|Ahead of print publication
Postexposure prophylaxis with oseltamivir in outbreak control of pH1N1 influenza onboard a naval warship: An observational study
Abir Mazumdar1, Sougat Ray2, Vijay Bhaskar3, Kavita B Anand4, B Vijay Bhaskar5
1 MO, Western Fleet, Department of Community Medicine, HQWNC, Mumbai, Maharashtra, India
2 Professor & Sr Adv, Department of Community Medicine, HQWNC, Mumbai, Maharashtra, India
3 Associate Professor, Department of Community Medicine, AFMC, Pune, Maharashtra, India
4 Associate Professor, Department of Microbiology, AFMC, Pune, Maharashtra, India
5 FMO, HQ Western Fleet, Mumbai, Maharashtra, India
|Date of Submission||06-Mar-2020|
|Date of Decision||01-Apr-2020|
|Date of Acceptance||17-May-2020|
|Date of Web Publication||25-Aug-2020|
Kavita B Anand,
Associate Professor, Department of Microbiology, AFMC, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Control measures such as maintenance of social distancing, hand hygiene, respiratory hygiene, regular disinfection, and keeping a high index of suspicion for probable cases form the basis of containing a pH 1N1 outbreak onboard a Naval ship. As per the present guidelines, though a quadrivalent vaccine is recommended for health-care workers in close contact, anti-flu postexposure prophylaxis strategies have been predicted to be effective in some mathematical models. Chemoprophylaxis with oseltamivir was assumed to be an effective measure to control the outbreak onboard ship while at sea. Materials and Methods: A total of 275 asymptomatic individuals were started on oral oseltamivir prophylaxis on board from day 17 onward for a duration of 10 days and side effects of the medication were noted. Results: With chemoprophylaxis of the entire crew with oseltamivir, the number of positive cases per day reduced. The outbreak cleared within 3 days of initiation of chemoprophylaxis. Active surveillance was continued for 14 days since the last positive case. Conclusion: In an afloat setting, with a rapidly spreading outbreak of airborne disease, mass chemoprophylaxis with oral oseltamivir along with aggressive public health control measures were found to have contained the spread with only mild side effects which were reported.
Keywords: Mass prophylaxis, navy ship, oseltamivir
|How to cite this URL:|
Mazumdar A, Ray S, Bhaskar V, Anand KB, Bhaskar B V. Postexposure prophylaxis with oseltamivir in outbreak control of pH1N1 influenza onboard a naval warship: An observational study. J Mar Med Soc [Epub ahead of print] [cited 2020 Nov 24]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=293325
| Introduction|| |
pH1N1 influenza is a highly contagious virus which transmits through inhalation of aerosols and by direct contact with fomites. In the setting of an operational Naval warship, there is congregation of the ships' crew in living spaces, mess decks and work spaces, closeness of susceptible contacts, abundance of fomites, recirculation of air in the microenvironment, and difficulty in ensuring absolute isolation of cases and undertaking quarantine measures. Chances of transmission of this highly contagious disease to susceptible population are thus higher than elsewhere. In addition to the increase in morbidity and loss of man-hours, it also leads to a low morale among the ship's company, and in turn, can affect the operational efficiency of a frontline warship.,
The composition of the influenza vaccine is changed annually to match the circulating virus type based on the recommendations of the World Health Organization (WHO). Traditionally, annual seasonal influenza vaccination is targeted to high-risk people, but in recent years, with increasing evidence in favor of universal vaccination, recommendations have been expanded to target larger numbers and diverse population subgroups. A quadrivalent vaccine is recommended for health-care workers in close contact, but the vaccine has limited efficacy and availability. Also, it needs to be administered at least a month prior to the commencement of a likely seasonal outbreak., Ring prophylaxis with oseltamivir was undertaken in a military cohort living in close proximity in Singapore with considerable success. Cost-effective studies have been conducted for use of antivirals for therapeutic and prophylactic use and have been recommended for influenza treatment and postexposure prevention for healthy and high-risk individuals and for seasonal prevention in high-risk individuals.
Anti-flu prophylaxis strategies have been predicted to be effective in some mathematical models. However, data are still needed to document their actual effectiveness during an outbreak. We report here the effects of aggressive preventive measures, diagnosis and isolation, and containment of the susceptible and mass postexposure chemoprophylaxis with oral oseltamivir in attenuating the transmission of the virus and evaluate the possible side effects due the medication in a closed environment.
| Materials and Methods|| |
All cases of influenza-like illness (ILI) occurring among personnel onboard, starting from the index case, were listed. The data of the cases over a period of 1 month were analyzed. Detailed data pertaining to demography, place of stay, history of travel or contact with suspected/confirmed cases of pH 1N1 Influenza, date of onset of illness, date of referral to/admission at a tertiary center, clinical details, laboratory reports, and any sign of complication were gathered from all cases.
The entire ships' crew were considered close contacts of the confirmed cases. They were closely monitored and reviewed twice daily for onset of symptoms. The contacts were contained onboard in separate cohorts and their movements were restricted to these cohorts. The individuals on chemoprophylaxis with oseltamivir were subjected to questionnaire-based survey and monitored for any side effects of the medication. Informed consent was obtained from everyone.
