Compassionate Use of Hydroxychloroquine in Clinical Practice for Patients With Mild to Severe COVID-19 in a French University Hospital.

BACKGROUND: Data from nonrandomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against coronavirus disease 2019 (COVID-19). METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe COVID-19 in a French university hospital. Patients who received hydroxychloroquine (200 mg 3 times daily dosage for 10 days) on a compassionate basis in addition to standard of care (SOC) were compared with patients without contraindications to hydroxychloroquine who received SOC alone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, obesity, National Early Warning Score 2 (NEWS2) score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed COVID-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOC alone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxychloroquine was not associated with a significantly reduced risk of unfavorable outcome (hazard ratio, 0.90 [95% confidence interval, .38-2.1], P = .81). Overall survival was not significantly different between the 2 groups (hazard ratio, 0.89 [0.23; 3.47], P = 1). CONCLUSION: In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC. Unmeasured confounders may have persisted however, despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of COVID-19. In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC.

Health Challenges of the Pacific Region: Insights From History, Geography, Social Determinants, Genetics, and the Microbiome.

The Pacific region, also referred to as Oceania, is a geographically widespread region populated by people of diverse cultures and ethnicities. Indigenous people in the region (Melanesians, Polynesians, Micronesians, Papuans, and Indigenous Australians) are over-represented on national, regional, and global scales for the burden of infectious and non-communicable diseases. Although social and environmental factors such as poverty, education, and access to health-care are assumed to be major drivers of this disease burden, there is also developing evidence that genetic and microbiotic factors should also be considered. To date, studies investigating genetic and/or microbiotic links with vulnerabilities to infectious and non-communicable diseases have mostly focused on populations in Europe, Asia, and USA, with uncertain associations for other populations such as indigenous communities in Oceania. Recent developments in personalized medicine have shown that identifying ethnicity-linked genetic vulnerabilities can be important for medical management. Although our understanding of the impacts of the gut microbiome on health is still in the early stages, it is likely that equivalent vulnerabilities will also be identified through the interaction between gut microbiome composition and function with pathogens and the host immune system. As rapid economic, dietary, and cultural changes occur throughout Oceania it becomes increasingly important that further research is conducted within indigenous populations to address the double burden of high rates of infectious diseases and rapidly rising non-communicable diseases so that comprehensive development goals can be planned. In this article, we review the current knowledge on the impact of nutrition, genetics, and the gut microbiome on infectious diseases in indigenous people of the Pacific region.

Effectiveness of co-trimoxazole to prevent Plasmodium falciparum malaria in HIV-positive pregnant women in sub-Saharan Africa: an open-label, randomized controlled trial.

BACKGROUND: Human immunodeficiency virus (HIV) and malaria during pregnancy cause substantial perinatal mortality. As co-trimoxazole (CMX) protects children and HIV-positive adults against malaria, we compared the effectiveness of daily CMX with sulfadoxine-pyrimethamine intermittent preventive treatment (IPT-SP) on malaria risk in HIV-positive pregnant women in a Plasmodium falciparum-endemic African area. METHODS: From January 2009 to April 2011, we included in a randomized noninferiority trial all HIV type 1-infected pregnant women (≤28 weeks' gestation, CD4 count ≥200 cells/µL, hemoglobin level ≥7 g/L) in 19 health centers in Togo. Women were randomly assigned to daily 800 mg/160 mg CMX, or IPT-SP. The primary outcome was the proportion of malaria-free pregnancies. Other outcomes included malaria incidence, parasitemia, placental malaria, anemia, and infants' birth weight. RESULTS: Of 264 women randomly assigned to the CMX or IPT-SP group, 126 of 132 and 124 of 132, respectively, were included in the analysis. There were 33 confirmed cases of clinical malaria among 31 women in the CMX group, and 19 among 19 women in the IPT-SP group. Ninety-five of 126 (75.4%) women in the CMX group and 105 of 124 (84.7%) in the IPT-SP group remained malaria-free during their pregnancy (difference, 9.3%; 95% confidence interval [CI], -.53 to 19.1, not meeting the predefined noninferiority criterion). The incidence rate in intention-to-treat analysis was 108.8 malaria episodes per 100 person-years in CMX (95% CI, 105.4-112.2) and 90.1 in IPT-SP (95% CI, 86.8-93.4) (not significant). Prevalence of parasitemia was 16.7% in the CMX group vs 28% in the IPT-SP group (P = .02). Histology revealed 20.3% placental malaria in the CMX group vs. 24.6% in the IPT-SP group (not significant). Grade 3-4 anemia was more frequent in the CMX group (10% vs 4%; P = .008). No pregnant women died. Median birth weight was similar. CONCLUSIONS: Daily CMX was not noninferior to IPT-SP for preventing maternal malaria but safe and at least similar regarding parasitemia or placental malaria and birth outcomes. Clinical Trials Registration ISRCTN98835811.

