Linked vaccination coverage surveys plus serosurveys among Ethiopian toddlers undertaken three years apart to compare coverage and serologic evidence of protection in districts implementing the RED-QI approach.

In low and middle-income countries, estimating the proportion of vaccinated toddlers in a population is important for controlling vaccine-preventable diseases by identifying districts where immunization services need strengthening. Estimates measured before and several years after specific interventions can assess program performance. However, employing different methods to derive vaccination coverage estimates often yield differing results. METHODS: Linked vaccination coverage surveys and seroprotection surveys performed among ~300 toddlers 12-23 months of age in districts (woredas), one per region, of Ethiopia (total, ~900 toddlers) in 2013 to estimate the proportion vaccinated with tetanus toxoid (a proxy for pentavalent vaccine) and measles vaccine. The surveys were followed by implementation of the Reaching Every District using Quality Improvement (RED-QI) approach to strengthen the immunization system. Linked coverage/serosurveys were repeated in 2016 to assess effects of the interventions on vaccination coverage. Indicators included "documented coverage" (vaccination card and/or health facility register records) and "crude coverage" (documented plus parent/caretaker recall for children without cards). Seroprotection thresholds were IgG-ELISA tetanus antitoxin ≥0.05 IU/ml and plaque reduction neutralization (PRN) measles titers ≥120 mIU/ml. FINDINGS: Improved markers in 2016 over 2013 include coverage of pentavalent vaccination, vaccination timeliness, and fewer missed opportunities to vaccinate. In parallel, tetanus seroprotection increased in the 3 woredas from 59.6% to 79.1%, 72.9% to 83.7%, and 94.3 to 99.3%. In 2015, the Ethiopian government conducted supplemental measles mass vaccination campaigns in several regions including one that involved a project woreda and the campaign overlapped with the RED-QI intervention timeframe; protective measles PRN titers there rose from 31.0% to 50.0%. INTERPRETATION: The prevalence of seroprotective titers of tetanus antitoxin (stimulated by tetanus toxoid components within pentavalent vaccine) provides a reliable biomarker to identify children who received pentavalent vaccine. In the three study woredas, the RED-QI intervention appeared to improve immunization service delivery, as documented by enhanced pentavalent vaccine coverage, vaccination timeliness, and fewer missed vaccination opportunities. A measles mass vaccination campaign was followed by a markedly increased prevalence of measles PRN antibodies. Collectively, these observations suggest that wider implementation of RED-QI can strengthen immunization, and periodic linked vaccination surveys/serosurveys can monitor changes.

Establishment of COVID-19 testing laboratory in resource-limited settings: challenges and prospects reported from Ethiopia.

The Coronavirus pandemic is recording unprecedented deaths worldwide. The temporal distribution and burden of the disease varies from setting to setting based on economic status, demography and geographic location. A rapid increase in the number of COVID-19 cases is being reported in Africa as of June 2020. Ethiopia reported the first COVID-19 case on 13 March 2020. Limited molecular laboratory capacity in resource constrained settings is a challenge in the diagnosis of the ever-increasing cases and the overall management of the disease. In this article, the Ethiopian Public Health Institute (EPHI) shares the experience, challenges and prospects in the rapid establishment of one of its COVID-19 testing laboratories from available resources. The first steps in establishing the COVID-19 molecular testing laboratory were i) identifying a suitable space ii) renovating it and iii) mobilizing materials including consumables, mainly from the Malaria and Neglected Tropical Diseases (NTDs) research team at the EPHI. A chain of experimental design was set up with distinct laboratories to standardize the extraction of samples, preparation of the master mix and detection. At the commencement of sample reception and testing, laboratory contamination was among the primary challenges faced. The source of the contamination was identified in the master mix room and resolved. In summary, the established COVID-19 testing lab has tested more than 40,000 samples (August 2020) and is the preferred setting for research and training. The lessons learned may benefit the further establishment of emergency testing laboratories for COVID-19 and/or other epidemic/pandemic diseases in resource-limited settings.

Rotavirus-associated acute diarrhea outbreak in West Shewa Zone of Oromia Regional State, Ethiopia, 2017.

INTRODUCTION: Rotavirus causes severe-diarrheal diseases in infants. An estimation of 138 million rotavirus-associated diarrheal cases and 215,000 deaths occur every year globally. In December 2016, West-Shewa zone in Ethiopia reported unidentified gastrointestinal diarrhea outbreak. We investigated to identify the causative agent of the outbreak to support response operations. METHODS: Medical records were reviewed, and the daily line list was collected from health facilities. Descriptive data analysis was done by time, person and place. Stool specimens were first tested by antigen capture enzyme immunoassay (EIA) technique and further confirmed by reverse-transcription polymerase chain reaction (RT-PCR) as a gold standard. The product of RT-PCR was genotyped for each gene using G1-G4, G8-G9 and G12 primers for VP7 gene and P(4), P(6), P(8) and P(14) primers for VP4 gene. RESULTS: A total of 1,987 diarrheal cases (5.7 per 1000) and five deaths (case-fatality rate 0.25%) were identified and epidemiologically-linked to confirmed rotavirus from December 2016 to February 2017. Among the cases, 1,946 (98%) were < 5 children. Fourteen (74%) of the 19 tested stool specimens were positive for rotavirus by EIA and RT-PCR. Majority of strains detected were G12P(6) (25%) and G-negative P(8) (25%) followed by G9P(8) (19%), G1P(8) (13%) and G3/G2 P(8), G12P(8), and G-negative P(6) (6% each). CONCLUSION: Diarrheal outbreak which occurred in West-Shewa zone of Ethiopia was associated with rotavirus and relatively more affected districts with low vaccination coverage. Routine rotavirus vaccination quality and coverage should be evaluated and the surveillance system needs to be strengthened to detect, prevent and control a similar outbreak.

Impact of rotavirus vaccine introduction and genotypic characteristics of rotavirus strains in children less than 5 years of age with gastroenteritis in Ethiopia: 2011-2016.

INTRODUCTION: A monovalent rotavirus vaccine was introduced in the Ethiopian Expanded Program on Immunization from November 2013. We compared impact of rotavirus vaccine introduction on rotavirus associated acute diarrhea hospitalizations and genotypic characteristics of rotavirus strains pre-and post-vaccine introduction. METHODS: Sentinel surveillance for diarrhea among children <5 years of age was conducted at 3 hospitals in Addis Ababa, Ethiopia from 2011 to 2017. Stool specimens were collected from enrolled children and tested using an antigen capture enzyme immunoassay. Rotavirus positive samples (156 from pre- and 141 from post-vaccination periods) were further characterized by rotavirus genotyping methods to identify the predominant G and P types circulating during the surveillance era. RESULTS: A total of 788 children were enrolled during the pre- (July 2011-June 2013) and 815 children during the post-vaccination (July 2014-June 2017) periods. The proportion of diarrhea hospitalizations due to rotavirus among children <5 years of age declined by 17% from 24% (188/788) in the pre-vaccine period and to 20% (161/185) in post-vaccine introduction era. Similarly, a reduction of 18% in proportion of diarrhea hospitalizations due to rotavirus in children <12 months of age in the post (27%) vs pre-vaccine (33%) periods was observed. Seasonal peaks of rotavirus declined following rotavirus vaccine introduction. The most prevalent circulating strains were G12P[8] in 2011 (36%) and in 2012 (27%), G2P[4] (35%) in 2013, G9P[8] (19%) in 2014, G3P[6] and G2P[4] (19% each) in 2015, and G3P[8] (29%) in 2016. DISCUSSION: Following rotavirus vaccine introduction in Ethiopia, a reduction in rotavirus associated hospitalizations was seen in all age groups with the greatest burden in children <12 months of age. A wide variety of rotavirus strains circulated in the pre- and post-vaccine introduction periods.

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.

Epidemiology of laboratory confirmed measles virus cases in the southern nations of Ethiopia, 2007-2014.

BACKGROUND: In Ethiopia, measles case-based surveillance was introduced in 2004 as one strategy for measles control by laboratory confirmation of suspected cases. In this article, epidemiological distribution of laboratory-confirmed measles cases were reported from the Southern Nation Nationalities and Peoples Region (SNNPR) of Ethiopia between 2007 and 2014, as the region is one of the highly measles affected areas in Ethiopia. METHOD: A serum sample was collected from all measles suspected cases, and patient information was captured by case reporting format (CRF). Samples were transported to the National Measles Laboratory for Measles IgM testing by ELISA technique. Data entry and analysis were done using Epi-Info 3.5.4 software. RESULT: A total of 4810 samples were tested for measles IgM using ELISA technique and 1507 (31.3%) were found positive during 2007-2014 in SNNPR of Ethiopia. Patients with age 1-4 years were the most affected regardless of sex. The incidence of measles confirmed cases increased from 15 in 2007 to 180 in 2013 per million population. The highest percentage of laboratory-confirmed cases were found in 2014. Measles was found distributed throughout the regional state. CONCLUSION: Measles was found a public health important disease in SNNPR of Ethiopia, mostly affecting children 1-4 years. The incidence of measles cases is increasing from time to time. Additional research to determine the genotype of circulating measles virus, knowledge, attitude and practice of professionals and the population for measles vaccination and infection in the region is important. A wide age group measles vaccination campaign is highly recommended.

