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NPJ Vaccines Jun 2024Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes...
Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.
PubMed: 38858423
DOI: 10.1038/s41541-024-00890-4 -
Journal of Medical Cases Jun 2024Eosinophilic enteritis (EoN) poses a distinctive challenge, affecting individuals with various clinical presentations depending on the layer and extent of the bowel...
Eosinophilic enteritis (EoN) poses a distinctive challenge, affecting individuals with various clinical presentations depending on the layer and extent of the bowel wall. We present a case of a 19-year-old female with abdominal pain, vomiting, and loose stools for 1 month. Labs were significant for persistent leukocytosis with peripheral eosinophilia. A computed tomography of the abdomen/pelvis demonstrated moderate abdominal ascites and moderately diffuse mucosal thickening of jejunal loops. A diagnostic paracentesis unveiled low serum ascites albumin gradient and 92% eosinophils. Push enteroscopy resulted in no significant biopsy findings, though a laparoscopic full-thickness jejunal biopsy exhibited increased eosinophils in the bowel wall. Intravenous steroid, proton pump inhibitor, and dietary changes resolved the symptoms and normalized the labs within a week. Our case report highlights a variable presentation of eosinophilic jejunitis uncommon in this disease population. EoN is an easily missed diagnosis and mandates frequent follow-up to prompt relevant investigations. Atopic clinical features are not prevalent in each case. While rare, EoN requires a strong clinical suspicion, even if endoscopic biopsies are unremarkable, prompting timely laparoscopic full-thickness biopsy. Per protocol, physicians must do the infectious and eosinophilia workup to rule out other etiologies. Our case also highlights that worsening clinical condition in EoN warrants early intravenous steroids with a favorable prognosis and considers a psychosocial aspect of the disease on the patient's health.
PubMed: 38855296
DOI: 10.14740/jmc4196 -
Cureus May 2024subspecies () is a zoonotic pathogen that primarily infects horses, pigs, and dogs. Although rare, it has also been shown to infect humans who consume unpasteurized...
subspecies () is a zoonotic pathogen that primarily infects horses, pigs, and dogs. Although rare, it has also been shown to infect humans who consume unpasteurized dairy food or have direct contact with horses. Here, we present a case of bacteremia in a patient without a clear mode of transmission. An 86-year-old male with a past medical history of coronary artery disease, heart failure with reduced ejection fraction, complete heart block status post pacemaker, hypertension, hyperlipidemia, and type 2 diabetes mellitus presented to the Emergency Department with fever and chills. He had fevers and rigors for three days but denied weight loss, cough, sore throat, or rashes. In the Emergency Department, vital signs revealed a fever of 101.2 degrees Fahrenheit and a heart rate of 110 with other stable vital signs. The physical exam was unremarkable except for tachycardia, and laboratory work revealed no leukocytosis but elevated inflammatory markers and elevated lactate. Computed tomography of the chest, abdomen, and pelvis did not reveal any source of infection. Blood cultures grew and the Infectious Diseases team was consulted, who started the patient on Penicillin G. Due to concern for pacer-lead infective endocarditis, transthoracic and transesophageal echocardiograms were performed, which did not show valvular vegetations. Repeat blood cultures showed clearance of the infection, and the patient was ultimately discharged on amoxicillin. While our patient denied consuming unpasteurized dairy products or having direct contact with horses, upon further questioning, he did endorse family members who occasionally interacted with horses. This case is valuable as it adds to the sparse literature on infections specifically in humans. Extensive history taking is of utmost importance when a clear source of infection is not easily identifiable. Further research is also needed to better understand the various modes of transmission of this bacterium to better target and caution those at an increased risk of infection.
PubMed: 38854287
DOI: 10.7759/cureus.59911 -
Cureus May 2024Post-transplantation lymphoproliferative disorders (PTLD) are a commonly occurring condition following solid organ transplantation (SOT) and, rarely, hematopoietic stem...
