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Cutaneous Anthrax outbreak in Chama District, Muchinga province, Zambia, 2016 as history repeats itself

P Mwambi1, J Mufunda1, P Mwaba2, N Kasese-Chanda2, CM Mumba2, T Kalumbi2,  M Chaula2, N Mweemba1, MB Hang’ombe3, H Higashi4, R Akamatsu4, ML Mazaba1,5
1.World Health Organization, Lusaka, Zambia
2.Ministry of Health, Lusaka, Zambia
3.Center for Zoonoses Control, University of Zambia, Lusaka, Zambia
4.Hokkaido University Research Center for Zoonosis Control, Global COE Program,Kita-ku, Sapporo, Japan
5.University Teaching Hospital, Lusaka, Zambia
Correspondence: Patricia Mwambi (mwambip@who.int)

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Mwambi PEM, Mufunda J, Mwaba P, Kasese-Chanda N, Mumba CM, Kalumbi T, et al. Cutaneous Anthrax outbreak in Chama District, Muchinga province, Zambia, 2016 as history repeats itself. Health Press Zambia Bull. 2017;1(1) pp38-49

An outbreak of anthrax has been confirmed in Chama district in Zambia affecting close to 80 persons. A previous outbreak in the same area was confirmed in 2011 with 521 humans affected and 6 human and over 80 hippos dead. To understand the disease situation and provide technical support the Ministry of Health in collaboration with the World Health Organization (WHO) in Zambia and Center for Zoonoses control University of Zambia investigated the outbreak in various villages. The index case, a 22-year-old male presented at Pondo rural health centre with eschar invariably accompanied by oedema on the cheek with onset 22nd September 2016. More patients mostly below 20 years of age from five RHCs were seen thereafter with varied lesions papules, vesicles and eschars and treated with ciprofloxacin. Most patients were associated with eating hippo meat. Various interventions were put in place to control the outbreak including case detection, case management, contact tracing and community awareness. Field investigations observed dead carcasses of Hippo and Buffalo. Bacillus anthracis was isolated from humans, buffalo, hippo and the environment confirming the outbreak link to Anthrax infection suggesting the need to strengthen surveillance, diagnosis, community sensitization and treatment of affected persons for effective disease control. The rapid response by the Ministry of Health, WHO Zambia, Center for Zoonosis Control, and  ZAWA necessitated by the availability of financial resources provided by MOH and WHO Zambia contributed significantly to the timely containment of the outbreak and avoidance of any fatalities.


 

Introduction

Anthrax is a zoonotic disease with its natural reservoirs being hoofed animals that are known to carry the Bacillus anthracis. Most commonly it is found in grazing herbivores such as cattle, sheep, goats, camels, horses, and pigs [1], but has also been associated with transmission from wildlife to humans by various modes, notably buffalo and hippos in Zambia [2,3]. It is a serious bacterial infection caused by Bacillus anthracis that occurs primarily in animals. Cattle, sheep, horses, mules, and some wild animals are highly susceptible [4]. Humans become infected when the spores of Bacillus anthracis enter the body by contact with animals infected with Bacillus anthracis or from contact with contaminated animal products, insect bites, ingestion, or inhalation [5].

The developed world has no or lower incidence of anthrax infection, meanwhile it continues to be a problem of public health concern in the developing world and countries that do not have veterinary public health programs that routinely vaccinate animals against anthrax [6]. Continued outbreaks in areas with previous outbreaks may occur because anthrax spores survive for decades, even under adverse conditions, contaminating the soil [7]. Anthrax infections in humans occur in three forms including cutaneous, gastrointestinal and pulmonary depending on route of exposure, with up to 95 % being cutaneous [8, 9].

Cutaneous infections initially appear as painless, itchy papules on the face, neck, forearms or hands and ulcerate within 7 to 10 days. These subsequently form a black painless eschar. The patient may also incur localised swelling, usually of the face and neck, with painful swollen lymph nodes and systematic symptoms. Literature reveals no human to human spread, no racial, sexual or age association with the disease, although commonly among young and middle ages as it is often related to industrial exposures, way of life and livestock farming [6]. A well managed outbreak with appropriate therapy will reduce and even exclude fatalities.

Zambia has had outbreaks of anthrax in human and animal populations with previous studies showing that clostridia infections and anthrax outbreaks are higher in the Western Province and Luangwa valley than the rest of the country [10-12]. Confirmed outbreaks affecting cattle in Western province from 1989-1995, in which 1,626 suspected cases of anthrax were identified, 51 cases were confirmed with Bacillus anthracis infection. During the 1990 outbreak alone, 220 cases of human anthrax cases and 248 human cases during 1991-1998 were confirmed with 19.1% and 7.7% case fatality rates, respectively [13].

Recurrence of anthrax outbreaks have been linked to various ecological factors such as cycles of heavy rainfall followed by periods of dry weather, high evaporation potential of flood water, the presence of calcareous soils and ambient temperatures above 15.5 degrees [14-16]. The Anthrax spores are very resistant, remaining dormant and viable in nature for >100 years [2]. Chama district recorded an outbreak of anthrax in August 2011 that saw over 80 hippopotamuses die after showing signs of infection with Bacillus anthracis, followed by 521 suspected human cases resulting in six human community deaths associated with Bacillus anthracis infection  and about 80 hippopotamus deaths [3, 17].  Five years later, Muchinga Provincial Medical Office received a report of a suspected anthrax outbreak on 27th September 2016 in the southern part of Chama district, recording up-to 79 human cases and 25 animals including hippos and buffalos by end of October 2016. A quick response team consisting of surveillance officers, epidemiologists, clinicians, laboratory scientists, veterinary staff and health promotion staff from the Ministry of Health, the World Health Organization in Zambia, Center for Zoonoses control University of Zambia, the Ministry of Fisheries and Livestock (MFL) as well as National Parks and Wildlife (NPW) investigated and provided technical support in managing the outbreak

Methods

A descriptive cross sectional study of a recent outbreak in Chama was undertaken. The outbreak response team reviewed case records at the local facilities, undertook field visitations to affected areas and conducted interviews with health providers, NPW staff at the camps, village scouts, individual clients, Community Based Volunteers (CBVs), community leaders, school teachers/pupils and community members and visited the risk areas, that is, Baghdad lagoon on the Luangwa river (GPS coordinates S 1161221, E03268300 and elevation 617), NPW camps and the affected villages in the RHCs catchment areas.

Local health officials in the affected area collected specimens from affected patients which, included swabs from vesicular lesions and blood. The specimens were collected by swabbing of cutaneous lesions from suspected patients. A total of 12 swabs and blood specimens were submitted for anthrax detection and confirmation.

In case of animals, sections of tissues and bones from carcasses were obtained from hippo and buffalo, while soil samples from hippo and buffalo grave sites and soil on land where hippos graze from were obtained. Water samples from the lagoon where hippos were struggling to survive were also collected. The collected samples were carefully transported to the laboratory for analysis.

Cuttings of flesh from the tongue, buccal mucosa and neck area of a Hippo and buffalo, as well as soil samples from hippo grave sites, soil on the land where the hippos died and water samples from Baghdad lagoon were tested for anthrax.

Study area
Chama district is one of the 7 districts in Muchinga Province in the north-eastern part of Zambia. It is a Game Management Area (GMA) and it experiences a lot of human-animal conflicts. Most agricultural activities are undertaken on the plateau while in the valley they heavily depend on wildlife. Chama South, the area affected by the outbreak is predominantly a game reserve with some game camps and lodges for professional hunters and tourists. Cases were recorded in Chigoma, Chikwa, Lundu, Kapichilasenga and Pondo Rural Health Centres (RHCs).

Case definition of Anthrax

  • A suspected case was defined as person with acute onset characterized by several clinical forms that are:
  • Cutaneous form-any person with skin lesion evolving over 1 to 6 days from a papular through a vesicular stage to a black eschar invariably accompanied by oedema that may be mild to extensive;
  • Gastro intestinal-any person with abdominal distress characterised by nausea, vomiting, anorexia and followed by fever;
  • Pulmonary (inhalation anthrax)-any person with a brief prodrome resembling acute viral respiratory illness, followed by rapid onset of hypoxia, dyspnoea and high temperature with x ray evidence of meditational widening.

A confirmed case of anthrax in human can be defined as clinically compatible case of cutaneous, inhalational or gastrointestinal illness that is laboratory confirmed by isolation of Bacillus anthracis from an affected tissue or site [18].

