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WEST AFRICAN JOURNAL OF MEDICINE

ORIGINAL ARTICLE Burden of Serious Fungal in Nigeria Les Fardeaux D’une Infection Mycosique Grave au Nigeria R. O Oladele*, D. W. Denning†‡

ABSTRACT RÉSUMÉ BACKGROUND: Nigeria is the most populous country in CONTEXTE: Le Nigeria est le pays le plus peuplé d’Afrique Africa with a high rate of tuberculosis and a moderate HIV avec un taux élevé de tuberculose et une charge modérée infection burden. Cutaneous and mucosal fungal d’infection au VIH. Les infections mycosiques cutanées et are reported from Nigeria but there are few reports of serious muqueuses sont rapportées au Nigéria, mais il y a peu de fungal infections. rapports sur les infections mycosiques graves. METHODS: A literature search was done to identify all METHODES: Une recherche dans la littérature a été effectuée epidemiology papers reporting fungal infection rates from afin d’identifier les papiers d’épidémiologie rapportant sur le Nigeria. We used specific populations at risk derived from the taux d’infection mycosique au Nigeria. Nous avons utilisé des WHO and literature and the fungal infection frequencies populations spécifiques à risque provenant de l’OMS et de la were used to estimate national incidence or prevalence. littérature et les fréquences d’infection mycosiques pour estimer l’incidence ou la prévalence nationale. RESULTS: 1.5M Nigerian women get recurrent vaginal thrush. RESULTATS: 1,5 million de femmes nigérianes ont une mycose occurs in >20% of school age children, vaginale récurrente. La teigne survient dans > 20 % des translating to over 15.5M children affected. Based on the enfants d’âge scolaire, traduisant une atteinte de plus de 15,5 3,459,363 cases of HIV infection; an estimated 1,449,166 millions d’enfants. A partir de 3.459.363 de cas d’infection au (55% children) of whom are on ARV therapy; there are VIH; environ 1.449.166 (55%) d’ enfants sont sous traitement 281,180 new AIDS cases, and an estimated 57,866 cases of ARV; il y a 281 180 nouveaux cas de sida, et environ 57 866 cas cryptococcal meningitis. 75,000 patients with AIDS cases de méningite à Cryptocoque. 75 000 patients atteints de sida are expected to develop (40% rate développeront une pneumonie à Pneumocystis ( 40% chez les in children), 253,000 oral and 144,000 oesophageal enfants), 253 000 de candidose buccale et 144 000 de candidose candidiasis. There were 78,032 cases of pulmonary TB in œsophagienne. Il y avait 78 032 cas de tuberculose pulmonaire 2010, and we anticipate 19,000 new cases of chronic en 2010, et nous prévoyons 19 000 nouveaux cas d’aspergillose pulmonary with a 5 year period prevalence of pulmonaire chronique avec une prévalence de 60 377 cas sur 60,377 cases. Prevalence of asthma in adults is 15.2%, une période de 5 ans. La prévalence de l’asthme chez les adultes estimated at 3.7M adult asthmatics of which 94,000 (2.5%) est de 15,2%, environ 3,7 million d’adulte asthmatiques dont will have ABPA and 124,000 severe asthma with fungal 94 000 (2,5%) auront ABPA et 124000 d’ asthme sévère à sensitisation (SAFS). Rates of candidaemia, Candida sensibilité fongique (SF). Le taux de candidémie, de péritonite peritonitis, invasive aspergillosis and were à Candida, d’ aspergillose invasive et de mucormycose ont estimated on a population basis, without supporting data and été estimés sur la base d’ une population, sans l’appui de are probably uncommon or rare. données et sont probablement peu fréquentes ou rares. CONCLUSION: Our estimates indicate that over 11.8% of CONCLUSION: Nos estimations indiquent que plus de 11,8% the Nigerian population is estimated to suffer from a serious de la population nigériane sont susceptible de souffrir d’une infection mycosique grave chaque année. Si la teigne et la fungal infection each year. If tinea capitis and recurrent vaginal mycose vaginale récurrente sont exclues, plus de 960 000 selon thrush are excluded, over 960,000 are estimated to be affected, les estimations, seront touchées , avec une mortalité importante. with substantial mortality. Epidemiological studies are Les études épidémiologiques sont nécessaires de toute urgence urgently required to validate or modify these estimates. WAJM pour valider ou modifier ces estimations. WAJM 2014; 33(2): 2014; 33(2): 107–114. 107–114. Keywords: Nigeria, candidaemia, cryptococcal meningitis, Mots clés: Nigéria, candidemia, méningite à cryptococcose, aspergillosis, keratomycosis, PCP, candidiasis. aspergillose, keratomycose , PCP, candidose.

Department of *Medical Microbilogy & Parasitology, College of Medicine, University of Lagos. Lagos, Nigeria †National Aspergillosis Centre, University Hospital of South Manchester; University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; ‡Global Action Fund for Fungal Infections, Geneva, Switzerland. †‡Correspondence: David W. Denning, National Aspergillosis Centre, University Hospital of South Manchester; University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Global Action Fund for Fungal Infections, Geneva, Switzerland. Email: [email protected] Abbreviations: AJOL, African Journals Online; COPD, Chronic Obstructive Pulmonary Disease; HAART, Highly Active Antiretroviral Therapy; HIV, Human Immunodeficiency Virus; HSCT, Hematopoietic Stem Cell Transplantation; IFDs, Invasive Fungal Infections; NTM, Nontuberculous Mycobacterial; rVVC, recurrent Vulvovaginal Candidiasis; SAFS, Severe Asthma with Fungal Sensitisation.

