Sunday, 24 September 2017

Immninisable Diseases Unit

Immunisable Diseases Unit     

The Immunisable Diseases Unit started work on the polio virus in the 1950s. Vaccine efficacy studies started in 1960’s. In the 1970’s work on polio and measles diseases and their vaccines continued. In 1999, the laboratory was designated as a WHO inter-country polio and measles laboratory surveillance. It has since served various countries in response to a WHO request. Sequencing technology for measles and rubella was established in the laboratory. This capacity will be used to expand the scope of work at the lab and the Institute in general. Currently the laboratory serves Uganda, Rwanda, Burundi, and Tanzania. In 2000 the Division was designated a WHO Regional Referral laboratory and is currently serving Kenya, Tanzania, Rwanda, Burundi, Ethiopia, Eritrea and Comoros.

The Unit lab is mandated to conduct surveillance and research on vaccine preventable diseases in support of Uganda National Expanded Program for Immunization (UNEPI). It also provides laboratory support for acute flaccid paralysis (AFP) surveillance to countries in the Great Lakes Region. It functions as a WHO measles regional reference laboratory (training, QC testing, accreditation visits, distribution of supplies, lab testing and research).

The Unit is mandated to:
•    Carry out surveillance and research on vaccine preventable diseases to support UNEPI, WHO, MOH and partners.
•    Provide lab support for AFP surveillance for the countries in the Great Lakes Region.
•    Function as a WHO Measles Regional Reference Laboratory.
•    Conduct vaccine efficacy studies.

Objectives

  • To conduct laboratory backed surveillance and related research on measles, polio and other vaccine preventable diseases in support of the Uganda National Expanded Program on Immunization (UNEPI)
  • To carry out laboratory analysis of AFP samples delivered from within the country and the countries served.  Analysis is done in cell cultures and at molecular levels. 
  • To carry out laboratory analysis of measles samples in support of the measles control strategies.  Analysis is done at serological and molecular levels. 
  • To distribute measles, rubella kits and PT panels to the national laboratories served in the region. 
  • To offer laboratory expertise and training in the area of vaccine preventable diseases to health workers, students of higher education and affiliated net work laboratories served in the region.
  • To maintain high standard bio-safety and bio-security procedures essential for the containment of polio as a pre-requisite in the eradication era and to contain other infectious agents handled in the laboratory.
  • To provide laboratory support on vaccination programs through laboratory based vaccine potency tests,  field support during vaccination activities, field monitoring of proper vaccine administration,  laboratory based detection of adverse events following vaccination (AEFI)  and establishment of sero-conversion following vaccination.

 

Unit Division Studies

 


Estimating the population immunity to polio among Ugandan adults and estimating the sero-prevalence to measles and rubella among Ugandan women - PLANNED


Polio, measles, and rubella are important vaccine-preventable diseases for which this study seeks to characterize the population susceptibility to each in Uganda. One objective is to estimate population immunity to polio by region, age, and sex by measuring neutralizing antibodies against poliovirus serotypes (P1, P2, and P3) in 3000 serum samples collected during the 2010 Uganda AIDS Indictor Survey (UAIS) using polio neutralization assays. The other objectives are to estimate sero-prevalence, as a surrogate for population immunity, to measles and rubella by measuring measles-specific and rubella-specific IgG antibodies in 1000 serum samples collected among pregnant mothers during the 2010 Antenatal care (ANC) sero-prevalence survey using commercial IgG ELISA kits with confirmatory testing of selected measles negative/indeterminate samples by plaque reduction neutralization testing. By estimating population immunity to polio, measles, and rubella through measuring seropositivity among adults, susceptible populations might be identified and preventive vaccination efforts planned to close immunity gaps in targeted age groups. Characterizing population immunity to polio in a variety of settings among adults, particularly in areas at high-risk of importations will help to better target global prevention efforts. Understanding rubella susceptibility in pregnant women will provide practical knowledge towards elucidating the burden of disease and need for introduction of rubella vaccine, and how that introduction might be combined with accelerated measles vaccination activities.


