RDTs vs. Presumptive Treatment: Medical Science vs. Pragmatism/ Economics
Started by Prashant Yadav on 07 Dec 2009
Last edited by Prashant Yadav on 07 Dec 2009
Traditional clinical practice for outpatients in field settings was to treat presumptively for malaria based on a history of fever. New studies are showing that in many instances over 50% of those treated may not have parasites.
Rapid diagnostic tests (RDTs) are available but their sensitivity , specificity and quality does not always make them the best choice. This leads to many clinics continuing to engage in presumptive treatment despite having RDTs in the system. Some argue that there are thresholds on endemicity at which having presumptive treatment as the norm is in fact a preferable strategy.
Thoughts?
Keywords: Diagnostics & Treatment, Operations & Logistics, Presumptive Treatment, RDT, policy
Peter Brown
This is a great question. Yet I wonder if any threshold will be adopted or taken seriously by clinicians in the near future.
Ultimately, in low endemicity settings, negative RDTs need to be believed; presumptive treatment of malaria is not the right thing to do.
There are good social and cultural reasons (in the culture of clinical medicine as well as the cultural beliefs of mothers seeking treatment for their children) that negative RDTs are ignored. I do not think that medical anthropologists have articulated those reasons very clearly.
Regarding the overall problem, I like the quote below from the Whitty et al's 2008 report to AMFm.
Opportunities and Threats in Targeting Antimalarials for the AMFm: The Role of Diagnostics
Christopher J.M. Whitty, Heidi Hopkins, Evelyn Ansah, Toby Leslie, and Hugh Reyburn
www.rff.org/RFF/Documents/RFF-DP-08-41.pdf
Consultative Forum on AMF
Washington 2008
Page 10:
The picture that emerges from the literature across Africa is clear: clinicians almost invariably respond to positive malaria tests by prescribing antimalarials, but often respond to negative tests by ignoring them and prescribing antimalarials anyway. When diagnostic facilities are available, half or more of those with negative test results are still treated for malaria (Hamer et al. 2007; Reyburn et al. 2007; Zurovac et al. 2008). When diagnostic facilities are not present, the proportion is even higher. Where malaria is common, most of those given an ant malarial actually have malaria parasites but a significant minority does not. In the many settings when malaria is not the predominant cause of febrile illness, that is, fewer than 10 percent of children presenting with fever have malaria parasites, the proportion of negative tests treated stays the same but the absolute numbers of those with a negative test treated with an antimalarial increase substantially. In low transmission settings more than 90 percent, and in very low transmission settings more than 99 percent, of children treated with an antimalarial do not have malaria, despite tests being available (Ndyomugyenyi et al. 2007).
Ndyomugyenyi, R., P. Magnussen, and S. Clarke. 2007. Diagnosis and Treatment of Malaria in
Peripheral Health Facilities in Uganda: Findings from an Area of Low Transmission in
South-Western Uganda. Malaria Journal 6: 39.
3:13 PM, 11 Dec 2009 | Permalink
Peter Brown
How much of childhood fever is actually malaria?
I found this study by D'Acremont and colleagues presented at MIM to be really fascinating. In these urban and rural Tanzanian populations the researchers used all possible diagnostic tests to determine the etiology of childhood fevers. Only 12% were malaria.
615
Etiology of fever in children from urban and rural Tanzania
[MIM16671706]
V. D’Acremont, M. Kilowoko, E. Kyungu, S. Philipina, W. Sangu,
J. Kahama-Maro, P. Kibatala, E. Kahigwa, C. Lengeler, B. Genton
Previous studies have looked at the proportion of either malaria,
pneumonia, diarrhea, or bacteremia among fevers, but none at
the overall spectrum of etiologies. We aimed at investigating precise
causes of fever episodes in children attending outpatient
clinics in urban/rural settings in Tanzania. All consenting children
aged 2 months to 10 years with temperature >38 ◦C were
recruited, except those requiring immediate support. Detailed
medical history and clinical examination were done and blood
taken to perform rapid tests for malaria and typhoid, blood cultures,
serological and molecular-analyses. All had nasal/throat
swabs taken for viral molecular investigation, urine when no
obvious cause was found and stools when diarrhea was present.
