The association between common mental disorders and tuberculosis: a case-control study from Guinea-Bissau.

OBJECTIVE: The aim of the study was to explore the association between tuberculosis (TB) and common mental disorders (CMD), in an area with high prevalence of TB. METHODS: We performed a case-control study of TB patients and unmatched healthy controls, from a demographic surveillance site in Guinea-Bissau. Screening for CMD was performed once for controls and at inclusion and follow-up for TB patients. Kessler 10 (K-10) and a brief version of Hopkins Symptom Checklist 25 (SCL-8d) were used as screening instruments. RESULTS: 571 controls were interviewed and 416 interviews were performed for 215 TB cases. Estimated CMD prevalence at the time of diagnosis of TB was 33.6 % (SCL-8d) and 46.2 % (K-10), compared with 6.8 % (SCL-8d) and 6.7 % (K-10) among controls; adjusted OR 7.18 (95 % CI 4.07 to 12.67) and 14.52 (95 % CI 8.15 to 25.84), respectively. No significant difference in CMD prevalence rates was observed between TB patients, after 6 months of treatment, and controls. CONCLUSION: Psychological distress and common mental disorders were more prevalent among TB patients at the time of diagnosis compared with the background population, but after completion of TB treatment no increased prevalence of psychological distress was found.

Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark.

BACKGROUND: Bone and joint infections (BJIs) are treated with intravenous antibiotics, which are burdensome and costly. No randomised controlled studies have compared if initial oral antibiotics are as effective as intravenous therapy. We aimed to investigate the efficacy and safety of initial oral antibiotics compared with initial intravenous antibiotics followed by oral antibiotics in children and adolescents with uncomplicated BJIs. METHODS: From Sept 15, 2020, to June 30, 2023, this nationwide, randomised, non-inferiority trial included patients aged 3 months to 17 years with BJIs who presented to one of the 18 paediatric hospital departments in Denmark. Exclusion criteria were severe infection (ie, septic shock, the need for acute surgery, or substantial soft tissue involvement), prosthetic material, comorbidity, previous BJIs, or antibiotic therapy for longer than 24 h before inclusion. Patients were randomly assigned (1:1), stratified by C-reactive protein concentration (<35 mg/L vs ≥35 mg/L), to initially receive either high-dose oral antibiotics or intravenous ceftriaxone (100 mg/kg per day in one dose). High-dose oral antibiotics were coformulated amoxicillin (100 mg/kg per day) and clavulanic acid (12·5 mg/kg per day) in three doses for patients younger than 5 years or dicloxacillin (200 mg/kg per day) in four doses for patients aged 5 years or older. After a minimum of 3 days, and upon clinical improvement and decrease in C-reactive protein, patients in both groups received oral antibiotics in standard doses. The primary outcome was sequelae after 6 months in patients with BJIs, defined as any atypical mobility or function of the affected bone or joint, assessed blindly, in all randomised patients who were not terminated early due to an alternative diagnosis (ie, not BJI) and who attended the primary outcome assessment. A risk difference in sequelae after 6 months of less than 5% implied non-inferiority of the oral treatment. Safety outcomes were serious complications, the need for surgery after initiation of antibiotics, and treatment-related adverse events in the as-randomised population. This trial was registered with ClinicalTrials.gov, NCT04563325. FINDINGS: 248 children and adolescents with suspected BJIs were randomly assigned to initial oral antibiotics (n=123) or initial intravenous antibiotics (n=125). After exclusion of patients without BJIs (n=54) or consent withdrawal (n=2), 101 patients randomised to oral treatment and 91 patients randomised to intravenous treatment were included. Ten patients did not attend the primary outcome evaluation. Sequelae after 6 months occurred in none of 98 patients with BJIs in the oral group and none of 84 patients with BJIs in the intravenous group (risk difference 0, one-sided 97·5% CI 0·0 to 3·8, pnon-inferiority=0·012). Surgery after randomisation was done in 12 (9·8%) of 123 patients in the oral group compared with seven (5·6%) of 125 patients in the intravenous group (risk difference 4·2%, 95% CI -2·7 to 11·5). We observed no serious complications. Rates of adverse events were similar across both treatment groups. INTERPRETATION: In children and adolescents with uncomplicated BJIs, initial oral antibiotic treatment was non-inferior to initial intravenous antibiotics followed by oral therapy. The results are promising for oral treatment of uncomplicated BJIs, precluding the need for intravenous catheters and aligning with the principles of antimicrobial stewardship. FUNDING: Innovation Fund Denmark and Rigshospitalets Forskningsfond.

