Connected diagnostics: linking digital rapid diagnostic tests and mobile health wallets to diagnose and treat brucellosis in Samburu, Kenya.

BACKGROUND: Despite WHO guidelines for testing all suspected cases of malaria before initiating treatment, presumptive malaria treatment remains common practice among some clinicians and in certain low-resource settings the capacity for microscopic testing is limited. This can lead to misdiagnosis, resulting in increased morbidity due to lack of treatment for undetected conditions, increased healthcare costs, and potential for drug resistance. This is particularly an issue as multiple conditions share the similar etiologies to malaria, including brucellosis, a rare, under-detected zoonosis. Linking rapid diagnostic tests (RDTs) and digital test readers for the detection of febrile illnesses can mitigate this risk and improve case management of febrile illness. METHODS: This technical advance study examines Connected Diagnostics, an approach that combines the use of point-of-care RDTs for malaria and brucellosis, digitally interpreted by a rapid diagnostic test reader (Deki Reader) and connected to mobile payment mechanisms to facilitate the diagnosis and treatment of febrile illness in nomadic populations in Samburu County, Kenya. Consenting febrile patients were tested with RDTs and patient diagnosis and risk information were uploaded to a cloud database via the Deki Reader. Patients with positive diagnoses were provided digital vouchers for transportation to the clinic and treatment via their health wallet on their mobile phones. RESULTS: In total, 288 patients were tested during outreach visits, with 9% testing positive for brucellosis and 0.6% testing positive for malaria. All patients, regardless of diagnosis were provided with a mobile health wallet on their cellular phones to facilitate their transport to the clinic, and for patients testing positive for brucellosis or malaria, the wallet funded their treatment. The use of the Deki Reader in addition to quality diagnostics at point of care also facilitated geographic mapping of patient diagnoses in relation to key risk areas for brucellosis transmission. CONCLUSIONS: This study demonstrates that the Connected Dx approach can be effective even when addressing a remote, nomadic population and a rare disease, indicating that this approach to diagnosing, treatment, and payment for healthcare costs is feasible and can be scaled to address more prevalent diseases and conditions in more populous contexts.

Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics.

Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models of thrombi formation in human lung microvessels that could also assess therapeutics and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet-endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor-1 (PAR-1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.

Role of child health clinics in promoting use of insecticide-treated nets among children under five years in Nyamira district, Kenya.

BACKGROUND: Maternal child health clinics are the ideal places to meet and sensitise all the mothers with children under five years on the use of insecticide-treated nets in the prevention of malaria. OBJECTIVE: To determine whether child health clinics are promoting the use of insecticide-treated nets in malaria prevention among children. DESIGN: Cross-sectional, descriptive study. SETTING: Eight health centres in Nyamira District. SUBJECTS: Four hundred mothers bringing their children aged five years and below to the child health clinics between August and October 2003. RESULTS: Two hundred and eighty four mothers (71%) had not received any information on the use of insecticide-treated nets while at the MCH clinics. Only 50% of the clinics had bed nets/ITNs posters mounted on their premises. Out of those clinics with posters, only in 50% of them had bed net posters seen. Very few mothers (36.2%) had seen the bed net/ITNs posters. None of the healthcare providers used bed net/ITNs posters to educate the mothers. None of the insecticide-treated net leaflets were issued. CONCLUSION: Despite the fact that maternal child health clinics were well placed in promoting the use of insecticide-treated nets to the mothers who brought their under five year children, very little was being done to this effect. MCH clinics need to be more aggressive in motivating mothers to use insecticide-treated nets.

Mothers' knowledge on malaria and vector management strategies in Nyamira District, Kenya.

