PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, sort=Date, newest first, q=subject:"Parasitic diseases"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&unformattedQuery=subject:%22Parasitic+diseases%22&sort=Date,+newest+firstAll PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-28T15:59:29ZCopayment mechanism in selected districts of Uganda: Availability, market share and price of quality assured artemisinin-based combination therapies in private drug outletsMoses OcanWinnie NambatyaCaroline OtikeLoyce NakalembeSam Nsobya10.1371/journal.pone.02951982024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Moses Ocan, Winnie Nambatya, Caroline Otike, Loyce Nakalembe, Sam Nsobya</p>
Background <p>Malaria remains one of the leading causes of morbidity, and mortality in Uganda. A large proportion of malaria symptomatic patients seek healthcare in private sector. However, availability and affordability are major barriers to access to effective treatment. The private sector copayment mechanism in Uganda aims to increase availability and affordability of antimalarial agents. Our study assessed availability, price, and market share of quality assured artemisinin-based combination therapies (QAACTs) in private drug outlets in selected districts during the implementation of copayment mechanism.</p> Methods <p>This was a cross-sectional survey of anti-malarial agents in private drug outlets in in selected moderate-to-high (Tororo, and Apac districts) and low (Kabale and Mbarara districts) malaria transmission settings. Following the World Health Organization/Health Action International (WHO/HAI) criteria, an audit of the antimalarial agents was done using a checklist to determine availability, price, and market share of QAACTs. Data were entered in Epi-data and analyzed in STATA <i>ver</i> 14.0 at 95% confidence level.</p> Results <p>A total of twenty-eight (28) private drug outlets (pharmacies and drug shops) were included in the survey. One in seven (20/144: 95%CI: 9.1, 20.6) of the antimalarial agents in private drug outlets were quality assured artemisinin-based combination therapies (QAACT). Artemether-lumefantrine (AL), 8.9% (11/124) and Artesunate-Amodiaquine (AQ), 7.3% (9/124) were the only QAACTs present in the drug outlets at the time of the survey. The majority, 86.1%% (124/144) of antimalarial agents present in stock in the drug outlets were artemisinin based. The most common, 38.9% (56/144) ACT in the drug outlets was Dihydroartemisinin-Piperaquine (DHP). Most, 69.4% (100/144) of the antimalarial agents were in high malaria transmission settings. The cost of ACT antimalarial agents is high in the country, USD 1.4 (Artemether-Lumefantrine, AL), USD 2.4 (Dihydroartemisinin-Piperaquine, DP), the first line and second-line agents respectively for treatment of uncomplicated malaria in Uganda. There was a statistically significant difference between the dispensing price of ‘Green leaf’ ACTs (QAACT) and the recommended price (<i>p<</i>0.001). Predictors of availability of QAACT in private drug outlets include pharmacy drug outlet (aPR:0.4; 95%CI: 0.2, 0.9) and dispensing price more than 3000UGX (USD 0.83) (aPR: 0.4, 95%CI: 0.1, 0.51).</p> Conclusion <p>Quality assured artemisinin-based combination therapies (QAACTs) are not common in private drug outlets in selected districts in Uganda. All the drug outlets had at least one ACT antimalarial agent present on the day of the survey. The dispensing price of QAACTs was significantly higher than the recommended markup price. There is need for awareness creation, surveillance, and monitoring of the implementation of Copayment mechanism in the country.</p>Reinfection of farm dogs following praziquantel treatment in an endemic region of cystic echinococcosis in southeastern IranMehdi BorhaniMohammad Ali MohammadiMahbod EntezamiMohammad Reza BaneshiSaeid NasibiJoaquin M. PradaMajid Fasihi Harandi10.1371/journal.pntd.00119392024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Mehdi Borhani, Mohammad Ali Mohammadi, Mahbod Entezami, Mohammad Reza Baneshi, Saeid Nasibi, Joaquin M. Prada, Majid Fasihi Harandi</p>
Cystic Echinococcosis (CE) as a prevalent tapeworm infection of human and herbivorous animals worldwide, is caused by accidental ingestion of <i>Echinococcus granulosus</i> eggs excreted from infected dogs. CE is endemic in the Middle East and North Africa, and is considered as an important parasitic zoonosis in Iran. It is transmitted between dogs as the primary definitive host and different livestock species as the intermediate hosts. One of the most important measures for CE control is dog deworming with praziquantel. Due to the frequent reinfection of dogs, intensive deworming campaigns are critical for breaking CE transmission. Dog reinfection rate could be used as an indicator of the intensity of local CE transmission in endemic areas. However, our knowledge on the extent of reinfection in the endemic regions is poor. The purpose of the present study was to determine <i>E</i>. <i>granulosus</i> reinfection rate after praziquantel administration in a population of owned dogs in Kerman, Iran. A cohort of 150 owned dogs was recruited, with stool samples collected before praziquantel administration as a single oral dose of 5 mg/kg. The re-samplings of the owned dogs were performed at 2, 5 and 12 months following initial praziquantel