dr. ehsan ahmadpour (orcid id : 0000-0003-1202-6147) …...strongyloides stercoralis, and affects...
TRANSCRIPT
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leDR. EHSAN AHMADPOUR (Orcid ID : 0000-0003-1202-6147)
Article type : Review
Strongyloides stercoralis Infection in Human Immunodeficiency Virus
(HIV)-Infected Patients and Related Risk Factors: a Systematic Review
and Meta-analysis
Ehsan Ahmadpour1,2,*, Mohammad Ali Ghanizadegan3, Atefeh Razavi3, Mahsa Kangari3, Rouhollah Seyfi3, Maryam Shahdust3, Ali Yazdanian3, Hanie Safarpour3, Hossein Bannazadeh Baghi2,1, Mehdi Zarean4, Seyed Abdollah Hosseini5, Roghayeh Norouzi6, Mina Ebrahimi7, Berit Bangoura8
1Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 3Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 4Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 5Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran 6Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran 7Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 8Department of Veterinary Sciences, College of Agriculture and Natural Resources, University of Wyoming, Laramie, Wyoming, USA
*Corresponding authors: Ehsan Ahmadpour, Ph.D
Email: [email protected], [email protected]
Address: Department of Parasitology and Mycology, Tabriz university of Medical Sciences,
Tabriz, Iran
Tel: +98 413 5428595, Fax: +98 413 337 3745
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/tbed.13310This article is protected by copyright. All rights reserved.
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Abstract
Strongyloidiasis is caused by nematode infections of the genus Strongyloides, mainly
Strongyloides stercoralis, and affects tens of millions of people around the world. S.
stercoralis hyperinfection and disseminated strongyloidiasis are unusual but potentially fatal
conditions mostly due to Gram-negative bacteremia and sepsis, primarily affecting
immunocompromised patients. Infections with immunosuppressive viruses such as human
immunodeficiency virus (HIV) and Human T-cell leukemia virus type 1 (HTLV-1) have been
reported as risk factors for strongyloidiasis. Hyperinfection syndrome has been described in
HIV-positive patients following the use of corticosteroids or during immune reconstitution
inflammatory syndrome (IRIS). In this research, we conducted a global systematic review
and meta-analysis to assess the seroprevalence and odds ratios (ORs) of S. stercoralis
infections in HIV infected patients. A total of 3,649 records were screened, 164 studies were
selected and evaluated in more detail, and 94 studies were included in the meta-analysis. The
overall pooled prevalence of S. stercoralis infection in HIV positive patients was 5.1 %
(CI95%: 4 % - 6.3 %), and a meta-analysis on six studies showed that with a pooled OR of
1.79 (CI95%: 1.18 - 2.69 %) HIV positive men are at a higher risk of S. stercoralis infections
(P<0.0052) compared to HIV positive women.
Keywords: Strongyloidiasis, Human immunodeficiency virus, prevalence, systematic review
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Introduction
Nematoda, or roundworms, represent an important phylum of human and animal parasites.
Within the roundworms, the genus Strongyloides comprises several soil transmitted parasitic
species, some of which are zoonotic like Strongyloides (S.) stercoralis and S. fuelleborni
(Keiser & Nutman, 2004; Thanchomnang et al., 2017). Of those, S. stercoralis is of
worldwide importance, being endemic to tropical, subtropical, and temperate areas (Garcia,
1999; Segarra-Newnham, 2007). Interestingly, this nematode features two different life-cycle
forms, a free-living and a parasitic cycle. S. stercoralis infections in animals and humans
occur predominantly percutaneously by filariform larvae though an infection can also result
from oral uptake (Thamsborg, Ketzis, Horii, & Matthews, 2017). After penetrating the skin,
major proportion of the larvae enter vessels and are carried to the lungs. The larvae then
migrate through the lung tissue, are coughed up and swallowed with sputum, and finally
reach the small intestine. Other larvae can travel directly to the small intestine (Thamsborg et
al., 2017). Larvae mature into adult females in the intestinal mucosa, especially the
duodenum and upper jejunum. Females produce eggs by parthenogenesis, and mostly
rhabditiform larvae hatch already before eggs are passed into the environment. These hatched
larvae can either cause autoinfection or be passed in stool to initiate a free-living cycle (Olsen
et al., 2009). This worm infects more than 100 million people worldwide annually
(Puthiyakunnon et al., 2014). Autoinfection is repeated generations that appears when the
non-infective larvae become infective filariform larvae in the same host. The filariform larvae
could enter the intestinal wall or the perianal skin and will cause a persistent infection (Keiser
& Nutman, 2004).