Post-transplantation lymphoproliferative disorders (PTLD) are a commonly occurring condition following solid organ transplantation (SOT) and, rarely, hematopoietic stem cell transplantation (HSCT). As the name suggests, a PTLD is a condition where there is a clonal proliferation of lymphoid cells that occurs as a complication after transplantation. Though the clonal origin cell is primarily associated with the B-cell lineage, there are existing cases in the literature describing PTLD from the T-cell lineage. Large granulocytic leukemia (LGL) is one rare T-cell lineage subtype that typically progresses with a passive clinical course and is discovered with leukocytosis and peripheral blood smears demonstrating large granules in lymphocytes. In this study, we describe two patients initially diagnosed with acute myeloid leukemia (AML) who were both found to have T-cell PTLD after undergoing allogeneic hematopoietic stem cell transplant. One was found with a clonal expansion of T-cells on flow cytometry and the other with LGL on peripheral blood and flow cytometry. This discovery was made at 16 and 20 months after their transplant respectively. Distinguishing factors for these two patients are demonstrated by the derivation of lymphoproliferative disorder from graft vs. host disease (GVHD) or viral etiology, which is significant as both of which have been shown to be associated with PTLD. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) positivity have been shown to be associated with PTLD, and both our patients were EBV-negative but had harbored prior CMV infections. Additionally, they had a benign course with no development of cytopenias or symptoms since the time of diagnosis. These two cases add to the growing literature that is working to better characterize the rare development of LGL and, in general, T-cell PTLD following allogeneic bone marrow transplantation.
PubMed: 38854253
DOI: 10.7759/cureus.59901 -
Annals of Medicine Dec 2024Miliary Tuberculosis (TB) remains an important infectious disease that threatens human health. The clinical characteristics and prognostic factors of miliary TB are...
BACKGROUND
Miliary Tuberculosis (TB) remains an important infectious disease that threatens human health. The clinical characteristics and prognostic factors of miliary TB are summarized in this study.
METHODS
The clinical information of miliary TB patients between 2010 and 2022 was retrospectively analyzed. Patients with miliary TB were characterized and compared to adverse outcomes cases. Factors independently associated with adverse outcomes were determined via multivariate logistic regression analysis.
RESULTS
A total of 288 patients were analyzed, including 181 with adverse outcomes. The clinical manifestations are atypical. 88.54% Of them experienced systemic symptoms, whilst 69.79% manifested respiratory symptoms. 40.97% Presented with neurologic symptoms, while 35.07% reported gastrointestinal symptoms. The major comorbidities were pharmacological immunosuppression (21.53%), pneumoconiosis (15.28%), diabetes (10.76%), and pregnancy or postpartum (7.29%). Regarding microbiology, most patients were diagnosed via sputum or Bronchoalveolar Lavage Fluid (BALF), pleural effusion, ascites, cerebrospinal fluid, urine TB-DNA, and tuberculosis culture. Meanwhile, 2.43% of patients were diagnosed via cerebrospinal fluid NGS. Independent risk factors predictive of adverse outcomes were current smoking, leukocytosis, elevated alanine aminotransferase (ALT) levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis. The accuracy of the model was validated by an area under the ROC curve of 0.753 (95% IC 0.697-0.810).
CONCLUSIONS
The clinical manifestations of miliary TB are atypical, and early diagnosis is challenging. The major comorbidities in miliary TB patients were pharmacological immunosuppression, pneumoconiosis, diabetes, pregnancy, and postpartum. Regarding etiological detection, multi-site and multi-type specimens should be collected for a timely diagnosis. Cerebrospinal fluid mNGS test may be a viable choice in some cases. Finally, current smoking, leukocytosis, elevated ALT levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis were identified as independent risk factors for adverse outcomes.
Topics: Humans; Tuberculosis, Miliary; Female; Male; Middle Aged; Retrospective Studies; Prognosis; Adult; Risk Factors; Aged; Comorbidity; China; Young Adult
PubMed: 38848041
DOI: 10.1080/07853890.2024.2356647 -
Medecine Tropicale Et Sante... Mar 2024Although a protective effect of hemoglobin S has been described, malaria has frequently been associated with increased morbidity and mortality in sickle cell disease...
