In vitro drug sensitivity and clinical aspects of Plasmodium falciparum malaria in African children.

In vitro Plasmodium falciparum drug sensitivity was investigated in 115 brazzavillians children, between 1 year and 10 years of age. On the basis of clinical aspects, four groups were constituted: Group 1: 39 asymptomatic school children, Group 2: 16 children with uncomplicated malaria, Group 3: 40 with severe but not pernicious malaria and Group 4: 20 with pernicious malaria. The drugs tested were chloroquine (CQ), quinine (QN) and mefloquine (MQ). The sensitivity level was assessed by a 48-hour in vitro maturation test involving the uptake of tritiated hypoxanthine, the initial blood level of parasite being > or = 0.1% in all cases. For QN and MQ, the median IC50 values showed no significant difference related to clinical status, age or parasitaemia levels. For CQ, the proportion of resistant strains and the 50 inhibitory concentration (IC50) values were greater in the cases of children hospitalised for malaria but there were no differences related to clinical severity of these hospitalised children nor, within each group, to the age or parasitaemia levels. The percentage of subjects with an IC50 value greater than the 90 percentile of the IC50 of the asymptomatic group, which we propose as the severity index related to chemoresistance, was 15% for uncomplicated malaria, 38% for severe but non-pernicious forms and 35% for pernicious malaria. The IC50 for QN was significantly higher in CQ-resistant strains and there was a positive correlation for CQ vs QN and for QN vs MQ.

[Plasmodium falciparum index and level of parasitemia: diagnostic and prognostic value in the Congo]. / Indice plasmodique et parasitemie à Plasmodium falciparum: valeur diagnostique et pronostique au Congo.

Parasitological data of various malarial studies performed in the Congo where Plasmodium falciparum malaria is holo-endemic in rural and suburban zones, between 1988 and 1991, were analyzed with the intention of establishing diagnosis and prognosis value of Plasmodium falciparum parasitaemia in areas with high perennial transmission. In such an area congolese school-children (6-10 years old) had 88% P. falciparum index, this is the same percentage as that for children hospitalized with a pernicious attack. However, the parasite load is distributed differently; parasitaemia is greater than 6,000 asexual form of P. falciparum/microliters (afPf/microL) in only 4.6% of cases in the former group versus 67% in the second group. A threshold of 10,000 afPf/microliters, above which the Plasmodium infection triggers a febrile attack in semi-immune children, is confirmed in school children in a rural context where the factor of taking antimalarial drugs within the preceding days is negligible; three out of four children with levels above this threshold are febrile versus 4.1% (7 out of 170) with lower blood parasite levels. Some adults were also asymptomatic carriers but much less frequently and with lower mean parasitaemia levels. The parasite load mirrors the clinical severity although this concept can be misleading as an individual prognostic criterion and for hospital studies carried out in areas where multiple drug administration before hospitalisation is common. For the studies recently performed in Brazzaville, the 5% threshold level of parasitized red cells, the WHO severity criterion, was never reached in asymptomatic subject or in cases of simple attack; it was reached in one out of two cases of pernicious attack.

Mortality and sequelae due to cerebral malaria in African children in Brazzaville, Congo.

This study was carried out on 170 children admitted to the University Hospital of Brazzaville (Congo) for cerebral malaria between January 1, 1988 and June 30, 1989. The selection criteria were 1) unarousable coma, cerebrospinal fluid without microorganisms or a marked cellular reaction, and the absence of other causes, and 2) that the children lived in Brazzaville. The case fatality rate was 15%. In 75% of the cases, death occurred within the first 48 hr. The prognosis worsened with the stage of the coma and a younger age. At discharge from the hospital, 9% of the cases presented with sequelae. The postcerebral malaria mortality was high; indeed, death occurred in six (7%) of 90 children discharged from the hospital whose parents were contacted between nine and 27 months later. Two deaths were directly related to neurologic sequelae. Among the 58 children examined under satisfactory conditions between nine and 27 months (mean 16.9 months) after discharge, 50% (3 of 6) still presented with attenuated forms of the sequelae observed immediately after the episode of cerebral malaria (cortical blindness had regressed completely, unlike ataxia and loss of balance). Disorders that may have been related to the episode of cerebral malaria were observed in 31% of these 58 cases.

Child morbidity and mortality due to cerebral malaria in Brazzaville, Congo. A retrospective and prospective hospital-based study 1983-1989.

This study was conducted in all four hospitals of Brazzaville, the capital of the Congo in order to assess the trend in malaria morbidity, the frequency of cerebral malaria and the related mortality between 1983 and 1989 in Brazzaville children. For the period 1983 to 1987 the study was retrospective, based on records. For the period 1988 and 1989 a prospective study was carried out in the two main hospitals in which a system for reporting cases of cerebral malaria was set up. This was completed by a retrospective analysis of data similar to that carried for the previous years. The population of Brazzaville children aged between 0 and 14 years and the distribution by district were estimated from the 1984 official census taking the annual demographic growth to be 5%. The results show a marked increase in hospitalizations for malaria, noticeable since 1985, and which now account for about 50% of the overall non-surgical hospitalizations. The number of cases of cerebral malaria and related deaths have probably increased. However, these severe forms of malaria were relatively rare. Indeed, in 1988 and 1989, for the 0-4, 5-9 and 10-14 year age groups, the annual incidence rates of cerebral malaria were estimated at respectively 240, 61 and 13 per 100,000 and the related mortality rates at respectively 58, 5 and 1 per 100,000. No obvious relationship was found between the intensity of malaria transmission, which varied considerably according to the district, and the level of mortality from cerebral malaria.

Evaluation of the efficacy of a low-passage bovine rotavirus (strain WC3) vaccine in children in Central Africa.

The safety and efficacy of a WC3 rotavirus vaccine was evaluated in a double-blind placebo-controlled trial involving 472 children in Bangui (Central African Republic). Each child received two doses of either placebo (235 children) or vaccine (237 children) at a 1-month interval, the first dose being given at 3 months of age. During the follow-up survey 9 months after the first dose, 117 rotavirus diarrhoeas were observed, 59 in the placebo group, 58 in the vaccinated group. The only positive effect of the vaccine was a significantly higher proportion of mild rotavirus diarrhoeal episodes in the vaccinated group than in the placebo group. Of the children in the vaccinated group, 60% had a positive immune response to WC3 rotavirus when tested by plaque reduction seroneutralization.

Detection of anti-HIV IgA in tears of children born to seropositive mothers is highly specific.

In order to improve the diagnosis of HIV infection in children born to seropositive mothers, 86 children were previously tested by Western blotting for anti-HIV IgA in tears and IgG in serum, at a median age of 9.2 months. To determine the exact value of the assay, 68/86 children of the same cohort were retested 9 months later. Nine children (13.4%) were seropositive and all had anti-HIV IgA in tears. Eight of them had possessed lachrymal antibodies 9 months earlier. The ninth child was seronegative when 9 months old and then seroconverted. Four children (6%), known to be seronegative, had an indeterminate Western blot pattern and no HIV IgA in tears. Fifty four (80.6%) were seronegative at 18 months; none of them had ever had anti-HIV IgA in tears. This highlights the fact that only the children without lachrymal HIV IgA at the age of 9 months became seronegative at the age of 18 months. Our results clearly show that the detection of anti-HIV IgA in tears is a highly specific and reliable diagnostic test in children aged less than 15 months, born to seropositive mothers.

Antibodies to human immunodeficiency virus in the breast milk of healthy, seropositive women.

Reports of rare cases of suspected transmission of the human immunodeficiency virus (HIV) from mother to children by breast milk have been recently published. To study the factors that possibly limit HIV transmission through breast-feeding, milk samples obtained from 15 healthy, seropositive mothers and 4 seronegative control subjects were studied for the presence of anti-HIV antibodies. All samples from seropositive women contained IgG antibody against envelope glycoproteins gp160 and/or gp120, and 11 of 15 samples contained IgA antibodies against gp160. IgA antibodies against other viral antigens were more rarely recovered, except against the internal proteins of the virus, p18 and p25. The finding of IgA antibodies to HIV-1 in breast milk establishes that the virus elicits a local immune response in heterosexual, seropositive women. The role of local antibodies in the postnatal transmission of HIV remains to be determined.

