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Complement C1q expression in Erythema nodosum leprosum

PLoS Neglected Tropical Diseases News - 2 March 2018 - 10:00pm

by Edessa Negera, Stephen L. Walker, Tsehainesh Lemma, Abraham Aseffa, Diana N. Lockwood, Hazel M. Dockrell

Complement C1q is a soluble protein capable of initiating components of the classical pathway in host defence system. In earlier qualitative studies, C1q has been implicated in the pathogenesis of Erythema Nodosum Leprosum (ENL). However, little is known about the role of this complement in ENL reaction. In the present study we described the protein level of C1q production and its gene expression in the peripheral blood and skin biopsies in patients with ENL reaction and lepromatous leprosy (LL) patient controls before and after treatment. Thirty untreated patients with ENL reaction and 30 non-reactional LL patient controls were recruited at ALERT Hospital, Ethiopia. Peripheral blood and skin biopsies were obtained from each patient before and after treatment. The level of circulating C1q in the plasma was determined by enzyme-linked immunosorbent assay. The mRNA expression of the three C1q components, C1qA, C1qB, and C1qC in the peripheral blood and skin biopsies was determined by qPCR. Circulating C1q in the peripheral blood of untreated ENL patients was significantly decreased compared to LL patient controls. Untreated ENL patients had increased C1q gene expression in the peripheral blood compared to LL controls. Similarly, C1qA and C1qC gene expression were substantially increased in the skin biopsies of untreated ENL patients compared to LL controls. However, after treatment none of these genes show significant difference in both groups. In conclusion, while circulating C1q is inversely correlated with active ENL reactions, its gene expression is directly correlated with ENL. The decreased circulating C1q may suggest the utilization of C1q in immune-complex formation in these patients. Therefore, C1q could be a potential diagnostic marker for active ENL reactions as well as for monitoring ENL treatment.

Molecular identification of Leishmania infection in the most relevant sand fly species and in patient skin samples from a cutaneous leishmaniasis focus, in Morocco

PLoS Neglected Tropical Diseases News - 2 March 2018 - 10:00pm

by Idris Mhaidi, Sofia El kacem, Mouad Ait Kbaich, Adil El Hamouchi, M’hammed Sarih, Khadija Akarid, Meryem Lemrani

Background

Cutaneous leishmaniasis (CL) is an infectious disease caused by various species of Leishmania and transmitted by several species of sand flies. CL is among the most neglected tropical diseases, and it has represented a major health threat over the past 20 years in Morocco. The main objectives of this study were to identify relevant sand fly species and detect Leishmania infection in the most prevalent species and patient skin samples in Taza, a focus of CL in North-eastern Morocco.

Methodology and finding

A total of 3672 sand flies were collected by CDC miniature light traps. Morphological identification permitted the identification of 13 species, namely 10 Phlebotomus species and 3 Sergentomyia species. P. longicuspis was the most abundant species, comprising 64.08% of the total collected sand flies, followed by P. sergenti (20.1%) and P. perniciosus (8.45%). Using nested-kDNA PCR, seven pools of P. sergenti were positive to Leishmania tropica DNA, whereas 23 pools of P. longicuspis and 4 pools of P. perniciosus tested positive for Leishmania infantum DNA. The rates of P. longicuspis and P. perniciosus Leishmania infection were 2.51% (23/915) and 7.27% (4/55), respectively, whereas the infection prevalence of P. sergenti was 3.24%. We also extracted DNA from lesion smears of 12 patients suspected of CL, among them nine patients were positive with enzymatic digestion of ITS1 by HaeIII revealing two profiles. The most abundant profile, present in eight patients, was identical to L. infantum, whereas L. tropica was found in one patient. The results of RFLP were confirmed by sequencing of the ITS1 DNA region.

