Risk factors for human immunodeficiency virus infection in Ethiopian children with tuberculosis.

BACKGROUND: Separate risk factors for HIV infection and for tuberculosis (TB) are well-studied, but it is unclear whether these risk factors still apply in the new epidemiologic situation of dual infection. This study examines risk factors associated with seropositivity for HIV in Ethiopian children with clinical TB. METHODS: A prospective, controlled study of children with TB diagnosed in Addis Ababa from December 11, 1995, to January 28, 1997, in which HIV-positive children were compared with HIV-negative children with regard to sociodemographic background, previous medical history and vaccination. RESULTS: HIV prevalence among children with clinical TB was 11.2%. High educational status of mothers, low age, loss of one or two parents and earlier Calmette-Guérin bacillus (BCG) vaccination of the child were factors independently related to HIV infection. CONCLUSION: Factors associated with HIV infection among children with clinical TB include higher education of parents, higher income and better living conditions. The HIV epidemic might thus modify traditional risk factors for tuberculosis. It might also decrease the overall effect of BCG vaccination given that BCG did not provide protection in children infected with HIV. An expected increase of dually infected children who are younger, more in need of hospitalization and often lacking one or both parents will put an additional burden on the Ethiopian health care system.

Oxygen delivery to children with hypoxaemia in small hospitals in developing countries.

Oxygen administration is one of the most important modalities of therapy for a patient with hypoxaemia to prevent death. This review summarises the methods of oxygen delivery applicable in small hospitals in developing countries, and evaluates information about their safety and efficacy. The following criteria were considered: cost and availability, efficiency/oxygen concentration achieved, tolerability/comfort of the method, requirement of humidification, demand for nursing care, and safety of the method and complications. In summary, it is concluded that all low-flow methods, i.e., nasopharyngeal catheters, nasal catheters and prongs, are effective in the oxygenation of sick children with severe pneumonia or bronchiolitis. Nasal prongs are the safest method of oxygen delivery, but nasopharyngeal catheters and nasal catheters are more easily available and less expensive. However, if they are used, they need close supervision to avoid serious complications. Nasal prongs are the method of choice for oxygen delivery in small hospitals in developing countries.

Childhood meningitis in a tertiary hospital in Addis Ababa: clinical and epidemiological features.

Hospital based prospective study of 136 children aged 3 months to 12 years admitted as cases of meningitis between June 1996 and May 1997 was undertaken to assess the epidemiological features, evaluate the outcome and measure the duration of clinical improvement after initiation of treatment. Infants accounted for 79 (58%) of cases and 23 (68%) of deaths. Next to fever and vomiting, neurologic signs were the commonest presentation. H. influenzae, S. pneumoniae and N. meningitidis accounted for 90% of culture isolates. Delayed presentation, partial treatment, altered sensorium at admission and pneumococcal meningitis were risk factors for mortality. The morbidity and mortality rates were 25% of total cases each. The mean duration of fever was 3.7 (+/- 2.27) days after treatment. The morbidity and mortality rates are still high in this hospital.

Quality of hospital care for seriously ill children in less-developed countries.

BACKGROUND: Improving the quality of care for sick children referred to hospitals in less-developed countries may lead to better outcomes, including reduced mortality. Data are lacking, however, on the quality of priority screening (triage), emergency care, diagnosis, and inpatient treatment in these hospitals, and on aspects of these potential targets that would benefit most from interventions leading to improved health outcomes. METHODS: We did a qualitative study in 13 district hospitals and eight teaching hospitals in seven less-developed countries. Experienced paediatricians used a structured survey instrument to assess initial triage, emergency and inpatient care, staff knowledge and practices, and hospital support services. FINDINGS: Overall quality of care differed between countries and among hospitals and was generally better in teaching hospitals. 14 of 21 hospitals lacked an adequate system for triage. Initial patient assessment was often inadequate and treatment delayed. Most emergency treatment areas were poorly organised and lacked essential supplies; families were routinely required to buy emergency drugs before they could be given. Adverse factors in case management, including inadequate assessment, inappropriate treatment, and inadequate monitoring occurred in 76% of inpatient children. Most doctors in district hospitals, and nurses and medical assistants in teaching and district hospitals, had inadequate knowledge and reported practice for managing important childhood illnesses. INTERPRETATION: Strengthening care for sick children referred to hospital should focus on achievable objectives with the greatest potential benefit for health outcome. Possible targets for improvement include initial triage, emergency care, assessment, inpatient treatment, and monitoring. Priority targets for individual hospitals may be determined by assessing each hospital.

A controlled estimate of the risk of HIV infection in Ethiopian children with tuberculosis.

To quantify the risk of human immunodeficiency virus (HIV) infection in children with tuberculosis (TB) a hospital-based, 1-year prospective, case-control study was performed in Addis Ababa, Ethiopia. Children with TB were compared to a control group of children admitted for elective surgery. The control group was also compared to a recent census of the background population. The crude odds ratio for HIV infection was 8.6 (95 % CI 2.2-73). After adjustment for possible confounders in a multivariate regression model, the odds ratio for HIV infection in children with TB was found to be 12.7 (95% CI 2.9-55). Of several independent determinants of TB assessed in the study, this association was the strongest. Until HIV transmission has reached its peak, an increasing burden of dual infection among Ethiopian children is to be expected.

Evaluation of clinical pallor in the identification and treatment of children with moderate and severe anaemia.

BACKGROUND: Anaemia from malaria is a common problem in developing countries. Blood transfusion in developing countries is available in few hospitals. Children who are severely anaemic and may require urgent blood transfusion usually present to peripheral first-level health facilities from where they must be referred to hospitals. Since most peripheral facilities do not determine haemoglobin levels, the decision on referral has to be made on clinical grounds. OBJECTIVES: To evaluate the sensitivity and specificity of clinical pallor of the palms, nailbeds, conjunctivae, buccal mucosa or tongue against haemoglobin values and their reproducibility among health workers. METHODS: A total of 2540 children 2 months to 5 years of age presenting to a rural health centre in Ethiopia were enrolled. Clinically detected pallor was compared with measured blood haemoglobin concentrations. RESULTS: Any anaemia (haemoglobin < 11 g/dl) was found in 61% of the children. Severe anaemia (haemoglobin < 5 g/dl) was found in 4%. The presence of any pallor clinically correlated with moderate anaemia (haemoglobin level < 8 g/dl) could be detected with a sensitivity of 95% and a specificity of 64-68% when the palm and nailbeds were used and a sensitivity of 84% and a specificity of 81% when the conjunctivae were used. Severe anaemia was detected clinically as severe pallor in 50-56% of cases (with a specificity of 95-96%). Agreement between physicians was highest for conjunctivae and nailbed pallor (87%) and lowest for palm pallor (73%). Using multivariate analysis, identification of a systolic ejection murmur or altered sensorium, the presence of splenomegaly or malarial parasitaemia were independently predictive of severe and moderately severe anaemia. CONCLUSIONS: Moderate and severe anaemia can be identified clinically in most cases for treatment and referral purposes. A systolic ejection murmur, altered sensorium, the presence of splenomegaly or malarial parasitaemia may be used as additional tools in considering urgent referral for blood transfusion.

Oxygen therapy for children with acute respiratory infections in small hospitals.

Oxygen administration is one of the most important modalities of therapy for a patient with hypoxaemia to prevent death and disability from common conditions such as acute lower respiratory tract infections. Oxygen needs to be available at all times in hospitals, however, it is too expensive for many developing countries. There is little information for health professionals regarding indications for initiating oxygen therapy, selecting appropriate method of oxygen administration and deciding on the source for oxygen. A review of the literature using medline citations and cross references from published articles and other manuscripts was made. The review described the two main sources of oxygen for small hospital-cylinders and oxygen concentrators and their advantages and disadvantages. It also looked at the evidences for clinical indications to initiate and discontinue oxygen therapy. Studies on efficient and safe methods of administration of oxygen were reviewed as well. The review concluded that oxygen may be administered in children with cyanosis, chest indrawing, inability to drink or breastfeed, tachypnea with respiratory rate above 70/minute or in a child who develops restlessness and improves on oxygen. The initial capital cost of concentrators is high but the running cost is low and it does not require transport while oxygen cylinders are expensive to transport and need continuous refilling. The safest method of oxygen administration are the prongs followed by the nasal catheters.

Prevalence of bacterial pathogens in children with acute respiratory infection in Addis Ababa.

A study was conducted in the Ethio-Swedish Children's Hospital and different schools and kindergartens in Addis Ababa to determine the prevalence of bacterial agents that are associated with acute respiratory infection in children from 1998-1999. A total of 883 subjects were studied, out of which 77% were cases from the Ethio-Swedish Children's Hospital and 23% were controls from different schools and kindergartens. From each case and control throat and nasopharyngeal specimens were collected. Culture and different biochemical tests were used to isolate the potential bacterial pathogens. Clinical findings like cough, difficult breathing and fever were correlated with laboratory findings. S. pneumoniae and H. influenzae type b were the most commonly isolated bacteria in both throat and nasopharyngeal specimens; 74% and 70% in the cases and 2% and 5% in the control groups, respectively. This paper discusses the association between throat and nasopharyngeal carriership of bacteria and acute respiratory infection in children in Addis Ababa.

Helicobacter pylori infection in Ethiopian children: a cohort study.

Risk factors for infection with Helicobacter pylori (HP) were investigated in a cohort study of 121 seronegative children in Ethiopia aged 2-4 y, who had previously participated in a case-control study. Blood samples were drawn at inclusion in the cohort study and again after 12 and 30 months. At 12 months the parents were also interviewed about putative risk factors for infection, using a structured questionnaire. Analyses were made by comparing risk factors in seropositive and seronegative children. The seroconversion rate during the first year was 31% (27/87) and during the following 18 months 34% (17/50; corresponding to an annual incidence of 24%). After a period of 30 months, 58% (14/24) of the children who were 24-29 months old at inclusion in the study had seroconverted, compared with 40% (4/10) of those who were 30-35 months old, 73% (22/30) of those who were 36-41 months old and 31% (4/13) of those who were 42 months old or more. These results indicate that peak age for HP infection is below 6 y in this cohort in Ethiopia, and might also reflect a pattern of repeated seroconversion and sero-reversion in early childhood. Independent predictors of HP-seroconversion were the variables 'drinking-water', comparing water from a well with water from rivers or pipes (RR = 1.46, 95% CI 1.0-2.15) and 'antibiotic treatment' (RR = 1.84, 95% CI 1.16-2.92).

Etiology of pneumonia, sepsis and meningitis in infants younger than three months of age in Ethiopia.

METHODS: Within a multicenter study coordinated by WHO, an investigation of the etiologic agents of pneumonia, sepsis and meningitis was performed among infants younger than 3 months of age seen at the Ethio-Swedish Children's Hospital in Addis Ababa for a period of 2 years. Of the 816 infants enrolled 405 had clinical indications for investigation. RESULTS: There were a total of 41 isolates from blood cultures from 40 infants. The study showed that the traditionally known acute respiratory infection pathogen Streptococcus pneumoniae was most common in this extended neonatal age group, found in 10 of 41 blood isolates. Streptococcus pyogenes was a common pathogen in this setting (9 of 41 blood isolates), whereas Salmonella group B was found in 5 of 41 isolates. Streptococcus agalactiae, which is a common pathogen in developed countries, was absent. A study of the susceptibility pattern of these organisms suggests that a combination of ampicillin with an aminoglycoside is adequate for initial treatment of these serious bacterial infections, but the combination is not optimal for the treatment of Salmonella infections. Among 202 infants on whom immunofluorescent antibody studies for viruses were performed based on nasopharyngeal aspirates, respiratory syncytial virus was found in 57 (28%) infants, and Chlamydia trachomatis was isolated in 32 (15.8%) of 203 infants.

Clinical algorithm for malaria during low and high transmission seasons.

OBJECTIVES: To assess the proportion of children with febrile disease who suffer from malaria and to identify clinical signs and symptoms that predict malaria during low and high transmission seasons. STUDY DESIGN: 2490 children aged 2 to 59 months presenting to a health centre in rural Ethiopia with fever had their history documented and the following investigations: clinical examination, diagnosis, haemoglobin measurement, and a blood smear for malaria parasites. Clinical findings were related to the presence of malaria parasitaemia. RESULTS: Malaria contributed to 5.9% of all febrile cases from January to April and to 30.3% during the rest of the year. Prediction of malaria was improved by simple combinations of a few signs and symptoms. Fever with a history of previous malarial attack or absence of cough or a finding of pallor gave a sensitivity of 83% in the high risk season and 75% in the low risk season, with corresponding specificities of 51% and 60%; fever with a previous malaria attack or pallor or splenomegaly had sensitivities of 80% and 69% and specificities of 65% and 81% in high and low risk settings, respectively. CONCLUSION: Better clinical definitions are possible for low malaria settings when microscopic examination cannot be done. Health workers should be trained to detect pallor and splenomegaly because these two signs improve the specificity for malaria.

Pneumococcal and Haemophilus influenzae meningitis in a children's hospital in Ethiopia: serotypes and susceptibility patterns.

Streptococcus pneumoniae and Haemophilus influenzae are responsible for most pyogenic meningitis cases in children in Ethiopia. Resistance of S. pneumoniae and H. influenzae to penicillin and chloramphenicol respectively has been reported globally. Resistance has been related to specific serotypes of S. pneumoniae or to beta-lactamase-producing H. influenzae strains. This study describes the serotypes/ serogroups and susceptibility pattern of the two organisms causing meningitis in Ethiopian children. There were 120 cases of meningitis caused by S. pneumoniae (46) and H. influenzae (74) over a period of 3 years (1993-95). Nineteen children died from pneumococcal and 28 from haemophilus meningitis. Penicillin-resistant pneumococcal meningitis (4/8 = 50%) caused a greater mortality rate than penicillin-susceptible pneumococcal meningitis (15/38 = 39%). Common serotypes accounting for 76% of S. pneumoniae were type 14, 19F, 20, 1, 18 and 5; and serotypes 14, 19F and 7 (accounting for 17% of strains) showed intermediate resistance to penicillin G. 97% of the H. influenzae isolates were type b, and in only two cases beta-lactamase-producing. 72% of isolates of the S. pneumoniae we identified belong to serotypes preventable by a 9-valent vaccine. Our study highlights the possibility of resistant pyogenic meningitis in children in Ethiopia due to emerging resistant strains of S. pneumoniae and H. influenzae isolates.

Risk factors for infection with Helicobacter pylori--a study of children in rural Ethiopia.

The public health impact of Helicobacter pylori (HP) infection is gradually becoming obvious, the bacterium now being implicated as an aetiologic agent in a variety of gastric diseases. Transmission routes still remain unknown, although single risk factors, such as domestic crowding (especially bed-sharing) in childhood and low parental socioeconomic status, have been pointed out in studies from developed countries. In an attempt to study the risk factors in a developing country, we performed a case control study of 242 randomly selected children aged 2-4 y in Butajira rural area in Ethiopia. Blood samples were drawn and a questionnaire administered. The total prevalence of IgG antibody to HP among the children in the region was 48% (116/242). Several risk factors such as: crowding, water, animals, sanitation, etc. correlated strongly to seropositivity in a univariate analysis. After controlling for possible confounding, independent predictors of seropositivity were: living in town (OR = 2.15, p = 0.001), increasing age (OR = 1.71, p = 0.060), and being a Muslim (OR = 1.54, p = 0.005). It could not be excluded that a bad water supply in town could explain the difference in seroprevalence between town and village. These results indicate that, in developing countries, factors relating to community and religion might be as important risk factors for infection with HP in children as characteristics of the family or the home.

Pattern of resolution of tachypnoea and fever in childhood pneumonia.

Acute lower respiratory infections (ALRI) account for one fifth of deaths among children below five years of age and pneumonia is responsible for about 70% of all ALRI deaths. Interventions with antibiotics have shown reduction in pneumonia case-fatality rates. However, there is room for further reduction of deaths from pneumonia through improved monitoring and follow up system. We studied the pattern of resolution of tachypnoea and fever among 108 children who presented to our outpatient clinic with non-severe pneumonia and among 102 children who were admitted for severe pneumonia. We found that tachypnoea was present in 18% and 23% after 72 hours of initiation of antibiotics and fever resolved completely after 48 hours and 72 hours of initiation of therapy in non-severe cases of pneumonia among children two to 11 months and 12 to 59 months of age respectively. Conversely, among cases of severe pneumonia on day 5 of initiation of treatment, tachypnoea and fever were present in 65% and 51% respectively in children two to 11 months old and in 53% and 60% respectively in children 12 to 59 months old. Respiratory rate increased with increase in body temperature at an average rate of four breaths per minute for every 1 degree C rise. Our study suggests that body temperature and respiratory rate can be used to monitor the clinical course of non-severe pneumonia. Further research is needed to identify other clinical signs that will help the health worker to decide improvement in attacks of severe pneumonia.

Development of a clinical prediction model for an ordinal outcome: the World Health Organization Multicentre Study of Clinical Signs and Etiological agents of Pneumonia, Sepsis and Meningitis in Young Infants. WHO/ARI Young Infant Multicentre Study Group.

This paper describes the methodologies used to develop a prediction model to assist health workers in developing countries in facing one of the most difficult health problems in all parts of the world: the presentation of an acutely ill young infant. Statistical approaches for developing the clinical prediction model faced at least two major difficulties. First, the number of predictor variables, especially clinical signs and symptoms, is very large, necessitating the use of data reduction techniques that are blinded to the outcome. Second, there is no uniquely accepted continuous outcome measure or final binary diagnostic criterion. For example, the diagnosis of neonatal sepsis is ill-defined. Clinical decision makers must identify infants likely to have positive cultures as well as to grade the severity of illness. In the WHO/ARI Young Infant Multicentre Study we have found an ordinal outcome scale made up of a mixture of laboratory and diagnostic markers to have several clinical advantages as well as to increase the power of tests for risk factors. Such a mixed ordinal scale does present statistical challenges because it may violate constant slope assumptions of ordinal regression models. In this paper we develop and validate an ordinal predictive model after choosing a data reduction technique. We show how ordinality of the outcome is checked against each predictor. We describe new but simple techniques for graphically examining residuals from ordinal logistic models to detect problems with variable transformations as well as to detect non-proportional odds and other lack of fit. We examine an alternative type of ordinal logistic model, the continuation ratio model, to determine if it provides a better fit. We find that it does not but that this model is easily modified to allow the regression coefficients to vary with cut-offs of the response variable. Complex terms in this extended model are penalized to allow only as much complexity as the data will support. We approximate the extended continuation ratio model with a model with fewer terms to allow us to draw a nomogram for obtaining various predictions. The model is validated for calibration and discrimination using the bootstrap. We apply much of the modelling strategy described in Harrell, Lee and Mark (Statist. Med. 15, 361-387 (1998)) for survival analysis, adapting it to ordinal logistic regression and further emphasizing penalized maximum likelihood estimation and data reduction.

Comparison of nasal prongs with nasal catheters in the delivery of oxygen to children with hypoxia.

Efficient, inexpensive, and safe methods of oxygen delivery are needed for children with severe pneumonia in developing countries. The objective of this study was to estimate the frequency of complications when nasal catheters or nasal prongs are used to delivery oxygen. Ninety-nine children between 2 weeks and 5 years of age with hypoxia were randomized to receive oxygen via nasal catheter (49 children) or nasal prongs (50 children). There was no difference in the incidence of hypoxaemic episodes or in the oxygen flow rates between the two groups. Mucus production was more of a problem in the catheter group. Nasal blockage, intolerance to the method of administration, and nursing effort were generally higher amongst the catheter group, but these differences were not significant, except for nursing effort, when all age groups were analysed together.

Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children.

BACKGROUND: Pneumonia is the most important cause of morbidity and mortality in children aged under 5 years worldwide. Studies in developing countries have suggested an association between nutritional rickets and pneumonia. Since both nutritional rickets and pneumonia are common in Ethiopia, we did a case-control study to determine the role of nutritional rickets in the development of pneumonia. METHODS: Cases were children younger than 5 years admitted to the Ethio-Swedish Children's Hospital during a 5-year period with a diagnosis of pneumonia (n = 521), but data were incomplete for 21 of these and they were not included. Controls (n = 500) were matched for admission within 3 months of cases and age within 3 months and had no evidence of pneumonia. Nutritional, demographic, and clinical and radiographic data for rickets and pneumonia were collected. Matched odd ratios and logistic regression were used to test the significance of the association of rickets and pneumonia. FINDINGS: Rickets was present in 210 of 500 cases compared with 20 of 500 controls (odds ratio 22.11). There were significant differences between cases and controls for family size, birth order, crowding, and months of exclusive breastfeeding (p < 0.05). After correction for these confounding factors by logistic regression, there was still a 13-fold higher incidence of rickets among children with pneumonia than among controls (13.37 [95% CI 8.08-24.22], p < 0.001). INTERPRETATION: Vitamin D or calcium deficiency may be important predisposing factors for pneumonia in children aged under 5 years in developing countries. Efforts to prevent vitamin D deficiency or calcium supplementation may result in significant reductions in morbidity and mortality from pneumonia in these children.

A four-year cohort study of HIV seropositive Ethiopian infants and children: clinical course and disease patterns.

Sixty-two HIV positive infants who were admitted to the Missionaries of Charity Orphanage in Addis Ababa were followed From July 25, 1991 to July 30, 1995 for a total period of 4 years. Regular clinical examination and treatment by a paediatrician was being offered to these infants in addition to monitoring of their HIV serostatus every three months until the age of 18 months and every year after that. Among those aged above 18 months, 14 children were HIV sero-positive and alive and 4 children were HIV sero-positive but died. Thirty-three children had sero-reverted to negative. The mother-to-child transmission was crudely estimated at 29% to 47%. Among the clinical signs, generalized lymphadenopathy, hepatomegaly, splenomegaly, wasting, stunting and delayed motor development were found more commonly in the definitely HIV positive children. Upper respiratory tract infections, acute diarrhoea, pneumonia, pyogenic skin infections, sepsis and candidal infections were the commonest causes of illness. Comparison of the HIV positive with the HIV negative cases indicates that the risk is higher for the indefinitely HIV positive group for episodes of acute diarrhoea, pneumonia, sepsis and candidal infections.

PIP: Mother-to-child rates of HIV transmission are high in Africa. Findings are presented on 62 HIV-positive infants admitted to the Missionaries of Charity Orphanage, Addis Ababa, who were followed from July 25, 1991, to July 30, 1995. The infants were provided with regular clinical examination and treatment by a physician, as well as the monitoring of their HIV serostatus every 3 months until age 18 months and every year thereafter. Among infants over age 18 months, 14 were HIV seropositive and alive, and 4 were HIV positive, but died. 11 children were HIV positive and died before age 18 months and 33 seroreverted to HIV seronegative status. The level of mother-to-child HIV transmission was 29-47%. Among the clinical signs presented, generalized lymphadenopathy, hepatomegaly, splenomegaly, wasting, stunting, and delayed motor development were more often found in the definitely HIV-positive children. Upper respiratory tract infections, acute diarrhea, pneumonia, pyogenic skin infections, sepsis, and candidal infections were the most commonly seen illnesses.

Oxygen administration to hypoxic children in Ethiopia: a randomized controlled study comparing complications in the use of nasal prongs with nasopharyngeal catheters.

Oxygen administration is one of the most important therapeutic interventions for a child with severe acute lower respiratory tract infection (ALRI). Inexpensive and efficient methods of oxygen administration are highly desirable in hospitals in developing countries. The objectives of this study were to compare the frequency and nature of complications when nasopharyngeal catheters or nasal prongs are used to deliver oxygen. One hundred and twenty-one children between the ages of 2 weeks and 5 years with hypoxia due to ALRI were randomized to receive oxygen via a catheter (61 children) or via nasal prongs (60 children). The two groups were similar in terms of diagnoses, clinical severity, oxygen saturation on admission and case fatality rates. There was no difference in the incidence of hypoxaemic episodes between the two groups. The oxygen flow rates required on the day of admission for adequate oxygenation (SaO2 > 90%) ranged from 0.8 litres per minute to 1.2 litres per minute. The required oxygen flow rate decreased during the course of treatment. Mucus production was more of a problem in the catheter group, and nasal blockage, intolerance of the method of oxygen administration and nursing effort were generally higher amongst the catheter group, but none of these differences was significant. Ulceration or bleeding of the nose was significantly more common in the catheter group (19.7% vs 6.7%, p < 0.05). Abdominal distension and nasal perforation were not seen in either group. This study suggests that nasal prongs are safer, more comfortable and require less nursing expertise than nasopharyngeal catheters for administration of oxygen to children.