administration. Stool samples were examined microscopically using Willis flotation method. Genomic DNA was extracted, and <i>E</i>. <i>granulosus sensu lato</i>-specific primers were used to PCR-amplify a 133-bp fragment of a repeat unit of the parasite genome. Survival analysis was performed using Kaplan-Meier method to calculate cumulative survival rates, which is used here to capture reinfection dynamics, and monthly incidence of infection, capturing also the spatial distribution of disease risk. Results of survival analysis showed 8, 12 and 17% total reinfection rates in 2, 5 and 12 months following initial praziquantel administration, respectively, indicating that 92, 88 and 83% of the dogs had no detectable infection in that same time periods. The monthly incidence of reinfection in total owned dog population was estimated at 1.5% (95% CI 1.0–2.1). The results showed that the prevalence of echinococcosis in owned dogs, using copro-PCR assay was 42.6%. However, using conventional microscopy, 8% of fecal samples were positive for taeniid eggs. Our results suggest that regular treatment of the dog population with praziquantel every 60 days is ideal, however the frequency of dog dosing faces major logistics and cost challenges, threatening the sustainability of control programs. Understanding the nature and extent of dog reinfection in the endemic areas is essential for successful implementation of control programs and understanding patterns of CE transmission.Predictors for participation in mass-treatment and female genital schistosomiasis re-investigation, and the effect of praziquantel treatment in South African adolescentsTakalani Girly NemungadiElisabeth KleppaHashini Nilushika Galappaththi-ArachchigePavitra PillaySvein Gunnar GundersenBirgitte Jyding VennervaldPatricia Doris NdhlovuMyra TaylorSaloshni NaidooEyrun Floerecke Kjetland10.1371/journal.pntd.00117982024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Takalani Girly Nemungadi, Elisabeth Kleppa, Hashini Nilushika Galappaththi-Arachchige, Pavitra Pillay, Svein Gunnar Gundersen, Birgitte Jyding Vennervald, Patricia Doris Ndhlovu, Myra Taylor, Saloshni Naidoo, Eyrun Floerecke Kjetland</p>
Objective <p>Female Genital Schistosomiasis (FGS) causes intravaginal lesions and symptoms that could be mistaken for sexually transmitted diseases or cancer. In adults, FGS lesions [grainy sandy patches (GSP), homogenous yellow patches (HYP), abnormal blood vessels and rubbery papules] are refractory to treatment. The effect of treatment has never been explored in young women; it is unclear if gynaecological investigation will be possible in this young age group (16–23 years). We explored the predictors for accepting anti-schistosomal treatment and/or gynaecological reinvestigation in young women, and the effects of anti-schistosomal mass-treatment (praziquantel) on the clinical manifestations of FGS at an adolescent age.</p> Method <p>The study was conducted between 2011 and 2013 in randomly selected, rural, high schools in Ilembe, uThungulu and Ugu Districts, KwaZulu-Natal Province, East Coast of South Africa. At baseline, gynaecological investigations were conducted in female learners in grades 8 to 12, aged 16–23 years (n = 2293). Mass-treatment was offered in the low-transmission season between May and August (a few in September, n = 48), in accordance with WHO recommendations. Reinvestigation was offered after a median of 9 months (range 5–14 months). Univariate, multivariable and logistic regression analysis were used to measure the association between variables.</p> Results <p>Prevalence: Of the 2293 learners who came for baseline gynaecological investigations, 1045 (46%) had FGS lesions and/or schistosomiasis, 209/1045 (20%) had GSP; 208/1045 (20%) HYP; 772/1045 (74%) had abnormal blood vessels; and 404/1045 (39%) were urine positive.Overall participation rate for mass treatment and gynaecological investigation: Only 26% (587/2293) learners participated in the mass treatment and 17% (401/2293) participated in the follow up gynaecological reinvestigations.Loss to follow-up among those with FGS: More than 70% of learners with FGS lesions at baseline were lost to follow-up for gynaecological investigations: 156/209 (75%) GSP; 154/208 (74%) HYP; 539/722 (75%) abnormal blood vessels; 238/404 (59%) urine positive. The grade 12 pupil had left school and did not participate in the reinvestigations (n = 375; 16%).Follow-up findings: Amongst those with lesions who came for both treatment and reinvestigation, 12/19 still had GSP, 8/28 had HYP, and 54/90 had abnormal blood vessels. Only 3/55 remained positive for <i>S</i>. <i>haematobium</i> ova.Factors influencing treatment and follow-up gynaecological investigation: HIV, current water contact, water contact as a toddler and urinary schistosomiasis influenced participation in mass treatment. Grainy sandy patches, abnormal blood vessels, HYP, previous pregnancy, current water contact, water contact as a toddler and father present in the family were strongly associated with coming back for follow-up gynaecological investigation.Challenges in sample size for follow-up analysis of the effect of treatment: The low mass treatment uptake and loss to follow up among those who had baseline FGS reduced the chances of a larger sample size at follow up investigation. However, multivariable analysis showed that treatment had effect on the abnormal blood vessels (adjusted odds ratio = 2.1, 95% CI 1.1–3.9 and p 0.018).