Data management plan for a community-level study of the hidden burden of cutaneous leishmaniasis in Colombia.

OBJECTIVES: Cutaneous leishmaniasis is a vector-borne parasitic disease whose lasting scars can cause stigmatization and depressive symptoms. It is endemic in remote rural areas and its incidence is under-reported, while the effectiveness, as opposed to efficacy, of its treatments is largely unknown. Here we present the data management plan (DMP) of a project which includes mHealth tools to address these knowledge gaps in Colombia. The objectives of the DMP are to specify the tools and procedures for data collection, data transfer, data entry, creation of analysis dataset, monitoring and archiving. RESULTS: The DMP includes data from two mobile apps: one implements a clinical prediction rule, and the other is for follow-up and treatment of confirmed cases. A desktop interface integrates these data and facilitates their linkage with other sources which include routine surveillance as well as paper and electronic case report forms. Multiple user and programming interfaces are used, as well as multiple relational and non-relational database engines. This DMP describes the successful integration of heterogeneous data sources and technologies. However the complexity of the project meant that the DMP took longer to develop than expected. We describe lessons learned which could be useful for future mHealth projects.

Adaptation and performance of a mobile application for early detection of cutaneous leishmaniasis.

BACKGROUND: Detection and management of neglected tropical diseases such as cutaneous leishmaniasis present unmet challenges stemming from their prevalence in remote, rural, resource constrained areas having limited access to health services. These challenges are frequently compounded by armed conflict or illicit extractive industries. The use of mobile health technologies has shown promise in such settings, yet data on outcomes in the field remain scarce. METHODS: We adapted a validated prediction rule for the presumptive diagnosis of CL to create a mobile application for use by community health volunteers. We used human-centered design practices and agile development for app iteration. We tested the application in three rural areas where cutaneous leishmaniasis is endemic and an urban setting where patients seek medical attention in the municipality of Tumaco, Colombia. The application was assessed for usability, sensitivity and inter-rater reliability (kappa) when used by community health volunteers (CHV), health workers and a general practitioner, study physician. RESULTS: The application was readily used and understood. Among 122 screened cases with cutaneous ulcers, sensitivity to detect parasitologically proven CL was >95%. The proportion of participants with parasitologically confirmed CL was high (88%), precluding evaluation of specificity, and driving a high level of crude agreement between the app and parasitological diagnosis. The chance-adjusted agreement (kappa) varied across the components of the risk score. Time to diagnosis was reduced significantly, from 8 to 4 weeks on average when CHV conducted active case detection using the application, compared to passive case detection by health facility-based personnel. CONCLUSIONS: Translating a validated prediction rule to a mHealth technology has shown the potential to improve the capacity of community health workers and healthcare personnel to provide opportune care, and access to health services for underserved populations. These findings support the use of mHealth tools for NTD research and healthcare.

Spatiotemporal Analysis of the Population Risk of Congenital Microcephaly in Pernambuco State, Brazil.

Since an outbreak in Brazil, which started in 2015, Zika has been recognized as an important cause of microcephaly. The highest burden of this outbreak was in northeast Brazil, including the state of Pernambuco. The prevalence of congenital microcephaly in Pernambuco state was estimated from the RESP (Registro de Eventos em Saúde Pública) surveillance system, from August 2015 to August 2016 inclusive. The denominators were estimated at the municipality level from official demographic data. Microcephaly was defined as a neonatal head circumference below the 3rd percentile of the Intergrowth standards. Smoothed maps of the prevalence of microcephaly were obtained from a Bayesian model which was conditional autoregressive (CAR) in space, and first order autoregressive in time. A total of 742 cases were identified. Additionally, high and early occurrences were identified in the Recife Metropolitan Region, on the coast, and in a north-south band about 300 km inland. Over a substantial part of the state, the overall prevalence, aggregating over the study period, was above 0.5%. The reasons for the high occurrence in the inland area remain unclear.

Prevalence of signs of trachoma, ocular Chlamydia trachomatis infection and antibodies to Pgp3 in residents of Kiritimati Island, Kiribati.

OBJECTIVE: In some Pacific Island countries, such as Solomon Islands and Fiji, active trachoma is common, but ocular Chlamydia trachomatis (Ct) infection and trachomatous trichiasis (TT) are rare. On Tarawa, the most populous Kiribati island, both the active trachoma sign "trachomatous inflammation-follicular" (TF) and TT are present at prevalences warranting intervention. We sought to estimate prevalences of TF, TT, ocular Ct infection, and anti-Ct antibodies on Kiritimati Island, Kiribati, to assess local relationships between these parameters, and to help determine the need for interventions against trachoma on Kiribati islands other than Tarawa. METHODS: As part of the Global Trachoma Mapping Project (GTMP), on Kiritimati, we examined 406 children aged 1-9 years for active trachoma. We collected conjunctival swabs (for droplet digital PCR against Ct plasmid targets) from 1-9-year-olds with active trachoma, and a systematic selection of 1-9-year-olds without active trachoma. We collected dried blood spots (for anti-Pgp3 ELISA) from all 1-9-year-old children. We also examined 416 adults aged ≥15 years for TT. Prevalence of TF and TT was adjusted for age (TF) or age and gender (TT) in five-year age bands. RESULTS: The age-adjusted prevalence of TF in 1-9-year-olds was 28% (95% confidence interval [CI]: 24-35). The age- and gender-adjusted prevalence of TT in those aged ≥15 years was 0.2% (95% CI: 0.1-0.3%). Twenty-six (13.5%) of 193 swabs from children without active trachoma, and 58 (49.2%) of 118 swabs from children with active trachoma were positive for Ct DNA. Two hundred and ten (53%) of 397 children had anti-Pgp3 antibodies. Both infection (p<0.0001) and seropositivity (p<0.0001) were strongly associated with active trachoma. In 1-9-year-olds, the prevalence of anti-Pgp3 antibodies rose steeply with age. CONCLUSION: Trachoma presents a public health problem on Kiritimati, where the high prevalence of ocular Ct infection and rapid increase in seropositivity with age suggest intense Ct transmission amongst young children. Interventions are required here to prevent future blindness.

Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies.

BACKGROUND: Efforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies. METHODOLOGY: Dried blood spots were collected in 2014 from children aged 1-9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1-90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared. PRINCIPAL FINDINGS: Seroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden's J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples. CONCLUSIONS: Internally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard.

The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study.

PURPOSE: To complete the baseline trachoma map worldwide by conducting population-based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h × c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit-level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015.

Sample size calculations for skewed distributions.

BACKGROUND: Sample size calculations should correspond to the intended method of analysis. Nevertheless, for non-normal distributions, they are often done on the basis of normal approximations, even when the data are to be analysed using generalized linear models (GLMs). METHODS: For the case of comparison of two means, we use GLM theory to derive sample size formulae, with particular cases being the negative binomial, Poisson, binomial, and gamma families. By simulation we estimate the performance of normal approximations, which, via the identity link, are special cases of our approach, and for common link functions such as the log. The negative binomial and gamma scenarios are motivated by examples in hookworm vaccine trials and insecticide-treated materials, respectively. RESULTS: Calculations on the link function (log) scale work well for the negative binomial and gamma scenarios examined and are often superior to the normal approximations. However, they have little advantage for the Poisson and binomial distributions. CONCLUSIONS: The proposed method is suitable for sample size calculations for comparisons of means of highly skewed outcome variables.

Are we nearly there yet? Coverage and compliance of mass drug administration for lymphatic filariasis elimination.

Lymphatic filariasis has been targeted for elimination by 2020, and a threshold of 65% coverage of mass drug administration (MDA) has been adopted by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage, defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance, defined as actual ingestion of tablets, was 22% lower on average. Moreover, the denominator for these coverage figures is the eligible, rather than total, population. By contrast, the 65% threshold, in the original modelling study, refers to ingestion of tablets in the total population. This corresponds to GPELF's use of 'epidemiological drug coverage' as a trigger for the Transmission Assessment Surveys (TAS), which indicate whether to proceed to post-MDA surveillance. The existence of less strict definitions of 'coverage' should not lead to premature TAS that could impair MDA's sustainability.

Reduction in acute filariasis morbidity during a mass drug administration trial to eliminate lymphatic filariasis in Papua New Guinea.

BACKGROUND: Acute painful swelling of the extremities and scrotum are debilitating clinical manifestations of Wuchereria bancrofti infection. The ongoing global program to eliminate filariasis using mass drug administration is expected to decrease this and other forms of filarial morbidity in the future by preventing establishment of new infections as a consequence of eliminating transmission by the mosquito vector. We examined whether mass treatment with anti-filarial drugs has a more immediate health benefit by monitoring acute filariasis morbidity in Papua New Guinean communities that participated in a 5-year mass drug administration trial. METHODOLOGY/PRINCIPAL FINDINGS: Weekly active surveillance for acute filariasis morbidity defined by painful swelling of the extremities, scrotum and breast was performed 1 year before and each year after 4 annual mass administrations of anti-filarial drugs (16,480 person-years of observation). Acute morbidity events lasted <3 weeks in 92% of affected individuals and primarily involved the leg (74-79% of all annual events). The incidence for all communities considered together decreased from 0.39 per person-year in the pre-treatment year to 0.31, 0.15, 0.19 and 0.20 after each of 4 annual treatments (p<0.0001). Residents of communities with high pre-treatment transmission intensities (224-742 infective bites/person/year) experienced a greater reduction in acute morbidity (0.62 episodes per person-year pre-treatment vs. 0.30 in the 4(th) post-treatment year) than residents of communities with moderate pre-treatment transmission intensities (24-167 infective bites/person/year; 0.28 episodes per person-year pre-treatment vs. 0.16 in the 4(th) post-treatment year). CONCLUSIONS: Mass administration of anti-filarial drugs results in immediate health benefit by decreasing the incidence of acute attacks of leg and arm swelling in people with pre-existing infection. Reduction in acute filariasis morbidity parallels decreased transmission intensity, suggesting that continuing exposure to infective mosquitoes is involved in the pathogenesis of acute filariasis morbidity.

Urine output on an intensive care unit: case-control study.

OBJECTIVE: To compare urine output between junior doctors in an intensive care unit and the patients for whom they are responsible. DESIGN: Case-control study. SETTING: General intensive care unit in a tertiary referral hospital. PARTICIPANTS: 18 junior doctors responsible for clerking patients on weekday day shifts in the unit from 23 March to 23 April 2009 volunteered as "cases." Controls were the patients in the unit clerked by those doctors. Exclusion criteria (for both groups) were pregnancy, baseline estimated glomerular filtration rate <15 ml/min/1.73 m(2), and renal replacement therapy. MAIN OUTCOME MEASURES: Oliguria (defined as mean urine output <0.5 ml/kg/hour over six or more hours of measurement) and urine output (in ml/kg/hour) as a continuous variable. RESULTS: Doctors were classed as oliguric and "at risk" of acute kidney injury on 19 (22%) of 87 shifts in which urine output was measured, and oliguric to the point of being "in injury" on one (1%) further shift. Data were available for 208 of 209 controls matched to cases in the data collection period; 13 of these were excluded because the control was receiving renal replacement therapy. Doctors were more likely to be oliguric than their patients (odds ratio 1.99, 95% confidence interval 1.08 to 3.68, P=0.03). For each additional 1 ml/kg/hour mean urine output, the odds ratio for being a case rather than a control was 0.27 (0.12 to 0.58, P=0.001). Mortality among doctors was astonishingly low, at 0% (0% to 18%). CONCLUSIONS: Managing our own fluid balance is more difficult than managing it in our patients. We should drink more water. Modifications to the criteria for acute kidney injury could be needed for the assessment of junior doctors in an intensive care unit.

