Publications

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    ABSTRACT: Although podoconiosis is one of the major causes of tropical lymphoedema and is endemic in Ethiopia its epidemiology and risk factors are poorly understood. Individual-level data for 129,959 individuals from 1,315 communities in 659 woreda (districts) were collected for a nationwide integrated survey of lymphatic filariasis and podoconiosis. Blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests. A clinical algorithm was used to reach a diagnosis of podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Bayesian multilevel models were used to identify individual and environmental risk factors. Overall, 8,110 of 129,959 (6.2%, 95% confidence interval [CI] 6.1–6.4%) surveyed individuals were identified with lymphoedema of the lower limb, of whom 5,253 (4.0%, 95% CI 3.9–4.1%) were confirmed to be podoconiosis cases. In multivariable analysis, being female, older, unmarried, washing the feet less frequently than daily, a
    The American journal of tropical medicine and hygiene 11/2014; · 2.53 Impact Factor
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    ABSTRACT: Background: An important factor influencing the transmission dynamics of vector-borne diseases is the contribution of hosts with different parasitemia (no. of parasites per ml of blood) to the infected vector population. Today, estimation of this contribution is often impractical since it relies exclusively on limited-scale xenodiagnostic or artificial feeding experiments (i.e., measuring the proportion of vectors that become infected after feeding on infected blood/host). Methodology: We developed a novel mechanistic model that facilitates the quantification of the contribution of hosts with different parasitemias to the infection of the vectors from data on the distribution of these parasitemias within the host population. We applied the model to an ample data set of Leishmania donovani carriers, the causative agent of visceral leishmaniasis in Ethiopia. Results: Calculations facilitated by the model quantified the host parasitemias that are mostly responsible for the infection of vector, the sand fly Phlebotomus orientalis. Our findings indicate that a 3.2% of the most infected people were responsible for the infection of between 53% and 79% (mean – 62%) of the infected sand fly vector population. Significance: Our modeling framework can easily be extended to facilitate the calculation of the contribution of other host groups (such as different host species, hosts with different ages) to the infected vector population. Identifying the hosts that contribute most towards infection of the vectors is crucial for understanding the transmission dynamics, and planning targeted intervention policy of visceral leishmaniasis as well as other vector borne infectious diseases (e.g., West Nile Fever).
    PLoS Neglected Tropical Diseases 11/2014; 8(10):e3288. · 4.57 Impact Factor
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    ABSTRACT: After the epidemics of L. donovani complex in 2004/05 in human patients, to investigate the presence of antibodies against L. donovani in domestic animals in Northwest Ethiopia.
    Tropical Medicine & International Health 10/2014; · 2.94 Impact Factor
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    ABSTRACT: Background Visceral leishmaniasis (VL, also called `¿kala-azar¿), is a life threatening neglected tropical infectious disease which mainly affects the poorest of the poor. VL is prevalent in Ethiopia particularly in the northwest of the country. Understanding the risk factors of VL infection helps in its prevention and control. The aim of the present study was to identify the factors associated with VL.MethodsA case¿control study was carried out during the period of January-July 2013 in northwest Ethiopia. Cases and controls were diagnosed using clinical presentation, the rk39 rapid diagnostic test and Direct Agglutination Test (DAT). A total of 283 (84.8% males versus 15.2% females) participants were interviewed. 90 cases and 193 controls were involved, matched by age, sex and geographical location with a ratio of 1:2 (case: controls). Univariate and backward multivariate conditional logistic regression were used to identify risk factors of VL.ResultsElevated odds of VL was associated with goat ownership (OR¿=¿6.4; 95%: confidence interval [Cl]: 1.5-28.4), living in houses with cracked wall (OR¿=¿6.4; 95% Cl: 1.6-25.6), increased family size (OR¿=¿1.3; 95%Cl: 1.0-1.8) and the number of days spent in the farm field (OR¿=¿1.1; 95% Cl: 1.0-1.2). However, daily individual activities around the home and farm fields, mainly sleeping on a bed (OR¿=¿0.2; 95%: Cl 0.03-0.9), sleeping outside the house under a bed net (OR¿=¿0.1; 95% Cl: 0.02-0.36)] and smoking plant parts in the house during the night time (OR¿=¿0.1; 95% Cl: 0.01-0.6) were associated with decreased odds of being VL case.Conclusion Our findings showed that use of bed net and smoke could be helpful for the prevention of VL in the area particularly among individuals who spend most of their time in the farm. VL control effort could be focused on improving housing conditions, such as sealing cracks and crevices inside and outside houses. Further research is warranted to elucidate the role of goats in the transmission of L. donovani, assess the impact of bed nets and the role of the traditional practice of smoking plants.
