Vaccine safety surveillance in Kenya using GAIA standards: A feasibility assessment of existing national and subnational research and program systems.

BACKGROUND: Active surveillance systems for monitoring vaccine safety among pregnant women address some of the limitations of a current passive surveillance approach utilized in low- and middle-income countries (LMIC). However, few active surveillance systems in LMIC exist. Our study assessed the feasibility of utilizing three existing data collection systems in Kenya for active surveillance of maternal immunization and to assess the applicability of Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions that were initially developed for clinical trials within these systems. METHODS: We assessed applicability of GAIA case definition for maternal Tetanus Toxoid exposure, stillbirth, low birth weight, small for gestational age, Neonatal Invasive Blood Stream Infection (NIBSI), prematurity and neonatal death in two routine web-based health information systems (Kenya EMR and DHIS-2), and a web-based population-based pregnancy research platform (ANCOV1) in Kenya. RESULTS: All three HIS were capable of reporting selected outcomes to varying degrees of GAIA certainty. The ANCOV platform was the most robust in collecting and collating clinical data for effective maternal pharmacovigilance. The utilization of facility- and district-aggregated data limits the usefulness of DHIS-2 in pharmacovigilance as currently operationalized. While the Kenya EMR contained individual level data and meets the key considerations for effective pharmacovigilance, it was used primarily for HIV care and treatment records in a small proportion of health facilities and would require additional resources to expand to all antenatal care facilities and to link maternal and infant records. DISCUSSION: Population-based research studies may offer a responsive short-term option for implementing maternal vaccine pharmacovigilance in LMICs. However, the foundation exists for long-term capacity building within the national health electronic data systems to provide this critical service as well as ensure participation of the country in international studies on maternal vaccine safety.

Country differences and determinants of yield in programmatic migrant TB screening in four European countries.

INTRODUCTION The WHO End TB Strategy emphasises early diagnosis and screening of TB in high-risk groups, including migrants. We analysed TB yield data from four large migrant TB screening programmes to inform TB policy.METHODS We pooled routinely collected individual TB screening episode data from Italy, the Netherlands, Sweden and the United Kingdom under the European Union Commission E-DETECT.TB grant, described characteristics of the screened population, and analysed TB case yield.RESULTS We collected data on 2,302,260 screening episodes among 2,107,016 migrants, mostly young adults aged 18-44 years (77.8%) from Asia (78%) and Africa (18%). There were 1,658 TB cases detected through screening, with substantial yield variation (per 100,000): 201.1 for Sweden (95% confidence intervals CI 111.4-362.7), 68.9 (95% CI 65.4-72.7) for the United Kingdom, 83.2 (95% CI 73.3-94.4) for the Netherlands and 653.6 (95% CI 445.4-958.2) in Italy. Most TB cases were notified among migrants from Asia (n = 1,206, 75/100,000) or Africa (n = 370, 76.4/100,000), and among asylum seekers (n = 174, 131.5/100,000), migrants to the Netherlands (n = 101, 61.9/100,000) and settlement visa migrants to the United Kingdom (n = 590, 120.3/100,000).CONCLUSIONS We found considerable variations in yield across programmes, types of migrants and country of origin. These variations may be partly explained by differences in migration patterns and programmatic characteristics.

Longitudinal evaluation of severely anemic children in Kenya: the effect of transfusion on mortality and hematologic recovery.

OBJECTIVE: To determine the effect of transfusion on hematologic recovery and mortality among severely anemic children during and after hospitalization in rural Kenya. DESIGN: Prospective cohort. METHODS: We collected clinical and laboratory information on all severely anemic children (hemoglobin < 5.0 g/dl) and a 33% sample of children with hemoglobin < or = 5.0 g/dl who were admitted to the pediatric ward of a rural Kenyan hospital during a 6 month study period. Children were followed during hospitalization and at 4 and 8 weeks after admission. RESULTS: Overall, 303 (25%) of the 1223 hospitalized children had hemoglobin < 5.0 g/dl, 30% of whom died during the study period. Severely anemic children who were transfused had a higher mean hemoglobin level at discharge (9.0 g/dl) than non-transfused children (5.8 g/dl, P < 0.001) and maintained a higher mean hemoglobin during the 8-week follow-up period. However, the presence of malaria parasitemia on follow-up negated the benefit of transfusion on hematologic recovery at both 4- and 8-week visits (longitudinal linear model, least square means, P > 0.05). Transfusion was associated with improved survival among children with respiratory distress who received transfusions within the first 2 days of hospitalization. CONCLUSIONS: The use of transfusion can be improved by targeting use of blood to severely anemic children with cardiorespiratory compromise, improving immediate availability of blood, and treating severely anemic children with effective antimalarial therapy.

