The Utility of the helicobacter pylori stool antigen test in managing dyspepsia: an experience from a low resource setting

Background: Dyspepsia is defined as a chronic or recurrent pain or discomfort centered in the upper abdomen. Endoscopy is the best strategy for confirming the cause of dyspepsia. Non- invasive strategies would be more appropriate in low resource countries where endoscopy is not readily available. However, there is concern that these strategies may miss serious disease like gastric cancer. One test that needs to be assessed in this regard is the Helicobacter pylori stool antigen test (HPSAT).Objective: To determine the validity of the stool antigen test in predicting H. pylori associated disease among patients with dyspepsia.Methods: In this prospective study patients with dyspepsia attending Mulago Hospital were recruited consecutively. Helicobacter pylori was determined using the Rapid Strip HpSA ®, endoscopy and gastric mucosal biopsy were done.Results: 167 patients with dyspepsia were recruited into the study. There were ninety six (57.5%) females and seventy one (42.5%) males with an average age of 48.1(±18.1) years. Patients presenting with dyspepsia in Mulago hospital were more likely to come from the Central 60 (36%) and western tribes 55 (33%). The commonest endoscopic finding was oesophagitis 25 (15%). Peptic ulcer disease was found in 32 (19.2%) and 54 (32.3%) had normal endoscopy findings. H pylori was found in 33.5% and 32.5% using the HPSAT and histology respectively. The validity of the HPSAT in predicting H.pylori associated diseases was generally low with an overall sensitivity of 55.8%, and specificity of 74.2%. However, the validity was higher in predicting the diagnosis of peptic ulcer disease with a sensitivity 59.4% and specificity 72.6%.Conclusion and recommendations: The HPSAT may be used in the test and treat strategy for young patients with dyspepsia without alarm signs and symptoms in low resource settings. However, because of its low validity in predicting H.pylori associated disease, it is important to follow up patients so that if symptoms persist or recur endoscopy is performedKeywords: helicobacter pylori, stool antigen, dyspepsia, low resource settin

Diagnosis of alcohol misuse and alcoholic liver disease among patients in the medical emergency admission service of a large urban hospital in Sub-Saharan Africa; a cross sectional study

Introduction: Uganda is among the top ten consumers of alcohol worldwide though there is little data on alcohol related liver disease. We describe alcohol use, alcohol misuse, and alcoholic liver disease among adults at the emergency admission service of a large urban hospital in Uganda. Methods: All adults who consented were prospectively evaluated for alcohol use by inquiry and alcohol misuse by the "Cutting down, Annoyance, Guilt and Eye-opener- CAGE" questionnaire. Alcohol related hepatocellular liver injury was assessed using aspartate aminotransferase, and alanine aminotransferase levels. A combination of CAGE score ≥2 and De Ritis ratio ≥2 defined alcoholic liver disease (ALD). Human Immunodeficiency Virus (HIV), and viral hepatitis B and C serologies were evaluated in all the patients. Descriptive and inferential statistics were generated to answer our research questions. Results: Three hundred and eighty individuals consented and participated in the study. Among these, 46.8% acknowledged use of alcohol while 21% and 10% met the study definition of alcoholic misuse and alcoholic liver disease respectively. Both alcohol misuse and alcoholic liver disease was significantly associated (p-value ≤ 0.05) with male gender, region of origin, number of life time sexual partners and serum albumin below 3.5 mg/dl after univariate and multivariate analysis. Conclusion: Alcohol misuse and alcoholic liver disease is frequent in this medical emergency unit. Our study suggests a link between alcohol misuse or alcoholic liver disease and male gender, region of origin, number of sexual partners, and serum albumin below 3.5mg/dl.Key words: Alcohol use, alcohol misuse, alcoholic liver disease, aspartate aminotransferase, alanine aminotransferase, CAGE questionnaire, De Ritisrati

Performance of Lipoarabinomannan Assay using Cerebrospinal fluid for the diagnosis of Tuberculous meningitis among HIV patients.

