Advancing genetic testing for neurological disorders in Tanzania: importance, challenges, and strategies for implementation.

This manuscript discusses the critical need for advancing genetic testing capabilities for neurological disorders (NDs) in Tanzania, emphasizing the importance, challenges, and strategies for implementation. Neurological disorders, often caused by a complex interplay of genetic and environmental factors, disproportionately affect low and middle-income countries like Tanzania. Patients with neurogenetic diagnoses in Tanzania face substantial obstacles, including lack of trust in medical professionals, stigmatization, and limited access to proper care. The manuscript underscores the infancy of genetic testing implementation for NDs in Tanzania, citing challenges such as high costs, limited availability, and the absence of routine testing in diagnostic procedures. The paper recommends establishing well-characterized cohorts, conducting a nationwide emergency census survey, and enhancing diagnostic services and healthcare financing. The paper stresses on the importance of collaboration, research, public awareness, and advocacy to address the challenges posed by NDs in Tanzania. The manuscript proposes a comprehensive plan, including training and capacity building in molecular diagnosis and bioinformatics, to establish genetic testing capabilities and reduce the burden of NDs in the country. Overall, the manuscript calls for a collaborative effort involving government support, stakeholder engagement, and international partnerships to advance genetic testing and improve healthcare outcomes for individuals with neurological disorders in Tanzania.

Stroke characteristics and outcomes in urban Tanzania: Data from the Prospective Lake Zone Stroke Registry.

BACKGROUND: Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania. METHODS: We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression. RESULTS: The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027). CONCLUSION: We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy.

Ischemic Stroke at a Tertiary Academic Hospital in Tanzania: A Prospective Cohort Study With a Focus on Presumed Large Vessel Occlusion.

Background: Large vessel ischemic strokes account for more than one-third of all strokes associated with substantial morbidity and mortality without early intervention. The incidence of large vessel occlusion (LVO) is not known in sub-Saharan Africa (SSA). Definitive vessel imaging is not routinely available in resource-limited settings. Aims: We aimed to investigate the burden and outcomes of presumed LVO among patients with ischemic stroke admitted to a large tertiary academic hospital in Tanzania. Methods: This cohort study recruited all consenting first-ever ischemic stroke participants admitted at a tertiary hospital in Tanzania. Demographic data were recorded, and participants were followed up to 1 year using the modified Rankin Scale (mRS). A diagnosis of presumed LVO was made by a diagnostic neuroradiologist and interventional neurologist based on contiguous ischemic changes in a pattern consistent with proximal LVO on a non-contrast computed tomography head. We examined factors associated with presumed LVO using logistic regression analysis. Inter-observer Kappa was calculated. Results: We enrolled 158 first-ever ischemic strokes over 8 months with a mean age of 59.7 years. Presumed LVO accounted for 39.2% [95% confidence interval (CI) 31.6-47.3%] and an overall meantime from the onset of stroke symptoms to hospital arrival was 1.74 days. Participants with presumed LVO were more likely to involve the middle cerebral artery (MCA) territory (70.9%), p < 0.0001. Independent factors on multivariate analysis associated with presumed LVO were hypertension [adjusted odds ratio (aOR) 5.74 (95% CI: 1.74-18.9)] and increased waist-hip ratio [aOR 7.20 (95% CI: 1.83-28.2)]. One-year mortality in presumed LVO was 80% when compared with 73.1% in participants without presumed LVO. The Cohen's Kappa inter-observer reliability between the diagnostic neuroradiologist and interventional neurologist was 0.847. Conclusion: There is a high burden of presumed LVO associated with high rates of 1-year morbidity and mortality at a tertiary academic hospital in Tanzania. Efforts are needed to confirm these findings with definitive vessel imaging, promoting cost-effective preventive strategies to reduce the burden of non-communicable diseases (NCDs), and a call for adopting endovascular therapies to reduce morbidity and mortality.

Predictors of 30-day mortality among patients with stroke admitted at a tertiary teaching hospital in Northwestern Tanzania: A prospective cohort study.

