Patient level barriers to accessing TB care services during the COVID-19 pandemic in Uganda, a mixed methods study.

INTRODUCTION: Lockdown measure has been utilized widely to mitigate COVID-19 pandemic transmission and recently during the 2022 Sudan Ebola Virus Disease outbreak in Uganda. These have setback effects on the continuity of essential health services such as tuberculosis (TB) care, reversing progress made in the fight against tuberculosis (TB) over the past decade. We set out to understand patient-reported barriers to accessing TB care services during the COVID-19 pandemic in Uganda. METHODS: Mixed methods study involving review of medical records of TB patients who received TB care from January to September 2020. We used quantitative and qualitative methods including phone questionnaires and in-depth interviews. We carried out descriptive statistics, a chi-square test and conducted a thematic analysis. RESULTS: We carried out phone interviews with 672 participants. The majority (60%) were male and with an average of 35 years (SD:11). A significantly higher proportion of patients reported a barrier to TB care access during the COVID-19 lockdown than pre-lockdown (79.9% vs. 68.1% p = 0.027). We carried out in-depth interviews with 28 participants (54% (15/28): male). Barriers experienced by these participants included lack of a means of transport to reach the health facility, lack of money to pay the transport fares, long distances to the facility, fear of COVID-19 infection, stigma due to overlap between TB and COVID-19 symptoms, and few health care workers available during the lockdown period. CONCLUSION: Lockdown measures instituted to mitigate the transmission of COVID1-19 affected access to TB care services in Uganda. Uganda is at risk of future emerging and re-emerging diseases of epidemic potential. Therefore, there should be measures to ensure the continuity of essential services such as tuberculosis care during the implementation of future epidemic response interventions such as a lockdown.

Risk perception and usage of non-occupational post-exposure prophylaxis among fisherfolk in Ggulwe parish on the shores of Lake Victoria in central Uganda.

Background: The use of non-occupational post-exposure prophylaxis (nPEP) to prevent HIV acquisition among those exposed as an approach to HIV prevention has expanded in Uganda. Although there are increased efforts to avail nPEP services among most at-risk populations, the usage of nPEP medicines remains low. Therefore, this study examined the risk perception and usage of non-occupational post-exposure prophylaxis (nPEP) among fisherfolk in the Ggulwe fishing parish, Bussi sub-county, Wakiso district. Methods: A cross-sectional study among adults was carried out from October 2020 to January 2021 in Ggulwe parish, Bussi sub-county, Wakiso district, to examine the usage of nPEP and factors influencing the usage. Data were collected using semi-structured questionnaires, and key informants' interviews were conducted among healthcare providers and the local leadership. The quantitative data were summarized using bivariate and multivariate logistic regression, while the qualitative data were analyzed thematically to enrich the quantitative results. Results: Overall, 248 fisherfolk encountered an event that required the use of nPEP, and of these, 55/248 (22.2%) were able to use nPEP to prevent them from acquiring HIV. The usage of nPEP among adults in the Bussi sub-county, Wakiso district, was associated with not knowing that HIV can be prevented using nPEP medicines (AOR:0.1, 95% CI 0.03-0.36, p < 0.001), lack of knowledge of the existence of nPEP (AOR: 0.3, 95% CI 0.13-0.76, p = 0.01), the perception that nPEP can effectively prevent HIV infection after exposure (AOR 0.0586, 95% CI: 0.0177-0.1944, p < 0.001), and the community's opinion affecting the willingness to take nPEP (AOR 0.1924, 95% CI: 0.0380-0.9727, p = 0.0462). Conclusion: The usage of nPEP among fisherfolk was low (22.2%). The low usage of nPEP was associated with a lack of knowledge and awareness about nPEP. This effort to improve the usage of nPEP should include community sensitization and HIV infection prevention using nPEP to raise awareness about HIV infection exposures and the risk of HIV infection during non-occupational exposures.

Source-tracking ESBL-producing bacteria at the maternity ward of Mulago hospital, Uganda.

