Factors associated with HIV infection among children in Larkana District, Pakistan: a matched case-control study.

BACKGROUND: In April, 2019, an HIV outbreak predominantly affecting children occurred in Larkana District, Sindh, Pakistan. By December, 2019, 881 (4·0%) of 21 962 children screened for HIV had tested positive. We aimed to assess factors associated with HIV infection in this outbreak. METHODS: In this individually matched case-control study, we sampled 406 cases (individuals aged <16 years who had registered for paediatric HIV care at the HIV Treatment Centre at Shaikh Zayed Children's Hospital in Larkana City, Pakistan) and 406 controls (individuals without HIV matched by age, sex, and neighbourhood residence, recruited through doorknocking at houses adjacent to case participants). An interviewer-administered questionnaire was used to collect data on possible risk factors for HIV acquisition and a blood sample was collected from all participants for hepatitis B and hepatitis C serology. Mothers of all participants underwent HIV testing. Odds ratios were estimated using conditional logistic regression to assess factors associated with HIV infection. FINDINGS: 406 case-control pairs were recruited between July 3 and Dec 26, 2019. Five pairs were excluded (three pairs had an age mismatch and two pairs were duplicate cases) and 401 were analysed. The prevalence of hepatitis B surface antigen was 18·2% (95% CI 14·5-22·3) among cases and 5·2% (3·3-7·9) among controls, and the prevalence of hepatitis C antibodies was 6·5% (95% CI 4·3-9·4) among cases and 1·0% (0·3-2·5) among controls. 28 (7%) of 397 mothers of cases for whom we had data, and no mothers of 394 controls, were HIV positive. In the 6 months before recruitment, 226 (56%) of 401 cases and 32 (8%) of 401 controls reported having more than ten injections, and 291 (73%) cases and 78 (19%) controls had received an intravenous infusion. At least one blood transfusion was reported in 56 (14%) cases and three (1%) controls in the past 2 years. HIV infection was associated with a history of more injections and infusions (adjusted odds ratio 1·63; 95% CI 1·30-2·04, p<0·0001), blood transfusion (336·75; 23·69-4787·01, p<0·0001), surgery (399·75, 13·99-11 419·39, p=0·0005), the child's mother being HIV positive or having died (3·13, 1·20-8·20, p=0·020), and increased frequency of private clinic (p<0·0001) and government hospital visits (p<0·0001), adjusting for confounders. INTERPRETATION: The predominant mode of HIV transmission in this outbreak was parenteral, probably due to unsafe injection practices and poor blood safety practices. General practitioners across Pakistan need training and systems support in reducing injection use, and in providing safe injections and transfusions only when necessary. FUNDING: Department of Pediatrics and Child Health, the Aga Khan University, Karachi, Pakistan.

Investigation of an extensive outbreak of HIV infection among children in Sindh, Pakistan: protocol for a matched case-control study.

INTRODUCTION: In April 2019, 14 children were diagnosed with HIV infection by a private healthcare provider in Larkana district, Sindh province, Pakistan. Over the next 3 months, 930 individuals were diagnosed with HIV, >80% below 16 years, the largest ever outbreak of HIV in children in Pakistan. In this protocol paper, we describe research methods for assessing likely modes of HIV transmission in this outbreak and investigate spatial and molecular epidemiology. METHODS AND ANALYSIS: A matched case-control study will be conducted with 406 cases recruited. Cases will be children aged below 16 years registered for care at the HIV treatment centre at Shaikh Zayed Children Hospital in Larkana City. Controls will be children who are HIV-uninfected (confirmed by a rapid HIV test) matched 1:1 by age (within 1 year), sex and neighbourhood. Following written informed consent from the guardian, a structured questionnaire will be administered to collect data on sociodemographic indices and exposure to risk factors for parenteral, vertical and sexual (only among those aged above 10 years) HIV transmission. A blood sample will be collected for hepatitis B and C serology (cases and controls) and HIV lineage studies (cases only). Mothers of participants will be tested for HIV to investigate the possibility of mother-to-child transmission. Conditional logistic regression will be used to investigate the association of a priori defined risk factors with HIV infection. Phylogenetic analyses will be conducted. Global positioning system coordinates of participants' addresses will be collected to investigate concordance between the genetic and spatial epidemiology. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Review Committee of the Aga Khan University, Karachi. Study results will be shared with Sindh and National AIDS Control Programs, relevant governmental and non-governmental organisations, presented at national and international research conferences and published in international peer-reviewed scientific journals.

Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis.

BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID.

Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination.

Background: The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. Methods: We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. Results: With no further treatment (currently ∼150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Conclusions: Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan's HCV burden will increase markedly.

Distressed setting and profound challenges: Pandemic influenza preparedness plans in the Eastern Mediterranean Region.

BACKGROUND: Influenza pandemics are unpredictable and can have severe health and economic implications. Preparedness for pandemic influenza as advised by the World Health Organization (WHO) is key in minimizing the potential impacts. Pandemic Influenza Preparedness (PIP) Framework is a global public-private initiative to strengthen the preparedness. A total of 43 countries receive funds through Partnership Contribution (PC) component of PIP Framework to enhance preparedness; seven of these fall in the WHO's Eastern Mediterranean Region. We report findings of a desk review of preparedness plans of six such countries from the Region. METHODS: The assessment was done using a standardized checklist containing five criteria and 68 indicators. The checklist was developed using the latest WHO guidelines, in consultation with influenza experts from the Region. The criteria included preparation, surveillance, prevention and containment, case investigation and treatment, and risk communication. Two evaluators independently examined and scored the plans. RESULTS: Pandemic preparedness plan of only one country scored above 70% on aggregate and above 50% on all individual criteria. Plans from rest of the countries scored below satisfactory on aggregate, as well as on individual preparedness criteria. Among the individual criteria, prevention and containment scored highest while case investigation and treatment, the lowest for majority of the countries. In general, surveillance also scored low while it was absent altogether, in one of the plans. CONCLUSIONS: This was a desk review of the plans and not the actual assessment of the influenza preparedness. Moreover, only plans of countries facilitated through funds provided under the PC implementation plan were included. The preparedness scores of majority of reviewed plans were not satisfactory. This warrants a larger study of a representative sample from the Region and also calls for immediate policy action to improve the pandemic influenza preparedness plans and thereby enhance pandemic preparedness in the Region.

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.

Dengue fever in patients admitted in tertiary care hospitals in Pakistan.

OBJECTIVES: To assess the gaps in the diagnosis and management of dengue fever cases. METHODS: The retrospective descriptive analytical study was done with a case record analysis of patients with dengue fever admitted from January to December 2010 at five tertiary care hospitals in different Pakistani cities. Using a questionnaire, information was gathered on demography, haematological profile, management, use of blood and platelet transfusions and the outcome. For comparison, data of serologically-confirmed dengue patients from a private laboratory in Islamabad was collected to see the age, gender and month-wise distribution of cases tested over the same period. SPSS 16 was used for statistical analysis. RESULTS: Out of the 841 confirmed dengue cases, 514 (79%) were males and 139 (21%) females. The overall mean age was 31.3 +/- 14.0 years. Dengue fever was seen in 653 (78%) and dengue haemorrhagic fever (DHF) in 188 (22%) patients. Most cases were between 20 and 49 years of age. A gradual increase in dengue fever and dengue haemorrhagic fever was seen from August, with a peak in October/November. Tourniquet test was done only in 20 (2.3%) cases, out of which 11 (55%) were positive and 9 (45%) were negative. Serial haematocrit was not done in any case. Total deaths were 5 (0.6%). CONCLUSIONS: Most cases were seen in October/November with the majority being in the 20-39 age group. Tourniquet test and serial haematocrit were infrequently used. No standard national guidelines were employed.