A woman in her seventies with fever and convulsions. / En kvinne i 70-årene med feber og krampeanfall.

Background: Chagas encephalitis is a rare but severe manifestation of reactivation in patients with chronic Chagas disease. Case presentation: A woman in her seventies who was immunosuppressed after a heart transplant due to Chagas disease was admitted with convulsions, headache and visual disturbances. She developed fever, confusion and repeated convulsions. Pleocytosis was found in spinal fluid. Wet-mount microscopy of spinal fluid revealed motile Trypanosoma cruzi trypomastigotes, and multiple trypomastigotes were seen on a Giemsa-stained smear, confirming reactivation of Chagas disease with meningoencephalitis. Despite benznidazole treatment, she deteriorated, exhibiting pharyngeal paralysis, aphasia and increasing somnolence. Brain CT showed pathology consistent with Chagas encephalitis. Nifurtimox was given as an adjunctive treatment. After a week of treatment, the patient began to improve. She completed 60 days of benznidazole and had regained normal cognitive and neurological function on subsequent follow-up. She had no signs of myocarditis reactivation. Interpretation: Chronic Chagas disease is common among Latin American immigrants in Europe. Reactivation with myocarditis after a heart transplant is well known, while encephalitis is a rare manifestation. We report on a case of Chagas encephalitis in an immunosuppressed patient. Microscopy of parasites in spinal fluid revealed the diagnosis. The WHO provided antiparasitic medications, and despite a severe prognosis, the patient made a full recovery.

Mortality among extrapulmonary tuberculosis patients in the HIV endemic setting: lessons from a tertiary level hospital in Mbeya, Tanzania.

Extrapulmonary tuberculosis (EPTB) has received less attention than pulmonary tuberculosis due to its non-contagious nature. EPTB can affect any organ and is more prevalent in people living with HIV. Low- and middle-income countries are now facing the double burden of non-communicable diseases (NCDs) and HIV, complicating the management of patients with symptoms that could be compatible with both EPTB and NCDs. Little is known about the risk of death of patients presenting with symptoms compatible with EPTB. We included patients with a clinical suspicion of EPTB from a tertiary level hospital in Mbeya, Tanzania, to assess their risk of dying. A total of 113 (61%) patients were classified as having EPTB, and 72 (39%) as having non-TB, with corresponding mortality rates of 40% and 41%. Associated factors for mortality in the TB groups was hospitalization and male sex. Risk factors for hospitalization was having disease manifestation at any site other than lymph nodes, and comorbidities. Our results imply that NCDs serve as significant comorbidities amplifying the mortality risk in EPTB. To strive towards universal health coverage, focus should be on building robust health systems that can tackle both infectious diseases, such as EPTB, and NCDs.

Predominance of multidrug-resistant Salmonella Typhi genotype 4.3.1 with low-level ciprofloxacin resistance in Zanzibar.

BACKGROUND: Typhoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia. METHODS: Consecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015-2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S. Typhi strains isolated in a pilot study 2012-2013. RESULTS: Sixty-three S. Typhi isolates (98%) were MDR carrying blaTEM-1B, sul1 and sul2, dfrA7 and catA1 genes. Low-level ciprofloxacin resistance was detected in 69% (43/62), with a single gyrase mutation gyrA-D87G in 41 strains, and a single gyrA-S83F mutation in the non-MDR strain. All isolates were susceptible to ceftriaxone and azithromycin. All MDR isolates belonged to genotype 4.3.1 lineage I (4.3.1.1), with the antimicrobial resistance determinants located on a composite transposon integrated into the chromosome. Phylogenetically, the MDR subgroup with ciprofloxacin resistance clusters together with two external isolates. CONCLUSIONS: We report a high rate of MDR and low-level ciprofloxacin resistant S. Typhi circulating in Zanzibar, belonging to genotype 4.3.1.1, which is widespread in Southeast Asia and African countries and associated with low-level ciprofloxacin resistance. Few therapeutic options are available for treatment of typhoid fever in the study setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.

