c-KIT is frequently mutated in bilateral germ cell tumours and down-regulated during progression from intratubular germ cell neoplasia to seminoma

Testicular germ cell tumours (TGCTs) are the most frequent cancer type in young men; 5% of these patients develop a second TGCT in the contralateral testis. The pathogenesis of TGCT is closely linked to primordial germ cells (PGCs) or gonocytes. The receptor tyrosine kinase (c-KIT) is necessary for migration and survival of PGCs and is expressed in intratubular neoplastic germ cells (IGCNUs) and seminomas. We studied the frequency of c-KIT exon 11 and 17 mutations in 155 unilateral (108 seminomas and 47 non-seminomas) and 22 bilateral (18 seminomas, two embryonal carcinomas, two IGCNU) cases. While no mutations were detected in exon 11, the mutation frequency in exon 17 was significantly higher in bilateral (14/22, 63.6%) compared to unilateral TGCT (10/155, 6.4%) (p < 0.001). Different activating mutations (Y823D, D816V, D816H and N822K) were detected in bilateral TGCT. Y823D mutation was identical in both testes in three cases and quantitative pyrosequencing showed that up to 76% of the cells analysed in tumour samples carried this mutation. One bilateral synchronous seminoma revealed a S821F mutation in one testis and a Y823D mutation contralaterally. To study the role of c-KIT in TGCT progression, we compared its expression in 41 seminomas and adjacent IGCNUs. Immunohistochemical analysis revealed that c-KIT expression was significantly reduced in seminomas compared to IGCNUs (p < 0.006) and that there were no significant changes in c-KIT mRNA copy numbers in progressed compared to low-stage seminomas. In summary, our study shows that patients with c-KIT mutations are more prone to develop a bilateral TGCT and suggests that in a portion of bilateral TGCTs, c-KIT mutations occur early during embryonal development, prior to the arrival of PGCs at the genital ridge. Furthermore, our findings show that c-KIT down-regulation occurs during the progression of IGCNU to seminoma.     

Changes in pattern of thyroid surgical diseases in Zewditu Hospital, Addis Ababa

Three hundred and thirty four patients were operated for thyroid diseases in five years time between 1996-2000. This figure constitutes 7 percent of all operations done in the same hospital during the same period. Female to male ratio was 6.6, and the majority (73.6%) of patients were in the age group between 20 and 50 years. Based on histopathology, their clinical findings, operative findings and biochemical analysis, the following pattern was observed: multinodular goiter made up the majority (54.2%) and solitary nodule accounted for 23.1% of the cases. Toxic goiter both nodular and diffuse together constituted 11.4%. Thyroid cystic diseases accounted for 2.7%. Only four patients were diagnosed and operated for thyroiditis. Post operative complication, hematoma and respiratory obstruction, were seen in 12% of the cases. There were only two deaths. They were cases of differentiated carcinoma that accounted for 2.7%. The study has observed significant increase (P < 0.05) in hyperthyroid thyroid diseases when compared with the findings observed in the same setting 25 years ago. Though it is not statistically significant, malignancy as an indication of operative management has increased. The number of deaths from thyroid surgery has decreased.     

Pneumocystis jiroveci pneumonia and other pulmonary infections in TB smear-negative HIV-positive patients with atypical chest X-ray in Ethiopia

