AIDS Care
ISSN: 0954-0121 (Print) 1360-0451 (Online) Journal homepage: http://www.tandfonline.com/loi/caic20
HIV infection in children C. A. Canosa To cite this article: C. A. Canosa (1991) HIV infection in children, AIDS Care, 3:3, 303-309, DOI: 10.1080/09540129108253077 To link to this article: http://dx.doi.org/10.1080/09540129108253077
Published online: 25 Sep 2007.
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Date: 06 November 2015, At: 22:47
AIDS CARE, VOL. 3, NO. 3,1991
303
HIV infection in children C. A. CANOSA Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Hospital “La Fe” Department of Pediatrics, Valencia, Spain
Introduction The first paediatric AIDS patient was described two years after the first adult case was reported (Oleske et al., 1983). Numerous new patients were soon identified and were directly related to either blood transfusions or vertical transmission (transplacental, perinatal and breast milk) (Rubinsein et al., 1983; Scott et al., 1984; O’Duffy & Isles, 1984; Mann et al., 1986). Various reports specify that 2 5 3 % of all AIDS cases worldwide occur among children (Chin et al., 1990; PHO/WHO, 1988). However, due to the peculiar characteristics of HIV infection in children and the difficulties in reporting, it is possible that the proportion is higher, of the order of 7-8%. The initial puzzling distribution of AIDS in Central Africa and Haiti, among homosexuals from San Francisco and New York, prostitutes, intravenous drug users (IVDU), heamophiliacs, blood transfused persons and newborns was soon solved once the identification and modes of transmission of HIV infection were determined (Barre-Sinoussi et al., 1983; Gallo et al., 1984). Since, in developed countries, systematic screening of HIV is now secured in all blood transfusions, the most likely possibility of HIV infection in the paediatric age group is mother to child (vertical) transmission. Transmission during adolescence could also be due to early injecting during use and sexual contacts. During the last ten years a great body of knowledge has been accumulated on the global distribution of HIV, patterns of transmission, clinical symptomatology, the evolution of the disease and immunologic alterations. However, much remains to be discovered: virus structure and its mutations, early and reliable diagnostic methods, risk factors and transmission rates, natural history, nutrition deficiencies, social and behavioural alterations, implications for health care systems, specific and supportive treatments, and vaccine development. Only long term, prospective and well coordinated studies of large series of HIV-infected newborns will provide answers to these questions (ECS, 1991; Blanche et al., 1989).
Vertical transmission
In utero HIV infection occurs across the placenta as early as 15 weeks of gestation (Sprecher et al., 1986), but little is known about the specific maternal factor(s) that can influence the risk of
Address for correspondence: Professor Cipriano A. Canosa, Hospital “La Fe”, Jefew Departmamento Pediatria, Avenida de Campanor 21,46009 Valencia, Spain.
304
C. A. CANOSA
transmission. Could mothers at various stages of HIV infection experience different rates of transmission? Could the most advanced evolution of the mother’s HIV infection imply that the foetus will be more severely infected? Will the foetus of a woman HIV infected four years prior to pregnancy be more severely affected than during seroconversion? When HIV infection is contracted during the first or third trimester of pregnancy, will the child have the same risk of transmission? Will different viraemia levels and virus strains affect the risk of infection of the foetus? These factors and their relative risks of vertical transmission remain unknown.
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Delivery
The second mode of vertical transmission is during delivery. HIV was isolated from vaginal and cervical secretions among infected women (Vogt et al., 1986; Wofsey et al., 1986), thus the possibility of transmission during delivery has to be considered. It was recommended that to prevent this type of transmission, caesarian section should be performed on all HIV infected pregnant women. Large longitudinal studies of HIV infected newborns do not support this hypothesis (ECS, 1991; Blanche et al., 1989). However, a recent twins study demonstrated that the first born twin has higher risk of being infected than the second. The proximity of the first born twin to the cervix during labour and parturition was suggested to be the cause for this difference. Caesarian section, vaginal delivery and zygocity did not discriminate between first and second twins (Goedert et al., 1991). Further research is necessary to establish the relationship between type of delivery and HIV infection. Breast milk
Cellular and accellular fractions of callostrum and breast milk contain HIV (Thiry et al., 1981; Ziegler et al., 1985). Well documented cases were reported where the only possibility of HIV infection was through breast milk (Ziegler et al., 1985) although the risk is considered small. Because of the limited risks of HIV infection through breast milk, WHO recommends natural feeding for developing countries and artificial feeding for developed ones (Chin et al., 1990; PHOIWHO, 1988).