Complete recovery after fulminant myocarditis in a patient with COVID-19.

The clinical spectrum of Coronavirus disease 2019 (COVID-19) varies from asymptomatic infection to severe disease with multiorgan dysfunction. Cardiovascular involvement is common and in rare cases can lead to serious complications, such as fulminant myocarditis. The clinical course of COVID-19 myocarditis varies from complete recovery to death in rare cases. The pathophysiology of COVID-19-related myocarditis is still unclear but is believed to involve direct viral injury and cardiac damage due to the host's immune response. Guidelines on the management of COVID-19-related myocarditis are yet to be established. We present here the case of a male patient in his early fifties admitted with life-threatening myocarditis in the course of COVID-19 infection who was successfully treated and recovered without any sequelae.

A man in his sixties with life-threatening febrile illness after travel abroad. / Ein mann i 60-åra med livstrugande febersjukdom etter utanlandsreise.

Background: African sleeping sickness is a neglected tropical disease seldom seen in European travellers. Case presentation: While working in Eastern Africa, a Norwegian man in his sixties developed weakness and fever. He was prescribed doxycycline after a negative malaria rapid test. On the third day of illness he returned to Norway and was admitted to the hospital upon arrival. On admission he was somnolent with fever, tachypnoea, tachycardia, jaundice, a hyperaemic rash, oliguria and haematuria. Blood tests revealed leukopenia, thrombocytopaenia, renal failure and liver dysfunction. Rapid tests were negative for malaria and dengue. Blood microscopy revealed high parasitaemia with trypanosomes indicating human African sleeping-sickness. He had been bitten by a tsetse fly 11 days prior in an area endemic for Trypanosoma brucei gambiense. However, the clinical picture was consistent with Trypanosoma brucei rhodesiense infection (East African sleeping sickness). Four days after starting treatment with suramin, spinal fluid examination revealed mild mononuclear pleocytosis but no visible parasites. Melarsoprol treatment for possible encephalitis was considered but suramin treatment was continued alone. He improved and remains healthy seven years later. PCR on blood was positive for T. b. rhodesiense. Interpretation: African sleeping sickness can also affect tourists to endemic areas. Onset can be acute, life-threatening and requires treatment with antiparasitic drugs not generally available in Norwegian hospitals.

Symptom trajectories of post-COVID sequelae in patients with acute Delta or Omicron infection in Bergen, Norway.

Introduction: A substantial proportion of the over 700 million COVID-19 cases world-wide experience long-term symptoms. The objectives of this study were to compare symptom trajectories and risk factors for post-COVID-19 condition after Delta and Omicron infection. Methods: This study consecutively recruited patients with SARS-CoV-2 infection from November 2021 to March 2022. We recorded demographics, comorbidities, vaccination status, sick leave, and 18 symptoms during acute infection and after 4 months. The primary outcome measures were symptoms during acute infection and after 4 months. Secondary outcome measures were work and school absenteeism. Results: We followed a cohort of 1,374 non-hospitalized COVID-19 patients in Bergen, Norway, at three time points. The median age was 39.8 years and 11% were children <16 years. Common acute upper respiratory symptoms waned during follow-up. Fatigue remained common from acute infection (40%) until after 4 months (37%). Four months post-infection, patients reported increased frequencies of dyspnea (from 15% during acute illness to 25% at 4 months, p < 0.001), cognitive symptoms (from 9 to 32%, p < 0.001) and depression (from 1 to 17%, p < 0.001). Patients infected with Omicron reported less dyspnea (22% versus 27%, p = 0.046) and smell/taste problems (5% versus 19%, p < 0.001) at 4 months follow-up than those with Delta infection. Comorbidities and female sex were risk factors for persistent dyspnea and cognitive symptoms. Ten percent reported sick leave after acute illness, and vaccination reduced the risk of absenteeism (adjusted risk ratio: 0.36, 95% confidence interval: 0.15, 0.72, p = 0.008). Conclusion: At 4 months, home-isolated patients infected with Omicron reported overall comparable symptom burden, but less dyspnea and smell/taste problems than Delta infected patients. Several acute symptoms waned during follow-up. It is worrying that dyspnea, neurocognitive symptoms, and particularly depression, increased significantly during the first 4 months after acute infection. Previous vaccination was protective against prolonged sick leave.