Background: The diagnostic utility of the Mycobacteria tuberculosis lipoarabinomannan (TB-LAM) antigen lateral flow assay on cerebrospinal fluid (CSF) for the diagnosis of tuberculous meningitis (TBM) has not been extensively studied and the few published studies have conflicting results. Methods: Lumbar CSF from 59 HIV-positive patients with suspected TBM was tested with TB-LAM and Xpert MTB/Rif Ultra. The diagnostic performance of CSF TB-LAM was compared to positive CSF Xpert MTB/Rif Ultra (definite TBM) and a composite reference of probable or definite TBM according to the uniform case definition.  Results: Of 59 subjects, 12 (20%) had definite TBM and five (9%) had probable TBM. With reference to definite TBM, CSF TB-LAM assay had a diagnostic sensitivity of 33% and specificity of 96%. When compared to a composite reference of definite or probable TBM, the sensitivity was 24% and specificity was 95%. There were two false positive tests with TB-LAM (3+ grade). In-hospital mortality in CSF TB-LAM positive patients was 17% compared to 0% in those with definite TBM by Xpert MTB/Rif Ultra but negative LAM. Conclusions: Lumbar CSF TB-LAM has a poor performance in diagnosing TBM. Both urine TB-LAM and Xpert Ultra should be further investigated in the diagnosis of TBM

The role of household labour for sustainable intensification in smallholder systems: a case study in cocoa farming systems

Sustainable agricultural intensification aims at increasing yields on existing agricultural land without negative environmental impacts. Managing pests and diseases contributes to increasing yields. Without synthetic pesticides, this management is labour intensive. Smallholder farming systems heavily rely on manual and household labour, which will be affected by future demographic changes. Knowledge on how these changes will affect sustainable intensification is limited. Based on a case study of Ugandan cocoa farms, we tested the impact of increased household labour availability on pest and disease management (PDM) practices and pesticide use. We made use of a unique quasi-experimental design, in which household labour increased during the national COVID-19 lockdowns as children did not attend school and family members returned from cities. Our interview data from 2019 to 2021 showed that household labour availability increased on average by 0.8 (±2.5) household members and 16% of labour days per hectare. Using different regression models complemented with qualitative insights, we found that the uptake of alternative PDM practices significantly reduced pesticide quantities and expenditures. The implementation of alternative PDM practices was only weakly influenced by household labour availability and increased with farmer training and trust in alternative practices. These results imply that alternative PDM practices are an important pillar for production with little or without synthetic pesticides and their adoption requires support and incentives, especially on labour or resource-constrained farms

Recent developments in Tuberculous meningitis pathogenesis and diagnostics [version 2; peer review: 1 approved]

The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM. For instance, neutrophils appear to play a significant role in the immunopathogenesis of TBM, and either a paucity or an excess of inflammation can be detrimental in TBM. Further, severity of HIV-associated immunosuppression is an important determinant of inflammatory response; patients with the advanced immunosuppression (CD4+ T-cell count of 150 cells/μL. Host genetics may also influence outcomes with LT4AH genotype predicting inflammatory phenotype, steroid responsiveness and survival in Vietnamese adults with TBM. Whist in Indonesia, CSF tryptophan level was a predictor of survival, suggesting tryptophan metabolism may be important in TBM pathogenesis. These varying responses mean that we must consider whether a “one-size-fits-all” approach to anti-bacillary or immunomodulatory treatment in TBM is truly the best way forward. Of course, to allow for proper treatment, early and rapid diagnosis of TBM must occur. Diagnosis has always been a challenge but the field of TB diagnosis is evolving, with sensitivities of at least 70% now possible in less than two hours with GeneXpert MTB/Rif Ultra. In addition, advanced molecular techniques such as CRISPR-MTB and metagenomic next generation sequencing may hold promise for TBM diagnosis. Host-based biomarkers and signatures are being further evaluated in childhood and adult TBM as adjunctive biomarkers as even with improved molecular assays, cases are still missed. A better grasp of host and pathogen behaviour may lead to improved diagnostics, targeted immunotherapy, and possibly biomarker-based, patient-specific treatment regimens

Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study.

INTRODUCTION: Tuberculous meningitis accounts for 1-5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis. METHODS: In this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard. FINDINGS: From Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5-87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6-96·2; 153 of 165), compared with 55·6% sensitivity (44·0-70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9-91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5-75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4-91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5-98·5; 39 of 42), higher than Xpert at 65·8% (48·6-80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9-86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture. INTERPRETATION: Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required. FUNDING: Wellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases

Preparedness for Highly Pathogenic Avian Influenza Pandemic in Africa

Africa’s strategies for pandemic influenza must also strengthen overall public health capacity

Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: A prospective cohort study.

OBJECTIVE: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. DESIGN: Prospective cohort. SETTING: Kagadi Hospital, Uganda. POPULATION: Non-anomalous singleton pregnancies. METHODS: Women underwent an early dating ultrasound and a third-trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. RESULTS: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09-21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small-for-gestational-age neonates (OR 3.75, 95% CI 1.18-11.88). CONCLUSION: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low- and middle-income countries are warranted. TWEETABLE ABSTRACT: Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low-resource settings

Standardized Urine-Based Tuberculosis (TB) Screening With TB-Lipoarabinomannan and Xpert MTB/RIF Ultra in Ugandan Adults With Advanced Human Immunodeficiency Virus Disease and Suspected Meningitis.

