J. Microbiol. Infect. Dis., (2023), Vol. 13(2): 82–86

Case Report

10.5455/JMID.2023.v13.i2.5

Epidemiological investigation of a death case infection with H9N2 avian influenza and HIV in Guizhou Province, China, 2021

Yun Gou^†, Yan Huang^†, Chun Yu, Kaike Ping, Zhongfa Tao, Jun Wu and Mingyu Lei^*

Guizhou Province Center for Disease Control and Prevention, Guiyang, China

^†Authors contributed equally to this work.

*Corresponding Author: Mingyu Lei. Institute for Communicable Disease Control and Prevention, Guizhou Center for Disease Control and Prevention, Guiyang 550004, Guizhou Province, China. Tel.: +86 17708512057. Email: 572168127 [at] qq.com

Submitted: 27/07/2022 Accepted: 11/06/2023 Published: 30/06/2023

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Abstract

Background: To be aware of infection combining the avian influenza H9N2 virus with human immunodeficiency virus (HIV) increases the risk of the disease. Through epidemiological investigation, a better grasp of the pathogenetic process and possible sources of infection. Diagnostic criteria and laboratory tests were used to confirm the pathogen.

Case Description: This patient was diagnosed with avian influenza H9N2 subtype and HIV infection according to diagnostic criteria. Environmental daub swab of two live poultry markets showed H9 positive. His family members were not detected with HIV and H9 subtype. The patient died from an H9N2 virus infection with HIV under specialists’ consultation.

Conclusion: The diagnostic capability of H9N2 and Acquired Immune Deficiency Syndrome in primary care should be noticed and improved. Infection with the H9N2 virus and HIV should be paid more attention to prevent public health events.

Keywords: Avian influenza, H9N2 virus, Severe pneumonia, HIV.

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Introduction

Guizhou Province Centre for Disease Control and Prevention (Guizhou CDC) received a call at 8:30 am on November 2, 2021, from Qiandongnan Miao and Dong Autonomous Prefectural CDC (Qiandongnan CDC) that an avian influenza A/H9 positive case was detected by severe pneumonia surveillance system in Qiandongnan Prefectural People’s Hospital which is one of the sentinel hospitals for severe pneumonia in Guizhou Province, and the patient has already died. The throat swab sample was promptly transported to the Experimental Center of Guizhou CDC to re-check it and identify the subtype of Neuraminidase. Consequently, it was identified as avian influenza A/H9N2 virus by quantitative reverse transcription-polymerase chain reaction (RT-PCR) at 5:00 pm on November 2.

Based on clinical manifestations and pharyngeal swab laboratory results, this patient was diagnosed with human infection with H9N2 avian influenza, referring to diagnosis and treatment standard of human infection avian influenza. Avian influenza H9N2 virus is a low pathogenic avian influenza in poultry and causes mild symptoms in humans usually, but the patient has died, which we have attracted close attention to. Subsequently, further investigations and dispositions were implemented by Guizhou CDC, Qiandongnan CDC, and the local county (Kaili Municipal) CDC.

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Case Details

Epidemiological investigation

Once a suspected case was found, the local county CDC would finish an initial investigation within 24 hours and collect respiratory specimens for laboratory testing. When the case was confirmed as H9N2 virus-positive, the municipal/autonomous prefectural CDC and province CDC would send a special epidemiology team to investigate with the county CDC to acquire more detailed information. The information included basic demography data, exposure history, clinical characteristics, and all close contacts. Epidemiologic characteristics were collected from infected individuals, family members, medical workers, and close contacts.

Diagnostic criteria

The diagnosis of H9N2 avian influenza is referred to Chinese diagnosis and treatment standard of human infection avian influenza. One was diagnosed as a suspected case of H9N2 avian influenza if he had epidemiological exposure history in 10 days and had a fever or influenza-like symptoms. One was identified as a laboratory-confirmed patient if respiratory tract specimens showed H9N2 virus-positive.

One was diagnosed as a severe pneumonia case when he had one of the main criteria and three of the secondary criteria. The main criterion: The case required mechanical ventilation; The case had a septic shock and required vasoactive drugs for supportive treatment. The secondary criteria: Respiration rate ≥30/minute; Oxygenation index (PaO₂/FiO₂) ≤250 mmHg; Multiple pulmonary infiltrates; Disorder of consciousness or disorientation; Azotemia (Blood urea nitrogen ≥20 mg/dl); Leukopenia (White blood cell <4.0 × 10⁹/l); Thrombocytopenia (Blood platelet <100.0 × 10⁹/l); Hypothermia (Temperature <36°C); Hypotension required strong fluid resuscitation.

Laboratory tests

Respiratory tract specimens came in nasal and pharyngeal swabs, and sputum or bronchoalveolar lavage fluid was detected by RT-PCR in laboratories. Enzyme-linked immunosorbent assay was used for the human immunodeficiency virus (HIV) screening test and Western blot for HIV confirmatory test, according to Chinese Acquired Immune Deficiency Syndrome (AIDS) Diagnosis and Treatment Protocol 2018 edition.

