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Gamma globulin combined with acyclovir for children with infectious mononucleosis and their effect on immune function
Li, Y., Chen, B.
American journal of translational research. 2023;15(6):4399-4407
Abstract
BACKGROUND Infectious mononucleosis (IM) is characterized by pharyngitis, cervical lymphadenopathy, fatigue and fever. IM is most commonly seen in primary Epstein-Barr virus (EBV) infection, with higher occurrence in children. OBJECTIVE To explore the value of gamma globulin combined with acyclovir for IM children and their impact on immune function. METHODS This prospective randomized controlled study recruited 111 children under 14 years old with IM from Anhui Provincial Children's Hospital during March 2019 and March 2022. Among them, 11 children dropped out, and 100 eligible children were randomized 1:1 into a control group and a study group. The control group received acyclovir, and the study group received additional gamma globulin. The baseline data, clinical efficacy, immune function, and adverse reactions were collected and compared. RESULTS The study group had a shorter antipyretic time, lymph node reduction time, pharyngitis improvement time, and hospital stay compared to the control group (P < 0.05). The study group yielded lower levels of total white blood cell count, alanine aminotransferase, and creatine kinase-MB than the control group (P < 0.05). After treatment, the levels of CD3+ and CD8+ were lower, and the levels of CD4+, CD4+/CD8+, IgA, and IgG were higher in the study group than those in the control group (all P < 0.05). The incidence of adverse reactions between the two groups was comparable (14.00% vs. 24.00%). The positive rates of EBV-specific antibody and nuclear antigen in the study group were lower than those in the control group (P < 0.05). CONCLUSION The combined treatment of gamma globulin and acyclovir is a promising alternative for patients with IM compared to acyclovir alone. This combined regimen shortens the duration of clinical manifestations in children, promotes the recovery of laboratory indices, improves clinical efficacy, and enhances immune function. Furthermore, its safety profile is acceptable, warranting its further promotion.
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Effect of oseltamivir phosphate versus placebo on platelet recovery and plasma leakage in adults with dengue and thrombocytopenia; a phase 2, multicenter, double-blind, randomized trial
Tunjungputri RN, Riswari SF, Pramudo SG, Kuntjoro L, Alisjahbana B, Nugraha HG, van der Ven A, Gasem MH, de Mast Q
PLoS Neglected Tropical Diseases. 2022;16(1):e0010051
Abstract
BACKGROUND Thrombocytopenia, bleeding and plasma leakage are major complications of dengue. Activation of endogenous sialidases with desialylation of platelets and endothelial cells may underlie these complications. We aimed to assess the effects of the neuraminidase inhibitor oseltamivir on platelet recovery and plasma leakage in dengue. METHODS We performed a phase 2, double-blind, multicenter, randomized trial in adult dengue patients with thrombocytopenia (<70,000/μl) and a duration of illness ≤ 6 days. Oseltamivir phosphate 75mg BID or placebo were given for a maximum of five days. Primary outcomes were the time to platelet recovery (≥ 100,000/μl) or discharge from hospital and the course of measures of plasma leakage. RESULTS A total of 70 patients were enrolled; the primary outcome could be assessed in 64 patients (31 oseltamivir; 33 placebo). Time to platelet count ≥100,000/μl (n = 55) or discharge (n = 9) were similar in the oseltamivir and placebo group (3.0 days [95% confidence interval, 2.7 to 3.3] vs. 2.9 days [2.5 to 3.3], P = 0.055). The kinetics of platelet count and parameters of plasma leakage (gall bladder thickness, hematocrit, plasma albumin, syndecan-1) were also similar between the groups. DISCUSSION In this trial, adjunctive therapy with oseltamivir phosphate had no effect on platelet recovery or plasma leakage parameters. TRIAL REGISTRATION ISRCTN35227717.
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Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial
Malavige GN, Jeewandara C, Wijewickrama A, Gunasinghe D, Mahapatuna SD, Gangani C, Vimalachandran V, Jayaratne G, Perera Y, Wanigatunga C, et al
PLoS neglected tropical diseases. 2022;16(6):e0010123
Abstract
BACKGROUND Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue. METHODS AND FINDINGS A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. However, there was no difference in the duration of illness and in the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo. CONCLUSIONS Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. It usefulness when used in combination with other treatment modalities should be explored. TRIAL REGISTRATION International Clinical Trials Registration Platform: SLCTR/2017/024.
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Efficacy of Gamma Globulin Combined with Azithromycin Sequential Therapy in the Treatment of RMPP and Its Effect on Th1/Th2 Cytokine Levels
Qi, J., Jia, F., Tian, H., Yang, S.