    Parasites & Vectors 10/2014; 7(1):470. · 3.25 Impact Factor
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    ABSTRACT: The development of rK39-based rapid diagnostic tests (RDTs) has greatly aided the diagnosis of visceral leishmaniasis, especially in the Indian subcontinent and Brazil, by offering high sensitivity and specificity. However, these tests have been less sensitive and less specific in sub-Saharan Africa. To improve upon the performance of rK39 in Africa, we engineered the fusion molecule rK28, which retained some of the rK39 repeats and combined them with repeat sequences from two additional Leishmania genes. This polyprotein was used in the development of several prototype RDTs by different commercial manufacturers with the goal of assessing relative performance in inexpensive formats. Here, we report field studies showing that the rK28 antigen could be readily adapted to a variety of RDT formats to achieve high sensitivity, generally > 90%, and adequate specificity to aid in the diagnosis of human visceral leishmaniasis in East Africa, Asia, and South America.
    The American journal of tropical medicine and hygiene 10/2014; · 2.53 Impact Factor
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    ABSTRACT: In regions where it is endemic, visceral leishmaniasis is an important opportunistic infectious disease in people living with HIV. Typically, clinical presentation of visceral leishmaniasis includes chronic fever, hepatosplenomegaly, and weight loss. In Leishmania infantum endemic regions in Europe, atypical visceral leishmaniasis presentations have been well documented, with almost every possible organ involved. However, such reports are rare in Leishmania donovani endemic regions such as east Africa. In this Personal View, we describe the various atypical disease presentations in patients screened as part of an HIV and visceral leishmaniasis clinical trial in north Ethiopia, where up to 40% of patients with visceral leishmaniasis are co-infected with HIV. Atypical presentations such as these are not covered in clinical guidelines used in these settings. Apart from the lack of diagnostic facilities, this gap contributes to the underdiagnosis of atypical visceral leishmaniasis, with associated morbidity and mortality. Involvement of clinicians experienced with the management of HIV and visceral leishmaniasis co-infection in the development of HIV clinical guidelines in affected regions is warranted.
    The Lancet. Infectious diseases. 10/2014;
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    ABSTRACT: Objective Visceral leishmaniasis (VL) in north-west Ethiopia is causing an overwhelming case load among adult migrant workers that masked the disease burden in children. This study describes the clinical profile and explores comorbidities in paediatric VL patients.MethodsA prospective study at two hospitals in this region (Gondar and Humera) was conducted in a year period, 2011–2012. The clinical manifestations and comorbidities such as malnutrition, intestinal parasitosis and vitamin D deficiency and HIV infection were assessed, and treatment outcomes noted.ResultsA total of 122 children with VL were detected during the study period with median age of 8.5 years (IQR 5–12 years); 23% were under 5 years. Eighty-five (69.7%) cases were male. The clinical manifestations were similar to the adult patients. High rates of malnutrition, intestinal parasitosis (47.5%) and hypovitaminosis D (56.4%) were detected. The proportion of stunting and wasting was 63% and 22.2% in children aged under five years, and 50.5% and 75.9% in 5-year and older children, respectively, using WHO standard growth curves. Only one child had HIV infection. In 95% of the cases, sodium stibogluconate (20 mg/kg/day for 30 days) was used for treatment. The treatment success rate at end of therapy was 98.3%, but the definitive outcome at 6 months could not be determined because of a high loss to follow-up (80.2%).Conclusion While HIV co-infection was rare, malnutrition, intestinal parasitosis and vitamin D deficiency were frequent indicating the need for further research on their role in the pathophysiology. Meanwhile, systematic assessment and management of malnutrition and intestinal parasitosis in VL programmes is recommended.
    Tropical Medicine & International Health 10/2014; · 2.94 Impact Factor
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    PLoS Neglected Tropical Diseases 09/2014; 8(9):e3132. · 4.57 Impact Factor
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    ABSTRACT: Kafta Humera lowlands are endemic for kala-azar (visceral leishmaniasis). These lowlands are characterized by black clay soil which is used for growing sesame, sorghum and cotton for commercial purposes.The aim of this study was to determine seasonal dynamics and habitat preferences of Phlebotomus orientalis, the vector of kala-azar, in extra-domestic habitats of Kafta Humera lowlands.
