Journal of Clinical Apheresis 29:194–198 (2014)

Benefits and Challenges of Starting a New Therapeutic Apheresis Service in a Resource-Constrained Setting Fatiu A. Arogundade,1 Abubakr A. Sanusi,1 Stephen O. Oguntola,1 Bolanle A. Omotoso,1,2 Emaad M. Abdel-Rahman,2,3 Adewale Akinsola,1 and Rasheed A. Balogun2,3* 1

Department of Medicine, Renal Unit, Obafemi Awolowo University Teaching Hospitals Complex, Osun State, Nigeria 2 Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia 22908 3 Department of Medicine, Renal Unit and Extracorporeal Therapies, University of Virginia Medical Center, Charlottesville, Virginia 22908 Therapeutic apheresis (TA) refers to a group of extracorporeal blood treatment modalities with clinical indications for which the clinicians’ knowledge, availability and applicability vary widely worldwide. Therapeutic plasma exchange (TPE), the most common TA technique, is neither readily available nor affordable in many parts of Africa. This article focuses on the challenges of starting a TPE program in a resource-constrained economy and the result of a survey of Nigerian nephrology professionals on TPE. A critical appraisal of published manuscripts from Nigeria on TA was undertaken to assess uses, methods, and challenges encountered followed by a survey of the perceptions of Nigerian nephrology professionals on TPE. Survey results: 56.7% of respondents had very little or no knowledge of TPE; 40.5% moderate and only 2.7% admitting to having a good knowledge. Only 18.9% of respondents have ever participated or observed a TPE procedure with the remaining 81.1% not having any exposure to the procedure. A vast majority of the respondents 97.3% felt they needed better exposure and training in TPE and its applications. Among consultants, 56% had little knowledge, 88% had never participated or observed the TPE procedure, and 94% felt they needed better exposure and training. There is significant limitation in accessibility, availability, and use of TPE in Nigeria; knowledge of TPE and its applications is minimal among nephrology professionals. Efforts should be concentrated on improving the knowledge and availability of TPE in resource-constrained economy like Nigeria. Centers that would be able to manage C 2014 Wiley Periodicals, Inc. cases requiring TA should be developed. J. Clin. Apheresis 29:194–198, 2014. V Key words: apheresis; resource constrained; plasmapheresis; Nigeria; therapeutic plasma exchange

INTRODUCTION

In some settings, automated therapeutic plasma exchange (TPE) is considered a relatively expensive extracorporeal treatment modality with widespread clinical applications in protean clinical scenarios. TPE can be lifesaving in the management of some nephrological, neurological, and hematological diseases like thrombotic thrombocytopenic purpura (TTP), Gullain– Barre syndrome, and anti-neutrophilic cytoplasmic antibody (ANCA) associated rapidly progressive glomerulonephritis and so forth. This is the reason why these diseases are classified as Category 1 indications by the American Society for Apheresis (ASFA) [1]. There are 78 recognized clinical conditions that could be managed by TPE although its effectiveness and efficacy in the management of different conditions vary widely [1,2]. Starting a new TPE service in any setting could be challenging but in resource-constrained settings, the challenges are multiple and beyond financial considerations. There may be limitation in the expertize, training, infrastructure, and necessary supplies for the procedure. Resource limitation is defined by World Bank as gross national income (GNI) per capita of less than C 2014 Wiley Periodicals, Inc. V

$1,345 and majority of the countries in Africa, particularly Sub-Saharan Africa (SSA) fall into category of resource poor economies. The total population of individuals in SSA is about 910.4 million and over 60% reside in rural areas, the average life expectancy at birth is 56 years [3]. According to the United Nations Population Fund, the population growth of 3% over the last 20 years has outpaced economic gains leaving Africans, on average 22% poorer than they were in the mid 1970s [4]. Nigeria has a population of over 168.8 million (2012) that is projected to increase to 264 million by 2050 with population growth rate of 2.3%. It has GNI per capita of $1,440 which has recently increased *Correspondence to: Rasheed A. Balogun, MD FACP FASN HP(ASCP), Division of Nephrology, University of Virginia School of Medicine, Medical Director, Renal Unit & Extracorporeal Therapies, Division of Nephrology, P O Box 800133, University of Virginia Health System, Charlottesville, VA 22908. E-mail: [email protected]. Received 23 March 2014; Accepted 1 May 2014 Published online 15 May 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21328

