NR: not reported; PLWH: people living with HIV
Adult active surveillance studies
Nine active surveillance studies contributed adult data (Table 2). All
were available as English full-text reports, except one Malian study
reported in both a French-language article39 and a
French-language thesis38 with English abstracts. An
Ethiopian study was reported in two complementary
articles49,50. Median quality score was 7/10, ranging
from 2/10 to 10/10. Studies were conducted in South Africa (two
studies37,47, both high quality), Nigeria (two
studies43,52), and in Eritrea48,
Ethiopia49,50, Malawi42,
Mali38,39, and Uganda41. Study
duration ranged from 1 month to 16 months, for a median of 6 months. Six
studies were single-centre studies at secondary- / tertiary-level
hospitals37-39,42,43,49,50,52, while three were
conducted in multiple hospitals41,47,48, including
primary-level hospitals in two41,48. Where reported,
all studies were conducted in medical
wards37-39,41,43,47,49,50,52, additionally including
intensive care units in one47. Only one study reported
universal sampling of all patients admitted to the study
wards47; non-random sampling of admitted patients was
described in the remainder. In these studies, large numbers of potential
participants were often excluded (35%41,
57%52, 69%49,50,
84%42, and 96%43 in five studies,
but only 1%37 and 4%38,39 in two
others). Reasons for excluding potential participants included no
consent41,48-50,52, missing
records37,42,49,50, being too ill to
cooperate41,49,50,52, admissions for cancer
chemotherapy38,39 or delivery48,
readmissions52, no drug
exposure49,50, or unclear reasons43.
Most studies37-39,41,47-50,52 used prospective folder
review as surveillance methodology, but only
four37,41,47,48 reported this to have been conducted
by multidisciplinary team. ADRs were mostly defined according to the WHO
definition37-39,41,43,48-50,52. Five
studies37,41,42,47,49,50 reported a clear two-step
method, with causality assessment conducted by a multidisciplinary team
other than the surveillance team. Naranjo’s causality assessment method
(in 4 studies41,42,48-50) and the WHO-UMC method (in
three studies37,47,52) were mostly used. Six studies
reported assessing the preventability of ADRs, using Schumock and
Thornton criteria in three studies37,41,47 and
unreported or other methods in three studies48-50,52.
Apart from summary demographic statistics, the population included in
studies’ denominator was generally poorly described. Mean or median age
ranged from 36 to 50 years (reported in six
studies37-39,41,47,49,50,52), and the proportion of
females from 42% to 56% (reported in seven
studies37-39,41,43,47,49,50,52). Only two studies
reported the proportion of patients included in the denominator that
were exposed to drugs before their admission47,49,50.
Only two studies described the most common reason for admission, being
malaria41 and cardiovascular
disease47 respectively. HIV prevalence among patients
included in the denominator was only reported in the South African
studies, being 32% in the earlier37 and 29% in the
later47 study. The proportion of patients in the
denominator who were taking ART increased in the interval between these
two studies from 5.2%37 to 14%47,
and was 11% in the Ethiopian study49,50.
Among the nine active surveillance studies in adult populations, the
median [IQR] proportion of admissions attributed to ADRs was 6.4%
[4.0% to 8.4%]. Although more studies assessed the preventability
of ADRs, only one study, from South Africa, reported the proportion of
admissions attributed to preventable ADRs, which was
3.7%47.
Four studies reported the drugs or drug classes implicated in ADRs
causing admission to hospital37,42,47,49,50, with
striking similarities: antiretroviral agents, antituberculosis therapy,
cardiovascular drugs and hypoglycaemic drugs predominated. Common
clinical presentations of these ADRs, as reported in five
studies37-39,42,47,49,50, mostly related to their
hepatotoxic and nephrotoxic effects, and hypoglycaemia. Bleeds from
non-steroidal anti-inflammatories and antithrombotic agents were less
frequently reported.47,49,50
Four studies reported HIV prevalence among patients who were admitted to
hospital for ADRs. This was 38% in both South African
studies37,47, 28% in the Ethiopian
study49,50, and 3/3 in the Malawian
study.42
Paediatric active surveillance studies
Five active surveillance studies contributed paediatric data (Table 3),
including two from Nigeria36,40, two from South
Africa51,53, and one from Eritrea48.
All were available as English full-text articles, with median quality
score 5/10, although two studies40,53 scored 10/10.
Study duration ranged from 1 month to 36 months. Three studies were
single-centre studies at secondary- / tertiary-level
hospitals36,40,51 while two were conducted in multiple
hospitals48,53, including primary-level hospitals in
one48. One study53 surveyed patients
admitted to intensive care units in addition to those admitted to
paediatric wards. Only one study reported universal sampling of all
patients admitted to the study wards36; non-random
sampling of admitted patients was described in the remainder. In these
studies, unknown numbers of potential participants were excluded for
reasons including no consent48,51, missing
records40, short duration
admissions40,51, admissions for
rehydration53, repeat admissions40,
elective admissions53, or neonatal
admissions48,53.
Four studies reported that multidisciplinary teams conducted the
surveillance36,40,48,53. Three
studies36,40,48 defined ADRs according to the WHO
definition. All studies included an assessment of causality, and
four36,40,48,53 included an assessment of
preventability, although precise methods varied.
Only one study reported the proportion of patients included in the
denominator that were exposed to drugs before their
admission53. Infectious diseases were frequently
reported as the reason for admission36,40,51,53. The
proportion of children in the denominator population who had HIV
infection was only reported in the two South African
studies51,53.
The proportion of admissions attributed to ADRs ranged from 0.4% to
5.7%, median [IQR] 1.8% [0.6% to 4.7%]. At the low end of
the range were the two large Nigerian studies which seemingly included
older children, with one study reporting the mean age among all
admissions being 6.4 years40. In contrast, the South
African studies’ populations were younger (median age 1.4
years51 and 0.9 years53).
Hypersensitivity reactions, including erythema multiforme, Stevens
Johnson syndrome, urticaria, and rashes were reported as the most common
presentations, and antimicrobial medicines were most commonly
implicated. Two studies reported the proportion of admissions attributed
to preventable ADRs, which were 0.1%40 and
0.5%53 respectively. Only one study, conducted in
South Africa, reported HIV prevalence among children admitted for ADRs,
being 15%.53