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Biomedical subjects

M Kombila

Publications and source records attributed to M Kombila.

At least 19 recordsLinked to original sources
PubMed2002

Plasma glutamine and glutamate concentrations in Gabonese children with Plasmodium falciparum infection.

BACKGROUND: Low plasma glutamine levels in critical illness, neonates and burns patients are associated with poor outcome and increased risk of intercurrent infection. AIM: To investigate the relationship between plasma glutamine/glutamate levels and severity/outcome of malaria. DESIGN: Two-hospital prospective study, with both febrile and healthy controls. METHODS: We measured plasma glutamine and glutamate concentrations in 239 Gabonese patients: 145 children with malaria (86 with severe, 36 with moderate and 23 with uncomplicated disease), 42 healthy children, 44 febrile controls and eight healthy adults, and related findings to conventional markers of disease severity such as plasma lactate. RESULTS: Median (IQR) plasma glutamine was lower in uncomplicated falciparum malaria and in moderate malaria than in healthy controls: 353 (287-474) and 379 (293-448) vs. 485 (428-531) micromol/l, respectively; p<0.01 for both malaria groups vs. controls. In contrast, plasma glutamine was within the normal range in those with severe malaria and in febrile control children: 431 (342-525) and 472 (338-547) micromol/l, respectively. Furthermore, plasma glutamine was significantly higher in the children who died with malaria than in survivors: 514 (374-813) (n=12) vs. 399 (316-475) micromol/l (n=133), respectively; p=0.001. There were no significant differences in plasma glutamate concentrations between any of the study groups. DISCUSSION: In severe malaria, there was a positive correlation between plasma glutamine and lactate levels (p=0.009, r=0.281). This correlation may reflect impaired gluconeogenesis. Glutamine supplementation is probably not justified in severe P. falciparum infection.

Biomarkers↗
PubMed2001

Ferrocene-chloroquine analogues as antimalarial agents: in vitro activity of ferrochloroquine against 103 Gabonese isolates of Plasmodium falciparum.

The in vitro activities of ferrochloroquine, chloroquine, quinine, mefloquine, halofantrine, amodiaquine, primaquine, atovaquone and artesunate were evaluated against Plasmodium falciparum isolates from children with uncomplicated malaria from Libreville (Gabon), using an isotopic, micro, drug susceptibility test. The IC(50) values for ferrochloroquine were in the range 0.43-30.9 nM and the geometric mean IC(50) for the 103 isolates was 10.8 nM (95% CI 8.6-13.5 nM), while the geometric means for chloroquine, quinine, mefloquine, amodiaquine and primaquine were 370 nM, 341 nM, 8.3 nM, 18.1 nM and 7.6 microM, respectively. Ferrochloroquine was active against P. falciparum isolates, 95% of which showed in vitro resistance to chloroquine. Weak positive significant correlations were observed between the responses to ferrochloroquine and that to chloroquine, amodiaquine and quinine, but too low to suggest cross-resistance. There was no significant correlation between the response to ferrochloroquine and those to mefloquine, halofantrine, primaquine, atovaquone or artesunate. Ferrochloroquine may be an important alternative drug for the treatment of chloroquine-resistant malaria.

Animals↗
PubMed2001

Comparison of methods for the rapid laboratory assessment of children with malaria.

Rapid diagnosis and accurate quantification of Plasmodium falciparum parasitemia are important for the management of malaria. The assessment of disease severity also depends on evaluation of metabolic indexes such as blood glucose and lactate concentrations. Here we describe an accurate and rapid alternative to conventional thick film examination (Lambaréné method). We also assess near-patient methods for measuring blood glucose (OneTouch) and lactate (Accusport). The accuracy of the Lambaréné method is similar to that of thin films. Results from the OneTouch glucose meter also are in good agreement with a YSI 2300 reference meter. Overall, the Accusport lactate meter agrees poorly with the YSI 2300 reference meter. However, the sensitivity and specificity to detect hyperlactatemia (blood lactate > or = 5 mmol/L) are 0.94 and 0.98, respectively.

Blood Glucose↗
PubMed2001

[Causes of adult acute bacterial diarrhea in an internal medicine department in Libreville, Gabon].

This retrospective study of patients treated between 1992 and 1996 was undertaken as a preliminary step to identifying the main bacterial causes of diarrheal disease in Libreville, Gabon. A total 371 files showing positive stool cultures were analyzed. From an epidemiological standpoint, data showed that the high risk population was young people of both sexes. The incidence of diarrhea was correlated with climatic conditions with an endemic-epidemic pattern characterized by peak activity during the rainy season. In the vast majority of cases, the underlying etiology was gastroenteritis due to invasive organisms. The most commonly identified agents were salmonellae (46.6%) and Shigellae (44.2%). Treatment should focus on rehydration. Fluoro-quinolones were the most commonly indicated drugs for antimicrobial treatment but cotrimoxazole was often useful. In general, the prognosis of bacterial diarrhea is favorable provided that it is treated early and concurrent conditions are taken into account.

