Background: Early and accurate diagnosis of febrile patients is essential to treat uncomplicated malaria cases properly, prevent severe malaria, and avert unnecessary anti-malarial treatments. Improper use of anti-malarials increases the risk of adverse drug reaction and the evolution of drug/parasite resistance. While microscopy is the most common form of malaria diagnosis, concerns over its accuracy have prompted the incorporation of malaria rapid diagnostic tests (RDTs) into many national malaria control programmes. Methods: Over a three-month period, a direct comparison between microscopy and RDTs was made in a rural, private dispensary in the Kilombero Valley, Morogoro District, southern Tanzania, with the aim of estimating the extent of malaria over-diagnosis and over-treatment with anti-malarials. The study cohort was made up of patients referred by the dispensary's clinician for malaria testing. One hundred percent of patients approached agreed to participate in this study and were then tested using both microscopy and RDTs. Using the results from the comparison of the two tests at this dispensary, the potential cost effectiveness of introducing RDTs to a neighbouring public health centre was estimated on the basis of this centre's past malaria records spanning December 2007 to August 2011. Results: At the private dispensary, the apparent prevalence of malaria was 78% based on microscopy whereas the true prevalence, calculated using RDTs as the gold standard, was estimated at 14%. This discrepancy indicates that when using microscopy as the sole diagnostic test, malaria is being over-diagnosed by approximately a factor of five in this setting. At the public clinic, apparent malaria prevalence based on microscopy was 74%. If similar rates of over-diagnosis are assumed, 5,285 patients of the 6,769 patients positively diagnosed with malaria using microscopy were likely given unnecessary anti-malarials, and their true cause of illness was not addressed. The introduction of RDTs to the public clinic would be highly cost-efficient, with an estimated net saving of over 96 USD/month. Conclusions: Compared with RDTs, microscopy led to almost four out of five patients being over-diagnosed with malaria in this rural part of Tanzania. A policy that encompasses both the private and public sectors of health care is needed to ensure quality diagnostic testing for febrile patients. With estimated prevalence at 14%, RDT introduction is recommended given WHO findings that RDTs are predicted to be cost-effective in prevalence areas of less than 20%. The use of RDTs in malaria diagnosis would not only reduce government spending but would prove beneficial to ensuring appropriate care and treatment of febrile illness.

Background: Long-lasting insecticidal nets (LLINs) are a cornerstone of malaria control at present, and millions are used each day across the globe. However, there is limited information about the durability of LLINs under different conditions of utilization and there is no consensus about when a LLIN ceases to be protective due to physical deterioration. This knowledge is important for malaria control programmes to plan for procurement and replacement. Methods: A cross-sectional survey of 208 households where Olyset(R) nets distributed five years ago were still present was conducted in the village of Sauri, western Kenya, in the context of the Millennium Villages Project. Information on bed net utilization and maintenance was collected in each household through a structured questionnaire, and one five-year old Olyset(R) net from each sampled household was randomly selected and collected for physical examination. All holes larger than 0.5 cm were measured in each net, registering their position, and a hole index was calculated following WHO guidelines. Nets were classified as in good condition, moderately damaged or badly torn based on the hole index. The analysis explored the associations between demographic and socioeconomic characteristics of households, patterns of bed net utilization and maintenance and physical condition of the nets. Additional analysis was conducted using malaria prevalence data collected in a separate survey to explore if there was any association between the condition of the net collected in a household and the presence of malaria parasites in members of that household. Results: 81.4% of Olyset nets distributed five years ago were still present in the surveyed households, and 98.97% of the nets were reportedly used the previous night. Nets had an average of 34.2 holes (95% CI 30.12-38.22), and the mean hole index was 849 (95% CI 711-986), IQR 174-1,135. Only 15% of nets were still in good condition, 48% were moderately damaged and 37% were badly torn after five years of utilization. There was no association between household characteristics or patterns of bed net utilization or maintenance and physical condition of the nets. The only predictor of the physical condition of the net was the cleanliness at the time of examination. There was a difference of 17.6 per cent points in the proportion of households with at least one blood smear positive for Plasmodium falciparum between those with a net in good condition (5.3%) and those with a moderately damaged or badly torn net (22.9%), with a 95% CI (0.04-0.305), t=2.77 with unequal variance, 37.2 df, p=0.008. Conclusions: Olyset nets were used extensively in Sauri, western Kenya after five years of distribution, regardless of their physical condition. However, nets had a large number of holes, and only 15% were found in good condition. Nets in good condition seem to be still protective after five years of utilization, while nets with more than 100 cm2 of holed surface may be associated with higher malaria parasitaemia at household level. Continued replacement of damaged nets and promotion of net maintenance and repair may be necessary to maintain the protective effectiveness of LLINs.

Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan Africa. . . .

