Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis

Palmeirim, Marta S.; Hürlimann, Eveline; Knopp, Stefanie; Speich, Benjamin; Belizario, Vicente Y.; Joseph, Serene A.; Vaillant, Michel; Olliaro, Piero; Keiser, Jennifer

doi:10.1371/journal.pntd.0006458

Cited by 95 publications

(67 citation statements)

References 55 publications

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“…Whilst shortening the time between MDA rounds may limit reestablishment of all STH species, if a single dose of albendazole is the treatment strategy in STH MDA programmes, the prevalence of T . trichiura will not be adequately reduced [37,38]. Research is ongoing into the efficacy of co-administrations with anthelminthics such as moxidectin, ivermectin or tribendimidine to target T .…”

Section: Discussionmentioning

confidence: 99%

Soil-transmitted helminth reinfection four and six months after mass drug administration: results from the delta region of Myanmar

et al. 2019

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Background Mass drug administration (MDA), targeted at school-aged children (SAC) is the method recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds and research suggests that only treating SAC will not be sufficient to bring prevalence to low levels and possibly interrupt transmission of STH. In countries with endemic infection, such as Myanmar, the coverage, who is targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term. Methods/principal findings In this paper, data from an epidemiological study on STH, comprising three surveys conducted between June 2015 and June 2016 in the delta region of Myanmar, are analysed to determine how STH prevalence and intensity in the study community changes over the course of a year, including reinfection after two MDA rounds in which the whole study sample (all age groups, n = 523) were treated with albendazole. Prevalence in the first survey (August 2015) was 27.92% for any STH, 5.54% for Ascaris lumbricoides , 17.02% for Trichuris trichiura and 9.75% for hookworm. Over the year (survey one to survey three), prevalence of any STH decreased by 8.99% ( P < 0.001) and mean EPG significantly decreased for T . trichiura ( P < 0.01) and hookworm ( P < 0.001). Risk ratios (RRs) for a four-month reinfection period (August to December) were statistically significant and were below one, indicating that STH prevalence had not bounced back to the prevalence levels recorded immediately prior to the last round of treatment (any STH RR = 0.67, 95% CI 0.56–0.81; A . lumbricoides RR = 0.31, 95% CI 0.16–0.59; T . trichiura RR = 0.70, 95% CI 0.55–0.88; hookworm RR = 0.69, 95% CI 0.50–0.95). The only statistically significant RR for the six-month reinfection period (December to June) was for A . lumbricoides infection in SAC (RR = 2.67, 95% CI 1.37–5.21). All six-month RRs were significantly higher than four-month RRs ( P < 0.05). Evidence of predisposition to infection (low and high), as measured by the Kendall Tau-b statistic, was found for all species overall and within most age groups stratifications, except for hookworm infection in preschool-aged children. Conclusions/significance This study demonstrates that, for certain demographic groups, a six-month gap between MDA in these communities is enough time for STH infection to return to STH prevalence levels recorded immediately before the previous MDA round, and that on averag...

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Section: Discussionmentioning

confidence: 99%

Soil-transmitted helminth reinfection four and six months after mass drug administration: results from the delta region of Myanmar

et al. 2019

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“…Another possibility to increase efficacy against T. trichiura infections may be the combination treatment with albendazole or mebendazole, 41,42 which seems promising, even though the cure rates for T. trichiura infections remain moderate. 43,44 Ivermectin is, however, known to be effective against other (soil-transmitted) helminths like Ascaris lumbricoides and Strongyloides stercoralis in children 30 and adults, 45 and in lower concentrations (following a dose of 150 μg/kg) also against onchocerciasis in children and adults. 1,24,35 With the proposed dose regimen of Table 2, equivalent exposure coverage can be achieved across pediatric age groups, providing a scientific rationale for adequate ivermectin dosing which is expected to improve treatment of these types of helminthiasis.…”

Section: Discussionmentioning

confidence: 99%

Ivermectin Dosing Strategy to Achieve Equivalent Exposure Coverage in Children and Adults

Brussee

Schulz

Coulibaly

et al. 2019

Clin Pharma and Therapeutics

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Ivermectin is a commonly used broad‐spectrum antiparasitic drug, yet doses that produce consistent exposure coverage across age have not been characterized, and no data are available in children weighing < 15 kg. First, a population pharmacokinetic model is developed based on data from 200 children and 11 adults, treated with 100–600 μg/kg ivermectin. Second, model‐based simulations are performed to identify a dosing strategy that achieves equivalent exposure coverage in children and adults. Median (90% confidence interval) clearance of 0.346 (0.12–0.73) L/hour/kg in pre–school‐aged (2–5 years) children is similar to 0.352 (0.17–0.69) L/hour/kg in school‐aged (6–12 years) children but higher than in adults (0.199 (0.10–0.31) L/hour/kg), resulting in significantly lower exposure in children following a 200 μg/kg dose. Simulations indicate that a dose increase to 300 and 250 μg/kg in children aged 2–5 and 6–12 years, respectively, will achieve equivalent ivermectin exposure coverage in children and adults.

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“…[13,14] Ivermectin is also efficacious against two other neglected tropical diseases endemic in Fiji, scabies and soil-transmitted helminths (STH). [2,[15][16][17][18] A national survey of scabies in 2007 found that all age groups and regions of Fiji are affected, with an estimated national prevalence of 18.5%. [16,19] Soil-transmitted helminths are also common in Fiji with a prevalence as high as 45% in school-aged children.…”

mentioning

confidence: 99%

“…Successful treatment of scabies and STH is expected to induce mild and transient symptoms primarily pruritus (scabies) and abdominal pain (STH). [16,18] We aimed to evaluate the safety of IDA in Fiji, providing a detailed account of AEs following DA and IDA mass drug administration in Fiji and an analysis of factors associated with their occurrence including filariasis, scabies, and STH infections.…”

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confidence: 99%

The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of Fiji: A cluster randomised trial

et al. 2020

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Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-PLOS NEGLECTED TROPICAL DISEASES PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0008106 March 16, 2020 1 / 17 OPEN ACCESS Citation: Hardy M, Samuela J, Kama M, Tuicakau M, Romani L, Whitfeld MJ, et al. (2020) The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of Fiji: A cluster randomised trial. PLoS Negl Trop Dis 14(3): e0008106. https://doi.org/10.

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Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis

Cited by 95 publications

References 55 publications

Soil-transmitted helminth reinfection four and six months after mass drug administration: results from the delta region of Myanmar

Soil-transmitted helminth reinfection four and six months after mass drug administration: results from the delta region of Myanmar

Ivermectin Dosing Strategy to Achieve Equivalent Exposure Coverage in Children and Adults

The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of Fiji: A cluster randomised trial

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