Nigeria epidemiology and challenges ifi

1. The Epidemiology and Burden of
Invasive fungal infections and
management challenges in Nigeria
Dr R. O. OLADELE
Clinical Mycologist,
LUTH Idi araba

2. Invasive fungal infections in
Nigeria, myth or real?
• 2003, Oduyebo et al (Nig quaterly J of med)
showed a prevalence of 5.0% invasive candidasis
in LUTH
• 2009 Oladele et al (J mycosis suppl) prevalence of
Candidaemia in UCH Ibadan was 5.2% amongst
immunocompromised in-patients. Candida spp
was 3rd in organisms causing BSI in these groups
of patients.
• A study in Zaria showed 12% incidence of
cryptococcosis.( Postgrad med 2003)
• There are no Nigeria data for Aspergillosis

3. Incidence of Invasive Fungal Infections
• During last two decades, incidence of invasive
fungal infections has increased significantly
worldwide.
• Epidemiology of invasive fungal infections
altered to predominantly nosocomial origin
• Crude mortality is 38-75%

4. The Majority of IFIs
Are Identified Post-mortem
Pre-mortem Post-mortem
33%†
How Can We
Better Identify
Patients With
IFI During Life?
12.3%*
Only 1/4
Diagnosed Pre-
mortem
Pagano 20061 Chamilos 20062
*Incidence of moulds and yeasts in AML patients (7.9% due to moulds).
†Prevalence of invasive moulds and Candida (22% due to moulds).
1. Pagano L et al. Haematologica. 2006;91:1068-1075. 2. Chamilos G et al. Haematologica. 2006;91:986-989.

5. Profile of invasive fungi
 Although Candida species remain the relevant
cause of IFI,
 other fungi (especially moulds) have become
increasingly prevalent. In particular, Aspergillus
species are the leading cause of mould infections
 also Glomeromycota (formerly Zygomycetes) and
Fusarium species are increasing in frequency, and
are associated with high mortality rates
• Many of these emerging infections occur as
breakthrough infections in patients treated with
new antifungal drugs.

6. Basics of Invasive Fungal Infections
Host/pathogen Balance: Normal Circumstances
Fungal factors
Anatomical Virulence
Host factors
Adaptive Fungal
Immunity Burden
Innate
Defenses
Protection Infection

7. Basics of Invasive Fungal Infections
Susceptible Hosts
Fungal Disease Predisposing
Candidemia and disseminated Impaired mucosal or cutaneous barriers,
candidiasis neutropenia
Invasive aspergillosis Neutropenia, solid organ and stem cell
transplantation, corticosteroids, graft
versus host disease, chronic
granulomatous disease
Zygomycoses Neutropenia, solid organ and stem cell
transplantation, corticosteroids, graft
versus host disease diabetic ketacidosis,
deferoxamine treatment

8. Major Risk Factors
• Neutropenia,prior antibiotic use, central
venous catheters, total parenteral
nutrition, major surgery within the preceding
week, steroids, dialysis and
immunosuppression.
• Intensive care unit length of stay is an
important risk factor, with the rate of
infections rising rapidly after 7-10 days.
Dimopoulos G, et al. Candidemia in immunocompromised and immunocompetent critically ill patients: a
prospective comparative study. Eur J Clin Microbiol Infect Dis. 2007

9. Risk Factor Selection
Underlying Fever
disease
Infection
Selection
Antibiotics
Skin or
mucosa
damage
Malignancy
Colonization
Diabetes
Renal disease
CTD on steroids
Malnutrition on TPN
Mechanical Ventilation > 48h
Burns
Prematurity and VLBW Instruments
Solid organ transplant CV Catheter
Long term ICU stay Knife

10. Invasive candidasis
• between 4,000 - 5,000 cases of invasive candidosis in UK per annum (D Denning)
• Department of Health Hospital Episode Statistics recorded 494 (consultant) episodes of
aspergillosis in England (2003/4)
• In the USA the prevalence ranged from 2.9-3.7 per 100,000 0f population
• Canad
• In African, a retrospective study in Tunisia showed an average 48 cases per annum over
15years
An Indian study gave a prevalence of 4.8%

11. laboratory surveillance of invasive
fungal infections England 1990-2004
2000
invasive candidosis
1600 invasive aspergillosis
number of reports
1200
800
400
0
*
90
92
94
96
98
00
02
04
19
19
19
19
19
20
20
20

12. Basics of Invasive Fungal Infections
Percentage of BSIs (rank) Crude Mortality %
Pathogen BSIs per 10,000 Total (n=20,978) ICU (n=10,442) Non-ICU Ward Total
admissions (n=10,442)
Cons 15.8 31.3 (1) 35.9 (1)a 26.6 (1) 20.7
Staphylococcus 10.3 20.2 (2) 16.8 (2)a 23.7 (2) 25.4
aureus b
Enterococcus 4.8 9.4 (3) 9.8 (4) 9.0 (3) 33.9
species c
Candida species c 4.6 9.0 (4) 10.1 (3) 7.9 (4) 39.2
E scherichia coli 2.8 5.6 (5) 3.7 (8)a 7.6 (5) 22.4
Klebsiella species 2.4 4.8 (6) 4.0 (7)a 5.5 (6) 27.6
Pseudomonas 2.1 4.3 (7) 4.7 (5) 3.8 (7) 38.7
aeruginosa
Enterobacter 1.9 3.9 (8) 4.7 (6)a 3.1 (8) 26.7
species
Serratia species c 0.9 1.7 (9) 2.1 (9)a 1.3 (10) 27.4
Acineto bacter 0.6 1.3 (10) 1.6 (10)a 0.9 (11) 34.0
baumannii
a P<.05 for patients in ICUs vs patients in non-ICU wards, b significantly more frequent in patients without neutropenia,
c Significantly more frequent in patients in neutropenia
Wisplinghoff H et al. CID 2004;39:309-317

13. Basics of Invasive Fungal Infections
N = 595 Patients
Patterson et al. Medicine 2000;79:250-260

14. The Pediatrics Picture
 Invasive fungal infection is an increasingly common cause
of mortality and morbidity in preterm infants (Kossoff
1998).
 The estimated incidence of invasive fungal infection is 2%
in very low birth weight infants (Saiman 2000).
 In extremely low birth weight infants, the incidence has
been estimated to be as high as 10% (Karlowicz 2002).
 Systemic fungal infection accounts for about 10% of all
cases of sepsis diagnosed in infants more than 72 hours old.
The estimated attributable mortality is about 25% (Saiman
2000).,
 Lack of data from Nigeria

15. Pediatrics UK
• Preliminary results
– 88 cases observed, 1 per 100 very low birth
weight (<1500g) infants
– 76 of 88 were of extremely low birth weight
(<1000g), 2 per 100
– 98% due to Candida species
– one fluconazole-resistant strain identified
– 45% of cases died

16. Management challenges in Nigeria
• Besides classical risk factors for IFI, liver failure, chronic
obstructive, and tuberculosis are the newly recognized
underlying diseases associated with IFI.
• The majority of the centers rely on conventional
techniques including direct
microscopy, histopathology, and culture to diagnose
IFI.
• Paucity of data
• The world is arguing the place of prophylaxis against
empirical therapy, here in Nigeria we are like the
ostrich

17. Challenges contd
• Poor diagnostic and laboratory technique due
to no formal training. Atleast two samples
• Engineering challenges in design and building
of wards……HEPA filters, positive pressure, air sanitisation
• Funding of researches
• Availability of drugs