Hlabisa Hospital

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

BACKGROUND: Malaria and HIV are two of the most important diseases facing Africa. It remains uncertain whether HIV-related immunosuppression adversely affects the clinical outcome of malaria. OBJECTIVE: To measure the association between HIV status and outcome from malarial infection in adults living in a region of unstable malaria transmission. DESIGN: Observational cohort study. SETTING: Four community clinics and the Government hospital in Hlabisa district, KwaZulu-Natal, South Africa; a region of high HIV prevalence. METHODS: Consecutive febrile adults were screened for malaria with a rapid antigen test. Those with malaria provided blood spots for HIV testing, a thick blood film for confirmation of malaria and clinical data. Outcome was established following management according to South African government guidelines. RESULTS: Malaria was microscopically confirmed in 613. HIV prevalence was 29.9% (180/613); 110 (18%) had severe/complicated malaria and 28 (4.6%) died. HIV-infected patients were more likely to vomit or be confused and were more likely to be admitted to hospital (P = 0.05). In patients admitted to hospital, HIV infection was associated with severe/complicated malaria [adjusted odds ratio (OR) 2.3; 95% confidence interval (CI), 1.4-3.9] and with death (OR 7.5; 95% CI, 2.2-25.1). Acidosis and coma were also strong independent risk factors for death. CONCLUSION: HIV infection had an unexpectedly large association with the outcome of falciparum malaria in a region of unstable transmission. Both diseases are widespread in Africa and these results add to the body of knowledge suggesting an interaction of significant public health importance between HIV and malaria in Africa.

In the years before human immunodeficiency virus (HIV) infection, the incidence of Kaposi's sarcoma varied markedly across the African continent, and it was a disease primarily affecting men. In contrast, the evidence reviewed here shows that the causal virus-Kaposi's sarcoma associated herpesvirus (KSHV)-is prevalent in many African countries, including places where Kaposi's sarcoma was almost unknown before HIV, and that it is as common in women as in men. Therefore, the geographical distribution of Kaposi's sarcoma in Africa before the spread of HIV and its predominance as a disease affecting men are not a simple reflection of the distribution of KSHV. Since the epidemic of HIV in Africa, Kaposi's sarcoma has become relatively more frequent in women, and the incidence has increased in countries where it was previously rare, but where KSHV is prevalent, as well as in countries where it was already common. These changes point to a role for other (as yet unknown) factors in the aetiology of Kaposi's sarcoma that may have the most effect in the absence of concurrent HIV infection.

To investigate transmission of human herpesvirus (HHV)-8, 2546 mother-child pairs were recruited from rural clinics in South Africa and were tested for antibodies against lytic and latent HHV-8 antigens. The prevalence of antibodies in children increased with increasing maternal antibody titer (lytic, chi 21=26, and P<.001; latent, chi 21=55, and P<.001). HHV-8 DNA was detectable in 145 of 978 maternal saliva samples (mean virus load, 488,450 copies/mL; range, 1550-660,000 copies/mL) and in 12 of 43 breast-milk samples (mean virus load, 5800 copies/mL; range, 1550-12,540 copies/mL). The prevalence of HHV-8 DNA in maternal saliva was unrelated to latent anti-HHV-8 antibody status but was higher in mothers with the highest titers of lytic antibodies than in other mothers (34% vs. 8%; P<.001). The prevalence of lytic anti-HHV-8 antibodies in children was 13% (70/528) if the mother did not have HHV-8 in saliva and was 29% (8/28) if the mother had a high HHV-8 load (>50,000 copies/mL) in saliva (odds ratio, 2.6; 95% confidence interval, 1.1-6.2). The presence of HHV-8 DNA in maternal saliva was unrelated to latent antibodies in children. Saliva could be a route of transmission of HHV-8 from person to person, although other routes cannot be ruled out.

