Respiratory Syncytial Virus (RSV), an enveloped RNA virus with a non-segmented single-stranded negative-sense genome, is the primary cause of hospitalization in the first year of life for children in most parts of the world. The global estimate in 2005 indicated that at least 33.8 million episodes of RSV associated acute lower respiratory infection (ALRI) occurred worldwide in children younger than 5 years and most of these deaths occurred in developing countries. This study aimed to systematically aggregate and analyze published epidemiological data on the seasonality of RSV lower respiratory tract infections in young children in developing countries. Articles in English published between 2002 and 2014 were identified through literature searches in PubMed, Web of knowledge, and . The season in which RSV epidemics occur typically depends on geographical location and altitude. It is likely that several factors interact in complex ways in the development of epidemics under favorable climatic conditions.

Keywords: Respiratory syncytial virus; RSV; Seasonality; Lower respiratory tract infection; Children; Developing countries

Lower respiratory tract infection (LRTI) is the leading global cause of death in children between 1 month and 5 years of age [1-4]. Clinical characteristics of RSV infection include upper respiratory infection with rhinorrhea and nasal congestion lasting between 7 and 12 days. Re-infection rates vary between 6% and 83% each year, showing that initial infection does not confer immunity to succeeding infection [5]. By the age of 2 years, nearly all children have had RSV infection [6]. More serious disease involving the lower respiratory tract may develop in older children especially in immunocompromised and cardiopulmonary disease patients [7,8]. RSV season varies over time and from location to location [9,10]. The start and end of RSV season can vary year to year, state to state, and can even vary within communities in the same region [9,11].

In countries with temperate climates, RSV causes epidemics of LRTI among infants and young children during late fall, winter, and early spring. In temperate climate regions, the RSV epidemic pattern depends on the temperature rather than the rainfall pattern. Most communities with temperate climates have a well-defined season of 3 to 5 months usually starting in the Northern hemisphere in October or November and continuing until February or March, followed by a peak in activity in the Southern hemisphere. In the southern hemisphere, wintertime epidemics occur from May to September. In addition, RSV studies conducted in temperate climates have identified a biannual pattern in the peak of RSV epidemics and RSV hospitalization rates, whereby the severity of RSV seasons alternates between milder and more severe. However, this is not predictable, and the differences may be more related to climatic changes [12].

This study aimed to systematically aggregate and analyze published epidemiological data on the seasonality of RSV lower respiratory tract infection in young children in developing countries (Table 1).

In tropical or semitropical climates, RSV outbreaks are frequently associated with the rainy rather than the colder season. The variation is less apparent in the tropics, where there is small fluctuation in ambient temperature. RSV epidemics appear regularly but with different patterns of seasonality. In northern tropical areas, the seasonality seems to be associated with a decrease in temperature and an increase in rainfall. In the equatorial regions, RSV appears to be present most of the year. There are definitely 7 to 8 months of the year when the prevalence is higher than in the other 4 or 5 months, with some increase during the dry months. Tropical areas south of equator have a seasonality that is associated with decrease in both temperature and rainfall. Geographic and climatic factors are clearly associated with epidemics, but it is uncertain whether this is related to spread of the virus, behavioral factors, or cyclic changes in a population’s immunologic susceptibility [13,14].

The concept of RSV epidemic seasonality across continents and within geographic areas has been addressed in some of the reviewed publications. Here we present a summary of the publications from Africa, Latin America, Eastern Mediterranean, Europe, Southeast Asia and Western Pacific.

Africa

Reviewed articles were from Southern Africa, West Africa, and East Africa. No information on seasonality could be obtained from or Central and North Africa. The association of RSV epidemic periods with the wet seasons in tropical African countries is similar to observations of other studies from tropical countries with seasonal rainfall. The typical RSV season corresponded to the cold season in South Africa, where a temperate climate is observed. The discrepancy found within the countries might be due to interannual variation on viral seasonality.

The epidemic peak generally starts early in east African countries (Kenya, Mozambique) and South Africa then progresses to the West African countries (Senegal, Gambia, Ghana, Nigeria). The overall picture of RSV seasonality is in line with a previous publication describing that epidemics start at the very southern coast of Africa during the early period of the year and then move northward during the next 6 months [13]. The isolation of RSV throughout the year in some African countries may be explained by the tropical climate and the concurrent HIV epidemic in the population which results in prolonged carriage of RSV and less evident seasonality.

Latin America

The seasonality studies in Latin America are from 4 countries -Mexico, Brazil, Argentina, and Chile. Mexico experiences the earliest RSV season, followed by Argentina and Chile. The seasonality of the RSV epidemics agrees with data from a previous study which found that epidemics occurred from north to south in South America [13]. Studies from Brazil have shown a diversified seasonal pattern for RSV, probably related to the wide diversity of climate characteristics in the country. While in the north [15-31], rainfall is the main climatic determinant, temperature variations play a more significant role in the south. RSV infections peaked in the coldest months in southern Brazil [32], the only region with temperate climate, similar to that observed in Argentina and Chile. In southeast region, the peak of RSV outbreaks have not been associated with rainy seasons nor the coldest months and the epidemics appeared to spread throughout many months [33-40] with one study detecting RSV cases throughout the year [41] (Table 2).

Eastern Mediterranean

In desert climates, RSV infection has been associated with the cold season, a finding consistent with the pattern found in this review [14]. The study from United Arab Emirates provided inconclusive data defining RSV seasonality as it was conducted for only 3 months (September to November) [54]. Seven out of eleven studies from the Eastern Mediterranean were spanned only for short periods less than 12 months, and probably were insufficient to obtain information on seasonality [42-57] (Table 3).