key: cord-0008299-z6a1e06s
authors: Al-Tawfiq, Jaffar A; Memish, Ziad A
title: Emerging respiratory viral infections: MERS-CoV and influenza
date: 2013-12-23
journal: Lancet Respir Med
DOI: 10.1016/s2213-2600(13)70255-8
sha: bfc0cb321a2db91722b28694fbbb21b96101cafa
doc_id: 8299
cord_uid: z6a1e06s

nan

Each year, the world faces the rising burden of viral respiratory infections. These infections are of major importance to public health because of the lack of specifi c therapeutic and preventive measures, and, more specifi cally, the lack of vaccines for most of these viruses. 1 In 2013, the emergence of three new respiratory viruses-varian infl uenza virus (H3N2v), H7N9, and Middle East Respiratory Syndrome coronavirus (MERS-CoV)-was of particular concern. These viruses all have the potential to cause widespread pandemics with substantial morbidity and mortality. The two infl uenza viruses (variant infl uenza virus and H7N9) were reported to cause, potentially severe, disease in human beings.

Infection with MERS-CoV was initially described in a patient from Saudi Arabia and then retrospectively identifi ed in patients from Zarqa, Jordan. 2,3 As of Dec 2, 2013, 163 cases of infection with MERS-CoV have been reported, with 71 fatalities. 4 MERS-CoV can cause sporadic infection, infection among families, and, of particular concern, infection among healthcare workers. 5 The largest outbreak of MERS-CoV was described in Al-Hasa, the eastern province of Saudi Arabia. 5 Fever and cough was present in most cases, with shortness of breath in almost half of all cases, and gastrointestinal symptoms in about a third. A study of the largest reported outbreak of MERS-CoV 6 estimated the median incubation period to be 5·2 days (95% CI 1·9-14·7), and reported a high rate of person-to-person transmission in 21 of 23 cases in health-care settings. 6 Case-fatality rate was high (65%) in this outbreak. 7 Of more than 417 household and health-care contacts, symptoms of MERS-CoV developed in only seven people. 6 A subsequent largescale phylogenetic analysis of 21 genome sequences and inclusion of the previous nine published MERS-CoV genomes showed that multiple introductions of MERS-CoV and lower R 0 values were possible. 7 Thus MERS-CoV has not yet reached pandemic potential. Transmission within Saudi Arabia was consistent with movement of an animal reservoir, animal products, or infected people. The source of the infection has yet to be identifi ed, although bats and camels have been implicated.

A clinical and epidemiological analysis of 47 cases showed that infection with MERS-CoV occurred predominantly in men, 5 although this fi nding did not hold after an interim analysis of 133 cases. 8 Most patients who were initially infected with MERS-CoV had underlying comorbid medical conditions and laboratory testing showed that most of these cases had raised concentrations of lactate dehydrogenase and aspartate aminotransferase associated with thrombocytopenia and lymphopenia. 5 In preparation for the Hajj this year, the largest recurring religious mass gathering worldwide, the Saudi Ministry of Health recommended that certain individuals postpone their participation. Groups particularly at risk from infection include pregnant women, children younger than 12 years, adults older than 65 years, and those with chronic or acute diseases. The concern over the pandemic potential of MERS-CoV was estimated in two recent publications. 9 In one optimistic view, 9 the estimated MERS-CoV R 0 was 0·69 compared with the R 0 for prepandemic severe acute respiratory syndromecoronavirus of 0·80. This optimistic estimate downplayed the possibility of a MERS-CoV pandemic, which supported the recommendations of the Third Meeting of the International Health Regulations Emergency Committee, 10 that MERS-CoV does not warrant international measures to curtail Hajj-related travel. Sporadic cases MERS-CoV continue to be reported, and thus continued vigilance and further studies are needed to close the knowledge gap in MERS-CoV epidemiology and clinical presentations. 5 A novel avian-origin infl uenza A virus, H7N9, was initially described in human beings in China on March 30, 2013. At that time, three patients developed fatal pneumonia and were subsequently diagnosed as infected with H7N9. 11, 12 Since this initial description, H7N9 has resulted in 139 infections and 45 fatalities. 13 Review of the initial 111 patients with H7N9 infection 14 showed a high rate of admission to intensive-care units (76·6%) with a mortality rate of 27%. Infected patients were older adults with a median age of 61 years, with twice as many men infected than women. It is also interesting to note that most patients infected with H7N9 had a pre-existing medical condition. Subsequent analysis of 136 laboratory confi rmed cases showed a mortality bias toward men older than 50 years. 15 Of the total cases, 7% were reported in individuals younger than 20 years, with no fatal cases in this age group. 15 The emergence of these viral respiratory infections (H7N9 and MERS-CoV) showed a similar initial pattern: the predominant involvement of older men and the presence of comorbid conditions in most cases. This pattern seems to be due to recognition bias, because younger cases are now being identifi ed who have no underlying medical conditions. In facing future challenges of emerging respiratory viruses such as infl uenza there is a clear need for the development of eff ective infl uenza vaccines that target the conserved antigenic structures of infl uenza virus. Continued contact of humans with animals creates an added risk of development of zoonotic diseases, adaptation of the new virus rendering it infectious to humans, and possible effi cient transmission of these viruses among the human population.

