Systematic review of empiric studies on lockdowns, workplace closures, and other non-pharmaceutical interventions in non-healthcare workplaces during the initial year of the COVID-19 pandemic: benefits and selected unintended consequences.

BACKGROUND: We conducted a systematic review aimed to evaluate the effects of non-pharmaceutical interventions within non-healthcare workplaces and community-level workplace closures and lockdowns on COVID-19 morbidity and mortality, selected mental disorders, and employment outcomes in workers or the general population. METHODS: The inclusion criteria included randomized controlled trials and non-randomized studies of interventions. The exclusion criteria included modeling studies. Electronic searches were conducted using MEDLINE, Embase, and other databases from January 1, 2020, through May 11, 2021. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Meta-analysis and sign tests were performed. RESULTS: A total of 60 observational studies met the inclusion criteria. There were 40 studies on COVID-19 outcomes, 15 on anxiety and depression symptoms, and five on unemployment and labor force participation. There was a paucity of studies on physical distancing, physical barriers, and symptom and temperature screening within workplaces. The sign test indicated that lockdown reduced COVID-19 incidence or case growth rate (23 studies, p < 0.001), reproduction number (11 studies, p < 0.001), and COVID-19 mortality or death growth rate (seven studies, p < 0.05) in the general population. Lockdown did not have any effect on anxiety symptoms (pooled standardized mean difference = -0.02, 95% CI: -0.06, 0.02). Lockdown had a small effect on increasing depression symptoms (pooled standardized mean difference = 0.16, 95% CI: 0.10, 0.21), but publication bias could account for the observed effect. Lockdown increased unemployment (pooled mean difference = 4.48 percentage points, 95% CI: 1.79, 7.17) and decreased labor force participation (pooled mean difference = -2.46 percentage points, 95% CI: -3.16, -1.77). The risk of bias for most of the studies on COVID-19 or employment outcomes was moderate or serious. The risk of bias for the studies on anxiety or depression symptoms was serious or critical. CONCLUSIONS: Empiric studies indicated that lockdown reduced the impact of COVID-19, but that it had notable unwanted effects. There is a pronounced paucity of studies on the effect of interventions within still-open workplaces. It is important for countries that implement lockdown in future pandemics to consider strategies to mitigate these unintended consequences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration # CRD42020182660.

Effectiveness of unsupervised primaquine regimen for preventing Plasmodium vivax malaria relapses in northeast Myanmar, a single-arm non-randomized observational study.

BACKGROUND: Plasmodium vivax presents a significant challenge for malaria elimination in the Greater Mekong Subregion (GMS). We evaluated the effectiveness of primaquine (PQ) for reducing relapses of vivax malaria. METHODS: Patients with uncomplicated P. vivax malaria from eastern Myanmar received chloroquine (CQ, 25 mg base/kg given in 3 days) plus unsupervised PQ (0.25 mg/kg/day for 14 days) without screening for glucose-6-phosphate dehydrogenase deficiency and were followed for a year. RESULTS: Totally 556 patients were enrolled to receive the CQ/PQ treatment from February 2012 to August 2013. During the follow-up, 38 recurrences were detected, presenting a cumulative rate of recurrence of 9.1% (95% confidence interval, 4.1-14.1%). Genotyping at the pvmsp1 and pvmsp3α loci by Amplicon deep sequencing and model prediction indicated that 13 of the 27 recurrences with genotyping data were likely due to relapses. Notably, all confirmed relapses occurred within the first six months. CONCLUSIONS: The unsupervised standard dose of PQ was highly effective as a radical cure for P. vivax malaria in eastern Myanmar. The high presumed effectiveness might have benefited from the health messages delivered during the enrollment and follow-up activities. Six-month follow-ups in the GMS are sufficient for detecting most relapses.

Engaging East Harlem, New York youth in action gun violence prevention research and child rights: a preliminary study.