PIP: The effect of blood transfusion on hematologic recovery and mortality both during and after hospitalization was investigated in a survey of children admitted to Siaya District Hospital (Kenya) in a 6-month period in 1991 with hemoglobin under 5.0 g/dl (n = 303) or 5.0 g/dl and above (n = 303). Children with hemoglobin under 5.0 g/dl (severe anemia) were younger and more likely to have malaria parasitemia and respiratory compromise than controls. 88 severely anemic children (30%) died during the study period. Severely anemic children who were transfused had a higher mean hemoglobin level at discharge (9.0 g/dl) than nontransfused children (5.8 g/dl) and maintained a higher mean hemoglobin in the 8-week post-discharge follow-up period. 15% of transfused and 17% of nontransfused children died after hospital discharge. Transfusion was associated with significantly improved survival among children with respiratory distress who were transfused within 2 days of hospital admission. However, the presence of malaria or parasitemia at follow-up negated the benefit of transfusion on hematologic recovery. These findings suggest that the effectiveness of transfusion can be enhanced by targeting severely anemic children with cardiorespiratory compromise, improving immediate access to blood, and effective antimalarial therapy. In addition, more information is needed on the causes of death among anemic children and the prevention of severe anemia.

Childhood mortality during and after hospitalization in western Kenya: effect of malaria treatment regimens.

Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Increasingly, the contribution of P. falciparum-associated severe anemia to pediatric mortality is being recognized while the impact of chloroquine resistance on mortality has not been evaluated. To address the issues of pediatric mortality, causes of death among hospitalized children less than five years of age in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were conducted to determine the child's clinical status posthospitalization. Of the 1,223 children admitted to Siaya District Hospital from March to September 1991, 293 (24%) were severely anemic (hemoglobin level < 5.0 g/dL). There were 265 (22%) deaths; 121 (10%) occurred in-hospital and 144 (13%) occurred out-of-hospital within eight weeks after admission; 32% of all deaths were associated with malaria. Treatment for malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens (pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for five days). The risk of dying was associated with younger age (P < 0.0001) and severe anemia (relative risk [RR] = 1.52, 95% confidence interval [CI] = 1.22, 1.90), and was decreased by treatment with an effective antimalarial drug (RR = 0.33, 95% CI = 0.19, 0.65). Effective drug therapy for P. falciparum with regimens that are parasitocidal in areas with a high prevalence of severe anemia and chloroquine resistance can significantly improve the survival of children in Africa.

PIP: Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Causes of death among hospitalized children less than age 5 years in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were then conducted to determine the child's clinical status posthospitalization. 293 of the 1223 children admitted to Siaya District Hospital during March-September 1991 were severely anemic. 265 children died; 32% of the deaths were associated with malaria. 121 of the deaths occurred in-hospital and 144 out-of-hospital within 8 weeks after admission. The treatment of malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens of pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for 5 days. The risk of dying was associated with younger age and severe anemia, and was decreased by treatment with an effective antimalarial drug.

Field detection of sulfonamides in urine: the development of a new and sensitive test.

A new, field-adapted, colorimetric method for detecting sulfonamide drugs in urine is described. The method uses the color reagent, p-dimethylaminocinnamaldehyde, and has a detection limit of about 1 microgram/ml. Analysis of 35 samples collected in the field, comparing results obtained with the colorimetric field test with those obtained using high-performance liquid chromatography, indicated a calculated sensitivity value of 94% and a specificity value of 94% for the test to detect the presence of sulfonamides. The field test can be modified to allow quantitation of sulfonamides in urine in field situations, using a hand-held, portable photometer for measuring the absorbance of test solutions. For this test, calculated coefficients of variation for day to day reproducibility were < or = 5% at sulfonamide concentrations > or = 3 micrograms/ml. This new test for detecting the presence of sulfonamides in urine is more sensitive and reliable than the presently used Bratton-Marshall test.