Profound and sustained reduction in Chlamydia trachomatis in The Gambia: a five-year longitudinal study of trachoma endemic communities.

BACKGROUND: The elimination of blinding trachoma focuses on controlling Chlamydia trachomatis infection through mass antibiotic treatment and measures to limit transmission. As the prevalence of disease declines, uncertainty increases over the most effective strategy for treatment. There are little long-term data on the effect of treatment on infection, especially in low prevalence settings, on which to base guidelines. METHODOLOGY/PRINCIPAL FINDINGS: The population of a cluster of 14 Gambian villages with endemic trachoma was examined on seven occasions over five years (baseline, 2, 6, 12, 17, 30 and 60 months). Mass antibiotic treatment was given at baseline only. All families had accessible clean water all year round. New latrines were installed in each household after 17 months. Conjunctival swab samples were collected and tested for C. trachomatis by PCR. Before treatment the village-level prevalence of follicular trachoma in 1 to 9 year olds (TF(%1-9)) was 15.4% and C. trachomatis was 9.7%. Antibiotic treatment coverage was 83% of the population. In 12 villages all baseline infection cleared and few sporadic cases were detected during the following five years. In the other two villages treatment was followed by increased infection at two months, which was associated with extensive contact with other untreated communities. The prevalence of infection subsequently dropped to 0% in these 2 villages and 0.6% for the whole population by the end of the study in the absence of any further antibiotic treatment. However, several villages had a TF(%1-9) of >10%, the threshold for initiating or continuing mass antibiotic treatment, in the absence of any detectable C. trachomatis. CONCLUSIONS/SIGNIFICANCE: A single round of mass antibiotic treatment may be sufficient in low prevalence settings to control C. trachomatis infection when combined with environmental conditions, which suppress transmission, such as a good water supply and sanitation.

The long-term natural history of trachomatous trichiasis in the Gambia.

PURPOSE: Trachoma is the leading infectious cause of blindness. However, there are few data on the natural history of trachomatous trichiasis to guide program planning or that investigate its pathogenesis. METHODS: A cohort of Gambians with trichiasis in one or both eyes who had declined surgery was observed. Clinical examinations were performed at baseline and 4 years later. Conjunctival swab samples were collected for Chlamydia trachomatis PCR and bacteriology. RESULTS: One hundred fifty-four people were examined at baseline and 4 years later (241 nonsurgical eyes). At baseline 124 (52%) eyes had major trichiasis (5+ lashes), 75 (31%) minor trichiasis (1-4 lashes), and 42 (17%) no trichiasis. By 4 years, trichiasis had developed in 12 (29%) of 42 previously unaffected eyes. Minor trichiasis progressed to major in 28 (37%) of 75 eyes. New corneal opacification more commonly developed in eyes that had major (10%) compared to minor (5%) trichiasis at baseline. Bacterial infection was common (23%), becoming more frequent with increasing trichiasis. C. trachomatis infection was rare (1%). Conjunctival inflammation was common (29%) and was associated with progressive trichiasis and corneal opacification. CONCLUSIONS: Trichiasis progressed in the long-term in this environment, despite a low prevalence of C. trachomatis. Blinding corneal opacification develops infrequently, unless major trichiasis is present. Epilation and early surgery need to be formally compared for the management of minor trichiasis. The pathologic correlates and promoters of conjunctival inflammation need to be investigated.

Operational evaluation of the use of photographs for grading active trachoma.

We evaluated the reliability of photographs to verify field diagnoses of active trachoma. We examined 956 residents of a trachoma-endemic village for signs of trachoma using the World Health Organization simplified grading system. Two photographs of the right eye of 948 persons were independently graded (masked to field assessment) by the field examiner and two other experienced graders. There was only moderate agreement between field assessment and the subsequent photographic evaluations by the three graders. When we counted ungradable photographs as disagreements, mean kappa scores for the signs trachomatous inflammation (follicular [TF]) and trachomatous inflammation (intense [TI]) were 0.44 and 0.51, respectively. There was also only fair-to-moderate agreement between the three assessments (by different examiners) of the photographs. Either the signs TF and TI themselves are not as reliable as previously believed, or photographs should be used for their diagnosis only when reliability testing demonstrates better agreement than found here.

