Typhoid Fever Surveillance, Incidence Estimates, and Progress Toward Typhoid Conjugate Vaccine Introduction - Worldwide, 2018-2022.

Typhoid fever, an acute febrile illness caused by Salmonella enterica serovar Typhi (S. Typhi), is endemic in many low- and middle-income countries† (1). In 2015, an estimated 11-21 million typhoid fever cases and 148,000-161,000 associated deaths occurred worldwide (2). Effective prevention strategies include improved access to and use of infrastructure supporting safe water, sanitation, and hygiene (WASH); health education; and vaccination (1). The World Health Organization (WHO) recommends programmatic use of typhoid conjugate vaccines for typhoid fever control and prioritization of vaccine introduction in countries with the highest typhoid fever incidence or high prevalence of antimicrobial-resistant S. Typhi (1). This report describes typhoid fever surveillance, incidence estimates, and the status of typhoid conjugate vaccine introduction during 2018-2022. Because routine surveillance for typhoid fever has low sensitivity, population-based studies have guided estimates of case counts and incidence in 10 countries since 2016 (3-6). In 2019, an updated modeling study estimated that 9.2 million (95% CI = 5.9-14.1) typhoid fever cases and 110,000 (95% CI = 53,000-191,000) deaths occurred worldwide, with the highest estimated incidence in the WHO South-East Asian (306 cases per 100,000 persons), Eastern Mediterranean (187), and African (111) regions (7). Since 2018, five countries (Liberia, Nepal, Pakistan, Samoa [based on self-assessment], and Zimbabwe) with estimated high typhoid fever incidence (≥100 cases per 100,000 population per year) (8), high antimicrobial resistance prevalence, or recent outbreaks introduced typhoid conjugate vaccines into their routine immunization programs (2). To guide vaccine introduction decisions, countries should consider all available information, including surveillance of laboratory-confirmed cases, population-based and modeling studies, and outbreak reports. Establishing and strengthening typhoid fever surveillance will be important to measure vaccine impact.

Introduction of Inactivated Poliovirus Vaccine and Trivalent Oral Polio Vaccine/Bivalent Oral Polio Vaccine Switch in the African Region.

The Polio Eradication and Endgame Strategic plan outlines the phased removal of oral polio vaccines (OPVs), starting with type 2 poliovirus-containing vaccine and introduction of inactivated polio vaccine in routine immunization to mitigate against risk of vaccine-associated paralytic polio and circulating vaccine-derived poliovirus. The objective includes strengthening routine immunization as the primary pillar to sustaining high population immunity. After 2 years without reporting any wild poliovirus (July 2014-2016), the region undertook the synchronized switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) as recommended by the Strategic Advisory Group of Experts on Immunization. Consequently the 47 countries of the World Health Organization (WHO) African Region switched from the use of tOPV to bOPV within the stipulated period of April 2016. Planning started early, routine immunization was strengthened, and technical and financial support was provided for vaccine registration, procurement, destruction, logistics, and management across countries by WHO in collaboration with the United Nations Children's Fund (UNICEF) and partners. National commitment and ownership, as well as strong coordination and collaboration between UNICEF and WHO and with partners, ensured success of this major, historic public health undertaking.

Introduction and Rollout of a New Group A Meningococcal Conjugate Vaccine (PsA-TT) in African Meningitis Belt Countries, 2010-2014.

BACKGROUND: A group A meningococcal conjugate vaccine (PsA-TT) was developed specifically for the African "meningitis belt" and was prequalified by the World Health Organization (WHO) in June 2010. The vaccine was first used widely in Burkina Faso, Mali, and Niger in December 2010 with great success. The remaining 23 meningitis belt countries wished to use this new vaccine. METHODS: With the help of African countries, WHO developed a prioritization scheme and used or adapted existing immunization guidelines to mount PsA-TT vaccination campaigns. Vaccine requirements were harmonized with the Serum Institute of India, Ltd. RESULTS: Burkina Faso was the first country to fully immunize its 1- to 29-year-old population in December 2010. Over the next 4 years, vaccine coverage was extended to 217 million Africans living in 15 meningitis belt countries. CONCLUSIONS: The new group A meningococcal conjugate vaccine was well received, with country coverage rates ranging from 85% to 95%. The rollout proceeded smoothly because countries at highest risk were immunized first while attention was paid to geographic contiguity to maximize herd protection. Community participation was exemplary.

