Cameroon's MDR-TB treatment programme jeopardised by cross-border migration

To the Editor:

We read with interest in a recent issue of the European Respiratory Journal, a paper by Lönnroth et al. [1] entitled. “Towards tuberculosis elimination: an action framework for low-incidence countries”. The authors highlight cross-border migration as a major challenge for tuberculosis (TB) control efforts and their action framework pleads for strong international partnerships for reaching global TB elimination targets. To further comment on the challenges posed by cross-border migration, we here report on a recent experience of Cameroon's National TB Programme (NTP).

Since 2005, Cameroon's NTP has been treating multidrug-resistant (MDR)-TB patients with standardised therapeutic regimens inspired by the experiences of Van Deun and colleagues [2, 3] in Bangladesh. From 2008 to 2012, patients were treated using a short duration regimen (12 months); a cohort assessment of the first 150 patients revealed an 89% therapeutic success rate [4]. Since 2013, patients have been treated using a 9-month regimen (4KmMfxPtoClzEZH/5MfxClzEZ; known as the “Bangladesh regimen”). Evaluation of a first cohort shows a therapeutic success rate of 82%. In 2014, a total of 91 patients were put on treatment. Unlike the World Health Organization (WHO) recommended regimens for the management of drug-resistant TB, short-course regimens are easily implemented, use less toxic drugs, are more tolerable, limit the use of injectables and reduce the risk of treatment interruption and defaulting [5, 6]. Moreover, the fact that patients in Cameroon have very little or no exposure to second-line anti-TB drugs, particularly to fluoroquinolones, for the treatment of diseases other than TB, might contribute to the programme success. How fluoroquinolone resistance in MDR-TB patients compromises favourable treatment outcomes was shown by Falzon et al. [7] in a large individual patient data meta-analysis.

For several years, MDR-TB patients from neighbouring countries not offering MDR-TB treatment, for example Equatorial Guinea, have been put on standardised treatment in Cameroon, based on the assumption that the epidemiological situation in these countries may possibly be similar to that of Cameroon. Since the beginning of 2015, Cameroon's NTP has seen a large influx of MDR-TB patients from Equatorial Guinea. 14 MDR-TB patients have been put on treatment on the basis of an Xpert MTB/RIF (Cepheid, Maurens-Scopont, France) test result “Rifampicin-resistance” in accordance with the national guidelines.

An early patient from Equatorial Guinea proved resistant to fluoroquinolones in late 2013 and eventually failed her treatment, and was considered as an “anecdotal” event. Recently, a second patient's cultures did not convert to negative after 6 months of treatment. Drug-resistance testing by line probe assay (LPA) once again brought to light resistance to fluoroquinolones. Interviews with patients revealed that most of them had been exposed to repetitive courses of ciprofloxacin (Cfx) for the treatment of typhoid fever, a pathology widely over-diagnosed and over-treated in Central Africa. Table 1 summarises epidemiological and clinical characteristics of the Equatorial Guinean patients put on treatment since 2013 with LPA results awaited for some of them.

Two practical questions arise immediately. Should the 9-month regimen of patients with a history of repetitive exposure to Cfx who are presently under treatment be changed and how? Also, how best could patients who do not convert be treated and where to perform the treatment?

Yet, this cross-border “invasion” of MDR-TB patients with hitherto unknown drug-resistant profiles from a neighbouring country with an apparently sub-optimally functioning NTP is worrying not only in practical terms. The management of drug-resistant TB in Cameroon was conceived and implemented following systematically gathered knowledge of the local endemic, continuous monitoring and careful evaluation. The programme functions thanks to entirely external funding (Global Fund) based on projected local endemic trends. The sudden and massive influx of patients with resistance profiles not taken into account when implementing the programme represents a heavy burden to the already limited resources and requires additional means (revised diagnostic and treatment protocols, training, procurement of additional drug etc.). At stake are also the programme's outcome indicators with failure, death and, in particular, lost to follow-up rates expected to increase. Ultimately, transmission and subsequent spread of fluoroquinolone-resistant MTB strains among the indigenous population should to be feared.

What next? Without delay, the NTPs of Equatorial Guinea and Cameroon should jointly assess the magnitude of the present MDR-TB problem in Equatorial Guinea. How many candidates for treatment are there, where should they be treated and under what conditions? Moreover, the performance of the NTP of Equatorial Guinea should be scrutinised, weaknesses identified and immediate and strong remedial measures taken. It would be worth considering a potentially very fruitful south–south collaboration under the aegis of the local WHO representations, supported by a technical north–south partnership, also in the interest of TB elimination in the north [8].

Finally, in 2014, participants of a symposium organised by the European Respiratory Society pleaded for the rational use of new and existing TB drugs [9]. And very recently, the Stop TB Partnership joined the call for urgent action of the G7 group of countries, highlighting antimicrobial resistance as a top priority on the global development agenda [10]. Indiscriminate prescription of broad-spectrum antibiotics like Cfx for doubtful pathologies, which still has to be confirmed for Equatorial Guinea, would be another example of the disastrous consequences of antibiotic misuse.