Comparison of Hemoglobin Concentration Before and After Trichuriasis Treatment with Albendazole Among Primary School Children

Background: Trichuriasis is a soil transmitted helminth that causes anemia and growth disturbance in children. This study aimed to compare hemoglobin concentration before and after Trichuriasis treatment with albendazole among primary school children.Subjects and Method: This was an experimental study with before and after quasi experiment design. This study was conducted at Medan Tembung Primary School, Medan, North Sumatera, from March to June, 2015. A total of 63 children were selected for this study. Blood sample was taken for hemoglobin concentration examination before and after the administration of albendazole. The treatment consisted of 400 mg albendazole that was administered in single dose 0nce a day for 3 days, both for single and mixed infection.Results: The prevalence of Trichuriasis among the school children under study was 33.3% (126/ 378), which was consisted of 37 children with single infection and 26 children with mixed infection. Albendazole increased hemoglobin concentration with mean= 11.88 g/dl; SD=1.26 before treatment and mean=12.53 g/dl; SD= 1.37 after treatment, among children with single infection, and it was statistically significant (p= 0.002). Albendazole increased hemoglobin concentration with mean= 11.69 g/dl; SD=1.04 before treatment and mean=12.36 g/dl; SD= 1.06 after treatment, among children with mixed infection, and it was statistically significant (p= 0.001).Conclusion: Albendazole is effective in increasing hemoglobin concentration among school children with anemia that is caused by Trichuriasis infection. Keywords: helminthiasis, trichuriasis, hemoglobin, anemia, albendazole, school childrenCorrespondence: Novreka Pratiwi Sipayung. Department Parasitology, Faculty of Medicine, HKBP Nommensen University, Medan. Email: [email protected]. Mobile: 085261145049.Indonesian Journal of Medicine (2016), 1(4): 201-208https://doi.org/10.26911/theijmed.2017.02.01.0

Comparison of Hemoglobin Concentration Before and After Trichuriasis Treatment with Albendazole among Primary School Children

Background: Trichuriasis is a soil transmitted helminth that causes anemia and growth disturbance in children. This study aimed to compare hemoglobin concentration before and after Trichuriasis treatment with albendazole among primary school children.Subjects and Method: This was an experimental study with before and after quasi experiment design. This study was conducted at Medan Tembung Primary School, Medan, North Sumatera, from March to June, 2015. A total of 63 children were selected for this study. Blood sample was taken for hemoglobin concentration examination before and after the administration of albendazole. The treatment consisted of 400 mg albendazole that was administered in single dose 0nce a day for 3 days, both for single and mixed infection.Results: The prevalence of Trichuriasis among the school children under study was 33.3% (126/ 378), which was consisted of 37 children with single infection and 26 children with mixed infection. Albendazole increased hemoglobin concentration with mean= 11.88 g/dl; SD=1.26 before treatment and mean=12.53 g/dl; SD= 1.37 after treatment, among children with single infection, and it was statistically significant (p= 0.002). Albendazole increased hemoglobin concentration with mean= 11.69 g/dl; SD=1.04 before treatment and mean=12.36 g/dl; SD= 1.06 after treatment, among children with mixed infection, and it was statistically significant (p= 0.001).Conclusion: Albendazole is effective in increasing hemoglobin concentration among school children with anemia that is caused by Trichuriasis infection. Keywords: helminthiasis, trichuriasis, hemoglobin, anemia, albendazole, school childrenCorrespondence: Novreka Pratiwi Sipayung. Department Parasitology, Faculty of Medicine, HKBP Nommensen University, Medan. Email: [email protected]. Mobile: 085261145049.Indonesian Journal of Medicine (2016), 1(4): 201-208https://doi.org/10.26911/theijmed.2017.02.01.0

Methaemoglobin as a surrogate marker of primaquine antihypnozoite activity in Plasmodium vivax malaria: A systematic review and individual patient data meta-analysis

Background: The 8-aminoquinolines, primaquine and tafenoquine, are the only available drugs for the radical cure of Plasmodium vivax hypnozoites. Previous evidence suggests that there is dose-dependent 8-aminoquinoline induced methaemoglobinaemia and that higher methaemoglobin concentrations are associated with a lower risk of P. vivax recurrence. We undertook a systematic review and individual patient data meta-analysis to examine the utility of methaemoglobin as a population-level surrogate endpoint for 8-aminoquinoline antihypnozoite activity to prevent P. vivax recurrence. Methods and findings: We conducted a systematic search of Medline, Embase, Web of Science, and the Cochrane Library, from 1 January 2000 to 29 September 2022, inclusive, of prospective clinical efficacy studies of acute, uncomplicated P. vivax malaria mono-infections treated with radical curative doses of primaquine. The day 7 methaemoglobin concentration was the primary surrogate outcome of interest. The primary clinical outcome was the time to first P. vivax recurrence between day 7 and day 120 after enrolment. We used multivariable Cox proportional-hazards regression with site random-effects to characterise the time to first recurrence as a function of the day 7 methaemoglobin percentage (log base 2 transformed), adjusted for the partner schizonticidal drug, the primaquine regimen duration as a proxy for the total primaquine dose (mg base/kg), the daily primaquine dose (mg/kg), and other factors. The systematic review protocol was registered with PROSPERO (CRD42023345956). We identified 219 P. vivax efficacy studies, of which 8 provided relevant individual-level data from patients treated with primaquine; all were randomised, parallel arm clinical trials assessed as having low or moderate risk of bias. In the primary analysis data set, there were 1,747 patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity enrolled from 24 study sites across 8 different countries (Indonesia, Brazil, Vietnam, Thailand, Peru, Colombia, Ethiopia, and India). We observed an increasing dose-response relationship between the daily weight-adjusted primaquine dose and day 7 methaemoglobin level. For a given primaquine dose regimen, an observed doubling in day 7 methaemoglobin percentage was associated with an estimated 30% reduction in the risk of P. vivax recurrence (adjusted hazard ratio = 0.70; 95% confidence interval [CI] [0.57, 0.86]; p = 0.0005). These pooled estimates were largely consistent across the study sites. Using day 7 methaemoglobin as a surrogate endpoint for recurrence would reduce required sample sizes by approximately 40%. Study limitations include the inability to distinguish between recrudescence, reinfection, and relapse in P. vivax recurrences. Conclusions: For a given primaquine regimen, higher methaemoglobin on day 7 was associated with a reduced risk of P. vivax recurrence. Under our proposed causal model, this justifies the use of methaemoglobin as a population-level surrogate endpoint for primaquine antihypnozoite activity in patients with P. vivax malaria who have normal G6PD activity

Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency

Background The World Health Organization recommends that primaquine should be given once weekly for 8-weeks to patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but data on its antirelapse efficacy and safety are limited. Methods Within the context of a multicentre, randomised clinical trial of two primaquine regimens in P. vivax malaria, patients with G6PD deficiency were excluded and enrolled into a separate 12-month observational study. They were treated with a weekly dose of 0.75 mg/kg primaquine for 8 weeks (PQ8W) plus dihydroartemisinin piperaquine (Indonesia) or chloroquine (Afghanistan, Ethiopia, Vietnam). G6PD status was diagnosed using the fluorescent spot test and confirmed by genotyping for locally prevalent G6PD variants. The risk of P. vivax recurrence following PQ8W and the consequent haematological recovery were characterized in all patients and in patients with genotypically confirmed G6PD variants, and compared with the patients enrolled in the main randomised control trial. Results Between July 2014 and November 2017, 42 male and 8 female patients were enrolled in Afghanistan (6), Ethiopia (5), Indonesia (19), and Vietnam (20). G6PD deficiency was confirmed by genotyping in 31 patients: Viangchan (14), Mediterranean (4), 357A-G (3), Canton (2), Kaiping (2), and one each for A-, Chatham, Gaohe, Ludhiana, Orissa, and Vanua Lava. Two patients had recurrent P. vivax parasitaemia (days 68 and 207). The overall 12-month cumulative risk of recurrent P. vivax malaria was 5.1% (95% CI: 1.3–18.9) and the incidence rate of recurrence was 46.8 per 1000 person-years (95% CI: 11.7–187.1). The risk of P. vivax recurrence was lower in G6PD deficient patients treated with PQ8W compared to G6PD normal patients in all treatment arms of the randomised controlled trial. Two of the 26 confirmed hemizygous males had a significant fall in haemoglobin (>5g/dl) after the first dose but were able to complete their 8 week regimen. Conclusions PQ8W was highly effective in preventing P. vivax recurrences. Whilst PQ8W was well tolerated in most patients across a range of different G6PD variants, significant falls in haemoglobin may occur after the first dose and require clinical monitoring. Trial registration This trial is registered at ClinicalTrials.gov (NCT01814683)

