Risk factors for graft failure after penetrating keratoplasty

The objective of our study was to define principal risk factors for graft failure in patients who underwent penetrating keratoplasty (PK).Retrospective data obtained from a cohort of 895 penetrating keratoplasties performed between 2001 and 2006 were analysed. Recipient related factors, graft characteristics, and surgical technique were assessed in a univariate analysis and with a multivariate proportional hazard model to detect principal risk factors for definitive graft failure.Multivariate analysis showed clear significance for diagnosis and number of previous grafts and border line significance for the oldest donor age group. Patients with keratoconus had the best 10-year survival estimate (95%), followed by endothelial and stromal dystrophies (both 55%), infectious leukomas (49%), trauma (33%) and chemical burns (14%). Primary PK grafts had a survival rate of 81%, second grafts of 33% and third or more grafts of 16%. Overall 10-year survival estimate based on univariate analysis was found to be 65%.In conclusion, we found that primary diagnosis and previous graft failures in the recipient are the most important risk factors of graft failure after a PK

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study.

BACKGROUND: Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. METHODS: Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A-(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes. RESULTS: In children, HbAS was associated, compared to wild type, with a lower incidence of malaria (IRR = 0.78, 95% CI 0.66-0.92, p = 0.003), lower parasite density upon infection (PR = 0.66, 95% CI 0.51-0.85, p = 0.001), and lower body temperature for any given parasite density (- 0.13 ℃, 95% CI - 0.21, - 0.05, p = 0.002). In children, HbSS was associated with a lower incidence of malaria (IRR = 0.17, 95% CI 0.04-0.71, p = 0.02) and lower parasite density upon infection (PR = 0.31, 95% CI 0.18-0.54, p < 0.001). α-/αα thalassaemia, was associated with higher parasite prevalence in both children and adults (RR = 1.23, 95% CI 1.06-1.43, p = 0.008 and RR = 1.52, 95% CI 1.04-2.23, p = 0.03, respectively). G6PD deficiency was associated with lower body temperature for any given parasite density only among male hemizygote children (- 0.19 ℃, 95% CI - 0.31, - 0.06, p = 0.003). CONCLUSION: RBC variants were associated with non-severe malaria outcomes. Elucidation of the mechanisms by which they confer protection will improve understanding of genetic protection against malaria

Assessing the role of multiple mechanisms increasing the age of dengue cases in Thailand

The mean age of dengue hemorrhagic fever (DHF) cases increased considerably in Thailand from 8.1 to 24.3 y between 1981 and 2017 (mean annual increase of 0.45 y). Alternative proposed explanations for this trend, such as changes in surveillance practices, reduced mosquito–human contact, and shifts in population demographics, have different implications for global dengue epidemiology. To evaluate the contribution of each of these hypothesized mechanisms to the observed data, we developed 20 nested epidemiological models of dengue virus infection, allowing for variation over time in population demographics, infection hazards, and reporting rates. We also quantified the effect of removing or retaining each source of variation in simulations of the age trajectory. Shifts in the age structure of susceptibility explained 58% of the observed change in age. Adding heterogeneous reporting by age and reductions in per-serotype infection hazard to models with shifts in susceptibility explained an additional 42%. Reductions in infection hazards were mostly driven by changes in the number of infectious individuals at any time (another consequence of shifting age demographics) rather than changes in the transmissibility of individual infections. We conclude that the demographic transition drives the overwhelming majority of the observed change as it changes both the age structure of susceptibility and the number of infectious individuals. With the projected Thai population age structure, our results suggest a continuing increase in age of DHF cases, shifting the burden toward individuals with more comorbidity. These insights into dengue epidemiology may be relevant to many regions of the globe currently undergoing comparable changes in population demographics

Scoping review on vector-borne diseases in urban areas : transmission dynamics, vectorial capacity and co-infection

BACKGROUND: Transmission dynamics, vectorial capacity, and co-infections have substantial impacts on vector-borne diseases (VBDs) affecting urban and suburban populations. Reviewing key factors can provide insight into priority research areas and offer suggestions for potential interventions. MAIN BODY: Through a scoping review, we identify knowledge gaps on transmission dynamics, vectorial capacity, and co-infections regarding VBDs in urban areas. Peer-reviewed and grey literature published between 2000 and 2016 was searched. We screened abstracts and full texts to select studies. Using an extraction grid, we retrieved general data, results, lessons learned and recommendations, future research avenues, and practice implications. We classified studies by VBD and country/continent and identified relevant knowledge gaps. Of 773 articles selected for full-text screening, 50 were included in the review: 23 based on research in the Americas, 15 in Asia, 10 in Africa, and one each in Europe and Australia. The largest body of evidence concerning VBD epidemiology in urban areas concerned dengue and malaria. Other arboviruses covered included chikungunya and West Nile virus, other parasitic diseases such as leishmaniasis and trypanosomiasis, and bacterial rickettsiosis and plague. Most articles retrieved in our review combined transmission dynamics and vectorial capacity; only two combined transmission dynamics and co-infection. The review identified significant knowledge gaps on the role of asymptomatic individuals, the effects of co-infection and other host factors, and the impacts of climatic, environmental, and socioeconomic factors on VBD transmission in urban areas. Limitations included the trade-off from narrowing the search strategy (missing out on classical modelling studies), a lack of studies on co-infections, most studies being only descriptive, and few offering concrete public health recommendations. More research is needed on transmission risk in homes and workplaces, given increasingly dynamic and mobile populations. The lack of studies on co-infection hampers monitoring of infections transmitted by the same vector. CONCLUSIONS: Strengthening VBD surveillance and control, particularly in asymptomatic cases and mobile populations, as well as using early warning tools to predict increasing transmission, were key strategies identified for public health policy and practice