Public Health response
The response to the outbreak included case detection, case management, contact tracing, community sensitizations and stakeholders’ involvement. All cases meeting the case definition were referred to the rural health centres for management as outpatients except for one who was treated as an inpatient for four days because of his presentation with abdominal pains, difficulties in breathing, extensive swelling of the face and head. The patient was discharged in a stable condition. A line list of cases was maintained and updated accordingly.  Active cases were treated with oral ciprofloxacin of varied dosages according to age twice daily for 7 days: below 4 years 125mg; 4 to <15 years 250mg ; ≥ 15 years 500mg. Contacts traced were given a prophylactic stat dosage according to age as above.

Communication on the outbreak was strengthened at all levels and regular briefing reports were made at different levels and appropriate times. The Minister of Health issued a press statement about the outbreak that contributed to raising public awareness of the outbreak and response interventions that were in place. Community sensitization was conducted through the community radio, Zambia News and Information Services public address system, community and school meetings, door to door visitations by community health workers and meetings with different stakeholders and community leaders. Standard messages were developed on the types of anthrax, causes, signs and symptoms, risk factors, prevention, treatment and the importance of early care seeking and were disseminated widely in the community. Another key message given to the community was about the importance of reporting deaths of domestic and wild animals and to avoid getting into contact or eating such animals.

Decontamination using lime was conducted on animal grave sites both on the river banks and other grave site on the land and the bush. All the dead buffaloes and hippos remains were burned and buried on their grave sites. A Mobile Bio-safety level 3 laboratory for quick confirmation of cases both in human and animal populations was put in place.

Laboratory investigations
A biosafety level 3 laboratory was deployed on site for analysis of samples from both human and animal cases. The samples were analysed for B. anthracis according to the World Health Organization (WHO) guidelines and involved culture, isolation and confirmation of the isolates by polymerase chain reaction (WHO, 2008). The swabs and blood from suspected patients were directly inoculated on Blood agar (Himedia Laboratories Ltd., Mumbai, India) containing 5% sheep blood. The samples from animals and soil were decontaminated by subjecting them to heating in normal saline at 75ºC for 5 minutes. The fresh samples of tissues were inoculated directly on Blood agar.
The confirmed isolates of Bacillus anthracis were then subjected to antimicrobial susceptibility tests to define the profile of antimicrobial sensitivity, using standard antimicrobial discs on Mueller-Hinton agar (Difco; Becton, Dickinson and Co, Franklin Lakes, NJ, USA) followed by an E-test to determine the minimum inhibitory concentration (CLSI, 2008). The antibiotics tested with the disc diffusion method were penicillin, chloramphenicol, cotrimoxazole, erythromycin, doxycycline, tetracycline, streptomycin and gentamicin (Himedia Laboratories Ltd., Mumbai, India). Others were ciprofloxacin, amoxicillin, ampicillin and vancomycin (Oxoid Ltd., Basingstoke, UK). The MIC was determined for chloramphenicol,doxycycline, tetracycline, cotrimoxazole (Oxoid), ciprofloxacin, penicillin and erythromycin (Himedia Laboratories Ltd., Mumbai, India)

Figure 1. Skin lesion of anthrax on the feet

 

Figure 2. An ulcer and eschar with surrounding oedema

 Results

In this outbreak, 79 human cases and 25 carcasses (18 hippos and 7 buffalos) were identified. Of these human cases and animals, 12 human specimens and all animal samples were tested for Bacillus anthracis. Furthermore, lagoon water samples, soil samples from animal grave sites and land/pasture where animals graze from were also tested for Bacillus anthracis.

Table 1: Analysis of samples through culture, isolation and PCR

The tested hippo samples were negative while buffalo samples (2 buffalos) were positive for Bacillus anthracis. The water samples were negative while some soil samples from the hippo and buffalo grave site and pasture were positive (Table 1). Antimicrobial sensitivity patterns on the cultured 6 B. anthracis isolates indicated sensitivity to a range of drugs used. Intermediate sensitivity was observed with cotrimoxazole and erythromycin, while resistance with vancomycin was noted. The minimum inhibitory concentration of antimicrobial agents was observed at various points: chloramphenicol (8 µg/mL); doxycycline (0.5 µg/mL); tetracycline (1 µg/mL); ciprofloxacin (0.5 µg/mL); cotrimoxazole (16 µg/mL); penicillin (0.12 µg/mL); and erythromycin (4 µg/mL).Of the human cases of clinically confirmed anthrax identified the majority 41 (52%) were from Chikwa RHC followed by 24 (30%) from Pondo RHC. Of the total anthrax cases 48 (61%) were males. Overall, most cases (28%) were from the 5 – 14 age group (p<0.01). These results are shown in Table 2.

Table 2 Anthrax cases by age groups, health facility and exposure

Analysis of age group in each sex group revealed that amongst the males, most of the cases were aged between the 15-24 age-group (33%) followed by the 5 -14 (29%) whereas for females, it was highest among the less than 5 years and 5 – 14 age-group at 26% in both groups followed by those above 45 years (23%), as shown in Table 2. Analysis of differences between sexes in age groups showed a significant difference (p<0.001) between the sexes only in the 15 – 24 years age group. There was no significant difference (p=0.525) between children (<15 years) and adults (≥15years).

Clinical investigations noted the following signs and symptoms: eschar, rash like lesions among others. One patient had an allergic reaction features (figure 1 & 2). All cases except two were associated with consumption of dead hippo and/or buffalo meat. Of the two who had not eaten, one had eaten fish from the Baghdad lagoon where anthrax was confirmed and the other participated in butchering the carcasses.

The outbreak was contained within one month of onset between 19th September and 20th October 2016 (Figure 3). There were no fatalities

Figure 3 Epi-curve on anthrax outbreak in Chama, 2016

Discussion

An outbreak of cutaneous anthrax associated with Bacillus anthracis occurred in Chama district affecting almost a total of 80 children and adults with no significant difference between age groups and about 25animals. In this case another animal, the buffalo has come into the transmission pattern of anthrax. There were no positive results from hippopotamus. This could have been due to the decomposed carcasses. Bacillus anthracis is easily overrun by anaerobic bacteria upon death. This outbreak was less than that in the 2011 outbreak in the same district which affected about 520 humans with 6 deaths and 80 hippopotamus. Although there was no significant difference between age groups, it was noted on further analysis that in the 15 -25 age group there was a significant difference between males and females, with males more likely to be infected than females. This could be attributed to the fact that the males of this age group were the ones handling the carcasses to dismember them for meat.

All human cases identified were associated with eating either one or both of hippo and buffalo meat obtained from carcases in the outbreak area. Literature documents an association of anthrax infection with eating meat from infected carcasses or drinking contaminated water, through the skin by contact with infected material or by insect bites, and through the lungs by inhaling spores has been documented [19]. Some parts of Zambia are endemic of anthrax as evidenced by continued outbreaks impacting negatively on the economy of the livestock industry and public health generally. Social and economic determinants include poor food security resulting from draught in Chama area have been noted as contributing factors in these outbreaks. Despite knowing the consequences of eating infected meat, people prefer to get the disease than die from starvation. Similar determinants are described in the outbreaks in Western province [10]. This gap between knowledge and behavior became a threat to the communication effort that was mounted and required more interactive communication methods within the community to emphasise the dangers of anthrax and the importance of prevention and to promote community ownership and local solutions

The Anthrax outbreak in Chama was fueled by human behaviour, particularly that of handling dead animals. These risky behaviours have been well documented in similar outbreaks of anthrax where the need to educate communities was emphasized [20, 21, 22]. Although the people in Chama were aware about anthrax from previous outbreaks, it was very critical to sensitise the community and reinforce the knowledge on the causes, risk factors, signs and symptoms and to promote early care seeking. Early reporting of deaths of animals and wildlife by community members can also prevent the spread of anthrax. Equally, effective communication during an outbreak is important particularly using credical sources and ensuring the use of channels which can reach all the target audiences. The practice of communicating at different levels on a regular basis helped to build and to maintain trust of the community in line with WHO recommendations [24].

Another anthrax outbreak occurred in the same area in 2011. Chama district is located within a wildlife sanctuary, where normal anthrax intervention strategies cannot be applied. It has been documented that while livestock anthrax is generally on the decline in many parts of the world, it remains enzootic in many national parks, for example, in southern Africa and North America. This scenario represents a persistent risk for surrounding livestock and public health [19].

