Emerging Infectious Diseases Volume 10 Issue 10

2004·7.9 MB·English

by  CDC

APeer-Reviewed Journal Tracking and Analyzing Disease Trends pages 1713–1894
EDITOR-IN-CHIEF
D. PeterDrotman
EDITORIALSTAFF EDITORIALBOARD
Founding Editor
Dennis Alexander, Addlestone Surrey, United Kingdom
Joseph E. McDade, Rome, Georgia, USA
Ban Allos, Nashville, Tennessee, USA
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Polyxeni Potter, Atlanta, Georgia, USA Barry J. Beaty, Ft. Collins, Colorado, USA
Associate Editors Martin J. Blaser, New York, New York, USA
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Emerging Infectious Diseases
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Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 10, October 2004
A Peer-Reviewed Journal Tracking and Analyzing Disease Trends Vol. 10, No. 10, October 2004
On the Cover Fluoroquinolone Resistance in
Piet Mondrian (1872–1944). Pneumococci . . . . . . . . . . . . . . . . .1751
Broadway Boogie Woogie (1942–1943). A.G. de la Campa et al.
Oil on canvas, 127 cm x 127 cm. The Of 75 clones isolated, 1 had cipfloxacin efflux and
Museum of Modern Art, New York, NY, USA 74 had mutations at the DNA- topoisomerase
Digital image: The Museum of Modern genes.
Art/Licensed by SCALA/ARTResource, NY
Sulfa Use and Dihydropteroate
About the Cover p. 1892
Synthase Mutations . . . . . . . . . . . .1760
C.R. Stein et al.
Meta-analysis shows increased risk for DHPS
mutations in patients exposed to sulfa prophylaxis
Perspectives for PCP, but clinical relevance of mutations is not
known.
Current Epidemiology of
Pneumocystis Pneumonia
Pneumocystis Pneumonia . . . . . .1713
Cluster . . . . . . . . . . . . . . . . . . . . . . .1766
A. Morris et al.
M. Rabodonirina et al.
Changes in incidence of PCP, groups at risk
Molecular evidence indicates that P. jirovecii
for PCP, and possible trends in the disease are
may be nosocomially transmitted to severely
discussed.
immunosuppressed patients.
Pneumocystis DHPS Mutations
SARS in China . . . . . . . . . . . . . . . .1774
and Sulfa Resistance . . . . . . . . . . .1721
G. Liang et al.
L. Huang et al. p. 1803 Four sporadic cases of SARS-associated
It remains unclear whether the presence of
coronavirus infection were identified through
dihydropteroate synthase mutations confers
collaboration of four laboratories.
clinical resistance to TMP-SMX or dapsone plus
trimethoprim for PCPtreatment.
Egg Quality Assurance
Programs . . . . . . . . . . . . . . . . . . . .1782
Strain Typing Methods of
G.A. Mumma et al.
Pneumocystis Pneumonia . . . . . .1729
A1% increase in number of eggs produced under
C.B. Beard et al.
Egg Quality Assurance was associated with a
Several typing methods, with different strengths
0.14% decrease in SalmonellaEnteritidis incidence.
and weaknesses, are available for studies of
Pneumocystispneumonia.
Dengue Emergence and
p. 1836
Adaptation to Mosquitoes . . . . . . .1790
West Nile Virus Economic
A.C. Moncayo et al.
Impact, Louisiana . . . . . . . . . . . . . .1736
Endemic dengue virus (DENV) type 2 strains
A. Zohrabian et al.
infect Aedes aegyptiand Ae. albopictusmore
2002 WNV epidemic in Louisiana incurred
efficiently than ancestral sylvatic strains, which
substantial short-term economic costs.
suggests that adaptation to these vectors mediated
DENV emergence.
Research
Escherichia coli
Virus and Antibody Detection Gastroenteritis . . . . . . . . . . . . . . . .1797
in SARS Patients . . . . . . . . . . . . . .1745 R.M. Robins-Browne et al.
