Strengthening pathogen genomic surveillance for health emergencies: insights from the World Health Organization's regional initiatives.

The onset of the COVID-19 pandemic triggered a rapid scale-up in the use of genomic surveillance as a pandemic preparedness and response tool. As a result, the number of countries with in-country SARS-CoV-2 genomic sequencing capability increased by 40% from February 2021 to July 2022. The Global Genomic Surveillance Strategy for Pathogens with Pandemic and Epidemic Potential 2022-2032 was launched by the World Health Organization (WHO) in March 2022 to bring greater coherence to ongoing work to strengthen genomic surveillance. This paper describes how WHO's tailored regional approaches contribute to expanding and further institutionalizing the use of genomic surveillance to guide pandemic preparedness and response measures as part of a harmonized global undertaking. Challenges to achieving this vision include difficulties obtaining sequencing equipment and supplies, shortages of skilled staff, and obstacles to maximizing the utility of genomic data to inform risk assessment and public health action. WHO is helping to overcome these challenges in collaboration with partners. Through its global headquarters, six regional offices, and 153 country offices, WHO is providing support for country-driven efforts to strengthen genomic surveillance in its 194 Member States, with activities reflecting regional specificities. WHO's regional offices serve as platforms for those countries in their respective regions to share resources and knowledge, engage stakeholders in ways that reflect national and regional priorities, and develop regionally aligned approaches to implementing and sustaining genomic surveillance within public health systems.

Serving the Vulnerable: The World Health Organization's Scaled Support to Countries During the First Year of the COVID-19 Pandemic.

The Inter-Agency Standing Committee (IASC), created by the United Nations (UN) General Assembly in 1991, serves as the global humanitarian coordination forum of the UN s system. The IASC brings 18 agencies together, including the World Health Organization (WHO), for humanitarian preparedness and response policies and action. Early in the COVID-19 pandemic, the IASC recognized the importance of providing intensified support to countries with conflict, humanitarian, or complex emergencies due to their weak health systems and fragile contexts. A Global Humanitarian Response Plan (GHRP) was rapidly developed in March 2020, which reflected the international support needed for 63 target countries deemed to have humanitarian vulnerability. This paper assessed whether WHO provided intensified technical, financial, and commodity inputs to GHRP countries (n = 63) compared to non-GHRP countries (n = 131) in the first year of the COVID-19 pandemic. The analysis showed that WHO supported all 194 countries regardless of humanitarian vulnerability. Health commodities were supplied to most countries globally (86%), and WHO implemented most (67%) of the $1.268 billion spent in 2020 at country level. However, proportionally more GHRP countries received health commodities and nearly four times as much was spent in GHRP countries per capita compared to non-GHRP countries ($232 vs. $60 per 1,000 capita). In countries with WHO country offices (n = 149), proportionally more GHRP countries received WHO support for developing national response plans and monitoring frameworks, training of technical staff, facilitating logistics, publication of situation updates, and participation in research activities prior to the characterization of the pandemic or first in-country COVID-19 case. This affirms WHO's capacity to scale country support according to its humanitarian mandate. Further work is needed to assess the impact of WHO's inputs on health outcomes during the COVID-19 pandemic, which will strengthen WHO's scaled support to countries during future health emergencies.

The World Health Organization's Actions Within the United Nations System to Facilitate a Whole-of-Society Response to COVID-19 at Country Level.

The coronavirus disease (COVID-19) pandemic highlighted that managing health emergencies requires more than an effective health response, but that operationalizing a whole-of-society approach is challenging. The World Health Organization (WHO), as the lead agency for health within the United Nations (UN), led the UN response at the global level through the Crisis Management Team, and at the country level through the UN Country Teams (UNCTs) in accordance with its mandate. Three case studies-Mali, Cox's Bazar in Bangladesh, and Uzbekistan-provide examples of how WHO contributed to the whole-of-society response for COVID-19 at the country level. Interviews with WHO staff, supplemented by internal and external published reports, highlighted that the action of WHO comprised technical expertise to ensure an effective whole-of-society response and to minimize social disruption, including those affecting peacekeeping in Mali, livelihood sectors in Cox's Bazar, and the education sector in Uzbekistan. Leveraging local level volunteers from various sectors led to both a stronger public health response and the continuation of other sectoral work. Risk communication and community engagement (RCCE) emerged as a key theme for UN engagement at country level. These collective efforts of operationalizing whole-of-society response at the country level need to continue for the COVID-19 response, but also in preparedness for other health and non-health emergencies. Building resilience for future emergencies requires developing and exercising multi-sectoral preparedness plans and benefits from collective UN support to countries. Coronavirus disease had many impacts outside of health, and therefore emergency preparedness needs to occur outside of health too.

Pandemic influenza preparedness (PIP) framework: Progress challenges in improving influenza preparedness response capacities in the Eastern Mediterranean Region, 2014-2017.

Influenza viruses with pandemic potential have been detected in humans in the Eastern Mediterranean Region. The Pandemic Influenza Preparedness (PIP) Framework aims to improve the sharing of influenza viruses with pandemic potential and increase access of developing countries to vaccines and other life-saving products during a pandemic. Under the Framework, countries have been supported to enhance their capacities to detect, prepare for and respond to pandemic influenza. In the Eastern Mediterranean Region, seven countries are priority countries for Laboratory and Surveillance (L&S) support: Afghanistan, Djibouti, Egypt, Jordan, Lebanon, Morocco and Yemen. During 2014-2017, US$ 2.7 million was invested in regional capacity-building and US$ 4.6 million directly in the priority countries. Countries were supported to strengthen influenza diagnostic capacities to improve detection, enhance influenza surveillance systems including sentinel surveillance for severe acute respiratory infection and influenza-like illness, and increase global sharing of surveillance data and influenza viruses. This paper highlights the progress made in improving influenza preparedness and response capacities in the Region from 2014 to 2017, and the challenges faced. By 2017, 18 of the 22 countries of the Region had laboratory-testing capacity, 19 had functioning sentinel influenza surveillance systems and 22 had trained national rapid response teams. The number of countries correctly identifying all influenza viruses in the WHO external quality assurance panel increased from 9 countries scoring 100% in 2014 to 15 countries in 2017, and the number sharing influenza viruses with WHO collaborating centres increased by 75% (from eight to 14 countries); more than half now share influenza data with regional or global surveillance platforms. Seven countries have estimated influenza disease burden and seven have introduced influenza vaccination for high-risk groups. Challenges included: protracted complex emergencies faced by nine countries which hindered implementation of influenza surveillance in areas with the most needs, high staff turnover, achieving timely virus sharing and limited utilization of influenza data where they are available to inform vaccine policies or establish threshold values to measure the start and severity of influenza seasons.

Seasonal Influenza and Avian Influenza A(H5N1) Virus Surveillance among Inpatients and Outpatients, East Jakarta, Indonesia, 2011-2014.

During October 2011-September 2014, we screened respiratory specimens for seasonal and avian influenza A(H5N1) virus infections among outpatients with influenza-like illness and inpatients with severe acute respiratory infection (SARI) in East Jakarta, an Indonesia district with high incidence of H5N1 virus infection among poultry. In total, 31% (1,875/6,008) of influenza-like illness case-patients and 15% (571/3,811) of SARI case-patients tested positive for influenza virus. Influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B virus infections were detected in all 3 years, and the epidemic season extended from November through May. Although 28% (2,810/10,135) of case-patients reported exposure to poultry, only 1 SARI case-patient with an H5N1 virus infection was detected. Therefore, targeted screening among case-patients with high-risk poultry exposures (e.g., a recent visit to a live bird market or close proximity to sick or dead poultry) may be a more efficient routine surveillance strategy for H5N1 virus in these types of settings.

Indonesian Hajj Cohorts and Mortality in Saudi Arabia from 2004 to 2011.

