Clinical presentation of childhood malaria in Savannakhet province, Lao PDR.

A descriptive study on the clinical presentation of childhood malaria was conducted in Savannakhet Province, Lao People's Democratic Republic. It is aimed to describe the clinical features and to determine the association between the severity of malaria and the initiation or delay of treatment. A total number of 92 children 1-14 years of age with confirmed malaria diseases were enrolled in this study. Fifty-six cases (60.9%) had illness for less than 3 days before hospitalized and 36 cases (39.1%) for more than 3 days. Twenty-nine cases (31.5%) had self antimalarial medication before admission (9 cases of chloroquine, 16 cases of quinine and 4 cases of artesunate). Ten cases (10.9%) had abnormal consciousness of which 7 cases (7.6%) had confusion but responded to verbal command and 3 cases (3.3%) were in coma not respond to painful stimuli but had reflex. Two cases 2.2%) had convsulsions, 11 cases (12.0%) had dehydration, 47 cases (51.1%) had vomiting, 18 cases (19.6%) had hepatomegaly and 19 cases (20.7%) had splenomegaly. There was a statistically significant association between consciousness levels and the duration of illness before admission < or = 3 days and > 3 days (p = 0.01) while there is no significant difference between parasitemia density and the duration of illness before admission (p > 0.05).

A new Vero cell rabies vaccine: results of a comparative trial with human diploid cell rabies vaccine in children.

We evaluated the immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) compared with human diploid cell rabies vaccine (HDCV) after pre-exposure immunizations (both primary and booster). Intramuscular doses of either 0.5 mL of CPRV or 1.0 mL of HDCV were given to 400 schoolchildren on days 0, 7, 28, and 365 (booster). Adequate titers of antibody (> or = 0.15 IU/mL, as defined by the Centers for Disease Control and Prevention) were observed in serum samples from all children 14 days after primary immunization with CPRV and HDCV; the antibodies persisted in all but one child up until 1 year. Fourteen days after the primary immunization series (day 42) and 7 days after booster immunization (day 372), all children had antibody titers of > or = 0.5 IU/mL. Local and systemic reactions after primary and booster immunizations occurred significantly less frequently in the CPRV group. A severe allergic reaction (angioedema) was reported in only one child after booster immunization with HDCV. CPRV has adequate immunogenicity for primary and booster pre-exposure immunizations in children and has a better safety profile than does HDCV.

Persistence of antibodies in children after intradermal or intramuscular administration of preexposure primary and booster immunizations with purified Vero cell rabies vaccine.

BACKGROUND: The use of intradermal (i.d.) injections of purified Vero cell rabies vaccine (PVRV) for preexposure prophylaxis has not been well-established. We studied the safety and immunogenicity of i.d. and intramuscular (i.m.) PVRV injections for primary and booster preexposure immunizations. METHODS: One of two rabies preexposure PVRV regimens comprising three doses of either 0.1 ml i.d. or 0.5 ml i.m. administered during 28 days was assigned at random to 190 school children. One booster dose was given 1 year later either i.d. or i.m., according to their initial randomization group. Serologic results were available from 155 (82%) children at 1 year after primary immunization and 118 (62%) children at 2 years after booster. RESULTS: Although children vaccinated i.d. had significantly lower rabies-neutralizing antibody titers after primary immunization as well as after booster than children vaccinated i.m. (P< 0.001 for all time points), there were no significant differences in the percentages of children with adequate titers (> or =0.15 IU/ml) between the i.d. and i.m. groups after both primary and booster immunizations. Mild local reactions were more frequent after i.d. vaccination. Mild or moderate systemic reactions were infrequent and similar after i.d. and i.m. vaccinations. Fever and headache were reported by < or =6%. The reactions after booster were not different from those of post-primary immunization. CONCLUSIONS: Purified Vero cell rabies vaccine appears to be safe and immunogenic for primary and booster preexposure immunizations. An i.d. PVRV preexposure regimen should be useful especially for rabies-endemic countries with low per capita income.

Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria.

The protective effect of African IgG antibodies against Plasmodium falciparum malaria was investigated by passive transfer in Thai patients. Sera from 333 African adults were collected in the Cote d'Ivoire and subjected to extensive screening. One hundred fifty-three samples were discarded for safety reasons, and IgG was extracted from those remaining under conditions allowing their use by the intravenous (iv) route. Eight Thai patients with P. falciparum parasitemia were treated by iv inoculation of the IgG: six with a 100 mg/kg dose given over three days, one with a single 20 mg/kg dose, and one with a single 200 mg/kg dose. To ensure a safety margin of at least 48 hours, subjects were chosen among patients having a recrudescent parasitemia following quinine treatment failure at the RI level. At that stage, symptoms were mild or absent and parasitemia was low but increasing (range 4, 200-9,000/microliters). The IgG pool exerted a profound, stage-specific, but non-sterilizing effect on each of the strains tested, and proved to be safe. Asexual parasitemia decreased by a mean 728-fold (range 46-1,086), while gametocytes were unaffected. Clearance of parasites and symptoms was as fast or faster than with drugs, and was consistent in the eight patients treated, suggesting that target antigens were equally expressed in geographically remote isolates. In peripheral blood smears, no mature forms were seen at any time during the followup, which does not support the hypothesis that reversal of cytoadherence occurred. After the disappearance of the transferred antibodies, recrudescent parasites from three patients were found to be susceptible to the same extent (mean decrease of 1,310-fold) to the same IgG preparation, indicating that selection of parasites able to escape the effect of antibodies had not occurred. No adverse side-effects were detected during the followup, which lasted one year.

A phase-III clinical trial of mefloquine in children with chloroquine-resistant falciparum malaria in Thailand.

Mefloquine is a highly effective drug for the treatment of falciparum malaria among adults, but studies of its effects on children are lacking. An open, noncomparative trial of mefloquine was therefore carried out among 84 children aged 5-12 years who were patients at the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand. The drug was administered as a single dose of 18-29 mg base per kg body weight. Eighty-two of the 84 children completed a 42-day period of post-treatment observation. The drug was well tolerated also by 11 children with glucose-6-phosphate dehydrogenase deficiency, and all the children in the study cleared their parasitaemia initially (average clearance time, 65 hours). Furthermore, the clinical-chemical parameters measured exhibited no drug-related changes during the study. The radical cure rate of nearly 98% and high tolerance indicate that mefloquine can be used effectively and safely for the treatment of children aged 5-12 years who are suffering from uncomplicated falciparum malaria.

Influence of circulating malarial antigens on cell mediated immunity in acute Plasmodium falciparum malaria.

In a group of Thai patients with P. falciparum acute malaria, circulating malarial antigens (CMA) were detected in 27/33 cerebral malaria (CM) cases and 31/43 noncerebral cases. Delayed cutaneous responses to phytohemagglutinin and candidin were found frequently negative in patients with CMA, especially in the CM group. Mean in vitro lymphocyte proliferative responses to lectins were lower in the group of patients with CMA. An inhibitory activity on proliferative responses to phytohemagglutinin of lymphocytes from healthy individuals was exerted by sera containing CMA. Data suggest that CMA from P. falciparum may suppress in vivo and in vitro cell mediated immune reactions.

Immunological evaluation of cell-mediated and humoral immunity in Thai patients with cerebral and non-cerebral Plasmodium falciparum malaria: I. Cutaneous delayed hypersensitivity, blood leukocytes and in vitro lymphocyte responses.

In Thai patients with acute P. falciparum malaria including cerebral cases, cell mediated immune functions were studied in vivo and in vitro. Initial cutaneous delayed reactions to phytohaemagglutinin and soluble protein antigens were negative in most cerebral malaria patients. No major alteration of the number of circulating T and B cells was observed. In lymphocytes cultures, proliferatives responses to lectins or protein antigens were generally found within normal ranges. This study shows a direct role of P. falciparum on the impairment of cell mediated immunity.