Prevalence and risk factors of syphilis infection among female sex workers in Shenzhen, China: an observational study (2009-2012).

OBJECTIVE: To investigate prevalence and risk factors of syphilis infection among female sex workers (FSWs) in Shenzhen, China. METHODS: Observational study among (2009-2012) 1653 FSWs recruited by venue-based sampling using questionnaire-based interviews for socio-demographics, behaviours and syphilis testing results. Logistic regression was used to assess risk factors of syphilis infection. RESULTS: The overall syphilis prevalence was 4.7%, showing a slightly decreasing trend. Factors significantly associated with syphilis infection were inconsistent condom use (OR = 1.87, P = 0.015), illicit drug use (OR = 5.45, P < 0.001) and older age in years (OR = 1.08, P < 0.001). Venues where FSWs were recruited and duration of commercial sex work were not significantly associated with syphilis infection (P > 0.05). CONCLUSIONS: Syphilis is still common among FSWs in Shenzhen, China. Current comprehensive prevention programmes (e.g. condom promotion and peer education) should be continued to maintain and increase safe sexual practices and to reduce illicit drug use among FSWs. Expanding point-of-care syphilis screening programmes may be an important strategy for early diagnosis. We recommend timely and effective treatment programmes to be linked to such screening programmes.

Unhealthy behaviour is contagious: an invitation to exploit models for infectious diseases.

We argue that the spread of unhealthy behaviour shows marked similarities with infectious diseases. It is therefore interesting and challenging to use infectious disease methodologies for studying the spread and control of unhealthy behaviour. This would be a great addition to current methods, because it allows taking into account the dynamics of individual interactions and the social environment at large. In particular, the application of individual-based modelling holds great promise to address some major public health questions.

The impact of mobility on HIV control: a modelling study.

Mobility is associated with HIV due to more risky sexual behaviour of mobile groups such as travellers and migrants. Limited participation of such groups may reduce the effectiveness of HIV interventions disproportionally. The established STDSIM model, which simulates transmission and control of HIV and STD, was extended to simulate mobility patterns based on data from Tanzania. We explored the impact of non-participation of mobile groups (travellers and recent migrants) on the effectiveness of two interventions: condom promotion and health education aiming at partner reduction. If mobile groups do not participate, the effectiveness of both interventions could be reduced by 40%. The impact of targeting travellers with a combined HIV campaign is close to that of a general population intervention. In conclusion, it is important to account for possible non-participation of migrants and travellers. If non-participation is substantial, impact of interventions can be greatly improved by actively approaching these people.

Under-reporting of HIV infection among cohorts of TB patients in the WHO European Region, 2003-2004.

SETTING: The World Health Organization (WHO) European Region, which includes 52 countries. OBJECTIVE: To assess an epidemiological data collection tool implemented in 2004 for recording human immunodeficiency virus (HIV) status among tuberculosis (TB) patients. DESIGN: Based on WHO estimates, the reported number of TB patients with HIV was compared with the number expected. The analysis included all forms of TB and was restricted to adults, wherever possible. The numbers of TB patients detected from HIV/acquired immune-deficiency syndrome (AIDS) programmes (NAPs) were also assessed. RESULTS: In 2003, 20 (38%) National TB Programmes (NTPs) reported 4602 (35%) HIV-infected TB cases of 13117 expected; in 2004, 23 (44%) NTPs reported 5902 (42%) cases of 13901 expected. In 2003, 47 (90%) NAPs reported 3575 (27%) TB cases as a new AIDS diagnosis, while in 2004, 40 (77%) NAPs reported 3901 (28%) TB cases. Those countries that did report, reported on average 60-65% of expected cases, irrespective of the kind of programme and the year. CONCLUSION: Most NTPs did not report TB cases with HIV infection. Overall, the number of cases reported in countries that reported data from either NTPs or NAPs was significantly lower than expected. Improved surveillance requires concerted efforts from both NTPs and NAPs.

MUSIDH, multiple use of simulated demographic histories, a novel method to reduce computation time in microsimulation models of infectious diseases.

