The Epidemiology and Burden of Invasive fungal infections andmanagement challenges in Nigeria Dr R. O. OLADELE Clinical Mycologist, LUTH Idi araba
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
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%
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.
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.
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
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: aprospective comparative study. Eur J Clin Microbiol Infect Dis. 2007
Risk Factor Selection Underlying Fever disease Infection Selection Antibiotics Skin or mucosa damageMalignancy ColonizationDiabetesRenal diseaseCTD on steroidsMalnutrition on TPNMechanical Ventilation > 48hBurnsPrematurity and VLBW InstrumentsSolid organ transplant CV CatheterLong term ICU stay Knife
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%
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
Basics of Invasive Fungal Infections N = 595 Patients Patterson et al. Medicine 2000;79:250-260
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
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
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
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