Acute Rubella Infection Research Articles

Susceptibility to Rubella Infection and Incidence of Congenital Rubella Infection: 6 Years Retrospective Study.

IntroductionRubella is considered one of the most serious and most common congenital infections. Despite global efforts for elimination, rubella cases are still being reported in many parts of the world. The purpose of this study is to determine the level of immunity to rubella in the community and most importantly among women at childbearing age in the eastern province of Saudi Arabia and compare it with the target set by the World Health Organization (WHO) along with the incidence of acute rubella infection and the associated congenital rubella infection and congenital rubella syndrome.MethodsThis is a retrospective cross-sectional study over the six years period (Jan 2014–Jun 2020) on all individuals tested for rubella IgM and IgG in a university teaching hospital.ResultsNighty one percent (15,894/17,469) of the population tested showed evidence of rubella immunity with 8.8% (1546/17,469) being susceptible. Among women at childbearing age, susceptibility to rubella was higher with 9.2% (1220/13,278) of women showing no evidence of immunity. In addition, acute rubella infection was reported for 0.17% (29/17,469) of the population tested and 0.15% (20/13,278) in women at childbearing age. No cases of congenital rubella infection were reported in the study period.DiscussionThe level of Rubella immunity in the population is 91% and is less than the WHO target for rubella control therefore, risk of resurge of cases is present, indicating the need for continued national surveillance and more efforts to improve vaccination coverage in the kingdom.

Impact of Syrian refugees on congenital TORCH infections screening in Turkey

To demonstrate the effect of the Syrian refugee population on the prevalence of congenital TORCH (Toxoplasmosis, Other [syphilis, varicella-zoster, parvovirus B19], Rubella, Cytomegalovirus [CMV] and Herpes) infections and to evaluate the cost-effectiveness of population-based TORCH screening during pregnancy in Turkey. Pregnant women (n = 9754) were enrolled. Ultrasonographic findings, immunoglobulin (Ig)M and IgG seropositivity, avidity, amniocentesis and DNA-polymerase chain reaction (PCR) results were compared. Costs were calculated based on invoice amounts from the Health Applications Communique pricing system. The prevalence of TORCH seropositivity in Turkey was not significantly different between all regions (P > 0.05). Overall, 1333 (13.67%) pregnant Syrian refugees were included in the study. Acute CMV, rubella and Toxoplasma gondii infections (according to low IgG avidity in IgM positive patients) were detected in 17.82%, 21.53% and 14.07% of women, respectively. Twenty-four women underwent an amniocentesis procedure and nine of them had positive DNA-PCR and reverse transcription-PCR results. All women with positive results opted to terminate the pregnancy. There was no statistical difference among groups according to the rate of low IgG avidity in IgM-positive patients and termination rates for T. gondii, rubella and CMV (P > 0.05). Total cost for screening the entire study population was presented in US dollars (USD). A total of 71 529 and prenatal diagnosis with positive invasive test results were obtained in nine women: toxoplasmosis in four, CMV in three and rubella in two women. Population-based screening for prenatal TORCH infections is not cost-effective in Turkey. Syrian refugees have a limited effect on the increasing prevalence of congenital TORCH infections.

Epidemiology of acute rubella infection in Zambia during the pre-vaccination period (2005\u20132016) as a baseline for monitoring rubella epidemiology in the post-rubella vaccine introduction era

