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A study of influenza 2017–2018 outbreak in Andhra Pradesh, India
Nagaraja Mudhigeti, Rishi Gowtham Racherla, Padmalatha Anjaneyulu Mahalakshmi, Madhavi Latha Pamireddy, Umapathi Nallapireddy, Meenakshi Kante, Usha Kalawat
Department of Microbiology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
Date of Web Publication 18-Mar-2019
Dr. Usha Kalawat
Department of Microbiology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, Andhra Pradesh
DOI: 10.4103/ijmm.IJMM_18_272
Background and Objectives: Influenza virus is a typical human pathogen causing serious respiratory illness resulting in significant mortality throughout the globe. Andhra Pradesh witnessed the first case of influenza A H1N1 in India from Hyderabad (now in Telangana) on May 16, 2009. In the recent past, Andhra Pradesh witnessed exponential increase in the number of confirmed cases of influenza infection. In this study, we present the salient features of the recent outbreak of influenza during 2017–2018 in the state of Andhra Pradesh, first of its kind after the division of the state. Materials and Methods: Clinically, suspected cases of influenza-like illness received in the Virus Research and Diagnostic Laboratory, Department of Microbiology, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, from January 2017 to May 2018 were included in the study. The samples were tested for influenza A, influenza A (H1N1) pdm09, influenza A (H3N2), influenza B, influenza B/Yamagata and influenza B/Victoria. Results: A total of 1286 samples were received for testing. The positive samples were influenza A unsubtypable (109), influenza A (H1N1) pdm09 (356), influenza A (H3N2) (38) and influenza B (19; Victoria - 2, Yamagata - 17). There was no significant difference in positivity between genders with 260 (49.81%) females and 262 (50.19%) males being positive. Conclusion: The outbreak started in the late monsoon (January) of 2017 and had two peaks; one in summer months and another in winter months. Influenza B virus was reported from December 2017 to May 2018. Age groups ≤5 years and 6–18 years had higher positivity as compared to other age groups. Regular surveillance programmes are required for assessing the trends of influenza infections due to various subtypes and to plan timely and adequate steps for preventing the spread to larger vulnerable population.
Keywords: Andhra Pradesh, India, influenza, outbreak
Mudhigeti N, Racherla RG, Mahalakshmi PA, Pamireddy ML, Nallapireddy U, Kante M, Kalawat U. A study of influenza 2017–2018 outbreak in Andhra Pradesh, India. Indian J Med Microbiol 2018;36:526-31
Mudhigeti N, Racherla RG, Mahalakshmi PA, Pamireddy ML, Nallapireddy U, Kante M, Kalawat U. A study of influenza 2017–2018 outbreak in Andhra Pradesh, India. Indian J Med Microbiol [serial online] 2018 [cited 2019 Jul 18];36:526-31. Available from: http://www.ijmm.org/text.asp?2018/36/4/526/254388
Influenza virus is a typical human pathogen causing serious respiratory illness, resulting in high mortality throughout the globe. It can cause widespread pandemics as it spreads easily from person to person.[1] Andhra Pradesh witnessed the first case of influenza A H1N1 in India from Hyderabad (now in Telangana) on 16th May 2009.[2] Outbreaks of various viral agents are common in India. Timely diagnosis of these outbreaks is critical to mount appropriate public health response. The inadequacy of specialised virology laboratories in the country was noticed in the past as well as during the recent 2009 H1N1 pandemic. After 2009 pandemic, fewer confirmed cases were reported from Andhra Pradesh.[3] However, in January 2017, there was an exponential increase in the cases with influenza-like illness with increased positivity for influenza A (H1N1) pdm09. In the present article, we have discussed the various highlights of influenza 2017–2018 outbreak in the state of Andhra Pradesh.
~ Materials and Methods
The study was conducted at Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, Sri Venkateswara Institute of Medical Sciences (SVIMS), a teaching hospital in Tirupati, Andhra Pradesh, during January 2017–May 2018. The study was approved by the Institutes Ethics Committee. Clinically, suspected cases belonging to Category C as per the Ministry of Health and Family Welfare guidelines on the categorisation of H1N1 cases [4] were included in the study. Throat swabs and nasal swabs/nasopharyngeal swabs were collected by clinician in the viral transport medium and transported to VRDL, SVIMS, where the samples were stored at 4°C and tested within 24 h. Samples were received from all parts of Andhra Pradesh. Cold chain was maintained for the samples received from distant places. Total number of samples processed during the study period were 1286.
