Calculation of Disease Dynamics in a Population of Households

Early mathematical representations of infectious disease dynamics assumed a single, large, homogeneously mixing population. Over the past decade there has been growing interest in models consisting of multiple smaller subpopulations (households, workplaces, schools, communities), with the natural assumption of strong homogeneous mixing within each subpopulation, and weaker transmission between subpopulations. Here we consider a model of SIRS (susceptible-infectious-recovered-susceptible) infection dynamics in a very large (assumed infinite) population of households, with the simplifying assumption that each household is of the same size (although all methods may be extended to a population with a heterogeneous distribution of household sizes). For this households model we present efficient methods for studying several quantities of epidemiological interest: (i) the threshold for invasion; (ii) the early growth rate; (iii) the household offspring distribution; (iv) the endemic prevalence of infection; and (v) the transient dynamics of the process. We utilize these methods to explore a wide region of parameter space appropriate for human infectious diseases. We then extend these results to consider the effects of more realistic gamma-distributed infectious periods. We discuss how all these results differ from standard homogeneous-mixing models and assess the implications for the invasion, transmission and persistence of infection. The computational efficiency of the methodology presented here will hopefully aid in the parameterisation of structured models and in the evaluation of appropriate responses for future disease outbreaks.     

The Relationship between Poverty and Healthcare Seeking among Patients Hospitalized with Acute Febrile Illnesses in Chittagong,Bangladesh

Delays in seeking appropriate healthcare can increase the case fatality of acute febrile illnesses, and circuitous routes of care-seeking can have a catastrophic financial impact upon patients in low-income settings. To investigate the relationship between poverty and pre-hospital delays for patients with acute febrile illnesses, we recruited a cross-sectional, convenience sample of 527 acutely ill adults and children aged over 6 months, with a documented fever ≥38.0°C and symptoms of up to 14 days’ duration, presenting to a tertiary referral hospital in Chittagong, Bangladesh, over the course of one year from September 2011 to September 2012. Participants were classified according to the socioeconomic status of their households, defined by the Oxford Poverty and Human Development Initiative’s multidimensional poverty index (MPI). 51% of participants were classified as multidimensionally poor (MPI>0.33). Median time from onset of any symptoms to arrival at hospital was 22 hours longer for MPI poor adults compared to non-poor adults (123 vs. 101 hours) rising to a difference of 26 hours with adjustment in a multivariate regression model (95% confidence interval 7 to 46 hours; P = 0.009). There was no difference in delays for children from poor and non-poor households (97 vs. 119 hours; P = 0.394). Case fatality was 5.9% vs. 0.8% in poor and non-poor individuals respectively (P = 0.001)—5.1% vs. 0.0% for poor and non-poor adults (P = 0.010) and 6.4% vs. 1.8% for poor and non-poor children (P = 0.083). Deaths were attributed to central nervous system infection (11), malaria (3), urinary tract infection (2), gastrointestinal infection (1) and undifferentiated sepsis (1). Both poor and non-poor households relied predominantly upon the (often informal) private sector for medical advice before reaching the referral hospital, but MPI poor participants were less likely to have consulted a qualified doctor. Poor participants were more likely to attribute delays in decision-making and travel to a lack of money (P<0.001), and more likely to face catastrophic expenditure of more than 25% of monthly household income (P<0.001). We conclude that multidimensional poverty is associated with greater pre-hospital delays and expenditure in this setting. Closer links between health and development agendas could address these consequences of poverty and streamline access to adequate healthcare.     

Improved Socio-Economic Status of a Community Population Following Schistosomiasis and Intestinal Worm Control Interventions on Kome Island,North-Western Tanzania

Research on micro-level assessment of the changes of socio-economic status following health interventions is very scarce. The use of household asset data to determine wealth indices is a common procedure for estimating socio-economic position in resource poor settings. In such settings information about income is usually lacking, and the collection of individual consumption or expenditure data would require in-depth interviews, posing a considerable risk of bias. In this study, we determined the socio-economic status of 213 households in a community population in an island in the north-western Tanzania before and 3 year after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention to control schistosomiasis and intestinal worm infections. We constructed a household ''wealth index'' based housing construction features (e.g., type of roof, walls, and floor) and durable assets ownership (e.g., bicycle, radio, etc.). We employed principal components analysis and classified households into wealth quintiles. The study revealed that asset variables with positive factor scores were associated with higher socio-economic status, whereas asset variables with negative factor scores were associated with lower socio-economic status. Overall, households which were rated as the poorest and very poor were on the decrease, whereas those rated as poor, less poor, and the least poor were on the increase after PHAST intervention. This decrease/increase was significant. The median shifted from -0.4376677 to 0.5001073, and the mean from -0.2605787 (SD; 2.005688) to 0.2605787 (SD; 1.831199). The difference in socio-economic status of the people between the 2 phases was highly statistically significant (P<0.001). We argue that finding of this study should be treated with caution as there were other interventions to control schistosomiasis and intestinal worm infections which were running concurrently on Kome Island apart from PHAST intervention.     

Estimating and interpreting secondary attack risk: Binomial considered biased

The household secondary attack risk (SAR), often called the secondary attack rate or secondary infection risk, is the probability of infectious contact from an infectious household member A to a given household member B, where we define infectious contact to be a contact sufficient to infect B if he or she is susceptible. Estimation of the SAR is an important part of understanding and controlling the transmission of infectious diseases. In practice, it is most often estimated using binomial models such as logistic regression, which implicitly attribute all secondary infections in a household to the primary case. In the simplest case, the number of secondary infections in a household with m susceptibles and a single primary case is modeled as a binomial(m, p) random variable where p is the SAR. Although it has long been understood that transmission within households is not binomial, it is thought that multiple generations of transmission can be neglected safely when p is small. We use probability generating functions and simulations to show that this is a mistake. The proportion of susceptible household members infected can be substantially larger than the SAR even when p is small. As a result, binomial estimates of the SAR are biased upward and their confidence intervals have poor coverage probabilities even if adjusted for clustering. Accurate point and interval estimates of the SAR can be obtained using longitudinal chain binomial models or pairwise survival analysis, which account for multiple generations of transmission within households, the ongoing risk of infection from outside the household, and incomplete follow-up. We illustrate the practical implications of these results in an analysis of household surveillance data collected by the Los Angeles County Department of Public Health during the 2009 influenza A (H1N1) pandemic.     

Poverty and blindness in Pakistan: results from the Pakistan national blindness and visual impairment survey

Objective To explore the association between blindness and deprivation in a nationally representative sample of adults in Pakistan.Design Cross sectional population based survey.Setting 221 rural and urban clusters selected randomly throughout Pakistan.Participants Nationally representative sample of 16 507 adults aged 30 or above (95.3% response rate).Main outcome measures Associations between visual impairment and poverty assessed by a cluster level deprivation index and a household level poverty indicator; prevalence and causes of blindness; measures of the rate of uptake and quality of eye care services.Results 561 blind participants (<3/60 in the better eye) were identified during the survey. Clusters in urban Sindh province were the most affluent, whereas rural areas in Balochistan were the poorest. The prevalence of blindness in adults living in affluent clusters was 2.2%, compared with 3.7% in medium clusters and 3.9% in poor clusters (P<0.001 for affluent v poor). The highest prevalence of blindness was found in rural Balochistan (5.2%). The prevalence of total blindness (bilateral no light perception) was more than three times higher in poor clusters than in affluent clusters (0.24% v 0.07%, P<0.001). The prevalences of blindness caused by cataract, glaucoma, and corneal opacity were lower in affluent clusters and households. Reflecting access to eye care services, cataract surgical coverage was higher in affluent clusters (80.6%) than in medium (76.8%) and poor areas (75.1%). Intraocular lens implantation rates were significantly lower in participants from poorer households. 10.2% of adults living in affluent clusters presented to the examination station wearing spectacles, compared with 6.7% in medium clusters and 4.4% in poor cluster areas. Spectacle coverage in affluent areas was more than double that in poor clusters (23.5% v 11.1%, P<0.001).Conclusion Blindness is associated with poverty in Pakistan; lower access to eye care services was one contributory factor. To reduce blindness, strategies targeting poor people will be needed. These interventions may have an impact on deprivation in Pakistan.     