The timely containment and lack of any case fatalities may be attributed to the rapid response by the Ministry of Health with the support of the WHO country office in Zambia that provided financial resources (USD$7,176) and technical support (NPO/National Surveillance Officer and NPO/Health Promotion), National Parks and Wildlife (NPW) and the University of Zambia (UNZA) School of Veterinary Medicine Laboratory and Centre for Veterinary Research Institute (CVRI) who provided laboratory confirmation. A paper by Siamudaala et al. (2006) on the ecology and epidemiology of anthrax in some parts of Zambia indicated that challenges of anthrax control are complex and comprise of socio-political, economic, environmental and cultural factors. They also site inadequate funding, lack of innovative disease control strategies and lack of cooperation from stakeholders as the major constraints to the control of the disease in Zambia [10].

Having confirmed a clear picture of anthrax, the response included as part of the disease containment and prevention measures the following activities: confiscation and destruction of hippo meat and carcasses; active surveillance and contact training; treatment of cases and prophylaxis management of contacts; and community sensitisation including discouraging the community from eating dead animals. As a preventive measure for another outbreak in the same area, formalin and lime were applied to the soils where animas died from (animal graves) and where animals were being cut and shared by the people.

In order to ensure prevention and control for anthrax, enhanced surveillance which would include mechanisms for disease detection, confirmation of diagnosis, reporting, collation of data and feedback of the data to the source, must be employed [20].

Conflict of interest Statement

We declare that we have no conflict of interest.

Acknowledgements

The authors wish to thank the patients and care givers for being cooperative. The authors also acknowledge the efforts by the health staff (Health centre, district level, provincial level) and the Provincial Medical Officer put into the investigation and control of the outbreak

References

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Antimicrobial susceptibility patterns and their correlate for urinary tract infection pathogens at Kitwe Central Hospital, Zambia.

J Chisanga1, ML Mazaba2,3, J Mufunda2, C Besa1, MC Kapambwe-muchemwa1, S Siziya1
1.Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia
2.World Health Organization, Lusaka, Zambia
3.University Teaching Hospital, Lusaka, Zambia
Correspondence: Joshua Chisanga (chisajosh@gmail.com)

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Chisanga J, Mazaba ML, Mufunda J, Besa C, Kapambwe-muchemwa MC, Siziya S. Antimicrobial susceptibility patterns and their correlate for urinary tract infection pathogens at Kitwe Central Hospital, Zambia. Health Press Zambia Bull. 2017;1(1), pp28-37

Inadequate data on antimicrobial susceptibility patterns in the Africa region and indeed in Zambia have led to ineffective empirical treatment before the culture and sensitivity results are made available. The purpose of this study was to determine the antimicrobial susceptibility patterns amongst the most common bacterial causes of UTIs amongst patients presenting at Kitwe Central Hospital (KCH), Zambia.  A 5-year record review of data captured in the laboratory urine register from 2008 to 2013 was conducted. Demographic data, culture and antimicrobial susceptibility data were entered in Epi Info version 7 and analysed using SPSS version 17.0. Associations were determined using the Chi-squared test at the 5% significance level.  A total of 1854 records were extracted from the laboratory register.  The highest frequency of UTI (43.9%) was in the 15–29 years age group. The overall sensitivity patterns indicated that E.coli was mostly sensitive to ciprofloxacin (69.8%), Klebsiella species to ciprofloxacin (68.2%), Proteus species to cefotaxime (66.7%) and Staphylococcus saprophyticus to nitrofuratoin (63.7%). Sensitivity for E. coli to nalidixic acid was higher for males (58.6%) than females (39.5%).  Sensitivity for E. coli to cefotaxime and norfloxacin varied with age (Chi-squared for trend=10.32, p=0.001).  Our results have shown that UTI pathogens isolated at KCH were less than 70% sensitive to the recommended and used antibiotic. Studies to establish highly sensitive antibiotics to UTI pathogens are needed to effectively treat patients.


Introduction

Urinary tract infections (UTIs) account for one of the major reasons for most hospital visits and the determination of the antimicrobial susceptibility patterns of uropathogens will help to guide physicians on the best choice of antibiotics to recommend to affected patients [1]. Bacterial infections that cause community-acquired urinary tract infections and upper respiratory tract infections are most frequently treated empirically. However, an increase in antimicrobial resistance has raised challenges in treating outpatients [2]. The increases in antibiotic resistance of urinary tract pathogens can be attributed mainly to frequent and indiscriminate use of antibiotics [3]. Increasing resistance in bacterial pathogens been reported widely [4]. Despite the widespread availability of antimicrobial agents, UTIs have continued to be increase resistance to antimicrobial agents [5]. The prevalence of antibiotic resistance in UTIs varies according to geographical and regional location [4].  Studies conducted in Pakistan and Washington showed variations in resistance to antibiotics by sex and age group [6,7]. UTIs are caused by different microbial pathogens. The most prevalent bacteria causing UTI are Escherichia coli, Staphylococcus saprophyticus, S. aureus, Proteus sp., Klebsiella pneumoniae, Pseudomonas aeruginosa, and enterococci [1].

The Ministry of Health [Zambia] recommends antibiotic prescription for UTIs to be guided by sensitivity results [8]. The recommended drugs for the treatment of UTI in Zambia are as follows: amoxicillin, nitrofurantoin, nalidixic acid, ciprofloxacin, cefotaxime and ceftriaxone [8]. Limited data on urinary tract pathogens and their in-vitro susceptibility pattern hinder effective empirical treatment. A retrospective study was conducted to determine susceptibility patterns for some of the commonly used antibiotics for the treatment of urinary tract infections at Kitwe Central Hospital, Zambia. 

Methods

The study was conducted at the Kitwe Central Hospital, which is a provincial referral facility for Copperbelt, North Western and Luapula provinces of Zambia. Ethics clearance was obtained from the Tropical Diseases Research Centre Ndola reference number TRC/C4/07/2015 to conduct the study.  

An analysis of secondary data was performed on data captured in the microbiology laboratory register from 2008 to 2013.  The data were captured using Epi info version 7 and analyzed using SPSS version 17.0.  Proportions were compared in 2 x 2 contingency tables using the Yates’ corrected Chi-squared test, while the uncorrected Chi-squared test was used to determine associations in higher contingency tables.  The Chi-squared test for trend was used to determine linear associations.  The cut off point for statistical significance was set at the 5% level.

The culture and sensitivity results that were analysed were results from routine analysis of urine specimen collected from both in- and out-patients. Mid-stream urine
and occasionally urine specimen collected suprapubically were analysed as outlined in the standard operating procedure. Culture was done on CLED agar. Susceptibility testing was done on Mueller Hinton agar using Disk diffusion method with the inoculums suspension in sterile distilled water prepared using a 0.5 McFarland standard.

Results

Table 1 shows susceptibility patterns of commonly isolated UTI pathogens to antibiotics. E.coli isolates were more sensitive to ciprofloxacin (69.8%), norfloxacin (64.0%) and cefotaxime (61.0%) and least to cotrimoxazole (12.7%). Klebsiella species isolates were more sensitive to ciprofloxacin (69.8%), norfloxacin (67.2%) and least to cotrimoxazole (8.4%). Proteus species were  more sensitive to cefotaxime (66.7%), norfloxacin (61.4%), ciprofloxacin (60.6%) and least to co-trimoxazole (17.7%). Staphylococcus saprophyticus isolates were more sensitive to nitrofurantoin (63.7%), ciprofloxacin (63.1%) and norfloxacin (60.5%).

Table 1 Susceptibility patterns of commonly isolated UTI pathogens at Kitwe Central Hospital (Zambia) from 2008-2013

Sensitivity levels for E. coli to antibiotics varied by year. Overall, E.coli was most sensitive to ciprofloxacin (69.8%), norfloxacin (64.0%) and cefotaxime (61.0%) with least sensitivity to co-trimoxazole (12.7%) as shown in Table 2.

Table 2. Susceptibility by year for E.coli to antibiotics at Kitwe Central Hospital (Zambia) from 2008-2013

Apart from ciprofloxacin and co-trimoxazole, sensitivity levels for the other drugs remained constant as shown in table 3.

Table 3 Linear trends in sensitivity levels by year

For both ciprofloxacin and co-trimoxazole, sensitivity levels declined between 2008 and 2013. A unit change in the year corresponded to about 6%(-6.48 for ciprofloxacin and -5.93 for co-trimoxazole).
Sensitivity levels varied by age for cefotaxime (p=0.010) and norfloxacin (p=0.010) as shown in Table 4.

