Active transmission of human chagas disease in Colima Mexico

Despite efforts to eradicate American trypanosomiasis (AT) and Chagas disease from the Americas, there are still areas of active transmission that can eventually become a source of reinfection in previously controlled regions. Mexico could be one of those areas, where there are no formal preventive control programs despite the presence of communities infested by Triatominae bugs infected with Trypanosoma cruzi. This study explored the prevalence of T. cruzi infection in 405 habitants of 17 communities in the state of Colima, on the Pacific Mexican coast, through a seroepidemiological probabilistic survey. The results revealed a point seroprevalence of 2.4% positive for anti-T. cruzi. In addition, 2 clinical cases of chronic and 2 of acute Chagas disease were detected in the explored communities. These findings confirm the risk of active transmission of AT in Western Mexico, especially in rural and suburban communities infested with intra-domestic triatominae, where control programs should be implemented.     

Transmission control for schistosomiasis - why it matters now

Current population-based schistosomiasis treatment programs are a first step to reducing the global burden of Schistosoma-related disease; however, they might not dramatically reduce parasite transmission in highly endemic areas. Consequently, the benefits of these programs remain in doubt because recurring low-level reinfection is likely to be associated with subtle but persistent morbidities such as anemia, undernutrition and diminished performance status. The real health benefits of transmission control need to be reconsidered and attention given to more aggressive and, ultimately, more affordable parasite elimination strategies. The next generation of schistosomiasis control can be optimized using new monitoring tools and effective transmission containment.     

Drug resistance in tuberculosis--a reinfection model

There is increasing recognition that reinfection is an important component of TB transmission. Moreover, it has been shown that partial immunity has significant epidemiological consequences, particularly in what concerns disease prevalence and effectiveness of control measures. We address the problem of drug resistance as a competition between two types of strains of Mycobacterium tuberculosis: those that are sensitive to anti-tuberculosis drugs and those that are resistant. Our objective is to characterise the role of reinfection in the transmission of drug-resistant tuberculosis. The long-term behaviour of our model reflects how reinfection modifies the conditions for coexistence of sensitive and resistant strains. This sets the scene for discussing how strain prevalence is affected by different control strategies. It is shown that intervention effectiveness is highly sensitive to the baseline epidemiological setting.     

Endemicity, focality and seasonality of transmission of human schistosomiasis in Amagunze Village, eastern Nigeria

The pattern of transmission of human schistosomiasis was studied in Amagunze Village, eastern Nigeria, during 1986-1987. The prevalence of Schistosoma haematobium in 119 schoolboys aged 5-12 years was 79%. The geometric mean of intensity of infection was 49 eggs/10 ml urine and the frequency of visible haematuria was 25.2%. No S. mansoni infections were demonstrated. A marked seasonality in population density of Bulinus truncatus, B. forskalii and Biomphalaria pfeifferi was demonstrated with reduced densities during the late rainy and early dry seasons. Schistosoma sp. infected B. truncatus were found in the late dry and early rainy seasons in 2 out of 7 major human water contact sites studied. Seasonality and focality of transmission of S. haematobium and its high endemicity in the area were thus demonstrated.     

Ultrasound monitoring of structural urinary tract disease in Schistosoma haematobium infection

A major advance in our understanding of the natural history of Schistosoma haematobium-related morbidity has come through the introduction of the portable ultrasound machines for non-invasive examination of the kidneys and bladder. With the use of generators or battery packs to supply power in non-clinical field settings, and with the use of instant photography or miniaturized thermal printers to record permanent images, it is possible to examine scores of individuals in endemic communities every day. Broad-based ultrasound screening has allowed better definition of age-specific disease risks in urinary schistosomiasis. Results indicate that urinary tract abnormalities are common (18% overall prevalence) in S. haematobium transmission areas, with a 2-4% risk of either severe bladder abnormality or advanced ureteral obstruction. In longitudinal surveys, ultrasound studies have shown that praziquantel and metrifonate therapy are rapidly effective in reversing urinary tract abnormalities among children. The benefits of treating adults are less well known, but research in progress should help to define this issue. Similarly, the prognosis of specific ultrasound findings needs to be clarified, and the ease of sonographic examination will make such long-term follow-up studies feasible. In summary, the painless, quick, and reproducible ultrasound examination has become an essential tool in the study of urinary schistosomiasis.     

