Clinical and pathological characteristics of the Uganda genotype of Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb), the aetiological agent of tuberculosis (TB) is the leading infectious cause of death globally. The outcome of Mtb infection is variable and depends on host, bacterial and environmental factors. Mtb has evolved into a number of lineages and sublineages exhibiting phylogeographical population structuring and diverse clinical consequences after infection. The Mtb Uganda genotype is the commonest cause of pulmonary TB (PTB) in Kampala, Uganda. Prominent inherited host factors that determine the outcome of TB are human leukocyte antigens (HLA). To investigate the impact of Mtb genomic diversity and host HLA allelic variability on the clinical outcome of TB infection in Ugandan patients, the clinical and pathological outcome of Mtb Uganda genotype, and the association between HLA II alleles and PTB due to Mtb were studied. The Uganda genotype was found less frequently in extrapulmonary TB (EPTB) than previously reported in PTB in the same setting (Paper I), and tuberculous lymphadenitis patients infected with Mtb Uganda genotype were significantly less prone to have abdominal lymphadenopathy (Paper IV). This may imply that Mtb Uganda genotype has reduced potential to disseminate. A study of the evolutionary relationships and worldwide distribution of the spoligotypes of Mtb isolates from Ugandan patients with tuberculous lymphadenitis indicated an ongoing evolution of the Uganda genotype, with Uganda at the center of this evolution (Paper II). HIV negative patients with pulmonary TB and their genetically related healthy household controls were typed for HLA class II alleles (Paper III). The HLA- DQB1*03:03 allele was significantly less frequent in patients compared to healthy controls suggesting that the HLADQB1*03:03 allele may be associated with resistance to TB. To establish the cause and pathology of fatal mycobacterial disease, the mycobacteria and pathology associated with fatal TB were studied (Paper IV). One quarter of fatal mycobacterial disease was associated with non tuberculous mycobacteria (NTM). Pleural effusions were significantly associated with Mtb disease compared to NTM infection (Paper IV). To explore the potential use of the CD4+ and CD8+ T cell immunoprofile to diagnose tuberculous effusion, CD4+ and CD8+ T cells from pleural effusions were characterized. CD4+ T cells were significantly more abundant in individuals with TB, and the CD4+/CD8+T cell ratios were significantly higher in tuberculous pleural effusion compared to non tuberculous effusion, however this significance was lost after adjusting for age and ethnicity. Analysis of pleural fluid for the quantity of CD4+ and CD8+ T cells may be useful for establishing a diagnosis of TB in suspicious cases (Paper V). In conclusion, this thesis highlights the genetic diversity of Mtb with Mtb Uganda as the predominant genotype in EPTB patients in Uganda. Both NTM and Mtb are associated with fatal mycobacterial disease and the pathology findings are indistinguishable, though NTM are significantly less likely to cause pleural effusion. Mycobacterial genetic diversity together with host HLA variability may have clinical consequences. This can be exploited in designing TB diagnostic, management and prevention strategies

Diagnostic accuracy of fine needle aspiration cytology in patients undergoing thyroidectomy in Uganda: tertiary hospital experience.

Background: Thyroid disease affects about 5% of the World\u2019s population. Fine Needle Aspiration Cytology (FNAC) helps in planning extent of surgery. In some studies, FNAC has been found to have a low accuracy for malignancy. Objective: To estimate the sensitivity and specificity of FNAC in detecting malignancy for thyroid disease using histopathology as the gold standard. Methods: Patients who underwent clinical and laboratory evaluation and thyroidectomy at Mulago National Referral hospital and the Pathology department of Makerere University College of Health Sciences were consecutively recruited over a four months period. Analysis using STATA version 10 focused on sensitivity, specificity and accuracy of FNAC in detecting malignancy. Results: In total, 99 patients were recruited, the F:M ratio was 15.5:1 and median age was 42 years (IQR 34-50). The median duration of symptoms was 364 weeks (IQR 104-986). The proportion of patients with malignancy was 13.3% with papillary thyroid carcinoma being the most predominant type and colloid goiter was the most predominant benign thyroid disease. The sensitivity was 61.5% and specificity 89.5% . Conclusion: This study revealed high specificity and low sensitivity of Fine Needle Aspiration Cytology (FNAC) at detecting malignancy in thyroid nodule

Atypical presentation of colon adenocarcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old). However, more recently, it has been observed that younger patients (less than 40 years of age) are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda.</p> <p>Case presentation</p> <p>A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon.</p> <p>Conclusions</p> <p>Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the diagnosis of colorectal malignancy in young African patients.</p

