Publications by authors named "Johan van Griensven"

164 Publications

Human filariasis in travelers and migrants: a retrospective 25-year analysis at the Institute of Tropical Medicine, Antwerp, Belgium.

Clin Infect Dis 2021 Aug 31. Epub 2021 Aug 31.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Background: Information on human filariasis in international travelers is scarce. We describe the epidemiology, clinical presentation and outcome of these infections in a reference travel clinic over the past decades.

Methods: We reviewed all cases of filariasis diagnosed at the Institute of Tropical Medicine, Antwerp, Belgium, from 1994 to 2018. Diagnosis was obtained by either parasitological methods (confirmed) or strict clinical case definitions (probable). We assessed the characteristics of cases at diagnosis and response to therapy within three to 12 months.

Results: A total of 320 patients (median age: 41 years; 71% males) were diagnosed with 327 filarial infections (Wuchereria bancrofti = 6; Onchocerca volvulus = 33, Loa loa = 150, Mansonella perstans = 130; unspecified species = 8). Diagnosis was confirmed in 213/320 (67%) patients. European long-term travelers accounted for 166 patients (52%) and visitors/migrants from tropical countries for another 110 (34%). Central Africa was the likely region of acquisition for 294 (92%) patients. The number of filariasis cases decreased from 21.5/year in average in the nineties to 6.3/year in the last decade, when loiasis became predominant. Cases reported symptoms in > 80% of all filarial infections but mansonellosis (45/123 single infections; 37%). Lymphatic filariasis and onchocerciasis cases responded well to conventional therapy. However, 30% of patients with loiasis and mansonellosis experienced treatment failure (with diethylcarbamazine and levamisole-mebendazole, respectively).

Conclusions: The burden and species distribution of filariasis in travelers evolved in the past decades. Most presentations were symptomatic. Case management would benefit from more effective therapies for loiasis and mansonellosis.
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http://dx.doi.org/10.1093/cid/ciab751DOI Listing
August 2021

Antibiotic Use in a Municipal Veterinary Clinic in Ghana.

Trop Med Infect Dis 2021 Jul 20;6(3). Epub 2021 Jul 20.

Kintampo Health Research Centre, Ghana Health Service, Kintampo North Municipality, Kintampo P.O. Box 200, Ghana.

Antimicrobial resistance (AMR) is a threat to public health, impacting both human and animal health as well as the economy. This study sought to describe antibiotic prescription practices and use in the Kintampo North Municipal Veterinary Clinic in Ghana using routinely collected data. Of the 513 animals presented for care between 2013 and 2019, the most common animals were dogs (71.9%), goats (13.1%), and sheep (11.1%). Antibiotics were prescribed for 273/513 (53.2%) of the animals. Tetracycline was the most commonly prescribed class of antibiotics, (99.6%). Of the 273 animals that received antibiotics, the route of administration was not documented in 68.9%, and antibiotic doses were missing in the treatment records in 37.7%. Details of the antibiotic regimen and the medical conditions diagnosed were often not recorded (52.8%). This study recommends appropriate documentation to enable continuous audit of antibiotic prescription practice and to improve quality of use. There is also the need for a national survey on antibiotic prescribtion and use in animal health to support policy implementation and decision making in One-Health in Ghana.
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http://dx.doi.org/10.3390/tropicalmed6030138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293393PMC
July 2021

Characteristics, utilisation and influence of viewpoint articles from the Structured Operational Research and Training Initiative (SORT IT) - 2009-2020.

F1000Res 2021 10;10:198. Epub 2021 Mar 10.

Research for Implementation , UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland.

: The Structured Operational Research and Training Initiative (SORT IT) teaches the practical skills of conducting and publishing operational research (OR) to influence health policy and/or practice. In addition to original research articles, viewpoint articles are also produced and published as secondary outputs of SORT IT courses. We assessed the characteristics, use and influence of viewpoint articles derived from all SORT IT courses. This was a cross-sectional study involving all published viewpoint articles derived from the SORT IT courses held from August 2009 - March 2020. Characteristics of these papers were sourced from the papers themselves and from SORT-IT members involved in writing the papers. Data on use were sourced from the metrics provided on the online publishing platforms and from Google Scholar. Influence on policy and practice was self-assessed by the authors of the papers and was performed only for papers deemed to be 'calls for action'. A total of 41 viewpoint papers were published. Of these, 15 (37%) were 'calls for action'. In total, 31 (76%) were published in open-access journals and the remaining 10 in delayed access journals. In 12 (29%) of the papers, first authors were from low and middle-income countries (LMICs). Female authors (54%) were included in 22, but only four (10%) and two (5%) of first and last authors respectively, were female. Only seven (17%) papers had available data regarding online views and downloads. The median citation score for the papers was four (IQR 1-9). Of the 15 'call for action' papers, six influenced OR capacity building, two influenced policy and practice, and three influenced both OR capacity building within SORT IT and policy and practice. Viewpoint articles generated during SORT IT courses appear to complement original OR studies and are valued contributors to the dissemination of OR practices in LMICs.
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http://dx.doi.org/10.12688/f1000research.27349.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218027PMC
July 2021

Blood Culture Testing Outcomes among Non-Malarial Febrile Children at Antimicrobial Resistance Surveillance Sites in Uganda, 2017-2018.

Trop Med Infect Dis 2021 May 6;6(2). Epub 2021 May 6.

Infectious Disease Institute, College of Health Sciences, Makerere University, Kampala 920102, Uganda.

Blood culture (BC) processes are critical to the utility of diagnostic testing, bloodstream infection (BSI) management, and antimicrobial resistance (AMR) surveillance. While Uganda has established BC guidelines, often laboratory practice does not meet the desired standards. This compromises pathogen recovery, reliability of antimicrobial susceptibility testing, and diagnostic test utility. This study assessed laboratory BC process outcomes among non-malarial febrile children below five years of age at five AMR surveillance sites in Uganda between 2017 and 2018. Secondary BC testing data was reviewed against established standards. Overall, 959 BC specimens were processed. Of these, 91% were from female patients, neonates, infants, and young children (1-48 months). A total of 37 AMR priority pathogens were identified; was predominant (54%), followed by (19%). The diagnostic yield was low (4.9%). Only 6.3% of isolates were identified. AST was performed on 70% (18/26) of identified AMR priority isolates, and only 40% of these tests adhered to recommended standards. Interventions are needed to improve laboratory BC practices for effective patient management through targeted antimicrobial therapy and AMR surveillance in Uganda. Further research on process documentation, diagnostic yield, and a review of patient outcomes for all hospitalized febrile patients is needed.
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http://dx.doi.org/10.3390/tropicalmed6020071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167719PMC
May 2021

Miltefosine for the treatment of cutaneous leishmaniasis-A pilot study from Ethiopia.

PLoS Negl Trop Dis 2021 05 28;15(5):e0009460. Epub 2021 May 28.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Background: Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.

Methodology And Principal Findings: In an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.

Conclusions/significance: Based on miltefosine's good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.

Trial Registration: ClinicalTrials.gov NCT04004754.
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http://dx.doi.org/10.1371/journal.pntd.0009460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191986PMC
May 2021

Detection of Cutaneous Leishmaniasis Foci in South Ethiopia.

Am J Trop Med Hyg 2021 May 10. Epub 2021 May 10.

2Evolutionary Ecology Group, University of Antwerp, Antwerp, Belgium.

Cutaneous leishmaniasis (CL) is a major public health problem in Ethiopia. The disease is endemic in Ochollo, a village in southern Ethiopia, but there are no reports of CL in the wider area, although it is ecologically very similar. We conducted a rapid assessment survey in the South Ethiopian Rift Valley and found 100 parasitologically confirmed CL cases in 38 villages not reported endemic for CL. Approximately half of the cases were children (57%), and most lesions occurred on the face (78%) and were older than 6 months (77%). Only 2% of the people was aware of the mode of transmission, and 9% sought modern treatment at a hospital. These preliminary data indicate that CL is much more widespread than previously reported and that the disease might have a large psychosocial impact. Hence, this study calls for larger surveys across the Ethiopian highlands. Additionally, health education and treatment capacity need to be implemented.
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http://dx.doi.org/10.4269/ajtmh.20-0708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274791PMC
May 2021

Case Report: Atypical Presentation of Visceral Leishmaniasis: Two Cases from Northwest Ethiopia.

Am J Trop Med Hyg 2021 Apr 12. Epub 2021 Apr 12.

4Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Human visceral leishmaniasis (VL) is a life-threatening disease caused by protozoan parasites belonging to the Leishmania donovani complex. Atypical cases of leishmaniasis and HIV coinfection have been documented in case reports, mostly associated with gastrointestinal tract, kidney, and skin involvement. We report two VL cases with atypical localizations not reported from east Africa before, both diagnosed and treated at the Leishmaniasis Research and Treatment Center, Gondar, Ethiopia. The first case was an HIV-infected patient with scrotal and penile involvement. Leishmania parasites were detected in the spleen and the scrotum. The second case was an immunocompetent individual with esophageal, laryngeal, and pharyngeal involvement and facial lesions. Leishmania parasites were detected in the spleen, skin, and esophageal biopsies. Current evidence suggests atypical presentation can occur in patients irrespective of their HIV status. Therefore; we suggest a high index of suspicion for VL among clinicians working in endemic areas of Ethiopia.
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http://dx.doi.org/10.4269/ajtmh.20-0666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176479PMC
April 2021

Abdominal ultrasound in the diagnostic work-up of visceral leishmaniasis and for detection of complications of spleen aspiration.

PLoS Negl Trop Dis 2021 02 16;15(2):e0009107. Epub 2021 Feb 16.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Introduction: Abdominal ultrasound (US) is increasingly used in the diagnostic work-up of infectious diseases, but studies on its diagnostic value in visceral leishmaniasis (VL) are lacking. US could help to identify complications of spleen aspiration (SA). We aimed to assess the diagnostic value of US and the evolution of findings after VL treatment; the incidence and degree of splenic injury; and the pain perceived during SA.

