Huma Qureshi

Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors §

BACKGROUND Pakistan carries one of the worlds highest burdens of chronic hepatitis and mortality due to liver failure and hepatocellular carcinomas. However, national level estimates of the prevalence of and risk factors for hepatitis B and hepatitis C are currently not available. METHODS We reviewed the medical and public health literature over a 13-year period (January 1994-September 2007) to estimate the prevalence of active hepatitis B and chronic hepatitis C in Pakistan, analyzing data separately for the general and high-risk populations and for each of the four provinces. We included 84 publications with 139 studies (42 studies had two or more sub-studies). RESULTS Methodological differences in studies made it inappropriate to conduct a formal meta-analysis to determine accurate national prevalence estimates, but we estimated the likely range of prevalence in different population sub-groups. A weighted average of hepatitis B antigen prevalence in pediatric populations was 2.4% (range 1.7-5.5%) and for hepatitis C antibody was 2.1% (range 0.4-5.4%). A weighted average of hepatitis B antigen prevalence among healthy adults (blood donors and non-donors) was 2.4% (range 1.4-11.0%) and for hepatitis C antibody was 3.0% (range 0.3-31.9%). Rates in the high-risk subgroups were far higher. CONCLUSIONS Data suggest a moderate to high prevalence of hepatitis B and hepatitis C in different areas of Pakistan. The published literature on the modes of transmission of hepatitis B and hepatitis C in Pakistan implicate contaminated needle use in medical care and drug abuse and unsafe blood and blood product transfusion as the major causal factors.

Noncirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and treatment

The Asian Pacific Association for the Study of the Liver (APASL) Working Party on Portal Hypertension has developed consensus guidelines on the disease profile, diagnosis, and management of noncirrhotic portal fibrosis and idiopathic portal hypertension. The consensus statements, prepared and deliberated at length by the experts in this field, were presented at the annual meeting of the APASL at Kyoto in March 2007. This article includes the statements approved by the APASL along with brief backgrounds of various aspects of the disease.

Incidence, patterns and severity of reported unintentional injuries in Pakistan for persons five years and older: results of the National Health Survey of Pakistan 1990–94

BackgroundNational level estimates of injuries are not readily available for developing countries. This study estimated the annual incidence, patterns and severity of unintentional injuries among persons over five years of age in Pakistan.MethodsNational Health Survey of Pakistan (NHSP 1990–94) is a nationally representative survey of the household. Through a two-stage stratified design, 18, 315 persons over 5 years of age were interviewed to estimate the overall annual incidence, patterns and severity of unintentional injuries for males and females in urban and rural areas over the preceding one year. Weighted estimates were computed adjusting for complex survey design using surveyfreq and surveylogistic option of SAS 9.1 software.ResultsThe overall annual incidence of all unintentional injuries was 45.9 (CI: 39.3–52.5) per 1000 per year; 59.2 (CI: 49.2–69.2) and 33.2 (CI: 27.0–39.4) per 1000 per year among males and females over five years of age, respectively. An estimated 6.16 million unintentional injuries occur in Pakistan annually among persons over five years of age. Urban and rural injuries were 55.9 (95% CI: 48.1–63.7) and 41.2 (95% CI: 32.2–50.0) per 1000 per year, respectively. The annual incidence of injuries due to falls were 22.2 (95% CI: 18.0–26.4), poisoning 3.3 (95%CI: 0.5–6.1) and burn was 1.5 (95%CI: 0.9–2.1) per 1000 per year. The majority of injuries occurred at home 19.2 (95%CI: 16.0–22.4) or on the roads 17.0 (95%CI: 13.8–20.2). Road traffic/street, school and urban injuries were more likely to result in handicap.ConclusionThere is high burden of unintentional injuries among persons over five years of age in Pakistan. These results are useful to plan further studies and prioritizing prevention programs on injuries nationally and other developing countries with similar situation.

The association of complex liver disorders with HBV genotypes prevalent in Pakistan

BackgroundGenotyping of HBV is generally used for determining the epidemiological relationship between various virus strains and origin of infection mostly in research studies. The utility of genotyping for clinical applications is only beginning to gain importance. Whether HBV genotyping will constitute part of the clinical evaluation of Hepatitis B patients depends largely on the availability of the relevance of the evidence based information. Since Pakistan has a HBV genotype distribution which has been considered less virulent as investigated by earlier studies from south East Asian countries, a study on correlation between HBV genotypes and risk of progression to further complex hepatic infection was much neededMethodsA total of 295 patients with HBsAg positive were selected from the Pakistan Medical Research Councils (PMRC) out patient clinics. Two hundred and twenty six (77%) were males, sixty nine (23%) were females (M to F ratio 3.3:1).ResultsOut of 295 patients, 156 (53.2%) had Acute(CAH), 71 (24.2%) were HBV Carriers, 54 (18.4%) had Chronic liver disease (CLD) Hepatitis. 14 (4.7%) were Cirrhosis and HCC patients. Genotype D was the most prevalent genotype in all categories of HBV patients, Acute (108), Chronic (39), and Carrier (53).Cirrhosis/HCC (7) were HBV/D positive. Genotype A was the second most prevalent with 28 (13%) in acute cases, 12 (22.2%) in chronics, 14 (19.7%) in carriers and 5 (41.7) in Cirrhosis/HCC patients. Mixed genotype (A/D) was found in 20 (12.8%) of Acute patients, 3 (5.6%) of Chronic and 4 (5.6%) of carriers, none in case of severe liver conditions.ConclusionMixed HBV genotypes A, D and A/D combination were present in all categories of patients except that no A/D combination was detected in severe conditions. Genotype D was the dominant genotype. However, genotype A was found to be more strongly associated with severe liver disease. Mixed genotype (A/D) did not significantly appear to influence the clinical outcome.