The emergence of respiratory viruses that cause signifi cant disease in human beings is a major risk to the global economy and the health of the human population. The potential eff ect of newly discovered viruses calls for a better understanding of the humananimal interface, the development of rapid diagnostic tests, and eff ective antiviral and immunomodulatory therapies. 13 The eradication of respiratory viruses is not possible and thus the development of eff ective vaccines directed against the conserved antigens of these viruses would be extremely welcome. Finding predictors of severe disease and the initiation of antiviral drugs early in the course of many respiratory viral infections might prove to be benefi cial. We declare that we have no confl icts of interest.

Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia

Middle East respiratory syndrome coronavirus (MERS-CoV) -update

Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study

Hospital outbreak of Middle East respiratory syndrome coronavirus

Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study

Taking stock of the fi rst 133 MERS coronavirus cases globally-is the epidemic changing?

Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk

WHO. WHO statement on the third meeting of the IHR Emergency Committee concerning MERS-CoV

Human infection with a novel avian-origin infl uenza A (H7N9) virus

Human infections with the emerging avian infl uenza A H7N9 virus from wet market poultry: clinical analysis and characterization of viral genome

Number of confi rmed human cases of avian infl uenza A(H7N9) reported to WHO

Clinical fi ndings in 111 cases of infl uenza A (H7N9) virus infection

Age-specifi c and sex-specifi c morbidity and mortality from avian infl uenza A(H7N9)

Although global tuberculosis control is improving, pro gress remains slow; about 1·3 million people died of tuberculosis in 2012, more deaths than from any other single infectious agent (other than HIV). 1 WHO emphasised two major challenges in 2013: identifying and treating the "missing 3 million" people who develop active tuberculosis every year and whose condition never becomes known to national tuberculosis control programmes; and the crisis of multidrug-resistant (MDR) tuberculosis, in which three of four people with MDR tuberculosis are never diagnosed, and less than half of those diagnosed are successfully treated. 1 New diagnostics, drugs, and vaccines are crucial for transformational progress. 2013 heralded both progress and disappointment in these areas. In diagnostics, progress was made in the global scale-up of Xpert MTB/RIF (Cepheid Inc, Sunnyvale, CA, USA), a molecular test for tuberculosis that also enables rapid detection of resistance to rifampicin. More than 4 million MTB/RIF cartridges had been procured under concessional pricing as of September, 2013, and a US$25·9 million UNITAID project was announced in March, 2013, for rollout in 21 countries. 2 Based on new evidence, WHO recommended in October, 2013, that Xpert MTB/RIF be used as the initial diagnostic test in adults and children with presumed MDR tuberculosis or HIV-associated tuberculosis (and, conditionally, for all forms of tuberculosis), as well as for diagnosis of certain types of extrapulmonary tuberculosis. 3 The fi rst randomised trial of Xpert MTB/RIF was published in October, 2013. 4 This pragmatic, multicentre trial of nurse-led Xpert MTB/RIF versus sputum-smear microscopy in people with symptoms of tuberculosis presenting to primary care clinics in four African countries showed Xpert MTB/RIF to be more accurate than smears and more eff ective in leading to same-day treatment initiation. However, the primary outcome of tuberculosis-related morbidity was equivalent between the two arms, as was treatment initiation by 56 days. 4 The authors postulated that this lack of diff erence in morbidity was the result of high empirical treatment rates among smear-negative individuals with ongoing symptoms. Results from additional trials in Brazil and