Efficacy of chloroquine plus primaquine treatment and pfcrt mutation in uncomplicated falciparum malaria patients in Rangamati, Bangladesh

A combination of chloroquine (CQ) and primaquine (PQ) had been used as the first-line treatment of uncomplicated Plasmodium falciparum malaria in Rangamati, Bangladesh until the end of 2004. Doctors or medical staffs had felt that CQ plus PQ had become less effective against uncomplicated falciparum malaria patients, but that it was more effective against the minority-indigenous patients than the Bengali patients. The efficacy of CQ plus PQ and the mutation status of the CQ resistance transporter (pfcrt) gene of infecting P. falciparum were, thus, investigated for 45 uncomplicated falciparum malaria patients in Rangamati in 2004. The total failure rate was 57.8%. One or two pfcrt sequences (CIETH and SMNTH at positions 72, 74-76, and 97, mutation underlined) with K76T mutation known to be related to CQ-resistant phenotype were detected in 38 patients' blood samples. Of the 38 patients, in total 15 patients (14/25 minority-indigenous and 1/13 Bengali patients) resulted in adequate clinical and parasitological response (ACPR). There was a statistically significant difference in ACPR rate between the minority-indigenous patients and the Bengali patients. P. falciparum with mutant or resistant pfcrt (pfcrt-resistant) was detected by PCR in blood samples on day 28 for 10 ACPR minority-indigenous patients but not for the only one Bengali ACPR patient, who all were infected with pfcrt-resistant P. falciparum on day 0. The minority-indigenous patients, but not Bengalis, are suggested to be often cured by CQ plus PQ, leaving a very few parasites detectable only by PCR, even when they are infected with pfcrt-resistant P. falciparum.     

Haemostatic alterations in malaria correlate to parasitaemia

Fibrin(ogen) degradation products, platelet counts, antithrombin III, and the components of the Factor VIII complex were studied in a total of 80 patients with Plasmodium falciparum, Plasmodium vivax or Plasmodium ovale infections. The haemostatic findings were correlated to the numbers of parasitized erythrocytes and to each other. The results indicate that haemostatic changes in malaria correlate with the degree of parasitaemia. Evidence for moderate hyperfibrinolysis was found in patients with high P. falciparum parasitaemias only. Thrombocytopenia closely corresponded to parasitaemia and to von Willebrand factor levels, but appeared not to be linked to a consumption of coagulation factors. It was concluded that thrombocytopenia in malaria is not indicative of disseminated intravascular coagulation (DIC) but may relate to endothelial damage.     

Imported Malaria in the United Kingdom

Over 2,000 cases of imported malaria have been confirmed by blood examination. Ninety percent. of cases from tropical Africa were infected with P. falciparum. Most of the patients were Caucasians and had primary infections. All developed fever within a month after arrival and most of them within two weeks of arrival. In some patients malaria parasites were seen in routine blood films.Developing forms of P. falciparum were always present in the peripheral blood of patients suffering from a primary attack which was not diagnosed or treated until a week or more after the onset of fever.All deaths investigated were caused by P. falciparum and were primary infections.In not one of the P. falciparum infections did the victim continue taking prophylactic drugs for more than a few days after leaving the endemic area. Had drugs been continued for one month probably not a single overt case of P. falciparum would have occurred.A primary attack of P. falciparum malaria is seldom, if ever, classical in that the fever is never tertian and may resemble clinically many other diseases.Children in boarding-schools returning from the tropics should be supplied with prophylactic tablets and instructions to the matron. If there is an epidemic of a fever any students who have recently returned from the tropics should have a blood film examined for malaria.The risk of contracting malaria among drug addicts is considerable, especially with P. falciparum.     

Sequential treatment with quinine and mefloquine or quinine and pyrimethamine-sulfadoxine for falciparum malaria.

Patients with falciparum malaria were studied in Thailand, an area of known chloroquine resistance. The patients were unselected and some had severe malaria, and they were randomly assigned to one of two sequential regimes. A short course of quinine (average 4 doses, equivalent to 2 g base) followed by a single dose of pyrimethamine-sulfadoxine (Fansidar) cured 92% of patients (36 out of 39), while a short course of quinine followed by a single 1-5-dose of mefloquine cured all of the 35 patients who could be followed up. Gastrointestinal side effects were minimal if at least 12 hours elapsed between the last dose of quinine and the mefloquine. Sequential quinine and mefloquine is the most effective treatment for patients with chloroquine-resistant falciparum malaria, including those with severe or complicated disease. Mefloquine, however, is not commercially available, and the similar regimen using Fansidar is almost as effective.     

Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities

ABSTRACT: BACKGROUND: Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance. METHODS: The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Jurua valley in the Amazon region. Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008. RESULTS: The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95%CI 0.20 [EN DASH] 0.58) for the P. falciparum malaria incidence rates, 0.67 (95%CI 0.50 [EN DASH] 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95%CI 0.41 [EN DASH] 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported. CONCLUSIONS: In the remote region of the Jurua valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria.     

Severe disease in children hospitalized with a diagnosis of Plasmodium vivax in south-eastern Pakistan

ABSTRACT: BACKGROUND: Infection by Plasmodium vivax has been considered rarely threatening to life, but recent studies challenge this notion. This study documented the frequency and character of severe illness in paediatric patients admitted to a hospital in south-eastern Pakistan with a laboratory-confirmed diagnosis of vivax malaria. METHODS: An observational study of all 180 paediatric patients admitted with any diagnosis of malaria during 2010 was conducted: 128 P. vivax; 48 Plasmodium falciparum; and four mixed infections of these species. Patients were classified as having severe illness with any of the following indicators: Glascow coma scale <11; >2 convulsions; haemoglobin <5g/dL; thrombocytes <50,000/mL; blood glucose <45mg%; >70 breaths/min; or intravenous antimalarial therapy. Additionally, 64 patients with a diagnosis of vivax malaria were treated during 2009, and the 21 of these having severe illness were included in analyses of the frequency and character of severe illness with that diagnosis. RESULTS: During 2010, 39 (31%) or 37 (77%) patients with a diagnosis of P. vivax or P. falciparum were classified as having severe disease. Including the 2009 records of 64 patients having vivax malaria, a total of 60 (31%) patients with severe illness and a diagnosis of P. vivax were available. Altered mental status (Glascow coma scale score <11; or >2 convulsions) dominated at 54% of the 83 indicators of severe illness manifest among the patients with vivax malaria, as was true among the 37 children with a diagnosis of falciparum malaria and being severely ill; 58% of the 72 indicators of severe disease documented among them. No statistically significant difference appeared in frequencies of any other severe disease indicators between patients diagnosed with vivax or falciparum malaria. Despite such similarities, a diagnosis of falciparum malaria nonetheless came with 3.8-fold (95% CI = 1.8- 8.1) higher risk of presenting with severe illness, and 8.0-fold (95% CI = 2.1-31) greater likelihood of presenting with three or more severe disease indicators. Two patients did not survive hospitalization, one each with a diagnosis of falciparum or vivax malaria. CONCLUSIONS: Vivax malaria caused a substantial burden of potentially life-threatening morbidity on a paediatric ward in a hospital in south-eastern Pakistan.     

Serological investigations in retrospective diagnosis of malaria.

Sera were obtained in 415 known cases of malaria (88 residents, 327 immigrants) at different times after diagnosis. Three antigens were used in the indirect fluorscence antibody test to detect antibodies to either Plasmodium falciparum or P vivax. Results in residents and immigrants were analysed separately. Most residents had detectable antibodies within one week after an attack, which began to wane after a month. The strongest reactions were obtained in cases of falciparum malaria with the homologous antigen and in cases of vivax malaria with P fieldi. The overall pattern of results was the same in the immigrants but the proportions positive for malaria antibodies, mean titres, persistence of antibodies, and the cross-reaction were usually greater. Testing for malaria antibodies is probably of value in the retrospective differential diagnosis of malaria in patients who have not been exposed to malaria before but must be interpreted with caution in others.     