Clinical signs and symptoms in infected humans vary greatly. More than 50 % of infected
patients are asymptomatic, while up to 2.5% of infected patients show a so-called
hyperinfection as result from autoinfection, i.e. reinfection with larvae produced by female
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worms present in the own intestine and subsequent systemic dissemination of disease (Lam,
Tong, Chan, & Siu, 2006; Segarra-Newnham, 2007). Hyperinfection occurs mostly in
patients with an impaired cell mediated immune system (Grove, 1996; Huis, Sun, Hung, &
Colebunders, 2012; Keiser & Nutman, 2004). Human immunodeficiency virus (HIV)
infection, Human T-cell leukemia virus type 1 (HTLV-1) infection, alcoholism, low
socioeconomic status, white race, male gender, corticosteroid therapy, hematologic
malignancy, and malnutrition have been reported as risk factors for strongyloidiasis
(Davidson, Fletcher, & Chapman, 1984; Jongwutiwes, Waywa, Silpasakorn,
Wanachiwanawin, & Suputtamongkol, 2014; Keiser & Nutman, 2004; Schär et al., 2013;
Walzer et al., 1982)
HIV infection is mainly sexually transmitted, however, people may also be infected by
contact with HIV-positive blood or vertically during pregnancy, childbirth and breast-feeding
(John-Stewart, 2018; UNICEF., HIV/AIDS., & Organization, 2002). The number of people
infected with HIV is estimated to be about 36.9 million (31.1 million–43.9 million)
worldwide (in 2017). Due to its detrimental effect on the human immune system, especially
depletion of CD4+ lymphocytes (Stricker et al., 1987; Veenhuis, Clements, & Gama, 2019),
HIV increases the probability of severe outcome in secondary infections by bacteria
(Pawlowski, Jansson, Sköld, Rottenberg, & Källenius, 2012), fungi (Moreira et al., 2016),
viruses - - -Samaniego, & Soriano, 2001), and also
parasites (Ahmadpour et al., 2014; Luft & Remington, 1992). Several studies have shown a
relation between HIV infection, S. stercoralis infection and hyperinfection (Hagelskjaer,
1994; Siegel & Simon, 2012). This systematic review and meta-analysis was designed to
comprehensively determine pooled seroprevalence of S. stercoralis in relation to confounding
factors for increased seropositivity in HIV positive population.
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Methods
Search strategy
The meta-analysis was performed in accordance with the Preferred Reporting Items for
Systematic Reviews and Meta-Analysis (PRISMA) statement (Moher, Liberati, Tetzlaff, &
Altman, 2009). Four databases, namely PubMed, Science Direct, Scopus, and Google scholar
were searched for articles solely in English that were published between January 2000 and
August 2017. Keywords f h w “ t n y i i i ” “Strongyloides
stercoralis” “S. stercoralis” “H n I n fi i n y Vi ” n “ HIV”.
Study selection
All descriptive, cross-sectional, case–control and epidemiology studies reporting on overall
prevalence rates for S. stercoralis infections in HIV infected populations were included.
Exclusion criteria included: articles that used diagnostic methods for detection of S.
stercoralis infection other than serological, microscopic, molecular test (PCR), culture,
and/or direct detection methods; articles written in a language other than English; non-peer
reviewed or popular scientific publications, abstracts, national conference proceedings; and
duplicate studies with overlapping data, studies with non-random sampling methods and
those studying specific limited populations (pregnant women, transplantation and cancer
patients). The suitability of all studies according to the defined criteria was judged
independently by three different authors. Any differences in judgment were resolved by
discussion among the authors. After selecting articles, the authors recorded relevant
information in a standard data extraction form. A flow diagram of the study selection process
is shown in Fig. 1.
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Data extraction
Precisely extracted information from the included studies (n = 94) was collected in a table.
Information collected referred to year of publication, first author, country and region of study,
study location, total sample size, number of male and female participants, number of subjects
with positive test results, age distribution, S. stercoralis diagnostic methods, CD4 count, and
cases of diarrhea.