BACKGROUND: The aim of the study was to have youth participate in the design and implementation of a research project set within a child rights framework to better understand high schoolers' perceptions of safety in their school and community. RESULTS: Between June 2020 and March 2021, a team of East Harlem, New York high school students, participated as co-researchers to modify the United Nations Children's Fund Child Friendly Cities Initiative Survey to suit their needs. Due to the COVID-19 pandemic, the final survey was conducted through an online remote classes system during advisory school classes, accompanied by brief focused group discussions. The novel process of conducting an interactive qualitative and quantitative virtual survey during a pandemic via youth participatory action research is outlined in this paper. CONCLUSIONS: Our results demonstrate that youth participatory action research can be utilized as part of a child rights framework approach to assess the views of youth regarding community safety and violence prevention.

Risk of hemolysis in Plasmodium vivax malaria patients receiving standard primaquine treatment in a population with high prevalence of G6PD deficiency.

BACKGROUND: Primaquine is essential for the radical cure of Plasmodium vivax malaria, but it poses a potential danger of severe hemolysis in G6PD-deficient (G6PDd) patients. This study aimed to determine whether primaquine is safe in a population with high G6PD prevalence but lacking G6PD diagnosis capacity. METHODS: In Myanmar, 152 vivax patients were gender- and age-matched at 1:3 for G6PDd versus G6PD-normal (G6PDn). Their risk of acute hemolysis was followed for 28 days after treatment with the standard chloroquine and 14-day primaquine (0.25 mg/kg/day) regimen. RESULTS: Patients anemic and non-anemic at enrollment showed a rising and declining trend in the mean hemoglobin level, respectively. In males, the G6PDd group showed substantially larger magnitudes of hemoglobin reduction and lower hemoglobin nadir levels than the G6PDn group, but this trend was not evident in females. Almost 1/3 of the patients experienced clinically concerning declines in hemoglobin, with five requiring blood transfusion. CONCLUSIONS: The standard 14-day primaquine regimen carries a significant risk of acute hemolytic anemia (AHA) in vivax patients without G6PD testing in a population with a high prevalence of G6PD deficiency and anemia. G6PD testing would avoid most of the clinically significant Hb reductions and AHA in male patients.

CD47 blockade reduces the pathologic features of experimental cerebral malaria and promotes survival of hosts with Plasmodium infection.

CD47 is an antiphagocytic "don't eat me" signal that inhibits programmed cell removal of self. As red blood cells (RBCs) age they lose CD47 expression and become susceptible to programmed cell removal by macrophages. CD47-/- mice infected with Plasmodium yoelii, which exhibits an age-based preference for young RBCs, were previously demonstrated to be highly resistant to malaria infection. Our study sought to test the therapeutic benefit of CD47 blockade on ameliorating the clinical syndromes of experimental cerebral malaria (ECM), using the Plasmodium berghei ANKA (Pb-A) murine model. In vitro we tested the effect of anti-CD47 mAb on Plasmodium-infected RBC phagocytosis and found that anti-CD47 treatment significantly increased clearance of Plasmodium-infected RBCs. Infection of C57BL/6 mice with Pb-A is lethal and mice succumb to the clinical syndromes of CM between days 6 and 10 postinfection. Strikingly, treatment with anti-CD47 resulted in increased survival during the cerebral phase of Pb-A infection. Anti-CD47-treated mice had increased lymphocyte counts in the peripheral blood and increased circulating levels of IFN-γ, TNF-α, and IL-22. Despite increased circulating levels of inflammatory cytokines, anti-CD47-treated mice had reduced pathological features in the brain. Survival of ECM in anti-CD47-treated mice was correlated with reduced cellular accumulation in the cerebral vasculature, improved blood-brain barrier integrity, and reduced cytotoxic activity of infiltrating CD8+ T cells. These results demonstrate the therapeutic benefit of anti-CD47 to reduce morbidity in a lethal model of ECM, which may have implications for preventing mortality in young African children who are the highest casualties of CM.

Lineage-Specific Expansion of Plasmodium falciparum Parasites With pfhrp2 Deletion in the Greater Mekong Subregion.