ILI included an acute respiratory infection (sudden cough and sore throat) with measured fever of ≥100.4 F, with onset within the last 7 days. Other associated symptoms taken into consideration were muscle or body aches, headaches, fatigue, vomiting, and diarrhea (though more common in children than adults), running or stuffy nose. A suspected case of H1N1 influenza was defined as a person with acute febrile respiratory illness (fever, with temperature >100.4°F) with onset within 7 days of close contact with a person, who is a confirmed case of A/H1N1pdm09 virus infection, or within 7 days of travel to areas where there are one or more confirmed cases, or resides in a community where there are one or more confirmed cases of A/H1N1pdm09 cases. A confirmed case was defined as an individual with laboratory-confirmed new A/H1N1pdm09 virus infection by real-time reverse transcriptase-polymerase chain reaction (Xpert Flu).,
Testing and treatment protocol
All suspected cases were referred to a tertiary care hospital for further management. Oropharyngeal swabs from all cases were subjected to Gene Expert cartridge-based nucleic acid amplification test for confirmation using the Centers for Disease Control (CDC)/WHO testing protocol. Cases which were positive for laboratory test for A/H1N1pdm09 were admitted in the isolation ward of the hospital, irrespective of their clinical condition (Category A, B, or C symptoms) and residential status (whether staying on board or in family accommodation).
Oseltamivir postexposure chemoprophylaxis
A total of 275 asymptomatic individuals were started on oral oseltamivir prophylaxis (75 mg once daily) on board from day 17 onward for a duration of 10 days. All personnel were informed about the chemoprophylaxis, its use, and other associated issues. The medication was given only after the consent by the individuals. They were followed up with a questionnaire about side effects of the medication [Table 1].
Cases were classified according to the case definition. Proportion of suspected and laboratory-confirmed cases, attack rate (AR), and case fatality rate (CFR) of the disease were calculated. To study the time and geographical distribution of cases, epidemic curve and area map were plotted, respectively. Active surveillance was continued for 14 days from the reporting of the last positive case to assess the effect of the employed control measures and detection of any fresh case. The side effects of oral oseltamivir prophylaxis if any were studied and analyzed.
Control measures initiated
The ship adhered to the international air-conditioning and ventilation standards. The ship had a two-bedded isolation ward which had relative negative pressure with respect to the ship's ventilation, along with dedicated air filtration unit. Cases with ILI were shifted to the isolation ward and then to the sick bay. The entire ships' crew was divided into different cohorts and could operate separately in that cohort, so that the transmission of the infection is limited. Disinfection with 5% cresol used every 12 h was adhered to at all times, and wet dusting of doorknobs, handles, railings, ladder supports, s, computer mouse pads, and keyboards with 1% sodium hypochlorite was carried out. Strict hand hygiene was followed by all individuals with alcohol-based sanitizers and soap and water. Common towels at dining halls and washrooms were replaced with disposable tissue papers. Cough etiquette was advised to be followed strictly. Health education drive was organized for the crew with special emphasis on infection control measures. N-95 masks and other personal protective equipment were used by the medical team and the ships' crew were advised to wear cloth masks. Daily demonstrations and supervision by the medical team ensured strict compliance to the above measures.
As per the standard protocol, the two health-care workers were started on prophylactic dosage of oral oseltamivir 75 mg daily for 10 days as soon as the index case was diagnosed. When the epidemic reached its peak on day 16, with four positive cases on the previous day and five positive cases diagnosed on that day, all personnel on board were recognized as susceptible contacts and a mass chemoprophylaxis with directly observed dosage of oral oseltamivir 75 mg OD for 10 days for the entire crew on board was initiated.
| Results|| |
A total of 305 Navy crew members and three civilians were present onboard during the outbreak. None of the crew had received any influenza vaccine prior to the deployment. Over a 30-day period from 12 March to 15 April, 33 patients with ILI sought treatment at sickbay of the ship. Maximum cases were from the age group of 20 to 25 years (58%) [Table 2]. The common symptoms were sore throat (93%), cough (89%), and fever (86%), with constitutional symptoms of myalgia (73%) and generalized headache (56%) and malaise (65%), with only three cases having gastrointestinal symptoms in the form of nausea (20%) and vomiting (18%).
Out of the 33 clinically suspected cases, swabs of 17 cases (i.e., 51.52% of suspected cases) were found to be positive for A/H1N1pdm09, all of whom were hospitalized and managed as in-patients. Out of the 17 positive cases, 11 had Cat “A” symptoms, 4 had Cat “B” symptoms, and 2 had only sore throat and dry cough without any fever. These 2 patients were afebrile all throughout, from their initial presentation till their treatment. Out of the 16 suspected cases who tested negative for A/H1N1pdm09, 12 had Cat “A” symptoms and 4 had Cat “B” symptoms, and these 4 patients with Cat “B” symptoms were admitted and managed as in-patients till symptomatic improvement. None of the 33 cases had Cat “C” symptoms during diagnosis or treatment thereafter [Table 1].
