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Ensuring no one is left behind: Urgent action required to address implementation challenges for NTD control and elimination

PLoS Neglected Tropical Diseases News - 7 June 2018 - 9:00pm

by Alison Krentel, Margaret Gyapong, Olumide Ogundahunsi, Mary Amuyunzu-Nyamongo, Deborah A. McFarland

Risk factors for human acute leptospirosis in northern Tanzania

PLoS Neglected Tropical Diseases News - 7 June 2018 - 9:00pm

by Michael J. Maze, Shama Cash-Goldwasser, Matthew P. Rubach, Holly M. Biggs, Renee L. Galloway, Katrina J. Sharples, Kathryn J. Allan, Jo E. B. Halliday, Sarah Cleaveland, Michael C. Shand, Charles Muiruri, Rudovick R. Kazwala, Wilbrod Saganda, Bingileki F. Lwezaula, Blandina T. Mmbaga, Venance P. Maro, John A. Crump

Introduction

Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania.

Methods

We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012–2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables.

Results

We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis.

Conclusions

In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease.

Long-read whole genome sequencing and comparative analysis of six strains of the human pathogen <i>Orientia tsutsugamushi</i>

PLoS Neglected Tropical Diseases News - 6 June 2018 - 9:00pm

by Elizabeth M. Batty, Suwittra Chaemchuen, Stuart Blacksell, Allen Richards, Daniel Paris, Rory Bowden, Caroline Chan, Ramkumar Lachumanan, Nicholas Day, Peter Donnelly, Swaine Chen, Jeanne Salje

Background

Orientia tsutsugamushi is a clinically important but neglected obligate intracellular bacterial pathogen of the Rickettsiaceae family that causes the potentially life-threatening human disease scrub typhus. In contrast to the genome reduction seen in many obligate intracellular bacteria, early genetic studies of Orientia have revealed one of the most repetitive bacterial genomes sequenced to date. The dramatic expansion of mobile elements has hampered efforts to generate complete genome sequences using short read sequencing methodologies, and consequently there have been few studies of the comparative genomics of this neglected species.

Results

We report new high-quality genomes of O. tsutsugamushi, generated using PacBio single molecule long read sequencing, for six strains: Karp, Kato, Gilliam, TA686, UT76 and UT176. In comparative genomics analyses of these strains together with existing reference genomes from Ikeda and Boryong strains, we identify a relatively small core genome of 657 genes, grouped into core gene islands and separated by repeat regions, and use the core genes to infer the first whole-genome phylogeny of Orientia.

Conclusions

Complete assemblies of multiple Orientia genomes verify initial suggestions that these are remarkable organisms. They have larger genomes compared with most other Rickettsiaceae, with widespread amplification of repeat elements and massive chromosomal rearrangements between strains. At the gene level, Orientia has a relatively small set of universally conserved genes, similar to other obligate intracellular bacteria, and the relative expansion in genome size can be accounted for by gene duplication and repeat amplification. Our study demonstrates the utility of long read sequencing to investigate complex bacterial genomes and characterise genomic variation.

Chikungunya outbreak (2017) in Bangladesh: Clinical profile, economic impact and quality of life during the acute phase of the disease

PLoS Neglected Tropical Diseases News - 6 June 2018 - 9:00pm

by Mohammad Sorowar Hossain, Md. Mahbub Hasan, Muhammad Sougatul Islam, Salequl Islam, Miliva Mozaffor, Md. Abdullah Saeed Khan, Nova Ahmed, Waheed Akhtar, Shahanaz Chowdhury, S. M. Yasir Arafat, Md. Abdul Khaleque, Zohora Jameela Khan, Tashmim Farhana Dipta, Shah Md. Zahurul Haque Asna, Md. Akram Hossain, KM Sultanul Aziz, Abdullah Al Mosabbir, Enayetur Raheem

Background

Chikungunya virus causes mosquito-transmitted infection that leads to extensive morbidity affecting substantial quality of life. Disease associated morbidity, quality of life, and financial loss are seldom reported in resources limited countries, such as Bangladesh. We reported the acute clinical profile, quality of life and consequent economic burden of the affected individuals in the recent chikungunya outbreak (May to September 2017) in Dhaka city, Bangladesh.