H.N. Leong et al. Atypical strains of enteropathogenic E. coliare a
Five (7.8%) of 64 patients continued to shed leading cause of gastroenteritis in Melbourne.
viral RNAin stool samples only, for up to
week 8 of illness.
Syndromic Surveillance for
Influenzalike Illness . . . . . . . . . . . .1806
B. Miller et al.
A Peer-Reviewed Journal Tracking and Analyzing Disease Trends Vol. 10, No. 10, October 2004
Detection algorithm using proxy data for a bioterror-
ism agent release and historical data for influenza
was effective. 1859 Mycobacterium triplex Disease,
Immunocompetent Host
Susceptibility to ST11
C. Piersimoni et al.
Complex Meningococci . . . . . . . . .1812
A.J. Pollard et al. 1863 Arcobacter Species in Humans
Study population was susceptible to ST11 complex O. Vandenberg et al.
meningococci bearing both C and W135 polysac-
charide capsules; vaccine against serogroup C 1868 Mycobacterium goodii
meningococci may not prevent ST11 disease.
Infections and Surgical
Helicobacter pylori Strains Implants
Transmission Analysis . . . . . . . . .1816 D.D. Ferguson et al.
J. Raymond et al.
1872 Nosocomial Dengue
Point mutations, intragenic recombination, and intro-
duction of foreign alleles enhanced strain diversity D. Wagner et al.
p. 1836
within the family.
1874 Recombinant Sapovirus
Influenzalike Illness, Japan . . . . . .1822 K. Katayama et al.
T. Sakai et al.
Kriging analysis will likely be a useful tool for Letters
influenza surveillance in Japan.
1877 SARS Patients and Need for
Nosocomial Gastroenteritis,
Treatment
England . . . . . . . . . . . . . . . . . . . . . .1827
1878 Malaria Following Needlestick
B.A. Lopman et al.
Implementing control measures rapidly may be 1880 Nosocomial Dengue
effective in controlling gastroenteritis outbreaks.
1881 Human Crimean-Congo
Dispatches Hemorrhagic Fever, Sénégal
1882 Influenza among U.K. Pilgrims
1835 Naegleria fowleri
to Hajj
Meningoencephalitis
1883 Streptomyces thermovulgaris
P.E. Cogo et al.
Bacteremia
1838 Scrub Typhus, Micronesia p. 1857 1885 West Nile Virus, France
A.M. Durand et al.
1886 SARS in Teaching Hospital,
1841 SARS Coronavirus Excretion, Taiwan
China
1887 Boiling and BacillusSpores
W. Liu et al.
News and Notes
1844 Campylobacteriosis, Québec
S. Michaud et al. Obituary
1889 Aniru Conteh (1942–2004)
1848 Laboratory-acquired
Brucellosis
1890 Correction; Vol. 10, No. 9
S. Noviello et al.
Conference Summary
1851 Emerging Escherichia coli
1891 New and Re-Emerging Infectious
Strains?
Diseases
T.A.T. Gomes et al.
1856 Escherichia coli O157 Cluster About the Cover
1892 Molecular Techniques and the
Evaluation
True Content of Reality
A. Gupta et al.
P. Potter
Current Epidemiology of
Pneumocystis Pneumonia
Alison Morris,*† Jens D. Lundgren,‡ Henry Masur,§ Peter D. Walzer,¶ Debra L. Hanson,#
Toni Frederick,# Laurence Huang,** Charles B. Beard,†† and Jonathan E. Kaplan#
Pneumocystispneumonia (PCP) has historically been antiretroviral drugs remain at high risk, and PCPcontinues
one of the leading causes of disease among persons with to develop in certain groups in industrialized countries.
AIDS. The introduction of highly active antiretroviral thera- The drug of choice for treatment and chemoprophylax-
py in industrialized nations has brought about dramatic
is of PCPis trimethoprim-sulfamethoxazole (TMP-SMX).
declines in the incidence of AIDS-associated complica-
In recent years, antimicrobial drug resistance has emerged
tions, including PCP. In the adult population, the incidence
as a possible cause of failure of patients to respond to
of PCPhas significantly decreased, but it remains among
TMP-SMX. Investigators have demonstrated an associa-
the most common AIDS-defining infections. Similar
declines have been documented in the pediatric popula- tion between exposure to sulfa drugs and mutations in the
tion. In much of the developing world, PCPremains a sig- dihydropteroate synthase (DHPS) gene of P. jirovecii, but
nificant health problem, although its incidence among the relationship between these mutations and treatment (or
adults in sub-Saharan Africa has been debated. This prophylaxis) failure is unclear. Understanding whether
review discusses the epidemiology of PCPduring the cur- DHPS mutations cause antimicrobial drug resistance is
rent era of the AIDS epidemic. Although fewer cases of
important in guiding clinicians who care for patients with
PCP occur in industrialized countries, increasing drug-
PCP.
resistant HIV infections, possible drug-resistant PCP, and
Aseries of articles in this issue of Emerging Infectious
the tremendous number of AIDS cases in developing
Diseases highlights the continuing importance of PCP, the
countries make this disease of continued public health
importance. potential for drug resistance, and laboratory techniques
that can be used to study the problem. We hope that these
articles will stimulate interest in exploring the relationship
Pneumocystis pneumonia (PCP), which is caused by
between DHPS mutations and resistance of P. jirovecii to
Pneumocystis jirovecii (formerly P. carinii f. sp.
sulfa-containing drugs and in assessing DHPS mutations
hominis), is frequently the first serious illness encountered
as possible causes of treatment failure in patients with
by HIV-infected persons. During the early years of the
PCP. In this introductory article, we summarize the
AIDS epidemic, PCPwas the AIDS-defining illness for as
changes in incidence of PCP since the introduction of
many as two thirds of patients in the United States.
HAART, discuss groups at risk for PCPin developing and
Although a decline in incidence of PCP occurred during
industrialized nations, and examine possible future trends
the era of highly active antiretroviral therapy (HAART),
in the disease. A data collection form has been included
PCP remains the most common serious opportunistic ill-
online with this series of articles to assist in the collection
ness in HIV-infected persons (1). Patients in the develop-
of appropriate and standardized data from patients with
ing world without access to PCP prophylaxis or
PCPand to facilitate comparing and pooling data from dif-
ferent centers (online Appendix available from http://
*University of Southern California, Los Angeles, California, USA; www.cdc.gov/ncidod/eid/vol10no10/03-0985_ app.pdf).
†University of Pittsburgh School of Medicine, Pittsburgh,
Pennsylvania, USA; ‡University of Copenhagen, Hvidovre,
PCPbefore HAART
Denmark; §National Institutes of Health, Bethesda, Maryland,
USA; ¶University of Cincinnati, Cincinnati, Ohio, USA; #Centers The first clinical cases of PCP were reported during
for Disease Control and Prevention, Atlanta, Georgia, USA; World War II in orphanages in Europe. These cases of
**University of California San Francisco, San Francisco, “plasma cell pneumonia” were common among malnour-
California, USA; and ††Centers for Disease Control and
ished children and were later reported in children in
Prevention, Fort Collins, Colorado, USA
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 10, October 2004 1713
PERSPECTIVES
Iranian orphanages. The disease was then recognized in per year from 1996 through 1998 (1). Despite this improve-
patients who were immunocompromised because of ment, PCPis still the most common AIDS-defining oppor-
malignancies, immunosuppressive therapy, or congenital tunistic infection in the United States.
