This post provides a synopsis of the PubMed paper COVID-19: The Ivermectin African Enigma. by R. Guerrero et al. (2020 Dec 30) Excerpts in italics with my bolds.

Overview

1) Why was this study conducted?
Ivermectin has been used since 1995 for the African Programme for Onchocerciasis Control (APOC). Currently, it is being considered as the possible target drug for SARS CoV-2. The low frequency of cases and deaths from the SARS-CoV-2 COVID-19 virus in some countries of Africa prompted us to assess the possible influence of this community-based strategy. (Note Onchocerciasis is commonly referred to as “river blindness.”)

2) What were the most relevant results of the study?
APOC Countries with a Community-directed treatment with ivermectin strategy show 28% lower mortality (RR= 0.72, 95% CI: 0.67-0.78) and 8% lower rate of infection (RR= 0.92, 95% CI: 0.91-0.93) due to COVID-19; compared with non-APOC countries.

3) What do these results contribute?
Our data suggest that a mass public health preventive campaign against COVID-19 may have taken place, inadvertently, in some African countries with massive community ivermectin use. Additional studies are needed to confirm it.

APOC is a partnership programme including 19 countries with active involvement of the Ministries of Health and their communities, several international and local NGDOs, the private sector (Merck & Co., Inc.), donor countries and UN agencies. The World Bank and WHO acted as Fiscal Agent as Executing Agency, respectively. A Community-Directed Treatment with Ivermectin was the delivery strategy of APOC. With the purpose of achieving sustainability, local communities were empowered to administer and distribute ivermectin in their own villages. The programme which was extended until 2015 intended to treat over 90 million people annually in the 19 countries, protecting an at risk population of 115 million, and to prevent over 40,000 cases of blindness every year 1,2. In 1998 the Program was expanded to some Asian countries to combat lymphatic filariasis and APOC countries continued to use ivermectin, in association with albendazole, in this program 3

We used generalized Poisson regression models to obtain effect estimates of APOC status on SARS-CoV-2 cumulative infection and mortality rates. The models included country characteristics to adjust for socioeconomic differences between countries that could affect their response capacity and quality to the pandemic. To measure the impact of confounding variables like health, education, and standard of living we decided to control them by using the Human Development Index (HDI)5. HDI is a geometric mean of normalized indices of the three key dimensions of human development: health, assessed by life expectancy at birth; education, measured by mean of years of schooling for adults aged ≥25 years and standard of living measured by gross national income per capita. Although it does not reflect poverty, security, empowerment, or inequalities, we consider that it is the best indicator that represents the global situation of a country.

Striking differences in the evolution of COVID-19 mortality are observed Figure 1B and APOC countries appear to have lower rates. Analysis of raw data, as shown in Table 1, indicate that APOC countries had lower infection (as indicated by lower case detection) and mortality rates due to COVID-19 (p <0.001). The ratio of mortality rates was 0.12 (95% CI: 0.12-0.13) and the ratio of infection rates was 0.16 (95% CI: 0.16-0.16), indicating that the APOC group was associated with lower mortality and infection rates compared to non-APOC countries, that is 88% and 84%, respectively. In addition, the APOC countries also had a lower number of detected cases and a lower frequency of tests.

Mortality, detection of new cases and number of tests performed were positively and significantly associated with HDI. The Figure 2 shows the COVID-19 Cumulative Mortality Rate per million in APOC countries compared with non-APOC countries.

Death rates were directly associated with HDI in all African countries, while number of infections were inversely associated in APOC countries, that is the higher the HDI the lower the expected number of infections. In African regions with HDIs above Z-score means, the expected number of deaths and infections was lower in APOC countries. In contrast, in the regions with the lowest HDI Z-score (less than 0), the estimated number of deaths and infections was lower in the non-APOC countries compared to APOC countries  (See Figure 15 at top).

No country knows with certainty the total number of subjects infected by SARS-CoV-2 within its territory, only an approximate number provided by the people who are tested; then, the number of tests performed largely determines the count of confirmed cases of the disease. In developed countries the number of tests performed can reach larger proportions of the population, like Iceland that had almost half of its population tested, 483 per thousand people7, however, on the African continent the tests performed per million inhabitants can be as low as in South Sudan 1,072 and Egypt 1,311 4.

A high HDI indicates longer life expectancy, better education and a higher standard of living. Our results coincide with others that show higher infections and death rates associated with high HDI 10,11. This can be explained because the component “life expectancy at birth is associated with a higher percentage of population >65 years. Our non-APOC group had a larger population in the >65 category and larger life expectancy (9 years) than the APOC group. That is why it is crucial to control for this confounding variable.

Mbow et al.12, analyzed the low morbi-mortality by COVID-19 in Africa compared to European countries and US, concluded that it is unlikely that it may be due to race, quality of reporting and death registration, different population age composition, lockdown stringency or other sociocultural aspects. Mbow mentions that studies of African COVID-19 patients show clear differences in the activation, proinflammatory and memory profiles of the immune cells compared not only versus Europeans but also among Africans with high and low exposure to microorganisms and parasites. Also suggest, that the virus may be spreading differently and with an attenuated outcome in Africa.

It is not known if a residual ivermectin effect increases the number of asymptomatic in the APOC countries. It is also unknown whether there are differences in susceptibility between populations of different African countries or regions. The ivermectin is considered a drug of choice for various parasitic and viral diseases and shown to have in vitro effects against SARS-CoV-2 13-16.  Although there have been suggestive clinical studies 17,18, and >50 trials are currently in progress worldwide 19. There is the need of good designed clinical trials to conclusively ascertain its benefits in humans.

Overall, the reasons are not clear, yet present data suggests that a mass public health preventive campaign against COVID-19 may have taken place, inadvertently, in some African countries with massive community ivermectin use.

For a more recent update on Ivermectin Covid effectiveness see Ivermectin Invictus: The Unsung Covid Victor