Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis.

BACKGROUND: We systematically assessed beneficial and harmful effects of monoclonal antibodies for coronavirus disease 2019 (COVID-19) treatment, and prophylaxis in individuals exposed to severe acute respiratory syndrome coronavirus 2. METHODS: We searched 5 engines and 3 registries until November 3, 2021 for randomized controlled trials evaluating monoclonal antibodies vs control in hospitalized or non-hospitalized adults with COVID-19, or as prophylaxis. Primary outcomes were all-cause mortality, COVID-19-related death, and serious adverse events; hospitalization for non-hospitalized; and development of symptomatic COVID-19 for prophylaxis. Inverse variance random effects models were used for meta-analyses. Grading of Recommendations, Assessment, Development, and Evaluations methodology was used to assess certainty of evidence. RESULTS: Twenty-seven randomized controlled trials were included: 20 in hospitalized patients (n = 8253), 5 in non-hospitalized patients (n = 2922), and 2 in prophylaxis (n = 2680). In hospitalized patients, monoclonal antibodies slightly reduced mechanical ventilation (relative risk [RR] 0.74; 95% confidence interval [CI], 0.60-0.9; I2 = 20%, low certainty of evidence) and bacteremia (RR 0.77; 95% CI, 0.64-0.92; I2 = 7%, low certainty of evidence); evidence was very uncertain about the effect on adverse events (RR 1.31; 95% CI, 1.02-1.67; I2 = 77%, very low certainty of evidence). In non-hospitalized patients, monoclonal antibodies reduced hospitalizations (RR 0.30; 95% CI, 0.17-0.53; I2 = 0%, high certainty of evidence) and may slightly reduce serious adverse events (RR 0.47; 95% CI, 0.22-1.01; I2 = 33%, low certainty of evidence). In prophylaxis studies, monoclonal antibodies probably reduced viral load slightly (mean difference -0.8 log10; 95% CI, -1.21 to -0.39, moderate certainty of evidence). There were no effects on other outcomes. CONCLUSIONS: Monoclonal antibodies had limited effects on most of the outcomes in COVID-19 patients, and when used as prophylaxis. Additional data are needed to determine their efficacy and safety.

Efficacy and harms of tocilizumab for the treatment of COVID-19 patients: A systematic review and meta-analysis.

INTRODUCTION: We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. METHODS: Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. RESULTS: Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81-0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44-1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71-0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. CONCLUSIONS: In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.

Helicobacter pylori infection in children.

Helicobacter pylori infection affects more than half of the world population and it occurs generally in childhood. It is associated with gastroduodenal ulcer, gastric atrophy, intestinal metaplasia, gastric adenocarcinoma and lymphoid tissue-associated lymphoma. It is difficult to eradicate this bacterium due to its high antimicrobial resistance. In children, the infection is asymptomatic in the majority of cases and complications are less common. Probable inverse relationships with allergic diseases and inflammatory bowel diseases are being studied. These reasons mean that the decision to diagnose and treat the infection in children is only considered in specific circumstances in which it provides true benefits. This review focuses on some current considerations regarding epidemiology, diagnosis and treatment of childhood infection, emphasising outcomes and treatment schemes in children.

Oesophageal eosinophilia and oesophageal diseases in children: are the limits clear?

Gastro-oesophageal reflux disease, eosinophilic oesophagitis and oesophageal motility disorders are among the most common diseases accompanying oesophageal eosinophilia. They have similarities and their limits are frequently not well defined. This article reviews the main characteristics relating to their similarities and differences, highlighting existing controversies among these diseases, in addition to current knowledge. In the case of a patient with symptoms of oesophageal dysfunction, it is suggested to carry out an integral analysis of the clinical features and diagnostic test results, including histology, while individualising each case before confirming a definitive diagnosis. Future investigation in paediatric patients is necessary to assess eosinophilic infiltration in the various layers of the oesophageal tissue, along with its clinical and pathophysiological implications.