Gametocyte clearance in uncomplicated and severe Plasmodium falciparum malaria after artesunate-mefloquine treatment in Thailand

Artemisinin-based combination therapy (ACT) is currently promoted as a strategy for treating both uncomplicated and severe falciparum malaria, targeting asexual blood-stage Plasmodium falciparum parasites. However, the effect of ACT on sexual-stage parasites remains controversial. To determine the clearance of sexual-stage P. falciparum parasites from 342 uncomplicated, and 217 severe, adult malaria cases, we reviewed and followed peripheral blood sexual-stage parasites for 4 wk after starting ACT. All patients presented with both asexual and sexual stage parasites on admission, and were treated with artesunate-mefloquine as the standard regimen. The results showed that all patients were asymptomatic and negative for asexual forms before discharge from hospital. The percentages of uncomplicated malaria patients positive for gametocytes on days 3, 7, 14, 21, and 28 were 41.5, 13.1, 3.8, 2.0, and 2.0%, while the percentages of gametocyte positive severe malaria patients on days 3, 7, 14, 21, and 28 were 33.6, 8.2, 2.7, 0.9, and 0.9%, respectively. Although all patients were negative for asexual parasites by day 7 after completion of the artesunate-mefloquine course, gametocytemia persisted in some patients. Thus, a gametocytocidal drug, e.g., primaquine, may be useful in combination with an artesunate-mefloquine regimen to clear gametocytes, so blocking transmission more effectively than artesunate alone, in malaria transmission areas.     

Intestinal helminth infections are associated with increased incidence of Plasmodium falciparum malaria in Thailand

In a prospective study of the total population of 5 hamlets on the western border of Thailand, all subjects were screened for helminth infections; during the following year, the incidence of malaria was recorded. Patients were not treated for helminth infections. Among 731 villagers, helminth-infected subjects were more likely to develop falciparum malaria during the following year (adjusted risk ratio 2.24, range 1.4-3.6; P = 0.001). The risk of developing falciparum malaria increased with the number of helminth species (P =0.036). Whereas in other studies helminths were associated with protection from severe complications of malaria, it seemed here that helminth-infected patients were more likely to develop malaria. It is suggested that a helminth-mediated Th2 shift may have complex consequences on malaria, decreasing antisporozoite immunity, but protecting against severe malaria.     

The treatment of malaria.

At least four doses of quinine followed by a single dose of mefloquine or by a single dose of sulfadoxine-pyrimethamine are two highly effective regimens for chloroquine-resistant falciparum malaria. Mefloquine alone is valuable in ambulant patients. Chloroquine-sensitive falciparum malaria can be treated with a course of chloroquine. Vivax and all other types of malaria should be treated with sequential chloroquine and primaquine. Quinine, by intravenous infusion, is the most effective drug for severe falciparum malaria. The optimum intravenous dose varies between 5 mg/kg and 10 mg/kg administered over four hours. Intravenous or oral quinine should be administered about every 12 hours and the total daily dose of quinine should rarely exceed 20 mg/kg. Intravenous fluid input should be controlled in falciparum malaria to prevent pulmonary oedema. Established renal failure is best treated by dialysis. The value of adrenocortical steroids for falciparum coma has not been established. Fresh blood transfusion may be helpful in small doses for severe anaemia and to replace clotting factors. Anticoagulants, such as heparin, should not be used in falciparum malaria.     