INTRODUCTION: Escherichia coli, Klebsiella pneumoniae and Enterobacter (EKE) are the leading cause of mortality and morbidity in neonates in Africa. The management of EKE infections remains challenging given the global emergence of carbapenem resistance in Gram-negative bacteria. This study aimed to investigate the source of EKE organisms for neonates in the maternity environment of a national referral hospital in Uganda, by examining the phenotypic and molecular characteristics of isolates from mothers, neonates, and maternity ward. METHODS: From August 2015 to August 2016, we conducted a cross-sectional study of pregnant women admitted for elective surgical delivery at Mulago hospital in Kampala, Uganda; we sampled (nose, armpit, groin) 137 pregnant women and their newborns (n = 137), as well as health workers (n = 67) and inanimate objects (n = 70 -beds, ventilator tubes, sinks, toilets, door-handles) in the maternity ward. Samples (swabs) were cultured for growth of EKE bacteria and isolates phenotypically/molecularly investigated for antibiotic sensitivity, as well as ß-lactamase and carbapenemase activity. To infer relationships among the EKE isolates, spatial cluster analysis of phenotypic and genotypic susceptibility characteristics was done using the Ridom server. RESULTS: Gram-negative bacteria were isolated from 21 mothers (15%), 15 neonates (11%), 2 health workers (3%), and 13 inanimate objects (19%); a total of 131 Gram-negative isolates were identified of which 104 were EKE bacteria i.e., 23 (22%) E. coli, 50 (48%) K. pneumoniae, and 31 (30%) Enterobacter. Carbapenems were the most effective antibiotics as 89% (93/104) of the isolates were susceptible to meropenem; however, multidrug resistance was prevalent i.e., 61% (63/104). Furthermore, carbapenemase production and carbapenemase gene prevalence were low; 10% (10/104) and 6% (6/104), respectively. Extended spectrum ß-lactamase (ESBL) production occurred in 37 (36%) isolates though 61 (59%) carried ESBL-encoding genes, mainly blaCTX-M (93%, 57/61) implying that blaCTX-M is the ideal gene for tracking ESBL-mediated resistance at Mulago. Additionally, spatial cluster analysis revealed isolates from mothers, new-borns, health workers, and environment with similar phenotypic/genotypic characteristics, suggesting transmission of multidrug-resistant EKE to new-borns. CONCLUSION: Our study shows evidence of transmission of drug resistant EKE bacteria in the maternity ward of Mulago hospital, and the dynamics in the ward are more likely to be responsible for transmission but not individual mother characteristics. The high prevalence of drug resistance genes highlights the need for more effective infection prevention/control measures and antimicrobial stewardship programs to reduce spread of drug-resistant bacteria in the hospital, and improve patient outcomes.

Risk factors for disruptions in tuberculosis care in Uganda during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, TB mortality increased while diagnoses decreased, likely due to care disruption. In March, 2020, Uganda-a country with high TB burden, implemented a COVID-19 lockdown with associated decrease in TB diagnoses. This study aims to examine patient level risk factors for disruption in TB care during the COVID-19 pandemic in Uganda. This retrospective cross-sectional cohort study included six TB clinics in Uganda. Clustered sampling included phases of TB care and three time-periods: pre-lockdown, lockdown and post-lockdown. Characteristics of patients with TB care disruption (TBCD), defined as those with > 2 months of symptoms prior to diagnosis or who missed a TB clinic, and those without TB care disruption (non-TBCD) were analyzed between time-periods. 1,624 charts were reviewed; 1322 were contacted, 672 consented and completed phone interview; pre-lockdown (n = 213), lockdown (n = 189) and post-lockdown (n = 270). TBCD occurred in 57% (385/672) of patients. There was an increase in the proportion of urban patients in the TBCD and non-TBCD groups during post-lockdown (p <0.001). There was no difference in demographics, HIV co-infection, socioeconomic status, or distance to TB clinic between TBCD and non-TBCD groups or within TBCD by time-period. There were few differences amongst TBCD and all TB patients by time-period. The increase in urban patients' post-lockdown may represent a portion of urban patients who delayed care until post-lockdown. Insignificant trends suggesting more TBCD amongst those who lived further from clinics and those without HIV-coinfection require more investigation.

Association of circulating serum free bioavailable and total vitamin D with cathelicidin levels among active TB patients and household contacts.

The free hormone hypothesis postulates that the estimation of free circulating 25 (OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D fraction. The unbound fraction is involved in biological activities since it is able to penetrate into the cell. Studies have shown that cathelicidin/LL-37 inhibits the growth of Mycobacterium tuberculosis in a vitamin D-dependent manner and therefore adequate vitamin D is required for its expression. The study aimed to determine the association between serum bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI, and individuals with no TB infection. This was a cross-sectional study in which bioavailable vitamin D and LL-37 levels were measured using competitive ELISA kits and total vitamin D was measured using electrochemilumiscence and consequently determined their association. The mean (SD) bioavailable vitamin D levels of the study participants were 3.8 ng/mL (2.6) and the median (IQR) of LL-37 levels were 320 ng/mL (160, 550 ng/mL). The mean (SD) of total vitamin D levels was 19.0 ng/mL (8.3) ng/mL. Similar weak correlations were observed between the bioavailable and total vitamin D with LL-37 levels, therefore, deviating from our hypothesis.

A systematic review of strategies adopted to scale up COVID-19 testing in low-, middle- and high-income countries.

OBJECTIVE: We undertook a systematic review of strategies adopted to scale up COVID-19 testing in countries across income levels to identify successful approaches and facilitate learning. METHODS: Scholarly articles in English from PubMed, Google scholar and Google search engine describing strategies used to increase COVID-19 testing in countries were reviewed. Deductive analysis to allocate relevant text from the reviewed publications/reports to the a priori themes was done. MAIN RESULTS: The review covered 32 countries, including 11 high-income, 2 upper-middle-income, 13 lower-middle-income and 6 low-income countries. Most low- and middle-income countries (LMICs) increased the number of laboratories available for testing and deployed sample collection and shipment to the available laboratories. The high-income countries (HICs) that is, South Korea, Germany, Singapore and USA developed molecular diagnostics with accompanying regulatory and legislative framework adjustments to ensure the rapid development and use of the tests. HICs like South Korea leveraged existing manufacturing systems to develop tests, while the LMICs leveraged existing national disease control programmes (HIV, tuberculosis, malaria) to increase testing. Continent-wide, African Centres for Disease Control and Prevention-led collaborations increased testing across most African countries through building capacity by providing testing kits and training. CONCLUSION: Strategies taken appear to reflect the existing systems or economies of scale that a particular country could leverage. LMICs, for example, drew on the infectious disease control programmes already in place to harness expertise and laboratory capacity for COVID-19 testing. There however might have been strategies adopted by other countries but were never published and thus did not appear anywhere in the searched databases.

Evaluation of circulating serum cathelicidin levels as a potential biomarker to discriminate between active and latent tuberculosis in Uganda.