User fees are used to recover costs and discourage unnecessary attendance at primary care clinics in many developing countries. In South Africa, user fees for children aged under 6 years and pregnant women were removed in 1994, and in 1997 all user fees at all primary health care clinics were abolished. The intention of these policy changes was to improve access to health services for previously disadvantaged communities. We investigated the impact of these changes on clinic attendance patterns in Hlabisa health district. Average quarterly new registrations and total attendances for preventive services (antenatal care, immunization, growth monitoring) and curative services (treatment of ailments) at a mobile primary health care unit were studied from 1992 to 1998. Regression analysis was undertaken to assess whether trends were statistically significant. There was a sustained increase in new registrations (P = 0.0001) and total attendances (P = 0.0001) for curative services, and a fall in new registrations (P = 0.01) and total attendances for immunization and growth monitoring (P = 0.0002) over the study period. The upturn in demand for curative services started at the time of the first policy change. The decreases in antenatal registrations (P = 0.07) and attendances (P = 0.09) were not statistically significant. The number of new registrations for immunization and growth monitoring increased following the first policy change but declined thereafter. We found no evidence that the second policy change influenced underlying trends. The removal of user fees improved access to curative services but this may have happened at the expense of some preventive services. Governments should remain vigilant about the effects of new health policies in order to ensure that objectives are being met.

Noncommunicable diseases (NCDs) such as hypertension, asthma, diabetes and epilepsy are placing an increasing burden on clinical services in developing countries and innovative strategies are therefore needed to optimize existing services. This article describes the design and implementation of a nurse-led NCD service based on clinical protocols in a resource-poor area of South Africa. Diagnostic and treatment protocols were designed and introduced at all primary care clinics in the district, using only essential drugs and appropriate technology; the convenience of management for the patient was highlighted. The protocols enabled the nurses to control the clinical condition of 68% of patients with hypertension, 82% of those with non-insulin-dependent diabetes, and 84% of those with asthma. The management of NCDs of 79% of patients who came from areas served by village or mobile clinics was transferred from the district hospital to such clinics. Patient-reported adherence to treatment increased from 79% to 87% (P = 0.03) over the 2 years that the service was operating. The use of simple protocols and treatment strategies that were responsive to the local situation enabled the majority of patients to receive convenient and appropriate management of their NCD at their local primary care facility.