The index case was diagnosed in middle of the month, though his travel history or contact history was not contributory to the exact source of the infection. The AR of A/H1N1pdm09 Influenza during the 32-day period was 5.82%. The epidemic curve [Figure 1] to study the time distribution of all cases (positive and negative) showed clustering of cases between day 15 and 18 of start of cases. Cases were evenly distributed across all areas of the ship, with no specific post or compartment showing an exceptionally high AR. The distribution of cases among all locations, age group, and ranks gave an indication of the entire crew to be considered contacts. No admitted case developed any complication and CFR in the outbreak was zero. A total of 3126 man-hours were lost due to pH1N1-related admissions (both positive and negative cases). Among the 275 healthy personnel on chemoprophylaxis, the peak of onset of side effects was 78 h after starting the first dose. Mild side effects were reported with most of them complaining of dyspepsia or nausea [Table3].
The outbreak reached its peak on day 16 with 05 diagnosed cases. The previous day had 4 cases. The chemoprophylaxis regime for the entire ship's crew after screening was initiated on day 16. The other preventive measures continued to be in place. Over next 2 days, the outbreak showed a dip in number of cases. Three cases on day 17 and 2 positive cases occurred on the next day. There were no cases reported thereafter. Active surveillance was kept on for 14 days since the last positive case. There were no new cases or resurgence of the outbreak after day 19 [Figure 1].
| Discussion|| |
The outbreak was controlled with aggressive preventive measures in a period of 19 days (the time period from the first positive case till the last positive case). The predominant age group affected were the young and the middle aged individuals, as is consistent with studies conducted on similar influenza outbreaks.,, Sore throat, cough, and fever were the most common symptoms at presentation, similar to other such studies conducted., The seasonality of the outbreak corresponded with the peak seasonal period of A/H1N1pdm09, which peaks in March in India. The CFR was nil in this outbreak, which was comparable to the estimates of 0.004%–5.5%, reported from similar outbreaks in other countries, and also may be because none of the cases had any preexisting morbidity.
The spread of the disease during an pH 1N1 outbreak can reach an AR as high as 51% in children. An outbreak among a vaccinated crew on board an U. S. Naval warship has documented an AR of 42%., A low AR of 5.82%, observed in this outbreak, cannot be attributed exclusively to the natural course of the disease, but is a definitive indicator that the preventive interventions had a significant beneficial effect in terminating the outbreak early. The explosive nature of the epidemic is evident in the clustering of maximum positive cases (14 out of 17) over a period of four days [Figure 1].
A study examined the antiviral drug resistance of Influenza A viruses circulating during 2009 Influenza season in Mumbai found no known mutations showing resistance to oseltamivir. Another study conducted between 2017 and 2109 found the absence of any oseltamivir-resistant mutation (H275Y) in the neuraminidase gene of the current isolates, suggesting continuing use of oseltamivir in this region. In fact, oseltamivir-sensitive A/H1N1pdm09 viruses isolated in this region was found to be antigenically similar to oseltamivir-sensitive reference vaccine strains recommended by the WHO. The CDC has also found that oseltamivir continued to be susceptible to most of the prevailing influenza strains. A provision for mass chemoprophylaxis is mentioned in the Ministry of Health and Family Welfare guideline if the cluster of population with the outbreak is limited by natural geographic boundaries. In an outbreak control of H1N1 influenza in Singapore Army barracks in June–July 2009, oseltamivir ring chemoprophylaxis was advocated on a mass scale basis. This showed significant positive results in reducing the impact of an Influenza H1N1 epidemic. The study is an observational study and is limited by not having a control group.
Few studies indicate that the use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults, and vomiting in children. In our study, only mild side effects were observed, comprising mainly nausea, which was relieved with antacid medications. Further, as maximum number of side effects were found after 78 h, few of them might have been unrelated to Oseltamivir. However, when determining the timing and duration for administering influenza antiviral medications for prophylaxis, factors related to potential side effects will have to be considered.
| Conclusion|| |
Aggressive public health control measures are indispensable and may result in keeping the pH 1N1 influenza outbreak as a “point-source” type rather than resulting in a 'propagated' epidemic. In an afloat setting, with a rapidly spreading epidemic, postexposure chemoprophylaxis with oral oseltamivir could be an effective adjunct to the control measure without causing harm to the ships' crew. It can also be an option for reducing the impact of the disease. Our experience provides evidence that early case detection, isolation of cases, and the use of antiviral postexposure prophylaxis effectively truncate the spread of infection during an outbreak of a highly contagious air borne disease in a close environment. Creation of negative air pressure isolation compartments onboard may be considered as a useful, long term control measure for outbreak of airborne diseases onboard Naval ships during long deployment. Other preventive measures such as use of face masks, frequent hand washing, and disinfection would remain the main stay of preventive strategy. There is a need for further research in this field to have considerable evidence for the use of oseltamivir in healthy adults for postexposure chemoprophylaxis in closed settings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]