Persistence of K103N-containing HIV-1 variants after single-dose nevirapine for prevention of HIV-1 mother-to-child transmission

K103N-containing human immunodeficiency virus (HIV)-1 variants are selected in some women who receive single-dose (SD) nevirapine (NVP) for prevention of HIV-1 mother-infant transmission. We examined the persistence of K103N in women who received SD NVP prophylaxis. K103N was detected using the LigAmp assay (assay cutoff, 0.5% K103N). K103N was detected at 6-8 weeks in 60 (41.7%) of 144 women. Fading (lack of detection) of K103N was documented in 16 women by 2 years, 43 women by 3 years, and 55 women by 4 and 5 years. Slower fading was independently associated with HIV-1 subtype (D>A) and higher pre-NVP viral load.     

Clone-specific immune colostrum induces increased resistance in goat kids challenged with Trypanosoma congolense.

The course of infection and the humoral immune response to Trypanosoma congolense clone ILNat 3.1 were studied in test goat kids receiving colostrum from dams immunized with the surface coat of ILNat 3.1 and control kids that received colostrum from nonimmunized dams. At 24-48 h after birth, all test kids had detectable serum antibodies to the trypanosome clone. There was no difference in the prepatent period between the test and control kids following challenge with 10(3) T. congolense ILNat 3.1 trypanosomes 8 days after birth. After the first 7 days of the experimental period, significantly lower parasitemia was recorded in test kids than in control kids. The mean packed red cell volume of test kids was not significantly different from that of control kids 7 days after infection. The test kids gained as much weight as noninfected control kids; both groups gained twice as much weight as infected control kids. Following infection, all kids developed antibodies against the infecting trypanosome clone. Fifteen test kids had titers equal to or greater than 1280 compared to only two control kids. The test kids survived longer after infection compared to control kids. The results suggest that colostrum from does immunized with the surface of a T. congolense clone did not prevent infection, but decreased parasitemia and prolonged survival of kids challenged with the same clone.     

Use of a mixture of lignocaine and bupivacaine vs lignocaine alone for male circumcision under local anaesthesia in Rakai, Uganda

Study Type – Therapy (case control) Level of Evidence 3a What's known on the subject? and What does the study add? Local anaesthetic drugs block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Lignocaine/Lidocaine has a rapid onset action and an intermediate duration of efficacy whereas Bupivacaine has a slower onset of action with a long duration of efficacy. A combination of the two drugs creates a mixture that has a short onset of action together with a long duration of action both of which are desirable qualities in provision of effective local anaesthesia. Documenting whether use of lignocaine alone predisposes men to more pain during and after surgery will inform policy makers on the type of local anaesthesia to recommend for male circumcision, especially as circumcision programs roll out. This is important since pain has been associated with reduced acceptance of the male circumcision procedure and therefore can negatively influence male circumcision roll out programs.

OBJECTIVE

• ? To assess self‐reported pain control during and after surgery with a mixture of lignocaine and bupivacaine compared with lignocaine alone among male circumcision (MC) service recipients in Rakai, Uganda.

PATIENTS AND METHODS

• ? The two formulations of local anaesthesia for MC were used alternatively at weekly intervals in 360 patients; 179 received lignocaine alone and 181 received the lignocaine and bupivacaine mixture (LBmix).
• ? The proportions of men reporting pain during or after surgery, and the need for additional anaesthesia during surgery were determined for the LBmix vs lignocaine using Poisson adjusted rate ratios (RRs).
• ? Characteristics including age, weight, surgeon (medical officer vs clinical officer), surgical method and duration of surgery were compared between the arms using two‐sample t‐tests and chi‐square tests.

RESULTS

• ? Patient and provider characteristics were comparable between the two anaesthetic groups.
• ? A higher proportion of patients reported pain during surgery in the lignocaine group (adjusted RR 11.6, 95% confidence interval [CI] 3.5–37.9, P < 0.001), required additional anaesthesia (adjusted RR 4.8, 95% CI 1.4–17.1, P= 0.015), and were more likely to report pain during the immediate postoperative period (adjusted RR 3.4, 95% CI 2.3–5.0, P < 0.001).
• ? These differences were particularly marked among patients with MC times longer than the median (adjusted RR 13.4, 95% CI 3.1–57.0, P < 0.001).

CONCLUSION

• ? The LBmix significantly reduced pain associated with MC and the need for additional anaesthesia during MC.

     

HIV-1 tropism and survival in vertically infected Ugandan infants

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) may utilize the CXCR4 coreceptor (X4 virus), the CCR5 coreceptor (R5 virus), or both (dual/mixed [DM] virus). We analyzed HIV-1 coreceptor tropism in Ugandan infants enrolled in the HIVNET (HIV Network for Prevention Trials) 012 trial. METHODS: Plasma or serum was analyzed using a commercial coreceptor tropism assay. HIV env subtype was determined by phylogenetic methods. RESULTS: Tropism results were obtained for 57 samples from infants collected 6-14 weeks after birth. Fifty-two infants had only R5 virus, and 5 had either X4 or DM virus. The mothers of those 5 infants also had X4 or DM virus. In infants, subtype D infection was associated with high-level infectivity in CCR5-bearing cells and also with the detection of X4 or DM strains. High-level infectivity in CCR5-bearing cells was associated with decreased infant survival, but infection with X4 or DM virus was not. HIV clones from infants with DM viral populations showed different patterns of coreceptor use. V3 loop sequence-based algorithms predicted the tropism of some, but not all, env clones. CONCLUSIONS: Complex patterns of HIV tropism were found in HIV-infected newborn infants. Subtype D infection was associated with X4 virus and with high-level replication in CCR5-bearing cells. High-level replication of R5 virus was associated with decreased infant survival.     

