Sudan Journal of Medical Sciences Volume 15, Issue no. 4, DOI 10.18502/sjms.v15i4.8172 Production and Hosting by Knowledge E Short Communication Diagnosis of Viral Diseases in Sudan: Coronaviruses Unveil the Concealed Venues Wadie M Y Elmadhoun1, Nadir Abuzeid2, Shahinaz Bedri3, and M H Ahmed4 11Department of Pathology, Faculty of Medicine, Sudan International University, Khartoum, Sudan 2Department of Microbiology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Khartoum, Sudan 3Department of Pathology, Faculty of Medicine, Ahfad University for Women, The National Public Health Laboratory, Sudan 4Department of Medicine, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, Buckinghamshire, UK Abstract Establishing the diagnosis of viral diseases often needs sophisticated settings, equipment, expertise, and strict laboratory methods. In Sudan, as in most developing countries, viral diseases are mostly diagnosed by clinical presentation. As most viral infections are self-limiting and there is no specific treatment for most of them, laboratory diagnosis has not been a focus for improvement, particularly in public sector until the current pandemic of COVID-19. During this pandemic, the vital need for well-equipped clinical virology laboratories is urged. The aim of this work is to highlight the various diagnostic methods and to describe the current situation of clinical virology diagnostics in Sudan. 1. Introduction Sudan is a developing country, having only one reference public health laboratory and four regional laboratories, with a limited diagnostic capacity and personnel [1]. Historically, many local viral outbreaks have been reported in Sudan. These include measles, polio, yellow fever, Dengue fever, West Nile, Rift Valley fever, Chikungunya, Crimean–Congo hemorrhagic fever, Ebola, Influenza Poliomyelitis, and lately the pan- demic of COVID-19 [2]. There are over 4,000 known viruses in plants, animals, and bacteria. These viruses are generally distributed in 71 families, 9 subfamilies, and 164 genera [3]. Clinical features of viral diseases are, to some extent, similar and therefore need laboratory assays to identify the causative agent. However, viral disease diagnosis is sophisticated and needs specific equipment and strict settings. In Sudan, as in most developing countries, the diagnosis of viral diseases has not been up to the level of the challenges faced. The aim of this paper is to highlight the various diagnostic modalities of viral diseases and to describe the current situation of clinical virology diagnostics in Sudan. How to cite this article: Wadie M Y Elmadhoun, Nadir Abuzeid, Shahinaz Bedri, and M H Ahmed (2020) “Diagnosis of Viral Diseases in Sudan: Coronaviruses Unveil the Concealed Venues,” Sudan Journal of Medical Sciences, vol. 15, issue no. 4, pages 455–460. DOI 10.18502/sjms.v15i4.8172 Page 455 Corresponding Author: Wadie M Y Elmadhoun; email: wadie2222@yahoo.com Received 2 December 2020 Accepted 27 December 2020 Published 31 December 2020 Production and Hosting by Knowledge E Wadie M Y Elmadhoun et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Editor-in-Chief: Prof. Mohammad A. M. Ibnouf http://www.knowledgee.com mailto:wadie2222@yahoo.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ Sudan Journal of Medical Sciences Wadie M Y Elmadhoun et al 2. Methods of Viral Disease Diagnosis Many laboratory methods are used for diagnosing viral diseases. These include electron microscopy, virus culture (also referred to as cell or tissue culture), immunological tests such as counter immunoelectrophoresis, latex agglutination, co-agglutination, immunochromtography test, enzyme linked-immunosorbent assays (ELISA), precipita- tion tests, complement fixation, immunofluorescence tests, neutralization tests, west- ern blot and line immunoassays, and antibody avidity assays. Furthermore, antigen detection, viral genome detections, and gene sequencing by molecular techniques are increasingly used in the virology laboratory. Table 1 summarizes the details about the advantages and limitations of the most common laboratory methods [4–8]. 3. Diagnostic Virology in Sudan Public health laboratories in Sudan conduct the most common tests for commonly encountered viral diseases, such as hepatitis B and C, HIV, and few screening tests for congenitally acquired viral diseases. Some tests are available only during epidemics or disease outbreaks. However, private sector laboratories may conduct some of the most uncommon tests, upon request. Table 2 summarizes the most commonly conducted laboratory tests for viral syndromes in Sudan. It is obvious that many tests for viral diseases are not available in public health laboratories in Sudan. 4. Discussion Oftentimes in large countries such as Sudan, viral infections are missed. It is difficult to establish a confident diagnosis based on clinical findings, as many viruses have similar clinical features. For example, the symptoms and signs of hepatitis can be caused by many viruses. On the other hand, a specific virus may have many different clinical presentations [9]. It is therefore essential to seek specific laboratory diagnosis to enable correct management of patient. Specific viral diagnosis is also important from an epidemiological perspective. It has been shown that even experienced clinicians are not able to clinically diagnose cases of rubella or measles correctly. A specific diagnosis of a viral infection is important, not only for the clinical management of the patient but also for the control of infection, outbreak control, and the public health perspective of continuing to ensure the efficacy of vaccination programs [10]. Diagnostic microbiology in Sudan is at a critical juncture and needs drastic improve- ment to cope with the growing healthcare complexities. Recent and emerging trends such as changing demographics, exponential growth in medical discoveries, appear- ance of superbugs are some examples. The diagnostic microbiology has to improve in better direction with best practices. There is a need for additional laboratory tests for the agents of the priority healthcare infections. Currently, there is an urgent need than ever for better viral diagnostics in the light of increased immunosuppressed individuals as a result of non-communicable diseases, chemotherapy, and the widespread use of other immunomodulant medications. DOI 10.18502/sjms.v15i4.8172 Page 456 Sudan Journal of Medical Sciences Wadie M Y Elmadhoun et al TABLE 1: Overview of viral diagnostic methods: advantages and limitations. Laboratory method Technique Assay time Advantages Limitations Viral isolation Conventional culture 1–21 days Allows isolation of many viruses; can detect unexpected or novel viruses; more sensitive than antigen detection Requires expertise to interpret CPE and maintain cell cultures; some viruses do not grow in routine cultures; biosafety concerns for zoonotic and emerging viruses Antibody detection ELISA, EIA, CLIA,IF, IC, IB, IgGavidity testing <30 min–24 hr Can document primary, recent, and past infections, and carrier states; can be automated; some tests can be done at point of care; fourth generation HIV tests combine antibody and antigen detection in one reaction Cross-reactivity between similar viruses is common (e.g., arboviruses); diagnosis often retrospective; IgM assays have moderately high false-positive rates; immunocompromised hosts may not make antibody Antigen detection IF ELISA/CLIA IC 1–2 hr < 2 hr < 30 min Can be done “on demand” as samples arrive in the laboratory; reagents available for eight respiratory and four herpesviruses; can assess sample quality Can be automated; requires less skill than IF Requires no equipment and little expertise; simply add sample and set timer; approved for use at “point of care Requires substantial expertise for accurate results; manual and labor-intensive; requires an adequate number of target cells for valid results Limited test menu Less sensitive than other methods; limited test menu NAAT Conventional PCR Real-time PCR 5–9 hr 1–5 hr Uses inexpensive conventional thermocyclers; less affected by genome variability and more amenable to multiplex testing than real-time assays Faster, less prone to cross-contamination, readily quantified; lab-developed assays can be readily updated; more commercial kits becoming available, including walk-away tests Prone to carryover contamination from amplified products since tube is opened after amplification; slower than real-time methods; ethidium bromide used for amplicon detection is toxic More prone to falsely negative or low values due to genetic variations in viral strains; lack of standardization; values