Pediatric burden and seasonality of human metapneumovirus over 5 years in Managua, Nicaragua.

BACKGROUND: Human metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the burden and seasonality of symptomatic hMPV infection in children. METHODS: NPICS is an ongoing prospective study of children in Managua, Nicaragua. We assessed children for hMPV infection via real-time reverse-transcription polymerase chain reaction (RT-PCR). We used classical additive decomposition analysis to assess the temporal trends, and generalized growth models (GGMs) were used to estimate effective reproduction numbers. RESULTS: From 2011 to 2016, there were 564 hMPV symptomatic infections, yielding an incidence rate of 5.74 cases per 100 person-years (95% CI 5.3, 6.2). Children experienced 3509 acute lower respiratory infections (ALRIs), of which 160 (4.6%) were associated with hMPV infection. Children under the age of one had 55% of all symptomatic hMPV infections (62/112) develop into hMPV-associated ALRIs and were five times as likely as children over one to have an hMPV-associated ALRI (rate ratio 5.5 95% CI 4.1, 7.4 p < 0.001). Additionally, symptomatic reinfection with hMPV was common. In total, 87 (15%) of all observed symptomatic infections were detected reinfections. The seasonality of symptomatic hMPV outbreaks varied considerably. From 2011 to 2016, four epidemic periods were observed, following a biennial seasonal pattern. The mean ascending phase of the epidemic periods were 7.7 weeks, with an overall mean estimated reproductive number of 1.2 (95% CI 1.1, 1.4). CONCLUSIONS: Symptomatic hMPV infection was associated with substantial burden among children in the first year of life. Timing and frequency of symptomatic hMPV incidence followed biennial patterns.

Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance.

Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted.

Can the combination of TasP and PrEP eliminate HIV among MSM in British Columbia, Canada?

INTRODUCTION: In British Columbia (BC), the HIV epidemic continues to disproportionally affect the gay, bisexual and other men who have sex with men (MSM). In this study, we aimed to evaluate how Treatment as Prevention (TasP) and pre-exposure prophylaxis (PrEP), if used in combination, could lead to HIV elimination in BC among MSM. METHODS: Considering the heterogeneity in HIV transmission risk, we developed a compartmental model stratified by age and risk-taking behaviour for the HIV epidemic among MSM in BC, informed by clinical, behavioural and epidemiological data. Key outcome measures included the World Health Organization (WHO) threshold for disease elimination as a public health concern and the effective reproduction number (Re). Model interventions focused on the optimization of different TasP and PrEP components. Sensitivity analysis was done to evaluate the impact of sexual mixing patterns, PrEP effectiveness and increasing risk-taking behaviour. RESULTS: The incidence rate was estimated to be 1.2 (0.9-1.9) per 1000 susceptible MSM under the Status Quo scenario by the end of 2029. Optimizing all aspects of TasP and the simultaneous provision of PrEP to high-risk MSM resulted in an HIV incidence rate as low as 0.4 (0.3-0.6) per 1000 susceptible MSM, and an Re as low as 0.7 (0.6-0.9), indicating that disease elimination was possible when TasP and PrEP were combined. Provision of PrEP to younger MSM or high-risk and younger MSM resulted in a similar HIV incidence rate, but an Re with credible intervals that crossed one. CONCLUSION: Further optimizing all aspects of TasP and prioritizing PrEP to high-risk MSM can achieve the goal of disease elimination in BC. These results should inform public health policy development and intervention programs that address the HIV epidemic in BC and in other similar settings where MSM are disproportionately affected.

The Impact of Different Types of Violence on Ebola Virus Transmission During the 2018-2020 Outbreak in the Democratic Republic of the Congo.

BACKGROUND: Our understanding of the different effects of targeted versus nontargeted violence on Ebola virus (EBOV) transmission in Democratic Republic of the Congo (DRC) is limited. METHODS: We used time-series data of case counts to compare individuals in Ebola-affected health zones in DRC, April 2018-August 2019. Exposure was number of violent events per health zone, categorized into Ebola-targeted or Ebola-untargeted, and into civilian-induced, (para)military/political, or protests. Outcome was estimated daily reproduction number (Rt) by health zone. We fit linear time-series regression to model the relationship. RESULTS: Average Rt was 1.06 (95% confidence interval [CI], 1.02-1.11). A mean of 2.92 violent events resulted in cumulative absolute increase in Rt of 0.10 (95% CI, .05-.15). More violent events increased EBOV transmission (P = .03). Considering violent events in the 95th percentile over a 21-day interval and its relative impact on Rt, Ebola-targeted events corresponded to Rt of 1.52 (95% CI, 1.30-1.74), while civilian-induced events corresponded to Rt of 1.43 (95% CI, 1.21-1.35). Untargeted events corresponded to Rt of 1.18 (95% CI, 1.02-1.35); among these, militia/political or ville morte events increased transmission. CONCLUSIONS: Ebola-targeted violence, primarily driven by civilian-induced events, had the largest impact on EBOV transmission.

