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Ruling out early trimester pregnancy when implementing community-based deworming programs

PLoS Neglected Tropical Diseases News - 30 January 2020 - 10:00pm

by Kariane St-Denis, Brittany Blouin, Elham Rahme, Martin Casapia, Antonio Montresor, Denise Mupfasoni, Pamela Sabina Mbabazi, Theresa W. Gyorkos

Background

Large-scale deworming programs have, to date, mostly targeted preschool- and school-age children. As community-based deworming programs become more common, deworming will be offered to women of reproductive age. The World Health Organization recommends preventive chemotherapy be administered to pregnant women only after the first trimester. It is therefore important for deworming programs to be able to identify women in early pregnancy. Our objective was to validate a short questionnaire which could be used by deworming program managers to identify and screen out women in early pregnancy.

Methodology/Principal findings

In May and June 2018, interviewers administered a questionnaire, followed by a pregnancy test, to 1,203 adult women living in the Peruvian Amazon. Regression analyses were performed to identify questions with high predictive properties (using the pregnancy test as the gold standard). Test parameters were computed at different decision tree nodes (where nodes represented questions). With 106 women confirmed to be pregnant, the positive predictive value of asking the single question ‘Are you pregnant?’ was 100%, at a ‘cost’ of a false negative rate of 1.9% (i.e. 21 women were incorrectly identified as not pregnant when they were truly pregnant). Additional questions reduced the false negative rate, but increased the false positive rate. Rates were dependent on both the combination and the order of questions.

Conclusions/Significance

To identify women in early pregnancy when deworming programs are community-based, both the number and order of questions are important. The local context and cultural acceptability of different questions should inform this decision. When numbers are manageable and resources are available, pregnancy tests can be considered at different decision tree nodes to confirm pregnancy status. Trade-offs in terms of efficiency and misclassification rates will need to be considered to optimize deworming coverage in women of reproductive age.

Reassessing therapeutic antibodies for neglected and tropical diseases

PLoS Neglected Tropical Diseases News - 30 January 2020 - 10:00pm

by Rob Hooft van Huijsduijnen, Somei Kojima, Dee Carter, Hisafumi Okabe, Akihide Sato, Wataru Akahata, Timothy N. C. Wells, Kei Katsuno

In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators. The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology. Other recent successes have included new antibodies for use in viral diseases, including HIV. The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty. However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited. Recent technology developments also indicate that several months of protection could be achieved with a single dose. Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients. This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.

Comparative specificity and sensitivity of NS1-based serological assays for the detection of flavivirus immune response

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Erick Mora-Cárdenas, Chiara Aloise, Valentina Faoro, Nataša Knap Gašper, Miša Korva, Ilaria Caracciolo, Pierlanfranco D’Agaro, Tatjana Avšič-Županc, Alessandro Marcello

Flaviviruses are relevant animal and human pathogens of increasing importance worldwide. The similarities of the initial clinical symptoms and the serological cross-reactivity of viral structural antigens make a laboratory diagnosis of flavivirus infection problematic. The main aim of the present study was the comparative specificity and sensitivity analysis of the non-structural protein NS1 as an antigen to detect flavivirus antibodies in sera from exposed individuals. A strategy for the purification of native recombinant non-structural protein 1 of representative flaviviruses including tick-borne encephalitis, West Nile, Zika and dengue virus was developed. The immunological properties of the purified antigens were analyzed using sera of immunized mice and of infected individuals in comparison with standard commercial assays. Recombinant NS1 protein was confirmed as a valuable option for the detection of flavivirus antibodies with reduced cross-reactivity and high sensitivity offering additional advantages for the detection of vaccine breakthrough cases.

World neglected tropical diseases day

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Peter J. Hotez, Serap Aksoy, Paul J. Brindley, Shaden Kamhawi

January 30, 2020 is the first-ever World Neglected Tropical Diseases Day (World NTD Day), a day when we celebrate the achievements made towards control of the world’s NTDs, yet recognize the daunting challenges we face in the control and elimination of these conditions.

Male predominance in reported Visceral Leishmaniasis cases: Nature or nurture? A comparison of population-based with health facility-reported data

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Kristien Cloots, Sakib Burza, Paritosh Malaviya, Epco Hasker, Sangeeta Kansal, Guy Mollett, Jaya Chakravarty, Nurpur Roy, Bibek Kumar Lal, Suman Rijal, Shyam Sundar, Marleen Boelaert

Background

Bangladesh, India, and Nepal aim for the elimination of Visceral Leishmaniasis (VL), a systemic parasitic infectious disease, as a public health problem by 2020. For decades, male patients have comprised the majority of reported VL cases in this region. By comparing this reported VL sex ratio to the one observed in population-based studies conducted in the Indian subcontinent, we tested the working hypothesis that mainly socio-cultural gender differences in healthcare-seeking behavior explain this gender imbalance.

Methodology/Principal findings

We compared the observed sex ratio of male versus female among all VL cases reported by the health system in Nepal and in the two most endemic states in India with that observed in population-based cohort studies in India and Nepal. Also, we assessed male sex as a potential risk factor for seroprevalence at baseline, seroconversion, and VL incidence in the same population-based data. The male/female ratio among VL cases reported by the health systems was 1.40 (95% CI 1.37–1.43). In the population cohort data, the age- and study site-adjusted male to female risk ratio was 1.27 (95% CI 1.08–1.51). Also, males had a 19% higher chance of being seropositive at baseline in the population surveys (RR 1.19; 95% CI 1.11–1.27), while we observed no significant difference in seroconversion rate between both sexes at the DAT cut-off titer defined as the primary endpoint.

Conclusions/Significance

Our population-based data show that male sex is a risk factor for VL, and not only as a socio-cultural determinant. Biological sex-related differences likely play an important role in the pathogenesis of this disease.

The detection of anti-dengue virus IgM in urine in participants enrolled in an acute febrile illness study in Puerto Rico

PLoS Neglected Tropical Diseases News - 29 January 2020 - 10:00pm

by Elba Caraballo, B. Katherine Poole-Smith, Kay M. Tomashek, Brenda Torres-Velasquez, Luisa I. Alvarado, Olga D. Lorenzi, Carmen Ramos, Jessica Carrión, Elizabeth Hunsperger

Background

Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study.

Methods

Between May 2012-March 2013, 1538 study participants with fever for ≤7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (≤5 days post-illness onset [DPO]) and late (6–14 DPO) in the clinical course was associated with dengue severity.

Results

Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course.

Conclusion

While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue.

<i>Anisakis</i> Sensitization in the Croatian Fish Processing Workers: Behavioral Instead of Occupational Risk Factors?

PLoS Neglected Tropical Diseases News - 27 January 2020 - 10:00pm

by Ana Jerončić, Diana Nonković, Anamarija Vrbatović, Jerko Hrabar, Ivana Bušelić, Victoria Martínez-Sernández, Santiago A. Lojo Rocamonde, Florencio M. Ubeira, Sonja Jaman, Esma Čečuk Jeličić, Marco Amati, Maria Angeles Gomez Morales, Boris Lukšić, Ivona Mladineo

We undertook the first study systematically evaluating the risk of Anisakis-sensitization in Croatian fish-processing workers and potential genetic susceptibility to anisakiasis. Anti-Anisakis IgE seroprevalence and risk factors for 600 employees of Croatian fish processing facilities and 466 blood donor controls, were assessed by indirect ELISA targeted with: recombinant Ani s 1 and Ani s 7 allergens, an Anisakis crude extract, the commercial ImmunoCAP kit, and questionnaires. Genetic susceptibility to anisakiasis was evaluated by genotypisation of human leukocytes alleles (HLA). Anti-Anisakis seropositive and a fraction of negative subjects were also assessed by ELISA and Western Blot (WB) for IgG seroprevalence to Trichinella spp. Overall, the observed anti-Anisakis seroprevalence inferred by indirect ELISA was significantly higher in fish processing workers (1.8%, 95% CI 0.9–3.3%) compared to the controls (0%, 0–0.8%). Seven out of 11 Ani s 1 and Ani s 7-positives and none of selected 65 negative sera, tested positive on whole-Anisakis extract (ImmunoCAP), whereas Anisakis crude extract ELISA detected 3.9% (2.4–6.0%) seropositives in fish processing workers, three (14%) of which showed IgE reactivity to milk proteins. The highest risk associated with Anisakis-sensitization among workers was fishing in the free time, rather than any of attributes related to the occupational exposure. Although no association was observed between anti-Anisakis seropositivity and wearing gloves or protective goggles, the majority of workers (92%) wore protective gloves, minimizing the risk for Anisakis sensitization via skin contact. Six HLA alleles within DRB1 gene were significantly associated with seropositivity under dominant, allelic or recessive models. All sera confirmed negative for anti-Trichinella spp. IgG. The study exhaustively covered almost all marine fish processing workers in Croatia, reflecting real-time Anisakis sensitization status within the industry, already under the influence of wide array of allergens.

Prescription of concomitant medications in patients treated with Nifurtimox Eflornithine Combination Therapy (NECT) for <i>T</i>.<i>b</i>. <i>gambiense</i> second stage sleeping sickness in the Democratic Republic of the Congo

PLoS Neglected Tropical Diseases News - 27 January 2020 - 10:00pm

by Andrea Kuemmerle, Caecilia Schmid, Victor Kande, Wilfried Mutombo, Medard Ilunga, Ismael Lumpungu, Sylvain Mutanda, Pathou Nganzobo, Digas Ngolo, Mays Kisala, Olaf Valverde Mordt

Background

Nifurtimox eflornithine combination therapy (NECT) to treat human African trypanosomiasis (HAT), commonly called sleeping sickness, was added to the World Health Organisation’s (WHO) Essential Medicines List in 2009 and to the Paediatric List in 2012. NECT was further tested and documented in a phase IIIb clinical trial in the Democratic Republic of Congo (DRC) assessing the safety, effectiveness, and feasibility of implementation under field conditions (NECT-FIELD study). This trial brought a unique possibility to examine concomitant drug management.

