Transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization

Malaria transmission-blocking immunity has been studied in natural malaria infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. Effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. Two general types of effector mechanism have been identified. One is an antibody mediated mechanism which acts against the extracellular sexual stages of the parasite within the midgut of a blood feeding mosquito. The other is a cytokine mediated mechanism which inactivates the gametocytes of the parasites while in the circulation of the vertebrate host. Both effects have been observed during natural infections and following artificial immunization. The basis of induction of transmission-blocking immunity, including the nature of the memory for such immunity, however, may be very different in different host/parasite systems and during natural infection of following artificial immunization. Following artificial immunization a strong immune memory for transmission blocking immunity has been observed in animal systems. By contrast, following natural infections in man immune memory for transmission blocking immunity has been found to be weak and short lived if it occurs at all. It is suggested that the immunogens which induce natural transmission blocking immunity may be CD4+ independent.

Transmission factors in malaria epidemiology and control in Africa

Genetic and environmental components of factors contributing in malaria transmission are reviewed. Particular attention is given to density dependent regulation of vector populations in relation to the survival rate anophelines. The expectation of vector activities are different according to the epidemiological characteristics of malaria, mainly its stability. In areas with perennial and high transmission (stable malaria) vector control could reduce malaria related morbidity and mortality, whithout any effect on the endemicity. However this need further investigations. In areas where the transmission period is very short (unstable malaria), vector control will have an important impact on the disease and the endemicity. Control projects using indoor spraying with insecticide and impregnated bed nets are discussed.

Is there an efficient trap or collection method for sampling Anopheles darlingi and other malaria vectors that can describe the essential parameters affecting transmission dynamics as effectively as human landing catches? - A Review

Distribution, abundance, feeding behaviour, host preference, parity status and human-biting and infection rates are among the medical entomological parameters evaluated when determining the vector capacity of mosquito species. To evaluate these parameters, mosquitoes must be collected using an appropriate method. Malaria is primarily transmitted by anthropophilic and synanthropic anophelines. Thus, collection methods must result in the identification of the anthropophilic species and efficiently evaluate the parameters involved in malaria transmission dynamics. Consequently, human landing catches would be the most appropriate method if not for their inherent risk. The choice of alternative anopheline collection methods, such as traps, must consider their effectiveness in reproducing the efficiency of human attraction. Collection methods lure mosquitoes by using a mixture of olfactory, visual and thermal cues. Here, we reviewed, classified and compared the efficiency of anopheline collection methods, with an emphasis on Neotropical anthropophilic species, especially Anopheles darlingi, in distinct malaria epidemiological conditions in Brazil.

The monitoring of hematopoietic stem cell transplant donors and recipients from endemic areas for malaria

Malaria is an unusual complication after hematopoietic stem cell transplantation in non-endemic countries. However, transplant candidates, recipients and donors living in endemic regions frequently report previous episodes of malaria. This fact could represent an important risk for immunosuppressed recipients that could develop severe malaria cases. We report a case of hematopoietic stem cell transplant (HSCT) in which the donor had a history of previous malaria, and close monitoring was performed before and after procedure by parasitological and molecular tests. The donor presented Plasmodium vivax in thick blood smears one month after transplant and was treated according to Brazilian Health Ministry guidelines. The polymerase chain reaction (PCR) was able to detect malaria infection in the donor one week earlier than thick blood film. Even without positive results, the recipient was pre-emptively treated with chloroquine in order to prevent the disease. We highlight the importance of monitoring recipients and donors in transplant procedures with the aim of reducing the risk of malaria transmission.

Transfusion-transmitted malaria: case report of asymptomatic donor harboring Plasmodium malariae

Malaria in Brazil is endemic in the Amazon region, but autochthonous cases with low parasitaemia occur in the Atlantic Forest area of the country. According to Brazilian legislation no test is mandatory for blood donors from non-endemic areas. However if they have traveled to malaria transmission regions they are deferred for six months before they can donate. This report describes a transfusion-transmitted malaria case in Sao Paulo, Brazil, where one recipient received infected blood and developed the disease. He lived in Sao Paulo and had no previous transfusion or trips to endemic areas, including those of low endemicity, such as Atlantic Forest. Thick blood smears confirmed Plasmodiummalariae. All donors lived in Sao Paulo and one of them (Donor 045-0) showed positive hemoscopy and PCR. This asymptomatic donor had traveled to Juquia, in the Atlantic Forest area of S ao Paulo State, where sporadic cases of autochthonous malaria are described. DNA assay revealed P. malariae in the donor's (Donor 045-0) blood. Serum archives of the recipient and of all blood donors were analyzed by ELISA using both P. vivax and P. falciparum antigens, and IFAT with P. malariae. Donor 045-0's serum was P. malariae IFAT positive and the P. vivax ELISA was reactive. In addition, two out of 44 donors' archive sera were also P. vivax ELISA reactive. All sera were P. falciparum ELISA negative. This case suggests the need of reviewing donor selection criteria and deferral strategies to prevent possible cases of transfusion-transmitted malaria.

Impact of dams and irrigation schemes in Anopheline (Diptera: Culicidae) bionomics and malaria epidemiology

Irrigation schemes and dams have posed a great concern on public health systems of several countries, mainly in the tropics. The focus of the present review is to elucidate the different ways how these human interventions may have an effect on population dynamics of anopheline mosquitoes and hence, how local malaria transmission patterns may be changed. We discuss different studies within the three main tropical and sub-tropical regions (namely Africa, Asia and the Pacific and the Americas). Factors such as pre-human impact malaria epidemiological patterns, control measures, demographic movements, human behaviour and local Anopheles bionomics would determine if the implementation of an irrigation scheme or a dam will have negative effects on human health. Some examples of successful implementation of control measures in such settings are presented. The use of Geographic Information System as a powerful tool to assist on the study and control of malaria in these scenarios is also highlighted.

Mercury exposure and malaria prevalence among gold miners in Pará, Brazil

Economic development, including resource extraction, can cause toxic exposures that interact with endemic infectious diseases. Mercury is an immunotoxic metal used in the amalgamation of gold, resulting in both occupational exposures and environmental pollution. A cross-sectional medical survey was conducted in 1997 on 135 garimpeiros in Para, Brazil, because of their risks of both mercury exposure and malaria transmission. Mean levels of blood and urine mercury were well above non-exposed background levels. Twenty-six subjects had malaria parasitemia: Health symptoms consistent with mercury exposure were reported, but neither symptoms nor signs correlated with mercury levels in blood or urine. We did not find a dose response relationship between mercury exposure and likelihood of prevalent malaria infection, but there was a possible reduction in acquisition of immunity that may be associated with conditions in gold mining, including mercury exposure.

Malaria outbreaks in a non-endemic area of Brazil, 2005

In March 2005, a resident of the municipality of Monte Alegre de Minas, State of Minas Gerais, without any history of traveling to endemic areas for malaria, was diagnosed with Plasmodium vivax infection and local mosquito-borne transmission was suspected. The epidemiological investigation identified another 10 cases with local transmission and all of them were related to the imported malaria case that was detected in this region. The potential exposure site was the banks of the river Tejuco, an area frequented by mineral prospectors. Some of these prospectors were known to have come from states with malaria transmission. In the autochthonous cases, Plasmodium vivax and Plasmodium falciparum were diagnosed. Entomological investigation identified Anopheles (Nyssorhynchus) darlingi, Anopheles (Nyssorhynchus) albitarsis, Anopheles (Nyssorhynchus) triannulatus and Anopheles (Nyssorhynchus) parvus. After the first outbreak, another three autochthonous cases were notified in municipality of Monte Alegre de Minas, in the same year. The occurrence of these outbreaks highlights the importance of surveillance systems in areas that are nonendemic for malaria.

The changing distribution of malaria in the Brazilian Amazon, 2003-2004 and 2008-2009

Introduction More than half of the malaria cases reported in the Americas are from the Brazilian Amazon region. While malaria is considered endemic in this region, its geographical distribution is extremely heterogeneous. Therefore, it is important to investigate the distribution of malaria and to determine regions whereby action might be necessary. Methods Changes in malaria indicators in all municipalities of the Brazilian Amazon between 2003-2004 and 2008-2009 were studied. The malaria indicators included the absolute number of malaria cases and deaths, the bi-annual parasite incidence (BPI), BPI ratios and differences, a Lorenz curve and Gini coefficients. Results During the study period, mortality from malaria remained low (0.02% deaths/case), the percent of municipalities that became malaria-free increased from 15.6% to 31.7%, and the Gini coefficient increased from 82% to 87%. In 2003, 10% of the municipalities with the highest BPI accumulated 67% of all malaria cases, compared with 2009, when 10% of the municipalities (with the highest BPI) had 80% of the malaria cases. Conclusions This study described an overall decrease in malaria transmission in the Brazilian Amazon region. As expected, an increased heterogeneity of malaria indicators was found, which reinforces the notion that a single strategy may not bring about uniformly good outcomes. The geographic clustering of municipalities identified as problem areas might help to define better intervention methods.

Malaria in the State of Amazonas: a typical Brazilian tropical disease influenced by waves of economic development

In Brazil, more than 99% of malaria cases are reported in the Amazon, and the State of Amazonas accounts for 40% of this total. However, the accumulated experience and challenges in controlling malaria in this region in recent decades have not been reported. Throughout the first economic cycle during the rubber boom (1879 to 1912), malaria was recorded in the entire state, with the highest incidence in the villages near the Madeira River in the Southern part of the State of Amazonas. In the 1970s, during the second economic development cycle, the economy turned to the industrial sector and demanded a large labor force, resulting in a large migratory influx to the capital Manaus. Over time, a gradual increase in malaria transmission was observed in peri-urban areas. In the 1990s, the stimulation of agroforestry, particularly fish farming, led to the formation of permanent Anopheline breeding sites and increased malaria in settlements. The estimation of environmental impacts and the planning of measures to mitigate them, as seen in the construction of the Coari-Manaus gas pipeline, proved effective. Considering the changes occurred since the Amsterdam Conference in 1992, disease control has been based on early diagnosis and treatment, but the development of parasites that are resistant to major antimalarial drugs in Brazilian Amazon has posed a new challenge. Despite the decreased lethality and the gradual decrease in the number of malaria cases, disease elimination, which should be associated with government programs for economic development in the region, continues to be a challenge.

Observations on the distribution of anophelines in Suriname with particular reference to the malaria vector Anopheles darlingi

A study was made on the distribution of anophelines in Suriname with special emphasis on the principal malaria vector Anopheles darlingi and on the occurrence of other possible vector species. Peridomestic human bait collections of adult mosquitoes and collections of larvae were made in many localities with a recent history of malaria transmission. Stable population of An. darlingi were only found in the interior, south of the limit of tidal influence, due to year-round availability of breeding habitats in quietly sunlit places in flooded forest areas and along river banks. In the area with tidal movement of the rivers, breeding is limited to flooded areas in the west season. Anopheles darlingi was only incidentally collected in low densities. In the interior, malaria transmission occurred in all places where An. darlingi was found. The absence of malaria transmission along the Upper Suriname River could be explained by the absence of An. darlingi. In the malaria endemic areas, An darlingi was the most numerous mosquito biting on man. In the tidal region, malaria outbreak are infrequent and might be explained by the temporary availability of favourable beeding habitats for An. darlingi. However, evidence is insufficient to incriminate an. darlingi as the vector of malaria in this region and the possible vectorial role of other anophelines is discussed.

Epidemiological risk sratification of malaria in the Américas

During the last years, malaria had a significant increase in Latin America, emerging again as one critical health problem in the Region of the Americas. More than 1.04 million new cases were reported in 1990. This resurgence of malaria needed a comprehensive strategy for its prevention and control. National malaria control programs recognized the epidemiological stratification of malaria as a valuable method to assist them in the recognition of local variations and factors that specifically contribute to the level and intensity of transmission in critical malarious areas. Also it serves as a useful instrument for the selection of needed malaria prevention and control activities. The principal feature of this approach is to provide a dynamic and ongoing process for assessing in the epidemiological importance of different risk factors (socio-economic, ecological, organizatuion of health services) in malaria transmission. health interventions are based on this assesment and are aimed directly at the reduction or elimination of the identified risk factors operating at the local level. Intersectorial co-participation and the integration of malaria programs in local health services are also important aspects of this public health approach.

Ecology of malaria vectors in the Americas and future direction

The resurgence of malaria in the Americas has renewed interest in Anopheles biology. Anopheles darlingi, An. albimanus, An. nuneztovai and An aquasalis are reconfirmed as major malaria vectors and other species are playing important roles in regional malaria transmission. Adultbiting activity and larval ecology are discussed in detail. Seasonal abundance and daily biting activity of Anopheles vary considerably among species and geographically for the same species. Anopheles albimanus has the least amount of variation in biting activity over its range and An. darlingi has the greatest. All species studied are more exophilic and exophagic than endophilic and endophagic. Anopheles darling is more antropophilic, endophilic and endophagic than other Anophelines. Larval studies remain more descriptive than comprehensive. Research on Anophelines is becoming more integrated and biologists are using new biochemical techniques and ecological principles to answer critical questions. This "pluralization" will help us understand species complexes, population dynamics and malaria transmission. integrated control programs will require more regional, in-depth ecological studies.

Diagnosis of malaria by acridine orange fluorescent microscopy in an endemic area of Venezuela

Fluorescent (acridine orange) microscopical examination of capillary centrifuged blood (quantitative buffy coat [QBC®] analysis) and Giemsa stained thick blood smears (GTS) were compared for diagnosis of malaria in blood specimens from adults living in malaria transmission areas of the States of Bolivar and Amazonas in southeastern and south Venezuela, respectively. Of a total of 198 GTS examined, 95 subjects (48%) showed parasitaemia. Among the 95 blood films with a positive GTS, 94 were judged positive by the QBC. However, positive QBC tubes were found in 29 out of 103 blood specimens with a negative GTS. Thus, relative to a GTS standard, the sensitivity and specificity of the QBC-test was 99.2% and 72%, respectively. Young trophozoites of Plasmodium vivax and P. falciparum could not be distinguished with certainty. It is confirmed that the QBC offers many advantages compared with the standard diagnosis of malaria parasites, specifically in the speed of staining and ease of interpretation. However, in places where P. falciparum and P. vivax occur, species and stage differentiation should be confirmed with the GTS.

Malaria vectors in the municipality of Serra do Navio, State of Amapá, Amazon Region, Brazil

We conducted a survey to determine the vectors of malaria in six localities of Serra do Navio municipality, State of Amapá, from 1990 to 1991. Malaria infection rates of 29.3%, 6.2% and 20.4% were detected by human blood smears in Colônia Água Branca, Porto Terezinha and Arrependido, respectively. There was no malaria infection detected in Serra do Navio. Fifteen species were identified among 3,053 anopheline mosquitoes collected by human bait and 64.4% were identified as Anopheles albitarsis s.l., 16.7% An. braziliensis, 9.5% An. nuneztovari and 5.8% An. triannulatus. An. darlingi, the main vector of malaria in the Amazon region of Brazil, was scare. Using enzyme-linked immunosorbent assay (ELISA), a total positive rate of 0.8% (23/2876) was found for six species: fifteen An. albitarsis s.l., four An. nuneztovari, and one of each: An. braziliensis, An. triannulatus, An. oswaldoi and An. rangeli. Nine of 23 positive mosquitoes were infected with Plasmodium malariae, eight with P. vivax VK210, three with P. vivax VK247 and three with P. falciparum. Since An. albitarsis s.l. was collected feeding on humans, was present in the highest density and was positive by ELISA for malaria sporozoites, it probably plays an important role in malaria transmission in this area.