Implementing Preventive Chemotherapy through an Integrated National Neglected Tropical Disease Control Program in Mali

Neglected tropical diseases (NTDs) are a group of chronic infections that affect the poorest group of the populations in the world. There are currently five major NTDs targeted through mass drug treatment in the affected communities. The drug delivery can be integrated to deliver different drug packages as these NTDs often overlap in distribution. Mali is endemic with all five major NTDs. The integrated national NTD control program was implemented through the primary health care system using the community health center workers and the community drug distributors aiming at long-term sustainability. After a pilot start in three regions in 2007 without prior examples to follow on integrated mass drug administration, treatment for the five targeted NTDs was gradually scaled up and reached all endemic districts by 2009, and annual drug coverage in the targeted population has since been maintained at a high level for each of the five NTDs. Around 10 million people received one or more drug treatments each year since 2009. The country is on the way to meet the national objectives of elimination or control of these diseases. The successes and lessons learned in Mali are valuable assets to other countries looking to start similar programs

Active Trachoma among Children in Mali: Clustering and Environmental Risk Factors

Active trachoma is not uniformly distributed in endemic areas, and local environmental factors influencing its prevalence are not yet adequately understood. Determining whether clustering is a consistent phenomenon may help predict likely modes of transmission and help to determine the appropriate level at which to target control interventions. In this work, we estimated the magnitude of clustering at different levels and investigated the influence of socio-economic factors and environmental features on active trachoma prevalence among children in Mali (1996–1997 nationwide survey). Clustering revealed significant results at the child, caretaker, household, and village levels. Moreover, beyond some well-established individual risk factors (age between 3 and 5, dirty face, and flies on the face), we found that temperature, sunshine fraction, and presence of rainy days were negatively associated with active trachoma prevalence. This study clearly indicates the importance of directing control efforts both at children with active trachoma as well as those with close contact, and at communities. These results support facial cleanliness and environmental improvements as population-health initiatives to combat blinding trachoma

Costs of Testing for Ocular Chlamydia trachomatis Infection Compared to Mass Drug Administration for Trachoma in The Gambia: Application of Results from the PRET Study

Background Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥10% in children aged 1–9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds. Methods The implementation unit in PRET The Gambia was a census enumeration area (EA) of 600–800 people. Personnel, fuel, equipment, consumables, data entry and supervision costs were collected for census and treatment of a sample of EAs and for the examination, sampling and testing for Ct infection of 100 individuals within them. Programme costs and resource savings from testing and treatment strategies were inferred for the 102 EAs in the study area, and compared. Results Census costs were $103.24 per EA plus initial costs of$108.79. MDA with donated azithromycin cost $227.23 per EA. The mean cost of examining and testing 100 children was$796.90 per EA, with Ct testing kits costing $4.80 per result. A strategy of testing each EA for infection is more expensive than two annual rounds of MDA unless the kit cost is less than$1.38 per result. However stopping or deciding not to initiate treatment in the study area based on testing a sample of EAs for Ct infection (or examining children in a sample of EAs) creates savings relative to further unnecessary treatments. Conclusion Resources may be saved by using tests for chlamydial infection or clinical examination to determine that initial or subsequent rounds of MDA for trachoma are unnecessary

Retinal Pathology of Pediatric Cerebral Malaria in Malawi

Introduction The causes of coma and death in cerebral malaria remain unknown. Malarial retinopathy has been identified as an important clinical sign in the diagnosis and prognosis of cerebral malaria. As part of a larger autopsy study to determine causes of death in children with coma presenting to hospital in Blantyre, Malawi, who were fully evaluated clinically prior to death, we examined the histopathology of eyes of patients who died and underwent autopsy. Methodology/Principal Findings Children with coma were admitted to the pediatric research ward, classified according to clinical definitions as having cerebral malaria or another cause of coma, evaluated and treated. The eyes were examined by direct and indirect ophthalmoscopy. If a child died and permission was given, a standardized autopsy was carried out. The patient was then assigned an actual cause of death according to the autopsy findings. The eyes were examined pathologically for hemorrhages, cystoid macular edema, parasite sequestration and thrombi. They were stained immunohistochemically for fibrin and CD61 to identify the components of thrombi, β-amyloid precursor protein to detect axonal damage, for fibrinogen to identify vascular leakage and for glial fibrillary acidic protein to detect gliosis. Sixty-four eyes from 64 patients were examined: 35 with cerebral malaria and 29 with comas of other causes. Cerebral malaria was distinguished by sequestration of parasitized erythrocytes, the presence and severity of retinal hemorrhages, the presence of cystoid macular edema, the occurrence and number of fibrin-platelet thrombi, the presence and amount of axonal damage and vascular leakage. Conclusions/Significance We found significant differences in retinal histopathology between patients who died of cerebral malaria and those with other diagnoses. These histopathological findings offer insights into the etiology of malarial retinopathy and provide a pathological basis for recently described retinal capillary non-perfusion in children with malarial retinopathy. Because of the similarities between the retina and the brain it also suggests mechanisms that may contribute to coma and death in cerebral malaria

Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

Control of neglected tropical diseases (NTDs) is suggested to be more cost-effective when drugs are co-administered through a single integrated delivery system rather than separate systems. An essential prerequisite for such efficiency gains is sufficient geographical overlap of the targeted diseases – lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminth infection and trachoma. Lack of data on geographical NTD distribution currently hampers the implementation of integrated control in many African countries. To generate the required data quickly and efficiently, integrated surveys of several NTDs simultaneously have been recommended. However, experience with integrated surveys is limited and requires additional research on cost and effectiveness to inform improvements in methodology and to guide scale-up. Here we analyse costs of the first integrated NTD survey round in Southern Sudan, generating average costs per implementation unit surveyed. Cost estimates are presented for use of the existing survey method and for modified versions. Key cost drivers were survey consumables and personnel, both of which are recurrent costs. These inputs could be reduced or put to more efficient use by modifying sampling for LF. To generate comparable cost estimates and identify key cost drivers in other settings we provide detailed cost data and guidance on how to replicate this work

The geographical distribution and burden of trachoma in Africa.