A Locally Acquired Falciparum Malaria via Nosocomial Transmission in Korea

A 57-year old man who was admitted to an emergency room of a tertiary hospital with hemoptysis developed malarial fever 19 days later and then died from severe falciparum malaria 2 days later. He had not traveled outside of Korea for over 30 years. Through intensive interviews and epidemiological surveys, we found that a foreign patient with a recent history of travel to Africa was transferred to the same hospital with severe falciparum malaria. We confirmed through molecular genotyping of the MSP-1 gene that Plasmodium falciparum genotypes of the 2 patients were identical. It is suggested that a breach of standard infection control precautions resulted in this P. falciparum transmission between 2 patients in a hospital environment. This is the first report of a nosocomial transmission of falciparum malaria in Korea.     

Transgenic parasites: improving our understanding of innate immunity to malaria

Clinical immunity to Plasmodium falciparum malaria takes years to develop and is never complete. One explanation for these observations is that antigenic variation enables malaria parasites to evade humoral immunity; another is that P. falciparum induces immune dysregulation, which inhibits the development of protective cellular immunity. Research described by D'Ombrain et al. in this Cell Host & Microbe issue probes how the parasite's main virulence factor PfEMP-1 might significantly alter human innate immune responses.     

The probability of a sequential Plasmodium vivax infection following asymptomatic Plasmodium falciparum and P. vivax infections in Myanmar,Vietnam, Cambodia,and Laos

Increasing numbers of aging individuals with chronic co-morbidities travel to regions where falciparum malaria is endemic. Non-communicable diseases are now leading risk factors for death in such countries. Thus, the influence of chronic diseases on the outcome of falciparum malaria is an issue of major importance. Aim of the present study was to assess whether non-communicable diseases increase the risk for severe imported falciparum malaria. A retrospective observational study of all adult cases with imported falciparum malaria hospitalized between 2001 and 2015 in the tertiary care Charité University Hospital, Berlin, was performed. A total of 536 adult patients (median age 37 years; 31.3% female) were enrolled. Of these, 329 (61.4%) originated from endemic countries, 207 patients (38.6%) from non-endemic regions. Criteria for severe malaria were fulfilled in 68 (12.7%) cases. With older age, lack of previous malaria episodes, being a tourist, and delayed presentation, well-characterized risk factors were associated with severe malaria in univariate analysis. After adjustment for these potential confounders hypertension (adjusted odds ratio aOR, 3.06 95% confidence interval, CI 1.34–7.02), cardiovascular diseases (aOR, 8.20 95% CI 2.30–29.22), and dyslipidaemia (aOR, 6.08 95% CI 1.13–32.88) were individual diseases associated with severe disease in multivariable logistic regression. Hypertension proved an independent risk factor among individuals of endemic (aOR, 4.83, 95% CI 1.44–16.22) as well as of non-endemic origin (aOR, 3.60 95% CI 1.05–12.35). In imported falciparum malaria hypertension and its related diseases are risk factors for severe disease.     

Serum concentrations of granulocyte-colony stimulating factor in complicated Plasmodium falciparum malaria

Involvement of neutrophils in the control of blood parasites in malaria has been reported. Both, mononuclear phagocytes and neutrophils are known to be stimulated by cytokines such as TNF-alpha in order to augment the defence potency against the parasites. Previously, it has been shown that serum-G-CSF concentrations are increased in patients with bacterial sepsis. In vitro studies have shown that P. falciparum - infected erythrocytes induce the release of G-CSF by several cells such as endothelial cells and monocytes, however, nothing is known about G-CSF serum concentrations during the clinical course of severe P. falciparum malaria. Thus, it was the aim of the present study to investigate the time course for G-CSF serum concentrations in patients with complicated P. falciparum malaria, and to correlate these values with other mediators of inflammation and hematopoesis. Twenty-six patients suffering from complicated P. falciparum malaria were included in the study, and 20, age and sex matched, healthy volunteers were used as the negative control group. Serum samples for determination of G-CSF were taken on day 0, 7 and 14, and measured by ELISA. We found significantly increased serum concentrations of G-CSF in patients with complicated P. falciparum malaria on day 0, values decreasing to within the normal range by day 7. A significant correlation was found between G-CSF (d0) and procalcitonin, the parasite count, erythropoietin and macrophage inflammatory protein, however no correlation could be shown for the neutrophil count. In conclusion, on the day of hospital admission, elevated serum concentrations of G-CSF were detected in patients with complicated P. falciparum malaria, which might indicate a role of G-CSF in the acute defence mechanism against the parasites.     