Methods

We conducted a cross-sectional study during the peak of chikungunya outbreak (July 24 to August 5, 2017) to document the clinical profiles of confirmed cases (laboratory test positive) and probable cases diagnosed by medical practitioners. Data related to clinical symptoms, treatment cost, loss of productivity due to missing work days, and quality of life during their first two-weeks of symptom onset were collected via face to face interview using a structured questionnaire. World Health Organization endorsed questionnaire was used to assess the quality of life.

Results

A total of 1,326 chikungunya cases were investigated. Multivariate analysis of major clinical variables showed no statistically significant differences between confirmed and probable cases. All the patients reported joint pain and fever. Other more frequently reported symptoms include headache, loss of appetite, rash, myalgia, and itching. Arthralgia was polyarticular in 56.3% of the patients. Notably, more than 70% patients reported joint pain as the first presenting symptom. About 83% of the patients reported low to very low overall quality of life. Nearly half of the patients lost more than 10 days of productivity due to severe arthropathy.

Conclusions

This study represents one of the largest samples studied so far around the world describing the clinical profile of chikungunya infection. Our findings would contribute to establish an effective syndromic surveillance system for early detection and timely public health intervention of future chikungunya outbreaks in resource-limited settings like Bangladesh.

Spatiotemporal variation of the association between climate dynamics and HFRS outbreaks in Eastern China during 2005-2016 and its geographic determinants

PLoS Neglected Tropical Diseases News - 6 June 2018 - 9:00pm

by Junyu He, George Christakos, Jiaping Wu, Bernard Cazelles, Quan Qian, Di Mu, Yong Wang, Wenwu Yin, Wenyi Zhang

Background

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-associated zoonosis caused by hantavirus. The HFRS was initially detected in northeast China in 1931, and since 1955 it has been detected in many regions of the country. Global climate dynamics influences HFRS spread in a complex nonlinear way. The quantitative assessment of the spatiotemporal variation of the “HFRS infections-global climate dynamics” association at a large geographical scale and during a long time period is still lacking.

Methods and findings

This work is the first study of a recently completed dataset of monthly HFRS cases in Eastern China during the period 2005–2016. A methodological synthesis that involves a time-frequency technique, a composite space-time model, hotspot analysis, and machine learning is implemented in the study of (a) the association between HFRS incidence spread and climate dynamics and (b) the geographic factors impacting this association over Eastern China during the period 2005–2016. The results showed that by assimilating core and city-specific knowledge bases the synthesis was able to depict quantitatively the space-time variation of periodic climate-HFRS associations at a large geographic scale and to assess numerically the strength of this association in the area and period of interest. It was found that the HFRS infections in Eastern China has a strong association with global climate dynamics, in particular, the 12, 18 and 36 mos periods were detected as the three main synchronous periods of climate dynamics and HFRS distribution. For the 36 mos period (which is the period with the strongest association), the space-time correlation pattern of the association strength indicated strong temporal but rather weak spatial dependencies. The generated space-time maps of association strength and association hotspots provided a clear picture of the geographic variation of the association strength that often-exhibited cluster characteristics (e.g., the south part of the study area displays a strong climate-HFRS association with non-point effects, whereas the middle-north part displays a weak climate-HFRS association). Another finding of this work is the upward climate-HFRS coherency trend for the past few years (2013–2015) indicating that the climate impacts on HFRS were becoming increasingly sensitive with time. Lastly, another finding of this work is that geographic factors affect the climate-HFRS association in an interrelated manner through local climate or by means of HFRS infections. In particular, location (latitude, distance to coastline and longitude), grassland and woodland are the geographic factors exerting the most noticeable effects on the climate-HFRS association (e.g., low latitude has a strong effect, whereas distance to coastline has a wave-like effect).

Conclusions

The proposed synthetic quantitative approach revealed important aspects of the spatiotemporal variation of the climate-HFRS association in Eastern China during a long time period, and identified the geographic factors having a major impact on this association. Both findings could improve public health policy in an HFRS-torn country like China. Furthermore, the synthetic approach developed in this work can be used to map the space-time variation of different climate-disease associations in other parts of China and the World.