Public Health Impact After the Introduction of PsA-TT: The First 4 Years.

BACKGROUND: During the first introduction of a group A meningococcal vaccine (PsA-TT) in 2010-2011 and its rollout from 2011 to 2013, >150 million eligible people, representing 12 hyperendemic meningitis countries, have been vaccinated. METHODS: The new vaccine effectiveness evaluation framework was established by the World Health Organization and partners. Meningitis case-based surveillance was strengthened in PsA-TT first-introducer countries, and several evaluation studies were conducted to estimate the vaccination coverage and to measure the impact of vaccine introduction on meningococcal carriage and disease incidence. RESULTS: PsA-TT implementation achieved high vaccination coverage, and results from studies conducted showed significant decrease of disease incidence as well as significant reduction of oropharyngeal carriage of group A meningococci in vaccinated and unvaccinated individuals, demonstrating the vaccine's ability to generate herd protection and prevent group A epidemics. CONCLUSIONS: Lessons learned from this experience provide useful insights in how to guide and better prepare for future new vaccine introductions in resource-limited settings.

Global epidemiology of invasive meningococcal disease.

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.

The status of hepatitis B control in the African region.

The World Health Organization (WHO) African Region has approximately 100 million people with chronic hepatitis B virus (HBV) infection. This review describes the status of hepatitis B control in the Region. We present hepatitis B vaccine (HepB) coverage data and from available data in the published literature, the impact of HepB vaccination on hepatitis B surface antigen (HBsAg) prevalence, a marker of chronic infection, among children, HBsAg prevalence in pregnant women, and risk of perinatal transmission. Lastly, we describe challenges with HepB birth dose (HepB-BD) introduction reported in the Region, and propose strategies to increase coverage. In 2015, regional three dose HepB coverage was 76%, and 16(34%) of 47 countries reported ≥ 90% coverage. Overall, 11 countries introduced HepB-BD; only nine provide universal HepB-BD, and of these, five reported ≥ 80% coverage. From non-nationally representative serosurveys among children, HBsAg prevalence was lower among children born after HepB introduction compared to those born before HepB introduction. However, some studies still found HBsAg prevalence to be above 2%. From limited surveys among pregnant women, the median HBsAg prevalence varied by country, ranging from 1.9% (Madagascar) to 16.1% (Niger); hepatitis B e antigen (HBeAg) prevalence among HBsAg-positive women ranged from 3.3% (Zimbabwe) to 28.5% (Nigeria). Studies in three countries indicated that the risk of perinatal HBV transmission was associated with HBeAg expression or high HBV DNA viral load. Major challenges for timely HepB-BD administration were poor knowledge of or lack of national HepB-BD vaccination guidelines, high prevalence of home births, and unreliable vaccine supply. Overall, substantial progress has been made in the region. However, countries need to improve HepB3 coverage and some countries might need to consider introducing the HepB-BD to help achieve the regional hepatitis B control goal of < 2% HBsAg prevalence among children < 5 years old by 2020. To facilitate HepB-BD introduction and improve timely coverage, strategies are needed to reach both facility-based and home births. Strong political commitment, clear policy recommendations and staff training on HepB-BD administration are also required. Furthermore, high quality nationally representative serosurveys among children are needed to inform decision makers about progress towards the regional control goal.

Impact of MenAfriVac in nine countries of the African meningitis belt, 2010-15: an analysis of surveillance data.

