identifying missed.html
ORIGINAL ARTICLE
IDENTIFYING MISSED OPPORTUNITIES FOR EARLY INTERVENTION AMONG
HIV-INFECTED PAEDIATRIC ADMISSIONS AT CHRIS HANI BARAGWANATH HOSPITAL,
SOWETO, SOUTH AFRICA
Angela Dramowski1, MB ChB, FCPaed, MMed (Paed), Cert Paed ID, DCH
Ashraf Coovadia2, MB ChB, FCPaed, Dip HIV Man, DCH
Tammy Meyers3, MB ChB, FCPaed, MMed (Paed), DTM&H
Ameena Goga4, MB ChB, FCPaed, DTM&H, MSc (MCH), MSc (Epid)
1Department of Paediatrics and Child Health, Tygerberg Children’s Hospital and Stellenbosch University, Tygerberg, W Cape
2Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences,
University of the Witwatersrand, Johannesburg
3Department
of Paediatrics and Child Health, Chris Hani Baragwanath Hospital,
Faculty of Health Sciences, University of the Witwatersrand
4South African Medical Research Council, Pretoria
Background and design.
HIV is a major contributor to childhood morbidity and mortality in
South Africa. We describe HIV prevalence, disease profile, outcome and
missed opportunities for early intervention in a cohort of HIV-infected
children admitted to Chris Hani Baragwanath Hospital’s general
paediatric wards between 1 October 2007 and 31 December 2007.
Results. Of 1 510
admissions, 446 (29.5%) were HIV infected. Many children (238, 54.1%)
were newly diagnosed in hospital and most had advanced HIV disease
(405, 92%). The principal admission diagnoses were pneumonia (165,
37.5%), gastro-enteritis (97, 22%), sepsis (86, 19.5%) and tuberculosis
(92, 21%). Of children identified as HIV infected before admission,
128/202 (63.4%) were not accessing antiretroviral treatment (ART),
although 121/128 (94.5%) met ART eligibility criteria. Of 364
ART-naïve eligible children, only 15 (4.1%) were commenced on ART
as inpatients. Problems with PMTCT implementation in infants under 6
months (N=166) included lack
of maternal antenatal HIV testing (51, 30.7%); poor uptake of
maternal/infant nevirapine prophylaxis (60, 36.2%); limited use of
co-trimoxazole (CTX) prophylaxis (44/147, 29.9%); and delayed infant
HIV polymerase chain reaction testing (98/147, 87.5%). Of infants known
to be HIV infected prior to hospitalisation, 37/51 (73%) had not
initiated ART. The in-hospital case fatality rate (CFR) among
HIV-infected children was triple that of the combined HIV-uninfected,
exposed and unknown group (12% v. 3.6%). Infants <12 months of age
accounted for 73.6% of all HIV-related deaths (CFR 17.1%).
Conclusions. HIV remains
highly prevalent and contributes to significant in-hospital mortality.
Missed opportunities for PMTCT, HIV diagnosis and ART initiation are
frequent. Interventions to optimise paediatric HIV outcomes should
target maternal HIV diagnosis, early infant diagnosis, uptake of CTX
prophylaxis and prompt initiation of ART, especially among infants.
Hospitalised ART-eligible children should be prioritised for inpatient
initiation of ART.
South Africa has 5.6 million people living with HIV, including approximately 280 000 children1 who suffer disproportionate morbidity and double the mortality of their HIV-uninfected counterparts.2
,
3
Past progress in reducing national child mortality has been reversed by
paediatric HIV, with under-5 mortality rates (U5MR) increasing from 56
to 67 deaths per 1 000 live births between 1990 and 2008.4
Much of the increase in the U5MR can be accounted for by deaths in
young HIV-infected infants, many of whom progress rapidly to AIDS and
death from opportunistic infections, without early initiation of
antiretroviral therapy (ART).5
,
6
South Africa introduced the prevention of
mother-to-child transmission (PMTCT) and ART programmes nationwide in
2001 and 2004, respectively. The national PMTCT guidelines at the time
of this study (2007) recommended HAART for pregnant women with a CD4
count <200 cells/µl or zidovudine (AZT) from 28 weeks’
gestation plus intrapartum single-dose nevirapine (sdNVP) at CD4 counts
>200 cells/µl. All infants were scheduled to receive sdNVP at
delivery. The policy for early infant diagnosis (EID) at the time
recommended HIV polymerase chain reaction (PCR) testing at 6 weeks of life, and for breastfed babies a repeat HIV PCR test 6 weeks after complete cessation of breastfeeding.