INTRODUCTION
Although a protective effect of hemoglobin S has been described, malaria has frequently been associated with increased morbidity and mortality in sickle cell disease patients in Africa. Various cytopenias are frequently found on the haemograms of these patients. In Benin, a malaria-endemic zone with a high prevalence of sickle cell disease, the aim of this study was to establish and compare the blood count profile according to hemoglobin type in the association of sickle cell disease and malaria.
MATERIAL AND METHOD
This was a prospective descriptive study. It covered a 24-month period from October 2020 to October 2022. It included all patients with major sickle cell syndrome seen in clinical haematology and with a positive thick drop/parasite density, whatever the parasitaemia value. For each patient, a blood count was performed on the Sysmex XT 4000i machine, supplemented by a smear study after staining with May-Grunwald Giemsa. Data were analyzed using R 3.6.1 software.
RESULTS
Three hundred non-redundant cases with a positive thick smear were identified in sickle cell patients, including 208 SS homozygotes (69.3%) and 92 SC heterozygotes (30.7%). In contrast, there were 181 non-redundant cases with a negative thick smear, including 119 SS homozygotes (65.7%) and 62 SC heterozygotes (34.3%). Among subjects with a positive thick smear, the majority of patients (70%) exhibited clinical symptoms. Severe malaria was observed in 58% of the cases. The proportion of severe malaria was higher in SS homozygote patients than in double heterozygote SC patients (p < 0.0001). The mean parasite density was higher in SS individuals (4 320.7 ± 2 185 trophozoites/pL) compared to SC individuals (1 564.4 ± 1 221 trophozoites/pL; p < 0.0001). was the only species identified. The mean hemoglobin level in impaludated SS subjects was 6.1 g/dL, significantly lower than that in non-impaludated SS subjects (p < 0.0001). The average white blood cell count in impaludated SS subjects was 16.58 G/L, compared to 13.2 G/L in those with a negative thick smear (p < 0.0001). Twenty cases of thrombocytopenia were found in SS subjects with a positive thick smear, compared to 6 cases in those with a negative thick smear. As for SC subjects with a positive thick smear, the average hemoglobin levels and white blood cell counts were 9.8 g/dL and 10.63 G/L, respectively, compared to 11.27 g/dL and 7.3 G/L in SC subjects with a negative thick smear. Eighteen cases of thrombocytopenia were found in subjects with a positive thick smear, compared to 17 cases in those with a negative thick smear.
DISCUSSION
Sickle cell disease and malaria represent two major public health problems. However, contrary to popular belief, sickle cell disease is not immune to malaria infestation. Malaria is recognized as one of the main causes of morbidity and mortality in sickle cell patients, particularly children. In Benin, its association with sickle cell emergencies has already been reported.Our study found that malaria was predominantly associated with the homozygous SS form (p < 0.00001). Severe malaria was the most common clinical form. All malaria infestations in our series were due to and parasitaemia was significantly higher in SS patients (p < 0.0001).The hematological profile of the association of sickle cell disease and malaria in homozygous SS individuals in our series showed characteristics of a normocytic normochromic anemia with neutrophil-predominant leukocytosis. Compared to non-malaria-infected SS individuals, there was a significant worsening of anemia, neutrophil-predominant leukocytosis, and a decrease in the average platelet count. In SC individuals, there was rather a microcytic normochromic regenerative anemia associated with neutrophil-predominant leukocytosis. Compared to non-malaria-infected SC individuals, there was a significant decrease in the rate of anemia and neutrophil-predominant leukocytosis. Anemia is a constant feature in homozygous sickle cell disease, and the low values recorded illustrate the hemolytic nature of malaria, especially in SS individuals, and the better tolerance of SC individuals. Furthermore, the low baseline hemoglobin levels make SS individuals more vulnerable to malaria-induced anemia compared to SC individuals. The observed leukocytosis is generally accompanied by reticulocytosis in the case of major sickle cell syndrome, which must be taken into account for result validation. It is the expression of compensatory bone marrow reaction to anemia and inflammatory mechanisms resulting from malaria infestation. Finally, thrombocytopenia was significantly more common in SC patients, even though they were adults living in malaria-endemic areas. Malaria can frequently induce thrombocytopenia through platelet consumption during the "rosetting" phenomenon. In SS patients, the effects of "rosetting" could be compensated for by the bone marrow stimulation induced by anemia. In our series with adult subjects living in an endemic area, thrombocytopenia is not a frequent biological disturbance. In a clinicalbiological context combining a systemic inflammatory response syndrome with anemia and neutrophil-predominant leukocytosis in a SS or SC sickle cell patient, the clinician should be able to consider malaria and confirm or rule out this diagnosis.