Microsimulation of infectious diseases requires simulation of many life histories of interacting individuals. In particular, relatively rare infections such as leprosy need to be studied in very large populations. Computation time increases disproportionally with the size of the simulated population. We present a novel method, MUSIDH, an acronym for multiple use of simulated demographic histories, to reduce computation time. Demographic history refers to the processes of birth, death and all other demographic events that should be unrelated to the natural course of an infection, thus non-fatal infections. MUSIDH attaches a fixed number of infection histories to each demographic history, and these infection histories interact as if being the infection history of separate individuals. With two examples, mumps and leprosy, we show that the method can give a factor 50 reduction in computation time at the cost of a small loss in precision. The largest reductions are obtained for rare infections with complex demographic histories.

Comparison of the Kato-Katz technique, hatching test and indirect hemagglutination assay (IHA) for the diagnosis of Schistosoma japonicum infection in China.

The Kato-Katz technique (duplicate 41.7 mg fecal smears), hatching test and indirect hemagglutination assay (IHA) were compared for their ability to detect human Schistosoma japonicum infection in two endemic villages (Zhonjiang and Zhuxi) in rural China. The hatching test (using a nylon bag, and based on about 30 g of feces) and IHA are conventional Chinese diagnostic methods. In both villages, the trends of prevalences with age and sex were comparable for the different methods. In Zhuxi, Kato-Katz examinations of stools from 7 different days and hatching were available, which could be used as a reliable gold standard. This resulted for IHA in a sensitivity of 80% and a specificity of 48%. The sensitivity of the Kato-Katz technique using one stool specimen was 68%, twice that of hatching (33%). In Zhonjiang, however, hatching resulted in more positive cases than Kato-Katz (prevalence 31% vs. 24%). Apparently, the result of the hatching test depends on environmental factors such as temperature and water quality. Although imperfect, Kato-Katz is recommended out of the three evaluated techniques as the method of choice for large-scale screening of S. japonicum. Hatching is much more tedious, provides inconsistent and only qualitative results, and is not much more sensitive than Kato-Katz. Its poor specificity makes IHA unsuitable for individual screening, but it may be more effective for community diagnosis.

Mathematical modelling of lymphatic filariasis elimination programmes in India: required duration of mass drug administration and post-treatment level of infection indicators.

BACKGROUND: India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation study with the individual-based model LYMFASIM to help clarify this. METHODS: We used a model-variant for Indian settings. We considered different hypotheses on detectability of antigenaemia (Ag) in relation to underlying adult worm burden, choosing the most likely hypothesis by comparing the model predicted association between community-level microfilaraemia (Mf) and antigenaemia (Ag) prevalence levels to observed data (collated from literature). Next, we estimated how long MDA must be continued in order to achieve elimination in different transmission settings and what Mf and Ag prevalence may still remain 1 year after the last required MDA round. The robustness of key-outcomes was assessed in a sensitivity analysis. RESULTS: Our model matched observed data qualitatively well when we assumed an Ag detection rate of 50 % for single worm infections, which increases with the number of adult worms (modelled by relating detection to the presence of female worms). The required duration of annual MDA increased with higher baseline endemicity and lower coverage (varying between 2 and 12 rounds), while the remaining residual infection 1 year after the last required treatment declined with transmission intensity. For low and high transmission settings, the median residual infection levels were 1.0 % and 0.4 % (Mf prevalence in the 5+ population), and 3.5 % and 2.0 % (Ag prevalence in 6-7 year-old children). CONCLUSION: To achieve elimination in high transmission settings, MDA must be continued longer and infection levels must be reduced to lower levels than in low-endemic communities. Although our simulations were for Indian settings, qualitatively similar patterns are also expected in other areas. This should be taken into account in decision algorithms to define whether MDA can be interrupted. Transmission assessment surveys should ideally be targeted to communities with the highest pre-control transmission levels, to minimize the risk of programme failure.

River Blindness: Mathematical Models for Control and Elimination.