Pneumocystis pneumonia (PCP) has been considered a rare disease in sub-Saharan Africa. However, a rising prevalence has been noted recently. The objective of this study was to determine the relative prevalence of PCP and other pulmonary opportunistic diseases in patients infected with HIV in Ethiopia. 131 consecutive patients with respiratory symptoms and atypical chest X-ray, who were sputum smear-negative for AFB and seroreactive for HIV, underwent clinical evaluation and investigation for Pneumocystis jiroveci and Mycobacterium tuberculosis from sputum and bronchoalveolar lavage (BAL), and fungal and bacterial pathogens from BAL alone. Bacterial infections, Pneumocystis pneumonia (PCP) and pulmonary tuberculosis (PTB) occurred in 44 (33.6%), 39 (29.7%) and 31 (23.7%) patients, respectively. Pulmonary Kaposi sarcoma and non-specific interstitial pneumonitis occurred in 4 patients each. In a multivariate regression model, predictors of PCP were typical chest X-ray and low CD4 count while purulent sputum predicted bacterial infection. The sensitivity of physicians and chest X-ray diagnosis was particularly low for PTB and bacterial infections. We conclude that chronic bacterial infection and Pneumocystis pneumonia are important differential diagnoses in HIV-infected, smear-negative PTB patients presenting with atypical chest X-ray. We therefore need to escalate the use of preventive and highly active antiretroviral (HAART) treatment in order to prevent a PCP epidemic.     

Diarrhoea-associated parasites in HIV-1 seropositive and sero-negative patients in a teaching hospital, Northwest Ethiopia

OBJECTIVE: to determine the prevalence and type of intestinal parasites in HIV infected and uninfected patients with diarrhea. DESIGN: A cross-sectional study was conducted at Gondar University hospital, Northwest Ethiopia, between March 2003 and October 2004. PATIENTS AND METHODS: A total 312 consecutive diarrheic patients were included in the study. Stool specimens were collected and examined for intestinal parasites following direct, formol-ether concentration and modified acid fast staining methods. RESULTS: Among the patients, 63.8% were found to be HIV seropositive. The prevalence of intestinal parasites in HIV seropositive and seronegative diarrheic patients was 30.6% and 33.6%, respectively. The most prevalent parasites were Strongyoides stercoralis (9.0%) and Entamoeba histolytica (8.3%) followed by Ascaris lumbricoides (5.4%) and Cryptosporidium species (5. 1%). CONCLUSION AND RECOMMENDATION: The prevalence of intestinal parasites in diarrheic patients was very high. Institution of appropriate intervention measures are needed to reduce morbidity in such patients.     

Candidatus Rickettsia hoogstraalii in Ethiopian Argas persicus ticks

Ethiopian soft ticks Argas persicus, hard ticks including both Amblyomma variegatum and Rhipicephalus (Boophilus) spp., and fleas were collected from livestock, traditional human dwellings, and cracks and crevices of trees. They were assessed in pools for the presence of Rickettsia using PCR-based methods. The extracted tick DNA was subjected to molecular screening for Rickettsia, which revealed 50.5% of the pooled samples to be positive for Rickettsia spp. These were then subjected to multi-gene analysis using both outer surface proteins and housekeeping genes with proven discriminatory potential. Sequencing of the citrate synthase and outer membrane genes clearly led to the identification of three distinct rickettsial species, Candidatus Rickettsia hoogstraalii in Argas persicus ticks; R. africae in hard tick pools, and R. felis in fleas. Furthermore, we demonstrated the presence of the plasmid-borne small heat-shock protein gene hsp2 in DNA from A. persicus ticks suggesting that Candidatus R. hoogstraalii carried by these ticks possess a plasmid. Unlike chromosomal gene sequences, the hsp2 gene failed to cluster with Candidatus R. hoogstraalii, instead falling into an isolated separate clade, suggesting a different origin for the plasmid.     

Sensory,psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: A cross-sectional deep profiling study

HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and a major source of morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with HIV in a high resource setting using a battery of measures which included the following: parameters of pain and sensory symptoms (7 day pain diary, Neuropathic Pain Symptom Inventory [NPSI] and Brief Pain Inventory [BPI]), sensory innervation (structured neurological examination, quantitative sensory testing [QST] and intraepidermal nerve fibre density [IENFD]), psychological state (Pain Anxiety Symptoms Scale-20 [PASS-20], Depression Anxiety and Positive Outlook Scale [DAPOS], and Pain Catastrophizing Scale [PCS], insomnia (Insomnia Severity Index [ISI]), and quality of life (Short Form (36) Health Survey [SF-36]). The diagnostic utility of the Brief Peripheral Neuropathy Screen (BPNS), Utah Early Neuropathy Scale (UENS), and Toronto Clinical Scoring System (TCSS) were evaluated. Thirty-six healthy volunteers and 66 HIV infected participants were recruited. A novel triumvirate case definition for HIV-SN was used that required 2 out of 3 of the following: 2 or more abnormal QST findings, reduced IENFD, and signs of a peripheral neuropathy on a structured neurological examination. Of those with HIV, 42% fulfilled the case definition for HIV-SN (n = 28), of whom 75% (n = 21) reported pain. The most frequent QST abnormalities in HIV-SN were loss of function in mechanical and vibration detection. Structured clinical examination was superior to QST or IENFD in HIV-SN diagnosis. HIV-SN participants had higher plasma triglyceride, concentrations depression, anxiety and catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN.     

Dermatophytosis in Tulugudu Island, Ethiopia.

The objective of this investigation was to assess the prevalence of dermatophytoses in children in a geographically restricted area in the Ethiopian countryside, and to determine the aetiological agents of these infections. Demographical and clinical-dermatological data were collected from all children 4-15 years of age on Tulugudu Island, Southern Ethiopia. Mycological specimens were taken and species identification determined through morphological observations and biochemical tests, complemented with sequencing of rDNA ITS2 region when necessary. Of 171 children, 96% shared combs, 85% shared beds and 97% had animal contact. Family size was > 5 persons in 50% of the test subjects and prevalence of tinea capitis was elevated in this group (P < 0.005). Dermatophytoses were clinically diagnosed in 136 cases (79.5%). Tinea capitis (T. capitis) was the most common manifestation with 104 cases (76.5%). T. capitis was combined with dermatophytic infections at other sites in 19 cases. Tinea faciae and Tinea corporis were found in four and two cases, respectively, and pediculosis capitis was diagnosed in 2.9% of the test subjects. Of 135 samples from hair (n = 112), skin (n = 19) and finger-nail (n = 4), 74.1% were microscopy-positive for dermatophytes, 73% were positive in culture, giving an overall prevalence of dermatophytoses in 57.3% of all children examined. Trichophyton violaceum was identified in 80.6% of cultures, Trichophyton verrucosum in 16.3% and Trichophyton tonsurans in 2.0%. One isolate was identified as a white variant of T. violaceum. Tinea capitis was highly prevalent in children on Tulugudu Island, Southern Ethiopia. The anthropophilic species T. violaceum dominated as an aetiological agent. Zoophilic dermatophytes were relatively rarely isolated from clinical specimens, despite the children's frequent contact with animals.     

Quality of Care Delivered to Tuberculosis Patients among Public Hospitals in Central Northeast Ethiopia

BackgroundInappropriate Tuberculosis (TB) diagnosis and treatment contributes to unfavorable health outcome among TB patients. Improving quality of healthcare service helps to avert TB related morbidity. Despite these facts, the level of quality of service is not known in the hospitals. Hence, the present study was conducted to assess the quality of care delivered to TB patients among public hospitals.MethodsA facility-based cross-sectional study was conducted from March 15 to April 30, 2019 in North Shewa Zone, Amhara region, Ethiopia. All TB patients who had follow-up in the hospitals were included. This resulted in the involvement of 82 TB patients. Data was collected by trained data collectors using facility audit, clinical observation checklists, structured questionnaire and in-depth interview. Data was analyzed using SPSS version 20. Binary logistic regression analysis was done to identify the predictors of patients'' satisfaction.ResultsIn this study, 82 respondents with a mean age of 36.48 (±13.27) years were participated. The mean quality score for structural dimension was 59.5%, and 53.7% of participants were found to be satisfied in outcome dimension. The mean score for process dimension of quality of service were 67.9%. Having TB symptoms were significantly associated with the level of patient satisfaction towards TB care [AOR = 0.217, p = 0.015].ConclusionQuality of TB services from structural and outcome dimension were low and higher in process dimension. Thus, careful attention on the quality of services will help to reduce the burden of TB.