SARS-CoV-2 specific immune responses in overweight and obese COVID-19 patients.

Obesity is a known risk factor for severe respiratory tract infections. In this prospective study, we assessed the impact of being obese or overweight on longitudinal SARS-CoV-2 humoral and cellular responses up to 18 months after infection. 274 patients provided blood samples at regular time intervals up to 18 months including obese (BMI ≥30, n=32), overweight (BMI 25-29.9, n=103) and normal body weight (BMI 18.5-24.9, n=134) SARS-CoV-2 patients. We determined SARS-CoV-2 spike-specific IgG, IgA, IgM levels by ELISA and neutralising antibody titres by neutralisation assay. RBD- and spike-specific memory B cells were investigated by ELISpot, spike- and non-spike-specific IFN-γ, IL-2 and IFN-γ/IL-2 secreting T cells by FluoroSpot and T cell receptor (TCR) sequencing was performed. Higher BMI correlated with increased COVID-19 severity. Humoral and cellular responses were stronger in overweight and obese patients than normal weight patients and associated with higher spike-specific IgG binding titres relative to neutralising antibody titres. Linear regression models demonstrated that BMI, age and COVID-19 severity correlated independently with higher SARS-CoV-2 immune responses. We found an increased proportion of unique SARS-CoV-2 specific T cell clonotypes after infection in overweight and obese patients. COVID-19 vaccination boosted humoral and cellular responses irrespective of BMI, although stronger immune boosting was observed in normal weight patients. Overall, our results highlight more severe disease and an over-reactivity of the immune system in overweight and obese patients after SARS-CoV-2 infection, underscoring the importance of recognizing overweight/obese individuals as a risk group for prioritisation for COVID-19 vaccination.

Antibiotic use at a tertiary hospital in Tanzania: findings from a point prevalence survey.

BACKGROUND: In Tanzania, data on antibiotic use at the patient level is scarce, and intervention measures to optimize antibiotic use and reduce antimicrobial resistance are rarely performed. OBJECTIVES: To describe antibiotic use at Muhimbili National Hospital. METHODS: This was a point prevalence survey on antibiotic use conducted at Muhimbili National Hospital in August-September 2022. The World Health Organization point prevalence survey data collection tool was used to collect patients' information from the files. All patients admitted to the wards on the day of the survey were included. RESULTS: Overall, 47% (185/397) of admitted patients were on at least one antibiotic during the survey. All antibiotics prescribed were for empirical treatment and guideline compliance was low, at 45%. Of 185 patients who received antibiotics, the most common indication was community acquired infection (55%) and 36% had no documentation of the reasons for prescribing antibiotics. Almost 75% of the antibiotics were administered parenterally, with only 2% switching to oral route. Microbiological tests were performed in only 9 (5%) patients out of 185 and results were available for only one patient. Of all participants, 52% received two or more antibiotic in combination, with the combination ceftriaxone-metronidazole being most frequently prescribed, followed by the combination of ampicillin, cloxacillin, and gentamicin. For individual antibiotics, ceftriaxone was the most frequently prescribed antibiotic accounting for 28% (79/283), followed by metronidazole (24%) and amoxicillin-clavulanic acid (11%). CONCLUSION: The findings of a high prevalence of antibiotic use, inadequate use of bacterial culture, and frequent empiric antibiotic treatment suggests the need for strengthening diagnostic and antimicrobial stewardship programs. Furthermore, this study has identified areas for quality improvement, including education programs focusing on prescription practice.

Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: A Review of Current Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a condition of immune dysregulation and hyperinflammation, leading to organ failure and death. Malignancy, autoimmune conditions, and infections, including Mycobacterium tuberculosis (TB), are all considered triggers of HLH. The aim of this study was to review all reported cases of TB-associated HLH in English literature, and to summarize the epidemiology, diagnostics, treatment, and mortality in patients with concomitant HLH and TB. A systematic review of described cases with TB-associated HLH, via a structured literature search in the medical database PubMed, is presented. Additional articles were included through cross-referencing with existing review articles. Articles were reviewed based on a predetermined set of criteria. A total of 116 patients with TB-associated HLH were identified with a male:female ratio of about 3:2. The age at presentation ranged from 12 days to 83 years. Malignancy, autoimmunity, and renal failure were the most common comorbid conditions. Most patients received both tuberculostatic and specific immunomodulating treatment, which was associated with a 66% (48/73) survival rate compared to 56% (15/27) in those receiving only tuberculostatic treatment, and 0% (0/13) in those receiving only immunomodulating treatment. The survival rate was 55% overall. The overlapping presentation between disseminated TB and HLH poses challenging diagnostics and may delay diagnosis and treatment, leading to increased mortality. TB should be considered as a potential trigger of HLH; clinicians' knowledge and awareness of this may result in the appropriate investigations needed to ensure diagnosis and proper treatment.

Cost-Effectiveness of Hydroxyurea for Sickle Cell Anemia in a Low-Income African Setting: A Model-Based Evaluation of Two Dosing Regimens.

BACKGROUND AND OBJECTIVE: The disease burden of sickle cell anemia (SCA) in sub-Saharan African (SSA) countries is substantial, with many children dying without an established diagnosis or proper treatment. The global burden of SCA is increasing each year, making therapeutic intervention a high priority. Hydroxyurea is the only disease-modifying therapy with proven feasibility and efficacy suitable for SSA; however, no one has quantified the health economic implications of its use. Therefore, from the perspective of the health care provider, we estimated the incremental cost-effectiveness of hydroxyurea as a fixed-dose regimen or maximum tolerated dose (MTD) regimen, versus SCA care without hydroxyurea. METHODS: We estimated the cost of providing outpatient treatment at a pediatric sickle cell clinic in Kampala, Uganda. These estimates were used in a discrete-event simulation model to project mean costs (2021 US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 mL units), for patients between 9 months and 18 years of age. We calculated cost-effectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3% annually. To test the robustness of our findings, and the impact of uncertainty, we conducted probabilistic and one-way sensitivity analyses, scenario analysis, and price threshold analyses. RESULTS: Hydroxyurea treatment averted an expected 1.37 DALYs and saved US$ 191 per patient if administered at the MTD, compared with SCA care without hydroxyurea. In comparison, hydroxyurea at a fixed dose averted 0.80 DALYs per patient at an incremental cost of US$ 2. The MTD strategy saved 11.2 (95% CI 11.1-11.4) units of blood per patient, compared with 9.1 (95% CI 9.0-9.2) units of blood per patient at the fixed-dose alternative. CONCLUSIONS: Hydroxyurea at MTD is likely to improve quality of life and reduce the consumption of blood products for children with SCA living in Uganda. Compared with a fixed dose regimen, treatment dosing at MTD is likely to be a cost-effective treatment for SCA, using realistic ranges of hydroxyurea costs that are relevant across SSA. Compared with no use of the drug, hydroxyurea could lead to substantial net savings per patient, while reducing the disease morbidity and mortality and increasing quality of life.

Post COVID-19 condition after delta infection and omicron reinfection in children and adolescents.