Conclusion

This is the first molecular detection of L. tropica and L. infantum in P. sergenti and P. longicuspis, respectively, in this CL focus. Infection of P. perniciosus by L. infantum was identified for the first time in Morocco. This study also underlined the predominance of L. infantum and its vector in this region, in which L. tropica has been considered the causative agent of CL for more than 20 years.

Global epidemiology of podoconiosis: A systematic review

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Kebede Deribe, Jorge Cano, Mei L. Trueba, Melanie J. Newport, Gail Davey

Background

Podoconiosis is one of the few diseases that could potentially be eliminated within one generation. Nonetheless, the global distribution of the disease remains largely unknown. The global atlas of podoconiosis was conceived to define the epidemiology and distribution of podoconiosis through dedicated surveys and assembling the available epidemiological data.

Methods

We have synthesized the published literature on the epidemiology of podoconiosis. Through systematic searches in SCOPUS and MEDLINE from inception to February 14, 2018, we identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used case reports and presence data. For a study to be included in the prevalence synthesis, it needed to be a population-based survey that involved all residents within a specific area. Studies that did not report original data were excluded. We undertook descriptive analyses of the extracted data. This study is registered with PROSPERO, number CRD42018084959.

Results

We identified 3,260 records, of which 27 studies met the inclusion criteria. Podoconiosis was described to exist or be endemic in 32 countries, 18 from the African Region, 3 from Asia and 11 from Latin America. Overall, podoconiosis prevalence ranged from 0·10% to 8.08%, was highest in the African region, and was substantially higher in adults than in children and adolescents. The highest reported prevalence values were in Africa (8.08% in Cameroon, 7.45% in Ethiopia, 4.52% in Uganda, 3.87% in Kenya and 2.51% in Tanzania). In India, a single prevalence of 0.21% was recorded from Manipur, Mizoram and Rajasthan states. None of the Latin American countries reported prevalence data.

Conclusion

Our data suggest that podoconiosis is more widespread in the African Region than in the rest of the regions, although this could be related to the fact that most podoconiosis epidemiological research has been focused in the African continent. The assembled dataset confirms that comprehensive podoconiosis control strategies such as promotion of footwear and personal hygiene are urgently needed in endemic parts of Africa. Mapping, active surveillance and a systematic approach to the monitoring of disease burden must accompany the implementation of podoconiosis control activities.

<i>Onchocerca volvulus</i> infection and serological prevalence, ocular onchocerciasis and parasite transmission in northern and central Togo after decades of <i>Simulium damnosum</i> s.l. vector control and mass drug administration of ivermectin

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Kossi Komlan, Patrick S. Vossberg, Richard G. Gantin, Tchalim Solim, Francois Korbmacher, Méba Banla, Koffi Padjoudoum, Potchoziou Karabou, Carsten Köhler, Peter T. Soboslay

Background

Mass drug administration (MDA) of ivermectin has become the main intervention to control onchocerciasis or “river blindness”. In Togo, after many years of MDA, Onchocerca volvulus infection has declined dramatically, and elimination appears achievable, but in certain river basins the current situation remains unknown. We have conducted parasitological, serological, ophthalmological, and entomological assessments in northern and central Togo within the river basins of Ôti, Kéran and Mô.

Methodology/Principal findings

Examinations were completed in 1,455 participants from 11 onchocerciasis sentinel villages, and O. volvulus transmission by Simulium damnosum sensu lato (s.l.) was evaluated. In children (aged 1–10 years), the prevalence of microfilariae (Mf) was 2.3% and in adults it ranged from 5.1 to 13.3%. Positive IgG4 responses to O. volvulus adult (crude) worm antigen (OvAg) and the recombinant Ov16 antigen were in all-ages 48.7% and 34.4%, and 29.1% and 14.9% in children, respectively. In the river basin villages of Kéran, Mô and Ôti, the IgG4 seroprevalences to OvAg in children were 51.7%, 23.5% and 12.7%, respectively, and to the Ov16 antigen 33.3% (Kéran) and 5.2% (Ôti). Onchocerciasis ocular lesions (punctate keratitis, evolving iridocyclitis and chorioretinitis) were observed in children and young adults. O. volvulus-specific DNA (Ov150) was detected by poolscreen in vector samples collected from Tchitchira/Kéran(22.8%), Bouzalo/Mô(11.3%), Baghan/Mô(2.9%) and Pancerys/Ôti(4.9%); prevalences of O. volvulus infection in S. damnosum s.l. were, respectively, 1%, 0.5%, 0.1% and 0.2%.

Conclusions/Significance

In the northern and central river basins in Togo, interruption of O. volvulus transmission has not yet been attained. Patent O. volvulus infections, positive antibody responses, progressive ocular onchocerciasis were diagnosed, and parasite transmission by S. damnosum s.l. occurred close to the survey locations. Future interventions may require approaches selectively targeted to non-complying endemic populations, to the seasonality of parasite transmission and national onchocerciasis control programs should harmonize cross-border MDA as a coordinated intervention.

Validation of rK39 immunochromatographic test and direct agglutination test for the diagnosis of Mediterranean visceral leishmaniasis in Spain

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Mathieu Bangert, María D. Flores-Chávez, Ivonne P. Llanes-Acevedo, Carolina Arcones, Carmen Chicharro, Emilia García, Sheila Ortega, Javier Nieto, Israel Cruz

Background

Visceral leishmaniasis (VL), the most severe form of leishmaniasis, is endemic in Europe with Mediterranean countries reporting endemic status alongside a worrying northward spread. Serological diagnosis, including immunochromatographic test based on the recombinant antigen rK39 (rK39-ICT) and a direct agglutination test (DAT) based on the whole parasite antigen, have been validated in regions with high VL burden, such as eastern Africa and the Indian subcontinent. To date, no studies using a large set of patients have performed an assessment of both methods within Europe.

Methodology/Principal findings

We selected a range of clinical serum samples from patients with confirmed VL (including HIV co-infection), Chagas disease, malaria, other parasitic infections and negative samples (n = 743; years 2009–2015) to test the performance of rK39-ICT rapid test (Kalazar Detect Rapid Test; InBios International, Inc., USA) and DAT (ITM-DAT/VLG; Institute of Tropical Medicine Antwerp, Belgium). An in-house immunofluorescence antibody test (IFAT), was included for comparison. Estimated sensitivities for rK39-ICT and DAT in HIV-negative VL patients were 83.1% [75.1–91.2] and 84.2% [76.3–92.1], respectively. Sensitivity was reduced to 67.3% [52.7–82.0] for rK39 and increased to 91.3% [82.1–100.0] for DAT in HIV/VL co-infected patients. The in-house IFAT was more sensitive in HIV-negative VL patients, 84.2% [76.3–92.1] than in HIV/VL patients, 79.4% [73.3–96.2]. DAT gave 32 false positives in sera from HIV-negative VL suspects, compared to 0 and 2 for rK39 and IFAT, respectively, but correctly detected more HIV/VL patients (42/46) than rK39 (31/46) and IFAT (39/46).

Conclusions/Significance

Though rK39-ICT and DAT exhibited acceptable sensitivity and specificity a combination with other tests is required for highly sensitive diagnosis of VL cases in Spain. Important variation in the performance of the tests were seen in patients co-infected with HIV or with other parasitic infections. This study can help inform the choice of serological test to be used when screening or diagnosing VL in a European Mediterranean setting.

An outbreak of <i>Leishmania major</i> from an endemic to a non-endemic region posed a public health threat in Iraq from 2014-2017: Epidemiological, molecular and phylogenetic studies

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Mariwan M. M. Al-Bajalan, Sirwan M. A. Al-Jaf, Sherko S. Niranji, Dler R. Abdulkareem, Khudhair K. Al-Kayali, Hirotomo Kato

Background

Cutaneous leishmaniasis (CL) is a neglected worldwide, zoonotic, vector-borne, tropical disease that is a threat to public health. This threat may spread from endemic to non-endemic areas. Current research has exploited epidemiological, molecular and phylogenetical studies to determine the danger of an outbreak of CL in the borderline area between northern and central Iraq from 2014–2017.

