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While it is unclear exactly how MERS is contracted, it is likely to spread via an infected person’s respiratory secretions like other coronaviruses. To date, there has not been widespread sustained community human-to-human transmission. It appears that close contact with an infected person is necessary for disease transmission. Close contact is defined as encountering a patient without appropriate protective gear within six feet or being in a care room for prolonged periods or having direct exposure to infected secretions. Healthcare facilities have reported spread from person-to-person much more so than in communities, possibly when suboptimal infection control was practiced for patients with higher viral loads than those not hospitalized.7
Reported cases have been linked to countries in and near the Arabian Peninsula either for persons who live in, have traveled to, or have had contact with an infected person who had been in the region. MERS is a zoonotic virus that is transmitted from animals to humans. It is believed to have originated in bats and then to have been transmitted to camels sometime in the distant past. According to epidemiologic and surveillance data, there is a strong likelihood that dromedary (one-hump) camels (Figure 2) serve as a reservoir for zoonotic transmission of the virus to humans.8 This has resulted in warnings to avoid close contact with camels and not drink raw camel milk or urine, or ingest raw camel meat.
Health care-associated infections have become more common and more complex. They are associated with significant morbidity, mortality, and cost. However, the dangerous are not just for patients. A total of 1706 (up to 20%) health care workers (HCWs) were infected in the outbreak of SARS between 2002 and 2003 in China and worldwide, a nightmare in the memories of HCWs who survived over the crisis. Will the nightmare be back again? The early symptoms of MERS are nonspecific and thus MERS patients are not always able to be identified and isolated early, HCWs are at high risk of acquiring this contagious infection while caring for patients or handling with human biologic material (respiratory secretions, blood, urine, or feces). In addition to that, unlike SARS-CoV, the infectors could be asymptomatic or sub-clinical, these cases could contribute to the transmission between patients and HCWs, and thus increase the risk of MERS-CoV infections hugely, as observed in previous study about MERS-CoV clusters, which showed that the relative contribution of hospital-based transmission is over 4 times higher than that of community transmission.
HCWs and patients would all be victims of health care-associated infections without strengthening awareness of contagious respiratory diseases in HCWs and general public. We strongly suggest plus droplet precautions (such as negative-pressure ventilating room, if not available, masking the patient, placing the patient in a private room with the door closed, and providing N95 or higher level respirators or masks to HCWs, etc.) to the standard precautions (e.g., hand hygiene, use of personal protective equipment) when providing care to any patient with symptoms of acute febrile respiratory infection. A better understanding of how HCWs are infected in health care settings is urgently needed. In addition to appropriate infection control procedure, early and rapid detection of suspected pathogen and qualified laboratories for assaying the potential contaminated clinical specimens are needed crucially.
Prevention of MERS-CoV transmission involves avoiding exposure. Travelers to regions where MERS has been detected should avoid close contact with potentially infected persons or dromedary camels. Healthcare personnel must practice strict standard, contact, and airborne precautions while caring for patients under investigation (including symptomatic close contacts) as well as patients with probable or confirmed MERS infections. Laboratory workers and others collecting and handling specimens for potential MERS patients should adhere to the same guidelines. Adequate respiratory protection is particularly important when performing aerosolizing procedures.
As a zoonotic disease, the exact way in which MERS-CoV transmits between different species is still unknown. Previous studies support that dromedary camels serve as the primary animal source and major reservoir, while bats may be the ultimate reservoir of the virus. But the time of initial infection in bat species and the way of the virus transmitted to camels have yet to be determined. Serological evidence shows that MERS-CoV has infected camels for at least 20 years, whereas the virus appear to have spread from camels-to-humans in the early 2010s. Camels-to-human transmission is through close contacts with camels or consumption of camel products. However, while camels appear as the likely source, other sources have not been ruled out. For example, except the history of visit to the middle east, the index case of South Korea was confirmed with no close contact with camel, no health care facility visit history, and no camel products consumption history, according to the investigation of WHO. There still could be another or some more common intermediate host exists.
The primary pattern that MERS spread among human being is close person-to-person contacts via droplets from patients, contaminated surfaces or equipment, and aerosol generated during aerosol-generating procedures. Nosocomial and home-based transmission have both occurred and have been proved by genome deep sequencing data in the past 3 years. MERS-CoV infection associated with considerable mortality (35.6%, as of June 26, according to data of WHO), especially in individuals with underlying comorbidities, such as diabetes, renal failure, chronic lung disease, and immunocompromised status. Fortunately, it does not seem to have the ability of sustainable human-to-human transmission. The basic reproduction number of MERS-CoV, Ro is <1 in early studies, which indicated the self-limited transmission and persistence of the disease requires continued animal-to-human infections. But the possibility of epidemic also had been warned because of the limited data, the potential impact of stringent control measures which had already been taken, and the assumption authors made that asymptomatic patients do not transmit infection. The ongoing outbreak in South Korea might confirm their fear. As of June 30, 2015, the Health Ministry of South Korea revealed 182 confirmed MERS cases, including 33 deaths (18.1%), 15 health care professionals (8.2%) infected, and 2638 contacts still in quarantine. Cases called “super-spreaders” (such as patient no. 1 and patient no. 14, which infected 36 and 70 patients, respectively) emerged without finding any remarkable mutations in MERS-CoV strains that could contribute to easy transmissibility. This outbreak is too fast and unexpected to be explained just by the suboptimal infection prevention practices and delayed diagnostic process, or regional habit variations like “doctor shopping” or “family nursing.” The possibility of airborne transmission through suboptimal central air conditioning system in hospital settings should be seriously taken into account as well. MERS-CoV might be able to survive in the central air conditioning system, and spread through the vent pipe to the whole health care facilities, just like the situation once occurred in 2003, when SARS cases increased dramatically attributing to the rapid spread of the virus through drainage systems, in Taoda Garden, Hong Kong Special Administrative Region, China. More details should be valued and investigated carefully for better understanding of MERS-CoV transmission patterns.
At least one pathogen was found in 83.1% (728/876) of tested patients of which 38.8% (340/876) were single infection and 44.3% (388/876) were multiple infections. The highest rate of infection was obtained in patients aged less than 5 years (85.2%; 605/710). For this age group, single and multiple infections were reported in 79.1% (269/340) and 86.6% (336/388) of cases, respectively. The type of infection (mono-infection vs. multiple infection) differed significantly between age groups (p = 0.03, Fisher’s exact test). Indeed, patients aged 30–64 years were significantly less likely at risk for being co-infected (OR = 0.4; p = 0.003) compared to those aged less than 5 years (S2 Table).
