PLoS Neglected Tropical Diseases最新文献

Background: Despite more than 27 years of ivermectin mass drug administration (MDA), onchocerciasis transmission persists in the Kwanware-Ottou focus within the Wenchi Health District of Ghana. This study examined participation in ivermectin MDA over time in this transmission focus.

Methods: In March 2024, two months after MDA using the community-directed treatment with ivermectin (CDTI) approach, settlements within Kwanware-Ottou focus were identified through community consultations and satellite imagery. A census was then conducted integrating an ivermectin treatment coverage evaluation survey (CES) to evaluate community participation in CDTI. Data were cleaned using STATA and analysed in R. Descriptive statistics, multiple logistic regression, and ordinal logistic regression were conducted to examine factors associated with point and effective participation in CDTI. Point participation is the percentage of individuals aged 15 + who took ivermectin during the last CDTI, while effective participation refers to those who have taken it at least ten times in past rounds. Pearson correlation was used to assess the relationship between participation and infection prevalence.

Results: Nineteen settlements were identified, with an overall point participation of 80.3% (n = 1461 participants; 95% Confidence Interval, CI:78.6 - 82) for the preceding CDTI. However, 10 settlements had coverage below 80%. Effective participation was only 53.5% (n = 974; CI: 51.2 -55.9), well below the recommended 80%. Participation was influenced by factors such as age, occupation, ethnicity, remoteness, length of stay in the settlement, and mobility (migration). Effective participation was correlated with infection levels, with correlation coefficients of -0.74 for microfilariae prevalence and -0.79 for anti-Ov16 seroprevalence, indicating a strong inverse relationship.

Conclusion: High point participation masks low effective participation and insufficient subdistrict geographical coverage. Conducting exhaustive CES in delineated foci is essential for evaluating CDTI performance, tailoring and strengthening CDTI, and informing alternative strategies to interrupt onchocerciasis transmission. This approach has contributed to effective, context-specific strategies to interrupt transmission in Wenchi and beyond.

Two consensus scorpion toxins derived from venoms of the genera Centruroides (NATx, North America), and Tityus (SATx, South America) were rationally designed and recombinantly expressed in Escherichia coli Origami. Both recombinant proteins were produced as inclusion bodies and subsequently purified and refolded in vitro to obtain biologically active isoforms. The expression yields were approximately 1 mg/L for rNATx and 0.5 mg/L for rSATx. Structural characterization by circular dichroism spectroscopy revealed that rNATx and rSATx exhibited folding patterns typical of scorpion β-toxins. The purified recombinant toxins were used as immunogens to raise polyclonal antibodies in New Zealand rabbits. The resulting antisera were evaluated for their capacity to neutralize isolated toxins and whole scorpion venoms. rNATx elicited a stronger immune response and showed superior immunogenicity compared to rSATx. Notably, 1-1.5 mg of anti-rNATx antibodies were sufficient to neutralize up to 3LD50 of venoms from the most medically relevant Centruroides species in México. On the other hand, approximately 20 mg of anti-rSATx antibodies were required to neutralize only 2LD50 of Tityus venoms. Additionally, T-cell subsets quantified by flow cytometry showed that rNATx is more immunogenic and probably confers improved antivenom efficacy, highlighting its potential application in the development of broad-spectrum antivenoms against scorpion envenomation.

Standardized surveillance and control of kissing bugs (Hemiptera: Reduviidae: Triatominae), the insect vectors of the Chagas disease parasite, Trypanosoma cruzi, which causes Chagas disease, remains difficult. The Kissing Bug Kill Trap consists of solar powered LED lights mounted over a column of black funnels. It operates autonomously to capture, kill and preserve adult triatomines. We conducted experiments from 2022-2024 testing potential ways to improve trap performance, ease of deployment, and minimize cost. Thirteen prototypes evaluated in Texas, Guatemala, and Mexico captured 1,531 triatomines. In 2022-2023 we selected a six-funnel trap suspended from a single support pole with an angle bracket, and with four LED lights and a solar panel mounted above the rain-guard, as a reference trap. In 2023, traps with smaller funnels, blue funnels, and blue lights were inferior to the reference trap based on high by-catch of other arthropods and/or fewer triatomines caught per day. In 2024, traps with more or fewer than six funnels or with LED lights mounted on or below the rain guard did not outperform the reference trap. The experiments added five new triatomine species to the four already known to be caught by the Kissing Bug Kill Trap and revealed differences and similarities in phenology of dispersal flights of Triatoma gerstaeckeri over a three-year period in Texas. The reference trap was selected as the pre-commercial prototype, based on its suitability for triatomine surveillance and potential for reducing the risk of T. cruzi infection by intercepting dispersing adult triatomines before they reach human habitats.

