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

Assessing the asymptomatic reservoir and dihydroartemisinin-piperaquine effectiveness in a low transmission setting threatened by artemisinin resistant Plasmodium falciparum

In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented.A cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014. Plasmodium spp. was assessed with high volume quantitative real-time polymerase chain reaction (qPCR). Plasmodium falciparum-positive samples were screened for mutations in the k13-propeller domain gene. Treatment effectiveness was established after 28 days (D28) using the same qPCR technique. Data from the provincial surveillance system targeting symptomatic cases, supported by Médecins Sans Frontières (MSF), were used to assess incidence.District P. falciparum prevalence was of 0.74 % [0.41; 1.21]; village prevalence ranged from 0 to 4.6 % [1.4; 10.5]. The annual incidence of P. falciparum was 16.8 cases per 1000 inhabitants in the district; village incidence ranged from 1.3 to 54.9 for 1000 inhabitants. Two geographical clusters with high number of cases were identified by both approaches. The marker for artemisinin resistance was found in six samples out of the 11 tested (55 %). 34.9 % of qPCR blood analysis of symptomatic patients were still positive at D28.The overall low prevalence of P. falciparum was confirmed in Chey Saen district in Cambodia, while there were important variations between villages. Symptomatic cases had a different pattern and were likely acquired outside the villages. It illustrates the importance of prevalence surveys in targeting interventions for elimination. Mutations in the k13-propeller domain gene (C580Y), conferring artemisinin resistance, were highly prevalent in both symptomatic and asymptomatic cases (realizing the absolute figures remain low). Asymptomatic individuals could be an additional reservoir for artemisinin resistance. The low effectiveness of dihydroartemisinin-piperaquine (DHA-PPQ) for symptomatic cases indicates that PPQ is no longer able to complement the reduced potency of DHA to treat falciparum malaria and highlights the need for an alternative first-line treatment

Assessing the Asymptomatic Reservoir and Dihydroartemisinin-Piperaquine Effectiveness in a Low Transmission Setting Threatened by Artemisinin Resistant Plasmodium Falciparum

In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented

Metal exposure among Frenc adults from the French Nutrition and Health Survey (ENNS 2006-2007)

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