BACKGROUND: There remains a lack of epidemiological data on the geographical distribution of trachoma to support global mapping and scale up of interventions for the elimination of trachoma. The Global Atlas of Trachoma (GAT) was launched in 2011 to address these needs and provide standardised, updated and accessible maps. This paper uses data included in the GAT to describe the geographical distribution and burden of trachoma in Africa. METHODS: Data assembly used structured searches of published and unpublished literature to identify cross-sectional epidemiological data on the burden of trachoma since 1980. Survey data were abstracted into a standardised database and mapped using geographical information systems (GIS) software. The characteristics of all surveys were summarized by country according to data source, time period, and survey methodology. Estimates of the current population at risk were calculated for each country and stratified by endemicity class. RESULTS: At the time of writing, 1342 records are included in the database representing surveys conducted between 1985 and 2012. These data were provided by direct contact with national control programmes and academic researchers (67%), peer-reviewed publications (17%) and unpublished reports or theses (16%). Prevalence data on active trachoma are available in 29 of the 33 countries in Africa classified as endemic for trachoma, and 1095 (20.6%) districts have representative data collected through population-based prevalence surveys. The highest prevalence of active trachoma and trichiasis remains in the Sahel area of West Africa and Savannah areas of East and Central Africa and an estimated 129.4 million people live in areas of Africa confirmed to be trachoma endemic. CONCLUSION: The Global Atlas of Trachoma provides the most contemporary and comprehensive summary of the burden of trachoma within Africa. The GAT highlights where future mapping is required and provides an important planning tool for scale-up and surveillance of trachoma control

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

Targeting Antibiotics to Households for Trachoma Control

Repeated ocular infection with the bacterium Chlamydia trachomatis leads to the development of trachoma, a major cause of infectious blindness worldwide. Mass distribution of antibiotics, a component of the current trachoma control strategy, has had success in reducing infection in some areas, but results in a large number of uninfected people receiving antibiotics. We have previously shown that transmission of the bacteria between people in the same household is very efficient. Here, we investigated the effectiveness and cost-effectiveness of targeting antibiotics to households with active trachoma (inflammatory disease) compared to mass distribution, using data from four trachoma-endemic populations and a mathematical model of transmission. We found a high correspondence between households with active trachoma and infected households. In all populations the household targeted approach was predicted to be as effective as mass distribution, but it reduced the number of uninfected individuals receiving antibiotics, making the targeted strategy more cost-effective when antibiotics are not donated. Assuming antibiotics are donated, we predicted the targeted strategy to be more cost effective if it increases the proportion of infected individuals receiving treatment. Further work to address the feasibility and the cost variability in implementing the targeted approach in different settings is now required

Diagnostic Accuracy of a Prototype Point-of-Care Test for Ocular Chlamydia trachomatis under Field Conditions in The Gambia and Senegal

Trachoma, caused by infection of the eye with the bacterium Chlamydia trachomatis, is the leading infectious cause of blindness and is associated with poverty. Antibiotic treatment of all community members is one of the recommended control strategies for trachoma. However, in places where the prevalence of clinical signs is low, C. trachomatis eye infection is often absent. Laboratory testing for C. trachomatis infection by polymerase chain reaction (PCR) is highly sensitive but expensive and requires well-trained staff. A simple point-of-care (POC) test that can be used in trachoma-affected communities could help trachoma control efforts. We evaluated a POC test for C. trachomatis eye infection. Children under 10 years of age were screened for clinical signs of trachoma and C. trachomatis eye infection. The POC test result was compared with laboratory PCR test results. The POC test detected just over half of PCR test positives correctly. However, the POC test tended to give false-positive results in hot and dry conditions, which is the typical environment of trachoma. The POC test requires high specificity since it would be used to make treatment decisions at the community level. Therefore, its present format requires improvement before it can be utilized in trachoma control

Risk Factors for Ocular Chlamydia after Three Mass Azithromycin Distributions

Trachoma, which is the leading infectious cause of blindness worldwide, is caused by repeated ocular infection with Chlamydia trachomatis. Treatment for trachoma includes mass azithromycin treatments to the entire community. The World Health Organization recommends at least 3 rounds of annual mass antibiotic distributions in areas with trachoma, with further mass treatments based on the prevalence of trachoma. However, there are other options for communities that have received several rounds of treatment. For example, programs could continue antibiotic treatments only in those households most likely to have infected individuals. In this study, we performed trachoma monitoring on children from 12 Ethiopian communities one year after a third mass azithromycin treatment, and conducted a household survey at the same time. We found that children were more likely to be infected with ocular chlamydia if they had ocular inflammatory signs or ocular discharge, or if they had missed the preceding antibiotic treatment, had an infected sibling, or came from a larger community. These risk factors suggest that after mass azithromycin treatments, trachoma programs could consider continuing antibiotic distributions to households that have missed prior antibiotic distributions, in households with children who have the clinical signs of trachoma, and in larger communities