BACKGROUND: The burden of COVID-19 in children and adolescents has increased during the delta and omicron waves, necessitating studies of long-term symptoms such as fatigue, dyspnoea and cognitive problems. Furthermore, immune responses in relation to persisting symptoms in younger people have not been well characterised. In this cohort study, we investigated the role of antibodies, vaccination and omicron reinfection upon persisting and long-term symptoms up to 8 months post-delta infection. METHODS: SARS-CoV-2 RT-PCR positive participants (n = 276, aged 10-20 years) were prospectively recruited in August 2021. We recorded the major symptoms of post COVID-19 condition and collected serum samples 3- and 8-months post delta infection. Binding antibodies were measured by spike IgG ELISA, and surrogate neutralising antibodies against Wuhan and delta variants by the hemagglutination test (HAT). FINDINGS: After delta infection, persisting symptoms at 3 months were significantly associated with higher delta antibody titres (OR 2.97, 95% CI 1.57-6.04, p = 0.001). Asymptomatic acute infection compared to symptomatic infection lowered the risk of persisting (OR 0.13, 95% CI 0.02-0.55, p = 0.013) and long-term (OR 0.28 95% CI 0.11-0.66, p = 0.005) symptoms at 3 and 8 months, respectively. Adolescents (16-20 years) were more likely to have long-term symptoms compared to children (10-15 years) (OR 2.44, 95% CI 1.37-4.41, p = 0.003). INTERPRETATION: This clinical and serological study compares long-term symptoms after delta infection between children and adolescents. The association between high antibody titres and persisting symptoms suggest the involvement of an immune mechanism. Similarly to adults, the dominant long-term symptoms in children are fatigue, dyspnoea and cognitive problems. FUNDING: This work was funded by the Ministry of Health and Care Services, Norway, the University of Bergen, Norway and Helse Vest, Norway (F-12621).

Fluoroquinolone resistance among fecal extended spectrum ßeta lactamases positive Enterobacterales isolates from children in Dar es Salaam, Tanzania.

BACKGROUND: Fluoroquinolones have been, and continue to be, routinely used for treatment of many bacterial infections. In recent years, most parts of the world have reported an increasing trend of fluoroquinolone resistant (FQR) Gram-negative bacteria. METHODS: A cross-sectional study was conducted between March 2017 and July 2018 among children admitted due to fever to referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were used to screen for carriage of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). ESBL-PE isolates were tested for quinolone resistance by disk diffusion method. Randomly selected fluroquinolone resistant isolates were characterized by using whole genome sequencing. RESULTS: A total of 142 ESBL-PE archived isolates were tested for fluoroquinolone resistance. Overall phenotypic resistance to ciprofloxacin, levofloxacin and moxifloxacin was found in 68% (97/142). The highest resistance rate was seen among Citrobacter spp. (100%, 5/5), followed by Klebsiella. pneumoniae (76.1%; 35/46), Escherichia coli (65.6%; 42/64) and Enterobacter spp. (31.9%; 15/47). Whole genome sequencing (WGS) was performed on 42 fluoroquinolone resistant-ESBL producing isolates and revealed that 38/42; or 90.5%, of the isolates carried one or more plasmid mediated quinolone resistance (PMQR) genes. The most frequent PMQR genes were aac(6')-lb-cr (74%; 31/42), followed by qnrB1 (40%; 17/42), oqx, qnrB6 and qnS1. Chromosomal mutations in gyrA, parC and parE were detected among 19/42 isolates, and all were in E. coli. Most of the E. coli isolates (17/20) had high MIC values of > 32 µg/ml for fluoroquinolones. In these strains, multiple chromosomal mutations were detected, and all except three strains had additional PMQR genes. Sequence types, ST131 and ST617 predominated among E. coli isolates, while ST607 was more common out of 12 sequence types detected among the K. pneumoniae. Fluoroquinolone resistance genes were mostly associated with the IncF plasmids. CONCLUSION: The ESBL-PE isolates showed high rates of phenotypic resistance towards fluoroquinolones likely mediated by both chromosomal mutations and PMQR genes. Chromosomal mutations with or without the presence of PMQR were associated with high MIC values in these bacteria strains. We also found a diversity of PMQR genes, sequence types, virulence genes, and plasmid located antimicrobial resistance (AMR) genes towards other antimicrobial agents.

Genetic determinants of macrolide and tetracycline resistance in penicillin non-susceptible Streptococcus pneumoniae isolates from people living with HIV in Dar es Salaam, Tanzania.

BACKGROUND: Over one million yearly deaths are attributable to Streptococcus pneumoniae and people living with HIV are particularly vulnerable. Emerging penicillin non-susceptible Streptococcus pneumoniae (PNSP) challenges therapy of pneumococcal disease. The aim of this study was to determine the mechanisms of antibiotic resistance among PNSP isolates by next generation sequencing. METHODS: We assessed 26 PNSP isolates obtained from the nasopharynx from 537 healthy human immunodeficiency virus (HIV) infected adults in Dar es Salaam, Tanzania, participating in the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890, registered on 23rd March, 2017). Next generation whole genome sequencing on the Illumina platform was used to identify mechanisms of resistance to antibiotics among PNSP. RESULTS: Fifty percent (13/26) of PNSP were resistant to erythromycin, of these 54% (7/13) and 46% (6/13) had MLSB phenotype and M phenotype respectively. All erythromycin resistant PNSP carried macrolide resistance genes; six isolates had mef(A)-msr(D), five isolates had both erm(B) and mef(A)-msr(D) while two isolates carried erm(B) alone. Isolates harboring the erm(B) gene had increased MIC (> 256 µg/mL) towards macrolides, compared to isolates without erm(B) gene (MIC 4-12 µg/mL) p < 0.001. Using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, the prevalence of azithromycin resistance was overestimated compared to genetic correlates. Tetracycline resistance was detected in 13/26 (50%) of PNSP and all the 13 isolates harbored the tet(M) gene. All isolates carrying the tet(M) gene and 11/13 isolates with macrolide resistance genes were associated with the mobile genetic element Tn6009 transposon family. Of 26 PNSP isolates, serotype 3 was the most common (6/26), and sequence type ST271 accounted for 15% (4/26). Serotypes 3 and 19 displayed high-level macrolide resistance and frequently carried both macrolide and tetracycline resistance genes. CONCLUSION: The erm(B) and mef(A)-msr(D) were common genes conferring resistance to MLSB in PNSP. Resistance to tetracycline was conferred by the tet(M) gene. Resistance genes were associated with the Tn6009 transposon.

Symptom Burden and Immune Dynamics 6 to 18 Months Following Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2): A Case-control Study.

BACKGROUND: The burden and duration of persistent symptoms after nonsevere coronavirus disease 2019 (COVID-19) remains uncertain. This study aimed to assess postinfection symptom trajectories in home-isolated COVID-19 cases compared with age- and time- matched seronegative controls, and investigate immunological correlates of long COVID. METHODS: A prospective case-control study included home-isolated COVID-19 cases between February 28 and April 4, 2020, and followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive controls. We collected clinical data at baseline, 6, 12, and 18 months postinfection, and blood samples at 2, 4, 6, and 12 months for analysis of SARS-CoV-2-specific humoral and cellular responses. RESULTS: Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared with controls, adult cases had a high risk of fatigue (27% excess risk, sex, and comorbidity adjusted odds ratio [aOR] 5.86; 95% confidence interval [CI], 3.27-10.5), memory problems (21% excess risk; aOR 7.42; CI, 3.51-15.67), concentration problems (20% excess risk; aOR 8.88; 95% CI, 3.88-20.35), and dyspnea (10% excess risk; aOR 2.66; 95% CI, 1.22-5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%; 95% CI, 1.5-21.5; P = .024) and among women (excess risk 18.7%; 95% CI, 4.4-32.9; P = .010). Longitudinal spike immunoglobulin G was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4+ T-cell receptor ß depth was significantly associated with both dyspnea and number of symptoms at 12 months. CONCLUSIONS: This study documents a high burden of persisting symptoms after mild COVID-19 and suggests that infection induced SARS-CoV-2-specific immune responses may influence long-term symptoms.

Clinical features and risk factors for death in acute undifferentiated fever: A prospective observational study in rural community hospitals in six states of India.