Methodology/Principal findings

For the first time, using sequence analysis of the cytochrome b gene, the occurrence of CL in the borderline area between northern and central Iraq was confirmed to be due to Leishmania major. The phylogenetic analysis indicated that it was closely related to the L. major MRHO/IR/75/ER strain in Iran.

Conclusions and significance

In conclusion, the genotype confirmation of the L. major strain will improve our understanding of the epidemiology of the disease. This is important for facilitating control programs to prevent the further spread of CL. Furthermore, this area could be considered as a model for further research on the risk of global CL epidemics in other non-endemic countries where both reservoir hosts and sandfly vectors are present.

Hyperendemic dengue transmission and identification of a locally evolved DENV-3 lineage, Papua New Guinea 2007-2010

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Dagwin Luang-Suarkia, Oriol Mitja, Timo Ernst, Shannon Bennett, Alfred Tay, Russell Hays, David W. Smith, Allison Imrie

Background

Dengue is endemic in the Western Pacific and Oceania and the region reports more than 200,000 cases annually. Outbreaks of dengue and severe dengue occur regularly and movement of virus throughout the region has been reported. Disease surveillance systems, however, in many areas are not fully established and dengue incidence is underreported. Dengue epidemiology is likely least understood in Papua New Guinea (PNG), where the prototype DENV-2 strain New Guinea C was first isolated by Sabin in 1944 but where routine surveillance is not undertaken and little incidence and prevalence data is available.

Methodology/Principal findings

Serum samples from individuals with recent acute febrile illness or with non-febrile conditions collected between 2007–2010 were tested for anti-DENV neutralizing antibody. Responses were predominantly multitypic and seroprevalence increased with age, a pattern indicative of endemic dengue. DENV-1, DENV-2 and DENV-3 genomes were detected by RT-PCR within a nine-month period and in several instances, two serotypes were identified in individuals sampled within a period of 10 days. Phylogenetic analysis of whole genome sequences identified a DENV-3 Genotype 1 lineage which had evolved on the northern coast of PNG which was likely exported to the western Pacific five years later, in addition to a DENV-2 Cosmopolitan Genotype lineage which had previously circulated in the region.

Conclusions/Significance

We show that dengue is hyperendemic in PNG and identify an endemic, locally evolved lineage of DENV-3 that was associated with an outbreak of severe dengue in Pacific countries in subsequent years, although severe disease was not identified in PNG. Additional studies need to be undertaken to understand dengue epidemiology and burden of disease in PNG.

Results of the first mapping of soil-transmitted helminths in Benin: Evidence of countrywide hookworm predominance

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Moudachirou Ibikounlé, Ablavi Onzo-Aboki, Justin Doritchamou, Jean-Jacques Tougoué, Pélagie Mimonnou Boko, Boris S. Savassi, Edoux Joel Siko, Aboudou Daré, Wilfrid Batcho, Achille Massougbodji, Dorothée Akoko Kindé-Gazard, Achille Kaboré

Background

National mapping of soil-transmitted helminth infections (STH) was conducted for the first time in all of the 77 districts of Benin (West Africa) from 2013 to 2015. This mapping aimed to provide basic epidemiological data essential for the implementation of the national strategy against the neglected tropical diseases (NTDs) in the context of achieving the WHO target of controlling these infections by 2020.

Methods

In each district, 5 schools were purposively selected in 5 villages and 50 school-children (25 girls and 25 boys) from ages 8 to 14 years were randomly enrolled in each school. In total, 19,250 stool samples of school children (9,625 girls and 9,625 boys) from 385 schools were examined by Kato-Katz technique.

Results

The three major species of STH (hookworm, Ascaris lumbricoides and Trichuris trichiura) were observed with intra- and inter-specific variations in the prevalence and the intensity of these parasites. Hookworm infection was present in all of the surveyed districts with an average prevalence of 17.14% (95% CI 16.6%-17.6%). Among the infected schoolchildren, at national level, 90.82%, 6.73% and 2.45% of infections were of light, moderate and heavy parasite intensities respectively. A. lumbricoides infection, with a national average prevalence of 5.35% (95% CI 5.00%-5.60%),was the second most prevalent STH, and 84.37%, 14.27% and 1.36% of the infections were of light, moderate and heavy parasite intensities, respectively. T. trichiura had a national average prevalence of 1.15% (95% CI 0.90%-1.20%) and 80.45%, 13.18% and 6.36% infections were of light, moderate and heavy parasite intensities, respectively. The national cumulative prevalence of the three STH infections was 22.74% (95% CI 22.15%-23.33%), with58.44% (45/77) of the districts requiring mass treatment according to WHO recommendations. In all of the surveyed districts, multiple infections by STH species were common, and boys seemed more at risk of hookworm and Ascaris infections.

Conclusions

This first national mapping provided an overview of the epidemiological pattern of STH infections and was essential for the implementation of a control strategy with an effective preventive chemotherapy treatment (PCT). Results show that while preventive chemotherapy is not indicated for children in 32/77 districts, 43 require annual deworming and two require twice yearly deworming. If no environmental change occurs, and no mass treatment is delivered, prevalence is likely to remain stable for many years owing to poor hygiene and sanitation.

Diagnostic tools for soil-transmitted helminths control and elimination programs: A pathway for diagnostic product development

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Mark D. Lim, Simon J. Brooker, Vicente Y. Belizario Jr., Françoise Gay-Andrieu, John Gilleard, Bruno Levecke, Lisette van Lieshout, Graham F. Medley, Zeleke Mekonnen, Greg Mirams, Sammy M. Njenga, Maurice R. Odiere, James W. Rudge, Lieven Stuyver, Jozef Vercruysse, Johnny Vlaminck, Judd L. Walson, the Annecy STH diagnostic experts group

Tegumentary leishmaniasis and coinfections other than HIV

PLoS Neglected Tropical Diseases News - 1 March 2018 - 10:00pm

by Dalila Y. Martínez, Kristien Verdonck, Paul M. Kaye, Vanessa Adaui, Katja Polman, Alejandro Llanos-Cuentas, Jean-Claude Dujardin, Marleen Boelaert

Background

Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by Leishmania parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.

Methodology and principal findings

This review focuses on the frequency of TL coinfections in human populations, interactions between Leishmania and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of Trypanosoma cruzi coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., Leishmania and Sporothrix schenckii), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.

Conclusions and significance

In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.

Why snakebite patients in Myanmar seek traditional healers despite availability of biomedical care at hospitals? Community perspectives on reasons

PLoS Neglected Tropical Diseases News - 28 February 2018 - 10:00pm

by Eliza Schioldann, Mohammad Afzal Mahmood, Mya Myitzu Kyaw, Dale Halliday, Khin Thida Thwin, Nyein Nyein Chit, Robert Cumming, David Bacon, Sam Alfred, Julian White, David Warrell, Chen Au Peh

Background

Snakebite is a major public health problem in many developing countries. Farmers are particularly exposed to snakes, and due to their rural location often experience delays in accessing formal healthcare. The reasons to use traditional healers may include difficulties in accessing formal healthcare, certain beliefs about snakes and snake venom, tradition, and trust in the capacity of traditional healers. Traditional healing, however, may have serious consequences in terms of delays or added complications. There is little in-depth current information about the reasons for its continued use for snakebite. As part of a health services development project to improve health outcomes for snakebite patients, community attitudes to the use of traditional healers were explored in the Mandalay region of Myanmar.

Methodology & findings

With the objective of learning from local communities, information was generated in three communities using participatory appraisal methods with the communities, and focus group discussions with the local healthcare staff. Many snakebite victims in these communities use traditional healing. Reasons include transport difficulties, low cost for traditional healing, inadequacy of anti-snake venom in the formal healthcare sector, and traditional beliefs, as traditional healing practices are rooted in many cultural and traditional factors. The communities reported that even if access to medical care were improved, traditional healing would continue to be used.

Conclusion

These findings point to the need for working with traditional healers for prevention, appropriate first aid and timely access to effective treatment for snakebite.

Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects

PLoS Neglected Tropical Diseases News - 28 February 2018 - 10:00pm

by Corey M. Peak, Amanda L. Reilly, Andrew S. Azman, Caroline O. Buckee

Background

Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations?

Methods and findings

We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016.

Conclusions

Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies.

Evaluation of the <i>Trypanosoma brucei</i> 6-oxopurine salvage pathway as a potential target for drug discovery

PLoS Neglected Tropical Diseases News - 26 February 2018 - 10:00pm

by Eva Doleželová, David Terán, Ondřej Gahura, Zuzana Kotrbová, Michaela Procházková, Dianne Keough, Petr Špaček, Dana Hocková, Luke Guddat, Alena Zíková

Due to toxicity and compliance issues and the emergence of resistance to current medications new drugs for the treatment of Human African Trypanosomiasis are needed. A potential approach to developing novel anti-trypanosomal drugs is by inhibition of the 6-oxopurine salvage pathways which synthesise the nucleoside monophosphates required for DNA/RNA production. This is in view of the fact that trypanosomes lack the machinery for de novo synthesis of the purine ring. To provide validation for this approach as a drug target, we have RNAi silenced the three 6-oxopurine phosphoribosyltransferase (PRTase) isoforms in the infectious stage of Trypanosoma brucei demonstrating that the combined activity of these enzymes is critical for the parasites’ viability. Furthermore, we have determined crystal structures of two of these isoforms in complex with several acyclic nucleoside phosphonates (ANPs), a class of compound previously shown to inhibit 6-oxopurine PRTases from several species including Plasmodium falciparum. The most potent of these compounds have Ki values as low as 60 nM, and IC50 values in cell based assays as low as 4 μM. This data provides a solid platform for further investigations into the use of this pathway as a target for anti-trypanosomal drug discovery.

Coverage, social mobilization and challenges of mass Zithromax administration campaign in south and south east zones of Tigray, northern Ethiopia; a cross sectional study

PLoS Neglected Tropical Diseases News - 26 February 2018 - 10:00pm

by Afework Mulugeta, Gebremedhin Berhe Gebregergs, Selamawit Asfaw, Dejen Yemane, Mengistu Mitiku, Beyene Meresa, Goitom Gigar, Amanuel Kidane

Background

The antibiotic treatment of people with trachoma helps to prevent transmission the disease in a community. Currently, Zithromax is the drug recommended for mass drug administration (MDA). MDA should be carried out annually for three to five years in trachoma endemic areas. Coverage survey is essential to track progress towards program goals and to identify communities with poor coverage in order to permit timely and appropriate actions. We assessed mass Zithromax administration coverage, social mobilization and campaign challenges in south and southeast zones of Tigray, Ethiopia.

Method

We conducted a survey in community in Southern and South East zones of Tigray region from August 15 to August 31, 2016. The survey included nine Woredas. It was supported by qualitative methods. A total of 3741 individuals were enrolled from 933 households using multistage sampling. We used structured questionnaire. In-depth interview and focus group discussion were also applied. Descriptive statistics was performed using SPSS version 20.We thematically analyzed the qualitative data using Atlas 7.