Determination of risk factors for hepatitis B and C in male patients suffering from chronic hepatitis

BackgroundHepatitis B and C is common in Pakistan and various risk factors are attributable to its spread.One thousand and fifty consecutive male cases suffering from chronic liver disease (327 HBV and 723 HCV) were selected from the OPD of public sector hospital and a private clinic dealing exclusively with the liver patients. To compare the results 723 age and gender matched controls were selected from the blood transfusion services of the public sector hospital. A standard questionnaire was filled for all patients and controls which included the information on possible risk factors.FindingsFamily history of liver disease was significantly higher (43% and 34%) in HBV and HCV positive cases as compared to 5% in controls [odds ratio 15.6; 95% Confidence Interval CI: 10.1 -- 24.1, 10.9; 95% Confidence Interval CI: 7.3 -- 16.4] and same trend was seen for death due to liver disease in the family. Majority 74% hepatitis B positive cases had their shaves done at communal barbers but this practice was equally prevalent amongst controls (68%), thus negating it as a possible risk factor, but there is a significant risk with p < 0.05 associated with HCV in male that get their shave in barber. Very strong association of the disease was found with history of dental treatment (38% HCV 36% HBV and 21% controls) [Odd ratio 2.3; 95% CI: 1.8-3.0, Odd ratio 2.1; 95% CI: 1.5-2.8], surgery (23% HCV cases,14% HBV cases and 12% controls), history of blood transfusion was significantly higher in HCV (6%) as compared to controls (2.1%) [Odd ratio 2.9; 95% CI: 1.5-5.5]. History of taking injections for various ailments by the general practitioners (over 90% patients in both hepatitis B and C cases) was significantly higher as compared to 75% in controls [Odds ratio 3.8, 6.9; 95% CI: 2.4-6.1, 4.5-10.4] but hospitalization was not significant in HBV and HCV cases.ConclusionInjections, surgery and dental treatment appear as major risk factors for the transmission of hepatitis B and C in the community. Massive health care awareness drives need to be done for both health care providers and the public to reduce this menace.

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.

Medical education and research in Pakistan

2234 www.thelancet.com Vol 381 June 29, 2013 The construction of health facilities, establishment of medical schools, and recruitment of health workers in the public sector have been important aspects of a popular political agenda in Pakistan, especially for elected governments. According to offi cial reports, the number of medical graduates has increased from 500 in 1947 to 171 450 in 2012 and the number of medical colleges has increased from two to 88, respectively. The total budget of the Pakistan Medical Research Council (PMRC) has increased 2·5 times between the fi scal years 2007–08 and 2011–12; and the number of health research publications has increased 7·5 times between 2001 and 2011 (fi gure). These increases give the illusion that the number of doctors in Pakistan who are capable and competent of providing needed clinical services to the population is adequate; that there is an increase in the number of research publications about health issues suggesting that we have skilled researchers; and that funding for health research by the government has gone up over the years. The truth is not so auspicious. Over recent years the real increase in the number of medical graduates Medical education and research in Pakistan health system and improving health outcomes for the country’s most vulnerable citizens. The Lancet Pakistan Series further shows the knowledge and public health capability in Pakistan, and clearly points the way to health reform, particularly in the postdevolution scenario. But tough questions remain. Will the commitment and generosity of communities throughout Pakistan be mobilised to address the most devastating day-to-day public health disaster the country faces? Will policy makers use experience of disasters to expand health-care services in diffi cult-toreach areas? Will political resolve be galvanised, reforms implemented, and resources made available? Pakistan has shown some public health success in response to natural disasters and humanitarian emergencies. The lessons and opportunities must be applied to the health system to prevent the continued death of more than 400 000 children and 12 000 women each year.

Sentinel Hospital-Based Surveillance for Assessment of Burden of Rotavirus Gastroenteritis in Children in Pakistan

Objectives To determine the burden and molecular epidemiology of rotavirus gastroenteritis in children hospitalized with severe acute watery diarrhea in Pakistan prior to introduction of rotavirus vaccine. Methods A cross-sectional study was carried out over a period of two years from 2006 – 2008 at five sentinel hospitals in the cities of Karachi, Lahore, Rawalpindi, and Peshawar. Stool samples collected from children under five years of age hospitalized with severe acute watery diarrhea were tested for rotavirus antigen via enzyme immunoassay (EIA) (IDEA REF K6020 Oxoid Ltd (Ely), Cambridge, United Kingdom). A subset of EIA positive stool samples were further processed for genotyping. Results 6679 children were enrolled and stool specimens of 2039 (30.5%) were positive for rotavirus. Rotavirus positivity ranged from 16.3% to 39.4% in the 5 hospitals with highest positivity in Lahore. 1241 (61%) of all rotavirus cases were in infants under one year of age. Among the strains examined for G-serotypes, the occurrence of G1, G2, G9 and G4 strains was found to be 28%, 24%, 14% and 13%, respectively. Among P-types, the most commonly occurring strains were P6 (31.5%) followed by P8 (20%) and P4 (12%). Prevalent rotavirus genotype in hospitalized children of severe diarrhea were G1P[8] 11.6% (69/593), followed by G2P[4] 10.4% (62/593), and G4P[6] 10.1% (60/593). Conclusions Approximately one third of children hospitalized with severe gastroenteritis in urban centers in Pakistan have rotavirus. Introduction of rotavirus vaccine in Pakistans national immunization program could prevent many severe episodes and diarrheal deaths.

Importance and contribution of community, social, and healthcare risk factors for hepatitis C infection in Pakistan

Pakistan has a high prevalence of hepatitis C virus (HCV) infection, estimated at 4.9% (2,290/46,843) in the 2007 national HCV seroprevalence survey. We used data from this survey to assess the importance of risk factor associations with HCV prevalence in Pakistan. Exposures were grouped as community (going to the barbers, sharing smoking equipment, having an ear/nose piercing, tattoo, or acupuncture), healthcare (ever having hemodialysis, blood transfusion, or ≥ 5 injections in the last year), demographic (marital status and age), and socio-economic (illiterate or laborer). We used mutually adjusted multivariable regression analysis, stratified by sex, to determine associations with HCV infection, their population attributable fraction, and how risk of infection accumulates with multiple exposures. Strength of associations was assessed using adjusted odds ratios (aOR). Community [aOR females 1.5 (95% confidence interval [CI]: 1.2, 1.8); males 1.2 (1.1, 1.4)] and healthcare [females 1.4 (1.2, 1.6); males 1.2 (1.1, 1.4)] exposures, low socio-economic status [females 1.6 (1.3, 1.80); males 1.3 (1.2, 1.5)], and marriage [females 1.5 (1.2, 1.9); males 1.4 (1.1, 1.8)] were associated with increased HCV infection. Among married women, the number of children was associated with an increase in HCV infection; linear trend aOR per child 1.06 (1.01, 1.11). Fewer infections could be attributed to healthcare exposures (females 13%; males 6%) than to community exposures (females 25%; males 9%). Prevalence increased from 3% to 10% when cumulative exposures increased from 1 to ≥ 4 [aOR per additional exposure for females 1.5 (1.4, 1.6); males 1.2 (1.2, 1.3)]. A combination of community, healthcare, and other factors appear to drive the Pakistan HCV epidemic, highlighting the need for a comprehensive array of prevention strategies.

Hepatitis B genotypes and surface antigen mutants present in Pakistani blood donors

Background The prevalence of chronic Hepatitis B Virus (HBV) infection is 2–4% in the Pakistani population, defining Pakistan as an intermediate prevalence country. In this study, hepatitis B surface antigen (HBsAg) reactive blood donations were screened using a combination of serological and molecular methods to identify immune escape HBV mutant strains and to determine the HBV genotypes and subtypes present in Pakistan. Methods Blood donations were collected at the Armed Forces Institute of Transfusion (AFIT) located in northern Pakistan and the Hussaini Blood Bank (HBB) located in the south. From 2009 to 2013 a total of 706,575 donations were screened with 2.04% (14,409) HBsAg reactive. A total of 2055 HBsAg reactive specimens, were collected and screened using a monoclonal antibody based research assay to identify immune escape mutants followed by PCR amplification and DNA sequencing to identify the mutation present. DNA sequences obtained from 192 specimens, including mutant candidates and wild type strains, were analyzed for escape mutations, genotype, and HBsAg subtype. Results Mutations were identified in approximately 14% of HBsAg reactive donations. Mutations at HBsAg amino acid positions 143–145 are the most common (46%) with the mutation serine 143 to leucine the most frequently occurring change (28%). While regional differences were observed, the most prevalent HBV strains are subgenotypes of D with subgenotype D1/subtype ayw2 accounting for the majority of infections; 90.2% at AFIT and 52.5% at HBB. Conclusions The high frequency of immune escape HBV mutants in HBV infected Pakistani blood donors highlights the need for more studies into the prevalence of escape mutants. Differences between vaccinated and unvaccinated populations, the correlation of escape mutant frequency with genotype, and impact of escape mutations in different genotype backgrounds on the performance of commercially available HBsAg assays represent avenues for further investigation.