Re-emergence of Chlamydia trachomatis infection after mass antibiotic treatment of a trachoma-endemic Gambian community: a longitudinal study.

BACKGROUND: Community-wide mass antibiotic treatment is a central component of trachoma control. The optimum frequency and duration of treatment are unknown. We measured the effect of mass treatment on the conjunctival burden of Chlamydia trachomatis in a Gambian community with low to medium trachoma prevalence and investigated the rate, route, and determinants of re-emergent infection. METHODS: 14 trachoma-endemic villages in rural Gambia were examined and conjunctival swabs obtained at baseline, 2, 6, 12, and 17 months. Mass antibiotic treatment with azithromycin was given to the community at baseline. C trachomatis was detected by qualitative PCR and individual infection load then estimated by real-time quantitative PCR. FINDINGS: C trachomatis was detected in 95 (7%) of 1319 individuals at baseline. Treatment coverage was 83% of the population (1328 of 1595 people). The effect of mass treatment was heterogeneous. In 12 villages all baseline infections (34 [3%] of 1062 individuals) resolved, and prevalence (three [0.3%]) and infection load remained low throughout the study. Two villages (baseline infection: 61 [24%] of 257 individuals) had increased infection 2 months after treatment (74 [30%]), after extensive contact with other untreated communities. Subsequently, this value reduced to less than half of that before treatment (25 [11%]). INTERPRETATION: Mass antibiotic treatment generally results in effective, longlasting control of C trachomatis in this environment. For low prevalence regions, one treatment episode might be sufficient. Infection can be reintroduced through contact with untreated populations. Communities need to be monitored for treatment failure and control measures implemented over wide geographical areas.

Mass treatment with single-dose azithromycin for trachoma.

BACKGROUND: Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is an important cause of blindness. Current recommended dosing intervals for mass azithromycin treatment for trachoma are based on a mathematical model. METHODS: We collected conjunctival swabs for quantitative polymerase-chain-reaction assay of C. trachomatis before and 2, 6, 12, 18, and 24 months after mass treatment with azithromycin in a Tanzanian community in which trachoma was endemic. For ethical reasons, at 6, 12, and 18 months, we gave tetracycline eye ointment to residents who had clinically active trachoma. RESULTS: At baseline, 956 of 978 residents (97.8 percent) received either one oral dose of azithromycin or (if azithromycin was contraindicated) a course of tetracycline eye ointment. The prevalence of infection fell from 9.5 percent before mass treatment to 2.1 percent at 2 months and 0.1 percent at 24 months. The quantitative burden of ocular C. trachomatis infection in the community was 13.9 percent of the pretreatment level at 2 months and 0.8 percent at 24 months. At each time point after baseline, over 90 percent of the total community burden of C. trachomatis infection was found among subjects who had been positive the previous time they were tested. CONCLUSIONS: The prevalence and intensity of infection fell dramatically and remained low for two years after treatment. One round of very-high-coverage mass treatment with azithromycin, perhaps aided by subsequent periodic use of tetracycline eye ointment for persons with active disease, can interrupt the transmission of ocular C. trachomatis infection.

Which members of a community need antibiotics to control trachoma? Conjunctival Chlamydia trachomatis infection load in Gambian villages.