Resistance after single-dose nevirapine prophylaxis emerges in a high proportion of Malawian newborns

The administration of single-dose nevirapine to women in labor and their infants can prevent HIV-1 mother-to-child transmission. We examined nevirapine resistance in infants who were HIV-1 infected despite single-dose nevirapine prophylaxis, including 18 Ugandan infants (HIVNET 012 trial, nine subtype A and nine subtype D) and 23 Malawian infants (NVAZ trial, all subtype C). Nevirapine resistance was more frequent in infants with subtype C than with subtypes A and D (87 versus 50%, P = 0.016).     

Presenting features of newly diagnosed rheumatic heart disease patients in Mulago Hospital: a pilot study

Introduction

Rheumatic heart disease (RHD) continues to cause gross distortions of the heart and the associated complications of heart failure and thromboembolic phenomena in this age of numerous high-efficacy drugs and therapeutic interventions. Due to the lack of contemporary local data, there is no national strategy for the control and eradication of the disease in Uganda. This study aimed to describe the presenting clinical features of newly diagnosed patients with RHD, with particular reference to the frequency of serious complications (atrial fibrillation, systemic embolism, heart failure and pulmonary hypertension) in the study group.

Methods

One hundred and thirty consecutive patients who satisfied the inclusion criteria were recruited over a period of eight months from June 2011 to January 2012 at the Mulago Hospital, Uganda. Data on demographic characteristics, disease severity and presence of complications were collected by means of a standardised questionnaire.

Results

Seventy-one per cent of the patients were female with a median age of 33 years. The peak age of the study group was 20 to 39 years, with the commonest presenting symptoms being palpitations, fatigue, chest pain and dyspnoea. The majority of the patients presented with moderate-to-severe valvular disease. Pure mitral regurgitation was the commonest valvular disease (40.2%), followed by mitral regurgitation plus aortic regurgitation (29%). Mitral regurgitation plus aortic regurgitation plus mitral stenosis was found in 11% of patients. There was only one case involving the tricuspid valve. The pulmonary valves were not affected in all patients; 45.9% of patients presented in severe heart failure in NYHA class III/IV, 53.3% had pulmonary hypertension, 13.9% had atrial fibrillation and 8.2% had infective endocarditis. All patients presented with dilated atria (> 49 mm).

Conclusion

A significant proportion of RHD patients present to hospital with severe disease associated with severe complications of advanced heart failure, pulmonary hypertension, infective endocarditis and atrial fibrillation. There is a need to improve awareness of the disease among the population, and clinical suspicion in primary health workers, so that early referral to specialist management can be done before severe damage to the heart ensues.     

An enzyme-linked immunosorbent assay for detection of Theileria parva antibodies in cattle using a recombinant polymorphic immunodominant molecule

Field and experimental bovine infection sera were used in immunoblots of sporozoite and schizont lysates of Theileria parva to identify candidate diagnostic antigens. Four parasite antigens of Mr 67,000 (p67), 85,000 (the polymorphic immunodominant molecule, PIM), 104,000 (p104), and 150,000 (p150) were selected for a more detailed analysis. The p67 and p104 antigens were present only in the sporozoite lysates, whereas PIM and p150 were found in both sporozoite and schizont lysates. The four antigens were expressed as recombinant fusion proteins and were compared with each other in an enzyme-linked immunosorbent assay (ELISA) and in the whole-schizont-based indirect fluorescent antibody test (IFAT) in terms of their ability to detect antibodies in sera of experimentally infected cattle. The PIM-based ELISA provided a higher degree of sensitivity and specificity than did the ELISA using the other three recombinant antigens or the IFAT. Further evaluation of the PIM-ELISA using experimental sera derived from cattle infected with different hemoparasites and field sera from endemic and nonendemic T. parva areas showed that the assay had a sensitivity of >99% and a specificity of between 94% and 98%. Received: 19 October 1997 / Accepted: 19 November 1997     

Identification of neutralization and diagnostic epitopes on PIM, the polymorphic immunodominant molecule of Theileria parva.

The polymorphic immunodominant molecule (PIM) of Theileria parva is expressed by the schizont and sporozoite stages of the parasite. We have recently cloned the cDNA encoding the PIM antigen from two stocks of the parasite: the cattle-derived T. parva (Muguga) stock and a buffalo-derived stock. The cDNAs were used in transient-transfection assays to assess the reactivity of the antigen with monoclonal antibodies (MAb) previously raised against schizont-infected cells and used for parasite strain identification. We demonstrate that 19 of the 25 MAb are specific for PIM. Antibody reactivities with deletion mutants of a fusion protein containing PIM and Pepscan analysis of the Muguga version of the molecule with 13 of the MAb indicate that there are at least 10 different epitopes throughout the molecule. None of the MAb react with a tetrapeptide repeat present in the central region of the molecule, probably because of an inability of BALB/c mice to produce antibodies to this repeat. In contrast, sera from infected cattle react strongly with the repeat region, suggesting that this region alone may be useful as a diagnostic reagent. Previous studies showed that MAb to PIM inhibit sporozoite infectivity of bovine lymphocytes in vitro, which suggests that the antigen may be useful in immunizing cattle against T. parva infection. Pepscan analysis revealed that sera from infected cattle reacted with peptides recognized by the neutralizing MAb, as did sera from cattle inoculated with a PIM-containing recombinant protein. The latter sera did not, however, neutralize sporozoite infectivity in vitro. These results will be useful in exploiting the strain identification, diagnostic, and immunizing potentials of this family of antigens.