Statistical analysis
The meta-analysis was performed using Comprehensive Meta-Analysis 2.2 software (Biostat
Inc., Englewood, NJ, USA). The pooled overall prevalence of S. stercoralis and its 95%
confidence interval was calculated using a random-effects model. In the subgroup analysis
the pooled prevalence of S. stercoralis, in different countries and regions and using different
diagnostic methods, was calculated. The forest plot, for the subgroup analysis of diagnostic
methods, was reported. Additionally, separate meta-analyses were performed on the eligible
studies to evaluate the effect of diarrhea, low CD4 count (< 200 /μ L) nd patient sex on
the risk of infection with S. stercoralis. Heterogeneity in all meta-analyses was assessed
using I2 in x n C h n’ Q t t. b i ti n bi w in E ’ int pt
and visual inspection of the funnel plot. The level of significance for all tests was p < 0.05.
Results
Study selection
The search in PubMed, Science Direct, Scopus, and Google scholar databases revealed 5,550
records. After removing duplicates, 3,649 records were screened using their titles and/or
abstracts. One-hundred sixty-four studies were selected to be evaluated in more detail using
their full-texts, and 94 studies were finally included in the meta-analysis (Fig. 1).
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Overall Prevalence
Collectively, a total of 26,473 individuals from 34 countries worldwide were included in the
meta-analysis (Table 1). The overall pooled prevalence of S. stercoralis infection in HIV-
positive (HIV+) patients was reported as 5.1 % (CI95%: 4 % - 6.3 %). Substantial
heterogeneity was observed between the included studies (I2: 95.1 %, p < 0.05). The
estimated pooled prevalence varied significantly using different diagnostic methods for
detection of S. stercoralis infection (p < 0.05). Most of the studies used microscopy to
diagnose the infection and detected a pooled prevalence of 3.6 % (CI95%: 2.6 % - 4.7 %)
(Fig. 2). The pooled estimate using culture (Fig. 3), serologic methods (Fig. 4) and PCR was
10.8 % (CI95%: 7.1 % - 15.1 %), 12.4 % (CI95%: 6.9 % - 19.3 %) and 3.9 % (CI95%: 2.1 %
- 6.1 %), respectively (Table 2). High heterogeneity was also observed in the subgroup meta-
analyses of diagnostic methods, except for PCR, which was only used by two studies. The
statistically significant E ’ i n p < 0.05) and the shape of funnel plot indicate that
there is a high probability of publication bias (Fig. 5).
Confounding Factors
The male to female ratio of participants was 45.5 % to 54.5 % and the average age was 34.2 ±
9.7 years. A meta-analysis on six studies showed that with a pooled OR of 1.79 (CI95%: 1.18
- 2.69) HIV+ men are at a higher risk of S. stercoralis infections (P<0.0052) compared to
HIV+ women (Table 3).
In a meta-analysis we performed on a subset of 14 eligible studies providing data on diarrhea
occurrence, participants with diarrhea had a pooled OR of 1.79 % (CI95%: 1.18 % - 2.69 %)
for the infection with S. stercoralis compared to participants without diarrhea (P<0.0005).
Moreover, a meta-analysis performed on eight eligible studies showed a pooled OR of 4.56
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(CI95%: 2.44 - 8.49) for acquiring an infection with S. stercoralis in patients with CD4+ cell
nt f t h n 200 /μ P<0.0001).
Geographic Distribution
The geographic distribution of studies significantly affected the pooled estimate (Fig. 6).
Regarding individual countries, the pooled estimate was highest in the US (25.5 %, CI95%:
20.3 % - 31.6 %) and lowest in Nepal (0.3 %, CI95%: 0.1 % - 1.1 %). Ethiopia was the
country with the highest number of studies with a pooled prevalence of 5.6% (CI95%: 3.7%-
8.3%). Moreover, the countries were grouped according to the WHO Global Burden of
Diseases regions and the pooled estimate significantly varied between the regions. Looking at
broader geographic regions, most of the studies were performed in the African Region with a
pooled prevalence of 4.2 % (CI95%: 3 % - 5.6 %). The highest prevalence was in the
Western Pacific region with 11.5 % (CI95%: 5.7 % - 22.0 %) and the lowest was in the
Eastern Mediterranean Region with 0.5 % (CI95%: 0.1 % - 1.8 %). The pooled estimate in
Region of the Americas, European Region and Asia Region were 11.3 % (CI95%: 5.7 % -
18.4 %), 8.6 % (CI95%: 3.5 % - 15.5 %) and 3.3 % (2.1 % - 4.9 %), respectively (Table 2).
Discussion
This study was designed to evaluate occurrence and risk factor for strongyloidiasis, a
neglected tropical disease which occurs worldwide, in HIV+ patients as a highly vulnerable
group. By reviewing published original articles on strongyloidiasis in HIV+ patients, we
assessed prevalence of S. stercoralis, geographic distribution, and additional risk factors for
this major risk population.
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Our analysis revealed a significant proportion of S. stercoralis positive cases within HIV+
patients (5.1 %). Immunocompromised people are the most at risk population for developing
fatal illnesses including strongyloidiasis (Henriquez-Camacho et al., 2016). Despite variable
strength of association, HIV infected individuals are more likely to acquire S. stercoralis
infections (Schär et al., 2013). Considering the differences in immunosuppression by drugs
such as corticosteroids and HIV, it was argued before that HIV patients may have a sustained
ability to control S. stercoralis infections making HIV less predisposing to this parasitosis
than other immunosuppressive conditions (Siegel & Simon, 2012). Accordingly, the most
severe clinical cases (hyperinfection syndrome) are seen rather in people with conditions like
the HLTV-1 infection than in HIV+ patients (Marcos, Terashima, DuPont, & Gotuzzo, 2008).
The results obtained from this systematic review showed that the prevalence rate of S.
stercoralis in HIV+ patients using serological method (12.4%) was higher than other methods
(3.6% microscopy, 10.8% culture and 3.9% molecular assays). According to our litterateur
review, the prevalence obtained though in general serological assays for detection of
pathogens can yield a low sensitivity in HIV+ individuals due to the potentially reduced
humoral immune response (Lindoso, Moreira, Cunha, & Queiroz, 2018; Segarra-Newnham,
2007). This is not attributed to certain diagnostic tests being preferred for studies in different
regions since all described tests have used widely in different regions (Table 2, Fig. 2-4).
Thus, serological testing, as a convenient method, is considered a suitable method for S.
stercoralis detection, along with direct detection methods (microscopy). Interestingly, the
serological methods for detecting S. stercoralis infection in HIV+ patients showed high rates
between the diagnostic methods deployed. This is in line with earlier findings of a generally
higher sensitivity of serological compared to microscopical assays (Gétaz et al., 2019) which
may lead to a comparatively high detection sensitivity of serology even in
immunocompromised individuals. Major complications arising from strongyloidiasis are a
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persistent infection following repeated autoinfection, systemic dissemination of larvae, and
accordingly the development of potentially fatal systemic disease. Though our study was not
designed to judge the prevalence differences between HIV+ and HIV- negative individuals, it
i t nn in t th inf ti n p v n ’ in HIV+ p ti nt f wi y within th n f
the (known) overall populations in the respective regions.
Over all analyzed studies in this review, 54% of participants in the study were female and
46% male which represents roughly even distribution with a minor underrepresentation of
male patients. However, male sex was identified as predisposing factor for the overall
prevalence, seemingly making male sex a risk factor for S. stercoralis infections among
HIV+ individuals (P= 0.0005). We assume sex to be a confounder since other factors and
conditions might be relevant that have been shown to represent risk factors for S. stercoralis
infections in regional populations (Gétaz et al., 2019) and may show a different distribution
over women compared to men (such as age, other health conditions, alcohol consumption,
etc.).
In this study, regarding clinical signs, the occurrence of diarrhea as a potential indicator of
S. stercoralis infection was analyzed. Accordingly, the likelihood of infection was
significantly higher among patients with diarrhea occurrence (P= 0.0052). Given that the
most important complications of S. stercoralis infections stem from larval dissemination,
leading to the hyperinfection syndrome.
Beside, HIV infection is progressively associated with decrease of CD4+ lymphocytes
(Bosinger & Utay, 2015). The results of this systematic review indicated that the lower CD4+
counts were correlated to a higher probability of S. stercoralis infection (P <0.0001),
underlining the importance of the immune system in eliminating the parasite without
prolonged auto-infections.
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General worldwide prevalence rates of S. stercoralis in humans have been assessed in
numerous studies. Estimated prevalence varies from three million to one hundred million
infected persons (Puthiyakunnon et al., 2014; Schär et al., 2013). However, more detailed
epidemiological data of national and local S. stercoralis infection rates and populations at risk
have increasing clinical value. To our knowledge, this is the first meta-analysis into report
prevalence rates on a country-by-country basis considering the sensitivity of the diagnostic
methods used. Regional differences may be linked to the general prevalence of the pathogen
in different areas. The results of the present systematic review show that there is a generally
higher human prevalence of S. stercoralis infection in America (11.3%) than in the rest of the
world (8.6% in Europe, 4.2% in Africa and 3.3% in Asia), however, these data are also
incomplete, and information on many countries is missing as of now (Schar et al., 2013;
Vermund, 2014). However, the comparatively low prevalence rates for S. stercoralis
infections in HIV+ patients in the Eastern Mediterranean region and the Southeast Asian
i n t t h th n y w p v n in th i n ’ p p ti n .
Looking at infection sources, circulation of S. stercoralis within the human population
occurs directly or via soil, while dogs seem host both S. stercoralis strains of zoonotic
potential and strains not transmissible to humans (Jaleta et al., 2017). Thus, prevalence in
animals may not be used directly to estimate the potential human prevalence. Besides the
obviously different infection pressure for humans in different areas of the world, the observed
publication bias in the analyzed studies (such as sample size, participant selection criteria,
study methodology, etc.) may contribute to our observations though we assume regional
differences to be present indeed (Schar et al., 2013).
Our review and analysis have several limitations. Looking at the available studies,
it becomes obvious that data on infection prevalence is scant for S. stercoralis. Many studies
are designed to detect other Soil Transmitted Helminthes (STHs), leading to use of direct
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diagnostic methods with a suboptimal sensitivity for S. stercoralis detection. Many studies
had to be excluded because of incomplete data and unspecific reports on helminth infections
though they may have included S. stercoralis. Thus, currently S. stercoralis prevalences are
probably underestimated, and the heterogeneous prevalence data reported may partially be
caused by flaws in methodology. Therefore, variations in study design and methodology
among the included studies are an important limitation of this analysis. Publication bias is an
important threat to the authority of systematic reviews. To decrease the risk of publication
bias, we did a comprehensive search across various databases. However, as for any
systematic review, we cannot dismiss the influence of publication bias.
We conclude that S. stercoralis is of great importance and available data on HIV+ patients
indicates a high prevalence. Thus, HIV+ patients globally should be checked routinely for
this neglected parasitic infection, since anthelmintic treatment is readily available for known
cases. Overall, future studies should be designed to specifically test for S. stercoralis in high
risk populations, such as HIV+ individuals, and should use highly sensitive diagnostic
methods, such as the Koga Agar plate culture or the Baermann technique or a serological
ELISA. Future studies should also include HIV- comparison groups to enable judgment of
HIV status as a risk factor, especially for severe outcomes (hyperinfection syndrome).
Acknowledgment
We appreciate the excellent help provided by Dr. Spotin.
Conflict of Interest
The authors declared that they have no competing interests.
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Ethical statement
Not applicable.
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Table 1 Baseline characteristics of the included studies
No. First Author Year of
publication
Country Number of
Samples
Number of
patients
% Pos Diagnostic Method
1 Prasad KN 2000 India 59 1 1.69 Microscopy
2 Dreyfuss ML 2001 Tanzania 822 12 1.45 Microscopy
3 Feitosa G 2001 Brazil 365 20 5.47 Culture
4 Gassama A 2001 Senegal 318 3 0.94 Microscopy
5 Lebbad M 2001 Guinea-Bissau 37 5 13.51 Microscopy
6 Waywa D 2001 Thailand 288 23 7.98 Culture
7 Wiwanitkit V 2001 Thailand 60 2 3.33 Microscopy
8 Dowling JJ 2002 Malawi 162 8 4.93 Culture
9 Joshi M 2002 India 94 5 5.31 Microscopy
10 Adjei A 2003 Ghana 21 1 4.76 Serology
11 Arenas-Pinto A 2003 Venezuela 304 32 10.52 Culture
12 Botero JH 2003 Colombia 36 2 5.55 Culture
13 Datta D 2003 England 525 1 0.19 Microscopy
14 Kassu A 2003 Ethiopia 23 5 21.7 Culture
15 Marchi Blatt J 2003 Brazil 211 21 9.95 Culture
16 Okodua M 2003 Nigeria 35 1 2.85 Microscopy
17 Brown M 2004 Uganda 547 68 12.43 Culture
18 Hailemariam G 2004 Ethiopia 78 4 5.12 Microscopy
19 Kaminsky RG 2004 Honduras 133 10 7.51 Culture
20 Viney ME 2004 Uganda 700 84 12 Culture
21 Zali MR 2004 Iran 206 2 0.97 Microscopy
22 Pinlaor S 2005 Thailand 78 14 17.94 Microscopy
23 Silva CV 2005 Brazil 100 12 12 Culture
24 Chhin S 2006 Cambodia 80 12 15 Culture
25 Garcia C 2006 Peru 217 15 6.91 NR
26 Hosseinipour MC 2007 Malawi 266 2 0.75 Microscopy
27 Meamar AR 2007 Iran 781 2 0.25 Microscopy
28 Vignesh R 2007 India 245 3 1.22 Microscopy
29 Bachur TP 2008 Brazil 582 156 26.8 Microscopy
30 Lillie PJ 2008 England 107 2 1.86 Microscopy
31 Mariam ZT 2008 Ethiopia 109 7 6.42 Microscopy
32 Assefa S 2009 Ethiopia 214 27 12.61 Microscopy
33 Kawai K 2009 Tanzania 971 13 1.33 Microscopy
34 Kurniawan A 2009 Indonesia 318 1 0.31 Microscopy
35 Lule JR 2009 Uganda 491 90 18.32 Microscopy
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36 Viriyavejakul P 2009 Thailand 64 2 3.12 Microscopy
37 Werneck-Silva AL 2009 Brazil 690 1 0.14 NR
38 Getaneh A 2010 Ethiopia 192 23 11.97 Microscopy
39 Telele NF 2010 Ethiopia 143 14 9.79 NR
40 Tian L.G. 2010 China 46 0 0 Culture
41 Walson JL 2010 Kenya 1541 4 0.25 Microscopy
42 Akinbo FO 2011 Nigeria 2000 23 1.15 Microscopy
43 Alemu A 2011 Ethiopia 188 3 1.59 Microscopy
44 Brites C 2011 Brazil 123 6 4.87 NR
45 Cardoso LV 2011 Brazil 500 1 0.2 Culture
46 Chordia P 2011 India 239 14 5.85 Microscopy
47 Hochberg NS 2011 US 128 33 25.78 Serology
48 Idindili B 2011 Tanzania 421 57 13.53 Microscopy
49 Mascarello M 2011 Italy 138 15 10.86 Serology
50 Ojurongbe O 2011 Nigeria 96 1 1.041 Microscopy
51 Sanyaolu A 2011 Nigeria 65 1 1.53 Microscopy
52 Abaver D.T. 2012 Nigeria 480 5 1.04 Microscopy
53 Boaitey Y.A. 2012 Ghana 500 2 0.4 Microscopy
54 Boaitey YA 2012 Ghana 500 2 0.4 Microscopy
55 Costiniuk CT 2012 Canada 96 10 10.41 Serology
56 Nabha L. 2012 US 103 26 25.24 Serology
57 Roka M. 2012 Guinea 260 23 8.84 Microscopy
58 Sivaram M 2012 England 263 3 1.14 Microscopy
59 Tabaseera N 2012 Tanzania 100 0 0 Microscopy
60 Arndt MB 2013 Kenya 153 5 3.26 PCR
61 Dash M 2013 India 115 3 2.6 Microscopy
62 Fekadu S. 2013 Ethiopia 343 56 16.32 Microscopy
63 Gupta K. 2013 India 100 1 1 Microscopy
64 Janagond AB 2013 India 100 2 2 Microscopy
65 Kulkarni S 2013 India 65 1 1.53 Microscopy
66 Llenas-García J 2013 Spain 237 13 5.48 Serology
67 Mehta K.D. 2013 India 100 3 3 Microscopy