Computational and Mathematical Methods in Medicine. 2022;2022:5162768
Abstract
OBJECTIVE To investigate the efficacy of gamma globulin combined with azithromycin sequential therapy in the treatment of children with refractory mycoplasma pneumonia and its effect on Th1/Th2 cytokine levels. METHOD From January 2021 to January 2022, 100 children diagnosed with refractory mycoplasma pneumonia were randomly divided into 2 groups (50 cases in each one), the control group was treated with azithromycin plus comprehensive basic treatment, and the treatment group was treated with combined treatment on the basis of the control group, gamma globulin therapy; the treatment effect and cytokine levels of the two groups were compared. RESULTS Th1, Th2, and Th1/Th2 before treatment were not significantly different between the two groups. Th1, Th2, and Th1/Th2 in the treatment group were significantly downregulated compared with those in the control group after treatment. The levels of IgG, IgA, and IgM in the treatment group were not significantly different from those in the control group before treatment but were significantly upregulated after treatment. IL-10, IL-6, and IL-2 levels were also significantly increased in the treatment group. The disappearance time of clinical symptoms such as fever, cough, and pulmonary rales in the treatment group was significantly shorter than that in the control group, and the cure rate in the treatment group was significantly better than that in the control group. CONCLUSION The clinical effect of gamma globulin combined with azithromycin sequential therapy in the treatment of children with refractory mycoplasma pneumonia is remarkable, which can reduce inflammatory factors, improve patients' immunity, and promote disease recovery.
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A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection
Hughes BL, Clifton RG, Rouse DJ, Saade GR, Dinsmoor MJ, Reddy UM, Pass R, Allard D, Mallett G, Fette LM, et al
The New England journal of medicine. 2021;385(5):436-444
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Abstract
BACKGROUND Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
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Adherence to community versus facility-based delivery of monthly malaria chemoprevention with dihydroartemisinin-piperaquine for the post-discharge management of severe anemia in Malawian children: A cluster randomized trial
Nkosi-Gondwe T, Robberstad B, Mukaka M, Idro R, Opoka RO, Banda S, Kühl MJ, O Ter Kuile F, Blomberg B, Phiri KS
PloS one. 2021;16(9):e0255769
Abstract
BACKGROUND The provision of post-discharge malaria chemoprevention (PMC) in children recently admitted with severe anemia reduces the risk of death and re-admissions in malaria endemic countries. The main objective of this trial was to identify the most effective method of delivering dihydroartemesinin-piperaquine to children recovering from severe anemia. METHODS This was a 5-arm, cluster-randomized trial among under-5 children hospitalized with severe anemia at Zomba Central Hospital in Southern Malawi. Children were randomized to receive three day treatment doses of dihydroartemesinin-piperaquine monthly either; 1) in the community without a short text reminder; 2) in the community with a short message reminder; 3) in the community with a community health worker reminder; 4) at the facility without a short text reminder; or 5) at the facility with a short message reminder. The primary outcome measure was adherence to all treatment doses of dihydroartemesinin-piperaquine and this was assessed by pill-counts done by field workers during home visits. Poisson regression was utilized for analysis. RESULTS Between March 2016 and October 2018, 1460 clusters were randomized. A total of 667 children were screened and 375 from 329 clusters were eligible and enrolled from the hospital. Adherence was higher in all three community-based compared to the two facility-based delivery (156/221 [70·6%] vs. 78/150 [52·0%], IRR = 1·24,95%CI 1·06-1·44, p = 0·006). This was observed in both the SMS group (IRR = 1·41,1·21-1·64, p<0·001) and in the non-SMS group (IRR = 1·37,1·18-1·61, p<0·001). Although adherence was higher among SMS recipients (98/148 66·2%] vs. non-SMS 82/144 (56·9%), there was no statistical evidence that SMS reminders resulted in greater adherence ([IRR = 1·03,0·88-1·21, p = 0·68). When compared to the facility-based non-SMS arm (control arm), community-based delivery utilizing CHWs resulted in higher adherence [39/76 (51·3%) vs. 54/79 (68·4%), IRR = 1·32, 1·14-1·54, p<0·001]. INTERPRETATION Community-based delivery of dihydroartemesinin-piperaquine for post-discharge malaria chemoprevention in children recovering from severe anemia resulted in higher adherence compared to facility-based methods. TRIAL REGISTRATION NCT02721420; ClinicalTrials.gov.
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Malaria Chemoprevention in the Postdischarge Management of Severe Anemia
Kwambai TK, Dhabangi A, Idro R, Opoka R, Watson V, Kariuki S, Kuya NA, Onyango ED, Otieno K, Samuels AM, et al
The New England journal of medicine. 2020;383(23):2242-2254
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BACKGROUND Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period. METHODS We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin-piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice-Williams-Peterson total-time approach. RESULTS From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin-piperaquine. CONCLUSIONS In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo. (Funded by the Research Council of Norway and the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT02671175.).