Definition of infection Maternal antibodies cross the placenta and are passively transmitted to the newborn (Oleske et al., 1983; Rubinstein et al., 1983; ECS, 1991; Blanche et al., 1989). Today there is no simple and accurate method that can differentiate between maternal and newborn produced antibodies. Maternal antibodies determined by ELISA and confirmed by Western blot (ECS, 1991; Blanche et al., 1989) may be present from birth up to 18 months. Children under 18 month of age who lose antibodies, have negative virus culture and negative p24 antigen, should be defined as not infected. HIV positive children under 18 months of age, with negative virus culture and negative p24 antigen, should be classified as indeterminate. HIV antibody loss Passively transmitted maternal HIV antibodies are present in the newborn. These antibodies begin to disappear as early as three months and as late as 18 months of age, mean 10.3 months (ECS, 1991). According to different reports, the proportion of children who remain antibody positive after 18 months of age varies from 40% (Henrion, 1988) to 12.9% (ECS,
H N INFECTION IN CHILDREN
305
1991) (Table 1). The methodology, selection criteria, frequency of visits, lack of follow up, tests used and types of studies could probably explain these differences. However, the final and definitive value of antibody loss on HIV positive newborns is not firmly established. A small proportion of children who became HIV negative had virus positive cultures and/or immunologic alterations; this phenomenon is not fully understood (ECS, 1988). From prospective studies there are no reports of children who, after they became HIV negative, sero-converted back to HIV positive status.
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Table 1. Rate of transmission of HIV infectionfiom mother to child in diJerent studies Transmission rate ( 4 6 )
Author Henrion (1988) Italian study (1988) European study (1988) Blanche (1989) Blanche (1989) Jason ( 1990) European study (1991)
40 33 24 40 27 25 13
Maternal characteristics Global estimates of HIV infection and AIDS in women are shown in Table 2 for 1990. Maternal characteristics differ between developed and developing countries. In Table 3 mothers’ characteristics in EEC countries are described (ECS, 1988, 1991; Canosa et al., 1990). In developed countries the sociolcultural status of HIV positive women is frequently low; common factors among this group are unstable and broken families, being unmarried, one parent families, marginal and discriminated populations, IVDU, and unemployment. In sub-Saharan African countries, the most frequent mode of transmission of HIV infection is through heterosexual contact; mothers’ age ranges from 18 to 40 years, the seroprevalence among women of child-bearing age is between 1 4 8 % (Table 4) (Plot et al., 1987). Table 2. HIV infection and AIDS. Global estimates for 1990for women aged 15-49 years
Cumulative total AIDS cases
Total HIV positive people
Total HIV positive women
HIV positive females as a percentage of all females aged 15-49
0.14 0.20 0.03 2.50 0.03 0.06
North America Latin America Europe Africa Asia Oceania
175,000 75,000 50,000 >500,000 >I,OOO C1,OoO
>50,000 >5,000,000 500,000 30,000
1 00,000 200,000 60,000 >2,500,000 200,000 3,000
Total
>800,000
>8,300,000
>3,043,000
Source: WHO, September 1990.
