Using (1,3)-ß-D-glucan concentrations in serum to monitor the response of azole therapy in patients with eumycetoma caused by Madurella mycetomatis.

INTRODUCTION: (1,3)-ß-D-glucan is a panfungal biomarker secreted by many fungi, including Madurella mycetomatis, the main causative agent of eumycetoma. Previously we demonstrated that (1,3)-ß-D-glucan was present in serum of patients with eumycetoma. However, the use of (1,3)-ß-D-glucan to monitor treatment responses in patients with eumycetoma has not been evaluated. MATERIALS AND METHODS: In this study, we measured (1,3)-ß-D-glucan concentrations in serum with the WAKO (1,3)-ß-D-glucan assay in 104 patients with eumycetoma treated with either 400 mg itraconazole daily, or 200 mg or 300 mg fosravuconazole weekly. Serial serum (1,3)-ß-D-glucan concentrations were measured at seven different timepoints. Any correlation between initial and final (1,3)-ß-D-glucan concentrations and clinical outcome was evaluated. RESULTS: The concentration of (1,3)-ß-D-glucan was obtained in a total of 654 serum samples. Before treatment, the average (1,3)-ß-D-glucan concentration was 22.86 pg/mL. During the first 6 months of treatment, this concentration remained stable. (1,3)-ß-D-glucan concentrations significantly dropped after surgery to 8.56 pg/mL. After treatment was stopped, there was clinical evidence of recurrence in 18 patients. Seven of these 18 patients had a (1,3)-ß-D-glucan concentration above the 5.5 pg/mL cut-off value for positivity, while in the remaining 11 patients, (1,3)-ß-D-glucan concentrations were below the cut-off value. This resulted in a sensitivity of 38.9% and specificity of 75.0%. A correlation between lesion size and (1,3)-ß-D-glucan concentration was noted. CONCLUSION: Although in general (1,3)-ß-D-glucan concentrations can be measured in the serum of patients with eumycetoma during treatment, a sharp decrease in ß-glucan concentration was only noted after surgery and not during or after antimicrobial treatment. (1,3)-ß-D-glucan concentrations were not predictive for recurrence and seem to have no value in determining treatment response to azoles in patients with eumycetoma.

Epidemiological cut-off values for itraconazole and ravuconazole for Madurella mycetomatis, the most common causative agent of mycetoma.

BACKGROUND: Eumycetoma is a neglected tropical disease. It is a chronic inflammatory subcutaneous infection characterised by painless swellings which produce grains. It is currently treated with a combination of itraconazole and surgery. In an ongoing clinical study, the efficacy of fosravuconazole, the prodrug of ravuconazole, is being investigated. For both itraconazole and ravuconazole, no clinical breakpoints or epidemiological cut-off values (ECV) to guide treatment are currently available. OBJECTIVE: To determine tentative ECVs for itraconazole and ravuconazole in Madurella mycetomatis, the main causative agent of eumycetoma. MATERIALS AND METHODS: Minimal inhibitory concentrations (MICs) for itraconazole and ravuconazole were determined in 131 genetically diverse clinical M. mycetomatis isolates with the modified CLSI M38 broth microdilution method. The MIC distributions were established and used to determine ECVs with the ECOFFinder software. CYP51A sequences were sequenced to determine whether mutations occurred in this azole target gene, and comparisons were made between the different CYP51A variants and the MIC distributions. RESULTS: The MICs ranged from 0.008 to 1 mg/L for itraconazole and from 0.002 to 0.125 mg/L for ravuconazole. The M. mycetomatis ECV for itraconazole was 1 mg/L and for ravuconazole 0.064 mg/L. In the wild-type population, two CYP51A variants were found for M. mycetomatis, which differed in one amino acid at position 499 (S499G). The MIC distributions for itraconazole and ravuconazole were similar between the two variants. No mutations linked to decreased susceptibility were found. CONCLUSION: The proposed M. mycetomatis ECV for itraconazole is 1 mg/L and for ravuconazole 0.064 mg/L.

Molecular detection of human papillomavirus-16 among Sudanese patients diagnosed with squamous cell carcinoma and salivary gland carcinoma.

