Scale-up of TB and HIV programme collaborative activities in Zambia - a 10-year review.

OBJECTIVE: To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade. METHODS: Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000-2010. RESULTS: The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti-retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV-infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co-trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010. CONCLUSIONS: The scale-up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti-retroviral (ARV) rollout with improved treatment outcomes among TB patients co-infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).

Trials and tribulations of an African-led research and capacity development programme: the case for EDCTP investments.

We describe the initiation and establishment of The University of Zambia - University College London Medical School (UNZA-UCLMS) Research and Training Project, an entirely African scientist-led, south-north partnership. In its 16 year existence, the project, by successfully obtaining competitive grant funding, has transformed itself into one of Africa's most productive African-led R&D programmes with training and visible research outputs. The project serves as a role model and now networks R&D and training activities with six southern African (10 institutions) and six European countries. This project case study illustrates that deep commitment is essential for success and that the factors which facilitate success in R&D in Africa need to be evaluated. The long-term prospects for sustaining the UNZA-UCLMS Project appear bright and are dependent on several factors: the ability to retain trained African scientists; obtaining continued competitive or donor grant funding support; and serious investment by the African governments involved. The recent 255 million Euros EDCTP investment in sub-Saharan Africa through south-north partnerships is expected to enhance existing African-led R&D programmes. African governments and scientists must rise to the challenge.

Disorders of the Basal Ganglia at the University Teaching Hospital; Lusaka

Objective: To determine the frequency of movement disorders among adult ethnic Zambians referred to the University Teaching Hospital (UTH) Lusaka; Zambia and logged as patients with primary neurological disorders. Background: The Human Genome Project data showed that humans are identical across 99.9of their genome. There is considerable evidence that despite being genetically identical; race and ethnicity appears to be an important factor in the prevalence and clinical characteristics of many; if not most; disorders. Literature review clearly shows that ethnicity has an essential role in the phenotypic expression of many movement disorders and their prevalence appears to be lowest amongst Africans. Patients and setting: Patients attending the neurology clinic and admitted to the UTH with various neurological disorders for 5 years (January 1999-January 2004) were analysed. We evaluated patients whose symptoms met the appropriate diagnostic criteria for movement disorders and experienced symptoms at least for three days. Results: Records were available for 4654 patients with various neurological disorders attending neurological clinic. Of the total number of patients seen; 163 (3.5) satisfied the criteria for movement disorders. The most frequent syndromes of the basal ganglia were: Parkinson's disease (31); tremor (24); chorea (20); and dystonia (16.5). Myoclonus; tic; tardive dyskinesia; and other movement disorders (8.5) were rare in adult Zambian patients. In 25 patients (11.3) akinetic-rigid syndromes and hyperkinetic movement disorders were manifestations of HIV/AIDS. Conclusions: Among patients referred for neurological services at Zambia's tertiary care teaching facility; movement disorders are relatively rare. Our study may seem to suggest that Parkinson's disease is one of the commonest movement disorders though further studies are needed to explore the role of genetics and ethnicity in the prevalence of these disorders. The presence of HIV/AIDS and its contribution to movement disorders needs to be studied further

Tuberculosis in children with human immunodeficiency virus infection.

For a number of reasons--but especially the human immunodeficiency virus (HIV) epidemic--tuberculosis (TB) is currently increasing in many parts of the world where it threatens the lives of millions of infants and children. The diagnosis of childhood TB, which has always been difficult, is now even more challenging in infants and children co-infected with HIV and Mycobacterium tuberculosis. Both TB and HIV infection require multiple drugs for effective treatment and to prevent the development of resistance by the infecting agents. Drug-drug interactions are therefore common, and knowledge of these is essential in the management of dually infected infants and children. Due to problems with drug toxicity and the need for prolonged treatment, compliance is also a major issue in these children. Chemoprophylaxis against TB in HIV-infected children needs further research, as do the pharmacokinetics of antiretroviral drugs in children. Integrated management of children co-infected with TB and HIV should be encouraged, especially in resource-poor settings.

Study of familial Parkinson's disease in Russia, Uzbekistan, and Zambia.

OBJECTIVE: The aims of this study were (A) to determine inheritance patterns of familial Parkinson's disease in three different geographical areas (Russia, Uzbekistan, and Zambia); (B) compare clinical characteristics of familial with sporadic Parkinson's disease; and (C) assess whether there were ethnic differences in clinical manifestations of the disease. METHODS: Fifty two index cases of familial Parkinson's disease in Moscow, 55 in Tashkent, and 27 in Lusaka were selected on the basis of the typical clinical features of Parkinson's disease with a familial history. The sex ratio, transmission patterns, and segregation ratio were determined by pedigree analysis. RESULTS: Familial Parkinson's disease was found in all three countries (30 families in Russia, 12 in Uzbekistan, and seven in Zambia), and appeared more common in Russia. Both autosomal dominant and autosomal recessive patterns of inheritance were seen, but autosomal dominance was more common in all countries. CONCLUSIONS: In all three countries men have a higher risk of developing Parkinson's disease than women and there are ethnic differences in clinical manifestations of the disease. The onset of both familial and sporadic Parkinson's disease in Zambian patients occurs at a younger age and is associated with slow progression and a benign course, and generally responds well to levodopa treatment.

