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The latest medical research on Tropical Medicine

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Leishmania blood parasite dynamics during and after treatment of visceral leishmaniasis in Eastern Africa: A pharmacokinetic-pharmacodynamic model.

PLoS Neglected Tropical Diseases

With the current treatment options for visceral leishmaniasis (VL), recrudescence of the parasite is seen in a proportion of patients. Understanding parasite dynamics is crucial to improving treatment efficacy and predicting patient relapse in cases of VL. This study aimed to characterize the kinetics of circulating Leishmania parasites in the blood, during and after different antileishmanial therapies, and to find predictors for clinical relapse of disease.

Data from three clinical trials, in which Eastern African VL patients received various antileishmanial regimens, were combined in this study. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during, and up to six months after treatment. An integrated population pharmacokinetic-pharmacodynamic model was developed using non-linear mixed effects modelling.

Parasite proliferation was best described by an exponential growth model, with an in vivo parasite doubling time of 7.8 days (RSE 12%). Parasite killing by fexinidazole, liposomal amphotericin B, sodium stibogluconate, and miltefosine was best described by linear models directly relating drug concentrations to the parasite elimination rate. After treatment, parasite growth was assumed to be suppressed by the host immune system, described by an Emax model driven by the time after treatment. No predictors for the high variability in onset and magnitude of the immune response could be identified. Model-based individual predictions of blood parasite load on Day 28 and Day 56 after start of treatment were predictive for clinical relapse of disease.

This semi-mechanistic pharmacokinetic-pharmacodynamic model adequately captured the blood parasite dynamics during and after treatment, and revealed that high blood parasite loads on Day 28 and Day 56 after start of treatment are an early indication for VL relapse, which could be a useful biomarker to assess treatment efficacy of a treatment regimen in a clinical trial setting.

Aspecific binding of anti-NK1.1 antibodies on myeloid cells in an experimental model for malaria-associated acute respiratory distress syndrome.

Malaria Journal

Conventional natural killer (cNK) cells play an important role in the innate immune response by directly killing infected and malignant cells and by producing pro- and anti-inflammatory cytokines. Studies on their role in malaria and its complications have resulted in conflicting results.

Using the commonly used anti-NK1.1 depletion antibodies (PK136) in an in-house optimized experimental model for malaria-associated acute respiratory distress syndrome (MA-ARDS), the role of cNK cells was investigated. Moreover, flow cytometry was performed to characterize different NK cell populations.

While cNK cells were found to be dispensable in the development of MA-ARDS, the appearance of a NK1.1+ cell population was observed in the lungs upon infection despite depletion with anti-NK1.1. Detailed characterization of the unknown population revealed that this population consisted of a mixture of monocytes and macrophages that bind the anti-NK1.1 antibody in an aspecific way. This aspecific binding may occur via Fcγ receptors, such as FcγR4. In contrast, in vivo depletion using anti-NK1.1 antibodies was proved to be specific for cNK cells.

cNK cells are dispensable in the development of experimental MA-ARDS. Moreover, careful flow cytometric analysis, with a critical mindset in relation to potential aspecific binding despite the use of commercially available Fc blocking reagents, is critical to avoid misinterpretation of the results.

Design, development, and validation of multi-epitope proteins for serological diagnosis of Zika virus infections and discrimination from dengue virus seropositivity.

PLoS Neglected Tropical Diseases

Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is the causative agent of Zika fever, a mild and frequent oligosymptomatic disease in...

Impact of conflict on the elimination targets of lymphatic filariasis, schistosomiasis and soil-transmitted helminths in Cabo Delgado province, Mozambique.

PLoS Neglected Tropical Diseases

Mozambique has one of the highest burdens of neglected tropical diseases in Africa. Lymphatic filariasis, schistosomiasis and soil-transmitted helminths are being targeted for elimination as part of integrated mass drug administration campaigns. The progress made towards interruption of transmission has been affected by recent conflict in Cabo Delgado province. The aim of this paper was to determine the potential impact of this crisis on the neglected tropical diseases programme and the challenges in reaching the elimination goals of 2030.

A desk-based secondary data analysis was conducted on publicly available sources of neglected tropical diseases, conflict incidents, internally displaced persons and geographical access between 2020 and 2022. Data were summarised and mapped using GIS software. A combined risk stratified assessment at district level was developed with five classifications i) Very high-risk; ii) High-risk; iii) Medium to high-risk; iv) Medium risk; and v) Not at risk due to conflict absence but co-endemic.

Lymphatic filariasis, schistosomiasis and soil-transmitted helminths were co-endemic in 115 out of 156 (74%) districts. Between 2020 and 2022 a total of 1,653 conflict-related incidents were reported, most of them in Cabo Delgado province (n = 1,397, 85%). A five-fold increase of internally displaced persons was recorded from April 2020 (n = 172,186) to November 2022 (n = 935,130). Geographical accessibility also deteriorated across the province with an increase from five (29%) in 2021 to seven (41%) districts in 2022 classified as hard-to-reach. The combined risk stratification identified that most districts (n = 7; 41%) in Cabo Delgado province had medium to high-risk; very high-risk (n = 5, 29%); medium risk (n = 3, 18%); high-risk (n = 2, 12%).

Most of the districts of Cabo Delgado were considered to be at risk of not meeting the neglected tropical diseases road map 2021-2030 targets due to the humanitarian crisis ongoing. There is the need for practical strategies and funding to overcome these hostile challenges.

Bayesian modeling of post-vaccination serological data suggests that yearly vaccination of dog aged <2 years old is efficient to stop rabies circulation in Cambodia.

PLoS Neglected Tropical Diseases

Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations...

MODELS: a six-step framework for developing an infectious disease model.

Infectious Diseases of Poverty

Since the COVID-19 pandemic began, a plethora of modeling studies related to COVID-19 have been released. While some models stand out due to their ...

Factors associated with the risk of malaria among children: analysis of 2021 Nigeria Malaria Indicator Survey.

Malaria Journal

Malaria remains a burden globally, with the African region accounting for 94% of the overall disease burden and deaths in 2019. It is the major cause of morbidity and mortality among children in Nigeria. Though different environmental factors have been assessed to influence the distribution and transmission of malaria vectors, there is a shortage of information on how they may influence malaria transmission among under-fives in Nigeria.

This study was based on the secondary data analysis of the Nigeria Malaria Indicator Survey 2021. The study sample comprised 10,645 women (aged 15-49) who delivered a child in the 2 years preceding the survey. The study was restricted to under-fives. Logistic regression was used to identify factors associated with the risk of malaria.

There was a positive association between the risk of malaria and heard/seen malaria messages in the last 6 months (AOR 1.39, 95% CI 1.19-1.62), houses with walls built using rudimentary materials (AOR = 1.38, 95% CI 1.04-1.83), at least 6 children living in the house (AOR 1.22, 95% CI 1.00-1.49), children being 1 or 2 years old was associated with increased odds (AOR 1.89, 95% CI 1.50-2.34 and AOR 1.89, 95% CI 1.52-2.36), children from households with only treated nets (AOR 1.23, 95% CI 1.04-1.46) and those from the North West or South East regions (AOR 1.50, 95% CI 1.10-2.05 and AOR 1.48, 95% CI 1.01-2.16), respectively. All other predictors were not associated with the risk of malaria.

The factors associated with the risk of malaria in this study included sleeping under treated mosquito nets, the age of the children, residing in the northwest and southeast regions, wall construction material, 6 children and above in the household and hearing/seen malaria messages in the last 6 months. Continuous health education and public health interventions, such as the provision of LLITNs, will reduce the risk of malaria and improve the health and well-being of children under 5 years of age.

Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine.

Malaria Journal

To gain a deeper understanding of protective immunity against relapsing malaria, this study examined sporozoite-specific T cell responses induced by a chemoprophylaxis with sporozoite (CPS) immunization in a relapsing Plasmodium cynomolgi rhesus macaque model.

The animals received three CPS immunizations with P. cynomolgi sporozoites, administered by mosquito bite, while under two anti-malarial drug regimens. Group 1 (n = 6) received artesunate/chloroquine (AS/CQ) followed by a radical cure with CQ plus primaquine (PQ). Group 2 (n = 6) received atovaquone-proguanil (AP) followed by PQ. After the final immunization, the animals were challenged with intravenous injection of 104 P. cynomolgi sporozoites, the dose that induced reliable infection and relapse rate. These animals, along with control animals (n = 6), were monitored for primary infection and subsequent relapses. Immunogenicity blood draws were done after each of the three CPS session, before and after the challenge, with liver, spleen and bone marrow sampling and analysis done after the challenge.

Group 2 animals demonstrated superior protection, with two achieving protection and two experiencing partial protection, while only one animal in group 1 had partial protection. These animals displayed high sporozoite-specific IFN-γ T cell responses in the liver, spleen, and bone marrow after the challenge with one protected animal having the highest frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. Partially protected animals also demonstrated a relatively high frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. It is important to highlight that the second animal in group 2, which experienced protection, exhibited deficient sporozoite-specific T cell responses in the liver while displaying average to high T cell responses in the spleen and bone marrow.

This research supports the notion that local liver T cell immunity plays a crucial role in defending against liver-stage infection. Nevertheless, there is an instance where protection occurs independently of T cell responses in the liver, suggesting the involvement of the liver's innate immunity. The relapsing P. cynomolgi rhesus macaque model holds promise for informing the development of vaccines against relapsing P. vivax.

Widespread pfhrp2/3 deletions and HRP2-based false-negative results in southern Ethiopia.

Malaria Journal

Rapid diagnostic tests (RDTs) play a significant role in expanding case management in peripheral healthcare systems. Histidine-rich protein-2 (HRP2) antigen detection RDTs are predominantly used to diagnose Plasmodium falciparum infection. However, the evolution and spread of P. falciparum parasite strains with deleted hrp2/3 genes, causing false-negative results, have been reported. This study assessed the diagnostic performance of HRP2-detecting RDTs for P. falciparum cases and the prevalence of pfhrp2/3 deletions among symptomatic patients seeking malaria diagnosis at selected health facilities in southern Ethiopia.

A multi-health facilities-based cross-sectional study was conducted on self-presenting febrile patients seeking treatment in southern Ethiopia from July to September 2022. A purposive sampling strategy was used to enroll patients with microscopically confirmed P. falciparum infections. A capillary blood sample was obtained to prepare a blood film for microscopy and a RDT using the SD Bioline™ Malaria Pf/Pv Test. Dried blood spot samples were collected for further molecular analysis. DNA was extracted using gene aid kits and amplification was performed using nested PCR assay. Exon 2 of hrp2 and hrp3, which are the main protein-coding regions, was used to confirm its deletion. The diagnostic performance of RDT was evaluated using PCR as the gold standard test for P. falciparum infections.

Of 279 P. falciparum PCR-confirmed samples, 249 (89.2%) had successful msp-2 amplification, which was then genotyped for hrp2/3 gene deletions. The study revealed that pfhrp2/3 deletions were common in all health centres, and it was estimated that 144 patients (57.8%) across all health facilities had pfhrp2/3 deletions, leading to false-negative PfHRP2 RDT results. Deletions spanning exon 2 of hrp2, exon 2 of hrp3, and double deletions (hrp2/3) accounted for 68 (27.3%), 76 (30.5%), and 33 (13.2%) of cases, respectively. The study findings revealed the prevalence of P. falciparum parasites lacking a single pfhrp2-/3-gene and that both genes varied across the study sites. This study also showed that the sensitivity of the SD Bioline PfHRP2-RDT test was 76.5% when PCR was used as the reference test.

This study confirmed the existence of widespread pfhrp2/3- gene deletions, and their magnitude exceeded the WHO-recommended threshold (> 5%). False-negative RDT results resulting from deletions in Pfhrp2/3- affect a country's attempts at malaria control and elimination. Therefore, the adoption of non-HRP2-based RDTs as an alternative measure is required to avoid the consequences associated with the continued use of HRP-2-based RDTs, in the study area in particular and in Ethiopia in general.

Mapping malaria vectors and insecticide resistance in a high-endemic district of Haryana, India: implications for vector control strategies.

Malaria Journal

Achieving effective control and elimination of malaria in endemic regions necessitates a comprehensive understanding of local mosquito species responsible for malaria transmission and their susceptibility to insecticides.

The study was conducted in the highly malaria prone Ujina Primary Health Center of Nuh (Mewat) district of Haryana state of India. Monthly entomological surveys were carried out for adult mosquito collections via indoor resting collections, light trap collections, and pyrethrum spray collections. Larvae were also collected from different breeding sites prevalent in the region. Insecticide resistance bioassay, vector incrimination, blood meal analysis was done with the collected vector mosquitoes.

