Clinical and histological features of inoculation site skin lesions in cynomolgus monkeys experimentally infected with Orientia tsutsugamushi

Cynomolgus monkeys, as animal models of scrub typhus, are typically infected with Orientia tsutsugamushi by intradermal inoculation. However, the clinical and histological features at the O. tsutsugamushi inoculation sites, akin to "eschars" at chigger inoculation sites in humans, have not been fully characterized. We intradermally inoculated one medial thigh of six cynomolgus monkeys with semi-purified O. tsutsugamushi (Karp). Within 7 days, two animals developed scrub typhus-like eschars and four had dusky plaques, accompanied by inguinal lymphadenopathy. Biopsies of eschars and an enlarged regional lymph node resembled human disease and stained positively for O. tsutsugamushi by Giemsa, anti-Karp fluorescent antibody, or streptavidin alkaline phosphatase. O. tsutsugamushi-specific IgM and IgG antibody levels measured in both of two monkeys rose steadily after infection. This pilot study shows that cynomolgus intradermally inoculated with O. tsutsugamushi replicate the localized cutaneous pathogenesis of human scrub typhus infections, strengthening the value of this animal model.     

Safety and immunogenicity of an HIV subtype B and E prime-boost vaccine combination in HIV-negative Thai adults

ALVAC-HIV (vCP1521) and AIDSVAX B/E were evaluated in a phase 1/2 trial of human immunodeficiency virus (HIV)-negative Thai adults. Of 133 volunteers enrolled, 122 completed the trial. There were no serious vaccine-related adverse events, nor were there intercurrent HIV infections. Lymphoproliferative responses to glycoprotein 120 E were induced in 63% of the volunteers, and HIV-specific CD8 cytotoxic T lymphocyte responses were induced in 24%. Antibody responses increased in frequency and magnitude in association with the dose level of AIDSVAX B/E. Binding and neutralizing antibodies to the MN strain were induced in 100% and 98%, respectively, of the volunteers receiving 600 microg of AIDSVAX B/E, and such antibodies to E strains were induced in 96% and 71%, respectively, of these volunteers. This vaccine combination was well tolerated and was immunogenic, meeting milestones for advancement to phase 3 evaluation.     

HPV genotyping in cervical cancer in Northern Thailand: adapting the linear array HPV assay for use on paraffin-embedded tissue

ObjectiveThe objective of this study was to review our experience with abdominal radical trachelectomy in patients with early-stage cervical cancer.MethodsWe performed a retrospective review of all patients who underwent an abdominal radical trachelectomy at the Instituto de Cancerologia—Clinica las Americas in Medellin, Colombia, between April 2002 and January 2008. Data collected included age, stage, histopathologic subtype, tumor size, evidence of lymph-vascular space invasion, estimated blood loss, number of perioperative blood transfusions, number and disease status of lymph nodes removed, disease status of surgical specimen, length of hospital stay, intraoperative and postoperative complications, follow-up time, and fertility outcomes.ResultsFifteen patients underwent an abdominal radical trachelectomy during the study period. The median patient age was 30 years (range, 25–38). Three patients had stage IA2 and 12 had stage IB1 cervical cancer. Eleven patients had squamous cell carcinoma and 4 had adenocarcinoma. Thirteen patients were diagnosed by cervical conization and 2 by colposcopically directed biopsy. All patients had tumors smaller than 2 cm. The median estimated blood loss was 400 ml (range, 200–1000). The median surgical time was 265 min (range, 210–330). The median number of units of packed red blood cells transfused per patient was 2. The median number of lymph nodes removed was 26 (range, 11–48). The median length of hospitalization was 3 days (range, 2–7). The median follow-up time was 32 months (range, 5–32). There was 1 intraoperative complication and 6 postoperative complications in 4 patients. No patient has had a recurrence. Three patients were able to conceive spontaneously; 1 delivered at 31 weeks' gestation, and 2 delivered at term.ConclusionAbdominal radical trachelectomy is feasible and can be performed safely in a developing country in well-selected patients with early cervical cancer who wish to preserve their fertility.     

Routine offer of antenatal HIV testing ("opt-out" approach) to prevent mother-to-child transmission of HIV in urban Zimbabwe

OBJECTIVE: To assess the impact of routine antenatal HIV testing for preventing mother-to-child transmission of HIV (PMTCT) in urban Zimbabwe. METHODS: Community counsellors were trained in routine HIV testing policy using a specific training module from June 2005 through November 2005. Key outcomes during the first 6 months of routine testing were compared with the prior 6-month "opt-in" period, and clients were interviewed. FINDINGS: Of the 4551 women presenting for antenatal care during the first 6 months of routine HIV testing, 4547 (99.9%) were tested for HIV compared with 3058 (65%) of 4700 women during the last 6 months of the opt-in testing (P < 0.001), with a corresponding increase in the numbers of HIV-infected women identified antenatally (926 compared with 513, P < 0.001). During routine testing, more HIV-infected women collected results compared to the opt-in testing (908 compared with 487, P < 0.001) resulting in a significant increase in deliveries by HIV-infected women (256 compared with 186, P = 0.001); more mother/infant pairs received antiretroviral prophylaxis (n = 256) compared to the opt-in testing (n = 185); and more mother/infant pairs followed up at clinics (105 compared with 49, P = 0.002). Women were satisfied with counselling services and most (89%) stated that offering routine testing is helpful. HIV-infected women reported low levels of spousal abuse and other adverse social consequences. CONCLUSION: Routine antenatal HIV testing should be implemented at all sites in Zimbabwe to maximize the public health impact of PMTCT.     

