Edward K. Waters

Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research

BackgroundThere is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration (neuroHAART) assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA. The current review aims to better synthesise existing literature by using an innovative two-phase review approach (qualitative and quantitative) to overcome methodological differences between studies.MethodsSixteen studies, all observational, were identified using a standard citation search. They fulfilled the following inclusion criteria: conducted in the HAART era; sample size > 10; treatment effect involved more than one antiretroviral and none had a retrospective design. The qualitative phase of review of these studies consisted of (i) a blind assessment rating studies on features such as sample size, statistical methods and definitions of neuroHAART, and (ii) a non-blind assessment of the sensitivity of the neuropsychological methods to HIV-associated neurocognitive disorder (HAND). During quantitative evaluation we assessed the statistical power of studies, which achieved a high rating in the qualitative analysis. The objective of the power analysis was to determine the studies ability to assess their proposed research aims.ResultsAfter studies with at least three limitations were excluded in the qualitative phase, six studies remained. All six found a positive effect of neuroHAART on neurocognitive function or CSF HIV suppression. Of these six studies, only two had statistical power of at least 80%.ConclusionsStudies assessed as using more rigorous methods found that neuroHAART was effective in improving neurocognitive function and decreasing CSF viral load, but only two of those studies were adequately statistically powered. Because all of these studies were observational, they represent a less compelling evidence base than randomised control trials for assessing treatment effect. Therefore, large randomised trials are needed to determine the robustness of any neuroHAART effect. However, such trials must be longitudinal, include the full spectrum of HAND, ideally carefully control for co-morbidities, and be based on optimal neuropsychology methods.

Unresolved questions concerning human papillomavirus infection and transmission: a modelling perspective

Mathematical transmission models are widely used to forecast the potential impact of interventions such as vaccination and to inform the development of health policy. Effective vaccines are now available for the prevention of cervical cancer and other diseases attributable to human papillomavirus (HPV). Considerable uncertainties remain regarding the characterisation of HPV infection and its sequelae, infectivity, and both vaccine-conferred and naturally-acquired immunity. In this review, we discuss the key knowledge gaps that impact on our ability to develop accurate models of HPV transmission and vaccination.

Aggregation and competitive exclusion: explaining the coexistence of human Papillomavirus types and the effectiveness of limited vaccine conferred cross-immunity.

Human Papillomavirus (HPV) types are sexually transmitted infections that cause a number of human cancers. According to the competitive exclusion principle in ecology, HPV types that have lower transmission probabilities and shorter durations of infection should be outcompeted by more virulent types. This, however, is not the case, as numerous HPV types co-exist, some which are less transmissible and more easily cleared than others. This paper examines whether this exception to the competitive exclusion principle can be explained by the aggregation of infection with HPV types, which results in patchy spatial distributions of infection, and what implications this has for the effect of vaccination on multiple HPV types. A deterministic transmission model is presented that models the patchy distribution of infected individuals using Lloyd’s mean crowding. It is first shown that higher aggregation can result in a reduced capacity for onward transmission and reduce the required efficacy of vaccination. It is shown that greater patchiness in the distribution of lower prevalence HPV types permits co-existence. This affirms the hypothesis that the aggregation of HPV types provides an explanation for the violation of the competitive exclusion principle. Greater aggregation of lower prevalence types has important implications where type-specific HPV vaccines also offer cross-protection against non-target types. It is demonstrated that the degree of cross-protection can be less than the degree of vaccine protection conferred against directly targeted types and still result in the elimination of non-target types when these non-target types are patchily distributed.

Iwao’s patchiness regression through the origin: biological importance and efficiency of sampling applications

Iwao’s mean crowding-mean density relation can be treated both as a linear function describing the biological characteristics of a species at a population level, or a regression model fitted to empirical data (Iwao’s patchiness regression). In this latter form its parameters are commonly used to construct sampling plans for insect pests, which are characteristically patchily distributed or overdispersed. It is shown in this paper that modifying both the linear function and statistical model to force the intercept or lower functional limit through the origin results in more intuitive biological interpretation of parameters and better sampling economy. Firstly, forcing the function through the origin has the effect of ensuring that zero crowding occurs when zero individuals occupy a patch. Secondly, it ensures that negative values of the intercept, which do not yield an intuitive biological interpretation, will not arise. It is shown analytically that sequential sampling plans based on regression through the origin should be more efficient compared to plans based on conventional regression. For two overdispersed data sets, through-origin based plans collected a significantly lower sample size during validation than plans based on conventional regression, but the improvement in sampling efficiency was not large enough to be of practical benefit. No difference in sample size was observed when through-origin and conventional regression based plans were validated using underdispersed data. A field researcher wishing to adopt a through-origin form of Iwao’s regression for the biological reasons outlined above can therefore be confident that their sampling strategies will not be affected by doing so.

Zoology: Here be dragons

Emerging evidence indicates that dragons can no longer be dismissed as creatures of legend and fantasy, and that anthropogenic effects on the worlds climate may inadvertently be paving the way for the resurgence of these beasts.