BackgroundRubella is highly under reported in Zambia as in most sub-Saharan countries despite being a disease of major public health concern especially among women of childbearing age. In September 2016, Zambia introduced a combined measles-rubella vaccine in children 0–14 years. In this study, we estimated the proportion positive for acute rubella among suspected but negative measles cases between 2005 and 2016 and determined its correlates for monitoring rubella epidemiology post-rubella vaccine introduction.MethodsIn a retrospective study, 4497 measles IgM negative serum samples from 5686 clinically suspected measles cases were examined for rubella IgM antibodies using the Siemens, Enzygnost® ELISA kit at the national measles laboratory. Data on demographics, year and month of onset were extracted from the surveillance data. Multivariate logistic regression analysis using backward variable selection was conducted to determine independent predictors for acute rubella. The magnitude of association was estimated using adjusted odds ratio with a 95% confidence interval.ResultsOverall, a proportion of 29.2% (1313/4497) affecting mostly those between 5 and 24 years was determined. Only age, province, month and year were independently associated with acute rubella. The regional proportions varied from 21.8–37.3% peaking in the month of October. Persons in the age group 10–14 years (Adjusted Odds Ratio [AOR] = 2.43; 95% CI [2.01–2.95]) were more likely while those aged < 1 year less likely (AOR = 0.31; 95% CI [021–0.48]) to have acute rubella compared to those aged 25 years or older. Persons in 2010 were less likely (AOR = 0.12; CI [0.05, 0.28]) to have acute rubella compared to those in 2016. While acute rubella was more likely to occur between July and November compared to December, it was less likely to occur between February and May.ConclusionsRubella virus was circulating in Zambia between 2005 and 2016 affecting mostly persons in the age group 5–24 years peaking in the hot dry season month of October. Although vaccination against rubella has been launched, these baseline data are important to provide a reference point when determining the impact of the vaccination program implemented.

Seroprevalence and pregnancy outcome in Rubella infection in antenatal women with bad obstetric history: A case control study

Seroprevalence and pregnancy outcome in Rubella infection in antenatal women with bad obstetric history: A case control study - IJOGR- Print ISSN No: - 2394-2746 Online ISSN No:- 2394-2754 Article DOI No:- 10.18231/2394-2754.2019.0006, Indian Journal of Obstetrics and Gynecology Research-Indian J Obstet Gynecol Res

Association of Interleukin-6, Interleukin-17 and Angiopoietin in Different Infections, Thyroid Stimulating Hormone, Demographic and Socioeconomic Characteristics in Women with Bad Obstetric History, Kirkuk, Iraq.

Background: Bad obstetric history [BOH] is associated with microbiological infections and abnormal immunological responses.Study design: Descriptive Case Control Study.Aim: to determine the association of interleukin-6 (IL-6), interleukin-17 (IL-17) and angiopoietin with infectivity inn female within Bad obstetric history, in Kirkuk city, Iraq.Materials and method: The study included 547 Bad obstetric histories within Bad obstetric history and 291 female with normal pregnancy outcome. The test performed to detect IL-6, IL-17 and angiopoietin in 60 women with BOH, of them 20 were pregnant and 20 were non-pregnant at time of enrolment in the study. In addition, 20 female with inevitable abortion be included in the study. Also thee study included 28 women with normal pregnancy as control and 14 of them were pregnant and 14 were non-pregnant. Serological study carried out to determine IL-6, IL-17 and Angiopoietin using ELISA kits.Results: IL-17 significantly lower in parvovirus 19 acute infection. Angiopoietin was significantly lower in Toxoplasma gondii infected women, while IL-6 was significantly higher in acute rubella infection as compared to non-infected. Angiopoietin was significantly higher in women with positive TPO autoantibodies. Smoking, animal exposure and low haemoglobin (&lt;11) were associated with decrease in IL-6, while IL-17 was significantly higher in women with history of animal exposure.Conclusion: IL-6, IL-17 and angiopoietin may be influenced by infections in women with BOH, however, this need to be evaluated in a large scale study.

DETECTION OF MEASLES AND RUBELLA ANTIBODIES IN DRIED BLOOD SPOTS

This study aimed to determine the frequency of detection of measles and rubella antibodies in dried blood spots in Bulgaria.&#x0D; Material and Methods: Two types of clinical material, serum samples and dried blood spots (DBS), were tested from a total of 101 patients. Serological methods (indirect ELISA) were used for detection of specific viral markers (IgM and IgG antibodies) indicating acute or past measles and rubella infection.&#x0D; Results: In the present study, the patients were with median age of 39 years and divided into 11 age groups. The majority of patients were under 30 years of age and from the capital of Sofia. In 3 patients acute measles infection was confirmed by positive ELISA-IgM results for the serum samples and DBS. No acute rubella infection was detected. Measles and rubella IgG seroprevalence was determined as 83/101 (82%, 95% CI: 74.51÷89.49) and 79/101 (78%, 95% CI: 69.92÷86.08) in serum samples, and 79/101 (78%, 95% CI: 69.92÷86.08) and 73/101 (72%, 95% CI: 63.25÷80.75) in DBS, respectively. In combination with immunoenzymatic testing for measles and rubella IgM/IgG markers, coincidence of results for both types of clinical material was found in &gt;90% of cases. No significant differences were found in the results in terms of gender and age.&#x0D; Conclusion: In recent years a variety of new and innovative applications of DBS are introduced in medicine, neonatology, virology, microbiology, etc. The optimisation of the DBS technique as an alternative approach to venepuncture in virology is very important for conducting seroepidemiological studies and to a certain extent for the surveillance of epidemic outbreaks.

