Sensitive, reliable and fast diagnostic tools that are applicable in low-resource settings, at the point of care (PoC), are seen as crucial in the fight against visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). Addressing the need for a PoC test, several diagnostic tests, including serological and molecular methods, have been developed and evaluated in the past. One promising molecular method, already implemented for diagnosis of a range of diseases, is the loop-mediated isothermal amplification (LAMP) protocol. In this systematic review and meta-analysis, using a comprehensive search strategy, we focus on studies evaluating the performance of LAMP for the diagnosis of leishmaniasis in humans and other mammals such as dogs, compared with microscopy and/or any other molecular diagnostic method. A meta-analysis, pooling sensitivity and specificity rates and calculating areas under the curve (AUCs) in summary receiver operating characteristic (SROC) plots, was conducted on datasets extracted from studies, grouped by clinical condition and sample type. We found high sensitivity and specificity for LAMP when compared with microscopy and PCR using blood samples, with pooled estimate values of > 90% for all subgroups, corresponding to calculated AUC values > 0.96, except for LAMP compared to microscopy for diagnosis of CL. However, only a limited number of studies were truly comparable. Most of the observed heterogeneity is likely based on true differences between the studies rather than sampling error only. Due to simple readout methods and low laboratory equipment requirements for sample preparation compared to other molecular methods, LAMP is a promising candidate for a molecular (near-)PoC diagnostic method for VL and CL. Graphical Abstract

Background: Research is urgently needed to reduce the morbidity and mortality of Lassa fever (LF), including clinical trials to test new therapies and to verify the efficacy and safety of the only current treatment recommendation, ribavirin, which has a weak clinical evidence base. To help establish a basis for the development of an adaptable, standardised clinical trial methodology, we conducted a systematic review to identify the clinical characteristics and outcomes of LF and describe how LF has historically been defined and assessed in the scientific literature. Methodology: Primary clinical studies and reports of patients with suspected and confirmed diagnosis of LF published in the peer-reviewed literature before 15 April 2021 were included. Publications were selected following a two-stage screening of abstracts, then full-texts, by two independent reviewers at each stage. Data were extracted, verified, and summarised using descriptive statistics. Results: 147 publications were included, primarily case reports (36%), case series (28%), and cohort studies (20%); only 2 quasi-randomised studies (1%) were found. Data are mostly from Nigeria (52% of individuals, 41% of publications) and Sierra Leone (42% of individuals, 31% of publications). The results corroborate the World Health Organisation characterisation of LF presentation. However, a broader spectrum of presenting symptoms is evident, such as gastrointestinal illness and other nervous system and musculoskeletal disorders that are not commonly included as indicators of LF. The overall case fatality ratio was 30% in laboratory-confirmed cases (1896/6373 reported in 109 publications). Conclusion: Systematic review is an important tool in the clinical characterisation of diseases with limited publications. The results herein provide a more complete understanding of the spectrum of disease which is relevant to clinical trial design. This review demonstrates the need for coordination across the LF research community to generate harmonised research methods that can contribute to building a strong evidence base for new treatments and foster confidence in their integration into clinical care.

