Fungal infections in Algeria

Invasive and superficial fungal infections are increasingly reported in Algeria, testifying to the increase in their frequency in parallel with the increase in risk factors and the availability of diagnostic means, at least in university hospitals (CHU). The latter, located in the major northern cities, are equipped with high‐performance diagnostic tools compared to hospitals in the interior of the country.

fungal infections. In Algeria, publications on fungal infections are few, even though many medical theses, biology and pharmacy dissertations on invasive and superficial fungal infections have been carried out in recent years.
The objective of this work is to report these different works and to estimate the incidence and prevalence of invasive and superficial fungal infections in Algeria. 1 This was done about 5 years ago and since then a substantial increase in data has been published, and some presented in so-called 'grey' publications. Our study also highlights the potential factors that have favoured the emergence of particular fungal disease and the practical consequences of these epidemiological changes.

| ME THODS
Our study is a review of the literature reporting the epidemiology of certain fungal infections that have been diagnosed in recent years and listed from thesis work in medical sciences, doctoral dissertations in pharmacy, master's degree in biology and other specialties.
We also report the results published in journals and have selected some results of pertinent work presented at the last national congress of parasitology-mycology in December 2021.
We sourced 2021 data on population from the Central Intelligence Agency, USA (CIA) fact book, 2 HIV/AIDS data for 2020 from UNAIDS 3 and deaths estimated from Spectrum, 4 2020 tuberculosis data from WHO (and assumed that the proportions of deaths for pulmonary TB mirrored overall deaths), 5 2019 prevalence asthma in adults from country reports, 6 chronic obstructive pulmonary disease (COPD) prevalence and hospitalisations from the BREATHE study in 2012, 7,8 2020 lung cancer incidence from the International Agency for Research in Cancer (IARC) 9 and nationally, 10 acute leukaemia incidence for 2020 from IARC and 2019 transplantation procedures from The International Registry on Organ Donation and Transplantation (Irodat). 11 To calculate incidence and prevalence of each fungal disease we applied the country data as a numerator with the at risk population as a denominator in a straightforward deterministic model, for most conditions. Invasive aspergillosis annual incidence was composed of several underlying risk groups: acute myeloid leukaemia (13.7% risk in the absence of anti-mould prophylaxis) 12 and an equal number of cases from all other risk haematological conditions, HSCT (10%), lung cancer (2.6%), 13 deaths from AIDS (4%) 14 and 1.3% of COPD hospitalisations. 15 Chronic pulmonary aspergillosis (CPA) incidence and prevalence was estimated using four components linked to pulmonary tuberculosis (PTB) data: Incorrect initial diagnosis -usually in smear/Xpert negative PTB cases (19% in HIV negative cases), dual PTB and CPA (3% in HIV negative patients), the development of CPA during or immediately after anti-PTB therapy (10%) and late development of CPA (1.5% annually). 16 We also assumed a 20% year 1 mortality and a 7.5% annual mortality for 5 years. 16 PTB as the underlying cause of CPA was assumed to be 50% of all CPA cases. 17 Allergic bronchopulmonary aspergillosis was assumed to affect 2.5% of adult asthmatics. 18,19 Severe asthma probably affects ~10% of and assuming at least 33% are sensitised to fungi, 20 then 3.3% of adults will likely have severe asthma with fungal sensitisation (SAFS). Mucormycosis was assumed to affect two persons per million per year. 21 We assumed that 6% of patients with advanced HIV disease and AIDS develop cryptococcal meningitis 22 and 15% develop Pneumocystis pneumonia. 23 We assumed that the HIV risk group is composed of one seventh of that not on antiretroviral therapy (ARVs) (7 year decline in immune function) and 29% of those on ARVs in view of the high ARV resistance rates ( Table 3). We assumed a 20% rate of oesophageal candidiasis in advanced HIV disease patients and an additional 5% (conservative) in those on ARVs. 24

| Demographically
The population of Algeria was estimated at 43.6 million on 1 January 2021 with an average density of 18.40 inhabitants per km 2 . This average hides an uneven distribution on the territory with a concentration of between 250 and 3500 inhabitants per km 2 in the coastal areas for a density of less than 20 inhabitants per km 2 in the Saharan region.
The breakdown by age shows that more than half (54%) of the population is under 30 years old. Children aged 0-14 represent 29.5% of the population. For the distribution by sex, the numerical difference generally observed between men and women is not very large with a slight predominance of the male population (50.7%).  (Table 1).