Adverse pregnancy outcomes among pregnant women with acute Rubella infections in Mwanza city, Tanzania

ObjectiveThis study investigated the adverse pregnancy outcomes among pregnant women with acute Rubella infections in the city of Mwanza, Tanzania. MethodsA longitudinal study was conducted between 2014 and 2016 among pregnant women attending antenatal clinics. Women were screened for Rubella IgG and IgM antibodies using enzyme immunoassay (EIA). IgM seropositive pregnant women were followed up until the end of the pregnancy to determine Congenital Rubella Syndrome, congenital infections and other pregnancy outcomes. ResultsThe median age of 685 enrolled pregnant women was 23 (IQR: 19–27) years. A total of 629(91.8%) were Rubella IgG seropositive while 61 (8.9%) were IgM seropositive. The IgM seropositivity was found to decrease significantly from first trimester to third trimester, p<0.001. Forty six (83.6%) of 55 Rubella IgM seropositive women had adverse pregnancy outcomes and 6 (10.9%) delivered neonates with CRS, making the overall incidence of CRS to be 6/685 (0.87%). First trimester IgM seropositive women had significantly higher adverse pregnancy outcomes than those in second/third trimesters (70.4% vs. 35.7, p=0.01). ConclusionThere is one case of CRS in every 100 pregnancies necessitating additional strategies to reach a goal of elimination of CRS in developing countries.

Rubella infection during first trimester of pregnancy, is it always termination of pregnancy? a case report

The clinical diagnosis of acute rubella infection in pregnancy is extremely difficult because the symptoms are not very specific nor particularly apparent, and most infectious cases are subclinical and therefore seroconversions and presence of high IgM titres is the primary mode of diagnosis of acute rubella in pregnancy. But a positive IgM doesn’t means she had acute rubella infection because there were false positive with IgM antibody positive. More other confirmation test should be done such as include isolation of rubella virus from an appropriate clinical specimen. Decision for termination of pregnancy should not solely base on IgM antibody finding. In case that the family keen to continued her pregnancy should offer amniotic fluid or cord blood PCR for detection and diagnostic of perinatal infection. In this case, we report a 42-years old pregnant woman at 7 weeks’ gestation complains acute onset of generalized maculopapular rash suspected of rubella infection with positive of IgM anti rubella and positive for IgG. Patient is informed that she has acute rubella infection and risk of perinatal infection and discussed about an option of termination of pregnancy. After families counselling they decided to continue the pregnancy because of a specific condition (baby will adopted by her younger brother). At 18 weeks of pregnancy we do amniotic fluid for rubella PCR RNA, and the result was negative. The pregnancy is continued with routine prenatal care. Unfortunately, she has very early preterm premature rupture of the membrane at 23 weeks and fetal death caused by umbilical cord compression, and the baby was do induction of labor and born a fetal death baby of 400 grams. A new protocol was made for management of acute rubella infection in early pregnancy.

Seroprevalence of HIV, HTLV, CMV, HBV and rubella virus infections in pregnant adolescents who received care in the city of Bel\xe9m, Par\xe1, Northern Brazil