Table 4 E.coli Susceptibility by age group at Kitwe Central Hospital (Zambia) from 2008-2013

Sensitivity levels for cefotaxime linearly decreased with age (Chi-squared test for trend=10.32, p=0.001) but not for nalidixic acid (Chi-squared test for trend=2.20, p=0.138).  The lowest sensitivity level was observed among the 45 years or older patients (48.4% for cefotaxime and 54.5% for norfloxacin). No  significant differences  in antibiotic sensitivity to E. coli were observed between females and males, except for nalidixic acid (p<0.001) with higher levels of sensitivity for males (58.6%) than females (39.5%) as shown in table 5.

Table 5 E.coli Susceptibility by sex at Kitwe Central Hospital (Zambia) from 2008-2013

Discussion

This study provides the information about the antibiotic susceptibility patterns of common bacterial pathogens isolated from urine specimen of patients with urinary tract infections at Kitwe Central Hospital on the Copperbelt province of Zambia. In this study, 1854 urine culture and sensitivity results were analyzed covering the period 2008 to 2013.

Of the 1854 culture results that were analyzed, the most common organisms were   E.coli (46.7%), Klebsiella species (17.1%), Proteus species (15.4%) and Staphylococcus saprophyticus (12.6%). These findings are slightly to what Ekwealor et al found in Nigeria that the most prevalent isolates were S. aureus (28%), E. coli (24.6%), and S. saprophyticus (20%) [1]. Analysis of the susceptibility pattern excluded Enterobacter species, Enterococcus faecalis and Pseudomonas because of small numbers. Susceptibility by age and sex were only done for E.coli because of large numbers.
In the current study, E.coli isolates were more sensitive to ciprofloxacin (69.8%), norfloxacin (64.0%) and cefotaxime (61.0%). The analysis of the trends revealed that apart from ciprofloxacin and co-trimoxazole, sensitivity levels for the other drugs in the table remained constant. For both ciprofloxacin and co-trimoxazole, sensitivity levels declined between 2008 and 2013. A unit change in the year corresponded to about 6%(-6.48 for ciprofloxacin and -5.93 for co-trimoxazole). A study conducted in Tumkur, Bangalore, revealed lower sensitivity level for E.coli to ciprofloxacin (24%), norfloxacin (25.5%) and co-trimoxazole (37%) [10]. Another study conducted in Chandigarh, northern India [11], revealed similar sensitivity for E.coli to ciprofloxacin (62%) among outpatients but higher than 48% sensitivity observed in in-patients.  However, the sensitivity level for E. coli to cefotaxime in the current study was lower than the 96% observed among out-patients and 80% among inpatients. A retrospective study carried out in Brazil revealed rate of resistance of E.coli to ciprofloxacin was higher than expected with highest of 36.0% [12]. A study by Cho et al placed ciprofloxacin (20.7%), levofloxacin (22.7%), co-trimoxazole (34.3%) and ampicillin-clavulanate (42.9%) as the least active substance compared to nitrofurantoin (93.1%) and fosfomycin (100%) [13]. A study by Ahmad et al revealed that E.coli had higher rates of rates of resistance to ampicillin (90%), tetracycline (70%), erythromycin (70%) and Cotrimoxazole (50%) [14]. Fasugba et al concluded that ciprofloxacin resistance in UTI caused by E.coli is increasing hence a need to reconsidered empirical treatment [15].  A study by Bryce et al revealed high rates of resistance ampicillin (23.6%), trimethoprim (8.2%), co-amoxiclav (26.8%) and lower rates for ciprofloxacin (2.1%) and nitrofurantoin (1.3%) [16]. Klebsiella species isolates were more sensitive to ciprofloxacin (68.2%), norfloxacin (67.2%) and the least sensitive to co-trimoxazole (8.4%). The study in Tumkur, Bangalore also showed that Klebsiella species had sensitivity of 63% (ciprofloxacin), 66% (norfloxacin) and 58% (co-trimoxazole) [11]. Proteus species were more sensitive to cefotaxime (66.7%), norfloxacin (61.4%) and ciprofloxacin (60.6%). A study done in Portugal revealed the sensitivity of Proteus species as 2.9% for nitrofurantoin, 75.1%  for norfloxicin,75.0% for ciprofloxacin and 73.2% for cefotaxime [17]. Staphylococcus saprophyticus isolates were more sensitive to nitrofurantoin (63.7%), ciprofloxacin (63.1%) and norfloxacin (60.5%). A study in Iran showed the sensitivity of coagulase negative staphylococci as 100% for ciprofloxacin and nitrofurantoin, 69.2% for co-trimoxazole, 23.1% for cefotaxime and 0% for nalidixic acid [18].

The Sensitivity levels of E.coli varied with age for cefotaxime and norfloxacin.  Furthermore, the sensitivity variation was linearly related to age for cefotaxime suggesting that the drug should be limited to younger age groups of <15 years.  Although no similar pattern emerged for norfloxacin, the least sensitivity was observed in the 45 years or older age group, indicating that the drug should not be used for persons in this age group. Sensitivity to cefotaxime decreased as age increased and this was the same for nalidixic acid and nitrofurantoin. Cefotaxime had the highest sensitivity in the under 15 years of age (70.6%) and lowest in the 45 years or older age group (48.8%). Chloramphenicol had the highest sensitivity in the 15-29 years age group (53.2%) and lowest in the <15 years age group (30.0%). Ciprofloxacin had highest sensitivity in the under 15 years age group (75.5%) and lowest in the 45 years or older age groups (60.5%). Co-trimoxazole had the highest sensitivity in the 45 years or older age group (17.2%) and the lowest in the under 15 years age group (0.0%). Nalidixic acid had the highest sensitivity in the under 15 years age group (56.5%) and lowest in the 45 years or older age group (33.6%). Nitrofurantoin had the highest sensitivity in the 15-29 years age group (61.2%) and the lowest in the under 15 years age group. Norfloxacin had the highest sensitivity in the   under 15 (80.0%) and lowest in the 45+ age group (54.5%).

The only sex difference in sensitivity levels was observed for nalidixic acid, with higher sensitivity for males (58.6%) than females (33.8%).  However, the level of sensitivity was too low to recommend the use of nalidixic acid among males only.

A study done in Pakistan on the resistance of E.coli across age groups and sex revealed variation in resistance patterns of E.coli to antibiotics. Nitrofurantoin was about  2-fold more resistant  in males than  females, while trimethoprim,  co-trimoxazole  and  ceftazidime showed 11%  more  resistance in males than females. Ceftriaxone, ciprofloxacin showed 13%, 14%, more resistance in males as compared to females, respectively. E.coli also manifested almost complete resistance to trimethoprim and co-trimoxazole in all the age groups. The isolates from below 40 years male patients and age groups 50-59 and 70-79 showed almost complete resistance to ciprofloxacin, while  it  was  effective  in  half  of male  patients  in  age  groups  40-49  and  60-69.  Nitrofurantoin showed 33% resistance in age groups 0-9, 20-29 and 30-39 and was found almost sensitive in all other age groups.  Ceftriaxone showed 60% resistance in age group 60+. Ceftriaxone was sensitive in   age group 10-19, while it showed variable resistance among other age groups.
Ciprofloxacin, co-trimoxazole and trimethoprim showed variable resistance patterns in all age groups except 40-49 in which these antibiotics were effective among half the female patients [6]. A study done in USA reported that differences in antibiotic susceptibility to common urinary anti-infectives among E. coli isolated from males versus females was meaningful hence recommending that male sex alone cannot be used as a basis for empirical treatment [7].

Our results have shown that the UTI pathogens isolated at KCH were less than 70% sensitive to the recommended and used antibiotic. Studies to establish high sensitive antibiotics to UTI pathogens are needed to effectively treat patients.

Authors’ contributions

JC obtained the data, conducted preliminary analysis and drafted the manuscript. JM revised the manuscript. CB research protocol development, analysed the findings and revised the manuscript. SS interpreted the findings and edited the manuscript MLM reanalyzed the data, interpreted the results and edited the manuscript.

Acknowledgement

We would like to thank the management of Kitwe Central Hospital for allowing us to use their records.

