School closures affecting more than 1.5 billion children are designed to prevent the spread of current public health risks from the COVID-19 pandemic, but they simultaneously introduce new short-term ...and long-term health risks through lost education. Measuring these effects in real time is critical to inform effective public health responses, and remote phone-based approaches are one of the only viable options with extreme social distancing in place. However, both the health and education literature are sparse on guidance for phone-based assessments. In this article, we draw on our pilot testing of phone-based assessments in Botswana, along with the existing literature on oral testing of reading and mathematics, to propose a series of preliminary practical lessons to guide researchers and service providers as they try phone-based learning assessments. We provide preliminary evidence that phone-based assessments can accurately capture basic numeracy skills. We provide guidance to help teams (1) ensure that children are not put at risk, (2) test the reliability and validity of phone-based measures, (3) use simple instructions and practice items to ensure the assessment is focused on the target skill, not general language and test-taking skills, (4) adapt the items from oral assessments that will be most effective in phone-based assessments, (5) keep assessments brief while still gathering meaningful learning data, (6) use effective strategies to encourage respondents to pick up the phone, (7) build rapport with adult caregivers and youth respondents, (8) choose the most cost-effective medium and (9) account for potential bias in samples.
Tuberculosis (TB) is one of the leading causes of mortality and morbidity, particularly in developing countries, presenting a major threat to the public health. The currently recommended long term ...treatment regimen with multiple antibiotics is associated with poor patient compliance, which in turn, may contribute to the emergence of multi-drug resistant TB (MDR-TB). The low global treatment efficacy of MDR-TB has highlighted the necessity to develop novel treatment options. Host-directed therapy (HDT) together with current standard anti-TB treatments, has gained considerable interest, as HDT targets novel host immune mechanisms. These immune mechanisms would otherwise bypass the antibiotic bactericidal targets to kill
(Mtb), which may be mutated to cause antibiotic resistance. Additionally, host-directed therapies against TB have been shown to be associated with reduced lung pathology and improved disease outcome, most likely via the modulation of host immune responses. This review will provide an update of host-directed therapies and their mechanism(s) of action against
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The antimicrobial peptide LL-37 is the only cathelicidin that has been described in humans. LL-37 exerts chemotactic, immunomodulatory and angiogenic effects; activities that are mediated through ...binding to the formyl peptide receptor like (FPRL)-1 receptor. Agonistic ligation of FPRL-1 can also induce down-regulation of HIV-1 chemokine receptors and reduce susceptibility to HIV-1 infection in vitro. Therefore, we have evaluated the capacity of LL-37 to inhibit HIV-1 infection in vitro. Here we demonstrate that LL-37 inhibits HIV-1 replication in PBMC, including primary CD4(+) T cells. This inhibition was readily reproduced using various HIV-1 isolates without detectable changes in the target cell expression of HIV-1 chemokine receptors. Accordingly, the HIV-1 inhibitory effect was shown to be independent of FPRL-1 signalling. Given the epithelial expression of LL-37, it may contribute to the local protection against HIV-1 infection.
Antibody deficiencies constitute the majority of primary immunodeficiencies in adults. These patients have a well-established increased risk of bacterial infections but there is a lack of knowledge ...regarding the relative risks upon contracting COVID-19. In this monocentric study the disease course of COVID-19 in 1 patient with Good's syndrome and in 13 patients with common variable immunodeficiency (CVID) is described. The severity of disease ranged from very mild to severe. Several patients required hospitalization and immunomodulatory treatment but all survived. Although viral infections are not a typical feature of humoral immunodeficiencies we recommend that vigilance is increased in the management of patients with Good's syndrome and CVID during the COVID-19 pandemic.
Low vitamin D (vitD₃) is one of the most common nutritional deficiencies in the world known to be associated with numerous medical conditions including infections such as tuberculosis (TB). In this ...study, vitD₃ status and its association with the antimicrobial peptide, human cathelicidin (LL-37), was investigated in Ethiopian patients with different clinical forms of TB. Patients with active TB (
= 77) and non-TB controls (
= 78) were enrolled in Ethiopia, while another group of non-TB controls (
= 62) was from Sweden. Active TB included pulmonary TB (
32), pleural TB (
= 20), and lymph node TB (
= 25). Concentrations of 25-hydroxyvitamin D₃ (25(OH)D₃) were assessed in plasma, while LL-37 mRNA was measured in peripheral blood and in samples obtained from the site of infection. Median 25(OH)D₃ plasma levels in active TB patients were similar to Ethiopian non-TB controls (38.5 versus 35.0 nmol/L) and vitD₃ deficiency (.
Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate ...could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (
= 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (
< 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (
= 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (
= 0.71), Shannon microbial diversity index (
= 0.82), or in principal component analyses (
= 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.
There is concern that the risky behaviors of teenagers, such as truancy, negatively influence the behaviors of others through their social networks. We use administrative data to construct social ...networks based on students who are truant together. We simulate these networks to document that certain students systematically coordinate their absences. We validate them by showing that a parent information intervention on student absences has spillover effects from treated students onto their peers. Excluding these effects understates the intervention’s cost-effectiveness by 43%. We show that there is potential to use networks to target interventions more efficiently given a budget constraint.
Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD₃) deficiency. We conducted a double-blinded, randomized, and placebo-controlled ...trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD₃ (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT,
= 197) and per-protocol (
= 173) analyses. Secondary endpoints: longitudinal HIV viral load, T cell counts, body mass index (BMI), middle-upper-arm circumference (MUAC), and 25(OH)D₃ levels in plasma. Baseline characteristics were detectable viral loads (median 7897 copies/mL), low CD4⁺ (median 410 cells/µL), and elevated CD8⁺ (median 930 cells/µL) T cell counts. Most subjects were vitD₃ deficient at enrolment, but a gradual and significant improvement of vitD₃ status was demonstrated in the vitD₃ + PBA group compared with placebo (
< 0.0001) from week 0 to 16 (median 37.5 versus 115.5 nmol/L). No significant changes in HIV viral load, CD4⁺ or CD8⁺ T cell counts, BMI or MUAC could be detected. Clinical adverse events were similar in both groups. Daily vitD₃ + PBA for 16 weeks was well-tolerated and effectively improved vitD₃ status but did not reduce viral load, restore peripheral T cell counts or improve BMI or MUAC in HIV patients with slow progressive disease. Clinicaltrials.gov NCT01702974.
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