Background: Visceral leishmaniasis (VL) is the most severe form of leishmaniasis, with East Africa accounting for ~70% of global burden. It primarily affects malnourished children, young adults, and HIV co-infected individuals. Clinical outcomes range from asymptomatic to fatal, with relapse mostly linked to HIV co-infection, splenomegaly, high parasite load, poor immune responses, and elevated IgG1 concentration. In rodent VL models, systemic immune and metabolic abnormalities persist at the end of the drug treatment regime. However, the immune status of VL patients in East Africa at the end of treatment is not fully understood.

Methodology/principal findings: We conducted ImmStat@cure, a multicentre clinical study to assess clinical and immune profiles of VL patients at admission and end of treatment (EoT) in East African countries. Clinical, haematological and inflammatory markers data were collected from patients from Ethiopia, Kenya, Sudan and Uganda on both time points and from convenience controls at a single time point. By integrating clinical data with haematological and inflammation markers, we have shown that patient clinical and inflammatory profiles varied at admission and partially reverted to healthy range at EoT. Partial least squares determination and logistic regression showed that concentrations of inflammatory markers, including soluble TNF receptors and sCD40L, consistently changed between admission and EoT in all four countries, and were associated with increased odds of hepatomegaly and splenomegaly.

Conclusions/significance: The recovery of haematological parameters, alongside a reduction in systemic inflammatory markers may be indicative of successful treatment of VL in East Africa. The biomarker dynamics suggest a partial resolution of inflammation and restoration of immune homeostasis during treatment. To confirm their predictive value, these markers should be evaluated in cohorts with a larger number of patients who experience treatment failure.

Scrub typhus, caused by Orientia tsutsugamushi, is a re-emerging zoonotic disease that is associated with significant morbidity and mortality in many parts of India. Early and accurate diagnosis, primarily through the detection of IgM antibodies, plays a pivotal role in patient management and disease surveillance. However, there is a paucity of diagnostic methods in our country, and only in recent years have more diagnostic assays been rolled out. To address the heterogeneity in the laboratory diagnosis of scrub typhus, an external quality assurance scheme (EQA Scheme) for the detection of O tsutsugamushi IgM (OTM) was conceptualized and implemented across a network of laboratories in India. This study provides detailed insight into the design, implementation, and outcomes of this EQA scheme initiative. Initially, a pilot phase was conducted among the 10 participant laboratories, and a total of 51 Virus Research and Diagnostic Laboratories (VRDLs) under DHR-ICMR undertaking OTM serology subsequently participated in the EQA Scheme. Proficiency testing (PT) panels consisting of 5 well-characterized and validated pooled serum samples were distributed to the participants for testing. Participating laboratories have employed various IgM detection methods, including ELISA and rapid immunochromatographic tests (ICTs). Performance was evaluated qualitatively based on the testing results and adherence to reporting timelines. Most laboratories demonstrated concordant results (n = 47) in OTM testing, while 4% of laboratories (n = 2) reported discordant results. The study underscores the vital role of an EQA scheme in ensuring quality-assured diagnostic testing for infectious diseases in the country and builds confidence in Indian laboratory results. Regular participation in such schemes, coupled with targeted capacity-building initiatives, can substantially improve laboratory diagnostics, facilitate timely clinical interventions, and contribute to a more robust national surveillance system. This model may serve as a foundation for strengthening quality assurance frameworks for other emerging infectious diseases in India and similar low- and middle-income settings.

Background: Visceral leishmaniasis (VL), a neglected tropical disease (NTD)continues to affect several countries worldwide, including Uganda, where it remains a significant public health concern in the Karamoja Region. This region borders Kenya, where VL is endemic. Globally and within East Africa, VL persists due to a combination of ecological suitability for sandfly vectors, chronic underdiagnosis, limited access to care in remote and pastoralist communities, high levels of malnutrition and poverty, and cross-border population movement that sustains transmission. The World Health Organization (WHO) targets to eliminate VL as a public health problem by reducing case fatality to <1%, but the current burden of VL is unknown. We described VL patients, their treatment outcomes, and identified factors associated with death in Uganda, from 2019-2024, to check progress towards meeting the country's targets.

Methods: We conducted a retrospective observational review of patient records from 2019-2024 at the main VL treatment center in Amudat District, Uganda, abstracting socio-demographic, clinical, treatment, and outcome dataWe used logistic regression to determine factors associated with death.

