Botulism outbreak in a rural Ethiopia: a case series.

BACKGROUND: Foodborne botulism, a toxin-mediated illness caused by Clostridium botulinum, is a public health emergency. Types A, B, and E C. botulinum toxins commonly cause human disease. Outbreaks are often associated with homemade and fermented foods. Botulism is rarely reported in Africa and has never been reported in Ethiopia. CASE PRESENTATION: In March 2015, a cluster of family members from the Wollega, Oromia region, western Ethiopia presented with a symptom constellation suggestive of probable botulism. Clinical examination, epidemiologic investigation, and subsequent laboratory work identified the cause of the outbreak to be accidental ingestion of botulinum toxin in a traditional chili condiment called "Kochi-kocha," cheese, and clarified butter. Ten out of the fourteen family members who consumed the contaminated products had botulism (attack rate 71.4%) and five died (case fatality rate of 50%). Three of the patients were hospitalized, they presented with altered mental status (n = 2), profound neck and truncal weakness (n = 3), and intact extremity strength despite hyporeflexia (n = 3). The remnant food sample showed botulinum toxin type A with mouse bioassay and C. botulinum type A with culture. Blood drawn on day three of illness from 2/3 (66%) cases was positive for botulinum toxin type-A. Additionally, one of these two cases also had C. botulinum type A cultured from a stool specimen. Two of the cases received Botulism antitoxin (BAT). CONCLUSION: These are the first confirmed cases of botulism in Ethiopia. The disease occurred due to the consumption of commonly consumed homemade foods. Definite diagnoses of botulism cases are challenging, and detailed epidemiologic and laboratory investigations were critical to the identification of this case series. Improved awareness of botulism risk and improved food preparation and storage may prevent future illnesses. The mortality rate of botulism in resource-limited settings remains high. Countries should make a concerted effort to stockpile antitoxin as that is the easiest and quickest intervention after outbreak detection.

An Epidemic of Scurvy, Identified Based on Lower Extremity Swelling, in a Southern Ethiopian Prison.

In October 2016, we received reports of five deaths among prisoners with leg swelling of unknown etiology in southwestern Ethiopia. A descriptive cross-sectional study was conducted to investigate the outbreak. A suspected case was defined as a prisoner with leg swelling of unknown etiology noted between May 15, 2016 and November 29, 2016. A total of 118 suspected cases were identified with unilateral or bilateral leg swelling without an identifiable cause from a total of 2,790 prisoners. Eight of the suspected cases were thoroughly examined, and seven of these suspected cases had clinical findings consistent with scurvy. Three of the clinical cases had undetectable vitamin C levels in the serum. The attack rate for the prison was 4.2% (118/2,790), and 11 deaths were identified, making the case fatality rate 9.3% (11/118). Clinical cases of scurvy had symptoms of fatigue, myalgia, arthralgia, and signs of follicular hyperkeratosis, petechiae, peripheral edema, and oral lesions. All clinical cases had severe anemia with hemoglobin < 6.0 g/dL. The diet provided by the prison excluded fruits and vegetables. Scurvy was determined to be the cause of the outbreak, and vitamin C supplementation was promptly initiated. All symptomatic prisoners improved, and no further cases were identified in a 4-week follow-up period of active surveillance.

Correction: Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pmed.1002299.].

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide study.

