Self-testing for falciparum malaria with antigen-capture cards by travelers with symptoms of malaria.

Kits for self-diagnosis of malaria by travelers in remote areas have been advocated. Antigen-capture test cards work reliably in the laboratory, but there is limited data regarding self-testing by ill patients. One hundred and fifty-three symptomatic patients presenting for a malaria test attempted self-diagnosis using these kits. Nine percent failed to perform a valid test. Against blood-film proven malaria, specificity was 97% (95% confidence intervals [CI] 93-99%) and sensitivity 95% (95% CI 74-99%). Although these results are encouraging, technical problems need to be addressed and test sensitivity proven by additional field-testing before this technology can be marketed to travelers.     

Antibodies against malaria sporozoites in patients with acute uncomplicated malaria and patients with cerebral malaria

Serum samples from 95 patients with acute uncomplicated falciparum malaria (AM) and 95 patients with cerebral malaria (CM) were tested by the indirect immunofluorescent assay (IFA) for IgG and IgM antibodies against Plasmodium falciparum and P. vivax sporozoites. Forty-six (48%) CM patients were positive for antibodies against P. falciparum sporozoites whereas only 23 (24%) were positive for antibodies against P. vivax sporozoites (P less than 0.002). A similar result was obtained in AM patients. However, CM patients had significantly lower mean IgG anti-sporozoite titer for P. falciparum than did AM patients (P less than 0.05), especially when only anti-sporozoite antibody-positive CM and AM patients were compared (P less than 0.0005), suggesting that CM patients had relatively less exposure and were probably less immune to malaria than were AM patients. The persistence of anti-sporozoite antibodies also was investigated in paired sera taken 63 days apart from 108 patients with acute falciparum malaria. There were significant decreases in the mean antibody titers in the follow-up sera during the period of stay in the malaria-free area. It was proposed that determination of anti-sporozoite antibody be made as a substitute for, or in addition to, anti-blood stage antibody for seroepidemiological study of malaria, especially in the monitoring of the success of the malaria control program.     

Behavior of people with respect to malaria in endemic areas with different levels of malaria transmission.

The present survey was carried out in two villages of the same malaria endemicity but different levels of transmission in Lamae District, Chumphon Province, southern Thailand with the aim to study whether behavior of people to malaria was similar or not. The total populations in low (village 11) and high (village 13) transmission areas were surveyed twice during low (February 1990) and high (June 1990) transmission periods. All subjects were interviewed by trained interviewers using a structured interview form. Among 410 and 614 people in villages 11 and 13, respectively, it was revealed that during the low transmission period behavior related to chemoprophylaxis and use of bed nets was similar in both villages, whereas risk behavior of night work was significantly higher in village 11 than village 13. This was likely due to their different principal occupations: farming of rubber plantation in village 11 and of coffee plantation in village 13. Concerning pattern of seeking malaria treatment, the malaria clinic and the district hospital were the common places attended by people in both villages. During the second survey in high transmission period, a cohort of 277 in village 11 and 430 in village 13 were available for follow up to study changes in their behavior between low and high transmission seasons. There were significant decrements related to night work and significant increments related to bed net use in both villages.     

Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria.

In an endemic area where malaria transmission is intense and continuous, reappearance of asexual parasites may be ascribed to either recrudescence or reinfection. To distinguish between recrudescence and reinfection after oral treatment with chloroquine, amodiaquine, pyronaridine, sulfadoxine-pyrimethamine, halofantrine, or artesunate, three polymorphic markers (circumsporozoite protein, merozoite surface antigens 1 and 2) from pre-treatment and post-treatment samples were amplified by the polymerase chain reaction, and the in vitro response to chloroquine was determined for comparison. Of 52 paired samples, 22 (42%) were reinfections. Recrudescence occurred more frequently on or before Day 14 (22 of 30 cases, 73%). Except for one case, all reinfections were observed beyond Day 14. The phenotype determination was not sufficiently precise to distinguish between recrudescence and reinfection. Our results suggest that beyond Day 14 (and until Day 42), recrudescence and reinfection cannot be distinguished at our study site unless molecular techniques are used and that some results derived from the polymerase chain reaction need to be compared with the microscopic examination of thick blood smear to exclude gametocyte carriers without asexual parasites after treatment.     

Falciparum malaria and pregnancy.

Falciparum malaria in pregnancy is a significant health problem in India. Pregnant women constitute an important high risk group for malaria infection which may cause abortion, still births, intra uterine growth retardation (IUGR), and pre-mature labour. Two hundred eighty-eight admitted female patients of falciparum malaria were included in the study out of which 45 were pregnant. The mortality rate was highly significant in pregnant females (37.77%) in comparison to non-pregnant females (14.81%); (p < 0.001). The incidence of various pernicious syndromes including cerebral malaria, severe anaemia (Hb < 5 g%) hepatic and renal failure were more in pregnant females in comparison to non-pregnant females. The incidence of infection was higher among primigravida and second gravida 30/45 (66.66%) as compared to multigravida 15/45 (33.33%) and the greater incidence of infection was seen during 14-28 wk of gestation 23/45 (51.11%). Pregnancy related complications in the form of preterm live birth (20%). Intra uterine death (IUD 31.11%), still births (13.33%) and abortions (11.11%) were more pronounced in primiparous women as compared to multiparous. Weight of placenta in majority of patients ranged between 200-400 g (22/31; 70.96%). Normal pregnancy continued in only 11 out of 45 pregnant females, out of which seven had low birth weight body (63.63%). As the pregnancy is associated with increased incidence and adverse outcome of falciparum malaria infection, chemoprophylaxis should be made an integral part of antenatal care along with antianaemic therapy to reduce the risk of serious maternal and fetal complications.     

Prevention of malaria.