Therapeutic efficacy of 3 treatment protocols for non-complicated Plasmodium falciparum malaria, Antioquia, Colombia, 2002

High resistance of Plasmodium falciparum malaria to chloroquine poses malaria as a major public health problem in Colombia. In this context, the therapeutic response of uncomplicated P. falciparum malaria patients to chloroquine (CQ), sulfadoxine/pirymethamine (SDXP) and combined therapy (SDXP/CQ) was evaluated according to the WHO/PAHO protocols of 1998. The comparisons were based on a sample of 160 patients with uncomplicated P. falciparum malaria in Turbo and Zaragoza (Antioquia, Colombia). Patients were randomly assigned each of the treatment categories. The results were statistically similar in each municipality. In Turbo percentage of treatment failure was 87.5%, 22.2% and 22.6% for CQ, SDXP and SDXP/CQ, respectively, whereas in Zaragoza, the corresponding treatment failure was 77.7%, 26.5% and 12.1%. During follow up, 50% of subjects with late treatment failure were asymptomatic in Turbo, while 33.3% were asymptomatic in Zaragoza. A high level of treatment failure occurred with CQ monotherapy, while SDXP and SDXP/CQ had acceptable levels of failure, i.e., below 25%. The high percentage of late treatment failure in asymptomatic patients may contribute to increased risk of persistent transmission.     

Cytokine Network in Adults with Falciparum Malaria and HIV-1: Increased IL-8 and IP-10 Levels Are Associated with Disease Severity

Background

Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection.

Methods

This was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines.

Results

We included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization.

Interpretations

Our findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.     

Deaths due to Plasmodium knowlesi malaria in Sabah, Malaysia: association with reporting as Plasmodium malariae and delayed parenteral artesunate

ABSTRACT: BACKGROUND: The simian parasite Plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in Sabah, Malaysia, but is morphologically indistinguishable from and still commonly reported as Plasmodium malariae, despite the paucity of this species in Sabah. Since December 2008 Sabah Department of Health has recommended intravenous artesunate and referral to a general hospital for all severe malaria cases of any species. This paper reviews all malaria deaths in Sabah subsequent to the introduction of these measures. Reporting of malaria deaths in Malaysia is mandatory. METHODS: Details of reported malaria deaths during 2010-2011 were reviewed to determine the proportion of each Plasmodium species. Demographics, clinical presentations and management of severe malaria caused by each species were compared. RESULTS: Fourteen malaria deaths were reported, comprising seven Plasmodium falciparum, six P. knowlesi and one Plasmodium vivax (all PCR-confirmed). Of the six P. knowlesi deaths, five were attributable to knowlesi malaria and one was attributable to P. knowlesi-associated enterobacter sepsis. Patients with directly attributable P. knowlesi deaths (N = 5) were older than those with P. falciparum (median age 51 [IQR 50-65] vs 22 [IQR 9-55] years, p = 0.06). Complications in fatal P. knowlesi included respiratory distress (N = 5, 100%), hypotension (N = 4, 80%), and renal failure (N = 4, 80%). All patients with P. knowlesi were reported as P. malariae by microscopy. Only two of five patients with severe knowlesi malaria on presentation received immediate parenteral anti-malarial treatment. The patient with P. vivaxassociated severe illness did not receive parenteral treatment. In contrast six of seven patients with severe falciparum malaria received immediate parenteral treatment. CONCLUSION: Plasmodium knowlesi was responsible, either directly or through gram-negative bacteraemia, for almost half of malaria deaths in Sabah. Patients with severe non-falciparum malaria were less likely to receive immediate parenteral therapy. This highlights the need in Sabah for microscopically diagnosed P. malariae to be reported as P. knowlesi to improve recognition and management of this potentially fatal species. Clinicians need to be better informed of the potential for severe and fatal malaria from non-falciparum species, and the need to treat all severe malaria with immediate intravenous artesunate.     