The Hajj is an annual pilgrimage that 1-2 million Muslims undertake in the Kingdom of Saudi Arabia (KSA), which is the largest mass gathering event in the world, as the world's most populous Muslim nation, Indonesia holds the largest visa quota for the Hajj. All Hajj pilgrims under the quota system are registered in the Indonesian government's Hajj surveillance database to ensure adherence to the KSA authorities' health requirements. Performance of the Hajj and its rites are physically demanding, which may present health risks. This report provides a descriptive overview of mortality in Indonesian pilgrims from 2004 to 2011. The mortality rate from 2004 to 2011 ranged from 149 to 337 per 100,000 Hajj pilgrims, equivalent to the actual number of deaths ranging between 501 and 531 cases. The top two mortality causes were attributable to diseases of the circulatory and respiratory systems. Older pilgrims or pilgrims with comorbidities should be encouraged to take a less physically demanding route in the Hajj. All pilgrims should be educated on health risks and seek early health advice from the mobile medical teams provided.

Attenuation of highly pathogenic avian influenza A(H5N1) viruses in Indonesia following the reassortment and acquisition of genes from low pathogenicity avian influenza A virus progenitors.

The highly pathogenic avian influenza (HPAI) A(H5N1) virus is endemic in Indonesian poultry and has caused sporadic human infection in Indonesia since 2005. Surveillance of H5N1 viruses in live bird markets (LBMs) during 2012 and 2013 was carried out to provide epidemiologic and virologic information regarding viral circulation and the risk of human exposure. Real-time RT-PCR of avian cloacal swabs and environmental samples revealed influenza A-positive specimens, which were then subjected to virus isolation and genomic sequencing. Genetic analysis of specimens collected at multiple LBMs in Indonesia identified both low pathogenicity avian influenza (LPAI) A(H3N8) and HPAI A(H5N1) viruses belonging to clade 2.1.3.2a. Comparison of internal gene segments among the LPAI and HPAI viruses revealed that the latter had acquired the PB2, PB1, and NS genes from LPAI progenitors and other viruses containing a wild type (wt) genomic constellation. Comparison of murine infectivity of the LPAI A(H3N8), wt HPAI A(H5N1) and reassortant HPAI A(H5N1) viruses showed that the acquisition of LPAI internal genes attenuated the reassortant HPAI virus, producing a mouse infectivity/virulence phenotype comparable to that of the LPAI virus. Comparison of molecular markers in each viral gene segment suggested that mutations in PB2 and NS1 may facilitate attenuation. The discovery of an attenuated HPAI A(H5N1) virus in mice that resulted from reassortment may have implications for the capability of these viruses to transmit and cause disease. In addition, surveillance suggests that LBMs in Indonesia may play a role in the generation of reassortant A(H5) viruses and should be monitored.

Japanese encephalitis in Indonesia: An update on epidemiology and transmission ecology.

The Japanese Encephalitis (JE) virus circulation in Indonesia was first documented in Lombok in 1960, and the virus was first isolated in 1972 from Culex tritaeniorhynchus in Bekasi, West Java and Kapuk, West Jakarta. Since then, Indonesia has been recognized as an endemic country for JE transmission. Up to now, JE cases have been found in at least 29 provinces, with Bali, West Kalimantan, East Nusa Tenggara, West Java and East Java, being the areas of highest incidence. However, routine surveillance on JE has not been established at the national level even though many surveys were conducted. JEV has been isolated from 10 mosquito species: Culex tritaeniorhynchus, Cx. gelidus, Cx. vishnui, Cx. fuscocephala, Cx. bitaeniorhynchus, Cx. quinquefasciatus, Anopheles vagus, An. kochi, An. annularis, and Armigeres subalbatus. Culex tritaeniorhynchus is the main JE vector in Indonesia. JE has been detected throughout the Indonesian archipelago from West to East. However, due to a lack of routine, systematic and standardized diagnostic approaches, the JE burden has still not been clearly established yet. Long term and systematic JE surveillance across Indonesia is a priority, the burden needs to be better assessed and appropriate control measures must be implemented.

Estimated incidence of influenza-associated severe acute respiratory infections in Indonesia, 2013-2016.