Shortening intradermal rabies post-exposure prophylaxis regimens to 1 week: Results from a phase III clinical trial in children, adolescents and adults

PLoS Neglected Tropical Diseases News - 6 June 2018 - 9:00pm

by Phirangkul Kerdpanich, Pornthep Chanthavanich, Mari Rose De Los Reyes, Jodor Lim, Delia Yu, Ma. Cecilia Ama, Zenaida Mojares, Daniela Casula, Ashwani Kumar Arora, Michele Pellegrini

Background

This phase III clinical trial compared the immunogenicity and safety of a purified chick-embryo cell rabies vaccine (PCECV) administered according to a shortened post-exposure prophylaxis (PEP) 4-site/1-week intradermal regimen, compared with the currently recommended 2-site/Thai Red Cross (TRC).

Methodology/Principal findings

This controlled, open-label, multi-center study (NCT02177032) enrolled healthy individuals ≥1 year of age, randomized into 4 groups to receive intradermal PCECV according to one of the 2 regimens, with or without human rabies immunoglobulin (HRIG) administration at first visit (in adults only). Rabies virus neutralizing antibody (RVNA) concentrations and percentages of participants with RVNA concentrations ≥0.5 IU/mL (considered as adequate concentrations following PEP) were assessed up to day (D) 365 post-first vaccination. Non-inferiority of the 4-site/1-week regimen to the 2-site/TRC regimen was demonstrated if at D49, the lower limit of the 95% confidence interval (CI) for the difference between groups in the percentage of participants with adequate RVNA concentrations was >-5%. Of the 443 participants receiving the 4-site/1-week regimen, 88 adults received HRIG; 442 participants received the 2-site/TRC regimen (88 with HRIG). All participants achieved adequate RVNA concentrations by D14. At D49, the difference in percentage of participants with adequate RVNA concentrations between the 4-site/1-week and the 2-site/TRC groups was -1 (95%CI: -2.4–0.0); thus, non-inferiority was concluded. RVNA geometric mean concentrations were 18 IU/mL in 4-site/1-week groups and 12 IU/mL in 2-site/TRC groups at D14, and subsequently declined in all groups. RVNA concentrations were consistently lower in adults with HRIG administration than in those without. The 2 regimens had similar safety profiles. Of the 15 serious adverse events reported in 4-site/1-week groups and 19 in 2-site/TRC groups, none were vaccination-related.

Significance

The data suggest that the 4-site/1-week regimen might be an alternative to current recommendations, with potential benefits in terms of improved cost-efficiency and compliance to vaccination.

Laboratory confirmation of Buruli ulcer cases in Ghana, 2008-2016

PLoS Neglected Tropical Diseases News - 5 June 2018 - 9:00pm

by Dorothy Yeboah-Manu, Sammy Yaw Aboagye, Prince Asare, Adwoa Asante-Poku, Kobina Ampah, Emelia Danso, Evelyn Owusu-Mireku, Zuleihatu Nakobu, Edwin Ampadu

Background

Buruli ulcer (BU), a necrotizing skin infection caused by Mycobacterium ulcerans is the third most important mycobacterial disease globally after tuberculosis and leprosy in immune competent individuals. This study reports on the retrospective analyses of microbiologically confirmed Buruli ulcer (BU) cases in seventy-five health facilities in Ghana.

Method/Principal findings

Pathological samples were collected from BU lesions and transported either through courier services or by car directly to the laboratory. Samples were processed and analysed by IS2404 PCR, culture and Ziehl-Neelsen staining for detection of acid-fast bacilli. From 2008 to 2016, we analysed by PCR, 2,287 samples of 2,203 cases from seventy-five health facilities in seven regions of Ghana (Ashanti, Brong Ahafo, Central, Eastern Greater Accra, Northern and Volta). The mean annual positivity rate was 46.2% and ranged between 14.6% and 76.2%. The yearly positivity rates from 2008 to 2016 were 52.3%, 76.2%, 56.7%, 53.8, 41.2, 41.5%, 22.9, 28.5 and 14.6% respectively. Of the 1,020 confirmed cases, the ratio of female to male was 518 and 502 respectively. Patients who were 15 years of age and below accounted for 39.8% of all cases. The median age was 20 years (IQR = 10–43). Ulcerative lesions were 69.2%, nodule (9.6%), plaque (2.9%), oedema (2.5%), osteomyelitis (1.1%), ulcer/oedema (9.5%) and ulcer/plaque (5.2%). Lesions frequently occurred on the lower limbs (57%) followed by the upper limbs (38%), the neck and head (3%) and the least found on the abdomen (2%).