PURPOSE: Trachoma is the leading cause of infectious blindness worldwide. Control strategies target antibiotic therapy to individuals likely to be infected with Chlamydia trachomatis on the basis of clinical signs. However, many studies have found chlamydial infection in the absence of clinical disease. It has been unclear whether such individuals represent a significant reservoir of infection. In the current study, a quantitative polymerase chain reaction (PCR) assay was used to investigate the distribution and determinants of chlamydial infection load in an endemic community, and the findings were used to evaluate the potential effectiveness of different control strategies. METHODS: Members of a trachoma-endemic community (n = 1319) in a rural area of The Gambia were examined for signs of disease, and tarsal conjunctival swab samples were collected. C. trachomatis was initially detected by qualitative PCR. The load of infection was then estimated by real-time quantitative PCR. RESULTS: Chlamydial infection was detected in 7.2% of the population. The distribution of infection load was skewed, with a few individuals having high loads. Only 24% of infected individuals had signs of active trachoma. Infection loads were higher in those with clinically active disease and were highest among those with severe inflammatory trachoma. High infection loads were associated with having no accessible latrine and living with a person with active disease. CONCLUSIONS: In this low-prevalence setting, infected individuals without signs of active trachoma constitute a significant reservoir of infection. Treatment of a defined unit of people who live with someone with clinically active trachoma would effectively target antibiotic treatment to infected people without signs of disease.

Strategies for control of trachoma: observational study with quantitative PCR.

BACKGROUND: Antibiotics are an important part of WHO's strategy to eliminate trachoma as a blinding disease by 2020. At present, who needs to be treated is unclear. We aimed to establish the burden of ocular Chlamydia trachomatis in three trachoma-endemic communities in Tanzania and The Gambia with real-time quantitative PCR. METHODS: Conjunctival swabs were obtained at examination from 3146 individuals. Swabs were first tested by the qualitative Amplicor PCR, which is known to be highly sensitive. In positive samples, the number of copies of omp1 (a single-copy C trachomatis gene) was measured by quantitative PCR. FINDINGS: Children had the highest ocular loads of C trachomatis, although the amount of pooling in young age groups was less striking at the site with the lowest trachoma frequency. Individuals with intense inflammatory trachoma had higher loads than did those with other conjunctival signs. At the site with the highest prevalence of trachoma, 48 of 93 (52%) individuals with conjunctival scarring but no sign of active disease were positive for ocular chlamydiae. INTERPRETATION: Children younger than 10 years old, and those with intense inflammatory trachoma, probably represent the major source of ocular C trachomatis infection in endemic communities. Success of antibiotic distribution programmes could depend on these groups receiving effective treatment.

Mass treatment to eliminate filariasis in Papua New Guinea.

BACKGROUND: The global initiative to eradicate bancroftian filariasis currently relies on mass treatment with four to six annual doses of antifilarial drugs. The goal is to reduce the reservoir of microfilariae in the blood to a level that is insufficient to maintain transmission by the mosquito vector. METHODS: In nearly 2500 residents of Papua New Guinea, we prospectively assessed the effects of four annual treatments with a single dose of diethylcarbamazine plus ivermectin or diethylcarbamazine alone on the incidence of microfilariae-positive infections, the severity of lymphatic disease, and the rate of transmission of Wuchereria bancrofti by mosquitoes. Random assignment to treatment regimens was carried out according to the village of residence, and villages were categorized as having moderate or high rates of transmission. RESULTS: The four annual treatments with either drug regimen were taken by 77 to 86 percent of the members of the population who were at least five years old; treatments were well tolerated. The proportion with microfilariae-positive infections decreased by 86 to 98 percent, with a greater reduction in areas with a moderate rate of transmission than in those with a high rate. The respective aggregate frequencies of hydrocele and leg lymphedema were 15 percent and 5 percent before the trial began, and 5 percent (P<0.001) and 4 percent (P=0.04) after five years. Hydrocele and leg lymphedema were eliminated in 87 percent and 69 percent, respectively, of those who had these conditions at the outset. The rate of transmission by mosquitoes decreased substantially, and new microfilariae-positive infections in children were almost completely prevented over the five-year study period. CONCLUSIONS: Annual mass treatment with drugs such as diethylcarbamazine can virtually eliminate the reservoir of microfilariae and greatly reduce the frequency of clinical lymphatic abnormalities due to bancroftian filariasis. Eradication may be possible in areas with moderate rates of transmission, but longer periods of treatment or additional control measures may be necessary in areas with high rates of transmission.