Background: In Brazil, case-fatality from visceral leishmaniasis (VL) is high and characterized by wide differences between the various political-economic units, the federated units (FUs). This study was designed to investigate the association between factors at the both FU and individual levels with the risk of dying from VL, after analysing the temporal trend and the spatial dependency for VL case-fatality.Methodology: The analysis was based on individual and aggregated data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health). The temporal and spatial distributions of the VL case-fatality between 2007 and 2017 (27 FUs as unit of analysis) were considered together with the individual characteristics and many other variables at the FU level (socioeconomic, demographic, access to health and epidemiological indicators) in a mixed effects models or multilevel modeling, assuming a binomial outcome distribution (death from VL).Findings: A linear increasing temporal tendency (4%/year) for VL case-fatality was observed between 2007 and 2017. There was no similarity between the case-fatality rates of neighboring FUs (non-significant spatial term), although these rates were heterogeneous in this spatial scale of analysis. In addition to the known individual risk factors age, female gender, disease’s severity, bacterial co-infection and disease duration, low level schooling and unavailability of emergency beds and health professionals (the last two only in univariate analysis) were identified as possibly related to VL death risk. Lower VL incidence was also associated to VL case-fatality, suggesting that unfamiliarity with the disease may delay appropriate medical management: VL patients with fatal outcome were notified and had VL treatment started 6 and 3 days later, respectively, in relation to VL cured patients. Access to garbage collection, marker of social and economic development, seems to be protective against the risk of dying from VL. Part of the observed VL case-fatality variability in Brazil could not be explained by the studied variables, suggesting that factors linked to the intra FU environment may be involved.Conclusions: This study aimed to identify epidemiological conditions and others related to access to the health system possibly linked to VL case-fatality, pointing out new prognostic determinants subject to intervention.

Although non-fatal and mostly self-healing in the case of Leishmania (L.) major, cutaneous leishmaniasis (CL) is mainly treated to reduce lesion healing time. Less attention is paid to the improvement of scars, especially in aesthetically relevant areas of the body, which can dramatically affect patients’ wellbeing. We explored patients’ perspectives about treatment options and the social and psychological burden of disease (lesion and scar). Individual in-depth interviews were conducted with ten confirmed CL patients at two L. major endemic sites in Southern Tunisia (Sidi Bouzid and Gafsa). Participants were selected using a sampling approach along a spectrum covering e.g. age, sex, and clinical presentation. Patients’ experiences, opinions and preferences were explored, and their detailed accounts gave an insight on the impact of CL on their everyday lives. The impact of CL was found to be considerable. Most patients were not satisfied with treatment performance and case management. They expected a shorter healing time and better accessibility of the health system. Tolerance of the burden of disease was variable and ranged from acceptance of hidden scars to suicidal thoughts resulting from the fear to become handicapped, and the stress caused by close relatives. Some believed CL to be a form of skin cancer. Unexpectedly, this finding shows the big gap between the perspectives of patients and assumptions of health professionals regarding this disease. This study provided valuable information for better case management emphasizing the importance of improving communication with patients, and accessibility to treatment. It generated context-specific knowledge to policy makers in Tunisia to implement effective case management in a country where access to treatment remains a challenge due to socio-economic and geographic barriers despite a long tradition in CL control.

Breast cancer is highly prevalent yet a more complete understanding of the interplay between genes and probable environmental risk factors, such as night work, remains lagging. Using a discordant twin pair design, we examined the association between night shift work and breast cancer risk, controlling for familial confounding. Shift work pattern was prospectively assessed by mailed questionnaires among 5,781 female twins from the Older Finnish Twin Cohort. Over the study period (1990–2018), 407 incident breast cancer cases were recorded using the Finnish Cancer Registry. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for potential confounders. Within-pair co-twin analyses were employed in 57 pairs to account for potential familial confounding. Compared to women who worked days only, women with shift work that included night shifts had a 1.58-fold higher risk of breast cancer (HR = 1.58; 95%CI, 1.16–2.15, highest among the youngest women i.e. born 1950–1957, HR = 2.08; 95%CI, 1.32–3.28), whereas 2-shift workers not including night shifts, did not (HR = 0.84; 95%CI, 0.59–1.21). Women with longer sleep (average sleep duration > 8 h/night) appeared at greatest risk of breast cancer if they worked night shifts (HR = 2.91; 95%CI, 1.55–5.46; P_intx=0.32). Results did not vary by chronotype (P_intx=0.74). Co-twin analyses, though with limited power, suggested that night work may be associated with breast cancer risk independent of early environmental and genetic factors. These results confirm a previously described association between night shift work and breast cancer risk. Genetic influences only partially explain these associations.