Public perceptions of genomic studies and hereditary diseases in Aari community, South Omo Zone, Ethiopia.

BACKGROUND: Genetic and genomic research is revolutionizing precision medicine; however, addressing ethical and cultural aspects is crucial to ensure ethical conduct and respect for community values and beliefs. This study explored the beliefs, perceptions and concerns of the Aari community in South Ethiopia regarding genetic concepts, hereditary diseases and ethical research practices related to sample collection, storage and sharing. METHODS: In-depth interviews and focus group discussions were conducted with community elders, health officials, tuberculosis patients and apparently healthy individuals. Data were thematically analysed using MAXQDA software. RESULTS: Participants identified diseases such as podoconiosis, leprosy, goitre and epilepsy as hereditary and perceived some as 'curses' due to generational impact and social stigma. Disease susceptibility was attributed to divine intervention or factors such as malnutrition and sanitation. Although hereditary diseases were considered unavoidable, in some cases environmental factors were acknowledged. Participants shared personal examples to demonstrate inheritance concepts. Blood held cultural significance, and concerns about its potential misuse resulted in scepticism towards giving samples. CONCLUSIONS: This study emphasizes the significance of comprehending local beliefs and perceptions and stresses the need to establish effective communication, build trust and address underlying causes of hesitancy to improve recruitment and ensure ethical conduct.

High rate of non-vaccine targeted high-risk HPV genotypes circulate among women in Eastern Ethiopia.

The World Health Organization [WHO] recommends a genotype-specific human papillomavirus [HPV] vaccination as a primary prevention strategy to control the burden of cervical cancer globally. In Ethiopia, where the non-vaccine-targeted HPV genotypes have not been adequately studied, a vaccination initiative was launched in 2018 targeting HPV-6,-11, -16, and -18 for girls aged 14-18 years. The co-existence of both vaccine-targeted and non-targeted genotypes is a serious concern, as it can accelerate cancer progression. Therefore, this study was conducted to determine the prevalence of non-vaccine-targeted HPV genotypes and assess the level of multiple infections with other genotypes in eastern Ethiopia. A health facility-based cross-sectional study including 110 women with positive HPV DNA results was conducted from April to August 2021. A structured questionnaire to collect demographic and clinical data was used. Cervical swabs were collected using L-shaped FLOQSwabs. Women's cytological profile was determined based on Pap smear test results. An automated nucleic acid extraction system using STARMag 96 ProPrep Universal Extraction Kit was utilized following the manufacturer's protocol. An amplification assay in real-time was employed to amplify and identify the HPV Late 1 [L1] gene, which is utilized for genotyping purposes. Following this, the collected data was entered into Epi data version 3.1 software, and the analysis was performed using STATA version 14. A total of 110 women [age range 30-60 years, mean age = 36.5 years and SD ± 6.9] had positive HPV DNA results and were included in the study. Among these, 108 women had valid co-testing [Pap test and HPV DNA test] results for further analysis, and the results of the remaining 2 women were rejected. Overall, the prevalence of non-vaccine-targeted HPV was 56 (51.8%, 95%CI [0.42, 0.61]), of which 28 women (25.4%, 95%CI [0.18, 0.34]) had a single non-vaccine HPV genotype infection. The remaining 29 women (26.4%, 95% CI: 0.190-0.355) experienced multiple infections. The non-vaccine-targeted genotypes of HPV-35 accounted for 11 cases (10%, 95%CI [0.06, 0.17]), HPV-68 was detected in 9 women (8.2%, 95%CI [0.04, 0.15]), HPV-56 and HPV-66 were both found in 8 cases each (7.3%, 95%CI [0.04, 0.14]) of the total. In addition, out of these 108 women, 93 (86.1%, 95%CI [0.78, 0.91]) had low-grade squamous intraepithelial lesions, 13 (12%, 95%CI [0.07, 0.20]) no intraepithelial lesion or malignancy, and two (1.9%, 95%CI [0.01, 0.07]) high-grade squamous intraepithelial lesions. Furthermore, there was no statistical difference [p = 0.755] between vaccine-targeted and non-vaccine-targeted genotypes as the primary cause of cervical lesions. In conclusion, the findings of the present study highlight the existence of a notable prevalence of multiple infections caused by non-vaccine-targeted HPV genotypes. Therefore, it is recommended that both the Federal and regional health bureaus to evaluate the range of hr HPV genotypes protected by the current HPV vaccine and explore the option of transitioning from the quadrivalent HPV vaccine to a novavalent vaccine that includes seven high-risk HPV genotypes.

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.

Mycobacterium tuberculosis Sub-Lineage 4.2.2/SIT149 as Dominant Drug-Resistant Clade in Northwest Ethiopia 2020-2022: In-silico Whole-Genome Sequence Analysis.

Introduction: Drug resistance (DR) in Mycobacterium tuberculosis complex (MTBC) is mainly associated with certain lineages and varies across regions and countries. The Beijing genotype is the leading resistant lineage in Asia and western countries. M. tuberculosis (Mtb) (sub) lineages responsible for most drug resistance in Ethiopia are not well described. Hence, this study aimed to identify the leading drug resistance sub-lineages and characterize first-line anti-tuberculosis drug resistance-associated single nucleotide polymorphisms (SNPs). Methods: A facility-based cross-sectional study was conducted in 2020-2022 among new and presumptive multidrug resistant-TB (MDR-TB) cases in Northwest Ethiopia. Whole-genome sequencing (WGS) was performed on 161 isolates using Illumina NovaSeq 6000 technology. The SNP mutations associated with drug resistance were identified using MtbSeq and TB profiler Bioinformatics softwares. Results: Of the 146 Mtb isolates that were successfully genotyped, 20 (13.7%) harbored one or more resistance-associated SNPs. L4.2.2.ETH was the leading drug-resistant sub-lineage, accounting for 10/20 (50%) of the resistant Mtb. MDR-TB isolates showed extensive mutations against first-line anti-TB drugs. Ser450Leu/(tcg/tTg) for Rifampicin (RIF), Ser315Thr/(agc/aCc) for Isoniazid (INH), Met306Ile/(atg/atA(C)) for Ethambutol (EMB), and Gly69Asp for Streptomycin (STR) were the leading resistance associated mutations which accounted for 56.5%, 89.5%, 47%, and 29.4%, respectively. The presence of both clustered and non-clustered drug resistance (DR) isolates indicated that the epidemics is driven by both new DR development and acquired resistance. Conclusion: The high prevalence of drug-resistant TB due to geographically restricted sub-lineages (L4.2.2.ETH) indicates the ongoing local micro epidemics. The Mtb drug resistance surveillance system must be improved. Further evolutionary analysis of L4.2.2.ETH strain is highly desirable to understand evolutionary forces that leads L4.2.2.ETH in to high level DR and transmissible sub-lineage.

A global research agenda on public health and social measures during emergencies.

The importance of strong coordination for research on public health and social measures was highlighted at the Seventy-fourth World Health Assembly in 2021. This article describes efforts undertaken by the World Health Organization (WHO) to develop a global research agenda on the use of public health and social measures during health emergencies. This work includes a multistep process that started with a global technical consultation convened by WHO in September 2021. The consultation included experts from around the world and from a wide range of disciplines, such as public health, education, tourism, finance and social sciences, and aimed to identify research and implementation approaches based on lessons learnt during the coronavirus disease 2019 pandemic. To prepare for future epidemics and pandemics, it is essential to adopt a more robust, comparable and systematic research approach to public health and social measures. Such comprehensive approach will better inform agile, balanced and context-specific implementation decisions during future emergencies. This article describes the methods used to develop global research priorities for public health and social measures and the next steps needed.

La soixante-quatorzième Assemblée mondiale de la Santé en 2021 a souligné l'importance d'une coordination solide pour la recherche sur la santé publique et les mesures sociales. Le présent article décrit les efforts entrepris par l'Organisation mondiale de la santé (OMS) pour élaborer un programme de recherche mondial sur l'utilisation des mesures de santé publique et des mesures sociales lors de situations d'urgence sanitaire. Ce travail comprend un processus en plusieurs étapes qui a commencé par une consultation technique mondiale organisée par l'OMS en septembre 2021. La consultation a réuni des experts du monde entier issus d'un large éventail de disciplines telles que la santé publique, l'éducation, le tourisme, la finance et les sciences sociales. Elle visait à identifier des approches de recherche et de mise en œuvre fondées sur les enseignements tirés de la pandémie de maladie à coronavirus de 2019. Pour se préparer aux futures épidémies et pandémies, il est essentiel d'adopter une approche de recherche plus solide, comparable et systématique en matière de santé publique et de mesures sociales. Cette approche globale permettra de mieux éclairer les décisions de mise en œuvre agiles, équilibrées et adaptées au contexte lors des futures situations d'urgence. Le présent article décrit les méthodes appliquées pour définir les priorités mondiales de recherche en matière de santé publique et de mesures sociales, ainsi que les prochaines étapes à franchir.

