However, these unmeasured confounders would have to be strongly associated with Covid-19 mortality to explain the observed 28% reduction. Colebunders that other factors could explain the observed association between APOC countries and COVID-19 mortality. Our study was an ecological study prompted by the low frequency of cases and deaths from the SARS-CoV-2 COVID-19 virus in some African countries. Colebunders for his comments regarding our manuscript 11. Helminth infections, such as onchocerciasis, may down regulate immune responses 9 and potentially inactivate the inflammatory signalling pathways that may induce acute respiratory distress syndrome (ARDS), one of the causes of death in COVID-19 infected persons 10. falciparum infection against severe COVID-19 disease 8. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis and therefore may protect persons with a recent P. falciparum, a parasitic infection highly prevalent in APOC countries, it has been hypothesised that the immunological memory against P. One of them could be exposure to parasitic infections and the immune response induced by these infections. Many factors could explain the lower COVID-19 mortality in APOC countries 7. Given the half-life of ivermectin, approximately 18h 6, it is unlikely that CDTI, only one dose of ivermectin once or twice a year, may be able to reduce COVID-19 related mortality. However, in a recent small double blind, randomized control trial in Colombia, five days of ivermectin, at a 10 times the recommended dose, did not reduce the duration of symptoms of mild COVID-19 disease compared to placebo 5. Ivermectin has an in vitro anti-COVID-19 effect 3 and also certain clinical trials suggested a beneficial effect of ivermectin on COVID-19 disease outcome 4. Moreover, April 1 st 2020, because of the COVID-19 pandemic, CDTI programs were interrupted and were only recently restarted 2. Indeed, in APOC countries ivermectin is distributed only once (most countries) or twice a year 2. However, we do not believe that this is related to CDTI programs. We agree that it remains to be explained why a lower COVID-19 mortality is observed in many APOC countries compared to other parts of the world. The authors suggested that this difference may be related to the community directed treatment with ivermectin (CDTI) programs established in APOC countries. After adjusting for Human Development Index (HDI) and number of performed test, COVID-19 mortality and infection rate were respectively 28% and 8% lower in non-APOC countries compared to APOC countries 1. In an ecological study they compared COVID-19 related mortality and infection rates between APOC (African Programme for Onchocerciasis Control) and non-APOC countries. We read with interest the paper by Guerrero et al “COVID-19: The Ivermectin African Enigma” 1.
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