leone, Nepal and Uganda) and included demographics, a verbal head to toe examination, and questions on access to care. Global estimates regarding surgical need among children were derived from combined data, accounting for country-level clustering. Results A total of 13,806 participants were surveyed and 6,361 (46.1%) were children (0–18 years of age) with median age of 8 (Interquartile range [IQR]: 4–13) years. Overall, 19% (1,181/6,361) of children had a surgical need and 62% (738/1,181) of these children had at least one unmet need. Based on these estimates, the number of children living with a surgical need in these four LMICs is estimated at 3.7 million (95% CI: 3.4, 4.0 million). The highest percentage of unmet surgical conditions included head, face, and neck conditions, followed by conditions in the extremities. Over a third of the untreated conditions were masses while the overwhelming majority of treated conditions in all countries were wounds or burns. Conclusion Surgery has been elevated as an “indivisible, indispensable part of health care” in LMICs and the newly formed 2015 Sustainable Development Goals are noted as unachievable without the provision of surgical care. Given the large burden of pediatric surgical conditions in LMICs, scale-up of services for children is an essential component to improve pediatric health in LMICs.

Geospatial analysis of unmet pediatric surgical need in Uganda

BACKGROUND In low- and middle-income countries (LMICs), an estimated 85% of children do not have access to surgical care. The objective of the current study was to determine the geographic distribution of surgical conditions among children throughout Uganda. METHODS Using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey, we enumerated 2176 children in 2315 households throughout Uganda. At the district level, we determined the spatial autocorrelation of surgical need with geographic access to surgical centers variable. FINDINGS The highest average distance to a surgical center was found in the northern region at 14.97km (95% CI: 11.29km-16.89km). Younger children less than five years old had a higher prevalence of unmet surgical need in all four regions than their older counterparts. The spatial regression model showed that distance to surgical center and care availability were the main spatial predictors of unmet surgical need. INTERPRETATION We found differences in unmet surgical need by region and age group of the children, which could serve as priority areas for focused interventions to alleviate the burden. Future studies could be conducted in the northern regions to develop targeted interventions aimed at increasing pediatric surgical care in the areas of most need. LEVEL OF EVIDENCE Level III.

Pathogen reduction combined with rapid diagnostic tests to reduce the risk of transfusion-transmitted infections in Uganda: REDUCTION OF TRANSFUSION INFECTIONS

Blood safety and transfusion‐transmitted infections (TTIs) are a major concern in low‐resource areas. Laboratory screening of donors, a key contributor to blood safety, is usually done by enzyme‐linked immunosorbent assay (ELISA) methods, which use expensive reagents and necessitate complex instruments and sophisticated laboratory staff. Rapid diagnostic tests (RDTs) are less expensive and easier to perform but have less sensitivity. Pathogen reduction technology (PRT) reduces transfusion transmission of malaria and may be effective in decreasing other TTIs. We explored the potential to improve blood safety by combining PRT and RDTs in comparison with current ELISA testing.

Prevalence of Surgically Untreated Face, Head, and Neck Conditions in Uganda: A Cross-Sectional Nationwide Household Survey

BACKGROUND The Surgeons OverSeas Assessment of Surgical Need tool (SOSAS) was created to evaluate the burden of surgically treatable conditions in low- and middle-income countries. The goal of our study is to describe the face, head, and neck (FHN) conditions that need surgical care in Uganda, along with barriers to that care and disability from these conditions. METHODS A 2-stage cluster randomized SOSAS survey was administered in a cross-sectional manner between August and September 2014. Participants included randomly selected persons in 105 enumeration areas in 74 districts throughout Uganda with 24 households in each cluster. The SOSAS survey collected demographic and clinical data on all respondents. Univariate and multivariate logistic models evaluated associations of demographic characteristics and clinical characteristics of the FHN conditions and outcomes of whether health care was sought or surgical care was received. RESULTS Of the 4428 respondents, 331 (7.8%) reported having FHN conditions. The most common types of conditions were injury-related wounds. Of those who reported an FHN condition, 36% reported receiving no surgical care whereas 82.5% reported seeking health care. In the multivariate model, literacy and type of condition were significant predictors of seeking health care whereas village type, literacy, and type of condition remained significant predictors of receiving surgical care. CONCLUSIONS Many individuals in Uganda are not receiving surgical care and barriers include costs, rural residency, and literacy. Our study highlights the need for targeted interventions in various parts of Uganda to increase human resources for surgery and expand surgical capacity.

Tranexamic Acid Reduced the Percent of Total Blood Volume Lost During Adolescent Idiopathic Scoliosis Surgery

Background Multilevel posterior spine fusion is associated with significant intraoperative blood loss. Tranexamic acid is an antifibrinolytic agent that reduces intraoperative blood loss. The goal of this study was to compare the percent of total blood volume lost during posterior spinal fusion (PSF) with or without tranexamic acid in patients with adolescent idiopathic scoliosis (AIS). Methods Thirty-six AIS patients underwent PSF in 2011-2014; the last half (n=18) received intraoperative tranexamic acid. We retrieved relevant demographic, hematologic, intraoperative and outcomes information from medical records. The primary outcome was the percent of total blood volume lost, calculated from estimates of intraoperative blood loss (numerator) and estimated total blood volume per patient (denominator, via Nadler’s equations). Unadjusted outcomes were compared using standard statistical tests. Results Tranexamic acid and no-tranexamic acid groups were similar (all p>0.05) in mean age (16.1 vs. 15.2 years), sex (89% vs. 83% female), body mass index (22.2 vs. 20.2 kg/m2), preoperative hemoglobin (13.9 vs. 13.9 g/dl), mean spinal levels fused (10.5 vs. 9.6), osteotomies (1.6 vs. 0.9) and operative duration (6.1 hours, both). The percent of total blood volume lost (TBVL) was significantly lower in the tranexamic acid-treated vs. no-tranexamic acid group (median 8.23% vs. 14.30%, p = 0.032); percent TBVL per level fused was significantly lower with tranexamic acid than without it (1.1% vs. 1.8%, p=0.048). Estimated blood loss (milliliters) was similar across groups. Conclusions Tranexamic acid significantly reduced the percentage of total blood volume lost versus no tranexamic acid in AIS patients who underwent PSF using a standardized blood loss measure. Level of Evidence: 3. Institutional Review Board status: This medical record chart review (minimal risk) study was approved by the University of Minnesota Institutional Review Board.