Frequency of Severe Asthma and Its Clinical Phenotypes at the Asthma Clinic in One of the Largest Sudanese Tertiary Pediatric Hospitals: A Cross-Sectional Hospital-Outpatient-Based Study.

Background: Asthma is one of the most common non-communicable diseases. Childhood asthma has been increasing in Sudan, with a 13-16% prevalence among Khartoum school children. To achieve and maintain good asthma control, proper diagnosis, assessment of severity, and appropriate medication administration are crucial, with phenotyping being a key factor in determining patients' specific treatment. Objective: To study the frequency of severe asthma and the distribution of its different phenotypes and to investigate associations between age and gender and different phenotypes of asthma. Methodology: This descriptive cross-sectional hospital-based study was conducted in the Asthma Clinic of Mohamed Al-Amin Hamid Pediatrics Hospital. It included 229 patients who were presented to the clinic from September 2021 to April 2022. Data were collected from the patients and/or their caregivers using a modified validated standard questionnaire and were analyzed using SPSS version 26.0. A p-value of 0.05 or less was considered statistically significant. Results: In this study of 229 participants, 14.4% had severe asthma, with 44.5% and 41% exhibiting mild and moderate asthma, respectively. Most were effectively managed in steps 2 or 3. The cohort, primarily aged 5 or younger (40.2%) with a male majority (62%), showed a mean diagnosis age of 2.9 ± 2.8 years. Impressively, 90% maintained well-controlled asthma. Within severe asthma cases (87% atopic), 39.4% represented a severe allergic asthma phenotype. Elevated eosinophil counts were noted in 45.5% (serum) and 78.8% (sputum cytology), while 57.6% had normal serum IgE levels. The predominant symptom pattern in severe asthma was episodic multi-trigger wheezing (48.5%). Age and gender displayed no significant association with severe asthma phenotype. Conclusion: This study reveals a concerning rise in childhood asthma prevalence in Sudan, emphasizing the importance of tailored treatment strategies. Severe asthma, characterized by atopic eosinophilic involvement, necessitates targeted interventions in pediatric asthma care for specific phenotypes.

Rare Biallelic Variants Affecting the Interdomain B Region of Zeta-Chain Associated Protein Kinase 70 (ZAP70) Protein in a Sudanese Patient: Case Report.

Introduction: A class of disorders known as inborn errors of immunity (IEI) is defined by a compromised or missing immune response, which increases the vulnerability to infections, immunological dysregulation, and cancer. Severe combined immunodeficiencies (SCIDs), affecting both T and B-cell function are rare but often severe diseases. In this report, we describe a 10-month-old SCID patient from Sudan with disseminated BCG infection. Case Presentation: A 10-month-old boy whose parents were first degree relatives, presented with a six-month history of repeated chest infections and fever. Physical examination revealed a very ill-looking boy with respiratory distress dependent on oxygen, had slight abdominal distention and hepatomegaly. Investigations revealed positive polymerase chain reaction (PCR) for M. tuberculosis complex infection and low CD4+ and CD8+ cells. Genetic testing showed compound heterozygosity in trans for two variants in the Zeta-chain Associated Protein Kinase 70 (ZAP70) gene associated with autosomal recessive SCID. The patient was started on BCG-related infection treatment, intravenous immunoglobulin (IVIG) replacement and trimethoprim/sulfamethoxazole prophylaxis with an excellent response and the patient responded well to the treatment. Conclusion: SCIDs are rare, and early management is crucial. In this case, a diagnosis of ZAP70 deficiency was based on next-generation sequencing and inhouse bioinformatic computational analysis of the ZAP70 gene, highlighting the importance of genetic testing in the workup of immunodeficiencies in low resource settings.

Assessment of the Implementation of Global Initiative for Asthma (GINA) 2019 Guidelines for Treatment of Mild Asthma Among Pediatric Registrars: A Quasi-Interventional Study.

Background and Aims: It is essential to have proper treatment and management for asthma in order to minimise symptoms, lessen the burden, and lower the chance of exacerbations. To better control asthma, the purpose of this study was to evaluate and enhance paediatric registrars' understanding and application of asthma treatment. Methods: The Sudan Medical Specialisation Board (SMSB) paediatric registrars provided data for this quasi-interventional study between April and September of 2021. Twice, both before to and following the intervention education sessions, the questionnaire was delivered. SPSS version 28 was used to analyse the data after it had been cleaned up in an Excel document. Results: 203 (or 77.8%) of the 261 were women. A substantial rise from 8.1 ± 4.12 SD to 18 ± 5.03 SD in the mean overall knowledge score of registrars between the pre-and post-intervention periods. A significant difference (p=0.001) was observed in the post-intervention phase, with first-year registrars (R1) demonstrating higher scores than their senior colleagues. The registrars' total knowledge scores did not differ significantly from one another during the pre-intervention period. The Global Initiative of Asthma (GINA) guidelines of management were implemented to a certain extent, according to the study. Of the registrars, 148 (56.7%) and 203 (77.8%) evaluated step one management in children ages 5 and under; 66 (25.3%) and 213 (81.6%) evaluated step one management in children ages 6 to 11; and 66 (25.3%) and 213 (81.6%) evaluated step one management in children ages 6 to 11 in pre- and post-intervention, respectively. Conclusion: Given that the intervention in this study greatly increased registrars' knowledge, doctors should obtain training on the GINA 2019 recommendations through conferences, workshops, and academic programmes. To find out why R1 outperforms their older counterparts, more investigation has to be done.

Clinical spectrum of childhood tuberculosis and outcome at Mohammed Alamin Hamid Pediatric Hospital, Omdurman, Sudan.

The World Health Organization report in 2018 estimated 234,000 deaths due to tuberculosis (TB) in children less than 15 years; 40,000 of them occurring in human immunodeficiency virus (HIV) infected children. These deaths represent 15% of all TB deaths. This study aimed to determine the clinical spectrum and outcome of childhood TB at Mohamed Alamin Hamid Pediatric Hospital TB management unit. Retrospective observational hospital-based study was conducted during January 2017-December 2018, in children aged 0-18 years who were diagnosed with TB. A total of 174 patients were enrolled in this study. The majority of patients' ages ranged from 5 to 17 years (111, 63.8%). Most of the patients were males (92, 52.9%) and (142, 81.6%) resided in Khartoum State. Lung opacity and hailer parenchymal shadows were the common presenting features (83, 47.7%) in chest X-ray. Sputum for acid fast bacilli was positive in only 20 (11.5%) patients. Testing for HIV was negative in 41 (23.6%) patients and was not done in 133 (76.4%). A total of 107 (61.5%) children were diagnosed as having pulmonary TB; extra pulmonary tuberculosis (EPTB) was 67 (38.5%). Tuberculous lymphadenitis was the commonest type of EPTB and was diagnosed in 38 (56.7%) patients. The majority 94 (87.9%) completed their treatment and 13 (12.1%) with smear positive results were cured. Defaulters were 20 (11.5%), and 6 patients (3.4%) were retreated after default, 11 (6.3%) were transferred out, and 14 (8%) are still on treatment. Thirteen patients (7.5%) died, and the outcome of three patients was not documented.

Risk Factors of Inpatients Mortality of Visceral Leishmaniasis, Khartoum State, Sudan.

BACKGROUND: Visceral leishmaniasis (VL) is one of the common infections in Sudan and can be associated with an increase in morbidity and mortality. The aim of this study was to assess the risk factors associated with mortality and morbidity with VL. MATERIALS AND METHODS: This is a cross-sectional hospital-based study that recruited 150 patients with VL from two centers in Khartoum. Secondary data were extracted from the patient records, and data were analyzed using SPSS version 24.0. RESULTS: The study included 2.5% of infants, 39.4% children, and 58% of adults. Male represents 77.3% of the cohort, and total mortality was 16%. Among the death reported 12.5% in infants, 16.7% were children, and 70.8% were in adults. Laboratory parameters significantly associated with mortality in univariate analysis were low white cell count, low platelets, high creatinine, and high liver enzymes. While risk factors such as infant, male, acquired infection from Eastern Sudan or White Nile, weight loss, morbid diseases, and concomitant bacterial infections were also associated with significant mortality in univariate analysis. Importantly, logistic regression analysis revealed significant association with infant (P = 0.02), concomitant bacterial infections (P = 0.003), comorbid disease (P = 0.001), low total blood cell count (P = 0.018), low platelets (P = 0.013), and high aspartate transaminase/alanine aminotransferase (P = 0.013). CONCLUSION: Health education and awareness are needed in terms of prevention and control, especially with high mortality seen in the infant. Treatment of underlying co-morbid diseases and bacterial infections are important to enhance survival. Patients with Leishmania are vulnerable; therefore, regular routine blood tests are an essential part of management to manage complications such as renal, hepatic failure, or severe anemia.