68 Mulu A 2013 Ethiopia 220 3 1.36 Microscopy
69 Rivero-Rodríguez 2013 Venezuela 56 15 26.78 Microscopy
70 Roka M. 2013 Guinea 273 28 10.25 Microscopy
71 Sadlier CL 2013 Ireland 90 2 2.22 Serology
72 Salvador F 2013 Spain 190 35 18.42 Serology
73 Teklemariam Z 2013 Ethiopia 371 15 4.04 Microscopy
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NR: not reported
74 Tiwari BR 2013 Nepal 745 2 0.26 Microscopy
75 da Silva H. 2014 Brazil 15 7 46.66 Culture
76 Mahmud M.A 2014 Ethiopia 372 1 0.26 Microscopy
77 Nkoa T 2014 Cameroon 332 3 0.9 Microscopy
78 Paboriboune P 2014 Laos 137 28 20.43 Microscopy
79 Salvador F 2014 Spain 28 13 46.42 Culture
80 Taye B 2014 Ethiopia 316 13 4.11 Microscopy
81 Vouking M.Z 2014 Cameroon 207 7 3.38 Microscopy
82 Ahmed NH 2015 India 142 5 3.52 Microscopy
83 Angal L 2015 Malaysia 131 9 6.87 Microscopy
84 Mengist HM 2015 Ethiopia 180 9 5 Microscopy
85 Mulu A. 2015 Ethiopia 105 4 3.8 Microscopy
86 Plumelle Y 2015 France 445 55 12.35 Microscopy
87 Hailu AW 2016 Ethiopia 18 5 27.77 Culture
88 Nsagha DS 2016 Cameroon 300 2 0.66 Microscopy
89 Shah S 2016 India 45 1 2.22 Microscopy
90 Shimelis T 2016 Ethiopia 491 22 4.48 Microscopy
91 Gedle D 2017 Ethiopia 323 5 1.54 Microscopy
92 Morawski BM 2017 Uganda 202 8 3.96 PCR
93 Senbeta D 2017 Ethiopia 238 7 2.94 Microscopy
94 Swathirajan CR 2017 India 829 15 1.8 Microscopy
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Table 2. Pooled prevalence of S. stercoralis in HIV positive patients and subgroup analyses.
Group Number of
studies
Pooled Prevalence
(CI 95%)
Heterogeneity
P value I2 Cochran Q
Total 94 5.1% (4%-6.3%) < 0.001 95.1% 2179.6
Diagnostic Method
Microscopy 73 3.6% (2.6%-4.7%) < 0.001 95% 1442.9
Culture 17 10.8% (7.1%-15.1%) < 0.001 92.3% 207.3
Serology 8 12.4% (6.9%-19.3%) < 0.001 88.7% 61.8
Molecular 2 3.9% (2.1%-6.1%) 0.763 - 0.09
The continent
America 17 11.3% (5.7%-18.4%) <0.0001 97.6 668.8
Europe 10 8.6% (3.5%-15.5%) <0.0001 95.9 221.8
Asia 29 3.3% (2.1%-4.9%) <0.0001 88.5 242.4
Africa 52 4.2% (3%- 5.6%) <0.0001 94.8 982.5
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leTable 3. Risk factors associated to Strongyloides stercoralis infection in HIV patients
Risk
factors Categories df
% Prevalence
(CI 95%)
Odds ratio Heterogeneity Publication bias
OR (95% CI) P-value I²
Cochran Q P-value Egger bias P-value
Sex Male
Female 5
14.43 (5 – 27.44)
10 (3 – 19) 1.93 (1.33-2.81) 0.0005 9.2% 5.51 0.357 -0.96 0.414
Diarrhea Yes
No 13
10.32 (5.89 – 15.82)
5.45 (1.56 – 11.52) 1.78 (1.18-2.69) 0.0052 28% 12.5 0.186 1.03 0.194
CD4+ < 200 cells/µl
> 200 cells/µl 7
8.14 (2.71 – 16.1)
1.41 (0.18 – 3.76) 4.56 (2.44-8.49) <0.0001 0% 5.29 0.624 0.82 0.19
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This article is protected by copyright. All rights reserved.
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This article is protected by copyright. All rights reserved.
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This article is protected by copyright. All rights reserved.
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This article is protected by copyright. All rights reserved.
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This article is protected by copyright. All rights reserved.
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This article is protected by copyright. All rights reserved.