Conclusions/Significance

Our findings show a decline in microbiological confirmed rates over the years and therefore call for intensive education on case recognition to prevent over-diagnosis as BU cases decline.

Toxoplasmosis seroprevalence in rheumatoid arthritis patients: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 5 June 2018 - 9:00pm

by Zahra Hosseininejad, Mehdi Sharif, Shahabeddin Sarvi, Afsaneh Amouei, Seyed Abdollah Hosseini, Tooran Nayeri Chegeni, Davood Anvari, Reza Saberi, Shaban Gohardehi, Azadeh Mizani, Mitra Sadeghi, Ahmad Daryani

Background

Toxoplasmosis is a cosmopolitan infection caused by an intracellular obligatory protozoan, Toxoplasma gondii. Infection to this parasite in immunocompetent patients is usually asymptomatic, but today it is believed that the infection can be a risk factor for a variety of diseases, including rheumatoid arthritis (RA). RA is an autoimmune disease and the most common type of inflammatory arthritis that is a major cause of disability. The aim of this systematic review and meta-analysis was to address the association between RA and toxoplasmosis in light of the available research.

Methods

Based on the keywords, a systematic search of eight databases was conducted to retrieve the relevant English-language articles. Then, the studies were screened based on the inclusion and exclusion criteria. The random effect model was used to calculate the odds ratio (OR) using forest plot with 95% confidence interval (CI).

Results

Overall, 4168 Individual, extracted from 9 articles were included for systematic review evaluation, with 1369 RA patients (46% positive toxoplasmosis) and 2799 individuals as controls (21% positive toxoplasmosis). Then, eight articles (10 datasets) were used for meta-analysis (1244 rheumatoid arthritis patients and 2799 controls). By random effect model, the combined OR was 3.30 (95% CI: 2.05 to 5.30) with P < 0.0001.

Conclusion

Although toxoplasmosis could be considered as a potential risk factor for rheumatoid arthritis, more and better quality studies are needed to determine the effect of T. gondii infection on induction or exacerbation of RA. Our study was registered at the International Prospective Register of Systematic Reviews (PROSPERO; code: CRD42017069384).

The small non-coding RNA response to virus infection in the <i>Leishmania</i> vector <i>Lutzomyia longipalpis</i>

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Flávia Viana Ferreira, Eric Roberto Guimarães Rocha Aguiar, Roenick Proveti Olmo, Karla Pollyanna Vieira de Oliveira, Emanuele Guimarães Silva, Maurício Roberto Viana Sant'Anna, Nelder de Figueiredo Gontijo, Erna Geessien Kroon, Jean Luc Imler, João Trindade Marques

Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.

High incidence of leptospirosis in an observational study of hospital outpatients in Vanuatu highlights the need for improved awareness and diagnostic capacities

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Junior George Pakoa, Marie-Estelle Soupé-Gilbert, Dominique Girault, Dexter Takau, Justina Gaviga, Ann-Claire Gourinat, Arnaud Tarantola, Cyrille Goarant

Background

Estimates of leptospirosis morbidity identified Oceania as the region with highest burden. Besides Australia and New Zealand, Oceania is home of Pacific Island Countries and Territories, most of which are developing countries facing a number of challenges. Their archipelago geography notably affects health infrastructure and access to healthcare. Although human leptospirosis was formerly identified in Vanuatu, there is a lack of knowledge of this disease in the country. We aimed to identify leptospirosis in outpatients visiting the hospital.

