Research Article: COVID-19: Are Africa’s diagnostic challenges blunting response effectiveness?

Date Published: April 17, 2020

Publisher: F1000 Research Limited

Author(s): Francis Kobia, Jesse Gitaka.

http://doi.org/10.12688/aasopenres.13061.1

Abstract

Since its emergence in Wuhan, China in December 2019, novel Coronavirus disease – 2019 (COVID-19) has rapidly spread worldwide, achieving pandemic status on 11
th March, 2020. As of 1
st April 2020, COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had infected over 800,000 people and caused over 40,000 deaths in 205 countries and territories. COVID-19 has had its heaviest toll on Europe, United States and China. As of 1
st of April 2020, the number of confirmed COVID-19 cases in Africa was relatively low, with the highest number registered by South Africa, which had reported 1,380 confirmed cases. On the same date (also the date of this review), Africa had reported 5,999 confirmed cases, of which 3,838 (almost 65%) occurred in South Africa, Algeria, Egypt, Morocco and Tunisia, with the remaining 2,071 cases distributed unevenly across the other African countries. We speculate that while African nations are currently experiencing much lower rates of COVID-19 relative to other continents, their significantly lower testing rates may grossly underestimate incidence rates. Failure to grasp the true picture may mean crucial windows of opportunity shut unutilized, while limited resources are not deployed to maximum effect. In the absence of extensive testing data, an overestimation of spread may lead to disproportionate measures being taken, causing avoidable strain on livelihoods and economies. Here, based on the African situation, we discuss COVID-19 diagnostic challenges and how they may blunt responses.

Partial Text

In December 2019, a spate of pneumonia cases of unknown cause was observed in Wuhan, Hubei province, China (
He
et al., 2020). Soon after, the causative agent for the novel illness was found to be a novel Coronavirus (2019-nCoV) (
Lu
et al., 2020;
Zhou
et al., 2020;
Zhu
et al., 2020). Coronaviruses (CoVs), are a large group of viruses that frequently cause mild respiratory disease in humans, including common cold (
Saif, 2004;
NIAID, 2020). Hundreds of coronaviruses exist in wild and domestic animals. In the last 20 years, 3 highly infectious CoVs have crossed from animals into humans through spillover events and spread globally, causing severe respiratory illnesses (
Andersen
et al., 2020;
Cui
et al., 2019). In November 2002, severe acute respiratory syndrome (SARS), a novel respiratory disease emerged in China and rapidly moved to other countries. Its causative agent was identified as a CoV and named SARS-CoV (
Drosten
et al., 2003;
Fung & Liu, 2019). The SARS mini pandemic infected over 8,000 people and caused almost 800 deaths (
Cherry, 2004). In 2012, a novel respiratory disease, named Middle East respiratory syndrome (MERS), was identified in Saudi Arabia and the causative agent identified as MERS-CoV (
de Groot
et al., 2013;
Zaki
et al., 2012). To date, MERS is estimated to have infected over 2,000 people and caused over 700 fatalities (
Ramadan & Shaib, 2019;
WHO, 2017). In December 2019, a novel respiratory disease presenting with severe unexplained pneumonia emerged in Wuhan, Hubei province – China (
Huang
et al., 2020;
Zhu
et al., 2020). Its causative agent was quickly identified as a novel CoV (2019-nCoV), which was named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) (
Lu
et al., 2020;
Zhou
et al., 2020). The disease caused by SARS-CoV-2 was named COVID-19 by the WHO (
WHO, 2020e). COVID-19 then rapidly spread within China, where it infected over 82,000 people and caused more than 3,000 fatalities, mainly in Hubei province (
WHO, 2020b). The disease’s spread accelerated globally, prompting the WHO to declare it a global pandemic on 11
th March 2020 (
Bedford
et al., 2020). As of 1
st April 2020, over 800,000 COVID-19 cases and more than 40,000 COVID-19-associated deaths had been confirmed in 205 countries and territories. Europe and North America are currently the continents most affected by COVID-19. So far, Africa has reported the lowest number of confirmed COVID-19 cases (
WHO, 2020b). As of writing, 5,999 COVID-19 cases have been reported in Africa with South Africa reporting the highest number. 5 countries (South Africa, Tunisia, Morocco, Egypt, and Algeria) account for close to 65% (3,838 cases) of the confirmed cases, with the remainder being unevenly distributed in the rest of the continent. Within the East African community, there have been a total of 222 confirmed cases (
African Arguments, 2020;
WHO, 2020b).

SARS-CoV2, is an enveloped single stranded positive sense RNA virus belonging to the family
Coronaviridae and genus Betacoronavirus (
Lai
et al., 2020). The SARS-CoV-2 virion ranges between 50-200nm in diameter and houses a 29,881 bp genome (
Chen
et al., 2020a;
Chen
et al., 2020b). Among other genes, the SARS-CoV-2 genome encodes 4 structural proteins named spike (S), envelope (E), membrane (M) and nucleocapsid (N). The N protein holds the viral genome while S, M and E construct the viral envelope, where S mediates viral entry into the host cell (
Wu
et al., 2020). SARS-CoV-2 is easily transmissible. According to the WHO, the main mode of COVID-19 transmission is direct/indirect human-human contact, where the virus is transmitted in respiratory droplets or via contact routes. Droplet transmissions happen when one gets into close proximity, (typically within a meter) with an individual exhibiting respiratory symptoms, such as sneezing or coughing. Indirect transmission may occur when one touches objects handled by an infected individual and then touches their mouth, nose or eyes. Transmission has also been reported to occur via airborne droplet transmission. In such cases, the virus is contained in droplet nuclei, which are typically <5µm in diameter and can remain airborne for extended periods. Airborne transmission can occur over distances beyond 1 meter but such nuclei are typically generated by processes that generate aerosols, usually patient care procedures ( WHO, 2020d). As such, social distancing, rigorous hand washing, and avoiding touching the face have been recommended as means of minimizing transmission risk ( WHO, 2020a). Once SARS-CoV-2 has gained access to the host’s respiratory mucosa, it enters the host cells through an interaction between its S protein and the host cell’s ACE2 (angiotensin-converting enzyme 2) receptors ( Hoffmann et al., 2020). Unlike other coronaviruses that cause upper respiratory tract disease only, SARS-CoV-2 is capable of colonizing the lower respiratory tract as well ( Heymann & Shindo, 2020). After infection, the virus incubates for a median period of about 5 days before the onset of symptoms and almost all infections become symptomatic by day 11 ( Lauer et al., 2020; Rothan & Byrareddy, 2020). Symptoms include fever, fatigue, headache, dry cough, diarrhea and lymphopenia. While most patients experience mild symptoms that they overcome without need for hospital care, some experience serious complications including severe pneumonia, acute respiratory distress syndrome (ARDS), acute cardiac injury and acute ground glass opacity (GGO) that may necessitate life support ( Heymann & Shindo, 2020; Rothan & Byrareddy, 2020). COVID-19 diagnostic testing is recommended for individuals that satisfy the suspect case definition ( Leitmeyer et al., 2020). According to the WHO organization, the decision to test should be based on clinical signs, epidemiological factors and the possibility of infection ( Leitmeyer et al., 2020), such as contact with an infected individual. The WHO ( WHO, 2020c) defines a suspect case as one that: In addition to suspect case diagnosis, widespread COVID-19 testing is critical for disease monitoring and surveillance. Such testing is recommended so as to meet the following objectives ( WHO, 2020c): The benefits of large-scale COVID-19 testing have been demonstrated in several countries. However, most low-middle income countries (LMICs), including the majority of African countries, lack capacity for large scale testing. These countries are facing numerous challenges in their efforts to diagnose suspect cases, trace contacts for further testing and roll out surveillance testing. For instance, as a consequence of inadequate testing capacity, at the time of preparing this review Kenya had carried out 2,563 tests only, of which 122 returned positive ( MOH - Kenya, 2020). While Kenya’s ministry of health has indicated it is embarking on mass testing ( Xinhua, 2020), many challenges remain, including test kit shortages that have been reported in many parts of Africa ( VOA, 2020) as a result of high global demand. COVID-19 diagnostic challenges are not unique to African countries and LMICs. Consequently, numerous private and public institutions have developed rapid diagnostic tests (RDTs) aimed at speeding and expanding testing, crucial factors in the struggle to slow COVID-19 spread. RDTs, which are largely based on immunoassays, may be direct, through detection of SARS-CoV-2 antigens or indirect, through detection of anti-SARS-CoV-2 antibodies ( ECDC, 2020). Advantages of RDTs include ease of use as they do not require special equipment or highly trained personnel and stability at room temperature, removing the need for constant refrigeration/freezing. RDTs are therefore highly suited for point of care diagnosis (POCD) and are highly amenable to deployment in low resource settings, removing the need for sample transportation. Several COVID-19 RDTs, capable of giving results in 10-30 minutes are now commercially available or in development ( ECDC, 2020). In many African contexts, RDTs would reduce the time needed to get test results from days to minutes. Therefore, RDTs offer a means to aggressively deploy mass testing across Africa. However, the cost of RDTs for mass testing may still be prohibitively high, calling for homegrown solutions. Evidently, COVID-19 testing by RT-PCR is not applicable in most parts of Africa considering that vast populations live in rural settings with poor transport and communication infrastructure. RT-PCR requires expensive equipment, skilled personnel, reagents and reliable power supplies. Additionally, the long turnaround time of 4-24 hours (and days in some contexts) ( NPR, 2020), may discourage many from seeking tests. Thus, there is an urgent need for deployable, COVID-19 point of care tests satisfying the ASSURED requirements of an ideal diagnostic test. Meaning that such tests should be Affordable, Sensitive, Specific, User-friendly, Rapid, Equipment-free, and Delivered to those in need ( Mabey et al., 2004; Urdea et al., 2006). Efficient and accurate testing will enable early diagnosis of Covid-19 for timely clinical care and tracing of contacts for isolation and quarantine measures. The need for prompt reliable testing is made dire by findings that COVID-19 positive people with mild or no symptoms may actually harbor high viral loads in the throat and may transmit it by ‘viral shedding’ ( Woelfel et al., 2020). COVID-19 has severely tested the adequacy of global diagnostic preparedness and ability to rapidly develop point of care tests for emerging infections. The prompt release of SARS-Cov-2 whole genomic sequence data by Chinese scientists helped with development of RT-PCR protocols that have been used worldwide. However, as the pandemic evolves, it is increasingly important to develop point of care tests that will facilitate proper last mile epidemiology, inform treatment and public health interventions. These POC tests will leverage available molecular platforms such as CRISPR, or be based on antigen or antibody detection. Critically, it should be understood that these strategies have inherent merits and demerits and synergy will only be achieved where all are used appropriately. Additionally, the COVID-19 pandemic has highlighted the need for development and growth of in-continent POC diagnostics development capacity ranging from assay development, device fabrication, prototyping, validation, implementation research and entrepreneurial ecosystems including venture capitalization and regulation.   Source: http://doi.org/10.12688/aasopenres.13061.1

 

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