Methodology/result: We conducted a cross-sectional prospective study at the Leishmaniasis Research and Treatment Center, Gondar, Ethiopia between Oct 2017 and Dec 2018. We enrolled VL suspects undergoing tissue aspiration; US were conducted before and after SA, and at the end of VL treatment. Splenic injury was graded using the American association of surgery trauma injury scale (grade 1-4). The pain perceived during SA was graded using a visual analogue scale. Out of 392 VL suspects, 192 (49%) were confirmed VL cases. The median age was 25 years (IQR 21-30). Massive splenomegaly and hepatomegaly were the most common US findings. Splenic nodules were seen in 3.7% of the 190 VL cases and 1.5% of the 197 non-VL cases. Ascites was more common in VL (16.4%) than in non-VL cases (9.1%). The frequency of US abnormalities decreased with treatment. None of the US findings had sufficient sensitivity and specificity to justify its use as a diagnostic test. US detected splenic injury in four of the 318 patients who had post-SA US. All four patients remained clinically stable. Pain was perceived as moderate or severe in 51% of patients.

Conclusion: The diagnostic value of abdominal US for VL was low but found useful to detect subclinical splenic injury. SA caries a risk of splenic injury and was perceived painful by most. Further research on less invasive diagnostic tools is needed.
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http://dx.doi.org/10.1371/journal.pntd.0009107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935305PMC
February 2021

Ebola virus antibody decay-stimulation in a high proportion of survivors.

Nature 2021 02 27;590(7846):468-472. Epub 2021 Jan 27.

Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK.

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.
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http://dx.doi.org/10.1038/s41586-020-03146-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839293PMC
February 2021

Surgical debulking of podoconiosis nodules and its impact on quality of life in Ethiopia.

PLoS Negl Trop Dis 2021 01 22;15(1):e0009053. Epub 2021 Jan 22.

Amsterdam UMC, University of Amsterdam, department of dermatology, Amsterdam Institute for Infection and Immunity (AII), location Academic Medical Centre, Amsterdam, The Netherlands.

Background: In Ethiopia, severe lymphedema and acute dermato-lymphangio-adenitis (ADLA) of the legs as a consequence of podoconiosis affects approximately 1.5 million people. In some this condition may lead to woody-hard fibrotic nodules, which are resistant to conventional treatment. We present a series of patients who underwent surgical nodulectomy in a resource-limited setting and their outcome.

Methods: In two teaching hospitals, we offered surgical nodulectomies under local anaesthesia to patients with persisting significant fibrotic nodules due to podoconiosis. Excisions after nodulectomy were left to heal by secondary intention with compression bandaging. As outcome, we recorded time to re-epithelialization after surgery, change in number of ADLA episodes, change in quality of life measured with the Dermatology Quality of Live Index (DQLI) questionnaire, and recurrence rate one year after surgery.

Results: 37nodulectomy operations were performed on 21 patients. All wounds re-reepithelialised within 21 days (range 17-42). 4 patients developed clinically relevant wound infections. The DLQI values were significantly better six months after surgery than before surgery (P<0.0001). Also the number of ADLA episodes per three months was significantly lower six months after surgery than before surgery (P<0.0001).

Conclusion: Nodulectomy in podoconiosis patients leads to a significant improvement in the quality of life with no serious complications, and we recommend this to be a standard procedure in resource-poor settings.
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http://dx.doi.org/10.1371/journal.pntd.0009053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857577PMC
January 2021

Evaluation of conventional and four real-time PCR methods for the detection of Leishmania on field-collected samples in Ethiopia.

PLoS Negl Trop Dis 2021 01 12;15(1):e0008903. Epub 2021 Jan 12.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

In most low-resource settings, microscopy still is the standard method for diagnosis of cutaneous leishmaniasis, despite its limited sensitivity. In Ethiopia, the more sensitive molecular methods are not yet routinely used. This study compared five PCR methods with microscopy on two sample types collected from patients with a suspected lesion to advise on optimal diagnosis of Leishmania aethiopica. Between May and July 2018, skin scrapings (SS) and blood exudate from the lesion spotted on filter paper (dry blood spot, DBS) were collected for PCR from 111 patients of four zones in Southern Ethiopia. DNA and RNA were simultaneously extracted from both sample types. DNA was evaluated by a conventional PCR targeting ITS-1 and three probe-based real-time PCRs: one targeting the SSU 18S rRNA and two targeting the kDNA minicircle sequence (the 'Mary kDNA PCR' and a newly designed 'LC kDNA PCR' for improved L. aethiopica detection). RNAs were tested with a SYBR Green-based RT-PCR targeting spliced leader (SL) RNA. Giemsa-stained SS smears were examined by microscopy. Of the 111 SS, 100 were positive with at least two methods. Sensitivity of microscopy, ITS PCR, SSU PCR, Mary kDNA PCR, LC kDNA PCR and SL RNA PCR were respectively 52%, 22%, 64%, 99%, 100% and 94%. Microscopy-based parasite load correlated well with real-time PCR Ct-values. Despite suboptimal sample storage for RNA detection, the SL RNA PCR resulted in congruent results with low Ct-values. DBS collected from the same lesion showed lower PCR positivity rates compared to SS. The kDNA PCRs showed excellent performance for diagnosis of L. aethiopica on SS. Lower-cost SL RNA detection can be a complementary high-throughput tool. DBS can be used for PCR in case microscopy is negative, the SS sample can be sent to the referral health facility where kDNA PCR method is available.
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http://dx.doi.org/10.1371/journal.pntd.0008903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802924PMC
January 2021

Diagnostic accuracy of direct agglutination test, rK39 ELISA and six rapid diagnostic tests among visceral leishmaniasis patients with and without HIV coinfection in Ethiopia.