BACKGROUND: Maternal knowledge on malaria and vector control measures are important because they enable mothers make an informed choice on the method of malaria control to use for their children under five years. OBJECTIVE: To determine the mothers' knowledge on malaria and vector control measures particularly use of insecticide treated nets. DESIGN: Cross sectional, descriptive study. SETTING: Eight health centres in Nyamira District, Kenya. SUBJECTS: Four hundred mothers bringing their children aged five years and below to the child health clinics. RESULTS: Mothers had a problem of defining malaria. Majority of them (91.8%) recognised mosquitoes as causing malaria. About 30% associated malaria with dirt, dirty compounds, dirty food/utensils, unboiled water and uncooked food. Many mothers identified basic malaria symptoms such as headache (70%), fever (68.8%), cold (65%), body or joint pain (65.5%) and abdominal pain/ vomiting (0.5%). Mothers (40.8%)were less knowledgeable on most vulnerable groups to malaria. A large number of mothers (55.5%) used nothing to protect themselves and their children under five years from mosquito bites. The radio (69%) tuned in the local language, played a very important role in the mothers' knowledge about the use of mosquito nets and insecticide treated nets. CONCLUSION: By virtue of the fact that majority of mothers (91.8%) recognised that mosquitoes caused malaria, it was an indicator that they were knowledgeable of its existence. Mothers were also informed of most of the malaria vector control measures particularly use of bed nets and insecticide treated nets. However, the general usage of those measures was very low.

Maternal use of insecticide-treated nets in the prevention of malaria among children under five years in Nyamira district, Kenya.

BACKGROUND: Insecticide treated nets (ITNs) have been proved as one of the most effective ways of reducing malaria morbidity and mortality in children and pregnant women. Proper use and care of insecticide treated nets reduce malaria health risk to children. OBJECTIVE: To determine maternal use of insecticide treated nets in the prevention of malaria among children under five years in Nyamira district. DESIGN: Cross-sectional, descriptive study. SETTING: Eight health centres in Nyamira district. SUBJECTS: Four hundred mothers bringing their children aged five years and below to the child health clinics between August and October 2003. RESULTS: There was very low usage of mosquito nets (33.8%) with the proportion of under five using bed nets and insecticide treated nets being 33.3% and 23.8% respectively. The possibility of a mother having an insecticide treated net was significantly related with the level of education of the mother (p = 0.003), occupation (p = 0.001) and knowledge (p = 0.000). Among the reasons given by mothers regarding non usage of insecticide treated nets included lack of money, they were expensive, ignorance and carelessness. CONCLUSION: There was low use of ITNs (23.8%) among children. There is need for health information, education and communication campaigns to sensitise the mothers on most risk groups from malaria so as to create awareness of who needed more protection through use of ITNs. There is need for ITNs intervention projects for malaria prevention in the area.

Adult Burkitt's lymphoma in patients with and without human immunodeficiency virus infection in Kenya.

Prior to the acquired immunodeficiency syndrome (AIDS) epidemic, one or two cases of adult Burkitt's lymphoma (BL) were seen annually at the Kenyatta National Hospital, the national referral medical center in Nairobi, Kenya. To investigate the influence of human immunodeficiency virus (HIV) infection in adult BL in Kenya, we conducted a national prevalence survey of all patients 16 years of age and older with BL. A systematic review of medical records of all patients diagnosed with BL between 1992 and 1996 was performed. The diagnosis of BL was based and confirmed on review of pathological material from time of original diagnosis. HIV serology was confirmed by enzyme-linked immunosorbent assay (ELISA). Twenty-nine adult patients with BL were identified during the 5-year study period. Of these patients, 17 (59%) were males, 12 (41%) were females, and the median age was 26 years. Nineteen patients (66%) with BL were HIV-seropositive. The proportion of men was similar in HIV-seropositive and -seronegative patients (58% vs 60%). HIV-seropositive BL patients were significantly older than seronegatives (median 35 vs 19.5 years, p < 0.001). HIV-seropositive patients uniformly presented with constitutional or B symptoms and advanced BL accompanied by diffuse lymph node involvement, whereas the clinical presentation of HIV-seronegative patients during this time period was reminiscent of the "typical" endemic pattern of disease with complete sparing of peripheral lymph nodes. The overall survival of HIV-seropositive cases was significantly worse than that of the HIV-seronegative cases; median survival in the HIV-seropositive patients was 15 weeks. There is an approximate 3-fold increase in the incidence of adult BL during the time period of this study, which is attributable to the AIDS epidemic. In this setting, patients often present with disseminated disease, diffuse peripheral lymphadenopathy and fever, the latter two of which heretofore have been commonly associated with non-lymphoproliferative disorders such as Mycobacterium tuberculosis and sexually transmitted diseases in Kenya. These observations warrant inclusion of AIDS-related BL in the differential diagnosis of the adult patient with unexplained fever and lymphadenopathy in Kenya. The corollary is that HIV infection is virtually excluded in an adult patient without peripheral lymphadenopathy and biopsy-proven BL.