1,000,000 l Y ~ Y ( K J 0
306
C. A.
CANOSA Table 3. Characteristics of mothers with HIV infection
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Mean age (years) Mean gestational age of child (weeks) Married-cohabiting (%) IVDU (%) Partner IVDU ( 4 6 ) AIDS (%) C-section (%) Rate of Transmission (%)
EEC
Spain
24 38 67 85 7 5 24 24-12.9
23 37 79 93 62 10 12 25
Table 4. HIV antibody prevalence among women of child-bearing age in selected Afncan populations % HIV antibody positive
Population studies
Countries
Year
Nos. studied
General population
Cameroon Central African Republic (Bagui) Congo (Brazzaville) Uganda (Kampala) Uganda (West Nile) Zaire (Equateur)
1985
1,273
1
Durand et al., 1986
1985 1985 1985 1985 1986
1,263 368 716 71 389
4 5 15 1.4 0.8
Merlin et al., 1986 Merlin et al., 1986 Carswell et al., 1986 Carswell et al., 1986 Nzila et al., 1987
Ivory Coast (Abidjan) Kenya (Nairobi) Uganda (Kampala) Zaire (Kinshasa) Zambia (Lusaka)
1986 1985 1986 1986 1985
42 1,100 1,011 449 184
2 14 8 9
Cameroon (Meiganga) Ivory Coast (Abidjan) Kenya (Nairobi) Rwanda (Butare) Zaire (Kinshasa)
221 101 286 33 377
8 20 61 88 27
Zaire (Equateur)
1985 1986 1985 1984 1985 1986
283
11
Durand et al., 1986 Denis et al., 1987 Piot et al., 1987 Van de Perre et al., 1985 Mann et al., 1987 Nzila et al., 1987
Kenya (Nairobi) Rwanda (Butare) Zambia (Lusaka)
1985 1984 1985
194 25 144
15 28 29
Piot et al., 1987 Van de Perre et al., 1985 Melbye et al., 1986
Pregnant women
Prostitutes
With STD
5
References
Denis et al., 1987 Piot et al., 1987
-
Quinn et al., 1986 Melbye et al., 1986c
Seroprevalence studies For epidemiologic and diagnostic purposes, seroprevalence surveys of child-bearing women and newborns are being conducted in 43 states in the USA (Hoff et al., 1988; Pappaioandu, 1990). Dried blood spots specimens are routinely collected on filter paper from neonates to study the unborn errors of metabolism; they provide information to assess the levels and trends of HIV infection in women and infants and to evaluate the efficacy of preventive programmes. Similar methods are also being utilized in the UK (Peckham et al., 1990) and Italy (Ippolito et al., 1989) with equally good results. These surveys ensure patients’
HIV INFECTION IN CHILDREN
307
anonymity due to the unlinked method design. For public health purposes, countries with high prevalence of HIV infection will have to consider the urgency and necessity of implementing seroprevalence surveys,unlinked and anonymous.
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Newborn Characteristics The offspring of HIV positive mothers have the following clinical characteristics. Mean birth weight 2.7-2.8 kg; (2500 g, 15-30%;
ISSN: 0954-0121 (Print) 1360-0451 (Online) Journal homepage: http://www.tandfonline.com/loi/caic20
HIV infection in children C. A. Canosa To cite this article: C. A. Canosa (1991) HIV infection in children, AIDS Care, 3:3, 303-309, DOI: 10.1080/09540129108253077 To link to this article: http://dx.doi.org/10.1080/09540129108253077
Published online: 25 Sep 2007.
Submit your article to this journal
Article views: 19
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=caic20 Download by: [NUS National University of Singapore]
Date: 06 November 2015, At: 22:47
AIDS CARE, VOL. 3, NO. 3,1991
303
HIV infection in children C. A. CANOSA Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Hospital “La Fe” Department of Pediatrics, Valencia, Spain
Introduction The first paediatric AIDS patient was described two years after the first adult case was reported (Oleske et al., 1983). Numerous new patients were soon identified and were directly related to either blood transfusions or vertical transmission (transplacental, perinatal and breast milk) (Rubinsein et al., 1983; Scott et al., 1984; O’Duffy & Isles, 1984; Mann et al., 1986). Various reports specify that 2 5 3 % of all AIDS cases worldwide occur among children (Chin et al., 1990; PHO/WHO, 1988). However, due to the peculiar characteristics of HIV infection in children and the difficulties in reporting, it is possible that the proportion is higher, of the order of 7-8%. The initial puzzling distribution of AIDS in Central Africa and Haiti, among homosexuals from San Francisco and New York, prostitutes, intravenous drug users (IVDU), heamophiliacs, blood transfused persons and newborns was soon solved once the identification and modes of transmission of HIV infection were determined (Barre-Sinoussi et al., 1983; Gallo et al., 1984). Since, in developed countries, systematic screening of HIV is now secured in all blood transfusions, the most likely possibility of HIV infection in the paediatric age group is mother to child (vertical) transmission. Transmission during adolescence could also be due to early injecting during use and sexual contacts. During the last ten years a great body of knowledge has been accumulated on the global distribution of HIV, patterns of transmission, clinical symptomatology, the evolution of the disease and immunologic alterations. However, much remains to be discovered: virus structure and its mutations, early and reliable diagnostic methods, risk factors and transmission rates, natural history, nutrition deficiencies, social and behavioural alterations, implications for health care systems, specific and supportive treatments, and vaccine development. Only long term, prospective and well coordinated studies of large series of HIV-infected newborns will provide answers to these questions (ECS, 1991; Blanche et al., 1989).
