Monitoring the Long-Term Effectiveness of Miltefosine in Indian Post-Kala-Azar Dermal Leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL), the dermal sequel to visceral leishmaniasis (VL), is characterized by hypopigmented macules (macular) and/or papules and nodules (polymorphic). Post-kala-azar dermal leishmaniasis plays a significant role in disease transmission, emphasizing the need for monitoring chemotherapeutic effectiveness. Accordingly, this study aimed to quantify the parasite burden in PKDL patients after treatment with miltefosine by a quantitative polymerase chain reaction (qPCR). A Leishmania kinetoplastid gene-targeted qPCR was undertaken using DNA from skin biopsy specimens of patients with PKDL at three time points, i.e., at disease presentation (week 0, n = 157, group 1), upon completion of treatment (week 12, n = 39, group 2), and at any time point 6 months after completion of treatment (week ≥36, n = 54, group 3). A cycle threshold (Ct) <30 was considered the cutoff for positivity, and load was quantified as the number of parasites/µg genomic DNA (gDNA); cure was considered when samples had a Ct >30. The parasite load at disease presentation (group 1) was 10,769 (1,339-80,441)/µg gDNA (median [interquartile range]). In groups 2 and 3, qPCR results were negative in 35/39 cases (89.7%) and 48/54 cases (88.8%), respectively. In the 10/93 (10.8%) qPCR-positive cases, the parasite burdens in groups 2 and 3 were 2,420 (1,205-5,661)/µg gDNA and 22,195 (5,524-100,106)/µg gDNA, respectively. Serial monitoring was undertaken in 45 randomly selected cases that had completed treatment; all cases in groups 2 or 3 had a Ct >30, indicating cure. Overall, qPCR confirmed an 89.2% cure (as 83/93 cases showed parasite clearance), and the persistent qPCR positivity was attributed to nonadherence to treatment or unresponsiveness to miltefosine and remains to be investigated.

Stakeholders' views and perspectives on treatments of visceral leishmaniasis and their outcomes in HIV-coinfected patients in East Africa and South-East Asia: A mixed methods study.

BACKGROUND: In visceral leishmaniasis (VL) patients coinfected with human immunodeficiency virus (HIV), combination therapy (liposomal amphotericin B infusion and oral miltefosine) is being considered as an alternative to liposomal amphotericin B monotherapy. We aimed to assess the views of stakeholders in relation to these treatment options. METHODOLOGY: In a mixed methods study, we surveyed and interviewed patients, government functionaries, programme managers, health service providers, nongovernmental organizations, researchers, and World Health Organization (WHO) personnel. We used the Evidence to Decision (EtD) framework for data collection planning and analysis. Constructs of interest included valuation of outcomes, impact on equity, feasibility and acceptability of the treatment options, implementation considerations, monitoring and evaluation, and research priorities. PRINCIPAL FINDINGS/CONCLUSION: Mortality and non-serious adverse events were rated as "critical" by respectively the highest (61%) and lowest percentages (47%) of survey participants. Participants viewed clinical cure as essential for patients to regain productivity. Non-patient stakeholders emphasized the importance of "sustained" clinical cure. For most survey participants, combination therapy, compared with monotherapy, would increase health equity (40%), and be more acceptable (79%) and feasible (57%). Interviews revealed that combination therapy was more feasible and acceptable than monotherapy when associated with a shorter duration of hospitalization. The findings of the interviews provided insight into those of the survey. When choosing between alternative options, providers should consider the outcomes that matter to patients as well as the impact on equity, feasibility, and acceptability of the options.

Changing clinico-epidemiology of post-kala-azar dermal leishmaniasis (PKDL) in India: Results of a survey in four endemic states.

BACKGROUND & OBJECTIVES: Detection and treatment of post-kala-azar dermal leishmaniasis (PKDL) cases is considered important for kala-azar elimination. The objective of our study was to find out the proportion of different forms of lesions, interruption of treatment and rate of treatment completion, cure rates of PKDL, risk factors for developing severe forms of PKDL and utilization of services offered by the kala-azar elimination program. METHODS: A cross-sectional survey of PKDL patients registered for treatment at all levels of care during 2015 and 2016 was done. RESULTS: 576 PKDL patients who had started treatment in 2015 and 2016 were studied. Three-fourths of all patients were found to be clinically cured after a year of follow-up. Around 90% lesions were of macular type. Interruption of treatment was observed in one-fourth of PKDL patients. Median duration between kala-azar treatment and development of PKDL was 4.5 years. Around 79% patients had past history of kala-azar treatment. Discontinuation of treatment during earlier kala-azar episode was significantly associated with the development of papular and nodular forms of lesion. 43% of patients had received the incentive of INR 2000 after completion of treatment. Around three-fourths women in the reproductive age group were found not to use any contraceptive method during PKDL treatment. INTERPRETATION & CONCLUSION: PKDL treatment interruption should be reduced through ensuring drug supply and timely retrieval of patients. Directly observed treatment should be implemented and combination regimen should be explored to improve final cure rate. Delivery of financial incentive to PKDL patients and counselling and contraception to women of reproductive age group should be improved.

Female Literacy Rate is a Better Predictor of Birth Rate and Infant Mortality Rate in India.

BACKGROUND: Educated women are known to take informed reproductive and healthcare decisions. These result in population stabilization and better infant care reflected by lower birth rates and infant mortality rates (IMRs), respectively. MATERIALS AND METHODS: Our objective was to study the relationship of male and female literacy rates with crude birth rates (CBRs) and IMRs of the states and union territories (UTs) of India. The data were analyzed using linear regression. CBR and IMR were taken as the dependent variables; while the overall literacy rates, male, and female literacy rates were the independent variables. RESULTS: CBRs were inversely related to literacy rates (slope parameter = -0.402, P < 0.001). On multiple linear regression with male and female literacy rates, a significant inverse relationship emerged between female literacy rate and CBR (slope = -0.363, P < 0.001), while male literacy rate was not significantly related to CBR (P = 0.674). IMR of the states were also inversely related to their literacy rates (slope = -1.254, P < 0.001). Multiple linear regression revealed a significant inverse relationship between IMR and female literacy (slope = -0.816, P = 0.031), whereas male literacy rate was not significantly related (P = 0.630). CONCLUSION: Female literacy is relatively highly important for both population stabilization and better infant health.