ART initiation was recommended for any child with clinically advanced
disease (WHO HIV stage 3 or 4) or immunological compromise (CD4 <20%
in children less than 18 months of age and CD4 <15% in children over
18 months).7
Despite national implementation of these programmes, coverage and
uptake of PMTCT, EID and paediatric ART programmes were highly variable
between provinces.8
More recently, improved coverage of these interventions has been
achieved; however, many infants miss entry points for the PMTCT
programme and routine HIV testing. Others may be identified but are
lost from the system or become ill before ART is initiated.9 These children typically present to hospital with advanced HIV disease and consequently have high mortality rates.10
,
11
Chris Hani Baragwanath hospital (CHBH) is South Africa’s
largest public sector hospital, delivering care to the burgeoning urban
and low-income population of Soweto, Johannesburg. Paediatric HIV
prevalence at CHBH (described in two previous studies prior to the
implementation of PMTCT programmes) rose from 3% to 19%12 to 29%13
between 1992 and 1996. Over the same period the proportion of
paediatric in-hospital mortality accounted for by HIV increased
dramatically from 6.7% to 46.1%.12
Similar trends in HIV prevalence and HIV-related mortality in other
South African hospitals have been reported from a national data
collection programme, Child PIP.10
,
11
We report on paediatric HIV period prevalence, disease profile and
outcome of children admitted to CHBH in the last quarter of 2007,
several years after introduction of national PMTCT and paediatric HIV
management programmes. In addition we describe missed opportunities for
HIV prevention, diagnosis and medical intervention among this cohort of
HIV-infected children.
METHODS
Ethics. The study was approved by University of the Witwatersrand Human Research Ethics Committee (reference No. M080202).
Study site. The
study was undertaken at CHBH, Soweto, Johannesburg, in the Gauteng
province of South Africa. This 2 964-bed referral hospital is the only
public hospital serving approximately 3.5 million Sowetans and accepts
referrals from local primary health care clinics, regional hospitals in
Gauteng and neighbouring provinces of South Africa. In 2010, the
estimated HIV prevalence in Gauteng province was 10.5%.14
The province’s health sector, although challenged by high TB and
HIV prevalence, is relatively well resourced and staffed when compared
with other areas of South Africa. The hospital and all referring
institutions follow national PMTCT and HIV management guidelines. A
dedicated paediatric HIV clinic on the hospital premises (Harriet Shezi
clinic) provides outpatient services to more than 3 500 HIV-infected
children and the Perinatal HIV Research Unit (PHRU) provides PMTCT
support in the Soweto area.
Study design and sampling.
A cross-sectional retrospective review of all children (from birth to
14 years of age) hospitalised in the general paediatric wards between 1
October 2007 and 31 December 2007 was performed. Newborns with reactive
HIV PCR test results during their stay in the neonatal unit were not
included in this study, unless they were subsequently admitted to the
general paediatric wards during the 3-month study period. Patient
admission numbers and profile over this 3-month period did not differ
significantly from the preceding three-quarters of 2007. Two
populations were of interest (Fig. 1). Firstly, admission register
lists of all hospitalised children were used to determine HIV status (collected from laboratory and/or hospital records)
and calculate HIV period prevalence. Secondly, individual patient
records for children identified as HIV infected were reviewed. Monthly
paediatric mortality reports were used to calculate in-hospital
mortality. Self-reported data on PMTCT coverage were analysed only for
HIV-infected infants less than 6 months of age, to minimise information
recall bias. For analysis of missed opportunities in provision of
co-trimoxazole (CTX) prophylaxis and uptake of EID, infants <6 weeks were excluded.
Determination of HIV status.
All HIV tests were performed by the accredited National Health
Laboratory Service (NHLS). A reactive HIV-DNA PCR test confirmed
HIV-infected status in children under 18 months. A reactive HIV
enzyme-linked immunosorbent assay (ELISA) confirmed HIV-infected status
in children older than 18 months of age. Mothers’ self-reported
HIV status (as documented in hospital records) was used. Four
definitions were used: HIV uninfected
refers to the infant or child being confirmed HIV uninfected; HIV infected refers to the infant or child being confirmed HIV infected; if
the mother’s status was reportedly HIV infected and her infant
had no HIV PCR result, the infant’s status was classified as HIV exposed. If
maternal HIV status was unknown or uninfected and the child had no HIV
test result in laboratory or folder records, the status was classified
as HIV unknown.
Case definitions and reference classifications. In
cases where laboratory confirmation was not obtained, a working
diagnosis was based on clinical suspicion and the World Health
Organization (WHO) published case definitions15 for the following conditions: Pneumocystis jiroveci pneumonia (PCP),16
,
17
pulmonary tuberculosis (pTB), cytomegalovirus (CMV) pneumonitis or
disseminated disease, septicaemia, meningitis and urinary tract
infection. HIV disease severity was assessed using the WHO clinical
staging system for children15 and nutritional status using the WHO 2006 growth standards18
for calculation of z-scores in children under 60 months of age.
Calculation of ART eligibility was based on the South African national
guidelines (2005)7
at the time of the study, using immunological (CD4% <20% under 18
months of age; CD4% <15% above 18 months of age) and clinical
criteria (WHO stage 3 and 4 disease) only. The WHO and the South
African Department of Health published extensively revised guidelines
for child ART initiation in 2010.
Statistical analysis. Data were analysed in SAS version 9.1 (SAS Institute Inc., Cary, NC, USA). Crude HIV period prevalence was calculated from ward records as total HIV-infected admissions/total admissions. Case fatality rates in the HIV-infected and combined
HIV-uninfected, HIV-unknown and HIV-exposed groups were calculated from
total number of deaths/total number of admissions for each group. For
the PMTCT sub-analysis, frequency calculations were performed for
maternal HIV status, sdNVP exposure, CTX prophylaxis and place of
birth. The uptake of PMTCT interventions was then compared by maternal
HIV status grouping using the chi-square test. A p-value of <0.05 was considered to be statistically significant.
RESULTS
HIV PREVALENCE
Of 1 510 children admitted during the 3-month study period, 446
(29.5%) were HIV infected, 780 (51.7%) were HIV uninfected, 57 (3.8%)
were HIV exposed and 227 (15%) were of unknown HIV status (Fig. 1). For
the 446 children identified as HIV infected, 440 (98.7%) individual
patient records were located.
HIV-INFECTED CHILDREN: PROFILE OF STUDY POPULATION
Table I outlines the demographic and disease profile of the
440 HIV-infected children. Almost 93% had advanced HIV disease (WHO
stage 3 or 4) and 55.3% of children <5 years of age had severe
malnutrition.
Across all age groups, 225/320 children (70.3%) had severe immune suppression.
REASON FOR HOSPITALISATION
Infectious disease was the principal reason for hospitalisation
(Table I). Lower respiratory tract infections (including presumed PCP
and presumed Cytomegalovirus
pneumonitis) accounted for the majority of admissions, with the highest
prevalence among infants. One hundred and ten children (25%) had a
confirmed bacterial, viral or fungal infection during their hospital
admission. Streptococcus pneumoniae and CMV were the most common bacterial and viral pathogens isolated.
MISSED OPPORTUNITIES
Prevention of mother-to-child transmission of HIV
Self-reported maternal HIV status and sdNVP exposure were analysed in HIV-infected infants under the age of 6 months (n=166). Uptake of CTX prophylaxis and EID were analysed only for infants >6 weeks of age (n=147)
so as to be consistent with programme guidelines. Fig. 2 highlights the
multiple levels of missed opportunities for PMTCT implementation in
infants (<6 months of age) whose mothers reported their status as
HIV infected versus HIV uninfected versus HIV unknown. Lack of maternal
antenatal HIV testing was documented among 51/166 (30.7%) mothers.
There was poor uptake of maternal/infant NVP prophylaxis (60/166,
36.2%). Usage of CTX prophylaxis was limited (44/147, 29.9%) and in
most cases infant HIV PCR testing was delayed or lacking (98/147,
87.5%). There was no association between place of birth (CHBH versus
clinic/other hospital/home) and access to NVP or CTX (p=0.1288 and p=0.5818, respectively). Of
the 147 HIV-infected infants 6 weeks - <6 months of age, 51 (34.7%)
were known to be HIV infected while the remainder, 96 (65.3%), were
newly diagnosed (i.e. had not previously had HIV PCR testing) at the
time of hospital admission. Sixty-seven
(45.6%) of the 147 infants received no PMTCT interventions at all. Only
20/147 (13.6%) infants received all recommended interventions, i.e. NVP
and CTX and EID. Table I reflects additional missed opportunities for
the provision of CTX prophylaxis among other categories of the study
population.
