Association between biomarkers of inflammation and dyslipidemia in drug resistant tuberculosis in Uganda.

BACKGROUND: Active tuberculosis (TB) significantly increases the risk of cardiovascular disease, but the underlying mechanisms remain unclear. This study aimed to investigate the association between inflammation biomarkers and dyslipidemia in patients with drug-resistant TB (DR-TB). METHODS: This was a secondary analysis of data from a cross-sectional multi-center study in Uganda conducted 2021. Participants underwent anthropometric measurements and laboratory tests included a lipid profile, full haemogram and serology for HIV infection. Dyslipidemia was defined as total cholesterol > 5.0 mmol/l and/or low-density lipoprotein cholesterol > 4.14 mmol/l, and/or triglycerides (TG) ≥ 1.7 mmol/l, and/or high density lipoprotein cholesterol (HDL-c) < 1.03 mmol/l for men and < 1.29 mmol/l for women. Biomarkers of inflammation were leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil/lymphocyte (NLR), platelet/lymphocyte, and lymphocyte/monocyte (LMR) ratios, mean corpuscular volume (MCV), and the systemic immune inflammation index (SII) (neutrophil × platelet/lymphocyte). Modified Poisson Regression analysis was used for determining the association of the biomarkers and dyslipidemia. RESULTS: Of 171 participants, 118 (69.0%) were co-infected with HIV. The prevalence of dyslipidemia was 70.2% (120/171) with low HDL-c (40.4%, 69/171) and hypertriglyceridemia (22.5%, 38/169) being the most common components. Patients with dyslipidemia had significantly higher lymphocyte (P = 0.008), monocyte (P < 0.001), and platelet counts (P = 0.014) in addition to a lower MCV (P < 0.001) than those without dyslipidemia. Further, patients with dyslipidemia had lower leucocyte (P < 0.001) and neutrophil (P = 0.001) counts, NLR (P = 0.008), LMR (P = 0.006), and SII (P = 0.049). The MCV was inversely associated with low HDL-C (adjusted prevalence ratio (aPR) = 0.97, 95% CI 0.94-0.99, P = 0.023) but was positively associated with hypertriglyceridemia (aPR = 1.04, 95% CI 1.00-1.08, P = 0.052). CONCLUSIONS: Individuals with dyslipidemia exhibited elevated lymphocyte, monocyte, and platelet counts compared to those without. However, only MCV demonstrated an independent association with specific components of dyslipidemia. There is need for further scientific inquiry into the potential impact of dyslipidemia on red cell morphology and a pro-thrombotic state among patients with TB.

Early culture conversion is a poor marker of treatment outcome among people with HIV and drug-resistant TB.

OBJECTIVE: Our objective was to determine associations between early (≤2 months) culture conversion (ECC) among people with HIV and drug-resistant tuberculosis (DRTB) in Uganda. METHODS: This was a countrywide retrospective cohort of people with bacteriologically confirmed DRTB and a positive baseline culture at 16 centres in Uganda between 2013 and 2019. Data were abstracted from treatment files and unit DRTB registers. Monthly sputum cultures were performed using the Lowenstein-Jensen solid medium. RESULTS: We included 664 people with DRTB and a positive baseline culture, of whom 353 (53.4%) also had HIV. Among those living with HIV, 225 (63.7%) were male and 331 (94.3%) were on antiretroviral therapy. The median month of culture conversion was 2 (interquartile range [IQR] 1-3). ECC was observed among 226 people living with HIV (64.0%; 95% confidence interval [CI] 58.9-68.9). A DRTB treatment regimen of six or more drugs was associated with ECC among people living with HIV (adjusted odds ratio [aOR]  3.82; 95% CI 1.06-13.82; p = 0.041). Cure and overall treatment success was observed among 232 (65.7%) and 269 (76.2%) people living with HIV, respectively. However, ECC was not associated with cure (crude odds ratio [OR]  0.97; 95% CI 0.61-1.54; p = 0.901), death (OR 1.12; 95% CI 0.61-2.29; p = 0.610), or overall treatment success (OR 1.29; 95% CI 0.78-2.13; p = 0.326). CONCLUSION: The majority of people living with HIV and DRTB achieve ECC. However, ECC does not predict cure, death, or treatment success. Moreover, it may require six or more drugs to achieve ECC. ECC is not an excellent indicator of the effectiveness of DRTB regimens among people living with HIV.

Higher intensive care unit consultations for COVID-19 patients living with HIV compared to those without HIV coinfection in Uganda.

Coronavirus disease-2019 (COVID-19) is the leading cause of death worldwide from a single infectious agent. Whether or not HIV infection affects clinical outcomes in patients with COVID-19 remains inconclusive. This study aimed to compare the clinical outcomes of people living with HIV (PLWH) and non-HIV-infected patients hospitalized during the second wave of the COVID-19 pandemic in Uganda. We retrospectively retrieved data on patients with COVID-19 who were admitted to the Mulago National Referral Hospital in Uganda between April 2021 and mid-July 2021. We performed propensity-score-matching of 1:5 to compare outcomes in COVID-19 patients living with and those without HIV coinfection (controls). We included 31 PLWH and 155 non-HIV controls. The baseline characteristics were similar across groups (all p values > 0.05). PLWH had close to threefold higher odds of having ICU consultation compared to controls (odds ratio [OR]: 2.9, 95% CI: 1.2-6.9, p = 0.015). There was a trend toward having a severe or critical COVID-19 illness among PLWHIH compared to controls (OR: 1.9, 95% CI: 0.8-4.7, p = 0.164). Length of hospitalization was not significantly different between PLWH and non-HIV controls (6 days vs. 7 days, p = 0.184). Seven-day survival was 63% (95% CI: 42%-78%) among PLWH and 72% (95% CI: 61%-82%) among controls while 14-day survival was 50% (95% CI: 28%-69%) among PLWH and 65% (95% CI: 55%-73%) among controls (p = 0.280). There was another trend toward having 1.7-fold higher odds of mortality among PLWH compared to controls (OR: 1.7, 95% CI: 0.8-3.8, p = 0.181). Our data suggest that PLWH may be at an increased risk of severe or critical COVID-19 illness requiring ICU consultation. Further studies with larger sample sizes are recommended.

Prevalence of anaemia and associated factors among people with pulmonary tuberculosis in Uganda.

Anaemia predicts delayed sputum conversion and mortality in tuberculosis (TB). We determined the prevalence and factors associated with anaemia among people with TB at the National Tuberculosis Treatment Centre in Uganda. People with bacteriologically confirmed TB were consecutively enrolled in a cross-sectional study between August 2017 and March 2018. Blood samples were tested for a full blood hemogram, HIV infection, and CD4+ and CD8+ T-cell counts. Anaemia was defined as a haemoglobin level of <13.0 grams per decilitre (g/dl) for males and <12.0 g/dl for females. Of 358 participants, 210 (58.7%, 95% confidence interval (CI) 53.4-63.8) had anaemia. Anaemia was associated with night sweats, a longer duration of fever, low body mass index (BMI), hyperthermia, high sputum bacillary loads, HIV co-infection, and low CD4 and CD8 counts at bivariate analysis. Factors associated with anaemia at multivariable analysis were low BMI (odds ratio (OR) 2.93, 95% CI 1.70-5.05, P < 0.001), low CD4:CD8 ratio (OR 2.54, 95% CI 1.07-6.04, P = 0.035) and microcytosis (OR 4.23, 95% CI 2.17-8.25, P < 0.001). Anaemia may be associated with the features of severe TB disease and should be considered in TB severity scores.

Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda.

BACKGROUND: Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda. METHODS: In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity. RESULTS: Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4-69.1), hypertension (40.6%; 33.8-47.9), central obesity (39.3%; 32.9-46.1), smoking (36.3%; 30.1-43.1), high BMI (8.0%; 5.0-12.8) and DM (6.5%; 3.7-11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06-1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14-3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21-0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00-1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00-1.06). CONCLUSION: There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.

Tuberculosis contact tracing yield and associated factors in Uganda.

BACKGROUND: The yield of tuberculosis (TB) contact tracing is historically low in Uganda. We determined factors associated with a positive contact tracing yield at an urban public TB clinic in Kampala, Uganda. METHODS: We reviewed contact tracing registers of index TB cases registered between 2015 and 2020 at Kitebi Health Center, a primary level facility. Contacts who had symptoms of TB were designated as having presumptive TB. A contact investigation that yielded a new TB case was designated as a positive yield. We used logistic regression to determine factors associated with a positive yield of contact tracing. RESULTS: Of 778 index TB cases, 455 (58.5%) had a contact investigation conducted. Index cases with a telephone contact in the unit TB register (adjusted odds ratio (aOR) 1.66, 95% CI 1.02-1.97, p = 0.036) were more likely to have a contact investigation conducted than those who did not. Of 1350 contacts, 105 (7.8%) had presumptive TB. Of these, 73 (69.5%) were further evaluated for active TB and 29 contacts had active TB. The contact tracing yield for active TB was therefore 2.1% (29/1,350). The odds of a positive yield increased tenfold with each additional presumptive contact evaluated for active TB (aOR 10.1, 95% CI 2.95-34.66, p < 0.001). Also, retreatment index TB cases were more likely to yield a positive contact (aOR 7.69 95% CI 2.08-25.00, p = 0.002) than to new cases. CONCLUSION: TB contact tracing should aim to evaluate all contacts with presumptive TB and contacts of retreatment cases to maximise the yield of contact tracing.

Trends of notification rates and treatment outcomes of tuberculosis cases with and without HIV co-infection in eight rural districts of Uganda (2015 - 2019).

BACKGROUND: The End TB Strategy aims to reduce new tuberculosis (TB) cases by 90% and TB-related deaths by 95% between 2015 - 2035. We determined the trend of case notification rates (CNRs) and treatment outcomes of TB cases with and without HIV co-infection in rural Uganda to provide an interim evaluation of progress towards this global target in rural settings. METHODS: We extracted retrospective programmatic data on notified TB cases and treatment outcomes from 2015 - 2019 for eight districts in rural Uganda from the District Health Information System 2. We estimated CNRs as the number of TB cases per 100,000 population. Treatment success rate (TSR) was calculated as the sum of TB cure and treatment completion for each year. Trends were estimated using the Mann-Kendall test. RESULTS: A total of 11,804 TB cases, of which 5,811 (49.2%) were HIV co-infected, were notified. The overall TB CNR increased by 3.7-fold from 37.7 to 141.3 cases per 100,000 population in 2015 and 2019 respectively. The increment was observed among people with HIV (from 204.7 to 730.2 per 100,000, p = 0.028) and HIV-uninfected individuals (from 19.9 to 78.7 per 100,000, p = 0.028). There was a decline in the TSR among HIV-negative TB cases from 82.1% in 2015 to 63.9% in 2019 (p = 0.086). Conversely, there was an increase in the TSR among HIV co-infected TB cases (from 69.9% to 81.9%, p = 0.807). CONCLUSION: The CNR increased among people with and without HIV while the TSR reduced among HIV-negative TB cases. There is need to refocus programs to address barriers to treatment success among HIV-negative TB cases.

Gender differences among patients with drug resistant tuberculosis and HIV co-infection in Uganda: a countrywide retrospective cohort study.

BACKGROUND: Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. METHODS: We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p < 0.05. RESULTS: Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p < 0.001). Men were significantly more likely to be on tenofovir-based antiretroviral therapy (ART), high-dose isoniazid-containing DRTB regimen and to have history of cigarette or alcohol use. They were also more likely to have multi-drug resistant TB, isoniazid and streptomycin resistance and had higher creatinine, aspartate and gamma-glutamyl aminotransferase and total bilirubin levels. Conversely, women were more likely to be unemployed, unmarried, receive treatment from the national referral hospital and to have anemia, a capreomycin-containing DRTB regimen and zidovudine-based ART. Treatment success was observed among 437 (65.6%) and did not differ between the genders. However, mortality was higher among men than women (25.7% vs. 18.5%, p = 0.030) and men had a shorter mean (standard error) survival time (16.8 (0.42) vs. 19.0 (0.46) months), Log Rank test (p = 0.046). Predictors of mortality, after adjusting for gender, were cigarette smoking (aHR = 4.87, 95% CI 1.28-18.58, p = 0.020), an increase in alanine aminotransferase levels (aHR = 1.05, 95% CI 1.02-1.07, p < 0.001), and history of ART default (aHR = 3.86, 95% CI 1.31-11.37, p = 0.014) while a higher baseline CD4 count was associated with lower mortality (aHR = 0.94, 95% CI 0.89-0.99, p = 0.013 for every 10 cells/mm3 increment). CONCLUSION: Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.

Surgical management of chronic pulmonary aspergillosis in Africa: A systematic review of 891 cases.

Chronic pulmonary aspergillosis (CPA) is an emerging fungal infectious disease of public health importance. We conducted a systematic review of studies reporting the outcomes of patients with CPA managed surgically in Africa. A search of Medline, Embase, Web of Science, Google Scholar and African Journals Online was conducted to identify studies indexed from inception to June 2021 that examined surgical management of CPA in Africa. All articles that presented primary data, including case reports and case series, were included. We excluded review articles. A total of 891 cases (557 males (62.5%), mean age 39.3 years) extracted from 27 eligible studies published between 1976 and 2020 from 11 African countries were included. Morocco (524, 59%) and Senegal (99, 11%) contributed the majority of cases. Active or previous pulmonary tuberculosis was reported in 677 (76.0%) cases. Haemoptysis was reported in 682 (76.5%) cases. Lobectomy (either unilateral or bilateral, n = 493, 55.3%), pneumonectomy (n = 154, 17.3%) and segmentectomy (n = 117, 13.1%) were the most frequently performed surgical procedures. Thirty (4.9%) cases from South Africa received bronchial artery embolisation. Empyema (n = 59, 27.4%), significant haemorrhage (n = 38, 173.7%), incomplete lung expansion (n = 26, 12.1%) and prolonged air leak (n = 24, 11.2%) were the most frequent complications. Overall, 45 (5.1%) patients died. The causes of death included respiratory failure (n = 14), bacterial superinfection/sepsis (n = 10), severe haemorrhage (n = 5), cardiopulmonary arrest (n = 3) and complications of chronic obstructive pulmonary disease (n = 3). The cause of death was either unknown or unspecified in 9 cases. We conclude that surgical treatment had very low mortality rates and maybe considered as first-line management option in centres with experience and expertise in Africa.

Estimation of the burden of tinea capitis among children in Africa.

Tinea capitis is a common and endemic dermatophytosis among school age children in Africa. However, the true burden of the disease is unknown in Africa. We aimed to estimate the burden of tinea capitis among children <18 years of age in Africa. A systematic review was performed using Embase, MEDLINE and the Cochrane Library of Systematic Reviews to identify articles on tinea capitis among children in Africa published between January 1990 and October 2020. The United Nation's Population data (2019) were used to identify the number of children at risk of tinea capitis in each African country. Using the pooled prevalence, the country-specific and total burden of tinea capitis was calculated. Forty studies involving a total of 229,086 children from 17/54 African countries were identified and included in the analysis. The pooled prevalence of tinea capitis was 23% (95% CI, 17%-29%) mostly caused by Trichophyton species. With a population of 600 million (46%) children, the total number of cases of tinea capitis in Africa was estimated at 138.1 (95% CI, 102.0-174.1) million cases. Over 96% (132.6 million) cases occur in sub-Saharan Africa alone. Nigeria and Ethiopia with the highest population of children contributed 16.4% (n = 98.7 million) and 8.5% (n = 52.2 million) of cases, respectively. Majority of the participants were primary school children with a mean age of 10 years. Cases are mostly diagnosed clinically. There was a large discrepancy between the clinical and mycological diagnosis. About one in every five children in Africa has tinea capitis making it one of the most common childhood conditions in the region. A precise quantification of the burden of this neglected tropical disease is required to inform clinical and public health intervention strategies.

Multidisciplinary management of difficult-to-treat drug resistant tuberculosis: a review of cases presented to the national consilium in Uganda.

BACKGROUND: Patients with drug resistant tuberculosis (DR-TB) with comorbidities and drug toxicities are difficult to treat. Guidelines recommend such patients to be managed in consultation with a multidisciplinary team of experts (the "TB consilium") to optimise treatment regimens. We describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda between 2013 and 2019. METHODS: We performed a secondary analysis of data from a nation-wide retrospective cohort of DR-TB patients with poor prognostic indicators in Uganda. Patients had a treatment outcome documented between 2013 and 2019. Characteristics and treatment outcomes were compared between cases reviewed by the consilium with those that were not reviewed. RESULTS: Of 1,122 DR-TB cases, 189 (16.8%) cases from 16 treatment sites were reviewed by the consilium, of whom 86 (45.5%) were reviewed more than once. The most frequent inquiries (N = 308) from DR-TB treatment sites were construction of a treatment regimen (38.6%) and management of side effects (24.0%) while the most frequent consilium recommendations (N = 408) were a DR-TB regimen (21.7%) and "observation while on current regimen" (16.6%). Among the cases reviewed, 152 (80.4%) were from facilities other than the national referral hospital, 113 (61.1%) were aged ≥ 35 years, 72 (40.9%) were unemployed, and 26 (31.0%) had defaulted antiretroviral therapy. Additionally, 141 (90.4%) had hepatic injury, 55 (91.7%) had bilateral hearing loss, 20 (4.8%) had psychiatric symptoms and 14 (17.7%) had abnormal baseline systolic blood pressure. Resistance to second-line drugs (SLDs) was observed among 9 (4.8%) cases while 13 (6.9%) cases had previous exposure to SLDs. Bedaquiline (13.2%, n = 25), clofazimine (28.6%, n = 54), high-dose isoniazid (22.8%, n = 43) and linezolid (6.7%, n = 13) were more frequently prescribed among cases reviewed by the consilium than those not reviewed. Treatment success was observed among 126 (66.7%) cases reviewed. CONCLUSION: Cases reviewed by the consilium had several comorbidities, drug toxicities and a low treatment success rate. Consilia are important "gatekeepers" for new and repurposed drugs. There is need to build capacity of lower health facilities to construct DR-TB regimens and manage adverse effects.

Missed opportunities in tuberculosis investigation and associated factors at public health facilities in Uganda.

BACKGROUND: The incidence of tuberculosis (TB) is high in Uganda; yet, TB case detection is low. The population-based survey on the prevalence of TB in Uganda revealed that only 16% of presumptive TB patients seeking care at health facilities were offered sputum microscopy or chest-X ray (CXR). This study aimed to determine the magnitude of, and patient factors associated with missed opportunities in TB investigation at public health facilities of Wakiso District in Uganda. METHODS: A facility-based cross-sectional survey was conducted at 10 high volume public health facilities offering comprehensive TB services in Wakiso, Uganda, among adults (≥18 years) with at least one symptom suggestive of TB predefined according to the World Health Organisation criteria. Using exit interviews, data on demographics, TB symptoms, and clinical data relevant to TB diagnosis were collected. A missed opportunity in TB investigation was defined as a patient with symptoms suggestive of TB who did not have sputum and/or CXR evaluation to rule out TB. Poisson regression analysis was performed to determine factors associated with missed opportunities in TB investigation. RESULTS: Two hundred forty-seven (247) patients with presumptive TB exiting at antiretroviral therapy (ART) clinics (n = 132) or general outpatient clinics (n = 115) at public health facilities were recruited into this study. Majority of participants were female (161/247, 65.2%) with a mean + SD age of 35.1 + 11.5 years. Overall, 138 (55.9%) patients with symptoms suggestive of TB disease did not have sputum and/or CXR examinations. Patients who did not inform health workers about their TB related symptoms were more likely to miss a TB investigation (adjusted prevalence ratio (aPR): 1.68, 95%CI; 1.36-2.08, P < 0.001). However, patients who reported duration of cough of 2 weeks or more were less likely to be missed for TB screening (aPR; 0.69, 95%CI; 0.56-0.86, p < 0.001). CONCLUSION: There are substantial missed opportunities for TB diagnosis in Wakiso District. While it is important that patients should be empowered to report symptoms, health workers need to proactively implement the WHO TB symptom screen tool and complete the subsequent steps in the TB diagnostic cascade.

Oral health seeking behaviors of adults in Nebbi District, Uganda: a community-based survey.

BACKGROUND: Dental health is often neglected by the majority of the population and has contributed to the global burden of oral diseases. We assessed awareness, utilization and barriers to seeking oral health care among adults in Nebbi District, Uganda. METHODS: A community-based, cross sectional study was conducted in the central division, Nebbi District in Uganda among adults between the age of 18 years or older. An interviewer-administered, semi-structured questionnaire was used for data collection on socio-demographic characteristics, oral health awareness, oral health utilization, associated factors and barriers. RESULTS: A total of 400 adults with a median age of 32 years (interquartile range 24-43) years were enrolled. More than half (57.5%, n = 230) of the participants were female. Participants identified smoking (42.8%, n = 171) and consumption of sugary foodstuffs (29.0%, n = 116) as risk factors for oral disease. Not brushing was also identified by 260 participants (65.0%) as the cause of tooth decay and 95.8% (n = 383) believed brushing one's teeth could prevent tooth decay. Of the 51.5% (n = 206) who had experienced a toothache or discomfort 12 months prior to the study but only about half (52%, n = 106) had sought healthcare from a dental clinic or facility. About 89.5% (n = 94) of the participants were able to see a dentist during their last visits. Dental carries (76.6%, n = 70) and gum bleeding (14.9%, n = 14) were the most frequent reasons for visiting a dental clinic, and 73.7% (n = 70) had their tooth extracted. Barriers to seeking oral healthcare were cost of treatment (47.5%, n = 190), and long waiting time (18.5%, n = 74). The odds of seeking oral healthcare was 2.8-fold higher in participants who were being married (Odds ratio (OR): 2.8, 95% CI 1.3-6.3, p = 0.011) and 3.5-fold higher among housewives (COR: 3.5, 95% CI 1.1-11.4, p = 0.040). CONCLUSION: About half of the participants had sought healthcare following a dental condition. Cost of treatment seems to be an important factor affecting utilization of oral health services. Optimization of costs, and creating awareness regarding benefits of utilizing preventive dental services are recommended.

Absolute eosinophil count correlates with temperature and CD4 count independently of HIV infection among tuberculosis patients.

OBJECTIVE: To determine clinical correlates of the peripheral absolute eosinophil count (AEC) among bacteriologically confirmed TB patients in Uganda. MATERIALS AND METHODS: We evaluated data of bacteriologically confirmed adult TB patients who had a peripheral blood AEC measurement at the National TB Treatment Center in Uganda during a cross-sectional study. We performed linear regression analysis for correlates of log-transformed AEC. RESULTS: We included 235 patients in this analysis with a median (interquartile range, IQR) age of 31 (24-39) years. 60.4% were male, and 33.6% had TB/HIV co-infection. In a multivariable linear regression model that controlled for age, residence type, HIV status, weight loss, anorexia, body mass index, CD8+ T-cell count, haemoglobin level and TB bacillary load, males had a 47.0% higher AEC than females (adjusted coefficient (R2 ) = 0.385, 95% confidence interval (CI) 0.012-0.759 P = 0.043). Also, a 1 °C raise in temperature resulted in an 11.5% decrease in the AEC (R2  = -0.122 95% CI (-0.233 to -0.011) P = 0.031) while a 1 cell/mm3 increase in the CD4+ T-cell count resulted in a 0.10% increase in the AEC (R2  = 0.001 95% CI (0.000-0.001) P = 0.032). CONCLUSION: The AEC was higher among males than females, consistent with the normal population distribution of AEC among Ugandans. The AEC was weakly but positively correlated with the CD4 count and negatively correlated with temperature.

OBJECTIF: Déterminer les corrélats cliniques du nombre absolu d'éosinophiles (AEC) périphériques chez les patients tuberculeux confirmés bactériologiquement en Ouganda. MATÉRIEL ET MÉTHODES: Nous avons évalué les données des patients adultes atteints de tuberculose (TB) confirmés bactériologiquement qui avaient une mesure de l'AEC du sang périphérique au Centre national de traitement de la TB en Ouganda au cours d'une étude transversale. Nous avons effectué une analyse de régression linéaire pour les corrélats de l'AEC convertis en log. RÉSULTATS: Nous avons inclus 235 patients dans cette analyse avec un âge médian (intervalle interquartile, IQR) de 31 (24-39) ans. 60,4% étaient des hommes et 33,6% avaient une coinfection TB/VIH. Dans un modèle de régression linéaire multivariée qui adustait pour l'âge, le type de résidence, le statut VIH, la perte de poids, l'anorexie, l'indice de masse corporelle, le nombre de lymphocytes T CD8+, le taux d'hémoglobine et la charge bacillaire de TB, les hommes avaient un AEC 47,0% plus élevé que les femmes (ajusté (R2 ) = 0,385, intervalle de confiance (IC) à 95%: 0,012 à 0,759 ; P = 0,043). Aussi, une augmentation de 1 °C de la température a entraîné une diminution de 11,5% de l'AEC (R2 = −0,122 ; IC95%: (−0,233 à −0,011) ; P = 0,031) tandis qu'une augmentation de 1 cellule/mm3 du nombre des cellules T CD4+ a entraîné une augmentation de 0,10% de l'AEC (R2 = 0,001 ; IC95% (0,000 à 0,001) ; P = 0,032). CONCLUSION: L'AEC était plus élevé chez les hommes que chez les femmes, ce qui correspond à la répartition normale de la population de l'AEC chez les Ougandais. L'AEC était faiblement mais positivement corrélée avec le nombre de CD4 et négativement corrélée avec la température.

Diagnostic Accuracy of Clinical Diagnostic Scoring Systems for Childhood Tuberculosis: A Systematic Review and Meta-analysis.

Background: Diagnosis of childhood tuberculosis (TB) poses several challenges. Therefore, point-based scoring systems and diagnostic algorithms have been developed to improve the diagnostic yields in this population. However, there are no updated systematic reviews of the existing childhood TB scoring systems and algorithms. Hence, we systematically reviewed the diagnostic accuracy of the childhood TB diagnostic scoring systems and algorithms. Methods: We systematically searched PubMed, CINAHL, Embase, Scopus, and Google Scholar databases for relevant articles published until 30 March 2023. QUADAS-2 was used to assess their study quality. Diagnostic accuracy measures (ie, sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios) were pooled using a random-effects model. Results: We included 15 eligible studies, with a total of 7327 study participants aged <15 years, with 10 evaluations of childhood TB diagnostic scoring systems and algorithms. Among these algorithms and scoring systems, only 3 were evaluated more than once. These were the Keith Edwards scoring system with 5 studies (sensitivity, 81.9%; specificity, 81.2%), Kenneth Jones criteria with 3 studies (sensitivity, 80.1%; specificity, 45.7%), and the Ministry of Health-Brazil algorithm with 3 studies (sensitivity, 79.9%; specificity, 73.2%). Conclusions: We recommend using the Keith Edwards scoring system because of its high sensitivity and specificity. Further research is necessary to assess the effectiveness of scoring systems and algorithms in identifying TB in children with HIV and malnutrition.

Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Distinguishing Lung Cancer in People with HIV.

Objective: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer. Methods: This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves. Results: Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38-51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14-7.71) vs. 0.92 (0.67-1.09), p < 0.001). Similarly, the PLR was higher among cases than controls (237.5 (177.8-361.6) vs. 123.6 (100.6-155.4), p=0.001). At a cutoff of 2.44, the respective Se, Sp, and AUC of the NLR were 87.5% (95% CI: 61.7%-98.4%), 100% (95% CI: 96.2%-100%), and 0.94 (95% CI: 0.85-1.00, p < 0.001). Similarly, the respective Se, Sp, and AUC for the PLR were 75% (95% CI: 47.6%-92.7%), 87.2% (95% CI: 78.8%-93.2%), and 0.81 (95% CI: 0.70-0.93, p < 0.001) at a cutoff of 196.3. Conclusion: The NLR and PLR discriminated PLWH with and without lung cancer and could be useful in PLWH with respiratory symptoms in whom lung cancer can easily be misdiagnosed as other lung pathology.

Death after cure: Mortality among pulmonary tuberculosis survivors in rural Uganda.

OBJECTIVES: To determine the incidence of mortality and its predictors among pulmonary tuberculosis (PTB) survivors treated at a rural Ugandan tertiary hospital. METHODS: We conducted a retrospective chart review of data between 2013 and 2023. We included all people that met the World Health Organisation's definition of tuberculosis cure and traced them or their next of kin to determine vital status (alive/deceased). We estimated the cumulative incidence of mortality per 1000 population, crude all-cause mortality rate per 1000 person-years, and median years of potential life lost for deceased individuals. Using Cox proportional hazard models, we investigated predictors of mortality. RESULTS: Of 334 PTB survivors enrolled, 38 (11.4%) had died. The cumulative incidence of all-cause mortality was 113.7 per 1000 population, and the crude all-cause mortality rate was 28.5 per 1000 person-years. The median years of potential life lost for deceased individuals was 23.8 years (IQR: 9.6-32.8). Hospitalization (adjusted hazard ratio (aHR): 4.3, 95% CI: 1.1-16.6) and unemployment (aHR: 7.04, 95% CI: 1.5-31.6) at TB treatment initiation predicted mortality. CONCLUSION: PTB survivors experience post high mortality rates after TB cure. Survivors who were hospitalized and unemployed at treatment initiation were more likely to die after cure. Social protection measures and long-term follow-up of previously hospitalized patients could improve the long-term survival of TB survivors.

Clinical features, resistance patterns and treatment outcomes of drug-resistant extra-pulmonary tuberculosis: A scoping review.

Background: Drug-resistant tuberculosis (DR-TB) is a threat to tuberculosis (TB) control. Extra-pulmonary forms of DR-TB (DR-epTB) are not well characterized. This review summarizes the clinical features, resistance patterns and treatment outcomes of DR-epTB. Methods: We searched EMBASE to identify studies that reported drug-resistance among extra-pulmonary TB sites. All age groups were included in this review. Studies which did not describe drug-resistance patterns at extra-pulmonary TB sites were excluded. We summarized the proportion of resistance to individual anti-TB drugs as well as multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) and extensively drug-resistant (XDR) TB. Results: Eighteen studies with a total of 10,222 patients with extra-pulmonary TB of whom 1,236 (12.0%) had DR-epTB, were included in this review. DR-epTB was mostly reported in young people aged 28 to 46 years. While TB meningitis is the most commonly studied form, adenitis is the commonest form of DR-epTB reported in 21% to 47%. Central nervous system TB (3.8% to 51.6%), pleural TB (11.3% to 25.9%), skeletal TB (9.4% to 18.1%), abdominal TB (4.3% to 6.5%), and disseminated TB (3.8%) are also encountered. The HIV co-infection rate is reported to be 5.0% to 81.3% while 2.6% to 25.4 % have diabetes mellitus. Clinical symptoms of DR-epTB are consistent with morbidity in the affected body system. Among patients with DR-epTB, the proportion of MDR TB was 5% to 53% while that for pre-XDR TB and XDR TB was 3% to 40% and 4% to 33%, respectively. Treatment success is achieved in 26% to 83% of patients with DR-epTB while death, treatment loss-to-follow up, and treatment failure occur in 2% to 76%, 7% to 15%, and 0% to 4% respectively. Patients with DR-epTB were reported to have poorer outcomes than those with pulmonary DR-TB and extra-pulmonary drug-susceptible TB. Conclusion: Clinical features of DR-epTB are similar to those observed among people with drug-susceptible EPTB but patients with DR-epTB post worse treatment outcomes.