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Keywords:

  • Respiratory syncytial virus;
  • developing countries;
  • acute respiratory infections;
  • child

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. The importance of RSV as a cause of ALRI in developing countries
  6. Comments
  7. Acknowledgements
  8. References

Little is known about the epidemiology of respiratory syncytial virus (RSV) infection in tropical and developing countries; the data currently available have been reviewed. In most studies, RSV was found to be the predominant viral cause of acute lower respiratory tract infections (ALRI) in childhood, being responsible for 27– 96% of hospitalised cases (mean 65%) in which a virus was found. RSV infection is seasonal in most countries; outbreaks occur most frequently in the cold season in areas with temperate and Mediterranean climates and in the wet season in tropical countries with seasonal rainfall. The situation on islands and in areas of the inner tropics with perennial high rainfall is less clear-cut. The age group mainly affected by RSV in developing countries is children under 6 months of age (mean 39% of hospital patients with RSV). RSV-ALRI is slightly more common in boys than in girls. Very little information is available about the mortality of children infected with RSV, the frequency of bacterial co-infection, or the incidence of further wheezing after RSV. Further studies on RSV should address these questions in more detail. RSV is an important pathogen in young children in tropical and developing countries and a frequent cause of hospital admission. Prevention of RSV infection by vaccination would have a significant impact on the incidence of ALRI in children in developing countries.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. The importance of RSV as a cause of ALRI in developing countries
  6. Comments
  7. Acknowledgements
  8. References

Respiratory syncytial virus (RSV) is the major pathogen of severe lower respiratory tract infections (ALRI) in children in developed countries with temperate climates (Glezen et al. 1971; Glezen & Denny 1973; Anonymous 1978). Outbreaks of RSV infection occur regularly during the winter months in countries with temperate climates (Martin et al. 1978; Gilchrist et al. 1994), affecting mainly young children between 2 and 12 months of age (Anonymous 1978; Glezen et al. 1986). Morbidity is considerable but mortality in previously healthy children is low. The main group of children at risk for severe disease or death is those with underlying conditions such as prematurity, lung disease or congenital heart disease (Krasinski 1985). In industrialized countries, it is thought that the risk of a secondary bacterial infection associated with an RSV infection is low (Hall et al. 1988).

In developing countries, RSV is overshadowed as a cause of severe lower respiratory tract infection by bacterial pathogens, especially Streptococcus pneumoniae and Haemophilus influenzae. This review attempts to bring together existing information on the epidemiology of RSV in developing countries and highlights the importance of this viral pathogen.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. The importance of RSV as a cause of ALRI in developing countries
  6. Comments
  7. Acknowledgements
  8. References

A literature search was done in Medline retrieving articles with ‘respiratory syncytial viruses’ as a medical subject heading or ‘respiratory syncytial virus’ as a text word. These articles were inspected for references describing patients in or having corresponding authors from tropical or developing countries. In a second step, the reference section of these articles was inspected further for secondary references from tropical or developing countries. Articles were included in this review if they contained details about at least one of the following: monthly number of cases, age or sex distribution, outcome, malnutrition, isolation of bacteria, wheezing after a previous RSV-ALRI. To ensure that no studies were excluded from the review in which RSV was looked for but not found as a pathogen, an additional search used ‘respiratory infections’ as a medical subject heading search term. This second search yielded only one study from Brazil which attempted to find RSV but failed to do so (de Arruda et al. 1991).

Climatic data were obtained from the retrieved articles, where quoted. For all other sites, meteorological data were retrieved from the US National Climatic Data Center, which stores data from over 8000 places around the globe (National Climatic Data Center 1996). If there were no data available from the place of the study, a nearby place was chosen. Monthly average maximum and minimum temperatures and rainfall were calculated from the data base for the study years. If the data for those years were incomplete, data for the nearest complete year were used.

Studies were grouped according to the virological methods used. Viral culture is the gold standard for detecting viruses, but, as it depends on viable virus and because RSV is a labile virus (Hambling 1964), its sensitivity is low. Serological studies require paired serum samples and young children especially often do not seroconvernt (Brandenburg et al. 1997). RSV-specific antigens in respiratory epithelial cells can be detected by immunofluorescence (IF) microscopy with the help of fluorescence-labelled, RSV-specific monoclonal antibodies or in an antigen detection ELISA (Welliver et al. 1981; Salomon et al. 1989). As a single method, IF or antigen detection ELISA is the most sensitive, a combination of all three methods is considered optimal (Welliver et al. 1981; Freymuth et al. 1986; Ahluwalia et al. 1987; Salomon et al. 1989; Thomas & Book 1991; Woodtayakorn & Punnarugsa 1991).

The importance of RSV as a cause of ALRI in developing countries

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. The importance of RSV as a cause of ALRI in developing countries
  6. Comments
  7. Acknowledgements
  8. References

Earlier studies on the aetiology used serology and/or viral culture. From the early 1980s onwards immunofluorescence became available and the proportion of isolates confirmed as RSV was almost double in studies using immunofluorescence than in other studies.

Community studies

Several community studies, which followed up children longitudinally, identified viruses as the cause of 11% (Forgie et al. 1992) to 36% (Monto & Johnson 1967) of episodes of ALRI. Five studies were performed without the use of immunofluorescence (Monto & Johnson 1967; Kloene et al. 1970; Ota & Bang 1972; Sutmoller et al. 1983; Borrero et al. 1990) and five with immunofluorescence (Hortal et al. 1990b; Tupasi et al. 1990a; Vathanophas et al. 1990; Forgie et al. 1992; Sutmoller et al. 1995) (Table 1). Whereas the overall viral isolation remained similar (mean 21% vs. 23%), the percentage of RSV isolates doubled from 23% to 44% (range 6 − 73%) in the studies that used immunofluorescence. As the overall isolation rate for viruses remained the same, viruses other than RSV were reported less frequently in studies which employed immunofluorescence. The highest decrease in isolation was found for adenoviruses. One study did not identify RSV activity over a period of 29 months despite apparently adequate methodology including antigen detection, immunofluorescence, and viral culture (de Arruda et al. 1991).