BackgroundPrenatal tests are important for prevention of vertical transmission of various infectious agents. The objective of this study was to describe the prevalence of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), cytomegalovirus (CMV), rubella virus and vaccination coverage against HBV in pregnant adolescents who received care in the city of Belém, Pará, Brazil.MethodsA cross-sectional study was performed with 324 pregnant adolescents from 2009 to 2010. After the interview and blood collection, the patients were screened for antibodies and/or antigens against HIV-1/2, HTLV-1/2, CMV, rubella virus and HBV. The epidemiological variables were demonstrated using descriptive statistics with the G, χ2 and Fisher exact tests.ResultsThe mean age of the participants was 15.8 years, and the majority (65.4%) had less than 6 years of education. The mean age at first intercourse was 14.4 years, and 60.8% reported having a partner aged between 12 and 14 years. The prevalence of HIV infection was 0.3%, and of HTLV infection was 0.6%. Regarding HBV, 0.6% of the participants had acute infection, 9.9% had a previous infection, 16.7% had vaccine immunity and 72.8% were susceptible to infection. The presence of anti-HBs was greater in adolescent between 12 and 14 years old (28.8%) while the anti-HBc was greater in adolescent between 15 and 18 years old (10.3%). Most of the adolescents presented the IgG antibody to CMV (96.3%) and rubella (92.3%). None of the participants had acute rubella infection, and 2.2% had anti-CMV IgM.ConclusionsThis study is the first report of the seroepidemiology of infectious agents in a population of pregnant adolescents in the Northern region of Brazil. Most of the adolescents had low levels of education, were susceptible to HBV infection and had IgG antibodies to CMV and rubella virus. The prevalence of HBV, HIV and HTLV was similar to that reported in other regions of Brazil. However, the presence of these agents in this younger population reinforces the need for good prenatal follow-up and more comprehensive vaccination campaigns against HBV due to the large number of women susceptible to the virus.

Rubella infection in pregnancy and congenital rubella in United Kingdom, 2003 to 2016.

Rubella vaccination has been included in the United Kingdom’s (UK) routine childhood schedule for nearly 30 years. The UK achieved World Health Organization (WHO) elimination status in 2016 and acute rubella infections are rare. In the period 2003–16, 31 rubella infections in pregnancy (0.23 per 100,000 pregnancies) were identified through routine surveillance, of which 26 were in women who were born abroad. Five of the 31 rubella infections led to congenital rubella syndrome in the infant and three had confirmed congenital rubella infection without congenital rubella syndrome. An additional seven babies were identified with congenital rubella syndrome, although rubella infection in pregnancy had not been reported. Place of birth was known for six of these seven mothers, all of whom were born outside the UK, and in five cases maternal infection was acquired abroad. WHO Europe has set targets for measles and rubella elimination and prevention of congenital rubella syndrome by 2015. Vaccination uptake and rubella immunity is high in the UK population and most infections in pregnancy since 2003 were acquired abroad and in unvaccinated women. Every contact with a health professional should be used to check that women are fully immunised according to UK schedule.

Acute Rubella Virus Infection among Women with Spontaneous Abortion in Mwanza City, Tanzania.

Acute rubella virus infection in early pregnancy has been associated with poor pregnancy outcome ranging from spontaneous abortion, stillbirth and multiple birth defects known as Congenital Rubella Syndrome (CRS). Despite its importance the prevalence of acute rubella virus infections is not known among women with spontaneous abortion in most centres in developing countries. The present study was aimed to determine the seroprevalence of acute rubella infection among women with spontaneous abortion in Mwanza city. A total of 268 women with spontaneous abortion were enrolled from four different hospitals in Mwanza city between November 2015 and April 2016. Blood samples were collected; sera were extracted and stored at -80°C until processing. Acute rubella virus infection was diagnosed by the detection of rubella specific IgM antibodies using indirect Enzyme Linked Immunosorbent Assay (ELISA) as per manufacturer's instructions. Data were analysed by using STATA version 11. The mean age of enrolled women was 26.3±5.6 years. The prevalence of acute rubella virus infection was found to be 9/268 (3.7%, 95% CI: 1-5). Only women residing in urban areas (AOR: 5.65, 95% CI: 1.15-27.77, p=0.035) were found to predict acute rubella virus infection among cases with spontaneous abortion in Mwanza city. About four out of hundred women residing in urban areas with spontaneous abortion in Mwanza are acutely infected with rubella virus highlighting the potential of this virus in contributing to poor pregnancy outcome in this setting.

Serological evidence of acute rubella infection among under-fives in Mwanza: a threat to increasing rates of congenital rubella syndrome in Tanzania.

