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A pooled testing strategy for identifying SARS-CoV-2 at low prevalence

Leon Mutesa, Pacifique Ndishimye, Yvan Butera, Jacob Souopgui, Annette Uwineza, Robert Rutayisire, Ella Larissa Ndoricimpaye, Emile Musoni, Nadine Rujeni, Thierry Nyatanyi, Edouard Ntagwabira, Muhammed Semakula, Clarisse Musanabaganwa, Daniel Nyamwasa, Maurice Ndashimye, Eva Ujeneza, Ivan Emile Mwikarago, Claude Mambo Muvunyi, Jean Baptiste Mazarati, Sabin Nsanzimana, Neil Turok () and Wilfred Ndifon ()
Additional contact information
Leon Mutesa: University of Rwanda
Pacifique Ndishimye: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Yvan Butera: University of Rwanda
Jacob Souopgui: University of Rwanda
Annette Uwineza: University of Rwanda
Robert Rutayisire: University of Rwanda
Ella Larissa Ndoricimpaye: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Emile Musoni: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Nadine Rujeni: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Thierry Nyatanyi: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Edouard Ntagwabira: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Muhammed Semakula: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Clarisse Musanabaganwa: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Daniel Nyamwasa: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Maurice Ndashimye: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Eva Ujeneza: African Institute for Mathematical Sciences
Ivan Emile Mwikarago: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Claude Mambo Muvunyi: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Jean Baptiste Mazarati: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Sabin Nsanzimana: Rwanda Joint Task Force COVID-19, Rwanda Biomedical Centre, Ministry of Health
Neil Turok: African Institute for Mathematical Sciences
Wilfred Ndifon: African Institute for Mathematical Sciences

Nature, 2021, vol. 589, issue 7841, 276-280

Abstract: Abstract Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT–PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries. Cost reductions can be achieved by pooling (or combining) subsamples and testing them in groups1–7. A balance must be struck between increasing the group size and retaining test sensitivity, as sample dilution increases the likelihood of false-negative test results for individuals with a low viral load in the sampled region at the time of the test8. Similarly, minimizing the number of tests to reduce costs must be balanced against minimizing the time that testing takes, to reduce the spread of the infection. Here we propose an algorithm for pooling subsamples based on the geometry of a hypercube that, at low prevalence, accurately identifies individuals infected with SARS-CoV-2 in a small number of tests and few rounds of testing. We discuss the optimal group size and explain why, given the highly infectious nature of the disease, largely parallel searches are preferred. We report proof-of-concept experiments in which a positive subsample was detected even when diluted 100-fold with negative subsamples (compared with 30–48-fold dilutions described in previous studies9–11). We quantify the loss of sensitivity due to dilution and discuss how it may be mitigated by the frequent re-testing of groups, for example. With the use of these methods, the cost of mass testing could be reduced by a large factor. At low prevalence, the costs decrease in rough proportion to the prevalence. Field trials of our approach are under way in Rwanda and South Africa. The use of group testing on a massive scale to monitor infection rates closely and continually in a population, along with the rapid and effective isolation of people with SARS-CoV-2 infections, provides a promising pathway towards the long-term control of coronavirus disease 2019 (COVID-19).

Date: 2021
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DOI: 10.1038/s41586-020-2885-5

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