Drought and economic differentiation among Ariaal pastoralists of Kenya

This paper examines the effects of the 1984 drought upon household wealth differences in a community of Ariaal pastoralists of northern Kenya. The database consists of 1985 post-drought livestock counts and informants' statements of species-specific drought loss, compared to 1976 livestock counts on the same 38 households. The analysis confirms the hypothesis that the drought resulted in increased household wealth inequalities. It is suggested that the combination of differential herd growth, differential participation in the cash market, and differential loss to the drought has contributed to a polarization within Ariaal of rich and poor, resulting in rural proletarianization and urban migration.     

Economic Impact of Maternal Death on Households in Rural China: A Prospective Cohort Study

Objective

To assess the economic impact of maternal death on rural Chinese households during the year after maternal death.

Methods

A prospective cohort study matched 183 households who had suffered a maternal death to 346 households that experienced childbirth without maternal death in rural areas of three provinces in China. Surveys were conducted at baseline (1–3 months after maternal death or childbirth) and one year after baseline using the quantitative questionnaire. We investigated household income, expenditure, accumulated debts, and self-reported household economic status. Difference-in-Difference (DID), linear regression, and logistic regression analyses were used to compare the economic status between households with and without maternal death.

Findings

The households with maternal death had a higher risk of self-reported “household economy became worse” during the follow-up period (adjusted OR = 6.04, p<0.001). During the follow-up period, at the household level, DID estimator of income and expenditure showed that households with maternal death had a significant relative reduction of US$ 869 and US$ 650, compared to those households that experienced childbirth with no adverse event (p<0.001). Converted to proportions of change, an average of 32.0% reduction of annual income and 24.9% reduction of annual expenditure were observed in households with a maternal death. The mean increase of accumulated debts in households with a maternal death was 3.2 times as high as that in households without maternal death (p = 0.024). Expenditure pattern of households with maternal death changed, with lower consumption on food (p = 0.037), clothes and commodity (p = 0.003), traffic and communication (p = 0.022) and higher consumption on cigarette or alcohol (p = 0.014).

Conclusion

Compared with childbirth, maternal death had adverse impact on household economy, including higher risk of self-reported “household economy became worse”, decreased income and expenditure, increased debts and changed expenditure pattern.     

Nutritional Consequences of Wealth Differentials in East African Pastoralists: The Case of the Datoga of Northern Tanzania

Among African pastoralists evidence that wealth is associated with other measures of household success is scant and the significance of wealth differentials for family welfare remains poorly understood. Predictions that wealth in livestock is associated with increased adequacy of household food supply and with improved child nutrition are tested with longitudinal data on herd size, household composition, food supply, and anthropometric status collected in 1992 for a sample of traditional Datoga households (n = 20) living in the Eyasi basin in northern Tanzania. Although a majority subsisted below poverty cutoffs estimated for east African pastoral populations, there was large variation among households in measures of wealth and resource availability. Individuals in relatively wealthy households did not appear to benefit either in terms of adequacy of household food supply or in terms of average growth performance of young children. Theoretical and methodological challenges in the study of the relationship between wealth and health in nomadic pastoralists are discussed.     

Rain forest ‘conservation-through-use’? Chambira palm fibre extraction and handicraft production in a land-constrained community, Peruvian Amazon

Does the use of non-timber forest products (NTFPs) lead to species conservation and protection of the tropical rain forest? This paper examines the use and fate of the chambira palm (Astrocaryum chambira) – a prime candidate for ‘conservation-through-use’– around a traditional peasant community in northeastern Peru where land scarcity has forced households to draw increasingly on NTFPs to supplement their incomes, including palm fibre for the production of handicrafts. Using household survey data (n = 36), we identify the specific factors that influence handicraft production, household use and economic reliance on palm fibre-based handicrafts, and the planting (semi-domestification) of the chambira palm. Our findings question the promise of rain forest ‘conservation-through-use’ and indicate the scope of challenges for species conservation, particularly among the rural poor.     

Is Poverty Driving Borana Herders in Southern Ethiopia to Crop Cultivation?

This study addresses whether or not crop cultivation by Borana herders in southern Ethiopia is motivated by poverty since 80% of the households belong to poor wealth classes (i.e., poor, very poor and destitute). Yet our findings showed little evidence that Borana communities have become self-sufficient in grain production. Compared to wealthy households, poor households generally cultivated the least land and sampled households, producing yields only 31% of the Ethiopian national average. Grain per capita met only 26% of the annual requirement per person, equivalent to three to four months of self-sufficiency per household. The livelihood response model (LRM) developed for testing the relationship between extent of croplands and household wealth showed that poverty alone cannot be motivating herders to cultivate crops. Factors such as shortage of labor, lack of sufficient traction animals, and unreliable rainfall also need to be considered. Crop cultivation has not enabled self-sufficiency, but it has resulted in fragmented grazing lands. Future policies address changes in land use, including improving soil fertility through manure-nutrient transfers, by promoting better integration of crop cultivation and pastoralism. Research is needed to (a) understand household time allocation between crop cultivation and livestock management, (b) improve the LRM by considering temporal variability in the wealth of households and extent of cultivated lands, and (c) understand the role of poverty in motivating the adoption of alternative livelihood coping strategies.     

Environmental Contamination as a Risk Factor for Intra-Household Staphylococcus aureus Transmission

Background

The household is a recognized community reservoir for Staphylococcus aureus. This study investigated potential risk factors for intra-household S. aureus transmission, including the contribution of environmental contamination.

Methods

We investigated intra-household S. aureus transmission using a sample of multiple member households from a community-based case-control study examining risk factors for CA-MRSA infection conducted in Northern Manhattan. During a home visit, index subjects completed a questionnaire. All consenting household members were swabbed, as were standardized environmental household items. Swabs were cultured for S. aureus. Positive isolates underwent further molecular characterization. Intra-household transmission was defined as having identical strains among two or more household members. Multiple logistic regression was used to identify independent risk factors for transmission.

Results

We enrolled 291 households: 146 index cases, 145 index controls and 687 of their household contacts. The majority of indexes were Hispanic (85%), low income (74%), and female (67%), with a mean age of 31 (range 1–79). The average size of case and control households was 4 people. S. aureus colonized individuals in 62% of households and contaminated the environment in 54% of households. USA300 was the predominant clinical infection, colonizing and environmental strain. Eighty-one households had evidence of intra-household transmission: 55 (38%) case and 26 (18%) control households (P<.01). Environmental contamination with a colonizing or clinical infection strain (aOR: 5.4 [2.9–10.3] P<.01) and the presence of a child under 5 (aOR: 2.3 [1.2–4.5] P = .02) were independently associated with transmission. In separate multivariable models, environmental contamination was associated with transmission among case (aOR 3.3, p<.01) and control households (aOR 27.2, p<.01).

Conclusions

Environmental contamination with a colonizing or clinical infection strain was significantly and independently associated with transmission in a large community-based sample. Environmental contamination should be considered when treating S. aureus infections, particularly among households with multiple infected members.     

Geospatial analysis of the associations between environmental contamination with livestock feces and children with chronic fascioliasis in the Anta province of Cusco,Peru

Fasciola hepatica is a neglected parasitic infection with significant human health and livestock industry impact. The Andean Altiplano harbors an estimated 50% of the Fasciola’s world infection burden. There is scarce data regarding the spatial associations between different Fasciola hosts. In this project, we aimed to determine the geospatial relationships between Fasciola eggs passed in feces of different livestock species and the risk of infection among each household as a unit. We used data from a cross-sectional study evaluating children and livestock feces for Fasciola infection around households in three districts of Anta province, in the Cusco region of Peru. Each sample was geographically tagged and evaluated for fascioliasis using microscopy methods. A total of 2070 households were included, the median age was 9.1 years (6.7–11.8), 49.5% were female, and 7.2% of the households had at least one infected child. A total of 2420 livestock feces samples were evaluated. The infection rate in livestock samples was 30.9%. The highest infection rate was found in sheep with 40.8%, followed by cattle (33.8%), and swine (26.4%). The median distance between a household with an infected child to a positive animal sample was 44.6 meters (IQR 14.7–112.8) and the distance between a household with no infected children to a positive animal sample was 62.2 meters (IQR 18.3–158.6) (p = 0.025). The multivariable logistic regression adjusted by presence of poor sanitation, unsafe water consumption, altitude, and presence of multiple infected children per household demonstrated an association between household infection and any cattle feces at a 50 meters radius (Uninfected: OR 1.42 (95%CI 1.07–1.89), p = 0.017. Infected: OR 1.89 (95%CI 1.31–2.73), p = 0.001), positive cattle feces at a 100 meters radius (OR 1.35 (95% CI 1.08–1.69), p = 0.008), and negative cattle feces at a 200 meters radius (OR 1.08 (95% CI 1.01–1.15), p = 0.022). We identified potential hot and cold spots for fascioliasis in the Anta province. An association between environmental contamination with feces from different livestock species and infected children in rural households was found in our study. Local health authorities may apply this strategy to estimate the risk of infection in human populations and apply targeted interventions.     