BackgroundNew anti-tuberculosis regimens that are shorter, simpler, and less toxic than those that are currently available are needed as part of the global effort to address the tuberculosis epidemic. We aimed to investigate the bactericidal activity and safety profile of combinations of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in the first 8 weeks of treatment of pulmonary tuberculosis.MethodsIn this multicentre, open-label, partially randomised, phase 2b trial, we prospectively recruited patients with drug-susceptible or rifampicin-resistant pulmonary tuberculosis from seven sites in South Africa, two in Tanzania, and one in Uganda. Patients aged 18 years or older with sputum smear grade 1+ or higher were eligible for enrolment, and a molecular assay (GeneXpert or MTBDRplus) was used to confirm the diagnosis of tuberculosis and to distinguish between drug-susceptible and rifampicin-resistant tuberculosis. Patients who were HIV positive with a baseline CD4 cell count of less than 100 cells per uL were excluded. Patients with drug-susceptible tuberculosis were randomly assigned (1:1:1) using numbered treatment packs with sequential allocation by the pharmacist to receive 56 days of treatment with standard tuberculosis therapy (oral isoniazid, rifampicin, pyrazinamide, and ethambutol; HRZE), or pretomanid (oral 200 mg daily) and pyrazinamide (oral 1500 mg daily) with either oral bedaquiline 400 mg daily on days 1–14 then 200 mg three times per week (BloadPaZ) or oral bedaquiline 200 mg daily (B200PaZ). Patients with rifampicin-resistant tuberculosis received 56 days of the B200PaZ regimen plus moxifloxacin 400 mg daily (BPaMZ). All treatment groups were open label, and randomisation was not stratified. Patients, trial investigators and staff, pharmacists or dispensers, laboratory staff (with the exception of the mycobacteriology laboratory staff), sponsor staff, and applicable contract research organisations were not masked. The primary efficacy outcome was daily percentage change in time to sputum culture positivity (TTP) in liquid medium over days 0–56 in the drug-susceptible tuberculosis population, based on non-linear mixed-effects regression modelling of log10 (TTP) over time. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov, NCT02193776, and all patients have completed follow-up.FindingsBetween Oct 24, 2014, and Dec 15, 2015, we enrolled 180 patients with drug-susceptible tuberculosis (59 were randomly assigned to BloadPaZ, 60 to B200PaZ, and 61 to HRZE) and 60 patients with rifampicin-resistant tuberculosis. 57 patients in the BloadPaZ group, 56 in the B200PaZ group, and 59 in the HRZE group were included in the primary analysis. B200PaZ produced the highest daily percentage change in TTP (5·17% [95% Bayesian credibility interval 4·61–5·77]), followed by BloadPaZ (4·87% [4·31–5·47]) and HRZE group (4·04% [3·67–4·42]). The bactericidal activity in B200PaZ and BloadPaZ groups versus that in the HRZE group was significantly different. Higher proportions of patients in the BloadPaZ (six [10%] of 59) and B200PaZ (five [8%] of 60) groups discontinued the study drug than in the HRZE group (two [3%] of 61) because of adverse events. Liver enzyme elevations were the most common grade 3 or 4 adverse events and resulted in the withdrawal of ten patients (five [8%] in the BloadPaZ group, three [5%] in the B200PaZ group, and two [3%] in the HRZE group). Serious treatment-related adverse events affected two (3%) patients in the BloadPaZ group and one (2%) patient in the HRZE group. Seven (4%) patients with drug-susceptible tuberculosis died and four (7%) patients with rifampicin-resistant tuberculosis died. None of the deaths were considered to be related to treatment.InterpretationB200PaZ is a promising regimen to treat patients with drug-susceptible tuberculosis. The bactericidal activity of both these regimens suggests that they have the potential to shorten treatment, and the simplified dosing schedule of B200PaZ could improve treatment adherence in the field. However, these findings must be investigated further in a phase 3 trial assessing treatment outcomes.FundingTB Alliance, UK Department for International Development, Bill & Melinda Gates Foundation, US Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and the Federal Ministry for Education and Research of Germany.

OBJECTIVE: To describe the scale-up of a decentralized HIV treatment programme delivered through the primary health care system in rural KwaZulu-Natal, South Africa, and to assess trends in baseline characteristics and outcomes in the study population. METHODS: The programme started delivery of antiretroviral therapy (ART) in October 2004. Information on all patients initiated on ART was captured in the programme database and follow-up status was updated monthly. All adult patients (> or = 16 years) who initiated ART between October 2004 and September 2008 were included and stratified into 6-month groups. Clinical and sociodemographic characteristics were compared between the groups. Retention in care, mortality, loss to follow-up and virological outcomes were assessed at 12 months post-ART initiation. FINDINGS: A total of 5719 adults initiated on ART were included (67.9% female). Median baseline CD4+ lymphocyte count was 116 cells/microl (interquartile range, IQR: 53-173). There was an increase in the proportion of women who initiated ART while pregnant but no change in other baseline characteristics over time. Overall retention in care at 12 months was 84.0% (95% confidence interval, CI: 82.6-85.3); 10.9% died (95% CI: 9.8-12.0); 3.7% were lost to follow-up (95% CI: 3.0-4.4). Mortality was highest in the first 3 months after ART initiation: 30.1 deaths per 100 person-years (95% CI: 26.3-34.5). At 12 months 23.0% had a detectable viral load (> 25 copies/ml) (95% CI: 19.5-25.5). CONCLUSION: Outcomes were not affected by rapid expansion of this decentralized HIV treatment programme. The relatively high rates of detectable viral load highlight the need for further efforts to improve the quality of services.