Background: Stroke is the second leading cause of death worldwide, with the highest mortality rates in low- to middle-income countries, particularly in sub-Saharan Africa. We aimed to investigate the predictors of 30-day mortality among patients with stroke admitted at a tertiary teaching hospital in Northwestern Tanzania. Methods: This cohort study recruited patients with the World Health Organization's clinical definition of stroke. Data were collected on baseline characteristics, the degree of neurological impairment at admission (measured using the National Institutes of Health Stroke Scale), imaging and electrocardiogram (ECG) findings, and post-stroke complications. The modified Rankin scale (mRS) was used to assess stroke outcomes. Kaplan-Meier analysis was used to describe survival, and the Cox proportional hazards model was used to examine predictors of mortality. Results: A total of 135 patients were enrolled, with a mean age of 64.5 years. Hypertension was observed in 76%, and 20% were on regular anti-hypertensive medications. The overall 30-day mortality rate was 37%. Comparing patients with hemorrhagic and ischemic stroke, 25% had died by day 5 [25th percentile survival time (in days): 5 (95% CI: 2-14)] versus day 23 [25th percentile survival time (in days): 23 (95% CI: 11-30) (log-rank p < 0.001)], respectively. Aspiration pneumonia was the most common medical complication, occurring in 41.3% of patients. ECG abnormalities were observed in 54.6 and 46.9% of patients with hemorrhagic and ischemic stroke, respectively. The most common patterns were as follows: ST changes 29.6 vs. 30.9%, T-wave inversion 34.1 vs. 38.3%, and U-waves 18.2 vs. 1.2% in hemorrhagic and ischemic stroke, respectively. Independent predictors for case mortality were as follows: mRS score at presentation (4-5) [aHR 5.50 (95% CI: 2.02-15.04)], aspiration pneumonia [aHR 3.69 (95% CI: 1.71-13.69)], ECG abnormalities [aHR 2.28 (95% CI: 1.86-5.86)], and baseline stroke severity [aHR 1.09 (95% CI: 1.02-1.17)]. Conclusion: Stroke is associated with a high 30-day mortality rate in Northwestern Tanzania. Concerted efforts are warranted in managing patients with stroke, with particular attention to individuals with severe strokes, ECG abnormalities, and swallowing difficulties to reduce early morbidity and mortality.

Prevalence and risk factors of acute kidney injury in polytrauma patients at Muhimbili Orthopedic Institute, Tanzania.

BACKGROUND: Polytrauma can lead to multi-organ dysfunction in addition to the local injuries. Acute kidney injury (AKI) is one of the most common causes and contributors to the high morbidity and mortality. Prevalence of acute kidney injury in trauma patients is as reported to be as high as 40.3%. Early detection and management leads to better outcomes. The prevalence of AKI among polytrauma patients remains unknown in our setting. METHODOLOGY: A cross-sectional study involving all adults with polytrauma who presented at the emergency department at Muhimbili Orthopedic Institute (MOI) was designed. A score of ≥18 on the New Injury Severity Score (NISS) screening tool was used to identify polytrauma patients. The Kidney Disease Improving Global Outcomes (KDIGO) criteria was used to identify patient with polytrauma who developed acute kidney injury. Descriptive statistics were then obtained followed by hypothesis testing between variables with the chi squared test. Logistic regression models were used to determine factors associated with acute kidney injury. RESULTS: More than half (56.4%) of the patients were between 26 and 40 years and 92.3% of the polytrauma patients were males. Almost 2/5th (38.5%) of the polytrauma patients had acute kidney injury - half of these had stage 1 AKI, 33.3% had stage 2 AKI and the remaining 16.7% had stage 3 AKI. On multivariate logistic regression, it was found that patients who were older than 45 years (OR 8.53, CI 1.65-43.89, p = 0.01) and those patients with Systemic Inflammatory Response Syndrome (SIRS) (OR 21.83, CI 1.66-286.2, p = 0.019) had higher risk of acute kidney injury. CONCLUSION: There is high prevalence of AKI among polytrauma patients. Elderly patients and those with SIRS were seen to have higher likelihood of AKI.

Lung functions among patients with pulmonary tuberculosis in Dar es Salaam - a cross-sectional study.

BACKGROUND: Approximately 40-60 % of patients remain sufferers of sequela of obstructive, restrictive or mixed patterns of lung disease despite treatment for pulmonary tuberculosis (PTB). The prevalence of these abnormalities in Tanzania remains unknown. METHODS: A descriptive cross-sectional study was carried out among 501 patients with PTB who had completed at least 20 weeks of treatment. These underwent spirometry and their lung functions were classified as normal or abnormal (obstructive, restrictive or mixed). Logistic regression models were used to explore factors associated with abnormal lung functions. RESULTS: Abnormal lung functions were present in 371 (74 %) patients. There were 210 (42 %) patients with obstructive, 65 (13 %) patients with restrictive and 96 (19 %) patients with mixed patterns respectively. Significant factors associated with abnormal lung functions included recurrent PTB (Adj OR 2.8, CI 1.274 - 6.106), Human Immunodeficiency Virus (HIV) negative status (Adj OR 1.7, CI 1.055 - 2.583), age more than 40 years (Adj OR 1.7, CI 1.080 - 2.804) and male sex (Adj OR 1.7, CI 1.123 - 2.614). CONCLUSION: The prevalence of abnormal lung functions is high and it is associated with male sex, age older than 40 years, recurrent PTB and HIV negative status.

Gastric Schwannoma: Case report from Tanzania and brief review of literature.

Upper gastrointestinal bleeding causes significant morbidity and mortality worldwide. We report a rare case of hematemesis secondary to a gastric schwannoma in a Tanzanian female. Gastric schwannomas should be considered in the differential diagnosis of gastric masses and distinguished from other etiologies, given their excellent postresection prognosis.