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Effectiveness and safety of autologous platelet-rich plasma therapy with total contact casting versus total contact casting alone in treatment of trophic ulcer in leprosy: An observer-blind, randomized controlled trial
Saha S, Patra AC, Gowda SP, Mondal N, Rahaman S, Ahmed SK, Debbarma S, Kumar Vitthal KP, Sarkar S, Sil A, et al
Indian journal of dermatology, venereology and leprology. 2020
Abstract
Background: Trophic ulcers secondary to leprosy pose a great stigma to patients and remain a challenge to the treating dermatologists. Platelet-rich plasma (PRP) introduces growth factors directly into the wound and aids in rapid healing. The role of PRP in the treatment of trophic ulcers in leprosy patients has not yet been established by randomized controlled trials. Aims: To study the effectiveness and safety of autologous PRP therapy with total contact casting versus total contact casting alone in the treatment of trophic ulcers in leprosy. Methods: In an observer-blind, randomized (1:1) controlled study, 118 patients were enrolled. PRP was prepared by the manual double-spin method (1600 rpm for 10 min followed by 4000 rpm for 10 min). After wound bed preparation, activated PRP was injected intra- and perilesionally, and platelet-poor plasma gel was applied over the ulcer bed. Occlusive dressings and total contact casting were then applied in Group A, and only total contact casting was applied in Group B. The same procedure was repeated every 2 weeks for 8 weeks. Results: In all, 56 patients were analyzable in Group A and 52 in Group B. The surface area of the ulcer decreased significantly from first follow-up onward in both the groups (P < 0.001 in both the groups). Intergroup comparison showed that the reduction in the surface area of the ulcer was significantly more in Group A than in Group B from the first follow-up onward (P = 0.038) and the difference was maintained till the fifth follow-up (P < 0.001). At the end of the study, 91.10 +/- 9.65% ulcer surface area reduction had occurred in Group A, whereas it was 79.77 +/- 17.91% in Group B (P < 0.001). Trophic ulcers healed completely more often in paucibacillary leprosy patients (P < 0.001) and in those with a lower initial surface area of the ulcer (P < 0.001). Limitation: Short duration of treatment (8 weeks). Conclusion: PRP combined with total contact casting accelerates the healing of trophic ulcers of leprosy and is more effective than total contact casting alone. Complete remission is more likely to occur when the duration and surface area of ulcer are less and in the paucibacillary spectrum.
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Comparison of an ordinal endpoint to time-to-event, longitudinal, and binary endpoints for use in evaluating treatments for severe influenza requiring hospitalization
Peterson RL, Vock DM, Babiker A, Powers JH 3rd, Hunsberger S, Angus B, Paez A, Neaton JD
Contemporary clinical trials communications. 2019;15:100401
Abstract
Background/aims: The Food and Drug Administration recommends research into developing well-defined and reliable endpoints to evaluate treatments for severe influenza requiring hospitalization. A novel 6-category ordinal endpoint of patient health status after 7 days that ranges from death to hospital discharge with resumption of normal activities is being used in a randomized placebo-controlled trial of intravenous immunoglobulin (IVIG) for severe influenza (FLU-IVIG). We compare the power of the ordinal endpoint under a proportional odds model to other types of endpoints as a function of various trial parameters. Methods: We used closed-form analysis and empirical simulation to compare the power of the ordinal endpoint to time-to-event, longitudinal, and binary endpoints. In the simulation setting, we varied the treatment effect and the distribution of the placebo group across the follow-up period with consideration of adjustment for baseline health status. Results: In the analytic setting, ordinal endpoints of high granularity provided greater power than time-to-event endpoints when most patients in the placebo group had either naturally progressed to the category of hospital discharge by day 7 or were far from hospital discharge on day 7. In the simulation setting, adjustment for baseline health status universally raised power for the proportional odds model. Across different placebo group distributions of the ordinal endpoint regardless of adjustment for baseline health status, only time-to-event endpoints yielded higher power than the ordinal endpoint for certain treatment effects. Conclusions: In this case study, the FLU-IVIG ordinal endpoint provided greater power than time-to-event, binary, and longitudinal endpoints for most scenarios of the treatment effect and placebo group distribution, including the target population studied for FLU-IVIG. The ordinal endpoint was only surpassed by the time-to-event endpoint when many patients in the placebo group were on the cusp of hospital discharge on day 7 and the follow-up period for the time-to-event endpoint was extended to allow for additional events. Our general approach for evaluating the power of several potential endpoints for an influenza trial can be used for designing other influenza trials with different target populations and for other trials in other disease areas.
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Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease
Gnann JW Jr, Agrawal A, Hart J, Buitrago M, Carson P, Hanfelt-Goade D, Tyler K, Spotkov J, Freifeld A, Moore T, et al
Emerging infectious diseases. 2019;25(11):2064-2073
Abstract
West Nile Virus (WNV) can result in clinically severe neurologic disease. There is no treatment for WNV infection, but administration of anti-WNV polyclonal human antibody has demonstrated efficacy in animal models. We compared Omr-IgG-am, an immunoglobulin product with high titers of anti-WNV antibody, with intravenous immunoglobulin (IVIG) and normal saline to assess safety and efficacy in patients with WNV neuroinvasive disease as part of a phase I/II, randomized, double-blind, multicenter study in North America. During 2003-2006, a total of 62 hospitalized patients were randomized to receive Omr-IgG-am, standard IVIG, or normal saline (3:1:1). The primary endpoint was medication safety. Secondary endpoints were morbidity and mortality, measured using 4 standardized assessments of cognitive and functional status. The death rate in the study population was 12.9%. No significant differences were found between groups receiving Omr-IgG-am compared with IVIG or saline for either the safety or efficacy endpoints.