PLOS Neglected Tropical Diseases: New ArticlesPLOShttps://journals.plos.org/plosntds/webmaster@plos.orghttps://journals.plos.org/plosntds/feed/atomAll PLOS articles are Open Access.https://journals.plos.org/plosntds/resource/img/favicon.icohttps://journals.plos.org/plosntds/resource/img/favicon.ico2024-03-19T10:50:39ZSero-prevalence and risk factors associated with occurrence of anti-<i>Brucella</i> antibodies among slaughterhouse workers in UgandaJames Katamba BugezaKristina RoeselDenis Rwabiita MugiziLordrick AlinaitweVelma KivaliClovice KankyaIgnacio MoriyonElizabeth Anne Jessie Cook10.1371/journal.pntd.00120462024-03-18T14:00:00Z2024-03-18T14:00:00Z<p>by James Katamba Bugeza, Kristina Roesel, Denis Rwabiita Mugizi, Lordrick Alinaitwe, Velma Kivali, Clovice Kankya, Ignacio Moriyon, Elizabeth Anne Jessie Cook</p>
Introduction <p>Brucellosis is a febrile zoonosis occurring among high-risk groups such as livestock keepers and abattoir workers and is a public health priority in Uganda. The technical complexities of bacteriological and molecular methods make serological approaches the cornerstone of diagnosis of human brucellosis in resource limited settings. Therefore, proper application and interpretation of serological tests is central to achieve a correct diagnosis.</p> Materials and methods <p>We conducted a cross-sectional study to estimate the seroprevalence and factors associated with anti-<i>Brucella</i> antibodies among slaughterhouse workers processing ruminants and pigs in three regions of the country with serial testing using a combination of the Rose Bengal Test (RBT) and the BrucellaCapt test. An authorized clinician collected 543 blood samples from consenting abattoir workers as well as attribute medical and social demographic data. Univariable and multivariable logistic regression were used to determine factors associated with anti-<i>Brucella</i> sero-positivity.</p> Results and discussion <p>The sero-prevalence among ruminant slaughterhouse workers ranged from 7.3% (95% CI: 4.8–10.7) using BrucellaCapt to 9.0% (95% CI: 6.3–12.7) using RBT. Slaughterhouse workers from the Eastern regions (AOR = 9.84, 95%CI 2.27–69.2, p = 0.006) and those who graze animals for alternative income (AOR = 2.36, 95% CI: 1.91–6.63, p = 0.040) were at a higher risk of exposure to <i>Brucella</i>. Similarly, those who wore Personal Protective Equipment (AOR = 4.83, 95%CI:1.63–18.0, p = 0.009) and those who slaughter cattle (AOR = 2.12, 95%CI: 1.25–6.0, p = 0.006) were at a higher risk of exposure to <i>Brucella</i>. Those who slaughter small ruminants (AOR = 1.54, 95%CI: 1.32–4.01, p = 0.048) were also at a higher risk of exposure to <i>Brucella</i>.</p> Conclusions and recommendations <p>Our study demonstrates the combined practical application of the RBT and BrucellaCapt in the diagnosis of human brucellosis in endemic settings. Both pharmaceutical (e.g., routine testing and timely therapeutic intervention), and non-pharmaceutical (e.g., higher index of suspicion of brucellosis when investigating fevers of unknown origin and observation of strict abattoir hygiene) countermeasures should be considered for control of the disease in high-risk groups.</p>Cross-sectional serosurvey of <i>Leptospira</i> species among slaughter pigs, goats, and sheep in UgandaLordrick AlinaitweChristopher Joshua AturindaAshiraf LubegaVelma KivaliJames BugezaMartin WainainaMartin H. RichterJolly Justine HoonaKristina RoeselAnne Mayer-SchollElizabeth Anne Jessie CookClovice KankyaSalome Dürr10.1371/journal.pntd.00120552024-03-15T14:00:00Z2024-03-15T14:00:00Z<p>by Lordrick Alinaitwe, Christopher Joshua Aturinda, Ashiraf Lubega, Velma Kivali, James Bugeza, Martin Wainaina, Martin H. Richter, Jolly Justine Hoona, Kristina Roesel, Anne Mayer-Scholl, Elizabeth Anne Jessie Cook, Clovice Kankya, Salome Dürr</p>
Introduction <p><i>Leptospira</i> are a group of bacteria, including pathogenic types that cause leptospirosis. In Uganda, <i>Leptospira</i> exposure has been reported in humans, with domesticated animals being speculated as the source. However, comparable evidence of <i>Leptospira</i> prevalence and circulating serovars/serogroups in animals is only documented for cattle, and dogs. Our study determined <i>Leptospira</i> seroprevalence, associated risk factors and serogroups circulating among slaughtered pigs, goats, and sheep in Uganda.</p> Methods <p>During an 11-month cross-sectional survey in selected slaughter facilities in three regions of Uganda, we collected blood from 926 pigs, 347 goats, and 116 sheep. The age, sex, breed, and origin of each sampled animal were noted. The samples were tested for anti-<i>Leptospira</i> antibodies using the microscopic agglutination test, based on a panel of 12 serovars belonging to 12 serogroups.</p> Results <p><i>Leptospira</i> seroprevalence was 26.67% (247/926, 95%CI 23.92–29.61) among pigs, and 21.81% (101/463, 95%CI 18.29–25.80) in goats and sheep (small ruminants). <i>L</i>. <i>interrogans</i> Australis and <i>L</i>. <i>kirschneri</i> Grippotyphosa were the commonest serovars among pigs, as was <i>L</i>. <i>borgpetersenii</i> Tarassovi in small ruminants. Pigs sourced from the Eastern (Odds Ratio [OR] = 2.82, 95%CI 1.84–4.30) and Northern (OR = 3.56, 95%CI 2.52–5.02) regions were more likely to be seropositive, compared to those from the Central region. For small ruminants, being female (OR 2.74, 95% CI 1.69–4.57) and adult (OR 4.47, 95% CI 1.57–18.80) was significantly more associated with <i>Leptospira</i> seropositivity.Conclusion/significance: Detection of a moderate seroprevalence, and several <i>Leptospira</i> serogroups among pigs, sheep, and goats from all regions of Uganda, supports existing reports in cattle and dogs, and implies widespread <i>Leptospira</i> exposure in domestic animals in Uganda. These findings may inform future programs for the control of leptospirosis in livestock in Uganda.</p>Comparative evaluation of four rapid diagnostic tests that detect human <i>Trypanosoma cruzi-</i>specific antibodies to support diagnosis of Chagas Disease in urban population of ArgentinaRocío RiveroM. Soledad SantiniConstanza López-AlbizuMarcelo RodriguezAdriana CalbosaDaniela OlivetoMónica EstevaMargarita BisioLaura C. Bohorquez10.1371/journal.pntd.00119972024-03-15T14:00:00Z2024-03-15T14:00:00Z<p>by Rocío Rivero, M. Soledad Santini, Constanza López-Albizu, Marcelo Rodriguez, Adriana Calbosa, Daniela Oliveto, Mónica Esteva, Margarita Bisio, Laura C. Bohorquez</p>
Background <p>Chagas disease (CD), caused by the parasite <i>Trypanosoma cruzi</i>, is the most important endemic anthropozoonosis in Argentina. Since 2010, the World Health Organization has highlighted the urgent need to validate diagnostic systems that allow rapid detection of <i>T</i>. <i>cruzi</i>, infection in primary healthcare centers. Serological rapid diagnostic tests (RDTs) for <i>T</i>. <i>cruzi</i>, infection could be used to improve case management, as RDTs do not require specialized laboratories or highly trained staff to use them. We aimed to generate unbiased performance data of RDTs in Argentina, to evaluate their usefulness for improving <i>T</i>. <i>cruzi</i>, diagnosis rates.</p> Methods and principal findings <p>This is a retrospective, laboratory-based, diagnostic evaluation study to estimate the clinical sensitivity/specificity of four commercially available RDTs for <i>T</i>. <i>cruzi</i>, using the Chagas disease diagnostic algorithm currently used in Argentina as the reference standard. In total, 400 serum samples were tested, 200 from individuals with chronic <i>T</i>. <i>cruzi</i> infection and 200 from individuals not infected with <i>T</i>. <i>cruzi</i>. All results were registered as the agreement of at least two operators who were blinded to the reference standard results. The sensitivity estimates ranged from 92.5–100% (95% confidence interval (CI) lower bound 87.9–98.2%); for specificity, the range was 76–96% (95% CI lower bound 69.5–92.3%). Most RDTs evaluated showed performances comparable with the reference standard method, showing almost perfect concordance (<i>Kappa</i> 0.76–0.92).</p> Conclusions <p>Our study demonstrates that, under controlled laboratory conditions, commercially available RDTs for CD have a performance comparable to the Argentinian diagnostic algorithm, which is based on laboratory-based serological tests. For the next stage of our work, the RDTs will be evaluated in real-world settings.</p>Analysis of diagnostic test outcomes in a large loiasis cohort from an endemic region: Serological tests are often false negative in hyper-microfilaremic infectionsLuzia VeletzkyKirsten Alexandra EberhardtJennifer HergethDaniel Robert StelzlRella Zoleko ManegoRuth KreuzmairGerrit BurgerJohannes MischlingerMatthew B. B. McCallGhyslain Mombo-NgomaAyôla Akim AdegnikaSelidji Todagbe AgnandjiPierre Blaise MatsieguiBertrand LellPeter KremsnerBenjamin MordmüllerDennis TappeMichael Ramharter10.1371/journal.pntd.00120542024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Luzia Veletzky, Kirsten Alexandra Eberhardt, Jennifer Hergeth, Daniel Robert Stelzl, Rella Zoleko Manego, Ruth Kreuzmair, Gerrit Burger, Johannes Mischlinger, Matthew B. B. McCall, Ghyslain Mombo-Ngoma, Ayôla Akim Adegnika, Selidji Todagbe Agnandji, Pierre Blaise Matsiegui, Bertrand Lell, Peter Kremsner, Benjamin Mordmüller, Dennis Tappe, Michael Ramharter</p>
