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Biomedical subjects

F Davachi

Publications and source records attributed to F Davachi.

At least 19 recordsLinked to original sources

Elevated levels of tumor necrosis factor-alpha in Zairian neonate plasmas: implications for perinatal infection with the human immunodeficiency virus.

Plasma levels of tumor necrosis factor-alpha (TNF alpha) and the ability of plasmas to induce HIV expression in chronically infected cell lines were measured in samples from adults, cord blood, and neonates from Zaire and North America. Plasma levels of TNF alpha were higher in Zairian neonates born to HIV-negative and -positive mothers than in uninfected Zairian adults (612 vs. 128 vs. 8 pg/mL, P < .001); this dichotomy persisted until children were 9 months old. Plasmas from neonates of HIV-negative Zairian mothers also stimulated higher levels of reverse transcriptase from HIV-infected cell lines than did plasma from HIV-negative Zairian adults (1339 vs. 110 cpm, P < .001). Similar patterns were noted in plasmas from HIV-negative North American adults and neonates; however, TNF alpha levels were markedly lower, and smaller differences were noted among North American adults and neonates than those in the Zairian cohort. Markedly elevated plasma TNF alpha levels in Zairian neonates and infants may play a role in the pathogenesis and progression of HIV disease in this patient population.

Adult↗

A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants.

BACKGROUND: Persistent diarrhea is a prominent feature of the acquired immunodeficiency syndrome in adults, but its cause and its effect on children with human immunodeficiency virus (HIV) infection are largely unknown, particularly in Africa. METHODS: We studied a birth cohort of 429 infants born to HIV-positive or HIV-negative mothers in Zaire to determine the incidence of acute, recurrent (> or = 2 episodes), and persistent (> or = 14 days) diarrhea; outcome; and risk factors. RESULTS: Of the 238 infants whose mothers were HIV-positive, 53 were infected, 139 were uninfected, and the HIV status of 46 could not be determined. As compared with uninfected infants, infected infants had higher incidence rates for acute diarrhea (170 vs. 100 episodes per 100 child-years, P = 0.003), recurrent diarrhea (21 vs. 11, P = 0.12), and persistent diarrhea (19 vs. 4, P < 0.003). Persistent diarrhea developed in 11 HIV-infected infants; all but 1 died. It also developed in 19 uninfected infants; all but 1 survived. The prevalence of stool pathogens was similar in the two groups. In a multivariate model, persistent diarrhea in an infant was independently associated with symptomatic HIV type 1 infection in the mother (relative hazard, 1.5; P = 0.08). The incidence of persistent diarrhea in the uninfected infants of seropositive mothers was nearly double that in the uninfected infants of seronegative mothers (4.9 vs. 2.7 episodes per 100 child-years), and the risk increased if the mother died (relative hazard, 10.4). Significant growth impairment and severe immunosuppression occurred in the six to eight weeks before the onset of persistent diarrhea. CONCLUSIONS: In Zaire, infants with HIV infection have an 11-fold increased risk of death from diarrhea, largely persistent diarrhea, which is often preceded by recurrent episodes of acute diarrhea, malnutrition, or immunosuppression. Illness and death of the mother increase that risk, even among her uninfected infants.

Acute Disease↗

Safety and immunogenicity of bacille Calmette-Guérin, diphtheria-tetanus-pertussis, and oral polio vaccines in newborn children in Zaire infected with human immunodeficiency virus type 1.

OBJECTIVE: To determine the safety and immunogenicity of childhood vaccines in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Nonrandomized, prospective cohort study; 12-month follow-up period. SETTING: Obstetric wards and outpatient pediatric clinics at two large hospitals in Kinshasa, Zaire. PATIENTS: A total of 8108 pregnant women were screened for HIV-1 antibodies. The 474 children born to 466 seropositive women identified during screening and the 616 children born to 606 seronegative, age- and parity-matched women were vaccinated. INTERVENTION: The following vaccines were administered at the stated ages: bacille Calmette-Guérin (BCG) vaccine (2 days); trivalent oral Sabin poliomyelitis vaccine (2 days and 6, 10, and 14 weeks); and adsorbed diphtheria-tetanus-pertussis (DTP) vaccine (6, 10, and 14 weeks). MEASUREMENTS AND MAIN RESULTS: Protective antibody titers to tetanus and poliovirus types 1, 2, and 3 were achieved in 95% of all children. Among children with HIV-1 infection, 70.8% had protective antibody titers to diphtheria compared with 98.5% of uninfected children (p < 0.05). Geometric mean antibody titers to diphtheria and poliovirus types 1, 2, and 3 were significantly lower in children with HIV-1 infection than in uninfected children. Vaccine-associated side effects were similarly low in all children. CONCLUSIONS: The low incidence of side effects and the high proportion of children with HIV-1 infection who achieved protective postimmunization antibody titers support the continuing use of BCG, DTP, and oral polio vaccines in childhood immunization programs in HIV-1 endemic areas.

Antibodies, Bacterial↗

Immunogenicity of high-titer Edmonston-Zagreb measles vaccine in human immunodeficiency virus-infected children in Kinshasa, Zaire.

The response to Edmonston-Zagreb vaccine (titer, 5.4 log10 pfu) was evaluated among children in a study of perinatal transmission of human immunodeficiency virus (HIV) in Kinshasa. Acute postvaccination adverse events were monitored for 49 HIV-infected and 376 non-HIV-infected infants, and measles antibody responses were assessed by ELISA for 34 HIV-infected and 255 non-HIV-infected infants. There was no increase in the incidence of common symptoms 7-10 days after vaccination. HIV-infected infants were more likely to have detectable prevaccination measles antibody, and seroconversion after vaccination was somewhat lower in HIV-infected (76.5%) than non-HIV-infected infants (85.5%). Seroconversion rates did not differ among children with or without rhinitis or fever at vaccination. High-titer Edmonston-Zagreb vaccine given at 6 months of age has the potential to provide earlier protection against measles; however, this vaccine is no longer recommended for routine use, and two doses of standard-titer vaccines remains the preferred option for measles vaccination of HIV-infected infants.

Child↗

Accurate detection of maternal antibodies to HIV in newborn whole blood dried on filter paper.

OBJECTIVE: The testing of neonatal blood specimens dried on filter paper for maternal HIV antibodies, using an enzyme immunoassay (EIA) with confirmation of repeatedly reactive specimens by immunoblot (IB), was first described in 1987. It has been used to conduct large, unlinked, anonymous HIV seroprevalence surveys for surveillance of HIV in child-bearing women in several countries. We directly assessed the sensitivity and specificity of this combination of tests to detect maternal HIV antibodies. SETTING: Serum samples obtained from mothers delivering at a major hospital in Kinshasa, Zaire were screened for HIV antibody using the rapid assay HIVCHEK. DESIGN: Plasma from HIVCHEK-positive women and age-matched negative controls were tested by enzyme-linked immunosorbent assay (ELISA); repeatedly reactive specimens were confirmed by Western blot (WB). Two days after delivery, whole blood was obtained from each newborn by heel-stick, dried on filter paper, and tested by EIA. Repeatedly reactive specimens were confirmed by IB. MAIN OUTCOME MEASURE: The serologic status of neonatal filter-paper specimens was compared with that of corresponding maternal plasma. RESULTS: The testing of neonatal filter-paper specimens using EIA, with confirmatory testing of repeatedly reactive specimens using IB, was 100.0% sensitive [of the 192 ELISA-positive and WB-positive maternal plasma specimens, 192 of the corresponding newborn filter-paper specimens were EIA-positive and IB-positive; 95% confidence interval (CI), 98.1-100]. The detection of maternal HIV antibodies was 99.6% specific using this combination of tests (of the 281 ELISA-negative or ELISA-positive but WB-negative maternal plasma samples, 280 of the corresponding newborn filter-paper specimens were EIA-negative or EIA-positive but IB-negative; 95% CI, 98.0-100). CONCLUSIONS: Maternal HIV antibodies can be detected accurately by testing neonatal blood dried on filter paper, using EIA with confirmation of repeatedly reactive specimens by IB. This approach can facilitate the determination of HIV seroprevalence in child-bearing women in countries with neonatal screening programs, or where serum or plasma is difficult to obtain.

Democratic Republic of the Congo↗

Plasmodium falciparum-associated anemia in children at a large urban hospital in Zaire.

Chloroquine-resistant Plasmodium falciparum malaria and human virus (HIV) infection through blood transfusions used to treat malaria-associated anemia are causes of increasing morbidity and mortality among children in Africa. To evaluate the role of malaria and other risk factors for pediatric anemia, we conducted a study of children brought to the emergency ward of a large urban hospital in Kinshasa, Zaire. A total of 748 children ages six through 59 months were enrolled; 318 (43%) children were anemic (hematocrit < 33%), including 74 (10%) who were severely anemic (hematocrit < 20%). Plasmodium falciparum parasites were detected in 166 children (22%); hematocrits for these children (mean 25.8%) were significantly lower than for aparasitemic children (mean 33.7%; P < 10(-6)). Fever with splenomegaly (odds ratio [OR] = 6.5, P = 0.02), parasitemia (OR = 3.5, P < 0.001), lower socioeconomic status (OR = 2.0, P = 0.004), and malnutrition (OR = 1.8, P = 0.06) were independently associated with anemia in a multivariate model. Recent antimalarial therapy was also associated with a lower hematocrit, suggesting that chloroquine may have aggravated the anemia. A reassessment of the effectiveness of strategies to diagnose and treat malaria and malnutrition is necessary to decrease the high prevalence of anemia and the resultant high rate of blood transfusions in areas endemic for malaria and HIV.

Analysis of Variance↗

Persistent diarrhea associated with AIDS.

Chronic diarrhea and wasting are very common manifestations of AIDS in adults in developing countries. Etiologic studies show that protozoa (including Cryptosporidium parvum, Isospora belli, and Enterocytozoon bieniusi) and Mycobacterium avium-intracellulara are the most frequently identified pathogens. Limited data in children suggest that common enteric pathogens are equally as likely in HIV+ and HIV- babies. Preliminary analysis of an ongoing longitudinal study of 469 babies born to mothers with known HIV serostatus in Kinshasa, Zaire, reveals progression of acute to persistent diarrhea is six times greater in HIV+ compared to HIV- babies, and 3.5 times greater in HIV- babies born of HIV+ mothers in comparison to HIV- babies with HIV- mothers. HIV+ babies were also at greater risk than HIV- babies to have recurrent episodes of diarrhea (RR = 2.3). Fifty percent of the deaths were due to acute or persistent diarrhea, and were strongly associated with HIV infection. Efforts to improve child survival in AIDS infected populations will need to address HIV infections in both mothers and infants.

Acquired Immunodeficiency Syndrome↗

[Evaluation of vaccine coverage in children under two years of age in Kinshasa (Zaire)].

BACKGROUND: Despite efforts to make immunization against preventable diseases available to all children in Zaire, only about 33% of the children living at Kinshasa were immunized in 1986. METHODS: The compliance with the vaccination schedules was evaluated in 211 children less than 2 years of age consulting in the largest medical center of Kinshasa during one week in September 1989. Socio-demographic data on the parents and histories of infectious preventable diseases in children were also collected. RESULTS: 93% of the children were immunized against tuberculosis, 85% against diphtheria, tetanus, pertussis and poliomyelitis, 76% against measles. Compliance with the vaccination schedule was higher when the mothers were better educated, or when they worked in the public service. 25% of the children had not been immunized against measles at the age of 9 months. CONCLUSION: The vaccine schedule and the strategy must still be improved.

Democratic Republic of the Congo↗

Pediatric AIDS and perinatal HIV infection in Zaire: epidemiologic and pathologic findings.

HIV infection in women and children is a special problem in Zaire and in other countries where heterosexual transmission is predominant. Nearly half of the cases of HIV infection are in women 15 to 30 years old and as many as seven infected infants may be born each year. Whether or not infected at birth, these children have mothers, and often fathers, who are infected and likely to die while they are still very young. Such orphaned children, as well as those whose families cannot provide adequate food and health care, add to the problematic economies of developing countries. The problems of children of HIV-infected mothers in developing countries may be compounded further by factors directly related to their mother's disease. Infected mothers who are sick may produce insufficient levels of antibodies and be unable to provide their children with adequate natural passive immunity before birth. Their infants may also receive inadequate levels of breast-milk-derived antibodies possibly enhancing their already increased susceptibility to perinatal infections, and lastly, the volume of breast milk produced by these mothers may be inadequate for the nutrition of these infants. All these factors may further compromise the already difficult task of distinguishing those infants of HIV-infected mothers who are ill because they are infected from those who are ill because of their mother's disease. Regardless of the mechanisms accounting for the increased vulnerability of infants of HIV--seropositive and AIDS-afflicted mothers to perinatal infections, infant mortality can be expected to increase significantly as a direct consequence of the progression of the HIV pandemic throughout Africa and possibly other developing countries; this in populations already with a total under five-years-of-age mortality rate exceeding 15%. The association of chorioamnionitis with HIV seropositivity and with the clinical status of the mother seems to suggest that impaired maternal immunity increases the risk of premature birth, its consequent lower birth weight, and to HIV or other perinatally acquired infections. The identification of women at higher risk of chorioamnionitis and their treatment might provide a means to decrease the risk of premature delivery and possibly reduce the rate of HIV transmission to their infants. The pathologic changes in organs of infants and children with HIV infection require in-depth, systematic study to better define the natural history of perinatal HIV disease and infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

Plasmodium Falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children.

BACKGROUND: It is uncertain whether Plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection and whether P. falciparum infection accelerates the progression of HIV-related disease. METHODS: We conducted a prospective, longitudinal cohort study in Kinshasa, Zaire. Two hundred sixty children 5 to 9 months of age who had been born to HIV-1-seropositive mothers and 327 children of the same age who had been born to seronegative mothers were monitored intensively for malaria over a 13-month period. All episodes of fever were evaluated with blood smears for malaria, and children found to be infected with P. falciparum were treated with a standard regimen of oral quinine. RESULTS: A total of 2899 fevers were evaluated, with 271 cases of malaria identified. No statistically significant differences were found in the incidence, severity, or response to therapy of malaria among four well-defined groups of children: those with the acquired immunodeficiency syndrome (AIDS), those who were HIV-1-seropositive throughout the study, those who were born to HIV-1-seropositive mothers but reverted to seronegative, and those who were seronegative throughout the study. During the 13-month period the incidence of malaria in the 36 children with HIV infection in whom AIDS developed was lower, although not significantly so, than in the 37 in whom AIDS did not. CONCLUSIONS: In this study malaria was not more frequent or more severe in children with progressive HIV-1 infection and malaria did not appear to accelerate the rate of progression of HIV-1 disease.

Acquired Immunodeficiency Syndrome↗

Tumor necrosis factor and severe malaria.

To investigate the relation of tumor necrosis factor-alpha (TNF alpha) to Plasmodium falciparum infection, plasma TNF alpha concentrations were measured in Zairian children with severe malaria, mild malaria, or other illnesses. The initial geometric mean plasma concentration of TNF alpha among 61 children with P. falciparum infection, (71 pg/ml) was higher than the level in 26 severely ill, aparasitemic children (10 pg/ml; P less than .001). Among 29 parasitemic children, initial geometric mean TNF alpha levels decreased from 77 to 5 pg/ml (P less than .001) at day 7. TNF alpha levels increased with parasite density and were associated with hyperparasitemia, severe anemia, hypoglycemia, and young age but not with cerebral malaria or fatal outcome. However, TNF alpha levels were elevated equally in children with cerebral malaria and with other signs of severe malaria. With multiple linear regression, TNF alpha levels were elevated independently in children with hyperparasitemia (P = .001) and severe anemia (P = .04). In this study, high TNF alpha levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria.

Animals↗

Prevention of transfusion-associated HIV transmission in Kinshasa, Zaire: HIV screening is not enough.

The purpose of this study was to develop a strategy to reduce transfusion-related HIV transmission which went beyond the limits of routine HIV screening of blood donors. Current blood transfusion practices were assessed in 1044 patients for whom staff physicians had requested a transfusion between 5 September and 19 October, 1988. Children under 5 years of age with malaria, and pregnant women with acute anaemia requiring blood transfusion were the two highest risk groups. Many of the transfusions were given without an obvious medical indication; 22.7% (214 out of 955) of the recipients were transfused without prior laboratory tests [haemoglobin (Hb) or haematocrit (Hct)], 7.2% with Hb greater than 6g/100ml or Hct greater than 25% and 16.6% without clinical signs of severe anaemia (pulse less than 100/min without shortness of breath). The data of this study were used to organize a workshop for all the physicians responsible for blood transfusions in Kinshasa and two nearby health zones. A consensus statement on the indications for blood transfusion was developed. Subsequently, transfusion centres adopted this consensus statement instead of previous guidelines.

Adolescent↗

Trends and risk factors for HIV-1 seropositivity among outpatient children, Kinshasa, Zaire.

To investigate recent trends in pediatric HIV-1 infection and the early impact of a blood screening program begun in one hospital in 1987 in Kinshasa, Zaire, we evaluated 1110 consecutive children seen in the pediatric emergency ward of the city's largest hospital in November 1988. The HIV-1 seroprevalence was 5.0%, not significantly higher than the rate of 3.8% found in 1986 (P = 0.2). The seropositivity rate was bimodally distributed; children less than 6 months of age had a higher rate (12.6%) than children 6-11 months old (1.9%; OR = 7.6; P less than 0.0001) and children 1-13 years old (4.1%; OR = 3.4; P less than 0.0001). Seropositive children greater than or equal to 1 year of age were more likely than seronegative children to be anemic and to have signs of malnutrition. A previous blood transfusion was associated with HIV-1 seropositivity among children greater than or equal to 1 year of age (OR = 5.4, P less than 0.0005), but not among younger children. Fifty-two per cent of seropositive children greater than or equal to 1 year of age received a transfusion (etiological fraction = 42%). The association with seropositivity was higher for those who had received a transfusion before 1987 than for those who had received a transfusion since 1987 (OR = 4.8, P = 0.01). These findings suggest a relatively stable, high pediatric HIV-1 seroprevalence in Kinshasa and a decreased but continued risk of transfusions. Expansion of currently limited blood transfusion screening programs, and the development of new strategies for limiting transfusions and preventing severe anemia, are needed.

Adolescent↗

New parameters for evaluating oral rehydration therapy: one year's experience in a major urban hospital in Zaire.

Oral rehydration therapy (ORT) is a simple treatment for diarrhoeal dehydration that must be administered correctly to be effective. In August 1984 an ORT service was established at Mama Yemo Hospital in Kinshasa, Zaire. During the first 12 months, 5530 children with diarrhoea were treated, and their clinical history and treatment evaluated. We used indicators traditionally used for individual case management as operational tools to monitor the quality of treatment on the ORT service as a whole. These included quantity of liquids prescribed and given, time spent at the centre, weight gained during rehydration, and discharge status. Analysis using these indicators showed that adverse outcome (death or hospitalization), when it did occur, was not associated with inadequate ORT treatment. Instead, it was associated with clinical antecedents including fever, measles or 'other' complaint. We conclude that indicators reflecting quality of treatment are useful in identifying operational problems associated with oral rehydration services and that our frequent conferences with the pediatric personnel helped to rectify these problems. To our knowledge, this study represents the largest hospital-based ORT population yet reported, and the first of its kind from an African country.

Child, Preschool↗

Intravenous quinine therapy of hospitalized children with Plasmodium falciparum malaria in Kinshasa, Zaire.

To examine the clinical and parasitologic efficacy of quinine, we studied 34 children (7 months-13 years old) with severe or moderately severe Plasmodium falciparum infections. Quinine 10 mg/kg every 8 hr for 3 days was administered, initially by intravenous infusion of quinine formate followed by oral quinine dihydrochloride when tolerated. Thirty-three of the 34 patients were clinically well and had negative malaria smears 7 days after the initiation of therapy; 1 child, who presented in coma, died 29 hr after enrollment. The mean fever clearance time was 44.1 hr, and the mean parasite clearance time was 59.6 hr. A mean peak quinine level of 9.7 ppm was attained after the second dose of quinine, and the minimum concentration was maintained at 5-7 ppm during the 2nd and 3rd hospital days. In vitro testing was conducted with parasites from 10 patients: 9 isolates were resistant to chloroquine, and inhibition of schizont development with quinine occurred at a concentration of 8-32 pmol/well.

Administration, Oral↗