Influenza is a highly contagious disease of global importance. The virus infects a variety of animals including birds, and infects humans. Three subtypes of influenza A were previously reported to infect humans, i.e., H1N1, H1N2, and H3N2. During the past few years, several subtypes of avian influenza A have been shown to cross the species barrier and infect humans. In the spring of 2013, a novel avian-origin influenza A virus, H7N9, emerged and spread among humans in China. The first documented case of human infection with the influenza H7N9 virus occurred in Shanghai in March. As of May 9, the World Health Organization (WHO) reported 131 laboratory-confirmed cases, including 32 deaths. Of the 111 patients with the H7N9 virus infection has been reported recently, 76.6% were admitted to an intensive care unit (ICU). On admission, 108 patients (97.3%) had findings consistent with pneumonia. The clinical features, blood cell counts, and laboratory and biochemical findings in patients with H7N9 virus infection have been described–. Patients usually presented with fever and cough, and with early sputum production. The illness progressed rapidly to severe pneumonia, with moderate-to-severe acute respiratory distress syndrome.
During the outbreak of avian flu, imaging studies provided important information for diagnosis, management, and control of H7N9 infection. On chest radiographs or computed tomographic (CT) scans, bilateral ground glass opacities and consolidation were the typical radiologic findings,.
Because H7N9 virus infection is potentially fatal disease and extremely contagious with mortality rate of 27%, it is important during the current influenza outbreak to identify initial imaging findings as potential risk stratification to help triage patient, guide treatment, and monitor disease progression and treatment response. We therefore investigated the association of initial chest radiographic findings and CT characteristics obtained at admission with clinical outcomes in patients with avian influenza H7N9 pneumonia.
Respiratory infections in pigs are very important factor affecting the profitability of pig production [1, 2]. Although various bacteria or viruses could induce the respiratory infection separately, it has commonly been caused by coinfection with more pathogens under field conditions [1–3]. The most important infectious agents responsible for infection of the respiratory tract in pigs are: swine influenza virus (SIV), porcine reproductive and respiratory syndrome virus (PRRSV), Pasteurella multocida (Pm), Actinobacillus pleuropneumoniae and Mycoplasma hyopneumoniae [2, 4–6]. Besides, the above mentioned pathogens, the Haemophilus parasuis (Hps) can also be recovered from the lungs of pigs with pneumonia [1, 7–10]. In these cases Hps is often isolated along with other bacterial or viral pathogens and, therefore, the role of Hps in producing pneumonia is not clear [8, 11].
Bacterial pneumonia secondary to influenza is often observed in pigs. SIV is a significant contributor to the respiratory diseases and may predispose to secondary bacterial infection. Hps is an important and common respiratory pathogen of pigs. It can be a primary pathogen or be associated with other diseases such as SIV [3, 8]. It could be also isolated from nasal cavity, tonsils and trachea of apparently healthy pigs [8, 14]. Under favorable conditions, Hps can cause severe systemic infection characterized by fibrinous polyserositis, arthritis and meningitis [8, 11, 14]. Factors leading to systemic infection by Hps have not been clarified to date [9, 14].
Although there are previous reports of experimental reproduction of Hps or SIV infection in conventional pigs, little is known about the effect of concurrent infection with SIV and Hps on the disease severity and inflammatory response in pigs, even if this coinfection is common under field conditions [13, 15–17]. There are also limited data on the role of Hps in the production of pneumonia in the absence of other respiratory pathogens. Furthermore, the kinetics of acute phase protein (APP) response in SIV/Hps co-infected pigs has not been studied to date. As it has been shown for other pathogens, the exposure to several pathogens can lead to a stronger APP response, as compare to single infection [18–20]. Thus, in order to investigate the influence of SIV and Hps coinfection on clinical outcome, both local and systemic inflammatory response as well as pathogen shedding and load at various time points following intranasal inoculation, three experimental infections (Hps- and SIV-single infection, SIV/Hps co-infection) has been performed in the present study. The correlation between local concentration of cytokines and severity of infection (clinical score, lung score) as well as serum APP concentration has been also studied.
A prospective hospital-based SARI surveillance was conducted from November 2010 to July 2013 in 2 selected sites: the Soavinandriana hospital of Antananarivo and the secondary level public hospital (CHD II) of Moramanga. The CENHOSOA is a national referral hospital and is among the 4 largest hospitals that deserve Antananarivo, the main capital city of Madagascar which has around 2.5 million inhabitants. The CHD II in Moramanga is the only local referral hospital for the health district of Moramanga that has 250 000 inhabitants. It is located 115 km east from the capital city. Antananarivo and Moramanga present the same climatic profile: hot and rainy in summer and cold and dry in winter, but Moramanga encompasses both semi-urban and rural areas.
The 22 patients included 5 women and 17 men, with median age of 67 years (interquartile range, IQR, 56–75 years). Of the 22 patients, 20 (91%) were admitted to an intensive care unit (ICU), including 14 directly admitted to ICU and 6 transferred to ICU during hospitalization. The main adverse outcome measure was in-hospital death. As of July 10, a total of 7 patients had died in hospital, and 15 patients were discharged in recovered condition. The median time from the onset of illness to death was 18 days (IQR, 12 to 54 days). All the patients were devided into mortality (n = 7) and survival (n = 15) groups.
Table 1 shows the comparison of patient age, sex, comorbid illnesses, outcomes as resulting in required mechanical ventilation or developing acute respiratory distress syndrome, and clinical symptoms, between mortality and survival groups. The mortality rate in this study was 32% (7 of 22 patients). There were no significant differences between the two groups with respect to patient age, sex, comorbidities, and clinical manifestations. All the patients in mortality group developed acute respiratory distress syndrome and all of them required mechanical ventilation, while in survival group 33% (5/15) developed acute respiratory distress syndrome (P = 0.004) and 27% (4/15) required mechanical ventilation (P = 0.005). Only two patients in mortality group required invasive mechanical ventilation, while others required non-invasive mechanical ventilation.
