Background: Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with amphotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival. Tamoxifen, a selective estrogen receptor modulator used to treat breast cancer, has anti-cryptococcal activity, appearing synergistic when combined in vitro with amphotericin, and fungicidal when combined with fluconazole. It is concentrated in the brain and macrophages, off-patent, cheap and widely available. We designed a randomized trial to deliver initial efficacy and safety data for tamoxifen combined with amphotericin and fluconazole. Method: A phase II, open-label, randomized (1:1) controlled trial of tamoxifen (300mg/day) combined with amphotericin (1mg/kg/day) and fluconazole (800mg/day) for the first 2 weeks therapy for HIV infected or uninfected adults with cryptococcal meningitis. The study recruits at Cho Ray Hospital and the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. The primary end point is Early Fungicidal Activity (EFA-the rate of yeast clearance from CSF), over the first two weeks of treatment. 50 patients will be recruited providing ≈80% and 90% power to detect a difference in the EFA of -0.11 or -0.13 log10CFU/ml/day, respectively. Discussion: The results of the study will inform the decision to proceed to a larger trial powered to mortality. The size of effect detectable has previously been associated with reduced mortality from this devastating disease. Particular side effects of interest include QT prolongation. Trial registration: Clinicaltrials.gov NCT03112031 (11/04/2017)

Dexamethasone may slow fungal clearance and worsen outcomes by increasing the rate of decline of TNF-α concentration.

Half the children under the age of 5 years in Papua New Guinea (PNG) are undernourished, more than double the global average with rural areas disproportionately affected. This study examines factors associated with stunting, wasting and underweight in cocoa growers’ children (<5 years) in the Autonomous Region of Bougainville (ARoB), using data from a comprehensive 2017 cross-sectional livelihoods survey. Sixteen independent predictors for stunting, wasting and underweight were selected based on the UNICEF Conceptual Framework of Determinants of Undernutrition. We used multilevel logistic mixed regression models to measure the association of the explanatory variables with stunting, wasting and underweight. At the household level, the adjusted OR (aOR) of stunting (aOR=1.71,95% CI 1.14 to 2.55) and underweight (aOR=2.11, 95% CI 1.16 to 3.82) increased significantly among children from households with unimproved toilet facilities. The aOR for underweight also increased among children from households without access to clean drinking water (aOR=1.97, 95% CI 1.19 to 3.29). Short maternal stature was significantly associated with child stunting, the odds increased as maternal height decreased (from 150 to <155 cm, aOR=1.52, 95% CI 1.02 to 2.26) (<150 cm, aOR=2.37, 95% CI 1.29 to 4.35). At the individual level, the odds of a child being underweight increased with birth order (second born, aOR=1.92, 95% CI 1.09 to 3.36; third born, aOR=6.77, 95% CI 2.00 to 22.82). Compared with children less than 6 months, children aged 6–23 months and 24–59 months had a higher odds of being stunted (aOR=3.27, 95% CI 1.57 to 6.78 and aOR=2.82, 95% CI 1.40 to 5.67) and underweight (aOR=4.83, 95% CI 1.36 to 17.24 and aOR=4.59, 95% CI 1.29 to 16.26). No variables were found to be significant for wasting. Interventions that simultaneously target key life stages for women and children and the underlying social and environmental determinants are required for sustained improvements to undernutrition.

Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive immunity, nonsteroidal anti-inflammatory drugs have divergent effects: augmenting cell-mediated immunity but inhibiting humoral immunity. Nonsteroidal anti-inflammatory drugs have demonstrated a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis in animals, and may be plausible adjuvants to antimicrobial agents in these diseases. There is a need to evaluate these findings rigorously in human clinical trials. There is preliminary evidence demonstrating antiviral effects of indomethacin in SARS CoV-2 in vitro; however, uncertainty regarding its