Results

According to the epidemiological investigation, the death case was a 39-year-old male farmer who had lived alone in the countryside to rebuild his house since February 2021. From his family members’ narrative, the patient did not have any comorbidity before and had no contact history with similar patients. It is an ordinary village with several backyard poultry farms. The only way must be passed near a backyard poultry farm, including two free-ranging ducks and six chickens. This village is approximately 7 km away from the nearest town, where two live poultry selling points are in the only market whose poultries come from the local municipal biggest live poultry market. His wife has been working as a vegetable seller with no fixed point at a live poultry market in Kaili Municipal which is 30 km far from the countryside. His other family members, two daughters and one son, who are primary school students, live with his wife.

The patient had a cold with cough, expectoration, and diarrhea symptoms 2 months ago and felt better after taking some pills bought himself at the drugstore. Afterward, he took some herbal medicines due to developed symptoms. The illness went back and forth, and he suffered from severe sickness for 2 months. With aggravating, he was sent to Kaili Municipal First People’s Hospital for treatment on October 29, then diagnosed with severe pneumonia. Medicines of piperacillin sodium tazobactam for anti-inflammatory, ibuprofen for fever reduction, and dobutamine hydrochloride for elevated blood pressure were used in the hospital. Nevertheless, he did not recover. On October 30 at 2 pm, he was transferred to another hospital, namely Qiandongnan Prefectural People’s Hospital for further treatment with a body temperature of 38.8°C. Then he was diagnosed with severe pneumonia, septic shock, type I respiratory failure, and severe anemia. This hospital, one of the sentinel hospitals of the severe pneumonia surveillance system in Guizhou Province, routinely reported the case of severe pneumonia. The chest X-ray and computed tomography demonstrated large shadows in both lungs. Laboratory test of blood count showed abnormal. A vital experiment, which is one of the mandatory tests of admission, reported afterward that the HIV screening test demonstrated positive, then the confirmatory test showed positive as well. Laboratory tests are illustrated in Table 1. Regarding the multiple infections, the combination of meropenem and vancomycin was used for anti-infective therapy. The maximum body temperature was 40.1°C during the disease. Unfortunately, the patient was so severe that he abandoned treatment. He was discharged from the hospital and died on his way home on November 1, 2021. There were no records of him in the Chinese HIV patients’ file, and people surrounding him did not know about his HIV historic infection by investigation, which means he may be the first diagnosed with HIV. Subsequently, a discussion of this death case concluded that the death cause was an AIDS patient with multiple bacterial infections resulting in septic shock and multiple organ failures attributed to immune deficiency, and the H9N2 virus was another inducing factor or just one of those mixed infections. Figure 1 shows the timeline of the patient’s course of the disease.

Table 1. The result of the laboratory test of the patient.

Fig. 1. Timeline for the patient’s course of the disease.

To figure out the source of infection, a total of 24 related samples were collected and detected. Four environmental daub swab samples were collected from the patient’s village house and tested for avian influenza A/H9 virus by RT-PCR, and all results were negative. In his neighbor’s backyard poultry farm, all seven samples showed negative, including two feces and five daub swab samples of drinking water, a feeding trough, and a chicken coop. Five samples were collected from two live poultry selling points in the town market, consisting of one feces and one hencoop daub swab sample H9 positive. One hencoop and two feces were confirmed A/H9 positive among eight related live poultry samples in his wife’s workplace. According to the requirements of the avian influenza-monitoring program in Guizhou Province, environmental samples from the live poultry market were collected for testing. There 391 related samples, including poultry feces, hencoop, drinking water, and chopping board daub swab, were collected from the local biggest live poultry market in Kaili Municipal since January 1, 2021, involving nine samples H5N1 positive (2.30%), nine samples H5N6 positive (2.30%), and 186 samples H9 positive (47.57%). The poultries of two live poultry selling points in the town market were just purchased from this local biggest live poultry market. Laboratory results are shown in Table 2.

Checking the latest 1-month records of 1,346 outpatients at the town hospital, there was no influenza-like illness found, under the background of patients with fever being not allowed to admit to the town hospital during the Coronavirus disease 2019 (COVID-19) pandemic. What’s more important, four throat swab samples of his four family members were negative sampling on November 2, 2021. Other contacts who attended his funeral without personal protection were closely observed for 7 days. Finally, his family members and other communications did not have similar symptoms for 7 days.