Table 1.  Aetiology of ALRI in developing countries in community-based studies Thumbnail image of

Hospital in- and out-patient studies

In studies performed in hospital outpatient departments or on patients admitted to hospital wards, a virus was found in 9% (Reeves et al. 1985) to 64% (Ruutu et al. 1990) of cases of ALRI (mean 41%). RSV was found in 4% (Capeding et al. 1994) to 96% (Sutmoller et al. 1995) of cases with a proven viral aetiology (mean 39%). RSV was the leading cause of viral ALRI, followed by influenza viruses, parainfluenza viruses and adenovirus (Table 2).

Table 2.  Aetiology of ALRI according to hospital-based studies Thumbnail image of

Studies based on culture and/or serology only, which were all undertaken before the early 1980s (Jennings & Grant 1967; Escobar et al. 1976; Sobeslawsky et al. 1977; Joosting et al. 1979; Doraisingham & Ling 1981; Ong et al. 1982; Berman et al. 1983; Shann et al. 1984; Reeves et al. 1985; Steinhoff et al. 1985; Zhang et al. 1986; Suwanjutha et al. 1990), found on average a virus in 28% of cases, and, on average, RSV accounted for 32% (range 6–72%) of the samples positive for viruses. Studies which used immunofluorescence before 1985 did not change these proportions considerably: a viral aetiology was found in 56% of cases, with RSV in 24% of culture positive cases (range 11–33%) (Wafula et al. 1985; Ravaoarinoro et al. 1986; Doraisingham & Ling 1986; Hazlett et al. 1988; Ruutu et al. 1990; Phillips et al. 1990). From 1985 onwards, immunofluorescence was used either alone or in combination with serology or culture in 18 studies from developing countries (Nunez et al. 1988; Weissenbacher et al. 1990; Hortal et al. 1990a; Cherian et al. 1990; Misra et al. 1990; Tupasi et al. 1990b; Puthavathana et al. 1990; Sunakorn et al. 1990; Huq et al. 1990; Rahman et al. 1990; Ghafoor et al. 1990; John et al. 1991; Forgie et al. 1991a, b; Sung et al. 1992; Capeding et al. 1994; Adegbola et al. 1994; Sutmoller et al. 1995) (Table 2). The overall viral aetiology rate did not change much from that found in earlier studies, with 33% of cases being attributed to a virus. However, RSV was held responsible for on average 65% (range 27–96%) of the samples positive for a virus. Thus RSV was, on average, responsible for 17% of acute respiratory infections in children admitted to hospital in the developing countries where those studies were carried out.

Measles played a major role in some earlier studies on ALRI done in Colombia (Escobar et al. 1976), the Philippines (Ruutu et al. 1990), Papua New Guinea (Phillips et al. 1990) and Kenya (Wafula et al. 1985; Hazlett et al. 1988). However, by the mid 1980s, measles virus was no longer a significant cause of paediatric ALRI in the studies reported, probably as a result of higher levels of immunization.

Incidence rates of RSV-ALRI

Few studies attempted to quantify the incidence rates of RSV-ALRI (Berman et al. 1983; Hayes et al. 1989; Borrero et al. 1990; Dagan et al. 1993; Sutmoller et al. 1995). The reported incidence rates vary between 10/1000 children under 1 year of life for hospitalization with RSV-ALRI in southern Israel (Dagan et al. 1993), to 198/1000 child years for the age group between birth and 18 months in a community-based study from Colombia (Borrero et al. 1990).

Age distribution

Few community-based studies have reported the age distribution of children with RSV infection (Monto & Johnson 1967; Hillis et al. 1971; Ota & Bang 1972; Sutmoller et al. 1983; Borrero et al. 1990; Sutmoller et al. 1995). Only one study used immunofluorescence and documented only 11 cases with RSV (Sutmoller et al. 1995). The study with the largest number of RSV cases followed a cohort of children in Colombia from birth to 17 months of age (Borrero et al. 1990). Forty percent of RSV cases were found in the first 6 months of life and 46% in the second half year. Overall, there is insufficient information on the age distribution of children affected by RSV in the community.

In hospital-based in- or out-patient studies, the proportion of children aged between birth and 5 months of age with RSV-ALRI varied between 9% (Ong et al. 1975) and 87% (Dagan et al. 1993). Taking only studies which included immunofluorescence or antigen detection and which reported on children up to at least 5 years of age (Doraisingham & Ling 1986; Hazlett et al. 1988; Tupasi et al. 1990b; Huq et al. 1990; Ghafoor et al. 1990; Chattopadhya et al. 1992; Sutmoller et al. 1995; Aderele et al. 1995), on average 39% (range 20–62%) were less than six 6 months old. On average, children aged 6–11 months comprised 24% of cases (range 14 –38%). Thus, on average, 63% of children were under 1 year of age. Three additional studies which did not differentiate in the age group under 1 year of age found 62% of children under one year of age (Nunez et al. 1988; John et al. 1991; Hijazi et al. 1995). On average, 20% (range 13–29%) of the children were between 1 and 2 years of age.

Sex distribution

Several studies reported the sex distribution of the patients (Ota & Bang 1972; Jamdar et al. 1979; Vellayappan et al. 1982; Ravaoarinoro et al. 1986; Dym et al. 1986; Nwankwo et al. 1988; Sunakorn et al. 1990; Kadi et al. 1990; Forgie et al. 1991b; Jamjoom et al. 1993; Colocho Zelaya et al. 1994; Sutmoller et al. 1995; Hijazi et al. 1995; Aderele et al. 1995). Twelve of 14 studies found a male predominance; on average 60% of infected children were male (range 43–88%). This male preponderance corresponds to the generally higher incidence of ALRI of any aetiology in boys (Reeves et al. 1985).