Chest X-rays were performed when IMCI criteria for clinical pneumonia
were met. Each diagnosis was assigned a probability
level (high/moderate/low) based on pre-defined criteria. 1010 (510
Dar es Salaam, 500 Ifakara) children were recruited. Preliminary
results (prior to molecular-analysis) on the causes of fever of high probability
were: 43% acute-respiratory-infection (ARI) (30% URTI,
6% clinical-pneumonia, 7% X-ray-confirmed), 12% malaria, 9% diarrhoea
(3% rotavirus, 6% bacterial/unknown), 8% urine-infection, 4%
typhoid, 2% skin-infection, 1% occult-bacteremia and 21% unknown
at this stage. 8% had more than one diagnoses (high-probability).
These results provide for the first time an accurate picture of the
diversity of causes of fever in African children. ARI (mainly URTI)
contributed to the largest burden of disease. Results of molecular
analyses will provide further insight on respective contribution of
bacteria versus viruses, a critical issue for appropriate management
of fever and rational use of antibiotics.
Email address for correspondence:
3:34 PM, 11 Dec 2009 | Permalink
Johanna Daily
There are many studies that support the mis-diagnosis of malaria when using clinical signs alone. This is bad for the patient as an alternative diagnosis is missed and not treated, and expensive antimalarials may be prescribed. The RDTs are suprisingly very sensitive and specific. Health care workers will have to expand the differential diagnosis if the RDT is negative-and the differential diagnosis may very from region to region. A study from Uganda of 2356 children with fever found that only 32% had malaria (by RDT); they followed the remaining 68% children for one week and only 0.8% went on to have a follow up RDT + for malaria; the vast majority had upper respiratory tract infections; thus 1589 treatment courses of antimalarials was saved and no child developed any severe outcomes (Njama_Meya Malaria Journal 2007 6:7). Such studies could be repeated in other regions to find out what the true prevalence of malaria is and define the other causes of fever to improve and inform local care.
11:00 AM, 29 Dec 2009 | Permalink
Peter Brown
I wonder what the MAP (Malaria Atlas Project) think of this idea? As far as I can tell all of the studies they use are based on microscopy surveys. I would think that RDTs wouyld be a boon to epidemiology, but I don't know what is going on in this regard.
4:38 PM, 11 Jan 2010 | Permalink
Prashant Yadav
RDTs have been rolled out by many malaria programs that I work closely with. But in the absence of a robust clinical algorithm around what should be done when the test is negative, the adherence to treatment guidelines remains moderate or poor.
10:53 AM, 13 Feb 2010 | Permalink
Jean Baptiste Mulongo Kaulu
Moi je suis convainçu que le traitement présomptif est à encourager ici chez nous en Afrique parceque
il nya pas partout des laboratoires fiables, la plus part des gens sont piqués par des moustiques vecteur du paludisme, alors on a pas des temps à perdre lorsque on est en présence d'un patient qui présente la fièvre,on doit d'abord penser à la malaria prémièrement avant toute autre chose.On doit administrer une cure d'un traitement curatif directement ;et on sauvera beaucoup des patients avec une stratégie,car généralement quatre vingt pourcent des cas de fièvre sont dues à la malaria .
Quand on aura pas trouvé des bon résultats alors on envisagera autre examens .Personellement j'ai toujours des bons résultat avec un traitement présomptif du paludisme ;en afrique une priorité à faire ,mais en europe ,usa, canada il faut toujours de examens de labo ,parceque au moins les centres sont équipés merci de réçevoir ma contribution
8:34 AM, 20 Feb 2010 | Permalink
Kileken ole-MoiYoi
Merci Jean Baptiste. From what I know (others please chime in), several studies have reported a high level of mis-diagnosis of malaria which not only results in poor patient outcomes, but also in the waste of expensive anti-malarials. As Johanna points out in the study from Uganda where 32% of fevers were caused by malaria (attached to this discussion as a resource), over 1,600 anti-malarial treatments were saved through diagnosis before treatment and the majority of children were treated for upper respiratory infection. However, as Jean Baptiste indicates, 80% of febrile cases in his region of the DRC were effectively cured with presumptive treatment for malaria. I wonder whether the regional level of malaria endemicity should then be used to guide presumptive treatment for malaria of patients presenting with fever. I envision a scenario where in hyper endemic zones, presumptive treatment is the norm; as Johanna indicates, it would still be crucial to confirm these diagnoses with RDTs or microscopy and a negative test result would then be fully investigated through a robust differential diagnosis as Prashant suggests. It would also follow that in low or non-endemic zones, RDTs or microscopy would be the first step to ensure that other causes of fever, such as upper respiratory infection are effectively treated in a timely manner. I am also curious about the availability of RDTs for malaria. Jean Baptiste and others, are RDTs readily available in the areas where you work and if so, how often are they used? In locations with laboratory infrastructure, is microscopy the norm or are RDTs used?
2:57 PM, 2 Mar 2010 | Permalink
Michelle Kiprop
I'm curious about these RDT's. I work in a clinic in rural clinic and we are using microscopy. However, our lab is only open Mon - Fri 8AM to 5PM. We frequently get patients after hours who are always treated for malaria if they have a fever. I'd be interested to learn more about the availability and reliability of them.
I'm also curious about doing education with national staff members in regards to this issue. I'm the only Westerner in our clinic. I've learned a great deal from my Kenyan colleagues, but I still feel that they sometimes jump-the-gun when it comes to treating malaria in children.
4:16 AM, 10 Mar 2010 | Permalink
Erin Meier
I work in Papua New Guinea. The majority of health care is done by nursing officers and community health workers (nurses aide training) especially in our rural settings. The majority of our aid posts and health centers have no ability to do laboratory testing of any kind. We have a Standard Treatment Book which gives an outline of what these workers should do with common conditions that they see every day. Just treating for malaria is a part of what they do for kids who have fevers. Would RDTs help, they probably would, but it would take a long time to convince the people out in the rural communities working that they could believe these tests and shouldn't give antimalarials. It would have to be adopted by our government and then the Fever section in the Standard Treatment Book would have to be rewritten before I could see our country adopting the use of them.
3:28 AM, 29 Jun 2010 | Permalink
Neil Pakenham-Walsh
Dear Erin,
I was interested to read your post. We have had similar discussions
on the HIFA2015 forum (Healthcare Information for All by 2015) -
www.hifa2015.org
For example, here is a comment from a HIFA2015 member working in the
Kenya ministry of health:
'They say "old habits don't die". This may be true when it comes to
prescription for malaria drugs in Kenya. We are training health
workers currently in all the provinces in Kenya on the new guidelines
on malaria case management where we are giving updates on the
treatment and diagnosis of malaria. As we strive to shift the focus
from just treatment but also to ensure confirmation of malaria to
strengthen diagnosis using microscopy or rapid test diagnostic kits
(RDTs), we are getting all sorts of comments and reactions from our
health workers especially those in level 2 and 3 i.e. at the
dispensaries and at the health centres. They still believe that every
fever is malaria.'
Best wishes,
Neil
Dr Neil Pakenham-Walsh MB,BS
Coordinator, HIFA2015
Co-director, Global Healthcare Information Network
16 Woodfield Drive
Charlbury, Oxfordshire OX7 3SE, UK
HIFA2015: http://www.hifa2015.org
5:20 AM, 29 Jun 2010 | Permalink
Ailis Tweed-Kent
Dear all,
I'd like to add some thoughts on the use of RDTs in detecting malaria. As many have mentioned, malaria is often over diagnosed and over treated. Even with accurate tests, it has been shown that health care providers continue to treat despite a negative result. In order to change these treatment habits, the health care providers or end users need confidence in the laboratory tests.
Many hope that RDTs will provide this confidence. Currently, there are upwards of 70 RDTs on the market. With so many tests, how do providers know which tests are good and which are bad? The WHO TDR did a survey in 2002 to see how many diagnostic point-of-care devices are regulated. They found that about 48% are regulated, which is surprisingly low. In response to the lack of regulated diagnostics, the WHO TDR then tested and published results on the performance of certain diagnostic tools including RDTs (please find WHO document on performance of RDTs attached).
With regards to RDTs, they analyzed the performance of approximately 68 different tests from a variety of manufacturers. The results provide comparative data and give an idea of clinical sensitivity. They also show ease of use and heat stability. As the authors point out, it is important to consider your particular population when interpreting product performance since the clinical sensitivity of an RDT is highly dependent on local conditions. They are referencing the importance of pre-test probability as well as positive predictive value.
In this report, they found significant variation between tests and between levels of parasite detection. Some were very accurate as listed on the product label, others performed poorly. They stated, in summary:
"This laboratory-based evaluation provides a comparative measure of RDT performance in a standardized way to distinguish between well and poorly performing tests to inform procurement decisions of malaria control programmes and guide UN procurement policy.
Several RDTs from Rounds 1 and 2 demonstrated consistent detection of malaria at low parasite densities (200 parasites/ μl), have low false positive rates, are stable at tropical temperatures, are relatively easy to use, and can detect P. falciparum, P. vivax infections, or both.
Performance between products varied widely at low parasite density (200 parasites/μl); however, most products showed a high level of detection at 2000 or 5000 parasites/μl.
P. falciparum tests targeting HRP2 antigen demonstrated the highest detection rates, but some tests targeting pLDH also exhibited high detection rates.
Test performance varied between lots, and widely between similar products, confirming the advisability of lot-testing post purchase and prior to use in the field.
The results underscore the need for manufacturers to have adequate reference materials for product development and lot-release. The WHO-FIND malaria RDT evaluation programme, in collaboration with the CDC, offers quality standard panels to manufacturers to assist in this process."
Many tests have quite different sensitivities and specificities from what is listed on the label. This document provides great detail and more information can be found on the WHO website at http://www.wpro.who.int/sites/rdt/documents/list.htm. I encourage you to read through these documents if you are interested.
I've also attached an article that outlines how to evaluate and what to consider in RDTs. It is part of a Nature series on point-of-care diagnostics for global health. Similar documents can be found for diagnostics in other diseases as well.
I hope this is helpful. Please feel free to contact me if you have any additional questions.
Sincerely,
Ailis Tweed-Kent (HMS IV)
12:56 AM, 12 Jul 2010 | Permalink
Ailis Tweed-Kent
Article on Evaluation of rapid diagnostics: Malaria
1:02 AM, 12 Jul 2010 | Permalink
Anat Rosenthal, PhD
Hi all,
While acknowledging the importance of accurate tests, and providers’ confidence in the results they provide, when it comes to over-diagnosis of malaria we should also acknowledge the role of social and cultural influences on decision making processes. An interesting study tackling the issue by Chandler et al 2008 (attached) provided a noteworthy outlook on the factors coming into play when a clinician is diagnosing (or misdiagnosing) malaria.
Namely, the authors claim that aside from the diagnostic tools themselves, three spheres of social influence could be identified as causes of over-diagnosis: providers’ initial training emphasizing malaria, the influence of peers, and the pressure to conform to patients’ preferences.
Based on these influences, the authors point to the existence of common “mindlines”, or shared rationales among clinicians, that effect diagnosis. According to these “mindlines” malaria is easier to diagnose than alternative diseases; malaria is a more acceptable diagnosis; and missing malaria is indefensible. When guidelines and “mindlines” clash, the broader social context and the organizational culture often promote over-diagnosis of malaria.
Chandler et al recommend accounting for the various social influences effecting clinicians and moving “mindlines closer to guidelines”. The question remains – how can this be done?
Best,
Anat
http://malariajournal.com/content/7/1/53/abstract
5:12 PM, 13 Jul 2010 | Permalink
Erin Meier
This was a very interesting article Anat, thanks for sharing it. I would say all those "mindlines" are true for us here in Papua New Guinea. Especially the patient preferences. They often come in and say I have malaria, and at times when you explain to them that they don't based on a blood test, or that based on the history another test is indicated, they get upset. Trying to educate them about alternative diagnosis outside of malaria or typhoid is difficult. They don't understand the concept of a viral infection, or another bacterial source. But we need to keep trying.
