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BACKGROUND: Rabies continues to pose significant public health challenges in many developing countries including Bhutan. A probable case of rabies was admitted to our hospital and its reporting led to the uncovering of an outbreak in domestic and wild animals. We discuss the challenges in the diagnosis and management of rabies in a resource-limited setting.
METHODS: A 35-year-old male presented with intermittent fever, bilateral lower limb weakness that was rapidly progressive, urinary incontinence with episodes of palpitations and sweating. He had sustained a Category III bite on the right lower thigh with four bite marks, inflicted by a stray dog. He had received post-exposure prophylaxis with intra-dermal anti-rabies vaccine. On initial examination, the patient was in distress but cooperative for the interview. He had pulse rate ranging from 60 to 100/min with episodes of diaphoresis and palpitations, but with normal capillary blood glucose. In the lower limb, the muscle power was zero with absent tendon reflexes in the lower limb and impaired abdominal reflex below T10 level. He had hyperaesthesia below T8, hydrophobia, aerophobia and photophobia. He had multiple spontaneous fasciculations in both the thighs and right deltoid and these later involved the intercostal muscles, neck and face muscles. He had altered sensorium and desaturation for which he required mechanical ventilation. Polymerase chain reaction for rabies virus was negative in cerebrospinal fluid and saliva. Rabies virus neutralizing antibody was negative in cerebrospinal fluid but had high titres in the serum. He received Human Rabies Immunoglobulin after admission. He was managed in the intensive care unit and died 23 days later. After this case was notified, a rapid response team was deployed in the field, and uncovered rabies outbreak in animals in the locality.
CONCLUSIONS: This case called for a serious evaluation of the country\'s efforts in achieving zero rabies deaths by 2030. The management of this case identified several critical areas of context-specific interventions in Bhutan. There is also an urgent need to improve diagnostic capabilities at the national reference laboratory and enhance the technical competencies of healthcare workers in the management of dog bite cases.

BACKGROUND: In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries\' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems.
METHODS: This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness.
RESULTS: The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9-10 times more patients were diagnosed and treated.
CONCLUSIONS: The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.

Neglected tropical diseases (NTDs) predominantly affect vulnerable and marginalized populations in tropical and subtropical areas and globally affect more than one billion people. In Guinea, the burden of NTDs is estimated to be >7.5 disability-adjusted life years per million inhabitants. Currently the Guinea NTDs master plan (2017-2020) has identified eight diseases as public health problems: onchocerciasis, lymphatic filariasis, trachoma, schistosomiasis and soil-transmitted helminthiasis, leprosy, human African trypanosomiasis and Buruli ulcer. In this review we discuss the past and the current case burden of the priority NTDs in Guinea, highlight the major milestones and discuss current and future areas of focus for achieving the 2030 target outlined by the World Health Organization.

BACKGROUND: Access to affordable, quality healthcare is the key element of universal health coverage (UHC). This study examines the effectiveness of the neglected tropical disease (NTD) mass drug administration (MDA) campaign approach as a means to deliver UHC, using the example of the Liberia national programme.
METHODS: We first mapped the location of 3195 communities from the 2019 national MDA treatment data reporting record of Liberia. The association between coverage for onchocerciasis and lymphatic filariasis treatment achieved in these communities was then explored using a binomial geo-additive model. This model employed three key determinants for community \'remoteness\': population density and the modelled travel time of communities to their supporting health facility and to their nearest major settlement.
RESULTS: Maps produced highlight a small number of clusters of low treatment coverage in Liberia. Statistical analysis suggests there is a complex relationship between treatment coverage and geographic location.
CONCLUSIONS: We accept the MDA campaign approach is a valid mechanism to reach geographically marginal communities and, as such, has the potential to deliver UHC. We recognise there are specific limitations requiring further study.

Arthropod-borne viral infections caused by dengue virus (DENV) and chikungunya virus (CHIKV) are prevalent in the same regions and are spread by the same mosquito type (Aedes) and have similar clinical manifestations. This study emphasized the challenges of diagnosing fever in a patient returning from a tropical area. We report a case of a 52-year-old patient who presented with fever, myalgia, and headache after travelling to Laos and Thailand. After ten days of the disease, the diagnosis of chikungunya was made. Recent travel history should be a standard part of assessment when consulting febrile patients and is essential for further diagnosis. Malaria should permanently be excluded from travellers returning from tropical regions with fever. In the differential diagnosis, dengue, chikungunya, and other mosquito-borne infections should be considered. Patients wishing to travel to such areas need to be educated beforehand on the necessary preventative measures.

UNASSIGNED: Chagas disease, caused by the protozoan Trypanosoma cruzi, is the most common parasitic aetiology of non-ischaemic cardiomyopathy in the Americas, causing significant morbidity and mortality. The clinical spectrum ranges from early asymptomatic disease to severe cardiac manifestations including dilated cardiomyopathy, heart failure, dysrhythmias, conduction abnormalities, thromboembolism, and sudden death.
UNASSIGNED: We present a case of Chagas disease in a 75-year-old patient originally from El Salvador who presented to our Canadian tertiary centre with heart failure and atrial fibrillation/flutter. The patient had dilated cardiomyopathy with severely reduced systolic function, which was thought to be early Chagas cardiomyopathy after confirmatory positive serologies for T. cruzi. The patient demonstrated significant clinical improvement and recovery of systolic function with benznidazole therapy that was sustained up to 12 months on follow up.
UNASSIGNED: The American Heart Association recommends considering treatment of early chronic Chagas cardiomyopathy with anti-trypanosomal therapy. Our case highlights the importance of multidisciplinary collaboration in the diagnosis of early Chagas cardiomyopathy and critical timing of benznidazole, as effectiveness is limited in late disease due to myocardial cell-death programme. Although the historical BENEFIT study is known to not have shown mortality reduction, we advocate that the significant reduction in cardiovascular-related hospitalizations should be considered for symptomatic patients with early Chagas cardiomyopathy with the potential benefit of improving cardiac function and avoiding need for heart transplantation.

BACKGROUND: Neglected tropical diseases (NTDs) affect poor populations with little or no \'political voice\' to influence control activities. While most NTDs have interventions that work, the biggest challenge remains in delivering targeted interventions to affected populations residing in areas experiencing weak health systems. Despite the upward development trends in most countries of sub-Saharan Africa (SSA), the healthcare worker to population ratio remains exceptionally low, with some areas not served at all; thus, there is a need to involve other personnel for school and community-based healthcare approaches. Nonetheless, the current community-based programs suffer from inconsistent community participation due to a lack of coordinated response, and an expanded intervention agenda that lacks context-specific solutions applicable to rural, urban, and marginalized areas.
METHODS: This research investigated the capacity of local communities to address the burden of NTDs. Informed by the social theory of human capability, the research collected primary qualitative data by conducting key informant interviews and focus group discussions of people infected or affected by NTDs. The interview data were collected and transcribed verbatim for thematic analysis using Nvivo version 12.
RESULTS: Our findings reveal, first, a need for intersectoral collaboration between governments and affected populations for inclusive and sustainable NTD solutions. Second, a \'bottom-up\' approach that enhances capacity building, sensitization, and behaviour change for improved uptake of NTD interventions. Third, the enforcement of Public Health Legislative Acts that mandates the reporting and treatment of NTDs such as leprosy. Fourth, the establishment of support groups and counseling services to assist persons suffering from debilitating and permanent effects of NTDs.
CONCLUSIONS: Our research demonstrates the importance of human agency in encouraging new forms of participation leading to the co-production of inclusive and sustainable solutions against NTDs.

Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design.
A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight.
The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO\'s Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences.
NCT03754322.

Integrated community case management (iCCM) of childhood illness in Uganda involves protocol-based care of malaria, pneumonia and diarrhoea for children under 5 years old. This study assessed volunteer village health workers\' (VHW) ability to provide correct iCCM care according to the national protocol and change in their performance over time since initial training.
VHWs affiliated with the Ugandan national programme provide community-based care in eight villages in Bugoye Subcounty, a rural area in Kasese District. The first cohort of VHWs began providing iCCM care in March 2013, the second cohort in July 2016.
All children receiving iCCM care in 18 430 clinical encounters occurring between April 2014 and December 2018.
The descriptive primary outcome measure was the proportion of patients receiving overall correct care, defined as adherence to the iCCM protocol for the presenting condition (hereafter quality of care). The analytic primary outcome was change in the odds of receiving correct care over time, assessed using logistic regression models with generalised estimating equations. Secondary outcome measures included a set of binary measures of adherence to specific elements of the iCCM protocol. Preplanned and final measures were the same.
Overall, VHWs provided correct care in 74% of clinical encounters. For the first cohort of VHWs, regression modelling demonstrated a modest increase in quality of care until approximately 3 years after their initial iCCM training (OR 1.022 per month elapsed, 95% CI 1.005 to 1.038), followed by a modest decrease thereafter (OR 0.978 per month, 95% CI 0.970 to 0.986). For the second cohort, quality of care was essentially constant over time (OR 1.007 per month, 95% CI 0.989 to 1.025).
Quality of care was relatively constant over time, though the trend towards decreasing quality of care after 3 years of providing iCCM care requires further monitoring.