    Parasites & Vectors 08/2014; 7(1):359. · 3.25 Impact Factor
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    PLoS neglected tropical diseases. 08/2014; 8(8):e3023.
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    ABSTRACT: In the wake of the HIV epidemic, visceral leishmaniasis (VL), a disseminated protozoan infection caused by the Leishmania donovani complex, has been re-emerging, particularly in North Ethiopia where up to 40% of patients with VL are co-infected with HIV. Management of VL in HIV co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. Tackling L. donovani infection before disease onset would thus be a logical approach. A screen-and-treat approach targeting latent or the early stage of infection has successfully been implemented in other HIV-associated opportunistic infections. While conceptually attractive in the context of VL-HIV, the basic understanding and evidence underpinning such an approach is currently lacking. Prospective cohort studies will have to be conducted to quantify the risk of VL in different risk groups and across CD4 cell count levels. This will allow developing clinical prognostic tools, integrating clinical, HIV and Leishmania infection markers. Interventional studies will be needed to evaluate prophylactic or pre-emptive treatment strategies for those at risk, ideally relying on an oral (combination) regimen. Issues like tolerability, emergence of resistance and drug interactions will require due attention. The need for maintenance therapy will have to be assessed. Based on the risk-benefit data, VL risk cut-offs will have to be identified to target treatment to those most likely to benefit. Such a strategy should be complemented with early initiation of antiretroviral treatment and other strategies to prevent HIV and Leishmania infection.
    PLoS neglected tropical diseases. 08/2014; 8(8):e3011.
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    ABSTRACT: We studied breeding sites of Phlebotomus orientalis (Diptera: Psychodidae) the vector of visceral leishmaniasis in northern Ethiopia and Sudan. Although numbers were rather small, 165 sand flies were captured emerging from vertisol cracks. The most productive breeding sites were cracked vertisols, dry river banks and close to trees. No sand flies were caught emerging from sandy clay loam soils in peri-domestic habitats but a few were captured emerging from gaps in a stone wall. Abiotic parameters in vertisols close to trees and in open field from which P. orientalis had emerged, were compared. Soil pH was slightly alkaline and salinity was low. Organic matter contents were similar in both sites. Temperatures and RH remained relatively stable near trees from the end of the rainy season through mid dry season, yet fluctuated markedly at the shallower depth in the open field. During the rainy season, cracks in the soil were sealed resulting in significant lowering of the oxygen concentrations near the tree. Gravimetric water content of soil near trees was lower than open field at shallow depth but similar deeper down. We conclude that ambient conditions suitable for sand fly larvae at shallow depths (45cm) are restricted to areas close to trees. However, deeper in vertisols (90cm) suitable conditions are apparently maintained throughout the dry season even in open fallow fields.
    Acta tropica. 07/2014;
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    ABSTRACT: Protozoan parasites of the genus Leishmania (Kinetoplastida:Trypanosomatidae) cause widespread and devastating human diseases. Visceral leishmaniasis (VL) is endemic in Ethiopia where it has also been responsible for fatal epidemics. It is postulated that genetic exchange in Leishmania has implications for heterosis (hybrid vigour), spread of virulent strains, resistance to chemotherapeutics, and exploitation of different hosts and vectors. Here we analyse 11 natural Ethiopian Leishmania donovani isolates consisting of four putative hybrids, seven parent-like isolates and over 90 derived biological clones. We apply a novel combination of high resolution multilocus microsatellite typing (MLMT, five loci) and multilocus sequence typing (MLST, four loci) that together distinguish parent-like and hybrid L. donovani strains. Results indicate that the four isolates (and their associated biological clones) are genetic hybrids, not the results of mixed infections, each possessing heterozygous markers consistent with inheritance of divergent alleles from genetically distinct Ethiopian L. donovani lineages. The allelic profiles of the putative hybrids may have arisen from a single hybridisation event followed by inbreeding or gene conversion, or alternatively from two or more hybridisation events. Mitochondrial sequencing showed uniparental maxicircle inheritance for all of the hybrids, each possessing a single mitochondrial genotype. Fluorescence activated cell sorting analysis of DNA content demonstrated that all hybrids and their associated clones were diploid. Together the data imply that intra-specific genetic exchange is a recurrent feature of natural L. donovani populations, with substantial implications for the phyloepidemiology of Leishmania.
    International Journal for Parasitology 07/2014; · 3.64 Impact Factor
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    ABSTRACT: BACKGROUND:The World Health Organization (WHO), international donors and partners have emphasized the importance of integrated control of NTDs. Integrated mapping of NTDs is a first step for integrated planning of programmes, proper resource allocation and monitoring progress of control. Integrated mapping has several advantages over disease specific mapping by reducing costs and enabling co-endemic areas to be more precisely identified. We designed and conducted integrated mapping of lymphatic filariasis (LF) and podoconiosis in Ethiopia; here we present the methods, challenges and lessons learnt.METHODS:Integrated mapping of 1315 communities across Ethiopia was accomplished within three months. Within these communities, 129,959 individuals provided blood samples that were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). Wb123 antibody tests were used to further establish exposure to LF in areas where at least one ICT positive individual was detected. A
    Parasites & Vectors 07/2014; 7:397. · 3.25 Impact Factor
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    ABSTRACT: Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.
    PLoS neglected tropical diseases. 06/2014; 8(6):e2869.
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    ABSTRACT: Sand flies belonging to the genus Sergentomyia Franca & Parrot, 1920, are hematophagous insects feeding mostly on reptiles and birds, but some species feed also on mammals including humans. Sergentomyia spp. frequently comprise the vast majority of sand flies trapped along with Phlebotomus spp., the vectors of mammalian leishmaniasis. Within the framework of a project on the ecology and transmission of visceral leishmaniasis in Ethiopia, putative breeding sites of phlebotomine sand flies were studied. Large horizontal sticky traps (LHSTs) covered with sand fly-proof mesh were deployed over cracked vertisol and related habitats for up to 3 nights, and emerging sand flies were collected daily. Emergence traps (ETs) were also adapted to sample other putative breeding sites including tree trunks, termite mounds, rock piles and vertical river banks. Productive breeding sites were identified in the trunks and roots systems of trees, vertisol fields, cracks and burrows in vertisol dry river banks and termite mounds. Emerging flies were also collected form a stone wall and a rock pile situated inside a village. Significantly more Sergentomyia spp. were trapped in vertisols by ETs deployed over root system than in open fields. Similarly, more sand flies emerged from cracks in the vertisol in fallow Sorghum than in fallow sesame fields. Productive breeding sites were characterized by stable micro-climatic conditions. Species composition of emerging sand flies varied with habitat, season and geographical location.
    Acta tropica. 05/2014;
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    ABSTRACT: Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.
    PLoS neglected tropical diseases. 05/2014; 8(5):e2875.
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    ABSTRACT: In East Africa, Phlebotomus orientalis serves as the main vector of Leishmania donovani, the causative agent of visceral leishmaniasis (VL). Phlebotomus orientalis is present at two distant localities in Ethiopia; Addis Zemen where VL is endemic and Melka Werer where transmission of VL does not occur. To find out whether the difference in epidemiology of VL is due to distant compositions of P. orientalis saliva we established colonies from Addis Zemen and Melka Werer, analyzed and compared the transcriptomes, proteomes and enzymatic activity of the salivary glands. Two cDNA libraries were constructed from the female salivary glands of P. orientalis from Addis Zemen and Melka Werer. Clones of each P. orientalis library were randomly selected, sequenced and analyzed. In P. orientalis transcriptomes, we identified members of 13 main protein families. Phylogenetic analysis and multiple sequence alignments were performed to evaluate differences between the P. orientalis colonies and to show the relationship with other sand fly species from the subgenus Larroussius. To further compare both colonies, we investigated the humoral antigenicity and cross-reactivity of the salivary proteins and the activity of salivary apyrase and hyaluronidase. This is the first report of the salivary components of P. orientalis, an important vector sand fly. Our study expanded the knowledge of salivary gland compounds of sand fly species in the subgenus Larroussius. Based on the phylogenetic analysis, we showed that P. orientalis is closely related to Phlebotomus tobbi and Phlebotomus perniciosus, whereas Phlebotomus ariasi is evolutionarily more distinct species. We also demonstrated that there is no significant difference between the transcriptomes, proteomes or enzymatic properties of the salivary components of Addis Zemen (endemic area) and Melka Werer (non-endemic area) P. orientalis colonies. Thus, the different epidemiology of VL in these Ethiopian foci cannot be attributed to the salivary gland composition.
    PLoS Neglected Tropical Diseases 02/2014; 8(2):e2709. · 4.57 Impact Factor

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