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.

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.

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.