Eur J Clin Microbiol Infect Dis

DOI 10.1007/s10096-017-2918-7

ORIGINAL ARTICLE

Serious fungal infections in the Philippines

M. C. R. Batac 1 & D. Denning 2

Received: 21 December 2016 / Accepted: 21 December 2016

# The Author(s) 2017. This article is published with open access at Springerlink.com

Abstract The Philippines is a low middle-income, tropical 391, oral candidiasis 3,467, esophageal candidiasis 1,522
country in Southeast Asia. Infectious diseases remain the main (all in HIV-infected people), invasive aspergillosis (IA)
causes of morbidity, including tuberculosis. AIDS/HIV prev- 3,085, candidemia 1,968, candida peritonitis 246,
alence is still low at <1%, but is rapidly increasing. Fungal mucormycosis 20, fungal keratitis 358, tinea capitis 846 and
disease surveillance has not been done, and its burden has mycetoma 97 annually. A total of 1,852,137 (1.9% of popu-
never been estimated. This becomes more important as the lation) are afflicted with a serious fungal infection.
population of immunocompromised patients increases, drawn Epidemiological studies are needed to validate these esti-
from patients with AIDS, TB, malignancies, and autoimmune mates, facilitating appropriate medical care of patients and
diseases requiring chronic steroid use. Using the methodology proper prioritization of limited resources.
of the LIFE program (www.LIFE-worldwide.org), estimates
were derived from data gathered from WHO, UNAIDS,
Philippine Health Statistics 2011, Philippine Dermatological Introduction
Society Health Information System database, HIV/AIDS and
ART registry of the Philippines, epidemiological studies such In the Philippines, most of the initial epidemiological studies
as The TREAT Asia HIV Observational Database 2005, and on mycoses focused on superficial fungal infections [1–3].
personal communication. Aspergillosis and candidiasis were Since the 1950s, superficial mycoses have been in the top five
the top causes of fungal infections in the Philippines. Chronic most common diagnoses in outpatient dermatology clinics [2].
pulmonary aspergillosis (CPA), drawn from the number of For several decades, fungal diagnostic procedures in the
tuberculosis patients, affects 77,172 people. Allergic Philippines were not routinely done and were limited to the
bronchopulmonary aspergillosis (ABPA) and severe asthma isolation, culture, and identification of fungi involved in skin,
with fungal sensitization (SAFS) frequencies, which were de- hair, and nail infections. Two university-based microbiology
rived from the number of asthmatic patients, affect 121,113 departments conduct short courses in Diagnostic Mycology
and 159,869 respectively. Recurrent vulvovaginal candidiasis on a regular basis. In the past, these used to cater solely for
(RVVC) affects 1,481,899 women. Other estimates dermatologists, because the course was a requirement in their
were cryptococcal meningitis 84, Pneumocystis pneumonia residency training. However, with the advent of AIDS and the
compromised patient, more infectious disease fellows and
medical laboratory personnel have enrolled in these courses.
* D. Denning The advent of AIDS, first described in the Philippines in
[email protected] 1984, led to a greater recognition of fatal fungal diseases [4].
M. C. R. Batac Out of 470 HIV/AIDS patients seen in a tertiary general hos-
[email protected] pital in the Philippines, 32.5% presented with opportunistic
infections [5]. Among the opportunistic infections, 32% were
1
University of Manchester, Manchester, UK due to Pneumocystis pneumonia, 4% to cryptococcal menin-
2
Education and Research Center, University Hospital of South gitis, and 3% to oral thrush [5]. HIV cases are climbing steeply
Manchester, Southmoor Road, Manchester M23 9LT, UK in the Philippines (20–30% annual increase in the years 2013–
 Eur J Clin Microbiol Infect Dis

2016), especially among men [4]. Patients who are on immu- Table 1 Important population statistics
nosuppressive agents, or are immunocompromised due to Percenta Number
medical conditions and/or are critically ill, are also at an in-
creased risk of acquiring serious fungal infections, and such Population (2013) 98,394,000
patients are common in the urban centres of the Philippines. Males 50.5 49,688,970
There is no active surveillance done for serious fungal infec- Females 49.5 48,705,030
tions in the country, and epidemiological studies even for be- Below 15 years old 34.0 33,453,960
nign superficial mycoses have been sparse. Although nation- Above 40 years old 25.6 25,188,864
ally based surveillance programs are the gold-standard in es- Above 60 years old 6.0 5,903,640
timating disease prevalence, they are usually costly and diffi- Females 15–50 years old 25.9 25,484,046
cult to implement [6]. Therefore, the actuarial method used by
a
previous researchers was used in this study to estimate the (Epidemiology Bureau, Department of Health 2011)
incidence and prevalence of serious fungal diseases, in which
results from previous epidemiological studies, populations at RVVC per month. There are around 4,000 to 5,000 obstetri-
risk, and epidemiological databases were used [6]. cians in the Philippines, so the maximum estimate for the
prevalence of RVVC would only be 240,000, ∼1.2 million
less than the estimate. Those with RVVC who consult a phy-
Methods sician do not represent everyone in the population, and many
women suffer in silence. It is likely that many patients self-
Applying the methodology of the LIFE program (www.LIFE- medicate, since patients may purchase topical antifungals
worldwide.org), prevalence and incidence of serious fungal without prescription or try local remedies. Clearly, this sub-
infections were derived from data gathered from WHO, stantial issue needs addressing in the Philippines.
UNAIDS, Philippine Health Statistics 2011, Philippine HIV/AIDS cases in the Philippines are few with a cumu-
Dermatological Society (PDS) Health Information System da- lative number of cases at 34,999 since the first case was
tabase, HIV/AIDS and ART registry of the Philippines, epi- reported in 1984. However, a sudden rise in cases has been
demiological studies such as The TREAT Asia HIV observed since 2009, with 83% of cumulative cases diag-
Observational Database 2005, and personal communication. nosed between 2009 to present. Most of the newly diag-
nosed cases are in the 25–29 age group, and among men
who have sex with men [4, 8]. Our estimated incidences of
Results and discussion Pneumocystis pneumonia, cryptococcal meningitis, and oral
candidiasis were based on HIV/AIDS cases in the recent
Population and country profile past, which were relatively low but are increasing rapidly.
Adequate diagnosis of opportunistic fungal disease with the
The Philippines is classified as lower middle income by the highly sensitive and specific cryptococccal antigen lateral
World Bank. It is considered one of the promising newly in- flow device [9, 10] and Pneumocystis PCR are required
dustrialized countries, enjoying a steady economic growth at [11, 12]. It is not known if disseminated histoplasmosis con-
the turn of the millennium, with a per capita 2013 gross do- tributes to illness and death in AIDS in the Philippines, but
mestic product of $2,765. Based on the 2013 WHO statistical it is likely. Histoplasmin reactivity has been documented,
profile, the population of the Philippines is 98,394,000, with and at least nine cases of histoplasmosis have been reported
34% under the age of 15, and 6% over the age of 60. The [2, 13, 14]. Hand in hand with an effective AIDS prevention
median age is 23. The number of hospital beds per population program and prompt and adequate treatment of cases with
was the lowest in Asia in 2010 [7]. Table 1 shows relevant antiretroviral drugs, proper management of opportunistic
population statistics. fungal infections is required.
The Philippine prevalence of IA, CPA, ABPA, and
Burden of fungal infections SAFS, diseases caused by Aspergillus sp., has never been
studied. However, several cases of pulmonary aspergillo-
In 2016, a total of 1,852,137 severe fungal infections are esti- sis have been documented. In 1975, a case of pulmonary
mated to have occurred in the Philippines. Table 2 shows the aspergillosis was reported in Manila in a 25-year-old male
incidence and prevalence for selected serious fungal infec- who presented with a 7-year history of hemoptysis with-
tions. Eighty percent of this is due to RVVC. However, local out fever and anorexia, and who was diagnosed with tu-
practicing obstetricians think this number is too high, and berculosis but did not respond to anti-tuberculosis medi-
approximate that each general obstetrician sees 12–15 patients cines [15]. From February 1982 to May 1990, 16 cases of
with vulvovaginal candidiasis, three to four of whom have pulmonary aspergillosis were seen at the Lung Center of
Eur J Clin Microbiol Infect Dis

Table 2 Prevalence and incidence of selected serious fungal infections in the Philippines, 2016

Serious fungal iInfection Estimation method Totals Rate/100,000

Cryptococcal meningitis 7% of new AIDS diagnosis 84 Annual incidence 0.09

Pneumocystis pneumonia 31% of new AIDS diagnosis 391 Annual incidence 0.40
Invasive aspergillosis (IA) 10% of AML + an equal number in other 3,085 Annual incidence 3
haematological conditions, 0.5% of
renal transplant patients, 4% of liver
transplant patients, and 1.3% of patients
hospitalized for COPD
Chronic pulmonary aspergillosis (CPA) 22% of cavitary pulmonary TB, 2% of 77,172 Prevalence 78
non-cavitary pulmonary TB, annually,
reduced by 15% for surgery and death.
Allergic bronchopulmonary 2.5% of adult asthmatics 121,113 Prevalence 123
aspergillosis (ABPA)
Severe asthma with fungal 33% of the most severe 10% of adult 159,869 Prevalence 162
sensitisation (SAFS) asthmatics
Candidaemia 2/100,000 general population, 1.5 in 1,968 Annual incidence 2
non-ICU and 0.5 in ICU
Candida peritonitis 50% of incidence of candidemia in ICU 246 Annual incidence 0.25
Oral candidiasis 90% of HIV patients not on antiretrovirals 3,467 Annual incidence 3.5
and CD4 < 200 × 106/L
Oesophageal candidiasis 20% of HIV patients not on antiretrovirals and 1,522 Annual incidence 1.5
CD4 < 200 × 106/l + 5% of HIV patients on
antiretrovirals
Recurrent vulvovaginal candidiasis 5% of women 15–50 years of age 1,481,899 Prevalence 3,012
(RVVC) (>4x/year)
Mucormycosis 0.2 cases per 1,000,000 population 20 Annual incidence 0.02
Fungal keratitis Based on cases seen at a tertiary government 358 Annual incidence 0.36
hospital in the NCR in 2015
Tinea capitis Based on cases seen at Philippine Dermatological 846 Annual incidence 0.86
Society training institutions in 2015
Mycetoma Based on cases seen at Philippine 97 Annual incidence 0.10
Dermatological Society training
institutions in 2015
Total serious fungal infection burden 1,852,137

the Philippines [16]. Nine of them had inactive pulmonary Candidemia among infants confined in the neonatal inten-
tuberculosis; 13 underwent lobectomy or segmentectomy sive care unit was reported to affect 56 of 7,830 infants in
or cyst removal. From Jan 2000 to December 2002, 37 2004, and 31 of 7,830 infants in 2005 [21]. A case–control
patients were diagnosed with aspergilloma, and all were study done in the same facility revealed that birthweight of
surgically managed. Ninety-two percent presented with 1,250 to 2,499 grams and gestational age of <28 weeks were
hemoptysis and 95% had tuberculosis [17]. In a retrospec- significantly associated with candidemia (p < 0.05) [21]. The
tive study done in a private hospital in Manila, there rate of candidemia in different countries varied from 1.2 to 25
were 14 cases of aspergillosis seen from 1998-2004; five per 100,000 population [22]. We have decided to use two per
were diabetics and three had renal transplants. Eleven 100,000 population since exposure to risk factors for
presented with pulmonary aspergillosis, and three had candidemia may be low, and there are remarkably few hospi-
extrapulmonary aspergillosis [18]. A case of primary la- tals for this populous country [7]. In some developed coun-
ryngeal aspergillosis in a 28-year-old who presented with tries, candidemia rates are increasing instead of decreasing
fever, cough, and cold a day after giving birth by caesar- and may be due to increased survival of patients with severe
ean section was reported [19]. The Philippines is endemic diseases or extremely low-birth weight, more aggressive in-
for TB, and urban and rural areas have high rates of terventions in the form of surgery, transplants, invasive proce-
COPD [20]. TB and COPD are both associated with dures and devices, immunosuppressive therapy, and use of
CPA, and therefore it is probable that there are many broad-spectrum antibiotics [22]. These are resources that are
undiagnosed CPA cases, with some of them managed as not accessible to most Filipinos.
resistant TB cases. It is important to determine baseline In 1955, dermatologists surveyed the schools where two
prevalence using available serological tests. children with tinea capitis studied; however, no additional
 Eur J Clin Microbiol Infect Dis

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