Background <p>The parasitic disease loiasis is associated with significant morbidity and mortality. Individuals with hyper-microfilaremia (greater than 20,000 microfilariae per mL of blood) may suffer from serious treatment-related or spontaneous adverse events. Diagnosing loiasis remains complex and primarily relies on direct parasite detection. In this study, we analyzed the performance of various diagnostic tests and the influence of parasitological and clinical factors on test outcomes in samples from individuals living in an endemic region.</p> Methods <p>Data and samples were collected from rural Gabon. Loiasis was defined as either detectable microfilaremia, or a positive history of eyeworm as assessed by the RAPLOA questionnaire. Diagnostic testing included a quantitative PCR (qPCR) for detection of <i>Loa loa</i> DNA in blood samples, an in-house crude <i>L</i>. <i>loa</i> antigen IgG ELISA, and a rapid test for antibodies against the Ll-SXP-1 antigen (RDT). Sensitivity and specificity were determined for each test and factors potentially influencing outcomes were evaluated in an exploratory analysis.</p> Results <p>ELISA, RDT and qPCR results were available for 99.8%, 78.5%, and 100% of the 1,232 participants, respectively. The ELISA and RDT had only modest diagnostic accuracy. qPCR was specific for <i>L</i>. <i>loa</i> microfilaremia and Cycle threshold values correlated with microfilarial density. Anti-<i>L</i>. <i>loa</i> IgG levels were highest in occult loiasis, and antibody levels correlated inversely with <i>L</i>. <i>loa</i> microfilarial density as did RDT line intensities. Only 84.6% and 16.7% of hyper-microfilaremic individuals tested positive by ELISA (11/13) and RDT (2/12), respectively.</p> Conclusion <p>None of the tests demonstrated high sensitivity and specificity for loiasis. Indirect diagnostic assays were characterized by low specificity. Additionally, hyper-microfilaremic individuals often tested negative by RDT and ELISA, indicating that these tests are not suitable for individual case management in endemic populations.</p>Absence of Anti-<i>Babesia microti</i> antibody in commercial intravenous immunoglobulin (IVIG)Julia KostkaAnu S. MaharjanSanjai KumarDouglas HackenyosPeter J. KrauseKevin Dieckhaus10.1371/journal.pntd.00120352024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Julia Kostka, Anu S. Maharjan, Sanjai Kumar, Douglas Hackenyos, Peter J. Krause, Kevin Dieckhaus</p>
Background <p>Babesiosis is a worldwide emerging protozoan infection that is associated with a spectrum of disease severity from asymptomatic infection to severe organ damage and death. While effective treatment strategies are available, some immunocompromised patients experience severe acute and prolonged/relapsing illness due in part to an impaired host antibody response. Intravenous immunoglobulin (IVIG) has been used as an adjunctive therapy in some immunocompromised babesiosis patients, but its therapeutic effect is uncertain. We evaluated the presence of <i>Babesia microti</i> antibodies in commercial samples of IVIG.</p> Methods/principle findings <p>The presence of <i>B</i>. <i>microti</i> antibodies in commercial samples of IVIG were tested using an immunofluorescence assay. A subset of samples was then tested for <i>B</i>. <i>microti</i> antibodies using an enzyme linked immunosorbent assay.Out of 57 commercial IVIG samples tested using IFA, and 52 samples tested using ELISA, none were positive for <i>B</i>. <i>microti</i> antibodies.</p> Conclusions <p>Commercially available IVIG may not be of therapeutic benefit for babesiosis patients. Additional sampling of IVIG for B. microti antibody and a clinical trial of babesiosis patients given IVIG compared with controls would provide further insight into the use of IVIG for the treatment of babesiosis.</p>Successful introgression of <i>w</i>Mel <i>Wolbachia</i> into <i>Aedes aegypti</i> populations in Fiji, Vanuatu and KiribatiCameron P. SimmonsWesley DonaldLekon TagaviLen TarivondaTimothy QuaiRaynelyn TavoaTebikau NoranErirau ManikaotiLavinia KareauaTabomoa Tinte AbwaiDip ChandVineshwaran RamaVimal DeoKharishma Karti DeoAminiasi TavuiiWame ValentineRavi PrasadEremasi SeruLeikitah NaitukuAnaseini RatuMark HeskethNichola KennySarah C. BeebeAnjali A. GoundarAndrew McCawMolly BuntineBen GreenTibor FrossardJeremie R. L. GillesD. Albert JoubertGeoff WilsonLe Quyen DuongJean B BouvierDarren StanfordCarolyn ForderJohanna M. DuyvestynEtiene C. PacidônioHeather A. FloresNatalie WittmeierKate RetzkiPeter A. RyanJai A. DentonRuth SmithymanStephanie K. TanamasPeter KyrylosYi DongAnam KhalidLauren HodgsonKatherine L. AndersScott L. O’Neill10.1371/journal.pntd.00120222024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Cameron P. Simmons, Wesley Donald, Lekon Tagavi, Len Tarivonda, Timothy Quai, Raynelyn Tavoa, Tebikau Noran, Erirau Manikaoti, Lavinia Kareaua, Tabomoa Tinte Abwai, Dip Chand, Vineshwaran Rama, Vimal Deo, Kharishma Karti Deo, Aminiasi Tavuii, Wame Valentine, Ravi Prasad, Eremasi Seru, Leikitah Naituku, Anaseini Ratu, Mark Hesketh, Nichola Kenny, Sarah C. Beebe, Anjali A. Goundar, Andrew McCaw, Molly Buntine, Ben Green, Tibor Frossard, Jeremie R. L. Gilles, D. Albert Joubert, Geoff Wilson, Le Quyen Duong, Jean B Bouvier, Darren Stanford, Carolyn Forder, Johanna M. Duyvestyn, Etiene C. Pacidônio, Heather A. Flores, Natalie Wittmeier, Kate Retzki, Peter A. Ryan, Jai A. Denton, Ruth Smithyman, Stephanie K. Tanamas, Peter Kyrylos, Yi Dong, Anam Khalid, Lauren Hodgson, Katherine L. Anders, Scott L. O’Neill</p>
Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of <i>Aedes aegypti</i> mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium <i>Wolbachia pipientis</i> (<i>w</i>Mel strain) into <i>Ae</i>. <i>aegypti</i> populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of <i>w</i>Mel-infected <i>Ae</i>. <i>aegypti</i> in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of <i>w</i>Mel-infected <i>Ae</i>. <i>aegypti</i> mosquitoes for between 2 to 5 months resulted in <i>w</i>Mel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of <i>w</i>Mel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years.Cryptic circulation of chikungunya virus in São Jose do Rio Preto, Brazil, 2015–2019Nathalia ZiniMatheus Henrique Tavares ÁvilaNatalia Morbi CezarottiMaisa Carla Pereira ParraCecília Artico BanhoLivia SacchettoAndreia Francesli NegriEmerson AraújoCintia BittarBruno Henrique Gonçalves de Aguiar MilhinVictor Miranda HernandesKarina Rocha DutraLeonardo Agopian TrigoLeonardo Cecílio da RochaRafael Alves da SilvaGislaine Celestino Dutra da SilvaTamires Fernanda Pereira dos SantosBeatriz de Carvalho MarquesAndresa Lopes dos SantosMarcos Tayar AugustoNatalia Franco Bueno MistrãoMilene Rocha RibeiroTauyne Menegaldo PinheiroThayza Maria Izabel Lopes dos SantosClarita Maria Secco AvillaVictoria BernardiCaroline FreitasFlora de Andrade GandolfiHélio Correa Ferraz JúniorGabriela Camilotti PerimMirella Cezare GomesPedro Henrique Carrilho GarciaRodrigo Sborghi RochaTayna Manfrin GalvãoEliane Aparecida FávaroSamuel Noah ScamardiKaren Sanmartin RogovskiRenan Luiz PeixotoLuiza BenfattiLeonardo Teixeira CruzPaula Patricia de Freitas ChamaMânlio Tasso OliveiraAripuanã Sakurada Aranha WatanabeAna Carolina Bernardes TerzianAlice de Freitas VersianiMargareth Regina DiboFrancisco Chiaravalotti-NetoScott Cameron WeaverCassia Fernanda EstofoleteNikos VasilakisMauricio Lacerda Nogueira10.1371/journal.pntd.00120132024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Nathalia Zini, Matheus Henrique Tavares Ávila, Natalia Morbi Cezarotti, Maisa Carla Pereira Parra, Cecília Artico Banho, Livia Sacchetto, Andreia Francesli Negri, Emerson Araújo, Cintia Bittar, Bruno Henrique Gonçalves de Aguiar Milhin, Victor Miranda Hernandes, Karina Rocha Dutra, Leonardo Agopian Trigo, Leonardo Cecílio da Rocha, Rafael Alves da Silva, Gislaine Celestino Dutra da Silva, Tamires Fernanda Pereira dos Santos, Beatriz de Carvalho Marques, Andresa Lopes dos Santos, Marcos Tayar Augusto, Natalia Franco Bueno Mistrão, Milene Rocha Ribeiro, Tauyne Menegaldo Pinheiro, Thayza Maria Izabel Lopes dos Santos, Clarita Maria Secco Avilla, Victoria Bernardi, Caroline Freitas, Flora de Andrade Gandolfi, Hélio Correa Ferraz Júnior, Gabriela Camilotti Perim, Mirella Cezare Gomes, Pedro Henrique Carrilho Garcia, Rodrigo Sborghi Rocha, Tayna Manfrin Galvão, Eliane Aparecida Fávaro, Samuel Noah Scamardi, Karen Sanmartin Rogovski, Renan Luiz Peixoto, Luiza Benfatti, Leonardo Teixeira Cruz, Paula Patricia de Freitas Chama, Mânlio Tasso Oliveira, Aripuanã Sakurada Aranha Watanabe, Ana Carolina Bernardes Terzian, Alice de Freitas Versiani, Margareth Regina Dibo, Francisco Chiaravalotti-Neto, Scott Cameron Weaver, Cassia Fernanda Estofolete, Nikos Vasilakis, Mauricio Lacerda Nogueira</p>
