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Anopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the South. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014S-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

Background The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of the World Health Organization first-in-class PBO-Py LLIN (Olyset Plus) versus the standard LLIN (Olyset net) against pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) and An. funestus in North-West Tanzania after 20 months of household use. Methods From a household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected. The physical integrity and hole index (HI) of the nets were assessed, and resting mosquitoes were collected from inside nets and from room walls. The indoor abundance was estimated using CDC light traps and species identified using PCR. The bioefficacy of PBO and standard LLINs against wild Anopheles was assessed using 30-minute cylinder bioassays. Results Of 2397 Anopheles collected, 8.9% (n = 213) were resting inside standard Olyset nets, while none were found inside Olyset Plus nets (PBO-Py LLINs) of any HI category. Resting density of blood-fed mosquitoes was higher on walls of sleeping rooms with Olyset nets compared to Olyset Plus (0.62 vs 0.10, density ratio [DR]: 0.03, 95% CI 0.01–0.13, p p = 0.037). In bioassay, mortality of An. gambiae s.l. was higher with Olyset Plus than with Olyset nets for new nets (76.8% vs 27.5%) and nets used for 20 months (56.8% vs 12.8%); similar trends were observed with An. funestus. Conclusion The PBO-Py LLINs provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid-resistant An. gambiae sensu stricto (s.s.) and An. funestus collected from inside Olyset Plus nets, irrespective of HI category, as compared to Olyset nets. Graphical Abstract

Background Long-lasting insecticidal nets (LLINs) are the most widely deployed vector control intervention in sub-Saharan Africa to prevent malaria. Recent reports indicate selection of pyrethroid insecticide resistance is widespread in mosquito vectors. This paper explores risk factors associated with malaria infection prevalence and vector density between mass distribution campaigns, changes in net coverage, and loss of protection in an area of high pyrethroid resistance in Northwest Tanzania. Methods A cross sectional malaria survey of 3456 children was undertaken in 2014 in Muleba district, Kagera region west of Lake Victoria. Vector density was assessed using indoor light traps and outdoor tent traps. Anophelines were identified to species using PCR and tested for Plasmodium falciparum circumsporozoite protein. Logistic regression was used to identify household and environmental factors associated with malaria infection and regression binomial negative for vector density. Results LLIN use was 27.7%. Only 16.9% of households had sufficient nets to cover all sleeping places. Malaria infection was independently associated with access to LLINs (OR: 0.57; 95% CI 0.34–0.98). LLINs less than 2 years old were slightly more protective than older LLINs (53 vs 65% prevalence of infection); however, there was no evidence that LLINs in good condition (hole index Anopheles funestus and 95.4% Anopheles gambiae of which 4.5% were Anopheles arabiensis and 93.5% were Anopheles gambiae sensu stricto. Conclusion Three years after the mass distribution campaign and despite top-ups, LLIN usage had declined considerably. While children living in households with access to LLINs were at lower risk of malaria, infection prevalence remained high even among users of LLINs in good condition. While effort should be made to maintain high coverage between campaigns, distribution of standard pyrethroid-only LLINs appears insufficient to prevent malaria transmission in this area of intense pyrethroid resistance.

Background: \ud Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings.\ud \ud Methods: \ud The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia.\ud \ud Findings: \ud The median estimated P(Detect) across all clusters was 12·5% (IQR 5·3–25·0) for P falciparum and 10·1% (5·0–18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57–0·69; adjusted OR for P vivax 0·52, 0·47–0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity.\ud \ud Interpretation: \ud The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission.\ud \ud Funding: \ud Wellcome Trust.

Anopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the south. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014F-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

Long lasting insecticidal nets (LLINs) are a proven tool to reduce malaria transmission, but in Africa efficacy is being reduced by pyrethroid resistance in the major vectors. A cluster randomized trial in Muleba district, Tanzania demonstrated that permethrin LLINs co-treated with piperonyl butoxide (PBO), a synergist that can block pyrethroid-metabolizing enzymes in the mosquito, had much greater efficacy than pyrethroid-only nets. Insecticide resistance profiles and underlying mechanisms were investigated in Anopheles gambiae and An. funestus from Muleba during the trial. Diagnostic dose bioassays using permethrin, together with intensity assays, suggest pyrethroid resistance that is both strong and very common, but not extreme. Transcriptomic analysis found multiple P450 genes over expressed including CYP6M2, CYP6Z3, CYP6P3, CYP6P4, CYP6AA1 and CYP9K1 in An. gambiae and CYP6N1, CYP6M7, CYP6M1 and CYP6Z3 in An. funestus. Indeed, very similar suites of P450 enzymes commonly associated with resistant populations elsewhere in Africa were detected as over expressed suggesting a convergence of mechanisms across Sub-Saharan African malaria vectors. The findings give insight into factors that may correlate with pyrethroid PBO LLIN success, broadly supporting model predictions, but revision to guidelines previously issued by the World Health Organization is warranted.