PLoS Negl Trop Dis 2020 12 31;14(12):e0008963. Epub 2020 Dec 31.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Diagnosis of a first-time visceral leishmaniasis (VL) infection in Ethiopia is established by use of a rapid diagnostic test (RDT) detecting antibodies against rK39, direct agglutination test (DAT) and microscopy according to the national algorithm. The performance of individual tests and algorithm is variable and depends on several factors, one being HIV status. Limited data are available on the performance of tests in VL-HIV coinfected patients. Assessment of the performance of DAT (ITM-A), rK39 ELISA (Serion) and six RDT (Onsite Leishmania Ab CTK, Antigen ICT Xinjier, IT Leish Biorad, Kalazar Detect Inbios, rK39 IgG1 Coris, rk28 IgG1 Coris) for the diagnosis of VL was done on a panel of 91 stored serum and plasma samples of 'first-episode' suspected VL patients, with HIV coinfection (n = 51) and without (n = 40). A combined reference standard was used: either positive microscopy on tissue aspirates, or in case of negative microscopy, positive PCR results on the aspirate slide. Additionally, endemic healthy controls (n = 20), non-endemic controls (n = 10) and patients with confirmed malaria infection (n = 10) were tested for specificity evaluation. Sensitivities ranged from 69.2% for DAT (applied cut-off ≥ 1/3200) to 92.2% for the Onsite RDT, whereas specificities ranged from 20.0% for Kalazar Antigen ICT to 100% for IT Leish and rK39 IgG1. Sensitivities from all assays decreased upon stratification according to HIV status but was only significantly different for rK39 Serion ELISA (p-value 0.0084) and the Onsite RDT (p-value 0.0159). In conclusion, performance of commercially available assays for VL on samples from Northern-Ethiopian patients varied widely with a substantial decrease in sensitivity in the VL-HIV coinfected group. Clear guidelines on minimal performance criteria of individual tests and algorithms are needed, as well as which reference standard should be used to determine the performance.
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http://dx.doi.org/10.1371/journal.pntd.0008963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774845PMC
December 2020

Clinical Profile and Treatment of COVID-19 Patients: Experiences from an Ethiopian Treatment Center.

Am J Trop Med Hyg 2020 Dec 30. Epub 2020 Dec 30.

Institute of Tropical Medicine, Antwerp, Belgium.

COVID-19 is not well studied in Africa. Understanding the clinical profile and management of COVID-19 will help to plan better prevention and treatment strategies taking the local context into consideration. In this study, we described the clinical profile, treatment used, and outcomes of COVID-19 patients in one of the COVID-19 treatment centers of Ethiopia, Boru Meda Hospital. An institution-based retrospective cross-sectional study was carried out using medical records of COVID-19 patients who were admitted to Boru Meda Hospital with a positive reverse transcription (RT)-PCR result from May 9, 2020 to September 20, 2020. All patients with a positive RT-PCR were admitted to the hospital, regardless of symptom and severity status. A total of 279 COVID-19 patients were included in the final analysis. The median age of patients was 28 years (interquartile range 23-40). The majority (69.5%) were male. Around a quarter ( = 73; 26.2%) of the patients were symptomatic, of which cough ( = 49; 67.1%) and fever ( = 32; 43.8%) were common symptoms. Among symptomatic patients, 48 (65.8%) were mild, four (5.5%) moderate, 12 (16.4%) severe, and nine (12.3%) were critical. The case fatality rate was 2.1%. Hypertension, age older than 25 years, and HIV/AIDS were significantly associated with symptomatic infection. In this study, most of the COVID-19 patients were asymptomatic. However, the proportion of severe and critical patients among those with symptoms was high. More studies are needed to assess the effect of HIV/AIDS on the severity and mortality of COVID-19.
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http://dx.doi.org/10.4269/ajtmh.20-1356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866348PMC
December 2020

A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.

Trials 2020 Nov 27;21(1):981. Epub 2020 Nov 27.

University Hospitals Leuven (UZ Leuven), Leuven, Belgium.

Background: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown.

Methods: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma.

Discussion: This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection.

Trial Registration: ClinicalTrials.gov NCT04429854 . Registered on 12 June 2020 - Retrospectively registered.
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http://dx.doi.org/10.1186/s13063-020-04876-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691949PMC
November 2020

Quality, Equity and Utility of Observational Studies during 10 Years of Implementing the Structured Operational Research and Training Initiative in 72 Countries.

Trop Med Infect Dis 2020 Nov 6;5(4). Epub 2020 Nov 6.

United Nations Childrens Fund (UNICEF), United Nations Development Programme (UNDP), World Bank, World Health Organization (WHO), Special Programme for Research and Training in Tropical Diseases (TDR), 1202 Geneva, Switzerland.

