Epidemiological, Serological, and Entomological Investigation of New Visceral Leishmaniasis Foci in Nepal.

The aim of this study was to explore epidemiological, serological, entomological, and social aspects of visceral leishmaniasis (VL) in new foci in Nepal. The study was conducted in 11 villages of five districts that had been previously free of VL but that reported new cases between 2019 and 2021. We screened 1,288 inhabitants using rK39 tests and investigated the epidemiological and clinical characteristics of 12 recent VL cases. A total of 182 community members were interviewed about knowledge, attitude, and practices regarding VL. They then underwent an awareness training; 40 of them had a second interview at 6 months to assess the training impact. Vector surveys were conducted in six houses per village to assess sandfly density and infection rates. The prevalence of VL infection was 0.5% and 3.2% among screened populations in Dolpa and Kavre districts, respectively, while the other districts had no rK39-positive cases. No association between travel history and VL infection was found. Phlebotomus argentipes sandflies were collected in three districts at high altitudes (from 1,084 to 4,450 m). None of the sandflies captured had Leishmania donovani DNA. People in new foci were not aware of VL symptoms, vectors, or preventive measures. The training significantly improved their knowledge and practice in seeking medical care in case of illness. The epidemiological, serological, and entomological investigations suggest indigenous focal transmission of VL. An integrated package of strategic interventions should be implemented by the national VL elimination program in districts with new VL foci.

Assessment of the impact of implementation research on the Visceral Leishmaniasis (VL) elimination efforts in Nepal.

Nepal, Bangladesh, and India signed a Memorandum of Understanding (MoU) in 2005 to eliminate visceral leishmaniasis (VL) as a public health problem from the Indian subcontinent by 2015. By 2021, the number of reported VL cases in these countries had declined by over 95% compared to 2007. This dramatic success was achieved through an elimination programme that implemented early case detection and effective treatment, vector control, disease surveillance, community participation, and operational research that underpinned these strategies. The experience offered an opportunity to assess the contribution of implementation research (IR) to VL elimination in Nepal. Desk review and a stakeholder workshop was conducted to analyse the relationship between key research outputs, major strategic decisions in the national VL elimination programme, and annual number of reported new cases over time between 2005 and 2023. The results indicated that the key decisions across the strategic elements, throughout the course of the elimination programme (such as on the most appropriate tools for diganostics and treatment, and on best strategies for case finding and vector management), were IR informed. IR itself responded dynamically to changes that resulted from interventions, addressing new questions that emerged from the field. Close collaboration between researchers, programme managers, and implementers in priority setting, design, conduct, and review of studies facilitated uptake of evidence into policy and programmatic activities. VL case numbers in Nepal are now reduced by 90% compared to 2005. Although direct attribution of disease decline to research outputs is difficult to establish, the Nepal experience demonstrates that IR can be a critical enabler for disease elimination. The lessons can potentially inform IR strategies in other countries with diseases targeted for elimination.

Follow-up assessment of visceral leishmaniasis treated patients and the impact of COVID-19 on control services in Nepal.

BACKGROUND: Follow-up assessment of visceral leishmaniasis (VL) treated cases is important to monitor the long term effectiveness of treatment regimens. The main objective of this study was to identify the gaps and challenges in the follow-up of treated VL cases, to monitor treatment outcome and to assess the impact of COVID-19 on VL elimination services and activities. METHODS: Clinicians treating VL patients, district focal persons for VL, and patients treated for VL in seven high endemic districts in Nepal during 2019-2022 were interviewed to collect data on challenges in the follow-up of VL treated patients as per national strategy. RESULTS: Follow up status was poor in two districts with the largest number of reported cases. The majority of cases were children under 10 years of age (44.2%). Among 104 VL treated cases interviewed, 60.6% mentioned that clinicians had called them for follow-up but only 37.5% had complied. Among 112 VL treated cases followed up, 8 (7.14%) had relapse and 2 (1.8%) had PKDL. Among 66 cases who had VL during the COVID-19 lock down period, 32 (48.5%) were diagnosed within 1 week; however, 10 (15.1%) were diagnosed only after 4 weeks or more. During the COVID-19 pandemic, there was no active search for VL because of budget constraints and lack of diagnostic tests, and no insecticide spraying was done. CONCLUSION: Relapses and PKDL are challenges for VL elimination and a matter of concern. Successful implementation of the national strategy for follow up of treated VL cases requires addressing elements related to patients (awareness, transport, communication) clinicians (compliance) and organization of service delivery (local health worker training and deployment). COVID-19 did not have much impact on VL diagnosis and treatment; however, public health programmes including active case detection and insecticide spraying for vector control were severely reduced.

Prevalence of post kala-azar dermal leishmaniasis (PKDL) and treatment seeking behavior of PKDL patients in Nepal.

BACKGROUND: In Nepal, the burden of post kala-azar dermal leishmaniasis (PKDL) is not known since there is no active case detection of PKDL by the national programme. PKDL patients could pose a challenge to sustain visceral leishmaniasis (VL) elimination. The objective of this study was to determine the prevalence of PKDL and assess PKDL patients' knowledge on VL and PKDL, and stigma associated with PKDL. METHODOLOGY/PRINCIPAL FINDINGS: Household surveys were conducted in 98 VL endemic villages of five districts that reported the highest number of VL cases within 2018-2021. A total of 6,821 households with 40373 individuals were screened for PKDL. Cases with skin lesions were referred to hospitals and examined by dermatologists. Suspected PKDL cases were tested with rK39 and smear microscopy from skin lesions. An integrated diagnostic approach was implemented in two hospitals with a focus on management of leprosy cases where cases with non-leprosy skin lesions were tested for PKDL with rK39. Confirmed PKDL patients were interviewed to assess knowledge and stigma associated with PKDL, using explanatory model interview catalogue (EMIC) with maximum score of 36. Among 147 cases with skin lesions in the survey, 9 (6.12%) were confirmed as PKDL by dermatologists at the hospital. The prevalence of PKDL was 2.23 per 10,000 population. Among these 9 PKDL cases, 5 had a past history of VL and 4 did not. PKDL cases without a past history of VL were detected among the "new foci", Surkhet but none in Palpa. None of the cases negative for leprosy were positive for PKDL. There was very limited knowledge of PKDL and VL among PKDL cases. PKDL patients suffered to some degree from social and psychological stigma (mean ± s.d. score = 17.89 ± 12.84). CONCLUSIONS/SIGNIFICANCE: Strengthening the programme in PKDL case detection and management would probably contribute to sustenance of VL elimination. Awareness raising activities to promote knowledge and reduce social stigma should be conducted in VL endemic areas.

Visceral leishmaniasis in new foci areas of Nepal: Sources and extent of infection.

Background & objectives: The successful elimination program of visceral leishmaniasis (VL) in Nepal decreased the incidence to less than 1 per 10,000 population leading to the consolidation phase. However, new VL cases have been recorded from new districts, threatening the elimination goal. This study monitors the geographical spread of VL and identifies potential risk factors. Methods: VL data of 2017-2020 were obtained from the Epidemiology and Disease Control Division (EDCD) of Nepal and mapped. Telephonic interviews with 13 VL patients were conducted. Results: The incidence maps indicate that VL is spreading to new areas. The target incidence exceeded four times in hilly and twice in mountainous districts. VL cases occurred in 64 of 77 districts in all three regions (mountainous, hilly and Terai). Interviews showed a correlation between travel history (private, commercial and for studies) and the spread of VL cases to new foci. Interpretation & conclusion: One major challenge of VL elimination in the maintenance phase is the spread of infection through travelers to new foci areas, which needs to be under continuous surveillance accompanied by vector control activities. This should be confirmed by a large-scale analytical study.

Response to Visceral Leishmaniasis Cases through Active Case Detection and Vector Control in Low-Endemic Hilly Districts of Nepal.

The visceral leishmaniasis (VL) elimination program in Nepal has largely completed the attack phase and is moving toward consolidation and maintenance phases. New VL foci are, however, appearing in Nepal, and therefore new innovative community-centered strategies need to be developed and tested. We conducted early case detection by an index case-based approach and assessed the feasibility, efficacy, and cost of an intervention for sandfly control through indoor residual spraying (IRS) or insecticidal wall painting (IWP) in new and low-endemic districts Palpa and Surkhet. IRS was performed in 236 households and IWP in 178 households. We screened 1,239 and 596 persons in Palpa and Surkhet, respectively, resulting in the detection of one VL case in Palpa. Both IWP and IRS were well accepted, and the percentage reductions in sandfly density after 1, 9, and 12 months of intervention were 90%, 81%, and 75%, respectively, for IWP and 81%, 59%, and 63% respectively for IRS. The cost per household protected per year was USD 10.3 for IRS and 32.8 for IWP, although over a 2-year period, IWP was more cost-effective than IRS. Active case detection combined with sandfly control through IWP or IRS can support to VL elimination in the consolidation and maintenance phase.

Insufficient Iodine Level in Urine among Children of a Secondary School: A Descriptive Cross-sectional Study.

Introduction: Iodine deficiency disorders are common endocrinopathies in Nepal. Children are at risk for iodine deficiency disorders. Irreversible mental retardation and brain damage in children are the devastating disorders lead by iodine deficiency. Therefore, the main objective of the study was to find out the prevalence of insufficient iodine level among the children of a secondary school. Methods: This descriptive cross-sectional study was conducted in urine from April 2019 to July 2019 after obtaining ethical approval from Nepal Health Research Council (Registration number: 802/2018). Forty-six urine samples were collected from school children for iodine estimation. Convenience sampling was done. Data were entered into Statistical Package for the Social Science version 21 and descriptive analyses were done. Point estimate at 95% confidence interval was calculated along with frequency and proportion for binary data. Results: Among the 46 students, majority 36 (78.30%) (95% Confidence Interval= 66.30-90.21) of the school children had insufficient urine iodine level. Among 36 salt samples collected from school children with low urine iodine level, 8 (22.2%) salt samples had iodine less than 15ppm. Conclusions: Iodine estimation revealed a very high percentage of urine samples containing insufficient levels of iodine is similar as compared to studies done in similar settings. Hence, the school children were at risk of iodine deficiency disorders. Iodine deficiency disorders prevention programs should be priority intervention based on available evidence.

Role of female community health volunteers for visceral leishmaniasis detection and vector surveillance in Nepal.

Background: As visceral leishmaniasis (VL) has recently expanded in previously non-endemic areas of Nepal, the health system is facing new challenges. Female community health volunteers(FCHVs) are playing an important role for VL elimination in Nepal. This study aimed to analyze the actual and potential role of FCHVs for VL elimination program as well as community awareness of the disease (VL) and protective measures. Methods: We used a concurrent embedded mixed methods design. Qualitative data were collected through in-depth interviews and focus group discussions with FCHVs of 22 VLendemic villages of 3 districts. Concurrently quantitative data were collected through formal interviews of 203 household heads of the same villages. Results: FCHVs are able to perform their duties in an efficient way with the support of their families and specific incentives. FCHVs in the VL-endemic region have a good ability to recognize the VL suspects and refer to health facilities. The feedback by the district health office on referred patients was weak thus missing the opportunity of involving FCHVs in the 6-months follow up. In houses with a previous VL case knowledge levels of prevention and treatment ofVL were significantly better than in houses without a previous VL case. More people in houses with a former VL patient were aware on VL transmission. Conclusion: FCHVs are playing an important role for VL elimination in Nepal through detection of suspected cases and referral and may play a role in vector surveillance.

Integrating Case Detection of Visceral Leishmaniasis and Other Febrile Illness with Vector Control in the Post-Elimination Phase in Nepal.

Nepal has completed the attack phase of visceral leishmaniasis (VL) elimination and now needs active case detection (ACD) and vector control methods that are suitable to the consolidation and maintenance phases. We evaluated different ACD approaches and vector control methods in Saptari district. We assessed 1) mobile teams deployed in villages with VL cases in 2015 to conduct combined camps for fever and skin lesions to detect VL/PKDL (post-kala-azar dermal leishmaniasis) and other infections; 2) an incentive approach by trained female community health volunteers (FCHVs) in villages with no VL cases in 2015. Both were followed by house-to-house visits. For vector control, four villages were randomly allocated to insecticide impregnation of bednets, insecticide wall painting, indoor residual spraying (IRS), and control. Sandfly density (by CDC light traps, The John W. Hock Company, USA) and mortality (World Health Organization cone bioassay) were assessed in randomly selected households. One VL, three tuberculosis, one leprosy, and one malaria cases were identified among 395 febrile cases attending the camps. Post-camp house-to-house screening involving 7,211 households identified 679 chronic fever and 461 skin lesion cases but no additional VL/PKDL. No VL/PKDL case was found by FCHVs. The point prevalence of chronic fever in camp and FCHV villages was 242 and 2 per 10,000 populations, respectively. Indoor residual spraying and bednet impregnation were effective for 1 month versus 12 months with insecticidal wall paint. Twelve-month sandfly mortality was 23%, 26%, and 80%, respectively, on IRS, bednet impregnation, and insecticide wall painting. In Nepal, fever camps and insecticidal wall paint prove to be alternative, sustainable strategies in the VL post-elimination program.

Barriers of Visceral Leishmaniasis reporting and surveillance in Nepal: comparison of governmental VL-program districts with non-program districts.

OBJECTIVES: At the time when Nepal is on the verge of reaching the maintenance phase of the Visceral Leishmaniasis (VL) elimination program, the country is facing new challenges. The disease has expanded to 61 of the country's 75 districts including previously non-endemic areas where there is no control or patient management program in place. This study aimed to assess which elements of the surveillance and reporting systems need strengthening to identify cases at an early stage, prevent further transmission and ensure sustained VL elimination. METHODS: In a cross-sectional mixed-method study, we collected data from two study populations in VL program and non-program districts. From February to May 2016, structured interviews were conducted with 40 VL patients, and 14 in-depth and semi-structured interviews were conducted with health managers. RESULTS: The median total delay from onset of symptoms to successful reporting to the Ministry of Health was 68.5 days in the VL-program and 83 days in non-program districts. The difference in patient's delay from the onset of symptoms to seeking health care was 3 days in VL-program and 20 days in non-program districts. The diagnostic delay (38.5 days and 36 days, respectively), treatment delay (1 vs. 1 days) and reporting delay (45 vs. 36 days) were similar in program and non-program districts. The diagnostic delay increased three-fold from 2012, while treatment and reporting delay remained unchanged. The main barriers to surveillance were: (i) lack of access and awareness in non-program districts; (ii) growing private sector not included in and not participating to referral, treatment and reporting; (iii) lack of cooperation and coordination among stakeholders for training and deployment of interventions; (iv) insufficient validation, outreach and process optimisation of the reporting system. CONCLUSIONS: Corrective measures are needed to maintain the achievements of the VL elimination campaign and prevent resurgence of the disease in Nepal. A clear patient referral structure, reinforcement of report notification and validation and direct relay of data by local hospitals and the private sector to the district health offices are needed to ensure prompt treatment and timely and reliable information to facilitate a responsive system of interventions.

Insufficient level of iodine content in household powder salt in Nepal.

Universal salt iodization (USI) is long term strategy for the control of iodine deficiency disorder (IDD) in Nepal. Standardized periodic testing of the iodine content in salt is a critical part of a salt iodisation programme. To achieve programmatic objective, this study was carried out to estimate the iodine content of household salt in Kavre, Lalitpur and Parsa districts of Nepal. Iodometric titration of 1803 salt samples collected from the households through the students of different schools revealed that 289 (16.0%) had less than 15 ppm iodine. Two hundred forty-one powder salt samples without two children logo (14.3% among total powder salt samples) had iodine below 15 ppm. It includes 25.8% of total salt samples from Parsa district of Terai ecological region. Among total, the largest proportion of the population accounting for almost 93.0% used powder salt. In total 1803 salt samples, mean and median iodine concentration were 31.8 ppm (95.0% CI=31.0-32.6) and 29.5 ppm respectively. The mean and median iodine concentration of phoda (dhike) salt were 22.1 ppm (95.0% CI= 19.2-25.1) and 18.9 ppm; powder salt were 32.6 ppm (95.0% CI= 31.7- 33.4) and 30.6 ppm respectively. In the community level, people are still using the non-iodized salt. To eliminate the IDD more efforts are required at program implementation and monitoring level.

Assessment of IDD problem by estimation of urinary iodine among school children.

Iodine deficiency disorder (IDD) is a major micronutrient deficiency problem in Nepal. Urinary iodine estimation has been the gold standard employed for the assessment of iodine status and of IDD. This study was conducted with objective to assess the urinary iodine among the school children of Kavre, Lalitpur and Parsa districts. Attempts were made to relate urinary iodine with salt use and other sociodemographic variables. Altogether 190 urine samples (74 samples from Kavre, 89 from Parsa and 27 from Lalitpur district) were collected from school children aged 5-13 years. The urinary iodine was analyzed by using urinary iodine assay kit (Bioclone Australia Pvt Limited). It was found that 3.2% children had urine iodine concentration below 20 microg/l. Similarly, the percentage of children with urine iodine concentration 21-50 microg/l, 51-99 microg/l, 100-299 microg/l and above 300 microg/l were 14.2%, 10.5%, 43.7% and 28.4% respectively. Iodine deficient population of school children was 39.2% of Kavre, 19.1% of Parsa and 25.9% of Lalitpur. Overall, it was found that 27.9% children had urine iodine level less than the normal WHO levels. The median urine iodine level was 139.0 microg/l of Kavre, 266.7 microg/l of Parsa and 244.4 microg/l of Lalitpur school children. Urinary iodine excretion (UIE) median value among male students was 211.9 microg/l, among female students was 190.2 microg/l and the difference was statistically insignificant (P > 0.05). There was no significant correlation between consumed salt iodine level and urine iodine excretion level (P > 0.05). Short-term iodine supplementation programs should be arranged for iodine deficient children in the study districts. This study shows that IDD continues to be prevalent in the country as a major public health problem, which requires strengthening effective intervention program and other preventive measures.