Deletion of the pfhrp2 gene in Plasmodium falciparum can lead to false-negative rapid diagnostic test (RDT) results, constituting a major challenge for evidence-based malaria treatment. Here we analyzed the whole genome sequences of 138 P. falciparum clinical samples collected from the China-Myanmar boarder for pfhrp2 and pfhrp3 gene deletions. We found pfhrp2 and pfhrp3 deletions in 9.4% and 3.6% of samples, respectively, with no samples harboring deletions of both genes. The pfhrp2 deletions showed 2 distinct breakpoints, representing 2 different chromosomal deletion events. A phylogenetic analysis performed using genome-wide single-nucleotide polymorphisms revealed that the 2 pfhrp2 breakpoint groups as well as all the pfhrp3-negative parasites formed separate clades, suggesting they might have resulted from clonal expansion of pfhrp2- and pfhrp3-negative parasites. These findings highlight the need for urgent surveys to determine the prevalence of pfhrp2-negative parasites causing false-negative RDT results and a plan for switching of RDTs pending the survey results.

Associations among Soil-Transmitted Helminths, G6PD Deficiency and Asymptomatic Malaria Parasitemia, and Anemia in Schoolchildren from a Conflict Zone of Northeast Myanmar.

In tropical areas of developing countries, the interactions among parasitic diseases such as soil-transmitted helminths (STHs) and malaria, and glucose-6-phosphate dehydrogenase deficiency (G6PDd), are complex. Here, we investigated their interactions and impact on anemia in school students residing in a conflict zone of northeast Myanmar. A cross-sectional survey was conducted between July and December 2015 in two schools located along the China-Myanmar border. Stool samples from the schoolchildren were analyzed for STH infections, whereas finger-prick blood samples were analyzed for G6PDd, hemoglobin concentrations, and Plasmodium infections. Among 988 enrolled children, Plasmodium vivax, Plasmodium falciparum, hookworm, Ascaris lumbricoides, and Trichuris trichiura infections occurred in 3.3%, 0.8%, 31.5%, 1.2%, and 0.3%, respectively. Glucose-6-phosphate dehydrogenase deficiency was present in 16.9% of the children, and there was a very high prevalence of anemia (73%). Anthropometric measures performed on all children showed that 50% of the children were stunted and 25% wasted. Moderate to severe anemia was associated with STH infections, stunting, and wasting. In addition, children had increasing odds of anemia with increasing burden of infections. This study revealed a high prevalence of G6PDd, STHs, and anemia in schools located in a conflict zone. In areas where malnutrition and STH infections are rampant, testing for both glucose-6-phosphate dehydrogenase and anemia should be considered before treating vivax malaria with 8-aminoquinolines.

Increasing trends of malaria in a border area of the Greater Mekong Subregion.

BACKGROUND: Intensive malaria transmission along international borders is a significant impediment to malaria elimination in the Greater Mekong Subregion (GMS) of Southeast Asia. Passive case detection (PCD) was used to study the dynamics and trends of malaria transmission at the China-Myanmar border to provide epidemiologic information for improved malaria control. METHODS: PCD was conducted in one hospital and 12 clinics near the Laiza town in northeast Myanmar from 2011 to 2016. Clinical malaria was diagnosed by microscopy and demographic information was captured using a structured questionnaire at the time of the patient's presentation for care. RESULTS: Over the study period, 6175 (19.7%) malaria cases were confirmed by microscopy from 31,326 suspected cases. The four human malaria parasite species were all identified, with Plasmodium vivax and Plasmodium falciparum accounting for 5607 (90.8%) and 481 (7.8%) of the confirmed cases, respectively. In contrast to the steady decline of malaria in the general GMS, the study site had an upward trend of malaria incidence with vivax malaria outbreaks in 2013 and 2016. Adult males, children under the age of 15, and those with occupations such as farming, being a soldier or student, had significantly higher risks of clinical malaria compared to having fevers from other aetiologies. A self-reported history of clinical malaria was also associated with a higher risk of confirmed malaria. CONCLUSIONS: The China-Myanmar border area has experienced an overall upward trend of malaria incidence in recent years with P. vivax becoming the predominant species. Evidence-based control strategies need to focus on high-risk populations.