Observational studies are often inadequately reported, making it difficult to assess their validity and generalizability and judge whether they can be included in systematic reviews. We assessed the publication characteristics and quality of reporting of observational studies generated by the Structured Operational Research and Training Initiative (SORT IT). A cross-sectional analysis of original publications from SORT IT courses. SORT IT is a global partnership-based initiative aimed at building sustainable capacity for conducting operational research according to country priorities and using the generated evidence for informed decision-making to improve public health. Reporting quality was independently assessed using an adapted version of 'Strengthening the Reporting of Observational Studies in Epidemiology' (STROBE) checklist. In 392 publications, involving 72 countries, 50 journals, 28 publishers and 24 disease domains, low- and middle-income countries (LMICs) first authorship was seen in 370 (94%) and LMIC last authorship in 214 (55%). Publications involved LMIC-LMIC collaboration in 90% and high-income-country-LMIC collaboration in 87%. The majority (89%) of publications were in immediate open access journals. A total of 346 (88.3%) publications achieved a STROBE reporting quality score of >85% (excellent), 41 (10.4%) achieved a score of 76-85% (good) and 5 (1.3%) a score of 65-75% (fair). The majority of publications from SORT IT adhere to STROBE guidelines, while also ensuring LMIC equity and collaborative partnerships. SORT IT is, thus, playing an important role in ensuring high-quality reporting of evidence for informed decision-making in public health.
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http://dx.doi.org/10.3390/tropicalmed5040167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709644PMC
November 2020

Evaluation of C-reactive protein and myxovirus resistance protein A to guide the rational use of antibiotics among acute febrile adult patients in Northwest Ethiopia.

Int J Infect Dis 2020 Dec 28;101:276-282. Epub 2020 Sep 28.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. Electronic address:

Objectives: In low-resource settings, treatment is often given empirically without knowledge of the aetiology due to a lack of diagnostics. In the search for reliable rapid tests to guide treatment work-up, this study was performed to determine whether two biomarkers could differentiate bacterial from non-bacterial infections in acute febrile patients.

Methods: Adults with acute fever were recruited at a referral hospital in Ethiopia. The QuikRead Go test was used to quantify C-reactive protein (qCRP) and the FebriDx test was used for combined qualitative detection of the bacterial CRP marker with myxovirus resistance protein A (MxA), a viral biomarker.

Results: Of the 200 patients included in this study, most presented with 2-3 days of fever, headache, and joint pain. Antibiotics were prescribed for 83.5% and antimalarials for 36.5%, while a bacterial infection was only confirmed in 5% and malaria in 11%. The median qCRP level for confirmed bacterial infections was 128 mg/l. The FebriDx and QuikRead Go test had an overall agreement of 72.0%.

Conclusions: An over-prescription of antibiotics for febrile patients was observed, even for those with low CRP levels and without a confirmed bacterial infection. The added value of the FebriDx was limited, while the combined use of rapid tests for qCRP and malaria should be considered for the management of acute febrile illness and antibiotic stewardship.
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http://dx.doi.org/10.1016/j.ijid.2020.09.1444DOI Listing
December 2020

Epidemiology, clinical pattern and impact of species-specific molecular diagnosis on management of leishmaniasis in Belgium, 2010-2018: A retrospective study.

Travel Med Infect Dis 2020 Nov - Dec;38:101885. Epub 2020 Sep 22.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Background: Species-directed therapy of leishmaniasis has been recommended for travelers since 2014, but little is known about species distribution and treatment practices in non-endemic countries. We aimed to describe leishmaniasis cases in Belgium since species typing became available and evaluate its impact on patient management.

Method: Retrospective analysis of all patients diagnosed by PCR at our national reference laboratory from 2010 to 2018. Species were typed by Hsp-70 sequencing.

Results: We identified 18 visceral leishmaniasis (VL) and 147 (muco)cutaneous leishmaniasis ((M)CL) cases. VL was exclusively due to L. infantum and consistently treated with liposomal amphotericin B, with four observed failures. (M)CL was caused by ten different species. Of 62 cases diagnosed and species typed after 2014 with timing information, 28 (45.2%) were treated before the species result was available. Therapy was not species-directed in 10/32(28.1%) of those treated after species identification. Patients treated according to the guidelines tended to have a favorable outcome more often than those who were not (36/44, 81.8% versus 8/19, 57.9%; p = 0.045).

Conclusions: In contrast to VL, various species caused (M)CL in our setting and species result was often not considered for treatment. Outcome tended to be better however when therapy was species-directed.
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http://dx.doi.org/10.1016/j.tmaid.2020.101885DOI Listing
July 2021

Activity limitation and social participation restriction among leprosy patients in Boru Meda Hospital, Amhara Region, Ethiopia.

PLoS Negl Trop Dis 2020 09 24;14(9):e0008702. Epub 2020 Sep 24.

Unit of neglected tropical diseases, Institute of Tropical Medicine, Antwerp, Belgium.

Background: Although Ethiopia eliminated leprosy as public health problem 20 years ago, still more than 3000 new cases are reported annually. Leprosy related disability affects patients' day to day physical activities and their participation in social activities. Assessing the degree of activity limitation and social participation is recommended to show disability and assess the efficacy of rehabilitation efforts.