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.

IntroductionThe massive scale-up of long-lasting insecticidal nets (LLINs) has led to major reductions in malaria burden in many sub-Saharan African countries. This progress is threatened by widespread insecticide resistance among malaria vectors. This cluster-randomised controlled trial (c-RCT) compares three of the most promising dual active ingredients LLINs (dual-AI LLINs), which incorporate mixtures of insecticides or insecticide synergists to standard LLINs in an area of pyrethroid insecticide resistance.MethodsA four-arm, single-blinded, c-RCT will evaluate the effectiveness of three types of dual-AI LLINs (1) Royal Guard, combining two insecticides, pyriproxyfen and the pyrethroid alpha-cypermethrin; (2) Interceptor G2, combining chlorfenapyr and alpha-cypermethrin; (3) Olyset Plus, an LLIN combining a synergist, piperonyl butoxide and the pyrethroid permethrin, compared with; (4) Interceptor LN, a standard LLIN containing the pyrethroid alpha-cypermethrin as the sole AI. The primary outcomes are malaria infection prevalence in children aged 6 months–14 years and entomological inoculation rate (EIR), as a standard measure of malaria transmission at 24 months postintervention and cost-effectiveness.Ethics and disseminationEthical approval was received from the institutional review boards of the Tanzanian National Institute for Medical Research, Kilimanjaro Christian Medical University College, London School of Hygiene and Tropical Medicine, and University of Ottawa. Study findings will be actively disseminated via reports and presentations to stakeholders, local community leaders, and relevant national and international policy makers as well as through conferences, and peer-reviewed publications.Trial registration numberNCT03554616.

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings., The role of subpatent infections for malaria transmission and elimination is unclear. Here, Slater et al. analyse several malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections.

By attaching infected erythrocytes to the vascular lining, Plasmodium falciparum parasites leave blood circulation and avoid splenic clearance. This sequestration is central to pathogenesis. Severe malaria is associated with parasites expressing an antigenically distinct P. falciparum erythrocyte membrane protein 1 (PfEMP1) subset mediating binding to endothelial receptors. Previous studies indicate that PfEMP1 adhesins with so-called CIDRα1 domains capable of binding endothelial protein C receptor (EPCR) constitute the PfEMP1 subset associated with severe pediatric malaria. To analyze the relative importance of different subtypes of CIDRα1 domains, we compared Pf emp1 transcript levels in children with severe malaria (including 9 fatal and 114 surviving cases), children hospitalized with uncomplicated malaria ( n = 42), children with mild malaria not requiring hospitalization ( n = 10), and children with parasitemia and no ongoing fever ( n = 12). High levels of transcripts encoding EPCR-binding PfEMP1 were found in patients with symptomatic infections, and the abundance of these transcripts increased with disease severity. The compositions of CIDRα1 subtype transcripts varied markedly between patients, and none of the subtypes were dominant. Transcript-level analyses targeting other domain types indicated that subtypes of DBLβ or DBLζ domains might mediate binding phenomena that, in conjunction with EPCR binding, could contribute to pathogenesis. These observations strengthen the rationale for targeting the PfEMP1-EPCR interaction by vaccines and adjunctive therapies. Interventions should target EPCR binding of all CIDRα1 subtypes.

OBJECTIVES: To determine the costs of Rapid Syphilis Test (RSTs) as compared with rapid plasma reagin (RPR) when implemented in a Tanzanian setting, and to determine the relative impact of a quality assurance (QA) system on the cost of RST implementation. METHODS: The incremental costs for RPR and RST screening programmes in existing antenatal care settings in Geita District, Tanzania were collected for 9 months in subsequent years from nine health facilities that varied in size, remoteness and scope of antenatal services. The costs per woman tested and treated were estimated for each facility. A sensitivity analysis was constructed to determine the impact of parameter and model uncertainty. FINDINGS: In surveyed facilities, a total of 6362 women were tested with RSTs compared with 224 tested with RPR. The range of unit costs was $1.76-$3.13 per woman screened and $12.88-$32.67 per woman treated. Unit costs for the QA system came to $0.51 per woman tested, of which 50% were attributed to salaries and transport for project personnel. CONCLUSIONS: Our results suggest that rapid syphilis diagnostics are very inexpensive in this setting and can overcome some critical barriers to ensuring universal access to syphilis testing and treatment. The additional costs for implementation of a quality system were found to be relatively small, and could be reduced through alterations to the programme design. Given the potential for a quality system to improve quality of diagnosis and care, we recommend that QA activities be incorporated into RST roll-out.

The pathogenesis of Plasmodium falciparum malaria involves a complex interplay between parasite adhesion and inflammatory response that includes release of cytokines and activation of the endothelium with accompanying release of Angiopoitin 2 (Ang2) to the plasma. A-disintegrin and metalloproteinase 17 (ADAM17) is a protein responsible for releasing cytokines, including Tumor Necrosis Factor α (TNFα), and shedding of adhesion proteins. In this study, we show that plasma levels of ADAM17 are increased in Tanzanian children hospitalized with a malaria infection compared with asymptomatic children but similar to children hospitalized with other infectious diseases. The plasma levels of ADAM17 decreased during recovery after an acute malaria episode. Plasma levels of Ang2 were associated with markers of malaria severity and levels of var transcripts encoding P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) containing Cysteine Rich Inter Domain Region α1 (CIDRα1) domains predicted to bind Endothelial Protein C receptor (EPCR). ADAM17 levels were not associated with expression of var genes encoding different PfEMP1 types when controlling for age. These data are the first to report ADAM17 plasma levels in malaria-exposed individuals, and support the notion that parasite sequestration mediated by EPCR-binding PfEMP1 is associated with endothelial activation and pathology in severe paediatric malaria.

Background Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to the control of malaria. In 2001 Tanzania replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as first-line drug, which in turn was replaced by artemisinin combination therapy in 2006. SP has however, continued to be used in intermittent preventive treatment of malaria in pregnancy (IPTp) despite reports of high levels of resistance to SP due to the lack of alternatives to SP for IPTp. Recent reports have indicated recovery of CQ-susceptibility in Malawi, Kenya, Mozambique, and Tanzania based on the prevalence of wild types at codon 76 of the Pfcrt gene in indigenous P. falciparum populations. The current prevalence of this Pfcrt- 76 CQ resistance marker from six regions of Tanzania mainland is hereby reported. Methods DNA extracted from filter-paper dried blood spots and rapid diagnostics kit strips collected from finger-prick blood were used to genotype the Pfcrt-76 resistance marker using PCR-RFLP. Data from previously published studies were used to generate CQ susceptibility recovery trends using logistic regression model. Results Seven hundred and forty one (741) samples were genotyped. The current frequency of the CQ-susceptible Pfcrt-K76 was above 92% and did not differ between regions in Tanzania (χ 2 = 2.37; p = 0.795). The K76 allelic prevalence was between 85.7 and 93% in regions (χ 2 = 7.88, p = 0.163). The CQ resistance recovery trends showed regional variability that may be caused by differences in malaria transmission intensity, but overall the trends converge as the susceptibility levels in all regions approach >90%. Conclusions CQ withdrawal in Tanzania has resulted into >90% recovery of susceptibility in ten years of withdrawal. These findings are in support of the search for CQ-based combination drugs as a possible future alternative to SP for IPTp in places where full recovery of CQ-susceptibility will be evident.

Background. Microbial transmission from patient to patient has been linked to transient colonization of health care workers attires. Contamination of health care workers’ clothing including white coats may play a big role in transmission of microbes.Study Objective. This study was conducted to determine the type of bacterial contamination on the white coats of medical doctors and students and associated factors.Methods. A cross-sectional study with purposive sampling of the bacterial contamination of white coats was undertaken. Demographic variables and white coats usage details were captured: when the coat was last washed, frequency of washing, washing agents used, and storage of the white coats. Swabs were collected from the mouth of left and right lower pockets, sleeves, and lapels of white coat in sterile techniques.Results. Out of 180 participants involved in the current study, 65.6% were males. Most of the coats were contaminated by staphylococci species and other bacteria such as Gram negative rods.Conclusion and Recommendations. White coats are potential source of cross infection which harbour bacterial agents and may play a big role in the transmission of nosocomial infection in health care settings. Effort should be made to discourage usage of white coats outside clinical areas.

