Introduction

Lower respiratory tract infections (LRTIs) are a leading cause of mortality in sub-Saharan Africa. Triaging identifies patients at high risk of death, but laboratory tests proposed for use in severity-of-illness scores are not readily available, limiting their clinical use. Our objective was to determine whether baseline characteristics in hospitalized participants with LRTI predicted increased risk of death.

Methods

This was a secondary analysis from the Mulago Inpatient Non-invasive Diagnosis-International HIV-associated Opportunistic Pneumonias (MIND-IHOP) cohort of adults hospitalized with LRTI who underwent standardized investigations and treatment. The primary outcome was all-cause mortality at 2 months. Predictors of mortality were determined using multiple logistic regression.

Results

Of 1887 hospitalized participants with LRTI, 372 (19.7%) died. The median participant age was 34.3 years (interquartile range, 28.0-43.3 years), 978 (51.8%) were men, and 1192 (63.2%) were HIV-positive with median CD4 counts of 81 cells/µL (interquartile range, 21-226 cells/µL). Seven hundred eleven (37.7%) participants had a microbiologically confirmed diagnosis. Temperature <35.5°C [adjusted odds ratio (aOR) = 1.77, 95% confidence intervals (CI): 1.20 to 2.60; P = 0.004], heart rate >120/min (aOR = 1.82, 95% CI: 1.37 to 2.43; P < 0.0001), oxygen saturation <90% (aOR = 2.74, 95% CI: 1.97 to 3.81; P < 0.0001), being bed-bound (aOR = 1.88, 95% CI: 1.47 to 2.41; P < 0.0001), and being HIV-positive (aOR = 1.49, 95% CI: 1.14 to 1.94; P = 0.003) were independently associated with mortality at 2 months.

Conclusions

Having temperature <35.5°C, heart rate >120/min, hypoxia, being HIV-positive, and bed-bound independently predicts mortality in participants hospitalized with LRTI. These readily available characteristics could be used to triage patients with LRTI in low-income settings. Providing adequate oxygen, adequate intravenous fluids, and early antiretroviral therapy (in people living with HIV/AIDS) may be life-saving in hospitalized patients with LRTI.

Background

Preserved ratio impaired spirometry (PRISm), defined as a normal ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity (≥0.70) with low FEV₁ (<80% predicted), has been associated with increased mortality in the general population. Female sex has been associated with increased odds of PRISm in people without HIV. People with HIV (PWH) are at increased risk for lung function abnormalities, but whether HIV modifies the effect of sex on PRISm development is largely unknown.

Methods

Adults with and without HIV underwent baseline followed by serial spirometry after completing therapy for pneumonia, predominantly tuberculosis (TB), in Kampala, Uganda. Using generalized estimating equations adjusted for age, body mass index, smoking, biomass fuel exposure, HIV, and TB status, we compared individuals with PRISm with those with normal spirometry. These models were stratified by HIV status.

Results

Of 339 baseline participants, 153 (45%) were women; 129 (38%) had HIV, of whom 53% were women. Overall, 105/339 participants (31%) had PRISm at baseline. HIV was associated with lower odds of PRISm (adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.68; P = .001). Female sex trended toward increased odds of PRISm among all participants (aOR, 1.65; 95% CI, 0.99-2.75; P = .052). The association between female sex and PRISm tended to be stronger among PWH (aOR, 3.16; 95% CI, 1.14-8.76; P = .03) than among those without HIV (aOR, 1.34; 95% CI, 0.73-2.45; P = .34); this study was underpowered to detect an HIV-sex interaction of this magnitude (P = .30).

Conclusions

Among Ugandan adults who recovered from pneumonia, female sex was associated with increased odds and HIV with decreased odds of PRISm, suggesting independent sex and HIV effects on PRISm pathogenesis.

Background

Stool is a potential sample for diagnosing Mycobacterium tuberculosis (Mtb) in patients with difficulty in expectorating. However, high mycobacterial culture contamination rates and Xpert MTB/RIF Ultra test error rates on stool samples have limited its use. OMNIgene SPUTUM (OM-S) is a sample transport reagent with characteristics of sputum decontamination while maintaining viable Mtb. We evaluated the impact of OM-S on Mtb diagnostic yield from stool using smear microscopy, Xpert MTB/RIF Ultra, and culture among presumptive TB patients.

Methods

Paired stool and expectorated sputum samples were collected from consecutive Ugandan adults undergoing diagnostic evaluation for pulmonary TB between June 2018 and June 2019. Stool was divided into 2 portions: one was homogenized in OM-S (OM-S stool) and the other in PBS (PBS stool) as control. Both sputum and processed stool were tested for Mtb using concentrated smear fluorescence microscopy (CFM), Xpert MTB/RIF Ultra (Xpert) and Mycobacteria Growth Indicator Tube (MGIT) culture. Sensitivity, specificity, and predictive values for each test were calculated against sputum MGIT culture as the reference standard.