Latent tuberculosis among pregnant mothers in a resource poor setting in Northern Tanzania: a cross-sectional study.

BACKGROUND: Untreated latent TB infection (LTBI) is a significant risk factor for active pulmonary tuberculosis, hence predisposing to adverse pregnancy outcomes and mother to child transmission. The prevalence of latent tuberculosis in pregnancy and its association, if any, with various socio-demographic, obstetric and clinical characteristics was evaluated. METHODS: Northern Tanzania was chosen as the study site. In a cross-sectional study, a total of 286 pregnant women from 12 weeks gestational age to term were assessed. Screening was undertaken using an algorithm involving tuberculin skin testing, symptom screening in the form of a questionnaire, sputum testing for acid fast bacilli followed by shielded chest X-rays if indicated. HIV serology was also performed on consenting participants. RESULTS: Prevalence of latent infection ranged between 26.2% and 37.4% while HIV sero prevalence was 4.5%. After multivariate logistic analysis it was found that age, parity, body mass index, gestational age, and HIV sero status did not have any significant association with tuberculin skin test results. However certain ethnic groups were found to be less vulnerable to LTBI as compared to others (Chi square = 10.55, p = 0.03). All sputum smears for acid fast bacilli were negative. CONCLUSION: The prevalence of latent tuberculosis in pregnant women was found to be relatively high compared to that of the general population. In endemic areas, socio-demographic parameters alone are rarely adequate in identifying women susceptible to TB infection; therefore targeted screening should be conducted for all pregnant women at high risk for activation (especially HIV positive women). As opposed to the current policy of passive case detection, there appears to be an imminent need to move towards active screening. Ethnicity may provide important clues into genetic and cultural differences which predispose to latent tuberculosis, and is worth exploring further.

A modern regimen of pre-operative concurrent chemo-radiation therapy in locally advanced rectal cancer.

PURPOSE: To evaluate the efficacy and toxicity of preoperative concurrent capecitabine and radiotherapy in the treatment of resectable locally advanced rectal cancer (LARC). MATERIALS AND METHODS: We conducted a phase II trial to assess pathological complete response, tumor downstaging, toxicity and survival of capecitabine (825 mg/m(2) orally, twice daily) with radiotherapy (50.4 Gy/28 fractions) in 31 patients with LARC (cT3/T4 or N+) staged by endoscopic ultrasound (EUS). RESULTS: Median age was 53 years; with M:F ratio of 1:1.58; 77.4% had Eastern Cooperative Oncology Group performance status of 1. EUS showed that 67.7% of tumors were T3, 19.4% were T4, and 58% were node positive. Of 30 patients who had surgery, 6.5% achieved pathological complete remission (pCR). Tumor and nodal downstaging were achieved in 53.9% and 50% of patients, respectively. Grade 3/4 toxicities were mainly diarrhea (35.5%) and proctitis (32.3%). Sphincter preservation was achieved in 4/21 (15%) of patients initially planned for abdominoperineal resection. The median follow-up was 46 months (Range: 1.47-63.9), and the 3-year disease-free and overall survival were 59.8% and 76.6%, respectively. CONCLUSION: Capecitabine given concurrently with radiation therapy is generally well tolerated, and proved to be an effective radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer, yielding results comparable to those reported with 5-FU.

Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial.

BACKGROUND: The British Columbia randomized radiation trial was designed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node-positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy. Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy (37.5 Gy in 16 fractions). Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance. We report the analysis of data from the 20-year follow-up. METHODS: Survival was analyzed by the Kaplan-Meier method. Relative risk estimates were calculated by the Wald test from the proportional hazards regression model. All statistical tests were two-sided. RESULTS: At the 20 year follow up (median follow up for live patients: 249 months) chemotherapy and radiation therapy, compared with chemotherapy alone, were associated with a statistically significant improvement in all end points analyzed, including survival free of isolated locoregional recurrences (74% versus 90%, respectively; relative risk [RR] = 0.36, 95% confidence interval [CI] = 0.18 to 0.71; P = .002), systemic relapse-free survival (31% versus 48%; RR = 0.66, 95% CI = 0.49 to 0.88; P = .004), breast cancer-free survival (48% versus 30%; RR = 0.63, 95% CI = 0.47 to 0.83; P = .001), event-free survival (35% versus 25%; RR = 0.70, 95% CI = 0.54 to 0.92; P = .009), breast cancer-specific survival (53% versus 38%; RR = 0.67, 95% CI = 0.49 to 0.90; P = .008), and, in contrast to the 15-year follow-up results, overall survival (47% versus 37%; RR = 0.73, 95% CI = 0.55 to 0.98; P = .03). Long-term toxicities, including cardiac deaths (1.8% versus 0.6%), were minimal for both arms. CONCLUSION: For patients with high-risk breast cancer treated with modified radical mastectomy, treatment with radiation therapy (schedule of 16 fractions) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone, and it is well tolerated, with acceptable long-term toxicity.