References

  1. Ekwealor PA, Ugwu MC, Ezeobi I, Amalukwe G, Ugwu BC, Okezie U, et al. Antimicrobial evaluation of bacterial isolates from urine specimen of patients with complaints of urinary tract infections in Awka, Nigeria. Int J Microbiol 2016;2016:9740273.
  2. Biedenbach DJ, Badal RE, Huang MY, Motyl M, Singhal PK, Kozlov RS, et al. In Vitro activity of oral antimicrobial agents against pathogens associated with community-acquired upper respiratory tract and urinary tract infections: A five country surveillance study. Infect Dis Ther 2016 ;5:139-53.
  3. Stamm WE. Urinary tract infections and pyelonephritis. In: Isselbacher KJ, Braunwald E, Wilson JD, editors. Harrison’s principles of internal medicine. 13th sed. Vol. New York: McGraw Hill; 1994.
  4. Tambekar DH, Dhanorkar DV, Gulhane SR, Khandelwal VK, Dudhane MN. Antibacterial susceptibility of some urinary tract pathogens to commonly used antibiotics. Afr J Biotechnol 2006;5:1562–5.
  5. Karlowsky JA, Kelly LJ, Thornsberry C, Jones ME, Sahm DF. Trends in antimicrobial resistance among urinary tract infection isolates of Escherichia coli from female outpatients in the United States. Antimicrob Agents Chemother 2002;46:2540–5.
  6. Nerurkar A, Solanky P, Naik SS. Bacterial pathogens in urinary tract infection and antibiotic susceptibility pattern. J Pharm Biomed Sci 2012;21:1-3.
  7. Bashir MF,  Qazi JI,  Ahmad N, Riaz S. Diversity of urinary tract pathogens and  drug resistant isolates of Escherichia coli different age and gender groups of Pakistanis. Trop  J  Pharm Res 2008;7:1025-31.
  8. McGregor JC, Elman MR, Bearden DT, Smith DH. Sex- and age-specific trends in antibiotic resistance patterns of Escherichia coli urinary isolates from outpatients. BMC Fam Pract 2013;14:25.
  9. Ministry of Health, Zambia National Formulary Committee. Standard Treatment Guidelines, Essential Medicines List, Essential Laboratory Supplies for Zambia. 2nd ed. Lusaka, Zambia: Zambia Ministry of Health, 2008.
  10. Karlowsky JA, Lagacé-Wiens PR, Simner PJ, DeCorby MR, Adam HJ, Walkty A, et al. Antimicrobial resistance in urinary tract pathogens in Canada from 2007 to 2009: CANWARD Surveillance Study.Antimicrob Agents Chemother 2011;55:3169–75.
  11. Manjunath GN, Prakash R, Vamseedhar A, Kiran S. Changing trends in the  spectrum of antimicrobial drug resistance pattern of uropathogens isolated from hospitals and community patients with urinary tract infections in Tumkur and Bangalore. Int J Biol Med Res 2011;2:504-7
  12. Mahesh E, Ramesh D, Indumathi VA, Punith K, Raj K, Anupama HA. Complicated urinary tract infection in a tertiary care centre in south India. Al Ameen J Med Sci 2010; 3:120-7.
  13. Linhares I, Raposo T, Rodrigues A, Almeida A. Frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections: a ten-year surveillance study. BMC Infect Dis 2013;13:19.
  14. Amin M, Mehdinejad M, Pourdangchi Z. Study of bacteria isolated from urinary tract infections and determination of their susceptibility to antibiotics. Jundishapur J Microbiol 2009; 2:118-23.
  15. Reis AC, Santos SR, Souza SC, Saldanha MG, Pitanga TN, Oliveira RR. Ciprofloxicin resistance pattern among bacteria isolated from patients with community acquired Urinary tract infection. Rev inst Med Trop Sao Paulo 2016;58:53.
  16. Cho YH, Jung SI, Chung HS. Antimicrobial susceptibilities of extended spectrum beta-lactamaseproducing Escherichia coli and Klebsiella pneumoniae in health care-associated urinary tract infection: focus on susceptibility to fosfomycin. Int Urol Nephrol 2015; 47:1059-7.
  17. Ahmad W, Jamshed F, Ahmad W. Frequency of Escherichia coli in patients with community acquired urinary tract infection and their resistance pattern against some commonly used anti bacterials. J Ayub Med coll Abbottabad 2015;27:333-7.
  18. Fasugba O, Gardner A, Mitchell BG, Mnatzaganian GC. Ciprofloxicin resistance in community and hospital acquired coli urinary tract infections: a systemic review and meta-analysis of observational studies. BMC Infect Dis 2015;15:545.
  19. Bryce A, Hay AD, Lane IF, Thornton HV, Wootton M, Costelloe C. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association in primary care: systematic review and meta-analysis. BMJ 2016;352:i939
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Anthrax outbreaks and epidemics in Zambia, 1990-2011: A review

S Siziya
Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia

Correspondence: Seter Siziya (ssiziya@gmail.com)

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Siziya S. Anthrax outbreaks and epidemics in Zambia, 1990-2011: A review. Health Press Zambia Bull. 2017;1(1) [Inclusive page numbers]

Anthrax is endemic in Zambia. A review was conducted for literature published on the epidemiology of anthrax in Zambia using google, google scholar and PubMed.  A total of 7 publications were obtained using search words: anthrax, Zambia, epidemiology, outbreak and surveillance; and of these, 2 were full PubMed Central articles, 4 were abstracts without full articles and one was a citation.  In Zambia in 1990, out of 220 human cases of anthrax, 19.1% died; between 1991 and 1998, 7.7% of 248 human cases died; between 1999 and 2007, out of 1790 human cases, 4.6% died; and in 2011, the case mortality rate was 1.2% out of 521 human cases.  In Western province of Zambia, the overall cattle:human anthrax ratio was 1:1.47 and a reduction (Slope=0.738, 95% CI [-1.394, -0.083]) in the human case fatality rate was observed between 1999 and 2007.  There is scanty information on anthrax in Zambia.  The cattle:human anthrax infection ratio was lower than the expected ratio of 1:10 suggesting under-reporting of human cases or good outbreak/epidemic control. A reduction in the case fatality rate indicates good case management.  An active surveillance of human cases of anthrax is recommended immediately there is an outbreak of bovine anthrax in order for people to start treatment early and avoid severe forms of anthrax.


Introduction

Anthrax is a disease of public health importance caused by the spore-forming gram-positive rod bacteria, Bacillus anthracis and its spores can remain viable in soil for a long time up to decades [1-5].  Outbreaks of anthrax generally occur after a prolonged hot dry period [6] and low pH [7].  Although there are inconsistencies in reports on effects of season, rainfall, temperature, soil, vegetation, host condition and population density on the epidemiology of anthrax, anecdotal evidence suggests that temperature and rains (or drought) and humidity are primary conditions affecting the seasonal variation of anthrax [8].

Animals are infected when they breathe in or ingest spores found in soil, plants, or water. Similarly, people are infected when they breathe in spores, eat food or drink water containing spores, or get infected when spores enter through broken skin [9]. CDC [10] suggests five forms of anthrax: Cutaneous characterized by a painless skin lesion with surrounding oedema, fever, malaise and lymphadenopathy; Inhalation characterized by a prodrome resembling a viral respiratory illness, hypoxia, dyspnoea or acute respiratory distress, mediastinal widening or pleural effusion; Gastrointestinal characterized by severe abdominal pain and tenderness, nausea, vomiting, hematemesis, bloody diarrhea, anorexia, fever, abdominal swelling and septicaemia; Oropharyngeal characterized by a painless mucosal lesion in the oral cavity or oropharynx, cervical adenopathy, oedema, pharyngitis, fever, and possibly septicaemia; Meningeal characterized by fever, convulsions, coma, or Meningeal signs; and Injection among injecting heroin users in which smoking and snorting heroin have been identified as possible exposure routes for anthrax [11].  The most fatal form of anthrax is the inhalation anthrax [12].  Mortality in untreated cutaneous cases can be up to 20% [13-15], 25-60% of untreated gastrointestinal form of anthrax [16,17] and 99% of untreated pulmonary anthrax cases [13,17].

Although antibiotics are not recommended for prophylaxis for fear of developing resistance, these can be given for a short time to persons who have been substantially exposed to anthrax [6].  The situations in which such exposure would occur include biological warfare and consumption of infected under-cooked meat.  Generally, an outbreak of anthrax may be controlled by eliminating the source of infection, disinfection, correct dispose of infected materials and vaccination of exposed domesticated animals.

