Dear Editor, Cough is a key symptom of TB and many other respiratory conditions. Until recently, assessments of cough burden have been largely subjective and limited to self-report. Quantitative data on the timing and frequency of coughing could help to identify patterns of cough that are unique to respiratory diseases, facilitating diagnosis and monitoring of response to treatment. Such data can now be obtained through smartphone applications which support longitudinal continuous cough monitoring as patients follow their normal daily routines. To further explore its potential, we conducted 14 days of smartphonebased longitudinal continuous cough monitoring of people with presumptive TB at health centers in five countries (Uganda, South Africa, the Philippines, Vietnam and India) using the Hyfe Research application,1 and compared patterns of cough between people with microbiologically confirmed TB, clinical TB, and other respiratory diseases (ORD). Eligible participants were 18 years or older and had new or worsening cough for at least 2 weeks. Participants were excluded if they had taken TB medicines in the previous 12 months or taken medication with anti-mycobacterial activity in the past 2 weeks. Participants were provided with smartphones loaded with the Hyfe Research app to continuously monitor participant cough for 14 days after enrollment. Participants recorded for a median of 23.9 hours a day.2 TB status was classified based on positive sputum Xpertw MTB/RIF Ultra (Cepheid, Sunnyvale, CA, USA) or mycobacterial culture results (microbiologically confirmed TB) or empiric TB treatment initiation (clinical TB). Empiric TB treatment decisions were made by non-study clinicians based on medical history (TB symptoms and risk factors), physical examination, and/or chest X-ray findings. Data and code are made available at https:// github.com/skhuddart/TBcoughmonitoring. As of August 15, 2022, a total of 565 participants completed cough monitoring and had results of TB reference standard testing. The median age was 38 years (interquartile range [IQR] 26–51), 54.5% of participants were female, and the median BMI was 22.1 kg/m2 (IQR 19.0–26.0). In the past 7 days, 21.4% of participants had smoked; 13.3% of participants were living with diabetes and 12.7% were living with HIV. The median self-reported duration of new or worse cough before the careseeking appointment was 28 days (IQR 15–58). Based on sputum Xpert and culture results, 144 (25.5%) participants had microbiologically confirmed TB, 48 (8.5%) were treated for clinical TB and 373 (66.0%) were classified as having ORD. Among the 144 participants with microbiologically confirmed TB, 93.8% (135/144) reported initiating TB treatment. TB treatment was initiated a median of 1 day (IQR 0–2.5) after study enrollment. On the first recording day, the overall median cough count per hour (medCPH) was 5.0 (IQR 3.0–9.0) (Figure). On Day 1, participants with microbiologically confirmed TB had a significantly higher medCPH (8.0, IQR 3.5– 19.0) than participants with ORD (5.0, IQR 3.0–8.0; P , 0.001). In contrast, there was no significant difference in medCPH between participants with clinical TB (5.0, IQR 2.0–9.0 vs. ORD; P1⁄40.76). By Day 14 of recording, the overall medCPH had fallen to 3.5 (IQR 2.0–6.0) and had decreased significantly compared to Day 1 values in all three groups (all Pvalues , 0.001). In addition, at Day 14 there was no significant difference in medCPH between participants with ORD (3.0, IQR 2.0–6.0) vs. either microbiologically confirmed TB (4.0, IQR 2.0–8.0; P1⁄40.38) or clinical TB (3.0, IQR 2.0–4.9; P1⁄40.24). Participants with TB showed unique cough frequency trajectories early in treatment that were distinct from those of participants with ORD. Furthermore, cough frequency improved more rapidly among participants with microbiologically confirmed TB than other groups. These findings support quantitative cough monitoring as a potential treatment monitoring tool.3 Further work is needed to assess the correlation between cough frequency and established treatment response biomarkers (such as time to positivity in liquid culture). In addition, future studies should explore whether cough features, including cough frequency, are able to improve the accuracy of current TB screening algorithms. The use of cough-based biomarkers for TB screening may help reduce the overtreatment of people without TB and improve detection of TB when missed by routine symptombased screening procedures. In summary, continuous cough monitoring should be further explored as a SH and LA contributed equally as first authors. AC and CY contributed equally as last authors.

