scholarly journals Identification of Novel Malaria Transmission-Blocking Vaccine Candidates

2021 ◽  
Vol 11 ◽  
Author(s):  
Eizo Takashima ◽  
Mayumi Tachibana ◽  
Masayuki Morita ◽  
Hikaru Nagaoka ◽  
Bernard N. Kanoi ◽  
...  
Keyword(s):  
Research And Development ◽  
Control Measures ◽  
Sub Saharan Africa ◽  
Parasite Transmission ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Malaria Vaccines ◽  
Sub Saharan ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

Control measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery.

scholarly journals Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition

2021 ◽  
Vol 11 ◽  
Author(s):  
Chiamaka V. Ukegbu ◽  
George K. Christophides ◽  
Dina Vlachou
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Disease Transmission ◽  
Sub Saharan Africa ◽  
Parasite Transmission ◽  
Targeted Disruption ◽  
Transmission Blocking ◽  
Essential Function ◽  
Sub Saharan ◽  
Transmission Biology

Plasmodium falciparum malaria remains a major cause of global morbidity and mortality, mainly in sub-Saharan Africa. The numbers of new malaria cases and deaths have been stable in the last years despite intense efforts for disease elimination, highlighting the need for new approaches to stop disease transmission. Further understanding of the parasite transmission biology could provide a framework for the development of such approaches. We phenotypically and functionally characterized three novel genes, PIMMS01, PIMMS57, and PIMMS22, using targeted disruption of their orthologs in the rodent parasite Plasmodium berghei. PIMMS01 and PIMMS57 are specifically and highly expressed in ookinetes, while PIMMS22 transcription starts already in gametocytes and peaks in sporozoites. All three genes show strong phenotypes associated with the ookinete to oocyst transition, as their disruption leads to very low numbers of oocysts and complete abolishment of transmission. PIMMS22 has a secondary essential function in the oocyst. Our results enrich the molecular understanding of the parasite-vector interactions and identify PIMMS01, PIMMS57, and PIMMS22 as new targets of transmission blocking interventions.

scholarly journals Antibodies to Malaria Vaccine Candidates Pvs25 and Pvs28 Completely Block the Ability of Plasmodium vivax To Infect Mosquitoes

2000 ◽  
Vol 68 (12) ◽  
pp. 6618-6623 ◽  
Author(s):  
Hajime Hisaeda ◽  
Anthony W. Stowers ◽  
Takafumi Tsuboi ◽  
William E. Collins ◽  
Jetsumon S. Sattabongkot ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Vaccine ◽  
Antibody Responses ◽  
Sexual Stage ◽  
Infected Blood ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Human Antibodies ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

ABSTRACT Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently clonedPlasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivaxmalaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed inSaccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response.

scholarly journals Biological Control of a Phytosanitary Pest (Thaumatotibia leucotreta): A Case Study

2021 ◽  
Vol 18 (3) ◽  
pp. 1198
Author(s):  
Sean D. Moore
Keyword(s):  
Biological Control ◽  
Systems Approach ◽  
Microbial Control ◽  
Codling Moth ◽  
Environmental Safety ◽  
Control Measures ◽  
Sub Saharan Africa ◽  
The European Union ◽  
Thaumatotibia Leucotreta ◽  
Sub Saharan

Thaumatotibia leucotreta, known as the false codling moth, is a pest of citrus and other crops in sub-Saharan Africa. As it is endemic to this region and as South Africa exports most of its citrus around the world, T. leucotreta has phytosanitary status for most markets. This means that there is zero tolerance for any infestation with live larvae in the market. Consequently, control measures prior to exporting must be exemplary. Certain markets require a standalone postharvest disinfestation treatment for T. leucotreta. However, the European Union accepts a systems approach, consisting of three measures and numerous components within these measures. Although effective preharvest control measures are important under all circumstances, they are most critical where a standalone postharvest disinfestation treatment is not applied, such as within a systems approach. Conventional wisdom may lead a belief that effective chemical control tools are imperative to achieve this end. However, we demonstrate that it is possible to effectively control T. leucotreta to a level acceptable for a phytosanitary market, using only biological control tools. This includes parasitoids, predators, microbial control, semiochemicals, and sterile insects. Simultaneously, on-farm and environmental safety is improved and compliance with the increasing stringency of chemical residue requirements imposed by markets is achieved.

scholarly journals An afebrile heartwater-like syndrome in goats

2013 ◽  
Vol 84 (1) ◽  
Author(s):  
Rhoda Leask ◽  
Kenneth P. Pettey ◽  
Gareth F. Bath
Keyword(s):  
Clinical Signs ◽  
Control Measures ◽  
Sub Saharan Africa ◽  
Limiting Factor ◽  
Febrile Reaction ◽  
Presumptive Diagnosis ◽  
Appropriate Treatment ◽  
Sub Saharan ◽  
Characteristic Features ◽  
And Control

Heartwater is a serious limiting factor for sheep and goat production in the major endemic area of sub-Saharan Africa and therefore most knowledge, research and control methods originate from this region. Whilst the usual or common clinical presentations can be used to make a presumptive diagnosis of heartwater with a good measure of confidence, this is not always the case, and animals suffering from heartwater may be misdiagnosed because their cases do not conform to the expected syndrome, signs and lesions. One aberrant form found occasionally in the Channel Island breeds of cattle and some goats is an afebrile heartwaterlike syndrome. The most constant and characteristic features of this heartwater-like syndrome comprise normal temperature, clinical signs associated with generalised oedema, and nervous signs, especially hypersensitivity. The presumption that the disease under investigation is the afebrile heartwater-like syndrome entails a tentative diagnosis based on history and clinical signs and the response to presumed appropriate treatment (metadiagnosis). The afebrile heartwater-like syndrome presents similarly to peracute heartwater but without the febrile reaction. Peracute cases of heartwater have a high mortality rate, enabling confirmation of the disease on post-mortem examination. Recognition of the afebrile heartwater-like syndrome is important to prevent deaths and identify the need for appropriate control measures.

scholarly journals Contrasting Response Mechanisms of Maize Lines to Striga hermonthica

Agriculture ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 485
Author(s):  
Nnanna N. Unachukwu ◽  
Abebe Menkir ◽  
Adekemi Stanley ◽  
Ebenezer O. Farombi ◽  
Melaku Gedil
Keyword(s):  
Cost Effective ◽  
Resistance Mechanisms ◽  
Control Measures ◽  
Sub Saharan Africa ◽  
Striga Hermonthica ◽  
Maize Line ◽  
Parasitic Weed ◽  
Resistant Lines ◽  
Sub Saharan ◽  
Better Than

Strigahermonthica (Del.) Benth is a parasitic weed that devastates cereals in Sub-Saharan Africa. Several control measures have been proposed for the parasite, of these, host plant resistance is considered the most cost-effective for poor farmers. Some tolerant/resistant lines have been developed and these lines display tolerance/resistance mechanisms to the parasite. A series of studies was done to investigate some of the mechanisms through which a resistant (TZISTR1108) and a susceptible (5057) maize line responds to S. hermonthica infestation, as well as the effects of parasitism on these lines. In this study, TZISTR1108 stimulated the germination and attachment of fewer S. hermonthica plants than 5057, both in the laboratory and on the field. In TZISTR1108, the growth of the S. hermonthica plants, that successfully attached, was slowed. When compared to the un-infested plants, the infested resistant plants showed fewer effects of parasitism than the infested susceptible plants. The infested TZISTR1108 plants were more vigorous, taller and resembled their un-infected counterparts. There were substantial reductions in the stomatal conductance and nitrogen content of the 5057 upon infestation. The resistant inbred line showed multiple mechanisms of resistance to S. hermonthica infestation. It thrives better than the susceptible line by reducing the attachment of S. hermonthica and it delays the parasite’s development.

scholarly journals Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Kavita Singh ◽  
Martin Burkhardt ◽  
Sofia Nakuchima ◽  
Raul Herrera ◽  
Olga Muratova ◽  
...  
Keyword(s):  
Membrane Surface ◽  
Structure And Function ◽  
Fab Fragment ◽  
Membrane Anchor ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Membrane Bound ◽  
And Function ◽  
Transmission Blocking Vaccine

AbstractProteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45. 4F12 appears to sterically interfere with Pfs230 function. Combining mAbs against different epitopes of Pfs230D1 or of Pfs230D1 and Pfs48/45, significantly increased TB activity. These studies elucidate a mechanism of action of the Pfs230D1 vaccine, model the functional activity induced by a polyclonal antibody response and support the development of TB vaccines targeting Pfs230D1 and Pfs230D1-Pfs48/45.

scholarly journals Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE): protocol for a multisite prospective observational study of the causes of fever in Africa and Asia

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e035632 ◽  
Author(s):  
Heidi Hopkins ◽  
Quique Bassat ◽  
Clare IR Chandler ◽  
John A Crump ◽  
Nicholas A Feasey ◽  
...  
Keyword(s):  
Social Science ◽  
Blood Sample ◽  
Venous Blood ◽  
Febrile Illness ◽  
Clinical Diagnostics ◽  
Control Measures ◽  
Sub Saharan Africa ◽  
Venous Blood Sample ◽  
Open Access Journals ◽  
Sub Saharan

IntroductionFever commonly leads to healthcare seeking and hospital admission in sub-Saharan Africa and Asia. There is only limited guidance for clinicians managing non-malarial fevers, which often results in inappropriate treatment for patients. Furthermore, there is little evidence for estimates of disease burden, or to guide empirical therapy, control measures, resource allocation, prioritisation of clinical diagnostics or antimicrobial stewardship. The Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study seeks to address these information gaps.Methods and analysisFIEBRE investigates febrile illness in paediatric and adult outpatients and inpatients using standardised clinical, laboratory and social science protocols over a minimum 12-month period at five sites in sub-Saharan Africa and Southeastern and Southern Asia. Patients presenting with fever are enrolled and provide clinical data, pharyngeal swabs and a venous blood sample; selected participants also provide a urine sample. Laboratory assessments target infections that are treatable and/or preventable. Selected point-of-care tests, as well as blood and urine cultures and antimicrobial susceptibility testing, are performed on site. On day 28, patients provide a second venous blood sample for serology and information on clinical outcome. Further diagnostic assays are performed at international reference laboratories. Blood and pharyngeal samples from matched community controls enable calculation of AFs, and surveys of treatment seeking allow estimation of the incidence of common infections. Additional assays detect markers that may differentiate bacterial from non-bacterial causes of illness and/or prognosticate illness severity. Social science research on antimicrobial use will inform future recommendations for fever case management. Residual samples from participants are stored for future use.Ethics and disseminationEthics approval was obtained from all relevant institutional and national committees; written informed consent is obtained from all participants or parents/guardians. Final results will be shared with participating communities, and in open-access journals and other scientific fora. Study documents are available online (https://doi.org/10.17037/PUBS.04652739).

scholarly journals Challenges and Economic Implications in the Control of Foot and Mouth Disease in Sub-Saharan Africa: Lessons from the Zambian Experience

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Y. Sinkala ◽  
M. Simuunza ◽  
D. U. Pfeiffer ◽  
H. M. Munang’andu ◽  
M. Mulumba ◽  
...  
Keyword(s):  
Economic Impact ◽  
Foot And Mouth Disease ◽  
Movement Control ◽  
Personal Communication ◽  
Mouth Disease ◽  
Control Measures ◽  
Sub Saharan Africa ◽  
Economic Implications ◽  
Foot And Mouth ◽  
Sub Saharan

Foot and mouth disease is one of the world’s most important livestock diseases for trade. FMD infections are complex in nature and there are many epidemiological factors needing clarification. Key questions relate to the control challenges and economic impact of the disease for resource-poor FMD endemic countries like Zambia. A review of the control challenges and economic impact of FMD outbreaks in Zambia was made. Information was collected from peer-reviewed journals articles, conference proceedings, unpublished scientific reports, and personal communication with scientists and personal field experiences. The challenges of controlling FMD using mainly vaccination and movement control are discussed. Impacts include losses in income of over US$ 1.6 billion from exports of beef and sable antelopes and an annual cost of over US$ 2.7 million on preventive measures. Further impacts included unquantified losses in production and low investment in agriculture resulting in slow economic growth. FMD persistence may be a result of inadequate epidemiological understanding of the disease and ineffectiveness of the control measures that are being applied. The identified gaps may be considered in the annual appraisal of the FMD national control strategy in order to advance on the progressive control pathway.