12:03 AM, 17 Jul 2010 | Permalink
Anat Rosenthal, PhD
Thank you for your comment Erin. I wonder what results a study into patients’ “mindlines” would have. Have you encountered the tendency to call every fever incident “malaria”?
9:10 AM, 19 Jul 2010 | Permalink
Erin Meier
Anat - In PNG we have a Standard Treatment Book - "a manual for nurses, health extension officers, and doctors" that is produced by the our medical societies. This is used by all of our health workers in our rural areas, especially those by themselves in the remote setting. Under Fever, it specifically says to look for causes of fever and treat the cause, but also to give antimalarials. So yes, lots of fevers here are treated as malaria. Only actual functioning hospitals have the ability to do malaria smears. RDTs aren't readily available at this point, but the country is getting some.
3:09 AM, 20 Jul 2010 | Permalink
Timothy Archampong
It looks like the sensitivities and specificities for RDTs vary as per demographic areas and parasitic type. I suppose this calls for more local data on its sensitivity profile depending on the dominant parasitic species so as to streamline RDTs.
4:30 PM, 23 Jul 2010 | Permalink
Anat Rosenthal, PhD
Hi Timothy and all,
Following up on your comment regarding the call for more local data, the following article is an example for one such model developed in Malawi.
Best,
Anat
http://www.malariajournal.com/content/9/1/209
5:03 PM, 23 Jul 2010 | Permalink
ELLIOTT MATOGA
INDEED PRESUMPTIVE TREATMENT REMAINS A CHALLENGE IN OUR SETTING ALSO BECAUSE IN THE PAST TEACHING SAYS THAT A NEGATIVE SLIDE DOES NOT RULE OUT MALARIA. IT IS HARD FOR CLINICIANS DROP THERE PREVIOUS HABITS AND FOLLOW THE NEW GUIDLINES. IN A NEEDS ASSESMENT FOR REVIEW OF OUR CURRICULLUM I VISITED PHARMANCY TECHNICIANS IN FIVE DISTRICTS SOUTHERN PART OF MALAWI WHERE THEY COMPLAINED OF IRRATIONAL PRESCREPTIONS WHICH RESULTED IN AN INCREASED USED OF ARTEMESISN DRUGS. WE ARE NOW ADVOCATING FOR THE NEW GUIDELINES IN OUR TEACHING AT THIS COLLEGE AND YET WHAT WE FIND IN THE CLINICAL AREA IS TOTALLY DIFFERENT. THERE COULD BE AN ATITUDE PROBLEM AS WELL. CLINICIANS DO NOT BELEIVES IN TEST RESULTS FROM RDTS WHY? THEN WHY DO WE DO THE TEST ANYWAY? WHAT CAN BE DONE TO IMPROVE THE SITUATION
7:56 AM, 17 Aug 2010 | Permalink
Anat Rosenthal, PhD
Hi Elliott and all,
Thank you for continuing this great discussion.
Elliott’s comment on presumptive treatment and the difference between guidelines and clinicians’ behavior, goes to the heart of the problem – behavior change. In other words, how do we convince clinicians to adopt new guidelines?
It seems that beyond the familiar factors that are common in many different areas (supply, costs, and diagnostic preferences) part of the problem is trust (trusting the RDTs, trusting the new guidelines, trusting the people who wrote the new guidelines…). However, factors like trust can be very local in their meanings. Maybe if we can isolate some of these factors, we can start addressing them as part of the efforts to change clinicians’ ‘mindlines’.
On the same matter, a study from south-east Nigeria (Uzochukwu et al 2010) identified the reasons for non use of RDTs as: unreliability, supply issues, costs, preference for other methods of diagnosis and providers’ ignorance. Once again, knowledge is a major factor.
Best,
Anat
http://www.biomedcentral.com/content/pdf/1471-2458-10-486.pdf
4:17 PM, 17 Aug 2010 | Permalink