Seasonality of RSV disease

In most published studies, RSV has been a highly seasonal infection. RSV outbreaks in areas with temperate or Mediterranean climates in the southern hemisphere appear mainly during the cold months as is the case in Western Europe and North America (Martin et al. 1978; Gilchrist et al. 1994). This temperature-dependent pattern appears to be independent of the rainfall pattern, as winter months have high rainfall in places such as Santiago in Chile (Avendano et al. 1991), but low rainfall in places such as Johannesburg in South Africa (Joosting et al. 1979) (Figure 1). In desert climates, such as Kuwait (Hijazi et al. 1995) or Saudi Arabia (Jamjoom et al. 1993), cases are also seen in the cold months.

image

Figure 1. Seasonality of RSV disease in subtropical climates from 35° to 25° latitude. Each graph depicts the mean monthly rainfall (▪), the mean monthly maximum (•) and the mean monthly minimum (○) temperature as lines and series of cases as bars. The meteorological data were retrieved from the US National Climatic Data Center (National Climatic Data Center 1996). Uruguay 1985–87 (Russi et al. 1989); Argentina 1984–87 (Weissenbacher et al. 1990); Chile 1988–89 (Avendano et al. 1991); South Africa 1966–72 (Joosting et al. 1979); Pakistan 1986–88 (Ghafoor et al. 1990); India (Agarwal et al. 1971), weather from Dehra Dun; Kuwait 1993–94 (Hijazi et al. 1995); Saudi Arabia 1991–92 (Jamjoom et al. 1993). Figures adapted with permission. ░ Year 1 of study; ▒ Year 2 of study; ▪ Year 3 of study; □ Sum >1year of study.

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In areas with tropical or subtropical climates and seasonal rainfall, RSV outbreaks are frequently associated with the rainy rather than the colder season (Figures 2 and 3). RSV transmission usually peaks one to two months after the onset of the rains.

image

Figure 2. Seasonality of RSV disease in tropical climates from 23° to 13° latitude. Each graph depicts the mean monthly rainfall (▪), the mean monthly maximum (•) and the mean monthly minimum (○) temperature as lines and series of cases as bars. India 1964–66 (Kloene et al. 1970) 1966–67 (Ota & Bang 1972) 1967–69 (Hillis et al. 1971) bars depict the sum of cases from all studies; Bangladesh 1986–88 (Huq et al. 1990); China 1978–79 (Shen et al. 1982); Hong Kong 1985–86 (Sung et al. 1992); Hawaii 1987–89 (Reese & Marchette 1991); Philippines 1984 (Ruutu et al. 1990) 1985–86 (Tupasi et al. 1990b); Thailand 1986–87 (Suwanjutha et al. 1990) 1988–89 (Sunakorn et al. 1990); Gambia 1994–96 (Weber et al. 1997). Figures adapted with permission. ░ Year 1 of study; ▒ Year 2 of study; ▪ Year 3 of study; □ Sum >1year of study.

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In countries close to the equator with perennial high rainfall, such as Singapore (Doraisingham & Ling 1981; Vellayappan et al. 1982) Colombia (Berman et al. 1983) or islands such as Hawaii (Reese & Marchette 1991), the situation is less clear-cut. These countries have a distinct pattern of RSV transmission, with most cases appearing in one half of the year, but not in the other. But neither temperature nor rainfall appear to be the main determinant of the timing of these outbreaks.

Studies from the north of the Indian subcontinent have shown contradictory patterns: Islamabad in Pakistan and Chandigarh in India have similar climates and are only 500 km apart but they show different seasonality patterns. Outbreaks in Pakistan were reported mainly in the cold season (Ghafoor et al. 1990), whereas an outbreak in Chandigarh was associated with the rainy season (Agarwal et al. 1971). The situation is similar with regard to Calcutta in West Bengal and Dhaka in Bangladesh: outbreaks in Calcutta were reported mainly in the rainy season (Kloene et al. 1970; Hillis et al. 1971; Ota & Bang 1972), whereas most of the cases from Bangladesh appeared in the drier, colder season (Huq et al. 1990).

Most recent studies from The Gambia, West Africa, have found RSV activity mainly in the rainy season (Weber et al. 1997). An earlier study in The Gambia, however, failed to identify RSV activity over the period of one whole year (Forgie et al. 1992), and another study from the same country had an outbreak in the dry season (Forgie et al. 1991b).

Bacterial co-infections

Twelve studies looked for concurrent bacterial infections in cases of RSV-ALRI (Shann et al. 1984; Wafula et al. 1985; Cherian et al. 1990; Tupasi et al. 1990b; Hortal et al. 1990a; Rahman et al. 1990; Ghafoor et al. 1990; John et al. 1991; Forgie et al. 1991b; Adegbola et al. 1994; Hijazi et al. 1995; Aderele et al. 1995) presenting to hospitals. The isolation rate of bacteria varied between 2% (Cherian et al. 1990; John et al. 1991) and 50% (Shann et al. 1984). Most studies were very small, involving less than 100 patients with RSV-ALRI. A study from the Gambia, where the bacterial coinfection rate was 22% (Forgie et al. 1991b) included serology as well as culture as an indicator of bacterial infection. The only large study with a high bacterial isolation rate was that conducted in Pakistan (Ghafoor et al. 1990), which found bacteria in 31% of all cases of RSV-ALRI. In most studies, S. pneumoniae was the most frequently isolated organism, followed by H. influenzae.

Malnutrition

Two studies from Africa report the influence of malnutrition on the prevalence of RSV. In a study from The Gambia (Adegbola et al. 1994), where malnourished and well-nourished children with pneumonia were investigated concurrently, RSV was found in 13% of well nourished children with ALRI, but in only 6% of malnourished children investigated. In a study from Nigeria (Nwankwo et al. 1994), RSV was found in 16% of malnourished children with ALRI, but in 55% of well nourished controls. In Papua New Guinea, Philipps et al. (Phillips et al. 1990) did not find any association between severe RSV infection and malnutrition. These observations suggest that malnutrition is less of a risk factor for the development of severe RSV infection than for ALRI of other aetiology.