Acute Disease↗
PubMed2001

[Evaluation of efficacy and tolerance of amodiaquine versus chloroquine in the treatment of uncomplicated malaria outbreak in children of Gabon].

We conducted a prospective study from September 1997 to January 1998 in Libreville (Gabon). Fifty-three (53) children with uncomplicated P. falciparum malaria were included and divided into two groups. The first group (27 patients) was treated with amodiaquine and the second (26 patients) with chloroquine. The efficacy and tolerance of amodiaquine 30 mg/kg base over 3 days (10 mg/kg daily) and chloroquine 25 mg/kg base over 3 days (10 mg/kg day 0, 10 mg/kg day 1, 5 mg/kg day 3) were estimated at days 7 and 14. Clinical examination and parasitaemia were assessed on days 0, 1, 2, 3, 7, 14. Haematological and biochemical parameters were determined on days 0 and 7. Amodiaquine was shown to be more effective than chloroquine in clinical response and ridding patients of parasites: adequate clinical response was significantly higher with amodiaquine than chloroquine [100% (27/27) versus 45% (9/20), p < 0.0005]. Rates for early treatment failure (ETF) and late treatment failure (LTF) were respectively 35% and 12% with chloroquine. The parasitological success rate was significantly higher with amodiaquine than chloroquine on days 7 [93% (25/27) versus 62% (13/21), p < 0.008] and 14 [100% (13/13) versus 44% (4/9), p < 0.01]. The RI resistance type was 7% in the amodiaquine group. The rate of in vivo chloroquino-resistance was 53%, essentially of RII and RIII type. Overall, the two drugs were well tolerated.

Adolescent↗
PubMed1999

In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine.

The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM. Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r2 = 0.26, P < 0.001), pyronaridine and quinine (r2 = 0.36, P < 0.001), pyronaridine and amodiaquine (r2 = 0.55, P < 0.001), and pyronaridine and halofantrine (r2 = 0.50, P < 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies.

Adolescent↗
PubMed1999

[In vitro sensitivity of Plasmodium falciparum isolates from Gabon to chloroquine and cycloguanil].

The in vitro susceptibility of 91 Plasmodium falciparum isolates obtained from malaria-infected children living near Libreville (Gabon) was evaluated against chloroquine and cycloguanil (biologically active metabolite of proguanil), using an isotopic micro-drug susceptibility test. In vitro resistance to chloroquine and cycloguanil was observed in 83% (35/42) and in 38% (30/78) of the patients, respectively. Our data showed that 41% (16/39) of Gabonese field isolates were resistant both to chloroquine and cycloguanil. These findings are of great importance because they might indicate imminent chloroquine-proguanil failure, and there are not many affordable antimalarial drugs to replace chloroquine-proguanil combination.

Adolescent↗
PubMed1999

[Salmonellosis in HIV infection in a hospital setting in Gabon].

A case-control study was carried out in Libreville, Gabon, to determine the incidence of salmonella infection in HIV patients and identify any special clinical, therapeutic, or prognostic features. The records of 3000 patients hospitalized in the Infectious Disease Department of the Jeanne Ebori Foundation between January 1990 and December 1994 were studied. The incidence of salmonella infection, serotype, clinical presentation, prognostic factors and therapeutic modalities were compared in 2759 HIV-positive patients and 441 HIV-negative patients. Salmonella infection was noted in a total of 208 patients (58 HIV-positive and 150 HIV-negative). The incidence of salmonella infection was 13 p. 100 (non-typhoid in 76 p. 100 of cases) in HIV-positive patients versus 5.4 p. 100 in HIV-negative patients. The predominant serotypes in HIV-positive patients were Salmonella typhimurium and Salmonella enteritidis which accounted 41 p. 100 and 26 p. 100 of the isolated strains. The only significantly difference in clinical presentation was a higher incidence of bacteremia (84 p. 100) and focal lesions (11.4 p. 100) in HIV-positive patients with low-grade salmonella infection. The duration of treatment was three weeks with cotrimoxazole and 10 days with fluoroquinolones and cephalosporines. The outcome in HIV-positive patients was recurrence-free cure in 40 p. 100, multiple relapses in 12 p. 100, and death in 24 p. 100. The remaining patients were lost from follow-up. This study demonstrates the gravity of low-grade salmonella infection in African HIV-positive patients. Early diagnosis is necessary to allow chemotherapy which can be effective despite immunodeficiency.

Adolescent↗
PubMed1998

In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine.

The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 34.8 nM (mean IC50 5.0 nM) and the 95% confidence interval (CI95%) was 3.6-6.3 nM. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2 = 0.45, P < 0.001), artemether and chloroquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.31, P < 0.001), and artemether and halofantrine (r2 = 0.19, P < 0.01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.

Adolescent↗
PubMed1998

Short- and long-term action of multiple doses of ivermectin on loiasis microfilaremia.

One hundred nine Gabonese patients infected with Loa loa microfilariae were treated with ivermectin (200 microg/kg of body weight) at the Parasitology, Mycology and Tropical Medicine Department (Faculte de Medecine et des Sciences de la Sante, Libreville, Gabon). Each was given one dose per month for six consecutive months. The peripheral blood microfilaria (mf) count before and after each dose showed an average decrease in the microfilaremia of 87.3% (short-term-single dose). An annual single-dose mass treatment with 200 microg/kg of ivermectin was sufficient to control the parasite in populations with low (< 400/ml) L. loa mf counts. One month after the sixth dose (short-term-multiple doses), the average microfilaremia rate had decreased by 99.2% compared with the initial infection (35 patients). Samples were taken from 28 patients one month after the first dose and one month after the sixth dose. The average mf count decreased by 96.4% after the first dose and by 99.6% after the sixth dose (average residual mf counts = 13.7 and 1.5 mf/ml, respectively). The mf count after the sixth dose was only 11.2% of the count after the first dose. The low mf count persisted for more than six months after the sixth treatment (long-term-multiple doses). Thus, mass treatment with multiple doses is more appropriate for areas where the blood mf count is very high. These results show that the number of the annual treatments used in mass chemotherapy with ivermectin can be adapted to each population to provide efficient protection.

Adolescent↗
PubMed1997

Light microscopic changes in Plasmodium falciparum from Gabonese children treated with artemether.

The changes in Plasmodium falciparum in four Gabonese children suffering from severe malaria and treated with pure artemether were observed in thin blood smears fixed and stained with Giemsa and examined by light microscopy. Peripheral blood samples were taken every 8 hr up to 72 hr from three children and every 3 hr up to 9 hr from the other child. The morphologic changes involved all development stages (trophozoites, schizonts, and gametocytes); they were first seen 3 hr after the start of treatment and all parasites were abnormal after 24 hr. After two days of treatment, all infected erythrocytes disappeared except for a few with necrotic trophozoites. The morphologic changes were similar to the ultrastructural changes previously described in vivo and in vitro in experimental models. They confirm the rapid effect of artemisinin derivatives on parasite clearance and clinical recovery, particularly in cases of cerebral malaria.

Animals↗
PubMed1997

[Aspects of malaria in the hospitalized child in Gabon].

To gain insight into the impact of malaria on children in terms of frequency and severity, a study was carried out in a department of the Owendo Children's Hospital in Libreville, Gabon, a fully endemic area. Diagnosis of Plasmodium falciparum malaria was confirmed by blood smears in 295 of the 1592 children admitted in 1992, i.e. 18.5% of admissions. Malaria was therefore the primary cause of hospitalization. Of 122 deaths observed during the study period 9 were due to malaria-associated complications for an overall mortality rate of 7.4% and malaria-related mortality rate of 3.1%. These rates are low in comparison with those reported by other departments in Central Africa. Convulsions were observed in 30.5% of children in the department and malaria was the underlying cause of convulsions in 62.9% of these cases. Severe anemia (< 5 g/dl) was noted in 23.7% of children overall and was associated with malaria in 54.7%. Severe malaria as defined by the criteria of the World Health Organization was observed in 33.2% of children. These findings illustrate the extent of the impact of endemic malaria on children in Gabon and emphasize the need to promote malaria control programs and improve treatment.

Age Distribution↗
PubMed1996

Detection of circulating antigens in Gabonese patients with Loa loa filariasis.

Circulating antigens were detected in sera of Gabonese patients with Loa loa filarial infection by co-electrosyneresis (Co-ES). The serum samples selected for this study were exposed to rabbit hyperimmune antifilarial antisera and human immune antisera: specific arcs were observed in 35/60 filarial patients, of whom 24/47 were microfilaraemic and 11/13 amicofilaraemic. The identity of rabbit hyperimmune antisera and loiasial immune sera was confirmed by the continuity of precipitation arcs. These preliminary studies were carried out to develop diagnostic tools for loiasis and to study the physiopathology of immune complexes.

Animals↗