Efficacy of 5-nitroimidazole compounds for giardiasis in Cuban children: systematic review and meta-analysis.

Five-nitroimidazole (5-NI) compounds are among the most commonly used medications in the treatment of giardiasis. However, after more than five decades of their initial indication for such treatment, there are some concerns about the efficacy of 5-NIs in giardiasis. This study sought to compare the efficacy of any 5-NI with any other antigiardial drug for the treatment of Cuban children with giardiasis. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched CUMED, EBSCOhost and PubMed databases. Two reviewers independently assessed trial eligibility, trial quality and extracted appropriate data. The primary outcome was the parasitological cure. The effect estimate was the pooled relative risk (RR) with 95% confidence intervals (CI). We included seven RCTs in the systematic review, involving a total of 1046 children. When the effect of 5-NIs was compared with that of benzimidazole compounds, the pooled effect was significant and favored 5-NIs [the relative risk (RR) is 1.35, 95% CI =1.05 to 1.75], with high heterogeneity (4 studies, I2 =79%). Compared with chloroquine, the pooled effects of the 5-NIs were not significant [RR is 0.96, 95% CI=0.79 to 1.18, (2 studies, I2=68%)]. Our results support the use of 5-NIs (mainly tinidazole) as first-line therapy for Cuban pediatric patients infected with Giardia and may continue being used as reference drugs in future RCTs of giardiasis. These data could help inform policy decisions in Cuba. Caution is needed in extrapolating such data in other settings.

Treatment of refractory paediatric giardiasis using secnidazole plus albendazole: a case series.

Giardia lamblia, the aetiological agent of human giardiasis, is a frequently identified protozoan infection of the upper small intestine. It mainly affects children and has a wide range of clinical manifestations, from asymptomatic carriage to acute or chronic diarrhoea with dehydration, abdominal pain, nausea, vomiting, excessive flatulence and weight loss. Standard treatment for giardiasis is commonly with 5-nitroimidazole (5-NI) compounds, or nitazoxanide; however, some individuals experience treatment failure. For such patients, a combination of two or more drugs may be a viable approach. We report our experience with 11 paediatric patients with drug-refractory giardiasis, for whom therapy with a combination of secnidazole (SNZ) (30 mg/kg/day, divided into 2 doses, for 3 days) and albendazole (ABZ) (400 mg daily for 5 days) resulted in cure for 9 of the 11 (82%) patients. This combination of drugs was well tolerated; only mild, transient, and self-limited side effects were reported and these did not require discontinuation of treatment. These results support the use of SNZ plus ABZ as an alternative treatment for paediatric patients with giardiasis who have failed conventional treatments. Further research is needed to establish the safety of this combination and how it compares to other combination strategies.

Efficacy of mebendazole in paediatric patients with giardiasis: A systematic review and meta-analysis.

Mebendazole (MBZ), a benzimidazole compound, has received attention in treating patients with giardiasis because it has shown beneficial effects both in vitro and in vivo. The aim of this study was to assess with a systematic review and meta-analysis of randomized controlled trials (RCTs) the efficacy of MBZ compared to other antigiardial agents in children. We searched RCTs of MBZ for the treatment of Giardia infections published in PubMed and EBSCOhost. Application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality were independently performed in duplicate. The primary outcome was the parasitological cure. We included 7 RCTs in the systematic review (639 patients). There was no clinical difference in the parasitological cure between MBZ and metronidazole (MTZ). The relative risk (RR) was 0.81 [95% Confidence Interval 0.61-1.09], with high heterogeneity (4 trials, I2 = 81%). The prediction interval expected to cover the results of a new trial was wide enough (0.22-2.96) to support both a clinically relevant difference favouring either MBZ or MTZ. The decision to support any treatment should be based not only on efficacy but also safety and cost. Although our results suggest that MBZ may be an effective treatment option for children with Giardia infection, they should also be interpreted and translated into clinical practice with caution, as the evidence is based on a limited number of RCTs presenting high heterogeneity.