BACKGROUND: Building on the declining trend of malaria in Ethiopia, the Federal Ministry of Health aims to eliminate malaria by 2030. As Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia, the use of primaquine is indicated for both transmission interruption and radical cure, respectively. However, the limited knowledge of the local prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its associated variants has hindered the use of primaquine. METHODS: Some 11,138 dried blood spot (DBS) samples were collected in 2011 as part of a national, household Malaria Indicator Survey, a multi-stage nationally representative survey of all malaria-endemic areas of Ethiopia. A randomly selected sub-set of 1414 DBS samples was successfully genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Considering the geographical position and ethnic mix of the country, three common variants: G6PD*A (A376G), G6PD*A- (G202A) and Mediterranean (C563T) were investigated. RESULTS: Of the 1998 randomly selected individuals, 1429 (71.5%) DBS samples were genotyped and merged to the database, of which 53.5% were from females. G6PD*A (A376G) was the only genotype detected. No sample was positive for either G6PD*A- (G202A) or Mediterranean (C563T) variants. The prevalence of G6PD*A (A376G) was 8.9% [95% confidence interval (CI) 6.7-11.2] ranging from 12.2% in the Southern Nations, Nationalities and Peoples' (95% CI 5.7-18.7) to none in Dire Dawa/Harari Region. CONCLUSION: The common G6PD*A- (G202A) or Mediterranean (C563T) variants were not observed in this nationwide study. The observed G6PD*A (A376G) mutation has little or no clinical significance. These findings supported the adoption of primaquine for P. falciparum transmission interruption and radical cure of P. vivax in Ethiopia. As the presence of other clinically important, less common variants cannot be ruled out, the implementation of radical cure will be accompanied by active haematological and adverse events monitoring in Ethiopia.

Epidemiology of influenza in Ethiopia: findings from influenza sentinel surveillance and respiratory infection outbreak investigations, 2009-2015.

BACKGROUND: Influenza is an acute viral disease of the respiratory tract which is characterized by fever, headache, myalgia, prostration, coryza, sore throat and cough. Globally, an estimated 3 to 5 million cases of severe influenza illness and 291 243-645 832 seasonal influenza-associated respiratory deaths occur annually. Although recent efforts from some African countries to describe burden of influenza disease and seasonality, these data are missing for the vast majority, including Ethiopia. Ethiopia established influenza sentinel surveillance in 2008 aiming to determine influenza strains circulating in the country and know characteristics, trend and burden of influenza viruses. METHODS: We used influenza data from sentinel surveillance sites and respiratory disease outbreak investigations from 2009 to 2015 for this analysis. We obtained the data by monitoring patients with influenza-like illness (ILI) at three health-centers, severe acute respiratory infection (SARI) at five hospitals and investigating patients during different respiratory infection outbreaks. Throat-swab specimens in viral transport media were transported to the national reference laboratory within 72 h of collection using a cold-chain system. We extracted viral RNA from throat-swabs and subjected to real-time PCR amplification. We further subtyped and characterized Influenza A-positive specimens using CDC real-time reverse transcription PCR protocol. RESULTS: A total of 4962 throat-swab samples were collected and 4799 (96.7%) of them were tested. Among them 988 (20.6%) were influenza-positive and of which 349 (35.3%) were seasonal influenza A(H3N2), 321 (32.5%) influenza A(H1N1)pdm2009 and 318 (32.0%) influenza B. Positivity rate was 29.5% in persons 5-14 years followed by 26.4% in 15-44 years, 21.2% in > 44 years and 6.4% in under five children. The highest positivity rate observed in November (37.5%) followed by March (27.6%), December (26.4%), October (24.4%) and January (24.3%) while the lowest positivity rate was in August (7.7%). CONCLUSION: In Ethiopia, seasonal Influenza A(H3N2), Influenza A(H1N1)pdm2009 and Influenza B viruses were circulating during 2009-2015. Positivity rate and number of cases peaked in November and December. Influenza is one of public health problems in Ethiopia and the need to introduce influenza vaccine and antivirus is important to prevent and treat the disease in future.

Epidemiology of measles in the metropolitan setting, Addis Ababa, Ethiopia, 2005-2014: a retrospective descriptive surveillance data analysis.