RNA Extraction: QIAmp ® viral RNA Mini Kit from Qiagen, USA, was used for RNA extraction.
Real-time polymerase chain reaction (PCR) testing of samples: Samples were tested by real-time reverse transcriptase PCR (RT-PCR) for influenza type A and B using AriaMx Real-time PCR machine, Agilent Technologies, Germany. Influenza A positives were further subtyped for influenza A H1N1 pdm09 and influenza A H3N2. Influenza B positives were subtyped for influenza B Yamagata and influenza B Victoria (CDC Primer probe)[5] using the reagents provided by the National Institute of Virology (NIV), the Resource Centre for VRDL (RCVDL), Pune.
The rRT-PCR amplification conditions: Reverse transcription at 45°C for 10 min, Taq inhibitor inactivation at 95°C for 10 min and PCR amplification (45 cycles) at 95°C for 15 s and at 58°C for 45 s. Fluorescence data for influenza A (FAM), influenza A H1N1 pdm09 (FAM), influenza A H3N2 (VIC), influenza B (CY3), influenza B/Yamagata (FAM), influenza B/Victoria (VIC) and RNase P (FAM) were collected during 58°C step.
All samples exhibited RNase P reaction curves that crossed the threshold line at or before 35 cycles, indicating the presence of sufficient RNA from human RNase P gene. Positivity for RNase P gene was important to assess the quality of the specimen. A sample was considered positive for influenza A H1N1 pdm09 if both the influenza A and the influenza A H1N1 pdm09 subtype reaction growth curves cross the threshold line within 35 cycles. Similarly, a sample was considered positive for influenza A H3N2 if both the influenza A and the influenza A H3N2 subtype reaction growth curves cross the threshold line within 35 cycles. If the sample is positive for influenza A and negative for influenza A H1N1 pdm09 and influenza A H3N2, it is considered as influenza A unsubtypable. A sample is considered as positive for influenza B Yamagata/Victoria if both influenza B and influenza B Yamagata/Victoria subtype reaction growth curves cross the threshold line within 35 cycles.
Patients were divided into four age groups for the analysis of the results. Age Group I, Group II, Group III and Group IV comprising ≤5, 6–18, 19–59 and 60 years and above, respectively.
Normally distributed continuous variables were summarised by mean and standard deviation; remaining variables were summarised as median (interquartile range). All categorical variables were summarised as percentages. For data analysis, statistical software IBM SPSS Statistics 20.0 for Windows version, IBM Corp., NY, USA was used.
During the study period, a total of 1286 samples from clinically suspected cases of influenza-like illness belonging to Category C as per case definition were received for testing. Of these 1286 samples, 522 samples tested positive for influenza A and B subtypes. The influenza A positive samples were further characterised as influenza A unsubtypable (109), influenza A H1N1 pdm09 (356) and influenza A H3N2 (38). The influenza B-positive samples were subtyped as influenza B (19; Victoria - 2, Yamagata - 17). Distribution of positive samples among the four age groups is presented in [Table 1]. Maximum number of suspected cases was in Group III, followed by Group I, Group IV and Group II in descending order. The highest number of positive cases belonged to age Group II, followed by Group III, Group I and Group IV in descending order. The lowest number of samples were received from age Group II (125), of which 56 (44.8%) tested positive for influenza. The age-specific positivity (data not shown) did not vary significantly across the ages I, II and III; however, it was significantly low in age Group IV.
Table 1: Age-wise distribution of influenza-positive cases
Of total suspected cases (1286), 606 were female and 680 were male. Of total 522 positive cases, 260 were female and 262 were male. There was no significant difference in positivity percentage between two genders with 49.81% females and 50.19% males being positive. Among 260 female influenza positive cases, 179 were influenza A H1N1 pdm09, 53 were influenza unsubtypable, 18 were influenza A H3N2 and 10 were influenza B cases. Among 262 male influenza positive cases, 177 were influenza A H1N1 pdm09, 56 were influenza unsubtypable, 20 were influenza A H3N2 and 9 were influenza B cases. Gender-wise distribution of confirmed cases among the influenza subtypes is represented in [Table 2]. Majority of the positive cases had the clinical manifestations of fever, breathlessness, cough and myalgia, followed by sore throat and nausea in decreasing order which was common among all influenza-positive cases. Twenty cases of haemorrhagic manifestations and 12 cases of conjunctivitis were also found. Cases with influenza A (H3N2) positivity had more severe complications such as haemorrhagic manifestations (five cases), conjunctivitis (five cases), diarrhoea (three cases), jaundice (five cases) and encephalitis (two cases). The data of clinical manifestations are given in [Table 3]. We received samples from 13 districts of Andhra Pradesh, which is depicted in [Table 4]. Chittoor district was the most affected district, followed by Kadapa, Krishna and Prakasam districts. The influenza outbreak had two peaks with highest number of positive cases during March and another peak during September 2017 with the domination of influenza A H1N1 pdm09. In 2017, influenza B cases were found only during the month of March whereas in 2018, cases of only influenza B were detected with nil cases of influenza A H1N1 pdm09 and influenza A H3N2. Month-wise distribution of influenza positive cases is depicted in [Figure 1].