Methodology/Principal findings

We conducted a clinical study to investigate leptospirosis as a cause of non-malarial acute febrile illness in Vanuatu. A total 161 outpatients visiting the outpatient clinics at Port Vila Central Hospital for internal medicine were recruited over 20 month. We showed that leptospirosis significantly affects humans in Vanuatu: 12 cases were confirmed by real-time PCR on acute blood samples (n = 5) or by high serology titers evidencing a recent infection (MAT titer ≥800 or ELISA≥18 Units, n = 7). A high rate of positive serology was also evidenced, by MAT (100 Conclusions/Significance

The high numbers of both seropositive patients and acute leptospirosis cases observed in outpatients visiting Port Vila Central Hospital suggest a high exposure to pathogenic Leptospira in the population studied. The MAT serology pointing to serogroup Australis as well as exposure history suggest that livestock animals largely contribute to the burden of human leptospirosis in Vanuatu. The analysis of residential and travel data suggests that the risk might even be higher in other islands of the Vanuatu archipelago. Altogether, our study emphasizes the need to increase awareness and build laboratory capacity to improve the medical care of leptospirosis in Vanuatu.

Diagnostic comparison between FECPAK<sup>G2</sup> and the Kato-Katz method for analyzing soil-transmitted helminth eggs in stool

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Wendelin Moser, Oliver Bärenbold, Greg J. Mirams, Piet Cools, Johnny Vlaminck, Said M. Ali, Shaali M. Ame, Jan Hattendorf, Penelope Vounatsou, Bruno Levecke, Jennifer Keiser

Background

Over one billion people are infected with soil-transmitted helminths (STH), i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura. For estimating drug efficacy and monitoring anthelminthic drug resistance, accurate diagnostic methods are critical. FECPAKG2 is a new remote-diagnostic tool used in veterinary medicine, which produces an image of the stool sample that can be stored on an internet cloud. We compared for the first time FECPAKG2 with the recommended Kato-Katz method.

Methodology/Principal findings

Two stool samples were collected from adolescent participants (age 15–18 years) at baseline and 14 to 21 days after treatment in the framework of a randomized clinical trial on Pemba Island, Tanzania. Stool samples were analyzed with different diagnostic efforts: i) one or ii) two Kato-Katz thick smears from the first sample, iii) two Kato-Katz thick smears from two samples and iv) FECPAKG2 from the first sample. Parameters were calculated based on a hierarchical Bayesian egg count model.Complete data for all diagnostic efforts were available from 615 participants at baseline and 231 hookworm-positive participants at follow-up. At baseline FECPAKG2 revealed a sensitivity of 75.6% (72.0–77.7) for detecting A. lumbricoides, 71.5% (67.4–95.3) for hookworm and 65.8% (64.9–66.2) for T. trichiura, which was significantly lower (all p<0.05) than any of the Kato-Katz methods and highly dependent on infection intensity. Despite that the egg counts based on FECPAKG2 were relatively lower compared to Kato-Katz by a ratio of 0.38 (0.32–0.43) for A. lumbricoides, 0.36 (0.33–0.40) for hookworm and 0.08 (0.07–0.09) for T. trichiura, the egg reduction rates (ERR) were correctly estimated with FECPAKG2.

Conclusions/Significance

The sensitivity to identify any STH infection was considerably lower for FECPAKG2 compared to Kato-Katz. Following rigorous development, FECPAKG2 might be an interesting tool with unique features for epidemiological and clinical studies.

The burden of Neglected Tropical Diseases in Brazil, 1990-2016: A subnational analysis from the Global Burden of Disease Study 2016

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Francisco Rogerlândio Martins-Melo, Mariângela Carneiro, Alberto Novaes Ramos Jr., Jorg Heukelbach, Antonio Luiz Pinho Ribeiro, Guilherme Loureiro Werneck

Background

Neglected Tropical Diseases (NTDs) are important causes of morbidity, disability, and mortality among poor and vulnerable populations in several countries worldwide, including Brazil. We present the burden of NTDs in Brazil from 1990 to 2016 based on findings from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016).

Methodology

We extracted data from GBD 2016 to assess years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for NTDs by sex, age group, causes, and Brazilian states, from 1990 to 2016. We included all NTDs that were part of the priority list of the World Health Organization (WHO) in 2016 and that are endemic/autochthonous in Brazil. YLDs were calculated by multiplying the prevalence of sequelae multiplied by its disability weight. YLLs were estimated by multiplying each death by the reference life expectancy at each age. DALYs were computed as the sum of YLDs and YLLs.