A meta-analysis of telemedicine success in Africa

The use of information and communication technologies (ICT) tools to improve the efficiency of professionalism at work is increasing every time under the dynamic digital environment. Tools such as telemedicine, tele-education, and health informatics have of late been incorporated in the health sector to enable easy access to essential services, for example, in medical areas from referral centers by the patients on one hand and enabling the doctor to doctor consultations for the benefit of patients. Unfortunately, observations indicate dearth efforts and commitment to optimize use of the tools in the majority of the countries south of the Sahara. Sub-Saharan Africa has been left almost behind the rest of the world in terms of development going through decades of economic exploitation by especially the west through its natural and human resources. These factors, ethnic conflicts and endless wars have continued to ruin sub-Saharan Africa′s socio-economic development. Information was obtained through a network of telemedicine practitioners in different African countries using internet communication, through E-mail and reviewing existing literature of their activities. This information was compiled from representative countries in each African region and the previous authors′experiences as telemedicine practioners. Most of these countries have inadequate ICT infrastructure, which yet creates sub-optimal application. Sub-Saharan Africa, made up of 33 of the 48 global poorest countries has to extend its ICT diffusion and policy to match the ever developing global economy. In some countries such as Ethiopia and South Africa there is significant progress in Telemedicine while in countries such as Burkina Faso and Nigeria the progress is slow because of lack of political support. Almost all reference to Africa is made in due respect to sub-Saharan Africa, one with big social, economic, and political problems with resultant high morbidity and mortality rates. This also highlights the under-representation of African researchers in the global whelm of information system research. Telemedicine in Africa though has not attracted enough political support is potentially a very useful conduit of health-care given the fact that the continent is resource limited and still enduring the effects of scarce human resource especially in health

Feasibility and diagnostic accuracy of Internet-based dynamic telepathology between Uganda and Germany

We assessed the feasibility and diagnostic accuracy of Internet-based telepathology compared with conventional microscopic examination. A total of 96 cases from the routine workload of the Department of Pathology at the Mulago Hospital in Uganda were examined by robotic telemicroscopy via the Internet at the Fuerth Hospital in Germany. The telepathology diagnoses were compared with those of conventional microscopy. Email and Skype telephony were used to exchange clinical and diagnostic information. The reference diagnosis (gold standard) was established by consensus between two or more experienced pathologists using both conventional microscopy and telemicroscopy; immunohistochemistry was used whenever it was necessary. It took approximately 30 min for a pathologist to learn to use the telepathology system and 4–25 min to read a case remotely. Internet speed was the main limiting factor. The images were of good quality and the pathologist at the remote site was able to navigate through the slide and change the magnification as necessary. In 92 of the specimens (97%), the pathologists at the two hospitals agreed exactly about the diagnosis. Agreement overall was moderate (kappa = 0.39). The discordant diagnoses were attributed to factors related to diseases morphologically difficult to diagnose, such as soft tissue sarcomas and primitive tumours. Internet-based conferencing systems offer an inexpensive method of obtaining a primary diagnosis by telepathology and consulting on cases that require subspecialty expertise

Predominance of Uganda genotype of Mycobacterium tuberculosis isolated from Ugandan patients with tuberculous lymphadenitis.

International audienceIn Uganda, the emerging Uganda genotype of Mycobacterium tuberculosis is the most common cause of pulmonary tuberculosis (PTB), and accounts for up to 70% of isolates. Extrapulmonary TB (EPTB) is less studied in Uganda. Molecular characterization using deletion analysis and spoligotyping was performed on 121 M. tuberculosis isolates from lymph node fine needle biopsy aspirates of Ugandan patients with tuberculous lymphadenitis. The evolutionary relationships and worldwide distribution of the spoligotypes were analyzed. Mycobacterium tuberculosis was the only cause of EPTB in this study. The T2 sublineage was the most predominant lineage and the Uganda genotype was the dominant genotype. There were 54 spoligotype patterns among the 121 study isolates. The dominant spoligotypes were shared international types (SIT) SIT420, SIT53, SIT 135, SIT 128 and SIT590 in descending order. All but SIT420 were previously reported in pulmonary TB in this setting. The phylogenetic analysis showed a long descendant branch of spoligotypes belonging to the T2-Uganda sublineage containing specifically SITs 135, 128 and 420. In most cases, the spoligotypes were similar to those causing PTB, but the Uganda genotype was found to be less common in EPTB than previously reported for PTB in Uganda. The phylogenetic analysis and the study of the worldwide distribution of clustered spoligotypes indicate an ongoing evolution of the Uganda genotype, with the country of Uganda at the center of this evolution

Injection and sexual risk among people who use or inject drugs in Kampala, Uganda: An exploratory qualitative study.

BackgroundCountries in Sub-Saharan Africa (SSA) have seen rapid increases in injection drug use since 2008. In Uganda, the Global Sate of Harm report and studies conducted by Makerere University Crane Surveys have estimated HIV prevalence among people who inject drugs (PWID) at approximately 17%. The objective of the research was to document injection and other drug-related risks among people who use drugs in Uganda to develop comprehensive HIV/HCV prevention interventions.MethodsBetween August and September 2018, we conducted qualitative interviews among male and female people who use drugs. Interview topics included the availability and accessibility of clean syringes, injection risks, overdose, sexual-risk behaviors, and the availability and accessibility of harm reduction and drug treatment services.ResultsParticipants reported several injection-related risks including sharing and reusing syringes, pooling and mixing drugs in the same container, measuring drugs using syringes, getting prefilled injections from dealers, being injected by other people who inject drugs, and using contaminated water or blood to dilute drugs. Participants reported a scarcity of harm reduction services, although a few appear to have participated in the syringe exchange pilot conducted by the Uganda Harm Reduction Network (UHRN). Even fewer reported knowing organizations that helped people who use drugs abstain from or reduce their use. Medication assisted therapy (MAT) and naloxone to reverse overdoses are not currently available.ConclusionsComprehensive prevention and treatment services are needed in Uganda and should include expanded syringe exchange programs, social network HIV testing, HCV testing, provision of naloxone and MAT, and linkage to and retention in HIV care