Table 2: Gender-wise distribution of influenza-positive cases
Table 3: Clinical manifestations of influenza-positive cases
Table 4: District-wise distribution of influenza-positive cases
Figure 1: Month-wise influenza-positive cases
Influenza A H1N1 pdm09 outbreak in 2009 had 27,236 confirmed cases and 981 deaths in India. The post-pandemic period in 2010 resulted in 20,604 confirmed cases with more deaths (1763). Severely affected states were Maharashtra, Delhi, Rajasthan, Gujarat, Madhya Pradesh, Karnataka, Haryana, Kerala, Tamil Nadu and Andhra Pradesh with high fatality in Rajasthan. Another influenza outbreak hit in India in 2015, during which highly affected states were Rajasthan, Gujarat, Delhi, Maharashtra, Karnataka and Madhya Pradesh with more number of deaths in Rajasthan and Gujarat. Very few cases were reported from Andhra Pradesh.[3],[6] After the 2009 outbreak, cases were reported intermittently from Andhra Pradesh.
The current outbreak was the first outbreak in the state after bifurcation from Telangana. A total of 522 confirmed influenza cases with 40.59% positivity were observed. Samples were received from all over the state comprising 13 districts. This number was high when compared with previous reports of influenza cases up to 2015.[3] Chittoor district was most severely affected with 199 influenza A H1N1 pdm09, 23 influenza A H3N2 and 16 influenza B (Victoria-2, Yamagata-14) cases, followed by Kadapa, Krishna, Prakasam and Nellore districts. More number of positive cases from Chittoor district compared to other districts could be due to referral bias as the testing centre was situated in Chittoor district itself. As Chittoor district is a tourist centre which attracts travellers from all over the globe might be another reason for acquiring or spreading the virus. Fewer cases from other districts were because of lack of awareness about the existence of the testing centre or truly the districts were spared from influenza infections could not be ascertained.
In a study by Arbat et al.[1] in 2015, the influenza epidemic peaked in the last week of February and first week of March and thereafter subsided till the first week of April. Similarly, Chudasama et al.[7] and Siddharth et al.[8] also reported more number of cases during winter months in India whereas Kashinkunti et al.[9] in their study reported that swine flu cases were more in summer months, that is, July–September.
Studies by Gurav et al.[10] from Panchgani (Maharashtra) and Biswas et al.[11] from Kolkata (West Bengal) reported that the outbreaks of influenza A H1N1 pdm09 were common in monsoon season.[10],[11] On the contrary, the first positive case of this outbreak was reported at the end of monsoon in mid-January. The outbreak started in January, progressed through February and peaked in the summer (March). Then, numbers came down gradually by the end of May. This was in concordance with other studies by Gurav et al.,[12] Rao.[13] and Rao et al.,[14] where outbreak was detected in summer. January is winter month for North India, but for South India, it marks the beginning of summer.
Once again, the positive cases started increasing in August, peaked for second time in September and declined thereafter with no positive case in November. Hence, there were two peaks for 2017 outbreak in the state of Andhra Pradesh; one in summer and another at the start of the winter. Studies from England and Vietnam have also reported two peaks; one in summer and another one in winter for seasonal influenza as well as influenza A H1N1.[15],[16] However, other studies from India did not report dual peaks for influenza. Change in influenza patterns was indicated by Arbat et al.[1] A study by Lin et al.[17] from Guangdong, China reported two peaks for influenza infection; one in July caused by seasonal influenza and another in November by pandemic 2009 strain.
No significant difference was observed among different sexes with males comprising 50.19% and females comprising 49.81%. This is in concordance to a study by Arbat et al.[1] In a study by Shukla et al.,[18] 86% of the patients were male and 14% were female. They suggested the poor accessibility of health services to females and more travel and outdoor movement for business purpose by males as the major contributing factors for this. Revdiwala et al.[19] also reported higher prevalence of influenza infection among males whereas Dee and Jayathissa [20] had contradictory findings with higher prevalence among women as compared to men.