BACKGROUND: Acute undifferentiated fever (AUF) ranges from self-limiting illness to life-threatening infections, such as sepsis, malaria, dengue, leptospirosis and rickettsioses. Similar clinical presentation challenges the clinical management. This study describes risk factors for death in patients hospitalized with AUF in India. METHODS: Patients aged ≥5 y admitted with fever for 2-14 d without localizing signs were included in a prospective observational study at seven hospitals in India during 2011-2012. Predictors identified by univariate analysis were analyzed by multivariate logistic regression for survival analysis. RESULTS: Mortality was 2.4% (37/1521) and 46.9% (15/32) died within 2 d. History of heart disease (p=0.013), steroid use (p=0.011), altered consciousness (p<0.0001), bleeding (p<0.0001), oliguria (p=0.020) and breathlessness (p=0.015) were predictors of death, as were reduced Glasgow coma score (p=0.005), low urinary output (p=0.004), abnormal breathing (p=0.006), abdominal tenderness (p=0.023), leucocytosis (p<0.0001) and thrombocytopenia (p=0.001) at admission. Etiology was identified in 48.6% (18/37) of fatal cases. CONCLUSIONS: Bleeding, cerebral dysfunction, respiratory failure and oliguria at admission, suggestive of severe organ failure secondary to systemic infection, were predictors of death. Almost half of the patients who died, died shortly after admission, which, together with organ failure, suggests that delay in hospitalization and, consequently, delayed treatment, contribute to death from AUF.

SARS CoV-2 Infection among Health Care Workers from Different Health Care Facilities in Western Norway: A Prospective, Cross-Sectional Study.

Background: Comparative data on COVID-19 among health care workers (HCWs) in different health care settings are scarce. This study investigated the rates of previous COVID-19 among HCWs in nursing homes, hospitals and a municipal emergency room (ER). Methods: We prospectively included 747 HCWs: 313 from nursing homes, 394 from hospitals and 40 from the ER. The diagnosis of COVID-19 was based on serological evidence of SARS-CoV-2 antibody positivity and self-reported RT-PCR positivity prior to inclusion. Information regarding age, sex and exposure to SARS-CoV-2 infection was collected. Results: A total of 4% (11/313) of nursing home HCWs and 6% (28/434) of HCWs in hospitals/the ER tested positive by serology and/or RT-PCR (p = 0.095). Fewer HCWs in nursing homes had occupational exposure to SARS-CoV-2 compared to those in hospitals/the ER (16% vs. 48%, p < 0, 001), but nursing homes had a higher proportion of HCWs with occupational exposure using partial/no PPE (56% vs. 19%, p < 0.001). Nevertheless, no significant differences in the risk for COVID-19 were found in relation to the rate of occupational exposure (p = 0.755) or use of inadequate PPE (p = 0.631). Conclusions: Despite a small sample size, the risk for COVID-19 among HCWs did not appear to be related to the type of health care facility, rates of occupational exposure or use of PPE.

The Performances of Three Commercially Available Assays for the Detection of SARS-CoV-2 Antibodies at Different Time Points Following SARS-CoV-2 Infection.

The aim of this study was to evaluate the performances of three commercially available antibody assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at different time points following SARS-CoV-2 infection. Sera from 536 cases, including 207 SARS-CoV-2 PCR positive, were tested for SARS-CoV-2 antibodies with the Wantai receptor binding domain (RBD) total antibody assay, Liaison S1/S2 IgG assay and Alinity i nucleocapsid IgG assay and compared to a two-step reference ELISA (SARS-CoV-2 RBD IgG and SARS-CoV-2 spike IgG). Diagnostic sensitivity, specificity, predictive values and Cohen's kappa were calculated for the commercial assays. The assay's sensitivities varied greatly, from 68.7% to 95.3%, but the specificities remained high (96.9-99.1%). The three tests showed good performances in sera sampled 31 to 60 days after PCR positivity compared to the reference ELISA. The total antibody test performed better than the IgG tests the first 30 days and the nucleocapsid IgG test showed reduced sensitivity two months or more after PCR positivity. Hence, the test performances at different time points should be taken into consideration in clinical practice and epidemiological studies. Spike or RBD IgG tests are preferable in sera sampled more than two months following SARS-CoV-2 infection.