 

Prospective evaluation of Acute Febrile Illness (AFI) epidemiology and associated impacts of climatic and environmental factors in Uganda-collaboration with the Arbovirology department at UVRI - ONGOING

This study is the second phase of a two-phase, one-year pilot collaborative investigation between U.S. Centers for Disease Control and Prevention (CDC) and Uganda Virus Research Institute (UVRI) to evaluate the impact of changing climatic and environmental factors on the incidence and distribution of AFI and a subset of AFI-causing agents in Uganda. The first phase study was a 10-year retrospective evaluation of clinical records for incident cases of AFI in selected survey regions in Uganda.

This study estimates the contribution to the overall burden of AFI of each of the specific AFI-causing diseases of interest identified by UVRI and the Uganda Ministry of Health (UMoH).These diseases are malaria, typhoid fever, leptospirosis, brucellosis, and selected arboviral and rickettsial pathogens. It is a clinic-based study which seeksto obtain clinical, epidemiological and diagnostic information on patients presenting with undifferentiated AFI at selected clinics within the survey regions in Uganda. Once completed, it will provide baseline data on the incidence and distribution of each of these diseases in each of the study regions. This baseline surveillance data will be introduced into the analytic models developed during the first, retrospective phase of this investigation to model the variations in the incidence and distribution of AFI and the specific AFI-causing diseases of interest relative to environmental and climatic changes and changes in those conditions. 

Development of Point of Care tests to assess immunity to tetanus and measles using oral fluid samples – ONGOING

WHO estimates that between 2 and 3 million child deaths are prevented through vaccination annually. However, many more deaths could be prevented through optimal use of currently existing vaccines. The identification of populations where vaccination programmes have failed to reach has a critical role to play in this objective. The implantation of routine immunization programmes has traditionally been measured by vaccine coverage achieved with the third dose of diphtheria-pertussis-tetanus (DPT3) among children aged 12-23months. A similar approach is used for measles. The gold standard methods for assessment of immunity to tetanus and to measles, which use serum samples, is by in-vivo toxin neutralisation tests using mice and in-vitro plaque reduction neutralisation tests (PRNT) respectively. These tests are technically demanding and require specialised laboratory facilities. Consequently, relatively simpler tests such as ELISA are widely used to measure antibodies in serum to tetanus and to measles but these assays have the disadvantage of requiring the sample to be transported and tested at sites remote from the point of collection. The delay in testing may result in lost opportunity to implement control measures. The objective of this study therefore, is to develop point of care tests for the detection of tetanus toxoid IgG and for measles specific IgG in capillary blood and oral fluid samples at the point of collection. The aim is to produce an impressive test that generates an unambiguous/objective result within 20minutes of collecting samples on a sustainable commercial basis. This will also enable the results to be accessed in real time and at remote local and national centres.

 

Rotaviruses in Uganda: Molecular epidemiology and potential of zoonotic transmission– ONGOING

Rotaviruses (RVs) are a major cause of severe acute diarrhoea in children and in the young of many mammalian and avian species. It has been reported that some RV strains isolated from humans and animals share genetic and antigenic features. The factors promoting inter-species transmission of animal RVs to humans and vice versa are poorly understood. Close contact between animals and humans may facilitate interspecies transmission, and genetic reassortment during co-infection with RV strains from different species may result in the generation of progeny viruses with novel or unusual genotypes. This may have implications for the efficacy and further development of RV vaccines and control of RV infections. The objectives of the study are to determine the prevalence of RV infection among hospitalized under five children in Uganda as well as prevalence among their household contacts and domestic animals; to describe the characteristics of RV diarrhea among under-fives as well as RV infection in household contacts and domestic animals i.e. demographic and clinical characteristics, genotypes and sequences, to compare the genotypes and sequences of RV in symptomatic children, asymptomatic family members and domestic animals and to identify the factors that contribute to interspecies transmission of RV (social- economic, clinical, demographic).

