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S Phiri

Publications and source records attributed to S Phiri.

6 recordsLinked to original sources

Providing HIV care for tuberculosis patients in sub-Saharan Africa.

Human immunodeficiency virus (HIV)/acquired immunedeficiency syndrome (AIDS) and tuberculosis (TB) cause an immense burden of disease in sub-Saharan Africa. A large amount of knowledge has been gathered in the last 15 years about the negative impact that HIV has on TB control, both at a programme level and at the level of the individual patient. Equally, interventions that are known to benefit patients have been tested and piloted, and these form important components of international TB-HIV guidelines, a TB-HIV strategic framework and an interim policy on TB-HIV coordination. Unfortunately, in sub-Saharan Africa there is little evidence that these interventions are being implemented on the ground, and one of the reasons for this paralysis is that the operational details are not well developed. This paper takes the three important HIV interventions of HIV testing and counselling, cotrimoxazole preventive treatment and antiretroviral treatment, and discusses some of the practical details of on-the-ground implementation. We hope that this will generate discussion, but above all, the impetus to start delivering services to patients.

Africa South of the Sahara↗

Preserved antigenicity of HIV-1 p24 produced and purified in high yields from plants inoculated with a tobacco mosaic virus (TMV)-derived vector.

Production of structural proteins from foot-and-mouth disease virus (FMDV) and bovine herpes virus (BHV-1) in Nicotiana benthamiana through the use of a tobacco mosaic virus-based vector (TMV-30B) has been reported previously. The development of the TMV-30B-HISc vector, a new version that adds a C-terminal histidine (His) sequence to the foreign protein expressed is described. Coding sequences from the FMDV VPl protein and the core protein, p24, from a clade C HIV-1 isolate from Zambia were cloned into the new vector and infective RNAs were generated for each construct to inoculate N. benthamiana plants. His-tagged proteins were purified from inoculated leaves using immobilized metal affinity chromatography (IMAC) as detected by Coomassie blue staining and proteins were further characterized in Western blot assays using a commercial anti-6xHis mAb and specific polyclonal antisera for each protein. While yields obtained for the VPl-His protein after purification were similar to those in crude extracts obtained with the previous TMV-VPl vector, p24-His yields were 10-15 times higher than those of VPl-His. Twenty-five grams of TMV-p24-HISc inoculated leaves were processed to obtain 2.5 mg of isolated p24-His and the recombinant protein was inoculated in rabbits to test immunogenicity and antigenic integrity of the plant-produced p24-His. Animals developed a strong and specific humoral response to the p24-His after the first booster and immune sera was able to recognize the native p24 from a different clade expressed on the surface of the HIV-1 chronically infected HUT78/ARV T-cell line. Importantly, the recombinant p24-His proved its efficiency by confirming the serology of 117 samples previously tested by two rapid HIV-1 tests, thus representing an excellent alternative for production of highly specific diagnostic reagents for HIV endemic regions in the developing world.

Animals↗

What causes smear-negative pulmonary tuberculosis in Malawi, an area of high HIV seroprevalence?

SETTING: The Central Hospital and the District Tuberculosis (TB) Registry in Lilongwe, the capital of Malawi. In this setting smear-negative pulmonary tuberculosis (PTB) is diagnosed using clinical and radiographic criteria for TB, and mycobacterial cultures are not routinely available. OBJECTIVE: To determine the proportion of patients being registered for smear-negative PTB treatment in Lilongwe who have TB that can be confirmed microbiologically. DESIGN: Prospective cohort study of patients about to start treatment under operational conditions for smear-negative PTB in Lilongwe between October 1997 and June 1998. Patients referred to the study team underwent a detailed clinical re-assessment, testing for human immunodeficiency virus (HIV), repeat sputum smear microscopy for acid-fast bacilli and mycobacterial cultures of sputum and blood. Bronchoscopy and bronchoalveolar lavage (BAL) were performed and BAL fluid was examined for TB, Pneumocystis carinii and other fungi. RESULTS: Of 352 smear-negative PTB suspects assessed, the diagnosis of TB was confirmed in 137 (39%) cases. Eighty-nine per cent of patients assessed were HIV-positive, of whom 81% met the expanded case definition for the acquired immune-deficiency syndrome (AIDS). CONCLUSION: TB was the most commonly confirmed diagnosis amongst patients about to start treatment for smear-negative PTB in an area of high background HIV seroprevalence.

Adolescent↗

Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi.

The National TB Control Programme of Malawi registers and treats large numbers of patients with chronic cough for smear-negative pulmonary tuberculosis (PTB). Smear-negative PTB is diagnosed according to clinical and radiographic criteria, as mycobacterial cultures are not routinely available. In an area of high HIV seroprevalence there is a concern that other opportunistic infections apart from TB, such as Pneumocystis carinii, may be missed owing to lack of diagnostic facilities. The aims of this study were to investigate (i) the extent of P. carinii pneumonia (PCP) in patients about to be registered for smear-negative PTB; (ii) whether there were any clinical or radiological features that could help identify PCP in the absence of more detailed investigations; and (iii) the treatment outcome of PCP patients. A cohort of 352 patients who were about to be started on treatment for smear-negative PTB were investigated further in 1997-99 by clinical assessment, HIV testing and bronchoscopy. HIV sero-prevalence was 89% (278/313). A total of 186 patients underwent bronchoscopy and bronchoalveolar lavage, and PCP was diagnosed by indirect immunofluorescence or polymerase chain reaction in 17 (9%) of this subgroup. Dyspnoea was significantly more common in PCP cases compared to non-PCP cases (RR 1.35; 95% CI 1.24-1.48; P = 0.008), but discrimination between the groups was difficult using clinical criteria alone. The outcome of PCP cases was poor despite management with high-dose co-trimoxazole and secondary co-trimoxazole prophylaxis, with a median survival of 4 months (25-75% range: 2-12 months).

Adult↗

Bloody diarrhoea of adults in Malawi: clinical features, infectious agents, and antimicrobial sensitivities.

In a prospective study, 132 hospital out-patients presenting with bloody diarrhoea ('cases') were evaluated in Malawi, Central Africa; 73 out-patient tuberculosis suspects acted as controls. Most (100/132, 76%) subjects reported an illness lasting < or = 5 d with > 5 bowel actions in the preceding 12 h; 39/132 (30%) reported use of systemic antimicrobial drugs in the preceding week; 57% (74/130) had a body mass index < 20; 4% (5/131) were febrile; and 18/130 (13%) had one or more sign(s) of dehydration. The 73 controls reported no diarrhoea and more systemic antimicrobial drug use (P = 0.0003), but were otherwise comparable to the subjects. All stool samples from controls and 38/124 (31%) from cases were macroscopically normal. Only 32% (40/124) of the cases had blood visible in the stool. Parasitic gut infections were found in 42/124 (34%) cases compared with 1/60 (2%) controls (P < 0.0001). The commonest parasite was Schistosoma mansoni. Bacterial cultures were positive in 32/124 (26%) of the subjects. Shigella dysenteriae (Sd) 1 accounted for 53% (17/32) of these. All bacterial isolates were sensitive in vitro to nalidixic acid and ciprofloxacin, while only 18% were sensitive to cotrimoxazole. Sd 1 with significant antimicrobial resistance continues to cause seasonal epidemics of dysentery in Malawi. During these, approximately two-thirds of patients presenting with bloody diarrhoea have no blood visible in the stool. Nalidixic acid remains the drug of choice but its use should be restricted to patients at greatest risk of complicated shigellosis.

Adult↗