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Impact of community-based integrated mass drug administration on schistosomiasis and soil-transmitted helminth prevalence in Togo

20 August 2018 - 9:00pm

by Rachel N. Bronzan, Ameyo M. Dorkenoo, Yao M. Agbo, Wemboo Halatoko, Yao Layibo, Poukpessi Adjeloh, Menssah Teko, Efoe Sossou, Kossi Yakpa, Mawèké Tchalim, Gbati Datagni, Anders Seim, Koffi S. Sognikin

Background

Togo has conducted annual, integrated, community-based mass drug administration (MDA) for soil-transmitted helminths (STH) and schistosomiasis since 2010. Treatment frequency and target populations are determined by disease prevalence, as measured by baseline surveys in 2007 and 2009, and WHO guidelines. Reported programmatic treatment coverage has averaged over 94%. Togo conducted a cross-sectional survey in 2015 to assess the impact of four to five years of MDA on these diseases.

Methodology/Principal findings

In every sub-district in the country outside the capital, the same schools were visited as at baseline and a sample of fifteen children age 6 to 9 years old was drawn. Each child submitted urine and a stool sample. Urine samples were tested by dipstick for the presence of blood as a proxy measure of Schistosoma haematobium infection. Stool samples were analyzed by the Kato-Katz method for STH and Schistosoma mansoni. At baseline, 17,100 children were enrolled at 1,129 schools in 562 sub-districts; in 2015, 16,890 children were enrolled at the same schools. The overall prevalence of both STH and schistosomiasis declined significantly, from 31.5% to 11.6% for STH and from 23.5% to 5.0% for schistosomiasis (p<0.001 in both instances). Egg counts from both years were available only for hookworm and S. mansoni; intensity of infection decreased significantly for both infections from 2009 to 2015 (p<0.001 for both infections). In areas with high baseline prevalence, rebound of hookworm infection was noted in children who had not received albendazole in the past 6 months.

Conclusions/Significance

After four to five years of MDA in Togo, the prevalence and intensity of STH and schistosomiasis infection were significantly reduced compared to baseline. Data on STH indicate that stopping MDA in areas with high baseline prevalence may result in significant rebound of infection. Togo’s findings may help refine treatment recommendations for these diseases.

Spatiotemporal prediction of infectious diseases using structured Gaussian processes with application to Crimean–Congo hemorrhagic fever

17 August 2018 - 9:00pm

by Çiğdem Ak, Önder Ergönül, İrfan Şencan, Mehmet Ali Torunoğlu, Mehmet Gönen

Background

Infectious diseases are one of the primary healthcare problems worldwide, leading to millions of deaths annually. To develop effective control and prevention strategies, we need reliable computational tools to understand disease dynamics and to predict future cases. These computational tools can be used by policy makers to make more informed decisions.

Methodology/Principal findings

In this study, we developed a computational framework based on Gaussian processes to perform spatiotemporal prediction of infectious diseases and exploited the special structure of similarity matrices in our formulation to obtain a very efficient implementation. We then tested our framework on the problem of modeling Crimean–Congo hemorrhagic fever cases between years 2004 and 2015 in Turkey.

Conclusions/Significance

We showed that our Gaussian process formulation obtained better results than two frequently used standard machine learning algorithms (i.e., random forests and boosted regression trees) under temporal, spatial, and spatiotemporal prediction scenarios. These results showed that our framework has the potential to make an important contribution to public health policy makers.

North American <i>Culex pipiens</i> and <i>Culex quinquefasciatus</i> are competent vectors for Usutu virus

17 August 2018 - 9:00pm

by Christian L. Cook, Yan-Jang S. Huang, Amy C. Lyons, Barry W. Alto, Isik Unlu, Stephen Higgs, Dana L. Vanlandingham

Background

Usutu virus (USUV) is a member of the Japanese encephalitis virus (JEV) serocomplex in the Flaviviridae family. Emergence of USUV in Europe has led to disease burdens in birds and created increasing concern for the potential zoonotic transmission to humans. Whilst USUV has not been detected in the New World, the identification of competent vector species in North America is critical in the assessment of the likelihood of its dispersal and establishment of enzootic transmission cycles. The objective of this study was to determine vector competence of potential mosquito vectors in North America for USUV. Three medically important mosquito species were selected for testing because of their involvement in the transmission of West Nile virus and St. Louis encephalitis virus, two related JEV serocomplex flaviviruses in the New World.