Methodology/Principal findings

This is a secondary analysis of the NECT-FIELD study where 629 second stage gambiense HAT patients were treated with NECT, including children and pregnant and breastfeeding women in six general reference hospitals located in two provinces. Concomitant drugs were prescribed by the local investigators as needed. Patients underwent daily evaluations, including vital signs, physical examination, and adverse event monitoring. Concomitant medication was documented from admission to discharge. Patients’ clinical profiles on admission and safety profile during specific HAT treatment were similar to previously published reports. Prescribed concomitant medications administered during the hospitalization period, before, during, and immediately after NECT treatment, were mainly analgesics/antipyretics, anthelmintics, antimalarials, antiemetics, and sedatives. Use of antibiotics was reasonable and antibiotics were often prescribed to treat cellulitis and respiratory tract infections. Prevention and treatment of neurological conditions such as convulsions, loss of consciousness, and coma was used in approximately 5% of patients.

Conclusions/Significance

The prescription of concomitant treatments was coherent with the clinical and safety profile of the patients. However, some prescription habits would need to be adapted in the future to the evolving available pharmacopoeia. A list of minimal essential medication that should be available at no cost to patients in treatment wards is proposed to help the different actors to plan, manage, and adequately fund drug supplies for advanced HAT infected patients.

Trial registration number

The initial study was registered at ClinicalTrials.gov, number NCT00906880.

Silencing of RpATG8 impairs the biogenesis of maternal autophagosomes in vitellogenic oocytes, but does not interrupt follicular atresia in the insect vector <i>Rhodnius prolixus</i>

PLoS Neglected Tropical Diseases News - 27 January 2020 - 10:00pm

by Jéssica Pereira, Calebe Diogo, Ariene Fonseca, Larissa Bomfim, Pedro Cardoso, Anna Santos, Uilla Dittz, Kildare Miranda, Wanderley de Souza, Adriana Gioda, Enrique R. D. Calderon, Luciana Araripe, Rafaela Bruno, Isabela Ramos

Follicular atresia is the mechanism by which the oocyte contents are degraded during oogenesis in response to stress conditions, allowing the energetic resources stored in the developing oocytes to be reallocated to optimize female fitness. Autophagy is a conserved intracellular degradation pathway where double-membrane vesicles are formed around target organelles leading to their degradation after lysosome fusion. The autophagy-related protein 8 (ATG8) is conjugated to the autophagic membrane and has a key role in the elongation and closure of the autophagosome. Here we identified one single isoform of ATG8 in the genome of the insect vector of Chagas Disease Rhodnius prolixus (RpATG8) and found that it is highly expressed in the ovary during vitellogenesis. Accordingly, autophagosomes were detected in the vitellogenic oocytes, as seen by immunoblotting and electron microscopy. To test if autophagosomes were important for follicular atresia, we silenced RpATG8 and elicited atresia in vitellogenic females by Zymosan-A injections. We found that silenced females were still able to trigger the same levels of follicle atresia, and that their atretic oocytes presented a characteristic morphology, with accumulated brown aggregates. Regardless of the difference in morphology, RpATG8-silenced atretic oocytes presented the same levels of protein, TAG and PolyP, as detected in control atretic oocytes, as well as the same levels of acidification of the yolk organelles. Because follicular atresia has the ultimate goal of restoring female fitness, we tested if RpATG8-silenced atresia would result in female physiology and behavior changes. Under insectarium conditions, we found that atresia-induced control and RpATG8-silenced females present no changes in blood meal digestion, survival, oviposition, TAG content in the fat body, haemolymph amino acid levels and overall locomotor activity. Altogether, we found that autophagosomes are formed during oogenesis and that the silencing of RpATG8 impairs autophagosome biogenesis in the oocytes. Nevertheless, regarding major macromolecule degradation and adaptations to the fitness costs imposed by triggering an immune response, we found that autophagic organelles are not essential for follicle atresia in R. prolixus.