OBJECTIVE: Human papillomavirus (HPV) gained momentum as a potential etiological factor for many types of cancers. Therefore, the aim of this study was to assess the prevalence of HPV-16 infection among Sudanese patients diagnosed with Squamous Cell Carcinoma (SCC) and Salivary Gland Carcinoma. A descriptive, hospital-based study was conducted. 150 formalin-fixed paraffin-embedded blocks were collected. RESULTS: The study population included a total of 150 patients aged between 18 to 87 years with a mean age of 48.8 ± 11.9 years. Based on gender, females constituted 46.7% while males constituted 53.3%. The 150 patients were classified into 40 (26.0%) esophageal, 30 (20.0%) nasopharyngeal, 18 (12.0%) conjunctival, 18 (12.0%) tongue 12 (8.0%) laryngeal, 8 (5.3%) lip, 6 (4.0%) oropharyngeal, 6 (4.0%) mucoepidermoid, and 6 (4.0%) adenoid cystic, and 6 (4.0%) myoepithelial carcinomas. Odds ratio for male and female diagnosed with carcinoma was 1.025 [0.439-2.394, 95% CI]. Molecular detection of HPV-16 revealed a prevalence of 26 (17.3%) patients were positive for HPV-16. According to cancer diagnosis, esophageal SCC patients showed a high proportion of HPV-16; 14/40 (35.0%). A statistically significant difference was seen for the distribution of HPV-16 positive patients based on cancer diagnosis, P value 0.001.

Malaria epidemic in humanitarian crisis settings the case of South Kordofan state, Sudan.

INTRODUCTION: Malaria remains one of the most common public health problems worldwide, especially in Sudan. With this short communication we aimed at reporting on the latest malaria epidemic that had occurred in the humanitarian settings in South Kordofan state, south-western Sudan, during 2018 and 2019. METHODOLOGY: This is a cross-sectional study analyzing malaria surveillance reports between February 2018 to September 2019. Malaria was reported from febrile patients with confirmed malaria diagnosis using Giemsa stain. According to age, patients were distributed across three categories: less than 5 years, 5 to 15 years, and more than 15 years. RESULTS: In 2019 and 2018, 63,214 and 63,224 cases of malaria were reported, respectively, constituting around 5.5% of the state population (1,152,900). In 2018, 3,571 malaria cases were reported in February, then they decreased in August followed by increase in September-October. In 2019, 15,610 malaria cases were reported in September. Malaria cases aged less than 5 years were 21,848 and 23,561 cases in 2018 and 2019, respectively. CONCLUSIONS: The reported sudden epidemic of malaria is alarming. Therefore, identifying the risk factors associated with this epidemic is crucial to malaria prevention and control, and hence successful achievement of malaria elimination.

Multi-parasite infection in an immigrant from Ghana: potential for new epidemic foci.

INTRODUCTION: Imported parasitosis, which do not require an invertebrate vector, are extremely dangerous and can lead to the occurrence of disease in currently parasite free areas. In the present study we report a case of multi-parasitic infection in a young immigrant from Ghana to Italy caused by filaria, Schistosoma sp. and Strongyloides sp. CASE PRESENTATION: A 27-year-old Ghanaian man attended the Hospital of Nuoro (Sardinia), Italy, at the end of August 2015, claiming pain to the kidney and hypertensive crisis; the patient presented with dyspnea and epistaxis, chronic itchy skin of the back, shoulders, arms and legs, anuria and high creatinine, metabolic acidosis and hypereosinophilic syndrome. Serological test for parasitic infections were done, and showed a marked positivity for filaria, Schistosoma sp. and Strongyloides sp. The patient started the treatment immediately with two doses per day of Bassado Antibiotic (tetracycline) for twenty days and then with a single dose of 3 mg of ivermectin that was repeated after 3 months. CONCLUSIONS: Immigrant patients from endemic areas who show clinical signs, such as a general itching on the back, shoulders and arms and legs, should have a thorough history in order to make early diagnosis and prevent further complications. Therefore, general practitioners and doctors in Europe and in other parasitosis non-endemic countries, should consider to test for parasites in any immigrant from endemic countries to aid in establishing the final diagnosis and prevent further complications.

A snapshot of Plasmodium falciparum malaria drug resistance markers in Sudan: a pilot study.

OBJECTIVES: Malaria infection is still known to be a worldwide public health problem, especially in tropical and sub-tropical African countries like Sudan. A pilot study conducted to describe the trend of P. falciparum drug resistance markers in 2017-2018 in comparison to CQ and AS/SP eras in Sudan. The Pfcrt, Pfmdr-1, Pfdhfr, and Pfdhps genes were investigated. Data deposited by the worldwide antimalarial resistance network was consulted, and the molecular markers previously reported from Sudan were analyzed. RESULTS: Drug molecular markers analysis was successfully done on 20 P. falciparum isolates. The Pfcrt K76 showed high frequency; 16 (80%). For the Pfmdr-1, 9 (45%) isolates were carrying the N86 allele, and 11 (55%) were 86Y allele. While the Y184F of the Pfmdr-1 showed a higher frequency of 184F compared to Y184; 16 (80%) and 4 (20%), respectively. In the Pfdhfr, 51I allele showed higher frequency compared to N51; 18 (90%) and 2 (10%), respectively. For S108N, 18 (90%) were 108 N and 2 (10%) were S108. In the Pfdhps, all isolates were carrying the mutant alleles; 437G and 540E. The frequency distribution of the Pfcrt, Pfmdr-1, Pfdhfr, Pfdhps was significantly different across the whole years in Sudan.

Immunohistochemical expression of PAX-8 in Sudanese patients diagnosed with malignant female reproductive tract tumors.

OBJECTIVES: Paired box protein-8 (PAX-8) immunohistochemical expression can be used as a diagnostic marker for epithelial cells tumors. This study aimed at investigating the immunohistochemical expression of PAX-8 among Sudanese females diagnosed with cervical, endometrial, and ovarian cancers between December 2017 and May 2019 by studying their Formalin-fixed paraffin embedded blocks. RESULTS: Sixty patients diagnosed with female reproductive tract cancers were included who aged 58.7 ± 6.9 years (range, 43-71). Cervix was the most common cancer site in 51/60 (85%) patients. Regarding cancer stage, there was 17 (28%) and 14 (23%) of the study population had stage 3B and 2B, respectively. The histopathological diagnosis included 20 (44%), 13 (29%), and 12 (27%) poorly, moderately, and well differentiated cervical squamous cell carcinoma (SCC) as well as 11 (73%), 2 (13%), 1 (7%), and 1 (7%) endometrial adenocarcinoma, metastatic adenocarcinoma, endocervical adenocarcinoma, and ovarian mucinous cyst adenocarcinoma, respectively. PAX-8 was positively expressed in 9 endometrial adenocarcinoma, 1 endocervical adenocarcinoma and 1 ovarian mucinous cyst adenocarcinoma, 2 poorly, and 1 moderately differentiated SCC. All patients diagnosed with well differentiated SCC and metastatic adenocarcinoma showed no expression of PAX-8. A statistically significant was seen for PAX-8 expression and the different histopathological diagnosis, P value < 0.001.

Frequency distribution of IL-17A G197A (rs2275913) and IL-17F A7488G (rs763780) polymorphisms among healthy Sudanese population.

OBJECTIVES: IL-17A G197A and IL-17F A7488G polymorphisms has been identified to be associated with the susceptibility to many diseases. This study aimed to investigate the frequency distribution of IL-17A G197A and IL-17F A7488G polymorphisms among healthy Sudanese population. A descriptive cross-sectional hospital-based molecular study conducted in different sites throughout Sudan. Two ml blood samples were collected from 717 healthy participants. Demographic data and the medical history of the participants were collected. RESULTS: Of the 717 participants, 355 (49.5%) were males and 362 (50.5%) were females, their mean age was 30.2 ± 17.2 and 32.2 ± 16.5, respectively. For IL-17A, the most frequent genotype detected among males and females was IL-17A heterozygote allele (AG); 215 (60.6%) and 194 (53.6%), respectively. Whereas, for IL-17F, the most frequent allele among males and females was the homozygote allele (AA); 298 (83.9%) for males and 322 (89.0%) for females. HWE for genotype distributions of IL-17A was showing statistical insignificance for IL-17A among males and females, P value 0.614. While HWE for IL-17F reached the equilibrium level, P value 0.048. The most frequent age group was those aged between 21 to 40 years; 281 (39.2%). Arab constituted the major ethnicity of the study participants; 418 (58.3%), P value 0.034.

Prevalence of Helicobacter pylori among Sudanese patients diagnosed with colon polyps and colon cancer using immunohistochemistry technique.

OBJECTIVES: Infection with the bacteria Helicobacter pylori has been classified as class one carcinogen associated with increasing susceptibility of gastritis and gastric carcinoma. This study is aiming at investigating the prevalence of H. pylori among colon polyps and colon cancer patients. A descriptive cross-sectional hospital-based study was conducted between February and June 2017. Sixty-nine formalin-fixed paraffin blocks collected from colon polyps and colon cancer patients to detect H. pylori using immunohistochemistry technique. RESULTS: Of the 69 patients included in the study, 39 (56.5%) males and 30 (43.5%) were females, their age ranged from 21 to 80 years with a mean age of 47.1 ± 19.7. Of the 69 colon polyps and colon cancer patients, 44 (63.8%) were diagnosed as adenocarcinoma, 10 (14.5%) colitis, 15 (21.7%) juvenile polyposis syndrome. The results of immunohistochemistry technique showed the presence of 16 (23.2%) positive patients for H. pylori infection. Of these 16, 13 (81.3%) patients were diagnosed with adenocarcinoma and 3 (18.7%) patients were diagnosed with juvenile polyps. The results of H. pylori detection among the different colon polyps and colon cancer patients were showing a statistically significant association for H. pylori infection and adenocarcinoma, P value 0.028.