BACKGROUND: In preparation for the introduction of MenAfriVac, a meningococcal group A conjugate vaccine developed for the African meningitis belt, an enhanced meningitis surveillance network was established. We analysed surveillance data on suspected and confirmed cases of meningitis to quantify vaccine impact. METHODS: We compiled and analysed surveillance data for nine countries in the meningitis belt (Benin, Burkina Faso, Chad, Côte d'Ivoire, Ghana, Mali, Niger, Nigeria, and Togo) collected and curated by the WHO Inter-country Support Team between 2005 and 2015. The incidence rate ratios (IRRs) of suspected and confirmed cases in vaccinated and unvaccinated populations were estimated with negative binomial regression models. The relative risk of districts reaching the epidemic threshold of ten per 100 000 per week was estimated according to district vaccination status. FINDINGS: The incidence of suspected meningitis cases declined by 57% (95% CI 55-59) in vaccinated compared with unvaccinated populations, with some heterogeneity observed by country. We observed a similar 59% decline in the risk of a district reaching the epidemic threshold. In fully vaccinated populations, the incidence of confirmed group A disease was reduced by more than 99%. The IRR for non-A serogroups was higher after completion of MenAfriVac campaigns (IRR 2·76, 95% CI 1·21-6·30). INTERPRETATION: MenAfriVac introduction has led to substantial reductions in the incidence of suspected meningitis and epidemic risk, and a substantial effect on confirmed group A meningococcal meningitis. It is important to continue strengthening surveillance to monitor vaccine performance and remain vigilant against threats from other meningococcal serogroups and other pathogens. FUNDING: World Health Organization.

A global review of national influenza immunization policies: Analysis of the 2014 WHO/UNICEF Joint Reporting Form on immunization.

INTRODUCTION: The WHO recommends annual influenza vaccination to prevent influenza illness in high-risk groups. Little is known about national influenza immunization policies globally. MATERIAL AND METHODS: The 2014 WHO/UNICEF Joint Reporting Form (JRF) on Immunization was adapted to capture data on influenza immunization policies. We combined this dataset with additional JRF information on new vaccine introductions and strength of immunization programmes, as well as publicly available data on country economic status. Data from countries that did not complete the JRF were sought through additional sources. We described data on country influenza immunization policies and used bivariate analyses to identify factors associated with having such policies. RESULTS: Of 194 WHO Member States, 115 (59%) reported having a national influenza immunization policy in 2014. Among countries with a national policy, programmes target specific WHO-defined risk groups, including pregnant women (42%), young children (28%), adults with chronic illnesses (46%), the elderly (45%), and health care workers (47%). The Americas, Europe, and Western Pacific were the WHO regions that had the highest percentages of countries reporting that they had national influenza immunization policies. Compared to countries without policies, countries with policies were significantly more likely to have the following characteristics: to be high or upper middle income (p<0.0001); to have introduced birth dose hepatitis B virus vaccine (p<0.0001), pneumococcal conjugate vaccine (p=0.032), or human papilloma virus vaccine (p=0.002); to have achieved global goals for diphtheria-tetanus-pertussis vaccine coverage (p<0.0001); and to have a functioning National Immunization Technical Advisory Group (p<0.0001). CONCLUSIONS: The 2014 revision of the JRF permitted a global assessment of national influenza immunization policies. The 59% of countries reporting that they had policies are wealthier, use more new or under-utilized vaccines, and have stronger immunization systems. Addressing disparities in public health resources and strengthening immunization systems may facilitate influenza vaccine introduction and use.

Enhancement of natural killer cell activation and antibody-dependent cellular cytotoxicity by interferon-alpha and interleukin-12 in vaginal mucosae Sivmac251-infected Macaca fascicularis.

We studied the innate immune system of Cynomolgus monkeys (Macaca fascicularis) experimentally infected via the vaginal mucosae with a virulent simian immunodeficiency virus isolate SIVmac251. Animals were evaluated for their natural killer (NK) cell activity, and for their antibody-dependent cellular cytotoxicity. NK cells from SIVmac251-infected macaques show impaired NK cell activity compared to cells from uninfected animals. Subsequent treatment of NK cells with interferon-a (IFN-alpha) or interleukin-12 (IL-12) alone partially restored the NK activity. However, either treatment of NK cells with both IFN-alpha and IL-12 completely reversed the impairment of cytotoxicity induced by simian immunodeficiency virus (SIV) infection. Incubation of NK cells from infected but not from uninfected monkeys with IFN-alpha and IL-12 for 8 days increased the percentage of CD16+/CD56+ cells twofold to five-fold and enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. Thus IFN-alpha and IL-12 greatly enhance both the NK cell and ADCC activities of peripheral blood cells from SIVmac251-infected animals and increase the number of NK cells in longer term culture. The combined effect of IFN-alpha and IL-12 in enhancing NK cell activity may provide a novel therapeutic approach for the restoration of depressed NK cell activity observed in human immunodeficiency virus (HIV)-infected patients.

Global practices of meningococcal vaccine use and impact on invasive disease.

A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs.