Improving the Quality of Medical

¶ … Improving the Quality of Medical Laboratory Services in Resource-Limited Settings

The critical nature of emergency medical services in Saharan and Sub-Saharan Africa is paramount as development during the 21st century is poised to arouse Africa to harness its power to become a global economic player. The Aforementioned emergency care is akin to emergency medical response teams that can arrive on-site with an onsite laboratory where blood testing, transfusion (if blood packs are obtained), where diagnosis of communicable diseases via laboratory testing is essential.

However, there are many issues associated with the availability of on-site diagnosis or locality over a large geographic region where a stand-alone facility with microbiology laboratory and diagnostic department is available. Economic constraints limit the development of such a network within the context of establishing the facilitation health structures. Tangential to the lack of resources for laboratories, are the high infection rates in African hospitals where at the highest, 25% of the wounds become infected (Loefler, 1998).

Poverty is the most cited reason for the lack of these services as, according to Loefler, "...shortage of facilities, equipment, dressings and drugs, notably antibiotics." (Loefler, 1998) Supporting variables include overcrowding in populated areas where stand-alone facilities exist, insufficient environmental hygiene conditions conducive to the spread of disease, and insufficient maggot control leading to a large infestation of flies throughout (Loefler, 1998).

Research from Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, characterized the aforementioned and observed the following.

"The relationship between the socio-economic status (SES) of a household and its sources of malaria diagnosis and treatment was explored in south-eastern Nigeria. One aim was to see if, as seems likely, the poorest people generally seek care from 'low-level' providers, such as traditional healers and community-based healthworkers, because of their severe budget constraints. Interviewer-administered questionnaires were used to collect information from 1197 randomly selected respondents from four villages where malaria is holo-endemic. An index was used to categorize the study households into SES quartiles. The self-diagnosis of presumptive malaria and the use of patent-medicine dealers for treatment were very common among all the SES groupings. Compared with the other interviewees, however, the least-poor were significantly more likely to rely on laboratory tests for diagnosis and to visit hospitals when seeking treatment for presumptive malaria. The most poor, in contrast, were significantly more likely to seek treatment from traditional healers or community-based healthworkers. Thus, even though the use of low-level providers was so common, there was still evidence of wealth-related inequity -- in terms of the probabilities of the good diagnosis and treatment of malaria. Improvements in the quality of malaria diagnosis and treatment by the providers patronised by the most-poor villagers would help to redress this inequity, at least in the short- to medium-term. (Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, 2005)

A case in Uganda as described by Dennis Burkitt, a physician of British descent:

"First described Burkitt's lymphoma (BL) among Ugandan children in 1958 (Burkitt 1958, 1985). Within the intervening 44 years, the disease has provided scientists with valuable insight into the pathogenesis of cancers, including the possibility of a link with a virus (Ambinder 2003). BL affects the body's lymph system and results in tumours composed of lymphocytes." (Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, 2005)

"Burkitt's tumours arise and grow rapidly. But in poor countries where it is endemic, many affected families can hardly afford even the cost of basic laboratory diagnostic tests, and this readily treatable condition can be a cause of considerable distress and early death in affected children. Our aim is to present an overview of some of the challenges encountered by children and their families in accessing care for BL in south-eastern Nigeria and the impact of this on the disease outcome for the children." (Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, 2005)

The effects of BL depend on the site of the tumour in the body. In African BL, the jaw is the commonest site, where it causes visible swelling of the cheek and loosening of the teeth (Ong et al. 2001). In non-African BL, the tumour commonly arises in the abdomen where it causes swelling and discomfort (Cavdar et al. 1994). Diagnosis is by biopsy from the suspected disease site. Common tests include a complete blood count (CBC), a platelet count, a bone marrow aspiration and biopsy, and lumbar puncture. Further tests may include radiographic examinations such as CT scan to identify occult masses, but the extensive X-ray procedures are not usually needed." (Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, 2005)