Result

The overall coverage of Zithromax MDA was 93.3%. It ranges from 90.0% in Seharti Samre to 97.9% in Endamokoni. The coverage was 93.4% for males and 93.1% for females. A higher proportion (98.3%) of children aged 5 to 15 years and 409 (87.8%) under five children took Zithromax. The coverage was 94% in rural and 91.2% in urban. Women development army (43.3%) and health extension workers (32.5%) were the main source of information. Frequent occurrence of drug side effects, rumors, lack of community and leaders’ engagement in the campaign, fasting, shortage of human power and short term unavailability of supplies were barriers during the campaign.

Conclusion

The Zithromax MDA coverage in the study zones was higher than the minimum WHO set criteria of 80%. There was a wide difference in coverage among Woredas and Kebeles. The MDA coverage was lower in urban than rural. Misconceptions and poor mobilization were common challenges. Thus, proper planning, community mobilization and uniform training will need to be done ahead of the campaign in the future.

Leprosy among schoolchildren in the Amazon region: A cross-sectional study of active search and possible source of infection by contact tracing

PLoS Neglected Tropical Diseases News - 26 February 2018 - 10:00pm

by Valderiza Lourenço Pedrosa, Luiz Claudio Dias, Enrique Galban, André Leturiondo, Jamile Palheta Jr, Monica Santos, Milton Ozório Moraes, Carolina Talhari

Background

The high rate of leprosy cases among children under 15 years of age in Brazil indicates ongoing transmission within the community. The identification of the new leprosy cases among contacts can help identify the source of infection and interrupt the transmission chain. This study aims to determine the detection rate of previously undiagnosed cases of leprosy among schoolchildren who are under 15 years of age living in Manaus, Amazonas, Brazil, and their possible source of infection by contact tracing.

Methodology/Principal findings

This was a school-based, cross-sectional study in which the identification of active leprosy cases was conducted in 277 out of 622 randomly selected public schools in Manaus, Amazonas, Brazil. Suspected cases of leprosy were referred to the Alfredo da Matta Foundation, a reference center for leprosy in Manaus. A total of 34,547 schoolchildren were examined, and 40 new leprosy cases were diagnosed. Among new cases, 57.5% were males, and 80.0% demonstrated paucibacillary leprosy. A total of 196 of 206 registered contacts were screened, and 52.5% of the newly diagnosed children’s cases had at least one positive household contact. In these contacts, grandparents (52.4%) were the most common co-prevalent cases, while 14.3% were uncles, 9.5% were parents and 9.5% were granduncles. Seven contacts (5.0%), including four siblings of child patients were newly diagnosed. Our data indicate that the prevalence is 11.58 per 10,000, which is 17 times higher than the registered rate.

Conclusions/Significance

This study suggests that the prevalence of leprosy among schoolchildren may have remained unchanged over the past thirty years. It also indicates that that active case finding is necessary for reaching the World Health Organization’s goals of zero detection among children, especially in endemic areas where the prevalence of leprosy is obscure. Moreover, we assert that all children must have their household contacts examined in order to identify the possible source of infection and interrupt the disease’s transmission. Novel strategies to reinforce contact tracing associated with large-scale strategies of chemo- and immune-prophylaxis should be expanded to prevent the perpetuation of the disease cycle.

Transformation of <i>Fonsecaea pedrosoi</i> into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-γ production

PLoS Neglected Tropical Diseases News - 26 February 2018 - 10:00pm

by Bilin Dong, Zhongsheng Tong, Ruoyu Li, Sharon C.-A. Chen, Weihuang Liu, Wei Liu, Yao Chen, Xu Zhang, Yiqun Duan, Dongsheng Li, Liuqing Chen