Methodology And Principal Finding: A hospital based cross sectional study was conducted among a total of 305 leprosy patients. Data were collected by face to face interview using Screening of Activity Limitation and Safety Awareness (SALSA) scale and participation scale. The analysis was done with SPSS version 25. Descriptive statistics was done and then binary logistic regression was used to identify factors associated with activity limitation as well as participation limitation. Most patients (219, 71.8%) had activity limitation; 41 (13.4%) with severe and 25 (8.2%) with extreme limitations. More than half of patients (168, 55.1%) were suffering from participation restriction; with 43 (14.1%) having severe restriction and 30 (9.8%) extreme restriction. Older age, low educational status, distance from treatment center, time of treatment and higher Eye, Hand, Foot disability score were associated with activity limitation. Similarly, older age, low educational status and being unmarried were significantly associated with participation restriction.

Conclusion: This study revealed that activity limitation and participation restriction are common among leprosy patients. Earlier diagnosis and improved rehabilitative services may help to decrease activity limitation, whereas community rehabilitation may improve social participation. The old and centralized leprosy rehabilitation services need to be decentralized and backed with modern equipment and trained staffs.
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http://dx.doi.org/10.1371/journal.pntd.0008702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537907PMC
September 2020

Sexual Transmission of Visceral Leishmaniasis: A Neglected Story.

Trends Parasitol 2020 12 15;36(12):950-952. Epub 2020 Sep 15.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

For visceral leishmaniasis (VL), a major vector-borne parasitic disease, an alternative sexual transmission route is well documented in dogs but evidence is lacking in humans. Here, we discuss the current knowledge and key questions to be answered as it may be an additional obstacle in ongoing VL elimination programs.
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http://dx.doi.org/10.1016/j.pt.2020.08.002DOI Listing
December 2020

Minimally Invasive Microbiopsies as an Improved Sampling Method for the Diagnosis of Cutaneous Leishmaniasis.

Open Forum Infect Dis 2020 Sep 17;7(9):ofaa364. Epub 2020 Aug 17.

Unit of Neglected Tropical Diseases, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Current sampling methods to diagnose cutaneous leishmaniasis are invasive and painful. An alternative and minimally invasive microbiopsy device was evaluated in a diverse range of cutaneous leishmaniasis lesions in Ethiopia. Using polymerase chain reaction-based diagnosis, the microbiopsy outperformed the routine skin slit sample by detecting more patients while pain scores were significantly lower.
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http://dx.doi.org/10.1093/ofid/ofaa364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486950PMC
September 2020

Hepatosplenic schistosomiasis, the ignored morbidity: experience from a referral hospital in Ethiopia.

Trans R Soc Trop Med Hyg 2021 01;115(1):57-62

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Background: Hepatosplenic schistosomiasis (HSS) is an important chronic complication of Schistosoma infection. However, its diagnosis and management are complicated due to lack of evidence and uniform guidance. In this study, we described the clinical profile and management of HSS in one of Ethiopia's referral hospitals.

Methods: A hospital-based, cross-sectional study was conducted using the medical records of patients diagnosed with HSS based on clinical symptoms and typical ultrasound findings observed at the gastroenterology clinic of Dessie referral hospital from September 2018 to December 2019.

Results: A total of 55 patient files were evaluated. Most patients (n=39; 70%) presented with upper gastrointestinal bleeding and severe anaemia. Nearly three-quarters of patients were admitted and 31 (56%) received a blood transfusion. Hepatitis B coinfection was documented in 11 patients (20%). Upper gastrointestinal endoscopy was performed in 31 patients (56%), in whom large oesophageal varices with red signs were the most common finding. Among patients who had endoscopy, band ligation was carried out in 21 cases (68%). Praziquantel was administered to 11 patients (20%).

Conclusion: HSS causes severe complications of portal hypertension, like variceal bleeding, which are currently not adequately treated. In addition to already existing preventive efforts, we advise control programmes to also address acute management and rehabilitation of these patients.
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http://dx.doi.org/10.1093/trstmh/traa082DOI Listing
January 2021

Neglecting the effect of COVID-19 on neglected tropical diseases: the Ethiopian perspective.

Trans R Soc Trop Med Hyg 2020 10;114(10):730-732

Department of Dermatology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.

Countries around the world are facing an enormous challenge due to the COVID-19 pandemic. The pressure that the pandemic inflicts on health systems could certainly impact on the care, control, and elimination of neglected tropical diseases (NTDs). From mid-January 2020, Ethiopia started to prepare for the prevention and treatment of COVID-19. The Federal Ministry of Health pledged to continue essential healthcare, including NTD care, during this pandemic. However, some hospitals have been closed for other healthcare services and have been turned into isolation and treatment centers for COVID-19. In addition to the healthcare facility measures, all community-based health promotion and disease prevention services have been stopped. The current shift in attention towards COVID-19 is expected to have a negative impact on NTD prevention and care.
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http://dx.doi.org/10.1093/trstmh/traa072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499774PMC
October 2020

Point-of-Care Biomarkers to Guide Antibiotic Prescription for Acute Febrile Illness in Sub-Saharan Africa: Promises and Caveats.

Open Forum Infect Dis 2020 Aug 30;7(8):ofaa260. Epub 2020 Jun 30.

Institute of Tropical Medicine, Antwerp, Belgium.

