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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 14  |  Issue : 1  |  Page : 12-21

Burden, mortality, and associated factors of Pneumocystis jerovesi pneumonia among human immunodeficiency virus/AIDS patients: Systematic review and meta-analysis


Department of Medical Laboratory Science, College of Health Science and Medicine, Dilla University, Dilla, Ethiopia

Date of Submission03-Apr-2020
Date of Acceptance15-Oct-2020
Date of Web Publication09-Feb-2021

Correspondence Address:
Mr. Ephrem Awulachew
Department of Medical Laboratory Science, College of Health Science and Medicine, Dilla University, Dilla, Ethiopia
Ethiopia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_104_20

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  Abstract 


Pneumocystis pneumonia has classically been described as a serious complication in human immunodeficiency virus (HIV) infected patients caused by Pneumocystis Jirovecii pneumonia formerly called Pneumocystis Carinii Pneumonia (PJP). During the early period of the Acquire Immunodeficiency Syndrome (AIDS) epidemic, PJP was recognized as one of the AIDS-defining illnesses for as many as two-thirds of patients in the United States. Despite the introduction of combination antiretroviral therapy for the human immunodeficiency virus (HIV), PJP remains one of the leading causes of morbidity and mortality. The aim of the present study was to review existing literature on the burden, a mortality rate of PJP among HIV/AIDS patients and its associated factors. A total of 65 studies were eligible and included in this review. A meta-analysis by random effect model showed that the estimated pooled prevalence of PJP 15% (38,881/293,239; 95% confidence interval [CI]: 12%–21%). According to pooled estimates of this study, the overall mortality rate of PJP among HIV/AIDS patients was about 25% We demonstrated that CD4 level was significantly related to PJP infection, where the highest risk patients are those with CD4 count <200 cells/μl (odds ratio: 1.81, 95% CI: 1.22–2.69, P < 0.01). According to the pooled estimates of this study, PJP among HIV/AIDS patients was the cause of a high rate of morbidity and mortality.

Keywords: Acquired immunodeficiency syndrome, Pneumocystis carinii pneumonia, Pneumocystis jirovecii pneumonia


How to cite this article:
Awulachew E, Diriba K, Anja A, Wudneh F, Gemede A. Burden, mortality, and associated factors of Pneumocystis jerovesi pneumonia among human immunodeficiency virus/AIDS patients: Systematic review and meta-analysis. Indian J Health Sci Biomed Res 2021;14:12-21

How to cite this URL:
Awulachew E, Diriba K, Anja A, Wudneh F, Gemede A. Burden, mortality, and associated factors of Pneumocystis jerovesi pneumonia among human immunodeficiency virus/AIDS patients: Systematic review and meta-analysis. Indian J Health Sci Biomed Res [serial online] 2021 [cited 2021 Apr 22];14:12-21. Available from: https://www.ijournalhs.org/text.asp?2021/14/1/12/308942




  Introduction Top


Pneumocystis jirovecii pneumonia (PJP) previously called Pneumocystis carinii pneumonia (PCP) is an obligate extracellular pathogen that exists in trophic and cystic forms.[1],[2] Initially, it was classified as a protozoan, but currently, it is reclassified as a fungus based on greater DNA sequence homology with fungal organisms.[3],[4] PCP infection thought to be acquired during childhood[5],[6] or the illness will be either developed from reactivation of latent infection when the host's immune system was compromised[7],[8] or de novo exposure from the environment or from individuals with PCP.[9],[10]

PJP cause of HIV-associated pneumonia called Pneumocystis pneumonia (PCP) that has classically been described as a serious complication in human immunodeficiency virus (HIV) infected patients.[11] During the early period of the acquired immunodeficiency syndrome (AIDS) epidemic, PCP was recognized as one of the AIDS-defining illnesses for as many as two-thirds of patients in the United States.[12],[13]

PCP occurs in advanced HIV disease usually in patients with a CD4 count < 200 cells/mm3.[14],[15] The symptoms are: Indolent with fever, nonproductive cough, and progressive dyspnea out of proportion to the cough. Fever is present in the majority of cases. Fatigue and night sweats may appear before respiratory symptoms.[16] Physical signs and radiological changes occur in the late stage of the infection.[8],[17]

Before the widespread use of PCP prophylaxis and antiretroviral therapy (ART), PCP occurred in 70%–80% of patients with AIDS. The mortality rate for HIV-infected patients with PCP ranged from 11% to 53%.[18] With the advent of highly active ART for the treatment of HIV infection, there has been a decrease in the incidence of PCP.[19] Despite the introduction of combination ART for the HIV infection, PCP remains one of the leading causes of morbidity and mortality in naïve HIV-infected patients, in a patient with poor adherence, in those who are unable to tolerate ART or in those with drug resistance HIV virus infection.[20],[21] The reemergence of PCP has been recognized after the advent of drug-resistant HIV strain.[22],[23]

Several factors associated with PJP infection in HIV-infected patients. The number of CD4 counts (<200/μl), age, AIDS stage, nutrition, and viral load have been established as a risk factor of PCP.[24],[25] However, among the patients who developed AIDS due to advanced HIV infection, the prevalence of PCP is varied between countries; around 10% and 50%.[26],[27] Because of high mortality rate, scholars take an effort to determine events affecting mortality earlier for providing better care and outcomes in hospitals. Early detection and treatment of P. pneumonia have been known to improve the quality and length of life of people living with HIV.[28]

Hence, knowledge of the burden of PCP among HIV infected patient and its associated factors have invaluable importance in improving management and care of HIV-infected patients. A better understanding of PJP prevalence will also help to inform health professionals to improve empiric prescription of drugs and will help manage cases with full awareness. To the best of our knowledge, limited data are available on the prevalence of PJP and associated factors in HIV/AIDS patients. Our main aim was to determine the prevalence of PJP infection among HIV-infected patients. Second, we aimed to include associated factors and attributable mortality and case fatality. This will help policymaker and it also helps health professionals in evidence-based clinical medicine.


  Methodology Top


Objectives

The aim of systematic review and meta-analysis was to review exiting literature on the prevalence of PJP infection and its associated factors among HIV/AIDS patients.

Types of participants

All HIV-infected patients with PCP are study participant


  Data Sources and Search Strategy Top


We searched literatures published in English January 2001 to March 20/2020 on electronic data bases PubMed, EMBASE, Escopus, Hinari, CINAHL, Open Access Journals, and Google scholar, for studies that reported the prevalence, associated factors of PCP in HIV-infected patients. We simultaneously searched reference lists of all recovered articles for potentially eligible studies. All identi?ed keywords, and mesh terms were combined using the “OR” operator and “AND” operator for searching literatures. Keywords used in the search included those that express PJP and Human Immuno Virus (HIV) infection (i.e., pneumocystis, PJP, PCP, opportunistic infections, HIV, HIV, AIDS, and HIV/AIDS). Full-text articles were retrieved after review of the title and abstract.

Inclusion and exclusion criteria

Inclusion criteria

All studies published in English from 2001 to March 20, 2020 were included in the review. The method of diagnosis is restricted to microscopy, ELISA and molecular techniques (i.e., Western blot, polymerase chain reaction [PCR], and DNA extraction).

Exclusion criteria

Case reports and case series were excluded.

Selection of studies

Two authors (EA and AA) independently checked the titles and abstracts resulting from the searches. Relevant titles and abstracts were then selected by EA, AA, and KD. EA and AA assessed all full-text articles for methodological quality. References of search results were manipulated using Endnote 5 citation manager.

Assessment of methodological quality

Studies selected for inclusion were assessed for methodological quality by two independent reviewers (EA and AA) using standard critical appraisal instruments of the Joanna Briggs Institute (JBI-MAStARI).[29] For inclusion in the review, both reviewers agreed that a cut off score of 6 out of 10 points be used to determine acceptable quality for inclusion.

Ten methodological assessment criteria for quality assessment of included study were the following: Objective of the study clearly described, study design clearly stated, sample size representativeness, method of detection of the fungi, outcome assessed with the objective criteria, were confounders reported, were potential biases reported, was outcome clearly described, appropriate statistical analysis method used.

Data extraction

Data were extracted from included study by three investigator (EA, AA, and KD) using a standardized data extraction form. Then, the extracted data were merged together for systematic review and meta-analysis. Primary outcomes extracted from each study were, the citation details, sample size, number of cases, year of publication, location of study, and method of identification of PJP. Secondary outcomes for this study included clinical data including whether the patient started ART treatment or not, a CD4 count of the patients, and distribution of PJP by age, sex of the patients

Statistical analysis

The R software was used to pool the mean from the included studies with user contributed commands for meta-analyses: Metaprop, metainf, metabias, and metareg. The random-effects meta-analysis models were chosen because heterogeneity was demonstrated

Risk of bias and sensitivity analysis

We tested the presence of heterogeneity with the Cochrane Q test and I2 statistic.[30] A significance level of P < 0.10 and I2 > 50% was interpreted as evidence of heterogeneity.[31] A potential source of heterogeneity was investigated by subgroup analysis and meta-regression analysis.[32] The presence of publication bias was assessed informally by visual inspections of funnel plots.[33] Sensitivity analysis was conducted to explores the effects of the addition/removal of lower quality studies on the results and conclusions of a review was reported.[30]


  Results Top


Identified studies

Following the initial search, 269 studies were reviewed by their title and abstract [Figure 1]. Of these 87 duplicate papers were removed. One hundred and eighty-two papers were retrieved for full-text review, 72 did not match the eligibility criteria for the study for most of the studies were conducted before 2001. Following methodological quality assessment, 65 articles were included in this systematic review and meta-analysis. In the included studies the total of 293,239 HIV-infected patients were assessed for PJP infection and the total events were about 38,881. All papers were published in English.
Figure 1: Flow chart of the search and study inclusion

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Characteristics of included study

Of the 65 studies included in the systematic review and meta-analysis, four studies was a cohort study,[13],[34],[35],[36],[37] eleven studies were retrospective studies,[38],[39],[40],[41],[42],[43] and 50 were cross sectional studies [Table 1].[13],[15],[16],[27],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72],[73],[74]
Table 1: Characteristics of included study

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Qualitative summary

From the total of 65 study included in the systematic review and meta-analysis, in most of eligible studies, cases of PJP infection were diagnosed using PCR (84.3%), 8 studies were identified PJP using ELISA, IFT, and other serologic techniques while only one study conducted microscopic examination techniques form bronchoalveolar lavage. Most of the studies conducted are of higher quality because of method of diagnosis using highly sensitive and specific PCR techniques.

Meta-analysis outcome

The prevalence of PJP infection among HIV/AIDS patients ranged between 2% and 88.8%.[34],[69] According to data from 65 included studies systematic review and meta-analysis by random effect model showed that the estimated pooled prevalence of PJP is 15% (38,881/293, 239; 95% confidence interval [CI]: 12%–21%) [Figure 2]. Test of heterogeneity showed that it is heterogeneous (t2 = 1.7512; I2 = 100%, P < 0.01). According to pooled estimates of included studies, the mortality rate of PJP among HIV/AIDS patients was about 25% (95% CI: 15%–35%, P < 0.01) [Figure 3]. Pre-ART HIV-infected patients had 1.64 times likely die off PJP infection than those already started ART. The highest mortality observed in Asia (42%, 95% CI: 27%–58%, P < 0.01) while the least mortality rate was observed in America (11%, 95% CI: 6%–19%, P < 0.01) [Table 2].
Figure 2: Prevalence of Pneumocystis jirovecii pneumonia among human immunodeficiency virus/AIDS patients

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Figure: 3 Association between CD4 count and prevalence of Pneumocystis carinii pneumonia infection among human immunodeficiency virus AIDS patients

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Table 2: Prevalence, mortality due to Pneumocystis carinii pneumonia among human immunodeficiency virus acquire immunodeficiency syndrome patients in different continents

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Additional analysis

This review also extracted additional data on PJP infection from the included study. Due to the variability of data quality and reporting system, we only extracted and analyzed the data on gender, ART, and CD4 count. This study demonstrated that males are more likely develop the highest incidence of PJP than females (odds ratio [OR]: 1.81, 95% CI: 1.22–2.69, P = 0.031). According to the pooled data of five studies, we demonstrated that CD4 level was significantly related to PJP infection, where the highest risk patients are those with CD4 level < 200 cells/μl (OR: 2.88, 95% CI: 2.24–3.7, P = 0.004) [Figure 3]. According to this study highly active anti-retroviral therapy was found to be protective against PJP infection where the highest incidence occurred in HIV/AIDS patients that had not started ART (OR: 1.37, 95% CI: 1.23–1.52).

Risk of bias and sensitivity analysis

Subgroup analysis was conducted to justify the cause of heterogeneity. The possible cause of heterogeneity probably is the continent, economic statue of the countries. Unfortunately, the specific cause of heterogeneity cannot be identified due to limited data are available.

Subgroup analysis of the included study showed that the highest incidence of PJP infection among HIV/AIDS was observed in Europe (24%, 95% CI: 15%–35%, P < 0.01) followed by Africa (14%, 95% CI: 9%–23%, P < 0.01) and Asia (12%) while the lowest prevalence of PJP observed in America (10%) [Figure 4].
Figure: 4 Mortality rate of Pneumocystis carinii pneumonia among human immunodeficiency virus/AIDS patients

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The funnel plot helped us distinguish between publication bias and other causes of the asymmetry. Funnel plots did not suggest a publication bias for the majority of the risk factors. We demonstrated no publication bias (P = 0.1927). We have also conducted influence analysis of individual studies.


  Discussion Top


Summary of evidence

The aim of the review was to estimate the prevalence of PJP and associated factors among HIV/AIDS patients. Our findings demonstrated evidence for a high prevalence of PJP among HIV-infected patients. A high burden of PJP infection in this review indicates the importance of critical consideration of P. pneumonia in all HIV-infected people.

The subgroup analysis by continent showed that high prevalence PJP among HIV/AIDS patients was seen in Africa (18%) followed by Asia (14%) and Europe (16%), while America had the list prevalence (11%) of PJP among HIV/AIDS patients. On the other hand, the highest mortality was observed in Asia (42%) followed by Europe (25%) and Africa (24%), while the least mortality rate was observed in America (11%). The mortality reported in Africa was probably low because of the absence of well-structured report of causes of death, and absences of laboratory facility diagnose PJP.

The prevalence of PJP varies depending on the CD4 count, ART status.[46] On the other hand, the prevalence of PJP infection among HIV/AIDS may vary even within a country and continent. Africa had the highest prevalence of PJV among HIV-infected patients followed by Asia. This might be due to socioeconomic status of the countries. According the pooled data of included studies; we demonstrated that ART, CD4 count was significantly related to PJP infection among HIV/AIDS patients in comparison with their control. HIV/AIDS patients with CD4 level lower than 200 cells/μl were 2.88 times likely to be infected by PJP and Naïve HIV patient were 1.75 times likely to develop PJP infection than ART started patients. According to finding from this study, the incidence of PJP infection in HIV-infected patients fell substantially with the widespread use of ART and PJP prophylaxis. Most cases of PJP now occur in patients who are not receiving ART and when the CD4 + cell count is below 200 cells/μl.

To explain the possible causes of heterogeneity, we conducted meta-regression and subgroup analyses on various sources including country, and continent found different main causes of heterogeneity for PJP infection. These may come from publication year (P < 0.001), difference in selection of participant and ART status (P < 0.01). Other potential causes of heterogeneity may include sample size, and detection methods. Due to missing data, we did not analyze them.

Limitation

However, this systematic review and meta-analysis came up with the burden, mortality rate of PJP, and associated factors among HIV/AIDS patients; we acknowledge few limitations of the present systematic review and meta-analysis, which may affect the results. First of all, two relevant studies which were identified through our literature search were excluded due to unavailability for full-text review. The other limitation was the high degree of heterogeneity in the prevalence findings from different studies. This might be due to the difference in study participant selection in different studies. It could also be by some undefined environmental or biological differences exist across geographic locations to explain the observed heterogeneity, but our study unable to address it because of limited data were available.


  Conclusions Top


The results of our systematic review and meta-analysis showed a heavy burden and mortality rate of PJP infection among HIV/AIDS patients. Thus, routine screening of P. pneumonia should be done, particularly for those who have a CD4 count < 200 cells/μl and early prophylaxis and treatment should be administered.

Availability of data and materials

All the datasets generated and analyzed during the review are included in this article.

Financial support and sponsorship

This manuscript was prepared independently without any funding support.

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Huang L. Clinical and translational research in pneumocystis and Pneumocystis pneumonia. Parasite 2011;18:3-11.  Back to cited text no. 1
    
2.
Carini A. Formas des eschizogonia do Trypanosoma lewisi. Soc Med Cir Sao Paulo 1910;38:8.  Back to cited text no. 2
    
3.
Edman JC, Kovacs JA, Masur H, Santi DV, Elwood HJ, Sogin ML. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988;334:519-22.  Back to cited text no. 3
    
4.
Lugli EB, Bampton ET, Ferguson DJ, Wakefield AE. Cell surface protease PRT1 identified in the fungal pathogen Pneumocystis carinii. Mol Microbiol 1999;31:1723-33.  Back to cited text no. 4
    
5.
Wakefield AE. DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora. J Clin Microbiol 1996;34:1754-9.  Back to cited text no. 5
    
6.
Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: Evidence for high prevalence in normal and immunosuppressed children. Pediatrics 1978;61:35-41.  Back to cited text no. 6
    
7.
Stringer JR, Walzer PD. Molecular biology and epidemiology of Pneumocystis carinii infection in AIDS. AIDS 1996;10:561-71.  Back to cited text no. 7
    
8.
Wolff L, Horch S, Gemsa D. The development of Pneumocystis carinii pneumonia in germ-free rats requires immunosuppression and exposure to the Pneumocystis carinii organism. Comp Immunol Microbiol Infect Dis 1993;16:73-6.  Back to cited text no. 8
    
9.
Casanova-Cardiel L, Leibowitz MJ. Presence of Pneumocystis carinii DNA in pond water. J Eukaryot Microbiol 1997;44:28S.  Back to cited text no. 9
    
10.
Gianella S, Haeberli L, Joos B, Ledergerber B, Wüthrich RP, Weber R, et al. Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients. Transpl Infect Dis 2010;12:1-0.  Back to cited text no. 10
    
11.
Harpaz R, Dahl RM, Dooling KL. Prevalence of immunosuppression among US adults, 2013. JAMA 2016;316:2547-8.  Back to cited text no. 11
    
12.
Anonymous. HIV/AIDS Surveillance Report. Atlanta, GA: Centers for Disease Control and Prevention; 2009. p. 19.  Back to cited text no. 12
    
13.
Mahdavi S, Malyuta R, Semenenko I, Pilipenko T, Thorne C: Ukraine European Collaborative Study Group. Treatment and disease progression in a birth cohort of vertically HIV-1 infected children in Ukraine. BMC Pediatr 2010;10:85.  Back to cited text no. 13
    
14.
Manzardo C, Esteve A, Ortega N, Podzamczer D, Murillas J, Segura F, et al. Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: The experience of the PISCIS Cohort. Clin Microbiol Infect 2013;19:646-53.  Back to cited text no. 14
    
15.
Gautam H, Bhalla P, Saini S, Uppal B, Kaur R, Baveja CP, et al. Epidemiology of opportunistic infections and its correlation with CD4 T-lymphocyte counts and plasma viral load among HIV-positive patients at a tertiary care hospital in India. J Int Assoc Physicians AIDS Care (Chic) 2009;8:333-7.  Back to cited text no. 15
    
16.
Chakaya JM, Bii C, Ng'ang'a L, Amukoye E, Ouko T, Muita L, et al. Pneumocystis carinii pneumonia in HIV/AIDS patients at an urban district hospital in Kenya. East Afr Med J 2003;80:30-5.  Back to cited text no. 16
    
17.
Datta S, Mahal S, Ravat V, Saroha B, Isidahome EE, Patel P. Hospitalization outcomes in Pneumocystis pneumonia inpatient population: A comparison between HIV and Non-HIV Patients. Cureus 2018;10:e3082.  Back to cited text no. 17
    
18.
Radhi S, Alexander T, Ukwu M, Saleh S, Morris A. Outcome of HIV-associated Pneumocystis pneumonia in hospitalized patients from 2000 through 2003. BMC Infect Dis 2008;8:118.  Back to cited text no. 18
    
19.
Helweg-Larsen J, Benfield T, Atzori C, Miller RF. Clinical efficacy of first- and second-line treatments for HIV-associated Pneumocystis jirovecii pneumonia: A tri-centre cohort study. J Antimicrob Chemother 2009;64:1282-90.  Back to cited text no. 19
    
20.
Kaplan JE, Hanson D, Dworkin MS, Frederick T, Bertolli J, Lindegren ML, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis 2000;30 Suppl 1:S5-14.  Back to cited text no. 20
    
21.
Kales CP, Murren JR, Torres RA, Crocco JA. Early predictors of in-hospital mortality for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Arch Intern Med 1987;147:1413-7.  Back to cited text no. 21
    
22.
Morris A, Lundgren JD, Masur H, Walzer PD, Hanson DL, Frederick T, et al. Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis 2004;10:1713-20.  Back to cited text no. 22
    
23.
Llibre JM, Revollo B, Vanegas S, Lopez-Nuñez JJ, Ornelas A, Marin JM, et al. Pneumocystis jirovecii pneumonia in HIV-1-infected patients in the late-HAART era in developed countries. Scand J Infect Dis 2013;45:635-44.  Back to cited text no. 23
    
24.
Mori S, Sugimoto M. Pneumocystis jirovecii pneumonia in rheumatoid arthritis patients: Risks and prophylaxis recommendations. Clin Med Insights Circ Respir Pulm Med 2015;9:29-40.  Back to cited text no. 24
    
25.
Pettit AC, Giganti MJ, Ingle SM, May MT, Shepherd BE, Gill MJ, et al. Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation. J Int AIDS Soc 2018;21:e2503.  Back to cited text no. 25
    
26.
Morrow BM, Samuel CM, Zampoli M, Whitelaw A, Zar HJ. Pneumocystis pneumonia in South African children diagnosed by molecular methods. BMC Res Notes 2014;7:26.  Back to cited text no. 26
    
27.
Huang L, Cattamanchi A, Davis JL, den Boon S, Kovacs J, Meshnick S, et al. HIV-associated Pneumocystis pneumonia. Proc Am Thorac Soc 2011;8:294-300.  Back to cited text no. 27
    
28.
Torres J, Goldman M, Wheat LJ, Tang X, Bartlett MS, Smith JW, et al. Diagnosis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients with polymerase chain reaction: A blinded comparison to standard methods. Clin Infect Dis 2000;30:141-5.  Back to cited text no. 28
    
29.
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation. BMJ 2015;350:g7647.  Back to cited text no. 29
    
30.
Armstrong R, Waters E, Jackson N. Guidel ines for Systematic Reviews of Heal th Promotion and Public Health Interventions. Ver. 2. Australia: Melbourne University; 2007.  Back to cited text no. 30
    
31.
Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: A comparison of methods. Stat Med 1999;18:2693-708.  Back to cited text no. 31
    
32.
The Joanna Briggs Institute. Joanna Briggs Institute Reviewers' Manual Edition; 2014.  Back to cited text no. 32
    
33.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.  Back to cited text no. 33
    
34.
Zar HJ, Alvarez-Martinez MJ, Harrison A, Meshnick SR. Prevalence of dihydropteroate synthase mutants in HIV-infected South African children with Pneumocystis jiroveci pneumonia. HIV/AIDS 2004;39:1047.  Back to cited text no. 34
    
35.
Sharma SK, Kadhiravan T, Banga A, Goyal T, Bhatia I, Saha PK. Spectrum of clinical disease in a series of 135 hospitalised HIV-infected patients from north India. BMC Infect Dis 2004;4:52.  Back to cited text no. 35
    
36.
Podlasin RB, Wiercinska-Drapalo A, Olczak A, Beniowski M, Smiatacz T, Malolepsza E, et al. Opportunistic infections and other AIDS-defining illnesses in Poland in 2000-2002. Infection 2006;34:196-200.  Back to cited text no. 36
    
37.
Jensen L, Jensen AV, Praygod G, Kidola J, Faurholt-Jepsen D, Changalucha J, et al. Infrequent detection of Pneumocystis jirovecii by PCR in oral wash specimens from TB patients with or without HIV and healthy contacts in Tanzania. BMC Infect Dis 2010;10:140.  Back to cited text no. 37
    
38.
Bonnet F, Lewden C, May T, Heripret L, Jougla E, Bevilacqua S, et al. Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France. Scand J Infect Dis 2005;37:482-7.  Back to cited text no. 38
    
39.
Kyeyune R, den Boon S, Cattamanchi A, Davis JL, Worodria W, Yoo SD, et al. Causes of early mortality in HIV-infected TB suspects in an East African referral hospital. J Acquir Immune Defic Syndr 2010;55:446-50.  Back to cited text no. 39
    
40.
Fontes AR, Aldama JC, Lopez LA, Flores-Treviño S, Almendarez-Sánchez CA, Ortiz AC. Preventable deaths among HIV-positive patients: A real-life perspective from a teaching hospital in Northern Mexico. HIV/AIDS Res Treat Open J 2018;5:9-14.  Back to cited text no. 40
    
41.
Deribe A, Estifanos W. Magnitude and determinants of opportunistic infections among Hiv/aids patients in Sphmmc, Addis Ababa, Ethiopia: Retrospective study. JOJ Pub Health 2018;4.  Back to cited text no. 41
    
42.
Jabs DA, Holbrook JT, Van Natta ML, Clark R, Jacobson MA, Kempen JH, et al. Risk factors for mortality in patients with AIDS in the era of highly active antiretroviral therapy. Ophthalmology 2005;112:771-9.  Back to cited text no. 42
    
43.
Lewden C, Salmon D, Morlat P, Bévilacqua S, Jougla E, Bonnet F, et al. Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: Emerging role of hepatitis and cancers, persistent role of AIDS. Int J Epidemiol 2005;34:121-30.  Back to cited text no. 43
    
44.
Jankowska M, Lemanska M, Trocha H, Gesing M, Smiatacz T. Opportunistic infections in HIV-positive patients hospitalized in the Clinic of Infectious Diseases AMG. Przegl Epidemiol 2001;55 Suppl 3:125-8.  Back to cited text no. 44
    
45.
Lanjewar DN, Duggal R. Pulmonary pathology in patients with AIDS: An autopsy study from Mumbai. HIV Med 2001;2:266-71.  Back to cited text no. 45
    
46.
Hargreaves NJ, Kadzakumanja O, Phiri S, Lee CH, Tang X, Salaniponi FM, et al. Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi. Trans R Soc Trop Med Hyg 2001;95:402-8.  Back to cited text no. 46
    
47.
Ennaifer-Jerbi E, Louzir B, Huerre M, Beji M, Tiouiri H, Daghfous J, et al. Frequency of Pneumocystis carinii pneumonia in HIV-infected patients in Tunisia. Tunis Med 2002;80:29-32.  Back to cited text no. 47
    
48.
Chintu C, Mudenda V, Lucas S, Nunn A, Lishimpi K, Maswahu D, et al. Lung diseases at necropsy in African children dying from respiratory illnesses: A descriptive necropsy study. Lancet 2002;360:985-90.  Back to cited text no. 48
    
49.
Ansari NA, Kombe AH, Kenyon TA, Mazhani L, Binkin N, Tappero JW, et al. Pathology and causes of death in a series of human immunodeficiency virus-positive and -negative pediatric referral hospital admissions in Botswana. Pediatr Infect Dis J 2003;22:43-7.  Back to cited text no. 49
    
50.
Serraino D, Puro V, Boumis E, Angeletti C, Girardi E, Petrosillo N, et al. Epidemiological aspects of major opportunistic infections of the respiratory tract in persons with AIDS: Europe, 1993-2000. AIDS 2003;17:2109-16.  Back to cited text no. 50
    
51.
Calderón EJ, Varela JM, Medrano FJ, Nieto V, González-Becerra C, Respaldiza N, et al. Epidemiology of Pneumocystis carinii pneumonia in Southern Spain. Clin Microbiol Infect 2004;10:673-6.  Back to cited text no. 51
    
52.
Udwadia ZF, Doshi AV, Bhaduri AS. Pneumocystis carinii pneumonia in HIV infected patients from Mumbai. J Assoc Physicians India 2005;53:437-40.  Back to cited text no. 52
    
53.
Klotz SA, Nguyen HC, Van Pham T, Nguyen LT, Ngo DT, Vu SN. Clinical features of HIV/AIDS patients presenting to an inner city clinic in Ho Chi Minh City, Vietnam. Int J STD AIDS 2007;18:482-5.  Back to cited text no. 53
    
54.
Grabar S, Lanoy E, Allavena C, Mary-Krause M, Bentata M, Fischer P, et al. Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy. HIV Med 2008;9:246-56.  Back to cited text no. 54
    
55.
Aderaye G, Woldeamanuel Y, Asrat D, Labrad M, Baser J, Worku A, et al. Evaluation of toluidine blue o staining for the diagnosis of Pneumocystis jiroveci in expectorated sputum sample and bronchoalveolar lavage from HIV-infected patients in a tertiary care referral center in Ethiopia. Infection 2008;36:237-43.  Back to cited text no. 55
    
56.
Asmal HS, Mustafa M, Abdullah S, Zaidah AR, Nurhaslindawati AR, Sarimah A, et al. Pneumocystis pneumonia among HIV patients in Malaysia. Southeast Asian J Trop Med Public Health 2009;40:1293-7.  Back to cited text no. 56
    
57.
Gutiérrez S, Morilla R, León JA, Martín-Garrido I, Rivero L, Friaza V, et al. High prevalence of Pneumocystis jiroveci colonization among young HIV-infected patients. J Adolesc Health 2011;48:103-5.  Back to cited text no. 57
    
58.
Graham SM, Mankhambo L, Phiri A, Kaunda S, Chikaonda T, Mukaka M, et al. Impact of human immunodeficiency virus infection on the etiology and outcome of severe pneumonia in Malawian children. Pediatr Infect Dis J 2011;30:33-8.  Back to cited text no. 58
    
59.
Beshah G. Study of Prevalence of Opportunistic Infections among HIV/AIDS Patients in Addis Ababa Public Hospitals; 2011.  Back to cited text no. 59
    
