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Why do patients refuse trichiasis surgery? Lessons and an education initiative from Mtwara Region, Tanzania

PLoS Neglected Tropical Diseases News - 14 June 2018 - 9:00pm

by Katherine M. Gupta, Jennifer C. Harding, Majid S. Othman, Shannath L. Merbs, Emily W. Gower

Background

Trachomatous trichiasis is one of the leading causes of preventable blindness worldwide. A relatively simple surgery can spare vision. Although this surgery is usually performed free of charge in endemic regions, multiple studies indicate that surgical refusal is common. Prior studies have attempted to examine these reasons, although they generally rely on patient recall months to years after the surgery was offered. This study set out to determine major decision-making factors at the time of refusal. In addition, this study looked for ways to help increase surgical uptake by targeting modifiable factors.

Methodology/Principal findings

We used a combination of focus groups, interviews with community health workers, and individual interviews with trichiasis patients who refused surgery to understand their decision-making.We found that several factors influenced surgical refusals, including misconception regarding recovery time, inability to find a post-surgical caregiver, and the time of year of the surgical campaign. Fear of the surgery itself played a minimal role in refusals.

Conclusions/Significance

Trichiasis patients refuse surgery for many reasons, but a large percentage is due to lack of information and education, and is, therefore, modifiable within the structure of a surgical outreach project. To address this, we developed a “frequently asked questions” (FAQ) document aimed at community health workers, which may have helped to decrease some of the misconceptions that had led to prior refusals.

Identification and validation of a novel panel of <i>Plasmodium knowlesi</i> biomarkers of serological exposure

PLoS Neglected Tropical Diseases News - 14 June 2018 - 9:00pm

by Lou S. Herman, Kimberly Fornace, Jody Phelan, Matthew J. Grigg, Nicholas M. Anstey, Timothy William, Robert W. Moon, Michael J. Blackman, Chris J. Drakeley, Kevin K. A. Tetteh

Background

Plasmodium knowlesi is the most common cause of malaria in Malaysian Borneo, with reporting limited to clinical cases presenting to health facilities and scarce data on the true extent of transmission. Serological estimations of transmission have been used with other malaria species to garner information about epidemiological patterns. However, there are a distinct lack of suitable serosurveillance tools for this neglected disease.

Methodology/Principal findings

Using in silico tools, we designed and expressed four novel P. knowlesi protein products to address the distinct lack of suitable serosurveillance tools: PkSERA3 antigens 1 and 2, PkSSP2/TRAP and PkTSERA2 antigen 1. Antibody prevalence to these antigens was determined by ELISA for three time-points post-treatment from a hospital-based clinical treatment trial in Sabah, East Malaysia (n = 97 individuals; 241 total samples for all time points). Higher responses were observed for the PkSERA3 antigen 2 (67%, 65/97) across all time-points (day 0: 36.9% 34/92; day 7: 63.8% 46/72; day 28: 58.4% 45/77) with significant differences between the clinical cases and controls (n = 55, mean plus 3 SD) (day 0 p<0.0001; day 7 p<0.0001; day 28 p<0.0001). Using boosted regression trees, we developed models to classify P. knowlesi exposure (cross-validated AUC 88.9%; IQR 86.1–91.3%) and identified the most predictive antibody responses.

Conclusions/Significance

The PkSERA3 antigen 2 had the highest relative variable importance in all models. Further validation of these antigens is underway to determine the specificity of these tools in the context of multi-species infections at the population level.

Exposure and infection to <i>Plasmodium knowlesi</i> in case study communities in Northern Sabah, Malaysia and Palawan, The Philippines

PLoS Neglected Tropical Diseases News - 14 June 2018 - 9:00pm

by Kimberly M. Fornace, Lou S. Herman, Tommy R. Abidin, Tock Hing Chua, Sylvia Daim, Pauline J. Lorenzo, Lynn Grignard, Nor Afizah Nuin, Lau Tiek Ying, Matthew J. Grigg, Timothy William, Fe Espino, Jonathan Cox, Kevin K. A. Tetteh, Chris J. Drakeley

Background

Primarily impacting poor, rural populations, the zoonotic malaria Plasmodium knowlesi is now the main cause of human malaria within Malaysian Borneo. While data is increasingly available on symptomatic cases, little is known about community-level patterns of exposure and infection. Understanding the true burden of disease and associated risk factors within endemic communities is critical for informing evidence-based control measures.

