Natural history of a visceral leishmaniasis outbreak in highland Ethiopia

In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemken, Ethiopia, a highland region where only few cases had been reported before. We analyzed records of VL patients treated from May 25, 2005 to December 13, 2007 by the only VL treatment center in the area, maintained by Médecins Sans Frontières-Ethiopia, Operational Center Barcelona-Athens. The median age was 18 years; 77.6% were male. The overall case fatality rate was 4%, but adults 45 years or older were five times as likely to die as 5-29 year olds. Other factors associated with increased mortality included HIV infection, edema, severe malnutrition, pneumonia, tuberculosis, and vomiting. The VL epidemic expanded rapidly over a several-year period, culminating in an epidemic peak in the last third of 2005, spread over two districts, and transformed into a sustained endemic situation by 2007

Factors associated with prelacteal feeding practices in Debre Berhan district, North Shoa, Central Ethiopia: a cross-sectional, community-based study

Abstract Background Prelacteal feeding is one of the major harmful newborn feeding practices and is top on the list of global public health concerns. The practice deprives newborns of valuable nutrients and protection of colostrum and exposes them to preventable morbidity and mortality. Studying the prevalence and factors influencing the prelacteal feeding practice of mothers will help program managers and implementers to properly address broad major public health problems. Therefore, this study aims to investigate the prevalence of prelacteal feeding practices and its associated factors among mother-infant dyads in the Debre Berhan district of North Shoa administrative zone, central Ethiopia. Methods A community-based cross-sectional study design was conducted from January through to April 2014 among 634 mother-infant dyads. The data were entered into EPI Info version 3.5.1. (CDC, Atlanta, Georgia). All statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) research IBM version 20.0. The prevalence of prelacteal feeding was determined using the ‘recall since birth’ method. Multi-variable logistic regression analysis was employed to control confounders in determining the association between prelacteal feeding practices and selected independent variables. Adjusted Odds Ratio (AOR), with 95% Confidence Interval (CI) and P < 0.05 was used to claim statistical significance. Results The prevalence of prelacteal feeding practice was 14.2% (95% CI: 11.00–17.00%). Slightly greater than half, 48 (53.3%) of prelacteal fed newborns were given butter. Home delivery was a major risk factor for practicing prelacteal feeding. Mothers who delivered their indexed infant at home practiced prelacteal feeding over four folds more than mothers who delivered in a health institution (Adjusted Odds Ratio (AOR) 4.70; 95% CI: 2.56–8.60, p-value = 0.001). Mothers who did not initiate breastfeeding within an hour were six times more likely to practice prelacteal feeding (AOR 5.58; 3.21–9.46, p-value = 0.001). Similarly, with regards to the occupation of mothers, farmers practiced prelacteal feedings (AOR 4.33; 95% CI: 1.73–10.81, p-value = 0.002) up to four folds more than their counterpart housewives. Mothers who can read and write are 54% less likely to practice prelacteal feeding than their counterpart, illiterate mothers, with (AOR 0.46; 95% CI: 0.22–0.98, p-value = 0.044). Conclusions In the Debre Berhan town of North Shoa administrative zone, central Ethiopia, almost one-sixth of mothers practiced prelacteal feeding. Therefore, improving access to information about appropriate newborn feeding practices, encouraging mothers to deliver their babies in health institutions and inspiring them to initiate breastfeeding within an hour of birth is recommended

Polymorphisms in Toll-like receptor 4 ( TLR4 ) are associated with protection against leprosy

Accumulating evidence suggests that polymorphisms in Toll-like receptors (TLRs) influence the pathogenesis of mycobacterial infections, including leprosy, a disease whose manifestations depend on host immune responses. Polymorphisms in TLR2 are associated with an increased risk of reversal reaction, but not susceptibility to leprosy itself. We examined whether polymorphisms in TLR4 are associated with susceptibility to leprosy in a cohort of 441 Ethiopian leprosy patients and 197 healthy controls. We found that two single nucleotide polymorphisms (SNPs) in TLR4 (896G>A [D299G] and 1196C>T [T399I]) were associated with a protective effect against the disease. The 896GG, GA and AA genotypes were found in 91.7, 7.8 and 0.5% of leprosy cases versus 79.9, 19.1 and 1.0% of controls, respectively (odds ratio [OR] = 0.34, 95% confidence interval [CI] 0.20-0.57, P < 0.001, additive model). Similarly, the 1196CC, CT and TT genotypes were found in 98.1, 1.9 and 0% of leprosy cases versus 91.8, 7.7 and 0.5% of controls, respectively (OR = 0.16, 95% CI 0.06--.40, P < 0.001, dominant model). We found that Mycobacterium leprae stimulation of monocytes partially inhibited their subsequent response to lipopolysaccharide (LPS) stimulation. Our data suggest that TLR4 polymorphisms are associated with susceptibility to leprosy and that this effect may be mediated at the cellular level by the modulation of TLR4 signalling by M. lepra

Adherence of healthcare providers to malaria case management guidelines of the formal private sector in north-western Ethiopia: an implication for malaria control and elimination