scholarly journals Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

2014 ◽  
Vol 21 (5) ◽  
pp. 712-721 ◽  
Author(s):  
Mary Adetinuke Boyd ◽  
Sharon M. Tennant ◽  
Venant A. Saague ◽  
Raphael Simon ◽  
Khitam Muhsen ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Content Type ◽  
Vaccine Candidates ◽  
Live Attenuated Vaccines ◽  
Bactericidal Antibody ◽  
Paratyphi B ◽  
Sub Saharan ◽  
Functional Antibodies ◽  
New Vaccines

ABSTRACTInvasiveSalmonellainfections for which improved or new vaccines are being developed include enteric fever caused bySalmonella entericaserovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidalSalmonella(NTS) serovars, particularlyS. entericaserovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developedin vitroassays to quantify serum bactericidal antibody (SBA) activity induced byS. Typhi,S. Paratyphi A,S. Typhimurium, andS. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. ForS. Enteritidis,S. Typhimurium, andS. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast,S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administeredS. Typhimurium,S. Enteritidis, andS. Paratyphi A but notS. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited bySalmonellavaccine candidates.

scholarly journals Transmission clusters, predominantly associated with men who have sex with men, play a main role in the propagation of HIV-1 in Northern Spain (2013-2018)

2021 ◽  
Author(s):  
Horacio Gil ◽  
Elena Delgado ◽  
Sonia Benito ◽  
Leonidas Georgalis ◽  
Vanessa Montero ◽  
...  
Keyword(s):  
Control Measures ◽  
Sub Saharan Africa ◽  
Effective Control ◽  
Main Role ◽  
Northern Spain ◽  
Factors Associated ◽  
Phylogenetic Relations ◽  
Sub Saharan ◽  
Sex With Men ◽  
Hiv 1

Viruses of HIV-1-infected individuals whose transmission is related group phylogenetically in transmission clusters (TCs). The study of the phylogenetic relations of these viruses and the factors associated with these individuals is essential to analyze the HIV-1 epidemic. In this study, we examine the role of TCs in the epidemiology of HIV-1 infection in Galicia and the Basque County, two regions of Northern Spain. A total of 1158 newly HIV-1-diagnosed patients (NDs) from both regions diagnosed in 2013-2018 were included in the study. Partial HIV-1 pol sequences were analyzed phylogenetically by approximately-maximum-likelihood with FastTree 2. In this analysis, 10,687 additional sequences from samples from HIV-1-infected individuals collected in Spain in 1999-2019 were also included to assign and determine the TCs sizes. TCs were defined as those which included viruses from ≤4 individuals, at least 50% of them Spaniards, and with ≤0.95 Shimodaira-Hasegawa-like node support in the phylogenetic tree. Factors associated to TCs were evaluated using odds ratios (OR) and their 95% confidence intervals (CI). Fifty one percent of NDs grouped in 162 TCs. Male patients (OR: 2.6; 95% CI: 1.5-4.7) and men having sex with men (MSM) (OR: 2.1; 95% CI: 1.4-3.2) had higher odds of belonging to a TC compared to female and heterosexual patients, respectively. Individuals from Latin America (OR: 0.3; 95% CI: 0.2-0.4), North Africa (OR: 0.4; 95% CI: 0.2-1.0), and especially Sub-Saharan Africa (OR: 0.02; 95% CI: 0.003-0.2) were inversely associated to belonging to TCs compared to native Spaniards. Differences in distribution and sizes of local TCs were observed in both regions reflecting a different epidemic pattern. Our results show that TCs play an important role in the spread of HIV-1 infection in the two Spanish regions studied, where transmission between MSM is predominant. The majority of migrants were infected with viruses not belonging to TCs that expand in Spain. Molecular epidemiology is essential to identify local peculiarities of HIV-1 propagation. The early detection of TCs and prevention of their expansion, implementing effective control measures, could reduce HIV-1 infections.

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