En la 74.ª Asamblea Mundial de la Salud, celebrada en 2021, se destacó la importancia de una sólida coordinación en la investigación sobre salud pública y medidas sociales. Este artículo describe los esfuerzos que ha emprendido la Organización Mundial de la Salud (OMS) para desarrollar un programa mundial de investigación sobre el uso de medidas sociales y de salud pública durante las emergencias sanitarias. Este trabajo incluye un proceso de varios pasos que comenzó con una consulta técnica mundial que convocó la OMS en septiembre de 2021. La consulta incluyó a expertos de todo el mundo y de una gran variedad de disciplinas, como la salud pública, la educación, el turismo, las finanzas y las ciencias sociales, y tuvo como objetivo identificar enfoques de investigación y aplicación basados en las lecciones aprendidas durante la pandemia de la enfermedad por coronavirus de 2019. Para prepararse ante futuras epidemias y pandemias, es esencial adoptar un enfoque de investigación más sólido, comparable y sistemático en materia de salud pública y medidas sociales. Este enfoque integral informará mejor las decisiones de aplicación ágiles, equilibradas y adaptadas al contexto durante futuras emergencias. En este artículo se describen los métodos utilizados para elaborar las prioridades mundiales de investigación sobre salud pública y medidas sociales, así como los próximos pasos necesarios.

Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia.

Ethiopia has the greatest burden of Plasmodium vivax in Africa, but little is known about the epidemiological landscape of parasites across the country. We analysed the genomic diversity of 137 P. vivax isolates collected nine Ethiopian districts from 2012 to 2016. Signatures of selection were detected by cross-country comparisons with isolates from Thailand (n = 104) and Indonesia (n = 111), representing regions with low and high chloroquine resistance respectively. 26% (35/137) of Ethiopian infections were polyclonal, and 48.5% (17/35) of these comprised highly related clones (within-host identity-by-descent > 25%), indicating frequent co-transmission and superinfection. Parasite gene flow between districts could not be explained entirely by geographic distance, with economic and cultural factors hypothesised to have an impact on connectivity. Amplification of the duffy binding protein gene (pvdbp1) was prevalent across all districts (16-75%). Cross-population haplotype homozygosity revealed positive selection in a region proximal to the putative chloroquine resistance transporter gene (pvcrt-o). An S25P variant in amino acid transporter 1 (pvaat1), whose homologue has recently been implicated in P. falciparum chloroquine resistance evolution, was prevalent in Ethiopia (96%) but not Thailand or Indonesia (35-53%). The genomic architecture in Ethiopia highlights circulating variants of potential public health concern in an endemic setting with evidence of stable transmission.

Loss to Follow-up and Death Among Individuals With Newly Diagnosed Human Immunodeficiency Virus Receiving Dolutegravir-Based First-Line Antiretroviral Treatment in Eastern Ethiopia: Implications for 95% United Nations Targets.

Background: Loss to follow-up (LTFU) and death are unfavorable outcomes of human immunodeficiency virus (HIV) treatment. This study aimed to identify the predictors of LTFU and death among individuals with newly diagnosed HIV receiving dolutegravir (DTG)-based first-line antiretroviral treatment (ART) in eastern Ethiopia. Methods: A multisite prospective cohort study was carried out between October 2020 and July 2022. New case patients who started ART were enrolled consecutively and then followed up for the next 6 months. A structured questionnaire and checklists were used to collect data. HIV viral load was determined using the Abbott RealTime HIV-1 assay. Bivariable and multivariable logistic regression models were used to identify baseline factors associated with the outcomes. Results: A total of 235 people with newly diagnosed HIV were enrolled; 16.6% (95% confidence interval, 12.3%-21.9%) were lost to follow-up, and 5.9% (3.5%-9.8%) died within 6 months of follow-up. Baseline World Health Organization clinical stage I (adjusted odds ratio, 3.93 [95% confidence interval, 1.34-11.57]), low viral load (3.67 [1.09-12.36]), and body weight (1.04 [1.01-1.07]) were predictors of LTFU, whereas nonfunctional status (10.02 [1.9-51.3]) was the only factor associated with death. Conclusions: LTFU and death rates among patients with DTG were relatively high, accounting for roughly a quarter of the attrition of people with newly diagnosed HIV from ART care and services. Thus, targeted interventions are required to reduce LTFU and death among individuals with HIV on ART. Further investigation is necessary to evaluate the long-term effects of DTG-based regimens on LTFU and its impact on HIV mortality rates, and qualitative research, specifically tracing LTFU, is recommended.

