Oral and Intravenous Amoxicillin Dosing Recommendations in Neonates: A Pooled Population Pharmacokinetic Study.

BACKGROUND: There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI. METHODS: In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used. RESULTS: The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9-42.4) and bodyweight of 2.6 kg (range, 0.5-5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks' gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration. CONCLUSIONS: This pooled population pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.

Probabilistic measures of HIV-1 transmission in different HIV-1 key population groups of Larkana, Pakistan.

OBJECTIVE: To estimate the probability of human immunodeficiency virus (HIV)-1 transmission from different key HIV population groups using probabilistic modelling. METHODS: This study was conducted in December 2020. A probabilistic model was used to estimate the probability of HIV-1 transmission from different key HIV population groups in Larkana. Our model was run on three probabilistic assumptions: 1) each replication gave two conceivable results: 'true' or 'false'; 2) the chance of giving a 'true' result is the same for each replication; and 3) the replications are independent - 'true' in one will not impact the likelihood of 'true' in another. RESULTS: The results estimated the probability of HIV transmission in key HIV population groups in Larkana to range between 0.42-0.54 per trial, where the highest probability of transmission was predicted for men who have sex with men (MSM; 0.54 per trial), followed by transgender (TG; 0.46 per trial) and people who inject drugs (PWID; 0.457 per trial). CONCLUSIONS: Our results suggest that there is a high likelihood of HIV transmission by key population groups in Larkana, such as MSM, TG, and PWID. Mathematic models, such as one proposed in our study can aid the HIV and acquired immunodeficiency syndrome (AIDS) control programmes in evaluating and optimising the strategies in controlling transmission of HIV from the key population groups.

Well-differentiated liposarcoma primary from thymic stroma: Case report and literature review.

Primary liposarcoma of thymic stroma is an exceptionally rare tumor. Histological findings are often definitive for diagnosis, however due to the variability of nuclear atypia and the overlapping with other adipocytic tumors, ancillary techniques are helpful as confirmatory tools. Currently, Fluorescent in situ hybridization for MDM2 is the gold standard for diagnosis of well-differentiated and dedifferentiated liposarcomas, however a panel of immunohistochemical stainings, including MDM2, CDK4 and p16 is available as alternative method, helping to distinguish liposarcoma from its benign counterpart lipoma, especially in borderline cases. We describe the case of a young female diagnosed with a well-differentiated lipomatous tumor primary of thymic stroma with near cut-off result for MDM2-FISHand positive immunohistochemical staining for the panel described above. We discuss the challenges in the diagnosis of this rare entity andpresent an updated literature review.

Non-human-papillomavirus-related malignancies of the vulva: A clinicopathological study.

BACKGROUND: Malignant tumor of the vulva is the fourth gynecological malignancy in frequency. Close to 70% of all vulvar malignancies are related to high-risk human papillomavirus (HPV) infection. METHODS: A search for non-HPV-related malignant tumors of the vulva was performed in the last 20 years (2000-2020) in the pathology database of a single tertiary institution. We aim to estimate the prevalence of non-HPV-related malignancies in our population, describe clinicopathological features of these tumors and investigate the expression of some potential therapeutic targets. RESULTS: A total of 71 patients were recovered; 26 patients (36%) had the diagnosis of extramammary Paget disease, 17 patients (24%) had basal cell carcinomas, 17 patients (24%) had primary melanomas, 10 patients (14%) had metastatic disease to the vulva and one patient (1%) had a primary dermatofibrosarcoma protuberans. Fifty-four percent of patients with extramammary Paget disease had a secondary malignancy and 12.5% had invasive disease. Programmed death-ligand 1 (PDL-1) was positive in seven out of nine primary melanomas and Her2/neu was overexpressed in six out of seven extramammary Paget disease. CONCLUSION: Non-HPV-related malignancies are important differential diagnoses in patient with vulvar lesions. Additional research is necessary to further understand these complex malignancies and potential new therapeutic targets.

Diagnostic methods to determine microbiology of postpartum endometritis in South Asia: laboratory methods protocol used in the Postpartum Sepsis Study: a prospective cohort study.

