Mulat Zerihun

Individual, household and environmental risk factors for malaria infection in Amhara, Oromia and SNNP regions of Ethiopia

We assessed malaria infection in relation to age, altitude, rainfall, socio-economic factors and coverage of control measures in a representative sample of 11437 people in Amhara, Oromia and SNNP regions of Ethiopia in December 2006-January 2007. Surveys were conducted in 224 randomly selected clusters of 25 households (overall sample of 27884 people in 5708 households). In 11538 blood slides examined from alternate households (83% of those eligible), malaria prevalence in people of all ages was 4.1% (95% CI 3.4-4.9), with 56.5% of infections being Plasmodium falciparum. At least one mosquito net or one long-lasting insecticidal net (LLIN) was present in 37.0% (95% CI 31.1-43.3) and 19.6% (95% CI 15.5-24.5) of households, respectively. In multivariate analysis (n=11437; 82% of those eligible), significant protective factors were: number of LLINs per household (odds ratio [OR] (per additional net)=0.60; 95% CI 0.40-0.89), living at higher altitude (OR (per 100 m)=0.95; 95% CI 0.90-1.00) and household wealth (OR (per unit increase in asset index)=0.79; 95% CI 0.66-0.94). Malaria prevalence was positively associated with peak monthly rainfall in the year before the survey (OR (per additional 10 mm rain)=1.10; 95% CI 1.03-1.18). People living above 2000 m and people of all ages are still at significant risk of malaria infection.

Integrating an NTD with one of "The big three": combined malaria and trachoma survey in Amhara Region of Ethiopia.

Background Amhara Regional State of Ethiopia has a population of approximately 19.6 million, is prone to unstable and epidemic malaria, and is severely affected by trachoma. An integrated malaria and trachoma control program is being implemented by the Regional Health Bureau. To provide baseline data, a survey was conducted during December 2006 to estimate malaria parasite prevalence, malaria indicators, prevalence of trachoma, and trachoma risk factors in households and people of all ages in each of the ten zones of the state, excluding three urban centers (0.4% of the population). Methodology/Principal Findings The study was designed to provide prevalence estimates at zone and state levels. Using multi-stage cluster random sampling, 16 clusters of 25 households were randomly selected in each of the ten zones. Household heads were interviewed for malaria indicators and trachoma risk factors (N = 4,101). All people were examined for trachoma signs (N = 17,242), and those in even-numbered households provided blood films for malaria parasite detection (N = 7,745); both thick and thin blood films were read. Zonal malaria parasite prevalence ranged from 2.4% to 6.1%, with the overall state-wide prevalence being 4.6% (95% confidence interval (CI): 3.8%–5.6%). The Plasmodium falciparum: Plasmodium vivax ratio ranged from 0.9–2.1 with an overall regional ratio of 1.2. A total of 14.8% of households reported indoor residual spraying in the past year, 34.7% had at least one mosquito net, and 16.1% had one or more long-lasting insecticidal net. Zonal trachoma prevalence (trachomatous inflammation follicular [WHO grade TF] in children aged 1–9 years) ranged from 12.6% to 60.1%, with the overall state-wide prevalence being 32.7% (95% CI: 29.2%–36.5%). State-wide prevalence of trachomatous trichiasis (TT) in persons aged over fifteen was 6.2% (95% CI: 5.3–7.4), and 0.3% (95% CI: 0.2–0.5) in children aged 0–14 years. Overall, an estimated 643,904 persons (lower bound 419,274, upper bound 975,635) have TT and require immediate corrective surgery. Conclusions/Significance The results provide extensive baseline data to guide planning, implementation, and evaluation of the integrated malaria and trachoma control program in Amhara. The success of the integrated survey is the first step towards demonstration that control of priority neglected tropical diseases can be integrated with one of the “big three” killer diseases.

Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial

Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities.

A novel electronic data collection system for large-scale surveys of neglected tropical diseases.

Background Large cross-sectional household surveys are common for measuring indicators of neglected tropical disease control programs. As an alternative to standard paper-based data collection, we utilized novel paperless technology to collect data electronically from over 12,000 households in Ethiopia. Methodology We conducted a needs assessment to design an Android-based electronic data collection and management system. We then evaluated the system by reporting results of a pilot trial and from comparisons of two, large-scale surveys; one with traditional paper questionnaires and the other with tablet computers, including accuracy, person-time days, and costs incurred. Principle Findings The electronic data collection system met core functions in household surveys and overcame constraints identified in the needs assessment. Pilot data recorders took 264 (standard deviation (SD) 152 sec) and 260 sec (SD 122 sec) per person registered to complete household surveys using paper and tablets, respectively (P = 0.77). Data recorders felt a lack of connection with the interviewee during the first days using electronic devices, but preferred to collect data electronically in future surveys. Electronic data collection saved time by giving results immediately, obviating the need for double data entry and cross-correcting. The proportion of identified data entry errors in disease classification did not differ between the two data collection methods. Geographic coordinates collected using the tablets were more accurate than coordinates transcribed on a paper form. Costs of the equipment required for electronic data collection was approximately the same cost incurred for data entry of questionnaires, whereas repeated use of the electronic equipment may increase cost savings. Conclusions/Significance Conducting a needs assessment and pilot testing allowed the design to specifically match the functionality required for surveys. Electronic data collection using an Android-based technology was suitable for a large-scale health survey, saved time, provided more accurate geo-coordinates, and was preferred by recorders over standard paper-based questionnaires.

Intestinal parasite prevalence in an area of ethiopia after implementing the SAFE strategy, enhanced outreach services, and health extension program.

Background The SAFE strategy aims to reduce transmission of Chlamydia trachomatis through antibiotics, improved hygiene, and sanitation. We integrated assessment of intestinal parasites into large-scale trachoma impact surveys to determine whether documented environmental improvements promoted by a trachoma program had collateral impact on intestinal parasites. Methodology We surveyed 99 communities for both trachoma and intestinal parasites (soil-transmitted helminths, Schistosoma mansoni, and intestinal protozoa) in South Gondar, Ethiopia. One child aged 2–15 years per household was randomly selected to provide a stool sample of which about 1 g was fixed in sodium acetate-acetic acid-formalin, concentrated with ether, and examined under a microscope by experienced laboratory technicians. Principal Findings A total of 2,338 stool specimens were provided, processed, and linked to survey data from 2,657 randomly selected children (88% response). The zonal-level prevalence of Ascaris lumbricoides, hookworm, and Trichuris trichiura was 9.9% (95% confidence interval (CI) 7.2–12.7%), 9.7% (5.9–13.4%), and 2.6% (1.6–3.7%), respectively. The prevalence of S. mansoni was 2.9% (95% CI 0.2–5.5%) but infection was highly focal (range by community from 0–52.4%). The prevalence of any of these helminth infections was 24.2% (95% CI 17.6–30.9%) compared to 48.5% as found in a previous study in 1995 using the Kato-Katz technique. The pathogenic intestinal protozoa Giardia intestinalis and Entamoeba histolytica/E. dispar were found in 23.0% (95% CI 20.3–25.6%) and 11.1% (95% CI 8.9–13.2%) of the surveyed children, respectively. We found statistically significant increases in household latrine ownership, use of an improved water source, access to water, and face washing behavior over the past 7 years. Conclusions Improvements in hygiene and sanitation promoted both by the SAFE strategy for trachoma and health extension program combined with preventive chemotherapy during enhanced outreach services are plausible explanations for the changing patterns of intestinal parasite prevalence. The extent of intestinal protozoa infections suggests poor water quality or unsanitary water collection and storage practices and warrants targeted intervention.

Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial

BACKGROUND In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains. METHODS We did a cluster-randomised trial in 24 subdistricts in northern Ethiopia, which we randomly assigned to receive annual or twice-yearly treatment for all residents of all ages. Random assignment was done with the RANDOM and SORT functions of Microsoft Excel. All individuals were offered their assigned treatment of a single, directly observed, oral dose of azithromycin. A 6 week course of topical 1% tetracycline ointment, applied twice daily to both eyes but not directly observed, was offered as an alternative to azithromycin in patients younger than 12 months, and in patients with self-reported pregnancy, with allergy, or who refused azithromycin. Our primary, prespecified outcome was the prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years at baseline and every 6 months for a total of 42 months within sentinel villages. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00322972. FINDINGS Antibiotic coverage of children aged 1-9 years was greater than 80% (range 80·9 to 93·0) at all study visits. In the groups treated annually, the prevalence of infection in children aged 0-9 years was reduced from a mean 41·9% (95% CI 31·5 to 52·2) at baseline to 1·9% (0·3 to 3·5) at 42 months. In the groups treated twice yearly, the prevalence of infection was reduced from a mean 38·3% (29·0 to 47·6) at baseline to 3·2 % (0·0 to 6·5) at 42 months. The prevalence of ocular chlamydial infection in children aged 0-9 years in groups treated annually was not different from that of the groups treated twice yearly at 18, 30, and 42 months (pooled regression p>0·99, 95 % CI -0·06 to 0·06). The mean elimination time in the twice-yearly treatment group was 7·5 months earlier (2·3 to 17·3) than that of the annual group (p=0·10, Cox proportional hazards model). INTERPRETATION After 42 months of treatment, the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly. However, elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly. FUNDING National Institutes of Health (NEI U10 EY016214).

Childhood Mortality in a Cohort Treated With Mass Azithromycin for Trachoma

BACKGROUND Mass azithromycin distributions are used to clear ocular strains of chlamydia that cause trachoma, but treatments may also affect respiratory infections, diarrhea, and malaria. Here, we monitor a large cohort in which almost 90% of individuals received azithromycin. We assess whether receiving treatment is associated with reduced all-cause and infectious childhood mortality. METHODS As part of a clinical trial for trachoma, a census was conducted in 24 communities in rural Ethiopia. All individuals ≥1 year of age were eligible for single-dose oral azithromycin, although antibiotic coverage was not universal. A follow-up census was performed 26 months after treatment to estimate all-cause mortality among children 1-5 years of age, and verbal autopsies were performed to identify infectious mortality. RESULTS The cohort included 35,052 individuals ≥1 year of age and 5507 children 1-5 years of age, of whom 4914 received a dose of azithromycin. All-cause mortality was significantly lower among those 1-5-year-old children who received azithromycin (odds ratio [OR]=0.35 [95% confidence interval {CI}, 0.17-0.74]), as was infectious mortality (OR=0.20 [95% CI, 0.07-0.58]). When individuals were compared only with members of the same household, azithromycin treatment was still associated with reduced all-cause mortality in children 1-5 years of age (OR=0.40 [95% CI, 0.16-0.96]), although this relationship was not statistically significant for infectious mortality (OR=0.35 [95% CI, 0.10-1.28]). CONCLUSIONS This study demonstrated an association between mass oral azithromycin treatment and reduced all-cause and infectious childhood mortality. This relationship could not be attributed to bias at the level of the household. Mass azithromycin distributions may have benefits unrelated to trachoma.

Evaluation of three years of the SAFE strategy (Surgery, Antibiotics, Facial cleanliness and Environmental improvement) for trachoma control in five districts of Ethiopia hyperendemic for trachoma:

Trachoma surveys were conducted at baseline in five districts of Amhara National Regional State, Ethiopia (7478 participants in 1096 households) and at 3-year evaluation (5762 participants in 1117 households). Uptake of SAFE was assessed with programme monitoring data and interviews, and children (1-6 years) were swabbed for detection of ocular Chlamydia. At evaluation, 23,933 people had received trichiasis surgery; 93% of participants reported taking azithromycin at least once; 67% of household respondents (range 46-93) reported participation in trachoma health education; and household latrine coverage increased from 2% to 34%. In children aged 1-9 years percentage decline, by district, for outcomes was: 32% (95% CI 19-48) to 88% (95% CI 83-91) for trachomatous inflammation-follicular (TF); 87% (95% CI 83-91) to 99% (95% CI 97-100) for trachomatous inflammation-intense (TI); and 31% increase (95% CI -42 to -19) to 89% decrease (95% CI 85-93) for unclean face; and in adults percentage decline in trichiasis was 45% (95% CI -13 to 78) to 92% (95% CI 78-96). Overall prevalence of swabs positive for ocular Chlamydia was 3.1%. Although there were substantial reductions in outcomes in children and adults, the presence of ocular Chlamydia and TF in children suggests ongoing transmission. Continued implementation of SAFE is warranted.

Efficacy of latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass antibiotic treatment: a cluster-randomized trial

The World Health Organization (WHO) recommends environmental improvements such as latrine construction in the integrated trachoma control strategy, SAFE. We report a cluster-randomized trial assessing the effect of intensive latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass treatment with antibiotics.Twenty-four communities in Goncha Seso Enesie woreda, Amhara Regional State, Ethiopia, were enumerated, and a random selection of 60 children aged 0- 9 years in each was monitored for clinical signs of trachoma and ocular chlamydial infection at baseline, 12 and 24 months. All community members were offered treatment with a single dose of oral azithromycin or topical tetracycline. After treatment, 12 subkebeles were randomized to receive intensive latrine promotion. Mean cluster ocular infection in the latrine and the non-latrine arms were reduced from 45.5% (95% CI 34.1-56.8%) and 43.0% (95% CI 31.1-54.8%) respectively at baseline to 14.6% (95% CI 7.4-21.8%) and 14.8% (95% CI 8.9-20.8%) respectively at 24 months (P=0.93). Clinical signs fell from 72.0% (95% CI 58.2-85.5%) and 61.3% (95% CI 44.0-78.5%) at baseline to 45.8% (36.0-55.6%) and 48.5% (34.0-62.9%) respectively at 24 months (P=0.69). At 24 months, estimated household latrine coverage and use were 80.8% and 61.7% respectively where there had been intensive latrine promotion and 30.0% and 25.0% respectively in the single treatment only arm. We were unable to detect a difference in the prevalence of ocular chlamydial infection in children due to latrine construction.

Risk factors for active trachoma in children and trichiasis in adults: a household survey in Amhara Regional State, Ethiopia

Identification of risk factors is essential for planning and implementing effective trachoma control programmes. We aimed to investigate risk factors for active trachoma and trichiasis in Amhara Regional State, Ethiopia. A survey was undertaken and eligible participants (children aged 1-9 years and adults aged 15 years and above) examined for trachoma. Risk factors were assessed through interviews and observations. Using ordinal logistic regression, associations between signs of active trachoma in children and potential risk factors were explored. Associations between trichiasis in adults and potential risk factors were investigated using conventional logistic regression. A total of 5427 children from 2845 households and 9098 adults from 4039 households were included in the analysis. Ocular discharge [odds ratio (OR)=5.9; 95% CI 4.8-7.2], nasal discharge (OR=1.6; 95% CI 1.3-1.9), thatch roof in household (OR=1.3; 95% CI 1.0-1.5), no electricity in household (OR=2.4; 95% CI 1.3-4.3) and increasing altitude (Ptrend<0.001) were independently associated with severity of active trachoma. Trichiasis was associated with increasing age (ORper 5 year increase=1.5; 95% CI 1.4-1.7), female gender (OR=4.5; 95% CI 3.5-5.8), increasing prevalence of active trachoma in children (Ptrend=0.003) and increasing altitude (Ptrend=0.015).