Review 1: "Efficacy and Safety of Albendazole 400 mg for 30 Days in Adult Patients with Low Loa loa Microfilaremia: A Non-Inferiority Randomized Controlled Trial Compared to Ivermectin"

RR\ID Evidence Scale rating by reviewer:

• Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review: This manuscript adds to a large body of literature that suggests that albendazole can in some circumstances reduce microfilarial loads in individuals infected with Loa loa.  The initial impetus for studying the effect of albendazole on L. loa microfilarial loads was to determine if albendazole pre-treatment could reduce the chances of severe adverse events resulting from mass ivermectin distribution to eliminate onchocerciasis in areas where L. loa was endemic.  This study puts a different spin on the efficacy of albendazole against L. loa, comparing the efficacy of daily treatment for 30 days with 400mg albendazole versus a single dose of ivermectin to reduce L. loa microfilarial loads. The protocol and data analysis performed by the authors follows standard clinical trial guidelines.  However, the sample size was small, reducing the power of the study to detect differences between the albendazole and ivermectin arms. Apart from the small sample size, I do have some questions regarding the design, rationale and outcome measurements of the study.

1. The authors state that albendazole might be more available to the population than ivermectin will be in a onchocerciasis post elimination era. The authors allude to the fact that onchocerciasis is no longer present in Gabon. However, the ESPEN web site indicates that ivermectin MDA for onchocerciasis in Gabon has not yet even begun.  

2. In all the onchocerciasis elimination programs I am aware of, the countries are encouraged to keep ivermectin on hand in the local clinics even after onchocerciasis has been eliminated for compassionate treatment of individuals with symptoms.  It is thus not clear to me that ivermectin will not be available to the population.

3. Why did the authors decide to use a 30 day course of daily albendazole? Other reported studies in the literature suggest a single dose of 600mg/kg significantly reduced L. loa circulating microfilaria levels, with the effect lasting up to 6 months.  It seems to me that a single dose regimen will be much easier for a poor rural population (or any population for that matter) to complete than a 30 day regimen.

4. Are the authors planning any follow-up studies to look at the effect of ivermectin and albendazole on microfilarial loads over a longer period than just 30 days?

5. To my knowledge, no one is proposing to develop an elimination campaign against loasis.  As such, it is likely that a focus should be on loasis as a disease and not transmission of the parasite.  While the authors do report a significant effect on loasis disease symptoms, the focus is on microfilarial load, which the authors acknowledge is not necessarily correlated with disease.  Again, a longer term follow-up concentrating on disease symptoms seems appropriate here.