immunodeficiencies. Solid organ transplantation increased The Multicenter AIDS Cohort study (MACS) has fol-
the number of patients at risk for PCP, although rates lowed >5,000 homosexual men since 1984 (6). Of these,
diminished after chemoprophylaxis was introduced. 2,195 were either HIV-infected at time of enrollment or
Without chemoprophylaxis, rates of PCP are 5%–25% in seroconverted to HIV during the study. Opportunistic
transplant patients, 2%–6% in patients with collagen vas- infection rates were compared for the HAART era
cular disease, and 1%–25% in patients with cancer. (1996–1998) and the era of antiretroviral monotherapy
Defects in CD4+ lymphocytes are a primary risk factor for (1990–1992) (7). For persons who seroconverted during
developing PCP, but the immune response to Pneumocystis the study period, the relative hazard for development of
is complex. CD8+ lymphocytes seem to be important in PCPfrom seroconversion to initial AIDS-defining oppor-
Pneumocystis clearance, and defects in B-cells and anti- tunistic infection was 0.06 during the HAART era com-
body production may also predispose to PCP. pared to the time of monotherapy. For those already
The beginning of the AIDS epidemic in the early 1980s diagnosed with AIDS, the study found a hazard of 0.16,
shifted the incidence of PCPfrom a rare disease to a more which demonstrated a dramatically lower risk for PCPdur-
common pneumonia. Clusters of PCPcases in homosexu- ing the HAARTera.
al men and intravenous drug users were one of the first In Europe, the EuroSIDAstudy has followed a cohort
indications of the HIVepidemic (2). PCPrapidly became of >8,500 HIV-infected patients. The investigators exam-
the leading AIDS-defining diagnosis in HIV-infected ined changes in incidence of AIDS-defining illnesses
patients. In the initial stages of the epidemic, PCP rates before and after HAARTwas introduced and found results
were as high as 20 per 100 person-years for those with similar to those in North America (8). PCPcases decreased
CD4+ cell counts <200 cells/µL(3). PCPwas responsible over time (1994–1998). Incidence of PCP fell from 4.9
for two thirds of AIDS-defining illnesses, and an estimat- cases per 100 person-years before March 1995 to 0.3 cases
ed 75% of HIV-infected patients would develop PCPdur- per 100 person-years after March 1998 (9).
ing their lifetime (4).
The first substantial decline in the incidence of PCP Occurrence in Relation to PCPProphylaxis
occurred after the introduction of anti-Pneumocystis pro- PCP still occurs in industrialized nations despite the
phylaxis in 1989 (5). Although absolute numbers of cases availability of HAARTand anti-Pneumocystis prophylaxis.
of PCP as an AIDS-defining illness in the United States
remained stable from 1989 to 1992 because of an increas-
ing incidence of AIDS, the percentage of AIDS cases with
PCPdeclined from 53% in 1989 to 49%, 46%, and 42% in
1990, 1991, and 1992, respectively (Centers for Disease
Control and Prevention, AIDS Surveillance Summaries,
1989–1992). The later use of combination antiretroviral
therapy further reduced the rates of PCPamong adults by
3.4% per year after 1992 (1).
PCPin Adults in Industrialized
Countries after HAART
Incidence
The advent of HAARThas resulted in further declines in
rates of PCPand other opportunistic infections (1). Several
large, multicenter studies have specifically tracked the inci-
dence and epidemiologic features of PCP. The largest is the
Figure 1. Yearly opportunistic infection rates per 1,000 person-
Adult and Adolescent Spectrum of HIV Disease (ASD) years, CDC Adult and Adolescent Spectrum of Disease Project,
Project. Data from this project indicated a marked reduc- 1994–2001. CMV, cytomegalovirus; HAART, highly active anti-
tion in the incidence of all opportunistic infections in 1996 retroviral therapy; KS, Kaposi’s sarcoma; MAC, Mycobacterium
avium complex; PCP, Pneumocystis pneumonia. Data are stan-
and 1997, when HAART first became widely available
dardized to the population of AIDS cases reported nationally in the
(Figure 1). PCPcases decreased 3.4% per year from 1992
same year by age, sex, race, HIV exposure mode, country of
through 1995; the rate of decline of PCPincreased to 21.5% origin, and CD4+ lymphocyte count.
1714 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 10, October 2004
Current Epidemiology of Pneumocystis Pneumonia
ASD investigated the history of prescriptions for PCPpro- cell levels. ASD found that the median CD4+ cell count in
phylaxis in HIV-infected adults in whom developed PCP persons with PCP while on HAART was extremely low
from 1999 through 2001 (Figure 2). Almost 44% of PCP (29 cells/µL), although the count was somewhat higher
cases occurred in patients not receiving medical care, most than for those not on HAART (13 cells/µL) (1). The
of whom were probably not known to be HIV-infected. EuroSIDA study reported that persons on HAART in
Forty-one percent of patients were prescribed prophylaxis whom PCPdeveloped had a median CD4+ cell count of 30
but did not adhere to treatment, or PCPdeveloped despite cells/µL, identical to those with PCPwho were not receiv-
their taking medications appropriately. Possible explana- ing HAART (8). Patients without improvement in their
tions for PCP in the “breakthrough” group include the CD4+ cell count despite use of HAARTremain at risk for
development of drug-resistant Pneumocystis or decreased PCP, and PCPstill rarely occurs in persons with CD4+ cell
efficacy of prophylaxis in those with low CD4+ cell counts >200 cells/µL.
counts. An additional 9.6% of patients were under medical Other clinical factors such as sex, race or ethnicity, and
care and should have received prophylaxis based on cur- HIV transmission category have been examined as risk
rent recommendations, but had not been prescribed pro- factors for PCP. Men and women appear to have an equiv-
phylaxis by their providers. Five percent of patients were alent risk for PCP (12). One study demonstrated that
under care but did not meet criteria for prophylaxis. African Americans have approximately one third the risk
for PCPas white persons (10), but this finding has not been
Risk Factors replicated (12). PCP risk according to HIV transmission
ACD4+ cell count <200 cells/µLwas the leading pre- category is also debated. One autopsy study found that
HAARTrisk factor for PCPand remains an important risk PCP was less common in intravenous drug users than in
factor in the HAARTera. The risk for PCPincreases expo- other risk groups (13). Kaplan et al. found a slightly
nentially the lower the CD4+ cell count is below 200 increased risk for those men who had sex with men and
cells/µL (10). When patients on HAART have sustained were intravenous drug users, but risk was equivalent in
increases in CD4+ cell counts >200 cells/µL, the risk for other transmission categories (12).
PCPdecreases sufficiently to safely discontinue both pri-
mary and secondary prophylaxis (9,11). Those in whom Risk forPneumocystisColonization
PCPdevelops while on HAARTtypically have low CD4+ Although PCP cases have declined, polymerase chain
reaction (PCR) has led to the discovery of Pneumocystis
DNAin asymptomatic persons. Pneumocystis in respirato-
ry specimens from persons who do not have signs or symp-
toms of clinical infection and who do not progress to
infection has been defined as colonization or subclinical
carriage. Often, Pneumocystis DNA is detected only by
PCR, and the organism is not seen on routine histochemical
staining. The clinical significance of Pneumocystis in respi-
ratory specimens and the viability of organisms detected
only by PCR are unknown. However, colonization may be
important for several reasons. Pneumocystis colonization
may increase the risk for progression to PCP, carriers of the
organism may transmit infection to others, and latent infec-
tion may lead to inflammation that is detrimental to the
lung. Most healthy persons do not have detectable
Pneumocystis in respiratory specimens, but rates of colo-
nization may be as high as 69% in HIV-infected persons
(14). Recent evidence suggests that non–HIV-infected per-
sons may also be colonized with Pneumocystis, thus
increasing the potential number of persons affected (15).
PCPin Children in Industrialized Countries
Incidence
Figure 2. Classification of Pneumocystis pneumonia cases from
Early in the HIV epidemic, PCP occurred in HIV-
1999–2001, CDC Adult and Adolescent Spectrum of HIV Disease
infected children at a rate of 1.3 cases per 100 child-years
Project, n = 1,073.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 10, October 2004 1715
PERSPECTIVES
from infancy to adolescence and was as high as 9.5 cases
per 100 child-years in the first year of life (16,17). In the
1990s, pediatric HIV infection decreased, primarily as a
result of improved prenatal HIV testing and use of HIV
treatment to prevent vertical transmission of the virus. The
Pediatric Spectrum of Disease (PSD) study found signifi-
cant decreases in the rates of most opportunistic infections
in HIV-infected children during the HAARTera (Figure 3).
PCPcases declined significantly from 1992 to 1997, with
an increase in the rate of decline after 1995, presumably
from HAART(1). Because widespread use of HAARTfor
children has occurred more recently than for adults, the full
effect of HAARTon pediatric PCPlikely has not yet been
realized.
Risk Factors
The occurrence of PCPin infants does not seem to be Figure 3. Yearly opportunistic infection rates per 1,000 HIV-infect-
ed children, CDC Pediatric Spectrum of Disease Project,
related to the CD4+ cell count in the same manner as in
1994–2001. Bacterial, bacterial infections; CMV, cytomegalovirus;
adults, although it is related to the percentage of CD4+
HAART, highly active antiretroviral therapy; LIP, lymphocytic inter-
cells and CD4+ cell counts are below normal in children stitial pneumonia; MAC, Mycobacterium avium complex; PCP,
<1 year of age with PCP(18). Furthermore, peak incidence Pneumocystis pneumonia. Incidence rates were calculated per
of PCPoccurs in infants 3–6 months of age, when HIVsta- 1,000 children at risk each year. All trends were significant at
p < 0.05 in chi-square for trend analysis for four age groups
tus may still be undetermined. Implementing recommen-
(<1 year, 1–5 years, 6–9 years, and >10 years) except for the
dations to initiate PCP prophylaxis in all infants born to
<1-year-old group for PCP, bacterial, and MAC.
HIV-positive mothers decreased the incidence of the dis-
ease in the pediatric population before the advent of
HAART (11). For children older than 6 years of age, the nasopharyngeal aspirates of 32% of 74 healthy Chilean
CD4+ cell count predicts disease in a manner similar to infants (20). Children dying of sudden infant death syn-
adults, and CD4+ cell counts <200 cells/µLare still con- drome (SIDS) also have a high rate of Pneumocystis (51
sidered an indication for prophylaxis (11). [30%] of 171), as seen on microscopy of lung specimens
Although HAART decreased the incidence of PCP in (22). The role Pneumocystis plays in SIDS is not under-
children, it has not eliminated the disease, mostly because stood. Similar to the adult population, effects of
of failure to identify HIV-infected mothers. PCPseems to Pneumocystis colonization and relationship to PCPdevel-
occur early in life among HIV-infected infants, which sug- oping or transmission of infection are not known.
gests that exposure to Pneumocystis is common. In fact,
anti-Pneumocystis antibodies develop in most nonim- PCPin the Developing World
munocompromised children in the first several years of life In contrast to the dramatic improvements in the indus-
(19,20). ABritish study of children with PCPin the begin- trialized world, persons living in developing nations con-
ning of the HAARTera found that PCPdeveloped in 83 of tinue to be devastated by HIV. The World Health
531 children with perinatally acquired HIV as their first Organization estimates that 42 million persons were living
AIDS indicator disease, which represented ≈50% of AIDS with HIVat the end of 2002 and that 95% of these persons
diagnoses (21). Most of these children were <12 months of live in developing countries. Large portions of the popula-
age, and 79% were born to mothers not previously diag- tions of Southeast Asia and sub-Saharan Africa are infect-
nosed with HIV. Given that the mothers had unrecognized ed with HIV, and an estimated 55 million persons will die
HIV disease, HAART would be expected to have little of AIDS in sub-Saharan Africa from 2000 through 2020.
effect on disease incidence in this population, and HIVis also increasing in areas such as Latin America, east-
improved maternal screening would be more important for ern Europe, and Asia. Despite increasing efforts to supply
disease prevention. affordable therapy to these nations, HAARTis not widely
available.
Risk for Pneumocystis Colonization PCPstill occurs frequently in many parts of the devel-
Colonization may occur at higher rates in healthy chil- oping world (23). Studies from Thailand show a preva-
dren than in healthy adults. Vargas recently documented lence of 27% to 40% among HIV-infected patients treated
that nested PCR was positive for Pneumocystis DNAin the at a university hospital clinic (24,25). Central and South
1716 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 10, October 2004
Current Epidemiology of Pneumocystis Pneumonia
America also have a large number of PCP cases. One pared to white Americans (10). Detailed molecular study
Brazilian study found that 55% of HIV-infected persons of the organism in different parts of the world is needed to
with respiratory complaints were diagnosed with PCP, resolve these issues.
although a small autopsy study of hospitalized Brazilian The incidence of PCPin Africa may be growing as the
patients found only 13% to have PCP(26,27). Other stud- AIDS epidemic progresses. Arecent review concluded that
ies in this region report PCPprevalence from 24% to 29%, cases of PCP seem to have increased over time (23), but
depending on the population studied (28,29). whether this increase resulted from actual changes in PCP
incidence or from improved detection techniques is
PCPin Adults in Africa unclear. Some studies have reported higher rates of PCPin
In contrast to the situation in many other developing Africa compared to past findings (Table 1). Malin et al.
regions, PCPhas been thought to be rare in African adults. studied a group of 64 hospitalized HIV-infected patients in
Several representative series are summarized in Table 1. Zimbabwe in 1995 (35). These patients had pneumonia
Most early studies reported prevalence rates of 0% to 11% unresponsive to penicillin, and sputum samples were
in HIV-infected patients (30,31,33,34), although one early smear-negative for acid-fast bacilli (AFB). All patients
study found a rate of 33% (35). underwent bronchoscopy with bronchoalveolar lavage
PCPmight not have been commonly reported in Africa (BAL). Twenty-one (33%) of these patients had PCP.
for several reasons. Limited resources for diagnosis may Reasons for a higher rate of PCP among these patients
have led to lower estimates of PCP. Experienced laborato- included use of definitive diagnosis and probable selection
ry personnel are required to prepare and interpret diagnos- bias by including only patients with severe pneumonia
tic specimens. Bronchoscopy is expensive, and induced when other diagnoses, such as tuberculosis, had been
sputum also requires specialized equipment and personnel excluded. Another study examined 83 patients hospitalized
to obtain adequate samples. Limited resources make with respiratory symptoms (36). All patients had sputum
empiric therapy of HIV-infected persons with pneumonia cultures that were negative for AFB and underwent bron-
common, possibly leading to inaccurate estimates of the choscopy with BAL for diagnosis. Thirty-two patients
true incidence of PCP. HIV-infected African adults also (38.6%) were diagnosed with PCP. Not all studies have
have high rates of bacterial pneumonia and tuberculosis, found high rates of PCP. Aderaye et al. reported that of 119
diseases that may result in death at higher CD4+ cell outpatients with respiratory symptoms and negative AFB
counts and prevent many HIV-infected patients from cultures, only 11% had PCP(32). Similarly, another recent
reaching a stage at which they would be susceptible to study found PCPin 11% of patients who underwent autop-
PCP. Environmental factors, such as seasonal variations, sy after dying as an inpatient with respiratory symptoms
might contribute to a low rate of PCPin Africa. However, (31). Future research will be needed to clarify the risk for
high rates of anti-Pneumocystis antibodies among African PCPin Africa.
children suggest that exposure to the organism is common
(19). Regional strains may be less virulent, or the popula- PCPin Children in Africa
tion may be more resistant, as HIV-infected African In contrast to adults, HIV-infected children in Africa
Americans have been shown to have lower PCPrates com- have high rates of PCP. Autopsy series describe rates of
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 10, October 2004 1717
PERSPECTIVES
PCPfrom 14% to 51.3%, depending on the age group stud- Four non–HIV-infected children also had PCP. The authors
ied (Table 2). Ikeogu et al. found that in Zimbabwe, 19 speculated that the lower rate of PCP in their study may
(15.5%) of 122 HIV-infected children who died <5 years have been attributable to their inability to follow negative
of age had evidence of PCP at autopsy (40). All cases sputum examinations with bronchoscopy.
except one were in infants <6 months. Another autopsy
study from the early 1990s found that PCPwas present in The Future of PCP
11 (31%) of 36 HIV-infected infants but was not found in The decline in PCP incidence in the industrialized
42 HIV-infected children >15 months (41). The largest world may be short-lived. Although current regimens are
autopsy series examined 180 HIV-infected children in effective in treating HIV, as many as 19% of patients start-
Zambia (38). Twenty-nine percent of the children died of ing HAART will have a viral level >10,000 copies/mL
PCP, making PCPthe third leading cause of death overall. after 48 weeks of treatment (45). In the EuroSIDAcohort,
Among children <6 months of age, PCPwas the most com- an increasing proportion of HIV-infected patients have
mon cause of pneumonia, detected in 51.3%. Six of 84 been exposed to all classes of antiretrovirals, with 47% of
HIV-negative children had evidence of PCP at autopsy. their cohort exposed to nucleoside reverse transcriptase
The most recent autopsy series reported that 10 (28.6%) of inhibitors, protease inhibitors, and non-nucleoside reverse
35 HIV-infected children had PCP(37). transcriptase inhibitors by 2001 (45). Of those patients in
Because autopsy studies examine terminal disease, the cohort with multidrug-resistant HIVwho received sal-
their assessment of disease prevalence might be biased. vage regimens, a new AIDS-defining opportunistic infec-
Several authors described prevalence of PCPamong chil- tion developed in 11%. Growing transmission of resistant
dren in clinic or hospital settings to estimate disease fre- HIVis also likely. If new drugs do not become available,
quency more accurately. Most studies reported rates higher the number of patients with resistant virus and opportunis-
than those in adults. Two authors found rates >40% among tic infections, including PCP, will continue to climb.
HIV-infected children hospitalized with pneumonia Not only is HIV developing resistance, but
(42,43). Ruffini studied children from 2 to 24 months of Pneumocystis may also develop resistance to standard pro-
age with pneumonia and found that 48.6% had PCP(43). phylaxis and treatment regimens. Many researchers have
Madhi found that in 231 episodes of pneumonia in HIV- reported mutations of Pneumocystis in response to use of
infected children, 101 (43.7%) were due to PCP(39). PCP sulfa- or sulfone-containing anti-Pneumocystis regimens.
was most common in infants <6 months, although 35.7% Whether these mutations increase the likelihood of pro-
of pneumonias in older children were also caused by PCP. phylaxis or treatment failure is unclear and is reviewed in
Graham, in a smaller study of 16 cases of PCPin 93 chil- other papers in this series.
dren with HIVinfection, also found that most cases of PCP
occurred in infants (42). The study reporting the lowest Conclusion
frequency of PCPamong children with pneumonia found Despite the declines in death and disease from HIVin
15 (9.9%) of 151 HIV-infected children to have PCP(44). the United States and western Europe, PCP remains an
1718 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 10, October 2004