BACKGROUND: Tuberculosis remains a major public health problem worldwide accounting for 1.4 million deaths annually. LL-37 is an effector molecule involved in immunity with both antimicrobial and immunomodulatory properties. The purpose of this study was to compare LL-37 circulatory levels among participants with active and latent tuberculosis and to determine its ability to discriminate between the two infectious states. METHODS: A cross-sectional study was performed among 56 active tuberculosis patients, 49 latent tuberculosis individuals, and 43 individuals without tuberculosis infection. The enzyme-linked immunosorbent assay was used to assess LL-37 levels. Data analysis was performed using STATA software and Graph pad Prism version 8. Mann-Whitney U test was used for correlation between variables with two categories and the Kruskal-Wallis test for three or more categories. RESULTS: The study had more female participants than males, with similar median ages across the three groups, 29.5, 25.0, and 23.0 years respectively. Active tuberculosis patients had significantly higher LL-37 levels compared to those with latent tuberculosis and without tuberculosis. The median/interquartile ranges were 318.8 ng/ml (157.9-547.1), 242.2 ng/ml (136.2-579.3), 170.9 ng/ml (129.3-228.3); p = 0.002 respectively. Higher LL-37 was found in the male participant with median/interquartile range, 424.8 ng/ml (226.2-666.8) compared to the females 237.7 ng/ml (129.6-466.6); p = 0.045. LL-37 had better discriminatory potential between active tuberculosis and no tuberculosis (AUC = 0.71, sensitivity 71.4% specificity = 69.8%) than with latent tuberculosis (AUC = 0.55, sensitivity = 71.4%, specificity = 44.9%). There was moderate differentiation between latent tuberculosis and no tuberculosis (AUC = 0.63, sensitivity = 44.9% specificity = 90.7%). CONCLUSION: Significantly higher LL-37 levels were observed among active tuberculosis patients than those without tuberculosis infection and were, therefore able to discriminate between active tuberculosis and other tuberculosis infectious states, especially with no tuberculosis. Further assessment of this biomarker as a screening tool to exclude tuberculosis is required.

Hypovitaminosis D among newly diagnosed pulmonary TB patients and their household contacts in Uganda.

An estimated one billion people globally live with hypovitaminosis D. Studies have indicated that vitamin D deficiency is a risk factor for active tuberculosis (TB) disease. The aim of this study was to determine the association between vitamin D deficiency and TB status among patients with active TB, latent TB infection (LTBI) and those without TB infection. In a cross-sectional study of active TB patients, LTBI, QuantiFERON GOLD testpositive and (QFN+TST+) household contact and controls QuantiFERON GOLD testnegative (QFN-TST-) samples vitamin D levels were compared. Vitamin D status was determined by measurement of total vitamin D levels with 56 samples of active TB patients, 17 with LTBI, and 22 without TB infection using electrochemiluminescence. The median interquartile range (IQR) age of the study participants was 28 (20-35) years, and the majority (63%) were females. The median (IQR) vitamin D levels were 18 ng/ml (14-24). All groups had vitamin D hypovitaminosis with significantly lower levels among active TB patients (17 ng/ml, 13, 2) than among LTBI individuals (23 ng/ml 16-29) and those without TB infection (22 ng/ml, 17-28).

Factors Associated with Linkage to HIV Care Among Oral Self-Tested HIV Positive Adults in Uganda.

BACKGROUND: HIV oral self-testing (HIVST) was rolled out in Uganda in 2018. However, data reported by public facilities show that less than 60% of oral self-tested HIV positive adults were linked to HIV care. This study set out to determine the factors associated with linkage to HIV care among adults with positive HIV oral self-test results in Uganda. METHODS: A cross-sectional study was carried out at Nabweru HCIII and Entebbe Hospital in central Uganda. The study reviewed medical records from January 2019 to May 2020 and successfully invited 144 self-tested HIV positive participants for the quantitative interview process. Data on socio-demographics and health-related characteristics were collected. Bivariate and multivariable analysis was used to determine the factors associated with linkage to care. RESULTS: The proportion of participants linked to HIV care was 69.6% (100/144). The majority of the participants were female (71%), with a mean age of 29 (±8) years. Participants within age groups of 31-35 years and 41-60 years, who used directly assisted HIVST, disclosed their HIV status to their sexual partners, are ready to start ART, do not consume alcohol and having a supportive sexual partner were more likely to be linked to HIV care. Single participants, separated/divorced, female, fear unfair treatment after HIV status disclosure and those who fear ART side effects were less likely to be linked to HIV care. CONCLUSION: Our study showed that less than 70% were linked to HIV care. It also shows that HIV status disclosure, readiness to start ART, type of HIVST used, fear of ART side effects, and being divorced/separated negatively associated with linkage to HIV care among self-test HIV positive adults. There is a need for HIV programs to address the above factors to improve linkage to HIV care to realize the national targets towards the UNAIDs 2035 goals.

Perceptions of Adolescents and Health Workers Towards Adolescents' TB Diagnosis in Central Uganda: A Cross-Sectional Qualitative Study.

