Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

A case of Kawasaki Disease with concomitant leptospirosis

A 7-year-old Malay girl was admitted to our institution presenting with fever for 4 days that was persistently above 38°C, with a maximum temperature of 39.9°C. This was associated with a papular and pruritic rash over her chest and limbs for 4 days, as well as a tender right neck swelling for 3 days, diarrhea, and bitemporal headaches for 2 days. This was accompanied by early morning vomiting and nausea, but no blurring of vision or other neurological deficits. She also had red eyes and a dry cough that was not accompanied by coryzal symptoms for 1 day. She initially presented to a family physician and was given 3 days of oral azithromycin. However, her right neck swelling grew in size and redness over the last 2 days prior to admission. It was reported that she did not have contact with any sick persons. However, she had travelled to South India a month ago.Published versio

A Case of Kawasaki Disease With Concomitant Leptospirosis

A 7-year-old Malay girl was admitted to our institution presenting with fever for 4 days that was persistently above 38°C, with a maximum temperature of 39.9°C. This was associated with a papular and pruritic rash over her chest and limbs for 4 days, as well as a tender right neck swelling for 3 days, diarrhea, and bitemporal headaches for 2 days. This was accompanied by early morning vomiting and nausea, but no blurring of vision or other neurological deficits. She also had red eyes and a dry cough that was not accompanied by coryzal symptoms for 1 day. She initially presented to a family physician and was given 3 days of oral azithromycin. However, her right neck swelling grew in size and redness over the last 2 days prior to admission. It was reported that she did not have contact with any sick persons. However, she had travelled to South India a month ago.Published versio

Typhoid and Scrub Typhus Coinfection in a Returned Traveler

This is a case report of a 12-year-old returned traveler with typhoid and scrub typhus coinfection. The diagnosis of typhoid was made early with blood cultures and Widal Weil Felix serology. Persistent fever despite appropriate antibiotics for typhoid fever prompted a search for concomitant infection, which led to the diagnosis of scrub typhus confirmed by Orientia tsutsugamushi serology. The patient was given doxycycline with good clinical response. Scrub typhus infection should be an early consideration in the differential diagnoses of fever in a returned traveler from regions where it is endemic. Coinfections should be taken into consideration particularly when fever or symptoms persist despite adequate therapy for a previously identified microorganism

Osteomyelitis in Immunocompromised children and neonates, a case series

10.1186/s12887-021-03031-1BMC Pediatrics21156

Impact of a Carbapenem Antimicrobial Stewardship Program on Patient Outcomes

Antimicrobial stewardship programs (ASPs) aim to improve appropriate antimicrobial use. However, concerns of the negative consequences from accepting ASP interventions exist, particularly when deescalation or discontinuation of broad-spectrum antibiotics is recommended. Hence, we sought to evaluate the impact on clinical outcomes when ASP interventions for inappropriate carbapenem use were accepted or rejected by primary providers. We retrospectively reviewed all carbapenem prescriptions deemed inappropriate according to institutional guidelines with ASP interventions between July 2011 and December 2014. Intervention acceptance and outcomes, including carbapenem utilization, length of stay, hospitalization charges, 30-day readmission, and mortality rates were reviewed. Data were analyzed in two groups, one in which physicians accepted all interventions (“accepted”) and one in which interventions were rejected (“rejected”). A total of 158 ASP interventions were made. These included carbapenem discontinuation (35%), change to narrower-spectrum antibiotic (32%), dose optimization (17%), further investigations (including imaging and procalcitonin) (11%), infectious diseases referral (3%), antibiotic discontinuation (other than carbapenem) (1%), and source control (1%). Of 220 unique patients, carbapenem use was inappropriate in 101 (45.9%) patients. A significant reduction in carbapenem utilization was observed in the accepted group versus rejected group (median defined daily doses, 0.224 versus 0.668 per 1,000 patient-days, respectively; P < 0.001). There was a significant reduction in 30-day mortality in the accepted (none) versus rejected group (10 deaths, P = 0.015), but there were no differences in length of stay, hospitalization charge, or 30-day readmission rates. Hypotension was independently associated with mortality in multivariate analysis (odds ratio, 5.25; 95% confidence interval, 1.34 to 20.6). In our institution, acceptance of carbapenem ASP interventions did not compromise patient safety in terms of clinical outcomes while reducing consumption.Published versio

Salmonella renal abscess in an immunocompetent child: case report and literature review

We describe a case of a 10-year-old immunocompetent girl with a left renal abscess due to Group C Salmonella (Salmonella serovar Oranienburg). Percutaneous drainage of the abscess was done. She also received 2 weeks of intravenous ceftriaxone, followed by 4 weeks of oral co-trimoxazole with resolution seen on ultrasound. A review of pediatric Salmonella renal abscesses is also presented.Published versio

Cytokine and Chemokine Profiling in Patients with Hand, Foot and Mouth Disease in Singapore and Malaysia

10.1038/s41598-018-22379-6SCIENTIFIC REPORTS8

Serotype distribution and incidence of invasive early onset and late onset group B streptococcal disease amongst infants in Singapore

Background: The current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD. Methods: A retrospective study of infants ≤90-day-old over an 8-year period (2010–2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared. Results: A total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n=42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n=58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0–243.1, p=0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0–250.0, p=0.012). Prematurity and intra partum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD. Conclusions: The LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country.Published versio