Plasmodium falciparum circumsporozoite vaccine immunogenicity and efficacy trial with natural challenge quantitation in an area of endemic human malaria of Kenya.

It has been hypothesized that antibody induced by Plasmodium falciparum circumsporozoite protein vaccine would be effective against endemic human malaria. In a malaria endemic region of Kenya, 76 volunteers, in 38 pairs sleeping adjacently, were immunized with subunit circumsporozoite protein Asn-Ala-Asn-Pro tetrapeptide repeat-pseudomonas toxin A, or hepatitis B vaccine. After quinine and doxcycycline, volunteers were followed for illness daily, parasitemia weekly, antibody, T-lymphocyte responses, and treated if indicated. Anopheles mosquitoes resting in houses were collected, and tested for P. falciparum antigen, or dissected for sporozoites and tested for blood meal ABO type and P. falciparum antigen. Vaccine was safe, with side-effects similar in both groups, and immunogenic, engendering IgG antibody as high as 600 micrograms ml-1, but did not increase the proportion of volunteers with T-lymphocyte responses. Estimation of P. falciparum challenge averaged 0.194 potentially infective Anopheles bites/volunteer/ day. Mosquito blood meals showed no difference in biting intensity between vaccine and control groups. Both groups had similar malaria-free survival curves, cumulative positive blood slides, cumulative parasites mm-3, and numbers of parasites mm-3 on first positive blood slide, during three post-vaccination observation periods. Every volunteer had P. falciparum parastemia at least once. Vaccinees had 82% and controls 89% incidences of symptomatic parasitemia (P = 0.514, efficacy 9%, statistical power 95% probability of efficacy < 50%). Vaccine-induced anti-sporozoite antibody was not protective in this study. Within designed statistical precisions the present study is in agreement with efficacy studies in Colombia, Venezuela and Tanzania.

Acute phase protein concentrations predict parasite clearance rate during therapy for visceral leishmaniasis.

Visceral leishmaniasis (VL) remains a major health problem in Kenya and other parts of Africa, Central America and Asia. Currently, splenic aspirate smear and culture are the standard methods of monitoring therapy and relapse. Acute phase reactant markers, C-reactive protein (CRP), serum amyloid A protein (SAA) and alpha 1-acid glycoprotein (AGP) were evaluated as less invasive techniques for monitoring therapy in 59 patients with VL before, during and after therapy. CRP, SAA and AGP were elevated in VL patients at admission and the concentrations decreased with effective therapy to reach normal levels by the end of therapy (SAA and AGP) or by 3 months follow-up (CRP). Two groups of patients were selected on the basis of rate of parasite clearance. The acute phase protein concentrations were significantly raised in those slower to clear parasites. Analysis of sensitivity and specificity of acute phase proteins as predictors of parasite clearance suggested that they might represent useful non-invasive markers for monitoring disease activity, response to therapy and relapse in VL.

Problems in the treatment of kala-azar: case report.

Frequent relapses after treatment for visceral leishmaniasis and apparent parasitological cure is not commonly reported. Seven year old boy who relapsed four times with clinical and parasitological evidence of the disease at each two months follow-up period is presented. He had Leishimania donovani Kenya strain. After treatment, review would be after two months, six months and twelve months periods. Splenic aspirates were routinely done weekly and on the last day of each treatment. The drugs administered for varying periods included intravenous sodium stibogluconate 20 mg/kg daily, P20 in combination with allopurinol 21 mg/kg three times daily, and Pentamidine 4 mg/kg three times weekly and antituberculous drugs. The presence of abundant extra cellular leishmania donovani bodies in the bone marrow and possible pulmonary tuberculosis might have precipitated the frequent relapses. It is not clear which of the drugs effected the cure. It was observed that inspite of prolonged antileishmanial drug administration no side effects were noted.

Phase 2 efficacy trial of an oral 8-aminoquinoline (WR6026) for treatment of visceral leishmaniasis.

The efficacy of an oral 8-aminoquinoline (8-[[6-(diethylamino)hexyl]amino]-6-methoxy-4-methylquinoline) (WR6026) in the treatment of 16 patients with kala azar was evaluated. The first 8 patients received therapy for 2 weeks at a dosage of 0.75-1.00 mg/(kg.d); 1 patient was cured, and in regard to the other 7, a 1-logarithm decrease in the number of splenic parasites and clinical improvement were noted. The next 8 patients received therapy for 4 weeks at the same daily dosage (1 mg/[kg.d]); 4 were cured, and for the other 4, 1- to 2-log decreases in the number of parasites and clinical improvement (in regard to weight, liver and spleen size, hemoglobin level, and leukocyte count) were noted. The therapy was associated with minimal toxicity; adverse effects included gastrointestinal distress, headache, and methemoglobinemia. The fact that one-half of the patients were cured indicates that future trials with longer regimens and higher dosages are warranted and should include patients for whom existing treatment methods have failed.

Relationship between direct agglutination test and splenic aspirate smear parasite load in visceral leishmaniasis at Baringo District, Kenya.

Direct agglutination test was carried out in Baringo District on 100 persons presenting with signs and symptoms suggestive of visceral leishmaniasis. Splenic aspirate smears and cultures were done on these 100 persons in order to parasitologically confirm the findings of the direct agglutination test. It was found that the direct agglutination test positively detected all 79 (79%) patients parasitologically confirmed to have visceral leishmaniasis. Irrespective of the splenic aspirate smear parasite rate, whether 1+ or 6+ on a logarithmic scale, direct agglutination test was positive. There were 21% false positives, two of whom had Schistosoma mansoni in their stools. It was not immediately known about the cause of the other false positives. It was concluded that the direct agglutination test is a good provisional serodiagnostic test for visceral leishmaniasis and should be considered for wider field application.

A comparison of amodiaquine and chloroquine in the treatment therapy of falciparum malaria in Kenya.

During June to August 1989, 158 symptomatic outpatients with P. falciparum malaria were randomly treated with either amodiaquine or chloroquine 25 mg/kg, divided over three days. Amodiaquine (Camoquin, Parke-Davis) was significantly more effective in terms of the rate of parasite clearance, 2.4 versus 3.1 days; parasite clearance day 7; 87% versus 41%; and clinical amelioration, 98% versus 68%. Moreover, this study demonstrates the lack of therapeutic toxicity of amodiaquine. Globally, tolerance was better with amodiaquine than with chloroquine; in particular, cutaneous side effects were less frequent with amodiaquine. There was no evidence of granulocyte or gross hepatic toxicity. These results suggest that WHO recommendations concerning amodiaquine should be questioned. In view of its low cost, demonstrated efficacy and lack of proven therapeutic toxicity, amodiaquine should be considered as a viable replacement for chloroquine in areas with high levels of clinical chloroquine failure.

Anaemia, blood transfusion practices, HIV and mortality among women of reproductive age in western Kenya.

Severe anaemia among women in sub-Saharan Africa is frequently treated with blood transfusions. The risk of transmission of human immunodeficiency virus (HIV) through blood products has led to a re-evaluation of the indications for transfusions. Prospective surveillance of women admitted to a district hospital in western Kenya was conducted from 1 December 1990 to 31 July 1991, for haemoglobin (Hb) transfusion status, and outcome. Of the 2986 enrolled women (mean Hb 10.4 g/dL, SD +/- 2.6, median age 24.4 years), 6% were severely anaemic (Hb < 6.0 g/dL). Severe anaemia was associated with a higher mortality rate (10.7% vs. 1.4%, odds ratio (OR) = 8.2, 95% confidence interval (CI) 2.6, 34.2) compared with women with Hb > or = 6.0 g/dL. Decreased mortality rates in hospital were observed with increasing Hb values (OR = 0.43, 95% CI 0.19, 0.98), but blood transfusions did not improve survival in hospital (OR = 1.56, 95% CI 0.22, 11.03). The attributable mortality due to HIV infection and severe anaemia was 75% and 31%, respectively. Maternal/child health care services must include prevention strategies for HIV transmission and the prevention, recognition, and treatment of severe anaemia.

PIP: This paper reports the findings of an evaluation of Western Kenyan blood transfusion practices used with a cohort of severely anemic women of child-bearing age. The potential of receiving HIV-infected blood puts these women at a definite health risk. Characteristics of severely anemic women included being older (P = 0.03, Wilcoxon rank sum test), lower likelihood of being pregnant when admitted to hospital (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.35-0.81), and greater likelihood of being HIV seropositive (OR = 2.92; 95% CI, 1.52-5.60) when compared to non-anemic women. Severely anemic women were also less likely to have malaria (OR = 0.58; 95% CI, 0.35-0.96). Women who had a transfusion ordered had a higher mortality rate than women who did not (25/240, 10.4% vs. 18/933, 1.9%)(OR = 5.91; 95% CI, 3.04-11.53). In this study, positive benefits were restricted to women who had a transfusion only for them. These were the severely anemic women. The attributed mortality caused by HIV infection and severe anemia was 75% and 31%, respectively. Detection of HIV infected blood is very critical. Prevention of anemia is considered more important than transfusing concerns. Preventing the need for transfusions would reduce the HIV transmission risk from potentially infectious blood during transfusion.

The effect of human immunodeficiency virus type-1 on the infectiousness of tuberculosis.

SETTING: Developing country tertiary referral hospital plus catchment community. OBJECTIVE: To determine the infectiousness of culture-confirmed pulmonary tuberculosis in patients infected with Human Immunodeficiency Virus type-1 (HIV-1). DESIGN: Comparison of the incidence of tuberculosis and the prevalence of tuberculin skin test positivity among the household contacts of both HIV-1 positive and negative cases with pulmonary tuberculosis. RESULTS: Of 255 contacts of HIV-1 negative index cases, 2 were HIV-1 positive and of 102 contacts of HIV-1 positive index cases, 14 were HIV-1 positive (odds ratio (OR) = 20.0 95% Confidence Interval (CI) 4.4-193). 21 cases of tuberculosis were diagnosed among contacts, of whom 3 were HIV-1 positive. The overall unadjusted OR for tuberculosis among contacts of HIV-1 positive index cases was 1.6 (95% CI 0.6-4.3) compared to contacts of HIV-1 negative index cases. Amongst HIV-1 negative contacts alone the OR was 1.5 (95% CI 0.4-4.4). In this group the best predictors of tuberculosis among contacts were female sex of the index case (OR = 3.4 95% CI 1.1-12), sharing the same bed as the index case (OR = 2.6 95% CI 0.9-7.4), and contact's age less than 5 years (OR = 3.3 95% CI 1.1-9.5). HIV-1 positive contacts were more likely to develop tuberculosis than HIV-1 negative contacts (OR = 4.1 95% CI 0.7-17). Tuberculin skin test positivity rates were the same among the HIV-1 negative contacts of HIV-1 positive and negative index cases (OR = 1.1 CI 0.7-1.6). CONCLUSIONS: HIV-1 associated pulmonary tuberculosis is not more infectious than tuberculosis alone. The presence of HIV-1 in a community does not mandate a change in the management of contacts of patients with pulmonary tuberculosis.

PIP: Using data on tuberculosis (TB) index cases over age 15 years seen at the Infectious Diseases Hospital in Nairobi and the Ngaira Avenue Chest Clinic over September 1, 1989 and October 10, 1990, and their contacts, the authors determined the infectiousness of culture-confirmed pulmonary TB in patients infected with HIV-1. Comparing the incidence of TB and the prevalence of tuberculin skin test positivity among the household contacts of HIV-1 positive and negative cases with pulmonary TB found HIV-1-associated pulmonary TB to be no more infectious than TB alone. The presence of HIV-1 in a community therefore does not require a change in the management of contacts of patients with pulmonary TB.

Human cutaneous leishmaniasis caused by Leishmania donovani s.l. in Kenya.

Our laboratory is characterizing Leishmania stabilates and isolates from active leishmaniasis cases. Smears and cultures from aspirates made on different dates from a single lesion on the bridge of the nose of an 18 years old Kenyan male from Nyandarua District contained Leishmania. The isolates, NLB-271 and NLB-271-IA, were characterized by cellulose acetate electrophoresis (CAE) using 20 enzyme systems and by Southern analysis using 2 deoxyribonucleic acid (DNA) probes (pDK10 and pDK20) from a Dakar strain of L. major (MHOM/SN/00/DK1) and a third probe, p7-059 from L. infantum strain ITMAP-263. Digestion of the two Leishmania DNAs with endonucleases HindIII and PstI, followed by hybridization with the 3 probes, revealed DNA fragment banding patterns indistinguishable from those of the L. donovani species complex. The CAE isoenzyme profiles of these 2 Kenyan isolates were indistinguishable from those of Kenyan L. donovani strains we designated as zymodeme Z6. Excluding post-kala-azar dermal leishmaniasis, this constitutes the first human case of cutaneous leishmaniasis caused by L. donovani s.l. in Kenya. Previously, cutaneous leishmaniasis cases in Kenya have been due to L. aethiopica, L. major and L. tropica only.

Factors affecting exflagellation of in vitro-cultivated Plasmodium falciparum gametocytes.

The environment of Plasmodium falciparum gametocytes changes when they make the transition from the vertebrate to the invertebrate host. Gametocytes of this species cultivated in vitro were used to evaluate the effect of serum, pH, pCO2 tension, bicarbonate ion, and temperature on gamete formation. Temperature was the only factor responsible for keeping P. falciparum gametocytes in the inactivated state. Mature gametocytes held at temperatures above 30 degrees C remained quiescent in 10% serum, even at low ambient pCO2 tension, alkaline pH, and in the presence of 25 mM bicarbonate ion. When the temperature of the medium was allowed to drop below 30 degrees C, gametocytes emerged from the red blood cells and microgametocytes consistently exflagellated at pH 7.4, even in the absence of bicarbonate ion. With regard to bicarbonate ion, exflagellation in P. falciparum is similar to P. berghei and different from P. gallinaceum gametocytes, which have an obligate requirement for bicarbonate ion.

Field application of an ELISA using redefined Leishmania antigens for the detection of visceral leishmaniasis.

Two soluble antigens from Leishmania donovani of 116 kDa and 70 kDa molecular mass, and a soluble mixture of crude antigens, were used in an enzyme-linked immunosorbent assay (ELISA) for the detection of visceral leishmaniasis (VL) in the field, and compared with the direct agglutination test (DAT). The tests were carried out on 8 VL patients, 34 normal individuals from an area endemic for the disease, and 68 former visceral leishmaniasis patients 1-5 years after treatment. The 70 kDa ELISA and the DAT had a sensitivity and specificity of 100% (95% confidence interval 63-100%), while the 116 kDa ELISA and the soluble crude antigen ELISA were 37.5% (9-76%) and 50% (16-84%) sensitive, respectively. When using ELISA (116 kDa or 70 kDa), 68-69% of sera tested 1-2 years, and 92-94% of sera tested 5 years, after treatment were negative. In contrast, when DAT or ELISA with crude antigen were used, the negativity rate was 31% 1-2 years, and 53% 5 years, after treatment. DAT was therefore not an accurate test for diagnosis in the field. The use of the 70 kDa antigen in ELISA was an accurate alternative to DAT in the detection of VL.

Blood transfusion practices and blood-banking services in a Kenyan hospital.

OBJECTIVES: To identify ways to improve the operation of blood-screening programs and to decrease the inappropriate use of blood by evaluating blood-transfusion practices and blood-banking services in a Kenyan hospital. DESIGN: Prospective cohort. SETTING: The study was conducted in a rural district hospital in western Kenya between September 1990 and July 1991. METHODS: We collected data on all transfusion requests (blood donation, grouping, HIV screening) and blood recipients (age, sex, diagnosis, and for a 3-month period on the pediatric, maternity, and female wards, admission hemoglobin and outcome). RESULTS: During the 11-month study period, 799 patients received 927 transfusions: 67% were children < 15 years of age, 27% were adult women and 6% were adult men. Transfusions were often delayed due to reliance on patient-recruited donors. Patients who received blood donated on or after the date of request waited longer for transfusion (median, 3 days) than patients who received blood that had been banked and screened before the request (median, 1 day). Patient-recruited donors had a higher HIV-seropositivity rate than volunteer donors (13.4 and 4.6%, respectively; chi 2 test, P < 0.001). Overall, 47% of pediatric transfusions were classified as inappropriate: 23% did not meet the criteria of having hemoglobin < 5.0 g/dl and clinical evidence of respiratory distress, and 27% were transfused 2 or more days after requested. Among adults, 68% received one unit of blood or less. CONCLUSIONS: Improved laboratory services, reduction of unnecessary transfusions, and increased recruitment of volunteer donors are critical for improving the appropriate and timely use of blood and reducing transfusion-associated HIV transmission.

PIP: Between September 1990 and July 1991, health workers and/or laboratory personnel at Siaya District Hospital in rural western Kenya (about 60 km northwest of Kisumu) gathered data on 799 patients who received 927 blood transfusions, including blood donation, grouping, and HIV screening. Most blood recipients were children (under 15 years old). Only 6% of all recipients were men. Just 30% of transfusions were performed the day of request. Blood donors recruited when it was most needed for survival. Their blood tended to be available 3 days after the request. The volunteer donated blood tended to be available for transfusion the day of request, however, because it had already been banked and screened. Patient-recruited donors were more likely to be HIV infected than volunteer donors (13.4% vs. 4.6%; relative risk = 2.91; p .001). 47% of the pediatric transfusions should not have taken place because 23% of these children did not suffer respiratory distress and their hemoglobin levels were greater than t gm/dl and because 27% received the transfusion 2 days after the day of request. 90% of all adult transfusions were inappropriate (i.e., transfusion of no more than 1 unit of blood or received the transfusion 2 days after the day of request). 30% of blood units that had been banked and screened at the time of request were not transfused until at least 2 days after request. These findings identified those areas which must be targeted to improve the appropriate and timely use of blood and reducing transfusion-induced HIV transmission: reduction of inappropriate transfusions, increased recruitment of volunteer donors, and improved laboratory services.

Immunochemotherapy for visceral leishmaniasis: a controlled pilot trial of antimony versus antimony plus interferon-gamma.

Twenty-four Kenyan patients with visceral leishmaniasis were treated for 30 days with either conventional therapy (daily pentavalent antimony, n = 14) or experimental immunochemotherapy (daily antimony plus interferon-gamma [IFN-gamma] every other day, n = 10). All 24 patients responded clinically to treatment, and microscopic splenic aspirate scores rapidly decreased in both groups. As judged by splenic aspirate culture results, IFN-gamma-treated patients responded more quickly (50% versus 22% culture-negative after one week and 75% versus 58% culture-negative after two weeks). While not statistically significant, these differences raise the possibility that combination therapy using IFN-gamma, which was safe and well-tolerated, may accelerate the early parasitologic response in patients with visceral leishmaniasis.

Effects of probenecid on the pharmacokinetics of allopurinol riboside.

Allopurinol riboside is an experimental agent for the treatment of leishmaniasis and American trypanosomiasis. Previous studies showed that after oral administration, unexpectedly low levels of allopurinol riboside in plasma are attributable to incomplete absorption and rapid renal clearance. In this randomized, crossover evaluation in healthy volunteers, probenecid reduces the renal clearance of allopurinol riboside, extends the half-life of allopurinol riboside in plasma, and triples the levels of allopurinol riboside in plasma.

Beyond chloroquine: implications of drug resistance for evaluating malaria therapy efficacy and treatment policy in Africa.

Emphasis on retaining chloroquine as the first-line therapy for Plasmodium falciparum infections in most of sub-Saharan Africa for as long as it remains effective has resulted in widespread reliance on chloroquine in areas where it can have little effect on P. falciparum parasitemia. To address this issue, clinical, parasitologic, and hematologic responses to chloroquine or pyrimethamine/sulfadoxine treatment were assessed among very young children in Malawi (n = 153) and Kenya (n = 73). The median time to resumption of clinical symptoms in chloroquine-treated children was 13.5 days in Malawi and 9.5 days in Kenya. Children treated with pyrimethamine/sulfadoxine maintained clinical improvement and had greater increases in their hemoglobin concentration during the follow-up period than did children treated with chloroquine. Treatment with chloroquine failed to produce either a durable clinical improvement or optimal hematologic recovery. Consequently, chloroquine can no longer be considered adequately effective therapy of clinical P. falciparum malaria in very young children in these areas of Africa.