Wolbachia is a maternally transmitted symbiotic bacterium of insects that has been proposed as a potential agent for the control of insect-transmitted diseases. . . .

In 2003, Ghana introduced the national health insurance scheme (NHIS) to promote access to healthcare. . . .

A 28-year-old woman (G2P1A), with 36 weeks gestation, reported to a health facility in Sunyani on 22(nd) February 2009 with history of labour pains, without fever. . . .

Current gene synthesis methods allow the generation of long segments of dsDNA. . . .

Protein export into the host red blood cell is one of the key processes in the pathobiology of the malaria parasite Plasmodiumtrl falciparum, which extensively remodels the red blood cell to ensure its virulence and survival. . . .

. . .

Insect-killing fungi such as Beauveria bassiana are being evaluated as possible active ingredients for use in novel biopesticides against mosquito vectors that transmit malaria. . . .

BACKGROUND: In high-resource settings, 'pay-for-performance' (P4P) programs have generated interest as a potential mechanism to improve health service delivery and accountability. . . .

In N Engl J Med, Vol. 365 (2011), 1863-75, doi:10.1056/NEJMoa1102287

BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).
ST Agnandji, B Lell, SS Soulanoudjingar, JF Fernandes, BP Abossolo, C Conzelmann, BG Methogo, Y Doucka, A Flamen, B Mordmuller, S Issifou, PG Kremsner, J Sacarlal, P Aide, M Lanaspa, JJ Aponte, A Nhamuave, D Quelhas, Q Bassat, S Mandjate, E Macete, P Alonso, S Abdulla, N Salim, O Juma, M Shomari, K Shubis, F Machera, AS Hamad, R Minja, A Mtoro, A Sykes, S Ahmed, AM Urassa, AM Ali, G Mwangoka, M Tanner, H Tinto, U D'Alessandro, H Sorgho, I Valea, MC Tahita, W Kabore, S Ouedraogo, Y Sandrine, RT Guiguemde, JB Ouedraogo, MJ Hamel, S Kariuki, C Odero, M Oneko, K Otieno, N Awino, J Omoto, J Williamson, V Muturi-Kioi, KF Laserson, L Slutsker, W Otieno, L Otieno, O Nekoye, S Gondi, A Otieno, B Ogutu, R Wasuna, V Owira, D Jones, AA Onyango, P Njuguna, R Chilengi, P Akoo, C Kerubo, J Gitaka, C Maingi, T Lang, A Olotu, B Tsofa, P Bejon, N Peshu, K Marsh, S Owusu-Agyei, KP Asante, K Osei-Kwakye, O Boahen, S Ayamba, K Kayan, R Owusu-Ofori, D Dosoo, I Asante, G Adjei, G Adjei, D Chandramohan, B Greenwood, J Lusingu, S Gesase, A Malabeja, O Abdul, H Kilavo, C Mahende, E Liheluka, M Lemnge, T Theander, C Drakeley, D Ansong, T Agbenyega, S Adjei, HO Boateng, T Rettig, J Bawa, J Sylverken, D Sambian, A Agyekum, L Owusu, F Martinson, I Hoffman, T Mvalo, P Kamthunzi, R Nkomo, A Msika, A Jumbe, N Chome, D Nyakuipa, J Chintedza, WR Ballou, M Bruls, J Cohen, Y Guerra, E Jongert, D Lapierre, A Leach, M Lievens, O Ofori-Anyinam, J Vekemans, T Carter, D Leboulleux, C Loucq, A Radford, B Savarese, D Schellenberg, M Sillman, P Vansadia, Rts

In Journal of immunology, Vol. 170 (2003), 3195-203

Cell-mediated immunity plays a crucial role in the control of many infectious diseases, necessitating the need for adjuvants that can augment cellular immune responses elicited by vaccines. It is well established that protection against one such disease, malaria, requires strong CD8(+) T cell responses targeted against the liver stages of the causative agent, Plasmodium spp. In this report we show that the dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1 (DC-CK1), which is produced in humans and acts on naive lymphocytes, can enhance Ag-specific CD8(+) T cell responses when coadministered with either irradiated Plasmodium yoelii sporozoites or a recombinant adenovirus expressing the P. yoelii circumsporozoite protein in mice. We further show that these enhanced T cell responses result in increased protection to malaria in immunized mice challenged with live P. yoelii sporozoites, revealing an adjuvant activity for DC-CK1. DC-CK1 appears to act preferentially on naive mouse lymphocytes, and its adjuvant effect requires IL-12, but not IFN-gamma or CD40. Overall, our results show for the first time an in vivo role for DC-CK1 in the establishment of primary T cell responses and indicate the potential of this chemokine as an adjuvant for vaccines against malaria as well as other diseases in which cellular immune responses are important.
O Bruna-Romero, J Schmieg, M Del Val, M Buschle, M Tsuji

In The Journal of infectious diseases, Vol. 196 (2007), 1553-64, doi:10.1086/522865

Infection with Plasmodium berghei ANKA is a well-established model of human cerebral malaria (CM). We show herein that Toll-like receptor (TLR) signaling influences the development of lethal CM in P. berghei ANKA-infected mice. Modulation of outcome was dependent on genetic background, such that deletion of myeloid differentiation factor (MyD) 88 on the susceptible C57BL/6 background resulted in resistance to CM, whereas deletion of MyD88 on the resistant BALB/c background led to increased mortality. Our data show that MyD88 influenced the production of T helper-polarizing cytokines, including interferon (IFN)- gamma, interleukin (IL)-4, and IL-17, as well as the total number of Foxp3(+) regulatory T (T(reg)) cells in a manner dependent on host genetic background. In addition, mRNA levels of IFN- gamma, CXCL10, and CXCL9 were strongly up-regulated in the brains of susceptible wild-type but not MyD88(-/-) infected mice. These results suggest that TLR signaling and host genetic background influences the pathogenesis of CM via modulation of cytokine production and T(reg) cell numbers.
JW Griffith, C O'Connor, K Bernard, T Town, DR Goldstein, R Bucala

In BMC medical genetics, Vol. 10 (2009), 65, doi:10.1186/1471-2350-10-65

BACKGROUND: The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers. METHODS: We assessed the TIRAP S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh. RESULTS: In Ghana, the TIRAP S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous TIRAP 180L tend to increase the risk of sepsis in the German study (P = 0.04). CONCLUSION: A broad protective effect of TIRAP S180L against infectious diseases per se is not discernible.
L Hamann, O Kumpf, RP Schuring, E Alpsoy, G Bedu-Addo, U Bienzle, L Oskam, FP Mockenhaupt, RR Schumann

In Nature genetics, Vol. 22 (1999), 145-50, doi:10.1038/9649

Genetic variation in cytokine promoter regions is postulated to influence susceptibility to infection, but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown. Through systematic DNA footprinting of the TNF (encoding tumour necrosis factor, TNF) promoter region, we have identified a single nucleotide polymorphism (SNP) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes. The OCT-1-binding genotype, found in approximately 5% of Africans, is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations, after correction for other known TNF polymorphisms and linked HLA alleles.
JC Knight, I Udalova, AV Hill, BM Greenwood, N Peshu, K Marsh, D Kwiatkowski

In Genes and immunity, Vol. 3 (2002), 414-8, doi:10.1038/sj.gene.6363909

Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore investigated whether IL12B polymorphisms may affect the outcome of severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated with increased mortality in Tanzanian children having cerebral malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B promotor polymorphism had decreased production of nitric oxide, which is in part regulated by IL-12 activity. These studies suggest that IL12B polymorphisms, via regulation of IL-12 production, may influence the outcome of malaria infection in at least one African population.
G Morahan, CS Boutlis, D Huang, A Pain, JR Saunders, MR Hobbs, DL Granger, JB Weinberg, N Peshu, ED Mwaikambo, K Marsh, DJ Roberts, NM Anstey

Homeopathy is a therapeutic method based on the application of similia principle, utilizing ultra-low doses of medicinal substances made from natural products. . . .

Background: Studies conducted thus far have demonstrated that the malaria vaccine (RTS,S) has a promising safety profile. Within the context of planning for future vaccine trials and for the purpose of building on previous research that has been undertaken in sub-Saharan Africa with regard to community perceptions about clinical studies, this research aimed to explore the community perceptions on the secondary health benefits established by the malaria vaccine trials (RTS,S Phase 2 and Phase 3) at the Korogwe site in Tanzania. Methods: An exploratory qualitative study design was used. Participants were recruited from the Korogwe site. Sampling techniques were purposive and random. A total of five focus group discussions and six in-depth interviews were conducted. Interview guides with open-ended questions were employed to collect data. Male and female parents whose infants participated and those whose infants did not participate in the trials, health workers and community leaders were interviewed. Thematic analysis framework was used to analyse the data. Results: The activities of a malaria vaccine project appeared to be well known to the community. Respondents had largely positive views towards the secondary health benefits which have been established by malaria vaccine trials. The project has led to a massive investment in health care infrastructure and an improvement in health care services across the study areas. The project was perceived by the community to have established major secondary health benefits. Misconceptions amongst respondents, especially with regard to blood samples, were also observed in this study. Conclusion: Despite some misconceptions with regard to the conduct of malaria vaccine trials, especially on blood sampling, generally this study observed that most participants were positive about the secondary health benefits brought about by the malaria vaccine trials in Korogwe.

Mosquitoes are deadly efficient disease transmitters. Research conducted at Michigan State University, however, demonstrates that they also can be equally adept in curing diseases such as malaria.