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.

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.

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.

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 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.

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.

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.

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.

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.

Sequence variations in the MBL gene and their relationship to pulmonary tuberculosis in the Chinese Han population.

SETTING: The mannan binding lectin (MBL) gene is thought to play a role in human innate immune response to tuberculosis (TB) infection. OBJECTIVE: To investigate the possible association between MBL sequence variants and TB infection in the Chinese Han population. DESIGN: A total of 152 male pulmonary tuberculosis (PTB) patients and 293 healthy male subjects were recruited. Six MBL single nucleotide polymorphisms (SNPs) (A/B, A/C, A/D, H/L, Y/X and P/Q) were genotyped and haplotyped using the combined analysis of polymerase chain reaction using sequence-specific primers (PCR-SSP) and the PCR-sequence specific oligonucleotide probe (PCR-SSOP) assay. The genotype and haplotype frequencies were compared between TB cases and controls using an unconditional logistic regression model. RESULTS: Neither the genotypes nor the haplotypes of the five loci were significantly associated with the disease when considered individually. After the haplotypes were regrouped, however, the XB haplotype group coding for diminished MBL levels was present at a significantly higher frequency in the patients compared with the YA group (OR 1.57, 95% CI 1.02-2.41, P < 0.05). CONCLUSION: No convincing evidence of association between MBL sequence variants and PTB was observed individually, although the low-producing XB haplotype group may serve as a minor risk factor for PTB infection in the male Chinese Han population.

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.

Meta-analysis of age-prevalence patterns in lymphatic filariasis: no decline in microfilaraemia prevalence in older age groups as predicted by models with acquired immunity.

The role of acquired immunity in lymphatic filariasis is uncertain. Assuming that immunity against new infections develops gradually with accumulated experience of infection, models predict a decline in prevalence after teenage or early adulthood. A strong indication for acquired immunity was found in longitudinal data from Pondicherry, India, where Mf prevalence was highest around the age of 20 and declined thereafter. We reviewed published studies from India and Subsaharan Africa to investigate whether their age-prevalence patterns support the models with acquired immunity. By comparing prevalence levels in 2 adult age groups we tested whether prevalence declined at older age. For India, comparison of age groups 20-39 and 40+ revealed a significant decline in only 6 out of 53 sites, whereas a significant increase occurred more often (10 sites). Comparison of older age groups provided no indication that a decline would start at a later age. Results from Africa were even more striking, with many more significant increases than declines, irrespective of the age groups compared. The occurrence of a decline was not related to the overall Mf prevalence and seems to be a chance finding. We conclude that there is no evidence of a general age-prevalence pattern that would correspond to the acquired immunity models. The Pondicherry study is an exceptional situation that may have guided us in the wrong direction.

Determinants of health-seeking behaviour for schistosomiasis-related symptoms in the context of integrating schistosomiasis control within the regular health services in Ghana.

Morbidity control of schistosomiasis through integration within existing health care delivery systems is considered a potentially sustainable and cost-effective approach. We conducted a questionnaire-based field study in a Ghanaian village endemic for both urinary and intestinal schistosomiasis to determine whether infected individuals self-reported to health centres or clinics and to identify factors that influenced their decision to seek health care. A total of 317 subjects were interviewed about having signs and symptoms suggestive of schistosomiasis: blood in urine, painful urination, blood in stool/bloody diarrhoea, abdominal pain, diarrhoea, swollen abdomen and fatigue within 1 month of the day of the interview. Fever (for malaria) was included as a disease of high debility for comparison. Around 70% with blood in urine or painful urination did not seek health care, whilst diarrhoea, blood in stool, abdominal pain and fever usually led to action (mainly self-medication, with allopathic drugs being used four to five times more often than herbal treatment). On average 20% of schistosomiasis-related signs and symptoms were reported to health facilities either as the first option or second and third alternative by some of those that self-medicated. A few of those who visited a clinic or health centre as first option still self-medicated afterwards. Children under 10 years and adults were more likely to seek health care than teenagers. Also, females were more likely to visit a health facility than males of the same age groups. Socio-economic status and duration of symptoms did not appear to affect health-seeking behaviour. 'Do not have the money' (43%) and 'Not serious enough' (41%) were the commonest reasons for not visiting a clinic, reported more frequently by lower and higher socio-economic classes, respectively, for both urinary or intestinal schistosomiasis. The regular health service shows some potential in passive control of schistosomiasis as some, but far too few, people visit a health facility as first or second option.

Effects of meteorological factors on epidemic malaria in Ethiopia: a statistical modelling approach based on theoretical reasoning.

This study was conducted to quantify the association between meteorological variables and incidence of Plasmodium falciparum in areas with unstable malaria transmission in Ethiopia. We used morbidity data pertaining to microscopically confirmed cases reported from 35 sites throughout Ethiopia over a period of approximately 6-7 years. A model was developed reflecting biological relationships between meteorological and morbidity variables. A model that included rainfall 2 and 3 months earlier, mean minimum temperature of the previous month and P. falciparum case incidence during the previous month was fitted to morbidity data from the various areas. The model produced similar percentages of over-estimation (19.7% of predictions exceeded twice the observed values) and under-estimation (18.6%, were less than half the observed values). Inclusion of maximum temperature did not improve the model. The model performed better in areas with relatively high or low incidence (>85% of the total variance explained) than those with moderate incidence (55-85% of the total variance explained). The study indicated that a dynamic immunity mechanism is needed in a prediction model. The potential usefulness and drawbacks of the modelling approach in studying the weather-malaria relationship are discussed, including a need for mechanisms that can adequately handle temporal variations in immunity to malaria.

[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.

Assessing density dependence in the transmission of lymphatic filariasis: uptake and development of Wuchereria bancrofti microfilariae in the vector mosquitoes.

Understanding density dependence in the transmission of lymphatic filariasis is essential for assessing the prospects of elimination. This study seeks to quantify the relationship between microfilaria (Mf) density in human blood and the number of third stage (L3) larvae developing in the mosquito vectors Aedes polynesiensis Marks and Culex quinquefasciatus Say (Diptera: Culicidae) after blood-feeding. Two types of curves are fitted to previously published data. Fitting a linearized power curve through the data allows for correction for measurement error in human Mf counts. Ignoring measurement error leads to overestimation of the strength of density dependence; the degree of overestimation depends on the accuracy of measurement of Mf density. For use in mathematical models of transmission of lymphatic filariasis, a hyperbolic saturating function is preferable. This curve explicitly estimates the Mf uptake and development at lowest Mf densities and the average maximum number of L3 that can develop in mosquitoes. This maximum was estimated at 23 and 4 for Ae. polynesiensis and Cx. quinquefasciatus, respectively.

Evaluation of case management in the integrated schistosomiasis-control programme in Mali.

Currently, schistosomiasis control in Mali is mainly based on treatment with praziquantel (PZQ). The policy is to ensure (1). the treatment, every 3 years, of school-age children in all areas where the prevalence of haematuria (an indicator of Schistosoma haematobium infection) in this age-group is >30%, and (2). the sound management of all patients presenting with haematuria or (bloody) diarrhoea (an indicator of S. mansoni infection) at health centres. In the present study, the application of case management was evaluated by visiting 60 healthcare facilities in four geographical areas and interviewing the health-workers at these facilities. The presence of S. haematobium and S. mansoni was reported in the coverage areas of 83% and 37%, respectively, of the healthcare facilities investigated. Health-worker knowledge of the main symptoms of schistosome infection was good and patients exhibiting symptoms attributable to schistosome infection were very likely to receive adequate treatment, particularly (at a frequency of about 80%) when they presented with haematuria. At health-centre level, patients were often directly treated with PZQ, whereas health-workers in district hospitals and private clinics requested a diagnostic test prior to any treatment. PZQ was available in most healthcare facilities but not in the private clinics. The mean cost of treatment of a patient with S. haematobium infection (euro; 2.30) was very similar to the corresponding cost for S. mansoni infection (euro; 2.37). The cost of the PZQ represented approximately 50% of the total costs borne by the patients when presenting at health centres. Patients with the symptoms of S. haematobium infection in Mali can expect adequate diagnosis and treatment in agreement with the recommendations of the World Health Organization. Patients presenting with symptoms related to S. mansoni infection are, however, less likely to be correctly diagnosed. The relatively high costs of treatment and the infrequency with which cases of schistosomiasis seek healthcare necessitate policy decisions, to ensure an affordable and more attractive, clinical system of case management.

Comparison of STD prevalences in the Mwanza, Rakai, and Masaka trial populations: the role of selection bias and diagnostic errors.

OBJECTIVES: To assess bias in estimates of STD prevalence in population based surveys resulting from diagnostic error and selection bias. To evaluate the effects of such biases on STD prevalence estimates from three community randomised trials of STD treatment for HIV prevention in Masaka and Rakai, Uganda and Mwanza, Tanzania. METHODS: Age and sex stratified prevalences of gonorrhoea, chlamydia, syphilis, HSV-2 infection, and trichomoniasis observed at baseline in the three trials were adjusted for sensitivity and specificity of diagnostic tests and for sample selection criteria. RESULTS: STD prevalences were underestimated in all three populations because of diagnostic errors and selection bias. After adjustment, gonorrhoea prevalence was higher in men and women in Mwanza (2.8% and 2.3%) compared to Rakai (1.1% and 1.9%) and Masaka (0.9% and 1.8%). Chlamydia prevalence was higher in women in Mwanza (13.0%) compared to Rakai (3.2%) and Masaka (1.6%) but similar in men (2.3% in Mwanza, 2.7% in Rakai, and 2.2% in Masaka). Prevalence of trichomoniasis was higher in women in Mwanza compared to women in Rakai (41.9% versus 30.8%). Herpes simplex virus type 2 (HSV-2) seroprevalence and prevalence of serological syphilis (TPHA+/RPR+) were similar in the three populations but the prevalence of high titre syphilis (TPHA+/RPR >/=1:8) in men and women was higher in Mwanza (5.6% and 6.3%) than in Rakai (2.3% and 1.4%) and Masaka (1.2% and 0.7%). CONCLUSIONS: Limited sensitivity of diagnostic and screening tests led to underestimation of STD prevalence in all three trials but especially in Mwanza. Adjusted prevalences of curable STD were higher in Mwanza than in Rakai and Masaka.