Impact of human immunodeficiency virus type 1 (hiv-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv network for prevention trials 012 study)

In Uganda, the HIV Network for Prevention Trials (HIVNET) 012 study recently demonstrated that single-dose nevirapine (Nvp) prophylaxis is effective for preventing mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1). This exploratory study examines the relationship between HIV-1 subtype, MTCT, and the development of Nvp resistance (Nvp(R)) in women enrolled in HIVNET 012. For 102 women (32 whose infants were HIV-1 infected by age 6-8 weeks and 70 whose infants were uninfected), HIV-1 subtypes included 50 (49%) subtype A, 35 (34%) subtype D, 4 (4%) subtype C, 12 (12%) recombinant subtype, and 1 unclassified. There was no apparent difference in the rate of MTCT among women with subtype A versus D (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI], 0.45-3.43). Nvp(R) mutations were detected more frequently at 6-8 weeks postpartum in women with subtype D than in women with subtype A (adjusted OR, 4.94; 95% CI, 1.21-20.22). Additional studies are needed to further define the relationship between HIV-1 subtype and Nvp(R) among women receiving Nvp prophylaxis.     

Emergence of multidrug-resistant gram-negative organisms in a neonatal unit and the therapeutic implications

Multidrug-resistant organisms are increasing worldwide. Over the years we have noted increasing resistance of organisms isolated in our neonatal unit. There is a need therefore to scrutinize the problem so as to be able to plan for the future. Over a 5-month period, 716 infants were admitted of which 192 were screened for sepsis. Overall, 121 (16.7 per cent) had positive blood cultures. The predominant organisms were Gram negative (73.6 per cent of isolates) with Klebsiella species topping the list at 31 per cent. Case fatality for infants infected with Gram negative organisms was 41 per cent. Resistance to gentamicin was 20 per cent chloramphenicol 23.6 per cent, and amoxicillin/ampicillin 66.3 per cent. Of worry is the resistance to ceftazidime 19.1 per cent, and cefuroxime 21.3 per cent, with the figures rising to 27 per cent when more specialized tests are done (disc approximation and potentiation tests). If these drugs cannot be used in 20-27 per cent of cases then the situation is serious. The contributory factors to increased resistance include: non-investigation of infants put on antibiotics (50 per cent of cases); prolonged (73 per cent) and sometimes unjustified (41.7 per cent) use of antibiotics; and non-utilization of investigations when these are done (52 per cent) together with the delay in getting results back in the ward (6 days).     

Resistance of cattle to tsetse-transmitted challenge with Trypanosoma brucei or Trypanosoma congolense after spontaneous recovery from syringe-passaged infections

Groups of cattle were inoculated intravenously with cloned populations of bloodstream forms of Trypanosoma brucei or Trypanosoma congolense. All five steers infected with T. brucei ILTat 2.1 and six of the eight steers infected with T. congolense IL 13-E14 became aparasitemic within 16 and 32 weeks postinfection, respectively. Examination of sera from animals infected with T. brucei by indirect immunofluorescence and neutralization assays revealed the presence of antibodies against all the metacyclic variable antigen types (VATs) of the infecting clone. The neutralizing capacity of the sera increased with the course of infection from 1:10 at 2 months to 1:100 at 3 to 4 months postinfection. The recovered animals were completely immune to challenge by Glossina morsitans subsp. centralis infected with clone IL Tat 2.1, which had initiated the infection, as well as with another clone (IL Tat 2.2) belonging to the same serodeme, but they were susceptible to a tsetse-transmitted heterologous challenge with isolate STIB 367-H. Similar results were obtained with sera from T. congolense IL 13-E14-infected steers. The six steers infected with a different T. congolense ILNat 3.1 clone did not recover spontaneously; however, 2 months postinfection, sera from five of them also contained neutralizing antibodies against ILNat 3.1 metacyclic VATs. These results indicate that some of the bloodstream VATs that arise during the course of a chronic infection possess surface epitopes in their variable surface glycoproteins that are identical to those of the metacyclic VATs. It is suggested that in chronic infection, the infecting trypanosomes could exhaust their VAT repertoire, including those that cross-react with metacyclics, thereby leading to both "self-cure" and subsequent immunity to homologous cyclically transmitted challenge.     

Characterization of nevirapine resistance mutations in women with subtype A vs. D HIV-1 6-8 weeks after single-dose nevirapine (HIVNET 012)

OBJECTIVE: To compare the number and type of nevirapine (NVP) resistance mutations detected in Ugandan women with subtype A vs. D HIV-1 infection after single-dose NVP prophylaxis. DESIGN: In the HIVNET 012 trial, a higher rate of NVP resistance (NVPR) was seen in women with subtype D than A after single-dose NVP. In this study, the number and type of NVPR mutations detected 6-8 weeks after NVP were compared in women with subtypes A vs. D. METHODS: Plasma samples were available for 282 (92%) of 306 women who received NVP in HIVNET 012. Samples were analyzed with the ViroSeq HIV-1 Genotyping System (Applied Biosystems, Foster City, CA). Subtyping was performed by phylogenetic analysis of pol region sequences. RESULTS: Results were obtained for 279 women, including 147 with subtype A, 98 with subtype D, 6 with subtype C, and 28 with recombinant HIV-1. NVPR mutations were detected in 70 (25%) of 279 women. NVPR was more common in women with subtype D vs. A (35.7 vs. 19%, P = 0.0035). Complex patterns of NVPR mutations were detected in both subtypes. Among women with NVPR, 43% of women with subtype A and 46% of women with subtype D had >/=2 NVPR mutations. The mean number and pattern of NVPR mutations detected in women with subtypes A and D were similar. CONCLUSIONS: This study confirms a higher rate of NVPR in women with subtype D than A and further defines the pattern of NVPR mutations that emerge 6-8 weeks after single-dose NVP prophylaxis in these subtypes.     