Mortality

Fifteen studies (Vellayappan et al. 1982; Berman et al. 1983; Dym et al. 1986; Nwankwo et al. 1988; Carballal et al. 1990; Hortal et al. 1990a; Borrero et al. 1990; Ruutu et al. 1990; Cherian et al. 1990; Avendano et al. 1991; Sung et al. 1992; Jamjoom et al. 1993; Dagan et al. 1993; Hijazi et al. 1995; Aderele et al. 1995) report case fatality for RSV infection; this ranged from 0% to 6%. The majority of the hospital-based studies (8 of 14) did not report any deaths. A study from Argentina (Carballal et al. 1990), which investigated 31 deaths from ALRI, found RSV in 4 children; 2 of whom were preterm, and one of whom had a combination of RSV, adenovirus and Streptococcus viridans infection. In 4 of 11 cases in whom no pathogen could be identified, a clinical diagnosis of bronchiolitis was made. On analysis of all studies reporting case fatality together, an association with a bacterial pathogen was made in 3 of the 18 reported RSV deaths (16%): two with Staphylococcus aureus (Berman et al. 1983; Cherian et al. 1990), and the already mentioned streptococcal infection. Six children (33%) had additional risk factors: 2 were preterm babies (Carballal et al. 1990), one had a low birth weight (Cherian et al. 1990), one had a ventricular septal defect, and two had neurological disease (Hijazi et al. 1995).

Two studies from the south Pacific, which report cases of bronchiolitis without virological diagnosis, reported a case fatality rate of 2% (Brewster 1989) and 11% (Hayes et al. 1989) respectively. A study from India (Khatua 1977) found a case fatality rate of 8.3% for clinical bronchiolitis, without determining the aetiology. Studies from Bangladesh (Rahman et al. 1990; Huq et al. 1990) and the Philippines (Tupasi et al. 1990b) report the case fatality rate of viral ALRI to be much lower than bacterial ALRI, 3% vs. 7%, without specifying RSV explicitly.

The impact of RSV on mortality in the community cannot be assessed from the published literature.

Further wheezing

In developed countries there is debate about whether RSV triggers further episodes of wheezing. (McConnochie & Roghmann 1984; Price 1990; Landau 1994; Openshaw & O'Donnell 1994) There is only one published study from a developing country, Qatar (Osundwa et al. 1993), which examines this issue. It found that 44% of children with RSV bronchiolitis had further episodes of wheezing over the next two years, in comparison to only 13% of controls.

Comments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. The importance of RSV as a cause of ALRI in developing countries
  6. Comments
  7. Acknowledgements
  8. References

Published studies have shown that RSV is the most important viral pathogen causing ALRI worldwide. The importance of RSV was probably underestimated in earlier studies which did not use immunofluorescence or antigen detection as one of the diagnostic methods, as RSV is a fragile virus. In all except one of the more recent studies, RSV was found with high frequency. The decreasing isolation of other viruses might reflect seasonal trends. Another possibility is an interaction with vaccinations coming into more widespread use through the EPI such as pertussis vaccination.

RSV was found in all climatic and geographical areas where it was sought. RSV appears in distinct outbreaks all over the world, in most climates with little activity during one half of the year, and often very sharp peaks of RSV activity over a period of 2–4 months. The seasonality of RSV varied considerably between regions. In temperate, Mediterranean and desert climates it was predominantly associated with the cold season, whereas in tropical climates with seasonal rainfall, it appears to be more associated with the rainy season. Outbreaks appear to be less constantly associated with climatic factors in the inner tropics, where little changes of temperature and rainfall occur. In the studies from Hawaii (Reese & Marchette 1991) and Singapore (Doraisingham & Ling 1981), the authors speculated whether the organism might have been introduced through travel activities from the northern hemisphere. The seasonality of RSV infection differs from that of bacterial infections spread by the respiratory route. In general, pneumococcal and meningococcal infections occur most frequently in the dry season in tropical areas with marked dry and rainy seasons, such as savannah Africa (Baird et al. 1976; Greenwood et al. 1979), and in winter in countries with temperate climate (Greenwood 1996a, b). The common climatic factor in these situations is a low absolute humidity, and it has been suggested that it is this that predisposes to those infections by damaging the defences of the upper respiratory tract. In the tropics measles is also seen most frequently in the dry season when it is hot, dry and dusty (Morley et al. 1963). Why RSV should behave in such a different way, generally occurring when absolute humidity is high in the tropics and when it is low in temperate climates, is difficult to explain. It is possible that for this virus seasonality is not related directly to climatic factors but to some associated changes in social behaviour or to an interaction with other infections that are seasonally determined.

The age distribution of RSV cases from developing countries is similar to that observed in developed countries (Glezen & Denny 1973; Glezen et al. 1981). Two thirds of hospitalised children with RSV are under one year of age. The information of community studies is so limited that it is difficult to draw conclusions. Thus, if RSV infection is to be prevented effectively by vaccination it will be necessary for this to be undertaken early in developing as well as in industrialised countries. Maternal vaccination offers a potential approach to the prevention of RSV infection during the first few months of life, an approach which is likely to be explored. This would be relatively easy to implement in many developing countries where tetanus toxoid is given routinely at antenatal clinics.

There is a male preponderance in most of the studies, similar to observations from the USA, where between 1.5 and 1.8 times more boys than girls are affected (Glezen 1977).

The frequency of isolation of bacteria from children with severe RSV infection is variable. Two studies from Bangladesh and Pakistan found high isolation rates of 21% and 31%, respectively. Most other studies found much lower rates, more in line with studies from North America, which found bacterial pathogens infrequently (Hall et al. 1988). The issue is important, because children with dual infection might be at higher risk for mortality, or, alternatively, if bacterial coinfection is rare, antibiotics might be safely withheld from children with presumptive RSV infection. Currently, children with ALRI of whatever aetiology are usually treated with antibiotics in most developing countries. As the number of studies, and the number of patients studied in those studies, is quite small, further evidence should be sought on the role of bacteria in severe RSV infection.

