COVID-19 and malaria: A symptom screening challenge for malaria endemic countries

The unprecedented global coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2 has rapidly spread to all continents (WHO, 2020aWHO Public health round-up WHO.Bull World Health Organ. 2020; 98: 155-156https://doi.org/10.2471/BLT.20.010320Crossref PubMed Scopus (2) Google Scholar). Whilst spread to Africa has been slow, there are now increasing numbers of COVID-19 being reported from African countries who are preparing themselves (Kapata et al., 2020Kapata N. Ihekweazu C. Ntoumi F. et al.Is Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic, lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future.Int J Infect Dis. 2020; 93 ([Published online ahead of print, 28 February 2020]): 233-236https://doi.org/10.1016/j.ijid.2020.02.049Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar) for an exponential rise in numbers of cases. As of 26th April 2020, there have been 2,804,796 confirmed COVIDD-19 cases reported to the WHO with 193,710 deaths. In Africa there have been 20,316 cases with 839 deaths reported from 49 countries (WHO, 2020bCoronavirus disease (COVID-2019) situation reports. WHO 2020b. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200426-sitrep-97-covid-19.pdf?sfvrsn=d1c3e800_6 (accessed 27th April, 2020.Google Scholar). In comparison, the WHO malaria report indicates that there were an estimated 228 million cases and 405,000 deaths due to malaria globally in 2018, majority of which were from the Africa region (WHO, 2020cWHO: Malaria factsheet.2020Google Scholar). COVID-19 currently imposes an additional burden to the already overstretched, resource strapped health services which are grappling to bring under control the high burden of existing infectious and non-infectious diseases, including TB, HIV, and malaria. Proactive screening for COVID-19 is ongoing in high malaria endemic African countries. A case of COVID-19 is deemed ‘confirmed’ based on a positive laboratory test result for SARS-Cov-2 virus infection regardless of symptoms (WHO, 2020bCoronavirus disease (COVID-2019) situation reports. WHO 2020b. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200426-sitrep-97-covid-19.pdf?sfvrsn=d1c3e800_6 (accessed 27th April, 2020.Google Scholar). Health care workers and community members alike are faced with an important challenge of quickly identifying symptoms and taking appropriate steps for laboratory investigation in line with the case definition based on surveillance or clinical characterisation (WHO, 2020aWHO Public health round-up WHO.Bull World Health Organ. 2020; 98: 155-156https://doi.org/10.2471/BLT.20.010320Crossref PubMed Scopus (2) Google Scholar). Key steps to identifying a COVID-19 case ultimately involves symptomatic or high risk patients presenting to health providers with complaints of any of the following symptoms or travel history: fever, cough, shortness of breath, fatigue, headache and others of acute onset or history of travel to affected areas or contact with an infected person. Thus, current screening approaches for COVID-19 are likely to miss approximately 50% of the infected cases even in countries with good health systems and available diagnostic capacities (Gostic et al., 2020Gostic K. Gomez A.C. Mummah R.O. Kucharski A.J. Lloyd-Smith J.O. Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19.ELife. 2020; 9 ([Published 24 February 2020]): e55570https://doi.org/10.7554/eLife.55570Crossref PubMed Scopus (234) Google Scholar). Malaria shares some of the highly recognisable symptoms with COVID-19 such as: fever, difficulty in breathing, fatigue and headaches of acute onset. Thus, a malaria case may be misclassified as COVID-19 if symptoms alone are used to define a case during this emergency period and vice versa. Malaria symptoms appear within 10-15 days after an infective bite; multi-organ failure is common in severe cases among adults while respiratory distress is also expected in children with malaria, mimicking what is usually reported in patients with COVID-19 (WHO, 2020cWHO: Malaria factsheet.2020Google Scholar, White et al., 2014White N.J. Pukrittayakamee S. Hien T.T. Faiz M.A. Mokuolu O.A. Dondorp A.M. Malaria.Lancet. 