Potential sexual transmission of Giardia in an endemic region: a case series.

We present four cases in which probable sexual transmission of Giardia lamblia was suspected. Diagnosing this mode of transmission in endemic areas is often difficult and should be considered only as possible, because exposure to poor sanitation and a potentially contaminated environment are always latent. However, as patients reported, there was no history of drinking tap water, exposure to recreational water, eating contaminated food, or other potential sources of infection but anilingus with an infected partner. We consider that in endemic countries, even when other more frequent modes of transmission could be playing the main role, the possibility of (re)infection due to sexual transmission should not be forgotten. Talking openly with patients, strengthening patient-specific preventive measures and counselling appear to be needed to reduce risks of Giardia infection transmission due to this often neglected route.

Giardiasis: a diagnosis that should be considered regardless of the setting.

Although Giardia, the aetiological agent of giardiasis, is one of the most prevalent intestinal parasitic infections world-wide, for industrialised countries, it is mainly appreciated as an imported disease with the minimal local transmission. However, the current evidence challenges this perception; Giardia has relevance beyond the high prevalence areas. This infection may be asymptomatic or cause gastrointestinal complains and long-term sequelae, including irritable bowel syndrome, chronic fatigue and impaired child growth and cognitive development. Its detection and diagnosis present a challenge to physicians who may not be familiar with this infection. To improve interventions to control this parasitosis, it is necessary to maintain a high index of suspicion and remain vigilant in finding cases at risk for infection. A better understanding of the characteristics of populations importing infections alongside improved methods to reliably classify infections as imported or acquired locally will help to ensure early and accurate diagnosis. The evidence shows that public health problems like giardiasis are global issues that need to be addressed collectively by both high and low prevalence countries.

Prevalence of zoonotic and non-zoonotic genotypes of Giardia intestinalis in cats: a systematic review and meta-analysis.

There are no meta-analyses specifically describing the prevalence of zoonotic and non-zoonotic genotypes of Giardia intestinalis in cats, which would be useful in defining the importance of cats as a source of zoonotic transmission. We performed a systematic review of the literature in three databases (PubMed, Scopus and SciELO) to assess the proportion of cats that were infected with specific G. intestinalis genotypes. A meta-analysis using a random effects model was performed to calculate the pooled prevalence and 95% confidence intervals (95%CI). A 2-tailed alpha level of 5% was used for hypothesis testing. Measures of heterogeneity, including Cochran's Q statistic, the I2 index, and the tau-squared test, were estimated and reported. Subgroup analyses were conducted by geographic area and animal origin, as well as coinfection. Publication bias was assessed using a funnel-plot. Up to November 1, 2015, the literature search yielded 780 articles, of which 29 studies were valid for analysis. The pooled prevalence rate was higher for genotype F (19 studies, n=368 cats) with 55.8% [95%CI (42.8%-68.7%), τ2=0.0463]. For genotype A (21 n=409) it was 38.7% [95%CI (29.0%-48.4%), τ2=0.0527], for genotype D (7, n=276) 8.9% [95%CI (2.1%-15.8%), τ2=0.0024], for genotype C (2, n=212) 3.1% [95%CI (2.5%-3.5%), τ2=0.0001], for genotype E (3, n=187) 2.9% [95%CI (0.0%-8.1%), τ2=0.0009], and for genotype B (4, n=230) it was 2.8% [95%CI (0.0%-5.7%), τ2=0.0002]. Genotypes A and B of G. intestinalis are present in a wide range of hosts, including humans and cats, whilst genotype E has been reported in bovines, ovines, caprine and porcine animals, as well as in dogs and cats; and genotype F is almost exclusive to cats. Thus genotypes A and B are the most important for zoonotic transmission. In this study, after genotype F (55.5%), genotype A yielded more than 38% in cats (95%CI 29-48). This has interesting possible implications in zoonotic transmission of giardiasis between cats and humans.