Gap analysis on BCSH 2022 Guidelines on the Laboratory Diagnosis of Malaria

 Today I used the BCSH audit template to perform a gap analysis on our procedures for the diagnosis of malaria,  in comparison to the BCSH 2022 guidelines. British Society for Haematology guidelines for the laboratory diagnosis of malaria - Rogers - 2022 - British Journal of Haematology - Wiley Online Library.

 I would recommend that all staff involved in laboratory malaria diagnosis, read the 2022 guidelines and also the following:

WHO information on ‘False Negative RDT results and p.falciparum histidine-rich protein 2/3 gene deletions MAY 2016 (REV. SEPTEMBER 2017 AND JULY 2019) https://apps.who.int/iris/bitstream/handle/10665/258972/WHO-HTM-GMP-2017.18-eng.pdf?sequence=1 Learning points- HPR2 deletions in P.Falciparum and how this may lead to a negative RDT, prozone effect, frequent negative RDT test for P.Ovale, inclusion of Babesia in the differential diagnosis when the RDT is negative.

Advisory Committee for dangerous Pathogens (2015) Management of Hazard Group 4 viral haemorrhagic fevers and similar human infectious diseases of high consequence (publishing.service.gov.uk)

Lots of learning points !

Date of completion	10/10/22
Name of lead author/ participants	Clare Saddington
Specialty	Haematology
Title	An audit of compliance with the British Society for Haematology guideline on laboratory diagnosis of malaria
Background	The British Society for Haematology (BSH) has published guidance on the laboratory diagnosis of malaria. This audit will review compliance with some of the recommendations made.
Aim & objectives	To review whether: 1.      suspected malaria cases are being appropriately tested 2.      cases of malaria are being accurately diagnosed and appropriately assessed.
Standards & criteria	If the target (specified as 100% or 0% for each criterion) is not achieved, there should be documentation in the case notes that explains the variance. 1.      Both thick and thin films should be routinely prepared for malaria diagnosis; target 100%. 2.      Thin films should be stained with a Giemsa stain and thick films with either a Giemsa or Field stain. Giemsa should be used at pH 7.2; target 100%. 3.      Thick films should be examined by two trained observers, each viewing a minimum of 200 high power fields; target 100%. 4.      If thick films are positive, the species should be determined by examination of a thin film, again by two trained observers; target 100%. 5.      In the case of Plasmodium falciparum or Plasmodium knowlesi infection, the percentage of parasitised cells or the number of parasites per microlitre should be estimated and reported; target 100%. 6.      Rapid diagnostic tests (RDTs) for malarial antigen should not be used instead of a film at any time including out of hours; target 0%. 7.      All positive specimens or discrepant results between RDT and films should be referred to a reference laboratory; target 100%.
Method	1.      Sample selection ·           All requests for investigation of possible malaria parasites, either in a period of one month or to give a total of 30 requests (whichever is more appropriate).   2.      Data to be collected on proforma (see below).
Results	The results of this audit show the following compliance with the standards. Investigation % compliance Both thick and thin films were prepared for diagnosis Compliant Thin films were stained with a Giemsa stain, and thick films with either a Giemsa or Field stain. Giemsa was used at pH 7.2 Compliant Thick films were examined by two trained observers, each viewing a minimum of 200 high power fields Compliant If thick films were positive, the species was determined by examination of a thin film by two trained observers Compliant In the case of P. falciparum or P. knowlesi infection, the percentage of parasitised cells or the number of parasites per microlitre was estimated and reported Compliant RDTs for malarial antigen were not used instead of the preparation and appropriate examination of blood films even out of hours Compliant . It would however be beneficial for staff to have an awareness of the reason why i.e HPR2 deletions, prozone, poor detection of LDH in Ovale. All positive specimens or discrepant results between RDT and films were referred to a reference laboratory Compliant
Conclusion	Laboratory procedure is compliant with the above standards in BCSH 2022 guidelines on the laboratory diagnosis of Malaria.   I would recommend however that all staff involved in Malaria diagnosis read the following: ·         British Society for Haematology guidelines for the laboratory diagnosis of malaria - Rogers - 2022 - British Journal of Haematology - Wiley Online Library. ·         WHO information on ‘False Negative RDT results and p.falciparum histidine-rich protein 2/3 gene deletions MAY 2016 (REV. SEPTEMBER 2017 AND JULY 2019) https://apps.who.int/iris/bitstream/handle/10665/258972/WHO-HTM-GMP-2017.18-eng.pdf?sequence=1 Learning points- HPR2 deletions in P.Falciparum and how this may lead to a negative RDT,  prozone effect, frequent negative RDT test for P.Ovale, inclusion of Babesia in the differential diagnosis when the RDT is negative.   ·         Also an awareness of guidance from Advisory Committee for dangerous Pathogens (2015) Management of Hazard Group 4 viral haemorrhagic fevers and similar human infectious diseases of high consequence (publishing.service.gov.uk)   These documents should be read as part of the Parasitology competency reassessment.   Staff where appropriate should participate in NEQAS Blood Films for Parasites on a regular basis.
Recommendations for improvement	Present the result with recommendations, actions, and responsibilities for action and a timescale for implementation. Assign a person(s) responsible to do the work within a time frame.   Some suggestions: ·           highlight areas of practice that are different ·           present findings.
Action plan	Incorporate recommendations of BCSH guidelines 2022 guidelines into new draft of parasitology SOP RWF-BS-HAEM-SOP50 version 1.5. Include section on False negative RDTs. Target date : October 2022 Responsibility : Clare Saddington   Distribute link (or a hardcopy) of BCSH guidelines 2022 for the laboratory diagnosis of Malaria British Society for Haematology guidelines for the laboratory diagnosis of malaria - Rogers - 2022 - British Journal of Haematology - Wiley Online Library  WHO document on ‘False Negative RDT results and p.falciparum histidine-rich protein 2/3 gene deletions MAY 2016 (REV. SEPTEMBER 2017 AND JULY 2019) https://apps.who.int/iris/bitstream/handle/10665/258972/WHO-HTM-GMP-2017.18-eng.pdf?sequence=1 and Advisory Committee for dangerous Pathogens (2015) Management of Hazard Group 4 viral haemorrhagic fevers and similar human infectious diseases of high consequence (publishing.service.gov.uk) Target date November 2022 Responsibility : Clare Saddington   Senior BMS to provide a training/ review session of the above guidelines. Target date: January 2023 Responsibility : Clare Saddington   BMS to participate in NEQAS blood films for parasites on a regular basis. Senior BMS to coordinate this.   Target date: May 2023 Responsibility : Clare Saddington/ Adam Schofield
Re-audit date	October 2023
Reference	Rogers CL, Bain BJ, Fernandes S, Garg M, Mooney C, Chiodini PL et al. British Society for Haematology guidelines for the laboratory diagnosis of malaria. Br J Haematol 2022 (Epub ahead of print). https://onlinelibrary.wiley.com/doi/10.1111/bjh.18092