BACKGROUND: As malaria transmission declines, continued improvements of prevention and control interventions will increasingly rely on accurate knowledge of risk factors and an ability to define high-risk areas and populations at risk for focal targeting of interventions. This paper explores the independent association between living in a hotspot and prospective risk of malaria infection. METHODS: Malaria infection status defined by nPCR and AMA-1 status in year 1 were used to define geographic hotspots using two geospatial statistical methods (SaTScan and Kernel density smoothing). Other malaria risk factors for malaria infection were explored by fitting a multivariable model. RESULTS: This study demonstrated that residing in infection hotspot of malaria transmission is an independent predictor of malaria infection in the future. CONCLUSION: It is likely that targeting such hotspots with better coverage and improved malaria control strategies will result in more cost-efficient uses of resources to move towards malaria elimination.

BACKGROUND: Within affected communities, Plasmodium falciparum infections may be skewed in distribution such that single or small clusters of households consistently harbour a disproportionate number of infected individuals throughout the year. Identifying these hotspots of malaria transmission would permit targeting of interventions and a more rapid reduction in malaria burden across the whole community. This study set out to compare different statistical methods of hotspot detection (SaTScan, kernel smoothing, weighted local prevalence) using different indicators (PCR positivity, AMA-1 and MSP-1 antibodies) for prediction of infection the following year. METHODS: Two full surveys of four villages in Mwanza, Tanzania were completed over consecutive years, 2010-2011. In both surveys, infection was assessed using nested polymerase chain reaction (nPCR). In addition in 2010, serologic markers (AMA-1 and MSP-119 antibodies) of exposure were assessed. Baseline clustering of infection and serological markers were assessed using three geospatial methods: spatial scan statistics, kernel analysis and weighted local prevalence analysis. Methods were compared in their ability to predict infection in the second year of the study using random effects logistic regression models, and comparisons of the area under the receiver operating curve (AUC) for each model. Sensitivity analysis was conducted to explore the effect of varying radius size for the kernel and weighted local prevalence methods and maximum population size for the spatial scan statistic. RESULTS: Guided by AUC values, the kernel method and spatial scan statistics appeared to be more predictive of infection in the following year. Hotspots of PCR-detected infection and seropositivity to AMA-1 were predictive of subsequent infection. For the kernel method, a 1 km window was optimal. Similarly, allowing hotspots to contain up to 50% of the population was a better predictor of infection in the second year using spatial scan statistics than smaller maximum population sizes. CONCLUSIONS: Clusters of AMA-1 seroprevalence or parasite prevalence that are predictive of infection a year later can be identified using geospatial models. Kernel smoothing using a 1 km window and spatial scan statistics both provided accurate prediction of future infection.

Assessing the readiness of health facilities to deliver safe male circumcision services is more important in sub-Saharan Africa because of the inadequacy state of health facilities in many ways. The World Health Organization recommends that only facilities equipped with available trained staff, capable to perform at least minor surgery, able to offer minimum MC package and appropriate equipment for resuscitation, and compliant with requirements for sterilization and infection control should be allowed to deliver safe circumcision services. A cross-sectional study using quantitative data collection technique was conducted to assess the readiness of the health facilities to deliver safe circumcision services in selected districts of Tanzania. All hospitals, health centres and 30% of all dispensaries in these districts were selected to participate in the study. Face-toface questionnaires were administered to the heads of the health facilities and to health practitioners. Overall, 49/69 (59%) of the facilities visited provided circumcision services and only 46/203 (24%) of the health practitioners performed circumcision procedures. These were mainly assistant medical officers and clinical officers. The vast majority – 190/203 (95%) – of the health practitioners require additional training prior to providing circumcision services. Most facilities – 63/69 (91%) – had all basic supplies (gloves, basin, chlorine and waste disposal) necessary for infection prevention, 44/69 (65%) provided condoms, HIV counselling and testing, and sexuallytransmitted infections services, while 62/69 (90%) had the capability to perform at least minor surgery. However, only 25/69 (36%) and 15/69 (22%) of the facilities had functioning sterilization equipment and appropriate resuscitation equipment, respectively. There is readiness for roll out of circumcision services; however, more practitioners need to be trained on circumcision procedures, demand forecasting. Sterilization equipment for infection prevention and resuscitation equipment should also be made available.

Background Male circumcision (MC) has been shown to be effective against heterosexual acquisition of HIV infection and is being scaled up as an additional strategy against HIV in several countries of Africa. However, the policy environment (whether to formulate new specific policy on MC or adapts the existing ones); and the role of various stakeholders in the MC scale up process in Tanzania was unclear. We conducted this study as part of a situation analysis to understand the attitudes of policy makers and other key community and health authority decision makers towards MC, policy and regulatory environment, and the readiness of a health system to accommodate scaling up of MC services. Methods We conducted 36 key informants' interviews with a broad range of informants including civil servants, religious leaders, cultural and traditional gatekeepers and other potential informants. Study informants were selected at the national level, regional, district and community levels to represent both traditionally circumcising and non-circumcising communities. Results Study informants had positive attitudes and strong beliefs towards MC. Key informants in traditionally non-circumcising districts were willing to take their sons for medically performed MC. Religious leaders and traditional gatekeepers supported MC as it has been enshrined in their holy scripts and traditional customs respectively. Civil servants highlighted the need for existence of enabling policy and regulatory environment in the form of laws, regulations and guidelines that will ensure voluntary accessibility, acceptability, quality and safety for those in need of MC services. Majority of informants urged the government to make improvements in the health system at all levels to ensure availability of adequate trained personnel, infrastructure, equipment, and supplies for MC scale up, and insisted on the involvement of different MC stakeholders as key components in effective roll out of medically performed MC programme in the country. Conclusions Findings from the situation analysis in Tanzania have shown that despite the absence of a specific policy on MC, basic elements of enabling policy environment at national, regional, district and community levels are in place for the implementation of MC scale up programme.

The World Health Organisation and the Joint United Nations Programme on AIDS recommend male circumcision (MC) as an additional intervention against HIV infection. Various sub-Saharan African countries are at different stages of rolling out MC programmes. Despite initial fears, studies conducted among traditionally non-circumcising communities in Africa have shown that MC is widely accepted as a biomedical intervention. However, little is known on how traditionally circumcising communities where MC carries considerable social meaning and significance would respond to such programmes. This study was conducted among a traditionally circumcising community in Tarime district in Tanzania as part of a national situation analysis prior to initiating a national MC programme. It employed key informant interviews and focus group discussions for data collection. Results show that the Kurya ethnic group practice MC as a rite of passage from childhood to adulthood. Each clan organises its own circumcision ceremony, which takes place every even numbered years. Clan leaders and traditional circumcisers are central to its organisation. Among the Kurya, there is high regard for traditional MC as it is perceived as upholding cultural practice and identity. It also embodies notions of bravery since anaesthetics are not used. On the other hand, medical MC is not viewed as prestigious since anaesthetics are used to suppress pain. Social pressure for traditional MC is applied through ridiculing of those uncircumcised or circumcised at health facilities. In general, there are positive attitudes towards MC as it is perceived as enhancing personal hygiene and having a protective effect against sexually transmitted infections. For the success of nation-wide MC programmes, there is need to develop programmes that incorporate both clinical and sociocultural interests.

Background Data from traditionally circumcising communities show that non-circumcised males and those circumcised in the medical settings are stigmatised. This is because traditional circumcision embodies local notions of bravery as anaesthetics are not used. This study was conducted to assess the acceptability of safe medical circumcision before the onset of sexual activity for HIV infection risk reduction in a traditionally circumcising community in Tanzania. Methods A cross-sectional study was conducted among males and females aged 18-44 years in traditionally circumcising communities of Tarime District in Mara Region, North-eastern Tanzania. A face-to-face questionnaire was administered to females to collect information on the attitudes of women towards circumcision and the preferred age for circumcision. A similar questionnaire was administered to males to collect information on socio-demographic, preferred age for circumcision, factors influencing circumcision, client satisfaction, complications and beliefs surrounding the practice. Results Results were available for 170 males and 189 females. Of the males, 168 (98.8%) were circumcised and 61 (36.3%) of those circumcised had the procedure done in the medical setting. Of those interviewed, 165 (97.1%) males and 179 (94.7%) females supported medical male circumcision for their sons. Of these, 107 (64.8%) males and 130 (72.6%) females preferred prepubertal medical male circumcision (12 years or less). Preference for prepubertal circumcision was significantly associated with non-Kurya ethnic group, circumcision in the medical setting and residence in urban areas for males in the adjusted analysis. For females, preference for prepubertal circumcision was significantly associated non-Kurya ethnic group and being born in urban areas in the adjusted analysis. Conclusions There is a shift of preference from traditional male circumcision to medical male circumcision in this traditionally circumcising population. However, this preference has not changed the circumcision practices in the communities because of the community social pressure. Male circumcision national program should take advantage of this preference of medical male circumcision by introducing safe and affordable circumcision services and mobilising communities in a culturally sensitive manner to take up circumcision services.

Interruption of vector-human contact is of priority in breaking the transmission chain of malaria parasites. The use of plant extracts as repellents against malaria vectors have been advocated in different studies. The objective of this study was to evaluate the protective efficacy of freshly distilled and ten years old essential oil of Ocimum suave against Anopheles gambiae s.s. The feeding inhibition of old and freshly prepared O. suave extracts in liquid paraffin or glycerine were compared with N,N-diethyl-3-methylbenzamide (DEET) using mosquito cage evaluation. There was no significant difference between the ten years stored and freshly prepared O. suave extract in either glycerine (t = 0.578, df = 58, P = 0.566) or liquid paraffin (t = 0.148, df = 58, P = 0.883). Neither ten years old (P = 0.423 in glycerine and P=0.423 in liquid paraffin) or freshly prepared (P=0.427 in glycerine and P = 0.412 in liquid paraffin) O. suave extracts had significant difference against DEET in protection efficacy. Comparison of the mean between O. suave in glycerine and in paraffin had no difference (t= 1.445, df = 24, P = 0.161). Therefore, promotion of plant extracts for commercialization is of priority in rural Tanzania where whole plants are currently used as repellents against malaria vectors.

Malaria is the most important public health problem in Sub-Saharan Africa. There is a pressing need for development and use of alternative control approaches, which will remain effective even with increasing threat of mosquito resistance to chemical control and smaller number of approved chemical insecticides. This study evaluated the effect of combined use of attractant baited Mosquito Magnet Liberty Plus™ (MM) trap and bed nets on human mosquito biting rates under semi-field conditions. Human landing catch done under holed bednets was used to assess the number of biting mosquitoes attracted to human bait. A combination of MM trap and untreated bednet reduced biting rates of Culex quinquefasciatus but not Anopheles gambiae s.s. However, combining an insecticide treated bednet (ITN) and MM trap greatly reduced biting rates of both Cx quinquefasciatus and An. gambiae s.s. Moreover, a treated bednet increased the MM trap catch of both Cx quinquefasciatus and An. gambiae s.s. The present study has shown the potential of a combination of MM trap and ITN in trapping and controlling vectors of malaria and lymphatic filariasis. Synergistic use of attractant baited traps and ITNs displays a ‘push-pull’ phenomenon. The findings indicate that the strategy could be incorporated in an integrated mosquito control approach to maximise the efficiency of mosquito populationreduction methods through the use of appropriately selected methods.

Background Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6–59 month children with uncomplicated malaria and in asymptomatic 2–10 month old infants. Methodology and Principal Findings An open label single arm (SP) standard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants. Enrolment was stopped early (87 in the symptomatic and 25 in the asymptomatic studies) due to the high failure rate. Molecular markers were examined for recrudescence, re-infection and markers of drug resistance and a review of literature of studies looking for the 581G dhps mutation was carried out. In symptomatic children PCR-corrected early treatment failure was 38.8% (95% CI 26.8–50.8) and total failures by day 28 were 82.2% (95% CI 72.5–92.0). There was no significant difference in treatment failures between asymptomatic and symptomatic children. 96% of samples carried parasites with mutations at codons 51, 59 and 108 in the dhfr gene and 63% carried a double mutation at codons 437 and 540. 55% carried a third mutation with the addition of a mutation at codon 581 in the dhps gene. This triple: triple haplotype maybe associated with earlier treatment failure. Conclusion In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful. The study found a new combination of parasite mutations that maybe associated with increased and earlier failure. Trial Registration ClinicalTrials.gov NCT00361114

BACKGROUND: Malaria transmission intensity is a crucial determinant of malarial disease burden and its measurement can help to define health priorities. Rapid, local estimates of transmission are required to focus resources better but current entomological and parasitological methods for estimating transmission intensity are limited in this respect. An alternative is determination of antimalarial antibody age-specific sero-prevalence to estimate sero-conversion rates (SCR), which have been shown to correlate with transmission intensity. This study evaluated SCR generated from samples collected from health facility attendees as a tool for a rapid assessment of malaria transmission intensity. METHODOLOGY AND PRINCIPAL FINDINGS: The study was conducted in north east Tanzania. Antibodies to Plasmodium falciparum merozoite antigens MSP-1(19) and AMA-1 were measured by indirect ELISA. Age-specific antibody prevalence was analysed using a catalytic conversion model based on maximum likelihood to generate SCR. A pilot study, conducted near Moshi, found SCRs for AMA-1 were highly comparable between samples collected from individuals in a conventional cross-sectional survey and those collected from attendees at a local health facility. For the main study, 3885 individuals attending village health facilities in Korogwe and Same districts were recruited. Both malaria parasite prevalence and sero-positivity were higher in Korogwe than in Same. MSP-1(19) and AMA-1 SCR rates for Korogwe villages ranged from 0.03 to 0.06 and 0.07 to 0.21 respectively. In Same district there was evidence of a recent reduction in transmission, with SCR among those born since 1998 [MSP-1(19) 0.002 to 0.008 and AMA-1 0.005 to 0.014 ] being 5 to 10 fold lower than among individuals born prior to 1998 [MSP-1(19) 0.02 to 0.04 and AMA-1 0.04 to 0.13]. Current health facility specific estimates of SCR showed good correlations with malaria incidence rates in infants in a contemporaneous clinical trial (MSP-1(19) r(2) = 0.78, p

Background Syphilis is still a major cause of morbidity and mortality in women and children. In Tanzania syphilis was shown to cause adverse pregnancy outcomes in 49% and stillbirth in 25% of pregnant women with high titre syphilis. Although syphilis screening and treatment is a national policy and is one of the most cost effective interventions, its implementation on a large scale is limited. Lack of a simple and rapid point of care diagnostic test for syphilis has been suggested as one of the major reasons for this limitation. We implemented a demonstration project in Geita district, Tanzania to assess the feasibility of introducing a rapid diagnostic test in antenatal care services. The objectives of the project were to determine (1) the feasibility of increasing access to antenatal syphilis screening using same day testing and treatment strategy, and (2) the acceptability of introducing rapid syphilis testing to service providers and clients. Methods A health facility based baseline survey was carried out using a structured questionnaire to determine syphilis uptake before rapid test introduction. A team of four district trainers and supervisors were trained on how to perform the test, on quality assurance and stock management. Health workers were also trained on how to perform the test, quality assurance and stock management. Then rapid tests were introduced in all health facilities and qualitative data were collected to assess acceptability of the test. The uptake of syphilis testing and treatment among pregnant women in 3 months before and after rapid test introduction were compared using χ 2 test. Results Numbers of pregnant women tested in the 3 months after rapid test introduction were significantly higher than those tested before its introduction in the same period (p Conclusions Introduction of rapid syphilis tests has made it possible to implement national policy for screening pregnant women in Tanzania. Increasing access to screening and treatment will prevent many perinatal deaths.

Background The burden of congenital syphilis remains high in many low-income countries, despite the availability of preventive therapy. Rapid syphilis tests (RSTs) could improve access to and cost-effectiveness of syphilis screening programs in low resource settings. The objective of this study was to inform programs how best to use RSTs based on relative efficiency, cost-effectiveness and access considerations. Methods Incremental costs for RST screening in existing antenatal care settings in Tanzania were collected from nine health facilities varying in size, remoteness, and scope of services provided. The number of DALYs averted was modelled from project outputs. Economic costs per: woman tested, treated, and DALY were calculated for each facility. A sensitivity analysis was constructed to determine the impact of parameter and model uncertainty. Results In surveyed facilities a total 6362 women were tested with RSTs over a costing period of 9 months, as compared with just 224 tested with RPR over a similar time period the previous year. Total economic costs for RST screening ranged from $1758 to $6375. Unit costs ranged from $1.90 to $6.06 per woman screened, $17.76–$63.19 per woman treated, and $1.20–$4.26 per DALY. Larger facilities had lower unit costs, suggesting that economies of scale exist in screening services. Results were sensitive to assumptions regarding supply wastage, frequency of supervision, and program duration. Conclusion RST screening costs fall well below the WHO threshold for ‘highly attractive’ cost-effectiveness. Although RST costs are slightly higher than those for RPR, the number of women reached by screening services was increased under RSTs. Results suggest that RSTs can overcome critical barriers to antenatal syphilis testing and treatment. Through removal of supply chain barriers, RSTs enable the realisation of economies of scale in screening services. This suggests that larger facilities will benefit from implementation of RSTs. RSTs further allow for screening where a lack of infrastructure prevents consistent RPR testing. Therefore, in the effort to increase equity in access to screening, roll-out is also recommended in facilities not able to provide RPR screening. RSTs are currently being expanded throughout the country in the effort to increase access to syphilis screening in antenatal care. This could facilitate control of congenital syphilis and prevent countless unnecessary fetal and infant deaths.

To determine the prevalence of HIV-1 infection and to identify the most important risk factors for infection.A cross-sectional population survey carried out in 1990 and 1991 in Mwanza Region, Tanzania.Adults aged 15-54 years were selected from the region (population, 2 million) by stratified random cluster sampling: 2434 from 20 rural villages, 1157 from 20 roadside settlements and 1554 from 20 urban wards. Risk factor information was obtained from interviews. All sera were tested for HIV-1 antibodies using enzyme-linked immunosorbent assay (ELISA); sera non-negative on ELISA were also tested by Western blot.The response rate was 81%. HIV-1 infection was 1.5 times more common in women than in men; 2.5% of the adult population in rural villages, 7.3% in roadside settlements and 11.8% in town were infected. HIV-1 infection occurred mostly in women aged 15-34 years and men aged 25-44 years. It was associated with being separated or widowed, multiple sex partners, presence of syphilis antibodies, history of genital discharge or genital ulcer, travel to Mwanza town, and receiving injections during the previous 12 months, but not with male circumcision.This study confirms that HIV-1 infection in this region in East Africa is more common in women than in men. The results are consistent with the spread of HIV-1 infection along the main roads. There is no evidence that lack of circumcision is a risk factor in this population.Between August 1990 and February 1991, health workers took blood samples from, and trained interviewers spoke to, 5145 15-to-54-year-old adults living in either an urban area (1554), in a rural village (2434), or in a roadside settlement (1157) in the Mwanza Region of Tanzania to determine the prevalence of HIV-1 infection and its most significant risk factors. The prevalence rate of HIV-1 infection was highest in urban areas, lower in roadside settlements, and lowest in rural areas (11.8%, 7.3%, and 2.5%, respectively), suggesting that HIV-1 had spread along main roads. Yet, there were as many people infected with HIV-1 in rural areas of the Mwanza Region as there were in Mwanza town. Women were 1.2 (rural) to 1.7 (urban) times more likely to be infected with HIV-1 than were men, indicating greater efficiency of HIV-1 transmission from men to women than from women to men. HIV-1 infection peaked in the 15-to-34-year-old group in women and in the 25-to-44-year-old group in men. Separated, divorced, or widowed men and women were at increased risk of being HIV-1 infected, even when controlled for numerous factors (odds ratio (OR) = 3.4 and 1.6, respectively). This may have been an indication of multiple partners, since the question concerning multiple partners was vague. Other important risk factors for women and men were syphilis antibodies (OR = 1.7 and 1.85), history of genital discharge or chancroid (OR = 2, 1.6 and 2.7, 1.6), travel to Mwanza town (OR = 2.1 and 1.7), and receiving injections during the previous 12 months (OR = 1.5 and 1.9). There was no link between male circumcision and HIV-1 infection. In fact, there seemed to be a moderate protective effect (OR = 0.8). This effect may be even more likely since urban men, who were at greatest risk of HIV-1 infection (8.7% vs. 5.4% [roadside] and 2.4% [rural]), had the highest rate of circumcision (61% vs. 29% and 17%, respectively).

Background Cholera outbreaks have occurred in Tanzania since 1974. To date, the genetic epidemiology of these outbreaks has not been assessed. Methods 96 Vibrio cholerae O1 isolates from five regions were characterized, and their genetic relatedness assessed using multi-locus variable-number tandem-repeat analysis (MLVA) and whole genome sequencing (WGS). Results Of the 48 MLVA genotypes observed, 3 were genetically unrelated to any others, while the remaining 45 genotypes separated into three MLVA clonal complexes (CCs) - each comprised of genotypes differing by a single allelic change. In Kigoma, two separate outbreaks, 4 months apart (January and May, 2015), were each caused by genetically distinct strains by MLVA and WGS. Remarkably, one MLVA CC contained isolates from both the May outbreak and ones from the 2011/2012 outbreak in Dar-es-Salaam. However, WGS revealed the isolates from the two outbreaks to be distinct clades. The outbreak that started in August 2015 in Dar-es-Salaam and spread to Morogoro, Singida and Mara was comprised of a single MLVA CC and WGS clade. Isolates from within an outbreak were closely related differing at fewer than 5 nucleotides. All isolates were part of the 3rd wave of the 7th pandemic and were found in four clades related to isolates from Kenya and Asia. Conclusions We conclude that genetically related V. cholerae cluster in outbreaks, and distinct strains circulate simultaneously. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2252-9) contains supplementary material, which is available to authorized users.

Background At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Methods Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Results Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. Conclusion The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings.