With the advancement of isothermal nucleic acid amplification techniques, detection of the pathogenic DNA in clinical samples at point-of-need is no longer a dream. The newly developed recombinase polymerase amplification (RPA) assay incorporated in a suitcase laboratory has shown promising diagnostic efficacy over real-time PCR in detection of leishmania DNA from clinical samples. For broader application of this point-of-need system, we undertook a current multi-country diagnostic evaluation study towards establishing this technique in different endemic settings which would be beneficial for the ongoing elimination programs for leishmaniasis. For this study purpose, clinical samples from confirmed visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) patients were subjected to both real-time PCR and RPA assay in Bangladesh, India, and Nepal. Further skin samples from confirmed cutaneous leishmaniasis (CL) patients were also included from Sri Lanka. A total of 450 clinical samples from VL patients, 429 from PKDL patients, 47 from CL patients, and 322 from endemic healthy/healthy controls were under investigation to determine the diagnostic efficacy of RPA assay in comparison to real-time PCR. A comparative sensitivity of both methods was found where real-time PCR and RPA assay showed 96.86% (95% CI: 94.45–98.42) and 88.85% (95% CI: 85.08–91.96) sensitivity respectively in the diagnosis of VL cases. This new isothermal method also exhibited promising diagnostic sensitivity (93.50%) for PKDL cases, when a skin sample was used. Due to variation in the sequence of target amplicons, RPA assay showed comparatively lower sensitivity (55.32%) than that of real-time PCR in Sri Lanka for the diagnosis of CL cases. Except for India, the assay presented absolute specificity in the rest of the sites. Excellent concordance between the two molecular methods towards detection of leishmania DNA in clinical samples substantiates the application of RPA assay incorporated in a suitcase laboratory for point-of-need diagnosis of VL and PKDL in low resource endemic settings. However, further improvisation of the method is necessary for diagnosis of CL.

Post Kala-azar Dermal Leishmaniasis (PKDL) is a sequel of Visceral Leishmaniasis (VL). The patients act as a reservoir for the causative parasite (i.e. Leishmania donovani) and thus should be diagnosed and treated with the utmost urgency to prevent the transmission of the disease. In this study, we tried to report the first instances of corneal complications supposedly associated with Miltefosine (MF), in PKDL patients and the probable pathophysiology of such events. The recently rejuvenated National Kala-azar Elimination Program in Bangladesh has put great emphasis on monitoring all the leishmaniasis patients to investigate possible adverse drug reactions (ADR). A total of 194 patients have received Miltefosine for the treatment of Post Kala-azar Dermal Leishmaniasis. So far five patients were found to have developed unilateral ophthalmic complications during the periods from May 2016 to October 2017, after being treated with MF for PKDL. Unfortunately, one of whom had to go through complete evisceration of the affected eyeball. Despite the fact that MF is the only oral formulation of choice to treat PKDL, occurrences of such unexpected ADRs after MF administration urges the exploration of the pathogenesis of such incidents and determine measures to avert such occurrences from happening in future. PKDL is a sequel of VL, which acts as a source of leishmaniasis and should be diagnosed and treated at the earliest possible time to prevent disease transmission. In Bangladesh during the period from May 2016 to October 2017, a total of 5 patients were diagnosed to have Miltefosine induced unilateral ophthalmic complications. Miltefosine was introduced as an anti-parasitic drug through drug repurposing, and it has a complex mechanism of acting towards the parasite killing. The mechanism itself in certain circumstances may produce ophthalmic complications by its metabolites or by causing dry eye disease. Miltefosine is the only oral drug for leishmaniasis. Hence the etiopathogenesis and prevention strategy of such severe adverse events must be explored.

Adverse effects of antileishmanial drugs can affect patients’ quality of life and adherence to therapy for visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). In Bangladesh, there are 26 treatment centers that manage leishmaniasis cases coming from 100 endemic upazilas (subdistricts) of 26 districts (these include VL, PKDL, treatment failure, and relapse VL and cutaneous leishmaniasis cases). This study aimed to investigate the feasibility of using focused pharmacovigilance for VL (VLPV) in Bangladesh’s National Kala-azar Elimination Programme for the early detection and prevention of expected and unexpected adverse drug reactions (ADRs). This activity has been going on since December 2014. Activity area includes secondary public hospital or Upazila health complex (UHC) in hundred sub districts and Surya Kanta Kala-azar Research Center (SKKRC) in Mymensingh District, a specialized center for management of complicated VL and PKDL cases. Communicable Disease Control (CDC) of the Directorate General of Health Services (DGHS) assigned twenty five of hundred UHCs and SKKRC (total 26) as treatment centers depending on their suitable geographical location. This was implemented for better management of VL cases with Liposomal Amphotericin B (AmBisome®) to ensure patient convenience and proper utilization of this expensive donated drug. A VLPV expert committee and a UHC VLPV team were established, an operational manual and pharmacovigilance report forms were developed, training and refresher training of health personnel took place at UHCs and at the central level, collected information such as patient data including demographics, treatment history and response, adverse events were analyzed. This report includes information for the period from December 2014 to December 2016. From December 2014 to December 2016, 1327 leishmaniasis patients were treated and 1066 (80%) were available for VLPV. Out of these, 57, 33, 9, and 1% were new VL, PKDL, VL relapse, and other cases, respectively. Liposomal amphotericin B was mostly used (82%) for case management, followed by miltefosine (20%) and paromomycin (3%). Out of the 1066 patients, 26% experienced ADRs. The most frequent ADR was fever (17%, 176/1066), followed by vomiting (5%, 51/1066). Thirteen serious adverse events (SAEs) (eight deaths and five unexpected SAEs) were observed. The expert committee assessed that three of the deaths and all unexpected SAEs were possibly related to treatment. Out of the five unexpected SAEs, four were miltefosine-induced ophthalmic complications and the other was an AmBisome®-induced avascular necrosis of the nasal alae. The Directorate General of the Drug Administration entered the ADRs into the World Health Organization Uppsala Monitoring Centre (WHO-UMC) VigiFlow database. This study found that VLPV through NKEP is feasible and should be continued as a routine activity into the public health system of Bangladesh to ensure patient safety against anti-leishmanial drugs.

Tetanus, a vaccine-preventable and potentially fatal disease, continues to remain prevalent in low- and middle-income countries. Furthermore, physicians are often unfamiliar with management of severe tetanus without ventilator support. Therefore, we proposed a modified treatment protocol that provides a low-cost and effective solution for the management of severe tetanus in resource-constrained settings. This is an observational study of 42 patients with severe tetanus treated during 2015–2016 at Surya Kanta Hospital, Bangladesh. This facility does not have an intensive care unit (ICU), and patients admitted here were provided treatment with the modified protocol. A total number of 42 patients with severe tetanus were treated with the modified protocol. Among them, 24 (57.1%) recovered completely, six (14.3%) recovered with the sequela, and 12 (28.6%) died. Among those who recovered with the sequela, four needed mechanical support during walking and two had a visual impairment. No significant adverse event was recorded during the treatment period. The results gathered during this case series provide a sustainable, low-cost, and effective solution to management of severe tetanus in resource-constrained settings where ICUs are unavailable.

Background: Treatment of acute organophosphorus (OP) insecticide poisoning is difficult, with many patients dying despite best care. Pre-clinical studies have shown benefit from salbutamol, possibly due speeding alveolar fluid clearance or reducing bronchoconstriction. In this small pilot dose-response study, we aimed to explore whether addition of nebulized salbutamol to standard care might improve resuscitation. Methods: We performed a single-blind phase II study comparing the effect of two different doses of nebulized salbutamol versus saline placebo, in addition to standard treatment. Primary outcome was oxygen saturations over the first 60 min of resuscitation; secondary outcomes included heart rate, incidence of dysrhythmias, time to ‘atropinization’, atropine dose required, and mortality. Result: Seventy-five patients were randomized to receive 5 mg (Salb5, n = 25) or 2.5mg (Salb2.5, n = 25) of salbutamol, or saline placebo (NoSalb, n = 25), by nebulizer. Oxygen saturations did not differ between groups over the first 60 min of resuscitation (median AUC NoSalb: 1376 [95% CI 1282 to 1470], Salb2.5: 1395 [1305 to 1486], Salb5: 1233 [1100 to 1367]; p = .9898). Heart rate was also similar across the three arms. Median time to full atropinization, and atropine dose required, were the same for all three arms (NoSalb 15.0 [10–16] min and 12.6 [8.0–13.4] mg, Salb2.5 15.0 [10–16] min and 12.6 [9.3–16.8] mg, and Salb5 15.0 [10–20] min and 12.6 [10.7–20.6] mg; p = .4805 and p = .1871, respectively). Three (12%) patients died in the Salb2.5 and Salb5 groups and two (8%) in the NoSalb group. Conclusion: This pilot study, within the limitations of its small size and variation between patients, found no apparent evidence that administration of nebulized salbutamol improved resuscitation of patients with acute OP insecticide self-poisoning. The data obtained provides a basis to design further studies to ultimately test the role of salbutamol in OP insecticide poisoning.

Para Kala-azar Dermal Leishmaniasis (Para-KDL) manifests the concomitant presence of Post Kala-azar Dermal Leishmaniasis and Visceral Leishmaniasis and works as a reservoir of infection. The study discusses the cases and their management and aims to address the gaps within existing methods of diagnosis and treatment. This retrospective cross-sectional study discusses 16 Para-KDL cases with one-year follow-up data, treated between 2012–2021 at the Surya Kanta Kala-azar Research Center, Bangladesh. We collected data from hospital records and used STATA 16 to analyze and see the frequency distribution and variable means. We found five patients without any history of kala-azar infection. All the patients were treated with 20 mg/kg Liposomal Amphotericin B in 4 divided doses except one with a history of AmBisome hypersensitivity. One year after treatment, all patients were free from skin lesions, with no hepatosplenomegaly, and observed significant improvement in BMI and hemoglobin levels. The Para-KDL patients are challenging to diagnose, and the relapse and treatment failure leishmania patients might have belonged to this rare group, contributing to their poor prognosis. Therefore, developing an appropriate diagnostic workflow and a new drug regimen is essential to sustain the success of our elimination efforts.