Mortality from RSV-ALRI is difficult to assess with the current knowledge. Only few deaths have been reported and a number of studies state that there had been no mortality from RSV during the course of the study. However, it is quite possible that a number of children die from undiagnosed RSV infection in the community. One approach to this problem could be to look for an excess in overall mortality in young children during an RSV season. However, as the RSV season in tropical climates with seasonal rainfall coincides with the malaria season, it might be difficult to separate out the effects of these two diseases. It is possible that only a vaccine trial with an effective vaccine will be able to show how much mortality and morbidity is attributable to RSV.

Studies on further wheezing are needed to assess the long-term morbidity associated with RSV. If further wheezing is common, an effective vaccine against RSV would prevent additional morbidity. The importance of introducing an RSV vaccine in developing countries would then lie in the prevention of long-term morbidity associated with severe RSV infection, as well as the prevention of the acute infection. An effective RSV vaccine is likely to be cost effective in developing as well as in industrialised countries.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. The importance of RSV as a cause of ALRI in developing countries
  6. Comments
  7. Acknowledgements
  8. References

We would like to thank Dr Andreas Weber for his help in retrieving meteorological data from the Internet and other accessible sources, and the authors and publishers of the abstracted figures for the seasonality for their permission to reproduce the data. We are grateful for comments from Dr Hilton Whittle and Dr Sam Walters.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. The importance of RSV as a cause of ALRI in developing countries
  6. Comments
  7. Acknowledgements
  8. References
  • 1
    Adegbola, RA Falade, AG Sam, BE, et al (1994) The etiology of pneumonia in malnourished and well-nourished Gambian children. Pediatric Infectious Disease Journal 13, 975982.
  • 2
    Aderele, WI Johnson, WB Osinusi, K, et al (1995) Respiratory syncytial virus – associated lower respiratory diseases in hospitalised pre-school children in Ibadan. African Journal of Medicine and Medical Sciences 24, 4753.
  • 3
    Agarwal, SC Bardoloi, JN Mehta, S (1971) Respiratory syncytial virus infection in infancy and childhood in a community in Chandigarh. Indian Journal of Medical Research 59, 1925.
  • 4
    Ahluwalia, G Embree, J McNicol, P Law, B Hammond, GW (1987) Comparison of nasopharyngeal aspirate and nasopharyngeal swab specimens for respiratory syncytial virus diagnosis by cell culture, indirect immunofluorescence assay, and enzyme-linked immunosorbent assay. Journal of Clinical Microbiology 25, 763767.
  • Anonymous, (1978) Respiratory syncytial virus infection: admissions to hospital in industrial, urban and rural areas. Report to the Medical Research Council Subcommittee on Respiratory Syncytial Virus Vaccines.
    British Medical Journal 2, 796–798.
  • 6
    De Arruda, E Hayden, FG McAuliffe, JF, et al (1991) Acute respiratory viral infections in ambulatory children of urban northeast Brazil. Journal of Infectious Diseases 164, 252258.
  • 7
    Avendano, LF Larranaga, C Palomino, MA, et al (1991) Community- and hospital-acquired respiratory syncytial virus infections in Chile. Pediatric Infectious Disease Journal 10, 564568.
  • 8
    Baird, DR Whittle, HC Greenwood, BM (1976) Mortality from pneumococcal meningitis. Lancet 2, 13441346.
  • 9
    Berman, S Duenas, A Bedoya, A, et al (1983) Acute lower respiratory tract illnesses in Cali, Colombia: a two year ambulatory study. Pediatrics 71, 210218,.
  • 10
    Borrero, I Fajardo, L Bedoya, A Zea, A Carmona, F de Borrero, MF (1990) Acute respiratory tract infections among a birth cohort of children from Cali, Colombia, who were studied through 17 months of age. Reviews of Infectious Diseases 12 (Suppl. 8), S950–S956.
  • 11
    Brandenburg, AH Groen, J van Steensel-Moll, HA, et al (1997) Respiratory syncytial virus specific serum antibodies in infants under six months of age: limited serological response upon infection. Journal of Medical Virology 52, 97104.
  • 12
    Brewster, D (1989) Acute bronchiolitis in the Solomon islands. Medical Journal of Australia 150, 605.
  • 13
    Capeding, MR Sombrero, LT Paladin, FJ, et al (1994) Etiology of acute lower respiratory infection in Filipino children under five years. Southeast Asian Journal of Tropical Medicine and Public Health 25, 684687.
  • 14
    Carballal, G Siminovich, M Murtagh, P, et al (1990) Etiologic, clinical, and pathologic analysis of 31 fatal cases of acute respiratory tract infection in Argentinian children under 5 years of age. Reviews of Infectious Diseases 12 (Suppl. 8), S10741080.
  • 15
    Chattopadhya, D Chatterjee, R Anand, VK Kumari, S Patwari, AK (1992) Lower respiratory tract infection in hospitalized children due to respiratory syncytial (RS) virus during a suspected epidemic period of RS virus in Delhi. Journal of Tropical Pediatrics 38, 6873.
  • 16
    Cherian, T Simoes, EA Steinhoff, MC, et al (1990) Bronchiolitis in tropical south India. American Journal of Diseases of Children 144, 10261030.
  • 17
    Colocho Zelaya, EA Pettersson, CA Forsgren, M Orvell, C Strannegard, O (1994) Respiratory syncytial virus infection in hospitalized patients and healthy children in El Salvador. American Journal of Tropical Medicine and Hygiene 51, 577584.
  • 18
    Dagan, R Landau, D Haikin, H Tal, A (1993) Hospitalization of Jewish and Bedouin infants in southern Israel for bronchiolitis caused by respiratory syncytial virus. Pediatric Infectious Disease Journal 12, 381386.
  • 19
    Doraisingham, S Ling, AE (1981) Acute non-bacterial infections of the respiratory tract in Singapore children: an analysis of three years' laboratory findings. Annals of the Academy of Medicine, Singapore 10, 6978.
  • 20
    Doraisingham, S Ling, AE (1986) Patterns of viral respiratory tract infections in Singapore. Annals of the Academy of Medicine, Singapore 15, 914.
  • 21
    Dym, AM Schuit, KE Nwankwo, MU Omene, JA (1986) Respiratory syncytial virus and acute lower respiratory infections in Benin City, Nigeria. Pediatric Infectious Disease Journal 5, 717718.
  • 22
    Escobar, JA Dover, AS Duenas, A, et al (1976) Etiology of respiratory tract infections in Children in Cali,Colombia. Pediatrics 57, 123130.
  • 23
    Forgie, IM O'Neill, KP Lloyd-Evans, N, et al (1991a) Etiology of acute lower respiratory tract infections in Gambian children: II. Acute lower respiratory tract infection in children aged one to nine years presenting at the hospital. Pediatric Infectious Disease Journal 10, 4247.
  • 24
    Forgie, IM O'Neill, KP Lloyd-Evans, N, et al (1991b) Etiology of acute lower respiratory tract infections in Gambian children: I. Acute lower respiratory tract infections in infants presenting at the hospital. Pediatric Infectious Disease Journal 10, 3341.
  • 25
    Forgie, IM Campbell, H Lloyd-Evans, N, et al (1992) Etiology of acute lower respiratory tract infections in children in a rural community in The Gambia. Pediatric Infectious Disease Journal 11, 466473.
  • 26
    Freymuth, F Quibriac, M Petitjean, J, et al (1986) Comparison of two new tests for rapid diagnosis of respiratory syncytial virus infections by enzyme-linked immunosorbent assay and immunofluorescence techniques. Journal of Clinical Microbiology 24, 10131016.
  • 27
    Ghafoor, A Nomani, NK Ishaq, Z, et al (1990) Diagnoses of acute lower respiratory tract infections in children in Rawalpindi and Islamabad, Pakistan. Reviews of Infectious Diseases 12 (Suppl. 8), S907–S914.
  • 28
    Gilchrist, S Torok, TJ Gary, HEJr, Alexander, JP Anderson, LJ (1994) National surveillance for respiratory syncytial virus, United States 1985–90. Journal of Infectious Diseases 170, 986990.
  • 29
    Glezen, PW (1977) Pathogenesis of Bronchiolitis – Epidemiologic Considerations. Pediatric Research 11, 239243.
  • 30
    Glezen, WP Denny, FW (1973) Epidemiology of acute lower respiratory disease in children. New England Journal of Medicine 288, 498505.
  • 31
    Glezen, WP Loda, FA Clyde, WA, et al (1971) Epidemiologic patterns of acute lower respiratory disease of children in a pediatric group practice. Journal of Pediatrics 78, 397406.
  • 32
    Glezen, WP Paredes, A Allison, JE Taber, LH Frank, AL (1981) Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. Journal of Pediatrics 98, 708715.
  • 33
    Glezen, WP Taber, LH Frank, AL Kasel, JA (1986) Risk of primary infection and reinfection with respiratory syncytial virus. American Journal of Diseases of Children 140, 543546.
  • 34
    Greenwood, BM Bradley, PG Haggie, HK, et al (1979) An epidemic of meningococcal infection at Zaria, Northern Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene 73, 557573.
  • Greenwood BM (1996a) Meningococcal infection. In
    Oxford Textbook of Medicine (eds. DJ Weatherall, JGG Ledingham & DA Warrell) Oxford University Press, Oxford, pp. 533–544.
  • Greenwood BM (1996b) Pneumococcal infection. In
    Oxford Textbook of Medicine (Eds. DJ Weatherall, JGG Ledingham & DA Warrell) Oxford University Press, Oxford., pp. 511–523.
  • 37
    Hall, CB Powell, KR Schnabel, KC Gala, CL Pincus, PH (1988) Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection. Journal of Pediatrics 113, 266271.
  • 38
    Hambling, MH (1964) Survival of the respiratory syncytial virus during storage under various conditions. British Journal of Experimental Pathology 45, 647655.
  • 39
    Hayes, EB Hurwitz, ES Schonberger, LB Anderson, LJ (1989) Respiratory syncytial virus outbreak on American Samoa. Evaluation of risk factors. American Journal of Diseases of Children 143, 316321.
  • 40
    Hazlett, DT Bell, TM Tukei, PM, et al (1988) Viral etiology and epidemiology of acute respiratory infections in children in Nairobi, Kenya. American Journal of Tropical Medicine and Hygiene 39, 632640.
  • 41
    Hijazi, Z Pacsa, A Eisa, S el Shazli, A Abd el-Salam, R, et al (1995) Respiratory syncytial virus infections in children in a desert country. Pediatric Infectious Disease Journal 14, 322324.
  • 42
    Hillis, WD Cooper, MR Bang, FB Dey, AK Shah, KV (1971) Respiratory syncytial virus infection in children in West Bengal. Indian Journal of Medical Research 59, 13541364.
  • 43
    Hortal, M Mogdasy, C Russi, JC Deleon, C Suarez, A (1990a) Microbial agents associated with pneumonia in children from Uruguay. Reviews of Infectious Diseases 12 (Suppl. 8), S915–S922.
  • 44
    Hortal, M Russi, JC Arbiza, JR Canepa, E Chiparelli, H Illarramendi, A (1990b) Identification of viruses in a study of acute respiratory tract infection in children from Uruguay. Reviews of Infectious Diseases 12 (Suppl. 8), S995–S997.
  • 45
    Huq, F Rahman, M Nahar, N, et al (1990) Acute lower respiratory tract infection due to virus among hospitalized children in Dhaka, Bangladesh. Reviews of Infectious Diseases 12 (Suppl. 8), S982–S987.
  • 46
    Jamdar, J Walia, BN Agarwal, SC Suri, S (1979) Clinical and radiological studies in children with respiratory syncytial virus infection. Indian Pediatrics 16, 685688.
  • 47
    Jamjoom, GA Al-Semrani, AM Board, A, et al (1993) Respiratory syncytial virus infection in young children hospitalized with respiratory illness in Riyadh. Journal of Tropical Pediatrics 39, 346349.
  • 48
    Jennings, R Grant, LS (1967) Respiratory viruses in Jamaica: a virologic and serologic study. American Journal of Epidemiology 86, 690699.
  • 49
    John, TJ Cherian, T Steinhoff, MC Simoes, EA John, M (1991) Etiology of acute respiratory infections in children in tropical southern India. Reviews of Infectious Diseases 13 (Suppl. 6), S463–S469.
  • 50
    Joosting, AC Harwin, RM Orchard, M Martin, E Gear, JH (1979) Respiratory viruses in hospital patients on the Witwatersrand. A 7-year study. South African Medical Journal 55, 403408.
  • 51
    Kadi, Z Bouguermouh, A Belhocine, Z, et al (1990) Acute respiratory infections of viral origin in the children of Algiers, Algeria based on a seroepidemiological study. Rev. Roum. Virol. 41, 197–:207.
  • 52
    Khatua, SP (1977) Acute bronchiolitis (a study of 205 cases). Indian Pediatrics 14, 285294.
  • 53
    Kloene, W Bang, FB Chakraborty, SM, et al (1970) A two-year respiratory virus survey in four villages in West Bengal,India. American Journal of Epidemiology 92, 307320.
  • 54
    Krasinski, K (1985) Severe respiratory syncytial virus infection: clinical features, nosocomial acquisition and outcome. Pediatric Infectious Disease Journal 4, 250257.
  • 55
    Landau, L (1994) Bronchiolitis and asthma: are they related? (editorial). Thorax 49, 293296.
  • 56
    Martin, AJ Gardner, PS McQuillin, J (1978) Epidemiology of respiratory viral infection among paediatric inpatients over a six year period in north-east England. Lancet 2, 10351038.
  • 57
    McConnochie, KM Roghmann, KJ (1984) Bronchiolitis as a possible cause of wheezing in childhood: new evidence. Pediatrics 74, 110.
  • 58
    Misra, PK Chaudhary, RS Jain, A Pande, A Mathur, A Chaturvedi, UC (1990) Viral aetiology of acute respiratory infections in children in north India. Journal of Tropical Pediatrics 36, 2427.
  • 59
    Monto, A Johnson, KM (1967) A community study of respiratory infections in the tropics. American Journal of Epidemiology 86, 7892.
  • 60
    Morley, D Woodland, M Martin, WJ (1963) Measles in Nigerian children. Journal of Hygiene (Cambridge) 61, 115134.
  • 1
    National Climatic Data Center (1996) Global Historical Climatology Network. Web site: http://www.ncdc.noaa.gov/pub/data/globalsod/ gsod.html. U.S.A.National Climatic Data Center, Asheville, N.C.
  • 62
    Nunez, RM Duque, J Henriquez, CW Villegas, AL Nino, JU de Gonzales, B (1988) Viral and chlamydial etiology of acute infections of the lower respiratory tract in Colombian children. Pediatric Infectious Disease Journal 7, 6970.
  • 63
    Nwankwo, MU Dym, AM Schuit, KE Offor, E Omene, JA (1988) Seasonal variation in respiratory syncytial virus infections in children in Benin-City, Nigeria. Tropical and Geographical Medicine 40, 309313.
  • 64
    Nwankwo, MU Okuonghae, HO Currier, G Schuit, KE (1994) Respiratory syncytial virus in malnourished children. Annals of Tropical Paediatrics 14, 125130.
  • 65
    Olson, LC Lexomboon, U Sithisarn, P Noyes, HE (1973) The etiology of respiratory tract infections in a tropical country. American Journal of Epidemiology 97, 3443.
  • 66
    Ong, SB Lam, KL Lam, SK (1975) Respiratory virus disease in Malaysian children: a serological study. Bulletin of the World Health Organization 52, 376378.
  • 67
    Ong, SB Lam, KL Lam, SK (1982) Viral agents of acute respiratory infections in young children in Kuala Lumpur. Bulletin of the World Health Organization 60, 137140.
  • 68
    Openshaw, PJ O'Donnell, DR (1994) Asthma and the common cold: can viruses imitate worms? Thorax 49, 101103.
  • 69
    Osundwa, VM Dawod, ST Ehlayel, M (1993) Recurrent wheezing in children with respiratory syncytial virus (RSV) bronchiolitis in Qatar. European Journal of Pediatrics 152, 10011003.
  • 70
    Ota, WK Bang, FB (1972) A continuous study of viruses in the respiratory tract in families of a Calcutta bustee. American Journal of Epidemiology 95, 371383.
  • 71
    Phillips, PA Lehmann, D Spooner, V, et al (1990) Viruses associated with acute lower respiratory tract infections in children from the eastern highlands of Papua New Guinea (1983–85). Southeast Asian Journal of Tropical Medicine and Public Health 21, 373382.
  • 72
    Price, JF (1990) Acute and long-term effects of viral bronchiolitis in infancy. Lung 168 (Suppl.), S414–S421.
  • 73
    Puthavathana, P Wasi, C Kositanont, U, et al (1990) A hospital-based study of acute viral infections of the respiratory tract in Thai children, with emphasis on laboratory diagnosis. Reviews of Infectious Diseases 12 (Suppl. 8), S988–S994.
  • 74
    Rahman, M Huq, F Sack, DA, et al (1990) Acute lower respiratory tract infections in hospitalized patients with diarrhea in Dhaka, Bangladesh. Reviews of Infectious Diseases 12 (Suppl. 8), S899–S906.
  • 75
    Ravaoarinoro, M Razafimihery, J Razanamparany, M Coulanges, P (1986) Viral etiology of acute respiratory infections in Madagascan children. Archives de l'Institut Pasteur de Madagascar 52, 147155.
  • 76