P. Falciparum Malaria evolving on Ethiopian border

 

https://rdcu.be/cIwcC

Have a look at this interesting article which I came across whilst looking into an alternative Rapid Diagnostic Testing (RDT) kit for Malaria.

It seems that Plasmodium Falciparum Malarial parasites are evolving at multiple sites along Ethiopias’s borders with Sudan and Eritea. As a result these parasites are escaping detection by RDTs and giving false negative results which is estimated to be at 9.7% overall and even higher in Tigray and Amhara regions.

Malaria RDTs detect antigens produced by Plasmodium parasites including Histidine Rich Protein 2 (HRP2, parasite Lactate Dehydrogenase (LDH) and Aldolase. The HRP2 methods appear to be more reliable than other methods but deletions in the plasmodium falciparum histidine protein 2 (pfhrp2) and 3 (pfhrp3) genes, are leading to strains of malaria giving false negative results.

In my laboratory, the RDTs are a supplementary test to microscopy, but in Ethiopia this is very concerning where RDTs are heavily relied upon. An alternative to the HPR2 RDT method is not easy. The WHO multiple rounds product testing publication, suggest that the LDH methods are inferior giving poor results. https://www.who.int/publications/i/item/9789241514965

Lack of high quality microscopy in and PCR means Malaria control and elimination in Ethiopa will become increasingly difficult if these expanding plasmodium falciparum strains cannot be detected by RDTs.

 

Malaria Parasitaemias

Dr Samuel Boadi who led Monday’s UK NEQAS Blood Parasitology course, made a very good suggestion for speeding up the calculation of Malaria percentage parasitaemias, in a busy laboratory. The laboratory should establish it’s own average number of red cells per field when using a x100 objective. This average number can be used every time, rather than the microscopist calculating it separately on every occasion. I’m going to ask number of different colleagues to count how many red cells they see on a film using a x100 objective, and take an average. I’ll fill out a quality improvement notice and see if this could be used and added to our SOP, as it will significantly improve turn around times!