Perceptions and acceptability of co-administered albendazole, ivermectin and azithromycin mass drug administration, among the health workforce and recipient communities in Ethiopia.

Several neglected tropical diseases (NTDs) employ mass drug administration (MDA) as part of their control or elimination strategies. This has historically required multiple distinct campaigns, each targeting one or more NTDs, representing a strain on both the recipient communities and the local health workforce implementing the distribution. We explored perceptions and attitudes surrounding combined MDA among these two groups of stakeholders. Our qualitative study was nested within a cluster randomized non-inferiority safety trial of combined ivermectin, albendazole and azithromycin MDA. Using semi-structured question guides, we conducted 16 key informant interviews with selected individuals involved in implementing MDA within the participating district. To better understand the perceptions of recipient communities, we also conducted four focus group discussions with key community groups. Individuals were selected from both the trial arm (integrated MDA) and the control arm (standard MDA) to provide a means of comparison and discussion. All interviews and focus group discussions were led by fluent Afaan oromo speakers. Interviewers transcribed and later translated all discussions into English. The study team synthesized and analyzed the results via a coding framework and software. Most respondents appreciated the time and effort saved via the co-administered MDA strategy but there were some misgivings amongst community beneficiaries surrounding pill burden. Both the implementing health work force members and beneficiaries reported refusals stemming from lack of understanding around the need for the new drug regimen as well as some mistrust of government officials among the youth. The house-to-house distribution method, adopted as a COVID-19 prevention strategy, was by far preferred by all beneficiaries over central-point MDA, and may have led to greater acceptability of co-administration. Our data demonstrate that a co-administration strategy for NTDs is acceptable to both communities and health staff.

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.

Assessment of treatment outcomes of visceral leishmaniasis (VL) treated cases and impact of COVID-19 on VL management and control services in Bangladesh.

BACKGROUND: COVID-19 has largely impacted the management of Visceral leishmaniasis (VL), like several other Neglected Tropical Diseases. The impact was particularly evident in Lower and Middle-Income countries where the already inadequate healthcare resources were diverted to managing the COVID-19 pandemic. Bangladesh achieved the elimination target for VL in 2016. To sustain this success, early diagnosis and treatment, effective vector control, and periodic surveillance are paramount. However, the specific control measures for VL in Bangladesh that were hampered during COVID-19 and their extent are unknown. METHODS: This study aimed at identifying the gaps and challenges in the follow-up of treated VL patients by interviewing both the treated VL cases and their health service providers. We followed VL cases treated between 2019 and 2020 in five VL endemic subdistricts (upazilas) both retrospectively and prospectively to monitor clinical improvement, relapse, or other consequences. Moreover, interviews were conducted with the health service providers to assess the impact of COVID-19 on VL case detection, treatment, reporting, vector control operations, and logistic supply chain management. RESULTS: There was no added delay for VL diagnosis; however, VL treatment initiation and reporting time increased almost two-fold due to COVID-19. Indoor Residual Spraying activity was significantly hampered due to a shortage of insecticides. Out of 44 enrolled and treated VL patients, two relapsed (4.5 %), two developed Para Kala-Azar Dermal Leishmaniasis (4.5 %), and three (6.8 %) Post Kala-Azar Dermal Leishmaniasis (PKDL). The health service providers highlighted patients` unwillingness to visit the hospital, financial constraints, and distance from the hospitals as the main reasons for missed follow-up visits (20.5 %). Building good communication in the community, awareness schemes, and incentive-based approaches were suggested as possible solutions to mitigate these problems. CONCLUSION: Long-term follow-up is required for the early detection and management of VL relapse and PKDL cases. Effective vector control measures, capacity development, and identification of new VL hotspots are pivotal in the VL endemic regions to sustain the elimination goal.

Zoonotic tuberculosis in a high bovine tuberculosis burden area of Ethiopia.

Background: Tuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide, caused by species of the Mycobacterium tuberculosis complex (MTBC), with Mycobacterium tuberculosis being the dominant pathogen in humans and Mycobacterium bovis in cattle. Zoonotic transmission of TB (zTB) to humans is frequent particularly where TB prevalence is high in cattle. In this study, we explored the prevalence of zTB in central Ethiopia, an area highly affected by bovine TB (bTB) in cattle. Method: A convenient sample of 385 patients with pulmonary tuberculosis (PTB, N = 287) and tuberculous lymphadenitis (TBLN, N = 98) were included in this cross-sectional study in central Ethiopia. Sputum and fine needle aspirate (FNA) samples were obtained from patients with PTB and TBLN, respectively, and cultures were performed using BACTEC™ MGIT™ 960. All culture positive samples were subjected to quantitative PCR (qPCR) assays, targeting IS1081, RD9 and RD4 genomic regions for detection of MTBC, M. tuberculosis and M. bovis, respectively. Results: Two hundred and fifty-five out of 385 sampled patients were culture positive and all were isolates identified as MTBC by being positive for the IS1081 assay. Among them, 249 (97.6%) samples had also a positive RD9 result (intact RD9 locus) and were consequently classified as M. tuberculosis. The remaining six (2.4%) isolates were RD4 deficient and thereby classified as M. bovis. Five out of these six M. bovis strains originated from PTB patients whereas one was isolated from a TBLN patient. Occupational risk and the widespread consumption of raw animal products were identified as potential sources of M. bovis infection in humans, and the isolation of M. bovis from PTB patients suggests the possibility of human-to-human transmission, particularly in patients with no known contact history with animals. Conclusion: The detected proportion of culture positive cases of 2.4% being M. bovis from this region was higher zTB rate than previously reported for the general population of Ethiopia. Patients with M. bovis infection are more likely to get less efficient TB treatment because M. bovis is inherently resistant to pyrazinamide. MTBC species identification should be performed where M. bovis is common in cattle, especially in patients who have a history of recurrence or treatment failure.

Long-Term Efficacy of Insecticidal Wall Painting for Controlling Visceral Leishmaniasis Vectors in Bangladesh.

The success of the visceral leishmaniasis (VL) elimination program largely depends on cost-effective vector control measures. Our goal was to investigate the longevity of the efficacy of insecticidal wall painting (IWP), a new vector control tool, compared with a routine indoor residual spraying (IRS) program for reducing the VL vector density in Bangladesh. This study is the extension of our recent IWP study for VL vector management in Bangladesh, which was undertaken in seven highly VL endemic villages of the Mymensingh district with a 12-month follow-up. In this 24-months follow-up study, we collected sand flies additionally at 15, 18, 21, and 24 months since the interventions from the IWP and control (where the program did routine IRS) clusters to examine the longevity of the efficacy of IWP on sand fly density reduction and mortality. The difference-in-differences regression models were used to estimate the effect of IWP on sand fly reduction against Program IRS. The IWP showed excellent performance in reducing sand fly density and increasing sand fly mortality compared with Program IRS. The effect of IWP for controlling sand flies was statistically significant for up to at least 24 months. The mean female Phlebotomus argentipes density reduction ranged from -56% to -83%, and the P. argentipes sand fly mortality ranged from 81% to 99.5% during the 24-month follow-up period. Considering the duration of the efficacy of IWP for controlling VL vectors, Bangladesh National Kala-azar Elimination Program may consider IWP as the best alternative to IRS for the subsequent phases of the program.

Epidemiological, serological, and entomological aspects of visceral leishmaniasis (VL) in suspected new VL foci in Bangladesh.

The study aimed to explore epidemiological, serological, and entomological aspects of visceral leishmaniasis (VL) in suspected new VL foci and assess the knowledge, attitude, and practices of the community living in the alleged new VL foci. The study investigated new visceral leishmaniasis (VL) cases reported between 2019 and 2020 in four sub-districts (Dharmapasha, Hakimpur, Islampur and Savar) where we tested 560 members using the rK39 rapid test and conducted vector collections in six neighbouring houses of the index cases to assess sandfly density and distribution, examined sandflies' infection, and determined the spatial relationship with VL infection. Furthermore, we highlighted the importance of early detection, and community awareness in controlling the spread of the disease. The study screened 1078 people from 231 households in the four sub-districts for fever, history of visceral leishmaniasis (VL), and PKDL-like skin lesions. Among sub-districts, positivity rate for rK39 rapid test was highest (3.5 %) in Savar. Sandflies were present across all areas except in Dharmapasha, but all 21 collected female P. argentipes sandflies were negative for Leishmania parasite DNA. We found one person from Islampur with a history of VL, and one from Islampur and another one from Savar had PKDL. After the awareness intervention, more people became familiar with VL infection (91.2 %), and their knowledge concerning sandflies being the vector of the disease and the risk of having VL increased significantly (30.1 %). The study found no active case in the suspected new foci, but some asymptomatic individuals were present. As sandfly vectors exist in these areas, the National Kala-azar Elimination Programme (NKEP) should consider these areas as kala-azar endemic and initiate control activities as per national guidelines.