A total of 34,974 adult Anopheles mosquitoes were caught during the survey period, out of which Anopheles subpictus was predominant (54.7%). Among vectors, Anopheles stephensi was predominant (15.5%) followed by Anopheles culicifacies (10.1%). The Human Blood Index (HBI) in the case of An. culicifacies and An. stephensi was 6.66 and 9.09, respectively. Vector incrimination results revealed Plasmodium vivax positivity rate of 1.6% for An. culicifacies. Both the vector species were found resistant to DDT, malathion and deltamethrin.

The emergence of insecticide resistance in both vector species, compromises the effectiveness of commonly used public health insecticides. Consequently, the implementation of robust insecticide resistance management strategies becomes imperative. To effectively tackle the malaria transmission, a significant shift in vector control strategies is warranted, with careful consideration and adaptation to address specific challenges encountered in malaria elimination efforts.

Factors influencing Thai university students' decisions to take COVID-19 vaccine booster doses: a cross-sectional survey.

Tropical Medicine and International Health

We aimed to describe the acceptance of COVID-19 vaccine booster doses and factors influencing this among Thai university students.

A cross-sectional survey was conducted between July and September 2022. All university students in Thailand were eligible to participate. We explored the acceptance rate of COVID-19 vaccine booster doses and regular vaccines (if available) among university students. Associations between factors influencing the acceptance of vaccination were analyzed by multiple logistic regression analysis.

A total of 322 participants were surveyed (78.9% female, age 18 to 49 years (mean = 22.6, standard deviation = 5.47)). Most participants (85.7%) were undergraduate students (Bachelor level), and a proportion (84.8%) had a background in health sciences studies. The proportions who accepted booster doses and regular vaccines were 52.8% and 69.3%, respectively. Vaccine accessibility was found to be significantly associated with the acceptance of booster doses (adjusted odds ratio (AOR) = 2.77, 95% confidence interval (CI) = 1.10-6.97), while the availability of scientific evidence (AOR = 3.44, 95% CI = 1.21-9.77) was significantly associated with the acceptance of regular vaccines.

This study contributes to addressing the knowledge gap regarding acceptance of COVID-19 vaccine booster doses among university students in Thailand. Our findings revealed that vaccine accessibility and the availability of scientific evidence, as well as vaccination costs, influenced individuals' decisions around accepting vaccine booster doses. Further research should focus on the dynamics of vaccine acceptance to facilitate the development of targeted strategies and support vaccination policymaking in Thailand.

Dengue vector control in high-income, city settings: A scoping review of approaches and methods.

PLoS Neglected Tropical Diseases

Dengue virus (DENV) is endemic to many parts of the world and has serious health and socioeconomic effects even in high-income countries, especially with rapid changes in the climate globally. We explored the literature on dengue vector control methods used in high-income, city settings and associations with dengue incidence, dengue prevalence, or mosquito vector densities.

Studies of any design or year were included if they reported effects on human DENV infection or Aedes vector indices of dengue-specific vector control interventions in high-income, city settings.

Of 24 eligible sources, most reported research in the United States (n = 8) or Australia (n = 5). Biocontrol (n = 12) and chemical control (n = 13) were the most frequently discussed vector control methods. Only 6 sources reported data on the effectiveness of a given method in reducing human DENV incidence or prevalence, 2 described effects of larval and adult control on Aedes DENV positivity, 20 reported effectiveness in reducing vector density, using insecticide, larvicide, source reduction, auto-dissemination of pyriproxyfen and Wolbachia, and only 1 described effects on human-vector contact.

As most studies reported reductions in vector densities, rather than any effects on human DENV incidence or prevalence, we can draw no clear conclusions on which interventions might be most effective in reducing dengue in high-income, city areas. More research is needed linking evidence on the effects of different DENV vector control methods with dengue incidence/prevalence or mosquito vector densities in high-income, city settings as this is likely to differ from low-income settings. This is a significant evidence gap as climate changes increase the global reach of DENV. The importance of community involvement was clear in several studies, although it is impossible to tease out the relative contributions of this from other control methods used.