Schistosoma haematobium (Egyptian strain): rate of development and effect of praziquantel treatment

This study investigates the development of the Egyptian strain of Schistosoma haematobium and the resultant immunohistopathology and biochemical changes in organs affected. In addition, the response of different developmental stages of S. haematobium worms to praziquantel (PZQ) was examined. Schistosoma haematobium-infected hamsters were classified into 4 groups and were treated at day 35, 55, 75, and 95 postinfection (PI), respectively. Each group was subdivided into 3 subgroups. Two of them were treated orally with PZQ (300 mg/kg or 500 mg/kg divided equally on 2 consecutive days), and the third group was left without treatment. Treated groups were killed 20 days posttreatment. Infection with S. haematobium became patent 73 days PI; tissue egg load and worm fecundity were higher at 95 days and maximal 115 days PI, with an oogram pattern comparable to that in Schistosoma mansoni infection. In the liver, small cellular granulomas were observed 75 days PI, with preponderance of CD4+ T-cell phenotypes. In the urinary bladder, only submucosal focal Brunn's-nest formation and angiogenesis without typical granulomas were observed. Ninety-five and 115 days PI, confluent granulomata with multiple eggs in the center were observed in the liver and urinary bladder, with a preponderance of CD8+ positive T cells in the liver and hyperplasia of the urinary bladder epithelium with cystitis cystica and papillae formation. One hundred percent worm eradication was recorded with the higher dose of PZQ in animals treated 75 and 95 days PI. In conclusion, in spite of the long prepatent period of the Egyptian strain of S. haematobium, sensitivity to PZQ was recorded soon after infection. Granulomata were similar to those of S. mansoni in the livers and urinary bladders, but they were confluent with multiple eggs in the centers, hyperplasia of the urinary bladder urothelium with cystitis cystica, papillae, and Brunn's-nest formation predictive of malignant changes with no hepatocyte dysplasia.     

Schistosoma haematobium infections in preschool children from two rural communities in Ijebu East, south-western Nigeria

There is an urgent need for information on schistosomiasis in preschool children, who are often excluded in mass treatment programmes. The prevalence and intensity of Schistosoma haematobium infection were determined in preschool children aged ≤ 6 years in two rural communities in Ijebu East, south-western Nigeria. Two urine samples each were collected from 83 preschool children from the two communities, tested for microhaematuria using reagent strips and then processed and examined with a microscope for S. haematobium eggs. Focus group discussions on perceptions of the disease and water contact practices were held in the communities with their guardians, caregivers and preschool children, using an interview guide. The prevalence of S. haematobium in the two communities was 14 (16.9%), with no significant differences (P = 0.661) in infection rate between boys (18.4%) and girls (14.7%). Both prevalence and intensity of infection did not increase significantly with age in both Korede and Obada community. However, there were significant differences in prevalence of infection between the two communities (P = 0.035). There was no association (P = 0.750) between intensity in boys (0.176 eggs/10 ml urine) and girls (0.110 eggs/10 ml urine). Focal group discussions with guardians and caregivers revealed that preschool children acquired infection early in their lives through exposure to infected stream water by their mothers, while the older children visit the stream for playing, bathing and swimming. It has therefore become imperative for preschool children to be included in the planning of schistosomiasis intervention programmes as a means of reducing transmission.     

Scanning electron microscope studies of miracidia suggest introgressive hybridization between Schistosoma haematobium and S. haematobium x S. mattheei in the Eastern Transvaal

Schistosoma haematobium miracidia were collected from a locality with a high prevalence of human infection with the animal parasite, S. mattheei, which hybridizes with S. haematobium, and from 2 localities with negligible infection rates. The terebratoria of the miracidia from these localities were compared with each other, with laboratory maintained S. haematobium and with four populations of S. mattheei by means of scanning electron microscopy. It was found that the terebratorial membrane of certain of the S. haematobium miracidia from the locality with a high S. mattheei prevalence in humans, resembled the more intricate membrane of S. mattheei. This suggests introgressive hybridization between S. haematobium and S. haematobium x S. mattheei.     

