Chloroquine resistant malaria in children

Malaria remains a major cause of childhood morbidity and mortality. The changing susceptibility of Malaria parasites to drugs means that it is no longer possible to make global generalization about its chemotherapy. This study was conducted in District Hospital, Mirpurkhas, Sindh. Over sixteen months period four hundred and six patients had slide documented malarial parasites. Sixty-five percent had plasmodium falciparum, 33% plasmodium vivax and 2% had both. Approximately, 81% responded to chloroquine while 19% were non-responders. Chloroquine non-responders were treated with halofantrine or sulfadoxine--pyrimethamine combination. P. falciparum being the dominant species and its emergence of resistance to Chloroquine, in life threatening and serious forms of malaria should be treated with parenteral quinine. Antimalarials other than Chloroquine should be reserved for non-responders. Therefore, rational use of drugs is essential.     

Cutaneous cancers in Togo

The dural tail on contrast-enhanced magnetic resonance (MR) images, frequently observed in meningiomas, has been used to distinguish between cerebellopontine angle meningiomas and vestibular schwannomas. We report on a 66-year-old female with vestibular schwannoma showing the dural tail on contrast-enhanced MR images. Histological examination revealed that the dural tail corresponded to the thickened dura mater comprising of collagen fibres and scattered hyalinization with no tumoral invasion.     

Severe and complicated malaria. Report of six cases

The major obstacle for successful xenotransplantation of islets to large animals and human diabetics is the host rejection. To address the rejection problem, we studied the efficacy of UV-B irradiation, cryopreservation and immunosuppression on the in vivo functional time and immunogenicity of adult porcine islets (PI) in outbred CD1 mice. Exposure of PI to UV-B irradiation between 300-1800J/M2 did not affect the cellular viability as assessed by fluorescein diacetate or their daily insulin secretion in vitro. Fresh PI normalized the blood glucose (BG) of diabetic CD1 mice for 3.1+/-0.6 (n = 8, mean+/-SEM) days. Islets treated with 600J/M2 UV-B irradiation or cryopreservation had similar graft functional times to fresh islets upon transplantation in diabetic CD1 mice. Immunosuppression with cyclosporin A (CsA), antilymphocyte serum (ALS) and FK506 prolonged the functional time of fresh pig islets to 7.9+/-0.9 (n = 9), 6.2+/-1.3 (n = 5) and 24.2+/-10.4 (n = 12) days, respectively. However, additional pretransplant treatment with either UV-B irradiation or cryopreservation did not further increase the functional time of pig islets in mice immunosuppressed with CsA. Furthermore, there was no apparent difference in the frequency of appearance of cytotoxic antibodies and antibody titers in the recipients of UV-B irradiated or cryopreserved pig islet compared with non-treated islets. The UV-B irradiation and cryopreservation of PI before transplantation with the present protocols did not appear to have significant effect on the islet immunogenicity when assessed by in vivo survival duration and anti-donor antibody titer production.     

The pathogenesis of severe malaria in African children

The ferrylmyoglobin <==> metmyoglobin redox transitions promoted by hydrogen peroxide and dietary phenolic acids and their potential role in the oxidation of LDL were studied. The use of parinaric acid incorporated in LDL as a probe for radicals (detected by fluorescence quenching of the probe) revealed an oxidative stress inside LDL shortly ( < 1 min) after addition of hydrogen peroxide to metmyoglobin in the aqueous phase outside the particle, reflecting an efficient access of the oxidant to LDL lipids. However, the propagation step of peroxidation only occurs after a lag phase, as detected by the kinetics of oxygen consumption. Triton X-100 decreases but does not suppress the lag phase of oxidation. Addition of metmyoglobin (without peroxide) to LDL was not followed by significant oxidation during the time of the experiment, unless Triton X-100 was present in the medium. When dietary phenolic acids were present in the medium before peroxide addition, an inhibition of parinaric acid fluorescence quenching and oxygen consumption was recorded as a function of concentration and substitution pattern on the phenol ring of the phenolic acids. This was associated with a conversion of ferrylmyoglobin to metmyoglobin. The results indicate that the naturally occurring phenolic acids prevent ferrylmyoglobin-dependent LDL oxidation in a way strongly dependent on the substitution pattern on the phenol ring. Among the phenolic compounds studied, the o-dihydroxy derivatives of cinnamic and benzoic acids (caffeic, chlorogenic, and protocatechuic acids), in a molar ratio of 1 to metmyoglobin, efficiently blocked LDL oxidation initiated by ferrylmyoglobin. Replacement of one OH group from catecholic structure with an H (p-coumaric acid) or methoxy group (ferulic acid) decreased the antioxidant activity. Also, the catechol structure fused in heterocyclic rings with adjacent carbonyl groups (ellagic acid) resulted in decreased antioxidant activity. These observations correlate with the efficiency of phenolic acids to reduce ferrylmyoglobin to metmyoglobin. Therefore, the protection of LDL against oxidation is assigned to the reduction of the oxoferryl moiety of the hemoprotein to the ferric form. Additionally, it is suggested that an access constraint of oxidants plays a minor role in the ferrylmyoglobin-induced oxidation against LDL.     

Quinine pharmacokinetics in young children with severe malaria

In this study, we determined selenium concentrations in serum samples of healthy women (146 pregnant and 74 nonpregnant) living in the Mediterranean area of the coast of Granada (southeast Spain). The subjects were distributed in two groups: group A (pregnant women), divided into three categories according to the trimester of pregnancy, and group B (nonpregnant women). No significant differences were observed in the selenium levels either among pregnant women according to the trimester of pregnancy or in the group of nonpregnant women. No other significant differences were determined as regards the age of pregnant women (P > 0.05). Serum selenium levels are slightly lower during pregnancy. Considering that serum selenium levels affect the body selenium status, the concentrations determined establish the non-existence of selenium problems in the daily dietary intake with respect to maternal and fetal necessities during pregnancy.     

Severe and complicated malaria treated with artemisinin, artesunate or artemether in Viet Nam

One hundred and seventy five Vietnamese adults with severe and complicated malaria admitted to a rural district hospital were entered into an open randomized comparative study to compare 4 treatment regimens based on artemisinin and its derivatives. The median time of defervescence was 48 h (95% confident interval [CI] 38-58 h) in those given intramuscular (i.m.) artemether, 42 h (95% CI 36-48 h) in those given artemisinin suppositories, 36 h (95% CI 30-42 h) in those receiving artesunate (i.m.) and 30 h (95% CI 18-42 h) in those receiving intravenous artesunate (P = 0.13). The respective median parasite clearance times were 30 h (95% CI 26-34 h), 30 h (95% CI 24-36 h), 24 h (95% CI 15-33 h), and 24 h (95% CI 15-33 h) (P = 0.30); the median times for recovery of consciousness were 47 h (95% CI 31-63 h), 24 h (95% CI 18-30 h), 30 h (95% CI 18-42 h), and 24 h (95% CI 4-44 h) (P = 0.18); and the mortality rates were 11.1%, 17.6%, 10.2% and 16.6%, respectively (P = 0.64). There was no significant difference in efficacy between the 4 treatments.     

Transient erythroblastopenia in children. Severe anemia with good prognosis

Transient erythroblastopenia of childhood (TEC) is an acute form of anaemia characterized by a transient red blood cell aplasia, of unknown cause, in the bone marrow. The incidence appears to be increasing. 16 patients were seen in our paediatric department during the period 1990 to 1996. The ages varied from two to 48 months. All patients had severe anaemia, the lowest mean haemoglobin values being 4.9 (2.2-7.8) g/100 ml. The reticulocyte count was low in 14 patients, whereas two patients had reticulocytosis. No underlying haematologic diseases were found. Ten patients were tested for parvovirus B19 infection, all of whom were serologically negative. Apart from transfusion of red blood cells in six patients, no therapy was given. Reticulocytosis, indicating beginning recovery, was observed after a mean interval of 11.8 days. This article gives a short overview of transient erythroblastopenia of childhood, a form of anaemia which can initially represent a diagnostic challenge.     

Randomised placebo-controlled study of atovaquone plus proguanil for malaria prophylaxis in children

BACKGROUND: The combination of atovaquone and proguanil is highly effective and safe for the treatment of Plasmodium falciparum malaria. We aimed in this randomised, double-blind, placebo-controlled study to assess the efficacy and safety of this combination for malaria prophylaxis. METHODS: 320 children who lived in a hyperendemic area for P falciparum malaria were stratified by weight and randomly assigned atovaquone plus proguanil or placebo once daily for 12 weeks. All children received initial curative treatment with atovaquone and proguanil before the start of chemosuppression. We recorded adverse events daily and collected thick blood smears once a week. The primary endpoint was a positive blood smear. FINDINGS: 25 of 140 children in the placebo group and none of the 125 children in the atovaquone plus proguanil group had positive smears during chemosuppression (p<0.001). Adverse events during the chemosuppression phase did not differ between the groups. INTERPRETATION: The combination of atovaquone plus proguanil is a highly effective and well-tolerated chemosuppressive antimalarial in children. This drug combination could replace current regimens.     

Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria

OBJECTIVES: To titrate a clinically effective eltenac dosage (0.1, 0.5, and 1.0 mg/kg of body weight), compared with vehicle only, and to compare efficacy of the most effective eltenac dosage with that of 1.1 mg of flunixin meglumine/kg. ANIMALS: 40 healthy horses, ranked after model induction on the basis of lameness severity, were randomly assigned to 5 treatment groups, with 4 replicates of 10 horses each. PROCEDURE: On day -5, after surgical preparation of the left carpal region, 0.7 ml of Freund's complete adjuvant was injected into the intercarpal space. Horses were observed daily, from the day of carpitis induction to day 0, when stride length was used as the method of ranking horses for randomization to treatment assignment. Treatments were administered i.v. once daily for 3 consecutive days, starting on day 0. Prior to carpitis induction on day -5, and at time 0 (pretreatment), 2, 4, 12, 24, 36, 48, 60, 72, and 96 hours after treatment initiation, resting respiratory rate and pulse, rectal temperature, carpal circumference, carpal flexion angle, stride length, carpal hyperthermia, and signs of carpal pain were recorded. RESULTS: Compared with the vehicle and 0.1 mg of eltenac/kg, 0.5 and 1.0 mg/kg caused statistically significant improvements (ie, reduction of carpal circumference, increase in carpal flexion angle, and increase in stride length of the affected limb), but values did not differ significantly between the 2 dosages. Thus, a dose-response plateau for eltenac was reached at 0.5 mg/kg. Comparison with flunixin meglumine at a dosage of 1.1 mg/kg did not indicate significant differences between the 2 treatment groups at the pivotal time of 96 hours for carpal circumference, carpal flexion angle, stride length, carpal hyperthermia, and signs of carpal pain. Adverse reactions were not observed. CLINICAL RELEVANCE: Under conditions of this study, a dosage plateau for eltenac was determined (0.5 mg/kg) that was statistically equivalent to eltenac (1.0 mg/kg) and flunixin meglumine (1.1 mg/kg) in a 3-day i.v. dosing regimen.     

Pharmacokinetics of mefloquine combined with artesunate in children with acute falciparum malaria

To study the biologic role of migration inhibitory factor (MIF), a pleiotropic cytokine, we generated a mouse strain lacking MIF by gene targeting in embryonic stem cells. Analysis of the role of MIF during sepsis showed that MIF-/- mice were resistant to the lethal effects of high dose bacterial lipopolysaccharide (LPS), or Staphylococcus aureus enterotoxin B (SEB) with D-galactosamine and had lower plasma levels of tumor necrosis factor alpha (TNF-alpha) than did wild-type mice, but normal levels of interleukin (IL)-6 and IL-10. When stimulated with LPS and interferon gamma, macrophages from MIF-/- mice showed diminished production of TNF-alpha, normal IL-6 and IL-12, and increased production of nitric oxide. MIF-/- animals cleared gram-negative bacteria Pseudomonas aeruginosa instilled into the trachea better than did wild-type mice and had diminished neutrophil accumulation in their bronchoalveolar fluid compared to the wild-type mice. Thioglycollate elicited peritoneal exudates in uninfected MIF-/- mice, but showed normal neutrophil accumulation. Finally, the findings of enhanced resistance to P. aeruginosa and resistance to endotoxin-induced lethal shock suggest that the counteraction or neutralization of MIF may serve as an adjunct therapy in sepsis.     

Severe hypophosphatemia in children with kwashiorkor is associated with increased mortality

Severe hypophosphatemia, serum phosphate concentration <0.32 mmol/L (<1.0 mg/dL), occurred in 8 of 68 (12%) of children with kwashiorkor within 48 hours of admission; 5 of 8 (63%) of these children died, compared with 13 of 60 (22%) children without severe hypophosphatemia (P <.02). Dermatosis and dehydration were significantly correlated with severe hypophosphatemia, but these clinical signs could not reliably predict fatal cases. Severe hypophosphatemia seems to be common and life-threatening in children with kwashiorkor in Malawi.     

Maternal and perinatal health in Mali, Togo and Nigeria

When healthcare executives speak of managed care, they often use the term generically to refer to any arrangement with a healthcare payer other than traditional fee-for-service reimbursement. All too often, the "management" aspect is missing from managed care, resulting in an arrangement that could more aptly be described as "discounted care." This lack of clinical representation is unfortunate, since there are numerous issues that have an impact on clinical care, including choice of referral providers, noncoverage of certain procedures or treatments, and similar issues that may influence the patient's plan of care. Organizations that approach managed care as a system that blends the resources of management, finance, and clinicians, will enjoy the greatest potential for success. With their practical experience and insight into the administrative and clinical issues that may be encountered, nurse case managers will ultimately be responsible for managing the care of the contracted population. As case managers are the vital link among payers, providers, patients, and families, it is essential that the case manager understand managed care concepts, be conversant in the terminology of managed care, function as a member of the team responsible for evaluating contracts, and periodically review existing arrangements. This article presents an overview of the managed care contract development process, and provides tools to enable the nurse case manager to participate in the contracting process.     

Osteoarthritis of limbs in hospital practice in Lomé (Togo)

Medical records of patients seen at the Lomé Teaching Hospital rheumatology clinic (Togo) were studied retrospectively to determine the prevalence and topographic patterns of osteoarthritis. Among the 2626 patients seen over a three-year period, 232 had appendicular osteoarthritis. Distribution of affected joints was as follows: knee, 212 patients (83% female, 17% male); hip, 17 patients with primary osteoarthritis; scapulohumeral joint, 2 patients; and fingers, 1 patient. At the knee, the lesions involved the medial femorotibial compartment in 114 patients, the lateral femorotibial compartment in 54 patients and the patellofemoral compartment in 44 patients. Mean age at onset of femorotibial osteoarthritis was 50 years. Among females with femorotibial osteoarthritis, 70% were obese and 90% had varus or valgus deformities. This study confirms that in black Africa the high prevalence of femorotibial osteoarthritis contrasts with the low prevalence of primary osteoarthritis of the hip and of osteoarthritis of the fingers. Female sex, obesity, and varus or valgus deformities are the main risk factors for femorotibial osteoarthritis in black Africa.     

Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles

A rapid, sensitive, and simple method was developed to detect the sapstain fungi Ophiostoma piceae and O. quercus in stained wood. By using microwave heating for DNA extraction and PCR with internal transcribed spacer-derived-specific primers, detection was feasible within 4 h, even with DNA obtained from a single synnema. This method can easily be extended for the detection of other wood-inhabiting fungi.     

Melanoma in Togo. A retrospective study over 20 years

INTRODUCTION: The malignant melanoma is a rare malignant tumour in black patients, but it is common in white patients. MATERIAL AND METHODS: Medical records were reviewed retrospectively during 20 years (1973-1992) to determine the epidemiological features of malignant melanoma in Togo. RESULTS: During this period 63 cases (31 males and 32 females) of malignant melanoma were histologically diagnosed; an average of 3.15 cases each year. The tumor takes place preferably on the feet 40 cases (63.49%), hands 15 cases (19.04%), legs and thigh 10 cases (15.87%). CONCLUSION: The results of this study confirm the particularity of malignant melanoma in black subjects: its rarity and the feet localizations.     

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children

BACKGROUND: Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. METHODS: A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. RESULTS: There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). CONCLUSIONS: In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.     

Lack of association between falciparum malaria parasitemia and acute diarrhea in Nigerian children

It is widely believed that malaria causes diarrhea. Yet, national and international diarrheal diseases control programs are silent about the overlap between these two major public health problems that coexist in most tropical countries. To test the hypothesis that malaria is associated with diarrhea and to define the role of malaria in morbidity due to diarrhea, 522 children 6-60 months of age presenting with acute diarrhea to the Children's Emergency Ward of the University College Hospital in Ibadan, Nigeria were routinely screened by means of thin and thick blood films for malaria parasitemia. Controls, without diarrhea, were studied in parallel. Detailed clinical features were recorded for every patient. Sixty-eight (13%) of the 522 diarrhea patients screened had malaria parasitemia. Among the controls (who had similar distributions of admission temperature, hemoglobin types, glucose-6-phosphate dehydrogenase deficiency, and prior treatment with antimalarial drugs), parasitemia was not significantly different, occurring in 56 (17.9%) of 313. In the dry season, however, a significantly higher prevalence of parasitemia was observed among the control group (15.5%) than in the diarrhea group (7.0%) (P = 0.004). Parasitemia was significantly more common in the dehydrated diarrhea patients than their well-hydrated counterparts (25% of 56 versus 11% of 466; P < 0.005). There were no significant differences in admission temperature, the presence of vomiting, or the home use of oral rehydration fluids between the dehydrated and the well-hydrated subsets of diarrhea patients. Consideration of parasite densities did not alter any of the foregoing relationships. These data contradict the widely held view that diarrhea is a symptom of malaria or that malaria causes diarrhea. They do, however, provide support for examining blood smears at least in dehydrated children with diarrhea in malaria-endemic areas and giving immediate antimalarial therapy to those who have malaria parasitemia.