Spectrophotometric determination of sulphamethoxazole and trimethoprim (co-trimoxazole) in binary mixtures and in tablets

Background

The formulation of sulphamethoxazole (S) and trimethoprin (T) (CO-TRIMOXAZOLE) in a combination mixture is very good pharmacologically since it enhances the efficacy of the individual drugs. However in this combination, difficulties in analysis on ordinary UV spectrophotometry are introduced because the two components give overlapping spectral bands on zero-order. The United States Pharmacopoea (USP)-recommended HPLC analytical method is quite expensive.

Objective

The objective of the present work was to assess whether derivative spectrophotometry could be used to circumvent the overlapping spectral bands of the components and hence use it for routine analysis of the drug.

Study design

Experimental

Methods

The aqueous solution of the individual drugs and their binary mixutres were scanned on zero order and on first derivative at the wave length between 200–300nm and at the pH of 4.5.

Results

The zero-order spectra of the compounds were completely overlapping. However the first-derivative scan offered better separation and hence T was determined from the absorbance at 237.6nm with negligible contribution from S (since at this point it was reading zero). Likewise S was determined at a wavelength of 259nm when T was reading zero. The linear calibration graphs were obtained for 4–25µgml⁻¹ of S and for 4–20µgml⁻¹ of T.

Conclusion

The method is rapid, simple and can be applied successfully to assay a mixture of the two drugs in pharmaceutical preparations.     

Implementation of a comprehensive AIDS education programme for schools in Masaka District, Uganda

As part of a large IEC (Information, Education and Communication)/STD intervention trial, a 19-lesson, comprehensive school-based AIDS education programme was implemented and evaluated in 50 primary and 16 secondary schools in 12 parishes of Masaka District, Uganda. A series of three teacher-training and evaluation workshops spread over a year was held in each parish, between which teachers implemented the programme in the classroom. One hundred and forty-eight teachers were trained and about 3,500 students were subsequently exposed to the programme. Both teachers and students responded positively, which suggests that this type of programme has much to offer young people who attend school. However, some problems were encountered: language, programme content, community resistance to teaching about condoms, and several practical issues. Proposed solutions include flexibility with the English language policy, alternative approaches to role play activities, targeting influential individuals with information about the need for young people to learn about safer sex, and a parallel community-based IEC programme to facilitate community acceptance of the need for the programme. In addition, implementation may be incomplete unless comprehensive AIDS education is fully incorporated into the curriculum, and properly examined. These findings are placed in the context of other life skills/AIDS education programmes being introduced both in Uganda and elsewhere in Africa.     

Apparent exhaustion of the variable antigen repertoires of Trypanosoma vivax in infected cattle.

Three groups of cattle, each group comprising six animals, were inoculated intravenously with populations of bloodstream forms of Trypanosoma vivax. The first group received T. vivax clone ILDat 1.3 derived from an isolate from Nigeria, while the other two received T. vivax stocks IL 1875 or IL 2133 isolated from Coast Province, Kenya. One animal from the group that was infected with IL 1875 died 8 weeks postinfection. The remaining 17 animals became aparasitemic in 8 to 12 weeks without intervention by drug therapy. The recovered animals developed serodeme-specific immunity against Glossina morsitans subsp. centralis-transmitted challenge. There was complete cross-protection between the two East African T. vivax stocks, although they were isolated from areas 80 to 90 km apart, indicating that they belong to the same serodeme. Antibodies to the homologous metacyclic variable antigen types (VATs) were not detected in sera from recovered animals, suggesting that the immunity displayed by the recovered animals was directed at the bloodstream and not the metacyclic VATs. It is thus suggested that recovery in these animals is due to exhaustion of the repertoire of bloodstream VATs expressed in the animals by the infecting T. vivax clone or stocks.     

Postnatal Weight Gain of Exclusively Breast Fed Preterm African Infants

The weight of 64 preterm appropriate for gestational age infants were followed closely during the period of stay in the newborn unit. They were subdivided into three groups: A (1001-1250 g), B (1250-1500 g), and C (1501-1750 g). The mean gestation for these groups were 28.7, 30.5, and 31 weeks, respectively, while mean birth weights were 1132 +/- 81.7 g, 1377 +/- 85.6 g, and 1641 +/- 88.6 g. All were fed their own mothers breast milk during the period of study with no supplements. During the first week, there was significant weight loss in all groups as follows: A (12.0 per cent), B (7.7 per cent), and C (4.4 per cent). Thereafter, only group A lost weight in the second week, but the loss was not significant. Birth weights were regained at 23, 16, and 15 days, respectively. The weight gain after the initial loss was A (20.0 g), B (20.4 g), and C (20.2 g) per day. Group A had the fastest growth rate.