HIV diagnosis and antiretroviral therapy (ART) eligibility and uptake
Most children, 238/440 (54.1%), were newly diagnosed at the time of
hospitalisation at CHBH. Newly diagnosed children were younger than
those already known to be HIV infected (median 6 v. 12 months of age) (p=0.001).
Children known to be infected and already on ART had a median treatment
duration of 2 months and were significantly older than ART-naïve
children (median age 38 v. 7 months) (p<0.0001).
Of children known to be infected but not on ART (128/202, 63.4%),
nearly all (121/128, 94.5%) were eligible for ART based on advanced
disease stage. Of 364 ART-naïve eligible children, only 15 (4.1%)
were commenced on ART as inpatients (Fig. 1). Table II compares
eligibility for ART with actual ART uptake among children who died.
OUTCOME OF HOSPITALISATION
Median duration of hospital stay was 7 days (interquartile range
(IQR) 4 - 10.) Fifty-three children died (Table I) with a median
duration of stay before death of 4 days (IQR 2 - 7.8). Only 13 children
(3.0%) were admitted to an ICU or underwent mechanical ventilation in
the high-care area of the acute admissions ward. Ten of these 13
children (76.9%) survived to hospital discharge.
Fifty-eight per cent of all paediatric deaths (53/91) occurred among
the HIV-infected group. The overall case fatality rate in the
HIV-infected children was 53/440 (12.0% (95% confidence interval (CI)
9.2 - 15.5%)). In contrast, the case fatality rate in the
HIV-uninfected, HIV-exposed and HIV-unknown group over the study period
was 38/1 064 (3.6% (95% CI 2.5 - 4.9%)). The highest case fatality rate
by age group was in infants aged less than 12 months (Table I). The
most prevalent causes of death included pneumonia/suspected PCP (18/53,
34%), TB (14/53, 26.3%) and gastro-enteritis (5/53, 9.4%). The
inpatient mortality rate did not differ significantly between children
receiving ART at the time of hospitalisation (7.9%, 6/76) versus
ART-naïve children (13.6%, 47/345) (p=0.17, odds ratio 0.54).
DISCUSSION
HIV PREVALENCE
This paper reports the first published data on paediatric HIV
prevalence, disease profile and outcome at CHBH subsequent to
widespread implementation of PMTCT and paediatric HIV management
programmes. The HIV period prevalence of 29.5% was almost identical to
that found in 1996. However, the true HIV prevalence remains
unquantified, since both cohorts had large numbers of untested
children. Several years after national roll-out of PMTCT and ART
programmes, there is therefore little evidence of a decreasing impact
of paediatric HIV at CHBH. Possible explanations for this could include
increasing antenatal HIV prevalence in Gauteng province (15.5 - 29.8%
between 1996 and 2009)19
with more vertical infections; failure of sdNVP PMTCT regimens; the
possibility of an even higher (undocumented) peak paediatric HIV
prevalence reached between 1996 and 2007; poor PMTCT coverage; improved
survival rates (particularly in older HIV-infected children on ART);
and the establishment of a dedicated paediatric HIV clinic at CHBH
(pooling children with complicated HIV disease).
MISSED OPPORTUNITIES
Prevention of mother-to-child transmission of HIV
A major limitation of the chosen study design is possible maternal
recall bias regarding PMTCT interventions. In addition, reported
maternal HIV status could not be verified in all cases. Healthcare
workers’ documentation of PMTCT interventions was poor. In order
to decrease missed opportunities among HIV-exposed infants, all PMTCT
interventions should be clearly explained to caregivers and documented
in all patient records, especially the infants’ Road to Health
Card (RTHC). This is the most important linkage and communication tool
for paediatric healthcare providers, especially when children access
care at multiple facilities.
Uptake of PMTCT interventions was poor, with
almost half of infants under 6 months of age receiving no PMTCT
interventions at all. Of particular concern was the large proportion of
mothers who reported their status as HIV uninfected (15.1%) or HIV
unknown/untested (30.7%). There are several possible explanations for
the 15.1% of mothers who reported their status as HIV uninfected: a
negative test in early pregnancy with subsequent seroconversion before
delivery (3% reported seroconversion of pregnant women);20
postnatal HIV infection with breastfeeding transmission; or fear of
stigmatisation after disclosure of HIV status. Antenatal identification
of HIV-infected pregnant women is the gateway to a successful PMTCT
programme, since all other interventions rely on this key step. Opt-out
antenatal HIV testing, and repeat HIV testing late in pregnancy, during
labour and at immunisation services, would maximise identification of
HIV-infected mothers. In addition, clear recording of maternal HIV
status on the infant’s RTHC would increase awareness of HIV
exposure and hopefully prompt prescription of CTX and uptake of infant
HIV PCR testing. This would allow for earlier infant diagnosis and
rapid ART initiation, resulting in improved infant outcomes.
The poor uptake rates reported for sdNVP and CTX prophylaxis in this study are alarming. Possible
factors contributing to this problem include mothers who test at a
clinic and then deliver in hospital; ‘cryptic’ written
communication between health facilities about patients’ HIV
status in an attempt to maintain confidentiality; women’s
reluctance to disclose HIV status due to stigma; and health care
workers’ reluctance to offer HIV testing or to enquire about HIV
status. Failure to provide CTX prophylaxis represents a major missed
opportunity to prevent early mortality from PCP, as demonstrated in
this cohort with 15% of deaths ascribed to PCP. Since 2007
there has been considerable improvement (but increased complexity) in
PMTCT regimens. However, these changes will be not be effective unless
universal uptake of PMTCT, CTX prophylaxis and early infant diagnosis
is achieved. High loss to follow-up of
HIV-exposed infants remains a major problem in the PMTCT programme,
both at CHBH and at a national level as reported by previous studies.21
,
22
HIV diagnosis and antiretroviral therapy eligibility and uptake
Despite calls for universal testing, 15% of children admitted to
CHBH had no documentation of HIV exposure status or HIV testing. In a
subgroup (3.8%) noted to be HIV exposed and symptomatic (requiring
hospitalisation), HIV PCR testing was not performed. Although usually
recommended at 4 - 6 weeks of age, immediate HIV PCR testing should be
performed in symptomatic HIV-exposed infants regardless of age so as to
expedite ART initiation.23
Maternal HIV status, PMTCT interventions and results of HIV PCR testing
should be routinely enquired about at every infant’s health care
visit. Similarly, any child who presents with malnutrition must be
screened for HIV, as reflected in this cohort, where 54.1% of children
were newly diagnosed in hospital despite a background of malnutrition
(in 72%) and previous hospitalisations. However, rapid HIV tests (used
for screening or to establish HIV exposure status in infants) have high
false-negative rates, especially among young infants.24
Despite growing awareness of the benefits of paediatric ART at the time, ART coverage of these hospitalised children was low (83% of eligible children were not accessing ART).
The short treatment duration and older age of children on ART at CHBH
highlights the fact that few children and even fewer infants had the
benefit of early ART initiation. To ensure timeous and equitable access
for children, ART must be initiated and monitored at entry levels of
the health care system (primary health care clinics). Furthermore,
hospitalised, symptomatic HIV-infected children should be fast-tracked
for inpatient ART initiation. This measure should be strongly
considered for every ART-eligible hospitalised child, and especially
for infants ≤12 months of age, who are at highest risk of disease
progression and death.23
In our study setting (a hospital with an established paediatric ART
service), only 4.1% of ART-naïve, ART-eligible children had
treatment commenced as an inpatient, despite weekly ward visits by
clinicians from the onsite HIV clinic. In addition, none of those
commenced on ART as inpatients were infants, despite this being the age
category with the highest case fatality rate. We postulate that
multiple hurdles to inpatient ART initiation exist, such as parental
illness or death, complex social circumstances, advanced HIV disease
and clinician inexperience with or reluctance to commence HAART.
Despite these obstacles, clinicians need to be more aggressive in
identifying and treating ART-eligible infants and children during ward
admission.
OUTCOME OF HOSPITALISATION
Infectious diseases such as diarrhoea, TB and PCP – which are
preventable by immunisation, prophylaxis or early ART initiation
– accounted for all of the deaths. Dual or multiple concurrent
infections are well recognised among HIV-infected children with
pneumonia. There were no documented cases in this cohort, but this may
simply reflect the lack of aggressive screening for multiple
respiratory pathogens. CMV was demonstrated on postmortem specimens
from several patients. It was difficult to distinguish CMV infection
from disease, additional laboratory testing was limited and ganciclovir
treatment was not readily accessible at CHBH at the time of the study.
The contribution of CMV disease to the burden of pneumonia and deaths
in this cohort is therefore uncertain.
During the study, only 3% of HIV-infected children were admitted to
ICU/high care; however, they demonstrated a 76.9% survival rate. Data
on ICU candidate selection policies, duration of stay, incidence of
complications and long-term morbidity and mortality compared with that
of HIV-negative children admitted to ICU were not available. With
expanding ART access and improved HIV outcomes, institutional policies
for the admission of HIV-infected children to paediatric ICU facilities
in South Africa should be reviewed.
AT CHBH from 1992 to 1996 the proportion of paediatric in-hospital
mortality accounted for by HIV increased from 6.7% to 46.1% and in 2007
(this study) to 58%. This figure shows striking concordance with the
2008 South African statistics from the Countdown to 2015 report, which attributed 57% of under-5 mortality to HIV/AIDS (current HIV-attributable mortality is 46%).25
Despite implementation of PMTCT and paediatric ART programmes, HIV
prevalence and in-hospital case fatality rates (among HIV-infected
children under 5 years of age) have remained static between 1996 and
2007. Over the same period, however, mortality among uninfected
children has declined. HIV-infected children at CHBH are at a 3-fold
increased risk of death compared with HIV-uninfected, HIV-exposed and
HIV-unknown children. Hospitalised HIV-infected infants under 12 months
of age at CHBH are a particularly vulnerable group with a high case
fatality rate (17.1%), and should be prioritised for early ART
initiation.
ART status at the time of hospitalisation did not significantly
impact on inpatient mortality; however, the median duration of ART in
the treatment group was only 2 months, reducing the likelihood of
treatment survival benefit. Early hospitalisations after initiation of
ART are a well-documented phenomenon,26
but no immune reconstitution inflammatory syndrome (IRIS) or ART
adverse event-related admissions were documented in this cohort. It is
possible that these conditions were unrecognised and thus
under-reported owing to lack of experience of hospital staff at that
time.
This study has several limitations that may impair its
generalisability: a retrospective study design; small sample size; a
short study period; and lack of an HIV-uninfected comparison group. The
large percentage of children (15%) with unknown HIV status also limits
the accuracy of the HIV prevalence data. Missed opportunities among
HIV-exposed, status unknown infants were also not captured. However,
the data provide a ‘snap-shot’ of HIV impact at a large
referral hospital and may reflect commonly encountered challenges to
paediatric HIV care provision. Experiences after introduction of PMTCT
and ART at CHBH may provide insights for other institutions struggling
to implement best practice guidelines for paediatric HIV care.
CONCLUSION
HIV remains highly prevalent and contributes to significant
in-hospital mortality at CHBH. Multiple missed opportunities for PMTCT,
HIV diagnosis and ART initiation were identified, demonstrating the
need to monitor and assist with HIV guideline implementation at service
delivery level. Interventions to optimise paediatric HIV outcomes
should target maternal HIV diagnosis, early infant diagnosis, uptake of
CTX prophylaxis and prompt initiation of ART, especially among infants.
Hospitalised ART-eligible children should be prioritised for inpatient
initiation of ART. Ongoing surveillance of HIV prevalence, disease
profile and mortality at CHBH and other hospitals may be used to
identify programmatic problems, plan service improvement interventions
and measure progress towards the millennium goal of a two-thirds
reduction in U5MR by 2015.27
Declaration of competing interests. The authors declare that they have no competing interests.
Authors’ contributions. All
authors contributed to study design, data interpretation and critical
revision of the manuscript. AD performed the data collection, data
analysis (supervised by AG) and drafted the manuscript.
Acknowledgements. This research was supported by a Medical Faculty Research Endowment Fund grant from the University of the Witwatersrand. Tammy Meyers is a Fogarty Fellow sponsored by grant No. 5U2RTW007370 and 5U2RTW007373.
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Fig. 1. Determination of HIV prevalence and study population and ART uptake among 440 HIV-infected children.
TABLE I. DISEASE PROFILE OF HIV-INFECTED CHILDREN (N=440)
Gender
Male 234 (53.2%)
Female 206 (46.8%)
Age category
≤11 months 228 (51.8%)
12 - 35 months 85 (19.3%)
36 - 59 months 29 (6.6%)
≥5 years 98 (22.3%)
Timing of HIV diagnosis
Newly diagnosed 238 (54.1%)
Known HIV-infected 202 (45.9%)
WHO HIV stage
I 3 (0.7%)
II 29 (6.6%)
III 188 (42.7%)
IV 220 (50%)
Median (IQR) weight-for-age z-score (WAZ)* (n=342)
≤11 months (n=228) -3.53 (-4.59 - -2.44)
12 - 35 months (n=85) -2.69 (-3.60 - -1.43)
36 - 59 months (n=29) -1.89 (-3.03 - -1.41)
No. 0 - 59 months with WAZ -3 - -2 (%) 56 (16.4)
No. 0 - 59 months with WAZ <-3 (%) 189 (55.3)
Median (IQR) CD4 percentage by age group† (n=320)
≤11 months (n=155) 18.6 (12.8 - 28)
12 - 35 months (n=57) 16.2 (9.6 - 23)
36 - 59 months (n=23) 9.1 (6.3 - 15.3)
≥5 years (n=85) 8.0 (4.5 - 14.7)
Median (IQR) CD4 absolute count (cells/µl) by age group† (N=320)
≤11 months (n=155) 700 (361 - 1294)
12 - 35 months (n=57) 565 (422 - 909)
36 - 59 months (n=23) 414 (197 - 863)
≥5 years (n=85) 171 (45 - 379)
Severe immunosuppression (all ages)‡ 225/320, 70.3.%
No. (%) of children receiving CTX prophylaxis
All HIV-infected infants <12 months of age 73/228 (32%)
Known to be HIV-infected and not yet on ART 86/127 (67.7%)
Known to be HIV-infected and on ART <12 months 53/55 (96.4%)
Reason for hospitalisation
Pneumonia 165 (37.5%)
Gastro-enteritis 97 (22%)
Tuberculosis (including pTB + extrapulmonary TB) 92 (21%)
Sepsis 86 (19.5%)
(including septicaemia (n=48), meningitis (n=23), and urinary tract infection (n=15)
Outcome of hospitalisation
Discharged alive 319 (72.5%)
Died 53 (12%)
Transferred to a step-down hospital facility 68 (15.5%)
Deaths by age group (case fatality rate§, 95% CI) by age group (n=53)
≤11 months 39 (17.1%, 12.5 - 22.6)
12 -35 months 4 (4.7%, 1.3 - 11.6)
36 - 59 months 2 (6.9%, 0.8 - 22.8)
≥5 years 8 (8.2%, 3.6 - 15.5)
* Calculation of WAZ scores was only done for children 0 - 59 months of age (n=342).
†CD4-positive
T-cell counts and percentages were analysed in a subgroup of the study
population who had had CD4 testing at any point 1 month before, during
or after hospitalisation (n=320/440).
‡Proportion of children with severe immunosuppression was defined using WHO (2007) criteria11
as follows: <11 months of age, CD4 <25%; 12 - 35 months, CD4
<20%; 36 - 59 months, CD4 <15%; >5 years, CD4 <200 or
<15%.
§Case fatality rate was calculated as total number of deaths per age group/total number of admissions per age group.
TABLE II. ELIGIBILITY FOR ART VERSUS ART ACCESS IN 53 HIV-INFECTED CHILDREN WHO DIED
Age categories
No. (%) with immunological
criteria qualifying for ART*
No. (%) with clinically advanced
disease (stage 3 or 4) qualifying
for ART
No. (%) of eligible children actually receiving ART at time of death
All deaths
(n=53)
18/27†
(66.7)
50/53
(94.3)
6/50
(12)
Deaths <18 months
(n=40)
10/17†
(58.8)
38/40
(95)
6/38
(15.8)
Deaths >18 months
(n=13)
8/10†
(80)
12/13
(92.3)
0/12
(0)
*CD4 percentage <20% for children <18 months old, CD4 <15% for children >18 months old.
†The
denominators differ from the overall group denominators because only a
proportion of the 53 HIV-infected children who died had recent CD4
percentage results available.
Fig. 2. Missed opportunities for PMTCT implementation, CTX prophylaxis, EID and ART initiation in infants (<6 months).