in low- and middle-income countries should give greater consideration to the
possibility that infants and children with HIV are presenting with symptoms of
cryptococcal disease, according to a report from South Africa published in the advance
online edition of AIDS.
A total of 361
(2%) of more than 16000 incident episodes of cryptococcosis reported to the
surveillance programme in South Africa over a three-year period were in
children, the largest number described to date, Susan T Meiring and colleagues
report in a prospective, population-based comparative review of adult and
among children was less frequent than among adults. However, contrary to
previous findings, it was not uncommon. In 2007, the authors note, among
children under one year of age incidence was comparable to that of haemophilus
influenza meningitis, a common cause of bacterial meningitis, with both at 4
per 100,000 population.
90% of all cases were HIV-infected and over two-thirds of both children and
adults were severely immunocompromised (CD4 cell counts under 50 cells/mm3)
at the time of diagnosis, with only 26% of the children on ART.
infection cannot be prevented because the Cryptococcus
fungus is ever-present in the environment, cryptococcal disease can be
prevented. It is believed that infection occurs through breathing in infectious
particles. Disease usually happens later in life when severely immunocompromised.
Cryptococcal disease presents chiefly in the form of meningitis, causing neck
stiffness, headache, fever, changes in mental status and eventual coma and
death, if not diagnosed and treated.
authors stress the importance of getting HIV-infected children diagnosed early
and on to ART treatment promptly before they become severely immunocompromised,
so putting them at increased risk for developing cryptococcal disease.
Africa’s Department of Health’s 2012 National Strategic Plan includes plans for
screening for cryptococcal antigenaemia in patients with CD4 cell counts under
100 cells/mm3, followed by pre-emptive treatment. A phased
implementation is in development. The laboratory screening process will include
patients of all ages and so may improve early diagnosis in children.
studies have described cryptococcus, a fungus, as a cause of life-threatening
disease among HIV-infected adults. In the United States, before effective
antiretroviral treatment, approximately 6 to 10% of HIV-infected
adults, notably those with CD4 cell counts under 100 cells/mm3, were
infected with cryptococcus. Incidence in the general population ranged from two
to seven cases per 100,000 people.
contrast, the authors cite a 2004 study in South Africa estimating an
incidence in the general population of 15.6 cases per 100,000 people, yet 14 cases per 1000 among
adults living with HIV. But little is known about its incidence and epidemiology in children.
is little evidence to explain why cryptoccocosis is seen more frequently in
immunocompromised adults than in immunocompromised children. Previous studies
have shown that, while children become infected after the age of two, it
generally affects older children at a median age of 9.8 years. However,
some cases have been reported among newborns suggesting vertical transmission
of the infection.
authors chose to compare the incidence and epidemiology of laboratory-confirmed cryptococcal disease in South Africa between children and
adults diagnosed from 1 January 2005 until 31 December 2007.
definition was determined by a positive India ink test, cryptococcal antigen
test or cryptococcal culture.
clinical data were obtained from people who were diagnosed at 21 enhanced
surveillance sites (ESSs) across South
authors found that, in 2007, incidence among the general paediatric and adult
populations was 1 and 19 cases per 100,000 people, respectively.
among HIV-infected children (47 per 100,000) was lower than among HIV-infected
adults (120 cases per 100,000); however, there was a peak incidence among 10 to 14
years-olds (517 cases per 100,000), an unexpected finding. This may reflect,
the authors note, an underestimation of the true HIV prevalence in this age
data from ESS was available for 23% (84/361) of paediatric cases and 28% (4378/15831)
of adults. While over 90% were HIV-infected, only one in four children was on
ART at the time of diagnosis.
authors suggest these findings may reflect inadequate uptake of the prevention
of mother-to-child transmission programme in South Africa in the early years. Implementation
has significantly improved so incidence may be considerably lower for children
born after 2007, they add.
among HIV-uninfected inidividuals there was a higher proportion of children
with cryptococcosis, compared to adults with cryptococcosis.
analysis showed that, compared to adults, children were more likely to be male,
diagnosed on blood culture, infected with cryptococcosis gattii, started on
amphotericin B and admitted to hospital for a longer stay.
children were less likely than adults to be discharged from hospital on
fluconazole maintenance therapy (83 compared to 93%, p=0.007). The authors
suggest this may have been due to the paediatrician either not knowing the
treatment guidelines (as it is seen as an adult-onset disease) or the paediatric
fluconazole suspension not being available.
on blood culture, the authors note, suggests a possible chance finding rather
than confirmation of a clinical suspicion of the disease.
though more children than adults were prescribed amphotericin B, the
recommended antifungal drug for managing cryptococcal disease in South Africa,
less than a third of adults and children got the drug.
age among children at the time of diagnosis was seven (range 0 to 14 years).
However, in contrast to previous findings, the authors found there were two time
periods of highest incidence: first among those under one year of age, then a
second sustained peak in incidence among children aged five to 10 years of age.
authors suggest that “since most paediatric HIV infection is vertically
transmitted and cryptococcosis is an AIDS-defining illness, this bimodal
distribution may reflect the occurrence of cryptococcal disease among rapid and
slow HIV progressors”.
include the fact that only laboratory confirmed disease was reported, so the true burden among
adults and children may have been underestimated. Many may have been too ill
to access health care services or specimens were not taken for diagnosis.
data were only available at ESSs, leading to the potential for bias. As an
observational study, clinical data sets were incomplete. Insufficient
information precluded differentiating between episodes of cryptococcosis
resulting from immune reconstitution inflammatory syndrome (IRIS).
authors conclude that their findings have clearly shown that “the diagnosis of
cryptococcosis must be considered in the paediatric HIV-infected population,
especially among those found to be severely immuno-compromised.”