2014; 383: 723-735Abstract Full Text Full Text PDF PubMed Scopus (796) Google Scholar). Human travel history is also a significant consideration, like with COVID-19, when screening for a suspected case of malaria as well as a means of curbing transmission (Tatem and Smith, 2010Tatem A.J. Smith D.L. International population movements and regional Plasmodium falciparum malaria elimination strategies.Proc Natl Acad Sci U S A. 2010; 107: 12222-12227Crossref PubMed Scopus (137) Google Scholar, Chuquiyauri et al., 2012Chuquiyauri R. Paredes M. Peñataro P. Torres S. Marin S. Tenorio A. et al.Socio-demographics and the development of malaria elimination strategies in the low transmission setting.Acta Trop. 2012; 121: 292-302Crossref PubMed Scopus (51) Google Scholar). Also, both COVID-19 and malaria infected individuals may be asymptomatic for a long time while transmitting the infections through their respective modes (Nishiura et al., 2020Nishiura H. Kobayashi T. Yang Y. Hayashi K. Miyama T. Kinoshita R. et al.The rate of underascertainment of novel coronavirus (2019-nCoV) Infection: estimation using Japanese passengers data on evacuation flights.J Clin Med. 2020; 9: 419https://doi.org/10.3390/jcm9020419Crossref Scopus (166) Google Scholar, Chourasia et al., 2017Chourasia M.K. Raghavendra K. Bhatt R.M. et al.Additional burden of asymptomatic and sub-patent malaria infections during low transmission season in forested tribal villages in Chhattisgarh, India.Malar J. 2017; 16: 320https://doi.org/10.1186/s12936-017-1968-8Crossref PubMed Scopus (17) Google Scholar). Globally, all countries are at very high risk of COVID-19 while half of the world is at risk of malaria, with sub-Saharan countries bearing the blunt of malaria cases and deaths while South East Asia remain at high risk of both malaria and COVID-19 (WHO, 2020bCoronavirus disease (COVID-2019) situation reports. WHO 2020b. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200426-sitrep-97-covid-19.pdf?sfvrsn=d1c3e800_6 (accessed 27th April, 2020.Google Scholar, WHO, 2020cWHO: Malaria factsheet.2020Google Scholar). Although in sub-Saharan Africa the scale of the COVID-19 outbreak is relatively lower than other regions, there are concerns that the situation may prove difficult with time considering the already weak health systems in the region (Sambo and Kirigia, 2014Sambo L.G. Kirigia J.M. Investing in health systems for universal health coverage in Africa.BMC Int Health Hum Rights. 2014; 14 ([Published 28 October 2014]): 28https://doi.org/10.1186/s12914-014-0028-5Crossref PubMed Scopus (44) Google Scholar). Thus COVID-19 and malaria converge symptomatically and geographically in most WHO regions. The definitive way to correctly identify the underlying infectious aetiology is through laboratory investigation and therefore availability of appropriate diagnostic capacity is essential for accurate surveillance and clinical management of cases. Currently, it is expected that a high index of suspicion is skewed towards COVID-19 given the alertness at community, health centre, country, regional and global level. In addition, another challenge is that people with fever may preferentially get tested for COVID-19 and sent home due to a negative result and conversely febrile patients may get tested for malaria when they may in fact have COVID-19 infection. The other case scenario is that patients may have malaria and COVID-19 co-infection and diagnosis and treatment of one may lead to missing the other. A single case of COVID-19 has the potential to transmit up to 3.58 susceptible individuals (Chen et al., 2020aChen T.M. Rui J. Wang Q.P. Zhao Z.Y. Cui J.A. Yin L. A mathematical model for simulating the phase-based transmissibility of a novel coronavirus.Infect Dis Poverty. 