C-reactive protein and procalcitonin use in adults in low- and middle-income countries: a narrative review

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objectives

C-reactive protein (CRP) and procalcitonin (PCT) are widely used biomarkers in high-income countries. However, evidence for their use in low- and middle-income countries (LMICs) is scant. Because many factors, including rates of endemic disease, comorbidities and genetics, may influence biomarkers’ behaviour, we aimed to review available evidence generated in LMICs.

Methods

We searched the PubMed database for relevant studies within the last 20 years that originated in regions of interest (Africa, Latin America, Middle East, South Asia or South East Asia), and full-text articles involving diagnosis, prognostication and evaluation of therapeutic response with CRP and/or PCT in adults ( n = 88) were reviewed and categorized in 12 predefined focus areas.

Results

Overall, results were highly heterogeneous, at times conflicting, and often lacking clinically useful cut-off values. However, most studies demonstrated higher levels of CRP/PCT in patients with bacterial versus other infections. HIV and TB patients had consistently higher levels of CRP/PCT versus controls. In addition, higher CRP/PCT levels at baseline and follow-up in HIV, TB, sepsis and respiratory tract infections were associated with poorer prognosis.

Conclusions

Evidence generated from LMIC cohorts suggests that CRP and PCT may have potential to become effective clinical guiding tools particularly in respiratory tract infections, sepsis and HIV/TB. However, more studies are needed to define potential scenarios for use and cost-effectiveness. Consensus across stakeholders regarding target conditions, laboratory standards and cut-off values would support the quality and applicability of future evidence.

Related collections

Most cited references 97

Record: found
Abstract: found
Article: not found

Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB.

Kim Stanley, Novel N Chegou, Jayne S. Sutherland … (2016)

User-friendly, rapid, inexpensive yet accurate TB diagnostic tools are urgently needed at points of care in resource-limited settings. We investigated host biomarkers detected in serum samples obtained from adults with signs and symptoms suggestive of TB at primary healthcare clinics in five African countries (Malawi, Namibia, South Africa, The Gambia and Uganda), for the diagnosis of TB disease.

0 comments Cited 78 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

Nga T T Do, Ngan T D Ta, Ninh T H Tran … (2016)

Summary Background Inappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is difficult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam. Method We did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1–65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecified in the protocol and the statistical analysis plan. All analyses were done on the intention-to-treat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579. Findings Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics within 14 days was 581 (64%) of 902 patients in the C-reactive protein group versus 738 (78%) of 947 patients in the control group (odds ratio [OR] 0·49, 95% CI 0·40–0·61; p<0·0001). Highly significant differences were seen in both children and adults, with substantial heterogeneity of the intervention effect across the 10 sites (I 2=84%, 95% CI 66–96). 140 patients in the C-reactive protein group and 137 patients in the routine care group missed the urine test on day 3, 4, or 5. Antibiotic activity in urine on day 3, 4, or 5 was found in 267 (30%) of 877 patients in the C-reactive protein group versus 314 (36%) of 882 patients in the routine treatment group (OR 0·78, 95% CI 0·63–0·95; p=0·015). Time to resolution of symptoms was similar in both groups. Adverse events were rare, with no deaths and a total of 14 hospital admissions (six in the C-reactive protein group and eight in the control group). Interpretation C-reactive protein point-of-care testing reduced antibiotic use for non-severe acute respiratory tract infection without compromising patients' recovery in primary health care in Vietnam. Health-care providers might have become familiar with the clinical picture of low C-reactive protein, leading to reduction in antibiotic prescribing in both groups, but this would have led to a reduction in observed effect, rather than overestimation. Qualitative analysis is needed to address differences in context in order to implement this strategy to improve rational antibiotic use for patients with acute respiratory infection in low-income and middle-income countries. Funding Wellcome Trust, UK, and Global Antibiotic Resistance Partnership, USA.

0 comments Cited 77 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Performance of C-reactive protein and procalcitonin to distinguish viral from bacterial and malarial causes of fever in Southeast Asia

Yoel Lubell, Stuart Blacksell, Susanna Dunachie … (2015)

Background Poor targeting of antimicrobial drugs contributes to the millions of deaths each year from malaria, pneumonia, and other tropical infectious diseases. While malaria rapid diagnostic tests have improved use of antimalarial drugs, there are no similar tests to guide the use of antibiotics in undifferentiated fevers. In this study we estimate the diagnostic accuracy of two well established biomarkers of bacterial infection, procalcitonin and C-reactive protein (CRP) in discriminating between common viral and bacterial infections in malaria endemic settings of Southeast Asia. Methods Serum procalcitonin and CRP levels were measured in stored serum samples from febrile patients enrolled in three prospective studies conducted in Cambodia, Laos and, Thailand. Of the 1372 patients with a microbiologically confirmed diagnosis, 1105 had a single viral, bacterial or malarial infection. Procalcitonin and CRP levels were compared amongst these aetiological groups and their sensitivity and specificity in distinguishing bacterial infections and bacteraemias from viral infections were estimated using standard thresholds. Results Serum concentrations of both biomarkers were significantly higher in bacterial infections and malaria than in viral infections. The AUROC for CRP in discriminating between bacterial and viral infections was 0.83 (0.81–0.86) compared with 0.74 (0.71–0.77) for procalcitonin (p < 0.0001). This relative advantage was evident in all sites and when stratifying patients by age and admission status. For CRP at a threshold of 10 mg/L, the sensitivity of detecting bacterial infections was 95 % with a specificity of 49 %. At a threshold of 20 mg/L sensitivity was 86 % with a specificity of 67 %. For procalcitonin at a low threshold of 0.1 ng/mL the sensitivity was 90 % with a specificity of 39 %. At a higher threshold of 0.5 ng/ul sensitivity was 60 % with a specificity of 76 %. Conclusion In samples from febrile patients with mono-infections from rural settings in Southeast Asia, CRP was a highly sensitive and moderately specific biomarker for discriminating between viral and bacterial infections. Use of a CRP rapid test in peripheral health settings could potentially be a simple and affordable measure to better identify patients in need of antibacterial treatment and part of a global strategy to combat the emergence of antibiotic resistance.

0 comments Cited 60 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Amin Lamrous:

ORCID: https://orcid.org/0000-0003-3003-8336

Ernestina Repetto

Tim Depp

Carolina Jimenez

Arlene C Chua

Rupa Kanapathipillai

Tomas O Jensen:

ORCID: https://orcid.org/0000-0003-0398-4431

Journal

Journal ID (nlm-ta): JAC Antimicrob Resist

Journal ID (iso-abbrev): JAC Antimicrob Resist

Journal ID (publisher-id): jacamr

Title: JAC-Antimicrobial Resistance

Publisher: Oxford University Press (US )

ISSN (Electronic): 2632-1823

Publication date Collection: June 2023

Publication date (Electronic): 17 May 2023

Publication date PMC-release: 17 May 2023

Volume: 5

Issue: 3

Electronic Location Identifier: dlad057

Affiliations

Médecins Sans Frontières, Operational Center Barcelona , Barcelona, Spain

Médecins Sans Frontières, Operational Center Geneva , Geneva, Switzerland

Infectious Diseases Department, Université Libre de Bruxelles (ULB), CHU Saint-Pierre , Brussels, Belgium

Emergency Medicine, University of South Carolina School of Medicine , Greenville, SC, USA

Médecins Sans Frontières, Operational Center Paris , Paris, France

Medical Department, Médecins Sans Frontières—International , Geneva, Switzerland

Médecins Sans Frontières, Operational Center Paris , Paris, France

CHIP Center of Excellence for Health, Immunity, and Infections, Rigshospitalet , Copenhagen, Denmark

Author notes

Corresponding author. E-mail: tomas.jensen@ 123456dadlnet.dk

Author information

Amin Lamrous https://orcid.org/0000-0003-3003-8336

Tomas O Jensen https://orcid.org/0000-0003-0398-4431

Article

Publisher ID: dlad057

DOI: 10.1093/jacamr/dlad057

PMC ID: 10190046

PubMed ID: 37206308

SO-VID: 1be5085e-338b-4f7b-b868-c8a76358fcd3

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

C-reactive protein and procalcitonin use in adults in low- and middle-income countries: a narrative review

Read this article at

Abstract

Objectives

Methods

Results

Conclusions

Related collections

Politics of the Low Countries

Most cited references 97

Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB.

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

Performance of C-reactive protein and procalcitonin to distinguish viral from bacterial and malarial causes of fever in Southeast Asia

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 354

Cited by 3

Most referenced authors 1,049