Short-term forecasting of the prevalence of clinical trachoma: utility of including delayed recovery and tests for infection.

BACKGROUND: The World Health Organization aims to control blinding trachoma by 2020. Decisions on whether to start and stop mass treatments and when to declare that control has been achieved are currently based on clinical examination data generated in population-based surveys. Thresholds are based on the district-level prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years. Forecasts of which districts may and may not meet TF control goals by the 2020 target date could affect resource allocation in the next few years. METHODS: We constructed a hidden Markov model fit to the prevalence of two clinical signs of trachoma and PCR data in 24 communities from the recent PRET-Niger trial. The prevalence of TF in children in each community at 36 months was forecast given data from earlier time points. Forecasts were scored by the likelihood of the observed results. We assessed whether use of TF with additional TI and PCR data rather than just the use of TF alone improves forecasts, and separately whether incorporating a delay in TF recovery is beneficial. RESULTS: Including TI and PCR data did not significantly improve forecasts of TF. Forecasts of TF prevalence at 36 months by the model with the delay in TF recovery were significantly better than forecasts by the model without the delay in TF recovery (p = 0.003). A zero-inflated truncated normal observation model was better than a truncated normal observation model, and better than a sensitivity-specificity observation model. CONCLUSION: The results in this study suggest that future studies could consider using just TF data for forecasting, and should include a delay in TF recovery. TRIAL REGISTRATION: Clinicaltrials.gov NCT00792922

Mass Azithromycin and Malaria Parasitemia in Niger: Results from a Community-Randomized Trial.

Studies designed to determine the effects of mass administration of azithromycin on trachoma have suggested that mass azithromycin distributions may also reduce the prevalence of malaria. These studies have typically examined the impact of a small number of treatments over short durations. In this prespecified substudy of a cluster-randomized trial for trachoma, we compared malaria parasitemia prevalence in 24 communities in Niger randomized to receive either annual or biannual mass azithromycin distributions over 3 years. The 12 communities randomized to annual azithromycin received three treatments during the high-transmission season, and the 12 communities randomized to biannual azithromycin received a total of six treatments: three during the high-transmission season and three during the low-transmission season. Blood samples were taken to assess malariometric indices among children in all study communities at a single time point during the high-transmission season after 3 years of the intervention. No significant differences were identified in malaria parasitemia, parasite density, or hemoglobin concentration between the annual and biannual treatment arms. When compared with annual mass azithromycin alone, additional mass azithromycin distributions given during the low-transmission season did not significantly reduce the subsequent prevalence of malaria parasitemia or parasite density after 3 years, as measured during the high-transmission season

Anthropometry and Malaria among Children in Niger: A Cross-Sectional Study.

The complex relationship between malnutrition and malaria affects morbidity and mortality in children younger than 5 years, particularly in parts of sub-Saharan Africa where these conditions occur together seasonally. Previous research on this relationship has been inconclusive. Here, we examine the association between anthropometric indicators and malaria infection in a population-based sample of children younger than 5 years in Niger. This cross-sectional study is a secondary analysis of a cluster-randomized trial comparing treatment strategies for trachoma in Niger. We included children aged 6-60 months residing in the 48 communities enrolled in the trial who completed anthropometric and malaria infection assessments at the final study visit. We evaluated the association between anthropometric indicators, including height-for-age z-score (HAZ) and weight-for-age z-score (WAZ) and indicators of malaria infection, including malaria parasitemia and clinical malaria. In May 2013, we collected data from 1,649 children. Of these, 780 (47.3%) were positive for malaria parasitemia and 401 (24.3%) had clinical malaria. In models of malaria parasitemia, the adjusted odds ratio (aOR) was 1.05 (95% confidence interval [CI]: 1.00-1.10) for HAZ and 1.07 (95% CI: 0.99, 1.15) for WAZ. In models of clinical malaria, the aOR was 1.07 (95% CI: 1.02-1.11) for HAZ and 1.09 (95% CI: 1.01-1.19) for WAZ. Overall, we did not find evidence of an association between most anthropometric indicators and malaria infection. Greater height may be associated with an increased risk of clinical malaria

Community-level chlamydial serology for assessing trachoma elimination in trachoma-endemic Niger.

BACKGROUND: Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met. METHODS: A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1-5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation-follicular [TF] and trachomatous inflammation-intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level. RESULTS: Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children. CONCLUSION: Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger. TRIAL REGISTRATION: ClinicalTrials.gov NCT00792922

Community Risk Factors for Ocular Chlamydia Infection in Niger: Pre-Treatment Results from a Cluster-Randomized Trachoma Trial

Trachoma is one of the most important neglected tropical diseases because it is the leading cause of blindness from an infection in the world. There are about 1.3 million persons blind from the disease and many more at risk of blindness in the future. It is caused by the common bacterium Chlamydia trachomatis and can be treated with mass drug administrations (MDA) of azithromycin. We have begun a clinical trial in Niger, a country with limited resources in Africa, to determine the best treatment strategy. Our study from May to July 2010, which began before MDA's were given, showed that 26% of children aged 0–5 years were infected with the disease. In these children, we found that discharge from the nose, presence of flies on the face, and the number of years of education completed by the head of the household were risk factors for infection in 48 different communities. We hope to use this information about risk factors of infection to help guide future studies for trachoma and also to help with the WHO goal of eliminating the disease worldwide by the year 2020

Impact of mass azithromycin distribution on malaria parasitemia during the low-transmission season in Niger: a cluster-randomized trial.

We assessed the effect of mass azithromycin treatment on malaria parasitemia in a trachoma trial in Niger. Twenty-four study communities received treatment during the wet, high-transmission season. Twelve of the 24 communities were randomized to receive an additional treatment during the dry, low-transmission season. Outcome measurements were conducted at the community-level in children < 1-72 months of age in May-June 2011. Parasitemia was higher in the 12 once-treated communities (29.8%, 95% confidence interval [CI] = 21.5-40.0%) than in the 12 twice-treated communities (19.5%, 95% CI = 13.0-26.5%, P = 0.03). Parasite density was higher in once-treated communities (354 parasites/μL, 95% CI = 117-528 parasites/μL) than in twice-treated communities (74 parasites/μL, 95% CI = 41-202 parasites/μL, P = 0.03). Mass distribution of azithromycin reduced malaria parasitemia 4-5 months after the intervention. The results suggest that drugs with antimalaria activity can have long-lasting impacts on malaria during periods of low transmission

Short-term forecasting of the prevalence of trachoma: expert opinion, statistical regression, versus transmission models

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