A role for protein kinase C-delta in the regulation of ornithine decarboxylase expression by oxidative stress.

The expression of genes that regulate cell growth, such as ornithine decarboxylase (ODC), can be modulated by oxidant tumor promoters. Treatment of murine papilloma PE cells with H2O2 led to a transient induction of ODC enzyme activity, which could be blocked by calphostin, a nonspecific inhibitor of protein kinase C (PKC). Peak activity (11-fold) occurred 5-6 h after treatment, followed by a rapid decline. The increase in ODC activity was associated with an elevation of both ODC mRNA (3-fold) and protein (7-fold). Direct involvement of PKC in the regulation of ODC by oxidants was determined by stable transfection of PE cells with a dominant-negative PKC-delta mutant. PKC-delta activity was completely inhibited in response to H2O2 in cells overexpressing mutant PKC-delta compared with cells transfected with a blank plasmid. Induction of ODC mRNA, protein, and activity was also completely inhibited in cells expressing the PKC-delta mutant after H2O2 treatment. Activation of an ODC promoter-luciferase reporter construct by H2O2 was attenuated in mutant cells compared with control cells, further confirming that ODC is regulated transcriptionally by PKC-delta. However, fold-increases in ODC mRNA and protein were much less than the increase in activity, suggesting that ODC may also undergo posttranscriptional regulation in the presence of oxidants. Taken together, these studies provide new insight into the regulation of ODC by oxidants and suggest that PKC-delta may play a critical role in this regulation.

Chemoprotective 3H-1,2-dithiole-3-thione induces antioxidant genes in vivo.

Several 1,2-dithiole-3-thiones are potent inhibitors of chemical-induced tumors in multiple tissues. Chemoprotection by 1, 2-dithiole-3-thiones has been associated with induction of detoxication enzymes, although several studies suggest that additional mechanisms may be involved. In this study, we examined the induction of hepatic antioxidant genes in rats treated with 3H-1, 2-dithiole-3-thione (D3T). After a 24 h D3T treatment, a 2.4-fold increase in catalase mRNA was observed, which was accompanied by a 1. 5-fold increase in catalase protein expression and a 2.3-fold increase in catalase activity. D3T also mediated 2.9-, 5.9-, and 3. 7-fold increases in the 1.0, 3.0, and 4.0 kb mRNA species of manganese superoxide dismutase (MnSOD), respectively. The induction of MnSOD mRNA by D3T was coincident with 1.7-fold and 4.6-fold increases in MnSOD protein and enzyme activity, respectively. Induction of gamma-glutamylcysteine synthetase mRNA by D3T was accompanied by an increase in glutathione levels. Nuclear run-on assays provided evidence that D3T enhances the transcription rate from MnSOD, catalase, and gamma-glutamylcysteine synthetase. In support of this view, D3T also activated an MnSOD promoter-reporter construct in transiently transfected HepG2 cells. In light of observations that antioxidant enzyme regulation may be altered during carcinogenesis, induction of these genes could provide a potentially important mechanism of action of chemoprotective 1, 2-dithiole-3-thiones.

Transmission of epidemic Vibrio cholerae O1 in rural western Kenya associated with drinking water from Lake Victoria: an environmental reservoir for cholera?

Sub-Saharan Africa has the highest reported cholera incidence and mortality rates in the world. In 1997, a cholera epidemic occurred in western Kenya. Between June 1997 and March 1998, 14,275 cholera admissions to hospitals in Nyanza Province in western Kenya were reported. There were 547 deaths (case fatality rate = 4%). Of 31 Vibrio cholerae O1 isolates tested, all but one were sensitive to tetracycline. We performed a case-control study among 61 cholera patients and age-, sex-, and clinic-matched controls. Multivariate analysis showed that risk factors for cholera were drinking water from Lake Victoria or from a stream, sharing food with a person with watery diarrhea, and attending funeral feasts. Compared with other diarrheal pathogens, cholera was more common among persons living in a village bordering Lake Victoria. Cholera has become an important public health concern in western Kenya, and may become an endemic pathogen in the region.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers.

In 1995, 234 adults from Qidong, People's Republic of China, were enrolled and followed in a Phase IIa 4-methyl-5-(N-2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz) chemoprevention trial. Residents of this area are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods. The intervention was a randomized, placebo-controlled, double-blind study. Elements of the study design and clinical outcomes have been recently published (Jacobson et al, Cancer Epidemiol. Biomark. Prev., 6: 257-265, 1997). The primary objective was to conduct a preliminary assessment of the ability of oltipraz to modulate levels of a validated biomarker of aflatoxin exposure and of the risk of hepatocellular carcinoma by determining levels of aflatoxin-albumin adducts in sera. Healthy eligible individuals were randomized into three arms to receive p.o. 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo for 8 weeks. There were no consistent changes in biomarker levels in the placebo arm over the 16-week observation period, nor was any apparent effect observed in the arm receiving 125 mg of oltipraz each day. However, individuals receiving 500 mg of oltipraz once a week for 8 weeks showed a triphasic response to oltipraz. No effect was observed during the 1st month of the intervention, whereas a significant (P = 0.001) diminution in adduct levels was observed during the 2nd month of active intervention and during the lst month of follow-up. A partial rebound in adduct levels toward baseline values was observed during the 2nd month postintervention. Linear regression models up to week 13 confirmed a significant (P = 0.008) weekly decline of biomarker levels in the group receiving 500 mg of oltipraz once a week. However, despite these effects relative to baseline values within the 500-mg weekly arm, there were no statistically significant differences in biomarker trajectories between treatment arms. The genotype for glutathione S-transferase M1, an oltipraz-inducible isoform involved in the detoxification of aflatoxin B1, did not appear to affect either baseline levels or rates of decline in the biomarker. A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term.

Cysteine S-conjugates activate transcription factor NF-kappa B in cultured renal epithelial cells.

Activation of NF-kappa B by the nephrotoxic and cytotoxic cysteine S-conjugate S-(1,2-dichlorovinyl)-L-cysteine (DCVC) was investigated in porcine kidney-derived LLC-PK1 cells. DCVC induced binding of nuclear proteins to an NF-kappa B consensus oligonucleotide from the immunoglobulin kappa-light chain enhancer region, as determined by electrophoretic mobility shift assays, and the activated proteins were identified as the p50/RelA heterodimeric complex of NF-kappa B. Transient transfection experiments with a kappa B-controlled luciferase reporter construct showed that the NF-kappa B complex activated by DCVC was transcriptionally active. NF-kappa B transactivation was blocked by inhibition of DCVC bioactivation with the cysteine conjugate beta-lyase inhibitor (aminooxy)acetic acid, by the antioxidants N,N'-diphenyl-p-phenylenediamine and N-acetyl-L-cysteine, and by the protein kinase inhibitor staurosporine. The cysteine S-conjugates S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine also activated NF-kappa B in LLC-PK1 cells. These results demonstrate that the NF-kappa B pathway is present in LLC-PK1 cells and is induced by cysteine S-conjugates. Inhibition of DCVC-induced transactivation of NF-kappa B by staurosporine and by antioxidants indicate roles for protein kinases and oxidative stress in the NF-kappa B pathway.

Stable transfection of LLC-PK1 cells with human microsomal glutathione S-transferase gene increases haloalkene glutathione S-conjugate formation and cytotoxicity.

Nephrotoxic haloalkenes undergo glutathione- and cysteine conjugate beta-lyase-dependent bioactivation, and glutathione S-conjugate formation with haloalkenes as substrates is preferentially catalyzed by the hepatic microsomal glutathione S-transferase (mGST). Porcine kidney-derived LLC-PK1 cells, which are competent to bioactivate glutathione and cysteine S-conjugates of haloalkenes, show low mGST activity. Stable transfection of LLC-PK1 cells with the gene encoding mGST would be expected to increase glutathione S-conjugate formation and, therefore, to increase haloalkene cytotoxicity. Transfection of LLC-PK1 cells with human mGST genes resulted in increased expression of mGST protein in microsomal fractions, in increased glutathione S-conjugate formation with hexachloro-1,3-butadiene and 1-chloro-2,4-dinitrobenzene as the substrates, and in increased cytotoxicity of hexachloro-1,3-butadiene. In addition, transfection with mGST gene also increased the activity of cytosolic glutathione S-transferases.

Immunolocalization of microsomal glutathione S-transferase in rat tissues.

Distribution of microsomal glutathione transferase (mGST) protein in rat tissues was investigated by immunohistochemistry. Studies on the localization of mGST are of interest because of its involvement in the detoxication and bioactivation of xenobiotics. mGST antigen was detected in the cytoplasm of some hepatocytes and in bile ducts. In kidney, focal staining of mGST was observed in distal tubules and collecting ducts. Cerebral cortical and cerebellar Purkinje neurons showed good immunoreactivity, and nuclear staining was observed in the choroid plexus. The antigen was detected in epithelial cells of respiratory bronchioles and in the crypt cells of the duodenum. Exocrine cells of the pancreas stained for mGST. Nuclear immunostaining for this protein was observed in primary spermatocytes. mGST antigen was detected in the cytoplasm of the adrenal medulla as a granular stain. Leydig and Sertoli cells in testis also stained for the antigen. Distribution of mGST protein differs from that observed with cytosolic transferases and may be important in determining cell-selective susceptibility to xenobiotics.

Effects of irradiation on surface carbohydrates of larvae of Schistosoma mansoni.

Ultra-violet irradiated larvae of Schistosoma mansoni stimulate high levels of resistance to challenge infection in experimental animals. In the experiments presented here, the binding patterns of antisera specific for the cercarial glycocalyx, and of various lectins, demonstrate that u.v. irradiation causes a pronounced modification of the carbohydrate antigens expressed at the surface of cercariae and newly transformed schistosomula. These alterations were dependent on the irradiation dose, and on the batch of cercariae used in each experiment. Our results strongly suggest that the changes in carbohydrate antigens consequent upon u.v. irradiation may be important in generating the enhanced immunogenicity of irradiated cercariae.

Menstrual disorders in patients with chronic renal failure.

Forty females, age 14 to 35 years (mean 28.6 years) with chronic renal failure (CRF) were included in the study. Their menstrual patterns were noted. The function of their hypothalamo-pituitary-ovarian axis was assessed by the serum levels of follicle stimulating hormone (FSH), Luteinising hormone (LH), prolactin (PrL), estradiol (E2) and progesterone (P) at different phases of the menstrual cycle in patients who continued to have normal menses (Group 1) and at weekly intervals for six weeks in patients with menstrual disturbances (Group II). The mean hormone levels during the initial contact Luteal phase in group I were FSH 12.0 IU/L (N, 1.0-3.0 IU/L), LH 1.8IU/L (N 1.5-101U/L), PrL 652mIU/L (N, 100-600 mIU/L) mE2 160 pmol/L (N 400-1400 pmol/L) and P5 nmol/L (N 14-60 nmol/L) for group I. Corresponding values for group II were 1.2, 10.3, 250, 600 and 3.0 in relevant units. All patients (fourteen) with end stage renal disease (ESRD) had amenorrhoae. On the other hand, most patients with stable CRF (22/26) had normal menses. Following initiation of therapy (conservative or dialytic), there was no significant alteration in the hormonal profile or menstrual pattern. We conclude that other factors apart from the hormonal imbalances, may be responsible for the menstrual disturbances noted in patients with CRF.

Human immunodeficiency virus in gestational trophoblastic neoplasias--is it a poor prognostic risk factor.

Three cases of HIV infection with choriocarcinoma are presented. One case had prolonged chemotherapy without remission, the second had remission only after combining hysterectomy with chemotherapy and the third who had extensively metastatic disease in the presence of other low risk factors are reported. HIV infection may predispose patients to extensive metastatic choriocarcinoma and influence the course of treatment. We propose that HIV infection be considered a poor prognostic risk for gestation trophoblastic neoplasias.

Audit of hysterectomies at the Aga Khan Hospital, Nairobi: justification of operative indications.

An audit of 381 hysterectomies performed over a 5 year period (1986-1990) was carried out. In order to assess justification of the indication for hysterectomy pre-operative diagnoses were divided into two groups: those potentially confirmable by pathologic study and those not potentially confirmable by pathologic study. Out of the 273 cases studied in the first group, 246 (90.1%) were justified, while out of the 108 cases studied in the second group, 82 (75.9%) were justified. An overall 86% justification rate was observed. Adenomyosis as a histopathologic finding was seen more commonly in Asian than African patients (P < 0.005). Morbidity rate was 20% and there were no mortalities. The procedure in general was considered safe and justified.

Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni.

A member of the glutathione S-transferase family, Sm28GST has previously demonstrated a good ability to protect rodents against experimental infection with Schistosoma mansoni. In order to evaluate its efficacy in a model closer to man, two different protocols of immunization with recombinant Sm28GST were tested on baboons in a large-scale trial. Three injections in the presence of aluminium hydroxide as adjuvant resulted in a significant 38% reduction in the adult worm burden together with a trend for a lower percentage of inflammatory tissue in the liver. Individual levels of protection, ranging from 0 to 80%, underlined the heterogeneity of the immune response to this purified molecule in outbred primates. On the other hand, two injections of Sm28GST in the presence of aluminium hydroxide and Bordetella pertussis reduced female schistosome fecundity by 33%, with a more pronounced effect (66%) on faecal egg output; there was also a trend, in this protocol, for decrease of the mean granuloma surface in the liver. Individual anti-Sm28GST IgG antibodies were apparently unrelated to levels of immunity, but there was partial evidence that cytophilic IgE might play a role in the immune mechanisms affecting worm viability, but not fecundity. In the mouse model, Sm28GST vaccination resulted in a lower hatching ability of tissue eggs recovered from immunized mice whereas passive transfer of specific anti-Sm28GST T-lymphocytes, one day before infection, significantly reduced the number of eggs in the liver of mice. We propose that different protocols of immunization with a recombinant molecule can impede Schistosoma mansoni worm viability and fecundity, but can also affect miracidium physiology, with important consequences for disease transmission and granuloma-derived pathology.

Maternal and foetal outcome of pregnant patients with sickle cell anaemia at Kenyatta National Hospital Nairobi. A retrospective study.

In a retrospective study we assessed pregnancy outcome in relation to sickle haemoglobin (HbS) and anaemia at Kenyatta National Hospital, Nairobi (KNH) from 1981-1986. There were 36% maternal and 45% foetal losses in sickle cell disease (SCD) pregnants and 7% foetal losses in sickle cell trait (HbAS) from 26 HbS-related pregnancies. 11 had homozygous sickle cell (SS) disease and 15 had HbAS. Age ranges for both groups were comparable. Mean haemoglobin-level for SS disease patients was 7.8 gm/dl (SD +/- 1.68), for AS patients 7.8 gm/dl (SD +/- 2.1). These maternal and foetal losses are quite high. Anaemia alone does not satisfactorily account for the higher losses in SS pregnancies. Other contributory factors need elucidation and intervention.

Partial protection of baboons against Schistosoma mansoni using radiation-attenuated cryopreserved schistosomula.

Three groups of five baboons were vaccinated in Kenya using three doses of 10,000 viable cryopreserved schistosomula attenuated with either 10, 20 or 60 krad 60Co-irradiation prepared in England. Animals were vaccinated at four-week intervals, challenged after a further six weeks with 2,000 cercariae and perfused at 10 weeks after challenge. High antibody titres to schistosomula mediating in vitro cytoadherence with P 388D1 macrophage-like cells were demonstrated in all vaccinated animals but not in controls. Significant titres to soluble egg antigen (SEA) were also demonstrated by ELISA in the 10 and 20 krad vaccinated groups following the first vaccination. The subsequent vaccinations and the challenge boosted this response considerably. Mean anti-SEA titres were only elevated above background in the 60-krad group six weeks after the third vaccination and in the challenge controls six weeks after challenge. Peripheral eosinophil counts were slightly reduced and neutrophil counts slightly elevated before challenge while eosinophil and erythrocyte counts were elevated and neutrophil counts depressed after challenge. PCV values were erratic in all groups. Eggs appeared in the faeces from six weeks after challenge and excretion rates were higher in all three vaccinated groups than in the challenge controls by necropsy 10 weeks after challenge. Body-weights were depressed in all groups after challenge but subsequently rose in the 10 and 20 krad groups. The 60 krad and challenge control groups lost 12.4% and 7.9% of body-weight respectively after challenge.(ABSTRACT TRUNCATED AT 250 WORDS)