Causes of fever in Tanzanian adults attending outpatient clinics: a prospective cohort study.

OBJECTIVES: Exploring fever aetiologies improves patient management. Most febrile adults are outpatients, but all previous studies were conducted in inpatients. This study describes the spectrum of diseases in adults attending outpatient clinics in urban Tanzania. METHODS: We recruited consecutive adults with temperature ≥38°C in a prospective cohort study. We collected medical history and performed a clinical examination. We performed 27 364 microbiological diagnostic tests (rapid tests, serologies, cultures and molecular analyses) for a large range of pathogens on blood and nasopharyngeal samples. We based our diagnosis on predefined clinical and microbiological criteria. RESULTS: Of 519 individuals, 469 (89%) had a clinically or microbiologically documented infection and 128 (25%) were human immunodeficiency virus (HIV) -infected. We identified 643 diagnoses: 264 (41%) acute respiratory infections (36 (5.6%) pneumonia, 39 (6.1%) tuberculosis), 71 (11%) infections with another focus (31 (4.8%) gastrointestinal, 26 (4.0%) urogenital, 8 (1.2%) central nervous system) and 252 (39%) infections without focus (134 (21%) dengue, 30 (4.7%) malaria, 28 (4.4%) typhoid). Of the 519 individuals, 318 (61%), 179 (34%), 30 (6%) and 15 (3%), respectively, had a viral, bacterial, parasitic and fungal acute infection. HIV-infected individuals had more bacterial infections than HIV-negative (80/122 (66%) versus 100/391 (26%); p < 0.001). Patients with advanced HIV disease had a higher proportion of bacterial infections (55/76 (72%) if CD4 ≤200 cells/mm3 and 25/52 (48%) if CD4 >200 cells/mm3, p 0.02). CONCLUSIONS: Viral diseases caused most febrile episodes in adults attending outpatient clinics except in HIV-infected patients. HIV status and a low CD4 level strongly determined the need for antibiotics. Systematic HIV screening is essential to appropriately manage febrile patients.

Post-transfusion hepatitis C seroprevalence in Tanzanian children.

In Tanzania, children with malaria-associated anaemia are frequently given blood transfusions, and donor blood is not screened for hepatitis C virus (HCV) infection. To determine the seroprevalence of HCV infection in Tanzanian children previously transfused with blood, 184 children (92 transfused, 92 not transfused) aged between 15 and 59 months matched for age and sex were screened for HCV antibodies by the particle agglutination test using Serodia anti-HCV (Fujirebio Inc., Japan). The overall prevalence of HCV infection was 7.1% (13/184). HCV seropositivity was 5.4% (5/92) among children with a history of blood transfusion and 8.6% (8/92) among the non-transfused. There was no significant difference in the prevalence of HCV infection between transfused and non-transfused children. None of the factors investigated, such as gender, the nutrition and HIV serostatus of the children and the marital and education status of their mothers, was associated with HCV seropositivity. Further studies are recommended to identify the factors associated with HCV infection in Tanzanian children.

Prevalence of HIV type 1 infection, associated clinical features and mortality among hospitalized children in Dar es Salaam, Tanzania.

The aim of this study was to determine the prevalence of HIV-1 infection, the clinical spectrum of HIV-1-associated conditions and HIV-1-associated mortality among children hospitalized in the medical paediatric wards at Muhimbili Medical Centre (MMC), Dar es Salaam, Tanzania. All children admitted to the medical paediatric wards of MMC between August 1995 and January 1996 were eligible for the study. Testing for HIV antibodies was done using 2 consecutive enzyme linked immunosorbent assays (ELISAs). ELISA-reactive samples from children aged 18 months and below were further tested by a recently developed heat-denatured p24 antigen assay. The prevalence of HIV-1 infection among the 2015 children studied was 19.2%. When present for 14 days or more, fever, cough, diarrhoea, ear discharge, oral ulcers and skin rash were all significantly more common in HIV-1-infected than in HIV-uninfected children (p < 0.001). In the multivariate analysis cough, ear discharge, oropharyngeal ulcers and skin rash were found to be the most important symptoms. Clinical signs found to be significantly associated with HIV-1 infection in the univariate analysis were wasting, stunting, hair changes, oral thrush, oropharyngeal ulcers, lymphadenopathy, lung consolidation and lung crepitations (p < 0.001). In the multivariate analysis, oral thrush, lung crepitations, cervical lymphadenopathy, wasting and inguinal lymphadenopathy were found to be the most important signs. The 3 most common diagnoses in HIV-1-infected children were acute respiratory infection (ARI) (39.4%), malnutrition (38.1%) and tuberculosis (19.3%), while in HIV-uninfected children they were malaria (47.0%), ARI (25.0%) and malnutrition (16.1%). The mortality rate was 21.4% in HIV-1-infected children and 8.4% in HIV-uninfected children (p < 0.001). In conclusion, the prevalence of HIV-1 infection among hospitalized children at the main hospital in Dar es Salaam was high and associated with high mortality. Many symptoms and signs are indicative of HIV-1 infection, but appropriate laboratory testing is required for diagnosis.

Late postnatal transmission of human immunodeficiency virus type 1 infection from mothers to infants in Dar es Salaam, Tanzania.

OBJECTIVE: To study late postnatal transmission of human immunodeficiency virus type 1 in a cohort of children born to HIV-1-seropositive mothers who delivered at Muhimbili Medical Centre in Dar es Salaam, Tanzania. MATERIALS AND METHODS: Since 1991 a prospective cohort study of mother-to-child transmission of HIV-1 has been conducted at Muhimbili Medical Centre in Dar es Salaam. HIV-1-seropositive mothers and age-matched seronegative controls were recruited into the cohort at delivery together with their newborns. Diagnosis of HIV-1 infection in children was based on polymerase chain reaction, HIV-1 p24 antigen tests and HIV antibody tests. Late postnatal transmission was defined as HIV-1 infection occurring after 6 months of age in a child who was uninfected at 6 months of age and who had an HIV-1-seropositive mother. Children born to HIV-seronegative mothers were used as controls. Breast-feeding was universal in this cohort. CD4 and CD8 T lymphocytes were assayed by flow cytometry in the mothers. RESULTS: Among 139 children born to HIV-1-seropositive mothers and known to be HIV-uninfected at 6 months of age, 8 children became HIV-1-infected at the end of their first year of life or later. No conversions were observed in children younger than 11 months. The 8 conversions were observed during a follow-up covering 1555 child months between 6 and 27 months of age corresponding to a conversion rate of 6.2 per 100 child years. Among 260 children with HIV-seronegative mothers no child became HIV-infected during the follow-up. The percentage of CD4 T lymphocytes was similar in mothers with early and late transmission but was significantly lower in transmitting than in nontransmitting mothers. CONCLUSION: Because no HIV-1 infection occurred in children with HIV-seronegative mothers, we conclude that the observed infections at the end of the first year of life or later among children born to HIV-seropositive women were caused by late transmission from mother to child, most likely through breast-feeding.

Performance of a modified HIV-1 p24 antigen assay for early diagnosis of HIV-1 infection in infants and prediction of mother-to-infant transmission of HIV-1 in Dar es Salaam, Tanzania.

The aim of this study was to determine the utility of an amplified human immunodeficiency virus type 1 (HIV-1) p24 antigen (ag) assay using heated plasma or serum samples for the early diagnosis of HIV-1 infection in infants and for the prediction of the risk of mother-to-infant (MTI) transmission of HIV-1 in Dar es Salaam, Tanzania. The study included 125 samples from 76 infants positive for HIV-1 DNA by the polymerase chain reaction (PCR), 106 samples from 101 PCR-negative infants and 116 and 160 samples from seropositive and seronegative mothers, respectively. Samples were boiled to dissociate immune complexes and tested for HIV-1 p24 ag using a p24 ag amplification assay. Reactive samples were confirmed by a neutralization assay. Altogether, 123 of 125 samples from 76 PCR-positive infants were positive for p24 ag (sensitivity = 98.7%). HIV-1 p24 ag was found in all 18 samples collected at 1-8 weeks, in 35 of 36 samples collected at 9-26 weeks, in all 40 samples collected at 27-52 weeks, and in 30 of 31 samples collected > 52 weeks after birth. Detection of HIV-1 p24 ag was significantly more common in transmitting mothers (12 of 29, 41.4%) than in nontransmitting mothers (nine of 87, 10.3%) (p < 0.001). Among mothers with p24 antigenemia, the vertical transmission rate was significantly higher (12 of 21, 57%) than in mothers without p24 antigenemia (17 of 95, 18%) (p < 0.001). All samples from 101 PCR-negative children and 160 seronegative mothers were negative for p24 ag (specificity = 100%). We conclude that using heated plasma or serum increases the sensitivity of the p24 ag assay significantly. This modified simple test may be sufficient for the early diagnosis of HIV-1 infection in infants in settings with limited laboratory facilities. It is also useful for prediction of the risk of MTI transmission of HIV-1.