Table 2 compares the frequency of chest radiographic findings, distribution patterns, and chest radiographic score of the affected lung parenchyma between the survival group and the mortality group. The predominant chest radiographic findings at presentation consisted of a bilateral mixed pattern of ground glass opacity and areas of consolidation in 18 patients (82%), air bronchograms in 11 patients (50%), and both central and peripheral distributions in 21 patients (95%). A small pleural effusion was found in 9 patients (41%). The mediastinal lymphadenopathies, pneumothorax and pneumomediastinum were not seen on chest radiographs.
The mean chest radiographic score of the mortality group (Figure 2) was 50% higher compared to survival group (Figure 3) (P = 0.035). In the receiver operating characteristic curve analysis (Figure 4), an optimal cutoff value of a chest radiographic score of 19 had a sensitivity of 71% and a specificity of 67% for the prediction of mortality. The area under the receiver operating characteristic curve was 0.738 (95% confidence interval: 0.568, 0.985). There was no statistically significant difference in the frequency and distribution of the chest radiographic findings between the survival and mortality groups.
Table 3 compares the frequency of CT findings, distribution patterns, and CT score of the affected lung parenchyma between the survival group and the mortality group. The predominant CT findings at presentation consisted of a bilateral mixed pattern of ground glass opacity and areas of consolidation in 20 patients (91%), air bronchograms in 15 patients (68%), and both central and peripheral distributions in 21 patients (95%). A small pleural effusion was found in 12 patients (55%). The mediastinal lymphadenopathies were observed in 2 patients (9%) with coexistent chronic obstructive pulmonary disease. Pneumothorax and pneumomediastinum were not seen on CT.
The mean CT score of the mortality group (Figure 5) was 50% higher compared to survival group (Figure 6) (P = 0.013). In the receiver operating characteristic curve analysis (Figure 7), an optimal cutoff value of a CT score of 21 had a sensitivity of 86% and a specificity of 73% for the prediction of mortality. The area under the receiver operating characteristic curve was 0.833 (95% confidence interval: 0.659, 1). There was no statistically significant difference in the frequency and distribution of the CT findings between the survival and mortality groups.
Table 4 presents the frequency of CT findings, distribution patterns, and CT score of the affected lung parenchyma among 12 patients of the survival group who underwent follow up CT scans at discharge. The mean score of the affected lung parenchyma at discharge was 30% lower than the initial CT examination (P = 0.029). There was no statistically significant difference in CT findings and distribution patterns between the initial and follow-up examination.
2019-nCoV is placed within the beta-coronavirus family, where SARS-CoV and MERS-CoV were also found. The 2019-nCoV genome has been reported to show a 70% similarity with the SARS CoV. The genomes of these viruses and beta coronaviruses have shown to be closely related to the bat SARS-like coronavirus isolate Bat-SL-CoVZC45. The origin of 2019-nCoVs is still under investigation [4, 5].
Cases of pneumonia of unknown etiology were first reported on December 31, 2019, in Wuhan City, Hubei Province, China. It is stated that there is a cluster in the employees of Wuhan South China Seafood City Market (a wholesale fish and livestock market selling different animal species) in the south of Wuhan. Findings compatible with fever, dyspnea and bilateral lung pneumonic infiltration were detected in most cases. Fatal cases were reported so far have generally been older individuals or individuals with concomitant systemic disease [6–8]. The first imported case is a 61-year-old Chinese woman reported from Thailand on January 13, 2020. On January 14, 2020, a male patient in his 30s was reported by the Ministry of Health of Japan as the second imported case. The two imported cases were reported from Thailand and Japan, who have a travel history to Wuhan province, with no history of visiting the seafood market where the first cluster was identified. The virus was defined by authorities as coronaviruses on January 7, 2020, and refined down the total number of the cases. As the number of cases has increased, Chinese authorities have quarantined the city of Wuhan and many other cities, suspended travel in and out in Hubei province [6–8].
An early report of 41 patients published in The Lancet, provided even more detailed information and many epidemiological and clinical studies have been reported consequently. Common symptoms of infection were respiratory symptoms, fever, cough, and dyspnea. More severe cases were presented with pneumonia, severe acute respiratory infection, kidney failure. Asymptomatic people reported carrying the virus in the respiratory tract. A 33 years old German businessman infected from a Chinese colleague who has no symptoms or signs.
At the end of January 2020, 2019-nCoV declared as global health emergency by the World Health Organization. The researchers tried to estimate the size of the epidemic in Wuhan and predict the risk for local and global dimensions. The mean incubation period was found to be 5.2 days (4.1 to 7), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). The researchers calculated the number of infected patients as 75.800 for January 2020 (about 10 times that reported) using travel data. They found doubling time as 6.4 days and R0 as 2.68. The researchers were assumed that the outbreak would peak in April and if necessary measures are taken and the growth rate of the epidemics slows down, the transmission of the virus can be reduced by 25%. Thus, the total number of cases can be decreased by 50%. The fatality rate of disease was reported as 2% by early February. Non-survivors that have been reported so far are generally older or have concomitant systemic disease. Systemic symptoms, lymphopenia and thrombocytopenia were found more common and radiological involvement was more severe among people over 60. High CRP and LDH levels were also reported more frequently among older patients. A study found that the median age of patients died as 75 (48–89). On the other hand, children were less susceptible to viruses or had a mild infection as compared with adults [7, 11]. Studies calculated a basic reproduction number (R0) of the disease to foresee how far the virus spread. A study of 425 patients found a basic reproduction number as 2.2% (95% CI, 1,4 to 3.9). The WHO (World Health Organization) estimated that each individual infected with 2019-nCoV transmitted the virus to an average of 1.4 to 2.5 others for the earlier phase of the outbreak. That means 2019-nCoV less contagious than SARS, which had an R0 of 3, but more contagious than seasonal flu.
An important group affected by these outbreaks is healthcare workers. During the SARS-CoV outbreak, Dr. Carlos Urbani has gone during his scientific investigations. In recent outbreak also Dr. Li, who tried to warn people about the virus, shared the same fate with his colleague and has also died from novel coronavirus.
Polymerase Chain Reaction-based tests are used for the diagnosis of the disease, preferably from the obtained low respiratory tract samples (such as sputum and/or endotracheal aspirate). Researches also detected the virus from the blood and feces specimens [7, 13]. To our knowledge, there is no specific antiviral treatment for 2019-nCoV. Since the pathogenesis is not fully known, the treatment is supportive and aimed to prevent secondary infections and complications. Randomized controlled studies are underway in China for some drugs, such as Remdesivir (a nucleotide analogue), which was first developed for the treatment of Ebola. Compassionate use of this drug also successfully experienced in a US patient during the outbreak. Also, chloroquine, interferon and protease inhibitors, such as ritonavir, lopinavir/ritonavir, reported being effective in inhibiting the virus invitro [13, 14]. To our knowledge, there is currently no vaccine to prevent 2019-nCoV infection.
On the 11th of February, WHO announced an official name for the disease caused by new coronavirus disease: COVID-19, which refers to Co (Corona), VI (virus), D (disease), and 19 (the year 2019 that it is first discovered). To date (15th February 2020), the virus was detected in 67.191 people worldwide, about 66 thousand of which are within the borders of mainland China. The other countries reporting the highest number of cases are Japan (338), Singapore (72), Hong Kong (56), Thailand (34) and South Korea (28). While nearly 200 thousand people were kept under observation, the number of people who lost their lives increased to 1,527. Only four deaths out of China were reported from Hong Kong (1), Philippines (1), Japan (1) and France (1).
The mean age was 37.97 ± 13.9 years (range, 18 to 76 years). There were 16 men (mean age, 30.06 ± 13) and 15 women (mean age, 40 ± 14.8 years). Seventeen (54%) had a co-existing medical condition (Table 1). The mean duration of stay in the hospital was 10.35 ± 9 days, range 2 to 50 days. Twelve (38.7%) patients were admitted to the ICU. Five (16.1%) died due to respiratory failure. Of our patients, 87.1% had fever, 58% cough, 80.6% dyspnea, 25.8% vomiting, 16.1% diarrhea and nine (29%) hemoptysis. Eight (25.8%) had normal radiographs. The abnormal pattern was unilateral in four (12.9%) and bilateral in 19 (61.3%). The most common abnormal radiographic pattern was consolidation (12/31, 38.7%) (Figure 1) observed most frequently in the peripheral region (11/31; 35.5%) followed by peribronchovascular infiltration (10/31; 32.3%) which was present in the left lower lung zone in 61.3% and the right lower lung zone in 45.2% (Table 2). Other findings included cardiomegaly in five (16.1%) patients. Five (16.1%) patients had bilateral and two (6.4%) had unilateral pleural thickening or effusion (Figure 2). Five (16.1%) had hilar or mediastinal adenopathy (Figure 3). CPK was elevated in 9/24 and LDH in 14/22 patient. The platelet count was low in 32.3%. Hb was low in 22.6%. White blood cell (WBC) was high in 22.6%. Twelve patients with a mean age of 39.5 (66.7% women) were admitted to ICU. Seven had a predisposing condition (three cardiovascular disease, two respiratory disease, one immunodeficiency, one cancer, three others). Four patients died. All had alterations on their radiographs, most commonly observed was multifocal (10/12; 83.3%) consolidation (6/12; 50%) in the lower zones (left 83.3%; right 66.7%). Four (33.3%) patients had more than two zones involved. Five (41.7%) had pleural thickening or effusion. Four (33.3%) had adenopathy. CPK was high in 6/10 and LDH in 10/10. The patients admitted to the ICU were more likely to have two or more lung zones involved (P = 0.005). Ten patients had an available CT scan and the most common pattern was ground glass opacities seen in six patients (60%) followed by consolidation in four (40%) which was most commonly observed in the peripheral region in six (60%) followed by the peribronchovascular region in five (50%) and in the upper lung zones in seven (70%) of patients.
By the end of April 2009, two cases of confirmed novel H1N1 were detected in the United States. These patients were resistant to rimantadine and amantadine and had no contact with swine. Further cases of the new swine flu were identified in Mexico and other countries. By June 2009, several confirmed cases were reported from 74 countries and the virus was known to have human-human transmission and by that time WHO raised the alert level to phase 6 which is the pandemic level. The H1N1 influenza is a negative-sense RNA virus of the orthomyxoviridae family. The center for disease control and prevention (CDC) recognizes it with an influenza like syndrome presenting with high fever, cough or sore throat. Its diagnosis is confirmed by real-time reverse transcription polymerase chain reaction PCR or viral culture. Its incubation period is between 1 and 7 days. The patients are thought to be contagious from one day before to 7-10 days after the onset of the disease. Patients with a background disease including respiratory tract and heart disease are more likely to require hospitalization. The clinical presentations have been reported as fever, headache, sore throat, dyspnea, diarrhea and rhinorrhea. Laboratory findings are high CPK, high LDH and lymphopenia. The new swine flu influenza S-OIV is known to be susceptible to neuraminidase inhibitors and there is recommendation to give oseltamivir as prophylaxis to the high risk group. Different radiologic manifestations have been reported in several studies of the new swine flu influenza virus. Perez Pallida reported the radiologic manifestations of 18 patients with documented H1N1 infection as bilateral alveolar opacities which are predominantly basal and other observations being interstitial opacities (including linear and reticular). In a study on 66 patients, the most common abnormal pattern was consolidation most commonly observed in the lower and central lung zones and patients admitted to the ICU were more likely to have three or more lung zones involved. This result was consistent with our study. The patients were more likely to have consolidations in the lower lung fields and those admitted to the ICU having two or more lung fields involved; however, in another study by Aviram et al. performed on 97 patients who underwent chest radiography at admission, the most frequent abnormal pattern on radiography was ground glass opacities in the central and middle lung zones, which was followed by consolidation with slightly less frequency. This is in contrast with our findings which showed predominant involvement of the lower lung zones and consolidation as the most common manifestation. In their study, patients with bilateral and peripheral involvement or four or more lung zone involvement were more likely to have severe outcome, which is in consistence with our findings in patients admitted to ICU. It should be noted that our study population included patients with a more severe presentation and was not a sample of the population diagnosed with H1N1 and the results may only be interpreted in the setting where the manifestation is more severe and not the entire population of patients diagnosed with H1N1. Another study reviewed the High Resolution Computed Tomography Scan (HRCT) findings of 18 patients with the new swine flu influenza. In this study, the abnormal pattern was most commonly the ground glass opacity present in the peripheral region which is consistent with our results. In their study, patients with high LDH were more likely to have consolidations on HRCT.
Considering the association of chest findings and patients’ prognosis, it was previously demonstrated that in patients with community acquired pneumonia, bilateral pleural effusion may predict short term mortality. In our group of patients, bilateral pleural effusion was not a predictor of mortality. Interestingly, in another report of patients with acute respiratory distress syndrome, involvement of more than two lung zones has been associated with the worst outcome. In our group of patients, we also found that those who were admitted to the ICU were more likely to have more than two lung zones involved. Detection of multiple consolidations on radiography may represent a severe viral infection or superimposed bacterial infection which would necessitate antibiotic and some advocate administration of antibiotic to patients suspected of H1N1 and radiologic manifestation of extensive involvement or consolidation. In our group of patients, those with severe presentation were also receiving antibiotic alongside oseltamivir.
In conclusion, we found our experience with our group of patients with H1N1 influenza consistent with previous reports as consolidation on the lower lung fields being most common on radiography and ground glass opacities most common on the CT scan. Becoming familiar with the clinical and radiographic presentations of this very infectious disease helps in early diagnosis, treatment and isolation of patients.
Identification of two groups of patients is important: those who are symptomatic, and those who are asymptomatic but have been exposed. Both groups may benefit from treatment. Symptomatic individuals may present in any one of the three classic stages of pertussis, as discussed above. Some may be in the initial catarrhal phase, reporting mild upper respiratory symptoms, and others may have progressed into the paroxysmal phase, exhibiting the classic “whooping cough.” Other symptoms commonly reported include post-tussive emesis, cyanosis and apnea. Patients who have had a persistent cough for weeks, and perhaps months, may be in the convalescent phase. All of the aforementioned presentations may represent a patient with pertussis, making careful reviews of exposure history and immunization status essential. Importantly, those with previous vaccinations may present atypically and not exhibit classic features of pertussis.
Another important group to consider are those who deny symptoms, but report having been exposed to a person with confirmed pertussis. Pregnant women and infants are especially at risk; thus, review of this type of exposure is critical when deciding whether to initiate treatment. Patients are considered most contagious three weeks after the onset of the paroxysmal phase, where coughing spells are most prevalent. Thus, asking exposed patients when they were with the source patient could aid in assessing their individual risks.
Human coronaviruses (HCoV) were first described in the mid-1960s. HCoV is an enveloped RNA virus with a single chain and positive polarity. The name “corona” comes from the crown-like spikes on the surface of the virus. Four major subgroups are known as follows: alpha, beta, gamma and delta. Subtypes of coronaviruses circulating in humans (HCoV-229E, HCoV-OC43, HCoV-NL63 and HKU1-CoV) are mostly viruses that cause colds. Coronaviruses are zoonotic viruses that infect many mammals and birds. There are many coronaviruses that have not been transmitted to humans yet but are detected in animals. Before the virus (most likely a bat virus) gained the ability to infect humans, it jumps an intermediate host as occurred in previous outbreaks. It has been revealed that for emerge of SARS-CoV (Severe acute respiratory syndrome), civet cats played an imported role for transmission of disease to humans, whereas one-humped camels played an intermediate host for MERS-CoV (Middle East Respiratory Syndrome). SARS-CoV was first defined in February 2003 in Asia (Guandong, China) and has spread to more than two dozen countries in North and South America, Europe and Asia. In about eight months, 8098 people are infected, and 774 people died. Since 2004, to our knowledge, there have been no new cases reported in the world. MERS- CoV also causes a severe respiratory disease with symptoms of fever, cough and shortness of breath. The disease was seen for the first time in September 2012 in Saudi Arabia, and all the patients with MERS- CoV had a history of travel or residence in the Arabian Peninsula and nearby countries. Outside the Arabian Peninsula, the disease was seen in the Republic of Korea in 2015. Again, the outbreak was associated with a traveler returning from the Arabian Peninsula. To date, 2494 people have been infected, and there 858 related deaths were reported related to MERS [2, 3].
Respiratory viruses of human origin have caused disease in wild apes across Sub-Saharan Africa and pose a significant and growing threat to wild ape health and conservation. For example, respiratory disease is the leading cause of morbidity and mortality among chimpanzees (Pan troglodytes) in Gombe Stream National Park, Tanzania and in Kibale National Park, Uganda, two populations that have been studied continuously for decades. Mortality from anthroponotic respiratory pneumoviruses (family Pneumoviridae) and paramyxoviruses (family Paramyxoviridae) has been documented in western chimpanzees (P. t. verus) in Cote d'Ivoire, eastern chimpanzees (P. t. schweinfurthii) in Tanzania, mountain gorillas (Gorilla beringei beringei) in Rwanda, lowland gorillas (G. g. gorilla) in Central African Republic and bonobos (P. paniscus) in the Democratic Republic of the Congo. Rhinovirus C and coronavirus OC43 of human origin have also caused chimpanzee mortality in Uganda and mild respiratory disease in Cote d'Ivoire, respectively.
Biological similarities between humans and apes predispose them to cross-species pathogen transmission, and habitat alterations may exacerbate inter-species contact and anthroponotic transmission risk. Although simultaneous infections of apes and people with the same respiratory virus have rarely been confirmed directly, viruses that are relatively benign in humans can cause lethal outbreaks in ape populations, indicating lack of resistance in apes. Suitable prevention strategies have included improved hygiene and sanitation, reduced human visitation and large-scale vaccination of apes (if effective vaccines someday become available). Such policies could also benefit human public health by reducing zoonotic transmission risk.
Here, we report simultaneous outbreaks of respiratory disease in two nearby chimpanzee communities in Uganda, caused by two distinct negative-sense RNA viruses of human origin. The outbreaks occurred from December 2016 to February 2017 in the Ngogo and Kanyawara chimpanzee communities in Kibale National Park (Figure S1). Only 10 km apart, the communities are interconnected by contiguous moist evergreen forest, separated by only one intervening chimpanzee community that is not currently studied, and both communities generally experience low mortality rates.
Although outbreaks of respiratory disease in wild chimpanzees are common, their causes often remain undiagnosed. Fresh carcasses are often not recovered, and the remoteness of field sites complicates sample storage and analysis. Non-invasive diagnostics (usually from feces) have proven highly informative, but negative results in such cases are inconclusive. In the present case, rapid recovery of carcasses, the presence of trained veterinarians and the availability of basic field laboratory capabilities on site provided an opportunity for etiologic diagnoses. Furthermore, coordinated, prospective collection of observational data between the two sites offered an unusual chance to compare the clinical and epidemiologic features of the outbreaks directly.
In addition to protective measures to avert disease transmission, the most important preventative measure is vaccination. In 2018, the Centers for Disease Control (CDC) and Prevention’s Advisory Committee on Immunization Practices published the following vaccine recommendations:21
From 31 December 2016 to 8 February 2017, the Ngogo chimpanzee community of Kibale National Park, Uganda (Figure S1), experienced an outbreak of severe respiratory disease. During the same period, the nearby Kanyawara community (Figure S1) also experienced a respiratory disease outbreak. At the onset of the epidemics, Ngogo community consisted of 205 chimpanzees from <1 year to 67 years old, and Kanyawara community consisted of 55 chimpanzees from <1 year to 51 years old. Epidemic curves (Figure 1) show that the Ngogo and Kanyawara outbreaks each occurred in a single phase, with most cases occurring in January 2017. At Ngogo, 43.8% of chimpanzees observed between 3 December 2016 and 28 February 2017 exhibited respiratory signs. At Kanyawara, 69.1% of chimpanzees observed during the same period exhibited respiratory signs. At Ngogo, 25 chimpanzees (12.2%) died during the outbreak period (Figure 1). In contrast, no chimpanzees at Kanyawara died during the outbreak period, with the exception of a female recovering from disease who died following conspecific aggression (see below). Respiratory signs consisted of coughing, sneezing, dyspnea, and nasal exudate; other signs included lethargy, immobility, and dramatic loss of body condition (Figure S2).
Epidemiologic modelling of the Ngogo and Kanyawara outbreaks (Table 1 and Figure S3) yielded daily transmission rate estimates of 1.13 and 0.338, and durations of infectivity of 1.12 and 4.55 days, respectively. These parameters yielded basic reproductive numbers (R0) of 1.27 and 1.48 for Ngogo and Kanyawara, respectively. These are similar to values estimated from an outbreak of rhinovirus C in Kanyawara in 2013 (Table 1) during which 8.9% of chimpanzees died, and to published values for the human “common cold”. However, 95% confidence limits around these estimates were non-overlapping for daily transmission rates of all three outbreaks and duration of infectivity and R0 in Ngogo (both lower than in Kanyawara in 2013 or 2016/2017).
Risk factor analysis (Table S2) showed that age significantly predicted morbidity at both Ngogo (χ2 = 10.097, DF = 3, p = 0.018) and Kanyawara (χ2 = 12.154, DF = 3, p = 0.007). In both communities, respiratory signs were least frequently observed among infants and increased through successive age categories. Sex did not affect morbidity or mortality at Ngogo, but females were significantly more likely to exhibit respiratory signs at Kanyawara than were males (χ2 = 6.310, DF = 1, p = 0.012). At Ngogo, age predicted mortality (χ2 = 19.153, DF = 3, p < 0.001), with mortality highest among infants (OR 5.01, 95% CI: 1.53–19.56) and individuals ≥30 years old (OR 3.86, 95% CI: 1.16–15.15), compared to intermediate ages.
At Ngogo, the carcass of a 20-year-old female chimpanzee was recovered immediately after the onset of respiratory signs and subsequent death. Post-mortem analysis of this individual revealed consolidation of the dependent lobes of both lungs and a serosanguinous pericardial effusion but no other gross pathologic abnormalities (Figure S4). At Kanyawara, the carcass of a 22-year-old female chimpanzee was recovered approximately 10 days after having recovered from respiratory signs (but still remaining weak), immediately after having been attacked by conspecifics (for unclear reasons). Post-mortem analysis of this individual showed severe, diffuse pleuropneumonia with fibrinous adhesions to the thoracic wall and severe consolidation of all lobes of both lungs, as well as a serosanguinous pericardial effusion (Figure S4).
Analysis of paired fecal samples (prior to and during the outbreak period) using a Luminex assay that tests for a suite of human respiratory agents revealed different viral etiologies for each community (Table 2). Metapneumovirus (MPV, Pneumoviridae: Metapneumovirus) was detected in 7 of 11 individuals (63.6%) from Ngogo chimpanzees exhibiting clinical signs during, but not before, the outbreak period (Fisher’s exact P = 0.0030). Human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3) was detected in 5 of 14 individuals (35.7%) from Kanyawara chimpanzees exhibiting clinical signs during, but not before, the outbreak period (Fisher’s exact P = 0.0005). Adenoviruses (Adenoviridae) were present in samples from both Ngogo (36.4%) and Kanyawara (78.6%) but showed no association with the outbreak period (Fisher’s exact P = 0.4545 and 0.5291, respectively) and have been previously characterized in this population at comparable frequencies. Enteroviruses (Picornaviridae) were also present at low frequency in samples from both communities, similarly showed no association with the outbreak period (Fisher’s exact P = 1.000 in both cases), and have also been previously characterized in this population at comparable frequencies.
Metagenomic analysis of respiratory tract swab samples from the chimpanzee examined postmortem at Ngogo yielded 16,107,924 reads after trimming, of which 27,393 assembled to yield a coding-complete MPV genome of 13,230 bases with average coverage of 196, consistent with the Luminex results described above. This genome (GenBank accession number MH428626) was most similar (98.69%) to a 2010 human-derived variant from Brazil (GenBank accession number MG431250). Intriguingly, the virus was nearly as similar (98.67%) to a variant from a mountain gorilla from Rwanda in 2008 (GenBank accession number HM197719) detected during a lethal outbreak. MPV RNA was present in all sections of the respiratory tract, including the lung parenchyma, with the proportion of viral sequence reads declining monotonically from the upper to the lower respiratory tract (Figure S5). Sequencing of a 480 nucleotide portion of the viral F gene from fecal samples was successful for three other Luminex-positive chimpanzees at Ngogo (AB, MI and WI; Table 2), yielding identical sequences within this variable genomic region (GenBank accession numbers MH428628- MH428630).
By contrast, neither HRV3 nor any other virus was detected in the respiratory tract of the chimpanzee that died at Kanyawara, likely reflecting prior infection and viral clearance. A coding-complete HRV3 genome (15,407 bases) was therefore reconstructed from a fecal sample from this same individual collected when she was coughing approximately 2 weeks earlier, using PCR with virus-specific primers and Sanger sequencing (Table S1). This genome (GenBank accession number MH428627) was most similar (99.38%) to a 2009 human-derived variant from the USA (GenBank accession number KY674929). Sequencing of a variable and epidemiologically informative 348-nucleotide portion of the viral F gene from fecal samples was successful for three other Luminex-positive chimpanzees at Kanyawara (AL, AN and AZ; Table 2), yielding identical sequences within this genomic region (GenBank accession numbers MH428631–MH428633). Re-analysis of respiratory tract metagenomic data from this individual and the individual from Ngogo revealed that a small proportion of reads in the upper respiratory tracts of both animals (0.05% and 0.16%, respectively) mapped to the reference genome of Staphylococcus pneumoniae (GenBank accession number NC_003098), which can infect chimpanzees secondarily during viral respiratory disease outbreaks, indicating the presence of this or a related bacterium; however no reads mapped to this organism in the lungs of either animal.
Phylogenetic analysis revealed MPV from the Ngogo outbreak to sort within a sub-clade of subtype B2 viruses from Brazil, Peru, Rwanda and the USA (Figure 2). This sub-clade contains recently collected viruses (2009–2015), including the mountain gorilla variant from Rwanda. The MPV variant from Ngogo belongs to a different subtype than a previously reported B1 virus from a chimpanzee outbreak in Tanzania, and it is less closely related to a previously reported B2 subtype from a chimpanzee outbreak in Cote d'Ivoire than to other variants within its subclade, including the gorilla-derived variant, based on the available 867 nucleotide region of the viral P gene (GenBank accession numbers EU240454-EU240456; not shown).
Phylogenetic analysis revealed HRV3 from the Kanyawara outbreak to sort within a sub-clade of highly similar human-derived viruses from Peru and the USA collected between 2006 and 2015 (no more recently than other sub-clades; Figure 2). Notably, HRV3 from Kanyawara was divergent from viruses from other non-human primates, including viruses from wild Zambian baboons (Papio cynocephalus) and simian agent 10, originally isolated from a blue monkey (Cercopithecus mitis) in South Africa.
The S. equi outbreak in a boarding facility began in late January 2017 and lasted approximately 1 month. Before S. equi was detected on the farm, 1 horse developed signs of colic, lethargy, and fever. This horse was isolated at a veterinary hospital. Fecal PCR testing was performed on this horse and was positive for equine coronavirus. After this horse was diagnosed, more horses were noted to have lethargy, fever, and occasional colic signs. Fifteen horses were presumed to be initially infected with coronavirus based on these clinical signs. Fecal PCR testing was performed on only 2 additional cases; however, they were negative for equine coronavirus. Approximately 2 weeks later, horses were noted to have submandibular lymphadenopathy and were confirmed to have S. equi infection. Quarantine of affected horses was attempted; however, during the course of the outbreak, horses in all housing areas had clinical signs. Movement on and off the property was stopped.
Forty‐eight horses were on the property during the S. equi outbreak. Ages ranged from 6 to 36 years (mean 15.8 years). Breeds included Quarter horse (QH) (n = 17), Tennessee Walking horse (TWH) (n = 4), Arabian (n = 4), Paint (n = 4), Thoroughbred (n = 2), Warmblood (n = 2), Morgan (n = 2), and 12 other breeds (n = 1 each). Thirteen (27%) were females, and 35 (73%) were castrated males.
Twenty‐eight (58%) horses developed clinical signs consistent with strangles. Of the affected horses, ages ranged from 6 to 36 years (mean 16.1 years). Breeds included QH (n = 10), Paint (n = 4), TWH (n = 3), Arabian (n = 3), Warmblood (n = 2), Morgan (n = 2), and 4 other breeds (n = 1 each). Seven (25%) were females, and 21 (75%) were castrated males. Signalment of affected horses was similar to the whole exposed population. Eight horses had a history of previous vaccination for S. equi. Five out of the 8 vaccinated horses (63%) did not develop clinical signs of disease, and 3 of 8 (38%) did develop clinical signs.
At 4 weeks after initial detection of S. equi, no new horses developed clinical signs, and clinical signs of affected horses had resolved. Testing to detect persistent GP infection was performed at 8 weeks after initial infection in conjunction with measurement of SeM antibody titer. Thirty‐five horses were tested for persistent GP infection via either nasopharyngeal lavage (n = 17) or GP endoscopy and lavage (n = 18) S. equi PCR and culture. The decision to perform nasopharyngeal lavage or GP endoscopy was based on attending veterinarian recommendations and client preference. Thirteen horses were not tested for persistent GP infection status based on owners declining testing. Twelve of these horses were categorized as having no signs of disease, and 1 was categorized as an uncomplicated case of strangles.
Of the 28 horses affected, 11 (39%) had uncomplicated strangles, 9 (21%) had persistent GP infection, 5 (18%) had complicated cases, and 3 (11%) had both persistent GP infection and complications. Of the horses with persistent GP infection, 3 of 12 (25%) had endoscopically visible chondroids. Of the 8 complicated cases, 3 had purpura hemorrhagica, 3 had metastatic abscess formation, 1 had secondary pleuropneumonia, and 1 had dysphagia. The mean age was similar for each disease category. Of the 3 vaccinated horses that developed clinical signs, 1 had uncomplicated strangles, 1 had persistent GP infection, and 1 had both persistent GP infection and complications. Twenty‐four of the 28 affected horses (86%) survived long term (>6 months after infection), whereas 4 of 28 (14%) were euthanized. The horses that were euthanized were all complicated cases, including metastatic abscess formation, infarctive purpura hemorrhagica, secondary pleuropneumonia, and dysphagia.
Bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) are frequently involved in the respiratory and enteric disease complexes of cattle. BCV is causing winter dysentery in adults, calf diarrhoea and also respiratory disease of young stock. BRSV is recognized as one of the most important causes of respiratory tract disease in beef and dairy cattle, especially in young animals.
Presence of antibodies to BCV and to BRSV has been reported worldwide in both dairy and beef cattle.