| Economic characteristics
Access to care in all of these public healthcare structures is provided free for the population.
As for the private sector, in 2020 there were 407 clinics and 28,705 medical practices between specialist doctors, general practitioners and dental surgeons, and just over 10,985 pharmacies (Table 2).

| Human resources for health
More than a hundred specialists in parasitology-mycology work in public hospitals across the national territory.

| Cancer and transplantation
Algeria registers nearly 50,000 new cases of all types of cancer every year, according to data from the national cancer registry of the National Institute of Public Health (INSP). According to a multicentric national study, the overall incidence of lung cancer in Algeria is 3.4 cases per 100,000 inhabitants or a total of 1482 cases; with a male predominance (5.8) compared to female (1.0) ( Table 3). 10 The incidence of acute myeloid leukaemia in Algeria is 2.5/100,000 inhabitants (WHO) corresponding to 1090 cases (Table 3). Other haematological conditions including non-Hodgkin lymphoma, Hodgkin lymphoma and multiple myeloma are also factors favouring fungal infections and these conditions totalled 2531 cases in 2020. 30 In Algeria, kidney transplants are performed only from living donors. In 2019, there were only 268 kidney transplants and 11 liver transplants (Table 3). 31 As for allogeneic transplants, 160 cases are performed annually according to the Director General of the National Transplant Agency. 32 can deduce that the number of deaths is between 225 and 350 (average of 270 deaths). 4 Primary resistance of HIV to the three classes of antiretrovirals (NRTIs, NNRTIs and PIs) is estimated at 23.1% and secondary resistance to the same molecules was 60% in 2017. 33

| Tuberculosis, asthma and COPD
Tuberculosis is endemic in Algeria. Pulmonary localisation of TB is a key background for chronic pulmonary aspergillosis (CPA). According to national institute of public health (INSP) data, the prevalence of pulmonary tuberculosis is 11.37 cases per 100,000 inhabitants, that is, a total of 5035 cases (Table 3). According to the WHO, it is estimated at 18.5/100,000 inhabitants, a total of 8060 cases.

Number of beds
Asthma is a frequent pathology in Algeria and its prevalence is 4% in adults, that is, 1,227,776 cases, and 8% in children, equivalent to another 1,032,000 cases (Table 3). 34 In the international BREATHE study, 7 the prevalence of COPD in Algeria was estimated at 3.7% of the population, which corresponds to a total of 1,613,200 cases (

| Fungal asthma and fungal rhinosinusitis
Poor asthma control is common in adults in Algeria with fewer than 50% of patients well controlled. Assuming that 3.3% of adults have SAFS, which is amenable to oral antifungal therapy, we estimate a SAFS prevalence of 40,517 cases ( Table 4). Using the same denominator for ABPA, our prevalence estimate is 30,721 affected patients (Table 4) with some overlap between these two conditions. SAFS occurs in children, but there are not sufficient data yet to estimate its prevalence. Chronic rhinitis is common, and the proportion attributable to fungal allergy is extrapolated from an Indian study -0.11% of the population. 29 The estimate prevalence of chronic fungal rhinosinusitis (all its manifestations) including allergic, chronic granulomatous, eosinophilic and maxillary or sphenoid fungal ball is 47,960 cases (Table 4). We could find no direct corroborative data from Algeria, despite an active allergy and ear, nose and throat community.

| Neuromeningeal cryptococcosis
Cryptococcal meningitis is a major opportunistic infection common in PHIV with an advanced stage of immunosuppression. It can also be seen in other conditions such as lymphoid haemopathies or inflammatory diseases but also in immunocompetent patients. In Europe, it has clearly regressed among PHIV since the advent of ARV According to French multicentre studies, the incidence of peritoneal candidiasis can be estimated at half of the candidemia found in intensive care, which corresponds to 264 cases. We have used the more conservative number here.
A study carried out in Batna showed that C. parapsilosis is predominant (45%) in blood culture followed by C. albicans (40%). 25 In Algiers a study of isolates from seven hospitals 39

| Fungal infections in burns
In burn victims, local or general fungal infections are often serious.