Results: Among 972 patients, 670 (69%) were male and 742 (76%) were age ≤ 18 years. Three hundred and seventy-three (38%) were from Kenya, while most, 434/599 (72%) Ugandan patients were from Moroto District. The highest number of cases (322) was recorded in 2022, with Ugandans making up 80% of all patients that year(259/322), unlike previous years (2019-2021) when Kenyan patients predominated. There was no identifiable seasonal pattern/variation in the number of cases diagnosed. The commonest symptoms were fever (98%), night sweats (77%), and abdominal swelling (72%). The average duration of sickness was 2.6 months (standard deviation (SD)=0.3 months). Severe anemia was common (512/972; 53%), and among the patients tested for co-infections, 175/969 (18%) were co-infected with malaria and 185/593 (31%) with Human Immunodeficiency Virus (HIV). For most patients, 898 (92%), this was their index episode of VL. Almost all patients [957 (98%)] were cured. and most [743 (76%)] patients were treated with the 1st- line regimen. The case fatality rate (CFR) declined from 2% in 2020 and 2021 to <1% in 2023 and 2024. Being HIV positive was associated with death (Adjusted odds ratios (AOR) 10, 95% Confidence Intervals (CI) 2.2-50, p = 0.003).

Conclusion: This study indicates progress towards the elimination of VL while highlighting the significance of cross-border transmission and the importance of screening/treatment of co-infections, especially HIV.

Following decades of progress, recent years have seen a resurgence of cholera. This has led to unprecedented demand for vaccines from the global emergency stockpile of oral cholera vaccines (OCVs), for outbreak and humanitarian use. As a consequence of chronic supply shortages, preventive vaccination has been suspended since 2022. Although strategic demand scenarios have been published for OCV, models that integrate OCV supply and demand across long time horizons are lacking. Therefore, a quantitative system dynamics model is presented to simulate OCV market dynamics between 2013-2035. The model considers the evolving OCV supply landscape as well as the impact of preventive efforts. Building on stakeholder-driven scenario design, simulations help identify leverage points to improve OCV market health and assess the individual and combined effect of interventions on accelerating cholera control. Specifically, country adoption of preventive vaccination programs and complementary investments in water and sanitation infrastructure are critical to reduce the risk of cholera. Although more resource-intensive, re-vaccination of at-risk populations helps sustain outbreak prevention. It also offers potential benefits such as increasing long-term demand predictability and the overall market size. These serve as important incentives to maintain supplier diversity, thus improving market health. However, since many cholera endemic countries rely on donor support to access OCV, budget constraints associated with reduced development aid can jeopardize programmatic ambitions. Interventions such as the use of rapid diagnostic tests and price competition of procurement can help meet country needs. Finally, market dynamics are influenced by the policies around when to resume preventive OCV use in endemic countries and 2-dose reactive vaccination. Specifically, inventory policies based on the current available stock level versus incoming stock in transit are compared. Aligning OCV supply with demand, both in time and quantity, will be critical to address immediate needs and support broader multi-sectoral activities towards cholera elimination.

Background: Onchocerciasis control strategies have focused on mass drug administration (MDA) to reduce morbidity in high-risk (HR) areas (sites close to blackfly breeding sites). However, with the current drive towards elimination, treatment must be extended to low-risk (LR) areas. It is uncertain how well HR and LR communities are connected for decision making in recommending treatment strategies to include the LR areas. We provided data on current onchocerciasis infection status, connectivity between HR and LR communities and rates of human movement within some endemic communities in Ghana.

Methods: Selected communities were 5km (HR) and 15km (LR) from breeding sites. Questionnaires were administered to obtain data on demographics and human movement patterns. Samples were collected from participants and tested for O. volvulus infections using Ov16 RDT and presence of microfilariae (mf) in skin snips using microscopy and quantitative PCR.

Results: We observed a significantly higher onchocerciasis prevalence in HR than LR sites for both sero-prevalence (42.5% vrs 16.0%) and mf prevalence (15.2% vrs 4.1%) [P < 0.0001]. There was a high connectivity between the HR and LR with about 64-82% people who moved from HR to LR and 3.2-10% from LR to HR daily or weekly. Infection levels in those who moved from HR to LR communities were higher than those who moved from LR to HR, although these were not statistically significant (P > 0.05). Some individuals in Lancha (a LR community) who tested positive for infection frequently visited the HR communities for farming.

Conclusions: A strong connectivity existed between HR and LR communities by human movement. On the average >60% of participants moved between endemic communities (between HR and LR) either daily, within the week or weekly. This supports the need to initiate treatment in LR areas; hence, such movement data would be useful during assessment of onchocerciasis elimination and delineation of transmission zones.