obtained in different laboratories can vary by 3 Log10; limited capacity to multiplex CLIA, chemiluminescent immunoassay; CPE, cytopathic effect; CSF, cerebrospinal fluid; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; HIV, human immunodeficiency virus; IB, immunoblot; IC, immunochromatography; IF, immunofluorescent assay; IgM, immunoglobulin M; NAAT, nucleic acid amplification test; PCR, polymerase chain reaction. DOI 10.18502/sjms.v15i4.8172 Page 457 Sudan Journal of Medical Sciences Wadie M Y Elmadhoun et al TABLE 2: Common viral syndromes and availability of their diagnostic tests in Sudan. Clinical syndrome Viruses Tests available in public health laboratories in Sudan Tests not available in public health laboratories in Sudan Respiratory infections Influenza NAAT Antigen, culture Parainfluenza Antigen, culture, NAAT RSV Antigen, culture, NAAT Coronaviruses Serology, NAAT for SARS-CoV-2, antigen Serology for other coronaviruses Adenoviruses NAAT, DFA, culture Rhinoviruses NAAT Enteroviruses NAAT, culture Gastro-intestinal syndromes Rotavirus Antigen, NAAT, EM Norovirus Antigen, NAAT, EM Enteric Adenoviruses Serology, NAAT Nervous System syndromes HSV-1 Serology, NAAT Rabies Antigen detection, NAAT, culture, serology; histopathology Poliovirus NAAT. Culture Systemic infections HIV Serology, NAAT Measles Serology Culture, NAAT EBV Serology NAAT CMV Serology Culture, NAAT Chikungunya Serology NAAT Coxsackie Serology, NAAT Hepatitis HAV Serology HBV Serology, antigen, NAAT HCV Serology Serology, NAAT HDV Serology, NAAT HEV Serology, NAAT Hemorrhagic and febrile conditions Dengue Serology NAAT, culture Yellow fever Serology NAAT Ebola Serology, NAAT Rift Valley fever Serology, NAAT, Isolation Mucocutaneous, genital, congenital and other syndromes HSV-1, HSV-2 Culture, DFA, or NAAT VZV DFA or NAAT Rubella Serology, NAAT Mumps Serology, culture, NAAT CMV, cytomegalovirus; DFA, direct fluorescent assay; EBV, Epstein–Barr virus; EM, electron microscopy; HBV, hepatitis B virus; HSV, herpes simplex virus; NAAT, nucleic acid amplification technique; VZV, varicella-zoster virus. DOI 10.18502/sjms.v15i4.8172 Page 458 Sudan Journal of Medical Sciences Wadie M Y Elmadhoun et al Factors jeopardizing virology diagnostics include: sophisticated machines and tech- nical difficulties, reagent and supply chain issues, maintenance and training needs, biosafety and ethical dilemmas, and hazardous waste disposal. The outbreak of COVID-19 pandemic brought to attention the importance for invest- ing in diagnostics of emerging pathogens. In this regard, the need for infrastructure, expertise, and diagnostic tools are the most important. In addition to logistics such as guidelines for handling specimens, personal protective equipment and legislations to deal with highly hazardous pathogens are also required. Noteworthy points of paramount importance that hamper health sector improvement are: economic constraints, political instability, rapid staff turnover, and brain drain that constitute constant challenges. The collaboration between the public and private sectors to import the test needs has made it possible for any individual who seeks the diagnostic service for COVID-19 to find it available at hand, whether due to the suspicion of the disease or for travel purposes. The same approach may prove successful for other viral conditions. 5. Conclusion The diagnosis of viral diseases in public health laboratories in Sudan is beyond the challenges. Many viral diseases cannot be accurately diagnosed due to lack of the diagnostic technology and expertise. Efforts to upgrade the laboratory capacity are urgently needed. These include health policies, human and material resources, in addition to better infrastructure, protocols, and quality control measures. Ethical considerations Not applicable. Competing interests None. References [1] El-Sony, A. I., Khamis, A. H., Enarson, D. A., et al. (2002).Treatment results of DOTS in 1797 Sudanese tuberculosis patients withor without HIV co-infection. 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Booss (Eds.), Handbook of Clinical Neurology (vol. 123, 3rd series). Elsevier. DOI 10.18502/sjms.v15i4.8172 Page 460 Introduction Methods of Viral Disease Diagnosis Diagnostic Virology in Sudan Discussion Conclusion Ethical considerations Competing interests References