New Therapeutic Apheresis Service

beyond the cut off value for low income countries making Nigeria a low middle income country. It has mainly rural population and average life expectancy of 52 years [5]. Nigeria has about 150 nephrologists and more than 55 dialysis units spread round the country with marked rural/urban dichotomy. Majority of these renal care centers are located in urban communities’ particularly state capitals and cosmopolitan cities [6]. There is very little or no documented evidence of the use of TPE as a treatment modality in any of these centers. It is, however, noteworthy that those diseases that are potentially treatable or curable abound in different proportions in different communities in the country.

PREVIOUSLY DOCUMENTED USE OF TPE OR PLASMAPHERESIS OR ITS APPLICATIONS IN NIGERIA

TPE utilization is still very limited in Nigeria, there are few anecdotal reports on the use of TPE in Nigeria. Search was conducted using engines such as PubMed, Biomed Central, Access Medicine, CINAHL database, Embase, emedicine, and google scholar with key words being plasma exchange, plasmapheresis, Nigeria, low resource economy and only three relevant publications were retrieved. Talabi et al. [7] reported a case of a patient managed for myasthenia gravis, who was on neostigmine, pyridostigmine, and steroids for 18 years. This patient not only developed myasthenic crisis and was thus admitted to ICU for respiratory support but also had modified plasmapheresis with resolution of symptoms. They concluded that modified plasmapheresis could be effective in the absence of standard plasmapheresis. Abjah et al. [8] also reported a case of a 56-year-old man who was managed for Waldenstrom’s macroglobulinemia with features of hyperviscosity syndrome. He had modified plasmapheresis with good control of symptoms. Arogundade et al. [9] reported the use of filter membrane-based plasma exchange in the management of two cases of lupus nephritis complicated by TTP with variable outcomes.

PECULIAR POTENTIAL INDICATIONS FOR TPE OR ITS APPLICATIONS IN NIGERIA

The clinical use of TPE or its applications cuts across several disciplines in the field of medicine. Its indications in clinical medicine have been stratified by the ASFA [1] into four different categories based on the level of evidence of its efficacy in treatment of such disease.

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1. Disorders for which apheresis is accepted as firstline therapy, either as a primary standalone treatment or in conjunction with other modes of treatment, for example, TTP, Gullain–Barre syndrome and so forth. 2. Disorders for which apheresis is accepted as secondline treatment, either as a primary standalone treatment or in conjunction with other modes of treatment, for example, acute disseminated encephalomyelitis, unresponsive chronic graft versus host disease 3. Disorders for which optimum role for apheresis is not established. Decision making should be individualized, for example, nephrogenic systemic fibrosis, sepsis with multiorgan failure 4. Disorders in which published evidence demonstrates or suggests that apheresis is ineffective or harmful, for example, uncomplicated systemic lupus erythematosus, active rheumatoid arthritis and so forth. Potential indications for plasmapheresis in Nigeria will include  TTP  Goodpasture’s syndrome or ANCA positive vasculitis with alveolar hemorrhage  Severe sickle cell crisis [10]  Severe malaria with central nervous system involvement or >10% parasitemia [11]  Guillain Barre Syndrome (5/10,000 medical admissions in Nigeria) [12]  Myastenic crisis  Waldestrom’s macroglobulinemia  Chronic inflammatory demyelinating polyneuropathy  Complicated systemic lupus erythematosus [13,14]  Multiple myelomas  Essential thrombocythemia (when platelet count is greater than 1,000,000/mm3; platelet apheresis)  Leukemias (leukapheresis)  Last resort treatment of life-threatening rheumatoid vasculitis Sickle cell disease is very common in Nigeria with about 25% of the population carrying the sickle cell hemoglobin. The estimated number of newborns with sickle cell anemia is projected to increase from 91,000 in 2010 to 140,800 in 2050, and hence, the number of patients that may require erythrocytapheresis will increase [10]. Malaria remains an endemic disease in Nigeria and severe forms as defined by WHO are commonly reported. TPE may assist in reducing the high morbidity and mortality seen in severe malaria [11]. Systemic lupus erythematosus (SLE) is increasingly being diagnosed in our setting with lupus nephritis being a major cause of morbidity and mortality. Journal of Clinical Apheresis DOI 10.1002/jca