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Discussion

The avian influenza virus H9N2 subtype has low pathogenicity for poultry, causing mild or no overt signs of illness for human beings by direct or indirect contact, most likely to attack minors, and rare deaths happened (Clements et al., 2020; Zhang et al., 2020). This case was reported by the severe pneumonia surveillance system of Guizhou Province, which highlights the superiority of monitoring for human infection avian influenza cases. It was just 4 days from conscious of the severity until death, which was too fast for a 39-year-old man. Unfortunately, we failed to sequence the genome of the H9N2 avian influenza virus, but we investigated the possible source of infection. For one thing, samples of his village house and his neighbor’s backyard poultry farm were negative, which cannot eliminate the possibility of infection. But it is noteworthy that samples of the town market and his wife working live poultry market were tested, of which five samples were confirmed A/H9 positive. Based on the rural market custom, it inferred that the patient was most likely to contact H9-positive poultries in the town market. He was also presumably infected through contact with contaminated clothing from his family members. For another, The H9-positive samples in the town market just originated from the local municipal biggest live poultry market. 186 out of 391 (47.57%) samples were H9 positive in Kaili Municipal since January 1, 2021 according to the requirements of the avian influenza monitoring program in Guizhou Province. The vast majority of live poultry comes from the local municipal biggest live poultry market. Besides, the H9 subtype of avian influenza is endemic to the poultry industry in the Middle East and Asia (Fallah Mehrabadi et al., 2020). For instance, 1,326 out of 2,569 (51.62%) related samples were H9 positive from November 1, 2020 to March 31, 2021 in Guizhou province, China. All mentioned above could be proved that the infectious factors exited the surroundings, and this patient probably contacted these live poultry directly or indirectly.

Table 2. The result of H9N2 subtype-related samples.

The human morbidity of avian influenza is low, the individual difference in susceptibility. Recent research reported that rare variant MX1 alleles increased human susceptibility to the zoonotic H7N9 influenza virus (Chen et al., 2021). Moreover, the overwhelming majority of avian influenza H9N2 subtypes caused mild symptoms and rare death (Song and Qin, 2020). This death case may be attributed to the individual susceptibility and the immune deficiency caused by HIV infection. Following the medical history, he had a cold 2 months ago and did not get better from then on. Soon after, the case was diagnosed with severe pneumonia, septic shock, type I respiratory failure, and severe anemia in the hospital. The study illustrated that human-infecting avian influenza virus with chronic diseases and pregnant were at high risk of severe illness and death (Alleva et al., 2010). It suggested HIV infection was the most critical risk factor for acute exacerbation and the primary death for an H9N2 virus-infected case.

The H9N2 subtype of avian influenza may differ from the H5N1 or H7N9 subtype which raised concerns. Nevertheless, the H9N2 virus could infect humanity directly and should not be ignored or underestimated because it is a contributor to emerging human-lethal reassortants impacting public health (Mehrabadi et al., 2018). H9N2 deserved deep concern. The first report of the isolation of the H9N2 virus from South America was recorded in 1966 (Perez et al., 2003). The H9N2 virus in Asia was first isolated in 1994 in Guangdong Province, China (Sun and Liu, 2015). However, only a few studies have presented in detail to explain the changing epidemiology of the avian influenza case. To improve the understanding of human infection of the avian influenza virus, increasing studies and in-depth investigation of the H9N2 subtype should be described.

As we all know, HIV-infected people could be effectively prevented further deterioration and have better-expected survival if early treatment nowadays. This patient was diagnosed with HIV positive only 1 day before he died, but he had a severe cold for 2 months and was not detected, which is an important and robust implication for public health. It deserves more consideration for improvement. This article reported an H9N2 virus-infected case with HIV infection who died of multiple bacterial infections resulting in septic shock and multiple organ failures due to immune deficiency like all AIDS patients under doctors’ consultation. It indicated that immune deficiency patients might be more prone to acquire multiple bacteria or virus infections, including the H9N2 virus, which undoubtedly increased the possibility of genetic recombination. The H9N2 subtype virus provides genetic information to emerging human-lethal H5N1, H7N9, and H5N6 reassortants, which may emerge as another novel lethal subtype causing major public health events. It is well known that the HIV infection rate is stubbornly high, and the positive rate of H9N2 in the external environment is steadily high at present. H9N2 virus infection caused mild symptoms and few deaths. However, this young patient died because of H9N2 and HIV infection, which implies that H9N2-infected patients aggravated or even died when combined with HIV. Therefore, enhanced monitoring of H9N2 and HIV should be taken notice of by health authorities and science researchers. It urges improving the diagnostic capability of H9N2 and AIDS in primary care and paying more attention to patients infected H9N2 virus and HIV may deteriorate or even die which threatens public health.

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Conclusion

Infection with the H9N2 virus and HIV increases the risk of the disease deteriorating the condition of illness or even death. The diagnostic capability of H9N2 and AIDS in primary care should be noticed and improved to prevent public health events.

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Acknowledgments

This work was encouraged by the China CDC and Guizhou CDC. We want to acknowledge the people who contributed to this investigation work for Qiandongnan Autonomous Prefectural CDC, Kaili Municipal CDC, and Qiandongnan Prefectural People’s Hospital.

Conflict of interest

The authors declare that there is no conflict of interest.

Funding

This work was supported by Guizhou Province Health Commission Science and Technology Fund Project gzwkj2021-549. It was also supported by Qian Ke He Support Plan [2020] 4Y169.

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