The relentless spread of tuberculosis in Zambia--trends over the past 37 years (1964-2000).

OBJECTIVE: To review trends in the rates of tuberculosis (TB) case notifications over a 37-year period. DESIGN: A retrospective study of Ministry of Health records on TB notifications between 1 January 1964 and 31 December 2000. SETTING: Zambia, sub-Saharan Africa. METHODS: Retrospective analysis of case-notification data for TB of the Zambia Ministry of Health annual returns. OUTCOME MEASURES: Annual TB case-notification rates and trends over the past 37 years. RESULTS: TB case-notification data from 1964 to 2000 show a 12-fold increase over the past two decades, and apparent gains in controlling TB seen in the 1960s and 1970s have been reversed over the past two decades. A stable situation during the period 1964-1984 (case-notification rate remained around 100 per 100,000 population) was followed by an exponential increase since the mid-1980s. The absolute number of new TB cases increased from 8,246 in 1985 (124/100,000) to 38,863 (409/100,000) in 1996 and 52,000 (512/100,000) in 2000. Comparison of case-notification rates over the past 2 decades with neighbouring countries (Zimbabwe, Malawi and Tanzania) show that Zambia has one of the highest case-notification rates in the region. CONCLUSIONS: Zambia, like many countries in Africa, is in the midst of a serious TB epidemic and there are no signs that it is abating. This increase was most likely due to the impact of the HIV/AIDS epidemic and subsequent breakdown of TB services. Concerted donor-government efforts should invest appropriately in long-term plans for TB control.

Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions.

SETTING: Inpatient medical wards, Department of Medicine, University Teaching Hospital, Lusaka, Zambia. OBJECTIVE: To define the natural history, clinical presentation, and management outcome of microbiologically confirmed cryptococcal meningitis in adult AIDS patients treated under local conditions where antifungal and antiretroviral therapies are not routinely available. DESIGN: A descriptive, longitudinal, observational study. METHODS: All adult patients admitted to the medical wards of the University Teaching Hospital, Lusaka, Zambia with cerebrospinal fluid culture proved, primary cryptococcal meningitis, during a 12 month period were enrolled into the study. The following details were acquired: clinical features, HIV status, laboratory data, treatment accorded, and survival. RESULTS: A total of 230 patients with primary cryptococcal meningitis were studied (median age 32 years; range 15-65 years; 112 males, 118 females). Cryptococcal meningitis was the first AIDS defining illness in 210 (91%) patients. One hundred and thirty of the 230 (56%) patients had received treatment with fluconazole monotherapy and 100 (43%) patients received palliative care only without any antifungal therapy. A 100% case fatality rate was observed in both groups at follow up: by seven weeks in the untreated group and at six months in the fluconazole treated group. The cumulative median survival from time of diagnosis was 19 days (range 1-164 days) for the fluconazole treated group and 10 days (range 0-42 days) for the untreated group. CONCLUSION: Cryptococcal meningitis, under current treatment accorded at the University Teaching Hospital, Lusaka, has a 100% mortality in young Zambian adults with AIDS. The current treatment accorded to Zambian adults with cryptococcal meningitis is inappropriate. An urgent need exists to improve strategies for the clinical management of AIDS patients in poor African countries. The wider ethical and operational issues of making available antifungals to African AIDS patients are discussed.

Helicobacter pylori infection in an urban African population.

We have studied 221 adults drawn from an impoverished urban population with high human immunodeficiency virus (HIV) seroprevalence (35%) to determine the prevalence of gastroduodenal pathology and its relationship to serological markers of Helicobacter pylori virulence proteins and other potential environmental and immunological determinants of disease including HIV infection. Eighty-one percent were H. pylori seropositive, and 35% were HIV seropositive. Urban upbringing and low CD4 count were associated with a reduced likelihood of H. pylori seropositivity, as was current Ascaris infection, in keeping with recent evidence from an animal model. One hundred ninety-one adults underwent gastroduodenoscopy, and 14 had gastroduodenal pathology. Mucosal lesions were a major cause of abdominal pain in this population. While the majority of patients with gastroduodenal pathology (12 of 14) were seropositive for H. pylori, none were seropositive for HIV. Smoking was associated with increased risk of macroscopic pathology, and a history of Mycobacterium bovis BCG immunization was associated with reduced risk. Antibodies to H. pylori lipopolysaccharide were associated with pathology. HIV infection was associated with protection against mucosal lesions, suggesting that fully functional CD4 lymphocytes may be required for the genesis of gastroduodenal pathology.