BackgroundControl of rubella infection is essential for preventing congenital rubella syndrome (CRS) and one of the important steps is to define a target population for vaccination. Therefore this study was done to determine serological evidence of acute rubella infection among under-fives in order to anticipate the magnitude of rubella virus transmission in Tanzania.MethodsA cross-sectional study involving children aged between 1 and 59 months was conducted between September and October 2014 before national rubella vaccination campaigns commenced. Rubella IgM antibodies were detected using commercial indirect enzyme-linked immunosorbent assay (ELISA). Data were analyzed using STATA version 11.ResultsA total of230 under-fives were enrolled, their median age was 14 (Interquartile range (IQR) 7–26) months. The overall seroprevalence of rubella IgM antibodies was 10.9 % (25/230) with two confirmed cases of CRS. Two-sample Wilcoxon rank-sum test showed that the median age of rubella IgM seropositive children was significantly higher than that of IgM seronegative children (39 IQR: 18-51months vs. 14 IQR: 7–24 months, P < 0.001). On multivariate logistic regression analysis increase in age (OR: 1.07, 95 % CI; 1.03–1.1, P < 0.001) and residing in rural areas (OR: 8.07, 95 % CI; 1.43–45.6, P = 0.018) were independently found to predict acute rubella infection among under-fives.ConclusionOur findings indicate that rubella virus is prevalent in our setting posing a risk of transmitting to childbearing aged women hence increasing the risk of CRS. Increasing prevalence of acute infection with age in under-fives indicates the protective role of maternal antibodies among infants. The sustained vaccination programme of under-fives as effective measure to control CRS should be emphasized in developing countries.

Serological makers of rubella infection in Africa in the pre vaccination era: a systematic review.

BackgroundRubella infections in susceptible women during early pregnancy often results in congenital rubella syndrome (CRS). World Health Organisation (WHO) recommends that countries without vaccination programmes to assess the burden of rubella infection and CRS. However; in many African countries there is limited data on epidemiology of rubella infection and CRS. This review was undertaken to assess the serological markers and genotypes of rubella virus on the African continent in order to ascertain the gap for future research.FindingsA systematic search of original literatures from different electronic databases using search terms such as ‘rubella’ plus individual African countries such as ‘Tanzania’, ‘Kenya’, ‘Nigeria’ etc. and different populations such as ‘children’, ‘pregnant women’ etc. in different combinations was performed. Articles from countries with rubella vaccination programmes, outbreak data and case reports were excluded. Data were entered in a Microsoft Excel sheet and analyzed. A total of 44 articles from 17 African countries published between 2002 and 2014 were retrieved; of which 36 were eligible and included in this review. Of all population tested, the natural immunity of rubella was found to range from 52.9 to 97.9 %. In these countries, the prevalence of susceptible pregnant women ranged from 2.1 to 47.1 %. Rubella natural immunity was significantly higher among pregnant women than in general population (P < 0.001). Acute rubella infection was observed to be as low as 0.3 % among pregnant women to 45.1 % among children. All studies did not ascertain the age-specific prevalence, thus it was difficult to calculate the rate of infection with increase in age. Only two articles were found to report on rubella genotypes. Of 15 strains genotyped; three rubella virus genotypes were found to circulate in four African countries.ConclusionDespite variations in serological assays, the seroprevalence of IgG rubella antibodies in Africa is high with a substantial number of women of childbearing age being susceptible to rubella infection. Standardized sero-epidemiological data in various age groups as well as CRS data are important to implement cost-effective vaccination campaigns and control strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1711-x) contains supplementary material, which is available to authorized users.

Acute rubella infections mimicking measles in children in Calabar, Nigeria

The clinical diagnosis of rubella is unreliable as the symptoms are often confused with other viral and non-viral exanthematic illnesses. Acquired forms are self-limiting whereas the congenital type has devastating consequences on the foetus. The aim of this study is to highlight rubella infections in children and to draw to the attention of relevant authorities the need for routine rubella immunization for children and women of childbearing ages. This was a prospective cross-sectional study conducted from February to December 2012. Thirty five children aged 2 to 18 years, were referred to selected health facilities in Calabar following reports of symptoms of fever and skin rash, clinically resembling measles. The demographic data of the children were obtained. Blood was collected from each child and sent for measles and rubella IgM ELISA. Data were analysed using SPSS version 16. Of the 35 children with fever and skin rash, 22 were males while 13 were females (1.7:1). Fourteen (40%) of the children were found to be IgM seropositive for rubella. Five (35.7%) of rubella IgM seropositive children were less than five years of age while 7 (50%) were 5-10 years old. There was no significant difference in the seropositivity for rubella IgM antibody according to age and sex of the patients and (P = 12.5). Only one child (2.8%) was positive for measles IgM. Acute rubella infection is clinically indistinguishable from measles and is confirmed to be present in Calabar, Nigeria. We therefore advocate for routine immunisation of children and women of childbearing ages to prevent the damaging effects of rubella to the unborn baby.