Early diagnosis of HIV-1 infection in infants in Dar es Salaam, Tanzania.

OBJECTIVES: To evaluate two simple methods, an immune complex dissociation (ICD) p24 antigen assay and an HIV-1-specific IgA antibody assay, for the early demonstration of HIV-1 infection in infants, using the polymerase chain reaction (PCR) as the reference method. DESIGN AND SETTING: Group A: 143 HIV-1-seropositive and 134 -seronegative mothers and their infants were recruited at delivery at the main hospital in Dar es Salaam, Tanzania. Group B: 26 HIV-PCR-positive hospitalized children in Dar es Salaam, 3-15 months old and suspected of having an HIV-related illness. METHODS: Blood samples were taken from mothers and infants in group A at intervals during the children's first 24 months and once from each of the children in group B. Peripheral blood mononuclear cells were tested by nested PCR for viral DNA. Plasma samples were tested by the Coulter p24 antigen (ag) enzyme-linked immunosorbent assay (ELISA) after acid dissociation of p24 antigen-antibody complexes. All p24-ag-positive reactions were confirmed by neutralization. Viral specific IgA antibodies were demonstrated in plasma by a modified ELISA. RESULTS: One hundred and sixty-three of 174 samples from seropositive mothers were PCR-positive (sensitivity 93.7%) and 612 of 614 samples from seronegative mothers and children of seronegative mothers were PCR-negative (specificity 99.7%). Twenty-nine of 145 (20.0%) children born to seropositive mothers were positive by PCR when tested during the first year of life. By use of both the p24 ag ELISA and the IgA antibody ELISA in combination, HIV-1 infection was detected in 9 of 17 (53%) PCR-positive children 1-8 weeks old, in 15 of 18 (83%) PCR-positive children 9-26 weeks old and in 23 of 24 (96%) PCR-positive children 27-52 weeks old. The specificities of the p24 ag ELISA and the IgA ELISA were 100%. CONCLUSIONS: The p24 ag assay and the IgA antibody ELISA, when used in combination, had a high sensitivity and specificity for detection of HIV-1 infection in infants, especially in those above the age of 6 months.

Predictive markers for mother-to-child transmission of HIV-1 in Dar es Salaam, Tanzania.

The aim of this study was to determine immunological factors associated with increased risk of mother-to-child transmission of HIV-1 that could be used as predictive markers in Tanzanian women. One hundred and thirty-eight HIV-1-seropositive and 117-seronegative mothers and their newborns were recruited at delivery and followed up at Muhimbili Medical Centre in Dar es Salaam, Tanzania. Blood specimens from the mothers were analyzed for HIV-1 p24 antigen, beta 2-microglobulin (B2M), T-lymphocyte subsets, and presence of viral DNA in blood mononuclear cells by the polymerase chain reaction (PCR). Among 138 seropositive mothers, 30 (21.7%) had transmitted HIV-1 to their children, as shown by a positive PCR in the child. The vertical transmission rate was significantly higher in women with a percentage of CD4 lymphocytes < or = 20 (eight of 24, 33%) or a level of B2M > or = 2 mg/L (21 of 62, 34%) than in women with a higher percentage of CD4 lymphocytes (10 of 73, 14%) or a lower level of B2M (eight of 57, 14%) (p = 0.034 and 0.018, respectively). In eight of 18 (44%) transmitting mothers the percentage of CD4 lymphocytes was < or = 20, and in 21 of 29 (72%) transmitting mothers the B2M level was > or = 2 mg/L. In women with both a low percentage of CD4 lymphocytes (< or = 20) and a high level of B2M (> or = 2 mg/L), the vertical transmission rate was 54%.(ABSTRACT TRUNCATED AT 250 WORDS)