Immunohistochemical expression of Cyclin D1 among Sudanese patients diagnosed with benign and malignant prostatic lesions.

OBJECTIVES: Prostate cancer (PC) is common cancer worldwide. Several markers have been developed to differentiate between benign prostatic hyperplasia (BPH) from PC. A descriptive retrospective hospital-based study aimed at determining the expression of Cyclin D1 in BPH and PC. The study took place at different histopathology laboratories in Khartoum state, Sudan, from December 2016 to January 2019. Formalin-fixed paraffin-embedded blocks were sectioned and fixed in 3-aminopropyltriethoxysilane coated slides incubated into primary antibody for Cyclin D1. The assessment of immunoreactivity of Cyclin D1 of each section was done using the Gleason scoring system. RESULTS: A total of 153 males' prostate sections included in this study, of them, 120 (78.4%) were PC, and 33 (21.6%) were BPH. Their age ranged from 45 to 88 years, mean age was 66.19 ± 8.599. 142 (92.8%) did not have a family history of PC, while 11 (7.2%) patients reported having a family history. The Gleason scoring showed a total of 81 (52.9%) patients with high-grade and 39 (25.5%) with low-grade. 118 (97.5%) patients had PC showed positive results for Cyclin D1, while BPH was 3 (2.5%). P value < 0.001. Cyclin D1 staining was associated with high-grade Gleason score and perineural invasion, P value 0.001.

Prevalence and risk factors profile of seropositive Toxoplasmosis gondii infection among apparently immunocompetent Sudanese women.

OBJECTIVES: Toxoplasma gondii is an opportunistic parasite that causes a clinical manifestation known as toxoplasmosis. We investigated the prevalence and potential risk factors of T. gondii infection among women in Khartoum, Sudan. A sero-parasitological cross-sectional study included 100 women aging between 15 and 50 years old was conducted between January and November 2018. Serum samples were collected and investigated for the presence of anti-T. gondii immunoglobulins. RESULTS: Mean age of the women population included was 26.75 ± 8.25 with a range between 15 and 50 years. Sero-prevalence of T. gondii antibodies was 27% (27/100) with a 95% confidence interval (CI) of 18.6-36.8%. Among seropositive population 81% (22/27), 15% (4/27) and 4% (1/27) were seropositive for IgG antibodies, IgM antibodies and both antibodies respectively. Age group 21-30 years old had the highest frequency of detected IgG (10/45) and IgM (3/45). Married women had the highest frequency of detected IgG or IgM, 18/79 and 3/79, respectively. Risk factors analysis showed a total of 37/100 participants were having direct contact with cats and 66/100 have a frequent raw meat consumption, neither direct cats contact nor raw meat consumption had a statistically significant association with seropositivity to T. gondii (P value = 0.052 and 0.565, respectively).

The Role of Interleukin-1 cytokine family (IL-1ß, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis.

Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1ß, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1ß and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1ß cytokine, where a unit increment in IL-1ß will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1ß and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.

Erratum to: Molecular Detection of Epstein - Barr virus in Nasopharyngeal Carcinoma among Sudanese population.

[This corrects the article DOI: 10.1186/s13027-016-0104-7.].

Molecular Detection of Epstein - Barr virus in Nasopharyngeal Carcinoma among Sudanese population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx that varies significantly from other cancers of the head and neck in its occurrence, causes, clinical behavior, and treatment. NPC caused by an interaction between infection with EBV and environmental and genetic factors, encompasses a multistep oncogenic process. The frequency of Epstein-Barr virus EBV among nasopharyngeal carcinoma is well known worldwide, however, in the Sudan there is barely a published data. The aim of this study was to detect Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC) biopsies obtained from Sudanese patients using Polymerase Chain reaction. METHODS: This is a descriptive, retrospective hospital based study, conducted at the National Center for ENT diseases and the Faculty of Medical Laboratory Science, University of Khartoum, Khartoum City, Sudan. Archival blocks were obtained from 82 patients diagnosed as having nasopharyngeal carcinoma were molecularly examined for the presence of Epstein-Barr virus. RESULTS: Eighty two Paraffin fixed tissue sections were examined for the presence of the virus using PCR, EBV was identified in 51/ 82 (62.2 %) samples and couldn't be identified in 31/ 82 (37.8 %) tissue samples. Out of the 51 infected samples, 33/51 (64.7 %) were found among males and 18/27 (66.7 %) were found among females. CONCLUSION: The present study is providing strong evidence supporting the general association of EBV infection in NPC among Sudanese patients.