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Low Detection Rate of Multidrug-Resistant and Rifampicin-Resistant Tuberculosis in the Democratic Republic of Congo: Trend Analysis 2013-2017

The Democratic Republic of Congo is one of the countries with a high prevalence of multidrug-resistant tuberculosis (MDR-TB) in Africa and worldwide. This study aims to describe the trends and level of screening since 2013. This is a retrospective descriptive study based on quarterly reports from the provinces. The number of cases, past histories, age, sex and HIV Co-infection was identified. It emerges that the number of cases increases significantly but does not reach the forecasts yet (912 cases of MDR/RR and XDR diagnosed in 2017 out of 3948 cases expected with a gap of 77%). Patients with a history of TB predominate (63.5% in 2017); but the proportion of patients with no history of TB increases (36.5% in 2017). This suggests high rates among contacts. Women (37.8%) and children under 15 (2.7%) are less represented. TB/HIV Co-infection is 12% as for sensitive cases. Efforts still need to be made to improve screening.


Introduction
Drug resistance to first-and second-line TB drugs represents a major challenge for overall control of TB [1] [2] [3] [4]. were reported [2]. The best estimate is that, worldwide in 2017, 558,000 patients (range 483,000 -639,000) developed TB that was resistant to Rifampicin (RR-TB) and of these, 82% had multi-resistant TB form (MDR-TB) with resistance to at least Rifampicin and Isoniazid [5]. The exact estimate of the incidence of this infection remains difficult because of variations in strategies and reporting across different countries. But three countries accounted for almost half of the world's cases of MDR/RR-TB: India (24%), China (13%), Russian Federation (10%) [3] [5]. Globally, 3.5% of new TB cases and 18% of previously treated cases had MDR/RR-TB in 2017 [3]. Among cases of MDR/RR-TB, 8.5% were estimated to have extensively drug-resistant TB (XDR), in which there is also associated fluoroquinolone and/or second-line injectables (kanamycin, amykacin, capreomycin) resistance [3].

Material and Method
This is a descriptive retrospective study. It is based on provincial quarterly reports validated during the annual reviews of the National Tuberculosis Program (NTP) for the period 2013-2017. The data concern children and adults. The concepts used meet WHO definitions [5]. The term "Multidrug Resistant" (MDR) applies to patients with at least rifampicin and isoniazid resistance without the combination of quinolones or injectables [5]. Cases with isolated resistance to rifampicin (RR) without isoniazid are also reported as such because they are more likely to be MDR. The quarterly reports were collected by the Central data manager of the NTP.
At this level annual synthesis is performed.
The descriptive statistics consisted of calculating the mean and standard deviation for the quantitative data and proportions (percentages) for the categorical data.  Table 1 presents results by year compared to all cases of tuberculosis detected.

1) Trend in the
Overall, the number of tuberculosis cases detected has increased by 38%.  Figure 1 shows the prevalence by province.
3) Patients with MDR/RR -TB by Gender in DRC: 2013-2017: Table 2 gives the distribution of MDR/RR-TB patients by sex and year.
Women are fewer. The sex ratio (M:F) is 1.6:1.

4) Patients with MDR/RR-TB by age:
Mean-age is 35.5 (11.3) years. Eighty-two patients are aged 0 to 14 years (2.7%). The group aged 15 years or more is predominant.

5) Previous history of tuberculosis
Patients with a history of tuberculosis predominate. However, the number of those without a history of tuberculosis is increasing substantially to double 2013 in 2017. Table 3 summarizes the data.

6) Co-infection TB-VIH
Analysis is based on 2017 data only. From 893 cases screened, 518 (58%) were tested for HIV, 61 (12%) were HIV positive. HIV testing depended on the availability of the device and reagents in the health facilities.    Strengthening the strategy for mapping contacts is advised.

Discussion
Four provinces screen 72% of MDR-RR TB cases in the country. They are considered as Hot Spots for drug-resistant TB. Two have areas with intense mining activities. For the 2 others, it is a big city and a harbor with intense activity. This context requires innovative approaches to manage particular patients such as mine workers, harbor residents and crowded cities with often comorbidities [17].
Women are fewer. This is seen even for sensitive TB. Marçôa D. et al. report a sex ratio of 1.6:1 for men [18]. On the one hand, they mention the difficulties women in resource-poor countries face in accessing health facilities. On the other hand, men have comorbidities that may expose them to tuberculosis and phamaco-resistant forms; include alcohol, tobacco, imprisonment, and HIV. In women, the overall prevalence of tuberculosis reported remains lower than in men and this has been reported for many infectious diseases. Interactions between sex hormones and the immune system are thought to be implied in the differences observed.  [17]. Algorithms are available but they require capacity building for the staff providing care.
Co-infection with HIV is found in 12% of patients in this study. This percentage is similar to that found in sensitive TB cases [19]. Although HIV infection is recognized as a potent risk factor for developing TB in a person with latent TB, it is not formally recognized as risk factor for the development of drug-resistant TB. [17] Person living with HIV will develop both sensitive and resistant TB.
However, during treatment with ARVs, some adverse effects may alter the absorption of antituberculosis drugs or lead to dysfunction that may lead to drug resistance.

Conclusion
The detection of MDR/RR TB cases in DRC has been increasing since 2013.
However, the gap to be covered compared to projections remains high. This can be explained by the difficult access to diagnostic sites. The small number of women and children requires an appropriate approach in the epidemiological context. Strengthening teams to identify suspects, supporting the dispatch network of samples from health centers to diagnostic laboratories and increasing the number of laboratories for performing culture and LPA will significantly improve screening.

Limitations of This Study
As retrospective study, it was not easy to have information about contacts track- ing and so answer the progressing rate of new cases among MDR/RR TB diagnosed. Also, the feedback from the main laboratories to the health structures was not always given to certify the results. These aspects will be corrected by a cohort study now undergoing.