Methodology/Principal findings

Oral challenge of Culex pipiens, Culex quinquefasciatus, and Aedes albopictus was performed to determine the susceptibility and vector competence of North American mosquitoes for USUV. Infection status was monitored by the isolation of virus from homogenized mosquito tissues. The disseminated form of infection was demonstrated by the detection of infectious virus in the head, wings, and legs of infected mosquitoes. The presence of viral RNA in saliva of infected Cx. pipiens and Cx. quinquefasciatus indicated that both species are competent for transmission of USUV.

Conclusions/Significance

Results indicate that members of the Cx. pipiens complex are susceptible to USUV and competent for its transmission potential in North America in the event of its introduction. In contrast, Ae. albopictus were highly refractory to USUV infection, suggesting that this species is unlikely to contribute to USUV transmission in North America.

Population genomics of <i>Culiseta melanura</i>, the principal vector of Eastern equine encephalitis virus in the United States

17 August 2018 - 9:00pm

by John Soghigian, Theodore G. Andreadis, Goudarz Molaei

Background

Eastern Equine Encephalitis (EEE) (Togaviridae, Alphavirus) is a highly pathogenic mosquito-borne arbovirus that circulates in an enzootic cycle involving Culiseta melanura mosquitoes and wild Passeriformes birds in freshwater swamp habitats. Recently, the northeastern United States has experienced an intensification of virus activity with increased human involvement and northward expansion into new regions. In addition to its principal role in enzootic transmission of EEE virus among avian hosts, recent studies on the blood-feeding behavior of Cs. melanura throughout its geographic range suggest that this mosquito may also be involved in epizootic / epidemic transmission to equines and humans in certain locales. Variations in blood feeding behavior may be a function of host availability, environmental factors, and/or underlying genetic differences among regional populations. Despite the importance of Cs. melanura in transmission and maintenance of EEE virus, the genetics of this species remains largely unexplored.

Methodology and principle findings

To investigate the occurrence of genetic variation in Cs. melanura, the genome of this mosquito vector was sequenced resulting in a draft genome assembly of 1.28 gigabases with a contig N50 of 93.36 kilobases. Populations of Cs. melanura from 10 EEE virus foci in the eastern North America were genotyped with double-digest RAD-seq. Following alignment of reads to the reference genome, variant calling, and filtering, 40,384 SNPs were retained for downstream analyses. Subsequent analyses revealed genetic differentiation between northern and southern populations of this mosquito species. Moreover, limited fine-scale population structure was detected throughout northeastern North America, suggesting local differentiation of populations but also a history of ancestral polymorphism or contemporary gene flow. Additionally, a genetically distinct cluster was identified predominantly at two northern sites.

Conclusion and significance

This study elucidates the first evidence of fine-scale population structure in Cs. melanura throughout its eastern range and detects evidence of gene flow between populations in northeastern North America. This investigation provides the groundwork for examining the consequences of genetic variations in the populations of this mosquito species that could influence vector-host interactions and the risk of human and equine infection with EEE virus.

Sphingosine-1-phosphate signaling in <i>Leishmania donovani</i> infection in macrophages

17 August 2018 - 9:00pm

by Mohd Arish, Atahar Husein, Rahat Ali, Shams Tabrez, Farha Naz, Zulfazal Ahmad, Abdur Rub

Background

Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array of cellular processes, such as apoptosis, cell proliferation, migration, and differentiation, but its role in Leishmania donovani infection is unknown.