Background <p>Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in <i>Aedes</i> mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent.</p> Methodology/principal findings <p>Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of <i>A</i>. <i>aegypti</i> and 9.09% of <i>A</i>. <i>albopictus</i> (although it was far less abundant than <i>A</i>. <i>aegypti</i>) by RT–qPCR.</p> Conclusions/significance <p>Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention.</p>Correction: Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2Pi-Chun LiMei-Ying LiaoPing-Chang ChengJian-Jong LiangI-Ju LiuChien-Yu ChiuYi-Ling LinGwong-Jen J. ChangHan-Chung Wu10.1371/journal.pntd.00120312024-03-13T14:00:00Z2024-03-13T14:00:00Z<p>by Pi-Chun Li, Mei-Ying Liao, Ping-Chang Cheng, Jian-Jong Liang, I-Ju Liu, Chien-Yu Chiu, Yi-Ling Lin, Gwong-Jen J. Chang, Han-Chung Wu</p>Prokaryotic and eukaryotic skin microbiota modifications triggered by <i>Leishmania</i> infection in localized Cutaneous LeishmaniasisJesús JaimesLuz Helena PatiñoGiovanny HerreraClaudia CruzJulie PérezCamilo A. Correa-CárdenasMarina MuñozJuan David Ramírez10.1371/journal.pntd.00120292024-03-13T14:00:00Z2024-03-13T14:00:00Z<p>by Jesús Jaimes, Luz Helena Patiño, Giovanny Herrera, Claudia Cruz, Julie Pérez, Camilo A. Correa-Cárdenas, Marina Muñoz, Juan David Ramírez</p>
Cutaneous Leishmaniasis (CL) is a tropical disease characterized by cutaneous ulcers, sometimes with satellite lesions and nodular lymphangitis. <i>Leishmania</i> parasites, transmitted by sandfly vectors, cause this widespread public health challenge affecting millions worldwide. CL’s complexity stems from diverse <i>Leishmania</i> species and intricate host interactions. Therefore, this study aims to shed light on the spatial-temporal distribution of <i>Leishmania</i> species and exploring the influence of skin microbiota on disease progression. We analyzed 40 samples from CL patients at three military bases across Colombia. Using Oxford Nanopore’s Heat Shock Protein 70 sequencing, we identified <i>Leishmania</i> species and profiled microbiota in CL lesions and corresponding healthy limbs. Illumina sequencing of <i>16S-rRNA</i> and <i>18S-rRNA</i> genes helped analyze prokaryotic and eukaryotic communities. Our research uncovered a spatial-temporal overlap between regions of high CL incidence and our sampling locations, indicating the coexistence of various <i>Leishmania</i> species. <i>L</i>. <i>naiffi</i> emerged as a noteworthy discovery. In addition, our study delved into the changes in skin microbiota associated with CL lesions sampled by scraping compared with healthy skin sampled by brushing of upper and lower limbs. We observed alterations in microbial diversity, both in prokaryotic and eukaryotic communities, within the lesioned areas, signifying the potential role of microbiota in CL pathogenesis. The significant increase in specific bacterial families, such as Staphylococcaceae and Streptococcaceae, within CL lesions indicates their contribution to local inflammation. In essence, our study contributes to the ongoing research into CL, highlighting the need for a multifaceted approach to decipher the intricate interactions between Leishmaniasis and the skin microbiota.Community’s knowledge, perceptions and preventive practices on Onchocerciasis in Jimma zone, Ethiopia, formative mixed studyDaba AbdissaYohannes KebedeMorankar SudhakarGelila AbrahamGebeyehu BulchaTeshome ShiferawNimona BerhanuFiranbon TeshomeHirpa MiechaZewdie Birhanu10.1371/journal.pntd.00119952024-03-13T14:00:00Z2024-03-13T14:00:00Z<p>by Daba Abdissa, Yohannes Kebede, Morankar Sudhakar, Gelila Abraham, Gebeyehu Bulcha, Teshome Shiferaw, Nimona Berhanu, Firanbon Teshome, Hirpa Miecha, Zewdie Birhanu</p>
Background <p>In Ethiopia, Onchocerciasis is a prevalent neglected tropical disease, currently targeted for elimination with mass drug administration and community behavioral changes towards sustained control and eventual elimination. This study aimed to elucidate the awareness, perceptions and practices of endemic communities in Jimma Zone, Ethiopia.</p> Methods and materials <p>Community-based cross-sectional study triangulated with qualitative method was conducted from October-November, 2021. A multistage sampling was employed and data were collected using a pre-tested interviewer-administered structured questionnaire. Logistic regression was used to identify the predictors of comprehensive knowledge and preventive practice. Adjusted odds ratios were calculated at 95% confidence interval (CI) and considered significant with a p-value of <0.05. Kruskal-Whallis and Mann-whitney tests were used to compare median risk perception score by socio-demographic factors. Qualitative data were collected through focus group discussions and key informant interviews and transcribed verbatim. Then the data were coded, categorized, and themes were developed.</p> Result <p>The overall prevalence of adequate comprehensive knowledge was 48.8% (95% CI: 44.9, 52.3), high risk perception was 18.7% (95%CI15.9, 21.4) and preventive practice was 46.9%(95%CI:(43.3,50.4). High risk perception[AOR = 1.95 95%CI: (1.32, 2.89] was statistically significant with comprehensive knowledge, likewise knowledge of mode of transmission [AOR = 2.64 95% CI: (1.44, 4.85)], knowledge of consequences [AOR = 2.12 95%CI: (1.21, 3.72)] and knowledge of preventive measures [AOR = 15.65,95%CI:(10.1, 24.2)] were statistically significant with preventive practice. The median risk perception was varied significantly between the groups by educational status, study district and age category. Qualitative evidence showed that there were great community knowledge gap about the disease.</p> Conclusion <p>Community knowledge, perceptions, and practices are unacceptably low. Risk perception was significantly associated with comprehensive knowledge, likewise knowledge of mode of transmission, consequences and preventive measures were significantly associated with preventive practice. This implies knowledge is a key component of effective prevention strategies as it is a necessary condition for the behavior change.</p>Factors related to willingness to participate in biomedical research on neglected tropical diseases: A systematic reviewVinícius Raimundo-SilvaCaio Torres MarquesJoão Rezende FonsecaMartha Silvia Martínez-SilveiraMitermayer Galvão Reis10.1371/journal.pntd.00119962024-03-12T14:00:00Z2024-03-12T14:00:00Z<p>by Vinícius Raimundo-Silva, Caio Torres Marques, João Rezende Fonseca, Martha Silvia Martínez-Silveira, Mitermayer Galvão Reis</p>
Background <p>Understanding the barriers to and facilitators of participation in research could enhance recruitment rates for biomedical research on Neglected Tropical Diseases (NTDs) and help to avoid the problems associated with poor recruitment.</p> Methodology/principal findings <p>We conducted a systematic review to identify factors related to willingness to participate in biomedical research on Neglected Tropical Diseases (NTDs). Our search included the following databases: Medline/PubMed, Embase (Embase.com), Global Index Medicus (WHO), Web of Science (Core collection), and gray literature. We included studies that analyzed or reported factors associated with willingness to participate in NTD research, using either quantitative methods (such as clinical trials, cohorts, and cross-sectional studies) or qualitative methods (such as focus group discussions, semi-structured interviews, and in-depth interviews). There were no language restrictions, but we excluded review articles, notes, case reports, letters to the editor, editor’s notes, extended abstracts, proceedings, patents, editorials, and other editorial materials.Screening of citations, data extraction, and risk of bias assessment was conducted by independent reviewers, according to the study protocol registered on PROSPERO. For analyses, we assessed the frequency of barriers, enablers, and the frequency of recruitment interventions mentioned in the included studies. The protocol for this systematic review was registered under registration number CRD42020212536. (S1 Appendix)We identified 2070 citations, 1470 from the databases, and 600 from other sources. From these, eleven studies were selected for data extraction and analysis. The studies were conducted in Africa, Asia, and North America. Personal health benefits, monetary benefits, and community engagement and sensitization strategies were identified as the main reasons for participating in biomedical research on Neglected Tropical Diseases (NTDs). However, distrust in researchers, lack of knowledge about research methods among potential participants, and previous negative experiences were identified as the main barriers to participating in biomedical research on NTDs.</p> Conclusions/significance <p>This systematic review provides recommendations for improving adherence to biomedical research on Neglected Tropical Diseases, which can be applied in practice.</p>One Health approach for <i>Brucella canis</i>: Serological and molecular detection in animal-hoarding individuals and their dogsLetícia SchiavoMatheus Lopes RibeiroMeila Bastos de AlmeidaGraziela Ribeiro da CunhaGiselle Almeida Nocera Espírito SantoVivien Midori MorikawaAcácia Ferreira VicenteClaire PonsartCarlos Eduardo de SantiLouise Bach KmetiukJane MegidAlexander Welker Biondo10.1371/journal.pntd.00119742024-03-12T14:00:00Z2024-03-12T14:00:00Z<p>by Letícia Schiavo, Matheus Lopes Ribeiro, Meila Bastos de Almeida, Graziela Ribeiro da Cunha, Giselle Almeida Nocera Espírito Santo, Vivien Midori Morikawa, Acácia Ferreira Vicente, Claire Ponsart, Carlos Eduardo de Santi, Louise Bach Kmetiuk, Jane Megid, Alexander Welker Biondo</p>
Animal hoarding disorder (AHD) is classified as a psychiatric obsessive-compulsive condition characterized by animal accumulation and often accompanied by unsanitary conditions and animal cruelty. Although AHD may increase pathogen transmission and spread, particularly for zoonotic diseases, human and dog exposure in such cases has yet to be fully established. Accordingly, this study aimed to assess <i>Brucella canis</i> in 19 individuals with AHD (11 households) and their 264 dogs (21 households) in Curitiba, the eighth largest city in Brazil, with approximately 1.8 million habitants. Anti-<i>B</i>. <i>canis</i> antibodies were detected by the 2-mercaptoethanol microplate agglutination test (2ME-MAT) and by a commercial lateral flow immunoassay (LFIA), while molecular detection of previously positive seropositive samples was performed by conventional PCR. Although all the human samples were 2ME-MAT negative, 12/264 (4.5%, 95% Confidence Interval: 2.0–7.0%) dog samples were 2ME-MAT and LFIA positive, with 2ME-MAT titers ranging from 20 to 640. At least one dog in 4/21 (19.0%, 95% CI: 2.0–46.0%) households was seropositive. Despite the absence of seropositivity in individuals with AHD and the comparatively low seroprevalence in dogs, <i>B</i>. <i>canis</i> circulation and outbreaks should be considered in such human populations due to the high burden and recurrent character of <i>B</i>. <i>canis</i> exposure in high-density dog populations and the constant introduction of susceptible animals.Efficacy and safety of therapeutic strategies for human brucellosis: A systematic review and network meta-analysisSarah Nascimento SilvaGláucia CotaDiego Mendes XavierGlaciele Maria de SouzaMarina Rocha Fonseca SouzaMoisés Willian Aparecido GonçalvesFelipe Francisco Bondan TuonEndi Lanza Galvão10.1371/journal.pntd.00120102024-03-11T14:00:00Z2024-03-11T14:00:00Z<p>by Sarah Nascimento Silva, Gláucia Cota, Diego Mendes Xavier, Glaciele Maria de Souza, Marina Rocha Fonseca Souza, Moisés Willian Aparecido Gonçalves, Felipe Francisco Bondan Tuon, Endi Lanza Galvão</p>
Background <p>Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its morbidity, generating socioeconomic impact. This review aims to update the current evidence on the efficacy and safety of therapeutic options for human brucellosis using the network meta-analysis (NMA).</p> Methodology <p>A systematic search was conducted in four different databases by independent reviewers to assess overall therapy failure, adverse events, and time to defervescence associated with different therapies. Randomized clinical trials (RCTs) evaluating any therapeutic drug intervention were selected, excluding non-original studies or studies related to localized forms of the disease or with less than 10 participants. Data were analyzed by frequentist statistics through NMA by random effects model. The risk of bias and certainty of evidence was assessed, this review was registered at PROSPERO.</p> Results <p>Thirty-one (31) RCTs involving 4167 patients were included. Three networks of evidence were identified to evaluate the outcomes of interest. Triple therapy with doxycycline + streptomycin + hydroxychloroquine for 42 days (RR: 0.08; CI 95% 0.01–0.76) had a lower failure risk than the doxycycline + streptomycin regimen. Doxycycline + rifampicin had a higher risk of failure than doxycycline + streptomycin (RR: 1.96; CI 95% 1.27–3.01). No significant difference was observed between the regimens when analyzing the incidence of adverse events and time to defervescence. In general, most studies had a high risk of bias, and the results had a very low certainty of evidence.</p> Conclusions <p>This review confirmed the superiority of drugs already indicated for treating human brucellosis, such as the combination of doxycycline and aminoglycosides. The association of hydroxychloroquine to the dual regimen was identified as a potential strategy to prevent overall therapy failure, which is subject to confirmation in future studies.</p>Female genital schistosomiasis is a neglected public health problem in Tanzania: Evidence from a scoping reviewGladys MbwanjiHumphrey D. MazigoJane K. MagangaJennifer A. Downs10.1371/journal.pntd.00119542024-03-11T14:00:00Z2024-03-11T14:00:00Z<p>by Gladys Mbwanji, Humphrey D. Mazigo, Jane K. Maganga, Jennifer A. Downs</p>
<i>Schistosoma haematobium</i>, the parasite that causes urogenital schistosomiasis, is widely prevalent in Tanzania. In addition to well-known effects on the urinary tract, <i>S</i>. <i>haematobium</i> also causes clinically- evident damage to the reproductive tract in approximately half of infected women, which is known as female genital schistosomiasis (FGS). FGS has major gynecologic and social consequences on women’s reproductive health, yet little information is available regarding FGS in Tanzania. To cover that gap, we conducted the present scoping review to examine the epidemiology of FGS in Tanzania (both in the mainland and Zanzibar island) and to make recommendations for future work in this area. The available evidence from community-based and hospital-based retrospective studies indicates that FGS is a significant health problem in the country. Very few community-based studies have been reported from mainland Tanzania, and Zanzibar. Our review highlights the scarcity of efforts to address FGS in Tanzania and the need for additional community-based studies. The studies will help us understand the true burden of the disease nationwide, to assess the impact of praziquantel on FGS lesions, and to address social and mental health in relation to FGS. This review emphasizes integration of delivery of FGS related services in primary health care systems through the reproductive health clinics which covers sexually transmitted infections, HIV and cervical cancer screening. These actions are essential if this neglected gynecological disease is to be addressed in Tanzania.Socio-ecological risk factors associated with human flea infestations of rural household in plague-endemic areas of MadagascarAdélaïde MiarinjaraAnnick Onimalala RavelosonStephen Gilbert MugelNick AnAndry AndriamiadanarivoMinoarisoa Esther RajerisonRindra Vatosoa RandremananaRomain GirodThomas Robert Gillespie10.1371/journal.pntd.00120362024-03-07T14:00:00Z2024-03-07T14:00:00Z<p>by Adélaïde Miarinjara, Annick Onimalala Raveloson, Stephen Gilbert Mugel, Nick An, Andry Andriamiadanarivo, Minoarisoa Esther Rajerison, Rindra Vatosoa Randremanana, Romain Girod, Thomas Robert Gillespie</p>
Plague is a flea-borne fatal disease caused by the bacterium <i>Yersinia pestis</i>, which persists in rural Madagascar. Although fleas parasitizing rats are considered the primary vectors of <i>Y</i>. <i>pestis</i>, the human flea, <i>Pulex irritans</i>, is abundant in human habitations in Madagascar, and has been found naturally infected by the plague bacterium during outbreaks. While <i>P</i>. <i>irritans</i> may therefore play a role in plague transmission if present in plague endemic areas, the factors associated with infestation and human exposure within such regions are little explored. To determine the socio-ecological risk factors associated with <i>P</i>. <i>irritans</i> infestation in rural households in plague-endemic areas of Madagascar, we used a mixed-methods approach, integrating results from <i>P</i>. <i>irritans</i> sampling, a household survey instrument, and an observational checklist. Using previously published vectorial capacity data, the minimal <i>P</i>. <i>irritans</i> index required for interhuman bubonic plague transmission was modeled to determine whether household infestations were enough to pose a plague transmission risk. Socio-ecological risk factors associated with a high <i>P</i>. <i>irritans</i> index were then identified for enrolled households using generalized linear models. Household flea abundance was also modeled using the same set of predictors. A high <i>P</i>. <i>irritans</i> index occurred in approximately one third of households and was primarily associated with having a traditional dirt floor covered with a plant fiber mat. Interventions targeting home improvement and livestock housing management may alleviate flea abundance and plague risk in rural villages experiencing high <i>P</i>. <i>irritans</i> infestation. As plague-control resources are limited in developing countries such as Madagascar, identifying the household parameters and human behaviors favoring flea abundance, such as those identified in this study, are key to developing preventive measures that can be implemented at the community level.Diagnosis of human brucellosis: Systematic review and meta-analysisMariana Lourenço FreireTália Santana Machado de AssisSarah Nascimento-SilvaGláucia Cota10.1371/journal.pntd.00120302024-03-07T14:00:00Z2024-03-07T14:00:00Z<p>by Mariana Lourenço Freire, Tália Santana Machado de Assis, Sarah Nascimento-Silva, Gláucia Cota</p>
Background <p>Brucellosis, a widely spread zoonotic disease, poses significant diagnostic challenges due to its non-specific symptoms and underreporting. Timely and accurate diagnosis is crucial for effective patient management and public health control. However, a comprehensive comparative review of available diagnostic tests is lacking.</p> Methodology/Principal findings <p>This systematic review addressed the following question: ‘What is the accuracy of the available tests to confirm human brucellosis?’ Two independent reviewers examined articles published up to January 2023. The review included original studies reporting symptomatic patients with brucellosis suspicion, through any index test, with sensitivity and/or specificity as outcomes. As exclusion criteria were considered: sample size smaller than 10 patients, studies focusing on complicated brucellosis, and those lacking essential information about index or comparator tests. Sensitivity and specificity were assessed, with consideration for the index test, and ‘culture’ and ‘culture and standard tube agglutination test (SAT)’ were used as reference standards. Bias assessment and certainty of evidence were carried out using the QUADAS-2 and GRADE tools, respectively. A total of 38 studies reporting diagnostic test performance for human brucellosis were included. However, the evidence available is limited, and significant variability was observed among studies. Regarding the reference test, culture and/or SAT are deemed more appropriate than culture alone. Rose Bengal, IgG/IgM ELISA, and PCR exhibited equally high performances, indicating superior overall diagnostic accuracy, with very low certainty of the evidence.</p> Conclusions/Significance <p>This systematic review underscores the potential of the Rose Bengal test, IgG/IgM ELISA, and PCR as promising diagnostic tools for brucellosis. However, the successful implementation and recommendations for their use should consider the local context and available resources. The findings highlight the pressing need for standardization, improved reporting, and ongoing advancements in test development to enhance the accuracy and accessibility of brucellosis diagnosis.</p>Challenges for maintaining post elimination phase of visceral leishmaniasis control programme in India: A field-based studySubhasish Kamal GuhaAshif Ali SardarPabitra SahaMoytrey ChatterjeeKingsuk JanaAnwesha SamantaDipankar MajiPrasanta BiswasRahul BhattacharyaArdhendu Kumar Maji10.1371/journal.pntd.00120282024-03-07T14:00:00Z2024-03-07T14:00:00Z<p>by Subhasish Kamal Guha, Ashif Ali Sardar, Pabitra Saha, Moytrey Chatterjee, Kingsuk Jana, Anwesha Samanta, Dipankar Maji, Prasanta Biswas, Rahul Bhattacharya, Ardhendu Kumar Maji</p>
Background <p>India is going through the maintenance phase of VL elimination programme which may be threatened by the persistence of hidden parasite pools among asymptomatic leishmanial infection (ALI) and PKDL. The present work was designed to determine the burden of VL, PKDL, and ALI and to assess the role of treatment of ALI in maintaining post-elimination phase.</p> Methods and finding <p>The study was undertaken in Malda district, West Bengal, India during October 2016 to September 2021. Study areas were divided into ‘Study’ and ‘Control’ arms. VL and PKDL cases of both the arms were diagnosed by three active mass surveys with an interval of one year and treated as per National guideline. ALI of study arm was treated like VL. ALI of control arm was followed up to determine their fate. Fed sand-fly pools were analysed for parasitic DNA. No significant difference was noted between the incidence of VL and PKDL in both the arms. Incidence of ALI declined sharply in study arm but an increasing trend was observed in control arm. Significantly higher rate of sero-conversion was noted in control arm and was found to be associated with untreated ALI burden. Parasitic DNA was detected in 22.8% ALI cases and 2.2% sand-fly pools.</p> Conclusion <p>Persistence of a significant number of PKDL and ALI and ongoing transmission, as evidenced by new infection and detection of leishmanial DNA in vector sand-flies, may threaten the maintenance of post-elimination phase. Emphasis should be given for elimination of pathogen to prevent resurgence of VL epidemics.</p>Prevalence of depressive symptoms in patients with advanced schistosomiasis in China: A systematic review and meta-analysisYu-Xin QiMeng-Rui HuangHui-Ying SunXiao-Yan WuZe-Ting LiuDa-Bing Lu10.1371/journal.pntd.00120032024-03-07T14:00:00Z2024-03-07T14:00:00Z<p>by Yu-Xin Qi, Meng-Rui Huang, Hui-Ying Sun, Xiao-Yan Wu, Ze-Ting Liu, Da-Bing Lu</p>
Background <p>Advanced schistosomiasis is the most serious outcome of infection and has a negative impact on both physical fitness and mental health of patients, the latter of which has long been overlooked. Therefore, we performed this systematic review and meta-analysis to estimate the overall prevalence of depressive symptoms, one of the most common mental problems, in patients with advanced schistosomiasis in China.</p> Methods <p>Six electronic databases were searched for studies reporting the prevalence of depressive symptoms in the targeted patients. Assessments were pooled using a fixed- or random-effects model based on heterogeneity test. Subgroup analyses were further performed and differences between/among groups were examined using the chi-squared test. The protocol had previously been registered in PROSPERO (CRD42023406708).</p> Results <p>A total of 11 studies with 1,673 participants were included. The pooled prevalence of depressive symptoms in advanced schistosomiasis in China was 62.01% (95% CI: 51.30% - 72.72%), with a significant heterogeneity among studies. Depressive symptoms were more prevalent in patients with complications and more than half of the patients suffered a mild- or moderate-level of depression. No publication bias was found, and sensitivity analysis showed a stable result.</p> Conclusions <p>The overall prevalence of depressive symptoms in advanced schistosomiasis in China was high enough to warrant psychotherapeutic interventions, especially for patients with complications. This would greatly prevent or/and reduce depression and improve their quality of life.</p>Cholangiohydatidosis. Clinical features, postoperative complications and hospital mortality. A systematic reviewCarlos ManterolaJosue RivadeneiraClaudio Rojas-PincheiraTamara OtzenHugo DelgadoCatalina SoteloAntonio Sanhueza10.1371/journal.pntd.00115582024-03-07T14:00:00Z2024-03-07T14:00:00Z<p>by Carlos Manterola, Josue Rivadeneira, Claudio Rojas-Pincheira, Tamara Otzen, Hugo Delgado, Catalina Sotelo, Antonio Sanhueza</p>