BACKGROUND: The South Asian region has the second highest risk of maternal death in the world. To prevent maternal deaths due to sepsis and to decrease the maternal mortality ratio as per the World Health Organization Millenium Development Goals, a better understanding of the etiology of endometritis and related sepsis is required. We describe microbiological laboratory methods used in the maternal Postpartum Sepsis Study, which was conducted in Bangladesh and Pakistan, two populous countries in South Asia. METHODS/DESIGN: Postpartum maternal fever in the community was evaluated by a physician and blood and urine were collected for routine analysis and culture. If endometritis was suspected, an endometrial brush sample was collected in the hospital for aerobic and anaerobic culture and molecular detection of bacterial etiologic agents (previously identified and/or plausible). DISCUSSION: The results emanating from this study will provide microbiologic evidence of the etiology and susceptibility pattern of agents recovered from patients with postpartum fever in South Asia, data critical for the development of evidence-based algorithms for management of postpartum fever in the region.

Utility and feasibility of integrating pulse oximetry into the routine assessment of young infants at primary care clinics in Karachi, Pakistan: a cross-sectional study.

BACKGROUND: Hypoxemia may occur in young infants with severe acute illnesses or congenital cardiac anomalies, but is not reliably detected on physical exam. Pulse oximetry (PO) can be used to detect hypoxemia, but its application in low-income countries has been limited, and its feasibility in the routine assessment of young infants (aged 0-59 days) has not been previously studied. The aim of this study was to characterize the operational feasibility and parent/guardian acceptability of incorporating PO into the routine clinical assessment of young infants in a primary care setting in a low-income country. METHODS: This was a cross-sectional study of 862 visits by 529 infants at two primary care clinics in Karachi, Pakistan (March to June, 2013). After clinical assessment, oxygen saturation (Sp02) was measured by a handheld PO device (Rad-5v, Masimo Corporation) according to a standardized protocol. Performance time (PT) was the time between sensor placement and attainment of an acceptable PO reading (i.e., stable SpO2 + 1% for at least 10 s, heart rate displayed, and adequate signal indicators). PT included the time for one repeat attempt at a different anatomical site if the first attempt did not yield an acceptable reading within 1 min. Parent/guardian acceptability of PO was based on a questionnaire and unprompted comments about the procedure. All infants underwent physician assessment. RESULTS: Acceptable PO readings were obtained in ≤ 1 and ≤ 5 min at 94.4% and 99.8% of visits, respectively (n = 862). Median PT was 42 s (interquartile range 37; 50). Parents/guardians overwhelmingly accepted PO (99.6% overall satisfaction, n = 528 first visits). Of 10 infants with at least one visit with Sp02 <92% on a first PO attempt, 3 did not have a significant acute illness on physician assessment. There were no PO-related adverse events. DISCUSSION: Using a commercially available handheld pulse oximeter, acceptable Sp02 measurements were obtained in nearly all infants in under 1 minute. The procedure was readily integrated into existing assessment pathways and parents/guardians had positive views of the technology. CONCLUSIONS: When incorporated into routine clinical assessment of young infants at primary care clinics in a low-income country, PO was feasible and acceptable to parents/guardians. Future research is needed to determine if the introduction of routine PO screening of young infants will improve outcomes in low-resource settings.

A rare case report: Left middle lobectomy in recurrent hemoptysis and chest infections of Kartagener syndrome patient.

INTRODUCTION: Kartagener syndrome is rare, with an incidence of 1 in 32,000 live births. It consists of a triad of bronchiectasis, situs inversus, and sinusitis. Normally, the middle lobe is part of the right lung, but due to situs inversus, the middle lobe is part of the left lung, making it prone to bronchiectasis and infections. CASE REPORT: We present a unique case of a 16-year-old adolescent with a known history of Kartagener syndrome who presented with recurrent chest infections and hemoptysis refractory to conservative management. He was diagnosed with bronchiectasis of the left middle lobe through a computed tomography (CT) scan and subsequently underwent a posterolateral thoracotomy and left middle lobectomy. This is a rare finding with limited literature available on such cases, to the best of our knowledge. DISCUSSION: Conservative treatment is usually the first line of approach. However, in cases of recurrent chest infections and hemoptysis, surgical management is considered to prevent the infection from spreading to the healthy lung and to avoid life-threatening complications when medical therapy fails. Surgical intervention, while more invasive, can provide a definitive solution and improve the patient's quality of life. CONCLUSION: Early diagnosis of Kartagener syndrome is crucial for determining the appropriate management course. In patients presenting with recurrent hemoptysis and chest infections, surgical resection is an effective treatment approach to prevent complications and enhance long-term outcomes.

Longevity of serologic responses following a single dose of typhoid conjugate vaccine among children living with HIV in Pakistan: A prospective cohort study.