Rapid shifts in the age-specific burden of malaria following successful control interventions in four regions of Uganda.

BACKGROUND: Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear. METHODS: Over a 10-year period (January 2009 to July 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites. RESULTS: Overall, 896,550 patient visits were included in the study; 211,632 aged  15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites. In the two LLINs-only sites, the proportion of malaria cases in  15 years increased from 40 to 61% and 29 to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19 to 44% and 18 to 31%, respectively. CONCLUSIONS: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies

Reconstruction of 60 Years of Chikungunya Epidemiology in the Philippines Demonstrates Episodic and Focal Transmission.

Proper understanding of the long-term epidemiology of chikungunya has been hampered by poor surveillance. Outbreak years are unpredictable and cases often misdiagnosed. Here we analyzed age-specific data from 2 serological studies (from 1973 and 2012) in Cebu, Philippines, to reconstruct both the annual probability of infection and population-level immunity over a 60-year period (1952-2012). We also explored whether seroconversions during 2012-2013 were spatially clustered. Our models identified 4 discrete outbreaks separated by an average delay of 17 years. On average, 23% (95% confidence interval [CI], 16%-37%) of the susceptible population was infected per outbreak, with >50% of the entire population remaining susceptible at any point. Participants who seroconverted during 2012-2013 were clustered at distances of 350 000 infections were missed by surveillance systems. Serological studies could supplement surveillance to provide important insights on pathogen circulation

Pareto rules for malaria super-spreaders and super-spreading

Heterogeneity in transmission is a challenge for infectious disease dynamics and control. An 80-20 “Pareto” rule has been proposed to describe this heterogeneity whereby 80% of transmission is accounted for by 20% of individuals, herein called super-spreaders. It is unclear, however, whether super-spreading can be attributed to certain individuals or whether it is an unpredictable and unavoidable feature of epidemics. Here, we investigate heterogeneous malaria transmission at three sites in Uganda and find that super-spreading is negatively correlated with overall malaria transmission intensity. Mosquito biting among humans is 90-10 at the lowest transmission intensities declining to less than 70-30 at the highest intensities. For super-spreaders, biting ranges from 70-30 down to 60-40. The difference, approximately half the total variance, is due to environmental stochasticity. Super-spreading is thus partly due to super-spreaders, but modest gains are expected from targeting super-spreaders

Estimating malaria incidence from routine health facility-based surveillance data in Uganda.

BACKGROUND: Accurate measures of malaria incidence are essential to track progress and target high-risk populations. While health management information system (HMIS) data provide counts of malaria cases, quantifying the denominator for incidence using these data is challenging because catchment areas and care-seeking behaviours are not well defined. This study's aim was to estimate malaria incidence using HMIS data by adjusting the population denominator accounting for travel time to the health facility. METHODS: Outpatient data from two public health facilities in Uganda (Kihihi and Nagongera) over a 3-year period (2011-2014) were used to model the relationship between travel time from patient village of residence (available for each individual) to the facility and the relative probability of attendance using Poisson generalized additive models. Outputs from the model were used to generate a weighted population denominator for each health facility and estimate malaria incidence. Among children aged 6 months to 11 years, monthly HMIS-derived incidence estimates, with and without population denominators weighted by probability of attendance, were compared with gold standard measures of malaria incidence measured in prospective cohorts. RESULTS: A total of 48,898 outpatient visits were recorded across the two sites over the study period. HMIS incidence correlated with cohort incidence over time at both study sites (correlation in Kihihi = 0.64, p < 0.001; correlation in Nagongera = 0.34, p = 0.045). HMIS incidence measures with denominators unweighted by probability of attendance underestimated cohort incidence aggregated over the 3 years in Kihihi (0.5 cases per person-year (PPY) vs 1.7 cases PPY) and Nagongera (0.3 cases PPY vs 3.0 cases PPY). HMIS incidence measures with denominators weighted by probability of attendance were closer to cohort incidence, but remained underestimates (1.1 cases PPY in Kihihi and 1.4 cases PPY in Nagongera). CONCLUSIONS: Although malaria incidence measured using HMIS underestimated incidence measured in cohorts, even when adjusting for probability of attendance, HMIS surveillance data are a promising and scalable source for tracking relative changes in malaria incidence over time, particularly when the population denominator can be estimated by incorporating information on village of residence