Methodology/ principal findings

In the present study, we observed that L. donovani infection in THP-1 derived macrophages (TDM) leads to decrease in the expression of S1pr2 and S1pr3 at mRNA level. We further observed that Leishmania infection inhibits the phosphorylation of sphingosine kinase 1 (sphK1) in a time-dependent manner. Exogenous S1P supplementation decreases L. donovani induced ERK1/2 phosphorylation and increases p38 phosphorylation in TDM, resulting in a decrease in the intracellular parasite burden in a dose-dependent manner. On the other hand, sphK inhibition by DMS increases ERK1/2 phosphorylation leading to increased IL-10 and parasite load. To gain further insight, cytokines expression were checked in S1P supplemented TDM and we observed increase in IL-12, while decrease IL-10 expression at mRNA and protein levels. In addition, treatment of antagonist of S1PR2 and S1PR3 such as JTE-013 and CAY10444 respectively enhanced Leishmania-induced ERK1/2 phosphorylation and parasite load.

Conclusions

Our overall study not only reports the significant role of S1P signaling during L. donovani infection but also provides a novel platform for the development of new drugs against Leishmaniasis.

Effectiveness of <i>Lonomia</i> antivenom in recovery from the coagulopathy induced by <i>Lonomia orientoandensis</i> and <i>Lonomia casanarensis</i> caterpillars in rats

16 August 2018 - 9:00pm

by Ida S. Sano-Martins, Camila Gonzalez, Isabelle Valle dos Anjos, Juana Diaz, Luis Roberto C. Gonçalves

In South America, accidental contact with Lepidoptera larvae can produce a diversity of reactions that vary from dermatological problems to severe hemorrhagic syndromes, such as those caused by contact with caterpillars of the genus Lonomia (Saturniidae). Lonomia venom can alter the hemostatic system and lead to renal failure, internal and brain bleeding, and in severe cases, death. The only specific treatment available for these envenomations is the Lonomia Antivenom (LAV) produced by the Butantan Institute, in Brazil, using an extract of Lonomia obliqua as the antigen. LAV has been used to treat exposure to other Lonomia species across South America. However, no experimental studies have been performed to test the efficacy of LAV in neutralizing the venom of species other than L. obliqua found in Southern Brazil. In this study, we tested the effectiveness of LAV in reversing the hemostatic disturbances induced by injecting Lonomia casanarensis (Lca) and Lonomia orientoandensis (Lor) scolus extracts into rats and compared the effects to the case of L. obliqua (Lob) scolus extract-induced envenomation. Lca and Lor caterpillars were collected in Colombia, and some of them were reared to adults for identification. The Minimum Defibrinating Doses (MDD) of Lca and Lor were estimated. Rats were injected (i.d.) with a dose of 3 MDD per rat of each scolus extract and treated (i.v.) with 1.5 mL of LAV or 1.5 mL of saline. Twenty-four hours after the treatment, the fibrinogen levels and platelet counts had recovered to the hemostatic levels in the groups treated with LAV. The groups treated with the saline solution had fibrinogen levels and platelet counts at non-hemostatic levels. Thromboelastometric analyses confirmed these results. In conclusion, the results showed that LAV is effective at neutralizing the envenomation induced by Lca and Lor spine extracts in rats and restoring hemostasis.

Human plague associated with Tibetan sheep originates in marmots

16 August 2018 - 9:00pm

by Ruixia Dai, Baiqing Wei, Haoming Xiong, Xiaoyan Yang, Yao Peng, Jian He, Juan Jin, Yumeng Wang, Xi Zha, Zhikai Zhang, Ying Liang, Qingwen Zhang, Jianguo Xu, Zuyun Wang, Wei Li