BACKGROUND: This study aimed to assess the longevity of serologic response and seroconversion rates at several time points following TCV vaccination among children living with HIV aged 6 months to 15 years in Pakistan. METHODS: From November 20, 2020, to January 2, 2021; 336 children were enrolled and followed up prospectively for 12 months. Blood samples were collected before the administration of TCV and at 4-6 weeks, 6 months, and 1 year after administration of a single dose (0.5 ml) of intramuscular Typbar TCV®. Samples were analyzed for anti-Vi-IgG antibodies using ELISA. Geometric mean titers (GMTs), seroconversion rates (fourfold rise in anti-Vi-IgG from baseline), and factors associated with sustained seroconversion at 1 year were evaluated using generalized linear mixed models. FINDINGS: The seroconversion rates were significantly lower in children aged 6 months to 5 years compared to children > 5 years; (127/216 (58·8%)) versus (81/111 (73·0%)) at 6 months and (110/217 (50·7%)) versus (78/109 (71·6%)) at 1 year, only two-third; 188/326 (57·7%) remained seroconverted at 1 year. The GMTs (95 % CI) were significantly lower in children aged 6 months to 5 years compared to children > 5 years, 9·6 (7·6, 12·0) versus 28·9 (20·2, 41·4) at 6 months, and 6·6 (5·4, 8·0) versus 23·1 (16·4, 32·5) at 1 year time point. The odds of sustained seroconversion significantly decreased with time (adjusted odds ratio (aOR): 0·232; 95 % CI: 0·136,0·396). The odds of sustained seroconversion following 1 year of TCV vaccination were significantly higher among children with non-severe HIV clinical disease (aOR: 10·6; 95 % CI: 1·5, 73·9) and children in elder age group (aOR: 7·45; 95 % CI: 11·2, 47·0). CONCLUSIONS: There was a decline in seroconversion after one year of TCV in children living with HIV. The decline was significant in children with severe or advanced HIV disease. A significant decrease in seroconversion rates was observed among children living with HIV following one year of TCV administration.

Madurella mycetomatis as an agent of brain abscess: case report and review of literature.

Fungal cerebral abscesses are rare and usually seen in immunocompromised individuals. We report a case and review published literature of Madurella mycetomatis as an agent of cerebral abscess. We found contiguous head and neck infections to be the principal cause of cerebral maduromycosis caused by M. mycetomatis. Early recognition of Madurella spp. as the causative agent is essential to avoid cerebral spread.

Community-based management and outcome of omphalitis in newborns in Karachi, Pakistan.

OBJECTIVES: To describe the clinical profile and outcome in newborns with omphalitis managed with home or clinic-based therapy. METHODS: The descriptive study was conducted from September 2004 to August 2007 in three low-income communities in Karachi, Pakistan. Newborns with omphalitis detected by community health workers through active surveillance were referred to local clinics. Those with physician-confirmed omphalitis were treated for 7 days with topical gentian violet or oral cephalexin (as monotherapy) or topical gentian violet and oral cephalexin (combination therapy) at physician discretion, or injectable therapy (procaine penicillin and gentamicin) if clinical signs of sepsis were also present and family refused hospital referral. Follow-up was at 48-72 hours and 7 days. SPSS 16 was used for statistical analysis. RESULTS: Among 1083 newborns with omphalitis, 578 (53.4%) had peri-umbilical cellulitis without purulent discharge; 365 (33.7%) had purulent discharge (with or without cellulitis); and 140 (13%) had omphalitis with sepsis Review of outcome data at one week showed that among 943 newborns without signs of sepsis, 938 (99.5%) had improved; 2 (0.2%) died, and 2 (0.2%) were lost to follow-up. There were 5 (3.6%) therapy failures, among 140 newborns with omphalitis and sepsis managed with parenteral antibiotics at 48 hours, but 139 (99.2%) had improved by one week, while 1 (0.8%) died. CONCLUSION: In resource-constrained environments, omphalitis can be managed in the community with minimal need for hospital referral. Further research to define optimal therapeutic regimens is needed.

Cumulative antimicrobial susceptibilities for respiratory clinical isolates of Mycobacterium avium Complex, Mycobacterium kansasii, and Mycobacterium abscessus from Pakistan 2018 to 2022.

