From the Guidelines
If a patient remains malaria smear positive after treatment, they should be evaluated for treatment failure and switched to an alternative regimen such as artemether-lumefantrine (Coartem) or atovaquone-proguanil (Malarone), considering drug resistance and the possibility of reinfection. The management of adult patients with malaria in non-endemic settings, as outlined in a 2024 study published in Clinical Microbiology and Infection 1, emphasizes the importance of monitoring and prompt treatment adjustment. For uncomplicated P. falciparum malaria that remains positive after first-line therapy, alternative regimens include artemether-lumefantrine (Coartem) 4 tablets twice daily for 3 days, or atovaquone-proguanil (Malarone) 4 tablets daily for 3 days.
Key considerations in managing persistent malaria smear positivity include:
- Confirming the species of malaria, particularly P. falciparum, and assessing for medication adherence, vomiting of doses, or use of expired medications.
- Monitoring parasitaemia, with targets such as a 75% reduction in parasite density by day 3 and a negative result by day 7 for uncomplicated falciparum malaria, as suggested by a 2024 study in Clinical Microbiology and Infection 1.
- Considering drug resistance, especially in regions with known artemisinin resistance, and the possibility of reinfection, particularly in endemic areas.
- The potential need for additional primaquine therapy to clear liver hypnozoites and prevent relapse in species like P. vivax and P. ovale.
- Prompt retreatment is essential to prevent severe complications, including cerebral malaria, severe anemia, and organ failure.
In cases of severe malaria, intravenous artesunate may be necessary, with monitoring for post-artesunate delayed haemolysis (PADH) as recommended 1. The choice of alternative regimens should be guided by factors such as drug availability, patient tolerance, and resistance patterns in the region where the malaria was acquired.
From the Research
Persistent Malaria Smear Positive after Treatment
- The persistence of malaria smear positivity after treatment can be due to various factors, including the type of treatment used and the individual's response to treatment 2.
- Studies have shown that rapid diagnostic tests (RDTs) can remain positive for a highly variable amount of time after treatment with anti-malarials, with half of RDTs that detect the antigen histidine-rich protein II (HRP2) still positive 15 days post-treatment 2.
- The duration of persistent positivity for combination RDTs that detect both antigens falls between that for HRP2- or pLDH-only RDTs, with half of RDTs remaining positive at 7 days post-treatment 2.
- Treatment with artemisinin-based combination therapies, such as dihydroartemisinin-piperaquine, has been shown to be effective in clearing malaria parasites and reducing the risk of persistent positivity 3, 4, 5.
- However, the persistence of gametocytes after treatment with dihydroartemisinin-piperaquine has been observed, which can contribute to the ongoing transmission of malaria 3, 4.
Factors Influencing Persistent Malaria Smear Positivity
- The type of RDT used can influence the duration of persistent positivity, with HRP2-based RDTs remaining positive for longer than pLDH-based RDTs 2.
- The individual's age and treatment regimen can also impact the duration of persistent positivity, with children displaying persistent RDT positivity for longer after treatment than adults, and treatment with artemisinin combination therapy resulting in longer persistence than other anti-malarials 2.
- The use of primaquine as an adjunctive treatment has been shown to reduce the persistence of gametocytes and transmission of malaria 3.