Background <p>Cholangiohydatidosis (CH) is an evolutionary complication of hepatic cystic echinococcosis, associated with increased morbidity and mortality. The aim of this study was to describe the available evidence regarding clinical characteristics of CH, postoperative complications and hospital mortality.</p> Methodology/Principal findings <p>Systematic review. Studies related to CH with no language or publication restriction were included. Sensitive searches were performed in Trip Database, SciELO, BIREME-BVS, WoS, PubMed, EMBASE and SCOPUS. MeSH and free terms were used, including articles up to April 2023. The main outcome variables were postoperative complications and hospital mortality; the secondary ones were publication year, origin and design of primary studies, main clinical manifestation, anatomical location and type of cysts, hospital stay, surgical procedure performed, reinterventions; and methodological quality of primary studies, which was assessed using MInCir-T and MInCir-P scales. Descriptive statistics, calculation of weighted averages and their comparison by least squares logistic regression were applied. 446 studies were retrieved from the searches performed, 102 of which met the inclusion and exclusion criteria. The studies analyzed represent 1241 patients. The highest proportion of articles was published in the last decade (39.2%). Reports are mainly from Turkey (28.4%), Greece (9.8%), Morocco and Spain (8.8% each). With a weighted mean of 14.3 days of hospital stance; it was verified that 26.2% of patients developed postoperative complications (74,3% Clavien y Dindo III y IV), 6.7% needed re-interventions, and 3.7% died. When comparing the variables age, postoperative complications, hospital mortality, and reinterventions in two periods of time (1982–2006 vs. 2007–2023), no statistically significant differences were found. When applying the MInCir-T and MInCir-P scales, the methodological quality of the primary studies was 9.6±1.1 and 14.5±4.3 points, respectively.</p> Conclusion/Significance <p>CH is associated with severe postoperative complications and significant hospital mortality, independent of the development of therapeutic support associated with the passage of time.</p>Diagnostic accuracy of serological rk-39 test for visceral Leishmaniasis: Systematic review and meta-analysisMihret GetnetAddisu Minaye DejenDessie AbebawGetachew Gedefaw FentahunEmebet Birhanu10.1371/journal.pntd.00119382024-03-06T14:00:00Z2024-03-06T14:00:00Z<p>by Mihret Getnet, Addisu Minaye Dejen, Dessie Abebaw, Getachew Gedefaw Fentahun, Emebet Birhanu</p>
Background <p>Visceral leishmaniasis (VL), or kala-azar, is a vector-borne tropical disease caused by a group of intracellular hemoflagellate protozoa belonging to the family of Trypanosomatide and the genus <i>Leishmania</i>. The disease is distributed around the world and transmitted via the bite of infected female <i>Phlebotomine</i> sandflies, and there is variation in the diagnostic accuracy. Therefore, this systematic review and meta-analysis aimed to determine the pooled global sensitivity and specificity of the rk-39 test and to evaluate if there is a difference between the different parts of the world.</p> Methods <p>A systematic review and meta-analysis have been conducted on the diagnostic accuracy of dermoscopy. After setting eligibility criteria, literature was searched in four databases and one searching engine. Articles were screened, critically appraised, and extracted independently by two reviewers, and any disagreements were resolved with the involvement of a third person. The quality of the included studies had been assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS 2) tool. Pooled sensitivity and specificity were determined by bivariate random effect analysis. Heterogeneity was assessed by Higgins’s <i>I</i><sup>2</sup>, and when it was present, mitigation was conducted by using sensitivity analysis.</p> Result <p>A total of 409 studies were identified, and finally 18 articles were eligible for the review with a total sample size of 5, 253. The bivariate random effect meta-analysis of the 7 diagnostic accuracy studies showed a pooled sensitivity of 0.89 (0.76–0.95) and specificity of 0.86 (0.72–0.94). The +LR was 6.32 (95% CI: 2.85–14.02), the–LR was 0.13 (95% CI: 0.06–0.30), and the diagnostic odds ratio (DOR) was 47.8 (95% CI: 11.3–203.2). Abdel-Latif (2018) was both an outlier and influential for sensitivity, and Walter (2011) was both an outlier and influential for specificity, and removing them from sensitivity and specificity, respectively, was beneficial for reducing the heterogeneity.</p> Conclusion <p>Rk-39 is found to have highly accurate measures in the diagnosis of visceral leishmaniasis. Both sensitivity and specificity were found to be highly accurate in the diagnosis of leishmaniasis, with a pooled sensitivity of 0.91 (0.88–0.93) and a pooled specificity of 0.89 (0.85–0.91).</p> Ethical consideration <p>As we will use secondary data for the systematic review and meta-analysis, ethical concerns are not necessary.</p>Epidemiological and clinical characteristics of scrub typhus in Guizhou Province, China: An outbreak study of scrub typhusJia HeQing MaZhongqiu TengJingzhu ZhouNa ZhaoWenqin LiangMiao LuShijun LiTian Qin10.1371/journal.pntd.00119632024-03-05T14:00:00Z2024-03-05T14:00:00Z<p>by Jia He, Qing Ma, Zhongqiu Teng, Jingzhu Zhou, Na Zhao, Wenqin Liang, Miao Lu, Shijun Li, Tian Qin</p>
The reported cases of scrub typhus (ST) have continued to escalate, with outbreaks occurring regionally in China. These pose an increasing public health threat at a time when public health has been overwhelmed. During the period from July to August 2022, in Rongjiang County, Guizhou Province, China, 13 out of 21 fever patients were diagnosed with scrub typhus, based on epidemiological investigation and blood test analysis. The major clinical symptoms of these patients showed fever, chills, headache, eschar, fatigue and pneumonia, which were accompanied by a rise in C-reactive protein, neutrophils, alanine transaminase (ALT) and aspartate aminotransferase (AST). Furthermore, nearly half of them exhibited abnormal electrocardiogram activity. Through semi-nested PCR, Sanger sequencing and phylogenetic tree construction, the Karp strain of <i>Orientia tsutsugamushi</i> (<i>O</i>. <i>tsutsugamushi</i>) was confirmed as the pathogen causing ST in Rongjiang County, which shared the same evolutionary branch with <i>O</i>. <i>tsutsugamushi</i> isolated from wild mouse liver or spleen, indicating that the wild mouse plays an important role in transmitting the disease. In contrast to the sporadic cases in the past, our study is the first to disclose an epidemic and the corresponding clinical characteristics of ST in Guizhou province, which is of great significance for the prevention and treatment of regional illnesses.Comparative evaluation of lateral flow assays to diagnose chronic <i>Trypanosoma cruzi</i> infection in BoliviaRonald LópezAndrea GarcíaJosé Jorge Chura AruniVictor BalboaAndrea RodríguezBerra ErkosarAurélie KamounMarcelo RodriguezEvelin FortunLaura C. Bohorquez10.1371/journal.pntd.00120162024-03-04T14:00:00Z2024-03-04T14:00:00Z<p>by Ronald López, Andrea García, José Jorge Chura Aruni, Victor Balboa, Andrea Rodríguez, Berra Erkosar, Aurélie Kamoun, Marcelo Rodriguez, Evelin Fortun, Laura C. Bohorquez</p>
Bolivia has the highest incidence of Chagas disease (CD) worldwide. Caused by the parasite <i>Trypanasoma cruzi</i>, CD is generally a chronic condition. Diagnosis is logistically and financially challenging, requiring at least two different laboratory-based serological tests. Many CD cases are missed; in Bolivia it is estimated just 6% of individuals chronically infected with <i>T</i>. <i>cruzi</i> get diagnosed. Achieving control on the way to elimination of CD requires a radical simplification of the current CD testing pathways, to overcome the barriers to accessing CD treatment. We aimed to generate unbiased performance data of lateral flow assays (LFAs) for <i>T</i>. <i>cruzi</i> infection in Bolivia, to evaluate their usefulness for improving <i>T</i>. <i>cruzi</i> diagnosis rates in a precise and efficient manner.
This retrospective, laboratory-based, diagnostic evaluation study sought to estimate the sensitivity/specificity of 10 commercially available LFAs for <i>T</i>. <i>cruzi</i>, using the current CD diagnostic algorithm employed in Bolivia as the reference test method. All tests were blinded at the study site and performed by three operators. In total, 470 serum samples were tested, including 221 and 249 characterized as CD-positive/-negative, respectively. The LFAs were scored according to their relative importance using a decision-tree-based algorithm, with the mean decrease in Gini index as the scoring metric.