| Ringworm of the scalp
Ringworm of the scalp (tinea capitis) is found especially in children 47,48 with a male predominance (Figure 1). The same situation pertains in Algeria. 49 The incidence varies from region to region. In one study carried out in schools in Tlemcen among 1631 children  (Table 4). This may be conservative as in Algiers, the prevalence was 33.5%. In Tlemcen Microsporum canis was the most frequent species, 50 whereas in Algiers it was Trichophyton violaceum (59.41%). 49

| Otomycosis
Otomycosis is a fungal infection mainly affecting the external auditory canal. It is often benign. Aspergillus niger complex are the most frequently responsible fungi. Candida otitis comes second in frequency. In Constantine, 59% of cases of otitis externa were mycotic with a predominance of Aspergillus niger (43%) followed by C. albicans (22%). 51 In Blida, the fungal proportion was nearly 33% (n = 267), including Candida spp. (62.5%), C. albicans (10.2%), A. niger (11.4%), A. flavus (9.1%) and A. fumigatus 4.6%. 52 In hearing aid wearers the prevalence of otomycosis is 51.9% with predominance of candidal aetiology compared to Aspergillus otitis. A. persii was described for the first time as an agent of otomycosis in three patients from western Algeria. 53

| Onychomycosis
Trichophyton rubrum is the predominant pathogenic fungus of onychomycosis in Algeria followed by C. albicans. 54 Cutaneous aspergillosis is a rare fungal disease in immunocompetent patients. Aspergillus flavus has been described as the causative agent of onychomycosis following traumatic plant inoculation (Figure 2). 55

| Neglected tropical fungal diseases
Sporadic cases of mycetoma have been reported in Algeria. The first case was described in 1894, by Vincent who isolated an actinomycete which he named Streptothrix madurae (probably Actinomadura madurae) from an Algerian case. 56 The latest was published in France in 2020 which reported a case of Actinomadura madurae in a patient from Kabylie in Algeria. 57 It was identified by molecular biology. Only two cases of chromoblastomycosis are described from Algeria, 58 and none of sporotrichosis.
Fungal keratitis is probably as common in Algeria as in other parts of North Africa, notably Egypt. 28 We have estimated an annual incidence based on population data from Egypt (14/100,000) indicating that there an estimated 6100 cases in Algeria each year ( Table 4).

| DISCUSS ION
Algeria is committed to setting up a health system accessible to all.  pathology. This inevitably means that some cases will be missed as standard haematoxylin and eosin staining is not sensitive enough.
On the other hand, serological methods to diagnose other common and rarer fungal infections such as aspergillosis (invasive or chronic), histoplasmosis (acute of chronic disseminated or chronic pulmonary), blastomycosis and coccidioidomycosis are not available.

The diagnostic capacity of invasive fungal infections in Algeria is
better provisioned in the north of the country, particularly in university hospitals.
In recent years, it has been observed that there is more interest in fungal infections as they are more and more frequent and serious with the increase in the risk factors already mentioned above.
Many end-of-study dissertations and medical science theses on fungal infections have been produced, but unfortunately the studies are short-lived and not published, which makes it difficult to utilise these data to estimate incidence or prevalence of specific fungal infections. These difficulties seem to be common to all the countries of North Africa.
According to studies, the risk factors for fungal infections are often underestimated. Asthma control in Algeria is sub-optimal, partly because of lack of use of use of long-acting bronchodilators and poor medication adherence in some patients. IgE testing in patients with poorly controlled asthma is infrequently done (23%), and so ABPA is likely to be frequently missed. Very few publications and specialists have focused on this topic area, leaving many patients undiagnosed and not optimally treated.
The primary limitation of this work is the lack of high quality epidemiological data for many fungal diseases. In the absence of large-scale epidemiological studies, estimates of fungal infections in methodology.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable to this article as no new data were created or analyzed in this study.