Principal findings

In 2016, there were 475,410 DALYs (95% uncertainty interval [UI]: 337,334–679,482; age-standardized rate of 232.0 DALYs/100,000 population) from the 12 selected NTDs, accounting for 0.8% of national all-cause DALYs. Chagas disease was the leading cause of DALYs among all NTDs, followed by schistosomiasis and dengue. The sex-age-specific NTD burden was higher among males and in the youngest and eldest (children <1 year and those aged ≥70 years). The highest age-standardized DALY rates due to all NTDs combined at the state level were observed in Goiás (614.4 DALYs/100,000), Minas Gerais (433.7 DALYs/100,000), and Distrito Federal (430.0 DALYs/100,000). Between 1990 and 2016, the national age-standardized DALY rates from all NTDs decreased by 45.7%, with different patterns among NTD causes and Brazilian states. Most NTDs decreased in the period, with more pronounced reduction in DALY rates for onchocerciasis, lymphatic filariasis, and rabies. By contrast, age-standardized DALY rates due to dengue, visceral leishmaniasis, and trichuriasis increased substantially. Age-standardized DALY rates decreased for most Brazilian states, increasing only in the states of Amapá, Ceará, Rio Grande do Norte, and Sergipe.

Conclusions/Significance

GBD 2016 findings show that, despite the reduction in disease burden, NTDs are still important and preventable causes of disability and premature death in Brazil. The data call for renewed and comprehensive efforts to control and prevent the NTD burden in Brazil through evidence-informed and efficient and affordable interventions. Multi-sectoral and integrated control and surveillance measures should be prioritized, considering the population groups and geographic areas with the greatest morbidity, disability, and most premature deaths due to NTDs in the country.

Persistence of Yellow fever virus outside the Amazon Basin, causing epidemics in Southeast Brazil, from 2016 to 2018

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Izabela Maurício de Rezende, Lívia Sacchetto, Érica Munhoz de Mello, Pedro Augusto Alves, Felipe Campos de Melo Iani, Talita Émile Ribeiro Adelino, Myrian Morato Duarte, Ana Luísa Furtado Cury, André Felipe Leal Bernardes, Tayrine Araujo Santos, Leonardo Soares Pereira, Maria Rita Teixeira Dutra, Dario Brock Ramalho, Benoit de Thoisy, Erna Geessien Kroon, Giliane de Souza Trindade, Betânia Paiva Drumond

Background

Yellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group.

Methodology/Principal findings

Aiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017–2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage YFV-BR_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014–2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil.

Conclusions

The results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.

Improving early epidemiological assessment of emerging <i>Aedes</i>-transmitted epidemics using historical data

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Julien Riou, Chiara Poletto, Pierre-Yves Boëlle

Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes-transmitted epidemics help improve these predictions. The approach was applied to the 2015–2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (Chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks.

Improving spatial prediction of <i>Schistosoma haematobium</i> prevalence in southern Ghana through new remote sensors and local water access profiles

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Alexandra V. Kulinkina, Yvonne Walz, Magaly Koch, Nana-Kwadwo Biritwum, Jürg Utzinger, Elena N. Naumova

Background

Schistosomiasis is a water-related neglected tropical disease. In many endemic low- and middle-income countries, insufficient surveillance and reporting lead to poor characterization of the demographic and geographic distribution of schistosomiasis cases. Hence, modeling is relied upon to predict areas of high transmission and to inform control strategies. We hypothesized that utilizing remotely sensed (RS) environmental data in combination with water, sanitation, and hygiene (WASH) variables could improve on the current predictive modeling approaches.

Methodology

Schistosoma haematobium prevalence data, collected from 73 rural Ghanaian schools, were used in a random forest model to investigate the predictive capacity of 15 environmental variables derived from RS data (Landsat 8, Sentinel-2, and Global Digital Elevation Model) with fine spatial resolution (10–30 m). Five methods of variable extraction were tested to determine the spatial linkage between school-based prevalence and the environmental conditions of potential transmission sites, including applying the models to known human water contact locations. Lastly, measures of local water access and groundwater quality were incorporated into RS-based models to assess the relative importance of environmental and WASH variables.

Principal findings

Predictive models based on environmental characterization of specific locations where people contact surface water bodies offered some improvement as compared to the traditional approach based on environmental characterization of locations where prevalence is measured. A water index (MNDWI) and topographic variables (elevation and slope) were important environmental risk factors, while overall, groundwater iron concentration predominated in the combined model that included WASH variables.

Conclusions/Significance

The study helps to understand localized drivers of schistosomiasis transmission. Specifically, unsatisfactory water quality in boreholes perpetuates reliance of surface water bodies, indirectly increasing schistosomiasis risk and resulting in rapid reinfection (up to 40% prevalence six months following preventive chemotherapy). Considering WASH-related risk factors in schistosomiasis prediction can help shift the focus of control strategies from treating symptoms to reducing exposure.

Molecular characterisation of <i>Vibrio cholera</i> responsible for cholera epidemics in Uganda by PCR, MLVA and WGS

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Godfrey Bwire, David A. Sack, Mathieu Almeida, Shan Li, Joseph B. Voeglein, Amanda Kay Debes, Atek Kagirita, Ambrose Wabwire Buyinza, Christopher Garimoi Orach, O. Colin Stine

Background

For almost 50 years sub-Saharan Africa, including Uganda, has experienced several outbreaks due to Vibrio cholerae. Our aim was to determine the genetic relatedness and spread of strains responsible for cholera outbreaks in Uganda.

Methodology/Principal findings

Sixty-three V. cholerae isolates collected from outbreaks in Uganda between 2014 and 2016 were tested using multiplex polymerase chain reaction (PCR), multi-locus variable number of tandem repeat analysis (MLVA) and whole genome sequencing (WGS). Three closely related MLVA clonal complexes (CC) were identified: CC1, 32% (20/63); CC2, 40% (25/63) and CC3, 28% (18/63). Each CC contained isolates from a different WGS clade. These clades were contained in the third wave of the 7th cholera pandemic strain, two clades were contained in the transmission event (T)10 lineage and other in T13. Analysing the dates and genetic relatedness revealed the V. cholerae genetic lineages spread between districts within Uganda and across national borders.

Conclusion

The V. cholerae strains showed local and regional transmission within Uganda and the East African region. To prevent, control and eliminate cholera, these countries should implement strong cross-border collaboration and regional coordination of preventive activities.

Transrenal DNA-based diagnosis of <i>Strongyloides stercoralis</i> (Grassi, 1879) infection: Bayesian latent class modeling of test accuracy

PLoS Neglected Tropical Diseases News - 1 June 2018 - 9:00pm

by Alejandro J. Krolewiecki, Artemis Koukounari, Miryam Romano, Nicolas N. Caro, Alan L. Scott, Pedro Fleitas, Rubin Cimino, Clive J. Shiff

For epidemiological work with soil transmitted helminths the recommended diagnostic approaches are to examine fecal samples for microscopic evidence of the parasite. In addition to several logistical and processing issues, traditional diagnostic approaches have been shown to lack the sensitivity required to reliably identify patients harboring low-level infections such as those associated with effective mass drug intervention programs. In this context, there is a need to rethink the approaches used for helminth diagnostics. Serological methods are now in use, however these tests are indirect and depend on individual immune responses, exposure patterns and the nature of the antigen. However, it has been demonstrated that cell-free DNA from pathogens and cancers can be readily detected in patient’s urine which can be collected in the field, filtered in situ and processed later for analysis. In the work presented here, we employ three diagnostic procedures—stool examination, serology (NIE-ELISA) and PCR-based amplification of parasite transrenal DNA from urine–to determine their relative utility in the diagnosis of S. stercoralis infections from 359 field samples from an endemic area of Argentina. Bayesian Latent Class analysis was used to assess the relative performance of the three diagnostic procedures. The results underscore the low sensitivity of stool examination and support the idea that the use of serology combined with parasite transrenal DNA detection may be a useful strategy for sensitive and specific detection of low-level strongyloidiasis.