"The study was retrospective and covers the period January 1987 to June 2004. Included in this report are children under 15 years of age who had clinical and histopathologic diagnosis of BL and complete hospital records (sociodemographical and medical). Some cases of jaw tumour were not confirmed by histopathology because the parents had no money for this and other laboratory tests." (Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, 2005)

"Facilities for laboratory confirmation were available but nine (22%) of the parents could not afford the fee. One of these parents had their child treated on the basis of clinical assessment only, but eight (19.5) children could not receive any treatment because the parents could not afford the cost. Frustrated by this experience, the parents either absconded or let against medical advice. Seven (17.1%) other cases had monotherapy (only cyclophosphamide), as the parents had only enough to buy this." (Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, 2005)

"Availability of diagnosis facilities and necessary chemotherapeutic agents at affordable cost are vital for effective management of BL. In this report, although laboratory facilities were available, they were not accessible to all the patients. Nearly a quarter of the parents could not afford the costs of confirmatory laboratory tests. One child was treated without histopathological confirmation would expose misdiagnosed cases to adverse effects of these agents with no clinical benefits at all." (Onwujekwe, Ojukwu, Uzochukwu, Dike, Ikeme, Shu, 2005)

The research clearly indicates a lack of not only a cohesive system but also a comprehensive system offering laboratory medical care with immediate access from the urban environment to elemental wild environment. Parasitical inhabitation within human tissue is a related medical issue that requires laboratory and diagnostic work. According to Chappuis, Loutan, Simarro, Lejon, and Buscher, 2005:

"Human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense or T. b. Rhodesiense remains highly prevalent in several rural areas of sub-Saharan Africa and is lethal if left untreated. Therefore, accurate tools are absolutely required for field diagnosis. For T.b. gambianse HAT, highly sensitive tests are available for serological screening but the sensitivity of parasitological confirmatory tests remains insufficient and needs to be improved. Screening for T.B. Rhodesiense infection still relies on clinical feastures in the absence of serological tests available for field use. Ongoing research is opening perspectives for a new generation of field diagnostics. Also essential for both forms of HAT is accurate determination of the disease stage because of the high toxicity of melarsoprol, the drug most widely used during the neurological stage of the illness." (Chappuis, Loutan, Simarro, Lejon, and Buscher, 2005)

"Quantitative buffy coat. The quantitative buffy coat (QBC; Beckton-Dickinson), initially developed for the rapid assessment of a better discrimination from white blood cells. After high-speed centrifugation of the blood in special capillary tubes containing EDTA, acridine orange, and a small floating cylinder, motile trypanosomes can be identified by their fluorescent kinetoplasts and nuclei in the expanded buffy coat." (Chappuis, Loutan, Simarro, Lejon, and Buscher, 2005)

"The QBC is a very sensitive technique that is very appreciated by most field laboratory workers. It also allows the diagnosis of concomitant malaria, which is very useful for patient care. With a 95% sensitivity for trypanosome concentrations of 450/ml, the QBC can detect more patients with low parasitemia than the mHCT when fewer than eight capillary tubes are used. It is as sensitive as the mini-anion-exchange centrifugation technique." (Chappuis, Loutan, Simarro, Lejon, and Buscher, 2005)

Table 1:

Items

Unit costs/details (local currency, Naira)

Total cost per child treated (Naira)

Cost per child treated (U.S.$)

Laboratory tests at first diagnosis: haematology, histopathology, biochemistry, X-ray, ultra sound

CBC = 350

18.9

Histopathology = 500

X-ray = 600

Ultrasound = 500

Biochemistry = 500

Laboratory tests during follow-up

9.6

Cost of cytotoxic drugs (for 6-course treatment regimen): vincristine, cyclophosphamide, methotrexate

Cyclophosphamide (1000 x 6) = 6000

13 500

Vincristine (900 x 6) = 5400

Methotrexate (350 x 6) = 2100

Other patient costs: bed fee, drips, infusion sets, including cross-match and screening blood for transfusion (1 unit)

Drips (@ 80 x 6) = 320

31.5

Infusion sets (@ 40 x 7) = 280

Bed fee (@ 50 x 28) = 1400

Blood transfusion (cross-match, screening for hepatitis B and HIV) = 2100

Total direct cost per child treated

21 300

US $163.8

Table 1. Direct costs of treating a 7-year-old with Burkitt's lymphoma in Nigeria

Source: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3156.2004.01348.x/full

According to Nicoll, Walraven, Kigadye, Klokke:

"The diagnostic process carried out by clinicians in any country should be supported by reliable laboratory services. In many small hospitals and health centres in developing countries laboratory facilities and services are rudimentary. This is particularly the case in sub-Saharan Africa where clinicians have often come to rely on signs and symptoms alone to make diagnoses." (Nicoll, Walraven, Kigadye, Klokke, 1995)

The laboratory environment is critical to administering testing to determine population rates of HIV / AIDS throughout nations and perhaps continents where the lacking of resources facilitates a substandard environment for care. In the case of the African nation of Mozambique, which perhaps can be understood as a case indicative of the environmental assessment one would find throughout Africa and therefore, can be labelled to be a median statistical nation. A nation representing the median would indicate that half of the population nations that are categorized as resourced deficient, half would be above Mozambique in terms of resource allocation and half would fall below.

Research into the quality of HIV / AIDS case-detection and case-reporting system in Mozambique was conducted by (Chilundo, Sahay, Sundby, 2004). The preliminary argument in the research proposes a fundamental lack of management systems necessary to do the basic work of hematology including medical laboratory procedures and analysis. These facilities, certainly at the mobile level, are lacking throughout Mozambique, from the "peripheral facilities through to those at the national levels." (Chilundo, Sahay, Sundby, 2004)

The inherent flaws in the system are of an interdisciplinary nature, such that the testing performed on ground level, may or may not obtain the correct analytical result of whether or not patient x is positive for HIV / AIDS. Such results, whether positive or negative, then are targeted for misplacement or another form of mismanagement along the transmission of data/information chain as the lack of a strong information system prevents the results from the field to entering into a manageable and reportable database at a central location at the national level.

According to Chilundo, Sahay, Sundby (2004), "HIV / AIDS case-reporting is compromised by poor data quality, including under-reporting and discrepancies across different reporting channels and organizational levels, as well as a lack of standardized data forms, data items collected and report formats. Our analysis of HIV / AIDS surveillance systems in Mozambique leads to the following key recommendations:" (Chilundo, Sahay, Sundby, 2004)

A strengthening and standardization of both the case-detection and case-reporting systems at all levels

The regular training of staff at all peripheral facilities, to allow for better testing and improved local data analysis, validation and interpretation

The redesign of reporting systems for blood banks, including integration of the AIDS case-reporting subsystems into one

The use of baseline data as a foundation for more comprehensive analysis across the country, in response to UNAIDS advice regarding second-generation HIV surveillance

Source: The quality of HIV / AIDS case-detection and case-reporting systems in Mozambique. (Chilundo, Sahay, Sundby, 2004) African Journal of AIDS research 2004. 145-155

The Chilundo et al. research did uncover the details of the current delivery of laboratory services that is currently in place within the geographic borders of Mozambique. Specifically, the measures used to identify patients with positive HIV samples are designed for field work. According to Chilundo et al. (2004), "Similar to most African countries (remember median), the majority of testing facilities in Mozambique use the rapid or simple assays as both a screening and confirmatory test (CDC/WHO-AFRO, 2001; UNAIDS/WHO, 2001)." (Chilundo et al., 2004)

The simple assays offer dual support as a screener and confirmatory test procedure. As with most HIV testing, the simple assay is a serum-based test and therefore detects for the presence of antibodies by the form of t-cell count instead of an exacting presence of the actual human immune-deficiency virus. It is termed a rapid test as the results are obtained in minutes and do not require the use of additional reagents or the use of any additional equipment (Chilundo et al., 2004).

According to Chilundo et al., 2004) "These tests can be easily conducted in a clinic (on-site testing) and in laboratories without electricity or those having limited infrastructure (i.e. lacking highly-skilled staff and special equipment). Thus, these rapid/simple assays are compatible with the existing constraints that exist nationwide in Mozambique's peripheral testing facilities. The commercial rapid tests currently used in all provinces and districts are Determine and Uni-gold. Both are in vitro qualitative immunochromatographic assays able to detect antibodies to HIV1 and HIV2, present in serum, plasma or in the whole blood of infected individuals." (Chilundo et al., 2004)

However, the major problem with the Determine and Uni-gold tests is the sensitivity to operating and environmental temperatures. This is to say, the operating temperature in Celsius/Centigrade will be consistent with temperature within a 'clinical' setting, inside of a 'structure' where patients are tested within a 'closed' environment. This may be within a van, truck, temporary free-standing laboratory facility, or similar, such as a tented field facility. The environmental temperature is that obtained in the raw environment, which is outside in the beating sun with no protection.

The tests have a strict operating temperature environment, operating ostensibly due to the likelihood of the tests being conducted within a structure or pseudo structure capable of reducing the heat and therefore core temperature of the testing equipment. According to Chilundo et al., (2004) "HIV tests are routinely performed in the VCT centres, blood banks and clinical laboratories. Usually the blood banks and laboratories are located in the same building, test kits have a shelf life of 18 months at temperatures of 2-28/30 degrees Celsius. The test kit called Determine has a specificity of 99.4%, and Uni-gold 100%. Determine is utilized to screen for 'positives', while Uni-gold is utilized for confirmation, given its higher specificity, to ensure that all truly negative tests results are identified as negative, thus ruling out false-positive results (UNAIDS/WHO, 2001)." (Chilundo et al., 2004) This is the equivalent to the range of 35.6-82.4/86 on the Farenheit scale. The tests have a sensitivity of approximately 100% (Chilundo et al., 2004)

Africa is a very hot continent and Mozambique's temperature throughout the year is certainly within three standard deviations of what would be the mean temperature of Sub-Saharan Africa. According to data obtained from climattemp.info, the maximum temperatures in Mozambique right at the maximum of 30 degrees Celsius from January through mid March and then decline to about 25 degrees Celsius by June then rising to 30 in mid December. The operating temperature of each type of test is just within the range of the environmental operating temperature.

The issue of Quality Control within these environments where laboratory resources are lacking is of additional concern. According to Chilundo et al., (2004) "External quality assessment (of laboratory results and procedures) is expected to be performed on a regular basis by an external agency or supervisor in order to identify and correct testing facilities that exhibit poor performance. We found such external checking was seldom done. However, we found that on-site evaluation through supervision visits by either provincial or national managers regularly occurred at VCT centres. Laboratories and blood banks appeared to be infrequently and irregularly supervised. For example, the testing facility using outdated test kits had not been visited by a supervisor in the previous two years, despite the fact it was only about 30 kilometres from provincial headquarters." (Chilundo et al., 2004)

According to Consultation on Technical and Operational Recommendations (2008), there is a tiered laboratory network in alignment with a public health delivery network in a country (Consultation on Technical and Operational Recommendations, 2008).

Level One/Primary: Health post and health center laboratories that mainly serve outpatients

Level Two-District: Laboratories in intermediate referral facilities, such as district hospitals

Level Three-Regional/Provincial: Laboratories in a regional or provincial referral hospital that may be a part of a regional or provincial health bureau.

Level Four-National/Multicountry Reference Laboratory: The national/multicountry public health reference laboratory for one or more countries.

Source: Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization. (2008)

The level One Laboratories as described by the Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization, these labs would act as the service outpost within the "peripheral branches of Level Two laboratories, which would be the center or hub." Health posts may collect and/or refer specimens to health center laboratories." (Consultation of Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization, 2008)

Level One Labs would be extremely efficient in operations, utilizing only the bare necessity needed to perform diagnostic and monitoring services for HIV / AIDS, TB and malaria. To obtain the data necessary to render a diagnosis, the labs must "perform specimen collection and simplified techniques such as the collection of dried blood spot (DBS) and rapid/dipstick tests. When required testing exceeds the scope of services available from Level I facilities, the "parent" Level II laboratories would provide a range of consultant services, including the receipt of referral specimens and patients. In many cases, such as with DBS or a TB culture, the specimen may bypass a Level II laboratory and go directly to the nearest performing laboratory." (Consultation of Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization, 2008)

The Level Two Labs would incorporate the district level hospital system or the primary hospital labs where testing is performed that is beyond the scope and ability of the Level One labs (Consultation of Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization, 2008). The size of the lab is larger than level one consisting of more technologists and a managerial technologist, indicating a data-management role at this level.

Specifically, the Level Two labs will provide an extensive list of services to Level One labs as a function of an integrated laboratory network. The consultant and support services include the following:

Managerial oversight of an outreach program of peripheral primary laboratories (Refer to Annex J, Reference No. 1)

Referral laboratory services with a more extensive test menu

On-site quality assessment visits

Assistance with resolving technical problems

Data management support with a strong paper-based laboratory information system (should be part of a national system of data collection by the Ministry of Health [MOH])

Development and implementation of QA activities (including, but not limited to QC, QI, and EQA/PT

Periodic review of QC

Information and training for adequate specimen collection

Collection of data for assessment of quality indicators

Approval and annual review of SOPs and policies to ensure alignment with current practices

Assistance with development of SOPs and safety procedures

Staff development/training, performance management, competency assessment, and retraining

Coordination of courier/transport services

Assistance with results reporting and record retention

Equipment maintenance and service support including review of maintenance logs

Follow-up on laboratory incident and accident reports

Assessment of safety management practices

Source: Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization. (2008)

The Level Three labs would provide comprehensive HIV / AIDS, TB and malaria testing including testing for additional diseases. The location of these facilities would be "tertiary facilities such as regional or provincial hospitals. Level III laboratories would act as laboratory resource groups for the facilities in their regions." Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization. (2008)

The Level Three labs will also perform the following services:

A more comprehensive test menu than that provided at Level II laboratories

Coordinate surveillance data collection from lower levels in an effort to obtain country wide statistics

May collect and submit inter-laboratory comparisons and EQA data for the region to the national reference laboratory

Develop training programs and coordination of continuing education

Assure adequate requisition and reporting mechanisms as well as record retention procedures

Standardize units, methodologies and reference ranges based on national reference laboratory recommendations

Determine the amount of patient history/clinical presentation required for tests referred to other levels

Provide logistical and management support to their service areas

Source: Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization. (2008)

The Level Four labs are the national level labs that also span multi-country in the sense that they act as reference laboratories for diseases of public health. (Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization, 2008)

The ideal link in the chain for the Level Four laboratory is as the link to research labs, academic research and medical institutions, and any additional public health laboratories and research facilities. The goal is to unify and form a "integrated laboratory network that can provide assistance in clinical trials, evaluation of new technologies and surveillance. Senior program employees, laboratory management and senior laboratory technologists/scientists would staff these laboratories. Level Four laboratories would possess the infrastructure, equipment, information systems, and logistical capabilities of sophisticated reference laboratories. In some countries lacking a unique national/multicountry reference laboratory, Level III laboratories may serve as national reference laboratories." (Consultation on Technical and Operational Recommendations for Clinical Laboratory Testing Harmonization and Standardization, 2008)