Pattern of the Antimalarials Prescription during Pregnancy in Bangui, Central African Republic.

Introduction. The aim of this study was to identify the antimalarials prescribed during the pregnancy and to document their timing. Method. From June to September 2009, a survey was conducted on 565 women who gave birth in the Castors maternity in Bangui. The antenatal clinics cards were checked in order to record the types of antimalarials prescribed during pregnancy according to gestational age. Results. A proportion of 28.8% ANC cards contained at least one antimalarial prescription. The commonest categories of antimalarials prescribed were: quinine (56.7%), artemisinin-based combinations (26.8%) and artemisinin monotherapy (14.4%). Among the prescriptions that occurred in the first trimester of pregnancy, artemisinin-based combinations and artemisinin monotherapies represented the proportions of (10.9%) and (13.3%). respectively. Conclusion. This study showed a relatively high rate (>80%) of the recommended antimalarials prescription regarding categories of indicated antimalarials from national guidelines. But, there is a concern about the prescription of the artemisinin derivatives in the first trimester of pregnancy, and the prescription of artemisinin monotherapy. Thus, the reinforcement of awareness activities of health care providers on the national malaria treatment during pregnancy is suggested.

Efficacy of praziquantel during the incubation and invasive phase of Schistosoma haematobium schistosomiasis in 18 travelers.

The efficacy of praziquantel started during the incubation period of schistosomiasis has not been studied. Eighteen tourists were infected by Schistosoma haematobium during summer 2003 after bathing once in the same cascade in Mali. We observed the efficacy of praziquantel given at different phases. They received praziquantel at the first consultation, from Days 10 to 15 after exposure in eight asymptomatic patients (Group 1), from Days 28 to 40 in 4 asymptomatic patients (Group 2), and from Days 20 to 39 in 6 patients with acute schistosomiasis (Group 3). All Group 1 patients developed acute schistosomiasis, compared with none of the Group 2 patients (P < 0.004). Among the 10 patients treated during the acute phase, clinical status deteriorated in four cases. Seventeen of the 18 patients developed chronic schistosomiasis. Early praziquantel treatment was thus less effective than later treatment in preventing acute schistosomiasis, while neither treatment effectively prevented chronic schistosomiasis.

Pneumonia among travelers returning from abroad.

BACKGROUND: Although respiratory tract infections represent a frequent cause of morbidity in travelers, and pneumonia a frequent cause of medical consultation among febrile travelers returning home, the etiologic spectrum of pneumonia in travelers has not been specifically studied. METHODS: We reviewed the medical charts of all travelers hospitalized during a 12-month period in our department with pneumonia after returning home. RESULTS: Seventeen patients (nine men, eight women, mean age 44 years, range 26 to 67 years) were included in this study. The etiology of pneumonia was established in 13 patients. Bacterial pneumonia was documented in 10 cases and was due to Streptococcus pneumoniae (n=2), Mycoplasma pneumoniae (n=2), Legionella pneumophila (n=1), Coxiella burnetti (n=1), Leptospira sp. (n=1) or Mycobacterium tuberculosis (n=3). Other etiologies included histoplasmosis, invasive schistosomiasis and dengue fever (one case each). CONCLUSION: These results show the wide range of causes of pneumonia among travelers returning from abroad.