Results

Of the 200 participants, 120 (60%) were male, 73 (37%) were HIV positive (median CD4 120 cells/uL (IQR 43-297)) and 128 (64%) had confirmed pulmonary TB by sputum MGIT culture. Seven (4%) OM-S stool Xpert samples reported errors while 47 (25%) and 103 (61%) were contaminated on OM-S stool MGIT and PBS stool MGIT, respectively. OM-S stool MGIT was able to accurately diagnose 56 of the contaminated PBS stool MGIT samples compared to only 5 of the contaminated OM-S stool MGIT samples diagnosed by PBS stool MGIT. Sensitivity (95% Confidence Interval, CI) 89% (83-94) for OM-S stool Xpert was higher compared to that of OM-S stool MGIT 60% (51-69) and PBS stool MGIT 42% (32-52). Specificity (95%CI) 91% (82-97) was also higher for OM-S stool Xpert compared to OM-S stool MGIT 64% (51-75) and PBS stool MGIT 26% (16-38).

Conclusion

Stool processed with OM-S showed potential to improve Mtb diagnostic yield and reduce rates of indeterminate results when tested on Xpert and MGIT culture. The method may thus be of value in Mtb detection among patients with difficulty to expectorate.

The objective of this prospective cross-sectional study, conducted at a national referral hospital in Kampala, Uganda, was to determine diagnostic performance of serum C-reactive protein (CRP) as a triage test for tuberculosis (TB) among HIV-seronegative inpatients. We calculated the sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values to determine the diagnostic performance of a CRP enzyme-linked immunosorbent assay (ELISA) (Eurolyser) in comparison to that of a reference standard of Mycobacterium tuberculosis culture on two sputum samples. We constructed receiver operating curves and reported performance in reference to the manufacturer's cutoff and also to a threshold chosen to achieve sensitivity of >90%, in accordance with the WHO's target-product profile for a triage test. Among 119 HIV-seronegative inpatients, 46 (39%) had culture-positive pulmonary TB. In reference to M. tuberculosis culture, CRP had a sensitivity of 78% (95% confidence interval [CI], 64 to 89%) and a specificity of 52% (95% CI, 40 to 64%) at the manufacturer's threshold of 10 mg/liter. At a threshold of 1.5 mg/liter, the sensitivity was 91% (95% CI, 79 to 98%) but the specificity was only 21% (95% CI, 12 to 32%). Performance did not differ when stratified by illness severity at either threshold. In conclusion, among HIV-seronegative inpatients, CRP testing performed substantially below targets for a TB triage test. Additional studies among HIV-seronegative individuals in clinics and community settings are needed to assess the utility of CRP for TB screening.

Objectives

Spirometric abnormalities are frequent, and obstructive lung disease (OLD) is a common comorbidity among people with HIV (PWH). HIV increases the risk of many comorbidities to a greater degree in women than in men. Few studies have evaluated whether sex modifies the HIV-associated risk of OLD.

Design and methods

To evaluate the associations between sex and HIV with abnormal lung function, women and men with and without HIV underwent spirometric testing after completing therapy for pneumonia, including tuberculosis (TB), in Kampala, Uganda. OLD was defined as a postbronchodilator forced expiratory volume in the first second to forced vital capacity (FEV 1 /FVC) ratio less than 0.70. Associations between sex, HIV, and lung function were evaluated using multivariable regression models including sex-by-HIV interaction terms after adjusting for age, BMI, smoking status, and TB status.

Results

Among 348 participants, 147 (42%) were women and 135 (39%) were HIV-positive. Sixteen (11%) women and 23 men (11%) had OLD. The HIV-sex interaction was significant for obstructive lung disease ( P  = 0.04). In the adjusted stratified analysis, women with HIV had 3.44 (95% CI 1.11-12.0; P  = 0.04) increased odds of having OLD compared with men with HIV. Women without HIV did not have increased odds of having OLD compared with men without HIV.

Conclusion

HIV appears to increase the risk of OLD to a greater degree in women than in men in an urban Ugandan setting. The mechanistic explanation for this interaction by sex remains unclear and warrants further study.

Introduction

Pneumonia is an important cause of morbidity and mortality in persons living with human immunodeficiency virus (HIV) infection. How immune activation differs among HIV-infected and HIV-uninfected adults with pneumonia is unknown.

Methods

The Inflammation, Aging, Microbes, and Obstructive Lung Disease (I AM OLD) Cohort is a prospective cohort of adults with pneumonia in Uganda. In this cross-sectional analysis, plasma was collected at pneumonia presentation to measure the following 12 biomarkers: interleukin 6 (IL-6), soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2), high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer, soluble CD27 (sCD27), interferon gamma-inducible protein 10 (IP-10), soluble CD14 (sCD14), soluble CD163 (sCD163), hyaluronan, and intestinal fatty acid binding protein. We asked whether biomarker levels differed between HIV-infected and HIV-uninfected participants, and whether higher levels of these biomarkers were associated with mortality.

Results

One hundred seventy-three participants were enrolled. Fifty-three percent were HIV-infected. Eight plasma biomarkers-sTNFR-1, sTNFR-2, hsCRP, D-dimer, sCD27, IP-10, sCD14, and hyaluronan-were higher among participants with HIV infection, after adjustment for pneumonia severity. Higher levels of 8 biomarkers-IL-6, sTNFR-1, sTNFR-2, hsCRP, IP-10, sCD14, sCD163, and hyaluronan-were associated with increased 2-month mortality.

Conclusions

As in other clinical contexts, HIV infection is associated with a greater degree of immune activation among Ugandan adults with pneumonia. Some of these are also associated with short-term mortality. Further study is needed to explore whether these biomarkers might predict poor long-term outcomes-such as the development of obstructive lung disease-in patients with HIV who have recovered from pneumonia.