Predictive score of uncomplicated falciparum malaria patients turning to severe malaria

In acute uncomplicated falciparum malaria, there is a continuum from mild to severe malaria. However, no mathematical system is available to predict uncomplicated falciparum malaria patients turning to severe malaria. This study aimed to devise a simple and reliable model of Malaria Severity Prognostic Score (MSPS). The study was performed in adult patients with acute uncomplicated falciparum malaria admitted to the Bangkok Hospital for Tropical Diseases between 2000 and 2005. Total 38 initial clinical parameters were identified to predict the usual recovery or deterioration to severe malaria. The stepwise multiple discriminant analysis was performed to get a linear discriminant equation. The results showed that 4.3% of study patients turned to severe malaria. The MSPS = 4.38 (schizontemia) + 1.62 (gametocytemia) + 1.17 (dehydration) + 0.14 (overweight by body mass index; BMI) + 0.05 (initial pulse rate) + 0.04 (duration of fever before admission) - 0.50 (past history of malaria in last 1 year) - 0.48 (initial serum albumin) - 5.66. Based on the validation study in other malaria patients, the sensitivity and specificity were 88.8% and 88.4%, respectively. We conclude that the MSPS is a simple screening tool for predicting uncomplicated falciparum malaria patients turning to severe malaria. However, the MSPS may need revalidation in different geographical areas before utilized at specific places.     

Notes about the impact of human seasonal migration on malaria spreading in rural Venezuela

This paper considers the effect of social and cultural factors on malaria spreading in rural Venezuela. It argues that standard vertical malaria control programs are inclined to ignore local workplace and living conditions instead of recruiting traditional practices into the planning scenario for more effective malaria control. An epidemiological survey on people migrating from malaria endemic areas to non-endemic region studied by blood films and a Plasmodium falciparum in vivo test. The results of the survey on people migrating from malaria endemic areas to non endemic regions revealed that 138 (118 males and 20 females) (23.3%) had fever (38.2-39 degrees C), malarial parasites were detected in the blood films of 49 (35.5%) from 138 febrile (parasitaemic) patients, and 45 (91.8%) of the parasitaemic cases were infected with P. falciparum; other four cases carried P. vivax only. Differences in prevalence, parasites load and the density of infection were observed between the three age groups. The asexual parasite load and the density of parasites (asexual and sexual forms) were appreciably higher in older children than in the other two age-groups (P < 0.001 for each). In the Plasmodium falciparum in vivo test, nine (22.5%) patients presented resistance grade III. People with transient jobs in malaria endemic areas could transport the parasites to non-endemic areas establishing a new malaria focus during seasonal migration activities.     

Effect of sequential infection with Plasmodium vivax and P. falciparum in the Aotus trivirgatus monkey.

Aotus trivirgatus monkeys with prior experience with Plasmodium vivax were inoculated with P. falciparum via the bites of infected mosquitoes. The animals with prior malaria had higher parasitemias and significantly higher levels of mosquito infectivity than monkeys with no prior P. vivax experience. Monkeys with a history of P. falciparum that were inoculated with P. vivax had essentially the same parasitemias as those with no prior malaria. However, levels of mosquito infectivity were markedly increased in those monkeys with a history of P. falciparum. The results imply that the introduction of another malaria species into a malarious area may result in higher levels of mosquito infection and more rapid establishment and distribution of that species.