BACKGROUND
Circulating markers of immune and endothelial activation risk stratify infection syndromes agnostic to disease aetiology. However, their utility in children presenting from the community remains unclear.
METHODS
This study recruited children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals in Bangladesh, Cambodia, Indonesia, Laos, and Viet Nam. Clinical parameters and biomarker concentrations were measured at presentation. The outcome measure was death or receipt of vital organ support within two days of enrolment. Prognostic performance of endothelial (Ang-1, Ang-2, sFlt-1) and immune (CHI3L1, CRP, IP-10, IL-1ra, IL-6, IL-8, IL-10, PCT, sTNFR-1, sTREM-1, suPAR) activation markers, WHO Danger Signs, and two validated severity scores (LqSOFA, SIRS) was compared.
RESULTS
3,423 participants were recruited. 133 met the outcome (weighted prevalence: 0.34%; 95% CI 0.28-0.41). sTREM-1 exhibited highest prognostic accuracy (AUC 0.86; 95% CI 0.82-0.90), outperforming WHO Danger Signs (AUC 0.75; 95% CI 0.70-0.80; p < 0.001), LqSOFA (AUC 0.74; 95% CI 0.70-0.78; p < 0.001), and SIRS (AUC 0.63; 95% CI 0.58-0.68; p < 0.001). Discrimination of immune and endothelial activation markers was particularly strong for children who deteriorated later in the course of their illness. Compared to WHO Danger Signs, an sTREM-1-based triage strategy improved recognition of children at risk of progression to life-threatening infection (sensitivity: 0.80 vs. 0.72), while maintaining comparable specificity (0.81 vs. 0.79).
CONCLUSIONS
Measuring circulating markers of immune and endothelial activation may help earlier recognition of febrile children at risk of poor outcomes in resource-constrained community settings.
BACKGROUND
After a history of poor treatments for rifampin-resistant tuberculosis (RR-TB), recent advances have resulted in shorter, more effective treatments. However, they are not available to everyone and have shortcomings, requiring additional treatment options.
METHODS
endTB is an international, open-label, Phase 3 non-inferiority, randomized, controlled clinical trial to compare five 9-month all-oral regimens including bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C) and pyrazinamide (Z), to the standard (control) for treatment of fluoroquinolone-susceptible RR-TB. Participants were randomized to 9BLMZ, 9BCLLfxZ, 9BDLLfxZ, 9DCLLfxZ, 9DCMZ and control using Bayesian response-adaptive randomization. The primary outcome was favorable outcome at week 73 defined by two negative sputum culture results or by favorable bacteriologic, clinical and radiologic evolution. The non-inferiority margin was 12 percentage points.
RESULTS
Of 754 randomized patients, 696 and 559 were included in the modified intention to treat (mITT) and per-protocol (PP) analyses, respectively. In mITT, the control had 80.7% favorable outcomes. Regimens 9BCLLfxZ [adjusted risk difference (aRD): 9.5% (95% confidence interval (CI), 0.4 to 18.6)], 9BLMZ [aRD: 8.8% (95%CI, −0.6 to 18.2)], and 9BDLLfxZ [3.9% (95%CI, −5.8 to 13.6)] were non-inferior in mITT and in PP. The proportion of participants experiencing grade 3 or higher adverse events was similar across the regimens. Grade 3 or higher hepatotoxicity occurred in 11.7% of the experimental regimens overall and in 7.1% of the control.
CONCLUSIONS
The endTB trial increases treatment options for RR-TB with three shortened, all-oral regimens that were non-inferior to a current well-performing standard of care.
RATIONALE
Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients.
OBJECTIVES
We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline.
METHODS
We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment.
MEASUREMENTS AND MAIN RESULTS
Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41).
CONCLUSIONS
High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs.
Though many studies on COVID have been published to date, data on COVID-19 epidemiology, symptoms, risk factors and severity in low- and middle-income countries (LMICS), such as Afghanistan are sparse.
OBJECTIVE
To describe clinical characteristics, severity, and outcomes of patients hospitalized in the MSF COVID-19 treatment center (CTC) in Herat, Afghanistan and to assess risk factors associated with severe outcomes.
METHODS
1113 patients were included in this observational study between June 2020 and April 2022. Descriptive analysis was performed on clinical characteristics, complications, and outcomes of patients. Univariate description by Cox regression to identify risk factors for an adverse outcome was performed. Adverse outcome was defined as death or transfer to a level 3 intensive care located at another health facility. Finally, factors identified were included in a multivariate Cox survival analysis.
RESULTS
A total of 165 patients (14.8%) suffered from a severe disease course, with a median time of 6 days (interquartile range: 2-11 days) from admission to adverse outcome. In our multivariate model, we identified male gender, age over 50, high O2 flow administered during admission, lymphopenia, anemia and O2 saturation <=93% during the first three days of admission as predictors for a severe disease course (p<0.05).
CONCLUSION
Our analysis concluded in a relatively low rate of adverse outcomes of 14.8%. This is possibly related to the fact, that the resources at an MSF-led facility are higher, in terms of human resources as well as supply of drugs and biomedical equipment, including oxygen therapy devices, compared to local hospitals. Predictors for severe disease outcomes were found to be comparable to other settings.