BACKGROUND: Measles is a highly infectious and serious respiratory viral disease which caused by a virus. It is a significant cause of illness and death worldwide. This data analysis was conducted to describe the trend and determine the reporting rate of measles cases in Addis Ababa to make recommendation for the government of the city to strengthening measles control interventions. METHODS: We obtained and extracted ten years (2005-2014) Addis Ababa city's measles surveillance data from national database. We carried out retrospective descriptive data analysis by time, place and person variables. We calculated cumulative and specific reporting rates by dividing measles cases (lab confirmed, epidemiologically linked and compatible cases) to respective population and multiplying by 100,000. We divided average of ten years measles cases to midyear population and multiplied by 100,000 to calculate annualized reporting rate. We analyzed non-measles febrile rash rate by dividing laboratory negative cases to total population and multiplying by 100,000. RESULTS: A total of 4203 suspected measles cases were identified. Among them 1154 (27.5%) were laboratory confirmed, 512 (12.2%) were clinically compatible, 52 (1.2%) were epidemiologically linked cases and the rest 2485 (59.1%) were IgM negative for measles which makes total measles cases 1718 (40.9%). Median age was 5 years with 2-18 years interquartile-range. The annualized measles reporting rate was 5.9, which was 40.2 among > 1 year, 11.5 among 1-4 years, 6.0 among 5-14 years, 4.1 among 15-44 years and 0.01 among ≥ 45 years per 100,000 population. Among the total measles cases; 380 (22%) were received at least one dose of measles containing vaccine (MCV) while 415 (24%) cases were not vaccinated and the vaccination status of 923 (54%) cases were not known. CONCLUSION: Our analysis revealed that the reporting rate was higher among young children than older age group. Among all the patients 22% were received at least one dose of measles vaccine whereas 13% were not vaccinated against measles antigen. Routine immunization should be strengthened to reach all children through well monitored vaccine cold chain management.

Sero-prevalence of yellow fever and related Flavi viruses in Ethiopia: a public health perspective.

BACKGROUND: Yellow fever (YF) is a viral hemorrhagic fever, endemic in the tropical forests of Africa and Central and South America. The disease is transmitted by mosquitoes infected with the yellow fever virus (YFV). Ethiopia was affected by the largest YF outbreak since the vaccination era during 1960-1962. The recent YF outbreak occurred in 2013 in Southern part of the country. The current survey of was carried out to determine the YF seroprevalence so as to make recommendations from YF prevention and control in Ethiopia. METHODOLOGY: A multistage cluster design was utilized. Consequently, the country was divided into 5 ecological zones and two sampling towns were picked per zone randomly. A total of 1643 serum samples were collected from human participants. The serum samples were tested for IgG antibody against YFV using ELISA. Any serum sample testing positive by ELISA was confirmed by plaque reduction neutralization test (PRNT). In addition, differential testing was performed for other flaviviruses, namely dengue, Zika and West Nile viruses. RESULT: Of the total samples tested, 10 (0.61%) were confirmed to be IgG positive against YFV and confirmed with PRNT. Nine (0.5%) samples were antibody positive for dengue virus, 15(0.9%) forWest Nile virus and 7 (0.4%) for Zika virus by PRNT. Three out of the five ecological zones namely zones 1, 3 and 5 showed low levels (< 2%) of IgG positivity against YFV. A total of 41(2.5%) cases were confirmed to be positive for one of flaviviruses tested. CONCLUSION: Based on the seroprevalence data, the level of YFV activity and the risk of a YF epidemic in Ethiopia are low. However additional factors that could impact the likelihood of such an epidemic occurring should be considered before making final recommendations for YF prevention and control in Ethiopia. Based on the results of the serosurvey and other YF epidemic risk factors considered, a preventive mass vaccination campaign is not recommended, however the introduction of YF vaccine in routine EPI is proposed nationwide, along with strong laboratory based YF surveillance.

Assessment of reporting sites for acute flaccid paralysis surveillance in Ethiopia: implications for planning of active case search visits.