    Reese, PE Marchette, NJ (1991) Respiratory syncytial virus infection and prevalence of subgroups A and B in Hawaii. Journal of Clinical Microbiology 29, 26142615.
  • 77
    Reeves, WC Dillman, L Quiroz, E et al (1985) Epidemiology of acute respiratory disease at the paediatric emergency room of the social security medical center in Panama City, Panama. Bulletin of the Pan American Health Organization 19, 221234.
  • 78
    Russi, JC Delfraro, A Arbiza, JR, et al (1989) Antigenic characterization of respiratory syncytial virus associated with acute respiratory infections in Uruguayan children from 1985 to 1987. Journal of Clinical Microbiology 27, 14641466.
  • 79
    Ruutu, P Halonen, P Meurman, O, et al (1990) Viral lower respiratory tract infections in Filipino children. Journal of Infectious Diseases 161, 175179.
  • 80
    Salomon, HE Grandien, M Avila, MM Pettersson, CA Weissenbacher, MC (1989) Comparison of three techniques for detection of respiratory viruses in nasopharyngeal aspirates from children with lower acute respiratory infections. Journal of Medical Virology 28, 159162.
  • 81
    Shann, F Gratten, M Germer, S Linnemann, V Hazlett, D Payne, R (1984) Aetiology of pneumonia in children in Goroka Hospital, Papua New Guinea. Lancet 2, 537541.
  • 82
    Shen, JP Chang, RX Zeng, LX, et al (1982) A study of etiology of respiratory syncytial virus pneumonia infantile in Guangzhou. Acta Microbiologica Sinica 22, 192196.
  • 83
    Sobeslawsky, O Sebikary, SRK Harland, PSEG Skrtic, N Fayinka, OA Soneji, AD (1977) The viral etiology of acute respiratory infections in children in Uganda. Bulletin of the World Health Organization 55, 625631.
  • 84
    Spence, L Barratt, N (1968) Respiratory syncytial virus associated with acute respiratory infections in Trinidadian patients. American Journal of Epidemiology 88, 257266.
  • 85
    Steinhoff, MC Padmini, B John, TJ Kingsley, J Pereira, SM (1985) Viral etiology of acute respiratory infections in South Indian children. Indian Journal of Medical Research 81, 349353.
  • 86
    Sunakorn, P Chunchit, L Niltawat, S Wangweerawong, M Jacobs, RF (1990) Epidemiology of acute respiratory infections in young children from Thailand. Pediatric Infectious Disease Journal 9, 873877.
  • 87
    Sung, RY Chan, RC Tam, JS Cheng, AF Murray, HG (1992) Epidemiology and aetiology of acute bronchiolitis in Hong Kong infants. Epidemiology and Infection 108, 147154.
  • 88
    Sutmoller, F Ferro, ZP Asensi, MD Ferreira, V Mazzei, IS Cunha, BL (1995) Etiology of acute respiratory tract infections among children in a combined community and hospital study in Rio de Janeiro. Clinical Infectious Diseases 20, 854860.
  • 89
    Sutmoller, F Nascimento, JP Chaves, JRS Ferreira, V Pereira, MS (1983) Viral etiology of acute respiratory diseases in Rio de Janeiro:first two years of a longitudinal study. Bulletin of the World Health Organization 61, 845852.
  • 90
    Suwanjutha, S Chantarojanasiri, T Watthana kasetr, S, et al (1990) A study of nonbacterial agents of acute lower respiratory tract infection in Thai children. Reviews of Infectious Diseases 12 (Suppl. 8), S923–S928.
  • 91
    Thomas, EE Book, LE (1991) Comparison of two rapid methods for detection of respiratory syncytial virus (RSV) (Testpack RSV and ortho RSV ELISA) with direct immunofluorescence and virus isolation for the diagnosis of pediatric RSV infection. Journal of Clinical Microbiology 29, 632635.
  • 92
    Tupasi, TE de Leon, LE Lupisan, S, et al (1990a) Patterns of acute respiratory tract infection in children: a longitudinal study in a depressed community in Metro Manila. Reviews of Infectious Diseases 12 (Suppl. 8), S940–S949.
  • 93
    Tupasi, TE Lucero, MG Magdangal, DM, et al (1990b) Etiology of acute lower respiratory tract infection in children from Alabang, Metro Manila. Reviews of Infectious Diseases 12 (Suppl. 8), S929–S939.
  • 94
    Vathanophas, K Sangchai, R Raktham, S, et al (1990) A community-based study of acute respiratory tract infection in Thai children. Reviews of Infectious Diseases 12 (Suppl. 8), S957–S965.
  • 95
    Vellayappan, K Teo, J Doraisingham, S (1982) Respiratory syncytial virus infections in children. Journal of the Singapore Paediatric Society 24, 6977.
  • 96
    Wafula, EM Tukei, PM Bell, TM, et al (1985) Aetiology of acute respiratory infections in children aged below 5 years in Kenyatta National Hospital. East African Medical Journal 62, 757767.
  • 97
    Weber, MW Dackour, R Usen, S, et al (1997) The clinical spectrum of RSV disease in The Gambia. Pediatric Infectious Disease Journal 17, 224230.
  • 98
    Weissenbacher, M Carballal, G Avila, M, et al (1990) Etiologic and clinical evaluation of acute lower respiratory tract infections in young Argentinian children: an overview. Reviews of Infectious Diseases 12 (Suppl. 8), S889–S898.
  • 99
    Welliver, RC Gallagher, MR Ogra, PL (1981) Clinical and laboratory diagnosis of respiratory syncytial virus infection. Critical Reviews in Clinical Laboratory Sciences 13, 213239.
  • 100
    Woodtayakorn, J Punnarugsa, V (1991) Comparative study of respiratory syncytial virus in nasopharyngeal aspirates using conventional cell culture, shell viral centrifugation culture, immunofluorescence and biotin-avidin enzyme linked immunosorbent assays. Asian Pacific Journal of Allergy and Immunology 9, 121124.
  • 101
    Zhang, ZJ Wang, ZL Cao, YP Zhu, ZH Liu, YL Lin, LM (1986) Acute respiratory infections in childhood in Beijing. Chinese Medical Journal 99, 695701