Human onchocerciasis (river blindness) is one of the few neglected tropical diseases (NTDs) whose control strategies have been informed by mathematical modelling. With the change in focus from elimination of the disease burden to elimination of Onchocerca volvulus, much remains to be done to refine, calibrate and validate existing models. Under the impetus of the NTD Modelling Consortium, the teams that developed EPIONCHO and ONCHOSIM have joined forces to compare and improve these frameworks to better assist ongoing elimination efforts. We review their current versions and describe how they are being used to address two key questions: (1) where can onchocerciasis be eliminated with current intervention strategies by 2020/2025? and (2) what alternative/complementary strategies could help to accelerate elimination where (1) cannot be achieved? The control and elimination of onchocerciasis from the African continent is at a crucial crossroad. The African Programme for Onchocerciasis Control closed at the end of 2015, and although a new platform for support and integration of NTD control has been launched, the disease will have to compete with a myriad of other national health priorities at a pivotal time in the road to elimination. However, never before had onchocerciasis control a better arsenal of intervention strategies as well as diagnostics. It is, therefore, timely to present two models of different geneses and modelling traditions as they come together to produce robust decision-support tools. We start by describing the structural and parametric assumptions of EPIONCHO and ONCHOSIM; we continue by summarizing the modelling of current treatment strategies with annual (or biannual) mass ivermectin distribution and introduce a number of alternative strategies, including other microfilaricidal therapies (such as moxidectin), macrofilaricidal (anti-wolbachial) treatments, focal vector control and the possibility of an onchocerciasis vaccine. We conclude by discussing challenges, opportunities and future directions.

Intraspecimen fecal egg count variation in Schistosoma mansoni infection.

To determine the degree of intraspecimen fecal egg count variation in Schistosoma mansoni infection and its impact on commonly used parasitologic parameters obtained by single egg counts, 10 25-mg Kato-Katz slides were prepared from each of three stool specimens collected on different days in a study group of 20 infected people. Individual fecal egg counts in these series of examinations varied considerably and this had profound consequences for the reliability of both qualitative and quantitative diagnosis. In light infections, S. mansoni eggs in stools appeared to be homogeneously mixed. However, this distribution became heterogeneous as the intensity of infection increased, indicating clustering of eggs in stool. The cumulative egg counts in the 10 slides of the same 20 people examined in this study were compared with those in 14 slides prepared from seven stool samples collected on different days. This revealed significantly different mean egg counts for six people, even after such exhaustive series of examinations. Intraspecimen variation also biased considerably some operational parameters used to determine the infection status at the group level, particularly when these were determined by the examination of single 25-mg slides. The examination of duplicate or multiple slides improved the intraspecimen estimates of these parameters but did not overcome day-to-day variation. The examination of fewer samples taken on different days proved to be more adequate than examining more slides from one stool specimen for the determination of precise estimates of the real infection status.

The microsimulation approach to epidemiologic modeling of helminthic infections, with special reference to schistosomiasis.

The microsimulation technique has been used since 1985 as a tool for epidemiologic modeling of helminthic infections. This technique is characterized by mimicking individual life histories, which makes it possible to include several relevant processes and mechanisms that have not so far been considered in applied modeling. Biological, epidemiologic, and social processes can be simulated in detail, which allows realistic prediction of the impact of control strategies. It is clear that careful quantification and validation of the many processes and parameters in the model requires close collaboration with experts working on control projects. In the development and application of a microsimulation model, we distinguish eight steps, ranging from the identification of questions the model will be designed to address, to the completion of a model that can be used as a routine decision-making tool in a control program.

Variations in fecal Schistosoma japonicum egg counts.

Variations in fecal Schistosoma japonicum egg counts were studied in ZhuXi administrative village, JiangXi Province, China. Population stool examinations were collected with duplicate, standard, 41.5-mg Kato-Katz thick smears on seven consecutive days for 570 individuals from two natural (individual) villages: village I with high endemicity and village II with low endemicity. The proportion of individuals with at least one positive count increased from 42.4% after a single measurement to 68.3% after seven measurements in village I (n = 356), and from 17.0% to 36.0% in village II (n = 214), respectively. This demonstrates a very high variation in repeated S. japonicum egg counts and a considerable lack of sensitivity of the Kato-Katz technique; light and moderate infections are especially missed with a single or a few measurements. The observed day-to-day variation in individual egg counts is highly aggregated (variance higher than the mean) and suggestive of a negative binomial distribution. For five individuals on three days, repeated sampling from different locations of a stool specimen shows a clear trend with egg counts decreasing from the beginning of the stool to the end and from the outside layer to the center. Ten multiple samples from a particular subsection (10-30 g) of a stool specimen for 44 positive individuals still showed aggregation in egg counts, particularly for high intensities of infection. This means that the aggregation in repeated daily S. japonicum egg counts cannot be explained alone by a specific day-to-day component and variation in the concentration of eggs at different locations in the stool. There also exists clustering of eggs within parts of the stool.