Vertical transmission
In utero HIV infection occurs across the placenta as early as 15 weeks of gestation (Sprecher et al., 1986), but little is known about the specific maternal factor(s) that can influence the risk of
Address for correspondence: Professor Cipriano A. Canosa, Hospital “La Fe”, Jefew Departmamento Pediatria, Avenida de Campanor 21,46009 Valencia, Spain.
304
C. A. CANOSA
transmission. Could mothers at various stages of HIV infection experience different rates of transmission? Could the most advanced evolution of the mother’s HIV infection imply that the foetus will be more severely infected? Will the foetus of a woman HIV infected four years prior to pregnancy be more severely affected than during seroconversion? When HIV infection is contracted during the first or third trimester of pregnancy, will the child have the same risk of transmission? Will different viraemia levels and virus strains affect the risk of infection of the foetus? These factors and their relative risks of vertical transmission remain unknown.
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Delivery
The second mode of vertical transmission is during delivery. HIV was isolated from vaginal and cervical secretions among infected women (Vogt et al., 1986; Wofsey et al., 1986), thus the possibility of transmission during delivery has to be considered. It was recommended that to prevent this type of transmission, caesarian section should be performed on all HIV infected pregnant women. Large longitudinal studies of HIV infected newborns do not support this hypothesis (ECS, 1991; Blanche et al., 1989). However, a recent twins study demonstrated that the first born twin has higher risk of being infected than the second. The proximity of the first born twin to the cervix during labour and parturition was suggested to be the cause for this difference. Caesarian section, vaginal delivery and zygocity did not discriminate between first and second twins (Goedert et al., 1991). Further research is necessary to establish the relationship between type of delivery and HIV infection. Breast milk
Cellular and accellular fractions of callostrum and breast milk contain HIV (Thiry et al., 1981; Ziegler et al., 1985). Well documented cases were reported where the only possibility of HIV infection was through breast milk (Ziegler et al., 1985) although the risk is considered small. Because of the limited risks of HIV infection through breast milk, WHO recommends natural feeding for developing countries and artificial feeding for developed ones (Chin et al., 1990; PHOIWHO, 1988).
Definition of infection Maternal antibodies cross the placenta and are passively transmitted to the newborn (Oleske et al., 1983; Rubinstein et al., 1983; ECS, 1991; Blanche et al., 1989). Today there is no simple and accurate method that can differentiate between maternal and newborn produced antibodies. Maternal antibodies determined by ELISA and confirmed by Western blot (ECS, 1991; Blanche et al., 1989) may be present from birth up to 18 months. Children under 18 month of age who lose antibodies, have negative virus culture and negative p24 antigen, should be defined as not infected. HIV positive children under 18 months of age, with negative virus culture and negative p24 antigen, should be classified as indeterminate. HIV antibody loss Passively transmitted maternal HIV antibodies are present in the newborn. These antibodies begin to disappear as early as three months and as late as 18 months of age, mean 10.3 months (ECS, 1991). According to different reports, the proportion of children who remain antibody positive after 18 months of age varies from 40% (Henrion, 1988) to 12.9% (ECS,
H N INFECTION IN CHILDREN
305
1991) (Table 1). The methodology, selection criteria, frequency of visits, lack of follow up, tests used and types of studies could probably explain these differences. However, the final and definitive value of antibody loss on HIV positive newborns is not firmly established. A small proportion of children who became HIV negative had virus positive cultures and/or immunologic alterations; this phenomenon is not fully understood (ECS, 1988). From prospective studies there are no reports of children who, after they became HIV negative, sero-converted back to HIV positive status.