Methodology/Principal findings

We conducted comprehensive surveys in three areas where P. knowlesi transmission is reported: Limbuak, Pulau Banggi and Matunggung, Kudat, Sabah, Malaysia and Bacungan, Palawan, the Philippines. Infection prevalence was low with parasites detected by PCR in only 0.2% (4/2503) of the population. P. knowlesi PkSERA3 ag1 antibody responses were detected in 7.1% (95% CI: 6.2–8.2%) of the population, compared with 16.1% (14.6–17.7%) and 12.6% (11.2–14.1%) for P. falciparum and P. vivax. Sero-prevalence was low in individuals <10 years old for P. falciparum and P. vivax consistent with decreased transmission of non-zoonotic malaria species. Results indicated marked heterogeneity in transmission intensity between sites and P. knowlesi exposure was associated with agricultural work (OR 1.63; 95% CI 1.07–2.48) and higher levels of forest cover (OR 2.40; 95% CI 1.29–4.46) and clearing (OR 2.14; 95% CI 1.35–3.40) around houses. Spatial patterns of P. knowlesi exposure differed from exposure to non-zoonotic malaria and P. knowlesi exposed individuals were younger on average than individuals exposed to non-zoonotic malaria.

Conclusions/Significance

This is the first study to describe serological exposure to P. knowlesi and associated risk factors within endemic communities. Results indicate community–level patterns of infection and exposure differ markedly from demographics of reported cases, with higher levels of exposure among women and children. Further work is needed to understand these variations in risk across a wider population and spatial scale.

The role of social determinants of health in the risk and prevention of group A streptococcal infection, acute rheumatic fever and rheumatic heart disease: A systematic review

PLoS Neglected Tropical Diseases News - 13 June 2018 - 9:00pm

by Pasqualina M. Coffey, Anna P. Ralph, Vicki L. Krause

Background

Rheumatic heart disease (RHD) poses a major disease burden among disadvantaged populations globally. It results from acute rheumatic fever (ARF), a complication of Group A Streptococcal (GAS) infection. These conditions are acknowledged as diseases of poverty, however the role of specific social and environmental factors in GAS infection and progression to ARF/RHD is not well understood. The aim of this systematic review was to determine the association between social determinants of health and GAS infection, ARF and RHD, and the effect of interventions targeting these.

Methodology

We conducted a systematic literature review using PubMed, the Cochrane Library and Embase. Observational and experimental studies that measured: crowding, dwelling characteristics, education, employment, income, nutrition, or socioeconomic status and the relationship with GAS infection, ARF or RHD were included. Findings for each factor were assessed against the Bradford Hill criteria for evidence of causation. Study quality was assessed using a standardised tool.

Principle findings

1,164 publications were identified. 90 met inclusion criteria, comprising 91 individual studies. 49 (50.5%) were poor quality in relation to the specific study question. The proportion of studies reporting significant associations between socioeconomic determinants and risk of GAS infection was 57.1%, and with ARF/RHD was 50%. Crowding was the most assessed factor (14 studies with GAS infection, 36 studies with ARF/RHD) followed by socioeconomic status (6 and 36 respectively). The majority of studies assessing crowding, dwelling characteristics, education and employment status of parents or cases, and nutrition, reported a positive association with risk of GAS infection, ARF or RHD. Crowding and socioeconomic status satisfactorily met the criteria of a causal association. There was substantial heterogeneity across all key study aspects.

Conclusion

The extensive literature examining the role of social determinants in GAS infection, ARF and RHD risk lacks quality. Most were observational, not interventional. Crowding as a cause of GAS infection and ARF/RHD presents a practical target for prevention actions.

Genetic manipulation of <i>Leishmania donovani</i> threonyl tRNA synthetase facilitates its exploration as a potential therapeutic target

PLoS Neglected Tropical Diseases News - 13 June 2018 - 9:00pm

by Sanya Chadha, Ramachandran Vijayan, Sakshi Gupta, Manoj Munde, Samudrala Gourinath, Rentala Madhubala

Background

Aminoacyl tRNA synthetases are central enzymes required for protein synthesis. These enzymes are the known drug targets in bacteria and fungi. Here, we for the first time report the functional characterization of threonyl tRNA synthetase (LdThrRS) of Leishmania donovani, a protozoan parasite, the primary causative agent of visceral leishmaniasis.

Methodology

Recombinant LdThrRS (rLdThrRS) was expressed in E. coli and purified. The kinetic parameters for rLdThrRS were determined. The subcellular localization of LdThrRS was done by immunofluorescence analysis. Heterozygous mutants of LdThrRS were generated in Leishmania promastigotes. These genetically manipulated parasites were checked for their proliferation, virulence, aminoacylation activity and sensitivity to the known ThrRS inhibitor, borrelidin. An in silico generated structural model of L. donovani ThrRS was compared to that of human.

