Recent Zika virus (ZIKV) epidemics necessitate the urgent development of effective drugs and vaccines, which can be accelerated by an enhanced understanding of ZIKV biology. One of the ZIKV structural proteins, precursor membrane (prM), plays an important role in the assembly of mature virions through cleavage of prM into M protein. Recent studies have suggested that prM protein might be implicated in the neurovirulence of ZIKV. Most vaccines targeting ZIKV include prM as the immunogen. Here, we review progress in our understanding of ZIKV prM protein and its application in ZIKV vaccine development.

BackgroundHuman African trypanosomiasis (HAT) has caused social–economic burden in remote rural communities mostly in sub-Saharan Africa for over a century. The World Health Organization had targeted the year 2020 for the elimination of HAT caused by Trypanosoma brucei rhodesiense, which is mainly endemic in Malawi, Uganda, Tanzania, and Zambia. Significant progress has been made in reducing reported HAT cases in some countries. Area-specific updated epidemiological and clinical data may facilitate in understanding the progress of such efforts as well as the development of new intervention strategies.MethodsWe analyzed HAT prevalence and demographics from epidemiological surveys carried out from 2012 to 2020 obtained from the Ministry of Health, Malawi. In addition, we analyzed blood samples and clinical profiles of HAT patients surveyed between 2016 and 2020 from Rumphi and Nkhotakota districts. From the blood samples, parasite observations and speciation were carried out, whereas disease staging and severity were ascertained from the clinical profiles.ResultsMalawi reported 315 HAT cases from 2012 to 2020. The majority of HAT cases were men (70.2%), and the mean age was 29.9 ± 15.3 with all HAT fatalities resulting from stage 2 disease. Clinical symptoms were not significantly associated with disease outcome; however, swollen lymph nodes (p = 0.004), weight loss (p = 0.010), headache (p = 0.019), and sleep disturbance (p = 0.032) were significantly associated with the HAT stage of patients. About 50% of all HAT patients were reported within 2 years from 2019 to 2020, suggesting a HAT outbreak in Malawi.ConclusionThis study has highlighted the current epidemiological insights of the rHAT trend in Malawi. We have shown that rHAT clinical phenotypes in Malawi are focus-dependent and that there has been a steady increase in rHAT cases compared to all countries with incidences of rHAT. We have also highlighted an outbreak of rHAT that occurred in Malawi from 2019 to 2020 with almost 50% of the total rHAT cases that we have presented in this study reported within 2 years of the outbreak. These should call for a review of Malawi’s rHAT control and elimination strategies. A One-Health approach with the inclusion of key stakeholders such as the department of parks and wildlife may also be considered.

Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression of T.b. rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where the disease is acute with more marked neurological impairment. This has raised the question of the role of host genetic factors in infection outcomes. A candidate gene association study was conducted in the northern region of Malawi. This was a case-control study involving 202 subjects, 70 cases and 132 controls. All individuals were from one area; born in the area and had been exposed to the risk of infection since birth. Ninety-six markers were genotyped from 17 genes: IL10, IL8, IL4, HLA-G, TNFA, IL6, IFNG, MIF, APOL, HLA-A, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH. There was a strong significant association with APOL1 G2 allele (p = 0.0000105, OR = 0.14, CI95 = [0.05–0.41], BONF = 0.00068) indicating that carriers of the G2 allele were protected against T.b. rhodesiense HAT. SNP rs2069845 in IL6 had raw p < 0.05, but did not remain significant after Bonferroni correction. There were no associations found with the other 15 candidate genes. Our finding confirms results from other studies that the G2 variant of APOL1 is associated with protection against T.b. rhodesiense HAT.

BackgroundTrypanosoma brucei rhodesiense is the causative agent of acute human African trypanosomiasis. Identification of T. b. rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessng human disease risk, and monitoring spatiotemporal trends and impact of control interventions. Accurate detection and characterisation of trypanosomes in vectors relies on molecular techniques. For the first time in Malawi, a molecular technique has been used to detect trypanosomes in tsetse flies in Nkhotakota Wildlife Reserve. MethodsA polymerase chain reaction (PCR) technique was used to identify the serum resistance associated (SRA) gene of T. b. rhodesiense in tsetse flies. Of 257 tsetse flies that were randomly caught, 42 flies were dissected for microscopic examination. The midguts of 206 flies were positive and were individually put in eppendorf tubes containing phosphate-buffered saline (PBS buffer) for DNA extraction. Internal transcribed spacer (ITS)-PCR was first used to isolate all trypanosome species from the flies. TBR PCR was then used to isolate the Trypanozoon group. T. brucei-positive samples were further evaluated by SRA PCR for the presence of the SRA gene.