Numerical study of discretization algorithms for stable estimation of disease parameters and epidemic forecasting.

In this paper we investigate how various discretization schemes could be incorporated in regularization algorithms for stable parameter estimation and forecasting in epidemiology. Specifically, we compare parametric and nonparametric discretization tools in terms of their impact on the accuracy of recovered disease parameters as well as their impact on future projections of new incidence cases. Both synthetic and real data for 1918 "Spanish Flu" pandemic in San Francisco are considered. The discrete approximation of a time dependent transmission rate is combined with the Levenberg-Marquardt algorithm used to solve the nonlinear least squares problem aimed at fitting the model to limited incidence data for an unfolding outbreak. Our simulation study highlights the crucial role of a priori information at the early stage of an epidemic in mitigating the lack of stability in over-parameterized models with insu cient data. Fortunately, our results suggest that a balanced combination of problem-oriented regularization techniques is one way in which scientists can still draw useful conclusions about system parameters and in turn generate reliable forecasts that policy makers could use to guide control interventions.

Whooping cough dynamics in Chile (1932-2010): disease temporal fluctuations across a north-south gradient.

BACKGROUND: The spatial-temporal dynamics of Bordetella pertussis remains as a highly interesting case in infectious disease epidemiology. Despite large-scale vaccination programs in place for over 50 years around the world, frequent outbreaks are still reported in many countries. METHODS: Here, we use annual time series of pertussis incidence from the thirteen different regions of Chile (1952-2010) to study the spatial-temporal dynamics of Pertussis. The period 1975-1995 was characterized by a strong 4 year cycle, while the last two decades of the study period (1990-2010) were characterized by disease resurgence without significant periodic patterns. RESULTS: During the first decades, differences in periodic patterns across regions can be explained by the differences in susceptible recruitment. The observed shift in periodicity from the period 1952-1974 to the period 1975-1995 across regions was relatively well predicted by the susceptible recruitment and population size. However, data on vaccination rates was not taken into account in this study. CONCLUSIONS: Our findings highlight how demography and population size have interacted with the immunization program in shaping periodicity along a unique latitudinal gradient. Widespread B. pertussis vaccination appears to lead to longer periodic dynamics, which is line with a reduction in B. pertussis transmission, but our findings indicate that regions characterized by both low birth rate and population size decreased in periodicity following immunization efforts.

Occupation and environmental heat-associated deaths in Maricopa county, Arizona: a case-control study.

BACKGROUND: Prior research shows that work in agriculture and construction/extraction occupations increases the risk of environmental heat-associated death. PURPOSE: To assess the risk of environmental heat-associated death by occupation. METHODS: This was a case-control study. Cases were heat-caused and heat-related deaths occurring from May-October during the period 2002-2009 in Maricopa County, Arizona. Controls were selected at random from non-heat-associated deaths during the same period in Maricopa County. Information on occupation, age, sex, and race-ethnicity was obtained from death certificates. Logistic regression analysis was used to estimate odds ratios for heat-associated death. RESULTS: There were 444 cases of heat-associated deaths in adults (18+ years) and 925 adult controls. Of heat-associated deaths, 332 (75%) occurred in men; a construction/extraction or agriculture occupation was described on the death certificate in 115 (35%) of these men. In men, the age-adjusted odds ratios for heat-associated death were 2.32 (95% confidence interval 1.55, 3.48) in association with construction/extraction and 3.50 (95% confidence interval 1.94, 6.32) in association with agriculture occupations. The odds ratio for heat-associated death was 10.17 (95% confidence interval 5.38, 19.23) in men with unknown occupation. In women, the age-adjusted odds ratio for heat-associated death was 6.32 (95% confidence interval 1.48, 27.08) in association with unknown occupation. Men age 65 years and older in agriculture occupations were at especially high risk of heat-associated death. CONCLUSION: The occurrence of environmental heat-associated death in men in agriculture and construction/extraction occupations in a setting with predictable periods of high summer temperatures presents opportunities for prevention.