WHO [6] recommends use of antibiotics with penicillin as a drug of choice for treatment of anthrax.  The other antibiotics that can be used in the treatment of anthrax are ciprofloxacin and doxycycline. In addition to the primary antibiotic (penicillin or ciprofloxacin), a supplementary antibiotic (clarithromycin, clindamycin, vancomycin, rifampicin, streptomycin, vancomycin or rifampicin) can be administered for severe cases.  Whilst the epidemiology of anthrax worldwide is well known, there is scanty information on the occurrence, its magnitude and factors associated with anthrax in Zambia.  The objective of the study was to review literature in order to tie up evidence on the epidemiology of anthrax in Zambia.

Methods

Zambia is a land locked country with three seasons: the rainy season (November to April), dry cool (May to August) and dry hot season (September to October/November).  In the dry seasons, animals will congregate around watering holes and graze on short grass, thereby, exposing to spores in the soil.  The disease is endemic in the Luangwa valley and Zambezi floodplain. The main source of the disease in the valley is game, while in the floodplain it is cattle [18].  Most livestock (cattle, goats and sheep) are found in Southern, Central, Lusaka, Copperbelt and Eastern provinces and mostly (83% of cattle, 64% of sheep and 97% of goats) reared by traditional farmers [19].

The Ministry of Health [20] adapted the WHO AFRO/CDC definitions for suspected and confirmed cases of anthrax as follows: A suspected case of anthrax is any person with acute onset of a disease characterized by several clinical forms of cutaneous form that is defined as any person with skin lesion evolving over 1 to 6 days from a popular through a vesicular stage, to a depressed black eschar invariably accompanied by oedema that may be mild to extensive; Any person with abdominal distress characterized by nausea, vomiting, anorexia and followed by fever is said to have gastro-intestinal form of anthrax; Any person suffering from Pulmonary (inhalation) form of anthrax has brief prodrome resembling acute viral respiratory illness, followed by rapid onset of hypoxia, dyspnoea and high temperature, with X-ray evidence of mediastinal widening; and any person with acute onset of high fever possibly with convulsions, loss of consciousness, meningeal signs and symptoms; commonly noted in all systemic infections, but may present without any other clinical symptoms of anthrax is said to have Meningeal anthrax.  Meanwhile, a confirmed case of anthrax is defined as a clinically compatible case of cutaneous, inhalational or gastrointestinal illness that is laboratory-confirmed by isolation or B. anthracis from an infected tissue or site; or other laboratory evidence of B. anthracis infection based on at least two supportive laboratory tests.

Literature was searched using google, google scholar and PubMed.  Literature not published in peer-reviewed journals as reports were obtained using google. Published works in peer-reviewed journals was gathered using google scholar and PubMed.

Results

A total of 7 publications were obtained using search words: anthrax, Zambia, epidemiology, outbreak and surveillance; and of these, 2 were full PubMed Central articles, 4 were abstracts without full articles and one was a citation. Animals reported to be affected in Zambia by anthrax include: cattle [21-23], hippopotamus, giraffe, buffalo, kudu, elephant, puku, wild dog, waterbuck, impala, wildebeest and hyena [24].

In Western province of Zambia, the overall cattle:human anthrax infection ratio was 1.47 between 1999 and 2007 in Western province of Zambia [23].  However, between 1991 and 1993, a ratio of 0.10 was observed [21].

Table 1. Cattle to human anthrax ratio in Western province of Zambia: 1991-1993 and 1999-2007

Table 1 shows the cattle:human anthrax infection ratios. A reduction of the human case fatality rate was observed in Zambia between 1990 and 2011 from 19.1% to 1.2% (Table 2; Siamudaala et al [22];Munang’andu et al. [23]; Hang’andu et al. [25]).  A similar observation was made between 1999 and 2007 in the upper Zambezi floodplain of western Zambia (Slope=-0.738, 95% CI [-1.394, -0.083]) as shown in Figure 1.

 Figure 1 Adapted from Munang’andu et al [22]

The common forms of human anthrax were cutaneous and gastrointestinal. Munang’andu et al [23] reported that human cases of the cutaneous form were higher than those for gastrointestinal in Western province.  Meanwhile, Siamudaala et al [21] found that gastrointestinal was more common than cutaneous in humans in Western and North-western provinces.  The signs and symptoms for cutaneous human anthrax cases were redness and oedema of the skin, oedema of the face, enlarged lymph nodes and fever.  Meanwhile the signs and symptoms for gastrointestinal human anthrax cases were vomiting, diarrhoea, abdominal pain and gastroenteritis [20,22].

Table 2 Cattle:Human ratio by year

Hang’ombe et al [24] reported that B. anthracis was susceptible to penicillin, chloramphenicol, doxycycline, tetracycline, streptomycin, ciprofloxacin, amoxicillin and gentamicin.  It was found to be resistant to vancomycin.  Meanwhile, it was intermediate susceptible to cotrimoxazole and erythromycin.

Discussion

Little has been published on both human and bovine anthrax in Zambia despite the frequent outbreaks and epidemics reported in the country.  Control of anthrax outbreaks and epidemic can only be effective if guided by results of research on the subject. Whilst control of anthrax in cattle through vaccination has a history of success in Zambia, it is practically impossible to control anthrax in game.  WHO [6] estimates that for a single carcass, there are 10 cutaneous and enteric human cases in Africa.  This high ratio may partly be attributed to hunger where people have to eat animals that died from anthrax [26,27].  Globally, WHO [8] estimates that there is one human cutaneous anthrax case to ten anthrax livestock carcasses. Although anthrax is a notifiable disease in Zambia, the observed numbers of human cases of anthrax in Western and North-western provinces are an underestimate partly due to inadequate disease surveillance and poor record keeping [28].

Cases of human anthrax cases maybe underreported because of fear of game rangers to suspect them to be poachers.  The other reason for underreporting of human cases maybe due to some nonspecific signs and symptoms of anthrax that may go unnoticed as cases of anthrax.  Alternatively, a timely and successful response to an outbreak would result in fewer infected humans in relation to infected cattle.  This would partly reflect a good cattle vaccination programme against anthrax.  Further, community’s acceptance of avoiding coming into contact with an infected animal by skinning, butchering or eating meat of such an animal would reduce human infection rate.

The change in the direction of the cattle:human anthrax ratio between 19911993 and 1999-2007 partly reflects changes in the control of the epidemic.

A reduction in the human case fatality rate indicates good case management.  An active surveillance of human cases of anthrax is recommended immediately there is an outbreak of anthrax in bovine so that people can start treatment as soon as possible in order to avoid severe cases of human anthrax. Although the common forms of human anthrax in Zambia are cutaneous and gastrointestinal, there are rare cases of inhalation anthrax.  People may be infected through the processing of hides and making of mats, drums or stools [23].   The most appropriate antibiotics to use to treat anthrax in Zambia include penicillin, chloramphenicol, doxycycline, tetracycline, streptomycin, ciprofloxacin, amoxicillin and gentamicin.  Although WHO [6] recommends use of vancomycin as a supplementary antibiotic in severe cases, it was found to be resistant to B. anthracis in Zambia [25].  Susceptibility tests are recommended to be conducted from time to time to monitor antibiotic resistance to B. anthracis.

Conclusion

Anthrax is endemic in Zambia but literature is scanty.  There is need for more research to inform policy.  A reduction in the human case fatality rate indicates good case management.  An active surveillance of human cases of anthrax is recommended immediately there is an outbreak of bovine anthrax in order for people to start treatment early and avoid severe forms of anthrax.