SCHISTOSIM: a microsimulation model for the epidemiology and control of schistosomiasis.

A computer simulation model, SCHISTOSIM, has been developed for the epidemiology and control of schistosomiasis, based on the stochastic microsimulation technique. The eventual aim is to evaluate and predict the effects of different control strategies. In the current state of the model, human-, worm-, and infection-related aspects have been included. However, many others, including most transmission and transmission-related mechanisms, have yet to be modeled. By simulating a series of surveys and treatments in Burundi, short-term effects of this program were satisfactorily explained by the model. However, long-term predictions did not match the observed data. Possible extensions of the model to properly describe these effects are identified. The potential of SCHISTOSIM as a tool for the prediction of outcomes of alternative control strategies is illustrated and discussed.

Statistical models for estimating prevalence and incidence of parasitic diseases.

The estimation of prevalence and incidence of parasitic infections is considered. As the detectability of such infections is not 100% and may furthermore depend on their intensity, statistical methods are often required to arrive at meaningful results. It appears to be essential to distinguish between parasites that multiply within the (human) host and those that do not. An overview of some models discussed in the literature is presented. These models can indeed be used in assessing detectability of infection, and they indicate that observations may lead to considerable misinterpretation of 'true' prevalences and incidences.

Validation of parasite transmission models: the example of onchocerciasis.

Most parasites have complex life cycles; and mathematical models can help in targeting interventions and predicting disease-control efforts. For actual applications, quantification and validation of models is a key issue. We illustrate the process of validation by presenting a (re)analysis of fly-feeding experiments carried out by the Onchocerciasis (river blindness) Control Programme (OCP/WHO) in West Africa, with the objective to validate ONCHOSIM, an onchocerciasis transmission model. In these experiments flies were fed on human patients and dissected to count the number of microfilariae they had ingested. To assess microfilarial skin densities, skin snips (biopsies) were taken and examined. Originally, the resulting curve was interpreted as showing saturation and considered the main regulating (density-dependent) mechanism of onchocerciasis transmission in the model. Taking into account measurement errors in the skin microfilarial density of human subjects (on whom the flies were fed) we now conclude that the relationship is essentially linear. This prompts us to requantify ONCHOSIM. Possible alternative density-dependent mechanisms are discussed.

[Hygiene practices and contamination risks of surface waters by schistosome eggs: the case of an infested village in Northern Senegal]. / Pratiques hygiéniques et risques de contamination des eaux de surface par des oeufs de schistosomes: le cas d'un village infesté dans le nord du Sénégal.

The transmission of intestinal schistosomiasis presumes that faecal materials containing viable schistosome eggs reach natural water bodies infested with snail intermediate host. So far there is little knowledge about the contamination dynamics of streams with schistosome eggs. We conducted a pilot study on defecating behaviour and hygienic practices in an Schistosoma mansoni endemic focus in Northern Senegal. Questionnaires were used to obtain quantitative data on hygienic practices and the use of latrines in 59 children. Although the community was well endowed with pit latrines, most of the children declared that they usually defecated somewhere else, in particular near the streams where the vegetation offers hideouts. Observations based on mapping of defecation sites showed that a considerable number of stools were left just a few meters from the riverbank, thus bearing a high risk of being washed off into the water. All these practices can easily lead to contamination of water bodies with schistosomae eggs. In order to improve hygienic practices and reduce fecal pollution of the environment, a health education model respecting local beliefs and customs would be indispensable.

Concurrence of dermatological and ophthalmological morbidity in onchocerciasis.

Prevalence of skin and eye disorders in African onchocerciasis (river blindness) is well documented. However, less is known about their joint occurrence. Information on concurrence may improve our understanding of disease pathogenesis and is required to estimate the disease burden of onchocerciasis. We analysed data from 765 individuals from forest villages in the Kumba and Ngambe Health districts, Cameroon. These data were collected in 1998, as baseline data for the evaluation of the African Programme for Onchocerciasis Control. Concurrence of symptoms was assessed using logistic regression. Onchocerciasis was highly endemic in the study population (63% nodule prevalence among males aged ≥20). Considerable overall prevalences of onchocercal visual impairment (low vision or blindness: 4%), troublesome itch (15%), reactive skin disease (19%), and skin depigmentation (25%) were observed. The association between onchocercal visual impairment and skin depigmentation (OR 9.0, 95% CI 3.9-20.8) was partly explained by age and exposure to infection (OR 3.0, 95% CI 1.2-7.7). The association between troublesome itch and reactive skin disease was hardly affected by adjustment (adjusted OR 6.9, 95% CI 4.2-11.1). Concluding, there is significant concurrence of morbidities within onchocerciasis. Our results suggest a possible role of host characteristics in the pathogenesis of depigmentation and visual impairment. Further, we propose a method to deal with concurrence when estimating the burden of disease.

A systematic review of economic evaluation studies of tuberculosis control in high-income countries.

Tuberculosis (TB) is a leading cause of death in developing countries and an important health threat in the industrialised world. Ideally, interventions in TB control are effective, acceptable and economically attractive. This review summarises all economic evaluation studies of TB control in high-income countries over the last 20 years. We provide indications on the relative economic attractiveness of TB interventions based on the reported conclusions. A total of 118 studies using different economic evaluation methodologies on a wide range of TB interventions are included. Most studies (70%) were from North America, and about half (47%) concerned interventions among the general population. Even though the large majority of studies (85%) aimed at preventing active TB disease, 44% of these ignored the prevention of secondary infections, thereby under- estimating the benefits of the intervention. Choosing a health care instead of a societal perspective (92% vs. 8%) further underestimated the benefits. Moreover, 74 studies (62%) disregarded discounting, and for 9 of them this led to overestimated future costs. In all, 66% of the studies reported conclusions favouring the evaluated intervention, which is modest given that a publishing bias towards favourable results is to be expected. In conclusion, we demonstrate that many studies in this review have put the evaluated TB intervention at a disadvantage by the choice of methodology, i. e., underestimating benefits and overestimating costs. This may have led to an overly conservative approach to the introduction of new interventions in TB control.

The impact of contact structure on infectious disease control: influenza and antiviral agents.

Planning adequate public health responses against emerging infectious diseases requires predictive tools to evaluate the impact of candidate intervention strategies. With current interest in pandemic influenza very high, modelling approaches have suggested antiviral treatment combined with targeted prophylaxis as an effective first-line intervention against an emerging influenza pandemic. To investigate how the effectiveness of such interventions depends on contact structure, we simulate the effects in networks with variable degree distributions. The infection attack rate can increase if the number of contacts per person is heterogeneous, implying the existence of high-degree individuals who are potential super-spreaders. The effectiveness of a socially targeted intervention suffers from heterogeneous contact patterns and depends on whether infection is predominantly transmitted to close or casual contacts. Our findings imply that the various contact networks' degree distributions as well as the allocation of contagiousness between close and casual contacts should be examined to identify appropriate strategies of disease control measures.

Evaluation of the standard membrane feeding assay (SMFA) for the determination of malaria transmission-reducing activity using empirical data.

Host responses to the transmittable stages of the malaria parasite may reduce transmission effectively. Transmission-reducing activity (TRA) of human serum can be determined as a percentage, using the Standard Membrane Feeding Assay (SMFA). This laboratory assay was evaluated using the results of 121 experiments with malaria-endemic sera among which many repeated measurements were obtained. The assay consists of the feeding of Anopheles stephensi mosquitoes with cultured Plasmodium falciparum gametocytes, mixed with human red blood cells, and control and experimental sera. The TRA of individual sera was determined by the comparison of oocyst densities between these sera. Bootstrap data on oocyst densities in individual mosquitoes in control feeds were used to construct confidence limits for TRA percentages of serum feeds. Low (<20%) and high TRA (>90%) values for individual sera were usually reproduced in a second experiment, whereas this was more difficult for values between 20% and 90%. The observed variability of TRA values is explained in part by the variability in oocyst density per mosquito. Oocyst densities in control feeds varied more between experiments than within experiments and showed a slight decline over the 3 years of experiments. Reproducibility of TRA of field sera was low (20%) between experiments, but much higher (61 %) within experiments. A minimum of 35 oocysts per mosquito in control feeds gave optimal reproducibility (44%) between experiments. We recommend that (1) sera are compared within an experiment, or (2) assays are only analysed where controls have at least 35 oocysts per mosquito. The SMFA is under the recommended conditions appropriate for the study of factors that may influence TRA, e.g. transmission blocking vaccines.