<i>In vivo</i> efficacy of the boron-pleuromutilin AN11251 against <i>Wolbachia</i> of the rodent filarial nematode <i>Litomosoides sigmodontis</i>

PLoS Neglected Tropical Diseases News - 27 January 2020 - 10:00pm

by Alexandra Ehrens, Christopher S. Lunde, Robert T. Jacobs, Dominique Struever, Marianne Koschel, Stefan J. Frohberger, Franziska Lenz, Martina Fendler, Joseph D. Turner, Stephen A. Ward, Mark J. Taylor, Yvonne R. Freund, Rianna Stefanakis, Eric Easom, Xianfeng Li, Jacob J. Plattner, Achim Hoerauf, Marc P. Hübner

The elimination of filarial diseases such as onchocerciasis and lymphatic filariasis is hampered by the lack of a macrofilaricidal–adult worm killing–drug. In the present study, we tested the in vivo efficacy of AN11251, a boron-pleuromutilin that targets endosymbiotic Wolbachia bacteria from filarial nematodes and compared its efficacy to doxycycline and rifampicin. Doxycycline and rifampicin were previously shown to deplete Wolbachia endosymbionts leading to a permanent sterilization of the female adult filariae and adult worm death in human clinical studies. Twice-daily oral treatment of Litomosoides sigmodontis-infected mice with 200 mg/kg AN11251 for 10 days achieved a Wolbachia depletion > 99.9% in the adult worms, exceeding the Wolbachia reduction by 10-day treatments with bioequivalent human doses of doxycycline and a similar reduction as high-dose rifampicin (35 mg/kg). Wolbachia reductions of > 99% were also accomplished by 14 days of oral AN11251 at a lower twice-daily dose (50 mg/kg) or once-per-day 200 mg/kg AN11251 treatments. The combinations tested of AN11251 with doxycycline had no clear beneficial impact on Wolbachia depletion, achieving a > 97% Wolbachia reduction with 7 days of treatment. These results indicate that AN11251 is superior to doxycycline and comparable to high-dose rifampicin in the L. sigmodontis mouse model, allowing treatment regimens as short as 10–14 days. Therefore, AN11251 represents a promising pre-clinical candidate that was identified in the L. sigmodontis model, and could be further evaluated and developed as potential clinical candidate for human lymphatic filariasis and onchocerciasis.

<i>Burkholderia pseudomallei</i> invades the olfactory nerve and bulb after epithelial injury in mice and causes the formation of multinucleated giant glial cells <i>in vitro</i>

PLoS Neglected Tropical Diseases News - 24 January 2020 - 10:00pm

by Heidi Walkden, Ali Delbaz, Lynn Nazareth, Michael Batzloff, Todd Shelper, Ifor R. Beacham, Anu Chacko, Megha Shah, Kenneth W. Beagley, Johana Tello Velasquez, James A. St John, Jenny A. K. Ekberg

The infectious disease melioidosis is caused by the bacterium Burkholderia pseudomallei. Melioidosis is characterised by high mortality and morbidity and can involve the central nervous system (CNS). We have previously discovered that B. pseudomallei can infect the CNS via the olfactory and trigeminal nerves in mice. We have shown that the nerve path is dependent on mouse strain, with outbred mice showing resistance to olfactory nerve infection. Damage to the nasal epithelium by environmental factors is common, and we hypothesised that injury to the olfactory epithelium may increase the vulnerability of the olfactory nerve to microbial insult. We therefore investigated this, using outbred mice that were intranasally inoculated with B. pseudomallei, with or without methimazole-induced injury to the olfactory neuroepithelium. Methimazole-mediated injury resulted in increased B. pseudomallei invasion of the olfactory epithelium, and only in pre-injured animals were bacteria found in the olfactory nerve and bulb. In vitro assays demonstrated that B. pseudomallei readily infected glial cells isolated from the olfactory and trigeminal nerves (olfactory ensheathing cells and trigeminal Schwann cells, respectively). Bacteria were degraded by some cells but persisted in other cells, which led to the formation of multinucleated giant cells (MNGCs), with olfactory ensheathing cells less likely to form MNGCs than Schwann cells. Double Cap mutant bacteria, lacking the protein BimA, did not form MNGCs. These data suggest that injuries to the olfactory epithelium expose the primary olfactory nervous system to bacterial invasion, which can then result in CNS infection with potential pathogenic consequences for the glial cells.

Plasma metabolomics of the time resolved response to <i>Opisthorchis felineus</i> infection in an animal model (golden hamster, <i>Mesocricetus auratus</i>)

PLoS Neglected Tropical Diseases News - 24 January 2020 - 10:00pm

by Daria Kokova, Aswin Verhoeven, Ekaterina A. Perina, Vladimir V. Ivanov, Elena M. Knyazeva, Irina V. Saltykova, Oleg A. Mayboroda

Background

Opisthorchiasis is a hepatobiliary disease caused by flukes of the trematode family Opisthorchiidae. Opisthorchiasis can lead to severe hepatobiliary morbidity and is classified as a carcinogenic agent. Here we investigate the time-resolved metabolic response to Opisthorchis felineus infection in an animal model.

Methodology

Thirty golden hamsters were divided in three groups: severe infection (50 metacercariae/hamster), mild infection (15 metacercariae/hamster) and uninfected (vehicle-PBS) groups. Each group consisted of equal number of male and female animals. Plasma samples were collected one day before the infection and then every two weeks up to week 22 after infection. The samples were subjected to 1H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical modelling.

Principal findings

The time-resolved study of the metabolic response to Opisthorchis infection in plasma in the main lines agrees with our previous report on urine data. The response reaches its peak around the 4th week of infection and stabilizes after the 10th week. Yet, unlike the urinary data there is no strong effect of the gender in the data and the intensity of infection is presented in the first two principal components of the PCA model. The main trends of the metabolic response to the infection in blood plasma are the transient depletion of essential amino acids and an increase in lipoprotein and cholesterol concentrations.

Conclusions

The time resolved metabolic signature of Opisthorchis infection in the hamster’s plasma shows a coherent shift in amino acids and lipid metabolism. Our work provides insight into the metabolic basis of the host response on the helminth infection.

Outcomes of visceral leishmaniasis in pregnancy: A retrospective cohort study from South Sudan

PLoS Neglected Tropical Diseases News - 24 January 2020 - 10:00pm

by Judith E. Pekelharing, Francis Gatluak, Tim Harrison, Fernando Maldonado, M. Ruby Siddiqui, Koert Ritmeijer

Introduction

Visceral leishmaniasis (VL) is endemic in South Sudan, where outbreaks occur frequently. Because of changes in the immune system during pregnancy, pregnant women are considered particularly vulnerable for developing complications of VL disease, including opportunistic infections. There is limited evidence available about clinical aspects and treatment outcomes of VL in pregnancy. We describe characteristics, maternal and pregnancy outcomes from a cohort of pregnant women with VL.

Methods

We conducted a retrospective analysis using routine programme data from a MSF health facility in Lankien, Jonglei State, South Sudan, between Oct 2014 and April 2018. Records were extracted of women diagnosed with VL while pregnant, and those symptomatic during pregnancy but diagnosed during the first two weeks postpartum. Records were matched with a random sample of non-pregnant women of reproductive age (15–45 years) with VL from the same period.

Results

We included 113 women with VL in pregnancy, and 223 non-pregnant women with VL. Women with VL in pregnancy presented with more severe anaemia, were more likely to need blood transfusion (OR 9.3; 95%CI 2.5–34.2) and were more often prescribed antibiotics (OR 6.0; 95%CI 3.4–10.6), as compared to non-pregnant women with VL. Adverse pregnancy outcomes, including miscarriage and premature delivery, were reported in 20% (16/81) where VL was diagnosed in pregnancy, and 50% 13/26) where VL was diagnosed postpartum. Postpartum haemorrhage was common. Pregnant women were more likely to require extension of treatment to achieve cure (OR 10.0; 95%CI 4.8–20.9), as compared to non-pregnant women with VL. Nevertheless, overall initial cure rates were high (96.5%) and mortality was low (1.8%) in this cohort of pregnant women with VL.

Conclusion

This is the largest cohort in the literature of VL in pregnancy. Our data suggest that good maternal survival rates are possible in resource-limited settings, despite the high incidence of complications.

Molecular xenomonitoring as a post-MDA surveillance tool for global programme to eliminate lymphatic filariasis: Field validation in an evaluation unit in India

PLoS Neglected Tropical Diseases News - 24 January 2020 - 10:00pm

by Swaminathan Subramanian, Purushothaman Jambulingam, Kaliannagounder Krishnamoorthy, Neelavathi Sivagnaname, Candasamy Sadanandane, Venkatesan Vasuki, Chokkalingam Palaniswamy, Balakrishnan Vijayakumar, Adinarayanan Srividya, Hari Kishan K. Raju

Background

Lymphatic filariasis (LF) is targeted for elimination by the year 2020. As of 2017, 67 of the 72 endemic countries have implemented annual Mass Drug Administration (MDA) for interrupting LF transmission. Transmission Assessment Survey (TAS) is the recommended protocol to evaluate the impact of MDA and to decide when to stop MDA in an Evaluation Unit (EU, population ≤2 million). As the human infection levels go down with repeated MDA rounds, it becomes a challenge to select the appropriate survey methods to assess transmission interruption. This study validates a standard protocol for molecular xenomonitoring of infection in vectors (MX) at an EU as a complementary tool for TAS to stop MDA and its utility for post-MDA or post-validation surveillance.

Methodology

The study was conducted in Cuddalore district, Tamil Nadu, India, which was found eligible for TAS after 15 annual rounds of MDA (4 with DEC alone and 11 with DEC plus albendazole). The district was divided into two EUs as per the TAS protocol and one EU was randomly selected for the study. A two-stage cluster design vector sampling, developed and validated at a sub-district level, was implemented in 30 randomly selected clusters in the EU. Female Culex quinquefasciatus were collected placing gravid traps overnight (1800–0600 hrs) inside the premises of systematically selected households. Pools of 20–25 blood-fed, semi-gravid and gravid Cx. quinquefasciatus were subjected to real-time quantitative PCR (polymerase chain reaction) assay for detecting Wuchereria bancrofti DNA. Pool infection rate (% of pools positive for W. bancrofti DNA), and the estimated prevalence of W. bancrofti DNA in mosquitoes and its 95% confidence interval were calculated. Additionally, in these 30 clusters, microfilaria (Mf) survey among individuals >5 years old was carried out. School-based TAS was conducted using Immunochromatographic Card Test (ICT) in the EU. Prepared itemized cost-menu for different cost components of MX survey and TAS were estimated and compared.

Results

MX survey showed that only 11 (3.1%) of the 358 pools (8850 Cx.quinquefasciatus females), collected from 30 clusters, were found positive for W. bancrofti DNA. The estimated vector infection rate was 0.13% (95% CI: 0.07–0.22%), below the provisional threshold (0.25%) for transmission interruption. Of 1578 children tested in the TAS, only four (0.25%) were positive for filarial antigenemia, and it is well below the critical cut-off (18 positives) for stopping MDA. Among 9804 persons tested in the 30 clusters, only four were found positive for Mf (0.04%; 95% CI: 0.01–0.1%). The Mf-prevalence was <1% threshold for transmission interruption in humans. The estimated costs for TAS and MX per EU were $14,104 USD and $14,259 USD respectively.

Conclusions

The result of MX protocol was in good agreement with that of TAS, providing evidence to recommend MX as a complementary tool to TAS to decide on stopping MDA. MX can also be a potential surveillance tool for post-MDA and post-validation phases as it could detect sites with residual infection and risk of resurgence of transmission. MX is economically feasible as its cost is slightly lower than that of TAS.

Hyperendemic <i>Chlamydia trachomatis</i> sexually transmitted infections among females represent a high burden of asymptomatic disease and health disparity among Pacific Islanders in Fiji

PLoS Neglected Tropical Diseases News - 23 January 2020 - 10:00pm

by Virginia Svigals, Alden Blair, Santha Muller, Aalisha Sahu Khan, Daniel Faktaufon, Mike Kama, Torika Tamani, Laila Esfandiari, Mollie O’Brien, Deborah Dean

Background

Chlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide with some of the highest prevalence rates among Pacific Island Countries where syndromic management is practiced. However, little is known about the true prevalence and risk indicators for infection among neglected populations in these countries that suffer from health disparities.

Methodology/Principal findings

Consecutive sampling was used to enroll sexually active females, aged 18–40 years, attending 12 Fijian Ministry of Health and Medical Services Health Centers and outreach locations from February to December, 2018. A Behavioral Surveillance Survey was administered to assess risk indicators for infection. Signs and symptoms were recorded, and vaginal swabs were tested for C. trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Candida and bacterial vaginosis. Bivariate and multivariate logistic regression analyses were performed using R-Studio. Of 577 participants, 103 (17.85%) were infected with C. trachomatis of whom 80% were asymptomatic and only 11 met criteria for syndromic management; 38.8% of infected women were 18–24 years old with a prevalence of 30.5%. 91.7% of participants intermittently or did not use condoms. C. trachomatis infection was associated with iTaukei ethnicity (OR 21.41 [95% CI: 6.38–133.53]); two (OR 2.12 [95% CI: 1.08–4.18]) lifetime partners; and N. gonorrhoeae co-infection (OR 9.56 [95% CI: 3.67–28.15]) in multivariate analyses.

Conclusions

A disproportionately high burden of C. trachomatis is present among young asymptomatic women in Fiji of iTaukei ethnicity despite the low number of lifetime partners. Syndromic management and lack of barrier contraceptives contribute to hyperendemic levels. Strategic STI education and screening of at-risk adolescents, young women, and their partner(s) with appropriate treatment are urgently needed to control the epidemic.

Implementation of a mass canine rabies vaccination campaign in both rural and urban regions in southern Malawi

PLoS Neglected Tropical Diseases News - 23 January 2020 - 10:00pm

by Carlos Sánchez-Soriano, Andrew D. Gibson, Luke Gamble, Jordana L. Burdon Bailey, Dagmar Mayer, Frederic Lohr, Patrick Chikungwa, Julius Chulu, Ian G. Handel, Barend M. deC. Bronsvoort, Richard J. Mellanby, Stella Mazeri

Rabies is a devastating zoonotic disease causing nearly 60,000 deaths globally each year. The disease causes Malawi an economic loss of 13 million USD and kills almost 500 people annually. Domestic dogs are the main reservoir for rabies and vaccinating over 70% of the dog population is the most efficient method to reduce its incidence in both humans and canines. However, achieving such coverages is often difficult and depend on many geospatial factors. Rural and pastoral regions are considered difficult to vaccinate efficiently due to low dog densities, and reports of campaigns spanning large areas containing vastly different communities are lacking. This study describes a mass canine vaccination campaign covering rural and urban regions in southern Malawi. The campaign achieved an average vaccination coverage of 83.4% across 3 districts, and vaccinated over 89,000 dogs through a combined static point and door-to-door effort. A dog population of 107,574 dogs was estimated (dog:human ratio of 1:23). The canine population was found to be almost completely owned (99.2%) and mostly kept for security purposes (82.7%). The dogs were mainly adults, males, and not neutered. Regression analysis identified education level and proportion of young dogs as the only factors influencing (positively and negatively, respectively) whether vaccination coverage over 70% was achieved in a region, independently of variables such as population density or poverty. A second regression analysis was performed predicting absolute vaccination coverage. While education level and the proportion of confined dogs were associated with positive vaccination coverage, higher proportions of young animals and female dogs were associated with a decrease in coverage. This study confirms the feasibility of homogeneously vaccinating over 70% of the dogs in a large area including rural and urban communities. These findings can inform the logistics of future campaigns and might be used as a template to facilitate high-number, high-coverage vaccination campaigns to other regions in sub-Saharan Africa.

Language and beliefs in relation to noma: a qualitative study, northwest Nigeria

PLoS Neglected Tropical Diseases News - 23 January 2020 - 10:00pm

by Elise Farley, Annick Lenglet, Aisha Abubakar, Karla Bil, Adolphe Fotso, Bukola Oluyide, Simba Tirima, Ushma Mehta, Beverley Stringer

Background

Noma is an orofacial gangrene that rapidly disintegrates the tissues of the face. Little is known about noma, as most patients live in underserved and inaccessible regions. We aimed to assess the descriptive language used and beliefs around noma, at the Noma Children’s Hospital in Sokoto, Nigeria. Findings will be used to inform prevention programs.

Methods

Five focus group discussions (FGD) were held with caretakers of patients with noma who were admitted to the hospital at the time of interview, and 12 in-depth interviews (IDI) were held with staff at the hospital. Topic guides used for interviews were adapted to encourage the natural flow of conversation. Emergent codes, patterns and themes were deciphered from the data derived from IDI’s and FGDs.

Results

Our study uncovered two main themes: names, descriptions and explanations for the disease, and risks and consequences of noma. Naming of the disease differed between caretakers and heath care workers. The general names used for noma illustrate the beliefs and social system used to explain the disease. Beliefs were varied; participant responses demonstrate a wide range of understanding of the disease and its causes. Difficulty in accessing care for patients with noma was evident and the findings suggest a variety of actions taking place before reaching a health center or health worker. Patient caretakers mentioned that barriers to care included a lack of knowledge regarding this medical condition, as well as a lack of trust in seeking medical care. Participants in our study spoke of the mental health strain the disease placed on them, particularly due to the stigma that is associated with noma.

Conclusions

Caretaker and practitioner perspectives enhance our understanding of the disease in this context and can be usedto improve treatment and prevention programs, and to better understand barriers to accessing health care. Differences in disease naming illustrate the difference in beliefs about the disease. This has an impact on health seeking behaviours, which for noma cases has important ramifications on outcomes, due to the rapid progression of the disease.

Heatwaves cause fluctuations in <i>w</i>Mel <i>Wolbachia</i> densities and frequencies in <i>Aedes aegypti</i>

PLoS Neglected Tropical Diseases News - 23 January 2020 - 10:00pm

by Perran A. Ross, Jason K. Axford, Qiong Yang, Kyran M. Staunton, Scott A. Ritchie, Kelly M. Richardson, Ary A. Hoffmann

Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia are being released into natural mosquito populations in the tropics as a way of reducing dengue transmission. High temperatures adversely affect wMel, reducing Wolbachia density and cytoplasmic incompatibility in some larval habitats that experience large temperature fluctuations. We monitored the impact of a 43.6°C heatwave on the wMel infection in a natural population in Cairns, Australia, where wMel was first released in 2011 and has persisted at a high frequency. Wolbachia infection frequencies in the month following the heatwave were reduced to 83% in larvae sampled directly from field habitats and 88% in eggs collected from ovitraps, but recovered to be near 100% four months later. Effects of the heatwave on wMel appeared to be stage-specific and delayed, with reduced frequencies and densities in field-collected larvae and adults reared from ovitraps but higher frequencies in field-collected adults. Laboratory experiments showed that the effects of heatwaves on cytoplasmic incompatibility and density are life stage-specific, with first instar larvae being the most vulnerable to temperature effects. Our results indicate that heatwaves in wMel-infected populations will have only temporary effects on Wolbachia frequencies and density once the infection has established in the population. Our results are relevant to ongoing releases of wMel-infected Ae. aegypti in several tropical countries.

Identification of trombiculid mites (Acari: Trombiculidae) on rodents from Chiloé Island and molecular evidence of infection with <i>Orientia</i> species

PLoS Neglected Tropical Diseases News - 23 January 2020 - 10:00pm

by Gerardo Acosta-Jamett, Constanza Martínez-Valdebenito, Esperanza Beltrami, María Carolina Silva-de La Fuente, Ju Jiang, Allen L. Richards, Thomas Weitzel, Katia Abarca

Background

Scrub typhus is an emerging vector-borne zoonosis, caused by Orientia spp. and transmitted by larvae of trombiculid mites, called chiggers. It mainly occurs within a region of the Asia-Pacific called the tsutsugamushi triangle, where rodents are known as the most relevant hosts for the trombiculid vector. However, the reservoir(s) and vector(s) of the scrub typhus outside Asia-Pacific are unknown. The disease has recently been discovered on and is considered endemic for Chiloé Island in southern Chile. The aim of the present work was to detect and determine the prevalence of chiggers on different rodent species captured in probable sites for the transmission of orientiae responsible for scrub typhus on Chiloé Island in southern Chile and to molecularly examine collected chiggers for the presence of Orientia DNA.

Methodology/Principal findings

During the austral summer 2018, rodents were live-trapped in six sites and examined for chigger infestation. All study sites were rural areas on Chiloé Island, previously identified as probable localities where human cases acquired the scrub typhus. During a total of 4,713 trap-nights, 244 rodents of seven species were captured: the most abundant was Abrothrix olivacea. Chiggers were detected on all seven rodent species with a 55% prevalence rate. Chiggers showed low host specificity and varied according to site specific host abundance. Three genera of trombiculids were identified. Herpetacarus was the most abundant genus (93%), prevalent in five of the six sites. Infestation rates showed site specific differences, which were statistically significant using a GLM model with binomial errors. Molecular analyses proved that 21 of 133 (15.8%) mite pools were positive for Orientia species, all of them belonged to the genus Herpetacarus.

Conclusions/Significance

This study firstly reports the presence of different rodent-associated chigger mites positive for Orientia sp., in a region endemic for scrub typhus in southern Chile. Herpetacarus and two other genera of mites were found with high infestation rates of rodents in sites previously identified as probable exposure of scrub typhus cases. A substantial percentage of mite pools were positive for Orientia DNA, suggesting that chigger mites serve as vectors and reservoirs of this emerging zoonosis in South America.

Combined <i>in vitro</i> IL-12 and IL-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis

PLoS Neglected Tropical Diseases News - 21 January 2020 - 10:00pm

by Sidnei Ferro Costa, Vinícius Oliveira Gomes, Marilene Oliveira dos Santos Maciel, Larissa Martins Melo, Gabriela Lovizutto Venturin, Jaqueline Poleto Bragato, Gabriela Torres Rebech, Catiule de Oliveira Santos, Bárbara Maria Nascimento de Oliveira, Geraldo Gileno de Sá Oliveira, Valéria Marçal Felix de Lima

Domestic dogs are the main reservoir of Leishmania infantum, a causative agent of visceral leishmaniasis (VL). The number of human disease cases is associated with the rate of canine infection. Currently available drugs are not efficient at treating canine leishmaniasis (CanL) and months after the treatment most dogs show disease relapse, therefore the development of new drugs or new therapeutic strategies should be sought. In CanL, dogs lack the ability to mount a specific cellular immune response suitable for combating the parasite and manipulation of cytokine signaling pathway has the potential to form part of effective immunotherapeutic methods. In this study, recombinant canine cytokines (rcaIL-12, rcaIL-2, rcaIL-15 and rcaIL-7) and soluble receptor IL-10R1 (rcasIL-10R1), with antagonistic activity, were evaluated for the first time in combination (rcaIL-12/rcaIL-2, rcaIL-12/rcaIL-15, rcaIL-12/rcasIL-10R1, rcaIL-15/rcaIL-7) or alone (rcasIL-10R1) to evaluate their immunomodulatory capacity in peripheral blood mononuclear cells (PBMC) from dogs with leishmaniasis. All the combinations of recombinant proteins tested were shown to improve lymphoproliferative response. Further, the combinations rcaIL-12/rcaIL-2 and rcaIL-12/rcaIL-15 promoted a decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and rcaIL-12/rcasIL-10R1 induced IFN-γ and TNF-α production in PBMC. Furthermore, the combination IL-12/IL-15 led to an increased in T-bet expression in lymphocytes. These findings are encouraging and indicate the use of rcaIL-12 and rcaIL-15 in future in vivo studies aimed at achieving polarization of cellular immune responses in dogs with leishmaniasis, which may contribute to the development of an effective treatment against CanL.

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