The Financial Burden of Morbidity in HIV-Infected Adults on Antiretroviral Therapy in C?te d'Ivoire

Background

Large HIV care programs frequently subsidize antiretroviral (ARV) drugs and CD4 tests, but patients must often pay for other health-related drugs and services. We estimated the financial burden of health care for households with HIV-infected adults taking antiretroviral therapy (ART) in Côte d''Ivoire.

Methodology/Principal Findings

We conducted a cross-sectional survey. After obtaining informed consent, we interviewed HIV-infected adults taking ART who had consecutively attended one of 18 HIV care facilities in Abidjan. We collected information on socioeconomic and medical characteristics. The main economic indicators were household capacity-to-pay (overall expenses minus food expenses), and health care expenditures. The primary outcome was the percentage of households confronted with catastrophic health expenditures (health expenditures were defined as catastrophic if they were greater than or equal to 40% of the capacity-to-pay). We recruited 1,190 adults. Median CD4 count was 187/mm³, median time on ART was 14 months, and 72% of subjects were women. Mean household capacity-to-pay was $213.7/month, mean health expenditures were $24.3/month, and 12.3% of households faced catastrophic health expenditures. Of the health expenditures, 75.3% were for the study subject (ARV drugs and CD4 tests, 24.6%; morbidity events diagnosis and treatment, 50.1%; transportation to HIV care centres, 25.3%) and 24.7% were for other household members. When we stratified by most recent CD4 count, morbidity events related expenses were significantly lower when subjects had higher CD4 counts.

Conclusions/Significance

Many households in Côte d''Ivoire face catastrophic health expenditures that are not attributable to ARV drugs or routine follow-up tests. Innovative schemes should be developed to help HIV-infected patients on ART face the cost of morbidity events.     

Herding Strategies of the Datoga Pastoralists of Tanzania: Is Household Labor a Limiting Factor

Datoga herding follows a cyclical pattern depending on the availability of grazing and water. This analysis focuses on two questions: (a) Is the herding strategy followed by individual households limited by the amount of labor available to that household? and (b) does the herding strategy followed by individual households influence the dynamics of cattle herds? The results show that the availability of labor on a household level does not influence either the herding strategies used by individual households, or the dynamics of cattle herds. This suggests that once minimum labor requirements are met, livestock productivity is insensitive to additional labor inputs.     

Reduced risk of malaria parasitemia following household screening and treatment: a cross-sectional and longitudinal cohort study

Background

In regions of declining malaria transmission, new strategies for control are needed to reduce transmission and achieve elimination. Artemisinin-combination therapy (ACT) is active against immature gametocytes and can reduce the risk of transmission. We sought to determine whether household screening and treatment of infected individuals provides protection against infection for household members.

Methodology/Principal Findings

The study was conducted in two areas in Southern Province, Zambia in 2007 and 2008/2009. To determine the impact of proactive case detection, households were randomly selected either to join a longitudinal cohort, in which participants were repeatedly screened throughout the year and those infected treated with artemether-lumefantrine, or a cross-sectional survey, in which participants were visited only once. Cross-sectional surveys were conducted throughout the year. The prevalence of RDT positivity was compared between the longitudinal and cross-sectional households at baseline and during follow-up using multilevel logistic regression. In the 2007 study area, 174 and 156 participants enrolled in the cross-sectional and longitudinal groups, respectively. In the 2008/2009 study area, 917 and 234 participants enrolled in the cross-sectional and longitudinal groups, respectively. In both study areas, participants and households in the longitudinal and cross-sectional groups were similar on demographic characteristics and prevalence of RDT positivity at baseline (2007: OR = 0.97; 95% CI:0.46, 2.03 | 2008/2009: OR = 1.28; 95% CI:0.44, 3.79). After baseline, the prevalence of RDT positivity was significantly lower in longitudinal compared to cross-sectional households in both study areas (2007: OR = 0.44; 95% CI:0.20, 0.96 | 2008/2009: OR = 0.16; 95% CI:0.05, 0.55).

Conclusions/Significance

Proactive case detection, consisting of screening household members with an RDT and treating those positive with ACT, can reduce transmission and provide indirect protection to household members. A targeted test and treat strategy could contribute to the elimination of malaria in regions of low transmission.     

Two-phase importance sampling for inference about transmission trees

There has been growing interest in the statistics community to develop methods for inferring transmission pathways of infectious pathogens from molecular sequence data. For many datasets, the computational challenge lies in the huge dimension of the missing data. Here, we introduce an importance sampling scheme in which the transmission trees and phylogenies of pathogens are both sampled from reasonable importance distributions, alleviating the inference. Using this approach, arbitrary models of transmission could be considered, contrary to many earlier proposed methods. We illustrate the scheme by analysing transmissions of Streptococcus pneumoniae from household to household within a refugee camp, using data in which only a fraction of hosts is observed, but which is still rich enough to unravel the within-household transmission dynamics and pairs of households between whom transmission is plausible. We observe that while probability of direct transmission is low even for the most prominent cases of transmission, still those pairs of households are geographically much closer to each other than expected under random proximity.     

Prevalence and Correlates of Food Insecurity among Palestinian Refugees in Lebanon: Data from a Household Survey

Lebanon hosts the highest per capita refugee concentration worldwide. The Palestinian presence in Lebanon dates from 1948 and they remain a marginalized population. No information on their food security status has been reported previously. A survey of a representative sample of Palestinian refugee households in Lebanon (n = 2501) was conducted using a stratified two stage cluster sampling approach. We measured food insecurity using a modified USDA household food security module, locally validated. We collected data on household demographic, socioeconomic, health, housing, coping strategies and household intake of food groups and analysed these by food security status. About 41% (CI: 39-43) of households reported being food insecure and 20% (CI: 18-22) severely food insecure. Poor households were more likely to be severely food insecure (OR 1.41 (1.06-1.86)) while higher education of the head of household was significantly associated with protection against severe food insecurity (OR 0.66 (0.52-0.84)). Additionally, higher food expenditure and possession of food-related assets were significantly associated with food security (OR 0.93 (0.89-0.97) and OR 0.74 (0.59-0.92), respectively). After adjusting for confounders, households where at least one member suffered from an acute illness remained significantly more likely to be severely food insecure (OR 1.31(1.02-1.66)), as were households whose proxy respondent reported poor mental health (OR 2.64 (2.07-3.38)) and poor self-reported health (OR 1.62 (1.22-2.13). Severely food insecure households were more likely to eat cheaper foods when compared to non-severely food insecure households (p<0.001) and were more likely to rely on gifts (p<0.001) or welfare (p<0.001). They were also more likely to have exhausted all coping strategies, indicating significantly more frequently that they could not do anything (p = 0.0102). Food insecurity is a significant problem among Palestinian refugees in Lebanon and is likely to be exacerbated at this time when the Syrian crisis amplifies the problem.     

Effect of anxiety on the function of the cardiorespiratory system

The effects of anxiety on the external respiration system and respiratory sinus arrhythmia (RSA) were studied in healthy subjects in real-life conditions. Changes in external respiration parameters and heart rate variability (HRV) in students going to take their end-of-term exams were assessed relative to a midterm period, and the cardiorespiratory system was monitored in a longitudinal study for 50 days. The function of the cardiorespiratory system was characterized by measuring external respiration parameters and calculating HRV parameters. State anxiety (SA) was assessed using Spielberger’s scale. An increase in SA before an exam was accompanied by a higher breathing rate, a higher tidal volume, and lower HRV indices, especially those related to respiratory sinus arrhythmia (HF and HF _norm). The changes in the parameters depended on the increase in SA. A negative correlation was observed between midterm HF and pre-exam SA. The longitudinal study revealed a distinct negative correlation between respiratory sinus arrhythmia parameters and peak expiratory flow (PEF) and a positive correlation between SA and PEF in the majority of subjects. Changes in cardiorespiratory parameters depended on the changes in SA in the longitudinal study. An increase in SA was accompanied by substantial changes in respiratory sinus arrhythmia (RAS) and external respiration parameters, and their correlation was assumed to indicate that modification of parasympathetic activity plays a leading role in increasing PEF.