TBscore II: refining and validating a simple clinical score for treatment monitoring of patients with pulmonary tuberculosis.

BACKGROUND: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing them, making the score less applicable. The aim of the present study was to simplify the TBscore. METHODS: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start score and failure (i.e. death or treatment failure), responsiveness using Cohen's effect size, and the relationship between severity class at treatment start and a decrease < 25% in score from the start until the end of the second treatment month and subsequent mortality. RESULTS: We analyzed data from 1070 Guinean (2003-2012) and 432 Ethiopian (2007-2012) pulmonary tuberculosis patients. For the refined score, items with less than substantial agreement (κ ≤ 0.6) and/or not associated with the underlying constructs were excluded. Items kept were: cough, dyspnea, chest pain, anemia, body mass index (BMI) < 18 kg/m(2), BMI < 16 kg/m(2), mid upper arm circumference (MUAC) < 220 mm, and MUAC < 200 mm. The effect sizes for the change between the start of treatment and the 2-month follow-up were 0.51 in Guinea-Bissau and 0.68 in Ethiopia, and for the change between the start of treatment and the end of treatment were 0.68 in Guinea-Bissau and 0.74 in Ethiopia. Severity class placement at treatment start predicted failure (p < 0.001 Guinea-Bissau, p = 0.208 Ethiopia). Inability to decrease at least 25% in score was associated with a higher failure rate during the remaining 4 months of treatment (p = 0.063 Guinea-Bissau, p = 0.008 Ethiopia). CONCLUSION: The TBscore II could be a useful monitoring tool, aiding triage at the beginning of treatment and during treatment.

Leukocyte transcript alterations in West-African girls following a booster vaccination with diphtheria-tetanus-pertussis vaccine.

BACKGROUND: Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. METHODS: To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. As a pilot experiment we extracted RNA from blood samples before, and 6 weeks after, vaccination to analyze the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analyzed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. RESULTS: We found very few transcripts to alter systematically. Those that did mainly belonged to the Interferon (IFN) signalling pathway. We scrutinized this pathway as well as the Interleukin (IL) pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. CONCLUSION: The transcriptome changes following DTP booster vaccination were subtle, but although the material was small, it was possible to identify sub groups that deviate from each other, mainly in the IFN response.

Impact of isoniazid preventive therapy on mortality among children less than 5 years old following exposure to tuberculosis at home in Guinea-Bissau: a prospective cohort study.

OBJECTIVE: In a cohort of children less than 5 years old exposed to adult intrathoracic tuberculosis (TB) in 1996-1998, we found 66% increased mortality compared with community controls. In 2005, we implemented isoniazid preventive therapy (IPT) for children exposed to TB at home, and the present study evaluates the effect of this intervention on mortality. SETTING: This prospective cohort study was conducted in six suburban areas included in the demographic surveillance system of the Bandim Health Project in Bissau, the capital city of Guinea-Bissau. PARTICIPANTS: All children less than 5 years of age and living in the same house as an adult with intrathoracic TB registered for treatment in the study area between 2005 and 2007 were evaluated for inclusion in the IPT programme. MAIN OUTCOME MEASURES (END POINTS): The all-cause mortality rate ratio (MRR) between exposed children on IPT, exposed without IPT and unexposed community control children. RESULTS: A total of 1396 children were identified as living in the same houses as 416 adult TB cases; of those, 691 were enrolled in the IPT programme. Compared with community controls, the IPT children had an MRR of 0.30 (95%CI 0.1 to 1.2). The MRR comparing exposed children with and without IPT was 0.21 (0.0 to 1.1). The relative mortality in IPT children compared with community controls in 2005-2008 differed significantly from the relative mortality of exposed untreated children compared with the community controls in 1996-1998 (test of interaction, p=0.01). CONCLUSIONS: In 2005-2008, exposed children on IPT had 70% lower mortality than the community control children, though not significantly. Relative to the community control children, the mortality among TB-exposed children on IPT in 2005-2008 was significantly lower than the mortality among TB-exposed children not on IPT in 1996-1998.