HIV-specific IgA antibodies in tears of children with AIDS or at risk of AIDS.

To improve on the diagnosis of human immunodeficiency virus (HIV) infection, 14 children with clinical evidence of AIDS, 86 children less than 15 months old and born to seropositive mothers, and 29 controls were tested for the presence of IgA antibody in tears directed against HIV antigens on Western blots. IgA antibodies in tears against env- and pol-encoded proteins were present in 13 of 14 children with AIDS and in 13 of 86 children born to seropositive mothers. No HIV-specific IgA was observed in tears of the 29 controls. Among the 86 children less than 15 months old, 11 had clinical evidence of AIDS and 7 of them (64%) had HIV-specific IgA in tears. Results show that the demonstration of lacrimal HIV-specific IgA may help to distinguish between truly infected children and those whose HIV antibodies are passively transferred from the mother. Therefore, this simple method is a good tool for laboratory diagnosis of paediatric AIDS.

Cluster of antibiotic-resistant Salmonella enteritidis infections in the Central African Republic.

Salmonella enteritidis strains which are multiply resistant to antimicrobial agents were isolated from the blood of 12 patients hospitalized at the Institut Pasteur of Bangui, Central African Republic, during a 4.5-month period. The lack of gas production in Kligler-Hajna medium initially suggested Salmonella typhi, but isolates were confirmed as unusual S. enteritidis strains. The occurrence of these unique strains in an unusual site of infection may indicate an epidemic due to an unusually invasive and resistant strain of S. enteritidis. Some variation in plasmid profile and susceptibility to antimicrobial agents was noted, possibly reflecting antibiotic pressures existing in the Central African Republic. All isolates were of the same bacteriophage lysis pattern, unlike patterns documented for recent U.S. and European isolates of S. enteritidis.

An outbreak of human Semliki Forest virus infections in Central African Republic.

Semliki Forest (SF) virus was responsible for an outbreak of febrile illnesses in Bangui, Central African Republic (CAR), during October-December 1987. The virus was isolated at first from mosquitoes, mainly Aedes africanus, collected August-October in a gallery forest 100 km from Bangui. During October-December, 22 isolations of SF virus were made from serum samples collected from patients in Bangui presenting with fever, severe persistent headache, myalgia, arthralgia, and a convalescence marked by asthenia. During the same period, 8 SF virus isolates were obtained from mosquitoes collected in Bangui, mainly from Ae. aegypti. Europeans, particularly soldiers who had recently arrived from France, were affected. Antibodies to alphaviruses had been previously detected in a high proportion of resident human populations in CAR. We conclude that SF virus is a human pathogen.

Lympho-cutaneous Kaposi's sarcoma in an African pediatric AIDS case.

A case of disseminated Kaposi's sarcoma with lymphoid and mucocutaneous involvement in an African infant with acquired immune deficiency syndrome is reported. The child died within 2 months after recognition.

PIP: Co-infection with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma is not uncommon in Europe, but is rare in Africa and not previously reported in infants. This article documents the case of an 11-month-old African boy with lymphocutaneous Kaposi's sarcoma. The infant was brought to a hospital in the Central African Republic with chronic diarrhea and disseminated lymphadenopathy. Also present were fever, cough, weight loss, a gingivostomatitis with herpes-like vesicles, hepatomegaly, splenomegaly, and cervico-axillo-inguinal lymphadenopathy. The adenopathies 1st occurred when the infant was 7 months of age and were followed 1 month later by the emergence of 12 dark brown or black velvet raised cutaneous nodules. The diagnosis of Kaposi's sarcoma was confirmed by lymph node and skin nodule biopsies. Also indicative of Kaposi's sarcoma was the presence of abortive vascular foci at a distance from the skin's surface and the cell proliferation. Both the infant and his asymptomatic mother were seropositive for antibodies to human immunodeficiency virus (HIV)-1. The skin lesions in this case presented the special infiltrative characteristic of AIDS-related Kaposi's sarcoma. The infant died 2 months after presentation at the hospital. By the last weeks of his life, the cutaneous nodules had covered the entire body. Death was from pleuropneumopathy. Given the high prevalence of HIV-1 infection in the Central African Republic, more such cases can be expected.