The feasibility of preventing mother-to-child transmission of HIV using peer counselors in Zimbabwe

Background

Prevention of mother-to-child transmission of HIV (PMTCT) is a major public health challenge in Zimbabwe.

Methods

Using trained peer counselors, a nevirapine (NVP)-based PMTCT program was implemented as part of routine care in urban antenatal clinics.

Results

Between October 2002 and December 2004, a total of 19,279 women presented for antenatal care. Of these, 18,817 (98%) underwent pre-test counseling; 10,513 (56%) accepted HIV testing, of whom 1986 (19%) were HIV-infected. Overall, 9696 (92%) of women collected results and received individual post-test counseling. Only 288 men opted for HIV testing. Of the 1807 HIV-infected women who received posttest counseling, 1387 (77%) collected NVP tablet and 727 (40%) delivered at the clinics. Of the 1986 HIV-infected women, 691 (35%) received NVPsd at onset of labor, and 615 (31%) infants received NVPsd. Of the 727 HIV-infected women who delivered in the clinics, only 396 women returned to the clinic with their infants for the 6-week follow-up visit; of these mothers, 258 (59%) joined support groups and 234 (53%) opted for contraception. By the end of the study period, 209 (53%) of mother-infant pairs (n = 396) came to the clinic for at least 3 follow-up visits.

Conclusion

Despite considerable challenges and limited resources, it was feasible to implement a PMTCT program using peer counselors in urban clinics in Zimbabwe.     

Sero-epidemiological survey of Rickettsia tsutsugamushi infection in a rural Thai village

A sero-epidemiological survey of a rural Thai village demonstrated a 77% prevalence of antibody against Rickettsia tsutsugamushi in adults. Acquisition of antibody occurred very early in life, especially in females, but the prevalence of antibody in the adult population showed no statistically significant sexual distinction. Antibody against all three prototype strains was present in Thailand but antibody titres did not vary by strain type or the age of the individual.     

Population pharmacokinetics of the new antimalarial agent tafenoquine in Thai soldiers

AIMS: To describe the population pharmacokinetics of tafenoquine in healthy volunteers after receiving tafenoquine for malaria prophylaxis. METHODS: The population consisted of 135 male Thai soldiers (mean age 28.9 years; weight 60.3 kg). All soldiers were presumptively treated with artesunate for 3 days plus doxycycline for 7 days to remove any pre-existing malaria infections. After the treatment regime, 104 soldiers (drug group) received a loading dose of 400 mg tafenoquine base daily for 3 days followed by 400 mg tafenoquine monthly for 5 consecutive months. In the placebo group, 31 soldiers were infected with malaria during the study period. They were re-treated with artesunate for 3 days plus doxycycline for 7 days followed by a loading dose of 400 mg tafenoquine daily for 3 days and then 400 mg tafenoquine weekly for prophylaxis. Blood samples were randomly collected from each soldier on monthly and weekly prophylaxis. Plasma tafenoquine concentrations were measured by h.p.l.c. Population pharmacokinetic modelling was performed using NONMEM. RESULTS: A one-compartment model was found best to describe the pharmacokinetics of tafenoquine after oral administration. Age and weight influenced volume of distribution (V/F), and subjects who contracted malaria had higher clearance (CL/F), but none of these factors was considered to have sufficient impact to warrant change in dosing. The population estimates of the first-order absorption rate constant (Ka), CL/F and V/F were 0.694 h(-1), 3.20 l h(-1) and 1820 l, respectively. The intersubject variability in these parameters (coefficient of variation, CV%) was 61.2%, 25.3% and 14.8%, respectively. The absorption and elimination half-lives were 1.0 h and 16.4 days, respectively. The residual (unexplained) variability was 17.9%. CONCLUSIONS: The population pharmacokinetics of orally administered tafenoquine have been determined in Thai soldiers under field conditions. This information, together with its known potent antimalarial activity, portends well for the application of tafenoquine as a useful prophylactic drug or for short-term radical treatment of vivax malaria.     

Cell-bound haemagglutinin (CHA) of V. cholerae 01 as protective antigen

The study of immunogenicity of cell-bound haemagglutinin (CHA) of Vibrio cholerae E1 Tor in mice revealed that the CHA was a good antigen when it was adsorbed onto the surface of sheep red blood cells and given orally to mice. The antigen not only induced high levels of various class antibodies which sustained in the intestinal tracts for a long period of time (longer than 6 months) but also the antibodies were protective against homologous cholera challenge. The degree of protection seems to correlate with the level of IgA in the intestinal washing. The protective ability was conferred mainly by anti-CHA.     

Human Infection with Rickettsia honei, Thailand

Human spotted fever rickettsiosis was detected molecularly by 2 real-time polymerase chain reaction (PCR) assays performed on DNA extracted from a Thai patient's serum sample. Sequences of PCR amplicons from 5 rickettsial genes used for multilocus sequence typing were 100% identical with those deposited with GenBank for Rickettsia honei TT-118.