2020; 9 ([Published 28 February 2020]): 24https://doi.org/10.1186/s40249-020-00640-3Crossref PubMed Scopus (531) Google Scholar). Untreated malaria on the other hand has the potential to cause further community infections which in turn continues to be a significant source of illness and deaths globally (WHO, 2020cWHO: Malaria factsheet.2020Google Scholar, Challenger et al., 2019Challenger J.D. Gonçalves B.P. Bradley J. et al.How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study.BMJ Glob Health. 2019; 4 ([Published 10 December 2019]): e001856https://doi.org/10.1136/bmjgh-2019-001856Crossref PubMed Scopus (9) Google Scholar, Chen et al., 2016Chen I. Clarke S.E. Gosling R. et al.“Asymptomatic” malaria: a chronic and debilitating infection that should be treated.PLoS Med. 2016; 13: e1001942https://doi.org/10.1371/journal.pmed.1001942Crossref PubMed Scopus (213) Google Scholar). Thus undetected COVID-19 virus and malaria parasite infections pose an immediate health challenge to the individual and public health consequences for the community (WHO, 2020bCoronavirus disease (COVID-2019) situation reports. WHO 2020b. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200426-sitrep-97-covid-19.pdf?sfvrsn=d1c3e800_6 (accessed 27th April, 2020.Google Scholar, WHO, 2020cWHO: Malaria factsheet.2020Google Scholar, Challenger et al., 2019Challenger J.D. Gonçalves B.P. Bradley J. et al.How delayed and non-adherent treatment contribute to onward transmission of malaria: a modelling study.BMJ Glob Health. 2019; 4 ([Published 10 December 2019]): e001856https://doi.org/10.1136/bmjgh-2019-001856Crossref PubMed Scopus (9) Google Scholar). Furthermore, there is concern that limited mobility and lockdowns, will interrupt the supply of malaria drugs. There is no specific treatment available for CVOID-19. Host-directed therapies including repurposed drugs such as anti-retrovirals zinc, nutraceuticals, chloroquine, hydroxychloroquine are being considered (Gautret et al., 2020Gautret P. Lagier J.C. Parola P. et al.Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.Int J Antimicrob Agents. 2020; ([Published online ahead of print, 20 March 2020]): 105949https://doi.org/10.1016/j.ijantimicag.2020.105949Crossref PubMed Scopus (3586) Google Scholar, Zumla et al., 2020Zumla A. Ippolito G. Ntoumi F. et al.Host-directed therapies and holistic care for tuberculosis.Lancet Respir Med. 2020; (S2213-2600(20)30078-3 [Published online ahead of print, 27 February 2020])https://doi.org/10.1016/S2213-2600(20)30078-3Abstract Full Text Full Text PDF Scopus (10) Google Scholar). What is required for Africa is a low cost, safe, orally administered therapeutic which can reduce morbidity, mortality and duration of illness. The preliminary data on the use of chloroquine/azithromycin were encouraging (Gautret et al., 2020Gautret P. Lagier J.C. Parola P. et al.Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.Int J Antimicrob Agents. 2020; ([Published online ahead of print, 20 March 2020]): 105949https://doi.org/10.1016/j.ijantimicag.2020.105949Crossref PubMed Scopus (3586) Google Scholar), although the trial was not randomised or controlled. Conversely a small controlled study published from China showed no significant effect (Chen et al., 2020bChen J.L.L. Liu L. Liu D. et al.A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19).J Zhejiang Univ (Med Sci). 2020; 49: 0-60http://www.zjujournals.com/med/Y2020/V49/I1/0Google Scholar). Several large randomised trials are now underway and these will determine the usefulness of chloroquine for COVID-19 treatment. Countries are struggling to meet the testing demand for COVID-19, while the malaria test kits are widely available at each point of care including the community level. There is need therefore for enhanced sensitisation on the potential of COVID-19/malaria co-infections and further guidance to clinicians on the importance of testing for other causes of illness more so in this period when there is much emphasis to early detect and isolate COVID-19 in a bid to contain further spread of the disease. Since malaria tests are relatively more available (Landier et al., 2016Landier J. Parker D.M. Thu A.M. et al.The role of early detection