The estimates of sensitivities ranged from 62.2–97.7% (95% confidence interval (CI) lower bound 55.0–94.7%); for specificities the range was 78.6–100% (95% CI lower bound 72.0–97.5%); 5/10 and 6/10 tests had sensitivity >90% and specificity >95%, respectively. Four LFAs showed high values of both sensitivity (93–95%) and specificity (97–99%). The agreement between 6 LFAs and the reference tests was almost perfect (Kappa 0.83–0.94). Most LFAs evaluated thus showed performances comparable with current laboratory-based diagnostic methods.Clinical and laboratory characterization of cutaneous leishmaniasis in Chinese migrant workers returned from IraqKuo BiXiaoli LiRui ZhangXiaoyan ZhengFei WangYang ZouLei Wang10.1371/journal.pntd.00120062024-03-04T14:00:00Z2024-03-04T14:00:00Z<p>by Kuo Bi, Xiaoli Li, Rui Zhang, Xiaoyan Zheng, Fei Wang, Yang Zou, Lei Wang</p>
Background <p>Imported cutaneous leishmaniasis (CL) is a growing problem with increasing global travel to endemic areas. Returned travelers with CL are easy to be misdiagnosed and mistreated due to the lack of awareness for the disease to the physicians in non-endemic region that may lead to unfavorable outcome. Our study intends to summarize the characteristics of <i>Leishmania</i> infection imported from Iraq, so as to help Chinese physicians diagnose and treat the disease. All CL patients were treated with intralesional injection of antimony.</p> Methods <p>The definitive diagnosis of CL is based on the parasite identification by microscopic examination directly on lesion smear or parasite culture, PCR amplification of <i>Leishmania</i>-specific internal transcribed spacer 1 (ITS-1). The phylogenetic analysis, the immunopathological examination and the cytokine detection were proceeded after the diagnosis.</p> Results <p>We have identified 25 CL cases in migrant Chinese workers returned from Iraq for the first time with <i>L</i>. <i>major</i> as the major species of infected <i>Leishmania</i> parasite. Clinical features of the Iraq-imported CL include the history of skin exposure to sandflies bite and the lesions mostly on the exposed limbs. More ulcerative wet lesion was observed than nodular dry lesion. PCR is not only used to detect <i>Leishmania</i> parasite with high sensitivity, but also to identify the species of infected parasite through sequencing the amplified <i>Leishmania</i>-specific ITS-1 gene. The phylogenetic analysis based on the amplified ITS-1 sequences revealed that the infected <i>Leishmania</i> was closed related to the species and strains endemic in Iraq. The immunopathological examination revealed the T-cell filtrated cellular immune response with less B cells and NK cells involved. The cytokine profile measured in the skin lesion also confirmed the Th1 cellular response with higher expression levels of IFN-γ, IL-6 and IL-8. The skin lesions in CL patients were healed after being treated locally with antimony.</p> Conclusions <p>The clinical and parasitological features of these Chinese CL cases imported from Iraq provide useful information for the diagnosis and treatment of CL that is not commonly seen in Chinese local population.</p>Novel <i>rpsK</i> / <i>rpsD</i> primer-probe assay improves detection of <i>Campylobacter jejuni</i> and <i>Campylobacter coli</i> in human stoolFrancesca SchiaffinoCraig T. ParkerPaul F. Garcia BardalesSteven HuynhKatia Manzanares VillanuevaEvangelos MourkasBen PascoePablo Peñataro YoriMaribel Paredes OlorteguiEric R. HouptJie LiuKerry K. CooperMargaret N. Kosek10.1371/journal.pntd.00120182024-03-01T14:00:00Z2024-03-01T14:00:00Z<p>by Francesca Schiaffino, Craig T. Parker, Paul F. Garcia Bardales, Steven Huynh, Katia Manzanares Villanueva, Evangelos Mourkas, Ben Pascoe, Pablo Peñataro Yori, Maribel Paredes Olortegui, Eric R. Houpt, Jie Liu, Kerry K. Cooper, Margaret N. Kosek</p>
<i>Campylobacter</i> causes bacterial enteritis, dysentery, and growth faltering in children in low- and middle-income countries (LMICs). <i>Campylobacter</i> spp. are fastidious organisms, and their detection often relies on culture independent diagnostic technologies, especially in LMICs. <i>Campylobacter jejuni</i> and <i>Campylobacter coli</i> are most often the infectious agents and in high income settings together account for 95% of <i>Campylobacter</i> infections. Several other <i>Campylobacter</i> species have been detected in LMIC children at an increased prevalence relative to high income settings. After doing extensive whole genome sequencing of isolates of <i>C</i>. <i>jejuni</i> and <i>C</i>. <i>coli</i> in Peru, we observed heterogeneity in the binding sites for the main species-specific PCR assay <i>(cadF) and</i> designed an alternative <i>rpsKD-</i>based qPCR assay to detect both <i>C</i>. <i>jejuni</i> and <i>C</i>. <i>coli</i>. The <i>rpsKD-</i>based qPCR assay identified 23% more <i>C</i>.<i>jejuni/ C</i>.<i>coli</i> samples than the <i>cadF</i> assay among 47 <i>Campylobacter</i> genus positive <i>cadF</i> negative samples verified to have <i>C</i>. <i>jejuni</i> and or <i>C</i>. <i>coli</i> with shotgun metagenomics. This assay can be expected to be useful in diagnostic studies of enteric infectious diseases and be useful in revising the attribution estimates of <i>Campylobacter</i> in LMICs.Evidence for circulation of Rift Valley fever virus in wildlife and domestic animals in a forest environment in Gabon, Central AfricaPierre BecquartLinda Bohou KombilaTelstar Ndong MebaleyChristophe PaupyDéborah GarciaNicolas NesiMarie-Marie OliveJessica VanhomwegenLarson BoundengaIllich Manfred MomboCamille Piro-MégyMatthieu FritzLéadisaelle Hosanna LenguiyaMeriadeg Ar GouilhEric M. LeroyNadine N’DilimabakaCatherine Cêtre-SossahGael Darren Maganga10.1371/journal.pntd.00117562024-03-01T14:00:00Z2024-03-01T14:00:00Z<p>by Pierre Becquart, Linda Bohou Kombila, Telstar Ndong Mebaley, Christophe Paupy, Déborah Garcia, Nicolas Nesi, Marie-Marie Olive, Jessica Vanhomwegen, Larson Boundenga, Illich Manfred Mombo, Camille Piro-Mégy, Matthieu Fritz, Léadisaelle Hosanna Lenguiya, Meriadeg Ar Gouilh, Eric M. Leroy, Nadine N’Dilimabaka, Catherine Cêtre-Sossah, Gael Darren Maganga</p>
Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by the Rift Valley fever virus (RVFV) that can infect domestic and wild animals. Although the RVFV transmission cycle has been well documented across Africa in savanna ecosystems, little is known about its transmission in tropical rainforest settings, particularly in Central Africa. We therefore conducted a survey in northeastern Gabon to assess RVFV circulation among wild and domestic animals. Among 163 wildlife samples tested using RVFV-specific RT-qPCR, four ruminants belonging to subfamily Cephalophinae were detected positive. The phylogenetic analysis revealed that the four RVFV sequences clustered together with a virus isolated in Namibia within the well-structured Egyptian clade. A cross-sectional survey conducted on sheep, goats and dogs living in villages within the same area determined the IgG RVFV-specific antibody prevalence using cELISA. Out of the 306 small ruminants tested (214 goats, 92 sheep), an overall antibody prevalence of 15.4% (95% CI [11.5–19.9]) was observed with a higher rate in goats than in sheep (20.1% <i>versus</i> 3.3%). RVFV-specific antibodies were detected in a single dog out of the 26 tested. Neither age, sex of domestic animals nor season was found to be significant risk factors of RVFV occurrence. Our findings highlight sylvatic circulation of RVFV for the first time in Gabon. These results stress the need to develop adequate surveillance plan measures to better control the public health threat of RVFV.Age-specific case data reveal varying dengue transmission intensity in US states and territoriesSarah KadaGabriela Paz-BaileyLaura E. AdamsMichael A. Johansson10.1371/journal.pntd.00111432024-03-01T14:00:00Z2024-03-01T14:00:00Z<p>by Sarah Kada, Gabriela Paz-Bailey, Laura E. Adams, Michael A. Johansson</p>
Dengue viruses (DENV) are endemic in the US territories of Puerto Rico, American Samoa, and the US Virgin Islands, with focal outbreaks also reported in the states of Florida and Hawaii. However, little is known about the intensity of dengue virus transmission over time and how dengue viruses have shaped the level of immunity in these populations, despite the importance of understanding how and why levels of immunity against dengue may change over time. These changes need to be considered when responding to future outbreaks and enacting dengue management strategies, such as guiding vaccine deployment. We used catalytic models fitted to case surveillance data stratified by age from the ArboNET national arboviral surveillance system to reconstruct the history of recent dengue virus transmission in Puerto Rico, American Samoa, US Virgin Islands, Florida, Hawaii, and Guam. We estimated average annual transmission intensity (i.e., force of infection) of DENV between 2010 and 2019 and the level of seroprevalence by age group in each population. We compared models and found that assuming all reported cases are secondary infections generally fit the surveillance data better than assuming all cases are primary infections. Using the secondary case model, we found that force of infection was highly heterogeneous between jurisdictions and over time within jurisdictions, ranging from 0.00008 (95% CrI: 0.00002–0.0004) in Florida to 0.08 (95% CrI: 0.044–0.14) in American Samoa during the 2010–2019 period. For early 2020, we estimated that seropositivity in 10 year-olds ranged from 0.09% (0.02%–0.54%) in Florida to 56.3% (43.7%–69.3%) in American Samoa. In the absence of serological data, age-specific case notification data collected through routine surveillance combined with mathematical modeling are powerful tools to monitor arbovirus circulation, estimate the level of population immunity, and design dengue management strategies.Potential selection of antimony and methotrexate cross-resistance in <i>Leishmania infantum</i> circulating strainsLorena BernardoAna Victoria Ibarra-MenesesNoelie DouanneAudrey CorbeilJose Carlos SolanaFrancis BeaudryEugenia CarrilloJavier MorenoChristopher Fernandez-Prada10.1371/journal.pntd.00120152024-02-29T14:00:00Z2024-02-29T14:00:00Z<p>by Lorena Bernardo, Ana Victoria Ibarra-Meneses, Noelie Douanne, Audrey Corbeil, Jose Carlos Solana, Francis Beaudry, Eugenia Carrillo, Javier Moreno, Christopher Fernandez-Prada</p>