Malaria is one of the most prevalent infectious diseases worldwide; it is transmitted in over 100 countries, and it is a major cause of serious morbidity and mortality in travelers. Clinicians should inform travelers of their risk, teach them the principles of personal protection, and offer individualized chemoprophylaxis regimens. The increasing prevalence of multiple drug-resistant Plasmodium falciparum in many parts of the world makes nonpharmacologic methods of malaria prevention important.     

Effect of antipyretic drugs in children with malaria.

A comparison of different antipyretics in children with malaria showed a small effect of naproxen, but not of metamizol, on the reduction of fever peaks. Antipyretic treatment had no effect on fever clearance and therefore should be used cautiously in the treatment of malaria.     

Association of hepatomegaly and jaundice with acute renal failure but not with cerebral malaria in severe falciparum malaria in Thailand.

We conducted a case record study comparing liver tests abnormalities in 20 malaria-related acute renal failure cases without cerebral malaria, 52 cerebral malaria cases without other organ impairment, 189 cases of nonsevere malaria associated with a high parasite burden, and 131 cases of mild Plasmodiumfalciparum malaria. Jaundice and hepatomegaly were significantly associated with renal failure (adjusted odds ratio [AOR], 3.3, 95% confidence interval [CI], 1.3-8.6, P = 0.01; and AOR, 1.7 95% CI, 1.13-2.4, P = 0.01) but not with cerebral malaria (AOR, 1, 95% CI, 0.5-2, P = 0.8; and AOR, 1.08, 95% CI, 0.8-1.8, P = 0.5). Patients with acute renal failure were significantly older and had increased liver abnormalities compared with other groups. Although an increase in the proportion of mature schizonts over ring forms was significantly associated with cerebral malaria, it did not seem to have affected acute renal failure. These results suggested that cytoadherence was not the main determinant for renal failure and that jaundice itself may have potentiated the effects of hypovolemia.     

Co-infection with malaria and leptospirosis

Malaria and leptospirosis are both common in the tropics. Simultaneous infections are possible, although not previously reported. We report two cases of malaria from an area of Thailand on the Thailand-Myanmar border with compelling serologic evidence of simultaneous acute leptospirosis. One was a case of infection with Plasmodium falciparum with acute and convalescent microscopic agglutination test (MAT) titers for Leptospira serovar icterohaemorrhagiae of 1:200 and 1:1,600, respectively. The other was a case of infection with P. vivax that seroconverted to a titer of 1:3,200 for Leptospira serovar bataviae. Additionally, there were five probable cases of leptospirosis with patent malaria parasitemia (three P. falciparum and two P. vivax) detected. Management of dual infections is complicated by their similar clinical presentations, and because the confirmatory diagnosis of malaria is readily available as opposed to that of leptospirosis. Treatment focusing on malaria mono-infections instead of dual infections could result in a delay of specific therapy for leptospirosis and possible consequences of serious complications.     

Neurological complications of malaria.

This paper reviews the neurological complications of malaria. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red blood cells causing blood sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes a nonspecific, immune-mediated, inflammatory response with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations in malaria remains unexplored, but offers excellent perspectives for research at clinical as well as experimental level.     

Thrombocytopenia in malaria.

The relationship between platelet counts and platelet bound (direct) or platelet directed (indirect) serum antibody concentrations was studied in 17 patients with Plasmodium falciparum malaria and 12 patients with P. vivax malaria. Platelet counts rose with recovery from infection from 196 +/- 84 x 10(9)/l (mean +/- SD) and 195 +/- 34 x 10(9)/l to 319 +/- 99 and 283 +/- 62 x 10(9)/l respectively (p less than 0.002), but there was no relationship between either absolute platelet count or changes in counts and either indirect or direct platelet antibody levels. These findings suggest that a non-immunologically mediated mechanism is involved in the pathogenesis of thrombocytopenia in malaria.     

Placental malaria in women with South-East Asian ovalocytosis.

Malaria during pregnancy, which is characterized by the accumulation of infected erythrocytes in the placenta, often has severe consequences for the mother and newborn. We assessed the effect of the genetic trait South-East Asian ovalocytosis (SAO) on placental malaria in women from Papua New Guinea. In children, this trait confers protection against cerebral malaria, but not against mild malaria disease, malaria parasitemia, or severe malaria anemia. Using a case-control approach, we found that SAO women suffer from placental malaria, and SAO-infected erythrocytes can sequester in the placenta, but heavy placental infections tended to be less common in SAO than in control pregnant women. Reduced prevalence and severity of placental infection associated with SAO were observed only for primigravid women, who are the group at highest risk of suffering from severe manifestations of placental malaria. Furthermore, we found that the prevalence of the SAO trait was lower among pregnant women than among non-pregnant controls.     

Immunity to placental malaria. IV. Placental malaria is associated with up-regulation of macrophage migration inhibitory factor in intervillous blood

Macrophage migration inhibitory factor (MIF) may play a role in immune responses to malaria during pregnancy by virtue of its ability to activate macrophages and to overcome the immunosuppressive effect of glucocorticoids. The present study investigated whether plasma MIF levels are altered in pregnant women with placental malaria (PM) and/or human immunodeficiency virus (HIV) infection. For the first time it is demonstrated that MIF levels in the intervillous blood (IVB) plasma were significantly elevated, compared with that in both peripheral plasma ( approximately 500-fold) and cord plasma (4.6-fold; P<.01). IVB mononuclear cells also produced significantly higher levels of MIF, compared with that of peripheral blood mononuclear cells. PM was associated with increased levels of MIF in the IVB plasma (P<.02). Primigravid and secundigravid women had significantly higher levels of MIF in their IVB plasma than did multigravid women (P<.05). HIV infection did not significantly alter MIF levels in any site examined.