Fonsecaea pedrosoi (F. pedrosoi) is the most common agent of chromoblastomycosis. Transformation of this fungus from its saprophytic phase into pathogenic sclerotic cells in tissue is an essential link to the refractoriness of this infection. Experimental studies in murine models have shown that the absence of CD4+ T cells impairs host defense against F. pedrosoi infection. Clinical research has also suggested that a relatively low level of the Th1 cytokine INF-γ and inefficient T cell proliferation are simultaneously present in patients with severe chromoblastomycosis upon in vitro stimulation with ChromoAg, an antigen prepared from F. pedrosoi. In the present study, we show that in mice intraperitoneally infected with F. pedrosoi-spores, -hyphae or in vitro-induced sclerotic cells respectively, the transformation of this causative agent into sclerotic cells contributes to a compromised Th1 cytokine production in the earlier stage of infection with impaired generation of neutrophil reactive oxygen species (ROS) and pan-inhibition of Th1/Th2/Th17 cytokine production with disseminated infection in the later stage by using a CBA murine Th1/Th2/Th17 cytokine kit. In addition, we have further demonstrated that intraperitoneal administration of recombinant mouse IFN-γ (rmIFN-γ) effectively reduces the fungal load in the infected mouse spleen, and dampens the peritoneal dissemination of F. pedrosoi-sclerotic cells. Meanwhile, exogeneous rmIFN-γ contributes to the formation and maintenance of micro-abscess and restores the decrease in neutrophil ROS generation in the mouse spleen infected with F. pedrosoi-sclerotic cells. Of note, we have once again demonstrated that it is a chitin-like component, but not β-glucans or mannose moiety, that exclusively accumulates on the outer cell wall of F. pedrosoi-sclerotic cells which were induced in vitro or isolated from the spleens of intraperitoneally infected BALB/c mice. In addition, our results indicate that decreased accumulation of chitin on the surface of live F. pedrosoi-sclerotic cells after chitinase treatment can be self-compensated in a time-dependent manner. Importantly, we have for the first time demonstrated that exclusive accumulation of chitin on the transformed sclerotic cells of F. pedrosoi is involved in an impaired murine Th1 cytokine profile, therefore promoting the refractoriness of experimental murine chromoblastomycosis.

Failure of fluconazole in treating cutaneous leishmaniasis caused by <i>Leishmania guyanensis</i> in the Brazilian Amazon: An open, nonrandomized phase 2 trial

PLoS Neglected Tropical Diseases News - 26 February 2018 - 10:00pm

by Valeska Albuquerque Francesconi, Fabio Francesconi, Rajendranath Ramasawmy, Gustavo Adolfo Sierra Romero, Maria das Graças Costa Alecrim

Background

The treatment of Leishmaniasis caused by Leishmania (Viannia) guyanensis is based on a weak strength of evidence from very few clinical trials and some case series reports. Current treatment guidelines recommend pentamidine isethionate or meglumine antimoniate (Glucantime) as the first-line choices. Both are parenteral drugs with a low therapeutic indexes leading to a high risk of undesired effects. Imidazole derivatives interfere with the production of leishmanial ergosterol, an essential component of their membrane structure. One drug that has been studied in different clinical presentations of Leishmania is fluconazole, a hydrophilic bis-triazole, which is easily absorbed through the oral route with a low toxicity profile and is considered safe for children. This drug is readily available in poor countries with a reasonable cost making it a potential option for treating leishmaniasis.

Methods and findings

An adaptive nonrandomized clinical trial with sequential groups with dose escalation of oral fluconazole was designed to treat adult men with localized cutaneous leishmaniasis (LCL) in Manaus, Brazil. Eligible participants were patients with LCL with confirmed Leishmania guyanensis infection.

Results

Twenty adult male patients were treated with 450 mg of fluconazole daily for 30 days. One patient (5%) was cured within 30 days of treatment. Of the 19 failures (95%), 13 developed a worsening of ulcers and six evolved lymphatic spreading of the disease. Planned dose escalation was suspended after the disappointing failure rate during the first stage of the trial.

Conclusion/Significance

Oral fluconazole, at the dose of 450mg per day, was not efficacious against LCL caused by Leishmania guyanensis in adult men.

Trial registration

Brazilian Clinical Trial Registration (ReBec)—RBR-8w292w; UTN number—1158-2421

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