Progress Toward Poliovirus Containment Implementation - Worldwide, 2019-2020.

Since 1988, when World Health Organization (WHO) Member States and partners launched the Global Polio Eradication Initiative, the number of wild poliovirus (WPV) cases has declined from 350,000 in 125 countries to 176 in only two countries in 2019 (1). The Global Commission for the Certification of Poliomyelitis Eradication (GCC) declared two of the three WPV types, type 2 (WPV2) and type 3 (WPV3), eradicated globally in 2015 and 2019, respectively (1). Wild poliovirus type 1 (WPV1) remains endemic in Afghanistan and Pakistan (1). Containment under strict biorisk management measures is vital to prevent reintroduction of eradicated polioviruses into communities from poliovirus facilities. In 2015, Member States committed to contain type 2 polioviruses (PV2) in poliovirus-essential facilities (PEFs) certified in accordance with a global standard (2). Member states agreed to report national PV2 inventories annually, destroy unneeded PV2 materials, and, if retaining PV2 materials, establish national authorities for containment (NACs) and a PEF auditing process. Since declaration of WPV3 eradication in October 2019, these activities are also required with WPV3 materials. Despite challenges faced during 2019-2020, including the coronavirus disease 2019 (COVID-19) pandemic, the global poliovirus containment program continues to work toward important milestones. To maintain progress, all WHO Member States are urged to adhere to the agreed containment resolutions, including officially establishing legally empowered NACs and submission of PEF Certificates of Participation.

Progress Toward Poliovirus Containment Implementation - Worldwide, 2018-2019.

Among the three wild poliovirus (WPV) types, type 2 (WPV2) was declared eradicated globally by the Global Commission for the Certification of Poliomyelitis Eradication (GCC) in 2015. Subsequently, in 2016, a global withdrawal of Sabin type 2 oral poliovirus vaccine (OPV2) from routine use, through a synchronized switch from the trivalent formulation of oral poliovirus vaccine (tOPV, containing vaccine virus types 1, 2, and 3) to the bivalent form (bOPV, containing types 1 and 3), was implemented. WPV type 3 (WPV3), last detected in 2012 (1), will possibly be declared eradicated in late 2019.* To ensure that polioviruses are not reintroduced to the human population after eradication, World Health Organization (WHO) Member States committed in 2015 to containing all polioviruses in poliovirus-essential facilities (PEFs) that are certified to meet stringent containment criteria; implementation of containment activities began that year for facilities retaining type 2 polioviruses (PV2), including type 2 oral poliovirus vaccine (OPV) materials (2). As of August 1, 2019, 26 countries have nominated 74 PEFs to retain PV2 materials. Twenty-five of these countries have established national authorities for containment (NACs), which are institutions nominated by ministries of health or equivalent bodies to be responsible for poliovirus containment certification. All designated PEFs are required to be enrolled in the certification process by December 31, 2019 (3). When GCC certifies WPV3 eradication, WPV3 and vaccine-derived poliovirus (VDPV) type 3 materials will also be required to be contained, leading to a temporary increase in the number of designated PEFs. When safer alternatives to wild and OPV/Sabin strains that do not require containment conditions are available for diagnostic and serologic testing, the number of PEFs will decrease. Facilities continuing to work with polioviruses after global eradication must minimize the risk for reintroduction into communities by adopting effective biorisk management practices.

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.

Identification of viral and bacterial pathogens from hospitalized children with severe acute respiratory illness in Lusaka, Zambia, 2011-2012: a cross-sectional study.

BACKGROUND: Morbidity and mortality from respiratory infections are higher in resource-limited countries than developed countries, but limited studies have been conducted in resource-limited settings to examine pathogens from patients with acute respiratory infections. Influenza surveillance has been conducted in Zambia since 2008; however, only 4.3% of patients enrolled in 2011-2012 were positive for influenza. Therefore, we examined non-influenza respiratory pathogens in children with severe acute respiratory illness (SARI) in Zambia, to estimate the scope of disease burden and determine commonly-identified respiratory pathogens. METHODS: Two reverse transcriptase polymerase chain reaction (rRT-PCR) methods (single and multiplex) were used to analyze nasopharyngeal and throat swabs collected from SARI cases under five years of age from January 2011 through December 2012. All specimens were negative for influenza by rRT-PCR. The panel of singleplex reactions targeted seven viruses, while the multiplex assay targeted thirty-three bacteria, fungi, and viruses. RESULTS: A set of 297 specimens were tested by singleplex rRT-PCR, and a different set of 199 were tested by multiplex rRT-PCR. Using the singleplex assay, 184/297 (61.9%) specimens were positive for one or more viruses. The most prevalent viruses were human rhinovirus (57/297; 19.2%), human adenovirus (50/297; 16.8%), and respiratory syncytial virus (RSV) (45/297; 15.2%). Using multiplex PCR, at least one virus was detected from 167/199 (83.9%) specimens, and at least one bacteria was detected from 197/199 (99.0%) specimens. Cytomegalovirus (415/199; 208.5%) and RSV (67/199; 33.7%) were the most commonly detected viruses, while Streptococcus pneumonie (109/199; 54.8%) and Moraxella catarrhalis (92/199; 46.2%) were the most commonly detected bacteria. CONCLUSIONS: Single infections and co-infections of many viruses and bacteria were identified in children with SARI. These results provide an estimate of the prevalence of infection and show which respiratory pathogens are commonly identified in patients. Further studies should investigate causal associations between individual pathogens and SARI.

Influenza surveillance in Zambia, 2008-2009.

BACKGROUND: Limited information exists about influenza viruses in Africa. We used data from a new sentinel surveillance system to investigate the seasonality and characteristics of influenza, including pandemic (pdm) influenza A H1N1, in Zambia. METHODS: In June 2008, we established sentinel surveillance for influenza-like illness (ILI) and severe acute respiratory illness (SARI) at 4 healthcare facilities in Zambia. Nasopharyngeal and oropharyngeal swabs and structured questionnaires were collected from eligible patients and samples were tested by real-time reverse-transcription polymerase chain reaction for influenza virus types and subtypes. RESULTS: From June 2008 to December 2009, we collected 1234 specimens, of which 334 (27%) were ILI, and 900 (63%) were SARI. Overall, 4% (57) of specimens were positive for influenza. The influenza detection rate in ILI and SARI cases was 5% (17/334) and 4% (40/900), respectively. Among all influenza cases, 54 (95%) were influenza A and 3 (5%) were influenza B. Of the influenza A viruses, 16 (30%) were A(H1N1)pdm09, 29 (54%) were seasonal A(H1N1), 6 (11%) were A(H3N2), and 4 (7%) were unsubtyped. The detection rate for A(H1N1)pdm09 cases was highest in persons aged 5-24 years (5/98; 5%), 25-44 years (4/78; 5%), and 45-64 years (1/17; 6%). Conversely, for seasonal influenza the detection rate was highest in children aged 1-4 years (18/294; 6%). Influenza virus circulation peaked during June-August in both years and A(H1N1)pdm09 occurred at the end of the influenza season in 2009. CONCLUSIONS: Seasonal influenza virus infection was found to be associated with both mild and severe respiratory illness in Zambia. Future years of surveillance are necessary to better define the seasonality and epidemiology of influenza in the country.

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.

High numbers of interferon-gamma-producing T cells and low titers of anti-tuberculous glycolipid antibody in individuals with latent tuberculosis.

Latent tuberculosis infection (LTBI) is defined as an infection with Mycobacterium tuberculosis (MTB) without clinical, bacteriological, or radiological findings, and its early diagnosis is essential for eradication of tuberculosis. To identify LTBI, we measured the numbers of interferon-gamma producing T cells, based on the ELISPOT assay, and the antibody titers in the sera to tuberculous glycolipid antigen (TBGL-Ab). Seventeen culture-confirmed TB patients, 13 controls from TB endemic areas (EC) and 13 controls from TB non-endemic areas (NEC) were enrolled. Peripheral blood mononuclear cells (2.5 x 10(5) per well) were cultured on plates precoated with antibody against interferon-gamma. ELISPOT response was defined as positive when the MTB-specific antigen-containing wells showed at least 6 spots and twice numbers of spots than negative control wells. ELISPOT responses were positive in 15 (88%), 8 (62%) and 4 (31%) subjects of TB, EC and NEC groups, respectively. The ELISPOT data differ between TB and NEC groups (p < 0.01) but not between TB and EC groups. In contrast, TBGL-Ab titers were elevated (> 2.0 U/ml) in 12 TB patients (71%), but only in one subject (8%) each from EC and NEC groups. These results indicate the high prevalence of LTBI in EC. In conclusion, LTBI is associated with positive ELISPOT assay and the low titer of TBGL-Ab, while positive results both in ELISPOT and TBGL-Ab assays indicate active TB. The low titer of TBGL-Ab is a helpful marker to identify LTBI in ELISPOT-positive individuals in TB endemic areas.