The highest influenza-like illness cases were from age Group III (555, 45.15%) with highest laboratory-confirmed cases (248, 47.50%). In a study by Pollock et al.,[21] the <5-year age group comprised 73.9% of the laboratory-confirmed cases and 78.3% of ILI cases. They also reported that the attack rate in the <1-year age group was higher as compared to other age groups.
Number of suspected as well as confirmed positive cases was significantly low in age Group IV which could be due to restricted outdoor activities in this age group as compared to the other age groups. Limited outdoor activities limit the exposure of the individuals to patients or their contacts, thus reducing transmission of infection.
Although the positivity for influenza A H1N1 pdm09 did not differ significantly across different age groups, the age Group I, that is, <6 years of age was most severely affected with 75.36% positivity. Similar findings were reported by Siddharth et al.,[8] Delaney et al.[22] and Dee and Jayathissa [20] wherein they reported that influenza A H1N1 pdm09 relatively spared the older population and had stricken the younger population more harshly.
Influenza A H3N2 positivity was observed in 7.28% (38 samples) of cases with maximum positivity in age Groups II and IV, that is, 6–18 years and 60 years and above, respectively. This is in contrast to the positivity for influenza A H1N1 pdm09, which was more in younger age group with maximum positivity in children <6 years. Majority of influenza A H3N2-positive cases had a history of contact from the household itself, that is, either from another sibling or parents.
Out of 38 influenza A H3N2 cases, four were reported in March 2017, six in August and 28 cases in September with no positive cases in the subsequent months. The median age was 24.5 years ranging 7.5–60 years. A total of 19 cases of influenza B were reported with maximum being from Chittoor district (16 cases), the rest three cases were reported one each from Kadapa, East Godavari and Anantapur. Influenza A H3N2 and influenza B were circulating in most parts of India such as Delhi, Chennai, Dibrugarh, Kolkata, Nagpur, Pune and Vellore. In our neighbouring state Tamil Nadu, influenza B Victoria and Yamagata strains were in circulation.[23] Vellore had predominant influenza B Victoria, whereas Chennai had the latter. Therefore, possible links of contacting the infections of influenza A H3N2 and influenza B Victoria from these cities cannot be ruled out as Chittoor district is a tourist place with more frequent visits by people from Tamil Nadu state.
As the samples belonged to Category C, fever was the most common symptom (100%) observed in all subtypes of influenza A and B. Majority of the positive cases had the clinical manifestations of fever, breathlessness, cough and myalgia, followed by sore throat and nausea in decreasing order. The influenza A H3N2-positive cases had severe manifestations as compared to influenza A H1N1 pdm09 and influenza B-positive cases. The clinical manifestations were rather less severe in influenza B and influenza A unsubtypable. In a study by Guadalupe et al.[24] from Southern Mexico, predominant clinical features included fever, cough and headache. Similar findings were also reported by other studies from India,[25] China [26] and the United States of America.[27] Arbat et al.[1] reported that there was a significant difference in the clinical presentations among positive cases versus negative cases. There was no significant difference for gender, age and symptoms among laboratory-confirmed versus suspected cases (data not shown), which is similar to a study by Pollock et al.[21]
The reports were shared with the concerned district health authorities for necessary action. In the current study, we could not follow up the cases for their outcome which is one of the drawbacks. In the future, further follow-up of the confirmed cases during the outbreaks will help us to know the severity of disease and to estimate morbidity and mortality.
This study had certain peculiarities such as no seasonal trend was observed and had two peaks of infections; one in summer months and another in winter months. Although more cases were reported for influenza A H1N1 pdm09, disease severity was high in influenza A H3N2. Circulation of influenza B in this part of country is also another mark. Young children and adults are the two age groups most affected. Influenza outbreaks in India ought to be additionally inspected to decide the harmfulness and potential danger of the infection. The silent spread of the virus is mainly because of lack of awareness. The need for spread of awareness regarding the modes of spread and the preventive measures which can be followed to curtail the rapid spread of influenza among masses was seriously felt. Further enhanced surveillance and checking of the influenza episode will altogether upgrade the alternatives of how best we can optimise efforts to both treat and in addition forestall spread of the infection.
We acknowledge the Department of Health Research (DHR), Indian Council of Medical Research (ICMR), New Delhi, India, and National institute of virology (NIV) for providing necessary infrastructure and reagents to carry out this study.
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[Table 1], [Table 2], [Table 3], [Table 4]