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.

Epidemiology of laboratory confirmed measles virus cases in Amhara Regional State of Ethiopia, 2004-2014.

BACKGROUND: Measles is a highly contagious viral infection causing large outbreaks all over the world. Despite the availability of safe and cost effective vaccine, measles remained endemic with persistent periodic outbreaks in the Horn of Africa. The aim of this study is to characterize laboratory confirmed measles cases in Amhara Regional State, which was one of the highly affected regions in Ethiopia. METHOD: A suspected measles case was defined as any person presenting with fever, maculopapular rash and one or more of the three symptoms cough, coryza or conjunctivitis or a patient in whom a clinician suspects measles. A blood sample was collected for any measles suspected patient with a case based investigation form and specimen transported to the National Measles Laboratory in good condition where it was to be tested for Measles IgM antibody by ELISA technique. Data was entered and analyzed using Epi-Info 3.5.4 software. RESULT: A total of 6579 samples were tested for measles IgM among 7296 samples collected in Amhara Regional State over 11 years (2004-2014). Of the tested samples, 2412 (36.7%) were found positive, while 3965 and 202 samples were found to be negative and equivocal (compatible) respectively. Patients with age ≥ 10 years were the most affected. The highest number of laboratory confirmed measles cases were detected in 2014 and cases were occurred in all of the 11 zones of the state. A seasonal peak was noted in the hot-dry season of the year. CONCLUSION: Measles remains to be a public health problem in Amhara Regional State of Ethiopia, mostly affecting people ≥ 10 years of age. Measles virus was detected in all zones of the state, reaching its peak in the hot-dry season. To reduce the incidence of measles, it is highly recommended to improve routine immunization, and conduct a wide age group campaign. Additional research to evaluate the knowledge, attitudes and practices of the general population and health care professionals about measles infection and vaccination is important. Genotyping of circulating measles virus strain is recommended.

Evaluation of anthelmintic potential of the Ethiopian medicinal plant Embelia schimperi Vatke in vivo and in vitro against some intestinal parasites.

BACKGROUND: Embelia schimperi has been used for the treatment of intestinal parasites especially tapeworm infestations for centuries in Ethiopia. However, there is lack of scientific based evidences regarding the efficacy, safety and phytochemical analysis of this plant despite its frequent use as an anthelmintic. This study has therefore evaluated the efficacy and acute toxicity of E. schimperi thereby generating relevant preclinical information. METHODS: The anthelmintic activities of the crude hydroalcoholic extract of E. schimperi and the isolated compound, embelin, were conducted using in vivo and in vitro models against the dwarf tapeworm, Hymenolepis nana, and the hookworm, Necator americanus, respectively. LD50 of the crude hydroalcoholic extract was determined using Swiss albino mice following the OECD guidelines. Chemical characterization of the isolated embelin was conducted using UV-spectroscopy, HPLC and NMR. RESULTS: In the acute toxicity study no prominent signs of toxicity and mortality were recorded among the experimental animals at the highest administered dose. Hence the LD50 of the plant was found to be higher than 5000 mg/kg. In vivo cestocidal activity of the crude hydroalcoholic extract of E. schimperi showed 100% parasite clearance at 1000 mg/kg, while the diammonium salt of embelin showed 85.3% parasite clearance at 750 mg/kg. The in vitro anthelminthic activity study revealed that the LC50 value of the crude extract and albendazole were 228.7 and 51.33 µg/mL, respectively. CONCLUSION: The results clearly indicated that the hydroalcoholic extract of E. schimperi and the diammonium salt of the isolated compound embelin had anthelmintic activity against hookworm larva in vitro and H. nana in vivo. Hence the findings of this study showed Embelia schimperi appears to possess some anthelmintic activity that may support the usage of these plants by local traditional healers to treat helminthic infestations.