INTRODUCTION: The World Health Organization acute flaccid paralysis (AFP) surveillance standards recommend documentation of the role of each potentially reporting site for evidence -based planning and tailoring support for active surveillance visits. This study assessed the contribution of various sites as source and quality of AFP cases reported over a five -year period in Ethiopia. METHODS: We conducted a retrospective analysis of AFP surveillance data collected from 2010-2014 in Ethiopia. Analyses were done using EPI-INFO version 7 for calculating frequencies and proportions, and testing possible associations between reporting sites and key dependent variables. RESULTS: Of the 5,274 AFP cases reported, hospitals and health centers reported 4627 (88%) of the cases. Hospitals in Addis Ababa (53%) and health posts in Benishangul Gumuz (48%) regions have contributed majority of the cases reported. Only 3% of cases were reported by private clinics nationally. The stool adequacy rate for health posts (81%) was lower than the overall national rate of 88% .Cases from health posts are more likely to be reported after 14 days of onset of paralysis, and 62% less likely to be investigated within two days of notification(OR: 1.82, 95% CI OR : 1.41-2.36, p-value <0.0001). Greater proportion (2.4%) of cases reported from health posts were either compatible, VDPV or WPV compared to cases reported by health centers (1.14%) or hospitals (1.4%). CONCLUSION: Though majority of the cases were reported by health centers followed by hospitals ,our findings suggest that all potentially reporting sites should be exhaustively identified, prioritized and regularly supported for quality case detection, investigation and reporting.

Elimination of Guinea Worm Disease in Ethiopia; Current Status of the Disease's, Eradication Strategies and Challenges to the End Game.

Dracunculiasis, also named Guinea Worm Disease (GWD), is one of the Neglected Tropical Diseases (NTDs) caused by a parasitic nematode known as Dracunculus medinensis and has been known since antiquity as 'fiery serpent' from Israelites. It is transmitted to humans via drinking contaminated water containing infective copepods. Given, its feasibility for eradication, the Guinea Worm Eradication Program (GWEP) was launched in 1980 with the aim of eradicating the disease. Since its inception, GWEP has made an extraordinary progress in interrupting transmission. Globally, the number of reported cases reduced from 3.5 million in 20 countries in 1986 to only 22 cases in 2015 from only four countries namely South Sudan, Mali, Chad and Ethiopia. Since Mali has interrupted transmission of GWD in 2016, currently, the disease remains endemic in only three sub-Saharan African countries namely, South Sudan, Chad and Ethiopia. Each endemic country has its own national Guinea Worm Eradication Program. In Ethiopia, the Ethiopian Dracunculiasis Eradication Program (EDEP) which was established in 1993 has made remarkable move towards interruption of disease transmission and now the endgame is fast approaching. The EDEP with support mainly from The Carter Center, WHO, and UNICEF has reduced GWD by more than 99% from 1994 to 2015. In 2015, only 3 indigenous cases in humans and 14 in animals (13 in dogs and 1 in baboon) were reported. In 2016, 3 human cases, 14 dogs and 2 baboon infections were reported.. Refugee influx from the Republic of South Sudan (RSS), increased animal infections with unknown role in transmission of Dracunculiasis, the presence of hard to reach communities and lack of safe water sources in remote non-village areas remain among important challenges at this final stage of GWD eradication in Ethiopia. This paper reviews progress made towards Guinea Worm Eradication with a focus on the experience of the Ethiopian Dracunculiasis Eradication Program (EDEP), and intervention strategies that need further intensification to realize the endgame. Eradication strategies encompassing community education for behavioral change including raising awareness towards cash reward for reporting Guniea Worm Disease (GWD) and animal infection, case containment, surveillance systems, provision of safe water supply, and ABATE chemical application are discussed. It also summarizes challenges the end game faces and recommendations to strengthen the eradication effort.

Reemergence of yellow fever in Ethiopia after 50 years, 2013: epidemiological and entomological investigations.

BACKGROUND: Yellow Fever (YF) is a viral hemorrhagic disease transmitted by aedes mosquito species. Approximately, 200,000 cases and 30,000 deaths occur worldwide every year. In Ethiopia, the last outbreak was reported in 1966 with 2200 cases and 450 deaths. A number of cases with deaths from unknown febrile illness reported from South Ari district starting from November 2012. This investigation was conducted to identify the causative agent, source of the outbreak and recommend appropriate interventions. METHODS: Medical records were reviewed and Patients and clinicians involved in managing the case were interviewed. Descriptive data analysis was done by time, person and place. Serum samples were collected for serological analysis it was done using Enzyme-linked Immunosorbent Assay for initial screening and confirmatory tests were done using Plaque Reduction and Neutralization Test. Breteau and container indices were used for the entomological investigation to determine the risk of epidemic. RESULTS: A total of 141 Suspected YF cases with 43 deaths (CFR = 30.5%) were reported from November 2012 to October 2013 from South Omo Zone. All age groups were affected (mean 27.5, Range 1-75 Years). Of the total cases, 85.1% cases had jaundice and 56.7% cases had fever. Seven of the 21 samples were IgM positive for YF virus. Aedes bromeliae and Aedes aegypti were identified as responsible vectors of YF in affected area. The Breteau indices of Arkisha and Aykamer Kebeles were 44.4% and 33.3%, whereas the container indices were 12.9% and 22.2%, respectively. CONCLUSION: The investigation revealed that YF outbreak was reemerged after 50 years in Ethiopia. Vaccination should be given for the affected and neighboring districts and Case based surveillance should be initiated to detect every case.

Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial.

BACKGROUND: Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia. METHODS AND FINDINGS: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia. CONCLUSIONS: Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. TRIAL REGISTRATION: ClinicalTrials.gov NCT01680406.

Epidemiology of rubella virus cases in the pre-vaccination era of Ethiopia, 2009-2015.

BACKGROUND: Rubella is a common mild rash illness caused by rubella virus. The majority of infections occur in children and young adults. The infection is the cause of a serious birth defect known as Congenital Rubella Syndrome (CRS) when a woman acquires infection early in pregnancy. Ethiopia has not yet established rubella virus surveillance and has not yet introduced rubella vaccine into the routine immunization program. We characterize the epidemiology of laboratory confirmed rubella virus cases collected through measles surveillance from 2009 to 2015 to better understand the burden of the disease in the country. METHODS: A descriptive analysis was made to characterize rubella cases reported through the national measles case based surveillance system. The measles case definition was used to capture potential rubella cases. A suspected measles case was a person with generalized rash and fever with cough, or coryza or conjunctivitis. Those cases whose sera were negative for measles IgM antibodies were tested for rubella IgM antibody. A confirmed rubella case was a person who tested positive for rubella IgM. Only laboratory confirmed rubella cases were analyzed in this article. RESULTS: Between 2009 and 2015, a total of 28,284 serum/plasma samples were collected and tested for measles IgM antibody and 11,151 (39.4%) were found positive. A total of 17,066 measles IgM negative or indeterminate samples were tested for rubella virus IgM and 2615 (15.3%) were found positive during the same period. Of 2615 confirmed rubella cases, 52.2% were females. The age of confirmed cases ranged from one month to 42 years with a mean age of 7.3 years. Three-fourth of all confirmed rubella cases were aged less than 10 years. The number of laboratory confirmed rubella cases linearly increased from 83 in 2009 to 856 in 2013 but dropped to 222 and 319 in 2014 and 2015 respectively. Higher number of cases occurred in the hot dry season (January through June) and in the central and western part of Ethiopia with 127 lab-confirmed outbreaks in the study period. CONCLUSIONS: Based on our analysis, rubella was found to be endemic throughout Ethiopia. Children below the age of 10 years were the most affected. The burden of rubella cases varied from year to year but had a seasonal peak in March. To better understand the magnitude of rubella prior to vaccine introduction, establishing rubella surveillance system, conducting sero-prevalence studies among child bearing age females and establishing CRS sentinel surveillance among young infants are critical.

SURVEILLANCE OF A CHRONIC LIVER DISEASE OF UNIDENTIFIED CAUSE IN A RURAL SETTING OF ETHIOPIA: A CASE STUDY.