Both BCV infection and BRSV infection are considered relatively contagious and are currently wide-spread in the Swedish dairy cattle population. Surveys of antibody levels in bulk tank milk have shown very high nationwide prevalences of both BCV and BRSV, with large variations between regions. The highest herd-prevalences (90 to 100%) were found in the southern parts of the country. It was suggested that a reason for the higher BCV prevalence in the south could be the high dairy-herd density, associated with an increased risk of spread between herds through infected animals, vectors and airborne transmission. In the Swedish beef cattle population however, no investigations have yet been performed regarding the prevalence and geographical distribution of BCV and BRSV.
The aim of the present study was to identify possible high risk areas for BCV and BRSV infections in the beef cattle population in Sweden, and further to explore whether a high beef herd-density was a risk factor for higher seroprevalences.
Streptococcus equi subspecies equi is the causative agent of strangles, a highly contagious upper respiratory tract infection of horses. Typical clinical signs of disease include fever, inappetance, lethargy, submandibular or retropharyngeal lymphadenopathy or purulent drainage, or purulent nasal discharge. Complications of S. equi infection can occur and include airway obstruction from lymphadenopathy, disseminated abscesses from hematogenous spread, or purpura hemorrhagica and various diseases caused by immune‐mediated processes.1, 2, 3, 4, 5
Streptococcus equi M protein (SeM) antibody titers are typically measured to determine if a horse has developed a complication of strangles, such as purpura hemorrhagica or metastatic abscess formation, or to determine if a horse is at risk of purpura hemorrhagica if they were to be vaccinated. Both the 2005 and 2018 American College of Veterinary Internal Medicine consensus statements on strangles state that a very high titer (≥1:12 800) is associated with metastatic abscess formation or purpura hemorrhagica and that high titers (1:3200‐1:6400) are detected 4‐12 weeks after infection.1, 2 Anecdotally, horses can have high titers (≥1:12 800) 4‐8 weeks after infection and no signs of complications (authors' personal observations, KMD, LAB, ACT). The objective of this study was to measure SeM antibody titers on horses after outbreak to determine if titers detect the presence of complications.2 An additional objective was to follow SeM antibody titers out to 7 months after infection to determine immunoglobulin decay and to monitor for development of additional complications. We hypothesized that the magnitude of SeM antibody titer after infection (SeM titer ≥1:12 800) will be useful to monitor for the presence of complications or for the risk of development of complications.
Infants under six months of age and nonimmune/nonimmunized pregnant women, if exposed, should receive passive immunity with intramuscular immune serum globulin. When administered within six days of virus exposure, these antibodies can prevent measles or reduce illness severity. If they are over six months, infants should receive a standard vaccination. Other nonimmunized persons who are exposed to measles should receive vaccination as well, ideally with 72 hours of the exposure. While vaccination might not prevent the disease, if illness develops it is generally less severe and for a shorter duration than in completely unvaccinated persons.
Household contacts should be advised that measles is highly contagious and infected family members should be isolated from four days before to four days after the rash manifests. Anyone at risk who is not fully vaccinated should receive vaccine as soon as possible. Most people born or living in the U.S. before 1957 have had measles and are therefore immune.
Preinoculation levels of Pig-MAP were found to be below 0.94 mg/ml (mean 0.91 mg/ml ± 0.23). Concentration of Pig-MAP increased significantly 72 h after coinfection (p<0.05) and remained significantly elevated till 7 dpi. The highest Pig-MAP concentrations in particular pigs were detected between 3 to 5 dpi. The maximum mean concentration of Pig-MAP, observed at 3 dpi in coinfected piglets, was almost 4 times higher as compared to day 0-level. From 10 dpi the Pig-MAP concentrations had decreased and did not differ significantly between control and infected pigs.
Significant positive correlations were found between maximal concentration of Hp and SAA and lung scores (respectively r = 0.85 and r = 0.87, p<0.05). Positive correlation was also observed between maximum concentration of Pig-MAP in serum and turbinate score (r = 0.87, p<0.05) and between clinical score and Pig-MAP and SAA maximal concentrations in the serum (r = 0.87 and r = 0.85, p<0.05, respectively).
Significant increase of SAA after coinfection, as compared to the control pigs, was observed only at 2 and 3 dpi (p<0.05). During first 24 h after inoculation the increases of SAA concentration was not significant as compared to control pigs (p>0.05). The mean peak level reached 155.20 ± 38.93 μg/ml, this was almost 40-fold higher compared to day 0-level. From 5 dpi the SAA concentration had decreased and did not differ from those observed in control animals.
Of 4,128 patients who were screened in the FRIDU, 114 patients were admitted to the resuscitation area due to clinical instability during FRIDU screening; three of these patients died in the ED. One of the 3 underwent cardiac arrest in the FRIDU and was moved to the resuscitation zone in the ED while cardiopulmonary resuscitation was performed. Twenty-nine of the 114 patients were discharged or referred elsewhere in the resuscitation area (Fig. 1) and were excluded from the analysis due to limited clinical and laboratory data. The 85 hospitalized patients who deteriorated during FRIDU screening are described in Table 5.
Of the 85 patients, 17 (20%) had contagious diseases and 37 (44%) were male. Most patients had fever (n = 64, 75%) and/or dyspnea (n = 66, 78%). Twenty-seven patients (32%) had septic shock, 33 (38%) had respiratory failure, 10 (12%) had heart failure, and 15 (18%) had an illness with an unknown cause.
All pigs from co-infected group had fever for at least one day (rectal temperature ≥40° C). In SIV – inoculated group fever was observed in 7 out of 11 pigs, while in Hps - inoculated pigs only in 3 out of 11 pigs (Fig. 1). The mean clinical scores (±SD) in all groups are presented in Fig. 2. In single-inoculated pigs, the individual clinical score ranged from 0 to 1 (Hps) or from 0 to 5 (SIV), while in co-inoculated pigs the individual clinical score ranged from 1 to 6. Pigs from the control group did not revealed clinical signs of any disease. Significant differences were observed between mean clinical score in SIV- and Hps + SIV – inoculated pigs and the controls (p≤0.05). There was also significant difference between co-inoculated and Hps-inoculated group (p≤0.05). No differences were observed between mean clinical score in SIV-single inoculated and co-inoculated animals as well as between Hps-inoculated and control animals.