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Background: Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence. Methods: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether–lumefantrine, artesunate–mefloquine, artesunate–amodiaquine, or dihydroartemisinin–piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5–7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470. Findings: Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2–53·9) in 1470 patients treated without primaquine, 19·3% (16·9–21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0–9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17–0·27; p<0·0001) and high-dose primaquine (0·10, 0·08–0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5–7 were reported by 4·0% (95% CI 0·0–8·7) of 893 patients treated without primaquine, 6·2% (0·5–12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8–10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7–16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias. Interpretation: Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms. Funding: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture

The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis

BACKGROUND Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. METHODS AND FINDINGS Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. CONCLUSIONS In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis

Warning sign as a predictor of dengue infection severity in children

Background: Dengue has emerged as a global public health problem, about 500,000 affected patients of 50–100 million cases will develop severe dengue infection. Therefore, early identification of severe dengue infection symptoms can save a patient’s life. The 2009 WHO dengue infection classification proposed seven warning signs to identify the risk of severe dengue. This study was conducted to predict the severity of dengue infection based on the number of warning signs. Methods: This was a diagnostic study conducted with a retrospective analytic observation of patients admitted to Adam Malik hospital with a diagnosis of dengue infection from January 2014–May 2016. The association between warning signs and severe dengue infection was analyzed using logistic regression. We also analyzed the sensitivity, specificity, positive predictive value and negative predictive value. Results: Of 140 patients who fulfilled the research criteria were collected from the medical records. The patients were classified as severe dengue (n=28) and nonsevere dengue (n =112). The warning signs that were associated with severe dengue were persistent vomiting (p<0.05, OR 31.9, 95%CI), fluid accumulation (p<0.05, OR 22.4, 95%CI), mucosal bleeding (p<0.05, OR 9.1, 95%CI), lethargy (p<0.05, OR 43.1, 95%CI). After analyzing the diagnostic tests, the combination of three or more warning signs showed that sensitivity of 92.9%, specificity of 78.6%, positive predictive value of 52%, negative predictive value of 97.7% was found to be associated with a severe dengue infection. Conclusion: The combination of three or more warning signs showed a high sensitivity and specificity for predicting a severe dengue infection

Comparison of Hemoglobin Concentration Before and After Trichuriasis Treatment with Albendazole among Primary School Children