BACKGROUND: An outbreak of a chronic liver disease of unidentified cause, known as "Unidentified Liver Disease (ULD)" by local communities was first observed in a rural village in Tigray, northern-Ethiopia in 2001. Little was known about the geographical extent, trend, and epidemiology of the disease. METHODS: The Ethiopian Public Health Institute (EPHI) by then Ethiopian Health and Nutrition Research Institute (EHNRI), Centers for Disease Control and Prevention, World Health Organization, and Tigray Regional Health Bureaue established the ULD surveillance system in 2009 to characterize and monitor trends for this emerging disease and to identify cases for treatment and follow up. A large-scale official training was provided to the surveillance staff on case identification, management and reporting. In absence of a confirmatory test, the system used simple case definitions that could be applied by frontline staff with varying clinical training. To maximize resources, health extension workers already conducting household visits in affected communities identified cases and increased community awareness about the disease. A team was placed in Shire, in close proximity to the outbreak region, to provide support and collect reports from health facilities and district health offices. RESULTS: As of September 2011, a total of 1,033 cases, including 314 deaths were identified. Contamination of locally produced grains with several pyrrolizidine alkaloid producing plants was identified cause of the disease. Staff interviews identified that shortage and turnover of trained staff were major challenges. LESSONS LEARNED: Long term dedication by frontline staff, using simple case definitions to identify cases, and active collection of missing reports were critical for surveillance of this chronic non-infectious disease of unknown cause in a rural, resource-limited setting.

Global Role and Burden of Influenza in Pediatric Respiratory Hospitalizations, 1982-2012: A Systematic Analysis.

BACKGROUND: The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. METHODS AND FINDINGS: We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (<6 mo, <1 y, <2 y, <5 y, 5-17 y, and <18 y). We applied this proportion to global estimates of acute lower respiratory infection hospitalizations among children aged <1 y and <5 y, to obtain the number and per capita rate of influenza-associated hospitalizations by geographic region and socio-economic status. Influenza was associated with 10% (95% CI 8%-11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%-7%) among children <6 mo to 16% (95% CI 14%-20%) among children 5-17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y-of which 228,000 (95% CI 150,000 to 344,000) occur in children <6 mo-and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza-associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings. CONCLUSIONS: Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo.

Time series analysis of trends in malaria cases and deaths at hospitals and the effect of antimalarial interventions, 2001-2011, Ethiopia.

BACKGROUND: The Government of Ethiopia and its partners have deployed artemisinin-based combination therapies (ACT) since 2004 and long-lasting insecticidal nets (LLINs) since 2005. Malaria interventions and trends in malaria cases and deaths were assessed at hospitals in malaria transmission areas during 2001-2011. METHODS: Regional LLINs distribution records were used to estimate the proportion of the population-at-risk protected by LLINs. Hospital records were reviewed to estimate ACT availability. Time-series analysis was applied to data from 41 hospitals in malaria risk areas to assess trends of malaria cases and deaths during pre-intervention (2001-2005) and post-interventions (2006-2011) periods. FINDINGS: The proportion of the population-at-risk potentially protected by LLINs increased to 51% in 2011. The proportion of facilities with ACTs in stock exceeded 87% during 2006-2011. Among all ages, confirmed malaria cases in 2011 declined by 66% (95% confidence interval [CI], 44-79%) and SPR by 37% (CI, 20%-51%) compared to the level predicted by pre-intervention trends. In children under 5 years of age, malaria admissions and deaths fell by 81% (CI, 47%-94%) and 73% (CI, 48%-86%) respectively. Optimal breakpoint of the trendlines occurred between January and June 2006, consistent with the timing of malaria interventions. Over the same period, non-malaria cases and deaths either increased or remained unchanged, the number of malaria diagnostic tests performed reflected the decline in malaria cases, and rainfall remained at levels supportive of malaria transmission. CONCLUSIONS: Malaria cases and deaths in Ethiopian hospitals decreased substantially during 2006-2011 in conjunction with scale-up of malaria interventions. The decrease could not be accounted for by changes in hospital visits, malaria diagnostic testing or rainfall. However, given the history of variable malaria transmission in Ethiopia, more data would be required to exclude the possibility that the decrease is due to other factors.

An outbreak of acute febrile illness caused by Sandfly Fever Sicilian Virus in the Afar region of Ethiopia, 2011.