Tongue dorsum swabs have shown promise as alternatives to sputum for detecting Mycobacterium tuberculosis (MTB) in patients with pulmonary tuberculosis (TB). Some of the most encouraging results have come from studies that used manual quantitative PCR (qPCR) to analyze swabs. Studies using the automated Cepheid Xpert MTB/RIF Ultra qPCR test (Xpert Ultra) have exhibited less sensitivity with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample preprocessing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of Xpert Ultra performed on tongue swabs collected from 183 adults with presumed TB in Kampala, Uganda. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 77.8% (95% confidence interval [CI] 64.4-88.0) and specificity was 100.0% (95% CI, 97.2-100.0). When compared to a microbiological reference standard (MRS) incorporating both sputum Xpert Ultra and sputum mycobacterial culture, sensitivity was 72.4% (95% CI, 59.1-83.3) and specificity remained the same. Semi-quantitative Xpert Ultra results were generally lower with tongue swabs than with sputum, and cycle threshold values were higher. None of the eight sputum Xpert Ultra "trace" or "very low" results were detected using tongue swabs. Tongue swabs should be considered when sputum cannot be collected for Xpert Ultra testing, or in certain mass-screening settings. Further optimization of tongue swab analysis is needed to achieve parity with sputum-based molecular testing for TB.

The performance of urine Xpert MTB/RIF Ultra (Xpert Ultra) for pulmonary TB diagnosis is unknown. HIV-positive and HIV-negative adults were enrolled at two health facilities in Kampala, Uganda. We compared the accuracy of urine Xpert Ultra and Determine TB-LAM in reference to sputum-based testing (positive Xpert MTB/RIF or culture), and assessed incremental yield. Urine Xpert Ultra had low sensitivity (17.2%, 95% CI 12.3-23.2) but high specificity (98.1%, 95% CI 94.4-99.6). Sensitivity reached 50.0% (95% CI 28.2-71.8) among HIV-positive patients with CD4 <100 cells/μL. Compared to Determine TB-LAM, urine Xpert Ultra was 9.4% (95% CI 3.8-14.9, P = 0.01) more sensitive, and 17.2% (95% CI 4.5-29.8, P = 0.01) more sensitive among HIV-positive patients. However, the incremental sensitivity of urine Xpert Ultra relative to sputum Xpert MTB/RIF was only 1% (95% CI -0.9 to 2.8). Urine Xpert Ultra could be an alternative for patients with advanced HIV infection unable to produce sputum.

OMNIgene·SPUTUM (OM-S) is a sample transport reagent designed to work with all tuberculosis diagnostics while eliminating the need for cold chain. OM-S-treated sputum samples were assayed in several tests after multiday holds. Raw sputa from 100 patients underwent direct smear microscopy, were manually split and assigned to the OM-S group [OM-S added at collection (no other processing required) and tested after 0- to 5-day holds at room temperature] or standard-of-care (SOC) group (NaOH/N-acetyl l-cysteine decontamination, all tested on day of collection). Concentrated smear microscopy, Lowenstein Jensen (LJ) culture, and mycobacteria growth indicator tube (MGIT) culture were performed. For patients with negative direct smear, a second sample was split, with SOC (raw sputum) and OM-S portions (sediment) tested in the Xpert MTB/RIF (Xpert) assay. OM-S group and SOC group results were strongly concordant on all four tests [range, 89% (MGIT)–97% (Xpert)]. OM-S MGIT, LJ, and Xpert tests were in statistical agreement with SOC MGIT as reference. OM-S specimens had lower culture contamination rates (3% vs. 10% LJ; 2% vs. 5% MGIT) but required, on average, 5.6 additional days to become MGIT-positive. The findings suggest that samples held/transported in OM-S are compatible with smear microscopy, LJ or MGIT culture, and Xpert, and perform comparably to fresh sputum samples. Larger feasibility studies are warranted.

Bronchoscopy is useful for diagnosing smear-negative tuberculosis in HIV-infected patientsTo the Editors:Tuberculosis (TB) is the leading cause of morbidity and mortality in HIV-infected patients in sub-Saharan Africa [1], in part because limited availability of diagnostic tests hinders early, directed treatment.Studies have demonstrated a substantial yield of bronchoscopy for diagnosing HIVassociated opportunistic pulmonary diseases, but few studies have explicitly considered whether bronchoscopy adds to the sensitivity of sputum culture in identifying Mycobacterium tuberculosis, or whether bronchoscopy shortens the time needed to diagnose TB.Although bronchoscopy is unavailable in many HIV and TB endemic settings, where it is available its usefulness for TB diagnosis is uncertain.Thus, we examined the performance of bronchoscopy to diagnose TB and other pulmonary diseases in HIV-infected inpatients with cough in Kampala, Uganda.We performed a prospective cross-sectional study enrolling consecutive HIV-infected patients aged o18 yrs hospitalised at Mulago Hospital with cough of o2 weeks but ,6 months duration.After providing informed consent, patients underwent a standard evaluation including chest radiography, sputum acid-fast bacillus (AFB) microscopy and bronchoscopy with bronchoalveolar lavage (BAL) if they were AFB smearnegative, according to previously described protocols [2].Trained technicians examined BAL by smear and/or culture for mycobacteria, Pneumocystis jirovecii, and other fungi.Specific pneumonia treatment was recorded.Patients were seen at a 2-month follow-up visit, after which a pulmonologist and a medical officer assigned final diagnoses based on all diagnostic information and according to a standardised protocol.A final diagnosis of pulmonary TB was based on a positive sputum mycobacterial culture (using Lowenstein-Jensen media), positive BAL AFB smear or BAL mycobacterial culture, or a clinical response to TB treatment at the 2-month follow-up visit.