Background: Trichuriasis is a soil transmitted helminth that causes anemia and growth disturbance in children. This study aimed to compare hemoglobin concentration before and after Trichuriasis treatment with albendazole among primary school children. Subjects and Method: This was an experimental study with before and after quasi experiment design. This study was conducted at Medan Tembung Primary School, Medan, North Sumatera, from March to June, 2015. A total of 63 children were selected for this study. Blood sample was taken for hemoglobin concentration examination before and after the administration of albendazole. The treatment consisted of 400 mg albendazole that was administered in single dose 0nce a day for 3 days, both for single and mixed infection. Results: The prevalence of Trichuriasis among the school children under study was 33.3% (126/ 378), which was consisted of 37 children with single infection and 26 children with mixed infection. Albendazole increased hemoglobin concentration with mean= 11.88 g/dl; SD=1.26 before treatment and mean=12.53 g/dl; SD= 1.37 after treatment, among children with single infection, and it was statistically significant (p= 0.002). Albendazole increased hemoglobin concentration with mean= 11.69 g/dl; SD=1.04 before treatment and mean=12.36 g/dl; SD= 1.06 after treatment, among children with mixed infection, and it was statistically significant (p= 0.001). Conclusion: Albendazole is effective in increasing hemoglobin concentration among school children with anemia that is caused by Trichuriasis infection. Keywords: helminthiasis, trichuriasis, hemoglobin, anemia, albendazole, school children Correspondence: Novreka Pratiwi Sipayung. Department Parasitology, Faculty of Medicine, HKBP Nommensen University, Medan. Email: [email protected]. Mobile: 085261145049

Efficacy of mebendazole and levamisole, alone or in combination, for soil-transmitted helminthiasis

Background The World Health Organization (WHO) recommends four, single-dose drugs (albendazole, levamisole, mebendazole, and pyrantel pamoate) for management of soil­transmitted helminthiasis (STH). Previous studies have shown varied and inconsistent outcomes of these STH treatments. Objective To compare the efficacy of mebendazole and levami­sole, alone or in combination, for the treatment of STH. Methods An open randomized controlled trial was conducted in Secanggang, North Sumatera from August to October 2009. School-aged children with STH infection were randomized into three groups. Group I received a single dose of mebendazole (500 mg); group II received a single dose of levamisole (2.5 mg/kg); and group III received a single dose of mebendazole-levamisole combined. Stool samples were collected at baseline, and the 1st, 2nd, 3rd, and 4th weeks after treatment and examined by the Kato-Katz technique. Statistical analyses were Kruskal-Wallis test for cure rate and Analysis of Variance (ANOVA) test for egg reduction rate. Results STH was diagnosed in 197 children with the following parasite species: Ascariasis (96 children, 48.7%), Trichuriasis (58 children, 29.4%), and mixed infection (43 children, 21.8%). We found no hookworm infection in any of our subjects. Groups I and III had significantly higher efficacy (P=0.0001) against STH (egg reduction rate 99.3% and 99.9%; cure rate 92.2% and 98.4%, respectively) at 4th week of treatment. Conclusion A single dose of mebendazole alone and combined with levamisole have better efficacy compared to a single dose of levamisole for the treatment of STH. The highest efficacy of these treatments is noted at the 4th week after drug administratio

Albendazole alone vs. albendazole and diethylcarbamazine combination therapy for trichuriasis

Background Trichuris trichiura is one of the most common soil-transmitted helminths, estimated to infect l billion people worldwide. Several studies have compared the efficacies of albendazole and diethylcarbamazine, but the efficacy of a combination of these two drugs has been inconclusive. Objective To assess the effectiveness of a single dose of albendazole compared to a combination of albendazole and diethylcarbamazine for trichuriasis treatment. Methods A randomized, clinical open trial was conducted from June to September 2009 on elementary school children with trichuriasis from two villages in the North Sumatera Province. Stool specimens were collected at baseline and at days 7, 14, 21, and 28 after treatment, and examined by the Kato Katz method. Subjects were randomized into two groups. Group I received a single dose of albendazole (400 mg) and group II received albendazole (400 mg) plus diethylcarbamazine (6 mg! kg). Statistical analyses used were Chi square test for cure rates and Wilcoxon rank test for egg reduction rates. Results One hundred eight children were enrolled and randomized into group l (53 children) and group II (55 children). The prevalence of T. trichiura infection was 54.7%. There were no significant differences (P=0.52) in the cure rate between groups I and II (66% and 60%, respectively) or in egg reduction rates at day 28 (54.5% and 60.07%, respectively, P= 0.10). Conclusion Albendazole alone and abendazole combined with diethylcarbamazine have similar efficacies for trichuriasis treatment, in terms of cure rates and egg reduction rates