The binding of erythrocytes infected with mature blood stage parasites to the vascular bed is key to the pathogenesis of malignant malaria. The binding is mediated by members of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. PfEMP1s can be divided into groups, and it has previously been suggested that parasites expressing group A or B/A PfEMP1s are most pathogenic. To test the hypothesis that the first malaria infections in infants and young children are dominated by parasites expressing A and B/A PfEMP1s, we measured the plasma Ab level against 48 recombinant PfEMP1 domains of different groupings in 1342 individuals living in five African villages characterized by markedly different malaria transmission. We show that children progressively acquire a broader repertoire of anti-PfEMP1 Abs, but that the rate of expansion is governed by transmission intensity. However, independently of transmission intensity, Abs are first acquired to particular duffy binding ligand-like domains belonging to group A or B/A PfEMP1s. The results support the view that anti-PfEMP1 Ab responses effectively structure the expenditure of the repertoire of PfEMP1 maintained by the parasite. Parasites expressing certain group A and B/A PfEMP1s are responded to first by individuals with limited previous exposure, and the resulting Abs reduce the fitness and pathogenicity of these parasites during subsequent infections. This allows parasites expressing less pathogenic PFEMP1s to dominate during later infections. The identification of PfEMP1 domains expressed by parasites causing disease in infants and young children is important for development of vaccines protecting against severe malaria.

Early diagnosis and timely treatment of malaria is recognized as a fundamental element to the control of the disease. Although access to health services in Tanzania is improved, still many people seek medical care when it is too late or not at all. This study aimed to determine factors associated with delay in seeking treatment for fever among children under five in Tanzania. A three-stage cluster sampling design was used to sample households with children under five in Dodoma region, central Tanzania between October 2010 and January 2011. Information on illness and health-seeking behaviours in the previous four weeks was collected using a structured questionnaire. A multivariable logistic regression was used to investigate determinants of delay in treatment-seeking behaviour while accounting for sample design. A total of 287 under-five children with fever whose caretakers sought medical care were involved in the study. Of these, 55.4% were taken for medical care after 24 hours of onset of fever. The median time of delay in fever care seeking was two days. Children who lived with both biological parents were less likely to be delayed for medical care compared to those with either one or both of their biological parents absent from home (OR = 0.42, 95% CI: 0.24, 0.74). Children from households with two to three under-five children were more likely to be delayed for medical care compared to children from households with only one child (OR = 1.54, 95% CI: 1.04, 2.26). Also, children living in a distance ≥5 kilometres from the nearest health facility were about twice (95% CI: 1.11, 2.72) as likely to delay to be taken for medical care than those in the shorter distances. Living with non-biological parents, high number of under-fives in household, and long distance to the nearest health facility were important factors for delay in seeking healthcare. Programmes to improve education on equity in social services, family planning, and access to health facilities are required for better healthcare and development of children.

Background: The planning and assessment of malaria interventions is complicated due to fluctuations in the burden of malaria over time. Recently, it has been reported that the burden of malaria in some parts of Africa has declined. However, community-based longitudinal data are sparse and the reasons for the apparent decline are not well understood. Methods: Malaria prevalence and morbidity have been monitored in two villages in north-eastern Tanzania; a lowland village and a highland village from 2003 to 2008. Trained village health workers treated presumptive malaria with the Tanzanian first-line anti-malarial drug and collected blood smears that were examined later. The prevalence of malaria parasitaemia across years was monitored through cross-sectional surveys. Results: The prevalence of malaria parasitaemia in the lowland village decreased from 78.4% in 2003 to 13.0% in 2008, whereas in the highland village, the prevalence of parasitaemia dropped from 24.7% to 3.1% in the same period. Similarly, the incidence of febrile malaria episodes in the two villages dropped by almost 85% during the same period and there was a marked reduction in the number of young children who suffered from anaemia in the lowland village. Conclusion: There has been a marked decline in malaria in the study villages during the past few years. This decline is likely to be due to a combination of factors that include improved access to malaria treatment provided by the trained village helpers, protection from mosquitoes by increased availability of insecticide-impregnated bed nets and a reduced vector density. If this decline in malaria morbidity is sustained, it will have a marked effect on the disease burden in this part of Tanzania.

Fetal hemoglobin (HbF) is an important modulator of sickle cell disease (SCD). HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) in 1,213 SCA (HbSS/HbSβ⁰) patients in Tanzania. Genotyping was done with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release data. Association with HbF was analysed using a linear mixed model to control for complex population structure within our study. We successfully replicated known associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms (HMIP), including multiple independent effects near BCL11A, consistent with previous reports. We observed eight additional associations with P<10⁻⁶. These associations could not be replicated in a SCA population in the UK. This is the largest GWAS study in SCA in Africa. We have confirmed known associations and identified new genetic associations with HbF that require further replication in SCA populations in Africa.

Malaria and lymphatic filariasis (LF) are diseases of great public health important in East Africa. Malaria is transmitted by Anopheles while LF is transmitted by both Anopheles and Culex mosquitoes. There is limited evidence on the effects of physicochemical parameters on these mosquitoes in rural settings of Tanzania. This study aimed at assessing the effects of physicochemical parameters on Anopheles and Culex larvae abundance in different breeding sites in a rural setting of Muheza district. A cross-sectional study was conducted in 13 villages in Muheza district, between December 2015 and May 2016. Mosquito larvae were sampled using standard dipping techniques. Physicochemical parameters were measured by a Multi-parameter pH meter in different mosquito breeding sites. Mosquito larvae and pupa densities were compared between the ≤33th (lower) and ≥67th (upper) percentiles of physicochemical parameters. An. gambiae (s.l.) and An. funestus were identified by polymerase chain reaction (PCR) to reveal their sibling species. Abundance of Anopheles larvae was significantly higher (76.6%) than Culex (66.9%) χ 2 = 5.73, df = 1, P = 0.017). The presence of late instars of Anopheles was significantly higher (78.2%) than that of Culex (64.5%) (χ 2 = 0.984, df = 1, P = 0.017). A model adjusted for larval stage showed that the likelihood of finding Culex larvae was lower by 38.2% (95% CI: 16.9–54.1, df = 1, P = 0.001) compared to Anopheles. Upper percentiles of salinity (OR = 7.05; 95% CI: 1.19–41.88, P = 0.032) and conductivity (OR = 5.47; 95% CI: 1.01–29.67, P = 0.056) were significantly associated with the presence and with increased density of Anopheles larvae. PCR results showed that, within the gambiae complex, 53.3% (n = 136) were An. gambiae (s.s.) and 46.7% (n = 119) were An. arabiensis. In An. funestus group, 91.1% (n = 41) were An. funestus (s.s.), 4.4% (n = 2) were An. rivulorum, 2.2% (n = 1) were An. leesoni and 2.2% (n = 1) were An. parensis. High salinity and conductivity were significantly associated with increased density of Anopheles larvae. To our knowledge, this is the first study to demonstrate the occurrence of Anopheles larvae in polluted breeding sites in rural settings of Tanzania. The study has found both Anopheles and Culex mosquito larvae co-existed in breeding sites. The possible reasons for tolerance to a higher level of physicochemical parameters among Anopheles mosquitoes need to be ascertained.

Despite some problems related to accuracy and applicability of malaria rapid diagnostic tests (RDTs), they are currently the best option in areas with limited laboratory services for improving case management through parasitological diagnosis and reducing over-treatment. This study was conducted in areas with declining malaria burden to assess; 1) the accuracy of RDTs when used at different community settings, 2) the impact of using RDTs on anti-malarial dispensing by community-owned resource persons (CORPs) and 3) adherence of CORPs to treatment guidelines by providing treatment based on RDT results.