Current options for treating tuberculosis (TB) that is resistant to rifampicin (RR-TB) are few, and regimens are often long and poorly tolerated. Following recent evidence from the TB-PRACTECAL trial countries are considering programmatic uptake of 6-month, all-oral treatment regimens.
METHODS
We used a Markov model to estimate the incremental cost-effectiveness of three regimens containing bedaquiline, pretomanid and linezolid (BPaL) with and without moxifloxacin (BPaLM) or clofazimine (BPaLC) compared with the current mix of long and short standard of care (SOC) regimens to treat RR-TB from the provider perspective in India, Georgia, Philippines, and South Africa. We estimated total costs (2019 USD) and disability-adjusted life years (DALYs) over a 20-year time horizon. Costs and DALYs were discounted at 3% in the base case. Parameter uncertainty was tested with univariate and probabilistic sensitivity analysis.
RESULTS
We found that all three regimens would improve health outcomes and reduce costs compared with the current programmatic mix of long and short SOC regimens in all four countries. BPaL was the most cost-saving regimen in all countries, saving $112-$1,173 per person. BPaLM was the preferred regimen at a willingness to pay per DALY of 0.5 GDP per capita in all settings.
CONCLUSIONS
Our findings indicate BPaL-based regimens are likely to be cost-saving and more effective than the current standard of care in a range of settings. Countries should consider programmatic uptake of BPaL-based regimens.
The objective of this study was to determine the validity of parent’s recall for immunization using the vaccination card as the reference in Yaounde-Cameroon.
SETTINGS
This study was a communitybased study in all the 6 health districts in Yaounde, Cameroon
PARTICIPANTS
The study targeting parents of children aged 0-59months who had their children’s vaccination cards. The immunization history of each child was taken based on both parent’s recall and vaccination card. Using the vaccination card as a reference, the sensitivity, specificity, positive predictive value and negative predictive value of parent’s recall were calculated. The degree of agreement and the kappa statistics between the two methods were calculated using R version 4.1.0 (2021-05-18).
RESULTS
A total of 529 households were visited and 87 eligible parents enrolled. Approximately 55.2% of the 27 children were girls and 53% of them were aged 12-59 months. In total, 94.25% of the participants enrolled were one of the biological parents of the children, with mothers making the majority 86.20% of participants. When combined for all vaccines, the sensitivity, specificity, positive predictive value, and negative predictive value of parent’s recall were 63%, 60%, 90%, and 23% respectively. The degree of agreement between the two sources was highest for BCG(94%) and lowest with Polio2(32%). Parent’s recall(94%) was most likely to correctly predict BCG vaccination status of a child than using the scars on the forarm(74%).
CONCLUSION
Our conclusion is that validity and reliability of parent’s recall vary a lot across different vaccines and parent’s recall is not very reliable for immunization status assessment in children. Parent’s recall is preferred for verifying BCG immunization to scars on the forarm. In general, we recommend that parent’s recall for routine immunization should be used only as a last resort or for BCG, and measles and Yellow Fever vaccines.
This study explores the clinical profiles and factors associated with COVID-19 in Cameroon.
RESEARCH DESIGN AND METHODS
In this prospective cohort study, we followed patients admitted for suspicion of COVID-19 at Djoungolo Hospital between 01st April and 31st July 2020. Patients were categorised by age groups and disease severity: mild (symptomatic without clinical signs of pneumonia pneumonia), moderate (with clinical signs of pneumonia without respiratory distress) and severe cases (clinical signs of pneumonia and respiratory distress not requiring invasive ventilation). Demographic information and clinical features were summarised. Multivariable analysis was performed to predict risk.
RESULTS
A total of 323 patients were admitted during the study period; 262 were confirmed cases of COVID-19 by Polymerase Chain Reaction (PCR). Among the confirmed cases, the male group aged 40 to 49 years (13.9%) was predominant. Disease severity ranged from mild (77%; N=204) to moderate (15%; N=40) to severe (7%; N=18); the case fatality rate was 1% (N=4). Dysgusia (46%; N=111) and hyposmia/anosmia (39%; N=89) were common features of COVID-19. Nearly one-third of patients had comorbidities (29%; N=53), of which hypertension was the most common (20%; N=48). Participation in a mass gathering (OR=5.47; P=0.03) was a risk factor for COVID-19. Age groups 60 to 69 (OR=7.41; P=0.0001), 50 to 59 (OR=4.09; P=0.03), 40 to 49 (OR=4.54; P=0.01), male gender (OR=2.53; P=0.04), diabetes (OR= 4.05; P= 0.01), HIV infection (OR=5.57; P=0.03), lung disease (OR= 6.29; P=0.01), dyspnoea (OR=3.70; P=0.008) and fatigue (OR=3.35; P=0.02) significantly predicted COVID-19 severity.
CONCLUSION
Unlike many high-income settings, most COVID-19 cases in this study were benign with low fatality. Such findings may guide public health decision-making.