Operational Research

1. Sero-prevalence and factors associated with rubella infection in pregnant women attending antenatal care at Mulago National Referral Hospital

Rubella infection occurring during pregnancy is of great public health concern since it may cause severe health outcomes in the fetus or embryo. These include: miscarriage (spontaneous abortion), stillbirth and critical birth defects such as deafness, blindness, congenital heart disease and mental retardation which together are referred to as congenital rubella syndrome (CRS). It is estimated that over 110,000 infants are born each year with CRS making rubella a global leading cause of preventable congenital defects. The highest global CRS burden is said to be found in the South-East Asia and African Regions of the World Health Organization (WHO) that account to approximately 48% and 38% respectively. Rubella is still endemic among developing countries because of absence of/poor control programs in place.  A global survey on rubella and CRS during 1995-1996 by WHO indicated a CRS incidence of 0.6 – 2.2 cases/1000 live births during epidemics in developing countries. However, in the American Region, elimination goal for rubella and CRS by 2010 was achieved while in the European Region, this goal is set for 2015.  In the Western Pacific Region (WPR), accelerated rubella control and CRS prevention strategies are already in place. Although rubella CRS cases are estimated to be high in Africa, lack of a good surveillance system in place results in underreporting of such cases. In addition, majority of the countries in the region lack rubella vaccination in their immunization schedules and hence underestimation of rubella and CRS burden in the region. In Uganda, rubella is not reportable and it is not screened for during pregnancy despite the serious consequences associated with it. However, there is laboratory evidence of rubella infection detected during measles laboratory-backed surveillance. Laboratory confirmation of rubella has continued to be reported as sporadic cases and sometimes in outbreak proportions in various parts of the country since 2005. Despite this evidence, rubella infection among pregnant women remains unknown and laboratory diagnostics are not available in all health facilities therefore, the aim of this study is to determine the sero-prevalence and factors associated with rubella infection in pregnant women attending ANC services at Mulago National Referral Hospital in order to estimate the magnitude of the disease burden in Uganda.

Characterization by the micro-neutralization test and demographic description of non-polio enteroviruses that grow on L20B cell line  

There is evidence of non-polio enteroviruses (NPENTs) that grow on L20B cell line even though the current polio isolation protocol recommended in the WHO polio laboratory network, assumes selectivity of this cell line for polio virus. A study done among children below 15 years who presented with AFP in Cuba indicated that the L20Bcell line had a selectivity of 90.7% and that a proportion of NPENTs (9.3%) such as coxsackieA virus types 4, 8, and 10 grew well on this cell line confounding the standard procedure used in polio identification. Thus the main objective of this study is to characterize by Micro-neutralization test, all the Non Polio Enteroviruses (NPENTs) that preferentially grow on L20B cell line as kept in the EPI laboratory Entebbe from 2000 to 2014.

 Follow up of AFP cases with Sabin isolates

The oral poliovirus vaccine (OPV) constitutes of live attenuated strains of each of the three serotypes which have been selected by numerous passages of wild-type strains in monkey tissues in vivo and in vitro. The OPV strains (Sabin 1, 2, and 3) replicates in the human gut and induce a strong and long-lasting immune-response. However, in rare cases, OPV strains have been implicated in vaccine-associated paralytic poliomyelitis (VAPP). The objectives of this research are to assess any case that has been confirmed as a Sabin for any residual paralysis; to assess the immunological status of the said case and to confirm whether the case is still excreting the virus.

Accuracy of in-house molecular assay for diagnosis of hepatitis E virus during active surveillance in northern Uganda

Determining the accuracy of a new hepatitis E Virus (HEV) diagnostic test is a challenge due to the absence of a gold standard test. The World Health Organization proposes the use of a composite reference standard (CRS) to address such a situation. The CRS combines the results of imperfect reference tests to define a better reference standard. The purpose of this study was to determine the accuracy of in-house RT-PCR (molecular) assay for HEV diagnosis, using a CRS obtained by use of IgG and IgM serological assays.




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