Abstract Background Malaria is an infectious disease which has been globally targeted for elimination in at least 35 of 90 endemic countries by 2030. Most successful malaria elimination country programmes have engaged the private health sector in an effort to identify, document, investigate, provide effective treatment, and follow-up cases. However, there has been limited rigorous research showing evidence of adherence among healthcare providers of the formal private health sector to national malaria diagnosis and treatment guidelines in Ethiopia, starting from malaria control to elimination phases. The aims of this study were to investigate and explain the level of adherence to malaria diagnosis and treatment guidelines among healthcare providers working in formal private health facilities in north-western Ethiopia. Methods An explanatory sequential mixed method design was conducted in the West Gojjam Zone of Ethiopia. Quantitative data were extracted from 1650 medical records of adult uncomplicated malaria outpatients served in 11 private-for-profit health facilities. In addition, using a qualitative approach, 33 in-depth interviews (IDIs) with healthcare providers were conducted. All interviews were audio-recorded, transcribed verbatim, and analysed using eight steps. Results Of 1650 suspected malaria cases in adult outpatients, 80.6% (1330/1650) were screen tested using microscopy and the remainder 19.4% (320/1650) were tested using multispecies rapid diagnosis tests (RDTs). Hence, the results revealed that private healthcare providers universally adhered to diagnosis guidelines. In addition, after following-up and excluding other causes of fever, 4.1% (56/1376) patients were clinically diagnosed with uncomplicated malaria. Despite this, the proportion of private healthcare provider adherence with confirmed malaria case treatment guidelines was 20.9% (69/330). In addition, 1320 (95.9%) of adult outpatients with negative laboratory results were not treated. Some of the identified determinant factors for sub-optimal adherence of healthcare providers to malaria guidelines were interruptions in supply and lack of availability of recommended anti-malarial drugs, lack of availability of quality assured laboratory supplies, and poor knowledge of the recommendations of the national standards. Conclusions Private healthcare providers adhered to universal parasitological diagnosis, providing comprehensive counseling, and linking patients with community health workers. In addition, almost all laboratory negative patients were not treated with anti-malarial drugs. However, only one-fifth of confirmed patients were treated in line with national guideline recommendations. Malaria control and elimination efforts across Ethiopia could be improved through establishing a collaborative function of a win-win public private mix partnership model. In addition, including the data of the private health sector in the health information system could show real malaria burden and use the information to improve the adherence to malaria diagnosis, treatment, and reporting standards within the targeted era of elimination. Therefore, building the capacity of private healthcare providers and ensuring the availability of all nationally recommended drugs and supplies in private health sector facilities is recommended to improve the quality of services

Rabies in Endangered Ethiopian Wolves

With rabies emerging as a particular threat to wild canids, we report on a rabies outbreak in a subpopulation of endangered Ethiopian wolves in the Bale Mountains, Ethiopia, in 2003 and 2004. Parenteral vaccination of wolves was used to manage the outbreak

Diagnostics to Support Elimination of Lymphatic Filariasis-Development of Two Target Product Profiles

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: Product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools

CXCR7 influences leukocyte entry into the CNS parenchyma by controlling abluminal CXCL12 abundance during autoimmunity

During CNS autoimmunity, brain endothelial cell CXCR7 internalizes CXCL12 from the perivascular space, thereby permitting leukocyte migration into the CNS parenchyma

Bovine Tuberculosis at the Wildlife-Livestock-Human Interface in Hamer Woreda, South Omo, Southern Ethiopia

Bovine tuberculosis (BTB) is endemic in cattle in the Ethiopian Highlands but no studies have been done so far in pastoralists in South Omo. This study assessed the prevalence of bovine tuberculosis (BTB) at an intensive interface of livestock, wildlife and pastoralists in Hamer Woreda (South Omo), Ethiopia. A cross-sectional survey including a comparative intradermal skin testing (CIDT) was conducted in 499 zebu cattle and 186 goats in 12 settlements. Sputum samples from 26 symptomatic livestock owners were cultured for TB. Fifty-one wildlife samples from 13 different species were also collected in the same area and tested with serological (lateral flow assay) and bacteriological (culture of lymph nodes) techniques. Individual BTB prevalence in cattle was 0.8% (CI: 0.3%–2%) with the >4 mm cut-off and 3.4% (CI: 2.1%–5.4%) with the >2 mm cut-off. Herd prevalence was 33.3% and 83% when using the >4 and the >2 mm cut-off respectively. There was no correlation between age, sex, body condition and positive reactors upon univariate analysis. None of the goats were reactors for BTB. Acid fast bacilli (AFB) were detected in 50% of the wildlife cultures, 79.2% of which were identified as Mycobacterium terrae complex. No M. bovis was detected. Twenty-seven percent of tested wildlife were sero-positive. Four sputum cultures (15.4%) yielded AFB positive colonies among which one was M. tuberculosis and 3 non-tuberculous mycobacteria (NTM). The prevalence of M. avium-complex (MAC) was 4.2% in wildlife, 2.5% in cattle and 0.5% in goats. In conclusion, individual BTB prevalence was low, but herd prevalence high in cattle and BTB was not detected in goats, wildlife and humans despite an intensive contact interface. On the contrary, NTMs were highly prevalent and some Mycobacterium spp were more prevalent in specific species. The role of NTMs in livestock and co-infection with BTB need further research

The Effects of Anthrax Lethal Toxin on Host Barrier Function

The pathological actions of anthrax toxin require the activities of its edema factor (EF) and lethal factor (LF) enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA). LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs), but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT) leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects