Molecular basis for evasion of host immunity and pathogenesis in malaria

AbstractThe article relates the ability of the malaria parasite Plasmodium falciparum to avoid a protective immune response, and to induce pathological changes, to the properties of specific parasite molecules. Cytoadherence and rosetting are important features of cerebral malaria and involve proteins located on the surface of the infected red blood cell. Proinflammatory cytokines, particularly tumour necrosis factor (TNF), play a role in protective immunity and in inducing pathology. Glycophosphatidyl inositol membrane anchors of parasite proteins possess insulin like activity and induce TNF synthesis. People subject to repeated infections in malaria endemic areas rarely develop complete or sterile immunity to malaria. They frequently carry small numbers of parasites in the blood, with little symptoms of the disease, illustrating a phenomenon termed semi-immunity. The basis for semi-immunity is incompletely understood. Malaria parasites are susceptible to several immunological effector mechanisms. The presence of extensive repetitive regions is a feature of many P. falciparum proteins. Available evidence suggests that the structural characteristics of the repeats and their location on the surface of parasite proteins promote immunogenicity. The repeats may help the parasite evade host immunity by (i) exhibiting sequence polymorphism, (ii) preventing the normal affinity and isotype maturation of an immune response, (iii) functioning possibly as B cell superantigens, (iv) generating predominantly thymus independent antibody responses, and (v) acting as a sink for binding protective antibodies. Sequence diversity in non-repetitive regions and antigenic variation in parasite molecules located on the surface of infected red blood cells also play a role in immune evasion. Some sequence homologies between parasite and human proteins may be due to molecular mimicry. Homologies in other instances can cause autoimmune responses. The immune evasion mechanisms of the parasite need to be considered in developing vaccines. Protective immunity and pathology may be delicately balanced in malaria

Global Climate Change and Its Potential Impact on Disease Transmission by Salinity-Tolerant Mosquito Vectors in Coastal Zones

Global climate change can potentially increase the transmission of mosquito vector-borne diseases such as malaria, lymphatic filariasis, and dengue in many parts of the world. These predictions are based on the effects of changing temperature, rainfall, and humidity on mosquito breeding and survival, the more rapid development of ingested pathogens in mosquitoes and the more frequent blood feeds at moderately higher ambient temperatures. An expansion of saline and brackish water bodies (water with <0.5 ppt or parts per thousand, 0.5–30 ppt and >30 ppt salt are termed fresh, brackish, and saline respectively) will also take place as a result of global warming causing a rise in sea levels in coastal zones. Its possible impact on the transmission of mosquito-borne diseases has, however, not been adequately appreciated. The relevant impacts of global climate change on the transmission of mosquito-borne diseases in coastal zones are discussed with reference to the Ross–McDonald equation and modeling studies. Evidence is presented to show that an expansion of brackish water bodies in coastal zones can increase the densities of salinity-tolerant mosquitoes like Anopheles sundaicus and Culex sitiens, and lead to the adaptation of fresh water mosquito vectors like Anopheles culicifacies, Anopheles stephensi, Aedes aegypti, and Aedes albopictus to salinity. Rising sea levels may therefore act synergistically with global climate change to increase the transmission of mosquito-borne diseases in coastal zones. Greater attention therefore needs to be devoted to monitoring disease incidence and preimaginal development of vector mosquitoes in artificial and natural coastal brackish/saline habitats. It is important that national and international health agencies are aware of the increased risk of mosquito-borne diseases in coastal zones and develop preventive and mitigating strategies. Application of appropriate counter measures can greatly reduce the potential for increased coastal transmission of mosquito-borne diseases consequent to climate change and a rise in sea levels. It is proposed that the Jaffna peninsula in Sri Lanka may be a useful case study for the impact of rising sea levels on mosquito vectors in tropical coasts

Possible impact of rising sea levels on vector-borne infectious diseases

<p>Abstract</p> <p>Background</p> <p>Vector-borne infectious diseases are a significant cause of human and animal mortality and morbidity. Modeling studies predict that changes in climate that accompany global warming will alter the transmission risk of many vector-borne infectious diseases in different parts of the world. Global warming will also raise sea levels, which will lead to an increase in saline and brackish water bodies in coastal areas. The potential impact of rising sea levels, as opposed to climate change, on the prevalence of vector-borne infectious diseases has hitherto been unrecognised.</p> <p>Presentation of the hypothesis</p> <p>Mosquito species possessing salinity-tolerant larvae and pupae, and capable of transmitting arboviruses and parasites are found in many parts of the world. An expansion of brackish and saline water bodies in coastal areas, associated with rising sea levels, can increase densities of salinity-tolerant vector mosquitoes and lead to the adaptation of freshwater vectors to breed in brackish and saline waters. The breeding of non-mosquito vectors may also be influenced by salinity changes in coastal habitats. Higher vector densities can increase transmission of vector-borne infectious diseases in coastal localities, which can then spread to other areas.</p> <p>Testing the hypothesis</p> <p>The demonstration of increases in vector populations and disease prevalence that is related to an expansion of brackish/saline water bodies in coastal areas will provide the necessary supportive evidence. However the implementation of specific vector and disease control measures to counter the threat will confound the expected findings.</p> <p>Implications of the hypothesis</p> <p>Rising sea levels can act synergistically with climate change and then interact in a complex manner with other environmental and socio-economic factors to generate a greater potential for the transmission of vector-borne infectious diseases. The resulting health impacts are likely to be particularly significant in resource-poor countries in the tropics and semi-tropics. Some measures to meet this threat are outlined.</p

Variations in salinity tolerance of malaria vectors of the Anopheles subpictus complex in Sri Lanka and the implications for malaria transmission

Abstract Background Anopheles subpictus sensu lato, a widespread vector of malaria in Asia, is reportedly composed of four sibling species A-D based on distinct cytogenetic and morphological characteristics. However An. subpictus species B specimens in Sri Lanka are termed An. subpictus B/ An. sundaicus because of recent genetic data. Differences in salinity tolerance and coastal/inland prevalence of An. subpictus sibling species that were not previously established in Sri Lanka are presented here. Results Specimens with morphological characteristics of all four Indian An. subpictus sibling species were found in Sri Lanka. Sibling species A, C and D tended to be predominant in inland, and An. subpictus species B/An. sundaicus, in coastal localities. Sibling species C was predominant in both adult and larval inland collections. Larvae of An. subpictus B/An. sundaicus were found in inland and coastal sites, including a lagoon, with salinity varying from 0 to 30 ppt. An. subpictus sibling species A, C and D larvae were present in water of salinity between 0 to 4 ppt. An. subpictus C, D and An. subpictus B/An. sundaicus larvae showed compatible differential salinity tolerance in laboratory tests. The first instar larvae of An. subpictus B/An. sundaicus showed 100% survival up to 15 ppt in comparison to species C and D where the corresponding values were 3 ppt and 6 ppt respectively. However all third instar larvae of An. subpictus B/An. sundaicus survived up to 30 ppt salinity whereas An. subpictus C and D tolerated up to 4 ppt and 8 ppt salinity respectively. Conclusions The results suggest that An. subpictus species B/An. sundaicus breed in fresh, brackish and nearly saline water while An. subpictus species C and D do so in fresh and less brackish waters in Sri Lanka, as in India. Because of the established role of An. sundaicus s.l. and An. subpictus s.l. as malaria vectors, the findings indicate a need for greater monitoring of brackish water breeding habitats in Asia. Tolerance to 15 ppt salinity may also constitute a simple method for differentiating An. subpictus B/An. sundaicus larvae from those of An. subpictus species C and D in field studies.</p

Genetic evidence for malaria vectors of the Anopheles sundaicus complex in Sri Lanka with morphological characteristics attributed to Anopheles subpictus species B

<p>Abstract</p> <p>Background</p> <p><it>Anopheles subpictus sensu lato</it>, a widespread malaria vector in Asia, is reportedly composed of four sibling species A - D. Mosquitoes morphologically identified as belonging to the Subpictus complex were collected from different locations near the east coast of Sri Lanka, and specific ribosomal DNA sequences determined to validate their taxonomic status.</p> <p>Methods</p> <p><it>Anopheles subpictus s.l</it>. larvae and blood-fed adults were collected from different locations in the Eastern province and their sibling species status was determined based on published morphological characteristics. DNA sequences of the D3 domain of 28 S ribosomal DNA (rDNA) and the internal transcribed spacer -2 (ITS-2) of mosquitoes morphologically identified as <it>An. subpictus </it>sibling species A, B, C and D were determined.</p> <p>Results</p> <p>Phylogenetic analysis based on D3 domain of rDNA resulted in two clades: one clade with mosquitoes identified as <it>An. subpictus </it>species A, C, D and some mosquitoes identified as species B, and another clade with a majority of mosquitoes identified as species B with D3 sequences that were identical to <it>Anopheles sundaicus </it>cytotype D. Analysis of ITS-2 sequences confirmed a close relationship between a majority of mosquitoes identified as <it>An. subpictus </it>B with members of the <it>An. sundaicus </it>complex and others identified as <it>An. subpictus </it>B with <it>An. subpictus s.l</it>.</p> <p>Conclusions</p> <p>The study suggests that published morphological characteristics are not specific enough to identify some members of the Subpictus complex, particularly species B. The sequences of the ITS-2 and D3 domain of rDNA suggest that a majority that were identified morphologically as <it>An. subpictus </it>species B in the east coast of Sri Lanka, and some identified elsewhere in SE Asia as <it>An. subpictus s.l</it>., are in fact members of the Sundaicus complex based on genetic similarity to <it>An. sundaicus s.l</it>. In view of the well-known ability of <it>An. sundaicus s.l</it>. to breed in brackish and fresh water and its proven ability to transmit malaria in coastal areas of many Southeast Asian countries, the present findings have significant implications for malaria control in Sri Lanka and neighbouring countries.</p

Anopheles culicifacies breeding in brackish waters in Sri Lanka and implications for malaria control

<p>Abstract</p> <p>Background</p> <p><it>Anopheles culicifacies </it>is the major vector of both falciparum and vivax malaria in Sri Lanka, while <it>Anopheles subpictus </it>and certain other species function as secondary vectors. In Sri Lanka, <it>An. culicifacies </it>is present as a species complex consisting of species B and E, while <it>An. subpictus </it>exists as a complex of species A-D. The freshwater breeding habit of <it>An. culicifacies </it>is well established. In order to further characterize the breeding sites of the major malaria vectors in Sri Lanka, a limited larval survey was carried out at a site in the Eastern province that was affected by the 2004 Asian tsunami.</p> <p>Methods</p> <p>Anopheline larvae were collected fortnightly for six months from a brackish water body near Batticaloa town using dippers. Collected larvae were reared in the laboratory and the emerged adults were identified using standard keys. Sibling species status was established based on Y-chromosome morphology for <it>An. culicifacies </it>larvae and morphometric characteristics for <it>An. subpictus </it>larvae and adults. Salinity, dissolved oxygen and pH were determined at the larval collection site.</p> <p>Results</p> <p>During a six month study covering dry and wet seasons, a total of 935 anopheline larvae were collected from this site that had salinity levels up to 4 parts per thousand at different times. Among the emerged adult mosquitoes, 661 were identified as <it>An. culicifacies s.l</it>. and 58 as <it>An. subpictus s.l</it>. Metaphase karyotyping of male larvae showed the presence of species E of the Culicifacies complex, and adult morphometric analysis the presence of species B of the Subpictus complex. Both species were able to breed in water with salinity levels up to 4 ppt.</p> <p>Conclusions</p> <p>The study demonstrates the ability of <it>An. culicifacies </it>species E, the major vector of falciparum and vivax malaria in Sri Lanka, to oviposit and breed in brackish water. The sibling species B in the <it>An. subpictus </it>complex, a well-known salt water breeder and a secondary malaria vector in the country, was also detected at the same site. Since global warming and the rise in sea levels will further increase of inland brackish water bodies, the findings have significant implications for the control of malaria in Sri Lanka and elsewhere.</p

Stability of Slopes - A Case History

A Lecture cum-cinema hall was constructed on a terrace developed at the top of a hillock at a site located in the north-eastern part of India. At the time of development of the site, excavated soil was dumped on the slopes and retaining walls were constructed to retain the earth. After the first monsoon, the retaining walls gave way. Further distress in the vicinity of the building was noticed in the subsequent three years. The paper describes the details of the above failure, the investigations carried out and the remedial measures suggested