West African Journal of Medicine Vol. 33, No. 2, April–June, 2014 R. O Oladele and D. W. Denning Serious Fungal Infection in Nigeria

INTRODUCTION candidiasis and about 20% esophageal knowledge.24–26 We therefore estimated Invasive fungal infections have candidiasis. 13 Many HIV-infected the burden of serious fungal infections emerged worldwide as an increasingly patients also developed , in Nigeria based on the populations at frequent cause of opportunistic Pneumocystis pneumonia and other lethal risk to provide useful data to highlight infections.1 The incidence of nosocomial mycoses, for example, penicilliosis and the burden of the diseases in our country fungal infections has continued to rise disseminated .4,12,13 and for comparison with data from other inexorably over the past three decades The increase in the burden of parts of the world. as improved therapies for previously serious fungal infections has been untreatable conditions renders patients demonstrated in some parts of the world. METHODOLOGY more susceptible.2,3 The populations of For instance, data from a survey of the The literature search for publica- patients at risk have expanded to include epidemiology of sepsis conducted in the tions on invasive fungal infections in those with usually multiple underlying USA revealed that the incidence of fungal Nigeria preceding 31 September 2013, was medical conditions, such as solid organ sepsis increased three-fold between 1979 performed using Medline, Google and hematopoietic stem cell and 200014 and most often the diagnosis Scholar, Pubmed website, African transplantation (HSCT), chronic was made postmortem implying a low Journals Online (AJOL) databases and obstructive pulmonary disease (COPD), index of suspicion and treatment.15 It has grey literature to identify all published novel immunosuppressive therapies for been estimated that 4% of all patients papers reporting fungal infection rates rheumatoid arthritis and other who die in hospitals die of invasive from Nigeria. The table of contents of inflammatory and malignant conditions, aspergillosis and 2% die of invasive medical journals listed on AJOL and human immunodeficiency virus (HIV) candidiasis.16,17 Late or no treatment are associated links (National Library of infection, premature birth, advanced age, independent predictors of death in both South Africa, Ingenta, and Quarterly complex surgery and cancer. 1 The conditions.6,18 Index to Periodical Literature of the etiology of invasive mycoses has also The overall incidence of crypto- Library of Congress) were also searched changed; Candida infections were the coccosis in the general population of electronically. Articles on worldwide most common in clinical practice, but South Africa was 15.6/100,000 with a 27% epidemiology of Invasive fungal have been supplemented in many patient mortality rate in 2002–2004.19 Other South infections (including World Health groups by mould infections. The most African studies revealed that, the Organization publications) were reviewed frequent filamentous fungi (moulds) prevalence of cryptococcal antigenemia for citations of publications (journal isolated are spp., but was 7%20 and 48.6% for Pneumocystis articles and books or monographs) from Fusarium spp., Scedosporium spp., jirovecii pneumonia (PCP).21 The rate of Nigeria and Africa. The references in all Penicillium spp. and Zygomycetes are cryptococcal infection in Uganda, (a sub- relevant papers were reviewed for increasingly seen.4 However the two Saharan African country where about 1.1 additional publications that may not have most common organisms in all million have HIV with an estimated 9.2% been cited elsewhere (“snow balling”). epidemiological studies of invasive (101,000) have a CD4 count <200 cells/ Articles published in other languages fungal infections are Candida spp. and m L) was 40.4 cases per 1,000 person years (e.g., French and Portuguese) were Aspergillus spp.4, 5 and 1.5 cases per 1,000 person years in considered if they were cited in any of Invasive aspergillosis complicates the pre-highly active antiretroviral the databases searched. The Boolean haematological malignancy treated with therapy (HAART) and HAART period, operator ‘AND’ was used to combine and chemotherapy and stem cell transplant.6,7 respectively.22 narrow the searches. Chronic pulmonary aspergillosis is HIV/AIDS is a huge problem in During the searching, abstracts were associated with nontuberculous Nigeria which has a population of about reviewed and the relevant full text articles mycobacterial (NTM) disease and may 160 million people. The estimated number were selected. The next step involved a follow tuberculosis as well as other of HIV/AIDS infected people was 3.3 manual search of the reference lists of all pulmonary conditions such as COPD and million in 2010, with 281,180 new AIDS the selected articles to identify other sarcoidosis.8–10 Critically ill patients and cases and 215,130 AIDS-related deaths.23 relevant articles for final selection. neutropenic patients have been shown About 25% of tuberculosis cases occur Articles were selected if the to be at risk of candidaemia11 and invasive in HIV positive patients (51/1,000) and following inclusion criteria were fulfilled: aspergillosis. There is a strong associa- 210/1,000 occur in the total population availability of full text article in English; tion between mucormycosis and annually for HIV negative and HIV studies were performed on humans and uncontrolled diabetes.12 The epidemic of positive cases respectively.23 The burden site of infection was unambiguously HIV is also a major factor that has of serious fungal infections has not been stated. The search terms used were “ contributed to a remarkable increase in properly described in Nigeria, despite fungal infections and Nigeria,” “ the frequency of mucosal candidiasis; these substantial underlying disease and Nigeria”, “candidaemia and Nigeria,” before the extensive use of highly active frequencies. There are very few epidemio- “candidiasis and Nigeria”, “aspergillosis antiretroviral therapy (HAART) in logical data on serious fungal infections and Nigeria,” “cryptococcosis and developed countries, 80% of HIV- in Nigeria; only few case reports of Nigeria,” “histoplasmosis and Nigeria,” infected patients developed oral invasive fungal are available to our and “fungal keratitis and Nigeria.” In

108 West African Journal of Medicine Vol. 33, No. 2, April–June, 2014 R. O Oladele and D. W. Denning Serious Fungal Infection in Nigeria addition, specific disease conditions and candidiasis was only estimated for new of these 33% occur in intensive care, “fungal infections” were searched. In AIDS cases and was assumed to occur including premature neonates. 39 each paper, study design including in 90% of them. 29 Oesophageal Candida peritonitis complicates complex population base (hospital, community, candidiasis was estimated to occur in 20% surgical cases in ICU, at a rate approxi- and special cohorts), diagnostic criteria of new AIDS patients and 5% of those mately 50% of candidaemia.40 We have for invasive fungal infections, survey with CD4 cell counts on ARVs.13,30 To not estimated urinary candidiasis, which methods, and results were reviewed. estimate cryptococcal meningitis, we is very common, but often of uncertain We used specific populations at risk have assumed this occurs primarily in significance. Mucormycosis was and fungal infection frequencies in the adults (cases do occur in children but are estimated to occur at a rate of 0.2/ population to estimate national incidence uncommon) and that the rate is 12.7% in 100,000 (a general literature estimate). or prevalence where no relevant studies screening in outpatients with HIV Fungal keratitis was not possible to were available. WHO population statistics infection and CD4 cell counts <200/m L,31 estimate. The estimate for tinea capitis of 2009, the 2010 WHO HIV infection 45% of the 1,400,000 estimated patient not was from study which documented a and ARV treatment rates; National receiving ARVs. In addition, new AIDS prevalence of 9.4% amongst school- Agency for the Control of AIDS child/ cases presenting to the hospital develop children.41 adult HIV split 2011, WHO 2010 TB cryptococcal meningitis (38% of all cases statistics, ISAAC estimate of asthma of meningitis in one hospital in Jos,32 RESULTS prevalence are some of the other probably at a rate of about 10%. This Five epidemiological or descriptive databases used for estimating population ignores all occurrences after ARVs studies were included in our analysis of at risk. commence, which varies between 4 and which only 3 were cited in Pubmed, one 12% in the first year.33 All cases occurring from AJOL database and a case report Study Design in other patient groups have been from a non-indexed online journal.. The Including population based ignored. To estimate the frequency of baseline characteristics of the studies are (hospital, community, and special PCP, we have assumed that 40% of new shown in Table 1. cohorts), diagnostic criteria for fungal AIDS cases in children present with this infections, survey methods, and results infection and 10% of adults.33,34 Again we Prevalence Based Superficial Fungal were reviewed and compared. The overall have ignored cases that occur while on Infections overall terminology used as previously ARV therapy and non-AIDS PCP. There have been a handful of studies listed above and diagnostic criteria for We estimated invasive, chronic and on superficial and cutanous fungi fungal infections with emphasis on allergic aspergillosis in adults only. infections in Nigeria. These studies have serious fungal infections especially IFIs Chronic pulmonary aspergillosis estimate been mainly on Tinea capitis, oral were considered.in calculating estimates. was taken from Denning DW (2001)10,35 candidiasis and vulvovaginal candi- Studies that were not invasive fungal which was based on population data from diasis. Of the 155 million Nigerian infections were excluded apart from a 2005 and TB data from 2007, and allergic population 50% are children and 38 handful of more serious superficial and bronchoplumonary aspergillosis from million are women between the age of 15 cutanous infections that were used to Denning, 2013.36 We have estimated the and 50 years. We estimate that ~1,500,000 estimate the burden of the disease. rate of severe asthma with fungal Nigerian women between the ages of 15 However, for clarity purpose, this review sensitization by taking the asthma rate in and 50 get recurrent vaginal thrush, ie at is focused on invasive fungal infections. adults and assuming that 10% are severe least 4 times annually. Local estimates of Due to the heterogeneity of the study and that 33% are sensitized to one or more tinea capitis at 9.4% of school age methodologies in this review it was not fungi. The number of adults with asthma children, suggesting that over 15,500,000 possible to apply the conventional were estimated from Ozoh et al, 2012, and children have tinea capitis. methods of a systematic review. A meta- Denning et al, 2013. 37,36 Invasive analysis is only appropriate if there is aspergillosis was only estimated in HIV/AIDS-related Invasive Fungal satisfactory similarity in the populations haematological malignancy by assuming Infections studied and the measurements used. This that 10% of acute myeloid leukaemia Based on the 3,459,363 cases of HIV was not the case with the studies patients (rate 3/100,000 population) infection reported (55% children) and identified in this review. Therefore, a develop IA and that an equal number of 1,449,166 on ARV therapy and 281,180 narrative approach was taken to report cases are found in all other haemato- new AIDS cases, we estimate 57,894 the findings of the included studies. logical patients, as in France and cases of cryptococcal meningitis Austria.7,38 Case frequency following annually. This number is derived from Data Extraction and Synthesis transplantation, others on corticosteroid 10% of new adult AIDS cases (12,600), Annual incidence estimates were therapy, including COPD and other 12.7% of adults with CD4 counts less derived as follows. 6% rate of recurrent immunocompromised patient groups are than 200/m L (40,005 patients) and 10% vulvovaginal candidiasis (rVVC) in 15– not known. additional cases in children (5,260 50-year-old age group, based on work by Candidaemia is assumed to occur at affected). In addition, 74,594 of the AIDS Ekpenyong et al. 2012. 27,28 Oral a relatively low rate of 6 per 100,000, and cases are expected to develop

West African Journal of Medicine Vol. 33, No. 2, April–June, 2014 109 R. O Oladele and D. W. Denning Serious Fungal Infection in Nigeria

Table 1: Baseline Characteristics of Studies on Invasive Fungal Infections in Nigeria

Authors (Year) Location in Type of Sample Size and Fungal Age Rates Nigeria Study Population Studied Infection (%) Gugnani et al Eastern Case report 36 Fungal Keratitis Adults 58.3 (1976)25 Nigeria Hospital-based Ekanem et al South-south Case report 1 Histoplasmosis Adult (2009)27 Nigeria Hospital-based Gomerep et al North-Central Propective 100 Cryptococcal Mixed 36.0 (2010)31 Nigeria Hospital-based meningitis (adults and children) Osazuwa et al Mid-Western Prospective 150 Cryptococcosis 20–50 12.9 (2012)30 Nigeria Hospital-based years Fayemimo et al Western Retrospective 48 Fungal Keratitis Mixed 8.4 (2013)60 Nigeria Hospital-based (adults and children)

Table 2: Estimated Burden of Serious Fungal Infections in Nigeria

Infection Underlying Disease Total Rate / None HIV/AIDS Respiratory Cancer/Tx ICU Burden 100K

Oesophageal candidiasis - 144,195 ? ? ? 144,195 93.2 - 253,062 ? ? ? 253,062 163.6 Candidaemia - ? ? 3,095 6,189 9,284 6.0 Candida peritonitis - - - - 2,321 2,321 1.5 Recurrent vaginal candidiasis (4x/year ) 1,521,520 - - - - 1,521,520 3800.0 ABPA - - 93,649 - - 93,649 60.5 SAFS - - 123,617 - - 123,617 79.9 Chronic pulmonary aspergillosis - - 120,753 - - 120,753 78.0 Invasive aspergillosis - ? ? 928 ? 928 0.6 Mucormycosis - - - 300 - 300 0.2 Cryptococcal meningitis ? 57,894 ? ? - 57,894 37.4 Oral candidiasis 253,062 253,062 163.6 Pneumocystis pneumonia - 74,594 ? ? ? 74,594 48.2 Histoplasmosis ? ? ? - - ? ? Fungal keratitis ? - - - - - ? Tinea capitis 15,581400 ? ? ? ? 15,581,400 10,070.0

Total burden estimated 17,983,517

Pneumocystis pneumonia (40% rate in candidiasis. cases.36 This assumes a 15% annual children), 253,000 oral candidiasis and There were 78,032 cases of mortality. Such post-tuberculous cases 144,000 based on pulmonary TB in 2010, most in HIV probably represent 50% (range 20– the WHO prevalence rate. All these negative people and based on pulmonary 85%)9 of the total chronic pulmonary estimates are likely to be underestimates cavity frequency and Aspergillus IgG aspergillosis caseload, therefore because we have not factored in serology, we expect 19,000 new cases of estimated at 120,754 patients affected infections occurring after starting ARV chronic pulmonary aspergillosis annually with chronic pulmonary aspergillosis in therapy, except for esophageal with a 5-year period prevalence of 60,377 Nigeria.

110 West African Journal of Medicine Vol. 33, No. 2, April–June, 2014 R. O Oladele and D. W. Denning Serious Fungal Infection in Nigeria

Population Based Invasive Fungal from Kenya which reveals a prevalence bacterial vaginosis and separately with Infections of 10.1–33.3% in rural and urban school transmissibility of HIV. 51 For example, a Asthma is common in Nigeria. pupils.44 This problem, while not life- high HIV seropositivity has been noted Prevalence studies in teenagers indicate threatening has an impact on public among fertile women with symptomatic a prevalence of 10.7–14.3% and in health, socioeconomic and psychological candidiasis in Cameroon, a neighbouring adults of 14–15.2%.37 We have used the wellbeing of the group at risk. In addition, west African country52 and the high latest study in adults of 15.2%41 and at least 2% of children develop or incidence of HIV and candidiasis among estimated 3,700,000 million adult favus, inflammatory uncomfortable, youths and adolescents in Dar es Salaam, asthmatics in Nigeria. Of these 2.5% are unsightly and scarring complications of Tanzania53 underlines the medical estimated to have ABPA(based in part on tinea capitis.45 Assuming our estimate is importance of vulvovaginal candidiasis a study from South Africa by Benatar et adequate, over 300,000 children develop in HIV infection. Recurrent VVC is an al 1980;42) an estimated 94,600 people. kerion, which is a substantial problem unpleasant problem for those affected, And if the worse 10% of adult asthmatics that needs addressing urgently. having a significant impact on quality of are sensitized to fungi and therefore have Oropharyngeal candidiasis is the life with vaginal soreness, irritation, severe asthma with fungal sensitization commonest opportunistic infection in vulvar burning, dyspareunia, and external (SAFS), we estimated 124,000 affected, HIV-infected individuals, and we estimate dysuria being common. with the possibility of some duplication over 250,000 patients are affected We have estimated 74,594 cases of between the ABPA and SAFS groups. annually; probably there would be many PCP in HIV/AIDS patients only, partly Rates of candidaemia, invasive more episodes than this. Adedigba et al.46 using from data from other African aspergillosis and mucormycosis were found it to be the commonest oral studies. PCP is found predominantly in estimated on a population basis (Table manifestation (43.1%) of HIV infection in the paediatric age group.21,34 PCP also 2), without supporting data from Nigeria Nigerian patients, reflecting the situation occurs in non-HIV infected patients, and and are probably uncommon or rare. in other parts of Africa, and indeed the the proportion varies substantially and Histoplasmosis exists in Nigeria, both world. 13,47 The symptoms of oro- so it is not possible make a reliable caused by H. capsulatum var capsulatum pharyngeal candidiasis include a estimate of this problem in Nigeria. and var dubosii,26,43 buts frequency is sensation of burning in the mouth, oral Accurate diagnosis requires immuno- very hard to estimate based on current pain, xerostomia (dry mouth), throat pain fluorescence microscopy or molecular data. and impaired taste (dysgeusia). 48 (PCR) methodology on high quality Symptoms are worse if untreated, respiratory samples, neither of which is DISCUSSION including in those with fluconazole available in Nigeria currently. Our estimates indicate that over resistance. In HIV infection, it often A study on cryptococcal antigen 11.8% of the Nigerian population is occurs together with oesophageal screening amongst HIV/AIDS patients in estimated to suffer from a serious fungal candidiasis which is a serious problem, a tertiary hospital in Mid-western Nigeria infection each year. If tinea capitis and causing nausea, vomiting and dysphagia revealed a prevalence of 12.7% in those recurrent vaginal thrush are excluded, in most patients. Our estimate in AIDS with CD4 cell counts less than 200.31 Given over 960,000 are estimated to be affected, patients of 144,000 patients affected is that probably 50% of the estimated 1.4M with substantial mortality. Invasive concerning, as not all may be receiving people not on ARV therapy have CD fungal infections (IFDs) are frequently life adequate therapy. We have not estimated counts <200/m L, and that only 45% of threatening infections with high oral or oesophageal candidiasis in any these patients are adults, there are morbidity and mortality rates and the other patient group, so our estimates will probably 40,000 people who could be groups of patients at risk are all seen and certainly be significant underestimates of identified by screening each year, many managed in Nigeria. There is however a the total Nigerian burden of these pre-symptomatic, before meningitis paucity of data on IFDs in Nigeria. The infections. For example, oesophageal occurs. This positivity rate on screening question therefore is “are there no IFDs candidiasis was endoscopically is higher than that in Uganda at 2.9%,54 in our environment?’ or is it just a case of documented in Korea in non- in neighbouring Cameroon at 9.86%55 and lack of awareness (a knowledge gap which immunocompromised well adults 8.4% in Ethiopia56 but lower than that of tends to lead to low clinical index of undergoing a health check at a prevalence 16.6% from a Ghanaian study.57 suspicion and thus management)? These rate of 0.32%,49 and of course in other Long term respiratory fungal questions must be answered to ensure immunocompromised patients with some infections such as chronic pulmonary proper management of the large numbers regularity. aspergillosis, ABPA and SAFS are of patients with infection and at risk. Vulvovaginal candidiasis preva- estimated in 338,000 people, a total rate Our findings revealed a number of lence rates ranges between 21%–35% in of 210/100,000 of the population, epidemiological reports on superficial Nigeria50 and we have estimated that ~1.5 Tuberculosis is common and 78,032 cases and mucocutanous fungal infections million Nigerian women suffer from of pulmonary TB were diagnosed in 2010, with an estimated total burden of recurrent episodes, irrespective of HIV so the relatively large number of patients 15,581.400 cases of tinea capitis in status. An association has been with chronic pulmonary aspergillosis is children.40 This is comparable to the data demonstrated between vaginitis and perhaps not a surprise. What is not

West African Journal of Medicine Vol. 33, No. 2, April–June, 2014 111 R. O Oladele and D. W. Denning Serious Fungal Infection in Nigeria known in Nigeria is how many cases of from a tertiary hospital in Nigeria showed 7. Lortholary O, Gangneux JP, Sitbon K, chronic pulmonary aspergillosis occur in a prevalence of fungal keratitis of 8.4% Lebeau B, de Monbrison F, Le Strat Y, other at risk groups such as ABPA, amongst cases of keratitis,61 this is et al. French Mycosis Study Group. sarcoidosis, COPD, following pneumo- inconsistent with findings from a Epidemiological trends in invasive aspergillosis in France: the SAIF theorax to name some examples. We have prospective study in Ghana where the network (2005–2007). Clin Microbiol estimated that TB accounts for 50% of prevalence rate was 37.6%. 62 This Infect 2011; 17: 1882–1889. the cases. Asthma is surprisingly disparity might be due to the fact that 8. Kunst H, Wickremasinghe M, Wells A, common in adults in Nigeria at ~15%58 one study proactively (prospective) Wilson R. Nontuberculous myco- and the fatality rate of hospitalised cases looked for keratomycosis while the other bacterial disease and Aspergillus-related of asthma ranges between 6–7.8%;37 was a retrospective (passive) study. A lung disease in Bronchiectasis. Eur these deaths are preventable. One area prospective Nigerian study is required to Respir J 2006; 28: 352–357. for further research in Nigeria is the give a clearer picture. 9. Smith NL, Denning DW. Underlying proportion of severe asthma who have The major limitations of our conditions in chronic pulmonary aspergillosis including simple asper- SAFS and would benefit from antifungal estimates and modeling are the paucity 58,59 gilloma. Eur Respir J 2011; 37: 865– therapy. Likewise the number of of data which has necessitated use of 872. patients with ABPA is uncertain but some data from neighbouring countries 10. Denning DW, Pleuvry A, Cole DC. estimates of the proportion of adult to make estimates. The studies that were Global burden of chronic pulmonary asthmatics with ABPA is consistently available were generally hospital based aspergillosis as a sequel to tuberculosis. around 2.5% in several countries frequencies which might not be Bull WHO 2011; 89: 864–72. including South Africa.36 representative of the whole population. 11. Silke Schelenz. Management of Estimated cases of other candidiasis in the intensive care unit. J immediately life threatening invasive CONCLUSION Antimicrob Chemother 2008; 61: 131– 134. fungal infections, (candidaemia, candida Epidemiological data on the burden 12. Chakrabarti A, Singh R. The emerging peritonitis, invasive aspergillosis and of fungal infections in Nigeria will be of epidemiology of mould infections in mucormycosis) is 8.2 per 100,000 of substantial public health value and developing countries. Curr Opin Infect population at risk. There are very few data potentially influence the management of Dis. 2011; 24: 521–6. available in Nigeria to corroborate or millions of patients at risk. In conclusion, 13. Patel PK, Erlandsen JE, Kirkpatrick otherwise these figures and no data our estimates indicate that over 960,000 WR, Berg DK, Westbrook SD, Louden published on histoplasmosis. There have of the Nigerian population suffer from life C, et al. The Changing Epidemiology of been no proactive searches for these life threatening fungal infections which have Oropharyngeal Candidiasis in Patients threatening infections probably related a high morbidity and mortality rate. with HIV/AIDS in the Era of Antiretroviral Therapy. AIDS Research to the fee for service health system in Epidemiological studies are urgently and Treatment Volume 2012, Article ID Nigeria, so most times clinicians usually required to validate or modify these 262471, 5 pages. prefer to commence empirical therapy estimates. 14. Wisplinghoff H, et al. Nosocomial rather than actively investigate the cause bloodstream infections in US hospitals: of the infection. Conventional diagnostic REFERENCES analysis of 24,179 cases from a pros- tests such as direct microscopy, 1. Hsu JL, et al. Diagnosing Invasive pective nationwide wide surveillance histopathology and culture are available Fungal Disease in Critically Ill Patients. study. Clin infect Dis 2004; 39: 309– for use, but not galactomannan, b -D Crit Rev Microbiol 2011; 37: 277–312. 317. 2. Martin GS, et al. (2003). Epidemiology 15. Denning DW, Stevens DA. Antifungal glucan, or DNA detection tests and this of sepsis in the United States from 1979 and surgical treatment of invasive may have impacted on the ability to through 2000. N Engl J Med 2003; 348: aspergillosis: review of 2,121 published diagnose invasive fungal infections. The 1546–54. cases. Rev Infect Dis 1990; 12: 1147– dearth of data makes the current situation 3. Horn DL, et al. Epidemiology and 201. very unsatisfactory, and it is likely that outcomes of candidemia in 2019 16. Sircar-Rameswak F, Kuti JL, Nicolau many fungal infections will be missed, and patients: data from prospective DO. Posaconazole: A novel triazole untreated. antifungal therapy alliance registry. Clin antifungal for the treatment of invasive The prevalence of blindness in Infect Dis 2009; 48: 1695–1703. fungal infections. Formulary. 2003; Nigeria is 0.78% (~12 million) with corneal 4. Warnock DA. Trends in epidemiology Jan:13–20. opacities accounting for 12% (~1.45 of invasive fungal infections. Jpn J med 17. Denning D. Antifungals: Where are we mycol 2007; 48: headed? DrugPlus Inter. 2004; 21 million). 60 However there are no 1–12. 5. Richardson MD. Changing patterns and Sep:1,7,8,11,16). epidemiological data on fungal keratitis trends in systemic fungal infections. J 18. Denning DW, Kibbler CC, Barnes RA., in Nigeria, a country with a large Antimicrob Chemoth 2005; 56: 1: i5– and on behalf of the British Society for population of rural dwellers and farmers i11. Medical . British Society for who have no access to secondary or 6. M von Eiff ,N. Roos, R. Schulten, M Medical Mycology proposed standards tertiary healthcare where this diagnosis Hesse, M. Zuhlsdorf, J. van de Loo of care for patients with invasive fungal would be made and treatment instituted. Pulmonary Aspergillosis: Early infections. Lancet Infect Dis 2003; 3: A retrospective laboratory based study Diagnosis Improves Survival. 230–240. Respiration 1995; 62: 341–347.

