Epidemiological scenario of leprosy in marginalized communities of India: Focus on scheduled tribes

The Scheduled Tribes (STs) are designated among the most disadvantaged social groups in India. Until the year 2005 (pre-elimination era of leprosy in India), several leprosy-specific control field programmes were implemented, which have been discontinued subsequently. Since then, leprosy diagnosis and treatment have been integrated with General Health Services. Thereafter, specialized expertise for the early diagnosis of leprosy has been gradually diminishing, especially at the peripheral clinics in remote areas. Hence, leprosy cases usually remain undetected for a long time and persist as endemic reservoirs. The tribal population of India accounts for just 8.6 per cent of the overall population. However, 18.5 per cent of the new leprosy cases were detected within the tribal community in the year 2020, indicating a disproportionately high burden of leprosy among the tribal population. Recent data suggest that these health disparities can be mainly related to the increased marginalization of STs as compared to other communities. This shows the need to further explore the current situation of leprosy in STs so that suitable interventions can address the contributing factors, leading to health inequalities in disadvantaged socio-economic groups. Therefore, this review aims to present the current distribution of leprosy in marginalized communities with a special emphasis on STs. Further, this review discusses how resources might be mobilized for such communities to find and treat undetected leprosy patients in STs to enable effective control of leprosy through early detection and timely treatment.

Access to healthcare among the Empowered Action Group (EAG) states of India: Current status and impeding factors .

Background. Access to healthcare is crucial for meeting the health needs of Indians. We explored factors impeding access to public sources of healthcare among the Empowered Action Group (EAG) states of India. We also examined the extent to which Indians depend on public and private sources of healthcare in the EAG states. Methods. Our study is based on the unit-level records of 9988 ailing persons, who were surveyed among the EAG states in the 71stround of the National Sample Survey (NSS), conducted during January–June 2014 on the theme ‘Social consumption: Health’. To analyse the socioeconomic factors, we did logistic regression using STATA version 12.0. Results. Despite a vast public health infrastructure in the EAG states, around three-fourths of inpatients are dependent on private sources of healthcare in both rural (70%) and urban (78%) areas. Poor quality and long waiting time in accessing healthcare from public health facilities remain big concerns for inpatients of the EAG states. Conclusion. To make public health services more accessible, there is a need to improve the quality of services, enlarge infrastructure to reduce waiting time, and enhance the physical reach to inpatients in the EAG states of India. Public health services will then be able to compete with those in the private sector. Natl Med J India 2016;29:267–73

Anti-tuberculosis activity of selected medicinal plants against multi-drug resistant Mycobacterium tuberculosis isolates.

Background & objectives: Emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of Mycobacterium tuberculosis has further complicated the problem of tuberculosis (TB) control. Medicinal plants offer a hope for developing alternate medicines for the treatment of TB. The present study was done to evaluate in vitro anti-tubercular activity of five medicinal plants viz., Acalypha indica, Adhatoda vasica, Allium cepa, Allium sativum and Aloe vera. Methods: Aqueous extracts of leaves of A. indica, A. vasica, bulbs of A. cepa, cloves of A. sativum and pure gel of A. vera leaves, were tested in vitro for their activity against two MDR isolates (DKU-156 and JAL-1236), reference susceptible strain M. tuberculosis H37Rv as well as rapid grower mycobacterial pathogen M. fortuitum (TMC-1529) using Lowenstein Jensen (L-J) medium and colorimetric BacT/ALERT 3D system. Activity in L-J medium was evaluated by percentage inhibition which was calculated by mean reduction in number of colonies on extract containing as compared to extract free controls. Results: Extracts of all the five plants A. indica, A. vasica, A. cepa, A. sativum and A. vera exhibited anti-tuberculosis activity in L-J medium, the proportion of inhibition of these plants extract in respect mentioned above is 95, 32, 37, 72, 32 per cent, respectively for MDR isolate DKU-156 and 68, 86, 79, 72, 85 per cent, respectively for another MDR isolate JAL-1236, while for sensitive M. tuberculosis H37Rv, inhibition was found to be 68, 70, 35, 63 and 41 per cent, at 4 per cent v/v concentration in L-J medium. There was no inhibition against rapid grower M. fortuitum (TMC-1529). In BacT/ALERT also, extracts of these plants showed significant inhibition against M. tuberculosis. Interpretation & conclusions: Our findings showed that all these plants exhibited activity against MDR isolates of M. tuberculosis. While the anti-TB activity of A. vera, A. vasica and A. sativum against MDR isolates confirm earlier results, activity of the extracts of A. indica and A. cepa is reported for the first time. Further studies aimed at isolation and identification of active substances from the extracts which exhibited promising activities, need to be carried out.

In vitro effect of fl uoroquinolones against Mycobacterium tuberculosis isolates from Agra & Kanpur region of north India.

Background & objectives: Fluoroquinolones (FQs) are important drugs used for treatment of drug resistant tuberculosis and are also now being considered as fi rst line drugs to shorten the duration of treatment of tuberculosis (TB). In order to fi nd out useful FQs for treatment of tuberculosis, the comparative effi cacy of fi ve FQs, namely, ofl oxacin (OFL), ciprofl oxacin (CIP), sparfl oxacin (SPX), gatifl oxacin (GAT) and levofl oxacin (LEVX) was studied against Mycobacterium tuberculosis (MTB) isolates obtained from both treated and untreated patients from Agra and Kanpur regions of north India. Methods: A total of 162 MTB isolates [including 110 MTB isolates obtained from untreated patients (Cat-I) and 52 isolates from treated patients (Cat-II)] were tested for their susceptibilities to FQs using standard minimum inhibitory concentration (MIC) method on Löwenstein-Jensen medium. Results: Keeping in view the therapeutically achievable drug levels, it was found that in Cat-I 97.2 per cent (107/110) isolates were sensitive to GAT, 89 per cent (98/110) to LEVX at 1 μg/ml whereas 92.7 per cent (102/110) isolates were inhibited by OFL at 2 μg/ml and 73.6 per cent (81/110) to SPX at 0.5 μg/ml. Only 63.6 per cent (70/110) isolates were found to be sensitive to CIP at 2 μg/ml which increased to 89 per cent (98/110) at 4 μg/ml (higher than achievable peak serum level). On the other hand, among 52 isolates for Cat-II, 37 (71.2%) were found to be sensitive to GAT and 33 (63.5%) to LEVX at 1 μg/ml concentration, 28 (53.8%) to SPX at 0.5 μg/ml whereas 33 (63.5%) and 24 (46.2%) isolates were found to be sensitive to OFL and CIP at 2 μg/ml, respectively. Interpretation & conclusions: It appears that GAT has higher activity against MTB isolates followed by OFL, LEVX and SPX whereas CIP showed the lowest activity. GAT was also found to be the most effective FQ against multi-drug resistant (MDR) isolates both from Cat-I and Cat-II patients. Thus, except CIP, other FQs showed potential to be included in the treatment regimens of tuberculosis including MDR-TB.

Multi-drug resistant tuberculosis: current status and emerging tools for its management in India.

Drug resistance in tuberculosis is a global problem and India is no exception. However, this rise is mainly among the previously treated cases, generally reported from the hospitals (majority of which are the tertiary health care centres). Primary resistance figures are still static and are mostly below 5% level. Detection of drug resistance in tuberculosis is conventionally performed by comparing the growth inhibition on the drug containing medium as compared to the drug free control (phenotypic methods). Since these methods are dependant on appearance of visible colonies of M. tuberculosis, these methods take longer time to provide susceptibility testing results and are labor-intensive. Therefore, alternate phenotypic methods based on the bacterial metabolism (CO2 production, Oxygen uptake, ATP bioluminescence etc) and thus the viability of organisms, have been tried and found promising in overcoming this hindrance of longer time requirement. These systems, besides having good sensitivity and impressive specificity as compared to the conventional methods, reduce the total turn around times for isolation as well as susceptibility testing of M. tuberculosis. Recent advances in our understanding of the molecular basis of drug resistance have led to the development of genotypic methods for detection of mutations/mechanisms associated with resistance. However, most of these phenotypic and genotypic advancements require expertise and expensive equipments/technologies, which limit their wider application. This article reviews current status of multi-drug resistance in tuberculosis (MDR-TB), the recent developments for its rapid and reliable detection and effective management with special reference to India.

The paradox of pyrazinamide: an update on the molecular mechanisms of pyrazinamide resistance in Mycobacteria.

Pyrazinamide (PZA) is an important front line anti-tuberculosis drug because of its sterilizing activity against semi-dormant tubercle bacilli. In spite of its remarkable role in shortening the treatment duration from 9 months to 6 months when used in combination with Rifampicin and Isoniazid, PZA remains a difficult paradox because of its incompletely understood mode of action and mechanism of resistance. PZA is a nicotinamide analog prodrug which is converted into the active bactericidal form pyrazinoic acid by the bacterial enzyme pyrazinamidase (PZase). PZA does not appear to have a specific cellular target and instead, exerts its bactericidal effect by disrupting the membrane energetics and acidification of cytoplasm. Majority (72-97%) of PZA-resistant isolates of M. tuberculosis exhibit mutations in their pncA gene or upstream area leading to loss of PZase activity. A wide diversity of pncA mutations scattered along the entire length of pncA gene is unique to PZA resistance. However, PZA resistant isolates with normal PZase activity and wild type pncA sequences have also been reported in several studies which indicate that alternate mechanisms of PZA resistance exist. Investigations into these mechanisms would be useful in developing alternative diagnostic/therapeutic measures. This review presents the update of various mechanisms of PZA resistance in different mycobacteria with special emphasis on mode of action of PZA and mechanisms of resistance in Mycobacterium tuberculosis.

Simultaneous use of two PCR systems targeting IS6110 and MPB64 for confirmation of diagnosis of tuberculous lymphadenitis.

PCR has emerged as a powerful technique for detection of various pathogens including Mycobacterium tuberculosis. In present study, eighty one samples of lymph node biopsies from clinically suspected cases of tuberculous lymphadenitis were examined for AFB, culture on Löwenstein Jensen medium and simultaneous use of two PCRs targeting IS6110 and MPB64. Positivity with M. tuberculosis culture and AFB was 13.6% and 28.4% respectively. All samples culture positive for nontuberculous mycobacteria were negative by both PCR systems. Higher proportion of positive results were observed with PCR targeting IS6110 by which 56 of 81 (69.1%) samples showed positive results as compared to PCR targeting MPB64 by which 39 of 81 (48.2 %) samples showed positive results. When combined, 63 out of 81 (77.8%) samples were detected positive for M. tuberculosis DNA. However, 7/81 (8.6 %) samples remained negative by IS6110 but positive by MPB64 method. Thus our data suggest that the use of one additional PCR (other than IS6110 system) can reduce false negativity of PCR results in the samples harboring zero copy of IS6110 element which is known to exist in Indian population.