The Qinghai-Tibet plateau is a natural plague focus and is the largest such focus in China. In this area, while Marmota himalayana is the primary host, a total of 18 human plague outbreaks associated with Tibetan sheep (78 cases with 47 deaths) have been reported on the Qinghai-Tibet plateau since 1956. All of the index infectious cases had an exposure history of slaughtering or skinning diseased or dead Tibetan sheep. In this study, we sequenced and compared 38 strains of Yersinia pestis isolated from different hosts, including humans, Tibetan sheep, and M. himalayana. Phylogenetic relationships were reconstructed based on genome-wide single-nucleotide polymorphisms identified from our isolates and reference strains. The phylogenetic relationships illustrated in our study, together with the finding that the Tibetan sheep plague clearly lagged behind the M. himalayana plague, and a previous study that identified the Tibetan sheep as a plague reservoir with high susceptibility and moderate sensitivity, indicated that the human plague was transmitted from Tibetan sheep, while the Tibetan sheep plague originated from marmots. Tibetan sheep may encounter this infection by contact with dead rodents or through being bitten by fleas originating from M. himalayana during local epizootics.

Hajj, Umrah, and the neglected tropical diseases

16 August 2018 - 9:00pm

by Mashal M. Almutairi, Waleed Saleh Alsalem, Mazen Hassanain, Peter J. Hotez

Rapid, inexpensive, fingerstick, whole-blood, sensitive, specific, point-of-care test for anti-<i>Toxoplasma</i> antibodies

16 August 2018 - 9:00pm

by Joseph Lykins, Xuan Li, Pauline Levigne, Ying Zhou, Kamal El Bissati, Fatima Clouser, Martine Wallon, Florence Morel, Karen Leahy, Bouchra El Mansouri, Maryam Siddiqui, Nicole Leong, Morgan Michalowski, Erin Irwin, Perpetua Goodall, Mahmoud Ismail, Monica Christmas, El Bachir Adlaoui, Mohamed Rhajaoui, Amina Barkat, Hua Cong, Ian J. Begeman, Bo Shiun Lai, Despina G. Contopoulos-Ioannidis, Jose G. Montoya, Yvonne Maldonado, Raymund Ramirez, Cindy Press, Francois Peyron, Rima McLeod

The effect of temperature increase on the development of <i>Rhodnius prolixus</i> and the course of <i>Trypanosoma cruzi</i> metacyclogenesis

15 August 2018 - 9:00pm

by Laura D. Tamayo, Felipe Guhl, Gustavo A. Vallejo, Juan David Ramírez

The increase in the global land temperature, expected under predictions of climate change, can directly affect the transmission of some infectious diseases, including Chagas disease, an anthropozoonosis caused by Trypanosoma cruzi and transmitted by arthropod vectors of the subfamily Triatominae. This work seeks to study the effects of temperature on the development of the life cycle, fertility and fecundity of the insect vector Rhodnius prolixus and on the metacyclogenesis of T. cruzi. All of the variables were subjected to 3 temperatures: 26°C, 28°C and 30°C. Hatching time was evaluated, along with time to fifth instar, time to adult, fecundity studied using the e-value, and egg viability during the first 3 reproductive cycles. In addition, the amounts of metacyclic trypomastigotes of the TcI and TcII DTUs in R. prolixus were evaluated from days 2 to 20 at two-day intervals and from weeks 6 to 8 post-infection. Decreases were observed in time to hatching (15–10 days on average) and in time to fifth instar (70–60 days on average) and transition to adult (100–85 days on average). No significant differences in egg viability were observed in any of the reproductive cycles evaluated, but an increase in fecundity was observed at 30°C during the third reproductive cycle. At 30°C, there was also an increase in the number of infective forms and a decrease in the time at which metacyclic trypomastigotes were detected in the rectal ampulla of the insects for both TcI and TcII. According to these results, the expected temperature increase under climate change would cause an increase in the number of insects and a greater probability of infection of the parasite, which affects the transmission of Chagas disease.

