Surgical pathology in sub-Saharan Africa--volunteering in Malawi

The breadth of material found in surgical pathology services in African countries differs from the common spectrum of "the West". We report our experience of a voluntary work in the pathology departments of Blantyre and Lilongwe, Malawi. During a 6-week period, 405 cases (378 histology and 27 cytology cases) were processed. The vast majority showed significant pathological findings (n = 369; 91.1 %): 175 cases (47.4 %) were non-tumoral conditions with predominance of inflammatory lesions, e.g., schistosomiasis (n = 11) and tuberculosis (n = 11). There were 39 (10.6 %) benign tumors or tumor-like lesions. Intraepithelial neoplasia of the cervix uteri dominated among premalignant conditions (n = 15; 4.1 %). The large group of malignancies (n = 140; 37.9 %) comprised 11 pediatric tumors (e.g., rhabdomyosarcoma, small blue round cell tumors) and 129 adult tumors. Among women (n = 76), squamous cell carcinomas (SCCs) of the cervix uteri predominated (n = 25; 32.9 %), followed by breast carcinomas (n = 12; 15.8 %) and esophageal SCC (n = 9; 11.8 %). Males (n = 53) most often showed SCC of the esophagus (n = 9; 17.0 %) and of the urinary bladder (n = 7; 13.2 %). Lymphomas (n = 7) and Kaposi's sarcomas (n = 6) were less frequent. Differences compared to the western world include the character of the conditions in general, the spectrum of inflammatory lesions, and the young age of adult tumor patients (median 45 years; range 18-87 years). Providing pathology service in a low-resource country may be handicapped by lack of personnel, inadequate material resources, or insufficient infrastructure. Rotating volunteers offer a bridge for capacity building of both personnel and the local medical service; in addition, the volunteer's horizons are broadened professionally and personally.

Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis

Objectives  To assess the proportion of patients lost to programme (died, lost to follow-up, transferred out) between HIV diagnosis and start of antiretroviral therapy (ART) in sub-Saharan Africa, and determine factors associated with loss to programme. Methods  Systematic review and meta-analysis. We searched PubMed and EMBASE databases for studies in adults. Outcomes were the percentage of patients dying before starting ART, the percentage lost to follow-up, the percentage with a CD4 cell count, the distribution of first CD4 counts and the percentage of eligible patients starting ART. Data were combined using random-effects meta-analysis. Results  Twenty-nine studies from sub-Saharan Africa including 148 912 patients were analysed. Six studies covered the whole period from HIV diagnosis to ART start. Meta-analysis of these studies showed that of the 100 patients with a positive HIV test, 72 (95% CI 60-84) had a CD4 cell count measured, 40 (95% CI 26-55) were eligible for ART and 25 (95% CI 13-37) started ART. There was substantial heterogeneity between studies (P < 0.0001). Median CD4 cell count at presentation ranged from 154 to 274 cells/μl. Patients eligible for ART were less likely to become lost to programme (25%vs. 54%, P < 0.0001), but eligible patients were more likely to die (11%vs. 5%, P < 0.0001) than ineligible patients. Loss to programme was higher in men, in patients with low CD4 cell counts and low socio-economic status and in recent time periods. Conclusions  Monitoring and care in the pre-ART time period need improvement, with greater emphasis on patients not yet eligible for ART.

Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America

OBJECTIVES: To describe temporal trends in baseline clinical characteristics, initial treatment regimens and monitoring of patients starting antiretroviral therapy (ART) in resource-limited settings. METHODS: We analysed data from 17 ART programmes in 12 countries in sub-Saharan Africa, South America and Asia. Patients aged 16 years or older with documented date of start of highly active ART (HAART) were included. Data were analysed by calculating medians, interquartile ranges (IQR) and percentages by regions and time periods. Not all centres provided data for 2006 and 2005 and 2006 were therefore combined. RESULTS: A total of 36,715 patients who started ART 1996-2006 were included in the analysis. Patient numbers increased substantially in sub-Saharan Africa and Asia, and the number of initial regimens declined, to four and five, respectively, in 2005-2006. In South America 20 regimes were used in 2005-2006. A combination of 3TC/D4T/NVP was used for 56% of African patients and 42% of Asian patients; AZT/3TC/EFV was used in 33% of patients in South America. The median baseline CD4 count increased in recent years, to 122 cells/microl (IQR 53-194) in 2005-2006 in Africa, 134 cells/microl (IQR 72-191) in Asia, and 197 cells/microl (IQR 61-277) in South America, but 77%, 78% and 51%, respectively, started with <200 cells/microl in 2005-2006. In all regions baseline CD4 cell counts were higher in women than men: differences were 22cells/microl in Africa, 65 cells/microl in Asia and 10 cells/microl in South America. In 2005-2006 a viral load at 6 months was available in 21% of patients Africa, 8% of Asian patients and 73% of patients in South America. Corresponding figures for 6-month CD4 cell counts were 74%, 77% and 81%. CONCLUSIONS: The public health approach to providing ART proposed by the World Health Organization has been implemented in sub-Saharan Africa and Asia. Although CD4 cell counts at the start of ART have increased in recent years, most patients continue to start with counts well below the recommended threshold. Particular attention should be paid to more timely initiation of ART in HIV-infected men.

Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality

BACKGROUND: Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa. METHODS AND FINDINGS: Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77). CONCLUSIONS: Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

Paediatric antiretroviral treatment programmes in sub-Saharan Africa: a review of published clinical studies

Knowledge of the experience and outcomes of current paediatric antiretroviral treatment (ART) programmes in sub-Saharan Africa can inform new programmes in the region as well as enhance existing ones. This is urgently needed to facilitate the scale-up of treatment, which is needed to address the burden of paediatric HIV cases on the continent. We reviewed the characteristics and outcomes of programmes with clinical paediatric ART studies published prior to 1 January 2008. The outcomes of the studies were comparable to similar ones from developed countries; however, the duration of follow-up was relatively limited in almost all the studies reviewed. One-year survival probability was between 84% and 91%, and considerable improvement in the clinical, immunologic and iral status of the paediatric patients was generally recorded. Loss to follow-up was less than 10% in all but two studies. Adherence to treatment was good and few adverse events were reported. This is despite the fact that many programmes were subject to enormous constraints in terms of health services, and despite widespread use of adult fixed-dose combinations for paediatric patients, including young infants. While the majority of children commencing ART were severely ill, most children were old (median age >5 years for almost all studies) with relatively few infants and young children (age <2 years) receiving treatment. This is in contrast to knowledge of rapid disease progression in the majority of HIV-infected infants and despite the World Health Organization’s recent recommendations to commence ART in all HIV-infected infants less than one year old. There is an urgent need to address barriers to ART for infants. Studies of the outcomes of programmes treating infants as well as those with longer-term follow-up are also needed.

A survey of paediatric HIV programmatic and clinical management practices in Asia and sub-Saharan Africa--the International epidemiologic Databases to Evaluate AIDS (IeDEA)

INTRODUCTION There are limited data on paediatric HIV care and treatment programmes in low-resource settings. METHODS A standardized survey was completed by International epidemiologic Databases to Evaluate AIDS paediatric cohort sites in the regions of Asia-Pacific (AP), Central Africa (CA), East Africa (EA), Southern Africa (SA) and West Africa (WA) to understand operational resource availability and paediatric management practices. Data were collected through January 2010 using a secure, web-based software program (REDCap). RESULTS A total of 64,552 children were under care at 63 clinics (AP, N=10; CA, N=4; EA, N=29; SA, N=10; WA, N=10). Most were in urban settings (N=41, 65%) and received funding from governments (N=51, 81%), PEPFAR (N=34, 54%), and/or the Global Fund (N=15, 24%). The majority were combined adult-paediatric clinics (N=36, 57%). Prevention of mother-to-child transmission was integrated at 35 (56%) sites; 89% (N=56) had access to DNA PCR for infant diagnosis. African (N=40/53) but not Asian sites recommended exclusive breastfeeding up until 4-6 months. Regular laboratory monitoring included CD4 (N=60, 95%), and viral load (N=24, 38%). Although 42 (67%) sites had the ability to conduct acid-fast bacilli (AFB) smears, 23 (37%) sites could conduct AFB cultures and 18 (29%) sites could conduct tuberculosis drug susceptibility testing. Loss to follow-up was defined as >3 months of lost contact for 25 (40%) sites, >6 months for 27 sites (43%) and >12 months for 6 sites (10%). Telephone calls (N=52, 83%) and outreach worker home visits to trace children lost to follow-up (N=45, 71%) were common. CONCLUSIONS In general, there was a high level of patient and laboratory monitoring within this multiregional paediatric cohort consortium that will facilitate detailed observational research studies. Practices will continue to be monitored as the WHO/UNAIDS Treatment 2.0 framework is implemented.

Integrating mitigation and adaptation into development: the case of Jatropha curcas in sub-Saharan Africa

Editorial

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis

OBJECTIVES Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. METHODS We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. RESULTS Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. CONCLUSIONS Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.