References

  1. Manchee RJ, Broster MG, Stagg AJ, Hibb SE. Formaldehyde solution effectively inactivates spores of Bacillus anthracis on the Scottish island of Gruinard. Appl Environ Microbiol 1994;60:4167–71.
  2. Wood JP, Meyer KM, Kelly TJ, Choi YW, Rogers JV, Riggs KB, et al. Environmental Persistence of Bacillus anthracis and Bacillus subtilis Spores. PLoS ONE 2015;10(9):e0138083.
  3. Wilson JB, Russell KE. Isolation of Bacillus anthracis from soil stored 60 years. J Bacteriol 1964;87:237–8.
  4. De Vos V. The ecology of anthrax in the Kruger National Park, South Africa. Salisbury Med Bull 1990;68S:19–23.
  5. Driks A. Overview: Development in bacteria: spore formation in Bacillus subtilis. Cell Mol Life Sci 2002;59:389-91.
  6. World Organisation for Animal Health, World Health Organization, Food and Agriculture Organization of the United Nations. Anthrax in humans and animals. 4th ed. Geneva: World Health Organization, 2008.
  7. Titball RW, Turnbull PC, Hutson RA. The monitoring and detection of Bacillus anthracis in the environment. Society for Applied Bacteriology Symposium Series 1991;20:9S–18S.
  8. World Health Organization. Guidelines for the surveillance and control of anthrax in humans and animals. 3rd ed. WHO/EMC/ZDI/98.6.
  9. CDC.  Anthrax: Basic Information. http://www.cdc.gov/anthrax/basics/index.html.
  10. CDC. Anthrax (Bacillus anthracis) 2010 Case Definition. URL: https://wwwn.cdc.gov/nndss/conditions/anthrax/casedefinition/2010/.
  11. Shadomy SV, Traxler RM, Marston CK.  Anthrax. In CDC. Infectious diseases related to travel. Chapter 3. URL: https://wwwnc.cdc.gov/travel/yellowbook/2016/infectiou s-diseases-related-to-travel/anthrax
  12. CDC. URL: http://www.cdc.gov/anthrax/basics/types/index.html.
  13. Clark CM. Anthrax – a real and present threat? Pharm J 1998;260: 374.
  14. Harrison LH, Ezzel JW, Abshire TG, Kidd S, Kaufmann Evaluation of ecological Tests for Diagnosis of Anthrax after an Outbreak of Cutaneous Anthrax in Paraguay. J Infect Dis 1989;160:706-10.
  15. Davies JCA. A Major Epidemic of Anthrax in Zimbabwe, Part II. Cent Afr J Med 1983;29:8-12.
  16. Ndyabahinduka DGK, Chu IH, Abdou AH, Gaifuba JK. An outbreak of Human Gastrointestinal Anthrax. Ann Ist Sanita 1984;20:205-8.
  17. Hambleton P, Carman JA, Melling J. Anthrax: the disease in relation to vaccines. Vaccine 1984;2:125-32.
  18. Zambezi Basin Wetlands Volume III: Land use change and human impacts. URL: http://www.zamsoc.org/wpcontent/uploads/2012/02/Wetlands-Phase-2-Vol-IIILand-Use.pdf.
  19. .Aregheore EM. Country pasture/forage resource profiles: Zambia II. Apia, Samoa, 2009. URL: http://www.fao.org/ag/agp/AGPC/doc/Counprof/zambia/ zambia2.htm.
  20. Ministry of Health [Zambia]. Technical guidelines for integrated disease surveillance and response in Zambia. Adapted from the 2010 2nd edition. Technical guidelines for integrated disease surveillance and response in the African region developed by WHO AFRO and CDC. Version 1.3. Lusaka, Zambia, Ministry of Health, 2011.
  21. Siamudaala VM, Bwalya JM, Munang’andu HM, Sinyangwe PG, Banda F, Mweene AS et al. Ecology and epidemiology of anthrax in cattle and humans in Zambia. Jpn J Vet Res 2006;54:15-23.

 

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Tuberculosis burden in Southern province, Zambia, 2004 to 2013: Analysis of routine Tuberculosis surveillance data

F Hadunka1,2, R Kumar3, NW Chilembo2, CN Jacobs4, R Hamoonga5, J Chinyonga2, C Michelo4 
1.Zambia Field Epidemiology Training Program, Lusaka, Zambia
2. Ministry of Health, Lusaka, Zambia
3. ASPPH/CDC Allan Rosenfield Global Health Fellow
4. University of Zambia School of Medicine, Department of Public Health, Lusaka,Zambia
5. Zambia National Public Health Institute (ZNPHI), Lusaka, Zambia
Correspondence: Francis Hadunka (fhadunka@yahoo.com)

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Hadunka F, Kumar R, Chilembo NW, Jacobs CN, Hamoonga R, Chinyonga J, et al. Tuberculosis Burden in Southern Province, Zambia, 2004 to 2013:  Analysis of Routine Tuberculosis Surveillance Data. Health Press Zambia Bull. 2017;1(1), pp11-20


Tuberculosis (TB) burden in Zambia is high (410/100,000 population incidence in 2013), but few data at subnational level for monitoring trends in incidence, case fatality rate (CFR), or district distribution are available and routinely collected surveillance data are not regularly analysed. The aim of this work was to determine the TB trends in incidence, treatment failure, HIV testing and positivity, and fatalities in Southern Province, Zambia, during the period 2004 to 2013.

Print and electronic TB registers in Southern Province were reviewed. The data were entered into MS Excel and descriptive analyses were performed. The annual incidence of TB by district and for Southern Province was calculated using population projections from Central Statistical Office. The proportion of TB patients tested for HIV was calculated.  Additionally, the proportion of TB patients who tested positive for HIV in each year.  

The results indicated a 42% decline in TB incidence from 425/100,000 persons in 2004 to 248/100,000 in 2013. Incidences of TB in by districts varied from year to within the districts. Percentage of sputum-positive TB patients with a negative sputum smear result after completing two months of rifampicin-based therapy improved from 86% (2008) to 88% patients (2013). Percentage of sputum positive TB patients with a negative sputum smear result after six months of the same regimen increased from 86% (2008) to 95% (2013). Percentage of all TB patients who were tested for HIV increased from 78% in 2008 to 96.5% in 2013, while HIV positivity among those tested decreased from 73% (2008) to 65% (2013).  CFR among TB patients fluctuated from 7% in 2008 to 5% in 2012 and 8% in 2013.

Although Southern Province experienced overall improvements in trends in TB incidence, cure rates, and HIV testing and positivity, TB CFR remained above the MOH target of 5%. Factors associated with TB mortality in Southern Province require further investigation.


 

Introduction

In 2013, an estimated nine million people developed TB and 1.5 million died from the disease globally, 360,000 of whom were HIV positive [1]. Over half (56%) of the nine million people with TB were from Southeast Asia and the Western Pacific Region. India and China accounted for 24% and 11% of the total, respectively [1]. In 2013, the treatment success rate continued to be high at 86% among all new TB cases and the HIV testing rate increased to over 75% in 2013 globally [1]. Although TB is slowly declining each year with an estimated 37 million lives being saved between 2000 and 2013 through effective diagnosis and treatment, TB remains a global challenge [1].

An estimated 1.1 million (13%) of the 9 million people who developed TB in 2013 were HIV positive [1]. In combination, HIV and TB enhance each other’s progress [1]. People who are infected with HIV are 21 – 34 times likely to become infected with TB depending on the stage of HIV [1,3] as HIV lowers the immune system [4]. Previous research in India [8], Russia [12], Chile [15], Ethiopia [13], and Zambia [10] reported that there is no marked difference on TB treatment outcomes between HIV positive and HIV negative TB patients.

A further 25% of the globally estimate of TB patients in 2013 were from the African region, which also had the highest rates of cases and deaths relative to the population [1]. The African continent also accounts for more than 20% of the TB/HIV co- infection, with more than 30% of these from the sub-Saharan region [1,5].

In Zambia, the incidence of TB has been declining from 591/100,000 in 2004 to 500/100,000 in 2008, 421/100,000 in 2012 and 410/100,000 in 2013 [1, 16, 14, 15]. Zambia has an HIV prevalence of 14.5% distributed among both males and females. Approximately 67% are co-infected with TB [6]. Southern Province is equally affected by HIV with a prevalence of 14.7%. The rural districts are less affected than the urban ones [6, 11].

However, the HIV disease burden is in Zambia is also among the highest globally [17]. And there are few data on the proportion of   TB patients who are co-infected with HIV, or the percentage of TB patients who die while on treatment. Although the national TB burden was high in Zambia in 2013 [1], there are few data on the prevalence, incidence, or distribution of tuberculosis and no previous analysis of routinely collected surveillance data has been conducted in Southern province.

In a country with a high burden of TB and HIV, local data are important to inform clinical management recommendations for HIV- TB co-infected patients to reduce morbidity and mortality.  The results of this review may be used at various levels of health care to inform targeted and cost effective decisions concerning medical supplies, drugs, and lab testing by policy makers and medical practitioners. Less than a quarter of health institutions have laboratory facilities able to diagnose TB while almost all the health facilities can treat TB.

The objectives of this study were to determine the trends in TB incidence, cure rates, HIV testing and positivity, and case fatalities in Southern Province, Zambia from 2004 to 2013.

Methods:

A descriptive analysis was carried out on secondary data, which were routinely collected at the health facility level in Zambia’s Southern Province. Only Livingstone district is urban while the rest of the districts are peri-urban and rural. The TB surveillance system in Southern Province is a paper-based from community level to the first level hospital becoming electronic from the district to national level. This surveillance system is passive from the community to first level hospital becoming active from the district to national level. (Figure 1) 

Figure 1. Summary of Southern Province Tuberculosis Surveillance System flow chart with red arrow for reporting while green arrow for feedback

Secondary data were extracted from the paper based and electronic TB registers which included children, women and men of all age groups. All cases diagnosed with and recorded as TB patients regardless of their sputum result and treated from 2004 to 2013 were included. TB/HIV officers extracted routinely collected TB data from both manual and electronic registers kept at the provincial medical office.

The surveillance case definition of a suspected case of pulmonary tuberculosis was any person who presented to any health facility in Southern Province between January 2004 and December 2013 with a cough of more than two weeks in duration with any of the following: night sweats, weight loss, fever, lymphadenopathy, general fatigue, loss of appetite. A confirmed case of tuberculosis was defined as any suspected case with any of the three sputum samples that were collected consecutively and testing positive for tubercle bacilli with Zeil-Nielsen (ZN) stain.

Sputum conversion rate was defined as the percentage of TB patients who were originally sputum positive and tested sputum negative, after completing two months of treatment. Cure rate was defined as the TB patients who were originally sputum positive and tested sputum negative after completing six months of treatment. Death rate was calculated as the percentage of all TB patients who died while on treatment, regardless of their sputum result at diagnosis. Data on geographical location of patients, sputum results, HIV status, and outcomes of treatment were collected; however, no laboratory tests were done although some cases of TB had sputum results available while others did not. Using a data extraction tool in MS Excel, all the data from all TB cases routinely documented and notified as positive between 2004 and 2013 regardless of laboratory confirmation were extracted.

 The annual incidence (per 100,000 persons) of TB for each district was calculated using total population of each district for that year as given by the Central Statistical Office. The overall incidence of TB for Southern Province was calculated by adding all the reported TB cases for all the districts for each year and dividing this by the total population of Southern Province. The percentage of sputum-positive TB patients who recorded a sputum-negative result after two and six months of Rifampicin-based therapy was calculated. The percentage of TB patients who died while on treatment, the proportion of TB patients who were tested for HIV, and the proportion of TB patients who tested positive for HIV were calculated.

Ethical waiver was obtained from the UNZABREC Ethics committee.

 

Results:

During the period under review, it was observed that the incidence of TB declined gradually by 42% from 425/100,000 population in 2004 to 248/100,000 in 2013 (Table 1). TB is prevalent in all districts of Southern Province with some districts having higher incidences than others. The district incidences also varied from year to year in the period under review 2004 – 2013.

Analysis of the sputum results revealed that the percentage of sputum conversion (sputum positive TB patients who recorded a negative sputum smear result after completing two months of Rifampicin-based therapy), increased from 86% in 2008 to 88% patients in 2013 (Figure 2).

Figure 2 Proportion of Patients with Sputum Smear-Positive Tuberculosis (TB) with a Negative Sputum Smear after Two Months and After Six Months of Anti-TB Therapy – South Province, Zambia, 2008-2013

The percentage of cure rate (sputum positive TB patients who recorded a negative sputum smear result after completing six months of rifampicin-based therapy), increased from 86% in 2008 to 95% in 2013 (Figure 2).

Table 1Reported Cases of Any Tuberculosis by District in Southern Province, Zambia, 2004 – 2009


Discussion

A review of the HIV testing data showed that the percentage of total TB patients who were tested for HIV at the time of TB diagnosis increased from 78% in 2008 to 96.5% in 2013. Among the total tested for HIV, the percentage of those who tested HIV positive decreased from 73% in 2008 to 65% in 2013. The case fatality rate (CFR) among the patients on TB therapy in Southern Province decreased from 7% in 2008 to 5% in 2012 then went up to 8% in 2013 Zambia.

The overall trends of TB incidence and treatment failure and HIV positivity declined over the study period in Southern province, while the HIV testing rate and TB cure rate increased. The case fatality rate fluctuated above the ministry of health (MoH) target rate throughout the period under review.

The provincial 2013 TB incidence declined to just over half of the 2006 incidence, while some district-specific incidences increased as others declined by different proportions. The declining incidences are consistent with the national decline in incidence and a global decline in TB incidences [1, 2, 15]. We hypothesize that this decline could be attributed to improved TB treatment regimen leading to reduced sputum positive cases in the community spreading the disease. The decline in incidence could also be attributed to improved accessibility to anti-retroviral therapy, leading to overall improved cellular immunity of the population living with HIV.The percentage of sputum conversions and cure rates increased to just over 75% over study period. This increase is consistent with global picture as shown in the WHO annual TB report of 2015. This increase in sputum conversions and cure rates could be due the introduction of the rifampicin-based, short and effective therapy, which encourages adherence to treatment.

The CFR among TB patients on TB therapy though not consistent throughout the period under review remained above the MOH target throughout the study period. This result is contrary to the expected finding of reducedAlmost all TB patients were tested for HIV during the study period, and the proportion of those who tested positive for HIV among those tested in Southern Province reduced from 75% to 67% over the study period. The improved HIV testing rates could be due to the availability of antiretroviral drugs provided with support of The United States President’s Emergency Plan for AIDS Relief (PEPFAR) and an increase in the numbers of patients currently on ART by more than three times in the period under review. The reduction in HIV positivity among TB patients could be due to increasing numbers of people tested, thereby increasing the total population at risk. However, the decrease in HIV positivity in Southern Province could also reflect a true decrease in the HIV prevalence of the general population in Zambia [6,7].

TB CFR,    considering improved case management of TB with the rifampicin-based regime. Important to note as a study limitation is that the cause death on TB treatment is not the same as TB-caused death.  This CFR defined is deaths while on TB treatment, which may not be a true reflection of death due to TB infection.

No laboratory tests were done as secondary data were analysed, additionally not all cases of tuberculosis had sputum results available, and less than a quarter of all health facilities in southern province have laboratory facilities. The limitation mentioned above may not have much influence on this study because secondary data was analysed to give us an idea of what happened over this period. The national TB reports show similar declining incidences in other provinces [8].

Despite the limitations, the study appears to have a number of strengths as these results describe trends as they were recorded over time. Therefore, this study may provide new information on outcomes of TB treatment as the results suggest that improving outcome of treatment by increasing HIV testing among TB patients, increasing ART uptake among HIV infected TB patients and ensuring all TB drugs are in place may not necessarily reduce TB mortality.

The possible causes of the persistent case fatality rate of over 5% in a situation where all the other parameters have improved could be due to various reasons including existence of Multi Drug Resistance TB, poor adherence to treatment by some patients. The health and lives of the people may be improved by investigating further the factors affecting TB mortality and using this information to improve case management of TB patients.

Our findings of declining incidences suggest the effectiveness of control measures and case management. This seems to indicate that even with the improvement in the prevention and treatment of tuberculosis, both morbidity and mortality due to tuberculosis still occurs in Southern province and that routinely collected data can be analysed and help in informed decision making and guiding policy.

Public health officials at district, province, and national levels in Zambia should regularly analyse routinely collected TB data to use for planning and policy direction. Surveillance officers at the district level should work closely with health facilities and local laboratories to maintain and update electronic TB registers to enable regular analysis. Although incidence trends in Southern Province cannot be generalized to the whole country, other provinces use a similar surveillance system and should routinely analyse their data to monitor the effectiveness of TB management.

Further analytical studies should be pursued to understand risk factors associated with TB mortality in Zambia and why CFR in Southern Province has remained above MOH target level of 5%.

Acknowledgements

This study was made possible by the Ministry of Health (MOH), Centers for Disease Control and Prevention (CDC), Presidents Emergency Plan for Aids Relief (PEPFAR) through the support to the Zambia Field Epidemiology Training Program (ZFETP). We would also like to thank the District Health Department staff, especially TB/HIV officers for assistance in collecting the data.  Dorothy L. Southern provided scientific writing guidance and critically reviewed this manuscript. I sincerely thank Dr Henry Kip Bagget for all the guidance during the development of this manuscript.

CDC authorship disclaimer: “The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.”

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