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Table 1. Rate of transmission of HIV infectionfiom mother to child in diJerent studies Transmission rate ( 4 6 )
Author Henrion (1988) Italian study (1988) European study (1988) Blanche (1989) Blanche (1989) Jason ( 1990) European study (1991)
40 33 24 40 27 25 13
Maternal characteristics Global estimates of HIV infection and AIDS in women are shown in Table 2 for 1990. Maternal characteristics differ between developed and developing countries. In Table 3 mothers’ characteristics in EEC countries are described (ECS, 1988, 1991; Canosa et al., 1990). In developed countries the sociolcultural status of HIV positive women is frequently low; common factors among this group are unstable and broken families, being unmarried, one parent families, marginal and discriminated populations, IVDU, and unemployment. In sub-Saharan African countries, the most frequent mode of transmission of HIV infection is through heterosexual contact; mothers’ age ranges from 18 to 40 years, the seroprevalence among women of child-bearing age is between 1 4 8 % (Table 4) (Plot et al., 1987). Table 2. HIV infection and AIDS. Global estimates for 1990for women aged 15-49 years
Cumulative total AIDS cases
Total HIV positive people
Total HIV positive women
HIV positive females as a percentage of all females aged 15-49
0.14 0.20 0.03 2.50 0.03 0.06
North America Latin America Europe Africa Asia Oceania
175,000 75,000 50,000 >500,000 >I,OOO C1,OoO
>50,000 >5,000,000 500,000 30,000
1 00,000 200,000 60,000 >2,500,000 200,000 3,000
Total
>800,000
>8,300,000
>3,043,000
Source: WHO, September 1990.
1,000,000 l Y ~ Y ( K J 0
306
C. A.
CANOSA Table 3. Characteristics of mothers with HIV infection
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Mean age (years) Mean gestational age of child (weeks) Married-cohabiting (%) IVDU (%) Partner IVDU ( 4 6 ) AIDS (%) C-section (%) Rate of Transmission (%)
EEC
Spain
24 38 67 85 7 5 24 24-12.9
23 37 79 93 62 10 12 25
Table 4. HIV antibody prevalence among women of child-bearing age in selected Afncan populations % HIV antibody positive
Population studies
Countries
Year
Nos. studied
General population
Cameroon Central African Republic (Bagui) Congo (Brazzaville) Uganda (Kampala) Uganda (West Nile) Zaire (Equateur)
1985
1,273
1
Durand et al., 1986
1985 1985 1985 1985 1986
1,263 368 716 71 389
4 5 15 1.4 0.8
Merlin et al., 1986 Merlin et al., 1986 Carswell et al., 1986 Carswell et al., 1986 Nzila et al., 1987
Ivory Coast (Abidjan) Kenya (Nairobi) Uganda (Kampala) Zaire (Kinshasa) Zambia (Lusaka)
1986 1985 1986 1986 1985
42 1,100 1,011 449 184
2 14 8 9
Cameroon (Meiganga) Ivory Coast (Abidjan) Kenya (Nairobi) Rwanda (Butare) Zaire (Kinshasa)
221 101 286 33 377
8 20 61 88 27
Zaire (Equateur)
1985 1986 1985 1984 1985 1986
283
11
Durand et al., 1986 Denis et al., 1987 Piot et al., 1987 Van de Perre et al., 1985 Mann et al., 1987 Nzila et al., 1987
Kenya (Nairobi) Rwanda (Butare) Zambia (Lusaka)
1985 1984 1985
194 25 144
15 28 29
Piot et al., 1987 Van de Perre et al., 1985 Melbye et al., 1986
Pregnant women
Prostitutes
With STD
5
References
Denis et al., 1987 Piot et al., 1987
-
Quinn et al., 1986 Melbye et al., 1986c
Seroprevalence studies For epidemiologic and diagnostic purposes, seroprevalence surveys of child-bearing women and newborns are being conducted in 43 states in the USA (Hoff et al., 1988; Pappaioandu, 1990). Dried blood spots specimens are routinely collected on filter paper from neonates to study the unborn errors of metabolism; they provide information to assess the levels and trends of HIV infection in women and infants and to evaluate the efficacy of preventive programmes. Similar methods are also being utilized in the UK (Peckham et al., 1990) and Italy (Ippolito et al., 1989) with equally good results. These surveys ensure patients’
HIV INFECTION IN CHILDREN
307
anonymity due to the unlinked method design. For public health purposes, countries with high prevalence of HIV infection will have to consider the urgency and necessity of implementing seroprevalence surveys,unlinked and anonymous.
Downloaded by [NUS National University of Singapore] at 22:47 06 November 2015
Newborn Characteristics The offspring of HIV positive mothers have the following clinical characteristics. Mean birth weight 2.7-2.8 kg; (2500 g, 15-30%;