Conclusions

Recombinant LdThrRS displayed aminoacylation activity, and the protein is possibly localized to both the cytosol and mitochondria. The comparison of the 3D-model of LdThrRS to human ThrRS displayed considerable similarity. Heterozygous parasites showed restrictive growth phenotype and had attenuated infectivity. These heterozygous parasites were more susceptible to inhibition by borrelidin. Several attempts to obtain ThrRS homozygous null mutants were not successful, indicating its essentiality for the Leishmania parasite. Borrelidin showed a strong affinity for LdThrRS (KD: 0.04 μM) and was effective in inhibiting the aminoacylation activity of the rLdThrRS (IC50: 0.06 μM). Borrelidin inhibited the promastigotes (IC50: 21 μM) stage of parasites. Our data shows that LdThrRS is essential for L. donovani survival and is likely to bind with small drug-like molecules with strong affinity, thus making it a potential target for drug discovery efforts.

Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 13 June 2018 - 9:00pm

by Lyda Z. Rojas, Marija Glisic, Laura Pletsch-Borba, Luis E. Echeverría, Wichor M. Bramer, Arjola Bano, Najada Stringa, Asija Zaciragic, Bledar Kraja, Eralda Asllanaj, Rajiv Chowdhury, Carlos A. Morillo, Oscar L. Rueda-Ochoa, Oscar H. Franco, Taulant Muka

Background

Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population.

Methods

Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model.

Results

Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants.

Conclusions

This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.

Filaricidal properties of <i>Lantana camara</i> and <i>Tamarindus indica</i> extracts, and Lantadene A from <i>L</i>. <i>camara</i> against <i>Onchocerca ochengi</i> and <i>Loa loa</i>

PLoS Neglected Tropical Diseases News - 13 June 2018 - 9:00pm

by Adela Ngwewondo, Meng Wang, Faustin Pascal T. Manfo, Moses Samje, Jessie N’kam Ganin’s, Emmanuel Ndi, Raymond J. Andersen, Fidelis Cho-Ngwa

Background

Ivermectin is the only drug currently recommended for the treatment of onchocerciasis, the second leading infectious cause of blindness in the world. This drug kills only the first stage larvae—microfilariae (mf) of Onchocerca volvulus and is to be used cautiously in areas where Loa loa is prevalent because of severe adverse events observed with coinfected patients.

Methodology/Principal findings

This study investigated the anti-filarial activities of two Cameroonian medicinal plants, Lantana camara and Tamarindus indica locally used to treat onchocerciasis. Twelve (12) extracts were prepared and tested in vitro on the bovine model parasite, O. ochengi as well as L. loa mf. Both mf and adult male worm viabilities were assessed by motility scoring, while adult female worm viability was determined biochemically by standard MTT/formazan colorimetry. Cytotoxicity and acute toxicity were determined respectively, in monkey kidney epithelial cells and in BALB/c mice. Pure compounds were isolated by LC/MS using a bio-assay guided strategy. All the extracts showed 100% activity at 500 μg/mL against O. ochengi adult worms and mf. The highest activity against O. ochengi was observed with the hexane extract of L. camara leaves (LCLhex), with IC50 of 35.1 μg/mL for adult females and 3.8 μg/mL for the mf. Interestingly, this extract was more active against O. ochengi mf than L. loa mf. Further studies on the extracts led to the isolation of lantadene A from the methylene chloride extract of L. camara leaves, with IC50s of 7.85 μg/mL for adult males, 10.38 μg/mL for adult females, 10.84 μg/mL for O. ochengi mf and 20.13 μg/mL for L. loa mf.

Conclusions/Significance

We report for the first time the anti-onchocercal activities of these locally consumed medicinal plants and lantadene A, a potential lead for further development as an onchocerciasis cure.

One round of azithromycin MDA adequate to interrupt transmission in districts with prevalence of trachomatus inflammation follicular of 5.0-9.9%: Evidence from Malawi

PLoS Neglected Tropical Diseases News - 13 June 2018 - 9:00pm

by Khumbo Kalua, Alvin Chisambi, David Chainyanya, Michael Masika, Ana Bakhtiari, Rebecca Willis, Paul M. Emerson, Anthony W. Solomon, Robin L. Bailey

Background

As highly trachoma-endemic countries approach elimination, some districts will have prevalences of trachomatous inflammation–follicular in 1–9-year-olds (TF1-9) of 5.0–9.9%. The World Health Organization (WHO) previously recommended that in such districts, TF prevalence be assessed in each sub-district (groupings of at least three villages), with three rounds of azithromycin treatment offered to any sub-district in which TF≥10%. Given the large number of endemic districts worldwide and the human and financial resources required to conduct surveys, this recommendation may not be practical. In a group of 8 Malawi districts with baseline TF prevalences of 5.0–9.9%, the Malawi Ministry of Health administered one round of azithromycin mass treatment, to the whole of each district, achieving mean coverage of ~80%. Here, we report impact surveys conducted after that treatment.

Methods

We undertook population-based trachoma surveys in 18 evaluation units of the 8 treated districts, at least 6 months after the MDA. The standardized training package and survey methodologies of Tropical Data, which conform to WHO recommendations, were used.

Results

Each of the 18 evaluation units had a TF1-9 prevalence <5.0%.

Conclusion

The study demonstrates that in Malawi districts with TF of 5.0–9.9%, one round of azithromycin MDA with ~80% coverage associates with a reduction in TF prevalence to <5%. Further evidence for this approach should be collected elsewhere.

Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 13 June 2018 - 9:00pm

by Despina Contopoulos-Ioannidis, Shoshana Newman-Lindsay, Camille Chow, A. Desiree LaBeaud

Background

Chikungunya virus (CHIKV) is an emerging arboviral infection with a global distribution and may cause fetal and neonatal infections after maternal CHIKV-infections during gestation.

Methodology

We performed a systematic review to evaluate the risk for: a) mother-to-child transmission (MTCT), b) antepartum fetal deaths (APFD), c) symptomatic neonatal disease, and d) neonatal deaths from maternal CHIKV-infections during gestation. We also recorded the neonatal clinical manifestations after such maternal infections (qualitative data synthesis). We searched PubMed (last search 3/2017) for articles, of any study design, with any of the above outcomes. We calculated the overall risk of MTCT, APFDs and risk of symptomatic neonatal disease by simple pooling. For endpoints with ≥5 events in more than one study, we also synthesized the data by random-effect-model (REM) meta-analysis.

Principal findings

Among 563 identified articles, 13 articles from 8 cohorts were included in the quantitative data synthesis and 33 articles in the qualitative data synthesis. Most cohorts reported data only on symptomatic rather than on all neonatal infections. By extrapolation also of these data, the overall pooled-MTCT-risk across cohorts was at least 15.5% (206/1331), (12.6% by REMs). The pooled APFD-risk was 1.7% (20/1203); while the risk of CHIKV-confirmed-APFDs was 0.3% (3/1203). Overall, the pooled-risk of symptomatic neonatal disease was 15.3% (203/1331), (11.9% by REMs). The pooled risk of symptomatic disease was 50.0% (23/46) among intrapartum vs 0% (0/712) among antepartum/peripartum maternal infections. Infected newborns, from maternal infections during gestation were either asymptomatic or presented within their first week of life, but not at birth, with fever, irritability, hyperalgesia, diffuse limb edema, rashes and occasionally sepsis-like illness and meningoencephalitis. The pooled-risk of neonatal death was 0.6% (5/832) among maternal infections and 2.8% (5/182) among neonatal infections; long-term neurodevelopmental delays occurred in 50% of symptomatic neonatal infections.

Conclusions/Significance

Published cohorts with data on the risk to the fetus and/or newborn from maternal CHIKV-infections during gestation were sparse compared to the number of recently reported CHIKV-infection outbreaks worldwide; however perinatal infections do occur, at high rates during intrapartum period, and can be related to neonatal death and long-term disabilities.

Mortality trends and risk factors in advanced stage-2 Human African Trypanosomiasis: A critical appraisal of 23 years of experience in the Democratic Republic of Congo

PLoS Neglected Tropical Diseases News - 13 June 2018 - 9:00pm

by Léon Mbiyangandu Kazumba, Jean-Claude Tshinzobe Kaka, Dieudonné Mumba Ngoyi, Désiré Tshala-Katumbay

We conducted a retrospective study on mortality trends and risk factors in 781 naïve cases of advanced stage-2 sleeping sickness admitted between 1989 and 2012 at the National Reference Center for Human African Trypanosomiasis (HAT), Department of Neurology, Kinshasa University, Democratic Republic of Congo (DRC). Death was the outcome variable whereas age, gender, duration of disease, location of trypanosomes in body fluids, cytorachy, protidorachy, clinical status (assessed on a syndromic and functional basis) on admission, and treatment regimen were predictors in logistic regression models run at the 0.05 significance level. Death proportions were 17.2% in the standard melarsoprol schedule (3-series of intravenous melarsoprol on 3 successive days at 3.6 mg/kg/d, with a one-week interval between the series, ARS 9); 12.1% in the short schedule melarsoprol (10 consecutive days of intravenous melarsoprol at 2.2 mg/kg/d, ARS 10), 5.4% in the first-line eflornithine (14 days of eflornithine at 400 mg/kg/d in 4 infusions a day DFMO B), 9.1% in the NECT treatment regimen (eflornithine for 7 days at 400, mg/kg/d in 2 infusions a day combined with oral nifurtimox for 10 days at 15 mg/kg/d in 3 doses a day); and high (36%) in the group with select severely affected patients given eflornithine because of their clinical status on admission, at the time when this expensive drug was kept for treatment of relapses (14 days at 400 mg/kg/d in 4 infusions a day, DFMO A). After adjusting for treatment, death odds ratios were as follows: 10.40 [(95% CI: 6.55–16.51); p = .000] for clinical dysfunction (severely impaired clinical status) on admission, 2.14 [(95% CI: 1.35–3.39); p = .001] for high protidorachy, 1.99 [(95% CI: 1.18–3.37); p = .010] for the presence of parasites in the CSF and 1.70 [(95% CI: 1.03–2.81); p = .038] for high cytorachy. A multivariable analysis within treatment groups retained clinical status on admission (in ARS 9, ARS 10 and DFMO B groups) and high protidorachy (in ARS 10 and DFMO B groups) as significant predictors of death. The algorithm for initial clinical status assessment used in the present study may serve as the basis for further development of standardized assessment tools relevant to the clinical management of HAT and information exchange in epidemiological reports.

Baseline trachoma prevalence in Guinea: Results of national trachoma mapping in 31 health districts

PLoS Neglected Tropical Diseases News - 11 June 2018 - 9:00pm

by André Géopogui, Christelly Flore Badila, Mamadou Siradiou Baldé, Cece Nieba, Lamine Lamah, Steven D. Reid, Mohamed Lamine Yattara, Jean Jacques Tougoue, Jeremiah Ngondi, Ibrahim Foungotin Bamba, Joseph J. Amon, Anthony W. Solomon, Yaobi Zhang

Background

Based on previous studies, historical records and risk factors, trachoma was suspected to be endemic in 31 health districts (HDs) in Guinea. To facilitate planning for the elimination of trachoma as a public health problem, national trachoma surveys were conducted between 2011 and 2016 to determine the prevalence of trachomatous inflammation—follicular (TF) and trachomatous trichiasis (TT) in all 31 endemic HDs.

Methodology/Principal findings

A total of 27 cross-sectional surveys were conducted, each using two-stage cluster sampling (one survey in 2011 covered five HDs). Children aged 1–9 years and adults aged ≥15 years were examined for TF and TT, respectively, using the World Health Organization (WHO) simplified grading system. Indicators of household access to water, sanitation and hygiene (WASH) were also collected. A total of 100,051 people from 13,725 households of 556 clusters were examined, of whom 44,899 were male and 55,152 were female. 44,209 children aged 1–9-years and 48,745 adults aged ≥15 years were examined. The adjusted prevalence of TF varied between 1.0% (95%CI: 0.6–1.5%) to 41.8% (95%CI: 39.4–44.2%), while the adjusted prevalence of TT ranged from 0.0% (95%CI: 0.0–0.2%) to 2.8% (95%CI: 2.3–3.5%) in the 27 surveys. In all, 18 HDs had a TF prevalence ≥5% in children aged 1–9 years and 21 HDs had a TT prevalence ≥0.2% in adults aged ≥15 years. There were an estimated 32,737 (95% CI: 19,986–57,811) individuals with TT living in surveyed HDs at the time of surveys.

Conclusions/Significance

Trachoma is a public health problem in Guinea. 18 HDs required intervention with at least one round of mass drug administration and an estimated 32,737 persons required TT surgery in the country. The results provided clear evidence for Guinea to plan for national trachoma elimination.

A transcriptomic survey of the impact of environmental stress on response to dengue virus in the mosquito, <i>Aedes aegypti</i>

PLoS Neglected Tropical Diseases News - 11 June 2018 - 9:00pm

by David S. Kang, Martin S. Barron, Diane D. Lovin, Joanne M. Cunningham, Matthew W. Eng, Dave D. Chadee, Jun Li, David W. Severson

Populations of Aedes aegypti naturally exhibit variable susceptibility to dengue viruses. This natural variation can be impacted by nutritional stress resulting from larval-stage crowding, indicating the influence of environment components on the adult mosquito immune response. In particular, larval crowding was previously shown to reduce the susceptibility of adult females of a Trinidad field isolate of A. aegypti to the dengue serotype 2 (JAM1409) virus. Here, we present the first whole transcriptome study to address the impact of environmental stress on A. aegypti response to dengue virus. We examined expression profiles of adult females resulting from crowded and optimum reared larvae from the same Trinidad isolate at two critical early time points—3 and 18 hours post dengue virus infected blood meal. We exposed specimens to either a dengue or naïve blood meal, and then characterized the response in ten gene co-expression modules based on their transcriptional associations with environmental stress and time. We further analyzed the top 30 hub or master regulatory genes in each of the modules, and validated our results via qRT-PCR. These hub genes reveal which functions are critical to the mechanisms that confer dengue virus refractoriness or susceptibility to stress conditioned A. aegypti, as well as the time points at which they are most important.

Humoral and cellular immune responses to <i>Yersinia pestis</i> Pla antigen in humans immunized with live plague vaccine

PLoS Neglected Tropical Diseases News - 11 June 2018 - 9:00pm

by Valentina A. Feodorova, Anna M. Lyapina, Maria A. Khizhnyakova, Sergey S. Zaitsev, Lidiya V. Sayapina, Tatiana E. Arseneva, Alexey L. Trukhachev, Svetlana A. Lebedeva, Maxim V. Telepnev, Onega V. Ulianova, Elena P. Lyapina, Sergey S. Ulyanov, Vladimir L. Motin

Background

To establish correlates of human immunity to the live plague vaccine (LPV), we analyzed parameters of cellular and antibody response to the plasminogen activator Pla of Y. pestis. This outer membrane protease is an essential virulence factor that is steadily expressed by Y. pestis.

Methodology/Principal findings

PBMCs and sera were obtained from a cohort of naïve (n = 17) and LPV-vaccinated (n = 34) donors. Anti-Pla antibodies of different classes and IgG subclasses were determined by ELISA and immunoblotting. The analysis of antibody response was complicated with a strong reactivity of Pla with normal human sera. The linear Pla B-cell epitopes were mapped using a library of 15-mer overlapping peptides. Twelve peptides that reacted specifically with sera of vaccinated donors were found together with a major cross-reacting peptide IPNISPDSFTVAAST located at the N-terminus. PBMCs were stimulated with recombinant Pla followed by proliferative analysis and cytokine profiling. The T-cell recall response was pronounced in vaccinees less than a year post-immunization, and became Th17-polarized over time after many rounds of vaccination.

Conclusions/Significance

The Pla protein can serve as a biomarker of successful vaccination with LPV. The diagnostic use of Pla will require elimination of cross-reactive parts of the antigen.

Epidemiology and risk factors for typhoid fever in Central Division, Fiji, 2014–2017: A case-control study

PLoS Neglected Tropical Diseases News - 8 June 2018 - 9:00pm

by Namrata Prasad, Aaron P. Jenkins, Lanieta Naucukidi, Varanisese Rosa, Aalisha Sahu-Khan, Mike Kama, Kylie M. Jenkins, Adam W. J. Jenney, Susan J. Jack, Debasish Saha, Pierre Horwitz, Stacy D. Jupiter, Richard A. Strugnell, E. Kim Mulholland, John A. Crump

Background

Typhoid fever is endemic in Fiji, with high reported annual incidence. We sought to identify the sources and modes of transmission of typhoid fever in Fiji with the aim to inform disease control.

Methodology/Principal findings

We identified and surveyed patients with blood culture-confirmed typhoid fever from January 2014 through January 2017. For each typhoid fever case we matched two controls by age interval, gender, ethnicity, and residential area. Univariable and multivariable analysis were used to evaluate associations between exposures and risk for typhoid fever. We enrolled 175 patients with typhoid fever and 349 controls. Of the cases, the median (range) age was 29 (2–67) years, 86 (49%) were male, and 84 (48%) lived in a rural area. On multivariable analysis, interrupted water availability (odds ratio [OR] = 2.17; 95% confidence interval [CI] 1.18–4.00), drinking surface water in the last 2 weeks (OR = 3.61; 95% CI 1.44–9.06), eating unwashed produce (OR = 2.69; 95% CI 1.48–4.91), and having an unimproved or damaged sanitation facility (OR = 4.30; 95% CI 1.14–16.21) were significantly associated with typhoid fever. Frequent handwashing after defecating (OR = 0.57; 95% CI 0.35–0.93) and using soap for handwashing (OR = 0.61; 95% CI 0.37–0.95) were independently associated with a lower odds of typhoid fever.

Conclusions

Poor sanitation facilities appear to be a major source of Salmonella Typhi in Fiji, with transmission by drinking contaminated surface water and consuming unwashed produce. Improved sanitation facilities and protection of surface water sources and produce from contamination by human feces are likely to contribute to typhoid control in Fiji.

‘When Ebola enters a home, a family, a community’: A qualitative study of population perspectives on Ebola control measures in rural and urban areas of Sierra Leone

PLoS Neglected Tropical Diseases News - 8 June 2018 - 9:00pm

by Nell Gray, Beverley Stringer, Gina Bark, Andre Heller Perache, Freya Jephcott, Rob Broeder, Ronald Kremer, Augustine S. Jimissa, Thomas T. Samba

Background

During the West Africa Ebola outbreak, cultural practices have been described as hindering response efforts. The acceptance of control measures improved during the outbreak, but little is known about how and why this occurred. We conducted a qualitative study in two administrative districts of Sierra Leone to understand Ebola survivor, community, and health worker perspectives on Ebola control measures. We aimed to gain an understanding of community interactions with the Ebola response to inform future intervention strategies.

Methodology/Principal findings

Participants (25 survivors, 24 community members, and 16 health workers) were recruited purposively. A flexible participatory method gathered data through field notes and in-depth, topic-led interviews. These were analysed thematically with NVivo10© by open coding, constant comparison, and the principles of grounded theory. The primary theme, ‘when Ebola is real’, centred on denial, knowledge, and acceptance. Ebola was denied until it was experienced or observed first-hand and thus health promotion was more effective if undertaken by those directly exposed to Ebola rather than by mass media communication. Factors that enabled acceptance and engagement with control measures included: access to good, proximate care and prevention activities; seeing that people can survive infection; and the co-option of trusted or influential local leadership, with bylaws implemented by community leaders being strongly respected. All participants noted that dignity, respect, and compassion were key components of effective control measures.

Conclusions

Successful control approaches need strong community leadership, with the aim of achieving collective understanding between communities and health workers. Health promotion for communities at risk is best conducted through people who have had close interaction with or who have survived Ebola as opposed to reliance on broad mass communication strategies.

Risk factors for <i>Cryptosporidium</i> infection in low and middle income countries: A systematic review and meta-analysis

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

by Maha Bouzid, Erica Kintz, Paul R. Hunter

Background

Cryptosporidium infection causes gastrointestinal disease and has a worldwide distribution. The highest burden is in developing countries.

Objectives

We sought to conduct a systematic review and meta-analysis to identify Cryptosporidium risk factors in Low and Middle Income countries (LMICs).

Methods

Medline Ovid and Scopus databases were searched with no restriction on year or language of publication. All references were screened independently in duplicate and were included if they presented data on at least 3 risk factors. Meta-analyses using random effects models were used to calculate overall estimates for each exposure.

Results

The most frequently reported risk factors in the 15 included studies were overcrowding, household diarrhoea, poor quality drinking water, animal contact, open defecation/ lack of toilet and breastfeeding. The combined odds ratio for animal contact was 1.98 (95%CI: 1.11–3.54) based on 11 studies and for diarrhoea in the household 1.98 (95%CI: 1.13–3.49) based on 4 studies. Open defecation was associated with a pooled odds ratio of 1.82 (95%CI: 1.19–2.8) based on 5 studies. Poor drinking water quality was not associated with a significant Cryptosporidium risk, odds ratio 1.06 (95%CI: 0.77–1.47). Breastfeeding was protective with pooled odds ratio 0.4 (95%CI: 0.13–1.22), which was not statistically significant.

Conclusions

Based on the included studies, crowded living conditions, animal contact and open defecation are responsible for the majority of Cryptosporidium cases in LMICs. Future studies investigating Cryptosporidium risk factors should have a good study design and duration, include appropriate number of cases, select suitable controls, investigate multiple relevant risk factors, fully report data and perform multivariate analysis.

Chikungunya virus vector competency of Brazilian and Florida mosquito vectors

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

by Nildimar Alves Honório, Keenan Wiggins, Daniel Cardoso Portela Câmara, Bradley Eastmond, Barry W. Alto

Chikungunya virus is a vector-borne alphavirus transmitted by the bites of infected female Ae. aegypti and Ae. albopictus. In Brazil between 2014 and 2016 almost 320 thousand autochthonous human cases were reported and in Florida numerous imported CHIKV viremic cases (> 3,800) demonstrate the potential high risk to establishment of local transmission. In the present study, we carried out a series of experiments to determine the viral dissemination and transmission rates of different Brazilian and Florida populations of Ae. aegypti and Ae. albopictus at 2, 5, and 13 days post-infection for the emergent Asian genotype of CHIKV. Our results show that all tested populations of Ae. aegypti and Ae. albopictus have a high proportion (> 0.80) of individuals with disseminated infection as early as 2 days-post exposure. We found no significant treatment effects of mosquito population origin effects on viral dissemination rates. Transmission rates had a heterogeneous pattern, with US Ae. aegypti and Brazilian Ae. albopictus having the highest proportion of individuals with successful infection (respectively 0.50 and 0.82 as early as 2 days-post infection). Model results found significant effects of population origin, population origin x species, population origin x days post-infection and population origin x species x days post infection.

Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination

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

by Christiane Costa-Pereira, Ana Carolina Campi-Azevedo, Jordana Grazziela Coelho-dos-Reis, Vanessa Peruhype-Magalhães, Márcio Sobreira Silva Araújo, Lis Ribeiro do Vale Antonelli, Cristina Toscano Fonseca, Jandira Aparecida Lemos, Luiz Cosme Cote Malaquias, Matheus de Souza Gomes, Laurence Rodrigues Amaral, Maria Rios, Caren Chancey, Harold Richard Persi, Jorge Marcelo Pereira, Maria de Lourdes de Sousa Maia, Marcos da Silva Freire, Reinaldo de Menezes Martins, Akira Homma, Marisol Simões, Anna Yoshida Yamamura, Roberto Henrique Guedes Farias, Alessandro Pecego Martins Romano, Carla Magda Domingues, Pedro Luiz Tauil, Pedro Fernando Costa Vasconcelos, Iramaya Rodrigues Caldas, Luiz Antônio Camacho, Andrea Teixeira-Carvalho, Olindo Assis Martins-Filho

In this investigation, machine-enhanced techniques were applied to bring about scientific insights to identify a minimum set of phenotypic/functional memory-related biomarkers for post-vaccination follow-up upon yellow fever (YF) vaccination. For this purpose, memory status of circulating T-cells (Naïve/early-effector/Central-Memory/Effector-Memory) and B-cells (Naïve/non-Classical-Memory/Classical-Memory) along with the cytokine profile (IFN/TNF/IL-5/IL-10) were monitored before-NV(day0) and at distinct time-points after 17DD-YF primary vaccination—PV(day30-45); PV(year1-9) and PV(year10-11). A set of biomarkers (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) were observed in PV(day30-45), but not in NV(day0), with most of them still observed in PV(year1-9). Deficiencies of phenotypic/functional biomarkers were observed in NV(day0), while total lack of memory-related attributes was observed in PV(year10-11), regardless of the age at primary vaccination. Venn-diagram analysis pre-selected 10 attributes (eEfCD4, EMCD4, CMCD19, EMCD8, IFNCD4, IL-5CD8, TNFCD4, IFNCD8, TNFCD8 and IL-5CD4), of which the overall mean presented moderate accuracy to discriminate PV(day30-45)&PV(year1-9) from NV(day0)&PV(year10-11). Multi-parameter approaches and decision-tree algorithms defined the EMCD8 and IL-5CD4 attributes as the top-two predictors with moderated performance. Together with the PRNT titers, the top-two biomarkers led to a resultant memory status observed in 80% and 51% of volunteers in PV(day30-45) and PV(year1-9), contrasting with 0% and 29% found in NV(day0) and PV(year10-11), respectively. The deficiency of memory-related attributes observed at PV(year10-11) underscores the conspicuous time-dependent decrease of resultant memory following17DD-YF primary vaccination that could be useful to monitor potential correlates of protection in areas under risk of YF transmission.

Assessment of animal hosts of pathogenic <i>Leptospira</i> in northern Tanzania

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

by Kathryn J. Allan, Jo E. B. Halliday, Mark Moseley, Ryan W. Carter, Ahmed Ahmed, Marga G. A. Goris, Rudy A. Hartskeerl, Julius Keyyu, Tito Kibona, Venance P. Maro, Michael J. Maze, Blandina T. Mmbaga, Rigobert Tarimo, John A. Crump, Sarah Cleaveland

Leptospirosis is a zoonotic bacterial disease that affects more than one million people worldwide each year. Human infection is acquired through direct or indirect contact with the urine of an infected animal. A wide range of animals including rodents and livestock may shed Leptospira bacteria and act as a source of infection for people. In the Kilimanjaro Region of northern Tanzania, leptospirosis is an important cause of acute febrile illness, yet relatively little is known about animal hosts of Leptospira infection in this area. The roles of rodents and ruminant livestock in the epidemiology of leptospirosis were evaluated through two linked studies. A cross-sectional study of peri-domestic rodents performed in two districts with a high reported incidence of human leptospirosis found no evidence of Leptospira infection among rodent species trapped in and around randomly selected households. In contrast, pathogenic Leptospira infection was detected in 7.08% cattle (n = 452 [5.1–9.8%]), 1.20% goats (n = 167 [0.3–4.3%]) and 1.12% sheep (n = 89 [0.1–60.0%]) sampled in local slaughterhouses. Four Leptospira genotypes were detected in livestock. Two distinct clades of L. borgpetersenii were identified in cattle as well as a clade of novel secY sequences that showed only 95% identity to known Leptospira sequences. Identical L. kirschneri sequences were obtained from qPCR-positive kidney samples from cattle, sheep and goats. These results indicate that ruminant livestock are important hosts of Leptospira in northern Tanzania. Infected livestock may act as a source of Leptospira infection for people. Additional work is needed to understand the role of livestock in the maintenance and transmission of Leptospira infection in this region and to examine linkages between human and livestock infections.

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