Establishment of a Viral Hepatitis Surveillance System --- Pakistan, 2009--2011

Establishment of a Viral Hepatitis Surveillance System --- Pakistan, 2009--2011Weekly
October 14, 2011 / 60(40);1385-1390

Hepatitis A is thought to infect almost all persons living in Pakistan by age 15 years (1), and hepatitis E is responsible for sporadic infections and outbreaks (2). The prevalence of hepatitis B virus (HBV) infection is estimated at 2.5% and the prevalence of hepatitis C virus (HCV) infection, estimated at 4.8%, is one of the highest rates in the world (3). Hepatitis surveillance in Pakistan has been syndromic, failing to confirm infection, distinguish among viruses, or collect information on risk factors. To understand the epidemiology of viral hepatitis in Pakistan more clearly, the Ministry of Health (MOH) asked the Pakistan Field Epidemiology and Laboratory Training Program (FELTP) to establish a hepatitis sentinel surveillance system in five large public hospitals in four provinces and Islamabad Capital Territory. This report describes the implementation of the viral hepatitis surveillance system in Pakistan and summarizes major findings from June 2010 through March 2011. A total of 712 cases of viral hepatitis were reported; newly reported HCV infection accounted for 53.2% of reported cases, followed by acute hepatitis A (19.8%), acute hepatitis E (12.2%), and newly reported HBV infection (10.8%). A history of health-care--related exposures, particularly receipt of therapeutic injections and infusions, commonly were reported by persons infected with HBV and HCV, and most patients reported drinking unboiled water. These findings point to the need for improved provider and community education about risks associated with unsafe injections, strengthening infection control practices in health facilities, increasing hepatitis B vaccination coverage, and improving access to clean drinking water in Pakistan.

Several studies have demonstrated the substantial burden of viral hepatitis in Pakistan (1--4). In response, MOH launched a National Program for Hepatitis Prevention and Control (NPHPC) in 2005. The program focused primarily on screening and treatment for HCV infection and did not establish laboratory-based viral hepatitis surveillance. At that time, hepatitis surveillance in Pakistan was syndromic, failing to provide laboratory confirmation of infection or information on the type of hepatitis virus, and failing to collect information on risk factors.

In August 2009, to monitor the effectiveness of NPHPC's activities and guide implementation of evidence-based prevention interventions, the Pakistan FELTP launched a hepatitis sentinel site surveillance system in collaboration with CDC's Division of Viral Hepatitis. Criteria for site selection were based on geographic distribution, patient load, capacity for laboratory testing, ability to conduct data entry, and capacity for transmitting viral hepatitis data to the National Institute of Health in Islamabad, where FELTP is housed.
Five public sector tertiary-care hospitals,* located in four provincial headquarters (Lahore, Peshawar, Karachi, and Quetta) and in Islamabad (the federal capital), were selected as sentinel sites for viral hepatitis surveillance. Staff members at each site were trained to identify cases of viral hepatitis from the pediatric and adult outpatient and inpatient departments using a range of criteria (e.g., specific symptoms and elevated liver enzymes in the blood, as detected by hospital-based laboratories). For those suspected cases, additional data were collected from consenting patients using a standard investigation form. The case reporting form was comprehensive, allowing for collection of information regarding patient demographics, symptoms, and risk-factor exposures during the 6 months before illness onset. Enzyme-linked immunoassay (ELISA) test kits were used to test serologic specimens for all types of viral hepatitis. Laboratory data were interpreted and cases classified based on preestablished case definitions† for each type of viral hepatitis. Data were entered into a database and transmitted to the FELTP office for analysis. Each month, viral hepatitis data were shared with NPHPC, sentinel surveillance sites, and federal and provincial health authorities. The hepatitis surveillance system was fully operational by June 2010.

During June 2010−March 2011, a total of 712 cases of viral hepatitis were reported by the five sentinel sites. Newly reported hepatitis C was the most common cause of viral hepatitis, accounting for 53.2% of cases, followed by acute hepatitis A (19.8%), acute hepatitis E (12.2%), and newly reported hepatitis B (10.8%). In addition, among patients, 28 (3.9%) had evidence of HBV and HCV coinfection, and 11 (14.3%) of those with HBV infection had evidence of coinfection with hepatitis D.

Most persons reported with viral hepatitis resided near the reporting hospital, all of which were in large cities (Figure). For all types of viral hepatitis, nearly twice as many cases were reported among males than females. Most reported cases occurred among persons aged 20--39 years (365 cases; 53.3%), although some variation occurred by type of hepatitis. Of 24 women with acute hepatitis E infection, 75% were of childbearing age (15--49 years), but information regarding pregnancy status was unavailable. Hospitalization rates ranged from 7.1% for acute hepatitis A infection to 10.4% for newly reported HBV infection (Table 1). No deaths were reported among persons with any type of viral hepatitis. Of the 25 persons with any type of hepatitis who reported being vaccinated against HBV, two (8%) were aged ≤5 years, three (12%) were aged 6--19 years, and 20 (80%) were aged ≥20 years. Of the 13 hepatitis cases reported among children aged ≤5 years, only two of the children previously were vaccinated against HBV, including one child with newly reported HBV infection.

Drinking unboiled water during the past 6 months was commonly reported by persons with all types of viral hepatitis. HBV-infected case patients reported having undergone surgery and dental procedures, and exposure to therapeutic injections, intravenous infusions, and skin piercing more commonly than did those with other types of viral hepatitis (Table 2).

Reported by

Rana M. Safdar, MBBS, Muhammad Salman, MBBS, Rana J. Asghar, MBBS, Abdullah K. Soomro, MBBS, Field Epidemiology and Laboratory Training Program; Aftab Mohsin, MBBS, National Program for the Prevention and Control of Hepatitis; Birjees M. Kazi, MBBS, National Institute of Health, Ministry of Health, Pakistan. Henry Walke, MD, Nabil Ahmed, MPH, Div of Public Health Systems and Workforce Development, Center for Global Health; Francisco Averhoff, MD, Div of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Rania A. Tohme, MD, EIS Officer, CDC. Corresponding contributors: Rania A. Tohme, rtohme@cdc.gov, 404-718-8577; Muhammad Salman, salman14m@yahoo.com, +92-333-538-4248.

Editorial Note

This report describes the establishment of the first sentinel surveillance system for viral hepatitis in Pakistan. Findings indicate that all types of viral hepatitis are highly prevalent in Pakistan, with newly reported HCV infection being the most frequently reported in this system. Continued transmission of enteric viral hepatitis A and E in Pakistan, as revealed by sentinel surveillance, can be attributed to lack of sanitation. Because most drinking water in Pakistan is contaminated, persons are encouraged to boil their drinking water. However, as revealed by sentinel surveillance, the majority of persons infected with any type of viral hepatitis reported drinking unboiled water, likely because of practicality and cost. Previous studies indicated that almost all persons living in Pakistan have been infected with hepatitis A virus by age 15 years (1). Although acute hepatitis A is usually a self-limited asymptomatic or mild illness in children, it can cause severe symptoms in adults. Reports of acute hepatitis A infections among persons aged >30 years might demonstrate an epidemiologic shift in age of infection, likely resulting from improved sanitation in some areas. Similar findings have been reported in a recent systematic review, which suggested a decrease in hepatitis A endemicity in the South Asia region that includes Pakistan (5). Furthermore, high prevalence of acute hepatitis E infection among women of childbearing age is an indicator of frequent exposure in a population at high risk for mortality from infection. These data underscore the need for improved access to safe drinking water in Pakistan to decrease hepatitis A and E transmission.

Surveillance data also revealed that despite initiation of childhood hepatitis B vaccination in 2002, the majority of children with hepatitis reported to the surveillance system were not vaccinated and cases of HBV infection were reported among persons aged <10 years, including children aged ≤5 years. In Pakistan, the first dose of hepatitis B vaccine is given at age 6 weeks as part of the pentavalent vaccine, which provides immunization against diphtheria, tetanus, pertussis, HBV, and Haemophilus influenzae type b infections. Three-dose vaccine coverage in 2009 was reported to be >85% among children aged 12--23 months, although the demographic and health survey conducted in 2005 reported a coverage of 57% (6). Based on the findings in this report and the coverage survey data, routine coverage needs to be improved, and implementation of the hepatitis B birth dose to prevent infection among infants should be considered.
Data obtained through this system point to several potential opportunities to improve viral hepatitis control and prevention, particularly in injection safety and infection control. Consistent with previous studies, HBV and HCV infections were associated with a history of medical injections and procedures, suggesting that unsafe injection practices and health-care procedures contribute to transmission of HBV and HCV in Pakistan (3,4,7), although these practices also were commonly reported among hepatitis A and E patients. Use of therapeutic injections is a common practice in Pakistan, with an estimated four to eight injections per person per year, one of the highest rates in the world (4). These injections frequently are unnecessary and are administered for common, minor complaints such as fever and fatigue (4). The high demand for these injections is driven by the popular but erroneous belief that medications administered by injection are more effective than those given orally, and by economic incentives for health-care providers, who can charge patients more for medicines administered by injection (8). In Pakistan, injections often are given by unqualified practitioners using unsterile syringes, which increases the risk for transmission of bloodborne infections, including viral hepatitis (4,7). Addressing unsafe injections is essential to curb the ongoing epidemic of HCV infection in this country.

Since 2000, a significant increase in injection drug use also has been reported in Pakistan (9), and high prevalence rates of HCV infection have been reported among injection drug users (IDUs) (60%--93%) (4). However, only one case of hepatitis C reported through the surveillance system involved a reported IDU. This finding might be explained by the social stigma associated with admitting to such a behavior.
This report is subject to at least four limitations. First, because sentinel hospital sites are public hospitals located in large cities, the catchment population for the surveillance sites mainly includes the urban poor. Persons with acute hepatitis who seek care in the private sector and sites run by nongovernmental organizations (NGOs), which account for 70% of health-care services in Pakistan and provide services for high-risk groups (e.g., IDUs, men who have sex with men, and persons with human immunodeficiency virus) (10) might not be captured in this surveillance system. Second, surveillance data only represent persons who came to a health-care facility and received viral hepatitis testing; infected persons with mild disease not requiring medical attention or lacking access to or failing to receive medical care were not included, leading to a likely underreporting of the number of persons with hepatitis infection. Third, because of resource constraints and lack of diagnostic capabilities, immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) testing was not available, which limited the ability to distinguish acute from chronic HBV infection; identification of HBV infections was therefore solely based on acute symptoms and elevation of liver enzymes, along with positive hepatitis B surface antigen (HBsAg) and total anti-HBc. Similarly, lack of confirmatory testing using high signal-to-cut-off ratios, nucleic acid testing, or recombinant immunoblot assay for cases of HCV infection reported to the surveillance system, based on positive ELISA test results, might have led to an overestimation of the number of newly reported HCV infections. Finally, the associations between risk factors and hepatitis infections might be confounded by differences in the age distribution of persons with various types of hepatitis infection.

Despite these challenges, the hepatitis sentinel surveillance system provided Pakistan's health authorities with valuable information regarding the epidemiology of viral hepatitis and could serve as a foundation for strengthening hepatitis control in the country. Even in the United States, availability of complete and accurate information on hepatitis risk factors is difficult to achieve through a national surveillance system; most data on hepatitis risk factors are now based on enhanced sentinel surveillance from the Emerging Infections Program and previously were based on data from just six sentinel counties (of the more than 3,000 counties in the United States). However, representativeness of the Pakistan viral hepatitis surveillance system would improve with the addition of surveillance sites in the private sector and NGOs. Improving laboratory testing capacity and quality assurance of serologic testing would improve data quality. Ultimately, addressing the actual burden of viral hepatitis in Pakistan will require a national surveillance system with adequate laboratory testing capacity and resources that could be incorporated with the proposed Integrated Disease Surveillance and Response System in Pakistan to provide long-term sustainability.

Data collected through Pakistan's sentinel surveillance system show that viral hepatitis remains a major public health problem in Pakistan. The data support the need for educating health-care providers and the public about the risk for HBV and HCV transmission through unsafe and unnecessary injections, promoting proper infection control practices and hepatitis B vaccination for infants, and improving access to clean water to prevent further transmission of hepatitis A and hepatitis E in Pakistan. Surveillance plays a key role in the identification of gaps and weaknesses in prevention and control efforts, providing useful information for decision makers and improving outbreak detection and response.

Acknowledgments

Jamshed Maqbool, MS, Jmail A. Ansari, MBBS, Zeeshan Hamid, MBBS; other Field Epidemiology and Laboratory Training Program staff members; Muhammad Munir, MBBS, King Edward Medical Univ, Lahore; Ghulam Sarwar Pirkani, MBBS, Bolan Medical Complex Hospital, Quetta; Fazle Raziq, MBBS, Hyatabad Medical Complex, Peshawar; Shakeel Malick, MBBS, Civil Hospital Karachi; staff members at the sentinel sites, Pakistan. Ryan Novak, PhD, Joseph Perz, DrPH, CDC.

References
1.Bosan A, Qureshi H, Bike KM, Ahmad I, Hafiz R. A review of hepatitis viral infections in Pakistan. J Pak Med Assoc 2010;60:1045--58.
2.Khan A, Tanaka Y, Kurbanov F, et al. Investigating an outbreak of acute viral hepatitis caused by hepatitis E virus variants in Karachi, South Pakistan. J Med Virol 2011;83:622--9.
3.Qureshi H, Bile KM, Jooma R, Alam SE, Afridi HUR. Prevalence of hepatitis B and C viral infections in Pakistan: findings of a national survey appealing for effective prevention and control measures. East Mediterr Health J 2010;16(Suppl):S15--23.
4.Ali SA, Donahue RMJ, Qureshi H, Vermund SH. Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors. Int J Infect Dis 2009;13:9--19.
5.Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1995 and 2005. Vaccine 2010;28:6653--7.
6.World Health Organization. WHO vaccine-preventable diseases: monitoring system---2010 global summary. Geneva, Switzerland: World Health Organization; 2010. Available at http://www.who.int/immunization/documents/who_ivb_2010/en/index.html. Accessed October 12, 2011.
7.Usman HR, Akhtar S, Rahbar MH, Hamid S, Moattar T, Luby SP. Injections in health care settings: a risk factor for acute hepatitis B virus infection in Karachi, Pakistan. Epidemiol Infect 2003;130:293--300.
8.Janjua NZ, Hutin YJ, Akhtar S, Ahmad K. Population beliefs about the efficacy of injections in Pakistan's Sindh province. Public Health 2006;120:824--33.
9.United Nations Office on Drug and Crime. Illicit drug trends in Pakistan. Islamabad, Pakistan: United Nations Office on Drug and Crime; 2008. Available at http://www.unodc.org/documents/regional/central-asia/Illicit%20Drug%20Trends%20Report_Pakistan_rev1.pdf . Accessed May 23, 2011.
10.Ejaz I, Shaikh BT, Rizvi N. NGOs and government partnerships for health systems strengthening: a qualitative study presenting viewpoints of government, NGOs and donors in Pakistan. BMC Health Serv Res 2011;11:122.

* Sentinel surveillance sites included King Edward Medical University in Lahore, Punjab Province; Hyattabad Medical Complex in Peshawar, Khyber Pakhtunkhwa Province; Civil Hospital in Karachi, Sindh Province; Bolan Medical Complex in Quetta, Balochistan Province; and Federal Government Services Hospital in Islamabad Capital Territory.
† A confirmed case of viral hepatitis was defined as 1) discrete onset of symptoms and 2) jaundice or elevated liver enzymes, along with 3) positive laboratory criteria. Laboratory criteria for each type of hepatitis were as follows: acute hepatitis A: immunoglobulin M antibody to hepatitis A virus (IgM anti-HAV) positive; newly reported hepatitis B: antibody to hepatitis B core antigen (anti-HBc) positive and hepatitis B surface antigen (HBsAg) positive; newly reported hepatitis C: antibodies to hepatitis C virus (anti-HCV) positive and IgM anti-HAV negative and anti-HBc negative and IgM antibody to hepatitis E virus (IgM anti-HEV) negative; hepatitis D coinfection: newly reported hepatitis B that is antibody to hepatitis D virus (anti-HDV) positive; acute hepatitis E: IgM antibody to hepatitis E virus positive.


Establishment of a Viral Hepatitis Surveillance System --- Pakistan, 2009--2011