Background <p>Visceral leishmaniasis (VL) resolution depends on a wide range of factors, including the instauration of an effective treatment coupled to a functional host immune system. Patients with a depressed immune system, like the ones receiving methotrexate (MTX), are at higher risk of developing VL and refusing antileishmanial drugs. Moreover, the alarmingly growing levels of antimicrobial resistance, especially in endemic areas, contribute to the increasing the burden of this complex zoonotic disease.</p> Principal findings <p>To understand the potential links between immunosuppressants and antileishmanial drugs, we have studied the interaction of antimony (Sb) and MTX in a <i>Leishmania infantum</i> reference strain (<i>Li</i>WT) and in two <i>L</i>. <i>infantum</i> clinical strains (<i>Li</i>FS-A and <i>Li</i>FS-B) naturally circulating in non-treated VL dogs in Spain. The <i>Li</i>FS-A strain was isolated before Sb treatment in a case that responded positively to the treatment, while the <i>Li</i>FS-B strain was recovered from a dog before Sb treatment, with the dog later relapsing after the treatment. Our results show that, exposure to Sb or MTX leads to an increase in the production of reactive oxygen species (ROS) in <i>Li</i>WT which correlates with a sensitive phenotype against both drugs in promastigotes and intracellular amastigotes. <i>Li</i>FS-A was sensitive against Sb but resistant against MTX, displaying high levels of protection against ROS when exposed to MTX. <i>Li</i>FS-B was resistant to both drugs. Evaluation of the melting proteomes of the two <i>Li</i>FS, in the presence and absence of Sb and MTX, showed a differential enrichment of direct and indirect targets for both drugs, including common and unique pathways.</p> Conclusion <p>Our results show the potential selection of Sb-MTX cross-resistant parasites in the field, pointing to the possibility to undermine antileishmanial treatment of those patients being treated with immunosuppressant drugs in <i>Leishmania</i> endemic areas.</p>MHC-I alleles mediate clearance and antibody response to the zoonotic Lassa virus in <i>Mastomys</i> rodent reservoirsAyodeji OlayemiDominik Werner SchmidRamona FleischerKerstin WilhelmAlexander Christoph HeniNadine Mueller-KleinLavinia HaikukutuElisabeth Fichet-CalvetStephan GüntherSimone Sommer10.1371/journal.pntd.00119842024-02-29T14:00:00Z2024-02-29T14:00:00Z<p>by Ayodeji Olayemi, Dominik Werner Schmid, Ramona Fleischer, Kerstin Wilhelm, Alexander Christoph Heni, Nadine Mueller-Klein, Lavinia Haikukutu, Elisabeth Fichet-Calvet, Stephan Günther, Simone Sommer</p>
West African <i>Mastomys</i> rodents are the primary reservoir of the zoonotic Lassa virus (LASV). The virus causes haemorrhagic Lassa fever and considerable mortality in humans. To date, the role of <i>Mastomys</i> immunogenetics in resistance to, and persistence of, LASV infections is largely unknown. Here, we investigated the role of Major Histocompatibility Complex class I (MHC-I) on LASV infection status (i.e., active vs. cleared infection, determined via PCR and an immunofluorescence assay on IgG antibodies, respectively) in <i>Mastomys natalensis</i> and <i>M</i>. <i>erythroleucus</i> sampled within southwestern Nigeria. We identified more than 190 and 90 MHC-I alleles by Illumina high throughput-sequencing in <i>M</i>. <i>natalensis</i> and <i>M</i>. <i>erythroleucus</i>, respectively, with different MHC allele compositions and frequencies between LASV endemic and non-endemic sites. In <i>M</i>. <i>natalensis</i>, the MHC allele ManaMHC-I*006 was negatively associated with active infections (PCR-positive) and positively associated with cleared infections (IgG-positive) simultaneously, suggesting efficient immune responses that facilitate LASV clearance in animals carrying this allele. Contrarily, alleles ManaMHC-I*008 and ManaMHC-I*021 in <i>M</i>. <i>natalensis</i>, and MaerMHC-I*008 in <i>M</i>. <i>erythroleucus</i>, were positively associated with active infection, implying susceptibility. Alleles associated with susceptibility shared a glutamic acid at the positively selected codon 57, while ManaMHC-I*006 featured an arginine. There was no link between number of MHC alleles per <i>Mastomys</i> individual and LASV prevalence. Thus, specific alleles, but not MHC diversity <i>per se</i>, seem to mediate antibody responses to viremia. We conclude that co-evolution with LASV likely shaped the MHC-I diversity of the main LASV reservoirs in southwestern Nigeria, and that information on reservoir immunogenetics may hold insights into transmission dynamics and zoonotic spillover risks.A haplotype-like, chromosome-level assembled and annotated genome of <i>Biomphalaria glabrata</i>, an important intermediate host of schistosomiasis and the best studied model of schistosomiasis vector snailsDaibin ZhongLijing BuMohamed R. HabibLijun LuGuiyun YanSi-Ming Zhang10.1371/journal.pntd.00119832024-02-29T14:00:00Z2024-02-29T14:00:00Z<p>by Daibin Zhong, Lijing Bu, Mohamed R. Habib, Lijun Lu, Guiyun Yan, Si-Ming Zhang</p>
Schistosomiasis is one of the world’s most devastating parasitic diseases, afflicting 251 million people globally. The Neotropical snail <i>Biomphalaria glabrata</i> is an important intermediate host of the human blood fluke <i>Schistosoma mansoni</i> and a predominant model for schistosomiasis research. To fully exploit this model snail for biomedical research, here we report a haplotype-like, chromosome-level assembled and annotated genome of the homozygous iM line of <i>B</i>. <i>glabrata</i> that we developed at the University of New Mexico. Using multiple sequencing platforms, including Illumina, PacBio, and Omni-C sequencing, 18 sequence contact matrices representing 18 haploid chromosomes (2n = 36) were generated (337x genome coverage), and 96.5% of the scaffold sequences were anchored to the 18 chromosomes. Protein-coding genes (n = 34,559), non-coding RNAs (n = 2,406), and repetitive elements (42.52% of the genome) were predicted for the whole genome, and detailed annotations for individual chromosomes were also provided. Using this genomic resource, we have investigated the genomic structure and organization of the <i>Toll-like receptor</i> (<i>TLR</i>) and <i>fibrinogen-domain containing protein</i> (<i>FReD</i>) genes, the two important immune-related gene families. Notably, <i>TLR-like</i> genes are scattered on 13 chromosomes. In contrast, almost all (39 of 40) <i>fibrinogen-related genes</i> (<i>FREPs</i>) (immunoglobulin superfamily (IgSF) + fibrinogen (FBG)) are clustered within a 5-million nucleotide region on chromosome 13, yielding insight into mechanisms involved in the diversification of <i>FREPs</i>. This is the first genome of schistosomiasis vector snails that has been assembled at the chromosome level, annotated, and analyzed. It serves as a valuable resource for a deeper understanding of the biology of vector snails, especially <i>Biomphalaria</i> snails.Modeling the persistence of <i>Opisthorchis viverrini</i> worm burden after mass-drug administration and education campaigns with systematic adherenceLars KamberChristine BürliHelmut HarbrechtPeter OdermattSomphou SayasoneNakul Chitnis10.1371/journal.pntd.00113622024-02-29T14:00:00Z2024-02-29T14:00:00Z<p>by Lars Kamber, Christine Bürli, Helmut Harbrecht, Peter Odermatt, Somphou Sayasone, Nakul Chitnis</p>
<i>Opisthorchis viverrini</i> is a parasitic liver fluke contracted by consumption of raw fish, which affects over 10 million people in Southeast Asia despite sustained control efforts. Chronic infections are a risk factor for the often fatal bile duct cancer, cholangiocarcinoma. Previous modeling predicted rapid elimination of <i>O. viverrini</i> following yearly mass drug administration (MDA) campaigns. However, field data collected in affected populations shows persistence of infection, including heavy worm burden, after many years of repeated interventions. A plausible explanation for this observation is systematic adherence of individuals in health campaigns, such as MDA and education, with some individuals consistently missing treatment.
We developed an agent-based model of <i>O. viverrini</i> which allows us to introduce various heterogeneities including systematic adherence to MDA and education campaigns at the individual level. We validate the agent-based model by comparing it to a previously published population-based model. We estimate the degree of systematic adherence to MDA and education campaigns indirectly, using epidemiological data collected in Lao PDR before and after 5 years of repeated MDA, education and sanitation improvement campaigns. We predict the impact of interventions deployed singly and in combination, with and without the estimated systematic adherence.
We show how systematic adherence can substantially increase the time required to achieve reductions in worm burden. However, we predict that yearly MDA campaigns alone can result in a strong reduction of moderate and heavy worm burden, even under systematic adherence. We predict latrines and education campaigns to be particularly important for the reduction in overall prevalence, and therefore, ultimately, elimination. Our findings show how systematic adherence can explain the observed persistence of worm burden; while emphasizing the benefit of interventions for the entire population, even under systematic adherence. At the same time, the results highlight the substantial opportunity to further reduce worm burden if patterns of systematic adherence can be overcome.