Phenotypic and genotypic drug susceptibility patterns of Mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Central and Southern Ethiopia.

INTRODUCTION: The persistence of tuberculosis (TB) infection in some patients after treatment has highlighted the importance of drug susceptibility testing (DST). This study aimed to determine the drug susceptibility patterns of Mycobacterium tuberculosis (M. tuberculosis) isolates from pulmonary TB (PTB) patients in Central and Southern Ethiopia. METHODS: A health institution-based cross-sectional study was conducted between July 2021 and April 2022. Sputum samples were collected from newly diagnosed smear microscopy and/or Xpert MTB/RIF-positive PTB patients. The samples were processed and cultivated in Lowenstein-Jensen (LJ) pyruvate and glycerol medium. M. tuberculosis isolates were identified using polymerase chain reaction (PCR) based region of difference 9 (RD9) deletion typing. Phenotypic DST patterns of the isolates were characterized using the BACTEC MGIT™ 960 instrument with SIRE kit. Isoniazid (INH) and Rifampicin (RIF) resistant M. tuberculosis isolates were identified using the GenoType® MTBDRplus assay. RESULTS: Sputum samples were collected from 350 PTB patients, 315 (90%) of which were culture-positive, and phenotypic and genotypic DST were determined for 266 and 261 isolates, respectively. Due to invalid results and missing data, 6% (16/266) of the isolates were excluded, while 94% (250/266) were included in the paired analysis. According to the findings, 14.4% (36/250) of the isolates tested positive for resistance to at least one anti-TB drug. Gene mutations were observed only in the rpoB and katG gene loci, indicating RIF and high-level INH resistance. The GenoType® MTBDRplus assay has a sensitivity of 42% and a specificity of 100% in detecting INH-resistant M. tuberculosis isolates, with a kappa value of 0.56 (95%CI: 0.36-0.76) compared to the BACTEC MGIT™ DST. The overall discordance between the two methods was 5.6% (14/250) for INH alone and 0% for RIF resistance and MDR-TB (resistance to both INH and RIF) detection. CONCLUSION: This study reveals a higher prevalence of phenotypic and genotypic discordant INH-resistant M. tuberculosis isolates in the study area. The use of whole-genome sequencing (WGS) is essential for gaining a comprehensive understanding of these discrepancies within INH-resistant M. tuberculosis strains.

Rapid Bioethical Assessment for Mycobacterium tuberculosis and Host Genetic Study in Amhara Regional State, Ethiopia: Towards a Context-Specific Ethical Approach.

Background: Rapid Ethical Assessment (REA) is a rapid qualitative study anticipated to understand the ethical sphere of the research setting prior to recruiting study subjects. This study assessed the communities' knowledge about tuberculosis (TB) and research, understand the social arrangements advisable for recruiting research participant and appraised the information provision and consent process. Methods: The study was conducted in Amhara region, Ethiopia from 5th-30th January 2021. Google-based survey, face-to-face in-depth interview and focus group discussion were carried out to collect the data from researchers, data collectors, health professionals, TB program officers. A structured questionnaire was administered to assess the knowledge of TB patients and healthy controls about TB, research, gene, (co)evolution and consent process. Results: Over 71% of researchers were not satisfied with the current consent process, and 82.7% of researchers agreed that the best interest of the research participants was not adequately addressed in the current research practices in ANRS. TB patients and healthy controls misunderstood research and its goals. Participants advised the researchers to approach the community with the assistance of health extension workers (HEW) or religious/local leaders. Combined use of verbal and written based information provision at individual participant level is the preferred way for information provision. Conclusions: The adherence of researchers to standard information provision and consent process was very low. Healthy controls and TB patients have low level of knowledge and awareness about research, ethics and genomic research-related common terms. Hence, public education is required to strengthen the research ethics in the region.

Virological Non-Suppression among Newly Diagnosed HIV-Positive Individuals on Dolutegravir-Based Antiretroviral Treatment in Eastern Ethiopia: Follow-Up Study.

There have been limited studies linking baseline factors, including the viral load (VL) test, with virological non-suppression since the introduction of dolutegravir (DTG)-based regimens as first-line antiretroviral treatment (ART) in Ethiopia. This study aimed to identify baseline factors associated with virological non-suppression between October 2020 and July 2022. A follow-up study was conducted in eastern Ethiopia among newly diagnosed people living with HIV (PLHIV). A questionnaire and a checklist were used to collect the data. Five milliliters of venous blood were obtained at baseline and six months to determine the VL. A VL test was performed using the Abbott RealTime HIV-1 assay. To determine predictors of virological non-suppression, bivariate and multivariate logistic regression analyses were used. There were 235 PLHIV enrolled, 70.6% of whom were female, with a mean age of 33.9 years. Of the 161 retained on ART, virological non-suppression was 8.7% at six months. Baseline predictors of virological non-suppression were age ≤ 30 years, a history of substance use, and a VL greater than 4-log10 copies/mL. In this cohort, virological non-suppression was found to be optimal but still lagged slightly behind the third 95%-target. Thus, targeted interventions, the introduction of baseline VL testing to improve treatment outcomes, and fostering the attainment of UNAIDS 95-95-95 targets are recommended. Furthermore, broader research is recommended to explore the reasons for virological non-suppression in the study area.

Corrigendum to "Safety of integrated mass drug administration of azithromycin, albendazole and ivermectin versus standard treatment regimens: a cluster-randomised trial in Ethiopia".

[This corrects the article DOI: 10.1016/j.eclinm.2023.101984.].

Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from pulmonary tuberculosis and tuberculous lymphadenitis patients in Northwest Ethiopia.

Background: Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), is a chronic infectious disease with both pulmonary and extrapulmonary forms. This study set out to investigate and compare the genomic diversity and transmission dynamics of Mycobacterium tuberculosis (Mtb) isolates obtained from tuberculous lymphadenitis (TBLN) and pulmonary TB (PTB) cases in Northwest Ethiopia. Methods: A facility-based cross-sectional study was conducted using two groups of samples collected between February 2021 and June 2022 (Group 1) and between June 2020 and June 2022 (Group 2) in Northwest Ethiopia. Deoxyribonucleic acid (DNA) was extracted from 200 heat-inactivated Mtb isolates. Whole-genome sequencing (WGS) was performed from 161 isolates having ≥1 ng DNA/µl using Illumina NovaSeq 6000 technology. Results: From the total 161 isolates sequenced, 146 Mtb isolates were successfully genotyped into three lineages (L) and 18 sub-lineages. The Euro-American (EA, L4) lineage was the prevailing (n = 100; 68.5%) followed by Central Asian (CAS, L3, n = 43; 25.3%) and then L7 (n = 3; 2.05%). The L4.2.2.ETH sub-lineage accounted for 19.9%, while Haarlem estimated at 13.7%. The phylogenetic tree revealed distinct Mtb clusters between PTB and TBLN isolates even though there was no difference at lineages and sub-lineages levels. The clustering rate (CR) and recent transmission index (RTI) for PTB were 30 and 15%, respectively. Similarly, the CR and RTI for TBLN were 31.1 and 18 %, respectively. Conclusion and recommendations: PTB and TBLN isolates showed no Mtb lineages and sub-lineages difference. However, at the threshold of five allelic distances, Mtb isolates obtained from PTB and TBLN form distinct complexes in the phylogenetic tree, which indicates the presence of Mtb genomic variation among the two clinical forms. The high rate of clustering and RTI among TBLN implied that TBLN was likely the result of recent transmission and/or reactivation from short latency. Hence, the high incidence rate of TBLN in the Amhara region could be the result of Mtb genomic diversity and rapid clinical progression from primary infection and/or short latency. To validate this conclusion, a similar community-based study with a large sample size and better sampling technique is highly desirable. Additionally, analysis of genomic variants other than phylogenetic informative regions could give insightful information. Combined analysis of the host and the pathogen genome (GXG) together with environmental (GxGxE) factors could give comprehensive co-evolutionary information.