Spatial heterogeneity in simple deterministic sir models assessed ecologically

Patchy or divided populations can be important to infectious disease transmission. We first show that Lloyd’s mean crowding index, an index of patchiness from ecology, appears as a term in simple deterministic epidemic models of the SIR type. Using these models, we demonstrate that the rate of movement between patches is crucial for epidemic dynamics. In particular, there is a relationship between epidemic final size and epidemic duration in patchy habitats: controlling inter-patch movement will reduce epidemic duration, but also final size. This suggests that a strategy of quarantining infected areas during the initial phases of a virulent epidemic might reduce epidemic duration, but leave the population vulnerable to future epidemics by inhibiting the development of herd immunity. doi:10.1017/S1446181113000035

Sampling a weighted pest complex: caterpillars in North Korean cabbage (Brassica oleracea var. capitata) crops.

The lepidopteran pests Plutella xylostella L. (Plutellidae) and Pieris rapae L. (Pieridae: Pierini) are responsible for major yield losses of cabbage, Brassica oleracea L. (Brassicaceae), in North Korea. Preliminary integrated pest management (IPM) programmes using economic thresholds (ETs) to schedule insecticide applications have proved promising and have demonstrated marked increases in yield compared to standard farming practice, which relies heavily on synthetic insecticides. To use ETs effectively on a routine basis, farmers need efficient yet sufficiently precise methods of surveying crops for pests. Here we construct and validate binomial sequential sampling plans for the two‐species pest complex and for P. rapae alone. The recommended plans would be practical to implement, demanding maximum sample sizes below 50 plants, and proved very slightly conservative with respect to classifying the population relative to the ET (i.e., they were slightly more likely to suggest control at the ET than not).

Zoonotic Transmission of Waterborne Disease: A Mathematical Model.

Waterborne parasites that infect both humans and animals are common causes of diarrhoeal illness, but the relative importance of transmission between humans and animals and vice versa remains poorly understood. Transmission of infection from animals to humans via environmental reservoirs, such as water sources, has attracted attention as a potential source of endemic and epidemic infections, but existing mathematical models of waterborne disease transmission have limitations for studying this phenomenon, as they only consider contamination of environmental reservoirs by humans. This paper develops a mathematical model that represents the transmission of waterborne parasites within and between both animal and human populations. It also improves upon existing models by including animal contamination of water sources explicitly. Linear stability analysis and simulation results, using realistic parameter values to describe Giardia transmission in rural Australia, show that endemic infection of an animal host with zoonotic protozoa can result in endemic infection in human hosts, even in the absence of person-to-person transmission. These results imply that zoonotic transmission via environmental reservoirs is important.

Losing hope: Mental health and religious service non-attendance in Australia

Religious beliefs and practices are related to mental health. Many individuals report a religious affiliation, but do not have specific religious beliefs or practices such as attending religious services. These non-attendees are often assumed to resemble the non-religious, but are poorly studied. This study explored the demographic characteristics and mental health outcomes associated with being a non-attendee using data from a nationally representative Australian sample. Non-attendees were more likely to be non-Christian than attendees at religious services. They had worse mental health than both non-religious individuals and attendees, especially compared to the non-religious. Whether non-attendance is a result of or cause of poor mental health outcomes is not clear and deserves further investigation. Non-attendees clearly differed in our sample from both non-religious individuals and attendees. Our results do not support the hypothesis that individuals who report a religious affiliation, but are not actively religious, are similar to non-religious individuals.

Cocoa Pod Borer (Conopomorpha cramerella Snellen) in Papua New Guinea: Biosecurity Models for New Ireland and the Autonomous Region of Bougainville

Cocoa Pod Borer (Conopomorpha cramerella Snellen) (CPB) is an important pest of cocoa. Following its emergence as a pest in East New Britain, Papua New Guinea, in 2006, it was considered relevant to assess its potential spread to other cocoa growing regions. Its likelihood of introduction to the islands of Bougainville and New Ireland from East New Britain Province, Papua New Guinea, was modeled using Monte Carlo simulation. This dispersal model was based around different scenarios, identifying trends rather than explicitly attempting to encapsulate true values. The model suggested that CPB is far more likely to establish on New Ireland than on Bougainville. More important, incertitude resulting from incomplete knowledge of the amount and frequency of cocoa transported between islands had a significant effect on model outputs. Quarantine and agriculture officials will be able to refine these parameter values, and then use the relevant scenarios from those presented here as a guide to develop quarantine procedures. In addition, a contingency model was employed to estimate the optimal sampling effort to use following an incursion of CPB into Bougainville or New Ireland and the seemingly successful implementation of an initial eradication program. The model suggests that at a 1% infestation level, sampling should continue for 2.5-2.7 years (90% CI) after claiming eradication, and this estimate changed little for higher infestation levels. Through modeling variations in sampling intensity, the model also suggested that determining the full spread of CPB is more important than increased sampling within one region.