Evaluation of fully automated assays for the detection of Rubella IgM and IgG antibodies by the Elecsys® immunoassay system

Screening for acute rubella infection in pregnancy is an important element of antenatal care. This study compared the sensitivity, specificity and reproducibility of two new, fully automated Elecsys® Rubella IgM and IgG immunoassays designed for the Elecsys 2010, Modular Analytics E170, COBAS e-411 and COBAS e-601 and e602 analytical platforms, with current assays using serum from patients with primary rubella infections, vaccinated patients, patients with potentially cross-reacting infections and on routine samples in clinical laboratories in France, Germany and Italy. Both assays showed good within-run and within-laboratory precision. A sensitivity of 79.8–96.0% was demonstrated for Elecsys IgM in primary, early acute infection, consistent with existing assays. In samples obtained from routine antenatal screening, the Elecsys Rubella IgM assay revealed high specificity (98.7–99.0%). A significantly (p<0.0001) lower reactivity was demonstrated in samples from previously infected patients where acute rubella infection was excluded, and the incidence of false positives in patients with potentially cross-reacting infections was lower with Elecsys Rubella IgM compared with other. The Elecsys Rubella IgG assay exhibited a relative sensitivity of 99.9–100.0% and specificity of 97.4–100.0% in samples from routine antenatal screening. The Elecsys Rubella IgM and IgG assays allow convenient, rapid and reliable determination of anti-rubella antibodies. Sensitivity, specificity and reproducibility were comparable with existing assay systems. Assay results were available in approximately half the time required for currently employed methods and the assays are compatible with widely used analytical platforms.

Rubella Diagnostic Issues in Canada

With the success of the rubella vaccination program, a goal for the elimination of rubella and congenital rubella syndrome (CRS) by 2010 has been established. To monitor the progress toward elimination, surveillance is critical. The laboratory plays an important role in both diagnostics and surveillance for rubella and CRS. In the elimination phase, there are particular issues and challenges that are important to consider when undertaking rubella diagnostics and surveillance activities. Although immunoglobulin (Ig) M serological testing is the primary diagnostic test used to confirm acute rubella infection, additional tests, such as paired IgG serological testing, molecular detection of rubella virus, and rubella IgG avidity testing need to be considered for confirming cases, depending on the clinical and epidemiologic context of a particular suspected rubella case.

Seroprevalence of TORCH infections in women of childbearing age in Croatia

During 2005–2009, a seroepidemiological study was carried out in Croatia to define the population susceptible to common TORCH agents among pregnant and non-pregnant women of childbearing age. The IgG seroprevalence was 29.1% forT. gondii, 94.6% for rubella, 75.3% for cytomegalovirus (CMV), 78.7% for herpes simplex virus type 1 (HSV-1), and 6.8% for HSV-2. Acute toxoplasmosis and CMV infection (positive IgM antibodies with low IgG avidity) were documented in 0.25% and 0.09% women, respectively. IgM prevalence was 1.2% for both HSV-1 and HSV-2. None of the participants showed acute rubella infection. Seropositivity to T. gondii and HSV-2 varied significantly between age groups (p = 0.001 and p = 0.036, respectively). Women residing in rural regions showed a significantly higher seroprevalence rate for T. gondii, CMV, and HSV-1 than urban women (T. gondii: 44.0% vs. 25.4%, p < 0.001; CMV: 85.0% vs. 73.1%, p = 0.018; HSV-1: 86.0% vs. 76.4%, p = 0.041).

Diagnosis of Acute Rubella infection during early Pregnancy in Iraq

Diagnosis of Acute Rubella infection during early Pregnancy in Iraq

Diagnosis of Acute Rubella infection during early Pregnancy in Iraq

Diagnosis of Acute Rubella infection during early Pregnancy in Iraq

Impact of human papillomavirus vaccination depends on effective vaccination strategy

Impact of human papillomavirus vaccination depends on effective vaccination strategy