In malaria-endemic regions, many medical facilities have limited capacity to diagnose non-malarial etiologies of acute febrile illness (AFI). As a result, the etiology of AFI is seldom determined, although AFI remains a major cause of morbidity in developing countries. An outbreak of AFI was reported in the Afar region of Ethiopia in August of 2011. Retrospectively, 12,816 suspected AFI cases were identified by review of medical records. Symptoms were mild and self-limiting within 3 days after the date of onset; no fatalities were identified. All initial test results of AFI patient specimens were negative for selected pathogens using standard microbiological and molecular techniques. High-throughput sequencing of nucleic acid extracts of serum specimens from 29 AFI cases identified 17 (59%) of 29 samples as positive for Sandfly Fever Sicilian Virus (SFSV). These results were further confirmed by specific reverse transcription polymerase chain reaction. This is the first study implicating SFSV as an etiological agent for AFI in Ethiopia.

In vivo efficacy of artemether-lumefantrine and chloroquine against Plasmodium vivax: a randomized open label trial in central Ethiopia.

BACKGROUND: In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used. METHODS AND FINDINGS: In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8-82.5) for AL and 90.8% (95% CI 83.6-94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1-95.1) for AL and to 97.2% (91.6-99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml. CONCLUSIONS: In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT01052584.

Influenza surveillance in 15 countries in Africa, 2006-2010.

BACKGROUND: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

Challenges of establishing routine influenza sentinel surveillance in Ethiopia, 2008-2010.

Ethiopia launched influenza surveillance in November 2008. By October 2010, 176 patients evaluated at 5 sentinel health facilities in Addis Ababa met case definitions for influenza-like illness or severe acute respiratory illness (SARI). Most patients (131 [74%]) were children aged 0-4 years. Twelve patients (7%) were positive for influenza virus. Most patients (109 [93%]) were aged <5 years, of whom only 3 (2.8%) had laboratory-confirmed influenza. Low awareness of influenza by healthcare workers, misperceptions regarding case definitions, and insufficient human resources at sites could have potentially led to many missed cases, resulting in suboptimal surveillance.

Analysis of malaria surveillance data in Ethiopia: what can be learned from the Integrated Disease Surveillance and Response System?

BACKGROUND: Routine malaria surveillance data is useful for assessing incidence and trends over time, and in stratification for targeting of malaria control. The reporting completeness and potential bias of such data needs assessment. METHODS: Data on 17 malaria indicators were extracted from the Integrated Disease Surveillance and Response System database for July 2004 to June 2009 (Ethiopian calendar reporting years 1997 to 2001). Reporting units were standardized over time with 2007 census populations. The data were analysed to show reporting completeness, variation in risk by reporting unit, and incidence trends for malaria indicators. RESULTS: Reporting completeness, estimated as product of unit-month and health facility reporting, was over 80% until 2009, when it fell to 56% during a period of reorganization in the Ministry of Health. Nationally the average estimated annual incidence of reported total malaria for the calendar years 2005 to 2008 was 23.4 per 1000 persons, and of confirmed malaria was 7.6 per 1,000, with no clear decline in out-patient cases over the time period. Reported malaria in-patient admissions and deaths (averaging 6.4 per 10,000 and 2.3 per 100,000 per year respectively) declined threefold between 2005 and 2009, as did admissions and deaths reported as malaria with severe anaemia. Only 8 of 86 reporting units had average annual estimated incidence of confirmed malaria above 20 per 1,000 persons, while 26 units were consistently below five reported cases per 1,000 persons per year. CONCLUSION: The Integrated Disease Surveillance and Response System functioned well over the time period mid 2004 to the end of 2008. The data suggest that the scale up of interventions has had considerable impact on malaria in-patient cases and mortality, as reported from health centres and hospitals. These trends must be regarded as relative (over space and time) rather than absolute. The data can be used to stratify areas for improved targeting of control efforts to steadily reduce incidence. They also provide a baseline of incidence estimates against which to gauge future progress towards elimination. Inclusion of climate information over this time period and extension of the dataset to more years is needed to clarify the impact of control measures compared to natural cycles on malaria.