Weight gain during treatment course of allogenic hematopoietic stem cell transplantation in patients with hematological malignancies affects treatment outcome.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for patients with hematological malignancies; however, allo-HSCT does not come without the cost of treatment-related morbidity and mortality. Early detection of risk factors could be helpful in identifying patients who could benefit from early interventions. Many patients gain weight during the allo-HSCT treatment, although little is known about the impact of weight gain. METHODS: Weight gain in 146 consecutively enrolled adult patients undergoing allo-HSCT was explored. RESULTS: In total, 141 patients (97%) gained weight along the course of allo-HSCT. Median weight increase was 4.8 kg (range 0.0-16.1 kg), with median increase in body weight 6.5% (range 0.0%-30.8%). Maximum weight increase was observed at day +7 (range day -8, +44). Weight gain was associated with increased incidence of acute graft-versus-host disease. Patients with weight gain >10% had a significantly greater 5-year mortality compared with those with lower weight gain (P = 0.031, rank sum test). CONCLUSIONS: Weight gain is a simple variable with the ability to provide prognostic information for patients undergoing allo-HSCT.

Gastrointestinal colonization of extended-spectrum beta-lactamase-producing bacteria among children below five years of age hospitalized with fever in Dar es Salaam, Tanzania.

OBJECTIVES: Gastrointestinal colonization of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) is of concern because prior colonization increases risk for subsequent infections. To date, the link between ESBL-PE faecal carriage and the risk of subsequent ESBL-PE infection has not been well established, and information on carriage of such pathogens among children with invasive infections such as bloodstream infections (BSI) remains to be explored worldwide. METHODS: This cross-sectional study was conducted among children under the age of 5 years admitted for febrile illness in Dar es Salaam, Tanzania, between March 2017 and July 2018. We used rectal swabs to screen for ESBL-PE using selective media, ChromID ESBL. Bacterial isolates were identified by MALDI-TOF. Blood cultures were drawn from all children. Antimicrobial susceptibility testing was done using a disk diffusion method. ESBL alleles were identified by real-time PCR and sequencing. RESULTS: The overall prevalence of ESBL-PE carriage was 56% (112/200) and was highest among children 4 to 6 months old (17/21, 81%) (P = 0.05). Children with BSI had high ESBL-PE carriage (78.4%) compared to those without BSI (53.1%) (P = 0.02; aOR 3.4, 95% confidence interval 1.20-9.58). The most common isolate was E. coli (64/112, 45%). Sixteen pairs of ESBL-PE isolates (from the gut and from blood) had a similar antimicrobial susceptibility profile. We detected blaCTX-M gene in 97% of all phenotypically detected ESBL-PE; among those, blaCTX-M-15 was dominant (99%). CONCLUSION: We report a high prevalence of ESBL-PE faecal carriage among children with BSI in Tanzania. Colonization of ESBL-PE was a risk factor for ESBL-BSI.

Intermittent left bundle branch block with septal flash and postural orthostatic tachycardia syndrome in a young woman with long COVID-19.

The emerging entity, long COVID -19 is characterised by long-lasting dyspnoea, fatigue, cognitive dysfunction and other symptoms. Cardiac involvement manifested as conduction abnormalities, left ventricle mechanical dyssynchrony, dyspnoea, palpitation and postural orthostatic tachycardia syndrome (POTS) are common in long COVID-19. The direct viral damage to the myocardium or immune-mediated inflammation are postulated mechanisms. A woman in her forties presented with a 2-month history of chest pain, functional dyspnoea, palpitation and an episode of syncope after having been home-isolated for mild COVID infection. During clinical workup, a clustering of ECG and echocardiographic abnormalities including left bundle branch block, septal flash, and presystolic wave on spectral Doppler echocardiography, and POTS were detected. The echocardiographic findings together with POTS and persistent dyspnoea indicated the presence of a long COVID-19 state. The prevalence and clinical significance of these finding, as well as the impact on long-term prognosis, should be investigated in future studies.