BACKGROUND: Diagnosis of extrapulmonary tuberculosis (TB) remains challenging. We sought to determine the prevalence of disseminated TB by testing urine with TB-lipoarabinomannan (TB-LAM) lateral flow assay and Xpert MTB/RIF Ultra (Ultra) in hospitalized adults. METHODS: We prospectively enrolled human immunodeficiency virus (HIV)-positive adults with suspected meningitis in Uganda during 2018-2020. Participants underwent standardized urine-based TB screening. Urine (60 mcL) was tested with TB-LAM (Alere), and remaining urine was centrifuged with the cell pellet resuspended in 2 mL of urine for Xpert Ultra testing. RESULTS: We enrolled 348 HIV-positive inpatients with median CD4 of 37 cells/mcL (interquartile range, 13-102 cells/mcL). Overall, 26% (90 of 348; 95% confidence interval [CI], 21%-30%) had evidence of disseminated TB by either urine assay. Of 243 participants with both urine TB-LAM and Ultra results, 20% (48 of 243) were TB-LAM-positive, 12% (29 of 243) were Ultra-positive, and 6% (14 of 243) were positive by both assays. In definite and probable TB meningitis, 37% (14 of 38) were TB-LAM-positive and 41% (15 of 37) were Ultra-positive. In cryptococcal meningitis, 22% (40 of 183) were TB-LAM-positive and 4.4% (6 of 135) were Ultra-positive. Mortality trended higher in those with evidence of disseminated TB by either assay (odds ratio = 1.44; 95% CI, 0.83-2.49; P = .19) and was 6-fold higher in those with definite TB meningitis who were urine Ultra-positive (odds ratio = 5.67; 95% CI, 1.13-28.5; P = .04). CONCLUSIONS: In hospitalized Ugandans with advanced HIV disease and suspected meningitis, systematic screening with urine TB-LAM and Ultra found a high prevalence of urine TB test positivity (26%). In those with TB meningitis, urine tests were positive in over one third. There was little concordance between Ultra and TB-LAM, which warrants further investigation

Trends of admissions and case fatality rates among medical in-patients at a tertiary hospital in Uganda; A four-year retrospective study.

BACKGROUND: Sub-Saharan Africa suffers from a dual burden of infectious and non-communicable diseases. There is limited data on causes and trends of admission and death among patients on the medical wards. Understanding the major drivers of morbidity and mortality would help inform health systems improvements. We determined the causes and trends of admission and mortality among patients admitted to Mulago Hospital, Kampala, Uganda. METHODS AND RESULTS: The medical record data base of patients admitted to Mulago Hospital adult medical wards from January 2011 to December 2014 were queried. A detailed history, physical examination and investigations were completed to confirm the diagnosis and identify comorbidities. Any histopathologic diagnoses were made by hematoxylin and eosin tissue staining. We identified the 10 commonest causes of hospitalization, and used Poisson regression to generate annual percentage change to describe the trends in causes of hospitalization. Survival was calculated from the date of admission to the date of death or date of discharge. Cox survival analysis was used to identify factors associate with in-hospital mortality. We used a statistical significance level of p<0.05. A total of 50,624 patients were hospitalized with a median age of 38 (range 13-122) years and 51.7% females. Majority of patients (72%) had an NCD condition as the primary reason for admission. Specific leading causes of morbidity were HIV/AIDS in 30% patients, hypertension in 14%, tuberculosis (TB) in 12%), non-TB pneumonia in11%) and heart failure in 9.3%. There was decline in the proportion of hospitalization due to malaria, TB and pneumonia with an annual percentage change (apc) of -20% to -6% (all p<0.03) with an increase in proportions of admissions due to chronic kidney disease, hypertension, stroke and cancer, with apc 13.4% to 24%(p<0.001). Overall, 8,637(17.1%) died during hospitalization with the highest case fatality rates from non-TB pneumonia (28.8%), TB (27.1%), stroke (26.8%), cancer (26.1%) and HIV/AIDS (25%). HIV-status, age above 50yrs and being male were associated with increased risk of death among patients with infections. CONCLUSION: Admissions and case fatality rates for both infectious and non-infectious diseases were high, with declining trends in infectious diseases and a rising trend in NCDs. Health care systems in sub-Saharan region need to prepare to deal with dual burden of disease