</p> Conclusion <p>Compliance to treatment and gynaecological reinvestigation was very low. There is need to embark on large scale awareness and advocacy in schools and communities before implementing mass-treatment and investigation studies. Despite challenges in sample size and significant loss to follow-up, limiting the ability to fully understand the treatment’s effect, multivariable analysis demonstrated a significant treatment effect on abnormal blood vessels.</p>Sexual and reproductive health among men with genital schistosomiasis in southern Tanzania: A descriptive studyTwilumba MakeneAbdallah ZachariaStanley HauleGift LukumayBilly Ngasala10.1371/journal.pgph.00025332024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Twilumba Makene, Abdallah Zacharia, Stanley Haule, Gift Lukumay, Billy Ngasala</p>
Male genital schistosomiasis (MGS) is a significantly neglected condition, and its consequences often receive inadequate attention. The disease is suggested to cause schistosomiasis-induced sexual and reproductive health problems among males. The study was conducted to investigate the prevalence of MGS, sexual and reproductive health problems that could be caused by MGS among adult males in Mtama district. A community-based cross-sectional study using quantitative methods was carried out among males aged ≥ 18 years in selected households. Semen and urine samples were collected from each participant to establish the prevalence of MGS and urogenital schistosomiasis respectively. Semen quality was macroscopically and microscopically assessed. Urine samples were analyzed using filtration technique. A structured questionnaire interview was carried out to collect socio-demographic data, sexual and reproductive health information. Descriptive statistics were used to provide a summary of each variable. The prevalence (proportions) were presented in percentages and their respective 95% confidence intervals. A total of 223 adult males participated in this study. The prevalence of MGS and urogenital schistosomiasis were 5.8% (95% CI; 3.1%-9.0%) and 22.4% (95% CI; 16.6%-27.8%) respectively. The prevalence of <i>Schistosoma haematobium</i> eggs in semen was found high among young adults 12/129 (9.3%, 95% CI; 4.9%-15.7%), who never attended to school 6/35 (17.1%, 95% CI; 6.6%-33.6%), petty traders 4/26 (15.4%, 95% CI; 4.4%-34.9%), never impregnated woman 9/70 (12.9%, 95% CI: 6.6%-33.6%), experienced pain during ejaculation 4/17 (23.5%, 95% CI; 4.9%-15.7%), and with brownish semen 2/5 (40%, 95% CI; 4.9%-15.7%). According to the findings, MGS, like urogenital schistosomiasis, is prevalent in southern Tanzania. The disease is prevalent among males with some reproductive and sexual issues. This highlight the need for more research to investigate the association of MGS and male reproductive and sexual health for improved health services among males.Factors associated with the uptake of intermittent preventive treatment for malaria during pregnancy in Cameroon: An analysis of data from the 2018 Cameroon Demographic and Health SurveyDominique Ken GuimsopAnge Faustine Kenmogne TallaHaoua KodjiJerome Ateudjieu10.1371/journal.pgph.00012452024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Dominique Ken Guimsop, Ange Faustine Kenmogne Talla, Haoua Kodji, Jerome Ateudjieu</p>
Malaria in pregnancy is a major public health concern that contributes to a significant increase in maternal and child mortality and morbidity. Intermittent preventive treatment of malaria during pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) is a key intervention recommended by the World Health Organization (WHO) and implemented in Cameroon to reduce the morbidity associated with malaria during pregnancy. This study aimed to assess the distribution of the poor uptake of IPTp-SP (i.e. fewer than three doses) in Cameroon and the factors associated. We conducted a secondary analysis of data extracted from the 2018 Cameroon Demographic and Health Survey. Data was collected using a face-to-face questionnaire administered to mothers with at least one child under the age of five. The participants were selected using a two-stage stratified sampling process. We estimated the frequencies of mothers receiving fewer than three doses of IPTp-SP. Multilevel logistic regression modeling was used to assess the associations between key suspected determinants and uptake of fewer than three doses of IPTp-SP. Crude and adjusted Odds-Ratio (ORs) were estimated. A total of 13,527 women of childbearing age were interviewed, of whom 5,528 (40.9%) met our selection criteria. Among them, 845 (15.3%) women had no antenatal consultation (ANC) visit, 1,109 (20%) had 1–3 visits, 3,379 (61.1%) had 4–7 visits, and only 195 (3.5%) had at least eight visits. Moreover, 3,398 (61.5%, CI: 60.2–62.8) had received fewer than three doses of IPTp-SP. Our findings show that the predictors of poor uptake of IPTp-SP include attending the first ANC visit after the third month of pregnancy (aOR = 1.52, CI: 1.30–1.77), attending fewer than four ANC visits (aOR = 1.29, CI: 1.06–1.56), and not being attended to by a healthcare professional during the prenatal period (aOR = 4.63, CI: 2.81–7.64). Residing in the Sahelian regions was not increasing the risk of poor IPTp-SP uptake on its own but was positively modifying the effect of not being attended by a healthcare professional (p < 0.001). We did not find a significant association between a higher level of education and the uptake of IPTp-SP (aOR = 1.10, CI: 0.90–1.32). Nearly two third of the pregnant women in Cameroon have a poor uptake of IPTp-SP. Interventions focused on ANC provision ought to be explored and tested to address this gap, with priority assigned to the Sahelian region.Use of a health worker-targeted smartphone app to support quality malaria RDT implementation in Busia County, Kenya: A feasibility and acceptability studyMalia SkjefteShawna CooperStephen PoyerChristopher LourençoSam SmedinghoffBrett KellerTonny WambuaChristine OduorSasha FradeWycliffe Waweru10.1371/journal.pone.02950492024-03-26T14:00:00Z2024-03-26T14:00:00Z<p>by Malia Skjefte, Shawna Cooper, Stephen Poyer, Christopher Lourenço, Sam Smedinghoff, Brett Keller, Tonny Wambua, Christine Oduor, Sasha Frade, Wycliffe Waweru</p>
Malaria rapid diagnostic tests (mRDTs) are an essential diagnostic tool in low-resource settings; however, administration and interpretation errors reduce their effectiveness. <i>HealthPulse</i>, a smartphone mRDT reader application, was developed by Audere to aid health workers in mRDT administration and interpretation, with an aim to improve the mRDT testing process and facilitate timely decision making through access to digitized results. Audere partnered with PSI and PS Kenya to conduct a pilot study in Busia County, Kenya between March and September 2021 to assess the feasibility and acceptability of <i>HealthPulse</i> to support malaria parasitological diagnosis by community health volunteers (CHVs) and private clinic health workers (private clinic HWs). Metadata was interpreted to assess adherence to correct use protocols and health worker perceptions of the app. Changes to mRDT implementation knowledge were measured through baseline and endline surveys. The baseline survey identified clear mRDT implementation gaps, such as few health workers correctly knowing the number of diluent drops and minimum and maximum wait times for mRDT interpretation, although health worker knowledge improved after using the app. Endline survey results showed that 99.6% of health workers found the app useful and 90.1% found the app easy to use. Process control data showed that most mRDTs (89.2%) were photographed within the recommended 30-minute time frame and that 91.4% of uploaded photos passed the app filter quality check on the first submission. During 154 encounters (3.5% of all encounters) a health worker dispensed an artemisinin-based combination therapy (ACT) to their patient even with a negative mRDT readout. Overall, study results indicated that <i>HealthPulse</i> holds potential as a mobile tool for use in low-resource settings, with future supportive supervision, diagnostic, and surveillance benefits. Follow-up studies will aim to more deeply understand the utility and acceptance of the <i>HealthPulse</i> app.Rapid and non-invasive detection of malaria parasites using near-infrared spectroscopy and machine learningMaggy T. Sikulu-LordMichael D. EdsteinBrendon GohAnton R. LordJye A. TravisFloyd E. DowellGeoffrey W. BirrellMarina Chavchich10.1371/journal.pone.02892322024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Maggy T. Sikulu-Lord, Michael D. Edstein, Brendon Goh, Anton R. Lord, Jye A. Travis, Floyd E. Dowell, Geoffrey W. Birrell, Marina Chavchich</p>
Background <p>Novel and highly sensitive point-of-care malaria diagnostic and surveillance tools that are rapid and affordable are urgently needed to support malaria control and elimination.</p> Methods <p>We demonstrated the potential of near-infrared spectroscopy (NIRS) technique to detect malaria parasites both, <i>in vitro</i>, using dilutions of infected red blood cells obtained from <i>Plasmodium falciparum</i> cultures and <i>in vivo</i>, in mice infected with <i>P</i>. <i>berghei</i> using blood spotted on slides and non-invasively, by simply scanning various body areas (e.g., feet, groin and ears). The spectra were analysed using machine learning to develop predictive models for infection.</p> Findings <p>Using NIRS spectra of <i>in vitro</i> cultures and machine learning algorithms, we successfully detected low densities (<10<sup>−7</sup> parasites/μL) of <i>P</i>. <i>falciparum</i> parasites with a sensitivity of 96% (n = 1041), a specificity of 93% (n = 130) and an accuracy of 96% (n = 1171) and differentiated ring, trophozoite and schizont stages with an accuracy of 98% (n = 820). Furthermore, when the feet of mice infected with <i>P</i>. <i>berghei</i> with parasitaemia ≥3% were scanned non-invasively, the sensitivity and specificity of NIRS were 94% (n = 66) and 86% (n = 342), respectively.</p> Interpretation <p>These data highlights the potential of NIRS technique as rapid, non-invasive and affordable tool for surveillance of malaria cases. Further work to determine the potential of NIRS to detect malaria in symptomatic and asymptomatic malaria cases in the field is recommended including its capacity to guide current malaria elimination strategies.</p>The national distribution of lymphatic filariasis cases in Malawi using patient mapping and geostatistical modellingCarrie BarrettJohn ChiphwanyaSquare MkwandaDorothy E. MatipulaPaul NdhlovuLimbikani ChapondaJoseph D. TurnerEmanuele GiorgiHannah BettsSarah MartindaleMark J. TaylorJonathan M. ReadLouise A. Kelly-Hope10.1371/journal.pntd.00120562024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Carrie Barrett, John Chiphwanya, Square Mkwanda, Dorothy E. Matipula, Paul Ndhlovu, Limbikani Chaponda, Joseph D. Turner, Emanuele Giorgi, Hannah Betts, Sarah Martindale, Mark J. Taylor, Jonathan M. Read, Louise A. Kelly-Hope</p>
Background <p>In 2020 the World Health Organization (WHO) declared that Malawi had successfully eliminated lymphatic filariasis (LF) as a public health problem. Understanding clinical case distributions at a national and sub-national level is important, so essential care packages can be provided to individuals living with LF symptoms. This study aimed to develop a national database and map of LF clinical case numbers across Malawi using geostatistical modelling approaches, programme-identified clinical cases, antigenaemia prevalence and climate information.</p> Methodology <p>LF clinical cases identified through programme house-to-house surveys across 90 sub-district administrative boundaries (Traditional Authority (TA)) and antigenaemia prevalence from 57 sampled villages in Malawi were used in a two-step geostatistical modelling process to predict LF clinical cases across all TAs of the country. First, we modelled antigenaemia prevalence in relation to climate covariates to predict nationwide antigenaemia prevalence. Second, we modelled clinical cases for unmapped TAs based on our antigenaemia prevalence spatial estimates.</p> Principle findings <p>The models estimated 20,938 (95% CrI 18,091 to 24,071) clinical cases in unmapped TAs (70.3%) in addition to the 8,856 (29.7%), programme-identified cases in mapped TAs. In total, the overall national number of LF clinical cases was estimated to be 29,794 (95% CrI 26,957 to 32,927). The antigenaemia prevalence and clinical case mapping and modelling found the highest burden of disease in Chikwawa and Nsanje districts in the Southern Region and Karonga district in the Northern Region of the country.</p> Conclusions <p>The models presented in this study have facilitated the development of the first national LF clinical case database and map in Malawi, the first endemic country in sub-Saharan Africa. It highlights the value of using existing LF antigenaemia prevalence and clinical case data together with modelling approaches to produce estimates that may be used for the WHO dossier requirements, to help target limited resources and implement long-term health strategies.</p>Phenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activityFarnaz ZahedifardMeenakshi BansalNeha SharmaSumit KumarSiqi ShenPriyamvada SinghBrijesh RathiMartin Zoltner10.1371/journal.pntd.00120502024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Farnaz Zahedifard, Meenakshi Bansal, Neha Sharma, Sumit Kumar, Siqi Shen, Priyamvada Singh, Brijesh Rathi, Martin Zoltner</p>
Pharmacophores such as hydroxyethylamine (HEA) and phthalimide (PHT) have been identified as potential synthons for the development of compounds against various parasitic infections. In order to further advance our progress, we conducted an experiment utilising a collection of PHT and HEA derivatives through phenotypic screening against a diverse set of protist parasites. This approach led to the identification of a number of compounds that exhibited significant effects on the survival of <i>Entamoeba histolytica</i>, <i>Trypanosoma brucei</i>, and multiple life-cycle stages of <i>Leishmania spp</i>. The <i>Leishmania</i> hits were pursued due to the pressing necessity to expand our repertoire of reliable, cost-effective, and efficient medications for the treatment of leishmaniases. Antileishmanials must possess the essential capability to efficiently penetrate the host cells and their compartments in the disease context, to effectively eliminate the intracellular parasite. Hence, we performed a study to assess the effectiveness of eradicating <i>L</i>. <i>infantum</i> intracellular amastigotes in a model of macrophage infection. Among eleven <i>L</i>. <i>infantum</i> growth inhibitors with low-micromolar potency, PHT-39, which carries a trifluoromethyl substitution, demonstrated the highest efficacy in the intramacrophage assay, with an EC50 of 1.2 +/- 3.2 μM. Cytotoxicity testing of PHT-39 in HepG2 cells indicated a promising selectivity of over 90-fold. A chemogenomic profiling approach was conducted using an orthology-based method to elucidate the mode of action of PHT-39. This genome-wide RNA interference library of <i>T</i>. <i>brucei</i> identified sensitivity determinants for PHT-39, which included a P-type ATPase that is crucial for the uptake of miltefosine and amphotericin, strongly indicating a shared route for cellular entry. Notwithstanding the favourable properties and demonstrated efficacy in the <i>Plasmodium berghei</i> infection model, PHT-39 was unable to eradicate <i>L</i>. <i>major</i> infection in a murine infection model of cutaneous leishmaniasis. Currently, PHT-39 is undergoing derivatization to optimize its pharmacological characteristics.Egg excretion patterns of soil-transmitted helminth infections in humans following albendazole-ivermectin and albendazole treatmentSophie WelschePierre H. H. SchneebergerJan HattendorfSomphou SayasoneEveline HürlimannJennifer Keiser10.1371/journal.pntd.00120732024-03-22T14:00:00Z2024-03-22T14:00:00Z<p>by Sophie Welsche, Pierre H. H. Schneeberger, Jan Hattendorf, Somphou Sayasone, Eveline Hürlimann, Jennifer Keiser</p>
