Gisela Schneider

Despite prompt treatment with an effective anti-malarial drug, cerebral malaria still has a mortality of 20-30%. To identify factors that may contribute to this high fatality rate, we have studied the relationship between clinical and laboratory features and a fatal outcome in 624 Gambian children with strictly defined cerebral malaria. One hundred twenty-four children (21.5%) died. Three-quarters of the deaths occurred within 24 hr of admission. Multiple logistic regression analysis showed that a cold periphery (odds ratio [OR] = 2.7), a deep coma (OR = 2.0), and hypoglycemia (OR = 4.1) were the clinical signs and laboratory parameters that predicted death most strongly. More than 90% of the children who died had at least one of these conditions. Also, children with elevated urea levels on admission or those who experienced multiple episodes of hypoglycemia or multiple convulsions subsequently were more likely to die. A combination of clinical and laboratory abnormalities can identify a group of children with cerebral malaria who are most at risk of dying, who require intensive care and who are candidates for new forms of therapy.

To evaluate the effects of the Infectious Diseases Institute's 4-week course for African doctors on comprehensive management of HIV including antiretroviral therapy on four outcomes: (1) clinical skills, (2) clinical activities, (3) monitoring of HIV patients, and (4) training activities Clinical exam at beginning and end of course and at follow-up 3 to 4 months later, and a cross-section telephone survey. Forty-seven doctors attending the course (October 2004, November 2004, March 2005, and April 2005) agreed to participate. A 17-item Clinical Exam Checklist was used to assess clinical skills. A telephone survey was conducted 1 month after the course to collect data in four areas: clinical activities, monitoring of HIV patients, case studies on initiation of ART, and training activities. The course improved the clinical skills of doctors. Between the beginning and end of the course, their clinical skills improved significantly in 11 of 17 areas (n = 34). Between the end of the course and follow-up, their skills improved significantly in three areas (n = 14). The trainees were practicing HIV care and training. The telephone survey (n = 46) showed that 93% of trainees treated HIV patients, 35% provided training on HIV, and 47% monitored the weight of the last HIV patient treated (patient's weight was a clinical end point to measure health status). At follow-up, everyone provided training and trained an average of 20 people per month.

Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%), 24 of 40 clinical o...

ABSTRACT: BACKGROUND: Deployment of highly effective artemisinin-based combination therapy for treating uncomplicated malaria calls for better targeting of malaria treatment to improve case management and minimize drug pressure for selecting resistant parasites. The Integrated Management of Malaria curriculum was developed to train multi-disciplinary teams of clinical, laboratory and health information professionals. METHODS: Evaluation of training was conducted in nine health facilities that were Uganda Malaria Surveillance Programme (UMSP) sites. From December 2006 to June 2007, 194 health professionals attended a six-day course. One-hundred and one of 118 (86%) clinicians were observed during patient encounters by an expert clinician at baseline and during three follow-up visits approximately six weeks, 12 weeks and one year after the course. Expert used a standardized tool for children less than five years of age and similar tool for patients five or more years of age. Seventeen...

In developing countries, pneumonia and meningitis due to Haemophilus influenzae type b (Hib) are common in children under age 12 months and the mortality from meningitis is high. Protein-polysaccharide conjugate vaccines have brought Hib disease under control in industrialised countries. We did a double-blind randomised trial in The Gambia to assess the efficacy of a Hib conjugate vaccine for the prevention of meningitis, pneumonia, and other invasive diseases due to Hib. Between March, 1993, and October, 1995, 42,848 infants were randomly allocated the conjugate vaccine Hib polysaccharide tetanus protein (PRP-T) mixed with diphtheria-tetanus-pertussis vaccine (DTP), or DTP alone at age 2 months, 3 months, and 4 months. Children who presented with signs of invasive Hib were investigated by blood culture and, where appropriate, by lumbar puncture, chest radiograph, or percutaneous lung aspirate. Children were followed up for between 5 and 36 months. The median ages at which children received the study vaccine were 11 weeks, 18 weeks, and 24 weeks. 83% of children enrolled received all three doses of vaccine. 17 cases of culture-positive Hib pneumonia, 28 of Hib meningitis, and five of other forms of invasive Hib disease were detected amongst the study children. The efficacy of the vaccine for the prevention of all invasive disease after three doses was 95% (PRP-T vaccinees 1, controls 19 [95% CI 67-100]), for the prevention of Hib pneumonia after two or three doses, 100% (vaccinees 0, controls 10 [55-100]), and for the prevention of radiologically defined pneumonia at any time after enrollment, 21.1% (PRP-T vaccinees 198, controls 251 [4.6-34.9]). PRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants. The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib. The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis.

Determination of the etiology of pneumonia in young children is difficult because blood culture, the usual method of diagnosis, is positive in only a small proportion of cases. For this reason vaccine trials that include bacterial pneumonia as an endpoint must be large. To determine whether a diagnostic test based on a polymerase chain reaction could be used as an alternative to conventional blood culture for diagnosis of invasive Haemophilus influenzae type b (Hib) infections in young children investigated during the course of a large vaccine trial. DNA was extracted from blood culture supernatants and probed for the presence of Hib DNA with a PCR assay with primers derived from the cap gene locus of Hib. Results of the PCR assay were compared with those obtained by conventional culture techniques. Blood cultures were obtained from 1544 children with suspected pneumonia, meningitis or septicemia and from 31 healthy control children who were contacts of cases. Blood culture supernatants were tested for Hib DNA in the PCR test. The sensitivity and specificity of a positive PCR test in blood culture supernatant as against culture of Hib from any normally sterile site were 100 and 99%, respectively. Eleven children had positive Hib PCR tests on blood culture supernatants but were negative by culture. In one of these cases Hib was isolated from a lung aspirate and in two other patients H. influenzae strains other than Hib were obtained from the cerebrospinal fluid. Eight of these 11 children were in the control group. When the results of the PCR assay were used to determine vaccine efficacy, a value of 86% was obtained compared with a figure of 95% obtained when conventional culture techniques were used. An Hib PCR assay on blood culture supernatants proved to be sensitive and specific for the diagnosis of Hib disease in children. The distribution of PCR-positive, culture-negative cases between Hib-vaccinated and control groups paralleled that of culture-positive cases, suggesting that most of these children had been infected with Hib. A trial of a highly efficacious vaccine provides a novel way for evaluating new diagnostic tests for which there is no standard diagnostic test of 100% reliability.

Respiratory syncytial virus (RSV) is a well-recognized cause of lower respiratory tract infections in early childhood in industrialized countries, but less is known about RSV infection in developing countries. Four outbreaks of RSV infection that occurred between 1993 and 1996 in The Gambia, West Africa, were studied. RSV was sought by immunofluorescent staining of nasopharyngeal aspirate samples among young children who presented with respiratory infections at three hospitals in the Western Region of the country. Five hundred seventy-four children with RSV infection were identified. The median ages of children seen in 1993 through 1996 were 3, 7, 8 and 5 months, respectively. Sixty-two percent of children <6 months old were boys. Thirteen children (2.4%) had conditions considered to increase the risk of severe RSV infection. On physical examination crepitations were heard in 80% of the children admitted to hospital, whereas wheezes were heard in only 39%. Eighty (16%) children received oxygen because of hypoxemia. Nine of 255 blood cultures (3.5%) were positive: 4 Streptococcus pneumoniae; 2 Haemophilus influenzae type b; 2 Staphylococcus aureus; and 1 Enterobacter agglomerans. Thirteen children died (2.4%). During the 4 study years 90, 25, 75 and 95% of isolates typed were RSV Subgroup A, respectively. RSV is a significant cause of lower respiratory tract infection in young children in The Gambia, causing epidemics of bronchiolitis. It poses a significant burden on the health system, especially through the demand for supplementary oxygen. The clinical spectrum of RSV disease in The Gambia is similar to that seen in developed countries; concomitant bacterial infections are uncommon.

Certain chronic diseases increase risk for invasive pneumococcal disease (IPD) and are indications for receipt of 23-valent pneumococcal polysaccharide vaccine (PPV23). Since the pediatric introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, incidence of IPD among adults has declined. The relative magnitude of these indirect effects among persons with and without PPV23 indications is unknown. We evaluated IPD incidence among adults with and without PPV23 indications using population- and laboratory-based data collected during 1998-2009 and estimates of the denominator populations with PPV23 indications from the National Health Interview Survey. We compared rates before and after PCV7 use by age, race, PPV23 indication, and serotype. The proportion of adult IPD cases with PPV23 indications increased from 51% before to 61% after PCV7 introduction (P < .0001). PCV7-serotype IPD declined among all race, age, and PPV23 indication strata, ranging from 82% to 97%. Overall IPD rates declined in most strata, by up to 65%. However, incidence remained highest among adults with PPV23 indications compared with those without (34.9 vs 8.8 cases per 100 000 population, respectively). Apart from age ≥65 years, diabetes is now the most common indication for PPV23 (20% of all cases vs 10% of cases in 1998-1999). Although IPD rates have declined among adults, adults with underlying conditions remain at increased risk of IPD and comprise a larger proportion of adult IPD cases in 2009 compared with 2000. A continued increase in the prevalence of diabetes among US adults could lead to increased burden of pneumococcal disease.