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IntroductionTrypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries, including Malawi. For a long time, untreated HAT infections were believed to be 100% fatal. However, recent studies show that infection by T.b. rhodesiense can result in a wide range of clinical outcomes in its human host. Apart from other factors such as parasite diversity, cytokines have been strongly implicated to play a major role in the outcome of T.b. rhodesiense infections. In this study, we quantify the levels of three cytokines Interleukin-8 (IL-8), Tumor Necrotic Factor alpha (TNF-α) and Interleukin -10 (IL-10) in plasma amongst HAT cases (treated and untreated) and controls recruited during medical survey. MethodsTwo-hundred and thirty-three plasma samples (HAT cases and controls) from Rumphi, one of the endemic areas in Malawi were used. Blood collected was centrifuged, plasma extracted and stored in cryovials at -800 C until processing. Plasma cytokine concentration was measured using ELISA. ResultsPlasma samples for 233 individuals, 76 HAT cases and 157 controls were quantified. Among the cases, nine had their plasma collected before treatment (untreated) and the rest were treated before blood for plasma analysis was collected. Controls had significantly higher mean plasmatic levels of TNF-α (94.5 ±474.12 pg/ml) and IL-8 (2258.6 ±5227.4 pg/ml) than cases TNF-α (29.35±181.58 pg/ml) and IL-8 (1191.3±4236.09 pg/ml). Controls and cases had similar mean levels of IL-10 in plasma. Only IL-8 had statistically significant higher median levels in the untreated than treated HAT cases P=0.006.ConclusionOur data suggest that cytokines could be considered as biomarkers of HAT infection and treatment. Further studies with a larger cohort of cases and additional cytokines which are known to be associated with HAT infection outcomes will be required to evaluate these cytokines further.

T. b. rhodesienseis the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between the different foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected withT. b. rhodesiensewas used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease focus. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 25 healthy controls and 23 r-HAT case samples of which 3 case samples were excluded for downstream analysis as outliers. 4519 genes were significantly differentially expressed (p adjusted T. b. rhodesienseinfection. We have further identified key biological pathways and transcripts during stage 1 and stage 2 r-HAT. Lastly, we have identified potential diagnostic biomarkers that may be used for staging of r-HAT disease.

Two-hundred and thirty-three plasma samples (HAT cases and controls) from Rumphi, one of the endemic areas in Malawi were used. Blood collected was centrifuged, plasma extracted and stored in cryovials at -80°C until processing. Plasma cytokine concentration was measured using ELISA.Plasma samples for 233 individuals, 76 HAT cases and 157 controls were quantified. Among the cases, nine had their plasma collected before treatment (untreated) and the rest were treated before blood for plasma analysis was collected. Controls had significantly higher mean plasmatic levels of TNF-α (94.5 ±474.12 pg/ml) and IL-8 (2258.6 ±5227.4 pg/ml) than cases TNF-α (29.35±181.58 pg/ml) and IL-8 (1191.3±4236.09 pg/ml). Controls and cases had similar mean levels of IL-10 in plasma. Only IL-8 had statistically significant higher median levels in the untreated than treated HAT cases P=0.006.Our data suggest that cytokines could be considered as biomarkers of HAT infection and treatment. Further studies with a larger cohort of cases and additional cytokines which are known to be associated with HAT infection outcomes will be required to evaluate these cytokines further.

Zika virus (ZIKV) is an important human pathogen associated with severe neurological disorders. Ubiquitination of viral proteins has diverse roles in viral life cycle and pathogenesis. Here, we found that perturbation of ubiquitin-proteasome system significantly suppressed production of infectious viral particles. Moreover, we demonstrated that ZIKV precursor membrane (prM) protein underwent ubiquitination and proteasomal degradation. Furthermore, we showed that co-expression of E protein with ubiquitination-deficient prM-6 K/6R mutant protein did not affect translocation of viral proteins into endoplasmic reticulum and trans-Golgi networks. Intriguingly, the co-expression of E and prM-6 K/6R mutant proteins led to formation of relatively aggregated viral protein complexes and resulted in diminishing secretion of viral proteins as compared to wild-type prM. Collectively, these results suggest that ubiquitinated ZIKV prM protein contributes to the release of viral proteins and provide a new insight into the mechanism involved in ZIKV replication biology.

Xenomonitoring is an important approach in assessing the progress of trypanosomiasis control as well as in estimating the endemicity of trypanosomes in affected areas. One of the major challenges in this approach is the unavailability of sensitive and easy to use xenomonitoring tools that can be used in the remote areas where the disease occurs. One tool that has been used successfully in detecting the parasites in tsetse flies is the repetitive insertion mobile element loop-mediated isothermal amplification (RIME LAMP). This tool has recently been modified from the liquid form to dry form for use in remote areas; however, uptake for use in the field has been slow. Field-collected tsetse flies were used to evaluate the performance of dry RIME LAMP over the conventional liquid RIME LAMP. All the samples were also subjected to internal transcribed spacer 1 (ITS1) ribosomal deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) as a standard. ITS1-PCR-positive samples were further sequenced for confirmation of the species. A total of 86 wild tsetse flies were left to dry at room temperature for 3 months and DNA was extracted subsequently. All 86 flies were Glossina morsitans morsitans. From these, dry RIME LAMP detected 16.3% while liquid RIME LAMP detected 11.6% as infected with trypanosomes. Ten positive samples on ITS1-PCR were sequenced and all were shown to be trypanosomes. The use of dry RIME LAMP in the field for xenomonitoring of trypanosomes in tsetse flies will greatly contribute towards control of this neglected tropical disease as it provides the cheapest, fastest and simplest way to estimate possible human infective trypanosome infection rates in the tsetse fly vectors.

This brief article focuses on the history of family planning in Zimbabwe available services community-based distribution contraceptive use and program problems. Family planning services were first available in Zimbabwe in 1953. The Rhodesian Family Planning Association (RFPA) was established formally in 1965. RFPA distributed contraceptives in 1966 and trained for the first time "field educators" in 1967. The first community-based distributors were trained in 1972. The Ministry of Health integrated the RFPA into its department in 1981. In 1985 the family planning association became a parastatal and was renamed the Zimbabwe National Family Planning Council (ZNFPC). Services today are provided through 37 family planning clinics. The distribution of contraceptives includes IUDs condoms pills and injectables. Harare and Bulawayo centers receive referrals and perform tubal ligation vasectomy and infertility counseling. 700 community-based distributors (CBDs) received a 6-week training course in order to educate about oral contraceptives encourage their use and screen clients for high blood pressure and side effects for oral contraceptives. CBDs use bicycles to make home visits and also have access to motorcycles. Each CBD averages 135 clients/month. Most visits are revisits. CBDs provided 25.3% of family planning in 1988. Local clinics provided 19.1% of family planning. Ministry of Health facilities provided 14.8% of services. ZNFPC clinics provided 13.7% of services. Private doctors or pharmacies provided 2.3% of services. 38% of women currently in a union used family planning in 1984 and 43% used it in 1988. 36% in 1988 used modern methods. The pill was the most common method followed by withdrawal. Logistics of supplies and equipment remain problematic.