AIMS: Delivering adequate diabetes care is difficult in rural Africa because of drug and equipment shortages; as well as lack of trained medical expertise. We aimed to set up and evaluate a nurse-led protocol and education-based system in rural Kwazulu Natal in South Africa. METHODS: A treatment algorithm and education system adapted from previously validated methods was used; care was devolved to primary health clinics and was delivered by two nurses. Glycaemic control was assessed by glycated haemoglobin (HbA1c), assayed off site and not available for clinical use during the study. Results A total of 284 patients were enrolled, with 197 followed for 18 months (13 died and 26% lapsed during the period). HbA1c was 11.6 +/- 4.5% (sd) at baseline, 8.7 +/- 2.3% at 6 months and 7.7 +/- 2.0% at 18 months. There was a small associated increase in weight but no increase in hypoglycaemia. Subgroup analysis showed that education alone, without drug type or dose changes, also improved control (HbA1c 10.6 +/- 4.2% baseline and 7.6 +/- 2.3% at 18 months). The service was very popular with patients, families and other health workers. CONCLUSIONS: We conclude that a simple protocol and education-based diabetes care system can be successfully introduced and run by nurses in rural Africa. Medium-term glycaemic improvements are excellent and the service has been very well received.

This ethnographic study was carried out in the aftermath of an epidemiological investigation, the first of its kind, on the health and social status of Somalis aged 60 years and over living in Tower Hamlets, east London. The main aims of the study are to explore views on mental health and well‐being and identify sources of stress and support so as to gain greater understanding of background factors of life satisfaction and depression in ‘first‐generation’ older Somali migrants in Tower Hamlets (males). Face‐to‐face interviews were conducted among 28 males in Somali with the help of a bilingual interpreter from the same age, sex and cultural background of participants. Several factors were perceived to decrease life satisfaction and increase vulnerability to depression in male Somalis, in particular low family support in the face of increasing physical disability, loneliness, inadequate access to community services and inability to return home. Social isolation, low level of control over one's life, helplessness and social degradation – ageism, perceived racial/religious discrimination and, to a lesser extent, racial harassment – were common themes identified in people who said to be depressed. Family support was the main buffer against depression; other coping resources were represented by religious practices and reliance on Somali peers. Avoidance coping seemed to encompass denial of depression in participants who had low mood. The study revealed multiple reasons for ill‐being, in particular in people who had high expectations about medical and social care. Low levels of distress were found in Somalis who felt supported by their families. There is a need for social workers and other health professionals to advance discussions of mental‐health issues in the community and for service providers to promote greater access to culturally relevant medical and social services for Somali elders in Tower Hamlets and strengthen their informal support networks.

BACKGROUND: Malaria and HIV are important pediatric problems in sub-Saharan Africa. It is uncertain how HIV-related immunosuppression and malaria interact in children. We aimed to describe associations among HIV status, presentation and outcome from malaria in children from Hlabisa district, KwaZulu-Natal, South Africa, a region of high HIV prevalence and unstable Plasmodium falciparum transmission. METHODS: Consecutive febrile children were screened for malaria with a rapid antigen test. After consent was given, clinical data were recorded, and blood spots were obtained for HIV antibody testing. Cases were managed according to national guidelines. RESULTS: Malaria was diagnosed in 663 children, of whom 10.1% were HIV antibody-positive. Semiquantitative asexual and sexual stage parasitemia densities were unrelated to HIV status. Overall 161 children were hospitalized; 19 (12%) were <1 year old; and 41 (25%) had severe/complicated malaria. Severe disease presented more frequently in HIV antibody-positive than in HIV-uninfected children (P = 0.05), particularly in those >1 year old with coma (P = 0.02) and hypoglycemia (P = 0.05). Receiving parenteral antibiotics was associated with severe disease (odds ratio, 3.0; 95% confidence interval, 1.3 to 6.7) whereas a low white blood cell count (<4 x 10(6)/l) was associated with nonsevere disease (odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Seven children (4.3%) died. Coma, age <1 year and low white blood cell count were the clearest predictors of poor outcome. CONCLUSION: HIV infection was associated with severe/complicated malaria, although the magnitude of the effect may be relatively small. Given that both malaria and HIV are widespread in Africa, even small effects may generate significant morbidity and mortality and major public health consequences.

BACKGROUND: Adults with dual tuberculosis (TB) and HIV infection have a poor outcome. Studies in West Africa suggest that cotrimoxazole prophylaxis may reduce this mortality. OBJECTIVE: To evaluate the effectiveness of cotrimoxazole in reducing mortality in adults with active TB, irrespective of HIV status, in a high prevalence setting. DESIGN: Cohort study using historical controls. METHODS: Adults treated for TB between 1998 and 2000 were traced and vital status at 6 months ascertained (2004: control group). All adults starting treatment for TB between June 2001 and June 2002 were offered cotrimoxazole prophylaxis 960 mg once daily for 6 months during TB treatment irrespective of HIV status (1321: intervention group). Mortality, adverse reactions and adherence were compared between intervention and control groups. RESULTS: HIV seroprevalence in patients with TB at the start of the intervention was estimated to be 78%. Mortality at 6 months was 29% lower in the group given cotrimoxazole than in the control group. The number needed to treat to prevent one death during the period of TB treatment was 24. The benefit was seen across all types of TB but was only evident in new patients; patients being retreated had similar outcomes in both groups. Adverse events were infrequent and minor, with only two participants having treatment stopped for this reason. CONCLUSION: Cotrimoxazole prophylaxis for all adults with TB, irrespective of HIV status, in an area of high HIV seroprevalence may be a feasible, safe and effective way to reduce mortality for the duration of treatment.

The relative contribution of reactivated and recently acquired tuberculosis to the disease burden in developing countries is unknown, as are the settings within which most transmission occurs. In an attempt to answer these questions, we combined molecular techniques (restriction fragment length polymorphism analysis) and conventional epidemiology (risk factor analysis and contact tracing) to study 246 consecutive cases of smear-positive tuberculosis in rural South Africa. We estimate that 29-43% of the cases were recently acquired, as they were clustered. We were unable to identify firm transmission links between 73% of clustered cases. Our findings suggest that most smear-positive tuberculosis in rural Africa is both recently acquired and casually transmitted. Tuberculosis control may depend more on promoting early presentation, rapid diagnosis and vaccine development than on chemotherapy.

OBJECTIVE: To determine the feasibility, accuracy and cost-effectiveness of a rapid, on-site, HIV testing strategy in a rural hospital, and to assess its impact on test turnaround time and the proportion of patients post-test counselled. DESIGN: Prospective comparison of two testing strategies [double rapid test on-site versus central enzyme-linked immunosorbent assay (ELISA)-based testing], and an economic evaluation. SETTING: Hlabisa Hospital, a rural South African district hospital. PATIENTS: A total of 454 consecutive adult inpatients requiring and consenting to HIV testing as part of their clinical management. MAIN OUTCOME MEASURES: Concordance between rapid tests, and between the rapid and ELISA strategies, test turnaround time, proportion of patients post-test counselled, and cost-effectiveness. RESULTS: HIV seroprevalence was 49.6%. Both rapid tests were concordant in all patients [one-sided 95% confidence interval (CI) of probability, 99.3-100]. The rapid strategy was 100% sensitive (95% CI, 97.9-100) and 99.6% specific (95% CI, 97.2-100) compared with the ELISA strategy. The mean interval between ordering a test and post-test counselling fell from 21 days prior to the introduction of the rapid test strategy to 4.6 days after its introduction (P < 0.00001). The proportion of patients post-test counselled increased to 96% from 17% after the introduction of the rapid test strategy (P < 0.00001). By using a double rapid test strategy the cost per patient post-test counselled was almost halved to US$ 11. Accuracy of the rapid strategy was not substantially increased by performing two tests. CONCLUSION: In high prevalence, resource-poor settings, rapid, on-site HIV testing is feasible, accurate and highly cost-effective, substantially increasing the number of patients post-test counselled. A single rapid test may be sufficient.

SETTING: Hlabisa health sub-district, KwaZulu-Natal, South Africa. OBJECTIVE: To describe the establishment of a community-based multidrug-resistant tuberculosis (MDR-TB) treatment programme embedded in the district TB control programme and to evaluate whether early outcomes are comparable to those in the traditional hospital-based model of care. DESIGN: Cases who initiated community-based MDR-TB treatment (CM) between March and December 2008 were compared with patients who initiated MDR-TB treatment under the traditional hospital-based model of care (TM) between January 2001 and February 2008. Time to initiation of treatment and time to sputum smear and culture conversion were compared for the two groups in Kaplan-Meier survival curves using the Mantel-Cox log-rank test. RESULTS: Overall, 50 CM cases and 57 TM cases were included; 39 of the 50 CM cases (78.0%) were human immunodeficiency virus positive. The median time to initiation of treatment was 84 days for CM and 106.5 days for TM (P = 0.002). Median time to sputum smear conversion was shorter for CM than TM (59 vs. 92 days, P = 0.055), as was time to sputum culture conversion (85 vs. 119 days, P = 0.002). CONCLUSION: Community-based treatment for MDR-TB can be implemented within the existing TB control programme in rural South Africa and should be scaled up where resources allow.

In Africa, human immunodeficiency virus (HIV)-associated extrapulmonary tuberculosis (TB) is common and poses diagnostic difficulties. Ultrasound is useful to find suggestive signs such as effusions or abdominal lymphadenopathy. Because trained radiologists are scarce in resource-poor settings, even this simple and relatively inexpensive diagnostic tool is frequently unavailable to patients in district hospitals in sub-Saharan Africa. We developed a focused protocol for assessment with sonography for HIV/TB and trained physicians in a rural district hospital in South Africa. In this pilot study, high levels of confidence in identifying specific signs were rapidly achieved and ultrasound was introduced into routine clinical practice.

OBJECTIVE: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). SETTING: Hlabisa, South Africa. PATIENTS: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. METHODS: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. RESULTS: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P<0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. CONCLUSION: Relapse rates are acceptably low following successful DOT with a twice weekly rifampicin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention.

During a prospective study of 147 patients with snakebite presenting to a rural South African hospital, 13 of 17 patients (76%) treated with South African Institute for Medical Research (SAIMR) polyvalent antivenom experienced potentially severe early (anaphylactoid) reactions. The most common reaction was generalized urticaria (12; 71%), but 3 cases of angio-oedema (18%), 2 of bronchospasm (12%), and 2 of hypotension (12%) were also observed. Reactions were controlled with adrenaline, antihistamines, and resuscitation. All patients fully recovered from envenoming although the full dose of antivenom was not given to most. Indications for the use of this antivenom should be reconsidered and patients should be given antivenom in a high care setting if possible. Use of antivenom by lay people outside hospital should be discouraged and antivenom manufacturing processes could usefully be reviewed.

OBJECTIVE: To investigate the diagnostic value of abdominal ultrasound in HIV-positive inpatients in a rural African setting. METHODS: This was a prospective case series over 3 months of adult HIV-positive patients with symptoms suggestive of abdominal tuberculosis (TB). Diagnostic ultrasound was performed for all patients: sonographic criteria included abdominal lymph node enlargement (>1.5cm) and focal splenic lesions; ascites was a supportive finding. Further diagnostic studies, e.g., aspiration or biopsy were not routinely performed. TB treatment was initiated on the basis of clinical and sonographic features. The patients were contacted after 4 months to evaluate the clinical outcome. RESULTS: One hundred and eighty adult HIV-positive patients were screened; 30 (16.7%) showed sonographic signs of abdominal TB. The median CD4 count was 78 cells/mm(3). Presenting symptoms were weight loss (86.7%), abdominal pain (76.7%), and diarrhea (60%). Abdominal lymph node enlargement was the diagnostic finding in almost all cases (96.7%); hypoechoic lesions of the spleen were seen in 50% and ascites in 73.3%. Follow-up information was available for 25 patients: 24% had died and the remaining 76% reported symptomatic improvement and weight gain. CONCLUSIONS: Characteristic sonographic features of abdominal TB are common in HIV-infected inpatients in a rural African setting. Ultrasound should be introduced into clinical algorithms for the diagnosis of extrapulmonary TB.

BACKGROUND: Despite the advent and increasingly wide availability of antiretroviral therapy, cryptococcal meningitis (CM) remains a significant cause of mortality and morbidity amongst individuals with HIV infection in resource-limited settings. The ideal management of CM remains unclear. The aim of this review is to assess the evidence for deciding on which antifungal regimen to use as well as other modalities of management to utilise especially resource poor settings in order to achieve the best possible outcome and enable an individual with CM to survive their acute illness and benefit from antiretroviral therapy. OBJECTIVES: To determine the most effective initial and consolidation treatment strategy for CM in HIV infected adults. SEARCH STRATEGY: The Cochrane HIV/AIDS group search strategy was used. Key words in the search included, meningitis, cryptococcus neoformans, treatment, trial, human immunodeficiency virus, acquired immunodeficiency syndrome, antifungal agents, amphotericin, flucytosine, fluconazole, azole, lumbar puncture, cerebrospinal fluid (CSF) pressure and acetazolamide. SELECTION CRITERIA: Randomised of HIV-infected adults with a first episode of CM diagnosed on CSF examination, by India ink staining, CSF culture or cryptococcal antigen testing. DATA COLLECTION AND ANALYSIS: Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software. MAIN RESULTS: Six studies are included in the review. Five of the studies compared antifungal treatments and one study addressed lowering intracranial pressure. This study was stopped early due to excess adverse effects. The results of the other five studies as summarised as follows.Mayanja-Kizza 1998 compared fluconazole to fluconazole with 5 flucytosine. The dose of fluconazole used 200mg initially is lower than the recommended initial dose of 400mg. No survival advantage was found with the use of 5 flucytosine in addition to fluconazole.Two studies Brouwer 2004 and van der Horst 1997 compared Amphotericin (AmB) to AmB with 5 flucytosine. Both drugs were given at currently recommended doses for 2 weeks. No survival difference was found at 14 days or at 10 weeks (only recorded in Brouwer 2004). There were significantly more patients with sterile CSF cultures at 14 days in the group that received AmB with flucytosine.Brouwer 2004 compared AmB given alone to AmB given with flucytosine and fluconazole alone or in combination. This was a small study and no differences in mortality were noted between the groups.Bicanic 2008 compared high to standard dose AmB both with flucytosine. There was no difference in mortality between the two groups or adverse events.Leenders 1997 compared standard AmB to liposomal AmB. There was no difference in death rates between the two groups. But there were significantly fewer side effects in the group treated with liposomal AmB. AUTHORS' CONCLUSIONS: The main aim of this review was to determine the best treatment for cryptococcal meningitis in resource-limited settings. In these settings usually only AmB and fluconazole are available. No studies suitable for inclusion in the review were found that compared these two drugs. Therefore we are unable to recommend either treatment as superior to the other. The recommended treatment for CM is a combination of AmB and flucytosine. The optimal dosing of AmB remains unclear. Liposomal AmB is associated with less adverse events than AmB and may be useful in selected patients where resources allow.Future research into the management of cryptococcal meningitis in resource-limited settings should focus on the most effective use of medications that are available in these settings.Flucytosine in combination with AmB leads to faster and increased sterilisation of CSF compared to using AmB alone. As Flucytosine is often not available in developing countries, policy makers and national departments of heath should consider procuring this drug for HIV treatment programmes.