A FRET flow cytometry method for monitoring cytosolic and glycosomal glucose in living kinetoplastid parasites

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Charles M. Voyton, Yijian Qiu, Meredith T. Morris, P. Christine Ackroyd, Jimmy Suryadi, Logan Crowe, James C. Morris, Kenneth A. Christensen

The bloodstream lifecycle stage of the kinetoplastid parasite Trypanosoma brucei relies solely on glucose metabolism for ATP production, which occurs in peroxisome-like organelles (glycosomes). Many studies have been conducted on glucose uptake and metabolism, but none thus far have been able to monitor changes in cellular and organellar glucose concentration in live parasites. We have developed a non-destructive technique for monitoring changes in cytosolic and glycosomal glucose levels in T. brucei using a fluorescent protein biosensor (FLII12Pglu-700μδ6) in combination with flow cytometry. T. brucei parasites harboring the biosensor allowed for observation of cytosolic glucose levels. Appending a type 1 peroxisomal targeting sequence caused biosensors to localize to glycosomes, which enabled observation of glycosomal glucose levels. Using this approach, we investigated cytosolic and glycosomal glucose levels in response to changes in external glucose or 2-deoxyglucose concentration. These data show that procyclic form and bloodstream form parasites maintain different glucose concentrations in their cytosol and glycosomes. In procyclic form parasites, the cytosol and glycosomes maintain indistinguishable glucose levels (3.4 ± 0.4mM and 3.4 ± 0.5mM glucose respectively) at a 6.25mM external glucose concentration. In contrast, bloodstream form parasites maintain glycosomal glucose levels that are ~1.8-fold higher than the surrounding cytosol, equating to 1.9 ± 0.6mM in cytosol and 3.5 ± 0.5mM in glycosomes. While the mechanisms of glucose transport operating in the glycosomes of bloodstream form T. brucei remain unresolved, the methods described here will provide a means to begin to dissect the cellular machinery required for subcellular distribution of this critical hexose.

Zika virus infection in Nicaraguan households

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Raquel Burger-Calderon, Karla Gonzalez, Sergio Ojeda, José Victor Zambrana, Nery Sanchez, Cristhiam Cerpas Cruz, Harold Suazo Laguna, Fausto Bustos, Miguel Plazaola, Brenda Lopez Mercado, Douglas Elizondo, Sonia Arguello, Jairo Carey Monterrey, Andrea Nuñez, Josefina Coloma, Jesse J. Waggoner, Aubree Gordon, Guillermina Kuan, Angel Balmaseda, Eva Harris

Zika virus (ZIKV) infection recently caused major epidemics in the Americas and is linked to congenital birth defects and Guillain-Barré Syndrome. A pilot study of ZIKV infection in Nicaraguan households was conducted from August 31 to October 21, 2016, in Managua, Nicaragua. We enrolled 33 laboratory-confirmed Zika index cases and their household members (109 contacts) and followed them on days 3–4, 6–7, 9–10, and 21, collecting serum/plasma, urine, and saliva specimens along with clinical, demographic, and socio-economic status information. Collected samples were processed by rRT-PCR to determine viral load (VL) and duration of detectable ZIKV RNA in human bodily fluids. At enrollment, 11 (10%) contacts were ZIKV rRT-PCR-positive and 23 (21%) were positive by IgM antibodies; 3 incident cases were detected during the study period. Twenty of 33 (61%) index households had contacts with ZIKV infection, with an average of 1.9 (range 1–6) positive contacts per household, and in 60% of these households, ≥50% of the members were positive for ZIKV infection. Analysis of clinical information allowed us to estimate the symptomatic to asymptomatic (S:A) ratio of 14:23 (1:1.6) among the contacts, finding 62% of the infections to be asymptomatic. The maximum number of days during which ZIKV RNA was detected was 7 days post-symptom onset in saliva and serum/plasma and 22 days in urine. Overall, VL levels in serum/plasma, saliva, and urine specimens were comparable, with means of 5.6, 5.3 and 4.5 log10 copies/ml respectively, with serum attaining the highest VL peak at 8.1 log10 copies/ml. Detecting ZIKV RNA in saliva over a similar time-period and level as in serum/plasma indicates that saliva could potentially serve as a more accessible diagnostic sample. Finding the majority of infections to be asymptomatic emphasizes the importance of silent ZIKV transmission and helps inform public health interventions in the region and globally.

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