<i>Trypanosoma brucei</i> triggers a marked immune response in male reproductive organs

15 August 2018 - 9:00pm

by Tânia Carvalho, Sandra Trindade, Sílvia Pimenta, Ana B. Santos, Filipa Rijo-Ferreira, Luísa M. Figueiredo

African trypanosomiasis is caused by the protozoan parasite Trypanosoma brucei, transmitted between mammals by the bite of a tsetse. It has been recently shown that parasites accumulate in large numbers in various organs and tissues, including the mouse testis. Whether parasites are protected from the immune system in the male reproductive organ or can be transmitted through sexual route remains unknown. Here we show that parasites can be detected by fine needle aspiration cytology of the male reproductive system in mice, and histopathological analysis revealed that T. brucei accumulates in the stroma of the epididymis, epididymal adipose tissue and fibrous tunics of the testis. No parasites were found in the lumen of intact epididymal ducts or seminiferous tubules of the testis, indicating that the large majority of the parasites are not located in immune-privileged sites. In fact, these parasites are associated with marked inflammatory cell infiltration, parasite degeneration, and severe tissue damage and rupture of epididymal ducts, which may be related with reduced fertility. Overall, we show that just like in the bloodstream and most other tissues, in the male reproductive organs, T. brucei are exposed to a strong immune response. The detection of a very high number of parasites in this organ and its accessibility opens the possibility of using fine needle aspiration cytology as a complementary diagnostic tool in Animal African Trypanosomiasis.

Toward the 2020 goal of soil-transmitted helminthiasis control and elimination

14 August 2018 - 9:00pm

by Sören L. Becker, Harvy Joy Liwanag, Jedidiah S. Snyder, Oladele Akogun, Vicente Belizario. Jr, Matthew C. Freeman, Theresa W. Gyorkos, Rubina Imtiaz, Jennifer Keiser, Alejandro Krolewiecki, Bruno Levecke, Charles Mwandawiro, Rachel L. Pullan, David G. Addiss, Jürg Utzinger

Shorter-course treatment for <i>Mycobacterium ulcerans</i> disease with high-dose rifamycins and clofazimine in a mouse model of Buruli ulcer

13 August 2018 - 9:00pm

by Paul J. Converse, Deepak V. Almeida, Rokeya Tasneen, Vikram Saini, Sandeep Tyagi, Nicole C. Ammerman, Si-Yang Li, Nicole M. Anders, Michelle A. Rudek, Jacques H. Grosset, Eric L. Nuermberger

Trial registration

ClinicalTrials.gov NCT03474198, NCT01659437

Low incidence of recurrent Buruli ulcers in treated Australian patients living in an endemic region

13 August 2018 - 9:00pm

by James W. Wynne, Timothy P. Stinear, Eugene Athan, Wojtek P. Michalski, Daniel P. O’Brien

We examined recurrent Buruli ulcer cases following treatment and assumed cure in a large cohort of Australian patients living in an endemic area. We report that while the recurrence rate was low (2.81 cases/year/1000 population), it remained similar to the estimated risk of primary infection within the general population of the endemic area (0.85–4.04 cases/year/1,000 population). The majority of recurrent lesions occurred in different regions of the body and were separated by a median time interval of 44 months. Clinical, treatment and epidemiological factors combined with whole genome sequencing of primary and recurrent isolates suggests that in most recurrent cases a re-infection was more likely as opposed to a relapse of the initial infection. Additionally, all cases occurring more than 12 months after commencement of treatment were likely re-infections. Our study provides important prognostic information for patients and their health care providers concerning the nature and risks associated with recurrent cases of Buruli ulcer in Australia.

<i>Campylobacter</i>, a zoonotic pathogen of global importance: Prevalence and risk factors in the fast-evolving chicken meat system of Nairobi, Kenya

13 August 2018 - 9:00pm

by Maud Carron, Yu-Mei Chang, Kelvin Momanyi, James Akoko, John Kiiru, Judy Bettridge, Gemma Chaloner, Jonathan Rushton, Sarah O’Brien, Nicola Williams, Eric M. Fèvre, Barbara Häsler

