Results from the first 30 months of national sentinel surveillance for influenza in Tanzania, 2008-2010.

Limited data exist on the burden of influenza in developing countries. In 2008, in order to better understand the epidemiology of influenza virus infection in Tanzania, the Tanzanian Ministry of Health and Social Welfare created a sentinel surveillance system for influenza. At 5 hospitals across the country, patients with influenza-like illness (ILI) and severe acute respiratory illness (SARI) had oropharyngeal and nasopharyngeal samples collected. At the National Influenza Center in Dar es Salaam, specimens were tested for influenza using real-time polymerase chain reaction tests. From May 2008 through November 2010, a total of 1794 samples were collected from 5 sentinel sites, of which 61% were from patients with ILI and 39% were from patients with SARI. Of all ILI and SARI samples, 8.0% were positive for influenza; 6.9% yielded influenza A virus, and 1.1% yielded influenza B virus. Most influenza A virus was subtype H3, which circulated in nearly every month of 2010. The proportion of influenza-positive cases was similar among ILI (8.5%) and SARI (7.3%) patients (P = .39). In multivariate logistic regression, influenza-positive SARI cases were more likely than influenza-negative SARI cases to have had rhonchi (adjusted OR [aOR], 2.31; 95% confidence interval [CI], 1.14-4.67), nasal discharge (aOR, 4.57; 95% CI, 1.30-16.10), and stridor (aOR, 2.63; 95% CI, 1.17-5.90). Influenza-positive ILI patients had a longer duration of fever on presentation, compared with influenza-negative ILI patients (median, 4 vs 3 days; P = .004). Otherwise, there was no difference in signs or symptoms among influenza-positive and influenza-negative ILI patients. During 2.5 years of surveillance for influenza at 5 geographically disbursed sites in Tanzania, we found that influenza circulated year-round. Surveillance should continue in order to fully understand the seasonality and epidemiology of influenza in Tanzania.

Antituberculosis drug resistance and anonymous HIV surveillance in tuberculosis patients in Botswana, 2002.

Two surveys undertaken in Botswana in the 1990s have recorded low rates of antituberculosis drug resistance, despite a three-fold rise in tuberculosis since 1989. We undertook a third survey to determine both trends since 1995 and HIV prevalence in tuberculosis patients in Botswana. Sputum specimens were obtained from patients nationwide in 2002 who also underwent anonymous, rapid HIV testing by use of Oraquick. Of 2200 sputum smear-positive patients and 219 previously treated patients with suspected recurrent tuberculosis, 1457 (60%) were infected with HIV. Resistance to at least one drug in new patients rose from 16 (3.7%) isolates in 1995 to 123 (10.4%; p<0.0001) in 2002. Interventions for tuberculosis control are urgently needed in Botswana to prevent further emergence of drug resistance.

Etiology of pulmonary infections in predominantly HIV-infected adults with suspected tuberculosis, Botswana.

SETTING: In countries with high HIV rates, diagnosis of lower respiratory disease etiology is both challenging and clinically important. OBJECTIVE: To determine the etiology of lower respiratory tract disease among persons with suspected tuberculosis (TB) and abnormal chest X-rays in a setting with very high HIV seroprevalence. DESIGN: Cross-sectional prevalence data from a prospective cohort of predominantly hospitalized adults with suspected TB in Botswana, January-December 1997. RESULTS: Of 229 patients, 86% were HIV-positive and 71% had a pathogen identified. TB was confirmed in 52%, 17% had acute mycoplasma pneumonia, 3% had Pneumocystis carinii, 27% grew a bacterial pathogen from sputum and 8% from blood. Ninety-four per cent of TB diagnoses were made through expectorated sputum and only 5% of TB cases were diagnosed by sputum induction alone. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis had positive and negative predictive values of 94% and 59%, respectively. Male sex, cough < 2 weeks, and tuberculin skin test > or = 5 mm were independently associated with culture-positive TB among persons with negative acid-fast bacilli smears. Co-infection with two or more pathogens occurred in 25%. CONCLUSIONS: Mycoplasma pneumoniae infection was quite common despite clinical suspicion of TB, and sputum induction and PCR did not significantly improve our ability to diagnose TB, although clinical presentation had some predictive value.

Control of anti-tuberculosis drug resistance in Botswana.

SETTING: Botswana, where in 2000 the prevalence of human immunodeficiency virus (HIV) infection among adults was 38%, and the tuberculosis (TB) rate was 591/100,000. A 1995-1996 survey demonstrated low levels of anti-tuberculosis drug resistance. OBJECTIVE: Because TB drug resistance may increase rapidly in HIV-infected populations, a second survey was undertaken in 1999 to determine any increase in anti-tuberculosis drug resistance. DESIGN: Sputum specimens positive for acid-fast bacilli from patients without prior TB treatment (new patients), and all sputum specimens from patients reporting prior TB treatment (retreatment patients) were collected nationwide. Specimens were cultured for Mycobacterium tuberculosis and tested for resistance to isoniazid, rifampicin, ethambutol, and streptomycin. RESULTS: From January to May 1999, 783 patients were consecutively enrolled from all districts. Of these, 483 (61.7%) were male, the median age was 33 years, and 82% were new patients. Drug resistance occurred in 6.3% of new patients (95 % confidence interval [CI] 4.6-8.6) and 22.8% of retreatment patients (95% CI 16.5-30.1). Resistance to at least isoniazid and rifampicin was found in 0.5% of new (95% CI 0.1-1.3) and 9.0% of retreatment patients (95% CI 5.1-14.5). CONCLUSION: Anti-tuberculosis drug resistance remains relatively low in Botswana, probably as a result of a well-functioning TB program. Periodic surveys will be essential to adequately determine any significant trend.

Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana.

OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana. DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection. METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results. Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed. A positive test was defined as > or = 10 mm induration. Skin test results were compared with results obtained from a population survey of children of similar age from the same community. RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005). Of the infected children, 22 (78.6%) were contacts of a close female relative. The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001). In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006). CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M. tuberculosis during the era of HIV. However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS.

Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients.

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.

DNA fingerprinting of a national sample of Mycobacterium tuberculosis isolates, Botswana, 1995-1996.

DNA fingerprinting may be useful to elucidate tuberculosis (TB) transmission in community settings, but its utility is limited if only few fingerprint patterns are observed or band numbers are low. We performed DNA fingerprinting on a national, population-based sample of Mycobacterium tuberculosis isolates from Botswana. During 1995-1996, a random sample of 213 isolates, representing 5% of all smear-positive TB cases, underwent DNA fingerprinting using restriction fragment length polymorphism (RFLP) IS6110 analysis. Eighty-two (38%) of the 213 isolates belonged to one of 18 clusters, with 2-9 isolates/cluster. The median number of bands was 10 (range 1-19); 183 (86%) had six or more bands. Sixty-three (49%) of 128 patients tested were infected with the human immunodeficiency virus (HIV). The degree of RFLP pattern heterogeneity and high band number support the feasibility of a prospective DNA fingerprinting study in Botswana.

Low levels of drug resistance amidst rapidly increasing tuberculosis and human immunodeficiency virus co-epidemics in Botswana.

SETTING: Botswana, southern Africa, where the tuberculosis (TB) case rate increased by 120% from 1989 to 1996 in spite of a decade of implementation of the directly observed therapy, short-course (DOTS) strategy. OBJECTIVE: To determine prevalence of and risk factors for drug-resistant tuberculosis in an epidemic setting. DESIGN: Systematic national random survey of newly diagnosed pulmonary TB and all patients with TB requiring retreatment during 1995-1996. Interviews were conducted, human immunodeficiency virus (HIV) testing was offered, and drug susceptibility testing was performed for isoniazid, rifampicin, streptomycin and ethambutol. RESULTS: Resistance to at least one drug was identified in 16 (3.7%) new cases and 18 (14.9%) retreatment cases. One (0.2%) new and seven (5.8%) retreatment cases had resistance to at least both isoniazid and rifampicin (multidrug-resistant TB). Retreatment cases with multidrug-resistant TB were significantly more likely to have worked in the mines in South Africa than were cases with fully susceptible isolates (6/7 [85.7%] versus 32/ 103 [31.1%], odds ratio 13.3, 95% confidence interval 1.5-311.0, P = 0.007). Of 240 patients tested for HIV, 117 (48.8%) were positive; prevalence was similar among new and retreatment cases, and was not a risk factor for drug resistance in either group. CONCLUSION: During the HIV and TB co-epidemics in sub-Saharan Africa, DOTS may help to control drug-resistant TB. However, the TB case rate can be expected to continue to climb in spite of the implementation of the DOTS strategy.

DNA fingerprinting and phenotyping of Mycobacterium tuberculosis isolates from human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients in Tanzania.

With the purpose of determining whether the risk of infection with a particular clone of Mycobacterium tuberculosis is influenced by the human immunodeficiency virus (HIV) status of the host, we analyzed and compared 68 mycobacterial isolates obtained from HIV-seropositive patients with tuberculosis (TB) in Dar es Salaam, Tanzania, with 66 mycobacterial isolates obtained from HIV-seronegative patients with TB in the same geographical region by using both DNA fingerprinting and classical phenotyping methods. One hundred one different IS6110 fingerprinting patterns were observed in the 134 isolates. The level of diversity of the DNA fingerprints observed in the HIV-seropositive group was comparable to the level of the diversity observed in the HIV-seronegative group. Resistance to a single anti-TB drug was found in 8.8% of the tested isolates, and 3.2% of the isolates were resistant to more than one anti-TB drug. The drug susceptibility profiles were not significantly difference between the two groups of isolates compared in the present study. Phenotypic characteristics which classify M. tuberculosis strains as belonging to the Asian subgroup correlated with a low IS6110 copy number per isolate. However, the occurrence of Asian subgroup strains was not associated with the HIV status of the patients. The results of the study suggested an equal risk of infection with a defined M. tuberculosis clone for HIV-seropositive and HIV-seronegative individuals.