and treatment in malaria elimination.Malar J. 2016; 15 ([Published 15 July 2016]): 363https://doi.org/10.1186/s12936-016-1399-yCrossref PubMed Scopus (77) Google Scholar), we recommend that health workers perform rapid tests for malaria as they screen for COVID-19. This presents an opportunity to respond to two infectious diseases timely and reduce unnecessary morbidity and deaths. By rapidly ruling out malaria, the health workers can focus on the true cause of illness and administer appropriate management. The health and economic benefits/consequences in a real setting will provide valuable lessons for planners, clinicians, funders and governments on integrated management of infectious diseases. This issue is more relevant for travellers and people in malaria endemic countries as this is a season when malaria transmission is at its peak in sub-Saharan Africa (Wang et al., 2020Wang J. Xu C. Wong Y.K. et al.Preparedness is essential for malaria-endemic regions during the COVID-19 pandemic.Lancet. 2020; (S0140-6736(20)30561-4 [Published online ahead of print, 16 March 2020])https://doi.org/10.1016/S0140-6736(20)30561-4Abstract Full Text Full Text PDF Scopus (57) Google Scholar). The Global Fund has already issued a guidance as of 4th March 2020 urging countries to ‘reprogram savings from existing grants and to redeploy underutilized resources to mitigate the potential negative consequences of COVID-19 on health and health systems’ (The Global Fund, 2020The Global Fund, 2020. Available from: https://www.theglobalfund.org/en/news/2020-03-04-global-fund-issues-new-guidance-in-response-to-covid-19/ [Accessed 16 March 2020].Google Scholar). On an operational level, countries should look at how services for malaria and COVID-19 are organised so as to efficiently use the available resources. For instance, malaria supplies could be moved to the laboratories or sites where the COVID-19 testing is being done so as to reduce missed opportunities for malaria testing as some patients may be lost if they are declared COVID-19 negative while in fact they may be malaria positive. The rollout of rapid malaria diagnostic tests (Cunningham et al., 2019Cunningham J. Jones S. Gatton M.L. et al.A review of the WHO malaria rapid diagnostic test product testing programme (2008–2018): performance, procurement and policy.Malar J. 2019; 18 ([Published 02 December 2019]): 387https://doi.org/10.1186/s12936-019-3028-zCrossref PubMed Scopus (69) Google Scholar), together with point of care tests for COVID-19 (Nguyen et al., 2020Nguyen T. Duong Bang D. Wolff A. 2019 novel coronavirus disease (COVID-19): paving the road for rapid detection and point-of-care diagnostics.Micromachines (Basel). 2020; 11 ([Published 14 March 2020]): E306https://doi.org/10.3390/mi11030306Crossref PubMed Google Scholar) when they are rolled out should be a priority. The reorganisation of services at health facility level has been a useful approach in TB/HIV collaborative activities (Burnett et al., 2018Burnett S.M. Zawedde-Muyanja S. Hermans S.M. Weaver M.R. Colebunders R. Manabe Y.C. Effect of TB/HIV integration on TB and HIV indicators in rural Ugandan health facilities.J Acquir Immune Defic Syndr. 2018; 79: 605-611https://doi.org/10.1097/QAI.0000000000001862Crossref PubMed Scopus (9) Google Scholar). There is a possibility that lymphopenia seen in patients with COVID-19 may increase vulnerability to malaria, TB and other infections. As the world commemorates world malaria day on 25th April, 2020 in the midst of the COVID-19 pandemic, the challenge still remains on how to ensure the progress made in malaria control is not setback. None declared. All authors have a specialist interest in emerging and re-emerging pathogens. Dr. Nathan Kapata and Sir Prof. Alimuddin Zumla are members of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET – https://www.pandora-id.net/) funded by the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Programme for Research and Innovation. Sir Zumla is in receipt of a National Institutes of Health Research senior investigator award.