Topics: Humans; Anemia, Sickle Cell; Prospective Studies; Male; Female; Benin; Adult; Adolescent; Young Adult; Child; Malaria; Blood Cell Count; Middle Aged; Child, Preschool; Hemoglobin, Sickle
PubMed: 38846115
DOI: 10.48327/mtsi.v4i1.2024.404 -
International Journal of Surgery Case... Jul 2024Brucellosis is a zoonotic illness caused by Brucella bacteria, primarily transmitted through contaminated dairy products or direct contact with infected animals....
INTRODUCTION
Brucellosis is a zoonotic illness caused by Brucella bacteria, primarily transmitted through contaminated dairy products or direct contact with infected animals. Brucellosis is highly prevalent in Iran, with Brucella melitensis biovar 1 being the primary causative agent. Musculoskeletal symptoms, including spondylitis, sacroiliitis, and peripheral arthritis, are common in brucellosis patients, but avascular necrosis of the hip joint is extremely rare.
CASE PRESENTATION
This case report presents a middle-aged woman from Iran with untreated brucellosis infection, who developed rapidly progressing avascular necrosis affecting both hip joints. The patient's social history did not indicate any use of tobacco or alcohol. Furthermore, there was no indication of any traumatic events affecting the patient's hip joints. The patient's family history did not reveal any rheumatologic disorders, and the patient had not been diagnosed with or reported using immune suppressant medications. Laboratory results confirmed that the patient was not diagnosed with sickle cell anemia. The patient had been intolerant to the prescribed medications, Rifampin and Doxycycline. Initially, she presented with severe bilateral hip pain, anorexia, vomiting, periodic chills and fever, myalgia, and night sweats. Pelvis X-ray confirmed bilateral hip avascular necrosis, and total hip arthroplasty was scheduled but subsequently canceled due to persistent brucellosis infection. Physical examination revealed limited hip motion, pain, and inability to bear weight. Laboratory tests indicated leukocytosis, elevated levels of CRP, and high titers on Wright and 2ME tests. Intravenous Ciprofloxacin was initiated, and further investigations were scheduled.
DISCUSSION
Osteoarticular complications are common in individuals with brucellosis. The sacroiliac joints are affected in 80 % of cases, while the spinal joints are affected in 50 %. Brucella-induced arthritis can be found in over 50 % of patients, with the lower limb joints being the most commonly affected. Failure to diagnose and treat hip arthritis caused by brucellosis promptly can lead to severe complications, including dislocation and avascular necrosis of the femoral head. Avascular necrosis is a condition where bone tissue dies due to compromised blood supply. It often remains asymptomatic initially and is usually found incidentally during radiographic imaging. Osteonecrosis of the femoral head can manifest as Legg-Calve-Perthes disease or as a complication of other medical conditions. Various factors can contribute to avascular necrosis, including hip dislocation or fracture, prolonged use of certain medications, excessive alcohol consumption, and certain medical conditions. Magnetic resonance imaging is considered the standard method for diagnosing avascular necrosis. Delay in diagnosing and treating brucellosis can result in permanent bone complications.
CONCLUSION
Brucellosis, a disease prevalent in endemic regions, should be considered as a cause of severe hip pain and other vague symptoms. Timely diagnosis and management are important, especially for high-risk patients with other health conditions and poor drug compliance, to prevent complications such as avascular necrosis.
PubMed: 38843623
DOI: 10.1016/j.ijscr.2024.109808 -
Journal of Medical Case Reports Jun 2024Kikuchi Fujimoto disease is a rare self-limiting disorder mainly affecting young Asian females. The typical presentation is unexplained fever with associated cervical...