Campylobacteriosis is a leading foodborne zoonosis worldwide, and is frequently associated with handling and consumption of poultry meat. Various studies indicate that Campylobacter causes a substantial human disease burden in low to middle-income countries, but data regarding the organism’s epidemiology in countries like Kenya are scarce. In sub-Saharan Africa, 3.8 million deaths of children under-5 years of age are reported annually. Of those, 25% are caused by diarrheal diseases, and Campylobacter is one of the most frequently isolated bacteria from diarrheic children. With the growth of urban conglomerates, such as Kenya’s capital, Nairobi, changes in diets, food production systems, and retailing dynamics, it is likely that exposure and susceptibility to this pathogen will change. Therefore, the importance of Campylobacter disease burden in Kenya may increase further. The objectives of this study were: 1) to determine the prevalence of Campylobacter spp. in Nairobi’s small-scale chicken farms and meat retailers, and 2) to identify potential risk factors associated with its presence in those sites. The prevalence data provides the first detailed baseline for this pathogen in the urban Kenyan context. The risk factors provide context-specific insights for disease managers. A cross-sectional study of broiler, indigenous chicken farms, and chicken meat retailers, was conducted in a peri-urban, low to middle-income area (Dagoretti), and a very-low income informal settlement (Kibera) of Nairobi. Chicken faeces were collected using one pair of boot socks per farm, and 3 raw chicken meat samples were purchased per retailer. Samples were cultured for viable Campylobacter spp. using mCCDA, followed by blood agar plates in aerobic/microaerobic conditions for prevalence calculations. A questionnaire-based survey on sanitary, sourcing and selling practices was conducted at each site for risk factor identification using logistic regression analyses. A total of 171 farm premises and 53 retailers were sampled and interviewed. The prevalence results for Campylobacter spp. were between 33 to 44% for broiler and indigenous chicken farms, 60% and 64% for retailers, in Dagoretti and Kibera, respectively. Univariable logistic regression showed an association between Campylobacter spp. presence and the easiness of cleaning the display material used by the retailer. Restricting access to the flock was also associated with the pathogen’s presence. Multivariable logistic regression identified the selling of defrosted meat as a retailer risk factor (OR: 4.69; 95% CI: 1.31–19.97), calling for more investigation of the reported repetitive freezing-thawing processes and cold chain improvement options. At the farm-level, having a pen floor of material not easy to clean was found to increase the risk (OR: 2.31; 95%CI: 1.06–5.37). The relatively high prevalence of Campylobacter spp. across different areas and value chain nodes indicates a clear human exposure risk. The open nature of both small-scale broiler and indigenous chicken production practices with low biosecurity, hygiene and informal transactions, likely plays a role in this. While gradual improvement of farm biosecurity is recommended, risk factors identified suggest that consumer education and enforcement of basic food safety principles at the retailer end of the food continuum represent key targets for risk reduction in informal settings.

Complement receptor 1 (CR1, CD35) association with susceptibility to leprosy

9 August 2018 - 9:00pm

by Gabriela Canalli Kretzschmar, Luana Caroline Oliveira, Renato Mitsunori Nisihara, Thirumalaisamy P. Velavan, Sérvio Túlio Stinghen, Ewalda R. S. Stahlke, Maria Luiza Petzl-Erler, Iara José T. de Messias-Reason, Angelica Beate Winter Boldt

Background

Pathophysiological mechanisms are still incompletely understood for leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1) binds complement fragments C3b/C4b deposited on mycobacteria, mediating its entrance in macrophages. We investigated CR1 polymorphisms, gene expression and soluble CR1 levels in a case-control study with Brazilian leprosy patients, aiming to understand the role of this receptor in differential susceptibility to the disease.

Methodology

Nine polymorphisms were haplotyped by multiplex PCR-SSP in 213 leprosy patients (47% multibacillary) and 297 controls. mRNA levels were measured by qPCR and sCR1 by ELISA, in up to 80 samples.

Principal findings

Individuals with the most common recombinant haplotype harboring rs3849266*T in intron 21 and rs3737002*T in exon 26 (encoding p.1408Met of the York Yka+ antigen), presented twice higher susceptibility to leprosy (OR = 2.43, p = 0.017). Paucibacillary patients with these variants presented lower sCR1 levels, thus reducing the anti-inflammatory response (p = 0.040 and p = 0.046, respectively). Furthermore, the most ancient haplotype increased susceptibility to the multibacillary clinical form (OR = 3.04, p = 0.01) and presented the intronic rs12034383*G allele, which was associated with higher gene expression (p = 0.043), probably increasing internalization of the parasite. Furthermore, there was an inverse correlation between the the levels of sCR1 and and mannose-binding lectin (initiator molecule of the lectin pathway of complement, recognized by CR1) (R = -0.52, p = 0.007).

Conclusions

The results lead us to suggest a regulatory role for CR1 polymorphisms on mRNA and sCR1 levels, with haplotype-specific effects increasing susceptibility to leprosy, probably by enhancing parasite phagocytosis and inflammation.

Is the priority review voucher program stimulating new drug development for tropical diseases?

9 August 2018 - 9:00pm

by Kirk W. Kerr, Thomas C. Henry, Kathleen L. Miller

Congress created the tropical disease priority review voucher program to stimulate new drug development for tropical diseases. An analysis of the pharmaceutical pipeline indicates that the development of drugs for these tropical diseases has increased. However, the effects of the program are not uniform across all diseases, as malaria and tuberculosis have seen significant new drug development, while other diseases have not.

Patients with cystic echinococcosis in the three national referral centers of Mongolia: A model for CE management assessment

9 August 2018 - 9:00pm

by Bolor Bold, Jan Hattendorf, Agiimaa Shagj, Bayar Tserendovdon, Tsendjav Ayushkhuu, Amgalan Luvsandorj, Jakob Zinsstag, Thomas Junghanss

Background

Mongolia is one of the endemic countries for cystic echinococcosis (CE), a zoonotic disease caused by the larval stage of Echinococcus granulosus. The goal of this study is to describe the current clinical management of CE in Mongolia, to capture the distribution of cyst stages of patients treated, and to contrast current practice with WHO-IWGE expert consensus.

Methods

Hospital records of CE patients treated between 2008 and 2015 at the three state hospitals and fulfilling the inclusion criterion ‘discharge diagnosis CE’ (ICD 10 code B.67.0–67.9) were reviewed. Demographical, geographical, clinical and ultrasonography (US) data were extracted and analyzed. The annual surgical incidence was estimated. The digital copies of US cyst images were independently staged by three international experts following the WHO CE cyst classification to determine the proportions of patients which ideally would have been assigned to the WHO recommended treatment modalities surgery, percutaneous, medical (benzimidazole) treatment and watch & wait.

Results

A total of 290 patient records fulfilled the inclusion criteria of the study. 45.7% of patients were below 15 years of age. 73.6% of CE cysts were located in abdominal organs, predominately liver. US images of 84 patients were staged and assessed for inter-rater agreement. The average raw agreement was 77.2%. Unweighted Kappa coefficient and weighted Kappa was 0.57 and 0.59, respectively. Mean proportions of images judged as stages CE1, CE2, CE3a, CE3b, CE4 and CL were 0.59, 0.01, 0.19, 0.08, 0.03 and 0.11, respectively. 40 cysts met the inclusion criteria of treatment modality analysis. The mean proportions of cases with a single cyst assigned to medical, percutaneous treatment, surgery and watch & wait were 52.5% (95% CI 42–65), 25.8% (95% CI 15–30), 5.1% (95% CI 0–10) and 3.3% (95% CI 0.0–10), respectively. 13.3% (95% CI 5–25) of cysts were staged as CL and therefore assigned to further diagnostic requirement.

Conclusion

WHO CE cyst classification and WHO-IWGE expert consensus on clinical CE management is not implemented in Mongolia. This results in exclusively surgical treatment, an unnecessary high risk approach for the majority of patients who could receive medical, percutaneous treatment or observation (watch & wait). Introduction of WHO-IWGE expert consensus and training in ultrasound CE cyst staging would be highly beneficial for patients and the health care services.

