Review 2: "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:

• Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: Since the conclusion of the onchocerciasis control program activities in Gabon, ivermectin (IVM) is not readily accessible to physicians and their patients. In Gabon, most loiasis patients have low Mf (< 8000 mf/mL) and reside in rural areas. The rural populations lack easy access to IVM and have limited financial resources to afford medical treatment. Clinically, low or absent Mf is often associated with frequent symptoms such as Calabar swellings. It would be beneficial for these populations to assess whether Albendazole (ALB), an inexpensive medication, could be used for curative purposes in patients with low Mf as an alternative to IVM. While several studies have highlighted the microfilaricidal effect of ALB, they underscore the lack of a standardized protocol for treating microfilaremic loiasis. This study aims to evaluate the efficacy and safety of ALB 400 mg daily for 30 days in adult patients compared to single dose IVM 200 mm per kg for treating infected patients in Gabon. The manuscript is well written with clear objectives and methodology, and the results are presented with appropriate statistical analysis. The derived conclusions are supported by the results. However, the authors need to make minor addition / deletion on the derived conclusions in the Abstract (pl. see below). I would recommend the manuscript for publication with minor revision. 

Minor comments:

• LL 31-32: “Eligible individuals were randomized into two treatment groups and followed for 30 days”. Rephrase the sentence qualifying eligible individuals, e.g. individuals with Mf-load < 8000 mf/mL, etc.

• LL 32-33: Please insert “for 30 days” after “albendazole tablets (400 mg)”.

• LL 33-34: Also, please give mean Mf-density prior to treatment in community.

• LL 37-38: Please add a sentence to indicate that “The 95% CI for the risk difference for both per-protocol and intent-to treat analysis did not exceed the non-inferiority margin of 20%”. Also, add a sentence on the safety of ALB and IVM.

• LL 42-43:

  • “….. and seems to diminish at very low microfilarial loads”. This is not clear, as the statement is supported with data. Needs more data analysis comparing the reductions between groups at each Mf-category.

  • The conclusion needs rewriting as shown here:” The prevalence of Loa loa infection (33.05%) is notably high in northern Gabon. Albendazole demonstrated less microfilaricidal effect than IVM in individuals with low Loa loa microfilaremia. However, as ALB is safe and non-inferior to IVM, it could be a viable alternative to IVM for curative treatment of rural populations lacking easy access to IVM and limited financial resources.”

• L 92: replace “survey” with “study”

• L 101: delete “survey”

• LL 133-135: Delete the sentence beginning with “Blood samples were collected……”, as it is repeated in the subsequent sections.

• LL 171: “assuming a first-species risk of 5.0% and a second-species risk of 10.0%”. This is not clear. What do the authors mean by “first-species risk of 5.0% and a second species risk of 10.0%. How were the species risk data used in the sample size calculation?

• Fig 1: The total microfilaraemic is 406. Among these 48 met the inclusion criteria, and the remaining did not meet the inclusion criteria should be 358. In the figure, it is given as 394. Please check and correct.

• Table 1: please check and correct the “n” for ALB. It should be 24 not 22.

• Please add “, range” within parentheses after “mf/ml” in the row for “Microfilaremia (mf/mL)” and after “%” in “Eosinophil rate (%)”

• Please give the ‘n’ for each Mf-category for the two treatment groups. Whether the reductions in Mf in each Mf-category is comparable between treatment groups. Please compare the reductions between treatment groups by Mf-category.

• L258: Insert “single dose” before IVM

• LL 264, 269 & 287: replace “monthly treatment” with “30-day treatment”

• L297: Replace “inferiority” with “non-inferiority”