PURPOSE: Prompt diagnosis of TB among adolescents may reduce transmission and improve individual outcomes. However, TB diagnosis in adolescents is challenging. This study sought to understand challenges to adolescent TB diagnosis. METHODS: We conducted qualitative focus group discussions (FGDs) to explore adolescents' and health workers' perspectives on challenges to TB diagnosis among adolescents seeking care at four secondary health care facilities in Uganda. Eight FGDs were conducted: four with 32 adolescents consulting for medical care and four with 34 health workers involved in TB care. RESULTS: Adolescents were aware of TB and associated risk factors and believed behaviours like smoking and alcohol use are risk factors for TB. They reported school schedules limit them from seeking TB care and have to miss school or wait for holidays to seek TB diagnosis. They noted school nurses do not take much interest in diagnosing TB and do not refer them to hospitals for further evaluation when they present with TB symptoms. Furthermore, adolescents reported cross-cutting issues like loss of trust in public health systems, encountering unfriendly, judgmental and uncooperative health workers. Health workers mentioned the school environment exposes adolescents to TB as the dormitories they sleep in are overcrowded. They indicated that it was difficult to make a diagnosis of TB in adolescents as the adolescents do not disclose health information. They reported fellow health workers perceive adolescents as being at low risk of TB as they believe most often adolescents are HIV negative and thus have reduced risk of TB. CONCLUSION: Adolescents present unique challenges that need to be addressed if TB diagnosis is to improve. These challenges could be handled by interventions that lead to minimal disruptions on school schedules, provision of adolescent-friendly services and intervention to build capacity of health care workers in the provision of adolescent-friendly services.

Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda.

Background: Type 2 diabetes mellitus (T2DM) is a major risk factor for the acquisition of latent tuberculosis (TB) infection (LTBI) and development of active tuberculosis (ATB), although the immunological basis for this susceptibility remains poorly characterised. Innate lymphoid cells (ILCs) immune responses to TB infection in T2DM comorbidity is anticipated to be reduced. We compared ILC responses (frequency and cytokine production) among adult patients with LTBI and T2DM to patients (13) with LTBI only (14), T2DM only (10) and healthy controls (11). Methods: Using flow cytometry, ILC phenotypes were categorised based on (Lin-CD127+CD161+) markers into three types: ILC1 (Lin-CD127+CD161+CRTH2-CD117-); ILC2 (Lin-CD127+CD161+CRTH2+) and ILC3 (Lin-CD127+CD161+CRTH2-NKp44+/-CD117+). ILC responses were determined using cytokine production by measuring percentage expression of interferon-gamma (IFN-γ) for ILC1, interleukin (IL)-13 for ILC2, and IL-22 for ILC3. Glycaemic control among T2DM patients was measured using glycated haemoglobin (HbA1c) levels. Data were analysed using FlowJo version 10.7.1, and GraphPad Prism version 8.3. Results: Compared to healthy controls, patients with LTBI and T2DM had reduced frequencies of ILC2 and ILC3 respectively (median (IQR): 0.01 (0.005-0.04) and 0.002 (IQR; 0.002-0.007) and not ILC1 (0.04 (0.02-0.09) as expected. They also had increased production of IFN-γ [median (IQR): 17.1 (5.6-24.9)], but decreased production of IL-13 [19.6 (12.3-35.1)]. We however found that patients with T2DM had lower ILC cytokine responses in general but more marked for IL-22 production (median (IQR): IFN-γ 9.3 (4.8-22.6); IL-13 22.2 (14.7-39.7); IL-22 0.7 (IQR; 0.1-2.1) p-value 0.02), which highlights the immune suppression status of T2DM. We also found that poor glycaemic control altered ILC immune responses. Conclusion: This study demonstrates that LTBI and T2DM, and T2DM were associated with slight alterations of ILC immune responses. Poor T2DM control also slightly altered these ILC immune responses. Further studies are required to assess if these responses recover after treatment of either TB or T2DM.