Research Article: Diagnostic system strengthening for drug resistant tuberculosis in Nigeria: impact and challenges

Date Published: March 31, 2017

Publisher: AOSIS

Author(s): Gambo Aliyu, Nicholas Ezati, Mosunmola Iwakun, Sam Peters, Alash’le Abimiku.


The increasing prevalence of drug-resistant tuberculosis and the threat of extensively-drug-resistant tuberculosis in HIV hotspots have made the detection and treatment of drug-resistant tuberculosis in the sub-Saharan Africa setting a global public health priority.

We sought to examine the impact and challenges of tuberculosis diagnostic capacity development for the detection of drug-resistant tuberculosis and bio-surveillance using a modular biosafety level 3 (BSL-3) laboratory in Nigeria.

In 2010, the United States President’s Emergency Plan for AIDS Relief (PEPFAR) programme, through the Institute of Human Virology at the University of Maryland in Baltimore, Maryland, United States, deployed a modular, BSL-3 laboratory to support the national tuberculosis programme in drug-resistant tuberculosis detection and bio-surveillance for effective tuberculosis prevention and control.

From 2010 until present, sputum samples from 11 606 suspected cases in 33 states were screened for drug-resistant tuberculosis. Of those, 1500 (12.9%) had mono-resistant tuberculosis strains, and 459 (4.0%) cases had multidrug-resistant tuberculosis. Over the last four years, 133 scientists were trained in a train-the-trainer programme on advanced tuberculosis culture, drug susceptibility testing, line-probe assays and Xpert® MTB/RIF, in addition to safety operations for biosafety facilities. Power instability, running cost and seasonal dust are notable challenges to optimal performance and scale up.

Movable BSL-3 containment laboratories can be deployed to improve diagnostic capacity for drug-resistant tuberculosis and bio-surveillance in settings with limited resources.

Partial Text

Nigeria has a limited high-level certified laboratory infrastructure and trained human resources to support a comprehensive public health response to the tuberculosis pandemic.1 Until recently, the conventional culture-based drug susceptibility testing (DST) platforms for detecting drug-resistant tuberculosis were available only in select public and private laboratories.2 Presumptive cases of multi-drug resistant (MDR) tuberculosis from different parts of the country went to the distant coastal city of Lagos for diagnosis and at the Nigerian Institute for Medical Research, which housed the only tuberculosis reference laboratory for a population of over 170 million. The number of culture reference laboratories has risen to seven, yet they covered only 4% to 8% of the World Health Organization-recommended population target of one functioning culture laboratory per 500 000 to one million population.3 According to a 2011 WHO report on global tuberculosis control, two in 100 of the newly detected tuberculosis cases and nine in 100 of re-treated cases in Nigeria were MDR tuberculosis.4 The National Tuberculosis and Leprosy Training Centre in Zaria has the largest tuberculosis referral center in northern Nigeria, with an average of 25–30 new smear-positive tuberculosis cases enrolled in treatment and care monthly; about 27% of the enrolled tuberculosis cases are co-infected with HIV.5 In addition to the reference laboratory, the centre has a large outpatient clinic for the management of tuberculosis, HIV and leprosy. It also has training facilities as the national training centre for tuberculosis and leprosy. It has a modest inpatient facility, mainly for the treatment of MDR tuberculosis, with a 20-bed capacity and two isolation rooms.

Following several failed attempts to upgrade or renovate existing structures and uncertainties about the structural building requirements to withstand the negative pressure required for such laboratories, Germfree Laboratories, Inc., based in Ormond Beach, Florida, United States, was contracted by the Institute of Human Virology at the University of Maryland to design, construct, deliver and assemble the movable BSL-3 laboratory with input from the Institute’s staff. Following several modeling sessions, the laboratory was designed using two 40-foot containers with all the equipment required to make it functional. It was then disassembled and the components and accessories were shipped to Lagos, Nigeria, and delivered to Zaria by oversized haulage truck to the National Tuberculosis and Leprosy Training Centre, where the laboratory is currently located (Figure 1).

The modular laboratory serves as one of the two tuberculosis national reference laboratories in Nigeria. Services were mostly limited to the northern states until 2013, but by 2015 both northern and southern states were served (Figure 3). The laboratory performs and builds in-country capacity to perform solid and liquid cultures, DST, line-probe assays and GeneXpert tests. The line-probe assay and GeneXpert tests are not performed in the BSL-3 laboratory, but in a separate laboratory in the same complex by the same laboratory personnel.

As in most developing countries, an erratic power supply is a major challenge in Nigeria. The modular BSL-3 laboratory was operated on stand-by generators supported with a high capacity inverter system to ensure a steady supply of electricity. This added to the cost of operationalising the laboratory. The dry Harmattan wind from the Sahara Desert generates a lot of dust in winter in the north of Nigeria, where the laboratory is located. Germfree Industries, Inc. designed a pre-filtration unit using easily replaceable filters to filter the air supply before it reaches the more costly high-efficiency particulate air supply filters of the heating, ventilation and air conditioning system.

There are few BSL-3 tuberculosis laboratory prototypes in the sub-Saharan African setting. The modular BSL-3 laboratory offers a useful alternative for construction of such a facility. Lack of indigenous firms with professional expertise in the construction and maintenance of a BSL-3 containment laboratory to international standards – which is a critical first step in establishing a biosafety laboratory11 – informed the decision to buy a pre-constructed model. A modular laboratory was deployed by ZAMSTAR in 2009 in Zambia to conduct a national prevalence survey. Like our model, it was constructed in a 40-foot container with all equipment and accessories.12 However, compared with the ZAMSTAR model, our model cost more, because of additional accessories including power backups, cameras, walk ways, and overhead water tanks required for optimal functioning of the laboratory. Although the establishment of this laboratory appears to be expensive in the beginning, given the unmet need for expertise in biosafety containment and development of local capacity, it is an investment worth the cost. During the five years after its instalment, operations have been optimised to meet the local needs of the national tuberculosis programme without a break in service delivery.

A modular BSL-3 laboratory was deployed to strengthen detection of tuberculosis and drug-resistant tuberculosis in Nigeria. It operates optimally and collaborates effectively with established international laboratories to strengthen the national tuberculosis programme. Priority should be given to modular laboratories in settings with limited expertise in building facilities for the isolation and characterisation of dangerous biological agents such as drug-resistant and MDR tuberculosis. Since the establishment of this first prototype model in a developing country setting, Germfree Laboratories, Inc. has used the knowledge acquired to establish a modified and more affordable biosafety level 2 system that has the capacity for BSL-3 practices with the addition of a Class III biosafety cabinet, also referred to as glove box. The addition of the Class III biosafety cabinet with a direct sample entry pass-box makes it possible to safely handle highly-infectious samples.




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