In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.
Transplanting organs from cytomegalovirus-seropositive donors into cytomegalovirus-seronegative recipients is an accepted practice. However, outcomes following transplantation of organs from donors with active cytomegalovirus disease are unknown. We present a case involving a patient aged 61 years with end-stage renal disease, seropositive for cytomegalovirus, who underwent dual kidney transplant from a donor with high-grade cytomegalovirus viraemia. The donor was on immunosuppressive therapy for systemic lupus erythematosus and interstitial lung disease and had been admitted with respiratory failure. The donor had high-grade cytomegalovirus viraemia with probable cytomegalovirus pneumonitis (cytomegalovirus viral load >100 000 international units [IU]/mL in plasma and 319 000 IU/mL in bronchoalveolar lavage). Renal biopsy at organ procurement showed the absence of cytomegalovirus inclusions. Following transplantation, the recipient had delayed graft function, with renal recovery after 1 week. The patient received basiliximab induction and standard tacrolimus-based maintenance immunosuppression. He received ganciclovir and valganciclovir treatment for 1 month, followed by valganciclovir prophylaxis (or viral load monitoring, when prophylaxis had to be paused) for 2 additional months to prevent donor-derived cytomegalovirus infection. Transient cytomegalovirus viraemia (peaking at 4480 IU/mL) developed at 4 months and resolved with 1 month of valganciclovir treatment. The patient is doing well 1 year after transplantation, with adequate kidney function. This case highlights the successful and safe transplantation of kidneys from a donor with cytomegalovirus disease into a cytomegalovirus-seropositive recipient. Further research is needed to confirm our findings and define post-transplantation management.
Background: In 2021, nationwide malaria molecular surveillance revealed a high prevalence of a validated artemisinin resistance marker, the kelch13 (k13) Arg561His mutation, in the Kagera region of northwestern Tanzania. We aimed to investigate the efficacy of artemether-lumefantrine and artesunate-amodiaquine and to confirm the presence of artemisinin partial resistance (ART-R) in the Karagwe district of this region.
Methods: This single-arm, therapeutic efficacy study was carried out at the Bukangara dispensary in the Karagwe district of the Kagera region in northwestern Tanzania. Eligible participants were aged between 6 months and 120 months, had confirmed Plasmodium falciparum asexual parasitaemia, and met other inclusion criteria according to WHO's standard protocol. Participants were enrolled, treated sequentially with either artemether-lumefantrine or artesunate-amodiaquine, and assessed clinically and parasitologically for 28 days as per WHO protocol. Parasitaemia was measured every 8 h until day 3, on day 7, and then during weekly follow-up visits until day 28. Mutations in the k13 gene and extended haplotypes with the mutations were analysed, and comparisons were made with previous samples collected in the same region of Kagera and in Rwanda and southeast Asia. The primary endpoint was PCR-corrected cure rate.
Findings: Between April 29 and Sept 1, 2022, 343 patients were screened, of whom 176 were enrolled: 88 in each treatment group. The PCR-corrected cure rate was 98% (95% CI 91-100) in the artemether-lumefantrine group and 100% (96-100) in the artesunate-amodiaquine group. Persistent parasitaemia on day 3 occurred in 11 (13%) of 88 patients in the artemether-lumefantrine group and 17 (19%) of 88 patients in the artesunate-amodiaquine group. Arg561His mutations on day 0 and parasitaemia on day 3 were reported in eight (9%) of 87 patients in the artemether-lumefantrine group and ten (12%) of 86 patients in the artesunate-amodiaquine group. The median parasite clearance half-life in patients harbouring parasites with Arg561His mutation was 6·1 h in the artemether-lumefantrine group and 6·0 h in the artesunate-amodiaquine group. Parasites with the Arg561His mutation were not similar to those from southeast Asia and Rwanda but had similar haplotypes to parasites reported in the same Tanzanian region of Kagera in 2021.
Interpretation: This study confirms the presence of ART-R in Tanzania, although artemether-lumefantrine and artesunate-amodiaquine showed high efficacy. A context-specific response strategy and vigilance to detect the reduced efficacy of current antimalarial treatments and ART-R in other parts of the country are urgently needed.
Funding: The Bill & Melinda Gates Foundation and the US National Institutes of Health.
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