Blockade of dengue virus entry into myeloid cells by endocytic inhibitors in the presence or absence of antibodies

9 August 2018 - 9:00pm

by Ana C. Carro, Luana E. Piccini, Elsa B. Damonte

Background

Dengue is the most prevalent arthropod-borne viral human disease in tropical and subtropical regions, caused by four dengue virus (DENV) serotypes. In spite of the increasing global incidence, no specific antiviral therapy is available. Cells of the mononuclear phagocyte lineage are the main targets either for direct antibody (Ab)-independent or Ab-mediated human DENV infection, usually associated to the severe forms of disease. Since the virus entry may be a convenient therapeutic alternative, this study aimed to investigate the mode of DENV internalization into myeloid cells in the absence and presence of DENV Ab and evaluate the inhibitory activity of diverse biochemical inhibitors of endocytosis.

Methodology/principal findings

By infectivity assays and quantitative RT-PCR determinations, it was demonstrated that DENV-2 entry into U937 and K562 cells in the absence of Ab was highly inhibited by the early treatment with ammonium chloride, chlorpromazine and dynasore, but it was not affected by methyl-β-cyclodextrin, indicating that DENV-2 utilizes a low pH-dependent, clathrin- and dynamin-mediated endocytic infectious pathway for the direct entry into both human myeloid cells. To study the Ab-mediated entry of DENV, the experimental conditions for enhancement of infection were established by inoculating immune complexes formed with DENV-2 and the Ab 2H2 or 3H5. The internalization of DENV-2-2H2 or DENV-2-3H5 complexes in both myeloid cells was also dependent on acid pH and dynamin but a differential requirement of the clathrin-mediated endocytic route was observed depending on the FcγR involved in the complex uptake: the infection through FcγRII was dependent on clathrin-coated vesicles whereas the internalization pathway mediated by FcγRI was independent of clathrin. This property was not serotype-specific.

Conclusions/significance

DENV entry into myeloid cells in the absence or presence of Ab can be blocked by diverse biochemical inhibitors affecting the cellular factors involved in endocytosis. The identification of the virus-host interactions involved in virus penetration may allow the finding of host-targeted antivirals widely active against diverse pathogenic flaviviruses with similar requirements for virus entry.

Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia

9 August 2018 - 9:00pm

by Ivonne Martin, Yenny Djuardi, Erliyani Sartono, Bruce A. Rosa, Taniawati Supali, Makedonka Mitreva, Jeanine J. Houwing-Duistermaat, Maria Yazdanbakhsh

Background

Microbiome studies suggest the presence of an interaction between the human gut microbiome and soil-transmitted helminth. Upon deworming, a complex interaction between the anthelminthic drug, helminths and microbiome composition might occur. To dissect this, we analyse the changes that take place in the gut bacteria profiles in samples from a double blind placebo controlled trial conducted in an area endemic for soil transmitted helminths in Indonesia.

Methods

Either placebo or albendazole were given every three months for a period of one and a half years. Helminth infection was assessed before and at 3 months after the last treatment round. In 150 subjects, the bacteria were profiled using the 454 pyrosequencing. Statistical analysis was performed cross-sectionally at pre-treatment to assess the effect of infection, and at post-treatment to determine the effect of infection and treatment on microbiome composition using the Dirichlet-multinomial regression model.

Results

At a phylum level, at pre-treatment, no difference was seen in microbiome composition in terms of relative abundance between helminth-infected and uninfected subjects and at post-treatment, no differences were found in microbiome composition between albendazole and placebo group. However, in subjects who remained infected, there was a significant difference in the microbiome composition of those who had received albendazole and placebo. This difference was largely attributed to alteration of Bacteroidetes. Albendazole was more effective against Ascaris lumbricoides and hookworms but not against Trichuris trichiura, thus in those who remained infected after receiving albendazole, the helminth composition was dominated by T. trichiura.

Discussion

We found that overall, albendazole does not affect the microbiome composition. However, there is an interaction between treatment and helminths as in subjects who received albendazole and remained infected there was a significant alteration in Bacteroidetes. This helminth-albendazole interaction needs to be studied further to fully grasp the complexity of the effect of deworming on the microbiome.

Trial registration

ISRCTN Registy, ISRCTN83830814.

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