scholarly journals Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia

2020 ◽  
Author(s):  
Lindsey Wu ◽  
Julia Mwesigwa ◽  
Muna Affara ◽  
Mamadou Bah ◽  
Simon Correa ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Fold Increase ◽  
Clinical Malaria ◽  
Incidence Rates ◽  
The Gambia ◽  
Antibody Responses ◽  
Malaria Surveillance ◽  
Targeted Interventions ◽  
River Region ◽  
The Individual

AbstractBackgroundAs malaria transmission declines, sensitive diagnostics are needed to evaluate interventions and monitor transmission. Serological assays measuring malaria antibody responses offer a cost-effective detection method to supplement existing surveillance tools.MethodsA prospective cohort study was conducted from 2013 to 2015 in 12 villages across five administrative regions in The Gambia. Serological analysis included samples from the West Coast Region at the start and end of the season (July and December 2013) and from the Upper River Region in July and December 2013, and April and December 2014. Antigen-specific antibody responses to eight Plasmodium falciparum (P.falciparum) antigens – Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175 RIII-V, PfMSP119, PfAMA1, PfGLURP.R2 - were quantified using a multiplexed bead-based assay. The association between antibody responses and clinical and parasitological endpoints was estimated at the individual, household, and population level.ResultsStrong associations were observed between clinical malaria and concurrent sero-positivity to Etramp5.Ag1 (aOR 4.60 95%CI 2.98 - 7.12), PfMSP119 (aOR 4.09 95%CI 2.60 - 6.44), PfAMA1 (aOR 2.32 95%CI 1.40 - 3.85) and PfGLURP.R2 (aOR 3.12, 95%CI 2.92 – 4.95), while asymptomatic infection was associated with sero-positivity to all antigens. Village-level sero-prevalence amongst children 2-10 years against Etramp5.Ag1, HSP40.Ag1, and PfMSP119 showed the highest correlations with clinical and P.falciparum infection incidence rates. For all antigens, there was increased odds of asymptomatic P.falciparum infection in subjects residing in a compound with greater than 50% sero-prevalence, with a 2- to 3-fold increase in odds of infection associated with Etramp5.Ag1, GEXP18, Rh2.2030, PfMSP119 and PfAMA1. For individuals residing in sero-positive compounds, the odds of clinical malaria were reduced, suggesting a protective effect.ConclusionsAt low transmission, long-lived antibody responses could indicate foci of malaria transmission that have been ongoing for several seasons or years. In settings where sub-patent infections are prevalent and fluctuate below the detection limit of polymerase chain reaction (PCR), the presence of short- lived antibodies may indicate recent infectivity, particularly in the dry season when clinical cases are rare. Serological responses may reflect a persistent reservoir of infection, warranting community- targeted interventions if individuals are not clinically apparent but have the potential to transmit. Therefore, serological surveillance at both the individual and household level may be used to target interventions where there are foci of asymptomatically infected individuals.

scholarly journals Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Lindsey Wu ◽  
Julia Mwesigwa ◽  
Muna Affara ◽  
Mamadou Bah ◽  
Simon Correa ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Clinical Malaria ◽  
The Gambia ◽  
Antibody Responses ◽  
Serological Markers ◽  
Malaria Surveillance ◽  
Diverse Range ◽  
Targeted Interventions ◽  
River Region ◽  
The Individual

Abstract Background As malaria transmission declines, sensitive diagnostics are needed to evaluate interventions and monitor transmission. Serological assays measuring malaria antibody responses offer a cost-effective detection method to supplement existing surveillance tools. Methods A prospective cohort study was conducted from 2013 to 2015 in 12 villages across five administrative regions in The Gambia. Serological analysis included samples from the West Coast Region at the start and end of the season (July and December 2013) and from the Upper River Region in July and December 2013 and April and December 2014. Antigen-specific antibody responses to eight Plasmodium falciparum (P. falciparum) antigens—Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175 RIII-V, PfMSP119, PfAMA1, and PfGLURP.R2—were quantified using a multiplexed bead-based assay. The association between antibody responses and clinical and parasitological endpoints was estimated at the individual, household, and population level. Results Strong associations were observed between clinical malaria and concurrent sero-positivity to Etramp5.Ag1 (aOR 4.60 95% CI 2.98–7.12), PfMSP119 (aOR 4.09 95% CI 2.60–6.44), PfAMA1 (aOR 2.32 95% CI 1.40–3.85), and PfGLURP.R2 (aOR 3.12, 95% CI 2.92–4.95), while asymptomatic infection was associated with sero-positivity to all antigens. Village-level sero-prevalence amongst children 2–10 years against Etramp5.Ag1, HSP40.Ag1, and PfMSP119 showed the highest correlations with clinical and P. falciparum infection incidence rates. For all antigens, there were increased odds of asymptomatic P. falciparum infection in subjects residing in a compound with greater than 50% sero-prevalence, with a 2- to 3-fold increase in odds of infection associated with Etramp5.Ag1, GEXP18, Rh2.2030, PfMSP119, and PfAMA1. For individuals residing in sero-positive compounds, the odds of clinical malaria were reduced, suggesting a protective effect. Conclusions At low transmission, long-lived antibody responses could indicate foci of malaria transmission that have been ongoing for several seasons or years. In settings where sub-patent infections are prevalent and fluctuate below the detection limit of polymerase chain reaction (PCR), the presence of short-lived antibodies may indicate recent infectivity, particularly in the dry season when clinical cases are rare. Serological responses may reflect a persistent reservoir of infection, warranting community-targeted interventions if individuals are not clinically apparent but have the potential to transmit. Therefore, serological surveillance at the individual and household level may be used to target interventions where there are foci of asymptomatically infected individuals, such as by measuring the magnitude of age-stratified antibody levels or identifying areas with clustering of above-average antibody responses across a diverse range of serological markers.

scholarly journals Community-based molecular and serological surveillance of subclinical malaria in Myanmar

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Katherine O’Flaherty ◽  
Win Han Oo ◽  
Sophie G. Zaloumis ◽  
Julia C. Cutts ◽  
Kyaw Zayar Aung ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Quantitative Polymerase Chain Reaction ◽  
Dried Blood Spots ◽  
Molecular Testing ◽  
Sample Collection ◽  
Malaria Surveillance ◽  
Surveillance Network ◽  
Targeted Interventions ◽  
Residual Malaria Transmission ◽  
Serological Surveillance

Abstract Background In the Greater Mekong Subregion (GMS), current malaria surveillance strategies rely on a network of village health volunteers (VHVs) reporting the results of rapid diagnostic tests (RDTs), known to miss many asymptomatic infections. Integration of more sensitive diagnostic molecular and serological measures into the VHV network may improve surveillance of residual malaria transmission in hard-to-reach areas in the region and inform targeted interventions and elimination responses. However, data on residual malaria transmission that would be captured by these measures in the VHV-led testing and treatment surveillance network in the GMS is unknown. Methods A total of 114 VHVs were trained to collect dried blood spots from villagers undergoing routine RDTs as part of VHV-led active and passive case detection from April 2015 to June 2016. Samples were subjected to molecular testing (quantitative polymerase chain reaction [qPCR]) to determine Plasmodium falciparum and P. vivax infection and serological testing (against P. falciparum and P. vivax antigens) to determine exposure to P. falciparum and P. vivax. Results Over 15 months, 114 VHVs performed 32,194 RDTs and collected samples for molecular (n = 13,157) and serological (n = 14,128) testing. The prevalence of molecular-detectable P. falciparum and P. vivax infection was 3.2% compared to the 0.16% prevalence of Plasmodium spp. by RDT, highlighting the large burden of infections undetected by standard surveillance. Peaks in anti-P. falciparum, but not P. vivax, merozoite IgG seroprevalence coincided with seasonal P. falciparum transmission peaks, even in those with no molecularly detectable parasites. At the individual level, antibody seropositivity was associated with reduced odds of contemporaneous P. falciparum (OR for PfCSP 0.51 [95%CI 0.35, 0.76], p = 0.001, PfAMA1 0.70 [95%CI 0.52, 0.93], p = 0.01, and PfMSP2 0.81 [95%CI 0.61, 1.08], p = 0.15), but not P. vivax infection (OR PvAMA1 1.02 [95%CI 0.73, 1.43], p = 0.89) indicating a potential role of immunity in protection against molecular-detectable P. falciparum parasitaemia. Conclusions We demonstrated that integration and implementation of sample collection for molecular and serological surveillance into networks of VHV servicing hard-to-reach populations in the GMS is feasible, can capture significant levels of ongoing undetected seasonal malaria transmission and has the potential to supplement current routine RDT testing. Improving malaria surveillance by advancing the integration of molecular and serological techniques, through centralised testing approaches or novel point-of-contact tests, will advance progress, and tracking, towards malaria elimination goals in the GMS.

scholarly journals Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

2020 ◽  
Vol 5 ◽  
pp. 136
Author(s):  
Tony I. Isebe ◽  
Joel L. Bargul ◽  
Bonface M. Gichuki ◽  
James M. Njunge ◽  
James Tuju ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
The Gambia ◽  
Antibody Responses ◽  
Transmission Intensity ◽  
Parasite Development ◽  
Natural Immunity ◽  
Malaria Transmission Intensity ◽  
Transmission Region ◽  
Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins in order to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Our findings show that children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against the PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in the Gambia, as compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses show a negative correlation between antibody levels and malaria transmission intensity for two PHIST antigens, Pf3D7_1102500 and Pf3D7_1401600. However, we report a correlation in antibody responses between schizont extract and Pf3D7_0532400 (p=0.00582). Acquisition of anti-PHIST antibodies was correlated with exposure to malaria for PHISTb protein Pf3D7_0532400 (p=0.009) but not the other PHIST antigens Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels, but the responses do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore potential for these parasite antigens as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

scholarly journals Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

2021 ◽  
Vol 5 ◽  
pp. 136
Author(s):  
Tony I. Isebe ◽  
Joel L. Bargul ◽  
Bonface M. Gichuki ◽  
James M. Njunge ◽  
James Tuju ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Negative Correlation ◽  
The Gambia ◽  
Antibody Responses ◽  
Transmission Intensity ◽  
Parasite Development ◽  
Malaria Transmission Intensity ◽  
Transmission Region ◽  
Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in Gambia, compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses indicate negative correlation between antibody levels and malaria transmission intensity for Pf3D7_1102500 and Pf3D7_1401600. We report a correlation in antibody responses between schizont and gametocyte extract, but this is not statistically significant (cor=0.102, p=0.2851, CI=95%) and, Pf3D7_0532400 (cor=0.11, p=0.249, CI=95%) and Pf3D7_1401600 (cor=0.02, p=0.7968, CI=95%). We report a negative correlation in antibody responses between schizont and Pf3D7_1102500 (cor=-0.008, p=0.9348, CI=95%). There is a correlation between gametocyte extract and Pf3D7_1401600 (cor=-0.0402, p=0.6735, CI=95%), Pf3D7_1102500 (cor=0.0758, p=0.4271, CI=95%) and Pf3D7_0532400 (cor=0.155, p=0.1028, CI=95%). Acquisition of anti-PHIST antibodies correlates with exposure to malaria for Pf3D7_0532400 (p=0.009) but not Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels which do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore their potential as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

scholarly journals Sero-epidemiological evaluation of malaria transmission in The Gambia before and after mass drug administration

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Lindsey Wu ◽  
Julia Mwesigwa ◽  
Muna Affara ◽  
Mamadou Bah ◽  
Simon Correa ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
West Coast ◽  
Malaria Infection ◽  
The Gambia ◽  
Antibody Responses ◽  
The West ◽  
Conversion Rates ◽  
Antibody Levels

Abstract Background As The Gambia aims to achieve malaria elimination by 2030, serological assays are a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions. Methods Within a mass drug administration (MDA) study in The Gambia, where reduced malaria infection and clinical disease were observed after the intervention, a serological sub-study was conducted in four study villages. Spatio-temporal variation in transmission was measured with a panel of recombinant Pf antigens on a multiplexed bead-based assay. Village-level antibody levels were quantified as under-15 sero-prevalence, sero-conversion rates, and age-adjusted antibody acquisition rates. Antibody levels prior to MDA were assessed for association with persistent malaria infection after community chemoprophylaxis. Results Seasonal changes in antibodies to Etramp5.Ag1 were observed in children under 15 years in two transmission settings—the West Coast and Upper River Regions (4.32% and 31.30% Pf prevalence, respectively). At the end of the malaria season, short-lived antibody responses to Etramp5.Ag1, GEXP18, HSP40.Ag1, EBA175 RIII-V, and Rh2.2030 were lower amongst 1–15 year olds in the West Coast compared to the Upper River, reflecting known differences in transmission. Prior to MDA, individuals in the top 50th percentile of antibody levels had two-fold higher odds of clinical malaria during the transmission season, consistent with previous findings from the Malaria Transmission Dynamics Study, where individuals infected before the implementation of MDA had two-fold higher odds of re-infection post-MDA. Conclusions Serological markers can serve dual functions as indicators of malaria exposure and incidence. By monitoring age-specific sero-prevalence, the magnitude of age-stratified antibody levels, or identifying groups of individuals with above-average antibody responses, these antigens have the potential to complement conventional malaria surveillance tools. Further studies, particularly cluster randomised trials, can help establish standardised serological protocols to reliably measure transmission across endemic settings.

scholarly journals Humoral Responses to Plasmodium falciparum Blood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa

2007 ◽  
Vol 76 (2) ◽  
pp. 759-766 ◽  
Author(s):  
Issa Nebie ◽  
Amidou Diarra ◽  
Alphonse Ouedraogo ◽  
Issiaka Soulama ◽  
Edith C. Bougouma ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Malaria Incidence ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Clinical Malaria ◽  
Blood Stage ◽  
Igg Subclass ◽  
Malaria Surveillance

ABSTRACT There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P = 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.

scholarly journals PO 8302 IMPACT OF TWO ANNUAL ROUNDS OF MASS DRUG ADMINISTRATION WITH DIHYDROARTEMISININ-PIPERAQUINE ON MALARIA TRANSMISSION IN A PROSPECTIVE COHORT STUDY

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A28.2-A28
Author(s):  
Julia Mwesigwa ◽  
Jane Achan ◽  
Miriam Wathuo ◽  
Archibald Worwui ◽  
Nuredin Mohammed ◽  
...  
Keyword(s):  
Cohort Study ◽  
Malaria Transmission ◽  
Drug Administration ◽  
Prospective Cohort Study ◽  
Mass Drug Administration ◽  
Prospective Cohort ◽  
Malaria Infection ◽  
Clinical Malaria ◽  
The Gambia ◽  
Transmission Season

BackgroundMass drug administration (MDA) may reduce malaria transmission in low-transmission areas and interrupt transmission. The impact of MDA with dihydroartemisinin-piperaquine (DP) on malaria infection and clinical malaria was determined in a prospective cohort study in The Gambia.MethodsSingle annual MDA rounds with DP were done in 2014 and 2015 in a prospective cohort among residents aged >6 months in twelve villages in The Gambia at the start of the transmission season in June. Monthly blood samples for microscopy and PCR were collected during the transmission season from July to December, post MDA and once before MDA during the dry season in April. The incidence of infection and clinical malaria post-MDA were compared to 2013 and mixed effects logistic regression models assessed the efficacy and risk of re-infection post MDA.ResultsCoverage of 3 DP doses was 68.22% in 2014 and 65.60% in 2015. Compliance to 3 doses was high, 83.11% in 2014 and 85.93% in 2015. Incidence of infection in 2014 (2014: IR=0.23 PPY, 2013: IR=1.12 PPY, p<0.01) and clinical malaria in 2014 (2014: IR=0.08 PPY, 2013: IR=0.39: IRR=0.22, p<0.01) and 2015 (2015: IR=0.19, 2013:IR=0.38, IRR=0.50, p<0.01) was significantly lower after MDA compared to 2013. The incidence of clinical malaria remained higher in eastern Gambia compared to the western region. Subjects that took 3 DP doses had lower odds of infection in 2014 at 28 days (OR=0.61, 95% CI: 0.38–0.99) and 42 days (2014: OR=0.52, 95% CI: 0.29–0.89)ConclusionA single annual MDA round with DP temporarily reduced malaria infection and clinical disease during the transmission season and subjects that took 3 doses had lower risk of infection. However, several MDA rounds covering the entire transmission season and some targeting the human reservoir during the dry season, are needed to achieve a more marked sustained reduction of transmission.

Differentiation of endemic areas by incidence rates of tick-borne infectious diseases as the basis for choosing prevention strategy and tactics

2019 ◽  
pp. 56-61
Author(s):  
N.V. Rudakov ◽  
N.A. Penyevskaya ◽  
D.A. Saveliev ◽  
S.A. Rudakova ◽  
C.V. Shtrek ◽  
...  
Keyword(s):  
High Risk ◽  
Infectious Diseases ◽  
Population Based ◽  
Preventive Therapy ◽  
Incidence Rates ◽  
Prevention Strategy ◽  
Individual Risk ◽  
The Individual ◽  
Integral Assessment ◽  
Very High

Research objective. Differentiation of natural focal areas of Western Siberia by integral incidence rates of tick-borne infectious diseases for determination of the strategy and tactics of their comprehensive prevention. Materials and methods. A retrospective analysis of official statistics for the period 2002-2018 for eight sub-federal units in the context of administrative territories was carried out. The criteria of differentiation were determined by means of three evaluation scales, including long-term mean rates of tick-borne encephalitis, tick-borne borreliosis, and Siberian tick-borne typhus. As a scale gradation tool, we used the number of sample elements between the confidence boundaries of the median. The integral assessment was carried out by the sum of points corresponding to the incidence rates for each of the analyzed infections. Results. The areas of low, medium, above average, high and very high risk of tick-borne infectious diseases were determined. Recommendations on the choice of prevention strategy and tactics were given. In areas of very high and high incidence rates, a combination of population-based and individual prevention strategies is preferable while in other areas a combination of high-risk and individual strategies is recommended. Discussion. Epidemiologic zoning should be the basis of a risk-based approach to determining optimal volumes and directions of preventive measures against natural focal infections. It is necessary to improve the means and methods of determining the individual risk of getting infected and developing tick-borne infectious diseases in case of bites, in view of mixed infection of vectors, as well as methods of post-exposure disease prevention (preventive therapy).

scholarly journals Epidemiological and clinical characteristics of immunocompromised patients infected with Pneumocystis jirovecii in a twelve-year retrospective study from Norway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Grønseth ◽  
Tormod Rogne ◽  
Raisa Hannula ◽  
Bjørn Olav Åsvold ◽  
Jan Egil Afset ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Fold Increase ◽  
Epidemiological Data ◽  
Opportunistic Pathogen ◽  
Incidence Rates ◽  
Clinical Findings ◽  
Pneumocystis Jirovecii ◽  
Common Denominator ◽  
Study Population ◽  
Cardinal Symptoms

Abstract Background Pneumocystis pneumonia (PCP) severely menaces modern chemotherapy and immunosuppression. Detailed description of the epidemiology of Pneumocystis jirovecii today is needed to identify candidates for PCP-prophylaxis. Methods We performed a 12-year retrospective study of patients with P. jirovecii detected by polymerase chain reaction in Central Norway. In total, 297 patients were included. Comprehensive biological, clinical and epidemiological data were abstracted from patients’ medical records. Regional incidence rates and testing trends were also assessed. Results From 2007 to 2017 we found a 3.3-fold increase in testing for P. jirovecii accompanied by a 1.8-fold increase in positive results. Simultaneously, regional incidence rates doubled from 5.0 cases per 100,000 person years to 10.8. A majority of the study population had predisposing conditions other than human immunodeficiency virus (HIV). Hematological (36.0%) and solid cancers (25.3%) dominated. Preceding corticosteroids were a common denominator for 72.1%. Most patients (74.4%) presented with at least two cardinal symptoms; cough, dyspnea or fever. Main clinical findings were hypoxia, cytopenias and radiological features consistent with PCP. A total of 88 (29.6%) patients required intensive care and 121 (40.7%) suffered at least one complication. In-hospital mortality was 21.5%. Three patients (1.0%) had received prophylaxis. Conclusions P. jirovecii is re-emerging; likely due to increasing immunosuppressants use. This opportunistic pathogen threatens the life of heterogenous non-HIV immunosuppressed populations currently at growth. Corticosteroids seem to be a major risk factor. A strategy to increase prophylaxis is called for.

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