[Simulating measles and rubella elimination levels according to social stratification and interaction]. / Simulación del nivel de eliminación de sarampión y rubéola según la estratificación e interacción social.

OBJECTIVE: The study was aimed at comparing measles and rubella disease elimination levels in a homogeneous and heterogeneous population according to socioeconomic status with interactions amongst low- and high-income individuals and diversity in the average number of contacts amongst them. METHODS: Effective reproductive rate simulations were deduced from a susceptibleinfected- recovered (SIR) mathematical model according to different immunisation rates using measles (1980 and 2005) and rubella (1998 and 2005) incidence data from Latin-America and the Caribbean. Low- and high-income individuals' social interaction and their average number of contacts were analysed by bipartite random network analysis. MAPLE 12 (Maplesoft Inc, Ontario Canada) software was used for making the simulations. RESULTS: The progress made in eliminating both diseases between both periods of time was reproduced in the socially-homogeneous population. Measles (2005) would be eliminated in high- and low-income groups; however, it would only be achieved in rubella (2005) if there were a high immunity rate amongst the low-income group. If the average number of contacts were varied, then rubella would not be eliminated, even with a 95 % immunity rate. CONCLUSION: Monitoring the elimination level in diseases like measles and rubella requires that socio-economic status be considered as well as the population's interaction pattern. Special attention should be paid to communities having diversity in their average number of contacts occurring in confined spaces such as displaced communities, prisons, educational establishments, or hospitals.

Simulación del nivel de eliminación de sarampión y rubéola según la estratificación e interacción social / Simulating measles and rubella elimination levels according to social stratification and interaction

Objetivo Comparar el nivel de eliminación de enfermedades como sarampión y rubéola en población homogénea y heterogénea según la existencia de estratos sociales con interacción entre individuos de estrato social alto y bajo y diversidad en el número promedio de contactos entre ellos. Métodos Simulaciones del ritmo reproductivo efectivo, derivado de un modelo matemático tipo SIR (Susceptibles Infectados Recuperados), según diferentes ritmos de inmunidad. Se utilizaron datos de incidencia de sarampión (1980 y 2005) y rubéola (1998 y 2005) de América Latina y el Caribe. Se analizó la interacción entre individuos del estrato social alto y bajo con diferente número promedio de contactos mediante análisis de red aleatoria bipartita. Las simulaciones se ejecutaron en MAPLE 12 (Maplesoft Inc, Ontario Canada). Resultados En la población socialmente homogénea se reprodujo el avance en la eliminación de ambas enfermedades entre los dos períodos de tiempo. En el estrato alto y bajo, se lograría la eliminación en sarampión (2005) pero en rubéola (2005) sólo se lograría si hay alto ritmo de inmunidad en el estrato bajo. Si varía el número promedio de contactos habituales, no se lograría la eliminación de rubéola ni con un ritmo de inmunidad de 95 por ciento. Conclusión El seguimiento del nivel de eliminación de enfermedades como sarampión y rubéola demanda la consideración de la situación socioeconómica y del patrón de interacción de la población. Especial atención se debe prestar a comunidades con diversidad en el número promedio de contactos en espacios confinados como comunidades desplazadas, carcelarias, educativas, hospitalarias, etc.

Objective The study was aimed at comparing measles and rubella disease elimination levels in a homogeneous and heterogeneous population according to socioeconomic status with interactions amongst low- and high-income individuals and diversity in the average number of contacts amongst them. Methods Effective reproductive rate simulations were deduced from a susceptibleinfected- recovered (SIR) mathematical model according to different immunisation rates using measles (1980 and 2005) and rubella (1998 and 2005) incidence data from Latin-America and the Caribbean. Low- and high-income individuals' social interaction and their average number of contacts were analysed by bipartite random network analysis. MAPLE 12 (Maplesoft Inc, Ontario Canada) software was used for making the simulations. Results The progress made in eliminating both diseases between both periods of time was reproduced in the socially-homogeneous population. Measles (2005) would be eliminated in high- and low-income groups; however, it would only be achieved in rubella (2005) if there were a high immunity rate amongst the low-income group. If the average number of contacts were varied, then rubella would not be eliminated, even with a 95 percent immunity rate. Conclusion Monitoring the elimination level in diseases like measles and rubella requires that socio-economic status be considered as well as the population's interaction pattern. Special attention should be paid to communities having diversity in their average number of contacts occurring in confined spaces such as displaced communities, prisons, educational establishments, or hospitals.