Uganda has had repeated outbreaks of Rift Valley fever (RVF) since March 2016 when human and livestock cases were reported in Kabale after a long interval. The disease has a complex and poorly described transmission patterns which involves several mosquito vectors and mammalian hosts (including humans). We conducted a national serosurvey in livestock to determine RVF virus (RVFV) seroprevalence, risk factors, and to develop a risk map that could be used to guide risk-based surveillance and control measures. A total of 3,253 animals from 175 herds were sampled. Serum samples collected were screened at the National Animal Disease Diagnostics and Epidemiology Centre (NADDEC) using a competition multispecies anti-RVF IgG ELISA kit. Data obtained were analyzed using a Bayesian model that utilizes integrated nested Laplace approximation (INLA) and stochastic partial differential equation (SPDE) approaches to estimate posterior distributions of model parameters, and account for spatial autocorrelation. Variables considered included animal level factors (age, sex, species) and multiple environmental data including meteorological factors, soil types, and altitude. A risk map was produced by projecting fitted (mean) values, from a final model that had environmental factors onto a spatial grid that covered the entire domain. The overall RVFV seroprevalence was 11.39% (95% confidence interval: 10.35–12.51%). Higher RVFV seroprevalences were observed in older animals compared to the young, and cattle compared to sheep and goats. RVFV seroprevalence was also higher in areas that had (i) lower precipitation seasonality, (ii) haplic planosols, and (iii) lower cattle density. The risk map generated demonstrated that RVF virus was endemic in several regions including those that have not reported clinical outbreaks in the northeastern part of the country. This work has improved our understanding on spatial distribution of RVFV risk in the country as well as RVF burden in livestock.

Background: Onchocerciasis, also known as “river blindness”, is caused by the bite of infected female blackflies (genus Simuliidae) that transmit the parasite Onchocerca volvulus. A high onchocerciasis microfarial load increases the risk to develop epilepsy in children between the ages of 3 and 18 years. In resource-limited settings in Africa where onchocerciasis has been poorly controlled, high numbers of onchocerciasis-associated epilepsy (OAE) are reported. We use mathematical modeling to predict the impact of onchocerciasis control strategies on the incidence and prevalence of OAE. Methodology: We developed an OAE model within the well-established mathematical modelling framework ONCHOSIM. Using Latin-Hypercube Sampling (LHS), and grid search technique, we quantified transmission and disease parameters using OAE data from Maridi County, an onchocerciasis endemic area, in southern Republic of South Sudan. Using ONCHOSIM, we predicted the impact of ivermectin mass drug administration (MDA) and vector control on the epidemiology of OAE in Maridi. Principal findings: The model estimated an OAE prevalence of 4.1% in Maridi County, close to the 3.7% OAE prevalence reported in field studies. The OAE incidence is expected to rapidly decrease by >50% within the first five years of implementing annual MDA with good coverage (≥70%). With vector control at a high efficacy level (around 80% reduction of blackfly biting rates) as the sole strategy, the reduction is slower, requiring about 10 years to halve the OAE incidence. Increasing the efficacy levels of vector control, and implementing vector control simultaneously with MDA, yielded better results in preventing new cases of OAE. Conclusions/Significances: Our modeling study demonstrates that intensifying onchocerciasis eradication efforts could substantially reduce OAE incidence and prevalence in endemic foci. Our model may be useful for optimizing OAE control strategies.

Background: Bunyavirus infections, including those caused by Bunyamwera serogroup orthobunyaviruses, represent a significant and yet likely still vastly underappreciated cause of mild to moderate human febrile infections. In severe cases, these infections can also cause neurological disease, particularly meningitis and encephalitis, and infection can even be fatal. However, with a few exceptions, information regarding the mechanisms underlying the neuroinvasion and neuropathogenesis of such infections is limited. This is due in part to a lack of animal models to facilitate such studies. Methodology/Principal findings: In an effort to develop an immunocompetent model of infection with Bunyamwera serogroup orthobunyaviruses, we infected 4-6-week-old female hamsters via either the intraperitoneal or subcutaneous route with 10⁶ pfu/animal of Bunyamwera virus (BUNV), Batai virus or Ngari virus. Only BUNV infection resulted in clinical disease, which was characterized by weight loss, lethargy and neurological signs (i.e. tremor of the head or limbs, loss of righting reflex, “waltzing”). While symptoms were of similar severity for both routes, they occurred more frequently following subcutaneous inoculation. Consistent with these clinical signs, both antigen staining and histopathological abnormalities were found extensively throughout the brain. Conclusions/Significance: The reported hamster model of BUNV infection provides a new tool for studying orthobunyavirus infection, and particularly neuroinvasion and the development of neuropathology. This model is particularly significant because it makes use of immunologically competent animals and relies on a subcutaneous inoculation route that more closely mimics the natural infection route for arboviruses, thereby providing a more authentic cellular and immunological context at the initial site of infection.

Carrion´s disease is caused by Bartonella bacilliformis, it is a Gram-negative pleomorphic bacterium. B. bacilliformis is transmitted by Lutzomyia verrucarum in endemic areas of the Peruvian Inter-Andean valleys. Additionally, the pathogenicity of B. bacilliformis involves an initial infection of erythrocytes and the further infection of endothelial cells, which mainly affects children and expectant women from extreme poverty rural areas. Therefore, the implementation of serological diagnostic methods and the development of candidate vaccines for the control of CD could be facilitated by the prediction of linear b-cell epitopes in specific proteins of B. bacilliformis by bioinformatics analysis. In this study, We used an in-silico analysis employing six web servers for the identification of epitopes in proteins of B. bacilliformis. The selection of B. bacilliformis-specific proteins and their analysis to identify epitopes allowed the selection of seven protein candidates that are expected to have high antigenic activity.

The gold standard for detection of Mycobacterium ulcerans is PCR due to its high accuracy in confirmation of suspected cases. But the available PCR assays are designed for standard size thermocyclers which are immobile and suited for reference laboratories often located long distances from endemic communities. This makes it a challenge to obtain immediate results for patient management. We validated and evaluated a dried reagent-based PCR assay adapted for a handheld, battery-operated, portable thermocycler with the potential to extend diagnostics to endemic communities with limited infrastructure. The diagnostic accuracy of the assay following a multi-center evaluation by three Buruli ulcer reference laboratories with over 300 clinical samples showed sensitivity and specificity of 100–97% and 100–94%, respectively using centralized IS2404 quantitative PCR platform as a reference standard. This assay coupled with a field-friendly extraction method fulfill almost all the target product profiles of Buruli ulcer for decentralized testing at the district, health center and community levels; a key critical action for achieving the NTD Road Map 2030 target for Buruli ulcer.

Background: Intestinal helminths, including Soil-Transmitted Helminth (STH), and Gastrointestinal Protist (GP) infections are major contributors to the global burden of disease, particularly in low-income countries such Ecuador. Their epidemiology in these settings is largely unknown. Methodology: This prospective cross-sectional study investigates the carriage of intestinal helminths, including STH, and GP in asymptomatic schoolchildren (3–11 years) in the Chimborazo and Guayas provinces, Ecuador. Single stool samples (n = 372) and epidemiological questionnaires on demographics and potential risk factors were collected from participating schoolchildren. Conventional microscopy examination was used as screening method, and molecular (PCR and Sanger sequencing) assays were used to further investigate the epidemiology of some GP. A multivariate logistic regression analysis was used to evaluate the strength of the association of suspected risk factors with the presence of helminths and GP. Principal findings: At least one intestinal parasite species was observed by microscopy in 63.2% (235/372) of the participating schoolchildren. Enterobius vermicularis (16.7%, 62/372; 95% CI: 13.0–20.9) and Blastocystis sp. (39.2%, 146/372; 95% CI: 34.2–44.2) were the most prevalent among helminths and GP, respectively. Assemblages A (50.0%), B (37.5%) and A+B (12.5%) were detected within Giardia duodenalis and ST3 (28.6%), ST1 and ST2 (26.2% each), and ST4 (14.3%) within Blastocystis sp. Three genotypes, two known (A: 66.7%; KB-1: 16.7%) and a novel (HhEcEb1, 16.7%) were identified within Enterocytozoon bieneusi. Municipality of origin, household overcrowding, and poor sanitation and personal hygiene habits were risk factors for childhood intestinal parasites colonization. Conclusions/Significance: Despite massive government drug administration programs, STH and GP infection remain a public health concern in paediatric populations living in poor-resource settings. Molecular analytical methods are required to better understand the epidemiology of these intestinal parasites. This study provides novel information on the occurrence of Blastocystis sp. and E. bieneusi genetic variants circulating in Ecuadorian human populations.

Background: There is limited epidemiological evidence on Lassa fever in pregnant women with acute gaps on prevalence, infection incidence, and risk factors. Such evidence would facilitate the design of therapeutic and vaccine trials and the design of control programs. Our study sought to address some of these gaps by estimating the seroprevalence and seroconversion risk of Lassa fever in pregnant women. Methodology/Principal findings: We conducted a prospective hospital-based cohort between February and December 2019 in Edo State, Southern Nigeria, enrolling pregnant women at antenatal clinic and following them up at delivery. Samples were evaluated for IgG antibodies against Lassa virus. The study demonstrates a seroprevalence of Lassa IgG antibodies of 49.6% and a seroconversion risk of 20.8%. Seropositivity was strongly correlated with rodent exposure around homes with an attributable risk proportion of 35%. Seroreversion was also seen with a seroreversion risk of 13.4%. Conclusions/Significance: Our study suggests that 50% of pregnant women were at risk of Lassa infection and that 35.0% of infections might be preventable by avoiding rodent exposure and conditions which facilitate infestation and the risk of human-rodent contact. While the evidence on rodent exposure is subjective and further studies are needed to provide a better understanding of the avenues of human-rodent interaction; public health measures to decrease the risk of rodent infestation and the risk of spill over events may be beneficial. With an estimated seroconversion risk of 20.8%, our study suggests an appreciable risk of contracting Lassa fever during pregnancy and while most of these seroconversions may not be new infections, given the high risk of adverse outcomes in pregnancy, it supports the need for preventative and therapeutic options against Lassa fever in pregnancy. The occurrence of seroreversion in our study suggests that the prevalence obtained in this, and other cohorts may be an underestimate of the actual proportion of women of childbearing age who present at pregnancy with prior LASV exposure. Additionally, the occurrence of both seroconversion and seroreversion in this cohort suggests that these parameters would need to be considered for the development of Lassa vaccine efficacy, effectiveness, and utility models.

Background: Canine Leishmaniasis (CanL) caused by the L. infantum species is one of the biggest threats to the health of the South American canine population. Chemotherapeutics currently used for the treatment of CanL fail to induce a total parasite clearance while inducing numerous side effects. As CanL is an immunomodulated disease, the use of immuno-treatments should strengthen the deficient immune response of infected dogs. In this study, we evaluated a nasally administered immunotherapy in dogs naturally infected with L. infantum (stage 2), with both visceral and cutaneous manifestations. Noteworthy, some of them were also infected by other parasites (E. canis, D. immitis, A. platys), what worsen their chance of survival. Methodology/Principal findings: The treatment was based on 2 intranasal (IN.) administrations of a killed L. infantum parasite loaded into maltodextrin nanoparticles, which treatment was compared with the classical oral administration of Miltefosine (2 mg/kg) for 28 days, as well as a combination of these 2 treatments. The results showed that two IN administrations significantly reduced the serology, and were at least as efficient as the chemotherapy to reduce the skin and bone marrow parasite burden, as well as clinical scores, and that unlike Miltefosine treatments, this nasally administered nanoparticle vaccine was without side effects. Conclusions: These results confirm the feasibility of a simple therapeutic immuno-treatment against L. infantum infected dogs, which is a promising tool for future developments.

Background: In leprosy patients, the most commonly reported non-viral co-infections are Tuberculosis, Leishmaniasis, Chromoblastomycosis and Helminths. The presence of a secondary infection is believed to increase the likelihood of leprosy reactions. The purpose of this review was to describe the clinical and epidemiological characteristics of the most reported bacterial, fungal, and parasitic co-infections in leprosy. Methodology/Principal findings: Following the PRISMA Extension for Scoping Reviews guidelines, a systematic literature search was conducted by two independent reviewers, resulting in the inclusion of 89 studies. For tuberculosis, a total of 211 cases were identified, with a median age of 36 years and male predominance (82%). Leprosy was the initial infection in 89% of cases, 82% of individuals had multibacillary disease, and 17% developed leprosy reactions. For leishmaniasis, 464 cases were identified, with a median age of 44 years and male predominance (83%). Leprosy was the initial infection in 44% of cases, 76% of individuals presented with multibacillary disease, and 18% developed leprosy reactions. Regarding chromoblastomycosis, we identified 19 cases with a median age of 54 years and male predominance (88%). Leprosy was the primary infection in 66% of cases, 70% of individuals had multibacillary disease, and 35% developed leprosy reactions. Additionally, we found 151 cases of co-infection with leprosy and helminths, with a median age of 43 years and male predominance (68%). Leprosy was the primary infection in 66% of cases, and 76% of individuals presented with multibacillary disease, while the occurrence of leprosy reactions varied from 37% to 81% across studies. Conclusion: We observed a male-dominated pattern of co-infections among working-age individuals with multibacillary leprosy. Unlike prior studies reporting increased leprosy reactions in chronic viral co-infections, our findings did not indicate any increase among bacterial, fungal, or parasitic co-infections. Rather, co-infections with tuberculosis and leishmaniasis appeared to reduce leprosy reactions.