Peltophorum africanum, a traditional South African medicinal plant, contains an anti HIV-1 constituent, betulinic acid.

The biodiversity of medicinal plants in South Africa makes them rich sources of leading compounds for the development of novel drugs. Peltophorum africanum (Fabaceae) is a deciduous tree widespread in South Africa. The stem bark has been traditionally employed to treat diarrhoea, dysentery, sore throat, wounds, human immunodeficiency virus/ acquired immune deficiency syndrome (HIV/AIDS), venereal diseases and infertility. To evaluate these ethnobotanical clues and isolate lead compounds, butanol and ethyl acetate extracts of the stem bark were screened for their inhibitory activities against HIV-1 using MAGI CCR5+ cells, which are derived from HeLa cervical cancer cells and express HIV receptor CD4, a chemokine receptor CCR5 and HIV-LTR-beta- galactosidase. Bioassay-guided fractionation using silica gel chromatography was also conducted. The ethyl acetate and butanol extracts of the stem bark of Peltophorum africanum showed inhibitory activity against HIV-1, CXCR4 (X4) and CCR5 (R5) tropic viruses. The ethyl acetate and butanol extracts yielded previously reported anti-HIV compounds, (+)-catechin, a flavonoid, and bergenin, a C-galloylglycoside, respectively. Furthermore, we identified betulinic acid from the ethyl acetate fraction for the first time. The fractions, which contained betulinic acid, showed the highest selective index. We therefore describe the presence of betulinic acid, a not well-known anti-HIV compound, in an African medicinal herb, which has been used for therapy, and claim that betulinic acid is the predominant anti-HIV-1 constituent of Peltophorum africanum. These data suggest that betulinic acid and its analogues could be used as potential therapeutics for HIV-1 infection.

The national burden of influenza-associated severe acute respiratory illness hospitalization in Zambia, 2011-2014.

BACKGROUND: Estimates of influenza-associated hospitalization are limited in low- and middle-income countries, especially in Africa. OBJECTIVE: To estimate the national number of influenza-associated severe acute respiratory illness (SARI) hospitalization in Zambia. METHODS: We conducted active prospective hospital-based surveillance for SARI at the University Teaching Hospital (UTH) situated in Lusaka Province during 2011-2014. Upper respiratory tract samples were tested for influenza virus using a reverse transcriptase polymerase chain reaction assay. We estimated age-specific rates of influenza-associated SARI hospitalizations for the UTH using census and secondary data on respiratory hospitalizations following estimation approaches recommended by the World Health Organization. We used the UTH hospitalization rates as a proxy for Lusaka Province. These rates were adjusted for each of the remaining 9 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. Rates were expressed per 100,000 population. RESULTS: SARI cases accounted for 77.1% (13 389/17 354) of respiratory admissions at the UTH; 82.7% (11 859/14 344) and 50.8% (1530/3010) among individuals aged <5 and ≥5 years, respectively. Among SARI cases tested, the influenza virus detection rate was 5.5% (152/2734), 4.8% (48/998), and 6.0% (104/1736) among individuals aged <5 and ≥5 years, respectively. The mean annual national number of influenza-associated SARI hospitalizations was 6181 (95% CI: 4321-8041-rate: 43.9; 95% CI: 30.7-57.1); 4669 (95% CI: 3287-6051-rate: 187.7; 95% CI: 132.1-243.3) among children aged <5 years; and 1512 (95% CI: 1037-1987-rate: 13.1; 95% CI: 9.0-17.2) among individuals aged ≥5 years. CONCLUSIONS: The burden of influenza-associated SARI hospitalizations was substantial and was highest among children aged <5 years.