Effect of praziquantel on the immature stages of Schistosoma haematobium

Schistosoma mansoni is known to be refractory to praziquantel treatment in the pre-patent period of infection. Since Schistosoma haematobium has a much longer pre-patent period (10-12 weeks vs. 5-6 for the former species), we asked the question whether a correspondingly longer period of insusceptibility exists in urinary schistosomiasis. In hamsters treated at different times after infection, S. haematobium was partially refractory to praziquantel when treatment was given at week 5, but showed practically full sensitivity at 7-8 weeks and later times. Schistosoma haematobium worms obtained at different times after infection and exposed in vitro to praziquantel were refractory to low drug concentrations between 4 and 6 weeks, but were clearly affected at higher concentrations and at later time points. We conclude that S. haematobium does not have a praziquantel-insensitive window longer than in S. manson, in spite of its much longer maturation period. In addition, refractoriness of immature stages can be overcome at higher drug concentrations.     

The challenge of effective surveillance in moving from low transmission to elimination of schistosomiasis in China

Until recently, intensified efforts in China to suppress the transmission of Schistosoma japonicum relied principally on routine praziquantel treatment, extensive use of molluscicides and health education programs. These efforts, now supplemented by a broader range of control measures, have been quite successful in reducing the prevalence and intensity of human infection to very low levels. However, re-emergent transmission has occurred in formerly endemic areas of several provinces, signalling the need for more locally effective, integrated control strategies. We argue that these low but persistent levels of transmission also require important changes in both the tactics and strategy of disease surveillance to move forward towards elimination. Here we present recent data exemplifying the low transmission environment which suggests that we are reaching limits of detection of current diagnostic techniques used for human infection surveillance in these communities. However, both epidemiological data and theoretical results indicate that (i) transmission in the human population can persist at very low infection intensities even in the presence of routine control activities; (ii) the parasite can be reintroduced into parasite-free environments by very modest external inputs; and (iii) transmission at these low infection intensities exhibits very slow inter-year dynamics. These observations motivate the need for new, sensitive tools to identify low-level infections in mammalian or snail hosts, or the presence of S. japonicum in environmental media. Environmental monitoring offers an alternative, and perhaps more efficient, approach to large-scale surveillance of human infections in low transmission regions.     

Reinfection after treatment of schistosome infections

Today, chemotherapy has a central role in the control of schistosome infections. Although the costs involved may be high in relation to local expenditures on health, externally funded mass treatment programmes can lead to large reductions in the prevalence and intensity of schistosome infections. But the benefits of treatment to a community that has been involved in a mass chemotherapy programme, or to an individual patient seen in a health centre, will be limited if reinfection after treatment is rapid and intense. Despite the efficacy of the available drugs few, if any, control programmes based on mass chemotherapy have interrupted transmission and come anywhere near to eradicating schistosome infection.     

Making the health care system 'safe' for persons with HIV infection or AIDS.

If health care reform is implemented in states and nationally, the safety of this process needs to be examined for persons with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS). Reform should assure ongoing prevention and transmission control of HIV and continuous coverage of medical costs for persons ill with HIV or AIDS. These persons currently benefit from various state and federal categoric programs designed to assure access to preventive and personal care services. Washington State has passed health care reform legislation that envisions integrating these programs to provide a system of population-based and personal health care. This legislation was analyzed using existing epidemiologic and entitlement information about persons with HIV infection or AIDS in the state to assess its effect. The relationship between public health and personal care services will be a central concern for those with HIV infection or AIDS, and complete coverage of this group may be achieved relatively late in the process of implementing health care reform. Health personnel planning under health care reform will affect the delivery of HIV- and AIDS-related services. Including treatment of AIDS in the basic benefit package merits particular attention. These issues parallel those being faced by the nation as a whole as it seeks to ensure epidemic disease control and compassionate care for long-term disabling illness if health care reform is implemented.     

Implications of partial immunity on the prospects for tuberculosis control by post-exposure interventions

One-third of the world population (approximately 2 billion individuals) is currently infected with Mycobacterium tuberculosis, the vast majority harboring a latent infection. As the risk of reactivation is around 10% in a lifetime, it follows that 200 million of these will eventually develop active pulmonary disease. Only therapeutic or post-exposure interventions can tame this vast reservoir of infection. Treatment of latent infections can reduce the risk of reactivation, and there is accumulating evidence that combination with post-exposure vaccines can reduce the risk of reinfection. Here we develop mathematical models to explore the potential of these post-exposure interventions to control tuberculosis on a global scale. Intensive programs targeting recent infections appear generally effective, but the benefit is potentially greater in intermediate prevalence scenarios. Extending these strategies to longer-term persistent infections appears more beneficial where prevalence is low. Finally, we consider that susceptibility to reinfection is altered by therapy, and explore its epidemiological consequences. When we assume that therapy reduces susceptibility to subsequent reinfection, catastrophic dynamics are observed. Thus, a bipolar outcome is obtained, where either small or large reductions in prevalence levels result, depending on the rate of detection and treatment of latent infections. By contrast, increased susceptibility after therapy may induce an increase in disease prevalence and does not lead to catastrophic dynamics. These potential outcomes are silent unless a widespread intervention is implemented.     

What is the impact of acquired immunity on the transmission of schistosomiasis and the efficacy of current and planned mass drug administration programmes?

Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5–14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R₀) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA programmes.     

Mycobacterial ecology as a modulator of tuberculosis vaccine success

Natural infection with Mycobacterium tuberculosis, as well as cross-immune reactions with the constituent of standard vaccines, attenuated M. bovis, and other species of mycobacteria confer partial immunity to subsequent M. tuberculosis infection. It has been shown in the past that the immune response to mycobacteria found naturally in the environment reduces the benefit of vaccination as assessed by means of vaccine efficacy. In this paper we show that efficacy is a poor measure of the potential success of new anti-tuberculous vaccines due to its inability to account for the relative weight of reinfection in disease dynamics. We advocate instead the use of vaccine effectiveness when evaluating the impact of new control methods against infections that confer partial immunity. Through the study of a simple model that incorporates cross-reactive responses to environmental mycobacteria (EM) and reinfection, we show how the particulars of the relation between EM abundance and vaccine effectiveness depend on the degree of protection conferred respectively by natural infection, vaccination and EM. The relative importance of reinfection as a transmission mechanism comes up as the most important source of variability in vaccine effectiveness. Our results suggest that control efforts should be placed in reducing the importance of reinfection through diminishing transmission rates. Vaccines that overcome preexisting immunity to other mycobacteria will still have varying degrees of success depending on the underlying rate of TB transmission.     

Estimating Plasmodium falciparum Transmission Rates in Low-Endemic Settings Using a Combination of Community Prevalence and Health Facility Data

As some malaria control programs shift focus from disease control to transmission reduction, there is a need for transmission data to monitor progress. At lower levels of transmission, it becomes increasingly more difficult to measure precisely, for example through entomological studies. Many programs conduct regular cross sectional parasite prevalence surveys, and have access to malaria treatment data routinely collected by ministries of health, often in health management information systems. However, by themselves, these data are poor measures of transmission. In this paper, we propose an approach for combining annual parasite incidence and treatment data with cross-sectional parasite prevalence and treatment seeking survey data to estimate the incidence of new infections in the human population, also known as the force of infection. The approach is based on extension of a reversible catalytic model. The accuracy of the estimates from this model appears to be highly dependent on levels of detectability and treatment in the community, indicating the importance of information on private sector treatment seeking and access to effective and appropriate treatment.     

The prevalence, intensity and clinical signs of urinary schistosomiasis in Imo state, Nigeria

Urine samples were assayed for urinary schistosomiasis in four local government areas (LGA) of Imo State, Nigeria between May 1998 and September 2000. A total of 3504 persons were sampled, with 880 (25.1%) being positive for urinary schistosomiasis, based on records of eggs of Schistosoma haematobium. The prevalence of S. haematobium infection differed in the various LGAs, with Oguta (38.9%) and Owerri-West (10.4%) showing the highest and the lowest values, respectively. Prevalence was higher in males (67.4%) than in females (32.6%) and in subjects 11-20 years of age (31.5%), while prevalence varied among different occupational groups, with farmers ranking the highest (41.6%). Visible haematuria was the predominant symptom (P<0.05). Of 880 persons positive for eggs of S. haematobium, 452 (51.4%) had visible haematuria, followed by suprapubic pains 214 (24.3%) and painful micturition 97 (11.0%). Although 367 (10. 5%) of the sampled subjects with eggs of S. haematobium showed no visible haematuria, 513 (14.6%) clearly demonstrated haematuria.     

The reinfection threshold promotes variability in tuberculosis epidemiology and vaccine efficacy

Population patterns of infection are determined largely by susceptibility to infection. Infection and vaccination induce an immune response that, typically, reduces susceptibility to subsequent infections. With a general epidemic model, we detect a 'reinfection threshold', above which reinfection is the principal type of transmission and, consequently, infection levels are much higher and vaccination fails. The model is further developed to address human tuberculosis (TB) and the impact of vaccination. The bacille Calmette-Guérin (BCG) is the only vaccine in current use against TB, and there is no consensus about its usefulness. Estimates of protection range from 0 to 80%, and this variability is aggravated by an association between low vaccine efficacy and high prevalence of the disease. We propose an explanation based on three postulates: (i) the potential for transmission varies between populations, owing to differences in socio-economic and environmental factors; (ii) exposure to mycobacteria induces an immune response that is partially protective against reinfection; and (iii) this protection is not significantly improved by BCG vaccination. These postulates combine to reproduce the observed trends, and this is attributed to a reinfection threshold intrinsic to the transmission dynamics. Finally, we demonstrate how reinfection thresholds can be manipulated by vaccination programmes, suggesting that they have a potentially powerful role in global control.     

Heterogeneity in susceptibility to infection can explain high reinfection rates

Heterogeneity in susceptibility and infectivity is inherent to infectious disease transmission in nature. Here we are concerned with the formulation of mathematical models that capture the essence of heterogeneity while keeping a simple structure suitable of analytical treatment. We explore the consequences of host heterogeneity in the susceptibility to infection for epidemiological models for which immunity conferred by infection is partially protective, known as susceptible-infected-recovered-infected (SIRI) models. We analyze the impact of heterogeneity on disease prevalence and contrast the susceptibility profiles of the subpopulations at risk for primary infection and reinfection. We present a systematic study in the case of two frailty groups.We predict that the average rate of reinfection may be higher than the average rate of primary infection, which may seem paradoxical given that primary infection induces life-long partial protection. Infection generates a selection mechanism whereby fit individuals remain in S and frail individuals are transferred to R. If this effect is strong enough we have a scenario where, on average, the rate of reinfection is higher than the rate of primary infection even though each individual has a risk reduction following primary infection. This mechanism may explain high rates of tuberculosis reinfection recently reported.Finally, the enhanced benefits of vaccination strategies that target the high-risk groups are quantified.     

How host heterogeneity governs tuberculosis reinfection?

Recurrent episodes of tuberculosis (TB) can be due to relapse of latent infection or exogenous reinfection, and discrimination is crucial for control planning. Molecular genotyping of Mycobacterium tuberculosis isolates offers concrete opportunities to measure the relative contribution of reinfection in recurrent disease. Here, a mathematical model of TB transmission is fitted to data from 14 molecular epidemiology studies, enabling the estimation of relevant epidemiological parameters. Meta-analysis reveals that rates of reinfection after successful treatment are higher than rates of new TB, raising an important question about the underlying mechanism. We formulate two alternative mechanisms within our model framework: (i) infection increases susceptibility to reinfection or (ii) infection affects individuals differentially, thereby recruiting high-risk individuals to the group at risk for reinfection. The second mechanism is better supported by the fittings to the data, suggesting that reinfection rates are inflated through a population phenomenon that occurs in the presence of heterogeneity in individual risk of infection. As a result, rates of reinfection are higher when measured at the population level even though they might be lower at the individual level. Finally, differential host recruitment is modulated by transmission intensity, being less pronounced when incidence is high.