60.
Alarcón JO, Freimanis-Hance L, Krauss M, Reyes MF, Cardoso Ca, Mussi-Pinhata MM, et al. Opportunistic and other infections in HIV-infected children in Latin America compared to a similar cohort in the United States. Aids Res Human Retrov 2012;28:282-8.  Back to cited text no. 60
    
61.
Taylor SM, Meshnick SR, Worodria W, Andama A, Cattamanchi A, Davis JL, et al. Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected persons in Uganda. PLoS One 2012;7:e49991.  Back to cited text no. 61
    
62.
Okwera A, Bwanga F, Najjingo I, Mulumba Y, Mafigiri DK, Whalen CC, et al. Aetiology of pulmonary symptoms in HIV-infected smear negative recurrent PTB suspects in Kampala, Uganda: A Cross sectional study. PLoS One 2013;8:e82257.  Back to cited text no. 62
    
63.
Vanspauwen MJ, Knops VEJ, Bruggeman CA, van Mook WNKA, Linssen CFM. Molecular epidemiology of Pneumocystis jiroveci in human immunodeficiency virus-positive and -negative immunocompromised patients in The Netherlands. J Med Microbiol 2014;63:1294-302.  Back to cited text no. 63
    
64.
Nowaseb V, Gaeb E, Fraczek MG, Richardson MD, Denning DW. Frequency of Pneumocystis jirovecii in sputum from HIV and TB patients in Namibia. J Infect Dev Ctries 2014;8:349-57.  Back to cited text no. 64
    
65.
Katano H, Hishima T, Mochizuki M, Kodama Y, Oyaizu N, Ota Y, et al. The prevalence of opportunistic infections and malignancies in autopsied patients with human immunodeficiency virus infection in Japan. BMC Infect Dis 2014;14:229.  Back to cited text no. 65
    
66.
Galisteu KJ, Cardoso LV, Furini AA, Schiesari Júnior A, Cesarino CB, Franco C, et al. Opportunistic infections among individuals with HIV-1/AIDS in the highly active antiretroviral therapy era at a Quaternary Level Care Teaching Hospital. Rev Soc Bras Med Trop 2015;48:149-56.  Back to cited text no. 66
    
67.
Saeed NK, Farid E, Jamsheer AE. Prevalence of opportunistic infections in HIV-positive patients in Bahrain: A four-year review (2009-2013). J Infect Dev Ctries 2015;9:60-9.  Back to cited text no. 67
    
68.
Coelho LE, Cardoso SW, Amancio RT, Moreira RI, Ribeiro SR, Coelho AB, et al. Predictors of opportunistic illnesses incidence in post combination antiretroviral therapy era in an urban cohort from Rio de Janeiro, Brazil. BMC Inf Dis 2016;16:134.  Back to cited text no. 68
    
69.
Rathee R, Atri S, Chaudhary A. Spectrum of opportunistic infections in HIV seropositive patients at ART Centre, PGIMS, Rohtak. Int J Contemp Med Res 2017;4:1219-22.  Back to cited text no. 69
    
70.
Pang W, Shang P, Li Q, Xu J, Bi L, Zhong J, et al. Prevalence of opportunistic infections and causes of death among hospitalized HIV-infected patients in Sichuan, China. Tohoku J Exp Med 2018;244:231-42.  Back to cited text no. 70
    
71.
Ramakrishnan K, Uma A, Senathipathy R., Vijayaraj S, Mondal PR. Pneumocystis carinii pneumonia in HIV infected patients from South India. Int J Curr Res 2019;11:4525-7.  Back to cited text no. 71
    
72.
Rivero A, Perez-Camacho I, Lozano F, Santos J, Camacho A, Serrano A, et al. Etiology of spontaneous pneumothorax in 105 HIV-infected patients without highly active antiretroviral therapy. Eur J Radiol 2009;71:264-8.  Back to cited text no. 72
    
73.
Lakoh S, Jiba DF, Kanu JE, Poveda E, Salgado-Barreira A, Sahr F, et al. Causes of hospitalization and predictors of HIV-associated mortality at the main referral hospital in Sierra Leone: A prospective study. BMC Public Health 2019;19:1320.  Back to cited text no. 73
    
74.
Nowaseb V, Denning DW, Richardson M, Gaeb E, Fraczek M. The frequency of Pneumocystis jirovecii in sputum samples of HIV and TB patients received at the central reference laboratory in Windhoek, Namibia. Mycoses 2012;55:296.  Back to cited text no. 74
    


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