Quantitative analysis of hydrogen and chalcogen bonds in two pyrimidine-5-carbonitrile derivatives, potential DHFR inhibitors: an integrated crystallographic and theoretical study.

Two potential bioactive pyrimidine-5-carbonitrile derivatives have been synthesized and characterized by spectroscopic techniques (1H and 13C-NMR) and the three dimensional structures were elucidated by single crystal X-ray diffraction at low temperature (160 K). In both structures, the molecular conformation is locked by an intramolecular C-H⋯C interaction involving the cyano and CH of the thiophene and phenyl rings. The intermolecular interactions were analyzed in a qualitative manner based on the Hirshfeld surface and 2D-fingerprint plots. The results suggest that the phenyl and thiophene moieties have an effect on the crystal packing. For instance, the chalcogen bonds are only preferred in the thiophene derivative. However, both structures uses a common N-H⋯O hydrogen bond motif. Moreover, the structures of 1 and 2 display 1D isostructurality and molecular chains stabilize by intermolecular N-H⋯O and N-H⋯N hydrogen bonds. The nature and extent of different non-covalent interactions were further characterized by the topological parameters derived from the quantum theory of atoms-in-molecules approach. This analysis indicates that apart from N-H⋯O hydrogen bonds, other non-covalent interactions are closed-shell in nature. A strong and linear N-H⋯O hydrogen bond shows intermediate bonding character between shared and closed-shell interactions. The molecular docking analysis suggests that both compounds display potential inhibitory effect against the dihydrofolate reductase (DHFR) enzyme from humans and Staphylococcus aureus.

Adult female with symptomatic AVPR2-related nephrogenic syndrome of inappropriate antidiuresis (NSIAD).

Activating mutations in AVPR2 are associated with nephrogenic syndrome of inappropriate antidiuresis (NSIAD). NSIAD causes hyponatremia, decreased serum osmolality and clinical symptoms, which may present from birth or in infancy and include hypotonia, irritability, vomiting and/or seizures. Symptoms in later life are often less specific and include malaise, dizziness, confusion, tiredness and headache. NSIAD is a rare X-linked condition, which is associated with a variable phenotype in males, of whom some present in infancy but others do not become symptomatic until adulthood, or occasionally, never. Female carriers may present with episodes of hyponatremia, usually found incidentally. Literature in this field is limited; namely, two clinical reports describing a female proband, both diagnosed in infancy. We describe, for the first time, the case of an adult female proband with NSIAD, who had longstanding associated symptoms of tiredness, headache, temporary memory loss and mood changes as well as hyponatremia and decreased serum osmolality. A water load test demonstrated an inability to dilute urine and gene sequencing confirmed a recurrent activating mutation in AVPR2. The variant was inherited from the proband's mother who had had longstanding episodes of transient asymptomatic hyponatremia. This is the third report of a female proband with NSIAD and is the first female reported who sought medical treatment for chronic symptoms from adulthood. This case acts as a reminder of the importance of considering NSIAD as a diagnosis in females of all ages with unexplained hyponatremia. LEARNING POINTS: Activating mutations in the AVPR2 gene are associated with the rare X-linked condition nephrogenic syndrome of inappropriate antidiuresis.NSIAD is associated with hyponatremia, decreased serum osmolality and inappropriately increased urinary osmolality. Early clinical symptoms in infancy include hypotonia, irritability, vomiting and/or seizures. Symptoms in later life include malaise, dizziness, confusion, tiredness and headache.NSIAD should be considered in female, as well as male, patients who present with unexplained hyponatremia and decreased serum osmolality. Family history may reveal relevant symptoms or biochemical features in other family members. However, family history may not always be informative due to the variable nature of the condition or if the proband has a de novo pathogenic variant.A water load test with measurement of AVP may be informative in distinguishing NSIAD from SIADH. Measurement of co-peptin levels may be considered, in substitution for direct measurement of AVP.Patients with NSIAD should be counseled about appropriate daily fluid volume intake. Potential episodes of fluid overload should be avoided.