SETTING: Mulago Hospital, Kampala, Uganda.OBJECTIVE: To evaluate the diagnostic performance of fluorescence microscopy (FM) for diagnosing pulmonary tuberculosis (TB) in a high human immunodeficiency virus (HIV) prevalence setting.DESIGN: Consecutive in-patients with cough for >2 weeks submitted two sputum specimens for smear microscopy. Smears were examined by conventional light microscopy (CM) and FM. The performance of the two methods was compared using mycobacterial culture as a reference standard.RESULTS: A total of 426 patients (82% HIV infected) were evaluated. FM identified 11% more smear-positive patients than CM (49% vs. 38%, P < 0.001). However, positive FM results were less likely than positive CM results to be confirmed by culture when smears were read as either 'scanty' (54% vs. 90%, P < 0.001) or 1+ (82% vs. 91%, P = 0.02). Compared to CM, the sensitivity of FM was higher (72% vs. 64%, P = 0.005), and the specificity lower (81% vs. 96%, P < 0.001). In receiver operating characteristic analysis, maximum area under the curve for FM was obtained at a threshold of >4 acid-fast bacilli/100 fields (sensitivity 68%, specificity 90%).CONCLUSION: Although FM increases the sensitivity of sputum smear microscopy, additional data on FM specificity and on the clinical consequences associated with false-positive FM results are needed to guide implementation of this technology in high HIV prevalence settings.

Gastrointestinal Schistosomiasis and Amebiasis are uncommon in the western world, while such infections are frequent in the African community. In addition to the problems associated with the clinical symptoms of these parasitic infections, it is important to stress the increase in cancer of the Gastro-Intestinal (GI) tract. In this study we evaluate the prevalence of cancer in patients affected by chronic inflammatory diseases caused by the above named parasites. In three years, from January 2000 to December 2003, we observed a total of 1199 subject. Of these, 950 presented with complaints of diarrhoea, vomiting, abdominal pain, melena, hematemesis, rectal discharges and alteration of bowel habits. A total of 818 patients were evaluated in Uganda (Mulago and Arua hospitals) and 381 at Luisa Guidotti Hospital in Zimbabwe. An exhaustive clinical history was collected for each patient and then physical and laboratory examinations were performed. The clinical files of all patients previously admitted to the respective hospitals were obtained and the information taken from these files was then integrated with our clinical findings. Subjects who were found free of gastro-intestinal disease after examinations and did not have a clinical history of infective GI disease but presented with other pathologies, were regarded as control group. The control group was composed of 249 subjects. The subjects who were positive on examination underwent further investigations. The number of patients affected by schistosomiasis and amebiasis were 221 and 224 respectively. The number of patients who suffered from aspecific enterocolitis was 454, intestinal tuberculosis was present in 21 patients and we found 30 patients with esophageal candidiasis. Patients who had the above mentioned GI diseases were then divided into 3 groups. First group was composed of patients who had a clinical history of infective GI diseases and were re-admitted for similar symptoms, and on examination were positive for the presence of the same infective GI diseases. Such patients were placed in the Chronic group. The second group was formed of patients who had previously undergone treatment for infective GI diseases but on readmission were found free of infective GI disease, and this group was described as the Cured group. They had symptoms associated with other pathologies. A third group, which we described as the Acute group was composed of patients who did not have any previous case of GI infection and were admitted for the first time. Such patients were found positive on examination for infective GI diseases. In the 950 patients, we found a total of 45 tumors. The tumors were prevalent (42 tumors) in the chronic group. In 34 patients the tumor was in the colo-rectal region, in 3 patients in the stomach, in 4 patients in the esophagus and 1 patient had cancer in the small bowel. Our results show a strong association between the chronic infection of the GI tract and the likelihood to develop tumors. However, it is not clear which biological mechanisms are implicated in such transformations. They may depend on the chronic inflammation of the GI mucous which permits the entrance of carcinogenic materials or on the effects of mutagenic products produced by the parasites or both.