Background <p>Control efforts of soil-transmitted helminthiases rely primarily on large scale administration with anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemotherapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14–21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of <i>Trichuris trichiura</i> after treatment has been conducted to date.</p> Methods <p>Within the framework of a multi-country trial to assess the efficacy and safety of ivermectin-albendazole combination therapy vs albendazole monotherapy against <i>T</i>. <i>trichiura</i> infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for <i>T</i>. <i>trichiura</i>, hookworm and <i>Ascaris lumbricoides</i> and stool sample aliquots were subsequently analyzed by qPCR for the detection of <i>T</i>. <i>trichiura</i> infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy.</p> Results <p>Egg excretion patterns varied across treatment arms. For <i>T</i>. <i>trichiura</i>, only the ivermectin-albendazole treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and <i>A</i>. <i>lumbricoides</i> were cleared in all participants after day 7. For <i>T</i>. <i>trichiura</i>, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity rates were found at days 17 and 25, respectively.</p> Conclusions <p>Based on our study the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections.</p> Trial registration <p>NCT03527732.</p>Prevalence of unqualified sources of antimalarial drug prescription for children under the age of five: A study in 19 low- and middle-income countriesMd Sabbir HossainTalha Sheikh AhmedMohammad Anamul HaqueMuhammad Abdul Baker ChowdhuryMd Jamal Uddin10.1371/journal.pone.03003472024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Md Sabbir Hossain, Talha Sheikh Ahmed, Mohammad Anamul Haque, Muhammad Abdul Baker Chowdhury, Md Jamal Uddin</p>
Background <p>Antimalarial drug resistance poses a severe danger to global health. In Low- and Middle-Income Countries (LMICs), there is a lack of reliable information on antimalarial prescriptions for recent malarial fever in children under five. Our study aims to determine the prevalence of unqualified sources of antimalarial drug prescription for children under the age of five in 19 low- and middle-income countries.</p> Methods <p>We performed a cross-sectional study of the Malaria Indicator Survey (MIS) datasets (n = 106265) across 19 LMICs. The recent MIS datasets were used, and the study only included children under five who had taken an antimalarial drug for a recent malarial fever. The outcome variable was classified into two distinct categories: those who had taken antimalarial drugs for malarial fever from qualified sources and those who did not.</p> Findings <p>Among LMICs, we found that 87.1% of children under five received an antimalarial prescription from unqualified sources who had recently experienced malarial fever. In several LMICs (Tanzania, Nigeria, and Ghana), a substantial portion of recent antimalarial prescriptions for malaria was taken from unqualified sources (about 60%). Some LMICs (Guinea (31.8%), Mali (31.3%), Nigeria (20.4%), Kenya (2.6%), and Senegal (2.7%)) had low rates of antimalarial drug consumption even though children under five received a high percentage of antimalarial prescriptions from qualified sources for a recent malarial fever. Living in rural areas, having mothers with higher education, and having parents with more wealth were frequently taken antimalarial from qualified sources for recent malarial fever in children under five across the LMICs.</p> Interpretation <p>The study draws attention to the importance of national and local level preventative strategies across the LMICs to restrict antimalarial drug consumption. This is because antimalarial prescriptions from unqualified sources for recent malarial fever in children under five were shockingly high in most LMICs and had high rates of unqualified prescriptions in certain other LMICs.</p>The biocontrol nematode <i>Phasmarhabditis hermaphrodita</i> infects and increases mortality of <i>Monadenia fidelis</i>, a non-target terrestrial gastropod species endemic to the Pacific Northwest of North America, in laboratory conditionsDee DenverDana K. HoweAndrew J. ColtonCasey H. RichartRory J. Mc Donnell10.1371/journal.pone.02981652024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Dee Denver, Dana K. Howe, Andrew J. Colton, Casey H. Richart, Rory J. Mc Donnell</p>
Inundative biological control (biocontrol) efforts in pest management lead to the mass distribution of commercialized biocontrol agents. Many ‘biocontrol gone awry’ incidents have resulted in disastrous biodiversity impacts, leading to increased scrutiny of biocontrol efforts. The nematode <i>Phasmarhabditis hermaphrodita</i> is sold as a biocontrol agent on three continents and targets pest gastropods such as <i>Deroceras reticulatum</i>, the Grey Field Slug; <i>P</i>. <i>hermaphrodita</i> is not presently approved for use in the United States. Investigations into the potential for <i>P</i>. <i>hermaphrodita</i> to infect non-target gastropod species of conservation relevance, however, are limited. We examined the effects of three strains of <i>P</i>. <i>hermaphrodita</i> on mortality in <i>Monadenia fidelis</i>, the Pacific Sideband, a snail species endemic to the Pacific Northwest of North America, in laboratory conditions. Across a 71-day laboratory infectivity assay, snails exposed to each of the three nematode strains, each analyzed at two doses, experienced a mean 50% mortality by days 20–42. All nematode-treated snails were dead by the end of the study. By contrast, 30/30 water-control snails experienced no mortality. Nematodes killed smaller, juvenile-stage snails significantly faster than those in larger and more developmentally advanced hosts. Our results provide direct evidence that the biocontrol nematode <i>P</i>. <i>hermaphrodita</i> infects and kills <i>M</i>. <i>fidelis</i>, a non-target gastropod species endemic to the Pacific Northwest, in laboratory conditions. This study suggests that introduction of <i>P</i>. <i>hermaphrodita</i> to new ecosystems might negatively impact endemic gastropod biodiversity and advocates for further investigation of non-target effects, including in conditions closer to the natural environments of non-target species.Parasitic contamination of fresh vegetables and fruits sold in open-air markets in peri-urban areas of Jimma City, Oromia, Ethiopia: A community-based cross-sectional studyAhmed ZeynudinTeshome DegefaTariku BelayJiru Batu MumichaAbdusemed HusenJafer YasinAbdulhakim AbamechaAndreas Wieser10.1371/journal.pone.02906552024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Ahmed Zeynudin, Teshome Degefa, Tariku Belay, Jiru Batu Mumicha, Abdusemed Husen, Jafer Yasin, Abdulhakim Abamecha, Andreas Wieser</p>
Background <p>Consuming contaminated raw vegetables and fruits is one of the primary means of parasite transmission to humans. Periodic monitoring of parasitic contamination in these food items is a crucial step in preventing the spread of parasitic disease in the community. This study was aimed at detecting intestinal parasitic contamination caused by consuming raw vegetables and fruits sold in three open-air markets and its associated factors in peri-urban areas of Jimma City, Oromia, Ethiopia.</p> Methods <p>A cross-sectional study was conducted on fruits and vegetables collected from three peri-urban open-aired markets (namely; Hora Gibe, Bore and Jiren markets) in peri-urban areas of Jimma City between July and September 2021. A total of 187 fresh vegetable samples and 188 fruits were collected and examined for intestinal parasite contamination. About 200g of fruit and vegetable samples were processed and examined microscopically for parasite contamination, utilizing direct wet mount and modified Zeihl-Neelson staining methods in accordance with standard protocols. A structured questionnaire was used to collect data on the socio-demographic characteristics of vendors and risk factors for fruit and vegetable contamination. All data were analyzed using SPSS version 20.0.</p> Result <p>Of the 187 fresh vegetable samples and 188 fresh vegetable samples, 105 (56.1%) and 68/188 (36.2%) of vegetables and fruit samples, respectively, were found contaminated with one or more intestinal parasites. Remarkably, high level of contamination in fresh vegetable samples was recorded both in Carrot (<i>Daucus carota</i>) 63.8% (30/46) and Lettuce (<i>Lactuca sativa</i>) 63.1% (29/46) while Green pepper (<i>Capsicum</i> spp.) is the least contaminated. In fruit samples, Avokado (<i>Persea americana</i>) 42.6% (20/47) and Banana (<i>Musa acuminata</i>) 14.9% (7/47) were the most and the least commonly contaminated items respectively. The identified helminthes and protozoans were <i>Ascaris lumbricoides</i>, <i>Strongyloides stercoralis</i>, <i>Hymenolepis nana</i>, <i>Entamoeba histolytica/dispar</i>, <i>Giardia lamblia</i>, <i>Cryptosporidium</i> spp., <i>Toxocara</i> spp. And <i>Fasciola</i> spp. The most predominant parasite encountered was <i>A</i>. <i>lumbricoides 46(12</i>.<i>3%)</i> whereas <i>both Toxocara</i> spp. 12(6.9) and <i>Fasciola</i> spp. 2(0.5) were the least detected parasites. It is worth-mentioned that the rate of contamination in Bore market (38.15%) was higher compared with Jiren market (34.7%) and Hora Gibe market (27%). However, the rate of contamination in vegetables and fruit obtained from the three district was non-significant (<i>p</i> = 0.19). Contamination was more common in vegetables than fruits (AOR = 5.78, p<0.001). It was also observed that decreased parasitic contamination was significantly associated with washing the products before displaying it for selling (<i>p</i> < 0.001).</p> Conclusion <p>The study has identified a high rate of raw vegetables and fruits contaminated with intestinal helminthes and protozoan. Contaminated fresh vegetables and fruits in open-aired peri-urban markets of Jimma city, Ethiopia may play a significant role in transmission of intestinal parasitic infections to humans, particularly <i>A</i>. <i>lumbricoides</i> infection. Therefore, it is urgently needed for health authorities to educate the public on the proper handling of vegetables and fruits prior to consumption.</p>Estimating multiplicity of infection, allele frequencies, and prevalences accounting for incomplete dataMeraj HashemiKristan A. Schneider10.1371/journal.pone.02871612024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Meraj Hashemi, Kristan A. Schneider</p>
Background <p>Molecular surveillance of infectious diseases allows the monitoring of pathogens beyond the granularity of traditional epidemiological approaches and is well-established for some of the most relevant infectious diseases such as malaria. The presence of genetically distinct pathogenic variants within an infection, referred to as multiplicity of infection (MOI) or complexity of infection (COI) is common in malaria and similar infectious diseases. It is an important metric that scales with transmission intensities, potentially affects the clinical pathogenesis, and a confounding factor when monitoring the frequency and prevalence of pathogenic variants. Several statistical methods exist to estimate MOI and the frequency distribution of pathogen variants. However, a common problem is the quality of the underlying molecular data. If molecular assays fail not randomly, it is likely to underestimate MOI and the prevalence of pathogen variants.</p> Methods and findings <p>A statistical model is introduced, which explicitly addresses data quality, by assuming a probability by which a pathogen variant remains undetected in a molecular assay. This is different from the assumption of missing at random, for which a molecular assay either performs perfectly or fails completely. The method is applicable to a single molecular marker and allows to estimate allele-frequency spectra, the distribution of MOI, and the probability of variants to remain undetected (incomplete information). Based on the statistical model, expressions for the prevalence of pathogen variants are derived and differences between frequency and prevalence are discussed. The usual desirable asymptotic properties of the maximum-likelihood estimator (MLE) are established by rewriting the model into an exponential family. The MLE has promising finite sample properties in terms of bias and variance. The covariance matrix of the estimator is close to the Cramér-Rao lower bound (inverse Fisher information). Importantly, the estimator’s variance is larger than that of a similar method which disregards incomplete information, but its bias is smaller.</p> Conclusions <p>Although the model introduced here has convenient properties, in terms of the mean squared error it does not outperform a simple standard method that neglects missing information. Thus, the new method is recommendable only for data sets in which the molecular assays produced poor-quality results. This will be particularly true if the model is extended to accommodate information from multiple molecular markers at the same time, and incomplete information at one or more markers leads to a strong depletion of sample size.</p>Impact of annual community-directed treatment with ivermectin on the incidence of epilepsy in Mvolo, a two-year prospective studyLuís-Jorge AmaralStephen Raimon JadaAimee Kemayou NdjanfaJane Y. CarterGasim Abd-ElfaragSamuel OkaroMakoy Yibi LogoraYak Yak BolThomson LakwoJoseph N Siewe FodjoRobert Colebunders10.1371/journal.pntd.00120592024-03-21T14:00:00Z2024-03-21T14:00:00Z<p>by Luís-Jorge Amaral, Stephen Raimon Jada, Aimee Kemayou Ndjanfa, Jane Y. Carter, Gasim Abd-Elfarag, Samuel Okaro, Makoy Yibi Logora, Yak Yak Bol, Thomson Lakwo, Joseph N Siewe Fodjo, Robert Colebunders</p>
Objectives <p>The potential impact of cumulative community-directed treatment with ivermectin (CDTI) on epilepsy epidemiology in Mvolo County, South Sudan, an onchocerciasis-endemic area with high epilepsy prevalence, was investigated. Annual CDTI was introduced in 2002 in Mvolo, with interruptions in 2016 and 2020.</p> Methods <p>Comprehensive house-to-house surveys in Mvolo (June 2020 and 2022) identified cases of epilepsy, including probable nodding syndrome (pNS). Community workers screened households in selected sites for suspected epilepsy, and medical doctors confirmed the diagnosis and determined the year of seizure onset. The incidence of epilepsy, including pNS, was analysed using 95% confidence intervals (CIs). Data on ivermectin intake and onchocerciasis-associated manifestations (itching and blindness) were collected.</p> Results <p>The surveys covered 15,755 (2020) and 15,092 (2022) individuals, identifying 809 (5.2%, 95% CI: 4.8–5.5%) and 672 (4.5%, 95% CI: 4.1–4.8%) epilepsy cases, respectively. Each survey reported that a third of the surveyed population experienced skin itching, and 3% were blind. Epilepsy incidence per 100,000 person-years gradually declined, from 326.5 (95% CI: 266.8–399.1) in 2013–2015 to 96.6 (95% CI: 65.5–141.7) in 2019–2021. Similarly, pNS incidence per 100,000 person-years decreased from 151.7 (95% CI: 112.7–203.4) to 27.0 (95% CI: 12.5–55.5). Coverage of CDTI was suboptimal, reaching only 64.0% of participants in 2019 and falling to 24.1% in 2021 following an interruption in 2020 due to COVID-19 restrictions. Additionally, while 99.4% of cases had active epilepsy in 2022, less than a quarter of these had access to antiseizure medication.</p> Conclusions <p>The observed decrease in epilepsy incidence despite suboptimal CDTI coverage highlights the potential impact of onchocerciasis control efforts and underscores the need to strengthen these efforts in Mvolo County and across South Sudan. As a proactive measure, Mvolo and neighbouring counties are transitioning to biannual CDTI. Furthermore, the substantial epilepsy treatment gap in Mvolo should be addressed.</p>