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TABLE I. Self perceived Level of Awareness and Knowledge of Therapeutic Apheresis Amongst Nephrology Professionals in Nigeria Assessment of knowledge Categories of professionals Nephrology consultants (n 5 16) Nephrology trainees (n 5 16) Nephrology nurses(n 5 4) Dialysis machine technician (n 5 1) TOTAL (n 5 37)

Nil

Minimal

Moderate

Significant/Good

— — 1 (25%) 1 (100%) 2 (5.4%)

9 (56%) 10(62.5%) — — 19 (51.3%)

6 (38%) 6(37.5%) 3 (75%) — 15 (40.5%)

1 (6%) — — — 1 (2.7%)

Adelowo and Oguntona [13] retrospectively reviewed 1,250 rheumatology cases managed over a 6-year period in a specialist rheumatology clinic in Nigeria and found that 66 (5.28%) had SLE out of which 79.5% of those that had urinalysis had urinary abnormalities. In our prospective follow-up study of lupus nephritis over a 12-year period, 28 cases lupus nephritis were seen out of 650 nephrology admissions amounting to 4.3%. An interesting phenomenon is the increasing rate of diagnosis of lupus nephritis observed [14]. This may lead to increased diagnosis of complicated lupus nephritis (Cerebral Lupus or TTP), which may benefit from TPE [9]. Based on the aforementioned, we conducted questionnaire survey of the perception of Nigerian nephrology professionals on TPE and its applications with the objective of identifying challenges to this therapy and proffering solutions in a bid to improve accessibility and availability when clearly indicated. Methodology

A pretested self-administered questionnaire was designed to assess the individual’s perception of the knowledge of TPE or its applications. Questions were culled from pretest questions previously used during the Annual Apheresis Academy in University of Virginia. The questionnaire sought to assess sociodemographic data, specialty, level of experience, exposure to the practice of TPE, the individual’s perception of the knowledge of TPE or its applications as well as factual assessment of knowledge. Data were analyzed using SPSS package, version 16 and most parameters were presented using descriptive/inferential statistics. Results

A total of 150 questionnaires were prepared to be administered to nephrology professionals during the Annual Conference of Nigerian Association of Nephrology. Only about 100 respondents accepted the questionnaires with majority of them citing their lack of exposure and inability to answer the questions as the reasons for not accepting. Only 37 of them returned completed questionnaires, of these 16 were consultant nephrologists, 13 senior registrars, 3 registrars, 4 Journal of Clinical Apheresis DOI 10.1002/jca

nephrology nurses, and 1 dialysis machine technician. Thirty (81%) of the respondents work in teaching hospitals or other tertiary care centers while only 14 (37.8%) accessed information on TPE from ASFA website with the remaining getting their information from other sources. Thirty-two (86.4%) of the respondents were aged between 30 and 50 years, only two (5.4%) were younger than 30 years while only three (8.1%) were older than 50 years. Twenty-one (56.7%) respondents admitted to very little or no knowledge of TPE while 15 (40.5%) had moderate knowledge with only one (2.7%) admitting to having significant knowledge. Only seven (18.9%) respondents have ever participated or observed a TPE procedure with the remaining 30 (81.1%) not having any exposure to the procedure. A vast majority of the respondents 36 (97.3%) felt they needed better exposure and training in TPE and its applications. Even among nephrology consultants, nine (56%) had little knowledge, 14 (88%) had never participated or observed the TPE procedure, and 15 (94%) felt they needed better exposure and training in TPE and its applications. The responses for other professionals and nephrology trainees are as shown on Tables I and II. DISCUSSION

TPE has wide clinical applications in protean clinical scenarios globally but the peculiar indications in tropical environment may lead to mortality. Aside the general indications listed above, it could find good uses in tropical and infective conditions that are very common in developing countries including Nigeria. Of note is the peculiar advantage of TPE in cerebral malaria, babesiosis, severe sickle cell crisis, complicated SLE, acute inflammatory demyelinating polyneuropathy, and haematological malignancies. Our survey revealed the very low level of knowledge and awareness of TPE and its applications among nephrology professionals in Nigeria. This may be a reflection of the deficiency in the training curriculum and lack of facilities and expertize in TPE and its wide applications. Challenges and Potential Solutions Knowledge and expertize

This is grossly lacking as most practicing nephrologists in Nigeria have minimal or no knowledge of the

New Therapeutic Apheresis Service TABLE II.