Four-year study of abdominal ultrasound in 900 Central African adults with AIDS referred for diagnostic imaging.

BACKGROUND: In the majority of sub-Saharan African countries, the absence of computed tomography facilities makes abdominal ultrasound (US) an alternative diagnostic tool in the clinical investigation of infectious and noninfectious complications of human immunodeficiency virus (HIV)-infected individuals. We studied the abdominal US findings in Central African adult AIDS patients to determine whether the findings were consistent between different population groups and neighboring countries. We performed a longitudinal study of AIDS patients and age- and sex-matched HIV-negative adults referred for abdominal US at two tertiary referral city hospitals: the Gecamines Sendwe Hospital (GSH), Lubumbashi, Congo, and the University Teaching Hospital (UTH), Lusaka, Zambia. METHODS: Between 1992 and 1996, abdominal US findings in 900 adults (300 Congolese adults from GSH and 600 Zambian adults from UTH; age range = 15-55 years) with a diagnosis of AIDS referred for diagnostic imaging from the inpatient medical wards were recorded; 900 abdominal ultrasound findings from age and sex-matched HIV-negative adults were studied for comparative purposes. RESULTS: Abdominal US for diagnostic purposes in AIDS patients is requested by clinicians for a range of primary clinical indications: abdominal pain, fever of unknown origin, hepatosplenomegaly, lymphadenopathy, and abnormal liver function tests. Compared with the HIV-individuals, the AIDS group of patients had a significantly higher proportion of splenomegaly (35% vs. 24%; p < or = 0.001), hepatomegaly (35% vs. 22%; p = 0.001), lymphadenopathy (31% vs. 11%; p < or = 0.001), biliary tract abnormalities (25% vs. 12%; p < or = 0.001), gut wall thickening (15% vs. 5%; p < or = 0.001), and ascites (22% vs. 9%; p < or = 0.001). There were no differences in renal tract and pancreatic abnormalities between the AIDS and HIV-groups. There were significantly fewer gallstones in the AIDS group (23% vs. 75%; p < or = 0.001). These patterns of abdominal US abnormalities were consistent across both hospitals. CONCLUSIONS: Diagnostic imaging by abdominal US is commonly used in the management of a variety of clinical indications in Central Africa. The changes seen on abdominal US in AIDS patients appear uniform across the two countries in Central Africa. These findings may have implications for the radiologist, especially in developing countries, where accurate microbiological or pathologic diagnosis of infectious and noninfectious diseases afflicting the HIV-infected patient is often not possible and US is sometimes relied upon as a "diagnostic" investigation by many physicians. Further studies are required to define patterns of clinical findings, plain films, and pathologic and laboratory correlates with US to develop and refine diagnostic algorithms for clinical use in resource-poor countries.

A study of maternal mortality at the University Teaching Hospital, Lusaka, Zambia: the emergence of tuberculosis as a major non-obstetric cause of maternal death.

SETTING: The Department of Obstetrics and Gynaecology, University Teaching Hospital, Lusaka, Zambia. OBJECTIVES: To ascertain 1) the non-obstetric causes of maternal mortality, 2) the importance of tuberculosis as a cause of maternal deaths, and 3) the trends in the aetiology of non-obstetric causes of maternal deaths during the past decade in the light of the human immunodeficiency virus epidemic. DESIGN: A 2-year retrospective study of the aetiology of all maternal deaths occurring at the University Teaching Hospital (UTH), Lusaka, Zambia between 1 January 1996 and 31 December 1997. Comparison of these data with available data published between 1974 and 1989. RESULTS: There were 251 maternal deaths recorded during the study period. Of these, 106 (42%) were due to direct (obstetric) causes and 145 (58%) were due to indirect (non-obstetric) causes. Malaria (30%), tuberculosis (25%) and unspecified chronic respiratory tract infections (22%) accounted for 77% of non-obstetric causes of maternal deaths and 44% of all causes of maternal deaths. The diagnosis of AIDS was closely linked with that of tuberculosis (92% of cases), and unspecified chronic respiratory illnesses (97%), but not with malaria (37%). The maternal mortality ratio for UTH was calculated at 921 per 100,000 live births, a significant increase from the 118 noted in 1982 and 667 in 1989. CONCLUSIONS: Despite improved obstetric services, the maternal mortality ratios at UTH, Lusaka, have increased eight-fold over the past two decades. This dramatic increase is mainly due to non-obstetric causes of death. Malaria and AIDS-associated tuberculosis and unspecified 'chronic respiratory illnesses' are now major causes of maternal death in Zambia. Greater emphasis is urgently required on early detection, accurate diagnosis, treatment and prevention of malaria and tuberculosis in pregnancy. Further definition of chronic 'unspecified' respiratory illnesses is also required.

Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.

BACKGROUND: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions. METHODS: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB. RESULTS: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group. CONCLUSION: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.