BACKGROUND: Indonesia's hospital-based Severe Acute Respiratory Infection (SARI) surveillance system, Surveilans Infeksi Saluran Pernafasan Akut Berat Indonesia (SIBI), was established in 2013. While respiratory illnesses such as SARI pose a significant problem, there are limited incidence-based data on influenza disease burden in Indonesia. This study aimed to estimate the incidence of influenza-associated SARI in Indonesia during 2013-2016 at three existing SIBI surveillance sites. METHODS: From May 2013 to April 2016, inpatients from sentinel hospitals in three districts of Indonesia (Gunung Kidul, Balikpapan, Deli Serdang) were screened for SARI. Respiratory specimens were collected from eligible inpatients and screened for influenza viruses. Annual incidence rates were calculated using these SIBI-enrolled influenza-positive SARI cases as a numerator, with a denominator catchment population defined through hospital admission survey (HAS) to identify respiratory-coded admissions by age to hospitals in the sentinel site districts. RESULTS: From May 2013 to April 2016, there were 1527 SARI cases enrolled, of whom 1392 (91%) had specimens tested and 199 (14%) were influenza-positive. The overall estimated annual incidence of influenza-associated SARI ranged from 13 to 19 per 100 000 population. Incidence was highest in children aged 0-4 years (82-114 per 100 000 population), followed by children 5-14 years (22-36 per 100 000 population). CONCLUSIONS: Incidence rates of influenza-associated SARI in these districts indicate a substantial burden of influenza hospitalizations in young children in Indonesia. Further studies are needed to examine the influenza burden in other potential risk groups such as pregnant women and the elderly.

Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia.

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 virus infections. Overall, a very low percentage of physician participants reported ever diagnosing hospitalized patients with seasonal, pandemic, or HPAI H5N1 influenza. Use of influenza testing was low in outpatients and hospitalized patients, and use of antiviral treatment was very low for clinically diagnosed influenza patients. Further research is needed to explore health system barriers for influenza diagnostic testing and availability of antivirals for treatment of influenza in Indonesia.

Healthcare-seeking behaviors for acute respiratory illness in two communities of Java, Indonesia: a cross-sectional survey.

Understanding healthcare-seeking patterns for respiratory illness can help improve estimations of disease burden and inform public health interventions to control acute respiratory disease in Indonesia. The objectives of this study were to describe healthcare-seeking behaviors for respiratory illnesses in one rural and one urban community in Western Java, and to explore the factors that affect care seeking. From February 8, 2012 to March 1, 2012, a survey was conducted in 2520 households in the East Jakarta and Bogor districts to identify reported recent respiratory illnesses, as well as all hospitalizations from the previous 12-month period. We found that 4% (10% of those less than 5years) of people had respiratory disease resulting in a visit to a healthcare provider in the past 2weeks; these episodes were most commonly treated at government (33%) or private (44%) clinics. Forty-five people (0.4% of those surveyed) had respiratory hospitalizations in the past year, and just over half of these (24/45, 53%) occurred at a public hospital. Public health programs targeting respiratory disease in this region should account for care at private hospitals and clinics, as well as illnesses that are treated at home, in order to capture the true burden of illness in these communities.

INA-RESPOND: a multi-centre clinical research network in Indonesia.

Nationally representative observational and translational research is needed to address the public health challenges in Indonesia due to the geographic disparity, recently decentralized health system, and diverse infectious disease priorities. To accomplish this, the Indonesian Ministry of Health in collaboration with the US National Institute of Health has established INA-RESPOND (Indonesia Research Partnership on Infectious Disease) - a clinical research network comprising 9 referral hospitals, 7 medical faculties, and 2 research centres across Indonesia. The network provides a forum to conduct research at a national scale and to address scientific questions that would be difficult to address in smaller research settings. Further, it is currently conducting multi-centre research on the etiologies of fever, sepsis, and tuberculosis. There are opportunities to leverage existing network resources for other public health research needs. INA-RESPOND is an Indonesian-led network in a country with diverse population groups and public health needs which is poised to collaborate with researchers, universities, donors, and industry worldwide. This paper describes the network and its goals and values, as well as the management structure, process for collaboration, and future vision.

Application of WHO's guideline for the selection of sentinel sites for hospital-based influenza surveillance in Indonesia.

BACKGROUND: A sentinel hospital-based severe acute respiratory infection (SARI) surveillance system was established in Indonesia in 2013. Deciding on the number, geographic location and hospitals to be selected as sentinel sites was a challenge. Based on the recently published WHO guideline for influenza surveillance (2012), this study presents the process for hospital sentinel site selection. METHODS: From the 2,165 hospitals in Indonesia, the first step was to shortlist to hospitals that had previously participated in respiratory disease surveillance systems and had acceptable surveillance performance history. The second step involved categorizing the shortlist according to five regions in Indonesia to maximize geographic representativeness. A checklist was developed based on the WHO recommended attributes for sentinel site selection including stability, feasibility, representativeness and the availability of data to enable disease burden estimation. Eight hospitals, a maximum of two per geographic region, were visited for checklist administration. Checklist findings from the eight hospitals were analyzed and sentinel sites selected in the third step. RESULTS: Six hospitals could be selected based on resources available to ensure system stability over a three-year period. For feasibility, all eight hospitals visited had mechanisms for specimen shipment and the capacity to report surveillance data, but two had limited motivation for system participation. For representativeness, the eight hospitals were geographically dispersed around Indonesia, and all could capture cases in all age and socio-economic groups. All eight hospitals had prerequisite population data to enable disease burden estimation. The two hospitals with low motivation were excluded and the remaining six were selected as sentinel sites. CONCLUSIONS: The multi-step process enabled sentinel site selection based on the WHO recommended attributes that emphasize right-sizing the surveillance system to ensure its stability and maximizing its geographic representativeness. This experience may guide other countries interested in adopting WHO's influenza surveillance standards for sentinel site selection.

Factors that influence adherence to antiretroviral treatment in an urban population, Jakarta, Indonesia.

INTRODUCTION: Although the number of people receiving antiretroviral therapy (ART) in Indonesia has increased in recent years, little is known about the specific characteristics affecting adherence in this population. Indonesia is different from most of its neighbors given that it is a geographically and culturally diverse country, with a large Muslim population. We aimed to identify the current rate of adherence and explore factors that influence ART adherence. METHODS: Data were collected from ART-prescribed outpatients on an HIV registry at a North Jakarta hospital in 2012. Socio-demographic and behavioral characteristics were explored as factors associated with adherence using logistics regression analyses. Chi squared test was used to compare the difference between proportions. Reasons for missing medication were analyzed descriptively. RESULTS: Two hundred and sixty-one patients participated, of whom 77% reported ART adherence in the last 3 months. The level of social support experienced was independently associated with adherence where some social support (p = 0.018) and good social support (p = 0.039) improved adherence compared to poor social support. Frequently cited reasons for not taking ART medication included forgetting to take medication (67%), busy with something else (63%) and asleep at medication time (60%). DISCUSSION: This study identified that an increase in the level of social support experienced by ART-prescribed patients was positively associated with adherence. Social support may minimize the impact of stigma among ART prescribed patients. Based on these findings, if social support is not available, alternative support through community-based organizations is recommended to maximize treatment success.

Influenza seasonality and vaccination timing in tropical and subtropical areas of southern and south-eastern Asia.

OBJECTIVE: To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator. METHODS: Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries. FINDINGS: Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator. CONCLUSION: Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.

Managing seasonal influenza: oseltamivir treatment policy in indonesia?

To manage cases of avian influenza A/H5N1 virus infection and in anticipation of a pandemic triggered by this virus, Indonesia purchased and distributed oseltamivir to the government health facilities. Oseltamivir is an antiviral drug that was developed for the treatment of influenza infections. Disease surveillance and research suggests that seasonal influenza (A/H1N1, A/H3N2 or B) results in considerable morbidity and mortality in Indonesia, where over 15% of influenza-like illness and severe acute respiratory illness patients test positive for the influenza virus. Indonesia currently limits oseltamivir for the management of avian influenza A/H5N1cases and in anticipation of a pandemic triggered by the A/H5N1 virus. We present the evidence for the use of oseltamivir in the treatment of seasonal influenza infections so that doctors have the option to prescribe the drug. We propose that the benefits of this approach will largely outweigh the risk of antiviral resistance. We recommend that oseltamivir be available for administration to patients with seasonal influenza infections, especially for those hospitalized and for groups with high risk of complications and adverse outcomes. Overall, this will reduce morbidity and mortality of seasonal influenza.