Program

MULTIFACETED RESEARCH AND IMPLEMENTING APPROACHES TO CONTROL EMERGING RESISTANCE FOR HIV-, MALARIA- AND TB-THERAPY IN CHILDREN AND PREGNANT WOMEN

[Speaker] Lars L. Gustafsson:1
[Co-author] Jaran Eriksen:1, Sarah Nanzigu:2, Lars Naver:3, Johanna Rubin:3, Sandra Soeria-Atmadja:3
1:Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden, 2:Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda, 3:Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

Global implementation of HIV-, malaria- and tb-therapy has drastically reduced the death toll since 2000. The progress is remarkable for children and pregnant women in sub-Saharan Africa (SSA). Emerging resistance and scanty knowledge about the use of medicines and treatment outcomes are challenges.

About 90 % of two million children (0-14 years) living with HIV reside in SSA. Annually 1.3 million HIV-pregnant women give births. The access to Antiretroviral Therapy (ART) in children living with HIV varies between 10 and 95% in SSA-countries. Prevalence of pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in adults ranged between 8 and 15% in four SSA countries. A South-African survey found pretreatment resistance in 64% of early infant diagnosed children <1.5 years. Retainment of pregnant women in care is low. However, as many as 70% of those included during pregnancy was still treated after three years in a Malawian study using medical record monitoring tools.

Annually up to 1 million tb cases and 80,000 deaths occur in children, most in SSA. Twenty percent of all cases can be children. A South-African study showed that 50% of children (13-18y) with multidrug resitant (MDR) tb had HIV. Robust data on efficacy, safety and optimal dosing regimens in children are lacking.

Every year 0.4 million patients die in malaria, the majority children <5 years in SSA. Less than 20% of children with reported fever diagnosed as malaria received the effective Artemisinin Combination Therapy in a multicountry SSA study. Low adherence to guideline recommendations for malaria case management in pregnancy is common. Only one third of pregnant women with fever seeking help at healthcare facilities received correct antimalarial therapy in an Ugandan study.

Needed future research includes: a. Pharmacokinetic and dosing studies for optimal treatment regimens in children and pregnant women. Population kinetic approaches require high quality clinical and drug analytical protocols and procedures. b. Longterm studies on clinical outcomes, resistance development, use and costs of medicines and diagnostic tools in multifaceted interventions. Preferably these studies involve demographic surveillance sites across Africa. Thereby risks of resistance to medicines in children and pregnant women can be controlled.


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