BACKGROUND
Kikuchi Fujimoto disease is a rare self-limiting disorder mainly affecting young Asian females. The typical presentation is unexplained fever with associated cervical lymphadenopathy. It can mimic many sinister diseases such as lymphoma, tuberculosis, and systemic lupus erythematosus. Aseptic meningitis due to Kikuchi disease is extremely rare, and majority were reported from Japan. There have been no published cases of aseptic meningitis due to Kikuchi disease in Sri Lanka.
CASE PRESENTATION
A 29 years old Sri Lankan female presented with a prolonged fever for three weeks with an associated headache for five days duration. She developed painful cervical lymphadenopathy during the hospital stay. She has been previously well and had been vaccinated against COVID-19 six weeks before. Her lumbar puncture showed lymphocytic pleocytosis with marginally elevated protein levels and reduced ratio of serum to CSF sugar. Lymph node biopsy was consistent with necrotizing lymphadenitis. She was subsequently diagnosed with Kikuchi disease complicated with aseptic meningitis. She responded to corticosteroids well and had an uneventful recovery.
CONCLUSION
Kikuchi disease is a rare self-limiting disorder that can be complicated with aseptic meningitis on infrequent occasions. Other conditions such as tuberculosis, lymphoma, systemic lupus erythematosus, and adult-onset Still's disease should be considered as differential diagnoses. Knowledge of Kikuchi disease and its complications will prevent unnecessary investigations which delay the early diagnosis and treatment.
Topics: Humans; Histiocytic Necrotizing Lymphadenitis; Female; Meningitis, Aseptic; Adult; COVID-19; COVID-19 Vaccines; Sri Lanka; SARS-CoV-2
PubMed: 38840233
DOI: 10.1186/s13256-024-04541-z -
Neuropsychopharmacology Reports Jun 2024Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with...
BACKGROUND
Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with adverse reactions to dopamine-blocking agents. This syndrome is normally characterized by features such as muscle rigidity, alteration in consciousness, autonomic instability, and leukocytosis.
AIM
The aim of this study is to investigate a borderline intellectual functioning (BIF) case in which NMS with insidious disease progression and long prodromal symptoms was developed.
CASE PRESENTATION
The investigated patient was a 38-year-old female diagnosed with bipolar disorder and a variety of corresponding disorders. The patient exhibited gastrointestinal symptoms and restlessness in the weeks leading up to the study, subsequent to the administration of elevated doses of haloperidol, risperidone, and lithium. In addition, she was hospitalized for restlessness and aggressiveness in the summer of 2023. Furthermore, due to her chief complaint, she received parenteral haloperidol twice in the emergency room, subsequently experiencing fever, altered consciousness, generalized rigidity, and dysphagia. Moreover, the patient's initial creatine phosphokinase (CPK) level was 2550 IU/L, and she was hospitalized in an intensive care unit with the diagnosis of NMS for 8 days.
CONCLUSIONS
This case study highlights the necessity of being attentive about prodromal symptoms of NMS and emergent interventions.
PubMed: 38832410
DOI: 10.1002/npr2.12454 -
Cureus May 2024Thyroid abscess is a rare occurrence and is characterized by an accumulation of pus within the thyroid gland. It most commonly forms as a sequela of acute suppurative...
Thyroid abscess is a rare occurrence and is characterized by an accumulation of pus within the thyroid gland. It most commonly forms as a sequela of acute suppurative thyroiditis, and it presents as a painful swelling of the anterior neck with fever. Patients may also develop referred ear pain and compressive symptoms such as difficulty breathing and swallowing as the abscess enlarges. On examination, the swelling is often associated with erythema, local rise of temperature, and tenderness. Laboratory investigations may reveal leukocytosis, elevated acute phase reactants, and an abnormal thyroid function test. Despite advancements in diagnostic modalities and treatment approaches, literature on thyroid abscesses remains limited. We present a unique case of a long-standing thyroid abscess resulting from chronic suppuration which did not exhibit any of the mentioned expected findings seen in other cases. This patient was euthyroid, and laboratory investigations showed no significant abnormality. It was successfully treated with total thyroidectomy and appropriate antibiotics.
PubMed: 38832164
DOI: 10.7759/cureus.59549