Empiric malaria treatment in Sub-Saharan Africa has significantly decreased with the scaling-up of malaria rapid diagnostic tests; this coincided with a pronounced increase in empiric antibiotic prescriptions. In high-income countries, guidance for antibiotic prescriptions using biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) has reduced antibiotic use while safe-guarding patient safety. Importantly, several low-cost point-of-care CRP/PCT tests are currently available. However, only a few studies on the role of CRP/PCT in differentiating bacterial vs viral infections in acute febrile illness have been conducted in Sub-Saharan Africa. Studies from Central and West Africa (most of which is malaria-endemic) are particularly scarce, and only 1 has included adults. The evidence base for point-of-care use of CRP/PCT biomarkers in acute fever in Sub-Saharan Africa should be urgently built. Before engaging in clinical trials to assess clinical impact, pilot studies should be conducted to address key knowledge gaps including recommended CRP/PCT cutoff values and the effect of malaria coinfection.
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http://dx.doi.org/10.1093/ofid/ofaa260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423291PMC
August 2020

Essential Healthcare Services in the Face of COVID-19 Prevention: Experiences from a Referral Hospital in Ethiopia.

Am J Trop Med Hyg 2020 Sep;103(3):1198-1200

Institute of Tropical Medicine, Antwerp, Belgium.

Globally, healthcare systems are facing the enormous challenge of the COVID-19 pandemic. Ethiopia is currently implementing different preventive measures to interrupt the transmission of SARS-CoV-2. The early effect of these preventive measures on essential healthcare service delivery is unknown. In this study, we looked at the number of essential healthcare visits over 8 weeks, 4 weeks before and 4 weeks after the implementation of preventive measures. During the implementation of these measures, patient flow decreased in all elements of essential healthcare service. The decline was dramatic for family planning (98%), emergency surgery (77%), and follow-up of chronic surgical conditions (70%). An understanding of the reasons behind the decrease in patient flow is urgently needed to design ways of sustaining essential care.
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http://dx.doi.org/10.4269/ajtmh.20-0464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470545PMC
September 2020

Does mass drug administration for community-based scabies control works? The experience in Ethiopia.

J Infect Dev Ctries 2020 06 29;14(6.1):78S-85S. Epub 2020 Jun 29.

Department of dermatology, Amsterdam Institute for Infection and Immunity (AI and II), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

Introduction: After a scabies outbreak in Amhara Region, Ethiopia in 2015/2016, the Regional Health Bureau performed an extensive Mass Drug Administration (MDA). In May 2017, we collected data to assess the impact of the treatment on the scabies control.

Methodology: We retrieved baseline data from the 2015/16 burden assessment: campaign organization and administration information. We did a community based cross-sectional study using a structured questionnaire on disease and treatment history plus the presence or absence of active scabies in three Zones. We selected households using stratified random sampling deployed 7581 questionnaires and performed key informant interviews.

Results: 46.3% had a previous scabies diagnosis in the last 2 years of which 86.1% received treatment, and the cure rate was 90.6%. Fifteen months after intervention the scabies prevalence was 21.0 % (67.3% new cases and 32.7% recurrences). The highest burden of new cases (93.1%) was found in the North Gondar zone. The likelihood of treatment failure was higher for treatments offered in clinics (12.2%) as opposed to via the campaign (7.9%). Failure to follow the guidelines, shortage of medicine and lack of leadership prioritization were identified as reasons for resurgence of the disease.

Conclusions: We demonstrated that community engagement is essential in the success of scabies MDA, alongside strong political commitment, and guideline adherence. Effectiveness and sustainability of the MDA was compromised by the failing of proper contact treatment, surveillance and case management.
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http://dx.doi.org/10.3855/jidc.11892DOI Listing
June 2020

Clinical features and treatment outcomes of visceral leishmaniasis patients admitted to three centers in Oromia, Ethiopia.

J Infect Dev Ctries 2020 06 29;14(6.1):42S-47S. Epub 2020 Jun 29.

KalaCORE Ethiopia, Addis Ababa, Ethiopia.

Introduction: In three health care facilities in the Oromia region, the aim of this study is to report on 1) the number of VL cases registered over time (2013-2018) and 2) the clinical profile, type of treatment used and response to treatment.

Methodology: A retrospective cohort study was conducted among all VL cases admitted with a diagnosis of VL.

Results: A total of 434 VL cases were registered at the three health facilities, but patient files were available for only 188. Most (51.6%) were children and only three presented with VL relapse. 78 (41.5%) of the 188 patients presented within one month of symptom onset. Concurrent severe acute malnutrition (27.1%), tuberculosis (6.4%) and malaria (6.4%) were common. There were only two cases with HIV coinfection. Fourty-three percent were treated with antimonials, 34% with antimonials combined with paromomycin and 23% with AmBisome. Amongst the 188 patients with patient files there were no deaths and one treatment failure. Six months outcome data were however missing for all. Aggregated data from the 434 VL cases reported three deaths, two treatment failures and one relapse.

Conclusions: Children were most commonly affected, suggesting long-term endemicity. While short-term outcomes are encouraging, long-term follow-up data are required.
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http://dx.doi.org/10.3855/jidc.11731DOI Listing
June 2020

Is vitiligo associated with wearing plastic shoes in a podoconiosis endemic region of Ethiopia?

J Infect Dev Ctries 2020 06 29;14(6.1):22S-27S. Epub 2020 Jun 29.

UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland.

Introduction: Endemic non-filarial elephantiasis also known as podoconiosis often affects bare footed farmers and is endemic in Ethiopia. The disease is prevented by wearing shoes. We recently observed several patients presenting to a dermatology clinic with skin depigmentation after wearing plastic shoes ("shoe-contact vitiligo") which may deter shoe-wearing. We report on their sociodemographic and clinical characteristics.

Methodology: This is a retrospective study of 17 months at tertiary level Hospital in Ethiopia. Patient data was retrieved from medical record department. We compared sociodemographic and clinical characteristics of patients presenting with idiopathic and shoe-contact vitiligo. Data was presented descriptively.

Results: Of 460 vitiligo cases, 190 (41%) were shoe-contact vitiligo and the rest, idiopathic. The former was more common in females (Odds Ratio, OR = 2.5, P < 0.001) and those in rural areas (OR = 4.8, P < 0.001). Fifty-five percent with shoe-contact vitiligo had itching and/or burning sensation, compared to just 2% with idiopathic vitiligo (P < 0.001) and some had ulcerations (8%). Idiopathic vitiligo had no such findings. Skin discoloration occurred within three weeks (on average) after wearing plastic shoes, 91% of lesions were symmetrical and involved areas of the feet covered with plastic shoes. Symmetric lesions were observed in only 11% of idiopathic vitiligo (OR = 81, P < 0.001).

Conclusions: Shoe-contact vitiligo was significantly associated with wearing cheap plastic shoes. The exact chemical culprit(s) needs to be identified. This will allow introducing quality control regulations and rigorous monitoring of shoe production sites.
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http://dx.doi.org/10.3855/jidc.11705DOI Listing
June 2020

Looking for NTDs in the skin; an entry door for offering patient centered holistic care.

J Infect Dev Ctries 2020 06 29;14(6.1):16S-21S. Epub 2020 Jun 29.

Institute of Tropical Medicine, Antwerp, Belgium.

Introduction: The majority of neglected tropical diseases (NTDs) have established primary skin manifestations or associated clinical feature. Skin NTDs often result in physical impairment and disfigurement, which can lead to disability. Skin diseases have been proposed as an entry point for integrated NTDs control. However, the magnitude and overlap of skin NTDs is poorly understood.

Methodology: An institution-based cross-sectional study was done using medical records of dermatology patients between July 2017 and June 2018 in a dermatology service in Northeast Ethiopia. A total of 661 patient records were selected using simple random sampling.

Results: A total of 656 complete records were included in analysis. Skin NTDs constituted 17.2% (n = 113) of the overall of skin diseases. Of skin NTDS, cutaneous leishmaniasis (n = 40; 35.4%), leprosy (n = 38; 33.6%), and scabies (n = 31; 27.4%) were the most common. Additionally, there were four cases of mycetoma. Of the non NTDs, poverty-related infections such as superficial fungal (n = 118; 21.1%) and bacterial (n = 33; 5.2%) infections were also frequent. Tinea capitis was the most common superficial fungal infections. Impetigo and cellulitis were the predominant bacterial infections.

Conclusions: Skin NTDsand other poverty related skin infections were common at the dermatology service. Dermatological services could act as a good entry point for integrated management of skin NTDs. Future studies should assess how different preventive strategies like contact tracing, early diagnosis and mass drug administration can be integrated.
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http://dx.doi.org/10.3855/jidc.11707DOI Listing
June 2020

Delayed diagnosis and ongoing transmission of leprosy in the post-elimination era in Boru Meda hospital, Ethiopia.

J Infect Dev Ctries 2020 06 29;14(6.1):10S-15S. Epub 2020 Jun 29.

Institute of Tropical Medicine, Antwerp, Belgium.

Introduction: Following the recommendation of the Global Leprosy Strategy, Ethiopia targeted to reduce the incidence of new leprosy cases, and the proportion with severe disability (grade 2) from 13.6% in 2016 to < 1% in 2020. This study assessed the clinical profile of new leprosy cases and the sequelae of previously treated ones 20 years after leprosy was eliminated as a public health problem in the country.

Methodology: Hospital based cross sectional study was conducted  by reviewing the medical records of all leprosy patients seen at the dermatology clinic of Boru Meda Hospital from August to December 2018.The  data were captured using a standard data collection form.

Results: Over the study period, 57 (27.4%) new cases and 151 (72.6%) previously treated cases were seen.The median age was 44 years (interquartile range 32-57). Among the newly diagnosed cases, two were under the age of 15 years , 51 (89.5%) were multibacillary and 34 (59.6%) had grade 2 disability. This included visual impairment in 10 (17.5%) and neurological complications in 44 (77.2%). Of the 151 previously treated cases, 104 (68.9%) presented with disabilities, including 97 (64.2%) with grade 2. Amongst previously treated cases, 130 (86.1%) had neurological complications. In addition, 53 (35.1%) had vision impairment.

Conclusions: This study showed evidence of ongoing leprosy transmission and delayed diagnosis in the country. This calls for operational research to determine the underlying reasons and provide ways forward. At the same time, the high burden of disabilities in previously treated cases should be addressed.
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http://dx.doi.org/10.3855/jidc.11706DOI Listing
June 2020
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