The effectiveness of disease management interventions on health-related quality of life of patients with established arthritogenic alphavirus infections: a systematic review protocol

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Abstract

Review question/objective

The objective of the proposed systematic review is to critically analyze currently available research studies and present the best available evidence related to the effectiveness of disease management interventions on health-related quality of life (HRQOL) of patients with established arthritogenic alphavirus infections.

Review question/objective

The primary review question is:

Review question/objective

What is the effectiveness of clinical manifestations management interventions on HRQOL outcomes among patients with established arthritogenic alphavirus infections?

Review question/objective

The secondary review questions are:

Review question/objective

What is the effectiveness of early diagnosis of disease on HRQOL outcomes among patients with established arthritogenic alphavirus infections?

Review question/objective

What is the effectiveness of arthritogenic alphavirus infections education on HRQOL outcomes among patients with established arthritogenic alphavirus infections?

Background

Alphavirus infections are increasingly prevalent throughout the world.1,2 Currently, seven alphaviruses are known to cause arthropathy in humans. They belong to the arthropod-borne genus Alphaviruses of the Togaviridae family and are the Chikungunya virus (CHIKV), O'Nyong-nyong virus (ONNV), Ross River virus (RRV), Barmah Forest virus(BFV), Mayaro virus (MAYV), Sindbis virus (SINV) and the Semliki Forest virus (SFV).3,4 These viruses are enveloped positive-sense, single-stranded RNA viruses with a genome of approximately 10-12kb in length.5-10 The alphavirus genome is transcribed as two open reading frames (ORF), with the first ORF encoding three structural (Capsid, p62, E1) proteins and the second ORF encoding four non-structural (nsP1, nsP2, nsP3, and nsP4) proteins, which then undergo proteolytic processing, necessary for the transcription and replication of the viral genome.11,12 Although the total number of people who are living at risk of the arthritogenic alphavirus infections is not recorded, it is estimated that 1.4 - 6.2 million people have been infected with CHIKV during the 2004-2011 epidemics,2,13 about 2 million people have been infected with ONNV in Uganda in 1959 epidemic14 and about 500,000 people have been infected with RRV in Fiji during the 1979 epidemic.15

Background

Arthritogenic alphavirus infections often produce similar acute clinical manifestations of fever, arthralgia/arthritis and rash. The fever may last from a few days to several weeks, usually accompanied by a persistent joint pain in the knees, ankles, wrists, fingers and elbows and a rash.3,4 In some patients, severe manifestations of the infection may occur, leading to chronic polyarthritis, intermittent fevers, neurological complications, hemorrhage and myocarditis and even death.16-18

Background

Epidemiology

Background

The epidemiology for each arthritogenic alphavirus infection is different. The first reported CHIKV infection in humans was at Tanganyika, East Africa in 1952. CHIKV was found to first circulate in a sylvatic cycle between forest-dwelling Aedes Africanus mosquitoes and non-human primates before it circulated between humans and mosquitoes Aedes Aegypti and Aedes Albopictus, the main vectors of CHIK disease. The first outbreak of CHIKV occurred in Bangkok, Thailand, in 1958, followed by another epidemic in India from 1963-1973. There was a hiatus of 30 years before the next large epidemic occurred in 2004 in Kenya, affecting an estimated 13,500 people of the Lamu province and the city of Mombasa. There was a rapid spread of the East African genotype of CHIKV from Kenya to the countries around the Indian Ocean, affecting more than 255,000 people at the Union of the Comoros and 266,000 people on the La Reunion Island. The epidemic reached India, causing millions of people to be infected with the disease over a course of three years and subsequently impacted Asian countries such as Singapore, Malaysia and Indonesia as well as European countries such as Italy and France.4,19,20

Background

The ONNV was first isolated from the Anopheline mosquitoes, primarily the Anopheles Funestus and the Anopheles Gambiae in 1959 in Northern Uganda during one of the worst arboviral epidemics recorded - with more than two million cases of ONNV. Fortunately, no deaths were reported.21,22

Background

The RRV is found mostly in Australia, New Guinea and the South Pacific islands and may be carried by more than 30 vectors, the main vector species being Aedes Vigilax, Aedes Camptorhynchus and Culex Annulirostris. The first reported RRV outbreak occurred in 1928 in New South Wales.23 Subsequently, more outbreaks of RRV occurred during World War II and in 1956. Currently, there are an estimated 5000 RRV infections reported yearly in Australia.24