112 West African Journal of Medicine Vol. 33, No. 2, April–June, 2014 R. O Oladele and D. W. Denning Serious Fungal Infection in Nigeria

19. McCarty KM, Morgan J, 30. Buchacz K, Baker RK, Palella FJ Jr, 43. Gugnani HC. Mutoe-Okafor FA, Wannemuehler KA, Mirza SA et al. Chmiel JS, Lichtenstein KA, Novak Dupont B, Kaufman L. A natural focus Population based surveillance for RM, et al. HOPS Investigators. AIDS- of var. duboisii cryptococcosis in antiretroviral-naïve defining opportunistic illnesses in US in a bat cave. Mycopathologia 1994; 127: South Africa province with a high HIV patients, 1994–2007: a cohort study. 151–157. seroprevalence. AIDS 2006; 20: 2199– AIDS. 2010; 24: 1549–59. 44. Chepchirchir C Bii, Ndinya-Achola JO. 2206. 31. Osazuwa F, Dirisu JO, Okuonghae PE, infections in primary 20. Jarvis JN, Lawn SD, Vogt M, Bangani Ugbebor O. Screening for Cryptococcal school children in kibera slums of N, Wood R, Harrison TS: Screening for Antigenemia in Anti-Retroviral Naïve Nairobi. East Afri Med J. 2009; 86: 59– cryptococcal antigenemia in patients AIDS Patients in Benin City, Nigeria. 68. accessing an antiretroviral treatment Oman Med J 2012; 27: 228–231. 45. Zaraa I , Hawilo A, Aounallah A, Trojjet program in South Africa. Clin Infect Dis 32. Gomerep SS, Idoko JA, Ladep NG, S, El Euch D, Mokni M et al. 2009; 48: 856–862. Ugoya SO, Obaseki D, Agbaji OA, et Inflammatory Tinea capitis: a 12-year 21. Donatella D. Ruffini, Shabir A. Madhi. al. Frequency of cryptococcal study and a review of the literature. The high burden of Pneumocystis meningitis in HIV-1 infected patients Mycoses, 2013; 56: 110–116. carinii pneumonia in African HIV-1- in north central Nigeria. Niger J Med. 46. Adedigba MA, Ogunbodede EO, infected children hospitalized for severe 2010; 19: 395–9. Jeboda SO, Naidoo S. Patterns of oral pneumonia. AIDS 2002, 16: 105–112. 33. GAFFI fact sheet 2013. www.GAFFI. manifestations of HIV/AIDS among 225 22. Oyella J, Meya D, Bajunirwe F, Kamya org, accessed 20th October 2013. Nigerian patients. Oral Dis. 2008; 14: MR. Prevalence and factors associated 34. Morris A, Lundgren JD, Masur H, 341–346. with cryptococcal antigenemia among Walzer PD, Hanson DL, Frederick T, et 47. Hamza OJM, Matee MI, Moshi MJ, severely immunosuppressed HIV- al. Current Epidemiology of Pneumo- Simon EN, Mugusi F, Mikx FH, et al. infected adults in Uganda: a cross- cystis Pneumonia Emerg Infect Dis. Species distribution and in vitro sectional study. Journal of the 2004; 10: 1713–1720. antifungal susceptibility of oral International AIDS Society 2012; 15: 15 35. Denning DW. Chronic forms of isolates from Tanzanian HIV infected 1758–2652. pulmonary aspergillosis. Clin Microbiol patients with primary and recurrent 23. WHO progress report 2011. http:// Infect. 2001; 7: 25–31. oropharyngeal candidiasis. BMC www.who.int/hiv/pub/progress_report 36. Denning DW, Pleuvry A, Cole DC. Microbiol 2008; 8: 135. 2011/en/index.html Global burden of ABPA in adults with 48. Hood SV, Hollis S, Percy M, Atkinson 24. Gugnani HC, Talwar RS, Njoku-Obi asthma and its complication chronic G, Williams K, Denning DW. Assess- AN, Kodilinye HC. Mycotic Keratitis: pulmonary aspergillosis. Med Mycol ment of Therapeutic Response of A Study Of 2i Cases In Nigeria. Brit J 2013; 51: 361–70. Oropharyngeal and Esophageal Ophthal 1976; 60: 607. 37. Ozoh OB and Bandele EO. A synopsis Candidiasis in AIDS with Use of a New 25. Jacyk WK, Lawande RV, Tulpule SS. of asthma research in Nigeria between Clinical Scoring System: Studies with Deep Mycoses in West Africa: A Report 1970 and 2010. Afr J Resp Med 201‘2; D0870. Clinical Infectious Diseases of 13 Cases and Review of the Nigerian 7:2: 9–11. 1999; 28: 587–96. Literature. J Natl Med Assoc. 1981; 73: 38. Perkhofer S, Lass-Flörl C, Hell M, Russ 49. Jae Hyeuk Choi, Chang Geun Lee, Yun 251–256. PMID:7009881 G, Krause R, Hönigl M, et al. The Jeong Lim, Hyoun Woo Kang, Chi Yeon 26. Ekanem BI, Jombo G, Asana U, Jibrin Nationwide Austrian Aspergillus Lim, Jong-Sun Choi. Prevalence and P. Histoplasmosis Masquerading as a Registry: a prospective data collection Risk Factors of Esophageal Candidiasis Burkitt’s Tumor and Challenges in on epidemiology, therapy and outcome in Healthy Individuals: A Single Center Diagnosis: A Case Finding at University of invasive mould infections in Experience in Korea. Yonsei Med J 2013; of Calabar Teaching Hospital, South- immunocompromised and/or immuno- 54: 160–165. South Nigeria. The Internet Journal of suppressed patients. International 50. Jombo GTA, Opajobi SA, Egah DZ, Ophthalmology and Visual Science. 2009 Journal of Antimicrobial Agents 2010; Banwat EB, Denen Akaa P. Volume 7 Number 1. DOI: 10.5580/15f 36: 531–536. Symptomatic vulvovaginal candidiasis 27. Ekpeyong C, et al. Recurrent vulvo- 39. Arendrup MC. Epidemiology of and genital colonization by Candida vaginal candidosis among young women . Curr Opin Crit species in Nigeria. J Public Health in south eastern Nigeria: the role of Care 2010; 16: 445–52. Epidemiol 2010; 2: 147–151. lifestyle and health-care practices. Int J 40. Montravers P, Mira JP, Gangneux JP, 51. Hilber AM, Francis SC, Chersich M, STD AIDS 2012; 23: 704–9. Leroy O, Lortholary O. A multicentre Scott P, Redmond S, Bender N, et al 28. Foxman B, Muraglia R, Dietz JP, Sobel study of antifungal strategies and (2010). Intravaginal practices, vaginal JD, Wagner J. Prevalence of recurrent outcomes of Candida peritonitis in infections and HIV acquisition: vulvovaginal candidiasis in 5 European intensive care units. Clin Microbiol systemic review and metaanalysis. countries and the United States: results Infect 2011; 17: 1061–1067. PLoS One 5(2): e9119 from an internet panel survey. J Low 41. Emele FE, Oyeka CA. Tinea capitis 52. Desmisseau AJ, Schmidt-Grimminger Genit Tract Dis. 2013;17: 340–5. among primary school children in DS, Welty E. Epidemiology of HPV in PubMed PMID: 23486072. Anambra state of Nigeria. Mycoses HIV-positive and HIV-negative fertile 29. Matee MI, Scheutz F, Moshy J. 2008; 51: 536–541. women in Cameroon, West Africa. Infect Occurrence of oral lesions in relation to 42. Benatar SR, Keen GA, Du Toit Naude Dis Obstet Gynaecol. 2009: e810596 clinical and immunological status among W. Aspergillus hypersensitivity in doi HIV-infected adult Tanzanians. Oral Dis asthmatics in Cape Town. Clin Allergy 53. Chalmilla G, Mbwana J, Mhalu F, 2000; 6: 106–11. 1980; 10: 285–291. Mmari E, Majigo M, Swai A, et al.

West African Journal of Medicine Vol. 33, No. 2, April–June, 2014 113 R. O Oladele and D. W. Denning Serious Fungal Infection in Nigeria

Patterns of sexually transmitted Antigenemia among HIV-infected Severe Asthma with Fungal Sensitiza- infections in adolescents and youths in Patients Receiving Antiretroviral tion. Journal of Asthma, 2012; 49: 423– Das es Salaam, Tanzania. BMC Infect Therapy in Ethiopia. PLoS ONE. 2013; 433. Dis 2006; 6: 22. 8(3): e58377. doi:10.1371/journal.pone. 60. Babalola OE. The peculiar challenges 54. Parkes-Ratanshi R, Wakeham K, Levin 0058377 of blindness prevention in Nigeria: a J, Namusoke D, Whitworth J, Coutinho 57. Owusu M, Nguah SB, Boaitey YA, review article. Afr J Med Med Sci 2011; A, et al on behalf of the Cryptococcal Badu-Boateng E, Abubakr A, Lartey RA 40: 309–19. Trial Team. Primary prophylaxis of et al. Aetiological agents of cere- 61. Fayemiwo SA, Ogunleye VO, Ashaye cryptococcal disease with fluconazole brospinal meningitis: a retrospective AO, Oladele R, Alli AJ, Bakare RA. in HIV-positive Ugandan adults: a study from a teaching hospital in Ghana. Causative agents of keratomycosis in double-blind, randomised, placebo- Annals of Clin Microbiol and Ibadan: review ofLaboratory reports. controlled trial. Lancet.2011: DOI:10. Antimicrob 2012; 12: 28. Afr J Cln Exper Microbiol. 2013; 14: 1016/S1473-3099(11)70245-6 58. Desalu OO, Busari OA, Onyedum CC, 105–108. 55. Dzoyem JP1, Kechia FA2, Ngaba GP3, et al. Evaluation of current knowledge, 62. Leck AK, Thomas PA, Hagan M, Lunga PK1, Lohoue PJ. Prevalence of awareness and practice of spirometry Kaliamurthy J, Ackuaku E, et al. cryptococcosis among HIV-infected among hospital-based Nigerian doctors. Aetiology of suppurative corneal ulcers patients in Yaounde, Cameroon African BMC Pulm Med 2009; 14: 49–50. in Ghana and south India, and Health Sciences Vol 12 No 2 June 2012. 59. Chishimba L, Niven RM, M.Fom. epidemiology of fungal keratitis. Br J 56. Alemu AS, Kempker RR, Tenna A, Cooley J, Denning DW. Voriconazole Ophthalmol 2002; 86: 1211–1215. Smitson C, Berhe N, Fekade D, et al. and Posaconazole Improve Asthma High Prevalence of Cryptococcal Severity in Allergic Aspergillosis and

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