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Previous Participation and Willingness to Learn About Therapeutic Apheresis Amongst Nephrology Professionals in Nigeria Participation in TPE procedure (observation)

Categories of professionals Nephrology consultants (n 5 16) Nephrology trainees (n 5 16) Nephrology nurses(n 5 4) Dialysis machine technician (n 5 1) TOTAL

Willingness to learn more

Yes

Nil

Yes

No

2 2 3 — 7 (18.9%)

14 14 1 1 30 (81.1%)

15 16 4 1 36 (97.3%)

1 — — — 1 (2.7%)

TPE or its applications. Our survey assessed selfperceived knowledge, practice and willingness to learn about TPE among Nigerian nephrology professionals, revealed that 58.4% had little or no knowledge of therapeutic apheresis (TA) while only 18.9% had ever participated or observed the procedure. This is unacceptably low considering the incidence and/or prevalence of conditions requiring this therapy. It, however, appears to be a global challenge as Berns [15] reported that despite the availability of expertize and infrastructure, a surveybased evaluation of nephrology fellowship training programs in United States identified plasmapheresis as a key area in requiring better training. Kohan [16] found that among US nephrologists that completed their training 2–6 years prior to his survey, 40% reported no training in apheresis, and only 30% described themselves as well trained and competent in the procedure. In contrast, we found that majority of practicing nephrologists felt they needed more training and exposure. Kohan [16] also found that more than 25% of fellows felt they needed better training in plasmapheresis [16]. When compared with our findings, all our nephrology trainees felt they needed better training, exposure, and expertize on TPE and its different applications. Based on these, there is the need to create awareness about this procedure, its relevance, uses and applications. This may require lectures or workshops. There will also be a need to further strengthen nephrology training curriculum globally such that trainees all over the world will have some exposure to the practice. It will also be mandatory to equip nephrologists and fellows in training that are interested in this area of nephrology with sufficient knowledge of the procedure, indications, and management of its complications when such develop. Infrastructure

There are a few centers that have the filter membrane-based apheresis machine but only one have been able to put it to use. There are no centrifugationbased separation machines as at the time of this report. To be able to fully explore the various applications of apheresis therapy (beyond TPE), the centrifugationbased machine will be indispensable, hence the need for procurement of this machine by interested centers after

sufficient training of respective staff. (Editorial addendum. A centrifugal machine was acquired by the main author’s institution in December 2013, after initial preparation and submission of this manuscript). This will further improve training and expertize in this procedure locally with its inherent benefits to the patients in need with consequent improvement in life expectancy. Supplies

The lines and replacement fluids would need regular supply, hence this must be assured to have a hitch free treatment plan. Funding of treatment

Funding of treatment is largely patient centered with most patients paying out of pocket as it is the case with dialysis and transplantation in Nigeria [17,18]. There will be a need for government subsidy of this care to improve accessibility and availability. The coverage for most acute conditions may be covered by health insurance. CONCLUSIONS

Although setting up a new TA service is challenging, its benefits as a lifesaving procedure in some conditions justifies the huge financial outlay that may be required. The challenges of technical expertize, training, infrastructures (machines and replacement fluid), and funding of treatments could be surmounted with good planning and health management. There is significant limitation in the accessibility, availability, and use of TPE in Nigeria even where it is clearly indicated. Knowledge of TPE and its applications are generally minimal among nephrology professionals in Nigeria. Efforts should be concentrated on improving the knowledge and availability of TPE in resource-constrained economy like Nigeria. A few centers that would be able to manage cases requiring this type of therapy should be developed. ACKNOWLEDGEMENT

The contents of this review were presented at the September 2013 Therapeutic Apheresis Academy, University of Virginia, Charlottesville, VA. Journal of Clinical Apheresis DOI 10.1002/jca

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