Effectiveness of innovative interventions on curbing transmission of Mycobacterium leprae

Leprosy or Hansen’s disease is a complex ancient infectious disease, caused by M.leprae and M.lepromatosis. The most believed frequent mode of transmission is airborne and therefore those in close contact with a new leprosy case are at the most risk of developing the disease although this depends on immunity heterogeneity. Despite leprosy has been the first infectious disease where the pathogen agent was identified, research and development have failed in the creation of reliable diagnostic tests for infection and disease. Therefore, the World Health Organization (WHO) recommends clinical cardinal signs and the ancient slit skin smear (SSS) for the diagnosis of the disease, and no diagnostic test for diagnosis of infection is currently recommended. Both clinical and laboratory skills and expertise are key for ensuring the reliability of diagnosis, which is dwindling due to the sustained decrease of leprosy prevalence worldwide. Nevertheless, the incidence has plateaued in the last decade around 200,000 new cases at the global scale and the highly effective treatment with multidrug therapy (MDT) has been insufficient to stop transmission. In 2018, the WHO has recommend single-dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for the contacts of new leprosy patients without signs of leprosy disease. The protection of PEP is around 60% and is based on the pivotal COLEP trial in Bangladesh. The Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP) study has documented the feasibility of PEP under programmatic conditions, and there is also evidence that PEP is cost-effective. Nevertheless, operational challenges for the most cost-effective approach to the provision of PEP for the high-risk population without causing harm to the persons eligible for SDR, and avoiding the increase of prevalence of rifampicin resistance, remain. In this Ph.D., we developed and estimated the effectiveness of innovative active case detection strategies based on Geographic Information Systems-based (GIS-based) technologies for stopping transmission of M. leprae in high-priority countries i.e. Comoros, India, and Madagascar. We discussed the latest evidence of the natural history of leprosy and the most recent control strategies in Chapter 1. In chapter 2, we analyzed door-to-door screening for leprosy in four endemic villages of Comoros that received SDR-PEP and we calculated the spatial risk of contracting leprosy for contacts including the protective effect of SDR-PEP for those who received it. We found 114 new cases among 5760 contacts screened (2.0% prevalence), in addition to the 39 cases detected in the two preceding years. There were statistically significant associations of incident leprosy with physical distance to index cases ranging from 2.4 (95% confidence interval (95% CI) 1.5–3.6) for household contacts to 1.8 (95% CI 1.3–2.5) for those living at 1–25 m, compared to individuals living at ≥75 m. The effect of SDR-PEP appeared protective but did not reach statistical significance due to the low numbers.Chapter 3, describes the protocol of Post ExpOsure Prophylaxis for Leprosy in the Comoros and Madagascar (PEOPLE), a cluster-randomized trial to assess the effectiveness of three modalities of implementing PEP. In the PEOPLE trial, four annual door-to-door surveys will be performed in four arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator where no PEP will be provided. In arms 2, 3, and 4, SDR-PEP will be administered at a double dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2, all household members of incident leprosy patients are eligible. In arm 3, not only household members but also neighborhood contacts living within 100-m of an incident case are eligible. In arm 4, such neighborhood contacts are only eligible if they test positive for anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome. In chapter 4, we describe the findings of the baseline survey of the first year of the PEOPLE trial in Comoros and Madagascar. We also assessed clustering at the village level fitting a purely spatial Poisson model by Kulldorff’s spatial statistic and measured the distance risk of contact to the nearest leprosy patient. There were 455 leprosy patients; 200 (44.0%) belonged to 2735 households included in a cluster. Thirty-eight percent of leprosy patients versus 10% of the total population live 25 m from another leprosy patient. Risk ratios for being diagnosed with leprosy were 7.3, 2.4, 1.8, 1.4, and 1.7, for those in the same household, at 1–&lt;25 m, 25–&lt;50 m, 50–&lt;75 m, and 75–&lt;100 m as/from a leprosy patient, respectively, compared to those living at ≥100 m. Chapter 5, describes active case finding of household members of new cases detected in the preceding four years (2017-2020) in 32 villages not included in the PEOPLE trial in Anjouan, Comoros. Some neighbors requested to be screened for leprosy. We screened 131 out of 226 index case households aimed (58.8%), and 32 other nearby households. There were 945 persons recorded, 671 household contacts, and 274 neighborhood contacts. We examined 896 persons detecting 48(5.4%) leprosy cases. Among cases detected, 13(27.1%) had multibacillary (MB) leprosy, the median age was 18 years (IQR 8-34), 43% were below 15 years and two (4.2%) had visible deformities. The risk of contacts of developing leprosy was higher among 11 households linked to MB compared to one linked to a paucibacillary (PB) index case (OR 12.6, 95% CI 1.6-99.6). There were 12 new cases among 668 household contacts with a leprosy prevalence of 18.0 per 1,000 (95% CI 9.3-31.1). We found 30 new cases in neighbors and six additional cases were diagnosed between their households with a residual prevalence of 26.3 per 1,000 (95% CI 9.7-56.4). We found a high prevalence above 26‰ among household contacts. In chapter 6, we document the mobility of new leprosy cases in two endemic blocks of the State of Bihar, India. We also screened household contacts for leprosy. Finally, we developed a GIS-based system to outline the lowest administrative level (hamlets known as Tola) including its population for assessing clustering. We visited 169 patients and screened 1,044 household contacts in Bisfi and Benipatti blocks in the state of Bihar. Median number of years of residing in the village was 17, interquartile range (IQR)12-30. We found 11 new leprosy cases among 658 household contacts examined (167 per 10,000), of which seven had paucibacillary leprosy, one was a child under 14 years, and none had visible disabilities. We identified 739 hamlets with a total population of 802,788(median 163, IQR 65–774). There were five high-incidence clusters at the hamlet level including 12% of the population and 46%(78/169) of the leprosy cases. One highly significant cluster with a relative risk (RR) of 4.7(p&lt;0.0001) included 32 hamlets and 27 cases in 33,609 population. A second highly significant cluster included 32 hamlets and 24 cases in 33,809 population with a RR of 4.1(p&lt;0.001). The third highly significant cluster included 16 hamlets and 17 cases in 19,659 population with a RR of 4.8(p&lt;0.001). There was a high yield of active household contact screening. Conclusion Our findings highlighted the crucial role of geographical information systems in the control of leprosy while ensuring rational and efficient use of resources. As clustering is beyond the household level, regardless of the provision of PEP, there is a need 1) to explore the efficacy of adapted active case detection and PEP, 2) to monitor the success of control activities, and 3) to ensure surveillance in a post-elimination phase. All the tools we used are open-source and user-friendly, and the expertise we developed includes multidisciplinary partners i.e. the national leprosy programs, non-governmental organizations, and research institutions making them ready for scaling up in different leprosy prevalence settings while maximizing their cost-effectiveness.<br/

American Tegumentary Leishmaniasis: Is Antimonial Treatment Outcome Related to Parasite Drug Susceptibility?

BackgroundAntimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes MethodsThirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined ResultsWe observed 29 SbV-resistant isolates among 4 species of subgenus Viannia most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy ConclusionAntimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factor

Genomic insights of mcr-1 harboring Escherichia coli by geographical region and a One-Health perspective

The importance of the One Health concept in attempting to deal with the increasing levels of multidrug-resistant bacteria in both human and animal health is a challenge for the scientific community, policymakers, and the industry. The discovery of the plasmid-borne mobile colistin resistance (mcr) in 2015 poses a significant threat because of the ability of these plasmids to move between different bacterial species through horizontal gene transfer. In light of these findings, the World Health Organization (WHO) recommends that countries implement surveillance strategies to detect the presence of plasmid-mediated colistin-resistant microorganisms and take suitable measures to control and prevent their dissemination. Seven years later, ten different variants of the mcr gene (mcr-1 to mcr-10) have been detected worldwide in bacteria isolated from humans, animals, foods, the environment, and farms. However, the possible transmission mechanisms of the mcr gene among isolates from different geographical origins and sources are largely unknown. This article presents an analysis of whole-genome sequences of Escherichia coli that harbor mcr-1 gene from different origins (human, animal, food, or environment) and geographical location, to identify specific patterns related to virulence genes, plasmid content and antibiotic resistance genes, as well as their phylogeny and their distribution with their origin. In general, E. coli isolates that harbor mcr-1 showed a wide plethora of ARGs. Regarding the plasmid content, the highest concentration of plasmids was found in animal samples. In turn, Asia was the continent that led with the largest diversity and occurrence of these plasmids. Finally, about virulence genes, terC, gad, and traT represent the most frequent virulence genes detected. These findings highlight the relevance of analyzing the environmental settings as an integrative part of the surveillance programs to understand the origins and dissemination of antimicrobial resistance

Effectiveness of innovative interventions on curbing transmission of Mycobacterium leprae

Leprosy or Hansen’s disease is a complex ancient infectious disease, caused by M.leprae and M.lepromatosis. The most believed frequent mode of transmission is airborne and therefore those in close contact with a new leprosy case are at the most risk of developing the disease although this depends on immunity heterogeneity. Despite leprosy has been the first infectious disease where the pathogen agent was identified, research and development have failed in the creation of reliable diagnostic tests for infection and disease. Therefore, the World Health Organization (WHO) recommends clinical cardinal signs and the ancient slit skin smear (SSS) for the diagnosis of the disease, and no diagnostic test for diagnosis of infection is currently recommended. Both clinical and laboratory skills and expertise are key for ensuring the reliability of diagnosis, which is dwindling due to the sustained decrease of leprosy prevalence worldwide. Nevertheless, the incidence has plateaued in the last decade around 200,000 new cases at the global scale and the highly effective treatment with multidrug therapy (MDT) has been insufficient to stop transmission. In 2018, the WHO has recommend single-dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for the contacts of new leprosy patients without signs of leprosy disease. The protection of PEP is around 60% and is based on the pivotal COLEP trial in Bangladesh. The Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP) study has documented the feasibility of PEP under programmatic conditions, and there is also evidence that PEP is cost-effective. Nevertheless, operational challenges for the most cost-effective approach to the provision of PEP for the high-risk population without causing harm to the persons eligible for SDR, and avoiding the increase of prevalence of rifampicin resistance, remain. In this Ph.D., we developed and estimated the effectiveness of innovative active case detection strategies based on Geographic Information Systems-based (GIS-based) technologies for stopping transmission of M. leprae in high-priority countries i.e. Comoros, India, and Madagascar. We discussed the latest evidence of the natural history of leprosy and the most recent control strategies in Chapter 1. In chapter 2, we analyzed door-to-door screening for leprosy in four endemic villages of Comoros that received SDR-PEP and we calculated the spatial risk of contracting leprosy for contacts including the protective effect of SDR-PEP for those who received it. We found 114 new cases among 5760 contacts screened (2.0% prevalence), in addition to the 39 cases detected in the two preceding years. There were statistically significant associations of incident leprosy with physical distance to index cases ranging from 2.4 (95% confidence interval (95% CI) 1.5–3.6) for household contacts to 1.8 (95% CI 1.3–2.5) for those living at 1–25 m, compared to individuals living at ≥75 m. The effect of SDR-PEP appeared protective but did not reach statistical significance due to the low numbers. Chapter 3, describes the protocol of Post ExpOsure Prophylaxis for Leprosy in the Comoros and Madagascar (PEOPLE), a cluster-randomized trial to assess the effectiveness of three modalities of implementing PEP. In the PEOPLE trial, four annual door-to-door surveys will be performed in four arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator where no PEP will be provided. In arms 2, 3, and 4, SDR-PEP will be administered at a double dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2, all household members of incident leprosy patients are eligible. In arm 3, not only household members but also neighborhood contacts living within 100-m of an incident case are eligible. In arm 4, such neighborhood contacts are only eligible if they test positive for anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome. In chapter 4, we describe the findings of the baseline survey of the first year of the PEOPLE trial in Comoros and Madagascar. We also assessed clustering at the village level fitting a purely spatial Poisson model by Kulldorff’s spatial statistic and measured the distance risk of contact to the nearest leprosy patient. There were 455 leprosy patients; 200 (44.0%) belonged to 2735 households included in a cluster. Thirty-eight percent of leprosy patients versus 10% of the total population live 25 m from another leprosy patient. Risk ratios for being diagnosed with leprosy were 7.3, 2.4, 1.8, 1.4, and 1.7, for those in the same household, at 1–<25 m, 25–<50 m, 50–<75 m, and 75–<100 m as/from a leprosy patient, respectively, compared to those living at ≥100 m. Chapter 5, describes active case finding of household members of new cases detected in the preceding four years (2017-2020) in 32 villages not included in the PEOPLE trial in Anjouan, Comoros. Some neighbors requested to be screened for leprosy. We screened 131 out of 226 index case households aimed (58.8%), and 32 other nearby households. There were 945 persons recorded, 671 household contacts, and 274 neighborhood contacts. We examined 896 persons detecting 48(5.4%) leprosy cases. Among cases detected, 13(27.1%) had multibacillary (MB) leprosy, the median age was 18 years (IQR 8-34), 43% were below 15 years and two (4.2%) had visible deformities. The risk of contacts of developing leprosy was higher among 11 households linked to MB compared to one linked to a paucibacillary (PB) index case (OR 12.6, 95% CI 1.6-99.6). There were 12 new cases among 668 household contacts with a leprosy prevalence of 18.0 per 1,000 (95% CI 9.3-31.1). We found 30 new cases in neighbors and six additional cases were diagnosed between their households with a residual prevalence of 26.3 per 1,000 (95% CI 9.7-56.4). We found a high prevalence above 26‰ among household contacts. In chapter 6, we document the mobility of new leprosy cases in two endemic blocks of the State of Bihar, India. We also screened household contacts for leprosy. Finally, we developed a GIS-based system to outline the lowest administrative level (hamlets known as Tola) including its population for assessing clustering. We visited 169 patients and screened 1,044 household contacts in Bisfi and Benipatti blocks in the state of Bihar. Median number of years of residing in the village was 17, interquartile range (IQR)12-30. We found 11 new leprosy cases among 658 household contacts examined (167 per 10,000), of which seven had paucibacillary leprosy, one was a child under 14 years, and none had visible disabilities. We identified 739 hamlets with a total population of 802,788(median 163, IQR 65–774). There were five high-incidence clusters at the hamlet level including 12% of the population and 46%(78/169) of the leprosy cases. One highly significant cluster with a relative risk (RR) of 4.7(p<0.0001) included 32 hamlets and 27 cases in 33,609 population. A second highly significant cluster included 32 hamlets and 24 cases in 33,809 population with a RR of 4.1(p<0.001). The third highly significant cluster included 16 hamlets and 17 cases in 19,659 population with a RR of 4.8(p<0.001). There was a high yield of active household contact screening. Conclusion Our findings highlighted the crucial role of geographical information systems in the control of leprosy while ensuring rational and efficient use of resources. As clustering is beyond the household level, regardless of the provision of PEP, there is a need 1) to explore the efficacy of adapted active case detection and PEP, 2) to monitor the success of control activities, and 3) to ensure surveillance in a post-elimination phase. All the tools we used are open-source and user-friendly, and the expertise we developed includes multidisciplinary partners i.e. the national leprosy programs, non-governmental organizations, and research institutions making them ready for scaling up in different leprosy prevalence settings while maximizing their cost-effectiveness

Less is more: Developing an approach for assessing clustering at the lower administrative boundaries that increases the yield of active screening for leprosy in Bihar, India

Background In India, leprosy clusters at hamlet level but detailed information is lacking. We aim to identify high-incidence hamlets to be targeted for active screening and post-exposure prophylaxis. Methodology We paid home visits to a cohort of leprosy patients registered between April 1st, 2020, and March 31st, 2022. Patients were interviewed and household members were screened for leprosy. We used an open-source app(ODK) to collect data on patients’ mobility, screening results of household members, and geographic coordinates of their households. Clustering was analysed with Kulldorff’s spatial scan statistic(SaTScan). Outlines of hamlets and population estimates were obtained through an open-source high-resolution population density map(https://data.humdata.org), using kernel density estimation in QGIS, an open-source software. Results We enrolled 169 patients and screened 1,044 household contacts in Bisfi and Benipatti blocks of Bihar. Median number of years of residing in the village was 17, interquartile range (IQR)12-30. There were 11 new leprosy cases among 658 household contacts examined (167 per 10,000), of which seven had paucibacillary leprosy, one was a child under 14 years, and none had visible disabilities. We identified 739 hamlets with a total population of 802,788(median 163, IQR 65–774). There were five high incidence clusters including 12% of the population and 46%(78/169) of the leprosy cases. One highly significant cluster with a relative risk (RR) of 4.7(p<0.0001) included 32 hamlets and 27 cases in 33,609 population. A second highly significant cluster included 32 hamlets and 24 cases in 33,809 population with a RR of 4.1(p<0.001). The third highly significant cluster included 16 hamlets and 17 cases in 19,659 population with a RR of 4.8(p<0.001). High-risk clusters still need to be screened door-to-door. Conclusions We found a high yield of active household contact screening. Our tools for identifying high-incidence hamlets appear effective. Focusing labour-intensive interventions such as door-to-door screening on such hamlets could increase efficiency

Community-supported self-administered tuberculosis treatment combined with active tuberculosis screening: a pilot experience in Conakry, Guinea

Directly observed treatment (DOT) for tuberculosis (TB) is recommended by the World Health Organization. However, DOT does not always meet patients’ preferences, burdens health facilities, and is hard to implement in settings where access to healthcare services is regularly interrupted. A model addressing these limitations of DOT is community-supported self-administered treatment (CS-SAT), in which patients who self-administer TB treatment receive regular visits from community members. Guinea is a country with a high TB burden, recurrent epidemics, and periodic socio-political unrest. We piloted a CS-SAT model for drug-susceptible TB patients in Conakry, led by community volunteers, who also conducted active TB case finding among household contacts and referrals for isoniazid preventive treatment (IPT) in children below 5 years old. We aimed to assess TB treatment outcomes of patients on CS-SAT and describe the number of patients identified with TB case finding and IPT provision. Prospectively enrolled bacteriologically confirmed TB patients, presenting to two facilities, received monthly TB medication. Community volunteers performed bi-weekly (initiation phase) and later monthly (continuation phase) home visits to verify treatment adherence, screen household contacts for TB, and assess IPT uptake in children under five. Among 359 enrolled TB patients, 237 (66.0%) were male, and 37 (10.3%) were HIV-positive. Three hundred forty (94.7%) participants had treatment success, seven (1.9%) died, seven (1.9%) experienced treatment failure, and five (1.4%) were lost-to-follow-up. Among 1585 household contacts screened for TB, 26 (1.6%) had TB symptoms, of whom five (19.2%) were diagnosed with pulmonary TB. IPT referral was done for 376 children from 198 households. In a challenging setting, where DOT is often not feasible, CS-SAT led to successful TB treatment outcomes and created an opportunity for active TB case finding and IPT referral. We recommend the Guinean CS-SAT model for implementation in similar settings

Injectables' key role in rifampicin-resistant tuberculosis shorter treatment regimen outcomes.

BackgroundSince a meta-analysis showed little or no effect of second-line injectables on treatment success, and using injectables may induce ototoxicity, injectable-free rifampicin-resistant tuberculosis (RR-TB) treatment regimens are recommended. However, acquired resistance preventing activity was overlooked. No previous study assessed the effect of shortening the duration of kanamycin administration to 2 months during the intensive phase of the RR-TB shorter treatment regimen (STR).MethodsRetrospective cohort study of the effect of using 2 months of kanamycin instead of the standard 4(+) months (extension if lack of smear conversion at 4 months) on recurrence (either treatment failure or relapse) and fluoroquinolone acquired drug resistance, in patients treated with a gatifloxacin-based STR in Damien Foundation supported clinics in Bangladesh. Logistic regression was used to estimate associations.ResultsFive of 52 (9.6%) treated with a STR containing two months of kanamycin had recurrence, compared to 21 of 738 (2.8%) patients treated with the standard STR containing 4(+) months of kanamycin (OR 3.7; 95%CI:1.5-10.3). In those with initially fluoroquinolone-susceptible TB, acquired resistance to fluoroquinolone was detected in none of 639 patients treated with 4(+) months of kanamycin and two (4.5%) of 44 treated with two months of kanamycin (OR 75.2; 95%CI:3.6-1592.1).ConclusionTwo months of kanamycin was insufficient to prevent recurrence with acquired resistance to gatifloxacin, the core drug of the most effective RR-TB STR. Injectable mediated resistance prevention is important to reach high effectiveness, to safeguard all treatment options after recurrence, and to prevent the spread of resistant TB. Studies on all-oral regimens should also assess the effect of regimen composition on resistance acquisition. Until evidence shows that other drugs can assure at least the same strong resistance preventing activity of the injectables, it seems wise to continue using this group of drugs, and adapt the regimen if any ototoxicity is detected

The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance.

BACKGROUND:Meta-analyses on impact of isoniazid-resistant tuberculosis informed the World Health Organization recommendation of a levofloxacin-strengthened rifampicin-based regimen. We estimated the effect of initial rifampicin resistance (Rr) and/or isoniazid resistance (Hr) on treatment failure or relapse. We also determined the frequency of missed initial and acquired Rr to estimate the impact of true Hr. METHODS:Retrospective analysis of 7291 treatment episodes with known initial isoniazid and rifampicin status obtained from individual patient databases maintained by the Damien Foundation Bangladesh over 20 years. Drug susceptibility test results were confirmed by the programme's designated supra-national tuberculosis laboratory. To detect missed Rr among isolates routinely classified as Hr, rpoB gene sequencing was done randomly and on a sample selected for suspected missed Rr. RESULTS:Initial Hr caused a large recurrence excess after the 8-month regimen for new cases (rifampicin for two months), but had little impact on rifampicin-throughout regimens: (6 months, new cases; 3.8%; OR 0.8, 95%CI:0.3,2.8; 8 months, retreatment cases: 7.3%, OR 1.8; 95%CI:1.3,2.6). Rr was missed in 7.6% of randomly selected "Hr" strains. Acquired Rr was frequent among recurrences on rifampicin-throughout regimens, particularly after the retreatment regimen (31.9%). It was higher in mono-Hr (29.3%; aOR 3.5, 95%CI:1.5,8.5) and poly-Hr (53.3%; aOR 10.2, 95%CI 4.4,23.7) than in susceptible tuberculosis, but virtually absent after the 8-month new case regimen. Comparing Bangladesh (low Rr prevalence) with a high Rr prevalence setting,true Hr corrected for missed Rr caused only 2-3 treatment failures per 1000 TB cases (of whom 27% were retreatments) in both. CONCLUSIONS:Our analysis reveals a non-negligible extent of misclassifying as isoniazid resistance of what is actually missed multidrug-resistant tuberculosis. Recommending for such cases a "strengthened" regimen containing a fluoroquinolone provokes a direct route to extensive resistance while offering little benefit against the minor role of true Hr tuberculosis in rifampicin-throughout first-line regimen

Intralesional Meglumine Antimoniate: Safe, Feasible and Effective Therapy for Cutaneous Leishmaniasis in Bolivia

The standard of care for cutaneous leishmaniasis includes the intramuscular/intravenous administration of pentavalent antimonials that are toxic and poorly tolerated. Primary health care usually lacks trained health staff for the diagnosis and treatment of leishmaniasis in Cochabamba Bolivia. Taking these aspects into account, a Bolivian consortium set out to explore the intralesional administration of meglumine antimoniate to treat cutaneous leishmaniasis during primary care under programmatic conditions. A four-step strategy consisting of clinical training for intralesional treatment and the promotion and periodic follow-up of health staff was carried out. The training process was applied in situ to personnel of nine primary health care centres. The intralesional treatment was applied five times every other day. Clinical follow-up after six-months of treatment showed a 77% healing proportion and 5% of therapeutic failure among 152 enrolled patients. The drug volume used in the intralesional procedure was on average 1.7 mL/ulcer treated. In conclusion, the strategy used was successful and effective, accomplishing a healing proportion similar to the long standardized treatment with a reduced time of administration, no severe side effects, and it is feasible to conduct by trained health staff. Our study supports the current PAHO/WHO recommendation for the intralesional administration of pentavalent antimonials for the treatment of cutaneous leishmaniasis