Background: Nontuberculous mycobacteria (NTM) are increasingly identified as causes of protracted pulmonary infections. Antibiotic susceptibility testing requires microdilution methods, which are often unavailable in laboratories in resource-poor settings. We report cumulative antibiograms for the most frequently isolated clinical pulmonary NTM from Pakistan to inform empiric antibiotic management of initial NTM infections. Methods: We analyzed data from 2018 to 2022 for the most frequently isolated and clinically relevant NTM isolated from respiratory specimens, i.e., Mycobacterium avium complex (MAC), Mycobacterium abscessus group (MAG), and Mycobacterium kansasii (MK). Antibiograms were developed using the Clinical Laboratory Standards Institute's M39ED5 standard. Percentage susceptibilities and 95% confidence intervals (CI) were calculated. Results: Over 4 years, 529 NTM, comprising 209 MAC, 249 MAG, and 71 MK were analyzed. For MAC and MAG, where clarithromycin (CLR)-based regimens are recommended, CLR was active for 94.8% (95% CI 91.3-96.9), and 77.5% (95% CI 71.4-82.7) isolates, respectively. Combination regimens comprising 3 active drugs CLR + linezolid (LZD) + moxifloxacin for MAC and CLR + LZD + Amikacin for MAG had 98.4% (95% CI 95.9-99.4) and 68.9% (95% CI 62.3-74.8) coverage for pulmonary disease, respectively. For MK, 91.5% (95% CI 82.8-96.1) isolates were susceptible to rifampin (RIF), with a combination of RIF + CLR covering 88.7% (95% CI 79.3-94.2) of MK pulmonary infections, respectively. Conclusions: These data can inform empiric treatment guidance for the most common NTM pulmonary infections, i.e., for MAC, MAG, and MK disease in Pakistan.

Etiology of Acute Infectious Meningitis and Meningoencephalitis in Karachi, Pakistan: Retrospective Observational Study from a Tertiary Care Center.

Meningoencephalitis (ME) is potentially fatal and is caused by a wide array of pathogens. Diagnostic and health-care access gaps prevent accurate estimation of the pathogen-specific burden in low-resource settings. We present pathogen-specific etiologies among patients hospitalized with ME in Karachi, Pakistan. We performed a retrospective hospital database evaluation of pathogen etiology and outcomes of community-acquired infectious ME at a single tertiary care center in Karachi, Pakistan. Annual rates of hospitalization (ARH) were calculated by adjusting for missed cases and are reported per 100,000 population. From May 2017 to April 2020, 522 episodes of infectious ME were identified in 514 patients. The overall ARH from ME was 5.7/100,000 population (95% CI, 5.1-6.1). Among children younger than 5 years, the ARH was 9.8/100,000 population (95% CI, 8.1-11.8). Unknown causes of ME resulted in the greatest burden, with an ARH of 1.9/100,000 population (95% CI, 1.7-2.2). Among known causes, the greatest burden of hospitalizations resulted from tuberculous ME (0.8/100,000; 95% CI, 0.6-0.97), followed by pneumococcal and enteroviral ME (both 0.6/100,000 population; 95% CI, 0.5-0.8). The burden of ME caused by pathogens preventable through vaccination or public health measures outweighed that of ME from other causes (P = 0.0092, Fisher's exact test). We report a broad range of pathogens causing ME in southern Pakistan and show a high burden of preventable illness. Synergistic actions to improve diagnostic strategies, increase vaccinations, and introduce measures to reduce water-borne and vector-borne diseases are required to reduce the ME burden in Pakistan and prevent future outbreaks.

Malignant effusions secondary to metastatic thyroid carcinomas: A review of 15 cases.

BACKGROUND: Malignant effusions secondary to thyroid carcinomas are rare, and publications on this topic are limited. This study presents a large cohort of thyroid carcinomas involving effusion cytology. METHODS: A 20-year computerized search for fluid cytology diagnosed with thyroid malignancy was performed. The following data were collected: patients' demographics, clinical findings, and histologic diagnoses. The cytology slides and ancillary tests were reviewed. RESULTS: Among 47,593 specimens, 15 thyroid carcinomas involving the pleural fluid from 11 patients were found. There were six males and five females with a mean age of 72 years. Ten patients with available follow-up died of their disease. Papillary thyroid carcinoma (PTC) was the only histologic type. Ten cytology cases were available for review. The cytologic findings common to all cases were nonspecific (clusters/three-dimensional architecture, enlarged irregular nuclei, and scant to abundant to vacuolated cytoplasm). The classic PTC features were not present in all cases (fine/powdery chromatin [80%], micronucleoli [70%], nuclear grooves [50%], papillary-like architecture [40%], psammoma bodies [40%], and pseudo-nuclear inclusions [20%; present on the cell block only]). In 11 of the 15 cases, the diagnosis was rendered with immunohistochemical stains performed on the cell block (paired box 8, thyroid transcription factor 1, and thyroglobulin). In four of the 15 cases, the cytologic diagnosis was made after a comparison with prior surgical pathology or fluid cytology. CONCLUSIONS: PTC is the most common histologic type of thyroid malignancy involving pleural effusion. Because the cytologic findings are nonspecific and classic PTC features are not always present, the clinical history in conjunction with immunohistochemical stains is helpful in arriving at the correct diagnosis.

Characterization of HIV-1 CRF02_AG/A3/G unique recombinant forms identified among children in Larkana, Pakistan.

Co-circulation of different human immunodeficiency virus type 1 HIV-1 subtypes among infected populations can lead to the generation of new recombinants. In Pakistan, subtype A1 and CRF02_AG are the dominant strains circulating among key populations. The high prevalence of new HIV infections among the key populations highlights the possibility of recombination between the dominant strains, which can lead to the generation of new recombinants. Here, we identified a recombinant cluster composed of CRF02_AG, sub-subtype A3, and subtype G among HIV-infected children in Larkana. For the study, 10 retrospectively collected samples, with recombination signals in the pol gene, were used to perform a near full-length genome NFLG sequencing. Of the 10 samples, NFLG was successfully sequenced from seven samples. Phylogenetic analysis of the seven NFLGs showed that all recombinants formed a distinct monophyletic cluster and were distinct from known HIV-1 circulating recombinant forms CRFs. Recombination analyses showed that all seven NFLGs shared a similar recombinant structure consisting of CRF02_AG, sub-subtype A3, and subtype G, with a sub-subtype A3 fragment inserted into pol and vif regions spanning from (HXB2: 4218-5518), and a subtype G fragment inserted into vpu, rev, tat and env regions spanning from (HXB2: 5957-8250) of the CRF02_AG backbone. The identification of unique recombinant forms may indicate the presence and transmission of several co-circulating lineages in Larkana, giving rise to newer CRFs. This study also highlights the importance of continuous molecular surveillance to fully understand HIV-1 genetic diversity in Pakistan, particularly in Larkana, which is the epicenter of HIV outbreaks.

Phenotypic Spectrum of STXBP1 Gene Mutations in an Emirati Case Series.

Genetic mutations are increasingly recognized as etiologic factors for epilepsy and neurodevelopmental disorders. Loss of function mutations in STXBP1, one of such genes, has, in recent years, been demonstrated to cause a broad spectrum of epilepsy syndromes and chronic neurodisabilities. Syntaxin-binding protein 1 (STXBP1) is a well-recognized membrane trafficking protein responsible for synaptic transmission and is expressed ubiquitously across the brain. Our case series presents the neurodevelopmental phenotype of children with STXBP1 mutations and is the first to be reported in an Emirati patient cohort. We gathered data on five children with genetically confirmed STXBP1 mutations, each displaying varying symptomatology, EEG features, response to antiepileptic medications, and eventual disease progression. This report reveals that a majority of STXBP1 mutations were de-novo in origin; heterozygous; pathogenic to likely pathogenic variants; clinical disease onset was predominantly during infancy in the form of developmental delays with or without seizures; most of the children had co-existing ADHD or autism spectrum disorders; typical seizure semiology at onset was in the form of infantile spasms, progressing to a melange of mixed seizure types; seizure control on antiepileptic drug therapy was variable, with all cases requiring more than two medications; global developmental delay was noted in all studied children; and MRI brain findings were unremarkable in all cases. This case series demonstrates a degree of uniformity of STXBP1 mutation disease phenotypes with international literature and provides a unique insight into the genetic profile of affected children within the Emirati population.

Risk factors for acute diarrhoea in children between 0 and 23 months of age in a peri-urban district of Pakistan: a matched case-control study.

BACKGROUND: Diarrhoea is a leading cause of preventable childhood morbidity and mortality worldwide. Unfortunately, Pakistan has the third-highest burden of diarrhoea-related deaths in children <5 y of age. Therefore we aimed to evaluate factors associated with diarrhoea among Pakistani children. METHODS: A retrospective 1:2 matched case-control study nested in a baseline cross-sectional survey was conducted from October to December 2018 in Taluka Kotri, a two-thirds urban locality in the Jamshoro district. Children between the ages of 0 and 23 months with a history of diarrhoea in the 2 weeks preceding the survey were labelled as cases. Age-matched controls were children without symptoms of diarrhoea. Univariate and multivariable conditional logistic regression was performed to identify diarrhoea-related factors. RESULTS: A total of 1558 cases were matched with 3116 controls. Factors significantly associated with lower odds of diarrhoea in the multivariate analysis included increasing maternal age (odds ratio [OR] 0.78 [95% confidence interval {CI} 0.67 to 0.90]), breastfeeding (OR 0.77 [95% CI 0.66 to 0.90]), higher paternal education (OR 0.79 [95% CI 0.65 to 0.97]) and belonging to the rich (OR 0.66 [95% CI 0.54 to 0.80]) and richest quintiles (OR 0.54 [95% CI 0.44 to 0.66]). CONCLUSIONS: This study identifies risk factors associated with diarrhoea in children <23 months of age, including younger maternal age, higher paternal education, not breastfeeding and poverty, which has implications for developing preventive programs and strategies that target populations with a higher risk of diarrhoea.

Genetic and antiretroviral drug resistance mutations analysis of reverse transcriptase and protease gene from Pakistani people living with HIV-1.

BACKGROUND: Antiretroviral therapy (ART) effectiveness is compromised by the emergence of HIV drug resistance mutations (DRM) and can lead to the failure of ART. Apart from intrinsic viral factors, non-compliance with drugs and/or the use of sub-optimum therapy can lead to the emergence of DRMs. In Pakistan HIV currently exists as a concentrated epidemic, however, ART coverage is very low, and drug adherence is poor. ART is selected assuming without baseline genotyping. Pakistan has recently seen a rise in treatment failures, but the country's actual burden of DRM is still unknown. In this study, we perform the genetic and drug resistance analysis of the pol gene from Pakistani HIV-positive ART-naïve and ART-experienced individuals. METHODS: In this study, HIV-1 pol was sequenced from 146 HIV-1 positive individuals, divided into ART-naïve (n = 37) and ART-experienced (n = 109). The sequences were also used to determine HIV-1 subtypes, the prevalence of DRM, and pol genetic variability. RESULTS: DRM analysis identified numerous DRMs against reverse transcriptase inhibitors in both ART-naïve and ART-experienced groups, including a few that are classified as rare. Additionally, the ART-experienced group showed mutations associated with resistance to protease inhibitors. Genetic analysis showed negative selection pressure in both groups, but a higher rate of evolution in the ART-naïve group. CONCLUSION: High prevalence of DRMs, especially against previous first-line treatment in ART- naïve and the accumulation of DRMs in ART-experienced groups is concerning and warrants that a more extensive DRM survey be carried out to inform first-line and second-line ART regimen recommendations.

Updates in Pediatric Tuberculosis in International Settings.

Childhood tuberculosis (TB) has been underreported and underrepresented in TB statistics across the globe. Contributing factors include health system barriers, diagnostic barriers, and community barriers leading to an underdetected epidemic of childhood tuberculosis. Despite considerable progress in childhood TB management, there is a concerning gap in policy and practice in high-burden countries leading to missed opportunities for active case detection, early diagnosis and treatment of TB exposure, and infection and disease in children regardless of human immunodeficiency virus status. Bridging this gap requires multisectoral coordination and political commitment along with an eye to research and innovation with potential to scale.

A Clinical Profile of Pediatric COVID-19 Testing in the Emergency Department, Dubai, United Arab Emirates.

Background: The COVID-19 pandemic marked a health and economic crisis of massive proportions. In its early months, literature was centered on adult medical and critical care. As time progressed, international reports of COVID-19 infection in children steadily grew; however, data on disease features in the United Arab Emirates' pediatric population was noticeably lagging. Method: The presented research was conducted at Latifa Women and Children Hospital Emergency Department to ascertain an association between a child's presenting features and basic investigations to a subsequent positive COVID-19 test result. Data was collected via electronic medical records and statistical analysis performed with SPSS version 22.0. Results: A total of four hundred and five (405) patients were analyzed, with 32 (8%) being COVID-19 positive on initial testing in emergency department. There is a statistically significant correlation (p < 0.05) between testing positive for COVID-19 infection and history of exposure to COVID-19-positive individuals; the presence of runny nose, cough, poor feeding, and abdominal pain with reassuring physical examination findings; and predominantly normal reports of basic blood investigations and chest X-ray images. Conclusion: This research demonstrates that a minority of children tested for COVID-19 in the initial wave of the pandemic tested positive. A significant proportion of COVID-19-positive pediatric patients exhibit history of exposure to COVID-19-positive individuals; the presence of runny nose, cough, poor feeding, and abdominal pain; normal physical examination; normal basic blood investigations and chest X-ray findings.