Background

The BFV is identified only in Australia, with about 400 cases reported in Queensland yearly. There were 15,592 BFV cases recorded during 1995-2008. The virus was first isolated in 1974 from the vectors Culex annulirostris mosquitoes collected from northern Victoria and southern Queensland, Australia.25

Background

The MAYV is found mostly in the rainforest regions of South America, with sporadic outbreaks and small-scale epidemics affecting countries such as Brazil, Peru, Venezuela and Columbia. It was first isolated at Trinidad in 1954 and data point to Haemagogus mosquitoes as the main vectors of the MAYV transmission.26,27

Background

The SINV was originally isolated from the Culex mosquitoes at the Sindbis village, Nile Delta, Egypt in 1952. The vectors are ornithophilic, involving mosquito species of the genera Culex, Culiseta, Coquillettidia, Ochlerotatus, Aedes and Anopheles. Fortunately, no fatalities have been reported; however, hundreds of SINV-infected cases have been confirmed in South Africa, Uganda, Australia and Finland.28,29

Background

The SFV was first isolated from mosquitoes at the Semliki forest of Uganda in 1942. The virus can be transmitted via infected mosquitoes as well as the air-borne contaminated aerosols. The SFV is found mostly in Africa, Asia and Europe. Infections are generally asymptomatic and mild.30,31

Background

Disease management

Background

Progress in understanding disease transmission and diagnosis in this field due to the recent attention to Chikungunya epidemics affecting countries in Africa, Asia, and Europe, and the on-going Ross River infections reported in Australia, have generally improved the awareness and preparedness of community and health professionals.32,33 However, progress has been slow in relation to symptom management of the arthritogenic alphavirus infections in patients and the available treatments are limited to symptom control and support, usually including antipyretics and analgesics.4 No licensed alphavirus vaccine is currently available. Arthritogenic alphavirus infection is thought to confer long-term immunity to the specific disease.34-37

Background

A broad approach to the management of arthritogenic alphavirus infections is essential to alleviate the burden of the infections on the society.38-40 For people without the infection, vector control and disease surveillance may help in alleviating the burden of the infections nationally and globally.41,42 For infected patients, the appropriate and timely clinical diagnosis by the physician, active management of clinical signs and symptoms by the physician and patient as well as the education of patient and physician on disease management interventions may have a positive association with the patient's health-related quality of life (HRQOL) and prevent severe morbidity and mortality.

Background

Health-related quality of life

Background

According to Bowling (1995), HRQOL is defined as

Background

‘The optimal levels of mental, physical, role (e.g. work, parent, carer, etc) and social functioning, including relationships and perceptions of health, fitness, life-satisfaction and well-being. It should include some assessment of the patient's level of satisfaction with treatment, outcome and health status and with future prospects. HRQOL excludes factors such as sufficiency of housing, salary and the opinions of the immediate environment’.43

Background

The World Health Organization Quality of Life (WHOQOL) group has a similar yet broader definition of quality of life, defined as

Background

‘An individual's perception of their position in life in the context of culture and value systems in which they line and in relation to their goals, expectations, standards and concerns. It is a broad ranging concept affected in a complex way by the person's physical health, psychological state, level of independence, social relationships to salient features of their environment’.44

Background

The impact of specific arthritogenic alphavirus infections such as CHIKV and RRV on HRQOL has been studied using generic and disease-specific HRQOL assessment tools.45-48 These assessment tools are self-reported and are fast gaining popularity due to the emphasis on patient-centered satisfaction and their feelings. One of the goals of medical treatment and care is to increase survival rates and to add quality to the survival. When quality of life is used as a measurement of outcome, physicians are more inclined to consider the impact of the disease and its management interventions on the physical, emotional and lifestyle aspects of patients.49

Background

Many questions still remain about the effectiveness of current management interventions of arthritogenic alphavirus infections on infected patient's HRQOL. The goal of this systematic review is thus to elucidate and gain a clearer understanding on the effectiveness of disease management on health-related quality of life of patients with arthritogenic alphavirus infections.

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